Recent insights into the roles of circular RNAs in human brain development and neurologic diseases.

Circular RNAs (circRNAs) are a novel class of non-coding RNAs. They are single-stranded RNA transcripts characterized with a closed loop structure making them resistant to degrading enzymes. Recently, circRNAs have been suggested with regulatory roles in gene expression involved in controlling various biological processes. Notably, they have demonstrated abundance, dynamic expression, back-splicing events, and spatiotemporally regulation in the human brain. Accordingly, they are expected to be involved in brain functions and related diseases. Studies in animals and human brain have revealed differential expression of circRNAs in brain compartments. Interestingly, contributing roles of circRNAs in the regulation of central nervous system (CNS) development have been demonstrated in a number of studies. It has been proposed that circRNAs play role in substantial neurological functions like neurotransmitter-associated tasks, neural cells maturation, and functions of synapses. Furthermore, 3 main pathways have been identified in association with circRNAs's host genes including axon guidance, Wnt signaling, and transforming growth factor beta (TGF-ß) signaling pathways, which are known to be involved in substantial functions like migration and differentiation of neurons and specification of axons, and thus play role in brain development. In this review, we have an overview to the biogenesis, biological functions of circRNAs, and particularly their roles in human brain development and the pathogenesis of neurodegenerative diseases including Alzheimer's diseases, multiple sclerosis, Parkinson's disease and brain tumors.

Association of Vitamin D Status with SARS-CoV-2 Infection or COVID-19 Severity: A Systematic Review and Meta-analysis.

This systematic review was conducted to summarize and clarify the evidence on the association between 25-hydroxyvitamin-D [25(OH)D] concentrations and coronavirus disease 2019 (COVID-19) risk and outcomes. PubMed, Scopus, and Web of Science databases and Google Scholar were searched up to 26 November 2020. All retrospective and prospective cohort, cross-sectional, case-control, and randomized controlled trial studies that investigated the relation between 25(OH)D and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19 severity were included. Thirty-nine studies were included in the current systematic review. In studies that were adjusted (OR: 1.77; 95% CI: 1.24, 2.53; I2: 44.2%) and nonadjusted for confounders (OR: 1.75; 95% CI: 1.44, 2.13; I2: 33.0%) there was a higher risk of SARS-CoV-2 infection in the vitamin D deficiency (VDD) group. Fifteen studies evaluated associations between VDD and composite severity. In the studies that were adjusted (OR: 2.57; 95% CI: 1.65, 4.01; I2 = 0.0%) and nonadjusted for confounders (OR: 10.61; 95% CI: 2.07, 54.23; I2 = 90.8%) there was a higher severity in the VDD group. Analysis of studies with crude OR (OR: 2.62; 95% CI: 1.13, 6.05; I2: 47.9%), and adjusted studies that used the Cox survival method (HR: 7.67; 95% CI: 3.92, 15.03; I2: 0.0%) indicated a significant association of VDD with mortality, while in adjusted studies that used logistic regression, no relation was observed (OR: 1.05; 95% CI: 0.63, 1.75; I2: 76.6%). The results of studies that examined relations between VDD and intensive care unit (ICU) admission, pulmonary complications, hospitalization, and inflammation were inconsistent. In conclusion, although studies were heterogeneous in methodological and statistical approach, most of them indicated a significant relation between 25(OH)D and SARS-CoV-2 infection, COVID-19 composite severity, and mortality. With regard to infection, caution should be taken in interpreting the results, due to inherent study limitations. For ICU admission, inflammation, hospitalization, and pulmonary involvement, the evidence is currently inconsistent and insufficient.

The effect of cinnamon supplementation on lipid profiles in patients with type 2 diabetes: A systematic review and meta-analysis of clinical trials.

