Prominent genetic variants and epigenetic changes in post-traumatic stress disorder among combat veterans.

Post-traumatic stress disorder (PTSD) is one of the most widespread and disabling psychiatric disorders among combat veterans. Substantial interindividual variability in susceptibility to PTSD suggests the presence of different risk factors for this disorder. Twin and family studies confirm genetic factors as important risk factors for PTSD. In addition to genetic factors, epigenetic factors, especially DNA methylation, can be considered as a potential mechanism in changing the risk of PTSD. So far, many genetic and epigenetic association studies have been conducted in relation to PTSD. In genetic studies, many single nucleotide polymorphisms have been identified as PTSD risk factors. Meanwhile, the variations in catecholamines-related genes, serotonin transporter and receptors, brain-derived neurotrophic factor, inflammatory factors, and apolipoprotein E are the most prominent candidates. CpG methylation in the upstream regions of many genes is also considered a PTSD risk factor. Accurate identification of genetic and epigenetic changes associated with PTSD can lead to the presentation of suitable biomarkers for susceptible individuals to this disorder. This study aimed to delineate prominent genetic variations and epigenetic changes associated with post-traumatic stress disorder in military veterans who have experienced combat, focusing on genetic and epigenetic association studies.

Developing and validating a national set of standards for undergraduate medical education using the WFME framework: the experience of an accreditation system in Iran.

BACKGROUND: Defining standards is the first step toward quality assurance and improvement of educational programs. This study aimed at developing and validating a set of national standards for the Undergraduate Medical Education (UME) program through an accreditation system in Iran using the World Federation for Medical Education (WFME) framework. METHODS: The first draft of standards was prepared through consultative workshops with the participation of different UME program stakeholders. Subsequently, standards were sent to medical schools and UME directors were asked to complete a web-based survey. The content validity index at the item level (I-CVI) was computed using criteria including clarity, relevance, optimization and evaluability for each standard. Afterward, a full-day consultative workshop was held and a wide range of UME stakeholders across the country (n = 150) discussed the survey results and made corrections to standards. RESULTS: Analysis of survey results showed that relevance criteria had the best CVI as only 15 (13%) standards demonstrated CVI < 0.78. More than two-thirds (71%) and a half (55%) of standards showed CVI < 0.78 for optimization and evaluability criteria. The final set of UME national standards was structured in 9 areas, 24 sub-areas, 82 basic and 40 quality development standards, and 84 annotations. CONCLUSIONS: We developed and validated national standards as a framework to ensure the quality of UME training with input from UME stakeholders. We used WFME standards as a benchmark while addressing local requirements. The standards and participatory approach to developing standards may guide relevant institutions.

Involvement of Cannabinoid Type 2 Receptors in the Favorable Effects of Sumatriptan on the Random-Pattern Skin Flap Survival in Rats: A Novel Potential Target.

INTRODUCTION: Recent investigations have indicated the potential therapeutic role of cannabinoid type 2 (CB2) receptors in various inflammatory-related disorders. However, the role of these receptors has not been studied in skin flap models to date. In this study, we aimed to evaluate the possible involvement of CB2 receptors in the anti-inflammatory effects of sumatriptan, improving the random-pattern skin flap survival in rats. METHODS: In a controlled experimental study, 36 male Wistar rats were randomly divided into 6 study groups (n = 6 per group). Two doses of sumatriptan (0.1 and 0.3 mg/kg) were administered intraperitoneally 30 min before harvesting the flap tissue. In a separate group, SR144528 (a selective CB2 receptor inverse agonist) was injected before the most effective dose of sumatriptan to determine the possible involvement of CB2 receptors in its action. Histopathological examinations, the expression level of CB2 receptors (Western blot analysis), and IL-1ß and TNF-α concentrations (ELISA) were explored in the skin flap sampled tissues. RESULTS: Sumatriptan 0.3 mg/kg remarkably enhanced the skin flap survival in all macroscopic and microscopic investigations compared to the control group (p < 0.001). IL-1ß and TNF-α levels were significantly attenuated (p < 0.001), and the expression of CB2 receptors in skin cells was amplified in rats treated with sumatriptan 0.3 mg/kg (p < 0.05) compared to the control group. However, the administration of SR144528 (2 mg/kg) nullified all the protective effects of sumatriptan 0.3 mg/kg. CONCLUSION: We discovered that CB2 receptors play a crucial role in the favorable effects of sumatriptan on skin flap survival as a novel mechanism of action. So, targeting these receptors seems to be a dependable method in skin flap surgeries to ensure its survival and prevent tissue necrosis. Further experimental and clinical investigations are needed to ensure the safe clinical application of this method.

