مجله دانشکده پزشکی دانشگاه علوم پزشکی تهران
سال هفتاد و ششم شماره 5 (پیاپی 209، امرداد 1397)

The cartilage is a connective tissue that, due to the strength of its extracellular matrix, allows the tissue to tolerate mechanical stress without undergoing permanent deformation. It is responsible for the support of soft tissues and due to its smooth surface and elasticity, gives the joints the ability to slip and bend. excessive weight, excessive activity, or trauma can all cause cartilage to injury. The injury can lead to swelling, pain and varying degrees of mobility loss. The process of repairing musculoskeletal (orthopedic) injuries has led to problems in the medical field, which can be attributed to the inherent weakness of adult cartilage tissue. Therefore, this necessitates research focused on the development of a new restructuring strategy by combining chondrocytes or stem cells with scaffolds and growth factors to address these problems. Correspondingly, the recent tissue engineering strategies strongly support the simultaneous use of stem cells, scaffolds and growth factors. It has also been observed that due to the relatively low proliferation of transplanted chondrocytes, new cartilage models construction have examined the use of adipose-derived stem cells. Mature adipose tissue is produced as an important source of multi-functional stem cells that can be easily separated from the stromal vascular fraction (SVF) by adipose liposuction digestion. The adipose-derived stem cells are easily accessible without any serious complications and have the power to differentiate into several cell lines, including chondrocytes as well as, they evidence self-renewal when trapped in gel scaffolds such as collagen. Also, recent studies demonstrate some of the mechanisms involved in the process of making cartilage of adipose-derived stem cells in vitro and their restorative ability in bio-engineered scaffolds in the presence of growth factors. In addition, the important role of non-encoding mRNA molecules (miRNAs) has been identified in the process of chondrogenic differentiation of adipose-derived stem cells. Furthermore, in several studies, the effect of several miRNAs has been confirmed on the regulation of the cartilage differentiation of the adipose-derived stem cells and has also been associated with effective results. In this article, we will present an overview of the advance in adipose-derived stem cells application in cartilage regeneration.

The natural killer group 2D (NKG2D) is a transmembrane protein and a member of the CD94/NKG2 family of C-type lectin-like receptors. NKG2D is encoded by the KLRK1 gene, which is located in the NK-gene complex (NKC) placed on chromosomes 6 and 12 in mice and humans, respectively. NKG2D forms a homodimer structure and binds through ectodomains with its related ligands. Each of its monomers consists of two β-sheets, two α-helices, and four disulfide bands and also contains a β-strand that distinguishes it from other C-type lectin-like receptors. NKG2D ligands are homologs of major histocompatibility complex (MHC) class I molecules in mice and humans. MHC class I chain-related protein A (MICA) and B (MICB) and human cytomegalovirus UL16-binding proteins (ULBP1-6) are recognized by the human NKG2D. In Natural Killer (NK) cells, NKG2D-mediated cytotoxicity can be elicited via two different systems by signaling from immunoreceptor tyrosine-based activation motifs in DAP12 or via a Syk-independent pathway activated by DAP10. Therefore, NKG2D is an activating immunoreceptor which was first recognized on NK cells but subsequently found on γδT cells, CD8 αβT cells, and macrophages. NKG2D-ligand diversity may facilitate the detection of the presence of a broad range of viruses and may provide protection against rapidly evolving cancers. NKG2D ligand recognition induces and/or improves immune responses to cancer cells. NK cells recognize a wide range of stressed cells. The activation of NKG2D receptor can lead to the lysis of the target cell and the production of various cytokines and chemokines depending on the nature of the stimulation as a result of NK and myeloid-mediated innate immunity and as well as T γδ and CD8 mediated-adaptive immune system. However, inappropriate expression of NKG2D ligands could cause autoimmune diseases in healthy cells, including rheumatoid arthritis, colitis, celiac disease, multiple sclerosis, alopecia areata, type 1 diabetes, and chronic obstructive pulmonary disease. Therefore, a precise understanding of the structure and function of NKG2D receptor and its interaction with various ligands may lead to the development of strategies to treat autoimmune diseases. Hence, the purpose of this review is to examine the detailed studies on the function of NKG2D receptor and their related ligands.