OBJECTIVE: The present systematic review and meta-analysis was performed to evaluate the effect of cinnamon supplementation on blood lipid profiles in patients with type 2 diabetes. METHODS: A systematic search (with no language restrictions) was performed in PubMed, Embase, Scopus, Web of Science, and Cochrane Library to identify relevant clinical trials up to 8th March 2020. Weighted mean differences (WMDs) and 95 % confidence intervals (CI) were pooled based on the random-effects model. Heterogeneity, publication bias, and sensitivity analyses were performed based on standard methods. RESULTS: Sixteen studies, involving 1025 participants, were included in the meta-analysis. This study found a significant decrease in triglycerides (TG) (WMD: -26.27 mg/dl, 95 % CI: [-38.93, -13.61], P < 0.001), total cholesterol (TC) (WMD: -13.93 mg/dl, 95 % CI: [-25.64, -2.22], P = 0.020), and low-density lipoprotein cholesterol (LDL-C) levels (WMD: -6.13 mg/dl, 95 % CI: [-10.72, -1.53], P = 0.009), while no change was observed on high-density lipoprotein cholesterol (HDL) concentration (WMD: 0.64 mg/dl, 95 % CI: [-0.18, 1.46], P = 0.128), in patients with type 2 diabetes. The reduction in TG, TC, and LDL-C was greater in; Eastern compared to Western countries, and studies with a duration of < 2 compared to ≥ 2 months. The increase in HDL was greater in; participants with a BMI ≥ 30 compared to <30, Western compared to Eastern countries, and intervention durations of ≥ 2 compared to < 2 months. CONCLUSIONS: Cinnamon supplementation significantly decreased serum TG, TC, and LDL-C concentrations, but did not change HDL-C levels, in patients with type 2 diabetes.

The Effect of Nutritional Education Based on Health Belief Model on Nutritional Knowledge, Health Belief Model Constructs, and Dietary Intake in Hemodialysis Patients.

BACKGROUND: Based on the results of many studies on the relationship between nutritional status and clinical implications in dialysis patients, malnutrition is one of the most important factors associated with mortality in these patients. The current study examined the effect of nutritional education based on Health Belief Model (HBM) on nutritional knowledge, HBM constructs, and dietary intake in Hemodialysis (HD) patients. MATERIALS AND METHODS: One-hundred chronic HD patients entered to this randomized clinical trial in 2017 in Iran; 41 in control group and 45 in intervention group completed the study. Demographic data and four 24-h recalls were collected. To evaluate the nutritional knowledge and HBM constructs, a researcher-made questionnaire was used. Patients were evaluated before, immediately after, and 3 months after intervention. Eight 1-h education sessions in 4 weeks were considered for intervention group. Independent samples t-test, Chi-square test, and repeated measures ANOVA were used to analyze the data. RESULTS: Repeated measures ANOVA test showed significant increases in scores of the nutritional knowledge test, perceived susceptibility, perceived severity, perceived barriers (p = < 0.001), perceived benefits (p = 0.010), and self-efficacy (p = 0.019) after the study in the intervention group. There were no significant differences between two groups in energy, protein, High Biologic Value (HBV) protein, carbohydrate, fat, cholesterol, fiber, vitamin B2, B3, B6, B12, E, calcium, phosphorus, and potassium intake. CONCLUSIONS: It seems that education based on HBM can improve nutritional knowledge but in order to influence on dietary intake, longer interventions that are more comprehensive are needed.

Effects of Daily Consumption of Cashews on Oxidative Stress and Atherogenic Indices in Patients with Type 2 Diabetes: A Randomized, Controlled-Feeding Trial.

BACKGROUND: Cashews, as the main source of monounsaturated (MUFAs) and polyunsaturated (PUFAs) fatty acids, are associated with reduced risk of cardiovascular diseases. Despite evidence for beneficial effects of nuts on lipid profile and glycemic control, to the authors' best knowledge, little is known about cashews. METHODS: An eight-week, randomized, isocaloric, controlled-feeding study was conducted on 50 patients with type 2 diabetes mellitus (T2DM) randomly assigned to either the control or intervention group (10% of total calorie from cashews). Weight, fasting plasma glucose (FPG), serum insulin concentration and sensitivity, lipid profile ratio, high-sensitive C-reactive protein (hs-CRP), total antioxidant capacity (TAC), and paraoxonase-1 (PON-1) were measured at baseline and after eight weeks of intervention adjusted for age, gender, baseline values of FPG, insulin, HOMA-IR (homeostatic model assessment of insulin resistance), fiber, and both baseline and post-intervention vitamin C levels as covariates. RESULTS: Weight, body mass index (BMI), and waist circumference (WC) were not significantly different in the groups after eight weeks of intervention, as well as between the two groups, compared with the baseline measures. At the end of the study, serum insulin and low-density lipoprotein-cholesterol-to-high-density lipoprotein-cholesterol (LDL-C/HDL-C) ratio significantly decreased in the cashews group compared with those of the controls (P = 0.01 and P = 0.04, respectively). Although, HOMA-IR decreased significantly in the cashews group (P = 0.03), changes were not significant compared with the baseline measures (P = 0.056). Despite more increase in PON-1 activity in the cashews group, the changes were not statistically significant. CONCLUSIONS: Daily consumption of cashews reduced serum insulin and LDL-C/HDL-C ratio in patients with T2DM. However, further studies with larger sample sizes and more duration are needed to confirm the current study results.

