Nonalcoholic steatohepatitis: A comprehensive updated review of risk factors, symptoms, and treatment.

Non-alcoholic steatohepatitis (NASH) is a subtype of nonalcoholic fatty liver disease and a progressive and chronic liver disorder with a significant risk for the development of liver-related morbidity and mortality. The complex and multifaceted pathophysiology of NASH makes its management challenging. Early identification of symptoms and management of patients through lifestyle modification is essential to prevent the development of advanced liver disease. Despite the increasing prevalence of NASH, there is no FDA-approved treatment for this disease. Currently, medications targeting metabolic disease risk factors and some antifibrotic medications are used for NASH patients but are not sufficiently effective. The beneficial effects of different drugs and phytochemicals represent new avenues for the development of safer and more effective treatments for NASH. In this review, different risk factors, clinical symptoms, diagnostic methods of NASH, and current treatment strategies for the management of patients with NASH are reviewed.

Evaluation the frequencies of HLA alleles in moderate and severe COVID-19 patients in Iran: A molecular HLA typing study.

Background: Severe acute respiratory syndrome coronavirus 2 was first reported in December 2019 and it has spread globally ever since. The HLA system is crucial in directing anti-viral immunity and recent studies are investigating the possible involvement of the HLA genes on the severity of immune inflammation in different phases of COVID-19. Methods: In this cross-sectional study, peripheral blood-extracted genomic DNAs of 109 COVID-19 patients and 70 healthy controls were genotyped for different alleles of HLA-A, HLA-B, and HLA-DRB1 loci using sequence-specific primer PCR method. Results: The results indicated that frequencies of HLA-DRB1*11:01 and HLA-DRB1*04:03 were significantly higher in severe patients rather than moderates (p: <0.001 and 0.004, respectively). Also, it was observed that HLA-DRB1*04:01 was more frequent in moderate patients and healthy controls (p:0.002). In addition, HLA-B*07:35, and HLA-DRB1*07:01 showed higher frequencies in patients compared with controls (p: 0.031 and 0.003 respectively). Inversely, due to the higher frequencies of HLA-B*51:01 (p:0.027), HLA-DRB1*11:05 (p:0.003), HLA-DRB1*13:05 (p:0.022), and HLA-DRB1*14:01 (p:0.006) in healthy individuals rather than patients, they may be associated with COVID-19 resistance. Conclusion: The results show that, based on the population differences, the type of alleles related to the severity of COVID-19 is different, which should be clarified by designing large-scale studies in order to develop HLA-based treatments and vaccines.

Effects of Gallic Acid on Memory Deficits and Electrophysiological Impairments Induced by Cerebral Ischemia/Reperfusion in Rats Following Exposure to Ambient Dust Storm.

We aimed to investigate the probable protective effects of gallic acid (GA) on cognitive deficits, hippocampal long term potentiation (LTP) impairments, and molecular changes induced by cerebral ischemia/reperfusion (I/R) in rats following exposure to ambient dust storm. After pretreatment with GA (100 mg/kg), or vehicle (Veh) (normal saline, 2 ml/kg) for ten days, and 60 minutes' exposure to dust storm including PM (PM, 2000-8000 g/m3) every day, 4-vessel occlusion (4VO) type of I/R was induced. Three days after I/R induction, we evaluated behavioral, electrophysiological, histopathological, molecular and brain tissue inflammatory cytokine changes. Our findings indicated that pretreatment with GA significantly reduced cognitive impairments caused by I/R (P < 0.05) and hippocampal LTP impairments caused by I/R after PM exposure (P < 0.001). Additionally, after exposure to PM, I/R significantly elevated the tumor necrosis factor α content (P < 0.01) and miR-124 level (P < 0.001) while pre-treatment with GA reduced the level of miR-124 (P < 0.001). Histopathological results also revealed that I/R and PM caused cell death in the hippocampus CA1 area (P < 0.001) and that GA decreased the rate of cell death (P < 0.001). Our findings show that GA can prevent brain inflammation, and thus cognitive and LTP deficits caused by I/R, PM exposure, or both.