Sub-Flap Use of Nano-Selenium Oxide Solution Enhances Skin Flap Viability in Rats: Study the Novel Role of mTOR and p-mTOR Expression.

BACKGROUND: Nano-selenium oxide (NSeO) particles are highly noticeable due to their tissue-protective and antioxidant properties. For this purpose, the effect of NSeO was evaluated on skin flap survival and flap oxidative stress markers in rats. Also, another effect of NSeO was investigated on the expression of mTOR and p-mTOR. MATERIALS AND METHODS: Fifty rats were divided into five groups of ten. Skin flap size was 3×8 cm in all groups. Groups were: (1) Sham, (2) Flap Surgery group, (3) Flap Surgery + NSeO, (4) Flap Surgery + Rapamycin (mTOR inhibitor), (5) Flap Surgery + Rapamycin + NSeO. The flap necrosis rate was computed using the paper pattern method on day seven after surgery. After day seven, flap tissues were collected for histological evaluations. Then, malondialdehyde (MDA) content and superoxide dismutase (SOD) activity were measured. Furthermore, the expression levels of mTOR and p-mTOR were measured using the Western blot method. RESULTS: Treatment with NSeO significantly reduced necrosis (P<0.05). It also resulted in a decrease in MDA level (P<0.05). Histologically, NSeO reduced inflammation and increased positive signs of tissue healing (epithelialization, neovascularization, fibroblast migration, and granulation tissue). NSeO increased SOD activity significantly (P<0.05), whereas, using rapamycin reversed these effects. Also, in all groups, mTOR changes were not significant. Additionally, p-mTOR expression was significantly reduced in groups that rapamycin was injected. CONCLUSION: NSeO can reduce flap necrosis and enhance tissue healing in rats. So, it can potentially be used clinically to promote tissue repair significantly, and its effects are independent of the mTOR pathway. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Sniffer dogs as a screening/diagnostic tool for COVID-19: a proof of concept study.

BACKGROUND: Sniffer dogs are able to detect certain chemical particles and are suggest to be capable of helping diagnose some medical conditions and complications, such as colorectal cancer, melanoma, bladder cancer, and even critical states such as hypoglycemia in diabetic patients. With the global spread of COVID-19 throughout the world and the need to have a real-time screening of the population, especially in crowded places, this study aimed to investigate the applicability of sniffer dogs to carry out such a task. METHODS: Firstly, three male and female dogs from German shepherd (Saray), German black (Kuzhi) and Labrador (Marco) breeds had been intensively trained throughout the classical conditioning method for 7 weeks. They were introduced to human specimens obtained from the throat and pharyngeal secretions of participants who were already reported positive or negative for SARS-COV-2 infection be RT-PCR. Each dog underwent the conditioning process for almost 1000 times. In the meantime another similar condition process was conducted on clothes and masks of COVID-19 patient using another three male and female dogs from Labrador (Lexi), Border gypsy (Sami), and Golden retriever (Zhico) breeds. In verification test for the first three dogs, 80 pharyngeal secretion samples consisting of 26 positive and 54 negative samples from different medical centers who underwent RT-PCR test were in a single-blind method. In the second verification test for the other three dogs, masks and clothes of 50 RT-PCR positive and 70 RT-PCR negative cases from different medical center were used. RESULTS: In verification test using pharyngeal secretion, the sniffer dogs' detection capability was associated with a 65% of sensitivity and 89% of specificity and they amanged to identify 17 out of the 26 positive and 48 out of the 54 true negative samples. In the next verification test using patients' face masks and clothes, 43 out of the 50 positive samples were correctly identified by the dogs. Moreover, out of the 70 negative samples, 65 samples were correctly found to be negative. The sensitivity of this test was as high as 86% and its specificity was 92.9%. In addition, the positive and negative predictive values were 89.6 and 90.3%, respectively. CONCLUSION: Dogs are capable of being trained to identify COVID-19 cases by sniffing their odour, so they can be used as a reliable tool in limited screening.

