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Current pharmacological approaches to treatment of post-traumatic stress disorder (PTSD) lack adequate effectiveness. As a result, identifying new molecular targets for drug development is necessary. Furthermore, fear learning and memory in PTSD can undergo different phases, such as fear acquisition, consolidation, and extinction. Each phase may involve different cellular pathways and brain regions. As a result, effective management of PTSD requires mindfulness of the timing of drug administration. One of the molecular targets currently under intense investigation is the N-methyl-D-aspartate (NMDA)-type glutamate receptor (NMDAR). However, despite the therapeutic efficacy of drugs targeting NMDAR, their translation into clinical use has been challenging due to their various side effects. One possible solution to this problem is to target signaling proteins downstream to NMDAR to improve targeting specificity. One of these proteins is the neuronal nitric oxide synthase (nNOS), which is activated following calcium influx through the NMDAR.In this paper, we review the literature on the pharmacological modulation of nNOS in animal models of PTSD to evaluate its therapeutic potential. Furthermore, we attempt to decipher the inconsistencies observed between the findings of these studies based on the specific phase of fear learning which they had targeted.Inhibition of nNOS may inhibit fear acquisition and recall, while not having a significant effect on fear consolidation and extinction. However, it may improve extinction consolidation or reconsolidation blockade.Modulation of nNOS has therapeutic potential against PTSD and warrants further development for use in the clinical setting.

/objectives. Single nucleotide polymorphisms (SNPs) located at the 3'-UTR region of the target genes of microRNAs (miRNAs) can dysregulate their expression via disrupting the binding site of miRNAs. Interleukin-16 (IL-16) is involved in the pathogenesis of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). In the current study, we assessed the possible association between rs1131445 polymorphism in IL-16 gene with risk and clinical characteristics of RA and SLE in the Iranian population.In this case-control study, 120 patients with RA, 120 patients with SLE, and 120 unrelated healthy subjects were collected to estimate rs1131445 (T C) polymorphism in IL-16 gene using real-time PCR high-resolution melting (HRM) method.Our results demonstrated considerable associations between TC genotype and C allele of rs1131445 with enhanced risk of RA (ORThese results proposed a significant association between IL-16 polymorphism and augmented risk of RA and clinical characteristics of RA and SLE.

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-1β 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-1β 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.

Curcumin has been previously shown to possess anti-myeloma effects. However, almost all of the previous reports are only based on observations from single viability methods in commonly used cell li...

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.

Introduction: Safe and efficacious vaccines against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), would contribute to contain the COVID-19 pandemic. In this study, we examined this question that if there is an association between the incidence of side effects and the COVID-19 breakthrough infections. Material and Methods: This descriptive-analytical cross-sectional study was conducted for two months from June 22 to August 22, 2021. The study method was complete enumeration and 1474 healthcare workers who were medical staff of seven hospitals in Tehran and were vaccinated with one of the AstraZeneca, Covaxin, Sputnik V, and Sinopharm vaccines. Two main questions of this questionnaire were the occurrence or non-occurrence of any side effects after receiving the vaccines and the presence or absence of COVID-19 infection after vaccination. Results: According to the results obtained, in recipients vaccinated with Sinopharm vaccine, the group that reported at least one side effects after receiving the vaccine had a significantly higher COVID-19 infection than the group reported no side effects after vaccination (P

Present study assessed whether Sinopharm, AstraZeneca, Sputnik V, and Covaxin's vaccinated womenbr /reveal a distinct incidence of menstruation disturbances, hirsutism, and metrorrhagia.br /Materials and Methods: Data collection was performed from June to August 2021, and 427 women working in sevenbr /selected hospitals in Tehran were studied in this descriptive-analytical cross-sectional study. All of these women hadbr /received one or both doses of the vaccines with one of the assessed vaccines. Required data was collected via questionnairebr /and imported to SPSS 16 for further assessment and analysis. Fisher's Exact Test and Chi-Squared test werebr /main statistical tests used to understand whether any significant relation exists or not.br /Results: The participant's mean age and body mass index (BMI) were 29.78 ± 10.55 and 23.27 ± 3.82, respectively.br /Three hundred ninety-five cases (92.4%) had received both doses of the vaccines. Also, 154 cases (36.1%) had a historybr /of COVID-19. A total of 38 cases (8.8%) of menstruation disturbances, 20 cases (4.6%) of metrorrhagia, and 7br /cases (1.6%) of hirsutism were reported after receiving the vaccines. There was a significant difference among thebr /vaccinated groups with the vaccines as mentioned earlier in terms of menstruation disturbances (hypermenorrhea,br /dysmenorrhea, Amenorrhea) (P=0.01). The highest and the lowest incidence of menstruation disturbances were recordedbr /in the group vaccinated with Covaxin (17.6%) and Sputnik V (5%), respectively. There was also no significantbr /difference amongst the vaccinated groups with the four vaccines regarding the incidence of metrorrhagia andbr /hirsutism (P=0.10 and P=0.12, respectively). There was no significant relationship between all three complicationsbr /incidence with the previous infection concerning all vaccines (coefficient=0.46, 1.27, -0.15 respectively for menstruationbr /disturbances, metrorrhagia, and, hirsutism).br /Conclusion: Seemingly, Covaxin revealed the most side effects in terms of menstruation disturbances. As a result, professionalsbr /must carry out several studies with reasonable samples to recommend the vaccine to those women confidently.