Sodium Hydrosulfide Modification of Mesenchymal Stem Cell-Exosomes Improves Liver Function in CCL4-Induced Hepatic Injury in Mice.

Background: Liver diseases and injuries are important medical problems worldwide. Acute liver failure (ALF) is a clinical syndrome characterized by severe functional impairment and widespread death of hepatocytes. Liver transplantation is the only treatment available so far. Exosomes are nanovesicles originating from intracellular organelles. They regulate the cellular and molecular mechanisms of their recipient cells and have promising potential for clinical application in acute and chronic liver injuries. This study compares the effect of Sodium hydrosulfide (NaHS) modified exosomes with non-modified exosomes in CCL4-induced acute liver injury to ascertain their role in ameliorating hepatic injury. Methods: Human Mesenchymal stem cells (MSCs) were treated with or without NaHS (1 µmol) and exosomes were isolated using an exosome isolation kit. Male mice (8-12 weeks old) were randomly divided into four groups (n=6): 1-control, 2-PBS, 3- MSC-Exo, and 4- H2S-Exo. Animals received 2.8 ml/kg body weight of CCL4 solution intraperitoneally, and 24 h later MSC-Exo (non-modified), H2S-Exo (NaHS-modified), or PBS, was injected in the tail vein. Moreover, 24 h after Exo administration, mice were sacrificed for tissue and blood collection. Results: Administration of both MSC-Exo and H2S-Exo reduced inflammatory cytokines (IL-6, TNF-α), total oxidant levels, liver aminotransferases, and cellular apoptosis. Conclusion: MSC-Exo and H2S-Exo had hepato-protective effects against CCL4-induced liver injury in mice. Modification of cell culture medium with NaHS as an H2S donor enhances the therapeutic effects of MSC exosomes.

Protective effects of gallic acid and SGK1 inhibitor on oxidative stress and cardiac damage in an isolated heart model of ischemia/reperfusion injury in rats.

Objectives: Oxidative stress and serum and glucocorticoid-induced Kinase 1 gene (SGK1) perform a central role in the consequences of ischemia in the heart. This research aimed to investigate the effect of coadministration of gallic acid and the GSK650394 (as SGK1 gene inhibitor) on the ischemic complications of a rat model of cardiac ischemia/reperfusion (I/R) injury. Materials and Methods: Sixty male Wistar rats were divided into 6 groups with or without pretreatment with gallic acid for 10 days. After that, the heart was isolated and perfused with Krebs-Henseleit solution. A 30 min of ischemia was performed followed by a 60 min reperfusion. In 2 groups, GSK650394 was infused 5 min before ischemia induction. Ten minutes after reperfusion commencement, cardiac marker enzyme (CK-MB, LDH, and cTn-I) activities were measured in the cardiac perfusate. At the end of reperfusion, the activity of anti-oxidant enzymes (Catalase, Superoxide dismutase, and Glutathione peroxidase), lipid peroxidation (MDA), total anti-oxidant capacity (TAC), intracellular reactive oxygen species (ROS), infarct size, and SGK1 gene expression were measured in the heart tissue. Results: The results indicated that dual therapy with both drugs significantly improved endogenous anti-oxidant enzyme activity and TAC more than each drug alone. However, the heart marker enzymes (CK-MB, LDH, and cTn-I), MDA, ROS, infarct size, and SGK1 gene expression were reduced significantly compared with the ischemic group. Conclusion: The results of this study suggest that concomitant administration of both drugs in the case of cardiac I/R injury may have a more beneficial effect than each one alone.

The effects of gallic acid and vagotomy on motor function, intestinal transit, brain electrophysiology and oxidative stress alterations in a rat model of Parkinson's disease induced by rotenone.

