مجله علوم پزشکی رازی
سال سی‌ام شماره 3 (پیاپی 229، خرداد 1402)

Patent ductus arteriosus (PDA) is one of the most common congenital heart defects in premature infants. Despite the relatively high prevalence of PDA in preterm infants, there is still no clear treatment pattern for these patients. The main treatment options for PDA include surgical obstruction of the duct or the use of medications such as prostaglandin synthetase inhibitors. Previous studies have reported that surgery leads to complications, the most important of which include pneumothorax, chylothorax, infections, and ultimately increased mortality. Therefore, the option of surgical treatment for PDA is largely limited. Finding a suitable treatment option for uncomplicated recovery of PDA in premature infants is very valuable to increase the life of premature infants. Indomethacin was the first prostaglandin synthetase inhibitor to be used to treat PDA. However, due to its relatively common side effects, attempts were made to replace the drug, and the US Food and Drug Administration eventually authorized the intravenous administration of ibuprofen lysine (neoprofen) to premature infants with PDA. At present, according to the results of previous studies, ibuprofen is mainly used to close PDAs. Ibuprofen is as effective as indomethacin and has fewer renal side effects. Recent studies have shown that acetaminophen can also be used effectively to treat PDA in premature infants. However, the use of this drug (orally and parenteral) has not been widely studied in clinical trials. On the other hand, recent studies have examined the positive and uncomplicated effect of intravenous acetaminophen as well as ibuprofen on treat PDA. Therefore, conducting a study comparing the oral use of acetaminophen and ibuprofen in PDA closure in preterm infants is valuable and will greatly help in choosing the best treatment option in them. Therefore, in this study, the effect of oral acetaminophen and ibuprofen on premature infants with PDA was investigated.

This interventional study was conducted from April to Nov 2020. A total of 60 preterm neonates with diagnosis of PDA admitted in NICU of Akbar Abadi Hospital Tehran were selected. Neonates were randomly assigned to two groups. In the first intervention group, oral Acetaminophen was prescribed every 6 hours at a dose of 15 mg/kg for 3 days. In the second intervention group, oral Ibuprofen was prescribed at a dose of 10 mg/kg for day one and 5 mg/kg for the next two consecutive days. Inclusion criteria included Parent's consent to participate in the study, Gestational age between 26 to 37 weeks, and Diagnosis of ductus arteriosus based on echocardiographic evidence at 24 to 72 hours after birth. Exclusion criteria included premature newborn with fever and seizure, life-threatening infections, clinical or radiographic evidence of necrotizing enterocolitis, evidence of bleeding, platelets less than 50,000 per ml, Liver failure, congenital brain-neurological disorders, metabolic and genetic syndromes, pulmonary hypoplasia syndrome, congenital heart anomalies or other fatal abnormalities. Finally, the extent and duration of PDA closure, and echocardiographic findings before and after the intervention and side effects in infants of both groups were evaluated. Data were entered in SPSS and analyzed.

The demographic characteristics in neonates showed that in terms of gender variability, the frequency  of boys and girls in the group of oral acetaminophen and ibuprofen were 16 (53.3%), 14 (46.7%) and 17 (56.7%) and 13(43.3%), respectively. The mean of gestational age was 33.15± 6 weeks. Total of 78.33% of patients underwent cesarean section. The mean birth weight of neonates at the time of diagnosis in the acetaminophen and ibuprofen groups was 2231.41± 690.25 and 1854± 453.47 gr, respectively. About 26.66% of patients had Large PDA. The results of statistical analysis showed that the mean gestational age and weight in the two groups receiving Acetaminophen and Ibuprofen were not significantly different (P = 0.14), (P = 0.746). The LA / AO ratio in the acetaminophen and ibuprofen groups at the beginning of treatment was 0.42 ± 1.57 and 0.56 ± 1.74, respectively, which were not significantly different from each other. At the end of the treatment period, patients in both groups had a significant decrease in LA / AO ratio. After the intervention in the acetaminophen group was 0.36 ± 1.20 and compared to before the intervention was statistically significant (P = 0.013) and in the Ibuprofen group was 0.40 ± 1.38 .There was a statistically significant decrease compared to the results before the intervention (P = 0.017). However, the LA / AO ratio at the end of the treatment period did not differ significantly between the Acetaminophen and Ibuprofen groups (P = 0.412). PDA size in acetaminophen and ibuprofen groups at the beginning of treatment was 2.85(0.48) and 2.81(0.75), respectively, which was not significantly different from each other, but at the end of treatment patients in both groups was significantly reduced. There was a significant decrease in PDA size, this ratio was 1.72(0.92) in the acetaminophen group after the intervention and had a statistically significant decrease compared to the results before the intervention. (P = 0.001) In the ibuprofen group, it was equal to 1.74(1.02) which was significantly lower than before the intervention (P = 0.024). But PDA size at the end of treatment was not significantly different between acetaminophen and ibuprofen groups.After the first course of treatment in the ibuprofen and acetaminophen groups, 43.33% and 46.66% of PDA s were closed, respectively, which was not significantly different between the two groups (P = 09.79). After the second course of treatment, PDA closure was observed in 33.3% and 26.66% of ibuprofen and acetaminophen groups respectively, and there was no statistically significant difference between the two groups (P = 0.653). The most common clinical complications in patients receiving acetaminophen and ibuprofen were short-term hyperbilirubinemia (26.66% and 43.33%, respectively), which was significantly higher in the ibuprofen group (p = 0.03).

Although the rate of PDA closure with oral acetaminophen compared to oral ibuprofen was not different, the incidence of side effects in acetaminophen group was lower than ibuprofen and this drug can be a suitable alternative for use in the treatment of preterm infants with PDA.

Studies have shown that participation in intense and increasing exercise causes delayed damage to the muscle fiber membrane. Because the best type of recycling is not known between training sessions, using methods such as active recycling or creatine supplementation may have beneficial effects through faster removal of fatigue-related factors or the availability of energy sources such as creatine phosphate. On the other hand, the processes of anemia - re-injection of blood, autoxidation of catecholamines, induction of the activity of inflammatory cells as well as neutrophils due to tissue damage in this active species, intensify this activity. Continuation of this process increases free radicals and consequently oxidative stress, and the body of living organisms needs an antioxidant system to limit the harmful effects of free radicals. The range of active antioxidants in the body includes endogenous enzymatic antioxidants and non-enzymatic antioxidants present in meals. Studies have shown that the production of free radicals during strenuous exercise stimulates the production of heat shock proteins (HSPs). Research shows that under physiological conditions, such as strenuous exercise, in which athletes at competitive levels experience excessive training, such as frequent repetitions of competitions throughout the day, to achieve high levels of performance, endogenous antioxidants cannot be completely eliminated. Prevent oxidative damage. For this reason, in recent years, researchers have been looking for strategies to reduce fatigue and maintain performance for athletes by reducing the factors that affect physical performance during and after intense intermittent exercise. Creatine supplementation is one of the most commonly used strategies by athletes. Therefore, the aim of the present study was to investigate the effect of high-intensity interval training with creatine supplementation and two types of active in-water and out-of-water recovery on heat shock protein in men and women swimmers.

 In this quasi-experimental study, 32 non-professional swimmers (16 men and 16 women) with at least 6 months of swimming experience and position in the city with an average anaerobic power of 497 watts per kg participated. Men and women were each randomly divided into two subgroups: in-water recovery (8 men and 8 women) and out-of-water recovery (8 men and 8 women). All groups performed 6 50-meter sprints with a 120-second rest interval (depending on the type of recovery in and out of the water) before and after 6 days of creatine supplementation (4 servings of 5 g per day for 6 days). Data were analyzed by two-way analysis of variance with repeated measures.

 The findings of the combined analysis of variance test showed that the main effect of measurement time was significant. The main effect of recovery was also significant. In addition, the interaction of measurement time with recovery was significant. The interactive effect (measurement time وری recovery × gender) was not significant. In addition, the results of intragroup analysis of variance test with repeated measures on the measurement factor showed that complementary intervention improves HSP72 in both sexes. Also, differences between groups using two-way analysis of variance test showed that the amount of HSP72 after rest, the third and sixth repetition without creatine was not significant. Also at rest and after the third repetition with creatine was not significant but after the sixth Recurrence with creatine supplementation was significant in both sexes.

 The results of the present study show that despite the relative decrease in the mean HSP of the groups after the supplementation period, this difference is not significant and there is no interaction between the independent variables in relation to HSP. Regarding the better condition of the in-water group than the out-of-water group, the present study on further reduction of HSP72 also pointed to the possibility of better regulation of body temperature in water during methionine recycling, which leads to removing or reducing the excitatory effect of heat as a production stimulus. HSP70 caused a drop in the group average after recycling. The lack of significant HSP adjustment among research groups after recovery probably led to the indirect inference that HSP was not highly adjusted in athletes following exercise. The researchers explain why HSP decreases in people who train with high repetition. When a muscle trains better progressively, there is a decrease in HSP due to cellular regulatory mechanisms. Also, when people who have not exercised begin to exercise, there is a false increase in their HSP, which will decrease over time and as the exercise progresses. The researchers said that the higher the amount of exercise, the thinner the amount of HSP. Researchers believe that HSP has a negative self-regulatory mechanism that is regulated by its own synthesis. It can probably be said that HSP does not change as much in trained people as it does in the untrained ones. However, in terms of the type of recycling, the in-water group was in a better position than the out-of-water group. In the present study, supplementation had no significant effect on HSP compared to the period without supplementation, and its interaction with the type of recycling did not make a significant difference in HSP. Studies show that 95% of creatine is stored in skeletal muscle, and creatine supplementation also increases muscle creatine content. Research on the effects of creatine supplementation on muscle phosphocreatine has provided evidence of increased creatine vigor. Another issue addressed in this study was the difference in HSP72 response between men and women to exercise, and the issue of gender impact was raised. In this study, it was concluded that the level of HSP72 in male and female athletes is similar on average and there is no significant difference. Although exercise increased HSP72, it was similar in male and female athletes and was not affected by gender. Also, in this study, the positive effects of specialized recovery in the mentioned indicators following high-intensity intermittent swimming were not found.

Diabetes mellitus is a disease that, is affected by environment and also genetics. The pathophysiological changes of diabetes are caused by dysfunction of peripheral β cells and ROS-dependent inflammation produced by tissues, all of these factors underlie insulin resistance and chronic inflammation, which gradually impairs blood glucose control (1). GATA4 is a cardiac-enriched transcription factor that is essential for various physiological and adaptive responses of cardiomyocytes. Recent studies have shown that GATA4 was able to protect cardiomyocytes from DOX-induced apoptosis, indicating that GATA4 also conveys a survival signal for cardiomyocytes (4). Recent studies have shown that physical activity has a significant effect on improving type 2 diabetes, reducing the risk of insulin resistance, metabolic syndrome and type 2 diabetes, and improving insulin sensitivity (8). Many studies show that by consuming more energy and training intensities, including high-intensity intermittent exercise, there is a greater response to insulin sensitivity throughout the body. During exercise, with muscle contraction and increased AMPK activity, stimulation of insulin sensitivity increases. After exercise, an increase in Akt inactivates TCB1D4 and thus increases the transport of glucose transporter (GLUT4) to the cell membrane, resulting Increases in absorption glucose (9). In recent years, in addition to the emphasis on exercise and physical activity, attention has been paid to dietary supplements and some herbs for the treatment of diabetes, among which there is great interest in the use of honey (15). Honey is primarily rich in carbohydrates and is also abundant in flavonoids and phenolic acids; thus, it is a promising therapeutic antioxidant for various disorders. it is a promising antidiabetic agent.  Although the use of honey due to its therapeutic and nutritional value has long been considered and approved in scientific texts, but its use in modern medical sciences is debatable (17). Therefore, considering the known physiological positive effects and protection of the heart, periodic exercise and thyme honey, as well as their positive role in improving cardiac function and the possibility of stimulating GATA4 gene expression in line with positive physiological adaptations of the heart, especially cardiomyocyte hypertrophy, we hypothesized that: 1- HIIT, Thyme honey  and The combination of both can be effective in increasing the expression of GATA4 gene in male type 2 diabetic rats. Therefore, the aim of the present study was to investigate the effects of eight weeks of HIIT and thyme honey on GATA4 gene expression in male type 2 diabetic rats.

In this experimental study, 36 young male Wistar rats, as a statistical sample, were purchased from Royan Research Institute and were move to the Razi Laboratory of Azad University of Science and Research.  After two weeks of getting acquainted with the laboratory environment and reaching a weight of 197± 20, undergo a high-fat diet (HFD) for 20 weeks on a high-fat diet prepared by the Royan Biotechnology Research Institute, which 45% HFD was given for 3 months and 60% HFD was given for 2 months (20, 21). Then Rats were randomly divided into four groups: control (n=8), HIIT (n=10), thyme honey (n=8) and HIIT*thyme honey (n=10) groups. At the end of the protocol, 28 rats were survived. In each group 2 rats died. To induce diabetes, a high-fat diet is used for 20 weeks and then intraperitoneal injection (25 mg / kg) of STZ solution is used. The HIIT training intervention of 8 weeks, with 2 min running at 80-90% VO2max and 1 min at 50-56% VO2max, was performed for 5 sessions per week including 2 to 8 intervals 16 Up to 34 minutes was done running on a treadmill, so that running time increased from 16 minutes in the first week to 34 minutes in last week. Additionally, during the 8 weeks of intervention, 3 g/kg of diluted thyme honey consumed, 5 days/week in supplement groups, honey and HIIT*honey groups.Cardiac tissue was isolated and transferred to a negative 80 freezer to measure the expression of genes. In the next step, the RNA is extracted by RiboEX Total RNA isolation solution (GeneAll) and finally the quantitative and qualitative study of the RNA by Nanodrop device is evaluated. After ensuring the quality of RNA, it was extracted, cDNA made using the TAKARA kit and transferred to negative 20 freezer. AMPLIQON Master Mix Cybergreen was used for real-time reverse transcription-polymerase chain reaction (real-time RT-PCR). In the present study, the GAPDH reference gene was used as a house keeping gene and the Delta Delta CT method was used to quantitatively analyze the Real Time PCR data. The expression of the GATA4 genes in heart tissue. The primers used in this study were designed by Allel ID6 software and synthesized by Sinaclon Biotechnology Company. The sequence of primers is given in Table 2. Temperature gradient was set. All samples were repeated 2 times in a real-time PCR machine. Also, the temperature and time program of Real Time PCR reaction in the present study is according to Table 3. Data were analyzed using SPSS22 software. Shapiro-Wilk test to determine the normality of data distribution and Levin test for homogeneity of variances and inferential statistics of one-way analysis of variance and tukey post hoc test were used to compare the differences between groups. Significance level in the tests was considered α 05 0.05.

According to the results of descriptive statistics, the scores of HIIT in the insulin resistance index are lower than the other groups. Also, the GATA4 scores in the HIIT and Theym honey are higher than the other groups.  ANOVA Analysis revealed that there was a significant difference between the groups in the variable of HOMA-IR (P = 0.001) and GATA4 gene expression (P = 0.016).The results of Tukey post hoc test showed that HOMA-IR was significantly decreased only in HIIT group when compared with other groups, whereas this finding was not repeated in other intervention groups (p>0.05).and expression of GATA4 gene was significantly increased in HIIT and Theym honey (p <0.05).

The aim of this study was to evaluate the effect of HIIT and thyme honey on insulin resistance index and expression of GATA4 gene in heart tissue of type 2 male diabetic rats. The results of the present study revealed that HOMA-IR were significantly decrease on the HIIT group when compared with others groups, though, there were no significant difference on the insulin resistance index  in thyme honey and  HIIT*thyme honey groups. These results were consistent with the study of Nova et al. (2017), Farazmandi and Rezaian (1399), Jelstad et al. (2021). also, Su et al. (2011) showed that exercise and physical activity can significantly reduce the insulin resistance index (34). Azimi Dokht et al. (2015) also showed in a study that eight weeks of intermittent exercise has a positive effect on fat profile and insulin resistance in type 2 diabetic men (35). Although, in concern with expression of GATA4 gene there are significantly increase in HIIT group in compared others group, there is no significant difference in the other intervention groups. These results are consistent with the findings of Hemmati et al. (2019), Xu et al. (2018), Naderi et al. (2019), Xiao et al. (2014). Xu et al. (2018) demonstrated GATA4 had a protective effect against endothelial dysfunction induced by hyperglycemia. Overexpression of GATA4 was demonstrated to lead to increased expression of NOX4 mRNA and protein. Furthermore, GATA4 overexpression resulted in increased nitric oxide (NO) production through the upregulation of endothelial NO synthase phosphorylation (38). Exercise imposes a higher cardiac workload, inducing angiogenesis and hypertrophy of cardiomyocytes, and GATA4 triggers this physiological process. However, overexpression of GATA4 is also associated with decompensated cardiac hypertrophy, as it occurs in neuroendocrine overactivation-induced HF. On the other hand, in postnatal hearts, GATA4 is essential for cardiomyocyte survival after injury or stress (38).For years, people have believed that diabetics cannot consume honey because honey is high in sugar. Regarding honey, it should be noted that according to the standard, the acceptable limit for the ratio of fructose to glucose of honey is a minimum of 0.9 (40).Due to the fact that the glycemic index of fructose is very low. These findings show that honey causes fewer changes in blood sugar compared to glucose and can prevent the adverse effects of postprandial hypertension (41) and therefore this ability It increases the expression of GATA4 gene. Therefore, it seems that interval exercise and consumption of thyme honey can be used in type 2 diabetes.

