shahin akhondzadeh

AbstractDuring wars, hospitals, medical staff, and civilians are protected by International Humanitarian Law (IHL). However, this importance is not observed in some instances. We examined the killing of medical staff and attacks on medical facilities during the Gaza war. In this scoping review, we gathered data from primary and secondary sources, such as newspapers, peer-reviewed journals, open-source platforms, social networks, and Non-Governmental Organization (NGO) websites from October 27, 2023 to May 21, 2024. Additionally, we collected data from some organizations, such as Physicians for Human Rights (PHR), the World Health Organization (WHO), Palestine Ministry of Health, World Bank, and United Nations Children’s Fund (UNICEF).According to different reports, between 400 to 800 incidents of violence against the healthcare services were documented in Gaza from the start of the war on October 27, 2023 until May 21, 2024. These incidents include obstruction of access to medical facilities, attack on ambulances, damage to hospital buildings, and targeting of medical staff and healthcare volunteers. Although the WHO issued warnings to stop the violence against medical staff and health facilities, these efforts were unsuccessful.The results revealed that unprecedented tragedies are occurring in Gaza, where medical facilities and staff are being targeted and killed. However, the response of international organizations appears to be passive and not appropriate to the extent of the war crimes. Moving forward, the international community should consider developing more effective solutions to address criminal behavior within the healthcare sector.

Age-related macular degeneration (ARMD) leads to impaired vision and potential blindness. Globally, it accounts for approximately 9% of vision loss cases, and a projected 288 million individuals will be affected by 2040. Current treatments have limitations such as variable effectiveness, high costs, and potential side effects. Additionally, atrophic ARMD management remains challenging. As saffron has shown promising neuroprotective and antioxidant effects by potentially delaying disease progression, this study aims to review the mechanistic, pre-clinical, and clinical evidence of the effects, safety, and tolerability of saffron in ARMD treatment.

The Scale for the Assessment of Narrative Review Articles was applied in this narrative review. To find relevant literature, the syntax “(saffron OR crocus) AND (retin* OR “geographic atrophy” OR “choroidal neovascular*” OR “macular degeneration”)” was searched in PubMed/MEDLINE. Pre-clinical and clinical original investigations of the effects of saffron in ARMD along with the eligible studies cited in their reference lists were identified and included.

Saffron and its active compounds, crocin and crocetin, have shown promising results in improving visual function and delaying ARMD progression. Several clinical studies have found that daily supplementation with 20–50 mg of saffron or 5–15 mg of crocin for 3–12 months significantly improved best-corrected visual acuity, contrast sensitivity, and retinal function as measured by electroretinogram and microperimetry, with benefits observed in both dry and wet forms of ARMD. The effects were independent of genetic risk factors and maintained during the follow-up periods, suggesting the potential role of saffron as a long-term treatment option. Saffron reduces ARMD progression via anti-angiogenic, neuroprotective, and antioxidant mechanisms. Moreover, saffron is safe and well tolerated.

Although further research is needed to confirm long-term safety and efficacy, current evidence supports the use of saffron or crocin supplements as a safe and tolerable adjunct therapy for ARMD management.

Exactly 30 years ago, when I graduated from the Institute of Neuroscience in the Glasgow School of Medicine and returned to Iran, I ended up in the Department of Psychiatry at Tehran University of Medical Sciences, Rouzbeh Hospital. To be hones t, in those days after the imposed war, there were no funds for research in Iran, and there was no national plan or desire to develop research. Unfortunately, there was no internet at that time, and due to Iran’s non-subscription of scientific journals, these paper journals for universities were not sent. The nature of the PhD course in the UK is not at all reading the books. In the UK, a good graduate in the PhD program becomes the owner of a school of thought so that he/she can design a plan for the future. I remember in one of the lectures on Tuesday afternoon at the University of Glasgow, a famous neuroscientis t, the title of his lecture was: How a neuroscientist can do research in the North Pole with the lens of his/her glasses. With this attitude, I came to the idea that the research path for me in Iran is drug repositioning in psychiatry (1). Of course, this terminology did not exis t at that time, and in that period, it was mos tly off-label drugs. During these three decades, inspired by neuroscience, I worked on the use of old drugs in psychiatry (2-7). Almost all of these projects were theses of psychiatry residents or fellows. Now that 30 years have passed, when I think again, I come to the conclusion that it was a good research line for a neuroscientist in the psychiatry department of Tehran University of Medical Sciences. In these 30 years, this has actually been a bridge between basic and clinical sciences. But remember that this is a low-cost way to do research in a developing country and in order to reach the edges of knowledge, there should be increased research funds and a specific 5-year plan for Iran’s scientific development. After the election of the president, Prof. Pezeshkian, to the presidency and the appointment of Prof. Zafarghandi to the Ministry of Health and Medical Education, researchers of Iran hope that we will once again return to the road of real development for the scientific development of Iran.