INTRODUCTION: The neuropathology of Parkinson's disease (PD) is complex and affects multiple systems of the body beyond the central nervous system. This study examined the effects of gallic acid (GA) and gastrointestinal vagotomy (VG) on motor, cognitive, intestinal transit time, and thalamic nuclei electrical power in an animal model of PD induced by rotenone. MATERIALS AND METHODS: Male Wistar rats were divided into 4 groups: Sham, ROT, ROT+GA, VG + ROT. Sham rats received vehicle, those in ROT received rotenone (5 mg/kg/2 ml, ig), PD rats in ROT+GA were treated with GA (100 mg/kg, gavage/once daily, for 28 days), and in VG + ROT, the vagal nerve was dissected. Stride length, motor coordination and locomotion, intestinal transit time, cognitive and pain threshold, and thalamic local EEG were evaluated. Oxidative stress indexes in striatal tissue were also measured. RESULTS: Rotenone diminished significantly the stride length (p < 0.001), motor coordination (p < 0.001), power of thalamic EEG (p < 0.01) and pain (p < 0.001). MDA increased significantly (p < 0.001) while GPx activity decreased (p < 0.001). Intestinal transit time rose significantly (p < 0.01). PD rats treated with GA improved all above disorders (p < 0.001, p < 0.01). Vagotomy prevented significant alterations of motor and non-motor parameters by rotenone. CONCLUSION: According to current findings, rotenone acts as a toxin in GI and plays a role in the pathogenesis of PD through gastric vagal nerve. Thus, vagotomy could prevent the severity of toxicity by rotenone. In addition, GA improved symptoms of PD induced by rotenone. Therefore, GA can be regarded as a promising therapeutic candidate for PD patients.

Sex-specific effects of developmental morphine exposure and rearing environments on hippocampal spatial memory.

Developmental morphine (MOR) exposure (DME) detrimentally affects the cognitive abilities of the next generation. It is shown that postnatal rearing environments and prenatal conditions effectively impact memory. The present study investigated the effects of DME, postweaning rearing, and sex on spatial learning and memory. At molecular level, we evaluated mRNA levels of brain-derived neurotrophic factor, cyclic AMP response element-binding protein (CREB), µ-opioid receptor, and ΔFosB in the hippocampus of male offspring. Female Wistar rats were treated with escalating doses of MOR or saline before mating, gestation, and lactation. On Postnatal Day 22, the male and female pups were divided into 12 groups and raised for 2 months under different conditions: standard, isolated (ISO), or enriched environment. Afterward, the Morris water maze task measured spatial learning and reference memory; rats were then sacrificed to assess hippocampus gene expressions. Results indicated the DME and isolated rearing increased latency to find the hidden platform in male offspring. DME was insignificant in female offspring, whereas rearing environments significantly altered escape latency in both sexes. We also found that the enriched environment upregulated the brain-derived neurotrophic factor mRNA in both saline and MOR groups, whereas it downregulated the mRNA levels of CREB1, µ-opioid receptor, and ΔFosB in the MOR group. In addition, the DME enhanced CREB1, µ-opioid receptor, and ΔFosB gene expression in the MOR + isolated group. Our findings signified the effects of DME, rearing environment, and sex on the spatial learning abilities of offspring. Also, we showed that DME and rearing conditions could manipulate hippocampal neurochemistry.

The hepato-protective effect of H2S-modified and non-modified mesenchymal stem cell exosomes on liver ischemia-reperfusion injury in mice: The role of MALAT1.

INTRODUCTION: Ischemia-reperfusion injury (IRI) by causing histopathological changes is considered one of the most important causes of liver failure and dysfunction after surgery which affect graft outcomes. Stem cells are new promising approaches to treating different diseases. One of the critical strategies to improve their function is the preconditioning of their culture medium. This study compared the effect of NaHS-modified and non-modified mesenchymal stem cell exosomes on liver ischemia-reperfusion injury in mice. METHODS: Human umbilical cord-derived MSC (MSC) cultured in a 75 cm3 flask and when confluency reached about 80%, the culture medium replaced with a serum-free medium, and 48 h later supernatants collected, concentrated, and then MSC-Exo extracted. To obtain H2S-Exo, MSC was treated with NaHS (1 µmol),the supernatant collected after 48 h, concentrated and exosomes extracted. Twenty-four male mice were randomly divided into four groups (n = 6) including: 1-ischemia, 2-sham-operated, 3- MSC-Exo, and 4- H2S-Exo. To induce ischemia, the hepatic artery and portal vein clamped using an atraumatic clip for 60 min followed by 3 h of reperfusion. Just upon ending the time of ischemia (removal of clamp artery), animals in MSC-Exo, and H2S-Exo groups received 100 µg exosomes in 100 µl PBS via tail vein. At the end of reperfusion, blood, and liver samples were collected for further serological, molecular, and histological analyses. RESULTS: Administration of both MSC-Exo and H2S-Exo improved liver function by reducing inflammatory cytokines, cellular apoptosis, liver levels of total oxidant status, and liver aminotransferases. The results showed that protecting effect of MSC exosomes enhanced following NaHS preconditioning of cell culture medium. CONCLUSION: MSC-Exo and H2S-Exo had hepato-protective effects against injuries induced by ischemia-reperfusion in mice. NaHS preconditioning of mesenchymal stem cells could enhance the therapeutic effects of MSC-derived exosomes.