Sedentary life and vitamin D deficiency are considered related factors to increased inflammation and oxidative stress in obese conditions. Being overweight and obese is determined by increased adipose tissue due to hypertrophy and hyperplasia of fat cells (1). Previous research has shown that overweight and obesity are associated with vitamin D deficiency (3). Vitamin D deficiency is one of the most important and common health problems associated with several diseases such as kidney disease, diabetes, cardiomyopathy and Alzheimer's disease. Vitamin D plays an important role in regulating several cellular pathways for the synthesis of antioxidants (4).The best biomarker to determine the status of vitamin D is the concentration of 25-hydroxyvitamin D. Serum levels below 20 ng /ml are defined as vitamin D deficiency (3).Large adipocytes with complete local oxygen consumption induce hypoxia, which may lead to cellular inflammation and secretion of inflammatory cytokines by activating oxidative stress pathways (4). Oxidative stress, in turn, plays a causal role in obesity (6). A strong association between oxidative stress and vitamin D deficiency has been reported (8).Vitamin D has anti-inflammatory effects and affects inflammatory processes and immune cells through different pathways, including regulating the production of anti-inflammatory cytokines (12).Interleukin 10(IL-10) is a potent anti-inflammatory cytokine that is synthesized in several organs (13). It has been observed in experimental studies that with obesity, serum IL-10 levels decreased in mice on a high-fat diet, and this reduction played a very important role in obesity-induced inflammation in other organs (15, 16). Exercise is recommended as an important non-pharmacological treatment for the prevention or treatment of obesity and its metabolic and somatic cellular complications (19). Systematic studies and available meta-analyzes have shown that high-intensity interval training (HIIT) has more significant effects on reducing abdominal and visceral fat and improving cardiorespiratory fitness in overweight and obese adults than moderate-intensity continuous exercise (21, 22). Today, lack of time is one of the main reasons for non-participation of people in regular sports activities (23). Due to the association of obesity and overweight with inflammatory factors and oxidative stress, it is necessary to conduct further studies focusing on the effect of low-risk and cheaper interventions such as HIIT and/or vitamin D consumption in the prevention or treatment of oxidative-inflammatory complications. Therefore, the present study investigated the HIIT with vitamin D intake on IL-10 and lipid peroxidation levels in overweight women with IL-10 deficiency.

This single-blind clinical trial was conducted on 52 overweight women with vitamin D deficiency and ages ranging 23-29 years old. After selecting the subjects by the available sampling method, they were randomly divided into control, interval, vitamin D and combination groups. The HIIT was performed with the 12x1-min running bouts at 80-90% maximum heart rate (HRmax) interspersed with 1-min active recovery at 50% HRmax in between bouts for 8 weeks. Vitamin D and combination groups took vitamin D once a week with food for 8 weeks (30).The vitamin D and combination groups received 50,000 IU of vitamin D per week (29). Levels of 25-hydroxyvitamin D less than 20 ng /ml were considered as vitamin D deficiency. Blood samples were collected in the pre- and post-test stages, followed by 12 hours of fasting and serum was frozen at -80 ° C. The serum was then frozen at -80 ° C and used to measure the research variables. Then, serum levels of variables were determined using a special commercial kit and laboratory methods. Malondialdehyde (MDA) levels were measured as an indicator of lipid peroxidation. One-way analysis of variance test with repeated measures and Bonferroni post hoc was also used to compare intergroup differences. In addition, the rate of change of variables was tested through Kruskal-Wallis and U Mann-Whitney tests. The significance level was considered P<0.05 and all statistical analysis was performed using SPSS software version 22.

The results of one-way analysis of variance test with repeated measures showed that there is a significant difference between IL-10 and MDA levels of inactive women during the two stages before and after eight weeks, regardless of the group factor. Also, the effect of group (regardless of time factor) and the interactive effect of time×group on the levels of these variables are significant (P<0.05). The MDA levels in interval, vitamin D and combination groups decreased significantly and IL-10 levels increased significantly after 8 weeks(P<0.001). But the combined intervention had a stronger effect on the change of MDA and IL-10 levels compared to the other two interventions (P<0.001). In addition, the effect of HIIT on decreasing MDA levels was greater than vitamin D intake (P= 0.018), and no significant difference was found between the amount of IL-10 changes in these two groups (P=0.184).

Both vitamin D deficiency (9) and obesity (33) cause overproduction of ROS, increasing oxidative stress. Reactive oxygen species (ROS) interacts with unsaturated lipids within the cell membrane and causes lipid peroxidation, which in turn significantly increases MDA levels, leading to the inactivation of many proteins and cellular receptors, causing cell membrane damage (34). Vitamin D can exert its strong anti-inflammatory activity by inhibiting the expression and activation of the pro-inflammatory transcription factor nuclear factor kappa B (NF-kB), which has optimal effects on oxidative stress (32). Regular exercise can greatly improve the efficiency of enzymatic and non-enzymatic antioxidant defense systems and enhance the body's ability to eliminate peroxidants. Exercise can inhibit NF-κB activation in human T cells by reducing ROS-producing factors, such as tumor necrosis factor-α (40). Exercise can also reduce oxidative stress by increasing the bioavailability of nitric oxide (42). However, the effect of HIIT on reducing MDA and consequent oxidative stress has been more effective than vitamin D supplementation, which may be related to the synergistic effects of these two interventions in the oxidation-antioxidant balance shift towards the superiority of antioxidant defense. It seems that HIIT and vitamin D intake can be exert their protective effects in overweight individuals with vitamin D deficiency by a decrease in the MDA and increasing the anti-inflammatory index of IL-10. Although these effects developed with combined intervention, but HIIT was associated with a greater reduction in MDA than vitamin D intervention.

Anterior cruciate ligament (ACL) injury is regarded as one of the most frequent knee joint injuries. ACL injury is typically non-contact and occurs during activities such as cutting, accelerating, and landing after a jump. According to the video analysis, the mechanism of non-contact ACL injuries consist of several common components such as hip adduction and internal rotation, knee valgus, tibia external rotation, and ankle eversion; Combination of these components called "dynamic knee valgus". In this situation, the role of hip abductor and external rotator muscles is to eccentrically control hip adduction and internal rotation. In closed-kinetic-chain, adequate stability in hip joint provides better knee control. Evidence for this is seen in a reported greater hip abduction correlated with less knee valgus during single leg squat. Specifi cally, lower eccentric hip abductor peak torque is associated with higher peak knee valgus during landing Although the literature showed the positive effects of the preventive programs, most of them include exercises that involve combination of muscles groups, so the mechanisms by which muscles group reduce dynamic knee valgus are unclear. To the best of our knowledge, no study has addressed the effectiveness of an isolated hip abductor and external rotator strengthening on dynamic knee valgus during jump-landing task. Therefore, the purpose of the current study was to determine whether an isotonic strengthening which targeting the hip abductor and external rotator would improve the dynamic knee valgus during landing. We hypothesized that dynamic knee valgus would improve post isolated hip abductor and external rotator strengthening program.

Present study is a randomized controlled trial carried out by single-blinded parallel group.  Thirty-two males with knee valgus angle more than 8 degree were randomized into a training (n=16) or control group (n=16). In pre-screen session, in order to determine dynamic knee valgus eligibility for participants, subjects were asked to perform single-leg jump-landing task. Subjects landed forward from the 31-cm height box with their dominant leg onto a marked place at a distance of 40% their height. The subjects landed on their dominant leg and immediately performed a countermovement jump to achieve maximal height. A digital video camera was set up on tripod at the height of the subject’s knee, 2 meter in front of the subjects landing place, and lined up vertical to the frontal plane. The frame that knee has highest medial displacement was exported into Auto CAD 2016 software (version 20.1) for calculation of knee dynamic valgus angle. In pre-test sessions, each subject warmed up for 5 minutes (walking and jogging around the laboratory at a self-selected pace), and then was instrumented with 40 retro-reflective markers. The positions of the markers were recorded at 200 Hz using a motion capture system (Qualisys AB, Gothenburg, Sweden) with eight Ocus cameras and were synchronized with a force plate (Kistler AG, made in Switzerland) collected data at 2000 Hz. Each subject completed an initial static, standing calibration trial to align local coordination system with global coordinate system, and then performed 3 attempts to single-leg jump-landing task (as described in pre-screen) with dominant leg (30 seconds rest between each attempt). Eccentric and concentric peak torques of dominant leg hip abductor (side-lying position) and external rotator (seated position with 90° flexion in the hip and knee) were quantified by a single examiner using KinCom 500H isokinetic dynamometer (Chattecx Corp. Inc. Hixson, TN). The training group carried out 8 weeks of bilateral hip abductor and external rotator strengthening 3 times per week. Each session included 3 phases: 1: warm-up, 5 minutes Walking and jogging, 2: strengthening exercises, 35 minutes hip abductor and external rotator muscles exercises, 3: cool down, 5 minutes walking. In the post-test session, participants followed the same procedure used for the pre-test session. Each participant wore the same shoes in pre and post-test sessions to prevent injury and control footwear differences effect, and all tests were completed at the same time in pre and post-test sessions.

During the course of the study, two subjects withdraw from the study due to personal problems (one subject in CG and one subject in TG) and one subject sustained injury due to an accident (in TG). So, data from 29 subjects were used for statistical analysis.The ANCOVA evaluating changes in hip strength from baseline to the end of the 8-week hip strengthening program revealed a significant difference between TG and CG for concentric (P<0.001) and eccentric hip abduction (P=0.002) and concentric (P=0.007) and eccentric hip external rotation (P=0.001) peak torques. Paired-sample t tests were performed to determine the training effect on the hip muscle strength. At the post-test, the TG demonstrated greater concentric (1.6±0.55 vs 2.01±0.42 Nm/Kg; P<0.001) and eccentric hip abductor (1.41±0.51 vs 1.77±0.43 Nm/Kg; P=0.004) and concentric (0.94±0.21 vs 1.07±0.19 Nm/Kg; P=0.01) and eccentric hip external rotator (0.92±0.18 vs 1.11±0.21 Nm/Kg; P<0.001) peak torques compared with pre-test. No significant differences in muscle strength were observed for the control group between pre-test and post-test.The ANCOVA evaluating changes in knee kinematic from baseline to the end of the 8-week hip strengthening program revealed a significant difference between TG and CG for peak knee valgus (P=0.02) and knee valgus range of motion (ROM) (P=0.04). After the 8-week intervention, the TG demonstrated lower peak (-5.62 ± 7.36 vs -2.74 ± 5.94; P=0.02) and range of motion (ROM) on dynamic knee valgus angle (-9.66 ± 5.56 vs -7.31 ± 3.87; P=0.04) compared with pre-test, whereas significant changes were not noted in the control group (P>0.05).

Hip abductor and external rotator weakness is a well-documented impairment in subjects with increased dynamic knee valgus during landing and has been postulated to contribute to non-contact ACL injury. This study was conducted to investigate the effects of isolated hip abductor and external rotator exercises on lower extremity kinematic, as well as concentric and eccentric abductor and external rotator torques in male subjects who present with excessive dynamic knee valgus during landing. The most important finding of the current study was a reduction in peak and knee valgus range of motion during landing in training group. These changes might be due to an increase in concentric and eccentric hip abductor and external rotator peak torques in training group as a result of the 8-weeks resistance training. Our findings support the isolated hip abductor and external rotator strengthening as a viable preventive and rehabilitative exercises program option for subjects who shows excessive dynamic knee valgus impairment in the hope of preventing non-contact ACL injury.

Diabetic neuropathy is the most common diabetic complication. In more than 50% of patients with diabetic neuropathy, significant and irreversible nerve damage occurs before diagnosis. Diabetic neuropathy is associated with increased mortality (2). Half of patients with diabetic neuropathy suffer from neuropathic pain. These painful symptoms are usually severe and often lead to depression, anxiety and sleep disorders and reduced quality of life (2). Oxidative stress caused by hyperglycemia causes damage to mitochondria in nerve cells, but its mechanisms are not fully understood (4, 5). Sequential oxidation reactions in the mitochondria cause unpaired electron leakage in the electron transfer chain in the inner mitochondrial membrane and the production of free radicals (4). Mitochondria are primary targets for ROS-induced injury; because they are the main site of ROS formation in diabetic hyperglycemia (4). Therefore, examining the factors affecting the structural and functional components of mitochondria, such as electron transfer chain components, can provide useful information for the goals and programs of treatment and prevention of neurological damage caused by diabetic neuropathy. Cytochrome C is a small hemoprotein in the inner membrane of the mitochondria; this protein is highly soluble in water and is a key component of the electron transfer chain (6). Velayutham et al. In a study stated that cytochrome C and Fe3 play a significant role in the harmful effects of ischemia / reperfusion and diabetes due to increased production of superoxide radicals (7). On the other hand, insulin therapy has been shown to modulate neurotrophin-dependent treatment of mitochondrial membranes and the expression of genes associated with metabolite pathways and the mitochondrial electron transport chain (8). Although much research has been done on the effect of exercise on diabetic neuropathy, there is no research specifically examining the effect of exercise on cytochrome C as one of the factors affecting the mitochondrial function of the nervous system in mice with diabetic neuropathy; Therefore, the aim of the present study was to determine the effect of six weeks of aerobic exercise on the level of cytochrome C in the sensory part of the spinal cord in rats with diabetic neuropathy.

In the present experimental study, 12 male Wistar rats were divided into 4 groups: healthy exercise, control exercise, control diabetes and control diabetes. In order to induce diabetes, half of the rats became intraperitoneally diabetic by injecting a single dose of streptozotocin (STZ) (55 mg / kg body weight). Forty-eight hours after STZ injection, hyperglycemic rats with serum glucose above 300 mg / dL were considered diabetic. To confirm the neuropathy of rats, the thermal hyperalgesia test was used with a tail-flick device (20). After confirmation of neuropathy, the animals were placed in the diabetic neuropathy group. The training program included 6 weeks of running training on the treadmill in 5 sessions per week. After dissection of the animals, the dorsal part of the spinal cord was analyzed as sensory neurons. Immunohistochemistry was used to measure the amount of cytochrome C protein. One-way analysis of variance and Tukey's post hoc test were used for statistical analysis. Statistical analysis was performed using SPSS software version 26 at a significant level of P ≤ 0.05.

The results showed that six weeks of aerobic training reduced blood glucose in the diabetic group compared to the control diabetic group (P = 0.002), but there was not observed make a significant difference in the weight of rats. The results also showed that after the training period, the level of cytochrome C protein in the healthy exercise group significantly increased compared to the healthy control group (P = 0.041) and in the diabetic group the exercise significantly decreased compared to the control diabetes group (P < 0.001).

The results of the present study showed that induction of diabetes increased the level of cytochrome C in spinal tissue in diabetic neuropathic rats compared to healthy groups. Previous research has shown that diabetic neuropathy is associated with mitochondrial degradation due to stress due to hyperglycemia and oxidative stress due to diabetes (21, 22); in the present study, an increase in cytochrome C in diabetic neuropathy groups was positively correlated with an increase in glucose levels. In the study of the effect of exercise on cytochrome C levels, the results of the present study showed that after six weeks of aerobic exercise, a significant increase in cytochrome C protein content of spinal cord sensory tissue was observed in healthy exercise rats compared to the healthy control group. While in the diabetic exercise group, the results showed a significant decrease in cytochrome C levels compared to the diabetic control group, which showed the difference in the effect of exercise on changes in cytochrome C of sensory neurons in mice with diabetic neuropathy compared to healthy mice. Scientific research has shown that exercise is one of the effective factors in reducing hyperglycemia due to diabetes (11, 25), on the other hand, by controlling blood sugar, the level of inflammatory factors and oxidative stress in these patients is reduced (26, 27); It can be said that aerobic exercise with glycemic control reduces mitochondrial stress and thus reduces cytochrome C as one of the mechanisms of apoptosis signaling (23, 24), in the cells of the spinal cord, Which can prevent the complications of diabetic neuropathy as well as neuropathic pain. The results of the present study also showed that six weeks of aerobic exercise increased the amount of cytochrome C protein in the spinal cord of healthy rats, this was consistent with the results of Yoo et al. (28) and Bashiri and Pourrazi (29) who studied the effect of exercise on cytochrome C in the myocardial of healthy rats. It can be said that the increase in cytochrome C levels in healthy rats is one of the adaptations associated with aerobic exercise and indicates an increase in mitochondrial capacity in ATP production. It can be said that changes in cytochrome C in spinal sensory tissue are different in adapting to six weeks of training in healthy rats with neuropathy, and the increase in cytochrome C in healthy rats is associated with increased mitochondrial capacity in energy production. While the reduction of cytochrome C in rats with diabetic neuropathy is associated with a reduction in hyperglycemia and indicates the protective role of exercise on nerve tissue and reducing neuropathic damage caused by diabetes. According to the results, in addition to controlling hyperglycemia in diabetic patients, aerobic exercise can be used as one of the non-pharmacological and useful treatment methods in reducing the complications of diabetic neuropathy.