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 previously. In this study, we aimed to evaluate the possible involvement of CB2 receptors in the anti-inflammatory effects of sumatriptan and improvement of the random-pattern skin flap survival in rats.In a controlled experimental study, 36 male Wistar rats were randomly divided into six study groups (n = 6 per group). Two doses of sumatriptan (0.1 and 0.3 mg/kg) were administered intraperitoneally (i.p) 30 minutes 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 (by western blot analysis), and IL-1 and TNF-α concentrations (ELISA) were explored in the skin flap samples.Sumatriptan 0.3 mg/kg remarkably enhanced the skin flap survival in all macroscopic and microscopic investigations compared to the control group (P0.001). IL-1 and TNF-α levels were significantly attenuated (P0.001), and the expression of CB2 receptors in skin cells was amplified in rats treated with sumatriptan 0.3 mg/kg (p0.05) compared to the control group. However, the administration of SR144528 (2 mg/kg) nullified all the protective effects of sumatriptan (0.3 mg/kg).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.

Background: Peripheral nerve injuries remain a great challenge for microsurgery despite the significant progress in recent decades. The current gold standard is autogenous nerve grafting with a success rate as low as 50% in long gaps. Current studies have focused on finding alternative methods for bridging nerve defects. Previous data have demonstrated the role of human amniotic membrane in stimulating neural regeneration. On the other hand, adipose-derived mesenchymal stem cells can differentiate into all three germ layers and could support nerve repair. The purpose of this study was to compare the role of the human amniotic membrane with and without adipose tissue stem cells in sciatic nerve injury with gap in rats. Objectives: We aimed to evaluate the effectiveness of the human amniotic membrane with and without adipose-derived mesenchymal stem cells in sciatic nerve injury with gap in rats. Methods: Twenty-four male Wistar rats in four random groups were used in our study. In the first group, the nerve gap was repaired using the inverse resected nerve segment (Control group), the second group was repaired with a human amniotic membrane (AM group), the third group was repaired with an amnion sheet with seeded adipose-derived mesenchymal stem cells (AM/ADMSCs group), and the last group was not repaired, and both stumps were sutured to muscles. Results: All the animals underwent the procedures and survived without complication. The sciatic function index and hot plate test results were significantly improved in the AM and AM/ADMSCs groups compared to the Control group (as a gold standard of care) (P>0.05). Based on histopathology findings, regenerative nerve fibers were seen in the implanted area of both AM and AM/ADMSCs groups; however, nerve fibers were surrounded by significant fibrosis (scar formation) in the AM/ADMSCs group. The axon count in the Control group was significantly higher than both experimental groups (P < 0.01). Conclusions: Our study showed the role of amniotic membrane in the promotion of nerve regeneration in sciatic nerve injury with a gap, but adding adipose-derived mesenchymal stem cells not only has no extra benefits, but also causes more tissue scar.

Background: Covid-19 is now global concern and widely spread to the world due to high mortality among the nations we tried to evaluate the efficacy of methylprednisolone pulse in COVID-19 patients with severe respiratory failure.Methods: This study was phase2, double-blind, randomized, clinical trial in adults with COVID-19 (aged ≥18 years old) admitted to the intensive care unit (ICU) of *. Patients with intermediate or severe COVID-19 with PaO2/FiO2 less than 300 and progressive disease unresponsive to standard treatments admitted to ICU. Patients were randomly allocated in either control or investigation group. The control group received recommended regimen for COVID-19. The investigation group received the recommended regimen plus Methylprednisolone (1000mg/day for three days) and oral prednisolone 1mg/kg with tapering of dose within ten days. Results: A total of 29 ICU patients with intermediate or severe COVID-19 pneumonia recruited in this study. Fourteen patients (4 female, ten male) allocated in the investigation group, and 15 patients (6 female, nine male) assigned to the control group. The participant’s average age was 64.03±13.545 (case: 61.07±12.83, control: 66.80±14.03). The patients with methylprednisolone pulse had significantly higher systolic (P=0.018) and diastolic (P=0.001) blood pressure, meanwhile, the Glasgow coma scale (GCS) of methylprednisolone group was considerably (PConclusion: This study demonstrated methylprednisolone pulse in COVID-19 severe respiratory failure dramatically improves the clinical condition of patients including, GCS, and SpO2 of patients.Clinical Trial Registration Number: IRCT20200406046963N1

The role of vitamin A in re-epithelialization of the damaged mucosal surfaces has been documented. The aim of this study was to evaluate the role of vitamin A in preventing renal scaring after acute pyelonephritis in children.This clinical trial study was conducted in children with acute pyelonephritis in Mofid Children Hospital (Tehran, Iran). Patients were randomly divided into two groups to receive ceftriaxone and vitamin A or ceftriaxone only. Dimercaptosuccinic acid (DMSA) renal scintigraphy was performed before the start of the treatment and 6 months later. Results were compared for renal scaring between the two groups.Seventy-six patients (11 boys and 65 girls) were enrolled. The mean age was 25 ± 24 months and 54 patients (71.1%) were under 2 years old. The average vitamin A level was 71 ± 24 microg/dL in the treatment group and it was 62 ± 18 µg/dL in the control group. Baseline DMSA scans were comparable between the two groups in terms of scarring (P = .53), but the second DMSA scans showed a significant change in progression of the renal injury and scaring in the control group compared to those treated with vitamin A as well as antibiotic (P.001).We found administration of the vitamin A was useful in decreasing the amount of the injury and scarring following the pyelonephritis. Based on our study, vitamin A can be used in conjunction with other treatments in the management of acute pyelonephritis in children.