Efficacy of the systemic co-administration of vitamin D3 in reversing the inhibitory effects of sodium alendronate on orthodontic tooth movement: A preliminary experimental animal study.

INTRODUCTION: Bisphosphonates can severely slow down orthodontic tooth movement (OTM) by reducing bone turnover. This calls for materials and methods to reverse or neutralize their effects on OTM. We propose systemic vitamin D3 (D3) for this purpose. METHODS: Thirty-two male Wistar rats were randomized into 4 groups of 8 each. Three groups were administered D3 (3 systemic doses of 24,000 IU/kg each), alendronate (ALN) (5 doses of 7 mg/kg each), and ALN+D3 (same doses as mentioned above). One group served as the negative control. The incisors were distalized at 30 g of force for 2 weeks. OTMs were measured blindly. Radicular pressure areas were searched histologically (blindly) for capillaries, Howship's lacunae, osteoclasts, and osteoblasts. Data were analyzed statistically (α = 0.05, α = 0.0083, ß <0.1). RESULTS: OTMs in the groups D3, ALN+D3, ALN, and control were 1.900 ± 0.237, 1.629 ± 0.219, 0.975 ± 0.145, and 1.565 ± 0.324 mm (analysis of variance, P <0.001), respectively. OTM in the ALN group was smaller than all other groups (Tukey, P <0.001). OTM in the D3 group was greater than in the control group (P = 0.054). The ALN+D3 group had greater OTM than the ALN group (P <0.001) but was not significantly different from the D3 (P = 0.153) or control (P = 0.951) groups. All histologic variables were significantly different across groups (Kruskal-Wallis, P <0.001). All the markers in the D3 group were more frequent than those of the other groups (Mann-Whitney U, P <0.001). There were fewer markers in the ALN group than in the control group (P ≤0.001). The ALN+D3 group had more markers than the ALN group in terms of capillaries, osteoclasts, and osteoblasts (P ≤0.007). The ALN+D3 group was similar to the control group regarding capillaries, osteoclasts, and osteoblasts (P ≥0.382). CONCLUSIONS: Systemic vitamin D3 may accelerate OTM and increase histologic biomarkers of bone turnover. ALN reduces OTM and its histologic biomarkers. Systemic vitamin D3 can reverse this inhibitory effect of ALN on OTM back to normal.

Autophagy Involves in Differentiation of Insulin-Secreting Cells from Adipose Derived Stem Cells.