As the editor of the Journal of Case Report in Clinical Practice and someone who has been teaching scientific writing in Iran and the Middle East for many years, I always emphasize two points regarding the case report. 1. Generally, your case report should be rare and not commonly seen. In the history of the last two centuries, which war do you think would kill more than 40,000 defenseless people in a few months with the weapons provided by the three member countries of the Security Council, and create more than two million refugees [1-4]? All the people of the West, including academics, protest, but with the efforts of the same three members of the Security Council, the United States, United Kingdom, and France, not a single resolution against the Zionist regime is passed. In my opinion, as the editor of the Journal, this is definitely a case report. 2. The purpose of writing a case report is for the medical doctor to do the best work with his/her practice in medicine, which in the case of killing the people of Gaza and documenting it as a tragic event unique in history, will probably cause the free people of the world in the future, to elect rulers who believe in human rights and respect for human life. Anyway, what is important is that despite the support and at best, indifference of the Western countries, this killing has offended the conscience of the free people of the West so much that after the Vietnam war, almost all the academics of the American universities have protested and this protest movement of the universities America has developed to other Western universities. The cruel killing of infants who needed NICU or were in NICU and died due to lack of electricity and oxygen will be written in the history of modern medicine [5, 6].

 Current therapies for depression are moderately effective, as response and remission rates were reported at 50% and 15-40%, following the first trial with current medications, respectively, and electroconvulsive therapy is not beneficial for more than half of the resistant patients. Recent research suggests that medication with glutamatergic modulatory properties may have antidepressant effects and would be of benefit to refractory patients. This study aims to review the efficacy of these medications in the treatment of unipolar depression. Ketamine, as the leading drug acting through the glutamatergic system, appears to be effective in treating depression IV and orally and in combination with electroconvulsive therapy. There is also clinical evidence of the promising effects of amantadine and lanicemine. Supplements and herbs such as L-carnosine, Crocus sativus (saffron), and Cinnamomum tamala, which were reported to be effective in randomized controlled trials on patients with depression, may act through this system as an antidepressant. Taken together, glutamate receptor modulators are alternative drugs for patients with resistant depression. Further high-quality clinical studies are recommended.

After the imposed war, Iran’s ranking in number of publications and citations, especially compared to Iran’s traditional competitor, Turkey, was not acceptable. Several approaches were used to surpass Turkey beginning in 2010 based on Scopus data and again in 2017 based on Clarivate Analytics data (1-3) (Figure 1).1. Increasing share of research funding from the GDP.2. Establishing and equipping research canters.  3. Revising policies to promote academic staff and successfully graduating students.4. Increasing postgraduate education programs.5. Awarding scholarships to students to study in postgraduate programs abroad.6. Increasing number of Iranian scientific journals indexed in Clarivate Analytics, Scopus and PubMed.7. Development of international relations.8. Meritocracy in scientific environments.9. Increasing salaries of academic staff members to accommodate for inflation.10. Most importantly, encouraging hope for the future and attracting young and elite professionals to Iran.Unfortunately, since 2021, due to economic problems in Iran and decrease in share of research funds from the GDP, as well as changes in the above-mentioned 10 approaches, we first lost our position in the Clarivate Analytics and then in Scopus. Turkey has surpassed Iran, and Saudi Arabia is developing scientifically due to proper investments. If we want to return to path of development, we must first invest in basic sciences. With our average research grants for basic science projects, we can no longer compete at any level in the world. Let’s think of a solution to attract young and elite graduates. There is no doubt that increasing income of academic staff members, especially in basic sciences, will help improve scientific development of Iran. For development of research in clinical fields, other solutions are needed, such as restarting MD-PhD programs and recruiting basic science faculty members in clinical departments. Comprehensive research training in the residency curriculum, recruitment of academic staff with research experience to clinical departments, development of biobanks, disease registry studies and cohort studies are just some of the steps we can initiate.