Nerve stem cell transplantation is one of the effective strategies for repairing nerve lesions. Oligodendrocytes are myelinated cells located in the central nervous system and are involved in the formation of myelin axons (8). Oligodendrocytes express O-A proteins, especially O4, which is a marker for the cell body and oligodendrocyte processes, during differentiation and maturation in the central nervous system (29). The results of some studies have shown that glial cells that express only O4 protein have the potential to become precursors of astrocytes and oligodendrocytes and can increase the growth stages in stem cells (29). Glial fibrillary acid protein (GFAP) is known as a specific marker for the identification of astrocytes in the central nervous system. This protein is the main cytoskeleton constituent of astrocytes (27) and plays an important role in maintaining, repairing and maintaining the white matter integrity of the central nervous system as well as the blood-brain barrier (35). The aim of this study was to compare the effect of High intensity interval training with hind limb suspension on the level of GFAP and O4 in glial and neuronal stem cell of male rats.

Twenty-four male wistar rats (body weight = 189.25 ± 5.71g.) were randomly divided into four groups: HIIT+HLS (n= 6), HIIT (n= 6), HLS (n= 6) or CON (n= 6). The exercise protocol was performed on a rodent treadmill for 6 weeks, 5 sessions per week. The rats were sampled and studied 24 h after last training session. Glial fibrillary acidic protein (GFAP) and monoclonal antibody O4 (O4) were analyzed before and after the training interventions.To suspend the lower limb, the animal's tail was first cleaned and dried using cotton and alcohol. Then two-thirds of the mouse tail was taped longitudinally from the beginning to the end third. Next, three pieces of kinesio-tape were placed transversely on the mouse tail, so that normal blood flow was not disturbed. We attached the upper end of the kinesio-tape to the suspension hook and then has been attached the hook to the cage movable bar chain so that the angle between the animal's chest and the floor of the cage is 30 degrees and the mouse legs do not come into contact with the floor of the cage. The suspension system, including a movable bar, pulley and hook, was mounted on top and on both parallel sides of the cage, allowing the animal to have full access to all parts of the cage by moving freely around a 360-degree axis. Data analysis was used using Shapiro-Wilk and Levine tests to investigate the natural distribution of data and homogeneity of variances and one-way and post-hoc Bonferroni statistics to test research hypotheses.

The results suggested that the percentage of changes in the amounts of fibrillary acidic protein of the cerebral hippocampus of the brain in the intense interval training group + group under the conditions of the hind legs compared to the control group showed a significant decrease (p≥0.001). Also, the percentage of changes in cerebral hippocampal glial fibrillary acid protein in the lower extremity suspension group increased significantly more than the control group (p≥0.001), but the percentage of changes in this protein in the intense interval training group compared to the group There was no significant difference in control (p≥1,000).The results of the data obtained from the percentage of changes in the O4 protein of the cerebral hippocampus of the groups showed that this change was significantly lower in the group of intense interval training with the conditions of the hind limb suspended than the control group (p≥0.001). Also, the percentage of O4 changes in the cerebral hippocampus in the lower extremity suspension group was significantly higher than the control (p≥0.001). In addition, the percentage of changes in the intense interval training group was not significantly different from the control group (p≥0.465).

The results of this study revealed that HIIT+HLS was being able to prevent damage to the cells of the central nervous system and direct the neural stem cells towards the production of neurons, astrocyte and oligodendrocyte.Mesenchymal stem cells are currently the main choice for cellular treatment of neuropsychiatric diseases. Mechanical stimuli have been reported to play a decisive role in the final fate of stem cells and their cell differentiation pathways, so that the path and flow of induced signals and activated factors determine cellular fate in time, position, and mediate an appropriate number (36). Studies have shown that the proliferation, differentiation, and cytoskeleton organization of stem cells are affected by microgravity and tend to produce neurons or nerve cells (31). Astroglia cells also act as neuronal stem cells and participate in neurogenesis. Evidence suggests a very important role for these cells during plasticity. These cells are involved in the neurogenesis of the adult mammalian brain in the ventricular region, and in the sub-granular region and the olfactory bulb. On the other hand, previous research has shown that lactate production during intense interval trainings and suspension of hind legs can play an important role in the development of oligodendrocytes and myelination, so that increasing lactate production as a substrate in myelination, and used by the nervous system. Considering this issue, it is possible to use this exercise mode in the condition of lower limb suspension as a treatment method or non-pharmacological supplement effective in neuromuscular disorders and other related diseases, to enhance fitness in athletes, improve injury and also prevention of adverse effects of being in weightlessness, especially on space missions.In general, the results show that intense interval training with hind leg suspension conditions had a greater effect on health and no damage to the hippocampus of the brain of a healthy male rat than other groups (intense interval, suspension or control group). Since no research has been done on the effect of intense interval training under the conditions of hind limb suspension on cellular changes in the hippocampus and human brain, judgment in this regard needs further study. Findings of this study may help in the rehabilitation process of people with neuromotor disorders, injured athletes, the elderly, sedentary people, as well as the conditioning program of athletes in various sports to adapt to the use of such exercises.

The family is the smallest unit of society and its health and disease are directly or indirectly involved in the health and disease of the community; but despite the importance of the family as a good environment for socializing and educating future generations, today many families suffer from traumas such as divorce, marital disputes, suicide, runaway children and other issues. They have shaken and in some cases destroyed the healthy family relationship that is necessary for the survival and strengthening of the family. The phenomenon of marital boredom is a kind of burnout and physical, emotional, and psychological exhaustion that is caused by the mismatch between expectations and reality in married life. Boredom is gradual and less sudden. In fact, love and intimacy gradually fade away and decay. At worst, boredom means the total breakdown of marital relationships. The behavioral-cognitive approach is one of the most important therapeutic approaches that has attracted the attention of psychologists. Today, the application of the behavioral-cognitive approach in couple therapy has been approved. Considering that the problem of marital boredom in couples, which is caused by annoyance, frustration, despair, and a large psychological-emotional distance between couples, is one of the main reasons for emotional divorce, and if not properly addressed and treated, It provides the ground for formal divorce of couples, so it is important to pay attention to this phenomenon and treat its destructive effects on the marital and family system. On the other hand, supervised and clinical research on emotion-oriented couple therapy and cognitive-behavioral couple therapy and their effect on conflict and boredom in couples are small, so the present study to compare the effectiveness of emotion-focused couple therapy and cognitive couple therapy- Behavior on the boredom of the couple seems necessary. Since in order to increase marital satisfaction and strengthen marital relations, it is necessary to pay attention to the cause and effect of incompatibility and as mentioned, both of these theories have completely different views on this category (incompatibility), in this study, the effectiveness of couples Emotion-oriented therapy is examined in comparison with rational-emotional-behavioral couple therapy to determine which of these two approaches is more effective in reducing boredom.

The present study is semi-experimental in terms of applied purpose and method of implementation. The research design of this study is a pre-test and post-test design with a control group. The statistical population of this study included all women who were referred to Azar Clinic in Kermanshah from the beginning of April 2017 to June 2017 due to marital conflicts and family conflicts to solve their problems and out of 200 patients, 30 people were randomly replaced in experimental group one (n = 10), experimental group two (n = 10) and control group (n = 10). They were selected and replaced using random sampling and random substitution. In general, the inclusion criteria in this study included those who had partial or desirable social and family commitments and mild or relative mental and physical health, and their performance in the way of adaptation and interpersonal relationships with their spouse was difficult and demanding. Eliminating marital problems and boredom, in other words, promoting mental health and increasing life satisfaction, have been intended to continue living together. Exclusion criteria were also couples with a history of severe addiction, long-term and frequent incarceration, leaving or running away from home, severe mental illness with psychiatric symptoms, extramarital sex complained of by one or more couples, or had severe physical illnesses that were medically diagnosed and were unable to maintain marital relationships, which according to the assessments that were made at the beginning of the referral were not included in the list of the statistical population of this study. In the present study, the marital boredom questionnaire was used. This scale was invented by Pines in 2003. The questionnaire has 21 items that include 3 main components of physical fatigue (eg feeling tired, lethargic, and having sleep disorders), emotional exhaustion (feeling depressed, hopeless, trapped), and mental exhaustion (such as feeling worthless, frustrated). And anger towards his wife). Also in this study, the experimental group participated in emotion-focused couple therapy sessions and cognitive-behavioral couple therapy sessions that lasted approximately two months and two sessions per week. Data were analyzed using Spss-21 statistical software.

The statistical results showed that emotion-oriented couple therapy and cognitive-behavioral couple therapy were effective in reducing marital boredom and also emotion-focused couple therapy and cognitive-behavioral couple therapy were equally effective in marital boredom (P <0.001).

In general, according to the results, it can be stated that to reduce couples' boredom, emotion-based couple therapy, and cognitive-behavioral couple therapy can be used, and couples can use these approaches to deepen their life expectancy. Emotional couple therapy is used to reduce turmoil in adult romantic relationships and to reconstruct couples' interactive patterns. During treatment, small steps are taken toward safe emotional engagement, which allows couples to reassure each other and reduce conflict. Like other studies in the field of behavioral sciences, the present study also faced limitations, including the study sample, which consisted of a couple who filed for divorce due to a severe marital dispute and went to family court counseling centers. They have referred. Due to this, the generalizability of research results to other couples who have not filed for divorce despite severe marital discord should be done with caution. Also, the participants in the study were couples who simultaneously announced their readiness to participate in the study, so caution should be exercised in generalizing the findings of this study. It is better that such interventions be performed at least on couples with a history of divorce without separation. They should also be referred. It is also suggested that the effectiveness of the approaches used in this study be compared with other approaches and follow-up should be considered in the study to evaluate the continuity of therapeutic effects over time.

 Today, sport is considered one of the most important human welfare needs. Exercise and physical activity as a main strategy in helping the goals of body and soul health and increase the level of activity of the immune system and prevention of various diseases, and creating mental and physical security in sports, highlights the issue of athletes' health. (1). One of the most important of these sports is football. Football is not just a sport and its situation has been undergoing growing and expanding changes due to economic, social, cultural, health and even political influences (2). Has created constructive competition (3). Accidents on sports fields are an integral part of sports events. Sports activities, even with the implementation of all reasonable precautions, will have a level of risk, and in addition to all the benefits of sports programs, there is a possibility of sports injuries (4). For this reason, having a specialist physician who is aware of sports injuries during sports injuries is a requirement whenholding sports competitions. Also, this physician must have full access to the athlete's medical information in order to perform better (8). Electronic storage of athletes' medical information can improve the physician's treatment process and lead to manypotential benefits such as scientific research, statistical records of diagnostic and treatment methods, reporting, and time and cost savings (11).Weinstein et al. (2013) state in their research that when one of the players is injured, the treatment of injuries and disorders should be done by a doctor. The first step for the injured person is to diagnose and manage the injury by the doctor when the injury occurs. The second is the doctor's referral to the medical record and the initial treatment and transfer of the athlete to medical centers (12). Consonon et al. (2014) say that the importance of injury diagnosis is one of the essential factors for treatment and this is possible only with the presence of a physician at that time to prevent the destructive effects of injury. Time is the relationship between intermittent injuries and medical records (13). But Nordstrom (2014) is of the opinion that during the period of complete treatment and recovery, the primary care physician should be aware of the athlete's treatment process because it is possible to ignore some injuries and all this process should be recorded in the sports medicine file. (14). According to Peterson (2020), the assessment of sports injuries should be done by a sports medicine specialist. A high percentage of sports experts believe that having a sports doctor in stadiums and having a sports medicine file is a necessity for holding a match. It is a sport and shows the attention of sports officials to the health of players (15).In order to achieve the desired success, sports organizations must not only think about meeting the material needs of their athletes, but also prioritize their expectations about physical health after sporting events, and to meet such expectations as a necessity for Athletes' loyalty look. (16). Aman et al. (2018) in their research pointed out that doing sports, both at the amateur and professional levels, has a high risk of injury. They also showed that the probability of lower limb injuries in rugby and football is the highest. Has; Therefore, the presence of a physician at the time of the race is very important and vital to accelerate treatment (17). Gritch (2019) concluded in his research that amateur athletes strongly advocated the use of sports medical services to protect themselves from potential injuries (18); Also, other researchers such as Mirza Kooshaki et al. (2017) in their research entitled Developing Health Development Strategies with the Approach to Physical and Sports Activities concluded that public knowledge through the media, support for workplaces in sports, and encouraging physicians To prescribe sports activities, provide facilities to sports investors, observe sports standards of schools and universities, develop monitoring and counseling centers for citizens' health, employ sports experts in urban and rural health centers and houses, determine the role of each Government agencies in the field of sports, determining the share of sports from the financial credit of the health system transformation plan, urban design with a healthy city approach, preventing the orientation of sports management from financial credits, preventing the orientation of sports management of government agencies to championship and professional sports, The formation of the Deputy Minister of Health in the Ministry of Sports and the use of information and monitoring system were among the health development strategies with the approach of physical activity and sports (19).

 In the present study, the paradigm of qualitative research has been used. One of the reasons for the need for qualitative research is that qualitative methods can provide more detailed details of phenomena that are difficult to present in quantitative ways. مختلف Among the various qualitative methods, the network of themes method has been used. Answering the first and second research questions related to determining the indicators and effective factors on the health of football players with a sustainable development approach and explaining the relevant model and to achieve this research goal tried to use a qualitative research method of descriptive exploratory type. The present study is a qualitative descriptive-exploratory study. The sampling method is non-random, targeted and available. Data collection in 1399-1400 and the method of data collection was semi-structured interview. The statistical population is all experts of sports managers and health managers (physicians and medical staff) of the Islamic Republic of Iran. Semi-structured interviews with the question "What do you think are the health indicators of football players with a sustainable development approach?" The beginning and the rest of the questions were based on the answers of the interviewees. After interviewing 12 people in the field of physical education and sports medicine, the researcher felt that he had reached a theoretical similarity, but to be more sure, he continued the interviews up to 15 people, but what was said after 14 people was completely repetitive, and at the same time the interview And the basic themes are over.

 After reviewing the interviews and removing similar codes; 113 codes were collected, which indicates the position of the health of football players with a sustainable development approach. These concepts were presented under three general topics: basic, organizing and comprehensive. Some of these topics include the coordination of sports federations with the Health Organization, the establishment and expansion of sports medical centers, the use of medical and sports specialists in sports clubs, determining the role of each One of the parts of sports medicine in providing services, forming the deputy of health in the Ministry of Sports, using the information and monitoring community system in the field of health, health development strategies, creating health networks in all parts of the country's football sport, creating upstream documents such as plan Health transformation, creating a document for the prevention of non-communicable diseases at all levels of football players, establishing organizations in the field of sports health at all levels of football in the country.

 The fact that the country's sports authorities pay the necessary attention to the health of athletes is a necessity for sustainable development and this issue should create a close relationship between medical staff and athletes.

The pituitary gland is located near the center of the cranium base, caudally surrounded by a bony basket structure of the sphenoid bone named “Sella Turcica." The adjacent structures, such as optic chiasma stated superiorly, are of clinical and surgical importance(1, 2). Surgery is the first-line treatment for the large nonfunctional pituitary adenomas with clinical signs and symptoms (e.g., optic chiasma compression) and most functional adenomas  (4). The very primary surgical access to pituitary adenomas was provided via trans-facial or trans-cranial approaches. The trans-sphenoidal approach was introduced later in the early 1900. However, this approach was abandoned due to serious complications and a higher mortality rate (5-8). With the advent of the microscope and later the endoscope and its application in the trans-sphenoidal approach, the endoscopic endonasal trans-sphenoidal approach (EETSA) has been rapidly accepted and well established for its advantages such as a better visualization, more complete tumor resection, and lower complications (8-10). However, as the access to a pituitary adenoma is provided through a bony defect in the sella turcica floor, postoperative cerebrospinal fluid (CSF) leak is a risk with the recently reported prevalence of 0/5-12% in endoscopic approach (11-16). To avoid it, various reconstruction strategies and materials have been introduced. In nonrigid reconstructions, materials such as fat, fascia, dural replacements, mucosal or muscular grafts, and pedicled mucosal flap of the nasal septum, middle or inferior turbinate are used. In rigid reconstructions, bone, cartilage, titanium mesh, ceramic implants, and bone cement are adopted (8,21). None of them being known superior to the other, heterogenous algorithms have been designed principally based on the grade or risk of CSF leak (22, 23). Rigid reconstruction is supposed to strengthen and protect the reconstructed area well. However,  donors cite morbidities in autografts (e.g., nasal bone or cartilage) (24), infection transmission in allografts (e.g., cadaveric iliac crest) (25), high costs, low biocompatibility, infection, and radiologic artifacts in synthetic grafts (e.g., Medpor) (26) are among the challenges both the patients and the surgeons encounter (19).Moreover, minimal data exist on the spontaneous sella turcica re-ossification following EETSA, which can debate the necessity of rigid reconstruction. This pilot study consequently aims to consider the possible self-repair of sella turcica without any rigid reconstruction in eight patients with pituitary adenoma.