OBJECTIVE: Destruction of pancreatic beta-cells induces an insulin deficiency and causes type 1 diabetes. The role of autophagy in inducing insulin-secreting cells (ISCs) from adipose-derived mesenchymal stem cells (AMSCs) was investigated in the current study. MATERIALS AND METHODS: In this experimental study, the isolated AMSCs were characterization and exposed to a cocktail differentiation medium (CDM) in the absence or presence of 3-methyladenine (3MA), an autophagy inhibitor. The differentiation of ISCs was confirmed by the evaluation of the expression of beta-cell-specific genes including pancreatic and duodenal homeobox 1 (PDX1), musculoaponeurotic fibrosarcoma oncogene homolog A (MAF-A), Nk class of homeodomain-encoding genes 6.1 and 2.2 (NKX6-1 and NKX2.2), Glucose transporter 2 (GLUT-2) and INSLIN. Using Newport Green (NG), insulin-positive cells were identified. Insulin secretion in response to various glucose concentrations was measured. Autophagy was evaluated by Acridine orange (AO) staining. Also, expression of autophagy-associated genes, including autophagy-related gene 5 (ATG-5), autophagy-related gene 7 (ATG-7), BECLIN-1, and mammalian target of rapamycin (mTOR), was evaluated by Real-time polymerase chain reaction (PCR) method. RESULTS: We observed a significant increase of beta-cell specific genes expression in the CDM-treated cells (P<0.01 or P<0.001), whereas the expression of these genes was down-regulated in 3MA-exposed cells. Expression of INSULIN and GLUT-2 genes (P<0.01 and P<0.05, respectively), insulin secretion in response to glucose (P<0.01), and percentage of NG-positive cells (P<0.05) in the 3MA-exposed cells were considerably lower than the cells treated with CDM. The percentage of AO-positive cells (P<0.01) and the expression of autophagy-related genes (P<0.001) was significantly enhanced in the CDM group. These events were significantly prevented by the 3MA. CONCLUSION: Our data showed that autophagy is necessary for beta-cell differentiation, and preventing autophagy by 3MA causes the reduction of beta-cell differentiation and insulin secretion.

Prevalence of impaired renal function and determinants in the southwest of Iran.

BACKGROUND: Chronic kidney disease (CKD) is a growing global health problem with faster progression in developing countries such as Iran. Here we aimed to evaluate the prevalence and determinants of CKD stage III+. METHODS: This research is part of the Khuzestan Comprehensive Health Study (KCHS), a large observational population-based cross-sectional study in which 30,041 participants aged 20 to 65 were enrolled. CKD was determined with estimated glomerular filtration rate (eGFR) less than 60 ml/min/1.73m2, based on two equations of Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI). The multivariate logistic regression was used to evaluate the CKD stage III+ determinants. RESULTS: Prevalence of CKD stage III+ is estimated to be 7.1, 5.5, and 5.4% based on MDRD, CKD-EPI, and combination of both equations, respectively. More than 89% of CKD subjects aged higher than 40 years. In regression analysis, age more than 40 years had the strongest association with CKD stage III+ probability (OR: 8.23, 95% CI: 6.91-9.18). Higher wealth score, hypertension, High-Density Lipoprotein levels less than 40 mg/dl, and higher waist to hip ratio were all associated with CKD stage III+ while Arab ethnicity showed a protective effect (OR: 0.69, 95% CI: 0.57-0.78). CONCLUSION: Our findings provide detailed information on the CKD stage III+ and its determinants in the southwest region of Iran. Due to strong association between age and CKD stage III+, within a few decades we might expect a huge rise in the CKD prevalence.

Impact of 2017 ACC/AHA guideline on prevalence, awareness, treatment, control, and determinants of hypertension: a population-based cross-sectional study in southwest of Iran.

BACKGROUND: In 2017, the American College of Cardiology/American Heart Association (ACC/AHA) provided a new guideline for hypertension prevention and management. We aimed to update the prevalence, awareness, control, and determinants of hypertension based on this guideline in Khuzestan province, southwest of Iran, and to estimate the number of people who are eligible for non-pharmacologic and pharmacologic intervention. METHODS: This population-based cross-sectional study was conducted in Khuzestan, a large province in the southwest of Iran. Comprehensive information about the potential relating factors of hypertension was collected, blood pressure was measured, and anthropometric measurements were obtained. Moreover, the dietary pattern was evaluated in 2830 individuals, using a qualitative food frequency questionnaire. RESULTS: Among 30,506 participants, 30,424 individuals aged 20-65 years were eligible for the study. In comparison with the previous guideline released by the Joint National Committee (JNC8), the prevalence of hypertension in Khuzestan dramatically increased from 15.81 to 42.85% after implementation of the ACC/AHA guideline, which was more dominant in the male population and the 45-54 age group. The sex and age adjustment of the hypertension prevalence was estimated to be 39.40%. The percentage of hypertension awareness, treatment, and control were 45.85%, 35.42%, and 59.63%, which dropped to 22.72%, 26.37%, and 28.94% after implementation of new guideline, respectively. CONCLUSIONS: In the ACC/AHA guideline, a higher number of individuals with the pre-hypertension condition were shifted into the hypertension category and the level of awareness, treatment, and control were dramatically decreased, which highlight a great need to expand the public health infrastructure for further managing the substantial increased burden on healthcare system. However, further studies with population over 65 years are required to estimate the eligibility for antihypertensive treatment in this province after implementation of new guideline.