Pancreatic cancer commonly refers to Pancreatic Ductal Adenocarcinoma (PDAC) which accounts for more than 90% of pancreatic cancers (1). The substantial burden of disease is characterized by the approximate deaths of as many as cases annually. PDAC as the seventh leading cause of cancer-induced mortalities globally, has been a focal point of research in the field of oncology (2).Despite the vast research and significant effort devoted to the treatment of PDAC, the 5-year survival rate for this cancer remained less than 5%. This scant survival rate is a consequence of late-onset diagnosis, accelerated tumor growth, and limited extant treatments. Hence, innovative strategies, such as immunotherapy, seek to enhance antitumor immune reactions, offering a more precise and targeted therapeutic alternative (1).Immunotherapy is categorically segmented into four primary subtypes: vaccines, cellular therapies, cytokines, and antibodies, with Immune Checkpoint Inhibitors (ICIs) falling under the latter classification (3).Cancer vaccines stimulate immune responses by leveraging tumor-associated antigens to activate cytotoxic T-lymphocytes. These antigens can be sourced from whole-cell tumor lysates, recombinant tumor peptides, or recombinant viruses (1). Regarding vaccines, messenger RNA (mRNA) vaccines have been more promising than conventional vaccines, which present various challenges, for a personalized therapeutic approach in pancreatic cancer. These vaccines utilize the genetic profile of an individual’s tumors, particularly those with mutant Kras, and custom proteins can be encoded (3). KRAS as a proto-oncogene has been recognized as mutated among 90% of patients diagnosed with PDAC, making it a valid target. They enhance antitumor immunity against oncogenic KRAS by presenting oncogenic KRAS neoantigens to major histocompatibility complex molecules, leading to the generation of cancer-specific memory T cells with long-term efficacy. In terms of other vaccines that are under investigation regarding their efficacy in PDAC, telomerase vaccines, gastrin vaccines, survivin-targeting vaccines, heat-shock protein peptide complex-based vaccines, MUC-1 targeting vaccines, listeria-based vaccines, dendritic cell-based vaccines, Granulocyte-Macrophage Colony-Stimulating Factor (GMCSF)-allogeneic pancreatic tumor cells (GVAX) vaccines, and Hyper-Acute-Pancreas algenpantucel-L (HAPa), Mucin-1 (MUC-1) vaccines can be mentioned (4–6).Adoptive cell therapy is a rapidly growing technology consisting of NK cells or T cells that are either allogeneic or autologous. and have been genetically modified to target specific proteins using chimeric antigen receptors and T-cell receptors. These engineered cells are designed to recognize a peptide/MHC complex to effectively eliminate cancer cells. Numerous Chimeric Antigen Receptor (CAR) T-cell therapies have been approved for the treatment of different hematological malignancies. In PDAC, mesothelin CAR-T therapy has shown promise in preclinical mouse models by extending survival. However, the translation of this strategy to clinical settings for solid tumors faces various obstacles. To address these challenges, the development of next-generation CAR-T cells is underway to enhance the effectiveness of this therapy (3,7).Cytokine therapies, including the use of Interleukin-2 (IL-2) and Interferon alpha (IFN-α), have been utilized as an early form of immunotherapy in the management of malignant conditions, establishing them as foundational components of this treatment approach. Cytokines with immune stimulatory properties, including IL-2, IL-15, GM-CSF, and IFN-α, have been incorporated as adjunctive elements in comprehensive immunotherapy strategies for PDAC. While monotherapy with cytokines showed promise during the peri-operative period, no recent studies have been published on this subject in the last ten years (3,8).ICIs are monoclonal antibodies that target specific extracellular proteins expressed by tumor cells or tumor-associated lymphocytes, leading to the suppression of the body’s immune response against the cancer (1). To address some of the main ICIs, Anti-PD-1/Anti-PD-L1, Anti-CTLA-4, Anti-TIM-3, Anti-TIGIT, and Anti-LAG-3 can be mentioned. Anti-PD-1/Anti-PD-L1 blocks the PD-1 pathway in which PD-1 ligation induces self-tolerance by preventing the activation of T cells as well as their proliferation. In PDAC, despite other solid tumors, the efficacy of Anti-PD-1/Anti-PD-L1 as monotherapy was not as promising as its effectiveness in combination with chemotherapy. The inhibitory CTLA-4 receptor on T cells competes with the co-stimulatory receptor CD28 for binding to the CD80 and CD86 ligands on antigen-presenting cells (APCs). CTLA-4 has a higher affinity for these ligands. Lower levels of CTLA-4 and higher expression of CD80 in PDAC are associated with increased survival rates. Binding of CTLA-4 primarily inhibits the activation of naïve T cells in lymphoid organs, but may also hinder the direct anti-tumor activity of T cells in the effector phase, potentially by reducing the presence of suppressive regulatory T cells. Based on a previous study, the co-administration of GVAX with anti-CTLA-4 appears to stimulate a T cell-mediated immune reaction and could potentially enhance the survival rate of patients with advanced PDAC. Numerous clinical trials are currently underway to assess the efficacy of the combination of anti-CTLA-4 therapy with other immunotherapeutic agents and/or radiotherapy in the treatment of PDAC (8). Both PD-L1 and CTLA-4 are often overexpressed in a subgroup of PDAC and are associated with poorer survival outcomes, making them potential targets for therapeutic intervention (1).In conclusion, despite the aforementioned substantial investigations regarding therapeutic approaches for PDAC, treatment of this highly impacting disease is hampered by so many obstacles. Further research is necessary to overcome the remission-disrupting factors such as immunity evasions, altered tumor microenvironment, immunosuppressive activities, etc.Conflict of InterestThe authors had no competing interests.