In this retrospective pilot study, the pituitary adenoma data bank of Rasoul Akram hospital's skull base research center was reviewed for the patients who had undergone EETSA between March 2014 to February 2018.Those with available pre-operation paranasal sinuses CT scan, data bank documented measures of the intra-operation bony defect, evidence of the complete tumor resection according to the MRI three months after the surgery, and no evidence of tumor recurrence based on the last MRI ( 2018 or 2019) were included if no revision surgery or radiotherapy before or/and after the operation was conducted. They were accidentally called, and the first ten patients accessible by the documented phone number were invited to take a paranasal sinuses CT scan to evaluate sella turcica spontaneous re-ossification after informed consent.The CT scans were evaluated, and measurements, including the maximum diameters of bone defect in the coronal and sagittal planes on the CT scans - using the Picture Archiving and Communication Systems (PACS) - Osirix system-, were compared with the defect size created intraoperatively. The area of the defect was calculated using the equation for the area of an Ellipse (major radius multiplying by minor radius Multiplying by pi.) All procedures performed in this study were in accordance with the ethical standards of the Iran University of Medical Sciences research ethics committee (IR.IUMS.REC.1395.29082) and with the 1964 Helsinki Declaration and its later amendments.Median and interquartile ranges (IQ) were used for the descriptive analysis of quantitative variables. Mann-Whitney test was used to compare independent quantitative variables, and Wilcoxon Signed Ranked test was used for quantitative dependent variables. The Spearman test evaluated the correlations. The statistical software IBM SPSS Statistics for Windows version 22.0 (IBM Corp. Released 2013, Armonk, New York) was used for the statistical analysis. P values <0.05 were considered statistically significant.

Eight patients with no rigid reconstruction were included in the final analysis, with a median age of 40/5 years old (IQ=17), of whom six were female. After a median of 46 months (IQ=20.5, range 12-60), length, width, and the area of the bony defect were significantly reduced (21.5 to 9.3 mm, 15.6 to 9.4, and 297.90 to 77.5 mm2, respectively p values=0.01) leading to the median of 74.1% (IQ=11.2%, range 67.8-99.2%) self-repair of the primary bony defect.The area of the intraoperative bony defect was significantly correlated with the final bony regenerated area and with the area of defect remaining after follow-up. (r=0.929, p value=0.001, and r=0.976, p value≤0.001, respectively).  A negative correlation between age and the bony regeneration speed (the monthly percentage of the repaired area) was also detected. (r=-0.762, p value= 0.02)

In this study, spontaneous bony regeneration was shown to occur in all eight studied individuals (median of 74.1%, range of 67.8-99.2%) with various types of pituitary adenomas and primary defect areas (median of 297.9, range of 78.5 to 575.52 mm2) after a median of 46 months. The results align with the only previous study that reported spontaneous ossification in 94% of the 17 patients with pituitary adenomas in the median of 36 months (27). There are no more available data on sella turcica spontaneous bony regeneration. However, there is evidence of potential spontaneous re-ossification of the mandible, which is of the same bone type (irregular), showing even better healing without reconstruction strategies (29, 32-35). CSF leak risk, which is the most salient concern in EETSA, determines the reconstruction strategy in the skull base surgeries. Nonrigid reconstruction, whether intraoperative CSF leak is present or not, has led to permissible postoperative CSF leak (38,42,43). Moreover, the postoperative CSF leak rate was not significantly different with or without the use of Buttress in a recent meta-analysis (38). Putting all these findings together and considering the natural sphenoid spontaneous bony regeneration capability, the authors suggest that rigid reconstruction of sella turcica following EETSA may not be necessary.

Overweight and obesity are related to increased risk of coronary heart disease, stroke, high blood pressure, type 2 diabetes and some specific cancers. In recent years, inactivity, obesity and metabolic syndrome have been increasing in developing societies (2). Among various diseases, polycystic ovary syndrome is among the cases that are strongly related to obesity (3).Studies in recent decades have shown that PCO syndrome can be a pro-inflammatory stage, because among them cardiovascular diseases, diabetes 2, insulin resistance and metabolic syndrome are seen with a high incidence (4). In the meantime, investigating and identifying the inflammatory causes of this condition for the above reasons can help specialists in its treatment with the process of reducing its negative effects through aerobic exercise. In this regard, the above research investigated some inflammatory factors such as E-selectin and nuclear factor kappa B (NF-κB).To improve the physical condition of obese people, instead of medicine, sports activities, both anaerobic and aerobic, are used, and each of these activities affects the improvement of physical condition through different mechanisms (2). Researchers believe that regular and not heavy exercise is a healthy and natural method for patients with polycystic ovary syndrome apart from clinical treatments (18). Physical activity improves menstrual irregularity, ovulation, ovarian morphology and fertility by reducing abdominal fat, blood sugar, blood fat, reducing insulin resistance, affecting hormone secretion and reducing cardiovascular risk factors. Be (7). But the question is, what exercise? With what intensity? And for how long?Treatment with all kinds of drugs may cause male characteristics, and unfortunately, most of the side effects are irreversible, so non-drug treatment strategies are necessary and need to be examined and studied. On the other hand, by reviewing the research done inside and outside the country, no research has been done on the effect of Tabata exercise on the research variables and even aerobic exercise on the research variables in women with polycystic ovary syndrome, so the purpose of this research is to determine The effect of a session of Tabata exercise in water and metformin on E-selectin and NF-κB in obese women with PCOS.

The current research was semi-experimental and applied with a pre-test-post-test research design. For this purpose, 30 women with a body mass index greater than 29.9 in Isfahan city, who were diagnosed with polycystic ovary syndrome by an endocrinologist or gynecologist and diagnostic tests and ultrasound, were considered as a statistical sample. They were selected and randomly divided into two experimental groups (metformin + exercise in water) and control. 24 Before starting the exercises, the subjects first completed the personal information questionnaire and blood was taken after 12 hours of overnight fasting to determine the level of the variables. Experimental group for 12 weeks, 3 sessions a week and each session 40 minutes of exercises in the water (including 10 minutes of walking forward, backward, sideways and soft running in the shallow part of the pool where the water level is below the neck and Then they performed stretching exercises. Then they performed Tabata exercise with a special exercise song played in the pool for 20 minutes, and then they did 10 minutes of stretching and cooling (22) and 500 mg metformin twice consumed during the day and after breakfast and dinner. 48 hours after the last training session, blood was taken again from all subjects. At the end, descriptive statistics (mean and standard deviation), Shapiro-Wilk test to check the normality of data distribution and covariance analysis to check research hypotheses using spss/21 software at a significance level of a≤0.05 were used. became.

The results showed that the E-selectin factor in obese women with PCOS at the end of the period in the group of Tabata exercise in water and metformin intake had a significant difference compared to the control group (P=0.001 and F=134.6). Tukey's post hoc test results It showed that there is a significant difference between the pre-test of the Tabata training group in water and the post-test of the Tabata training group in water on the one hand, and between the post-test of the Tabata training group in water and the pre-test and post-test of the control group on the other hand, but between the other groups. There is no significant difference. (Table 2).The results showed that Tabata exercise in water and metformin consumption have a significant effect on NF-Κb factor in obese women with PCOS (P=0.025 and F=354.3). The results of Tukey's post hoc test showed that there is a significant difference between the pre-test of the Tabata group in water and the post-test of the Tabata group in water, but there is no significant difference between the other groups (Table 3).

The results showed that the E-selectin factor was significantly higher in obese women with polycystic ovary syndrome at the end of the period in the aerobic exercise and metformin group than in the control group. The results of the follow-up test showed that there is a significant difference between the pre-test of the Tabata aerobic training group and the post-test of the Tabata aerobic training group on the one hand, and between the post-test of the Tabata aerobic training group and the pre-test and post-test of the control group on the other hand, but between the other There is no significant difference between the groups. Aerobic exercises decreased VCAM-1 and ICAM-1 adhesive molecules; While its effects on E-selectin and P-selectin have been inconsistent. Of course, it seems that the effect of aerobic exercise on these conditions depends on the type and duration of the exercise intervention and the disease conditions such as the presence of ischemia. As presented in this review, there is a high level of evidence that sports activity has a positive effect on key factors in the development of atherosclerosis. This can partly explain the scientifically proven anti-atherogenic effects of aerobic exercise and has significant clinical effects (23).The results showed that the NF-Κb factor in obese women with polycystic ovary syndrome was significantly lower in the aerobic exercise and metformin group at the end of the period than in the control group. The results of Tukey's post hoc test showed that there is a significant difference between the pre-test of the Tabata aerobic exercise group and the post-test of the Tabata aerobic exercise group, but there is no significant difference between the other groups. In the explanation above, it can be stated that NF-κb is stimulated and activated in response to cellular stimuli. So far, about 450 stimuli, including physical, chemical, physiological and oxidative stimuli, have been identified for NFκB. Also, mitogens, receptor ligands, bacteria, viruses, parasites, fungi and their products, pro-inflammatory cytokines and some pathological conditions are among the stimuli of this transcription factor (28). The transcription factor NFκB is responsible for supplying a large number of pro-inflammatory genes, including cytokines, chemokines, immune receptors, enzymes and other pro-inflammatory molecules (29). Inappropriate activity of NFκB is one of the mechanisms of some diseases, especially those associated with inflammation (30).

Myocardial infarction is one of the most important ischemic cardiopathies (1). Despite progressive improvement in medical therapy and standard care, Exercise-based rehabilitation programs have been shown to improve the exercise capacity of patients with myocardial infarction through a multifactorial effect (2). In this context, high-intensity interval exercise is a growing field of research (3). Many studies have shown that High-intensity interval training (HIIT) has more protective effects on myocardial tissue than aerobic exercise (6). Therefore, this study aimed to investigate the effect of a period of low-volume, high-intensity interval aerobic exercise on heart structural and functional indicators in patients with myocardial infarction.

In this semi-experimental study with pretest–A post testdesign,20 patients with documented MI (without regular exercise history) volunteered to participate in the research randomly in two control groups (n=10) and exercise group (n=10).The subjects trained for 3 d/week for 12 weeks (one session on a treadmill and another session on an exercise bike), under the supervision of an expert physician and exercise physiologistspecialists. We asked the control group patients not to engage in any other leisure exercise during the study.The rationale formixing bike and treadmill was to avoid the osteoarticular effects of two treadmill days by considering the HIIT program. We calculated the optimizedexercise zone using the Karvonen formula, which calculates the exercise heart rate as a percentage of the heart rate reserve, added to the resting heart rate (11).The training intensity was adjusted by constantly changing the treadmill's speed and incline or the bike's power and speed to ensure that we performed all training sessions with the target heart rate (HR)(9). Training intensity was controlled by monitoring participants’ heart rate (HR) using a Polar HR monitor (Polar Electro OY, Finland). Heart rate, blood pressure, and perceived exertion were evaluated using the Borg Scale (6 to 20 points) before, during, and after each session (12). We measured the structural and functional indices of the heart using an echocardiography device in baseline conditions and after 12 weeks of training. We performed all examinations at rest in the left lateral decubitus position according to the guidelines of the American Society of Echocardiography (16). We analyzed data using paired t-test and independent t-test.All statistical tests were performed with SPSS software version 28.0 (IBM SPSS, Inc, Armonk, NY). Values of p <0.05 were considered statistically significant.

End-diastolic diameter, end-diastolic volume, injection fraction, left ventricular stroke volume, and peak oxygen consumption of the training group wassignificantly increased compared to the baseline conditions and compared to the control group (P<0.05) and Resting heart rate, systolic and diastolic blood pressure showed a significant decrease (P<0.05).But there was no significant change in the thickness of the posterior wall at the end of the diastoleof the left ventricle.

The main results of this study showed that the HIITtraining protocol withthe lowvolume produced positive and significant changes in systolic blood pressure, diastolic blood pressure, resting heart rate and VO2 peak, which shows a positive training response in these patients. But we found no improvement in the control group and only systolic and diastolic blood pressure remained unchanged. Also, in the parameters of resting heart rate, systolic and diastolic blood pressure and VO2 peak, a significant difference was found between the HIIT group and the control group, which is related to the improvement of physical activity level and functional capacity. These findings show the effectiveness of a low-volume HIIT program in improving clinically important parameters. The results of the present study showed that left ventricular end-diastolic volume, left ventricular ejection fraction (EF) and stroke volume (SV) increased significantly after HIIT exercises compared to the control group. Recent studies have shown that physiological adaptations of the left ventricle following exercise are divided into three general sections: 1) physiological hypertrophy of existing myocytes, which is associated with increased production of specific growth factors; 2) activation of cardiac stem cells, which increase the number and their differentiation leads to myocytes and vascular cells and 3) accumulation of new heart cells called new myocytes and vascular cells (32, 33). These cellular changes depend on the intensity and duration of exercise, which is associated with increased contractile muscle mass, cardiac function, and decreased wall tension. Therefore, since the results of the present study show an improvement in left ventricular function index  in patients with MI following low volumes of HIIT training, it is likely that low volume of HIIT volumes could be stimulated the above mechanisms and play an important role in improving cardiovascular function. The results of the present study showed that the end-diastolic diameter of the left ventricle increased significantly in the HIIT group compared to the control group. Therefore, it can be said that 12 weeks of low-volume HIIT training has led to an increase in blood volume and venous return (because of skeletal muscle pumping and venous contraction), which according to Frank-Starling's law, increases ventricular stretch and ventricular contractility. It has led to an increase in injection fraction, which ultimately causes an increase in stroke volume and a decrease in resting heart rate, and one reason for the significant increase in VO2 peak after 12 weeks of low-volume HIIT training may be the increase in blood volume and ventricular end-diastolic diameter. Be left, because these two mechanisms cause an increase in the number of mitochondria and their enzyme contents, capillary density and better blood flow in active muscles and heart muscles (38). Also, the results showed that the average thickness of the posterior wall of the left ventricle at the end of diastole in the HIIT group had a slight and non-significant increase. Reports show that aerobic activity causes a volume load on the heart, an increase in the heart chambers, especially the left ventricle, and a relative increase in the ventricular walls of the heart (39). Perhaps the reason for the non-significant changes in the thickness of the posterior wall at the end of left ventricular diastole in this study was the rapid filling of the left ventricle during ventricular diastole or the small volume of the exercise program, because the volume of the exercise program was not enough to cause obvious structural changes. In summary,interval aerobic training with low volume and high intensity improves the structure and function of the left ventricle, but we need more training volume to achieve more obvious structural changes in the left ventricle of patients with MI.

On December 12, 2019, Covid-19 an infectious disease pandemic caused by the corona virus has become a major global threat to the city of Wuhan, China. Coronaviruses are a large family of viruses that can cause disease in humans and other animals. The new coronavirus seriously attacks lung epithelial cells and causes respiratory disorders that require ventilatory support in severe cases. Elderly people, especially those with underlying diseases such as diabetes, cardiovascular diseases, respiratory diseases, and high blood pressure, such as people who have a suppressed immune system, are exposed to severe symptoms and mortality. Also, in addition to the lung tissue, the new coronavirus also targets other organs such as the heart, kidney, digestive system and brain. In the pathogenesis of this disease, there is a cytokine storm and changes in immune responses. Two factors, the uncontrolled inflammatory response and the reduction of the immune system in people with corona can cause the symptoms to worsen during and after infection. The immune system and the digestive system both play key roles in terms of access to nutrients and the defense of the host body as the intestinal microbiota against external foreign factors. Therefore, one of the biggest concerns is related to reducing inflammation and not reducing the patient's immune response, and to solve this concern, in addition to drug therapy, diet therapy should also be at the top of these approaches. The importance of proper eating patterns and habits in the Covid-19 epidemic showed that this issue is not only to prevent the presence of non-communicable diseases that can subsequently lead to more severe infections but is also considered a solution for modulating the inflammatory condition of patients. It is a fact that ignoring the importance of nutrition in patients with Covid-19 leads to the worsening of symptoms and complications of the disease in these patients. Therefore, the purpose of this study is to investigate the relationship between nutrition, the body's immune system, and covid-19 to formulate appropriate food plans and patterns for prevention and improvement during treatment and after.

In this review study, we have examined the importance of proper nutrition on the immune system and its effects on the prevention and treatment of covid-19 disease. For this purpose, articles from international databases such as PubMed, Google Scholar, Science Direct, and Scopus were analyzed by entering the key words of the Covid-19 pandemic, immune system, nutritional factors, and food supplements.