Association of anthropometric indices with cardiovascular disease risk factors among adults: a study in Iran.

AIMS: Cardiovascular diseases (CVDs) are the leading cause of death in the world. Many modifiable risk factors have been reported to synergistically act in the development of CVDs. We aimed to compare the predictive power of anthropometric indices, as well as to provide the best cut-off point for these indicators in a large population of Iranian people for the prediction of CVDs and CVD risk factors. METHODS AND RESULTS: All the data used in the present study were obtained from Khuzestan comprehensive health study (KCHS). Anthropometric indices, including BMI (body mass index), WC (waist circumference), HC (hip circumference), WHR (waist-to-hip ratio), WHtR (waist-to-height ratio), ABSI (a body shape index), as well as CVD risk factors [dyslipidaemia, abnormal blood pressure (BP), and hyperglycaemia] were recorded among 30 429 participants. WHtR had the highest adjusted odds ratios amongst anthropometric indices for all the risk factors and CVDs. WC had the highest predictive power for dyslipidaemia and hyperglycaemia [area under the curve (AUC) = 0.622, 0.563; specificity 61%, 59%; sensitivity 69%, 60%; cut-off point 87.95, 92.95 cm, respectively], while WHtR had the highest discriminatory power for abnormal BP (AUC = 0.585; specificity 60%; sensitivity 65%; cut-off point 0.575) and WHR tended to be the best predictor of CVDs (AUC = 0.527; specificity 58%; sensitivity 64%; cut-off point 0.915). CONCLUSION: In this study, we depicted a picture of the Iranian population in terms of anthropometric measurement and its association with CVD risk factors and CVDs. Different anthropometric indices showed different predictive power for CVD risk factors in the Iranian population.

Premature Coronary Artery Disease Is More Prevalent in People Who Go to Bed Late.

BACKGROUND: Little is known regarding the impact of quantity and quality of sleep on the incidence of cardiovascular disease. The aim of this study was to investigate the possible independent association of late bedtime and premature coronary artery disease (PCAD). METHODS: Between October 2016 and November 2019, we conducted a cross-sectional population-based study on 30101 participants aged 20-65 years in Khuzestan Comprehensive Health Study (KCHS). Data on major risk factors of cardiovascular disease, habit history, physical activity, and sleep behavior was gathered and participants underwent blood pressure, anthropometric, and serum lipid and glucose profile measurements. PCAD was defined as documented history of developing obstructive coronary artery disease before 45 years in men and before 55 years in women. RESULTS: Of a total of 30101 participants (64.1% female, mean age: 41.7±11.7 years) included in this study, 1602 (5.3%, 95% confidence interval: 5.1%-5.6%) had PCAD. Late bedtime was reported in 7613 participants (25.3%, 95% confidence interval: 24.9%-25.8%). Age-sex standardized prevalence for PCAD and late bedtime were 3.62 (3.43-3.82) and 27.8 (27.2-28.4), respectively. There was no significant difference (P=0.558) regarding prevalence of PCAD between those with late bedtime (5.5%, 95% CI: 4.9%-6.0%) and those with early bedtime (5.3%, 95% CI: 5.0%-5.6%). However, after adjustment for potential confounders, late bedtime was independently associated with PCAD (OR=1.136, 95% CI=1.002-1.288, P=0.046). CONCLUSION: In this study, late bedtime was significantly associated with presence of PCAD. Future prospective studies should elucidate the exact role of late bedtime in developing coronary atherosclerosis prematurely.

Innate and Adaptive Immunity Imbalance With Severe COVID-19 Pneumonia in Children and Adults.