Postpartum depression (PPD) impairs mother-infant interaction and has negative effects on the child’s emotional, behavioral, and cognitive skills. There is considerable evidence to suggest that inflammation plays a role in the pathogenesis of depression. Controlled trials indicate that celecoxib has antidepressant effects in patients with major depressive disorder. A 34-year-old woman with mild to moderate PPD received a celecoxib capsule twice a day. This treatment has not been reported in previous studies and is novel in clinical practice. The patient was assessed using the Hamilton Depression Rating Scale (HDRS). Moreover, levels of brain-derived neurotrophic factor (BDNF) and inflammatory cytokines were measured at baseline and at the end of celecoxib therapy. This case suggests that celecoxib can improve depressive symptoms in patients with mild to moderate PPD. No adverse effects occurred during follow-up.

Chemical warfare agents are chemical, usually extremely toxic weapons of mass destruction, which, although they have been used for centuries, have not yet been fully and comprehensively described. Nowadays they are classified as nerve agents, blistering agents, blood agents, choking agents, tear gases, psychomimetic agents, and toxins. The mass production, and consequently, widespread deployment of these agents has been documented since the 19th century after the expansion of industrial chemistry. Since then, several large-scale attacks using them have been reported (1). Chemical weapons can be viewed from various aspects, including environmental, legal, ethical, medical, etc.; insufficient attention has been paid to its psychiatric aspect and considerations. The psychiatric aspect of chemical attacks has been neglected, or at least not sufficiently addressed. Indeed, if medical preparation for chemical attacks were to be practiced, it would probably not involve psychiatrists or consider sufficient psychiatric assistance. Meanwhile, mood, cognitive, and behavioral disorders are common due to trauma and chemical agents, both short-term and long-term. Psychiatrists have considerable multifaceted roles and duties in such a crisis, including helping to differentiate somatization and anxiety in patients referred to the emergency room, treating short-term and long-term psychiatric disorders, crisis management intervention to health workers, and providing recommendations and guidance to decision-makers (2). Several effects of chemicals on mental health in people exposed to them in war or research have been reported, including intellectual impairment, problems in concentration, anxiety disorders, sleep disorders, psychomotor retardation, depression, social withdrawal, antisocial thoughts, fatigue, amnesia, restlessness, and irritability (2-4). Psychiatric disorders caused by chemical weapons can afflict people long after the attack so that a study showed that psychiatric and psychological findings, including somatization, obsessive-compulsive disorder, depression, anxiety, and hostility, were higher in the population exposed to sulfur mustard and horror and fears, even up to 20 years after exposure (4). Sulfur mustard is a blister agent that still has no effective antidote. The city of Sardasht, West Azerbaijan, Iran was the victim of a chemical attack on June 28, 1987, during the invasion of Iran. On that sunset, many people were massacred, and since then, many people have suffered from the consequences, the psychiatric side of which is only a small part.