Does Alpha-lipoic Acid Supplementation Modulate Cardiovascular Risk Factors in Patients with Stroke? A Randomized, Double-blind Clinical Trial.

BACKGROUND: Stroke as a devastating condition is one of the major causes of death worldwide. It is accountable for long time disability with high personal and social cost in adults. There are several risk factors for stroke such as diabetes and hypertension. Alpha-lipoic acid (ALA) as an antioxidant can be a risk modifier in these patients. We designed this trial to scrutinize the possible effects of ALA consumption on some cardiovascular risk factors in patients experienced stroke. METHODS: In this randomized, double-blind, placebo-controlled clinical trial, 67 patients experienced stroke were randomly allocated into two groups (taking a 600 mg ALA supplement or placebo daily for 12 weeks). Fasting blood sugar (FBS), fasting insulin and systolic (SBP), and diastolic blood pressure (DBP) were measured before and after intervention in this study. Statistical analyses were performed using SPSS version 16 (SPSS Inc., Chicago, IL, USA) software. RESULTS: Primary features were similar in the intervention and placebo groups (P > 0.05). After the intervention period, SBP (P < 0.001), DBP (P < 0.001) and FBS (P < 0.001) reduced in ALA group compared with placebo group, significantly. No significant change was seen in insulin level (P = 0.82). CONCLUSIONS: Results of this trial indicated that 12 weeks supplementation with 600 mg ALA has beneficial effects on SBP, DBP, and FBS but has no effect on insulin level.

The effects of specific expression of apoptin under the control of PSES and PSA promoter on cell death and apoptosis of LNCaP cells.

OBJECTIVES: Apoptotic effect of apoptin has been demonstrated in numerous studies. However, its tumor specificity has been questioned by some reports. The aim of this study was to confine the expression of apoptin in the prostate tumor cells by inducing its gene expression under the control of a chimeric enhancer composing of prostate-specific membrane antigen (PSMA) and prostate-specific antigen (PSA) regulatory elements (PSES). Furthermore, we investigated the effects of apoptin expression on LNCaP prostate carcinoma cell survival and apoptosis using MTT assay and annexin V/7-AAD flow cytometry assay. MATERIALS AND METHODS: Recombinant plasmids containing apoptin gene under the control of PSES/PSA promoter or Cytomegalovirus (CMV) promoter were constructed. Tumor cell lines including LNCaP cells and HeLa cells, and LX-2 cells (as a normal control) were transfected with the plasmids and the expression of apoptin was evaluated by real time-PCR and western blot analyses. The effects of apoptin expression on cell survival and apoptosis were then investigated using MTT and annexinV/7-AAD flow cytometry assay, respectively. RESULTS: Western blot and real time PCR analyses confirmed the specific expression of apoptin under the control of PSES/PSA regulatory element in the LNCaP cells, while CMV promoter caused apoptin expression in both tumor and normal cell lines. Apoptin expression significantly increased cell death and apoptosis in tumor cells when compared with the normal cells (P<0.001). CONCLUSION: These results suggest that PSES/PSA regulatory element may be considered as an efficient approach for specific expression of apoptin gene in prostate tumor cells and treatment of prostate cancer.

The effect of alpha-lipoic acid supplementation on anthropometric indices and food intake in patients who experienced stroke: A randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND: Stroke as a devastating condition is a major cause of death worldwide. It is accountable for long-term disability with high personal and social cost in adults. Alpha-lipoic acid (ALA) is an eight-carbon, sulfur-containing compound with antioxidant properties which reduces body weight, changes other anthropometric indices, and regulates food intake by suppressing appetite and increasing metabolism This study was designed to evaluate the possible effects of ALA supplementation on anthropometric indices and dietary intake in patients with stroke. MATERIALS AND METHODS: In this randomized, double-blind, placebo-controlled clinical trial, 67 patients with stroke were randomly allocated to two groups (taking a 600 mg ALA supplement or placebo daily for 12 weeks). Weight, waist circumference, energy, carbohydrate, protein, and fat intake were measured, and body mass index (BMI) was calculated before and after intervention. Dietary intake and statistical analyses were carried out using Nutritionist IV and SPSS (version 16; SPSS Inc., Chicago, IL, USA) software, respectively. RESULTS: Primary features were similar in the intervention and placebo groups (P > 0.05). Waist circumference (P < 0.001), energy, carbohydrate, protein, and fat intake (P < 0.001) decreased significantly, after the intervention period, in ALA group compared with placebo. While no significant change was observed in weight (P = 0.26) and BMI (P = 0.56) in ALA supplementation group compared with placebo. CONCLUSION: Results of this trial indicated that 12-week supplementation with 600 mg ALA can decrease waist circumference and food intake (energy, carbohydrate, protein, and fat) in patients with stroke.