Introduction: Little is known about the laboratory and radiological characteristics and clinical significance of peripheral immune alterations in patients with coronavirus disease 2019 (COVID-19). This study aims to clarify these aspects in children and adults with COVID-19. Methods: In this consecutive pilot study, COVID-19 patients with the confirmed pneumonia and real-time RT-PCR were recruited prospectively in June 2020. The clinical, chest CT, and laboratory features, such as lymphocyte subpopulations, were analyzed for each individual. Results: Forty confirmed COVID-19 patients, 11 severe children, 12 severe adults, and 17 critical adult patients, besides 20 healthy pediatrics and 14 healthy adults as controls, were enrolled prospectively. Adult patients, especially critical ones, had a much higher prevalence of laboratory and chest CT abnormalities. Data regarding immune cell subsets in children patients, compared with matched controls, had higher CD3+ CD8+ T cells (p = 0.004) and lower CD4+/CD8+ ratio (p = 0.042), while adult patients, compared with matched controls, had lower CD14+ monocytes (p = 0.032). Adult patients were also categorized as experiencing critical or severe illness on admission and, compared with severe patients, had lower total lymphocytes (p < 0.047), CD3+ T-lymphocytes (p < 0.002), and CD3+ CD8+ T cells (p = 0.001) and, on the other hand, had higher CD3+ CD4+ T cells (p = 0.012) and CD4+/CD8+ ratio (p = 0.003). Non survived adults, compared with survived patients, had significantly lower CD3+ T-lymphocyte (p = 0.005). Conclusion: Unlike adult patients, who compared with matched controls and had more comorbidities, higher frequency of severe clinical symptoms, laboratory abnormalities, and immune cells alteration, clinical manifestations of COVID-19 in children (compared with matched controls) were relatively mild, and fewer clinical complications were seen either, perhaps because of a milder inflammatory response following their peripheral innate and adaptive immune cell alteration pattern.

Irritable Bowel Syndrome: Psychological Disorder or Poverty? Results of a Large Cross-sectional Study in Iran.

BACKGROUND: Irritable bowel syndrome (IBS) is a functional disease with no exact laboratory or imaging findings. IBS is more common in areas with a history of psychological trauma and war. This study aims to report the prevalence and possible determinants of IBS in southwestern Iran, an area with a notable history of war. METHODS: We randomly enrolled 1849 permanent residents in 29 cities aged 20 to 65 years. A validated for Farsi version Rome III criteria and a questionnaire, including demographic data and health history, were administered to each subject. Participants who fulfilled the Rome III criteria were categorized into three groups: Diarrhea dominant (IBS-D), Constipation dominant (IBS-C), and Mixed type (IBS-M). RESULTS: The total prevalence of IBS was 3.2%, with 70% of subjects being of Arab descent (P=0.004). IBS was more common in females, singles, illiterate subjects, and people younger than 30 years; however, none of these differences were statistically significant. People with depression, anxiety, self-report of psychological disorders, and very low socioeconomic status had a significantly higher prevalence of IBS (P<0.05). After multivariable logistic regression analysis, very low socioeconomic status had an independent role in IBS predictivity (OR: 2.28, 95% CI: 1.01-5.15). CONCLUSION: This study shows a higher prevalence of IBS symptoms in a population-based study in the region compared to counterparts in other regions of Iran. Considering the higher prevalence of self-reported psychological disorders, further studies are recommended to focus on the exact diagnosis of mental disorders and their influence on IBS.

Hepatoprotective properties of p-coumaric acid in a rat model of ischemia-reperfusion.