Depression is the most prevalent and debilitating disease with great impact on societies. Evidence suggests Brain-Derived Neurotrophic Factor (BDNF) plays an important role in pathophysiology of depression. Depression is associated with altered synaptic plasticity and neurogenesis. BDNF is the main regulatory protein that affects neuronal plasticity in the hippocampus. A wealth of evidence shows decreased levels of BDNF in depressed patients. Important literature demonstrated that BDNF-TrkB signaling plays a key role in therapeutic action of antidepressants. Numerous studies have reported antidepressant effects on serum/plasma levels of BDNF and neuroplasticity which may be related to improvement of depressive symptoms. Most of the evidence suggested increased levels of BDNF after antidepressant treatment. This review will summarize recent findings on the association between BDNF, neuroplasticity, and antidepressant response in depression. Also, we will review recent studies that evaluate the association between postpartum depression as a subtype of depression and BDNF levels in postpartum women.

More than three years after the all-society-inclusive outbreak of coronavirus disease 2019 (COVID-19) that quickly turned into a pandemic, situations have considerably improved, and public concerns have subsided. Nevertheless, about 800 million confirmed cases of COVID-19 and about seven million deaths have been reported to the World Health Organization (WHO) so far, and this pandemic is still far from over (1). However, now public awareness has increased, the virus is more predictable, communities are better prepared, the crisis has been contained, and in short, the disease and its subsequent concerns have been brought under control. But what led to this [imperfect] success? Certainly, this was beyond the power of one person, country, and discipline. It was a collaboration, a comprehensive collaboration of researchers and experts in basic and clinical sciences and medical specialties worldwide. The interdisciplinary approach has influenced the sciences more and more over time, aiming to overcome problems beyond the ability of a single science (2). This growing trend, which has rapidly been spreading over the last decades, is the solution to overcome crises like the COVID-19 pandemic. Interdisciplinary approaches in this era led to disease management, vaccine development, and better societal decisions. Basic science, with its curiosity-driven focus on understanding phenomena, served as a bridge connecting the laboratory to the clinic and the community and society to reach applied sciences, although it seems insufficient for the desired technological and medical applications. Indeed, basic sciences provided the necessary knowledge and understanding for further studies and applications. Current advances in clinical science are rooted in basic science research, so that without a background in basic research, applied science perspectives are incomplete and unstable (3). Bioinformatics and machine learning were two of the most important fields used to assess the situation, develop strategies, and decide on the appropriate response. In addition, physicists, chemists, and engineers developed protective and safety equipment, and biological scientists’ knowledge and science-centric research led to the development of diagnostic tools and vaccines (4,5). The production of effective vaccines, of which more than 13 billion doses have been injected worldwide, is one of the most prominent results of medical biotechnology collaborations (1,5). Collaboration and integration of science within medical specialties also caused beneficial results; the nature of COVID-19 with the involvement of different organs of the human body, including the respiratory system, the cardiovascular system, the digestive system, the nervous system, etc. (6), provoked and accelerated interdisciplinary collaborations. Interdisciplinary research clarified the mechanism of the disease being a multi-organ aggressor and proposed possible treatments, including anti-infective agents, organ-specific therapies, and complementary therapies to improve nutritional, inflammatory, and metabolic status (4,6,7). In the COVID-19 era, social scientists have modified social restrictions by considering the psychological and psychiatric effects, economists have explained resilience policies, and policymakers made their decisions by considering medical, economic, and social components (4,5). Although it may seem that the medical sciences have received most of the credit and prestige for overcoming the COVID-19 crisis, the role of other fields toward reducing their harms (3) and collaborating in this relative success is quite evident (8-10). It can be said that collaborations with an interdisciplinary approach in the pandemic era have led to pandemic collaborations and have produced an evidence-based, multidisciplinary science that can be used in crises.