Development and psychometric evaluation of a new instrument to assess nutritional perceptions and behaviors of diabetic men.

BACKGROUND: It is obvious that unhealthy nutritional behaviors have caused the increasing incidence of diabetes. This study aimed to design the Measure of Nutritional Perceptions and Behaviors in diabetic men and to evaluate its psychometric properties. METHODS: A questionnaire was developed within 7 factors. Three methods of face validity, content validity, and construct validity were employed to ensure the validity of the scale. 206 men with diabetes completed the questionnaires. Internal was used to evaluate the reliability of the scale. RESULTS: The mean age of men was 58.26 (9.74) years. Results showed that each item in the final questionnaire was highly correlated with the total score of each dimension P<0.05. Moreover, factor analysis led to the extraction of 36 items with acceptable factor loadings in the range of 0.41 to 0.84, which could account for 51% of the total variance. The Cronbach's alpha coefficient equal to 0.83 was obtained for the whole scale. CONCLUSION: The reliability and validity of diabetic men's beliefs about healthy nutritional behaviors were desired and the overall structure of the questions was confirmed. This questionnaire can be used to identify individuals at risk for unhealthy nutritional behaviors and also to conduct and evaluate the impact of educational interventions.

Does Alpha-lipoic Acid Supplement Regulate Blood Pressure? A Systematic Review of Randomized, Double-blind Placebo-controlled Clinical Trials.

Although several animal and human studies have investigated the effect of alpha-lipoic acid (ALA) on blood pressure (BP), these findings are inconsistent. This systematic review of randomized clinical trials was conducted to summarize the evidence on the effect of ALA on BP. PubMed, SCOPUS, and Google Scholar databases were searched based on MESH term ("Thioctic acid" in combination with "Hypertension" and "Blood pressure") to identify related papers published up to December 2015. We summarized the results of the relevant studies in this review. In total, nine studies included in this review, seven parallel-designed trials and two crossover-designed trials. The results of parallel-designed studies are inconsistent. Five studies indicate no significant effects for ALA supplementation on BP, but two trials show effects on BP. Unlike parallel-designed trials, two crossover-designed trials have shown similar results and both report no effect for ALA on BP. Several studies investigated the effect of ALA on BP. Most of the papers show no significant effect for supplementation and the studies have shown that associations are limited. However, these findings are limited and there is a need for further and more accurate researches to be clarified.

The Effect of Symbiotic Supplementation on Liver Enzymes, C-reactive Protein and Ultrasound Findings in Patients with Non-alcoholic Fatty Liver Disease: A Clinical Trial.

BACKGROUND: Regarding to the growing prevalence of nonalcoholic fatty liver disease (NAFLD), concentrating on various strategies to its prevention and management seems necessary. The aim of this study was to determine the effects of symbiotic on C-reactive protein (CRP), liver enzymes, and ultrasound findings in patients with NAFLD. METHODS: Eighty NAFLD patients were enrolled in this randomized, double-blind, placebo-controlled clinical trial. Participants received symbiotic in form of a 500 mg capsule (containing seven species of probiotic bacteria and fructooligosaccharides) or a placebo capsule daily for 8 weeks. Ultrasound grading, CRP, and liver enzymes were evaluated at the baseline and the end of the study. RESULTS: In the symbiotic group, ultrasound grade decreased significantly compared to baseline (P < 0.005) but symbiotic supplementation was not associated with changes in alanine aminotransferase (ALT) and aspartate transaminase (AST) levels. In the placebo group, there was no significant change in steatosis grade whereas ALT and AST levels were significantly increased (P = 0.002, P = 0.02, respectively). CRP values remained static in either group. CONCLUSIONS: Symbiotic supplementation improved steatosis in NAFLD patients and might be useful in the management of NAFLD or protective against its progression.