Recent evidence suggests that regular exercise training is effective in treating various aspects of cancer. Therefore, the purpose of this study was to determine the effect of 8 weeks of aerobic interval training on monocarboxylate transporter 1 (MCT1) protein and expression of p53 gene in tumor of colon cancer mice.
The present study was conducted experimentally from May to October 2014 at the Exercise Physiology Research Center of Baqiyatallah University of Medical Sciences, Tehran, Iran. Twenty BALB/c mice of age 3 weekly with a mean weight of 17.6±1.4 grams were selected and randomly divided into 4 groups: control (N=5), interval training (N=5), colon tumor (N=5) and interval training犉 tumor (N=5). The cancer was induced by subcutaneous injection of a carcinogenic azoxymethane (10 mg/kg) once a week for three weeks, and aerobic exercise was performed with rodent treadmill for 8 weeks and 5 days a week. Forty-eight hours after the last training session, the mice were cleared and colon removed. Measurement of MCT1 protein was performed by ELISA and commercial kits (ZellBio, Germany). Real-time polymerase chain reaction (PCR) was used to determine the relative expression of p53 gene. Data were analyzed by Kruskal-Wallis test and Mann-Whitney U tests.
The results showed a significant increase in MCT1 protein (P The findings of the study showed that aerobic interval training reduced the protein content of MCT1 and increased the expression of p53 gene (as a tumor inhibitor) in the tumor of colon cancer mice. These factors are portions of the mechanisms involved in cancer cell metabolism by which aerobic interval training shows part of its therapeutic effect in colon cancer.

Immunoglobulins are a group of proteins have important role in defense against microorganisms. Human immunoglobulins are divided into five classes: IgA, IgM, IgD, IgE and IgG. Immunoglobulin G (IgG) is the highest abundant antibody in serum and extravascular fluids. The extent of serum IgG is related to severity of several diseases such as infections, so IgG has great diagnostic worth. Accurate measurement of IgG, needs exact and sensitive diagnostic instruments such as human IgG- specific monoclonal antibodies. Moreover, targeting of IgG has been useful in treatment of a number of diseases. According to experimental studies the Fc region of human IgG is highly immunogenic. Immunoinformatic is a division of immunology uses the computational biology for more precise diagnosis of diseases. The aim of this study was determination of conformational epitopes in the fragment of crystallizable (Fc) fragment of human IgG by immunoinformatic.
The amino acid residues and third structure of reference human IgG were found in protein data bank (PDB). Second IgG structure was defined by Phyre2 software (http://www.sbg.bio.ic.ac.uk/~phyre2/). Conformational epitopes of the Fc fragment in human IgG were specified by ElliPro (http://tools.iedb.org/ellipro/) and DiscoTope (http://www.cbs.dtu.dk/services/DiscoTope) softwares.
In this study two conformational epitopes (one in constant heavy chain 2 (CH2) domain and another one common between CH2 and CH3 domains) sited in Fc fragment of human IgG were determined by ElliPro software. Also, two conformational epitopes (Both common between CH2 and CH3 domains) located to Fc fragment of human IgG were determined by DiscoTope software.
In this study a number of conformational epitopes located to Fc fragment of human IgG were determined by two immunoinformatic softwares (ElliPro and DiscoTope). The epitopes recognized by both softwares were situated in CH2, CH3 or both of these domains in the human IgG heavy chain. Thus, it seems that CH2 and CH3 domains of Fc region in human IgG are highly immunogenic. Moreover, ElliPro and DiscoTope softwares can be useful tools for identification of epitopes located to Fc fragment of human IgG.

Accurate detection of deep sleep (Due to the low frequency of the brain signal in this part of sleep, it is also called slow-wave sleep) from awakening increases the sleep staging accuracy as an important factor in medicine. Depending on the time and cost of manually determining the depth of sleep, we can automatically determine the depth of sleep by electroencephalogram (EEG) signal processing. In this paper a new EEG bispectrum based feature is introduced for deep sleep discrimination.
This cross-sectional study was conducted at Isfahan University of Medical Sciences, Faculty of Advanced Technologies in Medicine, from February to October 2017. In this study a gray scale image was made of electroencephalogram bispectrum amounts and converted to binary image with Otsu’s Thresholding. Then the ratio of white bits in the above of the secondary diagonal to white bits in the down of secondary diagonal (low to high frequencies bispectrum rate) is extracted as a new feature. This feature is an effective method for detecting deep sleep from awakening.
One of the important methods in biomedical signal processing is the use of the power spectrum or signal energy. In sleep studies, energy-related features have also been used to determine the depth of sleep. Low to high frequencies bispectrum rate is able to separate deep sleep from awakening by accuracy of 99.50 percent, while energy-based features as one of the most important approaches to sleep classification do not have this ability.
In this study we show that “Low to high frequencies bispectrum rate" feature has this capability to use in sleep staging. It is not used in previous works. The accuracy obtained in deep sleep separation from the awakening with the introduced feature (99.50 percent) is greater than the accuracy obtained by all the energy-based features (The simultaneous use of the 6 bands energy leads to 99.42 percent accuracy). This feature indicates the ratio of the phase coupling at low frequencies to high frequencies and can be used in all cases where the bispectrum is used (such as determining the depth of anesthesia).