Grandparents - Grandchildren Relationship in Iran, 2017.

INTRODUCTION: With the continuing growth of aged populations, it is imperative to find ways to maintain and improve the quality of life in old age. It has been documented that grandparents-grandchildren relationship is significantly contributed to quality of life of older adults. This study was conducted to identify the status and associated factors of grandparents-grandchildren relationship in a sample of Iran. METHODS: This cross-sectional study was conducted on 377 community dwelling older adults 60 years and over living in Kashan, Iran. A multistage proportional random sampling technique was applied to obtain the sample. The grandparent -grandchildren relationship was measured by a researcher-developed 16-item scale. The data were analyzed using SPSS version 23 and AMOS 23. RESULTS: The mean age of the respondents was 70.42(SD = 8.20) years. About 62% of the respondents were female and 60.7% were married. The average score of grandparents-grandchild relationship was 67.60(SD = 12.47). The multiple linear regression analysis revealed a significant model (F (11, 365) = 19.05, P < 0.001), where information communication technology of grandparents, geographical distance between grandparents and grandchildren, and the quality of relationship between grandparents and parents of grandchildren were the most important predictors of the grandparents-grandchildren relationship. CONCLUSION: The findings from the current study showed that status of grandparents-grandchildren relationship is moderate to high and influenced by some factors. It is, therefore, suggested that policymakers pay more attention to strengthening grandparent-grandchild relationship by providing educational programs for families and encouraging the elderly to learn and use information communication technology.

Micro-extraction, pre-concentration, and microfluidic-based separation of organophosphate insecticides followed by the miniaturized electrochemical detection system.

Introduction: A new analytical method based on the coupling of microextraction and microfluidics was developed and investigated for the pre-concentration, separation, and electrochemical detection of fenitrothion (FT) and parathion (PA) at the sub-ppm concentrations. Methods: In the first step, the microchip capillary electrophoresis technique was used to serve as a separation and detection system. Analytes were injected in the 40 mm long microchannel with 10 mm sidearms. Then, they were separated by applying a direct electrical field (+1800 V) between the buffer and detection reservoirs. 2-(n-morpholino)ethanesulfonic acid (MES) buffer (20 mM, pH 5) was used as a running buffer. The electrochemical detection was performed using three Pt microelectrodes with the width of working, counter, and reference electrodes (50, 250, and 250 µm, respectively) in the out-channel approach. Results: The system was devised to have the optimum detection potential equal to -1.2 V vs. pseudo-reference electrode. The dimensions of the SU-8 channel have 20 µm depth and 50 µm width. In the second step, an air-assisted liquid-liquid microextraction technique was used to extract and preconcentration of analytes from human blood plasma. Then, 1, 2 di-bromoethan was used as extractant solvent, the analytes were preconcentrated, and the sedimented solvent (50 µL) was evaporated in a 60 ˚C water bath followed by substitution of running buffer containing 10% ethanol. The optimal extraction cycles were found to be 8 with adding 1% NaCl to the aqueous phase. Analyzing time of the mentioned analytes was less than 100s, the precision range was 3.3 - 8.2 with a linear range of 0.8-100 ppm and 1.2-100 ppm for FT and PA, respectively. The extraction recoveries were about 91% and 87% for FT and PA, respectively. The detection limits for FT and PA were 240 and 360 ppb, respectively. Finally, the reliability of the method was investigated by GC-FID. Conclusion: The proposed method and device were validated and can be used as in situ and portable detection systems for detecting fenitrothion and parathion insecticides.

Side effects of COVID-19 vaccines among Iranian healthcare workers: a retrospective cohort study.