The immune system needs sufficient amounts of vitamin A for its various defense functions, such as keratin and mucus expression, cell death, growth, development, immune cell activity, antibody production, and cytokine expression against pathogens. Several studies have shown the effect of vitamin A deficiency on the disease severity of patients with coronavirus. Vitamin A and retinoid cause the secretion of compounds that inhibit virus replication in immune cells. Therefore, using this vitamin as a supplement in patients suffering from viral diseases reduces complications and mortality. This group of vitamins is an essential micronutrient that has different roles such as improving the function of the immune system and promoting the growth of cells. Also, this vitamin has an anti-inflammatory and inhibitory role in the entry of neutrophils into the damaged lung. Vitamin B6 plays a coenzyme role in T-cells production and interleukin 2. Therefore, when faced with a deficiency of group B vitamins, the immune system response in dealing with foreign agents becomes weaker. With these interpretations, group B vitamins can be considered as an auxiliary treatment in Covid-19 treatment. Vitamin C or ascorbic acid is a water-soluble vitamin that has a very strong antioxidant role, which becomes very important in the conditions of oxidative stress caused by coronaviruses. Vitamin C can strengthen the immune system and resistance against the infection caused by coronaviruses through various ways such as the migration of leukocytes to the sites of infection, phagocytosis and killing of bacteria, the activity of natural killer cells, the function of T lymphocytes (especially cytotoxic T lymphocytes) and the production of antibodies. Vitamin C supplementation has also been shown to reduce the duration and severity of upper respiratory tract infections such as the common cold, especially in people who are under severe physical stress. The role of vitamin D in bone health is known, but another essential role of this vitamin is in strengthening the response of the immune system and the growth and maturation of immune cells. Vitamin D can reduce the risk of viral infections such as coronaviruses by several mechanisms. Vitamin D moderates this process by reducing the secretion of inflammatory cytokines and increasing the expression of anti-inflammatory factors. New studies also reported that by detecting the presence of the virus, vitamin D can prevent the rapid multiplication of the virus through programmed death and autophagy in tissues infected with infectious agents. Therefore, this vitamin can be effective in treating and preventing the covid-19 coronavirus in different ways. Studies related to the roles of vitamin E in host immunity and susceptibility to infection have been reported. When infected with coronaviruses, cell membranes, especially lungs, undergo oxidation of unsaturated fatty acids and subsequently increase their permeability. By maintaining the of the T-Cell membrane, vitamin E plays a significant role in improving the performance of immune system responses and clearing bacterial and viral infectious agents. Vitamin E supplementation increases antibody production, lymphocyte proliferation, T helper 1 cytokine production, natural killer cell activity, and macrophage phagocytosis. Therefore, vitamin E can be used as an effective antioxidant in the prevention and improvement of symptoms caused by Covid-19.Selenium deficiency occurs in two forms: mild deficiency and impairment of human health, and severe deficiency and defects in the response of the humoral and cellular immune system.Zinc deficiency may exacerbate the effects of Covid-19 in several ways; including by destroying the balance between innate and acquired immune cells, intensifying inflammatory responses that can lead to failure of various organs, excessive thrombus formation that can lead to an increased risk of thromboembolism, and finally, by reducing the function of the mucous barrier in many organs and tissues. Therefore, the nutrient zinc can be helpful for the optimal functioning of the immune system when the symptoms of the disease of Covid-19 appear in affected people. The favorable effect of iron on the functioning of the immune system and protection against foreign factors is well known. Probiotics, especially some lactobacilli and bifidobacteria, reduce the incidence of respiratory infections in humans and improve their consequences. However, a total of the evidence suggests that lactobacilli and bifidobacteria may improve immune function. The role of probiotics in the prevention of viral respiratory infections has also been recently noticed. Even though oral probiotic supplements are not currently part of any specific protocol for the treatment and prevention of respiratory viral infections, many studies have shown that their use can be beneficial in modulating the systemic immune system.

Considering that a proper diet is effective in all diseases, including cardiovascular diseases, cancer, and metabolic diseases, there is no doubt that nutrition is also important in infectious diseases. A suitable diet that contains helpful macronutrients and micronutrients, by affecting homeostasis in immune cells, maintains their function throughout life and strengthens immune mechanisms, especially in people at risk like the elderly, pregnant women, and children, and is a key element in improving the functioning of the immune system and strengthening resistance against viral and microbial infections. Therefore, insufficient lack of nutrients inception such as zinc, selenium, iron, vitamins A, B, C, D, and E, proteins, and omega-3 fatty acids can cause weak immune responses and make people susceptible to infectious diseases such as covid-19.

Cancer is one of the causes of morbidity and mortality in developed and under-developed countries. Different strategies are under evaluation for cancer therapy including chemotherapy, radiotherapy, and surgery. However, the treatment can be affected because of the lack of the desired effect and severe side effects. For these reasons, discovering an improved cancer therapy strategy has been one of the most important research efforts worldwide. Cisplatin is considered one of the most effective used chemotherapy agents in the treatment of a variety of tumors. However, its use is limited because of its toxicity to normal cells. In addition, non-specificity and high dosage of drugs are the other important reasons which practically limit their application. Drug delivery systems can overcome these challenges by enhancing the therapeutic efficacy and reducing the adverse effects of anticancer agents. The application of nanoparticles as drug carriers has been widely studied for more than a decade (3). Magnetic nanoparticles are popular candidates in therapeutic systems and diagnostic applications that approved for clinical use by the Food and Medicine Administration (FDA) (5). In this study, we prepared superparamagnetic iron oxide nanoparticles Fe3O4 (SPIONs) that were modified through triblock poly (ethylene glycol)-poly (e-caprolactone)-poly (ethylene glycol) nanoparticles. These modified nanoparticles have been utilized for Cisplatin delivery on the lymphoma cell line (U937).

Magnetic nanoparticles were prepared by a co-precipitation method in the presence of Fe2+ and Fe3+ (9). In order to synthesize the polymer, ε-caprolactone and polyethylene glycol were polymerized by a ring-opening polymerization method. Triblock copolymer PCL-PEG-PCL was prepared through the ring-opening polymerization method (10). Magnetic iron nanoparticles were also prepared and confirmed using Fourier Transform Infrared Spectroscopy (FTIR) and X-ray diffraction spectrum (XRD). Superparamagnetic nanoparticles modified with PCL-PEG-PCL copolymers loaded with cisplatin were developed using the double emulsion solvent evaporation method (11). The encapsulation efficiency of cisplatin loaded in nanoparticles was evaluated through UV spectroscopy at 280 nm (12). Synthesized nanoparticles were evaluated in terms of particle size and morphology by dynamic light scattering (DLS) analysis and Scanning Electron Microscope (SEM), respectively. In addition, the chemical structure of PCL-PEG-PCL triblock copolymer and superparamagnetic nanoparticles modified with PCL-PEG-PCL copolymers loaded with cisplatin was confirmed using FTIR and proton nuclear magnetic resonance (1H-NMR). Finally, the effect of synthesized nanoparticles on the lymphoma cell line (U937) was investigated using MTT assay (13).

Magnetic iron nanoparticles were confirmed using FTIR and XRD. The size and shape of the nanoparticles were evaluated using DLS and SEM. The results show that the particle size was around 100-130 nm and the synthesized nanoparticles had uniform dispersion without aggregation. High entrapment of cisplatin was achieved using the double emulsion solvent evaporation method (98/07%). The hysteresis curves of iron magnetic nanoparticles and cisplatin-encapsulated magnetic nanoparticles PCL-PEG-PCL exhibited that in the presence of a magnetic field with an intensity up to 8000 Gauss, these particles have shown the magnetic properties (about 70 emu/g). When the magnetic field was removed, these nanoparticles lost their magnetic properties (0 emu/g). So, in the presence of a magnetic field, a magnetic orientation was demonstrated. The results of the cell viability assay using MTT dye showed that IC50 of free Cisplatin and Cisplatin-encapsulated magnetic nanoparticles PCL-PEG-PCL on the U937 cancerous cell line is 119.70 ± 4.46 µg/ml, 17.35 ± 1.48 µg/ml, 13.58 ± 1.59 µg/ml and 29.67 ± 1.99 µg/ml, 11.24 ± 0.82µg/ml, 7.10 ± 1.37µg/ml respectively for 24, 48 and 72 hours incubation time.  The anti-proliferative effect of cisplatin encapsulated in magnetic nanoparticles was more significantly cytotoxic on the cancerous target cells than free cisplatin.

Over the last decade, scientists have tried to develop new strategies for enhancing the therapeutic index while reducing side effects. In this regard, nanotechnology is considered one of the most effective strategies to which a huge share of research in this area is dedicated (3). Among all the nanoparticles SPIONs have attracted significant attention in cancer therapy because of their unique properties such as biocompatibility, biodegradability, and ease of chemical modification (5). The results of the study demonstrated that superparamagnetic nanoparticles modified with PCL-PEG copolymers efficiently delivered cisplatin into the U937 cells and demonstrated potent in-vitro anticancer activity which had a significant cytotoxic effect against lymphoma cell line (U937). Therefore, this delivery system can potentially be applied for the delivery of anti-cancer drugs and holds a great promise as an effective strategy for cancer treatment.

Several challenges, including rapid drug release from the carrier, repeated drug administration, fluctuations in plasma drug concentration, and reduced patient compliance have been reported for conventional drug delivery systems. Liposomes were first developed by a scientist, A.D. Bangham, in 1961. The word liposome is a combination of the two Greek words “lipos” meaning fat and “soma” meaning body. A liposome is a system, which its membrane is made up of fatty compounds such as lipids. The lipid membrane and its entrapped space are suitable for the loading of lipophilic and hydrophilic drug molecules, respectively. Liposomes, as optimal drug delivery systems, could be an appropriate solution to many of the challenges of conventional drug delivery systems.    Liposomes, which are made from phospholipid and cholesterol, have many benefits as optimal drug delivery systems. A wide range of therapeutics could be incorporated within liposomal carriers. They are biodegradable and biocompatible. They do not stimulate the immune system and are used as a synthetic membrane model. These systems increase the stability of drugs in the body by protecting the drug compounds within them and also reduce the toxic effects of drugs by minimizing drug exposure to sensitive tissues. Liposomes can also control drug release.    The particle size of liposomes varies from nanometers to micrometers depending on the preparation method. Liposomes can be classified on the basis of their size and bilayers number, into: giant unilamellar vesicles (GUVs) 0.5 – 10 µm;  multilamellar vesicles (MLV) 1 - 5 µm; large unilamellar vesicles (LUV) around 100 – 500 nm; small unilamellar vesicles (SUV) 20 - 100 nm; and multivesicular liposomes (MVL). MVL are characterized by their structure of multiple non-concentric aqueous chambers surrounded by a network of lipoidal membranes. The particle size of monolayer and multilayer liposomes is about a few hundred nanometers, while the average particle size of MVLs is 1 to 100 µm.    Methods of liposomes preparation include thin layer hydration, reverse phase evaporation, solvent injection, dehydration-rehydration, and ultrasonic. The MVL system is a water in oil in water emulsion (W / O / W) that organic phase contains hydrophobic material and liquid phase contains hydrophilic material. The double emulsification method is the most common method of MVL preparation.
Small drugs as well as large molecules such as peptides and proteins can be loaded in the unique structure of MVL. So far, several peptides or protein compounds have been successfully loaded in MVL and their therapeutic effects investigated in various diseases. In vitro and in vivo studies show that MVLs well control the drug release rate. There are some examples for MVL applications regarding these compounds.; MVL containing insulin or liraglutide in diabetes mellitus treatment, bevacizumab in laser-induced choroidal neovascularization, thymopentin in immune disorders, LXT-101 in the treatment of prostate cancer, angiotensin I converting enzyme (ACE) inhibitory peptide in the treatment of hypertension, alfa interferon in hepatitis C, and leridistim in chemotherapy-induced bone marrow suppression are some of the studies in this field.
    
   MVL consists of four compounds: phospholipids, cholesterol, neutral triglycerides, and negatively charged lipids. Phospholipid chains form the bilayer membrane of the liposome, and the cholesterol in the system is located between these chains. The cholesterol to phospholipids ratio, lipid to drug ratio, and lipidic composition affect the stability of the system and the rate of drug release. Neutral triglycerides such as triolein, tricaprylene, trilaureine and tributyrine allow the formation of this unique multivesicular structure, stabilize the membranes of internal vesicles at the point of contact with each other, preventing them from merging and controlling the drug release rate. Negatively charged lipids such as dicetyl phosphate (DCP) also control particle accumulation by inducing a negative charge on the surface of liposomes.
Observation and determination of MVL structure are usually performed by optical and electron microscopes. The sysyems should also be characterized regarding drug encapsulation, drug release profile and kinetics, storage stability, and drug-vesicle interaction.  Most studies on the MVL drug delivery system have been performed on drug-loaded MVLs. To date, application of MVLs containing tramadol in pain management, various compounds (include rose bengal, oxaliplatin, oleanolic acid, and cytarabine) in cancer, dexamethasone sodium phosphate in hearing impairment, acyclovir sodium in infectious diseases of herpes simplex virus (HSV), desferrioxamine mesylate in iron toxicity, celecoxib as an anti-inflammatory and analgesic agent, breviscapine in cardiovascular disease and cerebrovascular ischemia, flucinolone acetonide in ocular inflammatory diseases, naltrexone hydrochloride in opioid abuse and alcohol dependence and ropivacaine hydrochloride in local anesthesia has been investigated.  
In some treatment protocols, the simultaneous administration of two-drug combinations is required to achieve the desired result. The large aqueous space in the MVL and the division of this space into intravesicular and extra-vesicular parts, allows multiple drug combinations to be loaded in it and enter the body during an administration. The efficacy of co-delivery of mitoxantrone hydrochloride with horseradish peroxidase and insulin with metformin in a system was investigated in the treatment of cancer and diabetes mellitus, respectively, and showed satisfactory effects. Another class of drugs that have been successfully loaded in MVL is antibiotics. Antibiotics should have the least fluctuations in plasma concentrations in order to be more effective on microorganisms, so they should be prescribed according to a regular schedule. In MVL studies, researchers found satisfactory results from the study of the two antibiotics vancomycin and gentamicin.   
Many liposomal systems are used clinically to control drug release. These systems include daunorubicin, desferrioxamine mesylate, insulin-like growth factor 1 (IGF-1), doxorubicin, vincristine sulfate, and irinotecan respectively under the brand names DaunoXome®, DepoDFO®, DepoIGF-I®, Doxil®, Marqibo®, and Onivyde®. Depofoam is a type of MVL system with a particle size of 10 to 20 µm that could be a good depot in the body and releases the drug in a controlled manner. Depofoams are good choices for drug delivery to tumor areas and sensitive areas of the body such as the eyes, spinal cord, and epidural, and can reduce drug toxicity and side effects by minimizing drug exposure to healthy parts of the body.    There are several Depofoam systems which three of these systems have been approved by the US Food and Drug Administration (FDA). DepoCyt® is a Depofoam system of the anticancer drug cytarabine by intrathecal injection. This system releases the drug in the body for two weeks and makes an optimum concentration of it in the cerebrospinal fluid (CSF). DepoDur® is the second product, which contains morphine. It relieves post-surgery pain after epidural administration and reduces the use of other injectable analgesics. Exparel® is a new formulation of bupivacaine with an analgesic effect that is injected near the surgical site. Numerous animal and human studies showed that after intrathecal, epidural, intraocular, intramuscular, intravenous, intra-arterial, and subcutaneous administration of Depofoam.
This review article provides an overview of recent studies on the MVL system and its effect on optimizing rate of drug release. Successful loading of large molecules such as proteins and the possibility of loading multiple drug combinations into one system shows a hopeful view for the future of MVL in the pharmaceutical industry. It seems that this new technology, by overcoming the problems caused by frequent drug administration, has created an additional incentive for researchers to advance in this field. However, problems such as the high cost of these liposomes are some of the challenges that they face.

Background &

Systemic lupus erythematosus is a chronic, autoimmune, multisystem inflammatory disease that can cause skin lesions, inflammation of the joints and membranes covering the lungs and heart, nephritis, cardiovascular, hematological, gastrointestinal, and neurological diseases. In this way, the symptoms can appear slowly and gradually or quickly and change with the stages of activity and recovery (1). This disease significantly affects the quality of life in physical, emotional and social aspects (2).
On the other hand, the results show that about 80% of lupus patients complain of psychological problems that cause damage to their lives (7). In the meantime, the use of experiential avoidance is known as a maladaptive strategy that is the product and continuation of anxiety and depression (8). Research shows that the set of inflexible emotional avoidance measures is a factor of vulnerability and psychological risk factor for the development, persistence and exacerbation of psychological symptoms (10) and significantly reduces the quality of life (9). Therefore, for these patients, treatment methods or therapies are used to minimize the consequences of the disease and improve the quality of life and psychological symptoms. Performing effective interventions aimed at reducing the psychological and cognitive consequences of these patients can be effective in improving the quality of life as well as psychological symptoms such as experiential avoidance of these people. In this regard, one of the effective psychological therapies that has been able to be effective on a wide range of emotional disorders and anxiety, is Barlow integrated meta-diagnostic therapy. Transdiagnostic intervention focuses on emotion regulation, but sometimes due to lack of emotional control, there are approaches that do not target emotion regulation and behavioral change is targeted, including act intervention. Acceptance and commitment therapy or act is a behavioral therapy that focuses on valuable involvement in life.
The results showed that act-based therapy was effective in reducing depression, anxiety, and increasing quality of life (14,15,16). In general, due to the effectiveness of act in the treatment of anxiety and depression, this treatment is used for patients with systemic lupus erythematosus. Therefore, this study, in continuation of the evolution of non-drug therapies effective in reducing the symptoms and psychological symptoms of lupus erythematosus, systematically intends to study these two treatments (act and meta-diagnosis). Therefore, the present study seeks to ask whether the treatment of acceptance and commitment (act) and integrated meta-diagnosis affect the quality of life and cognitive symptoms of patients with systemic lupus erythematosus?