Cancer of the endometrium is the most common gynecologic malignancy in western and industrial countries, and is the second most common in developing countries, therefore it is of special importance. Adenocarcinoma of the endometrium is the most common type of uterine cancer. The prevalence of endometrial cancer in young women under the age of 40 in western country is very low and about 5 percent. The aim of this study was to determine the prevalence of endometrial cancer at age ≤40 years in our center during 4 years.
In a cross-sectional study, all medical records of patients with endometrial cancer in Ghaem University Hospital, Mashhad, Iran was reviewed to identify women A total of 119 patients with endometrial cancer that was admitted in our genecology oncology center were evaluated. 19 patients (15.9%) were younger than 40 years old. 16 cases (84.2%) with endometrial adenocarcinoma and 3 (15.7%) had endometrial stromal sarcoma. The youngest patient was 27 years old and the oldest was 39 years. Seven patients (8/36%) had infertility and we don’t know about fertility condition in 3, because they were single. 12 cases (63%) were overweight (BMI≥35) and 6 cases (5/31%) had polycystic ovarian disease (PCOD). In 2 patients, there was concomitant ovarian and endometrial cancer. Histology report of both ovaries was endometrioid and both patients were overweight. Obesity, poly cystic ovary syndrome (PCOD) and Infertility were the most important risk factors for endometrial cancer in young patients.
The prevalence of endometrial cancer in young women under the age of 40 in our country is so higher than the statistics provided in industrial countries.

Some studies show that frozen shoulder is due to the pathologic changes in the muscles around the shoulder. Measurement of the ultrasonic thickness of a muscle is a method for measuring the muscle changes. There is no study about the reliability of measurement of the muscle’s ultrasonic thickness around the shoulder in patients with frozen shoulder. The present study aims to investigate the intra-rater reliability of the ultrasonic thickness measurement of the supraspinatus, deltoid and upper trapezius muscles in women with frozen shoulder and healthy women.
This study was carried out during 4 months (June to October 2017). Twenty women consisted of 10 patients with frozen shoulder (mean age: 51.6±9.41 years) and 10 healthy subjects (mean age: 35.5±8.22 years) participated in this study. The patients from some clinics and hospitals in Tehran, and healthy subjects consisted of some personals and students in the School of Rehabilitation of Shahid Beheshti university of Medical Sciences participated in the present study. Measurements of ultrasonic thickness of the upper trapezius, supraspinatus and deltoid muscles in rest position carried out by the same rater two times in 48 hours. Ultrasonography instrument with linear probe (frequency: 7.5 MHz) were used for measurement of muscle thickness in millimeter.
Reliability of the ultrasonic measurements of the muscle thickness in patients and healthy subjects was respectively as follow: The upper trapezius muscle (0.81, 0.81), the supraspinatus muscle (0.90, 0.92) and the middle deltoid muscle (0.93, 0.96). The reliability of the ultrasonic measurements of the muscle thickness for the upper trapezius muscle and the supraspinatus muscle was higher in healthy subjects compared to the patients with frozen shoulder. The reliability of the ultrasonic measurements of the middle deltoid thickness for the patients and healthy subjects was similar.
It seems that ultrasonography is a reliable method for measuring the thickness of the muscles around the shoulder in patients with frozen shoulder and healthy subjects.