Psychiatric disorders are a major health problem in individual and societal aspects, due to their considerable prevalence and burden and treatment issues (1-3). Estimates indicated that about 792 million people, equivalent to 10.7% of the world population, had mental health disorders in 2017 (4). In 2019, mental disorders were among the top ten causes of burden worldwide, as before, and the Disability-Adjusted Life-Years (DALYs) attributed to them was 418 million (16% of global DALYs) (5,6). The associated economic costs have been estimated at $4.7 trillion – even up to $10 trillion (6). These statistics are related to disorders whose medications and alternative treatments have incomplete efficacy and debilitating side effects that result in limitations in both therapy and compliance so that only one-third of patients with major psychiatric disorders achieve complete and stable symptom remission (7). These data make access to a predictive tool of treatment response crucial and desirable. The uniqueness of each person along with the heterogeneity of diseases is the basis of the concept of personalized medicine, in which personalized psychiatry pursues the trends (8,9). Genetics is responsible for 20 to 95% of the variation in medication disposition and pharmacodynamics in the central nervous system (7). Each patient’s unique phenotype, comorbidities, dietary habits, and medication habits can potentially cause changes in the pharmacokinetics and pharmacodynamics of medications. Personalized psychiatry was presented to provide an individually adapted approach for prevention, diagnosis, treatment, follow-up, and rehabilitation. Parts of these depend on developing pharmacogenomics and pharmacogenetics (8,9). The study of the genetic causes of variation among patients in response to medications and the study of the simultaneous effects of multiple mutations in the genome determining the response to medications are called pharmacogenetic and pharmacogenomic, respectively. However, there is no consensus on the difference between the two, and in practice, they overlap (9). Personalized psychiatry that relates the response to medication to its pharmacokinetic and pharmacodynamic changes as a result of the patient’s genotype, in principle, indicates the application of pharmacogenetics in treatment. The primary focus of the pharmacogenetic-psychiatry link has been the YP2D6, CYP2C19, and CYP3A4 enzymes in the liver because of their responsibility for the metabolism of most antidepressants and antipsychotics (7,8). The translation of pharmacogenetic evidence into clinical practice is an important endeavor that began a few years ago. An example of the application of pharmacogenetic information to guide pharmacotherapy in psychiatry is using genetic information on CYP2D6, CYP2C19, CYP1A2, SLC6A4, and HTR2A for dosing, which increased the number of responders to antidepressants in a pioneering study. Overall, pharmacogenetically supported depression improvement was reported to be 1.71 times better than usual. Similarly for antipsychotics, the association of CYP2D6 genotype and risperidone in order to individualize dosing has been shown in a large-scale study. This evidence has grown and matured to the point where guidelines for implementation have been provided. Its psychiatry examples are the Dutch Pharmacogenetics Working Group recommendations regarding CYP2D6 and CYP2C19 genotypes for antidepressants and antipsychotics and the guidance for using genetic information in pharmacotherapy for psychiatry published by The Clinical Pharmacogenetic Implementation Consortium (7,10). In the application of pharmacogenetics in personalized medicine, attention to cost-effectiveness and ethical issues is essential. It seems that having a genetic passport providing polymorphic genes involved in common medications in which dosing is important, after full maturity and reaching the certainty of the evidence, is cost-effective. In other words, in this case, an advantage of integrating pharmacogenetics and psychiatry would be to reduce costs (7). In regard to ethical issues, the guidelines and instructions should be complied in a way so that ethical obstacles such as privacy and confidentiality and knowledge gap and informed consent are overcome, a balance between social and individual interests is established, and ethical decisions are also personalized (11,12). In conclusion, beneficial and adverse effects are intrinsic properties of medications, and pharmacogenetics can increase the possibilities of improving effectiveness and reducing risk. As a result, although the risk-benefit ratio cannot be guaranteed in a patient, it improves in the population. Moreover, determining the patient’s genotype may reduce the time needed to identify the correct medication and its dosage and minimize exposure to ineffective medications. Although the clinical applications of pharmacogenetics are certain, the use of all currently proposed genes is not consensus. In the future, pharmacogenetics can be extended to other genes, encoding enzymes, transporters, receptors, and other downstream molecules. Keywords Behavioral science, Cost effectiveness, Ethical issue, Genetics, Mental disorder, Personalized medicine, Pharmacogenomics, Precision medicine Acknowledgements This paper did not receive any specific grant from public, commercial, or not-for-profit funding agencies. Conflict of Interest The authors had no competing interests.