The research was a quasi-experimental study with a pretest-posttest design with a control group. The statistical population of the study included all patients with systemic lupus erythematosus in 2019 in the rheumatology clinic of Imam Ali hospital in Zahedan and private rheumatology clinics, 45 people were replaced in two experimental groups (act and meta-diagnosis) and one group (control) based on purposive sampling method.  The Lupus McIlham et al. (2007) Quality of Life Scale and the experience avoidance acceptance and practice of Bones et al. (2011) were used to collect data. Act Hayes et al. (2011) and integrated transdiagnostic therapy of Barlow et al. (2017) including were used 10 sessions of 60 minutes twice in a week.

The results showed a significant difference between the post-test means of the experimental and control groups; This means that act therapy and meta-diagnosis training can improve the level of experiential avoidance as well (p <0.001).

The results showed that in comparison with the control group, both treatments were effective in reducing the experimental avoidance and quality of life of lupus patients. However, a comparison of the two treatments showed that there was no significant difference between the effectiveness of these two treatments in reducing experimental avoidance and increasing the quality of life of lupus patients. The results are consistent with the results of studies that measure the effectiveness of act therapy on quality of life (24.18), depression (25) and anxiety and dysfunctional attitudes of patients with systemic lupus erythematosus (25) as well as the effectiveness of meta-diagnosis on health and emotion regulation (19). It seems that acceptance and commitment training, instead of ignoring emotions and inner experiences, leads the patient to become aware of feelings, inner and emotional experiences, accepting them and using them properly and instead, causing the patient to Establish appropriate situations and interactions and experience them with a fresh perspective. In addition, from the perspective of acceptance and commitment therapy, it avoids experiences of the traumatic process. Although short-term experience avoidance has a mitigating effect on unpleasant experiences, it has many destructive effects in the long run and can lead to inflexibility and functional impairment. On the other hand, acceptance and commitment therapy based on patients' quality of life through factors such as acceptance without judgment, being in the moment, coping with inner experiences without avoiding, suppressing or trying to change them, improving emotion regulation or mechanisms such as vulnerability to emotions Negative improves. Because this treatment causes patients with systemic lupus erythematosus to accept their feelings, emotions and thoughts in spite of being unpleasant and reduce hypersensitivity to the disease and thus increase their satisfaction and quality of life. Perhaps another reason for improving the experiential avoidance and quality of life in these patients is to clarify values and address important life values and goals rather than addressing everyday symptoms and issues. In other words, the goal here is to help the person to do what is important to him in life and in line with his values, instead of responding to the physical and psychological symptoms of his illness (29.30.31). Trans-diagnostic therapy helps patients deal with their negative emotions and respond to their emotions in a more adaptive way. This approach emphasizes changing emotional regulation habits to reduce the frequency and severity of maladaptive emotional habits, reduce harm, and increase performance. Dynamic interaction between thoughts, feelings and behaviors and their role in emotional experience has been considered in all meta-diagnostic approaches (34). In fact, this approach strengthens cognitive and behavioral control in the individual by interacting with thoughts, feelings and behaviors. Improving cognitive and behavioral control, in turn, leads to the use of thought and practical processes to moderate the effects of stress on patients, and in turn improves the quality of life and reduces experiential avoidance. It can be inferred that the present study has a positive strength that can be said that the treatment of act and meta-diagnosis has an important role in increasing the quality of life and reducing the experience avoidance of patients with systemic lupus erythematosus. A drug used these methods. There are some limitations for it, such as the statistical population of this study, which were only related to lupus patients, and in generalizing the results to other patients, caution should be observed. It is suggested that in future researches, statistical population and more diverse patients be used to select the sample. The results of this study are considered as important consequences of education and mental health promotion in patients with systemic lupus erythematosus. As a result, it is suggested to use acceptance and commitment-based therapy along with post-diagnosis educational treatment along with other treatment methods to improve the quality of life and cognitive symptoms, including experiential avoidance.

Background &

In today's societies, breast cancer has significantly threatened women's health (1). Successful cancer treatment can also destroy tumor germ cells (2, 3). Treatment methods based on immune checkpoint molecules are considered (4). PD-L1 overexpression suppresses the immune response to cancer cells and causes epithelial-to-mesenchymal transition (EMT) and cancer stem cell (CSC) phenotypes, metastasis and chemical resistance (5). Overexpression of PD-L1 and MUC1 is observed in approximately 90 TNBCs. In this present study, we investigated the inhibitory effect of miR-143-3p on MUC1 expression as an oncogene that has the most impact on PDL-1 overexpression in BC cell lines MCF-7 (less aggressive BC), MDA‐MB‐231, and BT-549 (metastatic BC model). The suppressive effect of miR-143-3p on the expression of this oncogene as a direct effect and PDL1 level as an indirect result in BC cell lines was investigated. Besides, the effect of miR-143-3p overexpression on BC cell lines proliferation through downregulation of candidate oncogene was investigated.

First, the targeting of miR-143-3P on MUC1 3 'UTR was confirmed by using bioinformatics software and then by dual luciferase assay. The expression level of miR-143-3P and MUC1 were measured in breast cancer lines compared to the normal line. After transfection of miR-143-3P into breast cancer cell lines, MUC1 and PD-L1 expression in mRNA levels were evaluated by using qRT-PCR. The miR-143-3p effects on MUC1 and PD-L1 expression and its impact on cell proliferation was investigated by using MTT assay, (mean ± SD).

The result of the dual luciferase assay was obtained from cloning the 3'UTR of the MUC1 gene in the psi-check2 vector and sequencing. According to the prediction analysis, the 3′-UTR of MUC1 gene has been considered as a putative miR-143-3p binding site (Target scan database). Transfecting miR-143-3p into MDA-MB-231, BT-549, MCF-7 cells harboring MUC1 3′-UTR decreased the luciferase activity to to 55% ± 1/73, 57% ± 1 /15 , 59 % ± 3/51% respectively, in comparison with the control (P < 0.01) (mean ± SD). he expression of miR-143-3p was significantly downregulated in BC cell lines compared to their control, and its downregulation was negatively correlated with MUC1 overexpression (r= -0.6419, p = 0.0244). Increased expression of miR-143-3P, decreased the mRNA level of MUC1 in MDA-MB231 to 1/3 ± 0/7, BT549 to 1/1± 0/45 and in MCF7 to 0/4/0 ±21, compared whit untransfected cells.
MiR-143-3p introduction to BC cells downregulates PDL-1 indirectly. Overexpression of miR-143-3P reduces the MUC1expression, and the reduction of MUC1 expression reduces PD-L1 expression mRNA level in MDA-MB231 to 3/4±0.45, BT549 to 3/1±0.56, MCF7 to 0/53±0.48, compared whit un transfected cells (fig4A). miR-143-3p inhibits BC cellular proliferation. An MTT assay revealed that miR-143-3p overexpression significantly suppressed the proliferation in MCF-7 to 52% ± 1.55, BT549 to 48% ± 2.45 MDA-MB231 to 43% ± 3.36, compared whit non-transfected cells 72 h after transfection.

 Breast cancer treatment has made significant progress in recent years, and a new treatment called immunotherapy, which uses the body's immune system to treat cancer, has become popular (6). One of the symptoms of breast cancer tumors is the overexpression of MUC1. A high expression level of MUC1 is associated with poor prognosis in cancer patients (7, 8). In an animal model of breast cancer, intravenous injection of MUC1 suppresses the immune system and accelerates the death of tumor-bearing mice. The serum level of MUCl expression is also associated with suppression of the immune system in patients with metastatic adenocarcinoma treated with active specific immunotherapy (8, 9). As we mentioned earlier, MUC1 can increase the expression of PD-L1 by recruiting MYC and NF -kB p65 to the PD-L1 promoter in some solid tumors, such as triple negative breast cancer (10). the mechanisms underlying PD-L1 expression in MUC1-positive tumor tissue were investigated, and the potential of targeting PD-L1 to inhibit the progression of MUC1-overexpressing colon cancer in mice, Therefore, the role of MUC1 in tumor immune evasion has been confirmed and can be a basis for using PD-L1 inhibitors in MUC1-positive colon cancer (8). microRNAs can regulate the expression of immune checkpoint receptors and their ligands (11). Changes in the expression of miR-143 often play a role in tumorigenesis (12). In 2020, Y Tokumaru and his colleagues showed by studying breast cancer samples with estrogen receptors that the high expression of microRNA-143 is associated with a favorable tumor immune microenvironment and better survival in breast cancer. They reported that miR-143 is a tumor suppressor microRNA that exhibits anti-tumor function by targeting KRAS signalling pathways in various malignancies. The high expression of miR-143 in cancer cells with a favorable tumor immune microenvironment regulates the positivity of anti-cancer immune cells. The suppression of pre-cancerous immune cells is related and leads to better survival of breast cancer patients (13).
In this study, we demonstrated MUC1 was potential as a novel target of miR-143-3p, therefore, the dual-luciferase reporter assay verified that miR-143-3p directly targeted MUC1 and inhibited this transcription. We found miR-143-3p downregulated in breast cancer cell lines compared to the normal line via qRT-PCR. In the current study, the qRT-PCR results illustrated an inverse relation between MUC1 mRNA expression and miR-143-3p expression in breast cancer cell lines. We investigated indirect targeting of PD-L1 via MUC1 targeting by miR-143-3p., be able to be prevent the cell proliferation in breast cancer cell line. Therefore we recognized, targeting MUC1 may be a novel strategy for BC therapy and prevent the progression of breast cancer and miR-143-3p as a promising candidate for miR restoration therapy in BC patients.

Background &

rug abuse is a major health challenge all over the world, and the majority of society thinks that drug abuse is mainly a male phenomenon. While drug abuse in women is increasing. Women experience a stressful life with drug abuse and need more support from family and society. If they do not receive the necessary support, they will be stuck in the cycle of addiction and it will be difficult for them to bear failures. Pregnancy with substance abuse poses serious risks to women's mental, psychological, physical and physical health and threatens the mental, social, political and economic health and safety of the society. In this context, midwifery personnel play a role as active people in the health care team and as one of the important sources of information to the community members in increasing social support and bearing more failures. The present study was conducted with the aim of determining the role of social support in coping with the failure of pregnant women with substance abuse who referred to Hazrat Zainab Hospital in Shiraz in 2021.

The current study is a descriptive-cross-sectional study and the statistical population of all pregnant women with substance abuse referring to the clinic, laboratory, IVF unit, ultrasound, emergency department, and inpatient departments who, based on their self-report, declared that they suffered from substance abuse in a 12-month period. The consumption of substances such as cigarettes, opium, opium juice, heroin, crack, glass, hashish, morphine, cocaine, amphetamine, methadone, marijuana, NAS, pan, bong, flower, alprazolam, buponorphine and other substances and in different sections. Hazrat Zainab Hospital was in Shiraz. 200 people were included in the study by continuous sampling. The inclusion criteria included: having Iranian nationality, women aged 18 and above, ability to read and write, being married and with drug abuse according to the individual, mental and physical conditions were suitable.While respecting the privacy and confidentiality of information, demographic questionnaires, VAX social support and Harrington's failure tolerance were completed. Sampling continued from Mehr to Esfand 1400. Data analysis was done with SPSS 22 software with descriptive and analytical statistics tests of frequency, percentage, mean and standard deviation, Pearson correlation coefficient and multiple regressions.

In the present study, 200 Iranian pregnant mothers with substance abuse with an average age of 34 years, average age of marriage 21.70 ± 4.51 years, majority of married women, housewives, with unfavorable economic status and no insurance were examined. Women and spouses with primary and secondary education levels had the highest frequency compared to other people. Women with working spouses also had the highest frequency compared to other people. 56% of these women had an unwanted pregnancy and 50 of these women had a history of prison and half of them had a history of prison once. The reason for the conviction of 60% of women was for carrying drugs, 30% for theft and 10% for other reasons. Women with 2 children had the highest frequency. The average social support score of pregnant women with substance abuse was 53.4 ± 2.32, which indicates unfavorable social support. Social support in the support of friends dimension had the highest mean (2.44 ± 0.91) and the support of community members had the lowest mean (2.24 ± 0.64). Social support was more in wives and husbands with middle and higher education levels. The mean failure tolerance score was 136.73±22.5, and failure tolerance was inversely correlated with social support (P=0.012) in the dimension of not tolerating stress, not tolerating discomfort, and not tolerating injustice and dissatisfaction.

The social support received by pregnant women with drug abuse is not optimal and these women receive most of their support from friends, family and acquaintances, which provides the basis for more harm to them and makes them more prone to fall into the trap. Addictive Most of these women have not been able to bear failures, so it seems necessary to design and hold life-enhancing programs. Social support in these women was related to the level of education and favorable economic status, which can be helped by promoting education and improving the economic situation by creating simple jobs and educational spaces for these women.

Background &

Staphylococcus aureus is one of the human pathogens that causes a wide range of diseases such as endocarditis, blood, bone, skin and soft tissue infections (1). One of the resistant strains of this bacterium is methicillin-resistant strains of Staphylococcus aureus (MRSA), which has been reported as a serious risk by the Centers for Disease Control and Prevention. One of the pathogenic mechanisms and antibiotic resistance of this bacterium is the formation of biofilm, which causes this bacterium to bind to different surfaces (2). Biofilm-forming strains have become resistant to many antibiotics, so that biofilm-forming strains form extracellular matrices that are immune to the immune system and antibiotics. Various genes are involved in biofilm production, one of which is the icaB gene, which plays a key role in the production of poly N-acetyl glucose amine and biofilm production. The design of new antimicrobial drugs for the treatment of this bacterium is important, so finding a suitable treatment option for the treatment of infections caused by this bacterium is one of the challenges of researchers (3). Recent advances in nanotechnology have suggested alternative solutions, such as drug delivery systems, that increase drug specificity and efficiency (4). One of these drug delivery systems is nanosystems, which are composed of bilayer nonionic surfactants. Due to the importance of nanosystems, the aim of this study was to synthesize nanoparticles containing naproxen, to investigate their physicochemical properties and their antimicrobial and antifouling effects against Staphylococcus aureus strains.

Nanosomes containing naproxen were synthesized by thin layer hydration method. The confinement efficiency is indicative of the drug encapsulated in the nanosystem structure relative to the drug used. For this purpose, the nanonosomal formulation was first centrifuged at 4 ° C at 14000 g for 45 minutes. The nanosystem containing the drug precipitates and the free drug remains in the supernatant. The absorbance of the supernatant sample at 270 nm was read by a spectrophotometer and the amount of free drug was calculated from the initial value.
The Physico-chemical characteristics of prepared nanoniosome encapsulated naproxen was determined using scanning electron microscopy (SEM), Dynamic light scattering (DLS). The in vitro drug release study was done using dialysis bag (6). The Staphylococcus aureus strains were recovered from 100 clinical samples and their antibiotic resistance patterns were studied using disk diffusion method. The antibacterial activity of nanoniosome loaded naproxen and free naproxen were investigated using well diffusion and micro-dilution methods (7). The icaB biofilm gene expression analysis in S. aureus isolates which are treated with nanoniosome loaded naproxen and free naproxen were examined using Real Time PCR methods (8).
Draw diagrams and Statistical analysis was performed by GraphPad Prism software version 7 and SPSS version 23, and one-way analysis of variance was used for statistical analysis and p <0.05 was considered significant.

In this study, using different molar ratios of surfactant, cholesterol and drug, different formulations of nanosystems containing naproxen were synthesized. The optimal niosome size synthesis was measured by DLS method. The results of electron microscopy (SEM) show that the synthesized nanonosomes have a spherical structure. In this study, the dialysis bag method was used to evaluate the drug release pattern. Figure 2 shows the pattern of naproxen release from nanosystems and free naproxen over 72 hours.
Out of 100 clinical specimens, 15 specimens of Staphylococcus aureus were isolated and identified using microbiological methods. The results of antibiotic resistance profile test showed that out of 15 strains, 10 strains were methicillin resistant (MRSA).
The antibacterial activity of nanoniosome encapsulated naproxen and free naproxen showed that the MIC was reduced by 2 to 4 times. The results of the well diffusion method showed that nanoniosomes containing naproxen had more significant antimicrobial power than free naproxen, so that the diameter of the growth inhibition zone increased with increasing nanosystem concentration. Real-Time PCR was used to evaluate the effect of nanoniosoms containing naproxen and free naproxen on icaB biofilm gene expression in Staphylococcus aureus strains. Also, after treating Staphylococcus aureus strains with naproxen-containing nanosystem sub-inhibitory concentration, it was shown that the expression of icaB gene was significantly reduced compared to the 16S rRNA reference gene (p <0.05).