INTRODUCTION: This study assessed the incidence and severity of side effects associated with coronavirus disease 2019 (COVID-19) vaccination among healthcare workers registered with the Medical Council of the Islamic Republic of Iran. METHODOLOGY: A retrospective cohort study was conducted on the healthcare workers focusing on the side-effects of COVID-19 vaccines from March to June 2021. Data were collected using online questionnaires. Multivariable logistic regression was used to assess the association between side effects of the vaccines and demographic variables, comorbidities, vaccine type, and history of COVID-19. RESULTS: Out of 42,018 people who were included, 55.85% reported at least one side effect after receiving the first vaccine dose. 4.59% of those with side effects sought diagnostic intervention or were referred to treatment centers. Multivariable logistic regression indicated that being a woman, higher education, having a history of COVID-19 infection, and having comorbidities increased the risk of side effects. The AstraZeneca vaccine significantly increased the risk of side effects compared to the Sputnik vaccine, while the Sinopharm vaccine decreased this risk. The risk of developing a side effect decreased with age. The risk of moderate and severe side effects was significantly associated with gender, younger age, comorbidities, and a history of COVID-19 infection. Moderate and severe side effects were less reported by those who received the Sinopharm vaccine. CONCLUSIONS: Clinical complications after COVID-19 vaccination, directly or indirectly caused by the vaccines, are common. However, the benefits of COVID-19 vaccines greatly outweigh the risk of reversible side effects, especially among the high-risk population.

Changes in gait pattern and quality of life of adolescents with flexible flat foot after Calcaneal Lengthening Osteotomy.

BACKGROUND: Calcaneal Lengthening Osteotomy is a surgical technique to correct flexible flat foot deformities in patients who did not show any change in their symptoms after conservative treatment. In this study, the effects of CLO on the kinematic and kinetic changes of gait was analyzed and the clinical and quality of life improvements in children treated by CLO for moderate to severe symptomatic flexible flat foot deformities were assessed. METHODS: Participants were seven adolescents (13 feet) with symptomatic FFF who underwent during 2019-2022 and seven (10 feet) healthy children as control group. Three items were evaluated in each foot before and after surgery including: 1. Clinical examination 2.quality of life (using Pediatric Quality of Life Inventory version 4 questionnaire) 3. Gait analysis (Vicon motion systems, Oxford metrics Inc., UK). Also, the kinetic and kinematic analysis between patients and healthy groups were compared. RESULTS: Kinematic results of control was significantly better than FFF group. Ankle range of motion(32.94 ± 13.39 compared to 32.94 ± 13.39,P-Value:0.01),foot progression angle (-9.26 ± 7.67 compared to -16.07 ± 9.00,P-Value:0.01),and internal rotation of ankle was higher in control group compared to FFF. FFF patients demonstrated improvement in kinematic results after CLO surgery. Foot progression angle was improved after surgery (-11.31 ± 6.07 compared to -16.19 ± 7.06, P-value:0.00), maximum plantar flexion decreased after CLO surgery due to achil tendon procedure during CLO surgery. Kinetic results of FFF patients showed significant increase in ankle Power in coronal and transverse plane, Also knee and hip power showed similar results.Quality of life parameters showed significant improve in all parameters (Physical,Social, emotional and school function), Also ADKE and ADKF improved after surgery. CONCLUSION: CLO surgery significantly improved patients' quality of life of patients with symptomatic FFF. Also, kinetic results showed improvement in some parameters of gait results after CLO surgery. Thus, our study suggested CLO surgery as an excellent surgical option for symptomatic FFF.

Viewpoint of operating room nurses about factors associated with the occupational burnout: A qualitative study.