Ovarian cancer risk and nonisoflavone flavonoids intake: A systematic review of epidemiological studies.

BACKGROUND: Although several studies have investigated the association between ovarian cancer risk and nonisoflavone flavonoids intake, these findings are inconsistent. This systematic review of published epidemiological studies was conducted to summarize and clarify the evidence on the association between ovarian cancer incidence and nonisoflavone flavonoids intake. MATERIALS AND METHODS: PubMed, Scopus, Google Scholar, and EMBASE databases were searched based on MeSH term (ovarian neoplasm in combination with flavonoids) to identify related English and non-English papers published up to June 2016. We summarized the results of the relevant studies in this review. RESULTS: In total, seven studies (four with cohort and three with case-control design) included in this review. The results of conducted cohort studies show no relation between ovarian cancer risk and total nonisoflavone flavonoids intake, and only one study reported a significant reduction between ovarian cancer incidence and kaempferol and luteolin intake. Similar to those in the cohort studies, also in case-control studies, no association was found between total nonisoflavone flavonoids intake and ovarian cancer risk, just an inverse association between flavonols intake and ovarian cancer was reported. CONCLUSION: Several studies investigated the relation of nonisoflavone flavonoids intake and ovarian cancer risk; none of them reported any association for total nonisoflavone flavonoids intake, but some reported an inverse association between certain subclasses or individual flavonoids. These findings are limited, and there is a need for further and more accurate researches to be confirmed.

Effects of blackberry (Morus nigra L.) consumption on serum concentration of lipoproteins, apo A-I, apo B, and high-sensitivity-C-reactive protein and blood pressure in dyslipidemic patients.

BACKGROUND: This study investigated blackberry (Persian mulberry) effects on apo A-I, apo B, high-sensitivity-C-reactive protein (hs-CRP), and systolic blood pressure (SBP) and diastolic blood pressure (DBP) in dyslipidemic patients. MATERIALS AND METHODS: In this 8-week randomized clinical trial, 72 dyslipidemic patients were randomly divided into two groups: Intervention (300 mL/day blackberry juice with pulp) and control group (usual diets). Before and after the intervention, fasting blood samples were taken from both groups and serum concentration of lipoprotein, apo A-I and apo B, serum lipids (total cholesterol, low-density lipoprotein, high-density lipoprotein [HDL], and triglyceride), hs-CRP were measured. Blood pressure before and after the study was measured with a mercury manometer. RESULTS: At week 8 in the intervention group, apo A-I and HDL increased significantly (P = 0.015, P = 0.001, respectively), apo B and hs-CRP decreased significantly (P = 0.044, P = 0.04, respectively). Mean changes in apo A-I and HDL and apo B/apo A-I ratio were significant between the groups (P = 0.005, P = 0.014, and P = 0.009, respectively). After 8 weeks, there was a significant difference between hs-CRP mean values (P = 0.01) of the groups. At week 8, SBP decreased significantly (P = 0.005) in the intervention group with no significant differences for SBP mean values between the groups. No significant changes were observed in other lipid parameters and DBP in the intervention group and between the groups. CONCLUSION: Blackberry consumption may exert beneficial effects on apolipoproteins, blood pressure, and inflammatory markers in individuals with lipid disorders.

A survey of sued physicians' self-reported reactions to malpractice litigation in Iran.

OBJECTIVE: To illustrate the psychological effect of grievances and negligence litigation on doctors sued by Legal Medicine Organization Complaints Commissions. METHODS: Retrospective survey regarding the views of a large sample of Iranian sued physicians by using a piloted anonymous questionnaire. RESULTS: The answer rate was 77.5%. Seventy-six per cent of participants encountered monitoring criteria for psychiatric disturbance. Rate of psychological morbidity in between study cluster was much higher than Iranian general population, Iranian non-sued general practitioners, interns and medical students. There was, however, minimal dysfunction of work, public or family life. The survey form to estimate the doctor's realization of lawful risk displayed that doctors yet misconceive medico-legal risk. Doctors being sued or having legal protests against them depict the process as an exceedingly demanding event. CONCLUSIONS: Grievance or legal action is unusual in the daily practice of doctors, but in today's medico-legal domain they face a continuous possible threat. The threat of, or real, legal process can cause psychological, corporeal and behavioral practice changes.