In this study, naproxen was encapsulated as a drug compound in the nanoniosome structure and its physical and chemical properties including size, morphology, drug enclosure percentage and drug release were studied. The results of this study showed that the synthesized nanoniosome in the optimal formulation had a spherical shape, the average size was 125.3 nm with a confinement percentage of 66.84%. Drug release results also showed that naproxen in the formulated form in nanonosomes has a much slower release pattern than free naproxen, which is a suitable feature of a drug delivery system. The results of the antimicrobial test showed that naproxen-containing nanoniosome had more significant antimicrobial effects than free naproxen compared to free naproxen, reducing the MIC by 2 to 4 times. One of the antimicrobial mechanisms of nanoniosome containing naproxen is the fusion of nanoniosome with bacterial cell membranes, which can deliberately release the drug into the cytoplasm of the cell and cause bacterial cell death (10). The results of this study showed that nanoparticles containing naproxen have more significant anti-biofilm effects than free naproxen compared to free naproxen and can significantly reduce the expression of biofilm gene (11). One of the reasons for the anti-biofilm effects of naproxen-containing nanosystems is the greater penetration of naproxen-containing nanosystems into the biofilm structure, which can cause the death of bacteria, a decrease in the number of bacteria, and the conversion of biofilms into planktonic cells (12).

Background &

Obesity and related diseases such as type 2 diabetes, cardiovascular disease, and various types of cancer are major global health concerns. Increased adipose tissue in the body is one of the causes of obesity. Adipose tissue consists of two categories of white adipose tissue which store energy and brown adipose tissue, which controls the body's thermogenesis. Fatty acids in brown adipose tissue produce heat by burning and maintaining body temperature. Brown adipose tissue contains polyunsaturated lipid stores that provide rapid storage of fatty acids to generate heat and maintain body temperature, and thermogenesis, and has the flexibility to adapt to external stimuli such as cold and sympathetic stimulation for thermogenesis. Brown adipose tissue plays a regulatory role in whole-body metabolism and body weight. Thermogenesis is activated via the β3-adrenoceptor pathway and occurs in mitochondria in brown adipose tissue containing Mitochondrial uncoupling protein-1 (UCP-1). The family of Mitochondrial uncoupling proteins (UCPs) plays an important role in the thermogenesis of brown adipose tissue and the regulation of mitochondrial ROS excretion in various tissues. Changes in lifestyle and diet are one of the achievements of modern life today, which can be attributed to the tendency to overeat fast foods among family members or the community. Consumption of heated oils, in addition to increasing oxidative stress and apoptosis in tissues, leads to obesity by reducing the lipolysis pathway, inhibiting beta-adrenergic receptors, and increasing the accumulation of fat in visceral tissues. Aerobic exercise is used to prevent and treat obesity, insulin resistance, or type 2 diabetes because of its ability to improve mitochondrial function and fatty acid oxidation, reduce body fat, improve insulin sensitivity, and absorb glucose into skeletal muscle. Octopamine is an antioxidant and endogenous antioxidant biogenic amine that has properties similar to catecholamines such as norepinephrine. Octopamine has the ability to stimulate lipolysis and fat metabolism. The aim of the present study was to determine the interaction effect of 4 weeks of aerobic training and octopamine on the activity of brown adipose tissue of male rats fed with deep frying oil.

In an experimental study, 30 adults male Wistar rats weighing an average of 300 to 350 g and aged 8 weeks were purchased. All rats were kept in polycarbonate cages (5 mice per cage) at 22 2 2 ° C, 55% humidity, and under the light and dark cycle for 12:12 hours without restriction on water and food. Rats were randomly divided into five groups: healthy control (n=6), DFO (n=6), aerobic training + DFO (n=6), octopamine + DFO (n=6), and aerobic training + octopamine + DFO (n=6). Intraperitoneal injections of 10 ml/kg of octopamine and Gavage of deep frying oil were done five times a week and every day, respectively.
In order to adapt the rats in the aerobic training group, before starting the main training program, the rats in this group ran at a speed of 9 m / min for 20 minutes for a week. The aerobic exercise protocol consisted of 4 weeks of aerobic exercise and 5 sessions per week. The training session included 5 minutes of warm-up at 7 m / min and 5 minutes of cooling at 5 m / min. The intensity of training started in the first week with 50% vo2max and a speed of 16 m / min, and in the last week, it reached 65% vo2max and a speed of 26 m / min. To prepare deep frying oil, 8 liters of sunflower oil was heated for 190 consecutive days at a temperature of 190 to 200 ° C for 4 consecutive days.
48 hours after the last training session and 8 hours of fasting, all rats were anesthetized with chloroform and then sacrificed. The brown adipose tissue was immediately removed from the body and stored in a nitrogen tank at -80 ° C. Gene expression of UCP-1 was measured by Real-time PCR. Independent t-test, two-way analysis of variance, and Bonferroni post hoc tests were used to analyze the data. All the analyses were done by SPSS software version 21 and the charts were drawn using Microsoft Excel software version 16. The significance level was p <0.05.

The results showed that consumption of deep frying oil induced a significant decrease in gene expression of UCP-1 (P < 0.05) compared to the healthy control group. The aerobic training and octopamine caused a significant increase in gene expression of UCP-1 (P >0.05) compared to the DFO group. The interaction effect of aerobic training and octopamine caused a nonsignificant increase in UCP-1 gene expression (P >0.05) in comparison with the DFO group.

Decreased expression of UCP-1 following consumption of deep heated oil may be due to disruption of metabolic pathways that have reduced metabolism. Regarding the significant increase in UCP-1 gene expression under the influence of aerobic exercise and octopamine supplementation, each of them alone, we can first mention the antioxidant properties of aerobic exercise and octopamine. According to previous studies, the variable UCP-1 itself is an antioxidant. And since aerobic exercise and octopamine, each has antioxidant properties on their own, they can enhance and increase the expression of the UCP-1 gene in brown adipose tissue. Increasing UCP-1 can reduce the excess ROS produced and act as a compatible mechanism to reduce the harmful effects of ROS. It is possible that exercise was able to stimulate brown adipose tissue through sympathetic enhancement, which in turn increased UCP-1 gene expression and mitochondrial biogenesis. Another reason is that octopamine is similar to norepinephrine. Octopamine can bind rapidly to β3 adrenergic receptors, increase cAMP gene expression, and increase lipolysis and fat metabolism in general. It seems that exercise and octopamine can activate brown adipose tissue.

Background &

Considering the lack of research in finding an effective approach in the field of bipolar disorder management and the career success of people with this disorder, the present study aims to compare the effectiveness of vocational rehabilitation programs with career counseling based on the cognitive-behavioral approach on the career success of them, and the following questions were answered: Is the effect of a vocational rehabilitation program with career counseling based on the cognitive-behavioral approach different on the subjective career success of people with bipolar disorder? Is the effect of the vocational rehabilitation program different from career counseling based on the cognitive-behavioral approach to the objective job success (income) of people with bipolar disorder? Is the effect of the vocational rehabilitation program different from career counseling based on the cognitive-behavioral approach to the objective career success (promotion) of people with bipolar disorder?

The design of the current research was semi-experimental, of a pre-test-post-test-fallow-up type with a waiting group. All participants referred by a psychiatrist to a counseling clinic and diagnosed as having bipolar disorder were purposefully selected for the research, and among them, the volunteers were interviewed and diagnosed with a clinical interview based on the criteria of the DSM-5.  To select the research sample, inclusion and exclusion criteria were considered. 24 people were selected by the available sampling method and randomly assigned to groups. 8 people in the experimental group with a vocational rehabilitation program, 8 people in the experimental group with career counseling based on the cognitive-behavioral approach, and 8 people in the waiting group. Before starting the interventions, a pre-test was taken from all 24 participants. After that, the people assigned to the two test groups received the relevant interventions in 10 sessions of 100 minutes (in the experimental intervention with the vocational rehabilitation program and the career counseling intervention based on the cognitive-behavioral approach) and the people present in the waiting group did not receive any intervention. The people participating in the interventions did not have any knowledge or contact with each other, and they tried to maintain is lack of knowledge and communication until the end of the intervention and prevent the exchange of information. For the vocational rehabilitation program and career counseling based on the cognitive-behavioral approach, a pre-developed program was used separately, the validity and reliability of which had been checked and confirmed (5). Moreover, the vocational rehabilitation program, in addition to 10 intervention sessions for the individual with bipolar disorder, included two intervention sessions for the family and two sessions for the employer or his colleague, which are carried out if the individual needs and consents to these two intervention sessions were down. At the end of the interventions, all the people in the experimental and waiting groups filled out the questionnaires again as a post-test. One month after the implementation of the post-test, the research samples filled out the research questionnaires for the third time to implement the follow-up phase. To measure the subjective dimension of career success, the job satisfaction questionnaire (29) and the objective dimension of career success were measured by measuring the amount of income and job promotion. Research data were analyzed using descriptive statistics (mean and standard deviation) and inferential (variance analysis with repeated measures) using SPSS V. 16 software (30). Based on the background of the research, pre-test variables, age, and gender were covariate.

In the post-test stage, the vocational rehabilitation program showed more effectiveness in subjective career success than the career counseling based on the cognitive-behavioral approach (p<0.007) and the waiting group (p<0.006), but none of the two interventions, there was no significant effect on objective career success (p<1). Also, in the follow-up phase of the vocational rehabilitation program, it was more effective on subjective career success than the career counseling based on the cognitive-behavioral approach (p<0.003) and the waiting group (p<0.0001), but between the scores of the participants in the intervention of career counseling based on the cognitive-behavioral approach and the waiting group no significant difference was observed (p<0.26). Besides, there was no significant difference between the objective career success scores (income) of the participants in the two research interventions and the waiting group (p<0.2). In comparison, between the objective career success scores (promotion) of the participants in the two research interventions, there was no significant difference with the waiting group (p<0.36).

According to the data obtained from the results of the research, it can be said that the vocational rehabilitation program has been effective in increasing subjective career success scores, and even after one month of receiving the intervention, the effectiveness of this method has not decreased. Also, career counseling based on the cognitive-behavioral approach has not been effective in the subjective career success of people with bipolar disorder. Besides, none of the two interventions have been effective on the objective career success (income and promotion) of the people participating in the research. In general, according to the results of the research and the explanations presented, it seems that considering the clinical observations, the subjective career success of people with bipolar disorder during the interventions, especially in the vocational rehabilitation program, compared to the career counseling based on the Cognitive-behavioral approach more specifically deals with the career and its appendices, and in addition to managing people, it teaches a person how to build and deal with a real career future. Therefore, it is not far-fetched that a specialized vocational rehabilitation program that is specially designed for vocational interventions will be more effective (5). It is also important to note that increasing income is not a short-term process and requires a long time (34). In addition, this research coincided with the era of Coronavirus and the recession and closure of businesses (36), but under the influence of the interventions, at least the previous income level of the individual in these challenging conditions was maintained. Based on the clinical evidence from the reports of the people present in the research, especially the people who participated in the intervention of the vocational rehabilitation program, after participating in the intervention, these people were able to achieve a higher human credit status in the workplace than before, and the positive feedback of people around these people has confirmed that. Therefore, it seems that in addition to the objective promotion, maybe we can have a word called spiritual promotion, which based on the positive feedback these people received from the people around them at the workplace, is considered a great career success for these people. Will be In fact, it may be possible to talk about the existence of a kind of spiritual promotion in the workplace, which has not been mentioned in research so far (5). This study provides evidence of the effectiveness of the vocational rehabilitation program in increasing the career success of people with bipolar disorder. This new perspective can be used as a reliable source on the career interventions of people with bipolar disorder and can be effective as an early rehabilitation intervention in reducing the career issues of these people.

Background &

Osteosarcopenia, the presence of osteopenia/osteoporosis and sarcopenia, is an emerging geriatric giant, which poses a serious global health burden.

The latest studies conducted in recent years in the field of pathophysiology, epidemiology, diagnosis and treatment of osteosarcopenia were reviewed.

Getting old and being healthy is contingent on maintaining the integrity of several physiological systems such as the musculoskeletal system which is important for both human movement and storing calcium and glucose. As individuals get to their sixtieth, their muscle mass and bone minerals will decrease and the elderly will become susceptible to sarcopenia and osteoporosis. According to the World Health Organization, the definition of osteopenia and osteoporosis is a T score of less than -1 and -2.5 standard deviations, respectively. Sarcopenia is defined by cut-off amounts for low muscle mass, strength, and/or functional capability and is related to different metabolic conditions. Both diseases have common risk factors and are associated with falls, frailty, fractures, hospitalizations, and mortality as well as causing an increase in healthcare expenses. These disorders put a heavy burden on societies, especially the geriatric population to the extent that in 2010 there were 27.5 million people diagnosed with osteoporosis in the European Union. Osteosarcopenia is defined as low bone density and low muscle mass. As in individual ages, the prevalence of osteosarcopenia increases as well with 59.4 percent and 48.3 percent in men and women above 75 years old. It has been shown in a study of 590 post-menopausal women that the risk for osteoporosis will be 12.9 times higher in the presence of sarcopenia.  A recent study of 3334 older individuals reported that individuals with sarcopenia (compared with no sarcopenia) had lower BMD when employing the 2019 European definition of sarcopenia. So there is a bidirectional relationship between osteoporosis and sarcopenia, which results in  the development of osteosarcopenia. Major risk factors for this disorder are age and sex, however body mass index and physical activity are reversely related to osteosarcopenia and high fat mass will increase its risk. Glycine-N-acyltransferase (GLYAT) genes polymorphisms, peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), and myocyte enhancer factor-2 (MEF2C) are related to muscle atrophy and bone loss. Furthermore, genetic traits determine peak muscle and bone volume in early life which may be a mechanism for delaying sarcopenia and osteoporosis in old ages.
In comparison with non-osteosarcopenic subjects, the risk of falls (ORs: 2.83–3.63; P < 0.05) and fractures (ORs: 3.86– 4.38; P < 0.05) is significantly higher in osteosarcopenic older individuals attending a falls and fractures clinic. The risk of o a minccurance of a minimal-trauma or no trauma fracture when the patient is sarcopenic was also reported to be much greater than in non sarcopenic older persons (relative risk 1.37, 95% CI 1.18–1.58).
It has been suggested that clinicians should be alert to the fact that, recognition of one of these conditions makes the investigation for the other one necessary because of their co-occurance.  A physical examination must be typical in the comprehensive geriatric investigation. But additional physical assessments are needed to diagnose sarcopenia. Physical assessments are considered to assess muscle strength (grip strength, sit to stand test) or functional capacity (gait speed, short physical performance battery, timed up and go test). The two most used and accurate assessments are gait speed grip power Osteosarcopenia cannot be screened and there is no efficient tool for predicting this condition, but there are tools for osteoporosis and sarcopenia such as SARC-F questionare which is highly specific and most accurate. Bone Marrow Densitometry through DXA is used for osteoporosis in individuals with age more than 50, post-menopausal women, adults with Rheumatoid Arthritis and adults who are on corticosteroid medications. FRAX© is the best tool for risk stratification of osteoporosis.
Increased risk for falls and following fractures are identifiable by testing for 25 OH vitamin D, serum calcium, parathyroid hormone and serum testosterone. BMD and muscle mass assessment are the essentials of osteosarcopenia workup. DXA is the greatest tool to assess BMD accurately, and has the benefits of estimating the lean body mass and appendicular lean mass in an accurate manner. Bioelectrical impedance analysis which assesses the fat-free mass, peripheral quantitative computerized tomography, muscle cross-sectional area and intramuscular adipose tissues and magnetic resonance imaging. A new technique named as the D3-creatine dilution method has been found to have strong associations with falls, fractures and risk of mortality in old men. This technique needs further assessment to be considered a typical clinical tool.
Resistance training exercises which stimulate muscle protein synthesis and the activity of osteoblasts will improve the activity of older individuals with osteosarcopenia. In addition, this kind of exercise will also improve the cardiometabolic and cognitive health in different populations. This kind of exercise is recommended for preventing osteosarcopenia. As the ability of muscles to absorb dietary amino acids will decline with age, supplementation with dietary proteins in addition to resistance exercises is proposed as an ideal therapy for maintaining the optimal musculoskeletal function in older adults. Whey protein which is rich in Leucine and stimulates mTORC1 in skeletal muscles is the best way to increase muscle protein synthesis on condition that the individual has optimal vitamin D levels. The most prevalent micronutrient in bone structure is calcium and its kinetic is remarkable in muscle contractility force. It has been offered that 1000–1300 mg/day of calcium should be administered in populations with insufficient diets. Creatine is also believed to boost the exercise induced increase in muscle mass and also it causes an increase in bone density.
Peripheral DXA, quantitative computerized tomography and radiographic absorptiometry are alternative techniques to DXA that estimate BMD include. Most older adults who experience a low-trauma fracture have BMD in the normal or osteopenic range. BMD assessment techniques are highly sensitive but  not so specific for prediction of fracture.
Although there is no FDA approved drug for sarcopenia, there are numerous drugs for osteoporosis including antiresorptive (denosumab, bisphosphonates), anabolic (teriparatide, abaloparatide), antisclerostin (romosozumab), and hormonal (hormone replacement therapy, selective oestrogen receptor modulators) agents. Adults with T score of -2.5 or less on DXA, or a FRAX© 10-year fracture risk of ≥3% at the hip or ≥20% for any other osteoporotic fracture will mostly benefit from antiresorptive or anabolic treatment. Denosumab which is a RANK ligand inhibitor has promising effects on bone and muscle and those who consume this drug experience significant increase in lean body mass and handgrip strength; however bisphosphonates have no such effects. Osteosarcopenia requires ongoing monitoring and assessment of falls and fracture risk, quality of life impact, and response to treatment.