OBJECTIVE: The liver as a highly metabolic organ, has a crucial role in human body. Its function is often impressed by changes of the blood flow, hypovolemic shock, transplantation, etc. Maintaining liver function is a major challenge and there are many approaches to potentiate this organ against different stresses. Antioxidants protect organs against oxidative stress. P-coumaric acid (PC) as an oxidant has many beneficial effects. Therefore, PC was used as a pretreatment to test its potential against oxidative stress induced by liver Ischemia-reperfusion injury in rats. MATERIALS AND METHODS: In order to test the potential hepatoprotective effect of PC against IR injury, five groups of rats were used: Normal (NC; intact group); Sham; p-coumaric acid (PC); IR-CO, and PC-IR. PC, Sham, NC, PC-IR and IR-CO groups that received vehicle or p-coumaric acid at a dose of 100 mg/kg for 7 consecutive days as pretreatment before IR induction. Animals in PC-IR, and IR-CO groups underwent hepatic IR injury. Liver levels of antioxidants were determined and functional liver tests were done. Hematoxylin and eosin staining was done to determine the structural changes of the liver. Gene expression of caspase-3 was also assessed. RESULTS: Hepatic IR injury disrupted liver function by increasing the levels of AST, and ALT, and decreasing GSH, SOD and catalase. PC significantly decreased liver inflammation, reverted liver functional enzymes and antioxidants levels to normal, reduced the gene expression of caspase-3 in PC-IR rats compared to the IR-CO group. CONCLUSION: These findings revealed that PC through improving liver´s antioxidants, liver functional tests and down-regulating apoptotic gene protein, caspase-3, protects the liver against injury induced by IR.

Objective Structured Practical Examination in Experimental Physiology Increased Satisfaction of Medical Students.

BACKGROUND: Medical education is a dynamic process, which needs to be improved to meet the new expectations of medical practitioners, health workers, and communities from different countries. An important part of medical students' education is to select an appropriate assessment method. In this regard, the objective structured practical examination (OSPE) can evaluate practical capabilities in a suitable step-wise, scientific, targeted and scheduled manner with direct consideration of student's performance during programmed test stations. The purpose of this study is to investigate the outcomes of the OSPE utilization versus traditional practical examination (TPE) for evaluating students in experimental physiology. METHODS: Totally, 120 medical students were chosen as the participants of this study: 1. TPE group (TPE used as a final exam; n=40); 2. TPE + OSPE group (TPE applied for half of topics and OSPE for another half; n=41); and 3. OSPE group (OSPE performed as a final exam; n=39). In order to evaluate the effect of OSPE, the average final grade of studied groups was compared. In addition, a 5-point Likert scale questionnaire, consisting of 10 questions was used to evaluate the students' attitudes toward using this method. RESULTS: The obtained results showed that the total grade in TPE group was significantly higher in comparison to TPE+OSPE and OSPE groups (respectively, P<0.01 and P<0.05), while according to students' expression, the average score for all of the items in feedback questionnaire was increased significantly in TPE+OSPE and OSPE groups compared with TPE group (P<0.001). CONCLUSION: In summary, feedback from students showed that they were in favor of OSPE compared with the TPE, and according to their statements in a feedback questionnaire, OSPE can improve learning in physiology as well as increasing students' satisfaction.

The Khuzestan Comprehensive Health Study (KCHS): Methodology and Profile of Participants.

BACKGROUND: Non-communicable diseases (NCDs) are the leading cause of death worldwide, with a disproportionally rising burden among low- and middle-income populations. While preventable risk factors highly contribute to this burden, population-based studies assessing these factors and the health status of these populations, are scarce. METHODS: The Khuzestan Comprehensive Health Study (KCHS)-a cross sectional study-was conducted between 2016-2019, including 30,506 Iranians aged 20 to 65 years, from 27 counties of Khuzestan province, southwest of Iran. KCHS aimed to provide a comprehensive health overview by investigating the prevalence and risk factors of NCDs and psychological disorders, along with viral hepatitis as a common communicable disease. Upon registration, 15 mL of blood and anthropometric measurements were obtained from participants. Afterwards, several interviewer-administered questionnaires were completed to gather data on demographics, socioeconomic status, sleep quality, physical activity, lifestyle habits, nutrition, and medical history. RESULTS: The mean ± SD age of participants was 41.7 ± 11.9 years. The majority were female (64.3%), of the Arab ethnicity (49%), married (83%), and urban residents (73.1%). About 70% had an educational level below high school diploma. Overall, 10.8%, 5.2%, and 2.8% of participants had used cigarettes, hookah, and drugs at least once in their lifetime, respectively. While body mass index and serum cholesterol levels were higher in females, blood pressure was higher in males (P<0.001). CONCLUSION: KCHS assessed many aspects of health in the Khuzestan province. In addition to develop a biobank along with a comprehensive dataset, KCHS will serve as a valuable infrastructure for future research.