With aging, muscles strength decrease. Balance disorder is one of the common aging problems which can cause falls and serious injuries. The purpose of this study was to present a model along with the determinants of balance status in the elderly.
This cross-sectional study is part of a cohort study, "investigation of the health status of elderly in Amirkola City", which was performed on 1616 old people aged≥ 60 years, (response rate 72 %). The baseline data of this study were collected in the Center for Social Determinants of Health (SDH) Research Centre of the Babol University of Medical Sciences during March 2011 to July 2012. We considered the age, sex, physical activity, quadriceps muscle strength, daily activity, serum level of vitamin D, BMI, number of comorbidities and orthostatic hypotension as independent variables. Using the results of Berg balance test, the balance status of participants (as dependent variable) was categorized into two groups: score between 41-56 as normal (low risk of fall) and score The mean and standard deviation of participant's age was 69.37±7.6 years, 54.7% of them were men and 7.5% of them had balance disorder. The odds ratio of medium or high falls in women to men, the number of comorbidities, having strong quadriceps to weak muscles, seniors aged 80 years and over, to 60-69, seniors with high physical activity to low physical activity, daily activities were (OR=2.1, 95%CI: 1.0-4.1), (OR=1.7, 95%CI: 1.0-2.9), (OR=0.05, 95%CI: 0.0-0.4), (OR=5.0, 95%CI: 2.3-10.6), (OR=0.3, 95%CI: 0.1-0.6), (OR=14.4, 95%CI: 3.4-60.4), respectively and statistically significant. The odds ratio of fall for vitamin D, orthostatic blood pressure and BMI variables did not show any statistically significant differences. The results of the analysis showed that the balance in all age groups in men was better than women.
Weak quadriceps, aging, being a woman and having comorbidities are the most important risk factors of balance disorder in the elderly.

Hospital accreditation is a systematic external evaluation of a hospital’s structures, processes and results by an independent professional accreditation body using pre-established optimum standards. This study aimed to evaluate the hospital accreditation system.
This descriptive and cross-sectional study was carried out between November 2015 and February 2016 using a questionnaire covering accreditation standards, methods, surveyors, implementation and effects. The study population consisted of 161 hospital managers in Tehran province, Iran. Overall 87 hospital managers were surveyed through stratified random sampling.
The mean score of managers’ satisfaction of hospital accreditation system was 2.93 out of 5 score. About 16 percent of managers were satisfied with the hospital accreditation system. Hospital managers were most satisfied with accreditation effects (3.14) and least satisfied with accreditation standards (2.54). Hospital managers were satisfied with surveyors’ attitude, number of survey days and the number of surveyors in the accreditation team. They were least satisfied with the lack of consistency among surveyors, lack of transparency of standards, too many standards and low competency of surveyors. Hospital managers mostly believed that accreditation should be done by Ministry of Health, compulsory, and every two years. About 97 percent of managers agreed that self-assessment is necessary and beneficial prior to the accreditation survey.
Accreditation was moderately successful in Tehran hospitals. Accreditation had the most effect on improving patient safety and meeting patient's rights and least effect on improving employee's job satisfaction and involving doctors in quality improvement. Strengthening Iran hospital accreditation system, training managers and employees on implementing standards, and providing necessary resources make it possible to achieve accreditation goals.

Association of Addison's disease with connective tissue diseases such as scleroderma and Sjogren have been rarely reported. Anti-centromere antibody (ACA) has been associated with exocrine gland dysfunction in anti-Ro, anti-La negative Sjogren’s syndrome and may be one of the causes of xerostomia in community. The purpose of this article was to introduce a rare case of scleroderma-Sjogren intermediate phenotype with positive anti-centromere antibody in a known case of Addison’s disease admitted for dental caries and xerostomia.
A 29-year-old woman with Addison’s disease referred to a dental clinic due to recurrent dental caries. Addison’s disease was confirmed by low basal serum cortisol level and unresponsive serum cortisol level to adrenocorticotropin hormone (rapid ACTH stimulation test). Signs of xerostomia, xerophthalmia, Raynaud’s phenomenon, gastro-esophageal reflux, masked face, osteoporosis, positive anti-centromere antibody, negative anti-Ro and anti-La antibodies and failure to match the pathology of the minor salivary gland of lip with Sjogren's disease were found. The diagnosis of scleroderma-Sjogren intermediate phenotype was raised with considering some of the symptoms of scleroderma and Sjogren and not the exact classification criteria for each of these two diseases. Hydroxychloroquine, fluoride and Biotene® mouthwash (Laclede, Inc., CA, USA) (oral moisturizing saliva), chewing gum containing xylitol plus artificial tear droplet was prescribed. Drinking plenty of fluids was recommended. Due to gastroesophageal reflux and osteoporosis, Pantoprazole and CinnoPar® (Cinnagen, Iran) (parathyroid hormone analogue) plus calcium and vitamin D supplements was administered. Regarding adrenal insufficiency, Prednisolone and Fludrocortisone were continued.
For evaluation of recurrent dental caries, especially in patients with autoimmune disease, anti-centromere antibody may be useful to identify the cause of dry mouth, as well as early detection of limited scleroderma or scleroderma-Sjogren intermediate phenotype.