Osteosarcopenia is a hot topic in geriatric research. Lifestyle, genetic, mechanical factors and endocrine factors are altogether effective in occurrence of osteosarcopenia. Resistance training exercise and nutritional supplementation is a way to hinder osteosarcopenia. There is a definite need for further clinical trials for investigating pharmacologic interventions for this condition and providing new diagnostic methods, screening tools and therapies.

Background &

The social developments of the past decades at the global level have faced the family system with new and diverse changes, challenges, issues, and needs. During this period, the family has been increasingly threatened by multiple and complex causes and factors. When the functions of the family, such as biological, social, cognitive, and emotional functions are damaged one after the other, its members gradually lose their sense of satisfaction. The gradual decrease in the satisfaction of family members due to incompatibility between couples first causes psychological dissociation and then social dissociation. In fact, the functioning of the family is formed based on the relationship between the spouses, and the conflicts between them cause the family system to undergo serious problems. One of the factors that can be mentioned as an influential factor in the occurrence of marital conflicts is intimacy, which in fact, with the reduction of this factor, the process of incompatibility moves forward quickly, and as an essential factor, it can be paid. Marital compatibility can be more in couples that have a higher level of intimacy. In other words, couples with higher intimacy are more capable of facing problems and changes related to their relationship, and as a result, they experience higher marital satisfaction and compatibility. On the other hand, communication skills are considered to be complex processes that enable a person to behave in such a way that others consider him/her adequate. Skills are the necessary abilities to perform purposeful and successful behaviors. Communication skills are the ability to symbolically and efficiently convey the meanings and messages that a person has in mind. When the couple's communication is of better quality, they can be closer to each other and can share their thoughts and feelings, as a result, they feel more intimate and avoid possible misunderstandings that arise in marital conflicts. They prevent seizures. Various treatment methods have been used to solve marital problems. The existence of incompatibility and unhealthy functioning of the family leads to the emergence of various family complications and damages. Therefore, it is necessary to implement therapeutic interventions to increase the functioning of couples, and one of the most effective therapeutic approaches in this field is schema therapy. Schema therapy is effective in improving the sense of closeness and psychological state of couples, marital relations, communication documents and sexual performance of couples, communication beliefs, and marital compatibility, and reducing the desire for divorce. The schema therapy approach is a fundamental evolution in cognitive therapy. The schema therapy approach was formed and developed at the heart of the cognitive therapy approach, based on the attachment theory. Schemas, as traces of a complex set of cognitions, feelings, and tendencies to react, are placed in the neural networks of the brain based on previous experiences. As soon as these patterns are activated in the later stages of life, people will feel trapped. By presenting the role of schemas and coping responses in conceptualizing psychological problems, schema therapy has been able to play a greater role in explaining psychological problems. Despite conducting various studies in the field of the effect of the use of treatment protocols on marital psychological characteristics, there are still many gaps in this field. Each of the conducted research is limited to certain statistical societies and cannot be generalized to the whole society. Also, the way of implementing treatment protocols may be of different quality, which requires repeating these training and comparing their results to reach the final conclusion. Conducting the present research can bring significant and interesting results by examining the effectiveness of the schema therapy protocol. Despite the effectiveness of schema therapy in improving subjects' behaviors in various studies, there have been few studies that have been conducted to investigate the effectiveness of schema therapy on intimacy and communication skills. Therefore, the research gap in this field is quite evident. Considering that the compatibility of couples plays an important role in the stability of the family, schema therapy can be used to achieve this goal, so the research question is whether schema therapy can affect intimacy and communication skills in incompatible couples. Is it effective for counseling centers in Tehran?

It is a semi-experimental research method with a pre-test-post-test design and a control group and a follow-up period. The statistical population included all incompatible couples who referred to the counseling centers of Tehran in the first half of 1400, and by taking possession of the existing files of incompatible couples who referred to the counseling centers of Tehran, the number of 10 couples (10 men and 10 women) who due to conflicts Marital have referred to counseling centers in Tehran using available sampling method and were placed in two groups of 5 couples (5 couples in the experimental group, 5 couples in the control group). The data collection tool was Thompson and Walker's Marital Intimacy Questionnaire (1983), Matson's Communication Skills Questionnaire (1983), and Spanier's Marital Compatibility Questionnaire (1976). In this research, Yang's schema therapy protocol was used for schema therapy training, which was used for three months and in 10 sessions of 120 minutes, as shown in table no. The mixed variance analysis test with repeated measurements was used to analyze the data.

The results showed that schema therapy is effective and stable in intimacy and related skills in incompatible couples. Also, the difference between the scores of all components in the pre-test and post-test stages, as well as pre-test and follow-up is significant (P<0.01), while the difference between the post-test and the follow-up stage is not significant. (P>0.01). This finding means that schema therapy has not only improved the marital intimacy components of couples in the experimental group, but this effect has also been stable in the follow-up phase. Also, the results of Table 6 show that the difference between the scores of communication skills in the pre-test and post-test stages as well as pre-test and follow-up is significant (P<0.01), while the difference between The test and the follow-up phase are not significant (P>0.01). This finding means that schema therapy has not only improved the communication skills of couples in the experimental group, but this effect has also been stable in the follow-up phase.

According to the results of this research, in general, schema therapy has a significant and stable effect on intimacy and communication skills in incompatible couples. In other words, schema therapy has improved intimacy and communication skills in incompatible couples. Every study has some limitations, and this study, like other studies, is not exempt from this case, which can be mentioned as the following limitations. In this research, only questionnaires were used to collect information, and due to practical limitations, interviews were not used to collect knowledge data. Also, the limitation of the sample size and the sampling method inevitably used the available sampling method. The main limitation of this research is that the current research sample was selected from among incompatible couples referring to counseling centers in Tehran, and the generalization of the results of this research to other people should be done with caution. Also, in this research, the possible effect of some intervening variables such as family, cultural, social, and economic factors and personality traits such as mental health or underlying family problems and their role in the research variables were not investigated, which found generalizability. It reduces research.

 The emergence of electronic education has further enhanced the field for the widespread application of learning-based training and other changes in educational procedures. Therefore, it is essential to understand the adaptability of the e-learning behavior of university students. Therefore, the present study is designed to design a quantitative model of influential factors affecting the establishment of an e-learning system in medical universities.

 Survey research strategy and quantitative research method. The statistical population of all professors and scholars of virtual education at the North Khorasan University of Medical Sciences has been 440. The statistical sample was obtained by 206 random sampling methods. The research tool contains a researcher-made questionnaire with 51 questions or items. SPSS software and structural equations were used to analyze the data.

 Research findings in the quantitative model of the factors affecting the establishment of an e-learning system in medical universities consisting of 13 categories and 51 components. According to the results of the dimensions of the Electronic Education System establishment and its prioritization, including specialist staff, content and content, student, hardware, cultural infrastructure, Pedeggy infrastructure, human infrastructure, requirements, economic infrastructure, external factors, Office infrastructure, technology infrastructure, and management and leadership were identified.

 Data results showed that the e-learning system in medical universities could be enhanced by strengthening the identified dimensions.

 Suicide is a tragedy for the individual, family, and society. The probability of suicide is operationally defined based on four indicators of hopelessness, suicidal thoughts, hostility-impulsivity, and negative self-evaluation, and it has been shown that these four factors can distinguish normal people from suicidal people. The suicide process also includes thinking, planning, acting, and finally completing the suicide. This behavior is inherently self-motivated, meaning that the person is doing it themselves, and intentionality is an inherent characteristic of doing it. According to studies conducted in this field, these events depict the progressive behavior of suicide in such a way that the occurrence of each increases the risk of the next stage in this circle. Knowing the risk and protective factors that can reduce suicidal thoughts will play a major role in preventing people from entering this costly and deadly chain, especially in early adulthood. Self-efficacy is one of the compatible cognitive characteristics that are considered important factors in the protection of suicidal thoughts and have significant effects on the perception of stress and coping mechanisms in the fields of psychological and physical medicine. Also, self-efficacy has a significant effect on a person's behavioral style, effort, and persistence. People with low self-efficacy usually feel powerless, unlike people with high self-efficacy who are more in control and less threatened in stressful situations, so a person with suicidal thoughts is likely to have a lower sense of self-efficacy. The relationship between attachment styles and self-efficacy and suicidal thoughts has been examined in past research, and the results have shown that secure attachment style has a positive relationship with self-efficacy and a significant negative relationship with suicidal thoughts or factors related to suicide attempts. But at the same time, the mediating role of self-efficacy about attachment styles with suicidal thoughts has not been investigated. In this research, the researcher seeks to fill this research gap. Those were considered the main predictive variables for suicidal thoughts. Also, considering the role of self-efficacy in adjusting and regulating one's emotions, it can be considered a mediating role as in past research.

 The statistical population of this correlation study included all the students of Shiraz Azad University in 1402-1401, which was equal to 19635 people based on the statistics obtained from the education of Shiraz Azad University. To determine the sample size, Cochran's formula was used and according to the calculations, the sample size was determined to be 380 people. Collins and Reed's (1990) attachment style questionnaire, Scherer et al.'s self-efficacy (1982), and Beck's suicidal thoughts (1961) were used. SPSS and Lisrel software were used for data analysis.

 The results showed that secure attachment style has a direct and significant effect on the feeling of self-efficacy and an inverse and significant effect on suicidal thoughts, and at the same time, the feeling of self-efficacy has an inverse and significant effect on suicidal thoughts. Also, the results showed that the mediating role of self-efficacy in the impact of attachment styles (secure, avoidant, ambivalent) on students' suicidal thoughts is significant at the 99% confidence level.

 In general, it can be concluded that increasing attachment styles can be a solution to increase the sense of self-efficacy, so it can be introduced as a solution to reduce suicidal thoughts. Self-efficacy leads to greater effort and persistence with obstacles and difficulties. Also, self-efficacy affects motivation through goal setting. If a person feels highly efficient in a specific field, he sets higher goals for himself, is less afraid of failure, and finds new strategies if the old strategies fail. But if the feeling of efficiency is low, the person avoids the task completely. Or quickly clears the scene if it encounters problems. It is suggested that therapists and health professionals use the results of this research in addition to prevention as a therapeutic intervention to prevent the emergence of dysregulated behaviors such as suicide. According to the results of the present study, it is suggested that health experts prioritize and choose the type of treatment for people with suicidal thoughts, as well as save time and money and achieve the maximum benefit from the methods of teaching self-efficacy and resilience skills. To use in this study, subjects were not interviewed and clinically evaluated, and self-report tools were used to collect data. Therefore, the results of the current research, like many other research, due to the use of questionnaires and self-report tools, may lead the participants to use methods based on obtaining social approval and avoiding stigma related to inadequacy, instead of actual behavior. Someone has encouraged me. As a result, caution should be used in the interpretation of research data.

The global epidemic of the disease caused by the coronavirus (COVID-19), a severe acute respiratory syndrome that appeared in December 2019, not only as a threat to the health and lives of millions of people around the world was considered Although Covid-19 could have negative effects on educational activities, social distancing has stimulated the growth of online educational activities so that there is no disruption in education. The electronic learning system has created educational environments that are not dependent on any specific location or time and allows teachers to teach a course simultaneously or asynchronously or use a combination of these two modes. Electronic learning as an educational medium in the classroom is a new experience for the teacher and students, which can be an effective step towards stabilizing and accelerating students' learning. On the other hand, the most important characteristics of secondary school learners that teachers should pay attention to can be classified into three types: cognitive, emotional, and social. The primary period is one of the most important and sensitive periods of study, and since it is essential for teachers and educators to pay attention to the different characteristics of students' growth, and to know that electronic learning requires a series of hardware tools and its extensive use may increase the level of violence. Mental Health Mental health is an issue beyond the absence or absence of mental illness. The positive aspect of mental health, which the World Health Organization relies on, is included in health: "Health is a state of physical, mental, and social well-being, not just the absence of illness or disability." Therefore, mental health is a state of well-being in which a person recognizes his abilities and can adapt to the normal stresses of life and be useful and productive in terms of work. Since there is no social interaction (compared to the common and usual form in the real environment) in the context of electronic learning, learners must be able to maintain their level of mental health. As a result, students who have more mental health and have the necessary abilities to deal with common academic challenges can be more self-regulated and self-efficient than other students, and as a result, they are more successful. It seems that virtual education has entered a new phase in our country and more attention has been paid to virtual education. On the other hand, those involved have become more aware of the importance of distance and e-learning-based education. Therefore, it is expected that with the development of the necessary infrastructure, such as the development of the nationwide Internet network and increasing its speed, the production of interactive educational software, and the use of the experiences gained in this pandemic, we will witness the increasing prosperity of virtual education. According to the research findings, there is little information on the relationship between electronic learning and the mental health of students, so the present study was conducted to investigate the structural relationship between electronic learning and the mental health of secondary school students in Golpayegan city, and seek answers to This question will be whether there is a significant relationship between e-learning and mental health of secondary school students in Golpayegan city.

The present research is applied in terms of purpose and descriptive and correlational in terms of method, and the statistical population of this research includes all male students in the second year of high school in Golpayegan city who were studying in the academic year of 2021-2022. The number of the statistical population was equal to 850 people according to the inquiry from the Statistics Unit of the Golpayegan Education Department. According to the Keywords E-Learning, Mental Health, Viral Crises Received: 27/09/2022 Published: 07/06/2023 ID [Downloaded from rjms.iums.ac.ir on 2023-12-30] 318 مجله علوم پزشکی رازی دوره 30 ، شماره 3، خرداد 1402 http://rjms.iums.ac.ir Farhang Esfahani M. Cite this article as: Farhang Esfahani M. Investigating the Relationship Between Electronic Learning and Mental Health of Secondary School Students in Golpayegan City in the Situation of Viral Crises. Razi J Med Sci. 2023;30(3): 316- 323. *This work is published under CC BY-NC-SA 3.0 licence. table of Karjesi and Morgan, 265 people were selected through a simple random sampling method. The research tools included three electronic learning questionnaires by Watkin et al. (2004) and Goldberg's mental health questionnaire (1972), both of which were standard questionnaires. Descriptive statistics were used to describe the demographic variables and SPSS software was used to check the research hypotheses.

The results of the research showed that there is a relationship between electronic learning and the mental health of secondary school students in Golpayegan city.

In general, it can be acknowledged that in viral crisis conditions, electronic learning can be used to improve the academic performance of students, and in this way, their mental health level can be improved to stay away from the study environment due to the conditions. Viral, saved. The Department of Education is one of the most fundamental organizations in the world today, and students have a direct relationship with this organization, this shows the key and vital role of this department in their complex lives. Knowledge of electronic learning and better use of it can facilitate and predict the quality and continuity of mental health and lead to the implementation of programs in a scientific manner and avoid unwise actions. Mental health refers to having understanding and decision-making and positive psychological characteristics that facilitate the growth and development of a person and enable the achievement of goals. While students are thinking about their survival, they should take a step beyond this view and pay attention to the consequences and effects on society. E-learning is considered an important issue for education and the factor of its survival, in this, paying attention to the mental health of students and using an effective solution for it is discussed. An office-like education must pay attention to all levels of education (in-person and out-of-person) properly. According to the results of the study, it is suggested that the Department of Education must create workshops with the title of e-learning and the importance of virtual space (by explaining the new global concepts and approaches to using virtual space in education). To strengthen the level of knowledge development in students. To increase the desired psychological outcomes, sufficient and suitable training courses should be held to familiarize teachers and students with the principles and basics of mental and physical health. Human considerations such as respondents' dishonesty and the interference of others' opinions, especially classmates, could be effective in people's responses to questionnaires. Restrictions in attracting the cooperation of some people with the researcher due to the spread of Corona regarding the distribution of questionnaires and the delay in returning several questionnaires were limiting factors of the research.