Background: Occupational burnout is a mental health problem that among nurses may lead not only to physical and psychological complications, but also to a decrease in the quality of patient care. Considering the stressful nature of surgery, operating room nurses may be at a greater risk. Therefore, the present study aimed to identifying factors associated with the occupational burnout from the perspective of operating room nurses. Materials and methods: This qualitative study was conducted in Iran in 2021 using conventional content analysis. Sampling was performed using purposeful sampling method with maximum variation. In order to collect data, individual, semi-structured interviews were performed with 18 operating room nurses. Interviews continued until data saturation. Data were recorded, transcribed and analyzed using steps proposed by Graneheim and Lundman. Data management was performed using MAXQDA-2020 software. Four criteria provided by Guba and Lincoln were used to improve the study's trustworthiness and rigor. Results: A main theme, 4 categories and 15 subcategories were extracted from the data. The main theme is "gradual burnout due to job tension" and categories and subcategories include organizational factors (manager incompetence, organizational indifference, ambiguity in organizational role, organizational inconsistency), interpersonal factors (surgeon aggression, surgeon authoritarianism, surgeon failure to manage stress, unprofessional behavior of nurses), Occupational nature factors (psychological factors and occupational hazards) as well as individual factors (occupational attitude, unprofessional behavior, emotional involvement, demographic factors, physical factors). Conclusion: Numerous factors associated with burnout in operating room nurses, which may put the personnel under more pressure. According to these factors, nursing managers and operating room nurses can consider effective strategies to prevent or coping with burnout.

The cardioprotective effects of nano-curcumin against doxorubicin-induced cardiotoxicity: A systematic review.

Although the chemotherapeutic drug, doxorubicin, is commonly used to treat various malignant tumors, its clinical use is restricted because of its toxicity especially cardiotoxicity. The use of curcumin may alleviate some of the doxorubicin-induced cardiotoxic effects. Especially, using the nano-formulation of curcumin can overcome the poor bioavailability of curcumin and enhance its physicochemical properties regarding its efficacy. In this study, we systematically reviewed the potential cardioprotective effects of nano-curcumin against the doxorubicin-induced cardiotoxicity. A systematic search was accomplished based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for the identification of all relevant articles on "the role of nano-curcumin on doxorubicin-induced cardiotoxicity" in the electronic databases of Scopus, PubMed, and Web of Science up to July 2021. One hundred and sixty-nine articles were screened following a predefined set of inclusion and exclusion criteria. Ten eligible scientific papers were finally included in the present systematic review. The administration of doxorubicin reduced the body and heart weights of mice/rats compared to the control groups. In contrast, the combined treatment of doxorubicin and nano-curcumin increased the body and heart weights of animals compared with the doxorubicin-treated groups alone. Furthermore, doxorubicin could significantly induce the biochemical and histological changes in the cardiac tissue; however, coadministration of nano-curcumin formulation demonstrated a pattern opposite to the doxorubicin-induced changes. The coadministration of nano-curcumin alleviates the doxorubicin-induced cardiotoxicity through various mechanisms including antioxidant, anti-inflammatory, and antiapoptotic effects. Also, the cardioprotective effect of nano-curcumin formulation against doxorubicin-induced cardiotoxicity was higher than free curcumin.

Cardiac Complications in COVID-19: A Systematic Review and Meta-analysis.

BACKGROUND: The newly emerged coronavirus disease 2019 (COVID-19) seems to involve different organs, including the cardiovascular system. We systematically reviewed COVID-19 cardiac complications and calculated their pooled incidences. Secondarily, we compared the cardiac troponin I (cTnI) level between the surviving and expired patients. METHODS: A systematic search was conducted for manuscripts published from December 1, 2019 to April 16, 2020. Cardiovascular complications, along with the levels of cTnI, creatine kinase (CK), and creatine kinase MB (CK-MB) in hospitalized PCR-confirmed COVID-19 patients were extracted. The pooled incidences of the extracted data were calculated, and the unadjusted cTnI level was compared between the surviving and expired patients. RESULTS: Out of 1094 obtained records, 22 studies on a total of 4,157 patients were included. The pooled incidence rate of arrhythmia was 10.11%. Furthermore, myocardial injury had a pooled incidence of 17.85%, and finally, the pooled incidence for heart failure was 22.34%. The pooled incidence rates of cTnI, CK-MB, and CK elevations were also reported at 15.16%, 10.92%, and 12.99%, respectively. Moreover, the pooled level of unadjusted cTnI was significantly higher in expired cases compared with the surviving (mean difference = 31.818, 95% CI = 17.923-45.713, P value <0.001). CONCLUSION: COVID-19 can affect different parts of the heart; however, the myocardium is more involved.