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Exome sequencing has readily enabled the discovery of the genetic mutations responsible for a wide range of diseases. This success has been particularly remarkable in the severe epilepsies and other neurodevelopmental diseases for which rare, often de novo, mutations play a significant role in disease risk. Despite significant progress, the high genetic heterogeneity of these disorders often requires large sample sizes to identify a critical mass of individuals with disease-causing mutations in a single gene. By pooling genetic findings across multiple studies, we have identified six individuals with severe developmental delay (6/6), refractory seizures (5/6), and similar dysmorphic features (3/6), each harboring a de novo mutation in PPP3CA. PPP3CA encodes the alpha isoform of a subunit of calcineurin. Calcineurin encodes a calcium- and calmodulin-dependent serine/threonine protein phosphatase that plays a role in a wide range of biological processes, including being a key regulator of synaptic vesicle recycling at nerve terminals. Five individuals with de novo PPP3CA mutations were identified among 4,760 trio probands with neurodevelopmental diseases; this is highly unlikely to occur by chance (p = 1.2 × 10-8) given the size and mutability of the gene. Additionally, a sixth individual with a de novo mutation in PPP3CA was connected to this study through GeneMatcher. Based on these findings, we securely implicate PPP3CA in early-onset refractory epilepsy and further support the emerging role for synaptic dysregulation in epilepsy.

Few dietary patterns are related to reduce the Bladder Cancer (BC) risk. One of the well-known dietary patterns is the Mediterranean diet (MD). This case-control study investigated the association between MD and the odds of BC among Iranian population. The present case-control study was performed on 103 eligible cases and 200 controls age 45 to 92 years. Diet of participants was assessed by a validated 168-item food frequency questionnaire (FFQ). Adherence to MD was measured by Mediterranean-Style Dietary Pattern Score (MSDPS). Multivariate logistic regression was used to estimate the relationship between MSDPS and risk of BC. After controlling for potential confounders, a negative association was observed between MSDPS and risk of BC (OR = 0.22; 95%CI = 0.09–0.52; p trend = 0.001). Furthermore, significant negative associations were observed for dairy, fish and other seafood, whole-grain, bread intake and risk of BC (p for trend < 0.05). In contrast, the risk of BC increased for high intake of poultry (OR = 1.09; 95%CI = 1.03–1.15; p trend = 0.003), sweets (OR = 1.24; 95%CI = 1.03–1.48; p trend = 0.018) and egg (p for trend = 0.01). Our results suggested that dietary habit in concordance with the principles of the Mediterranean dietary pattern may protect against BC. [ABSTRACT FROM AUTHOR]

Background: Evidence suggests that dietary pattern is related to incidence and grades of nonalcoholic fatty liver disease (NAFLD). The aim of this study was to investigate the relationship between major dietary patterns and hepatic histologic features of newly diagnosed patients with NAFLD. Methods: This cross-sectional study included 260 newly diagnosed NAFLD patients. Hepatic fibrosis and steatosis were diagnosed using Fibroscan. Dietary information was obtained using a validated 168-item semiquantitative food frequency questionnaire. The association between dietary patterns and odds ratio of the grade of fibrosis and steatosis was examined by multinomial logistic regression. Results: The mean ± SD age participant was 46.53 ± 11.71 years. Fifty-seven percent of the participants were women. Two major dietary patterns were recognized: "Western dietary pattern" and "Mediterranean dietary pattern." After adjustment for various confounders, adherence to the two extracted dietary patterns was not associated with odds of fibrosis and steatosis (P > 0.05). However, P was not significant. Patients in the second quartile of the Mediterranean dietary pattern had a higher risk for being in the F1 grade compared to those in the reference group in the crude and adjusted model. Conclusions: The major dietary patterns of NAFLD patients living in Gilan were not related to the severity of their disease. More precise study design such as cohort or interventional studies is suggested to reveal the strength of this study findings. [ABSTRACT FROM AUTHOR]

Destructive outcomes of coronavirus pandemic call for medical research which can report all of the influential agents not only for the treatment of the disease but also preventing its severe impacts on the societal health in the most efficient manner. Zinc plays an integral role in the function of cellular enzymes and transcription factors. Owing to its anti-inflammatory and cellular immunity regulation activity, zinc is regarded to be effective on strengthening the immune system. Its crucial antiviral effects have long been established as well. Studies suggest that low serum zinc level predisposes the patient to severe COVID-19 infection, which makes patient's zinc profile a potential determinant of prognosis and severity of this disease. Furthermore, zinc supplementation has indicated promising outcomes of coronavirus infection management. Zinc modulates cell-mediated immunity and participates in the killing of microorganisms in cytotoxic immune cells. Zn2+ has anti-inflammatory effects by inhibiting IL-6 production. Although there is still not enough evidence, it seems that zinc could be a promising supplementary treatment for COVID-19 especially in zinc-deficient patients. The aim of this review is to clarify the role of zinc in pathogenesis and therapy of COVID-19 in detail. [ABSTRACT FROM AUTHOR]

Background: The aim of the present study was assessing the changes in Iranian household food basket. The Households Income and Expenditure Survey (HIES) data of 717,432 of Iranian households from 1991 to 2017 were used in this repeated cross-sectional study. Methods: A cross-classified random-effects modeling (CCREM) specifications of hierarchical age-period-cohort (HAPC) in two models, one without controlling for the effects of key individual characteristics, namely socioeconomic status; household size; place; and household head sex, and another one with controlling for the effect of mentioned variables, was used in the present study. Results: The present study showed that the equivalent to an adult male daily consumption of "total calorie" (P value = 0.0001) and "fats, oils, sugars, and sweets" (P value = 0.0002) had an increasing trend from 1991 to 2004 and a decreasing trend from 2005 to 2017 among Iranian households. The daily consumption of "bread, cereal, rice, and pasta" (P value = 0.0001) had a decreasing and "fruits" (P value = 0.0002) had a rising trend during periods. After an increasing trend for the "meat, poultry, fish, eggs, legumes, and nuts" (P value = 0.0002) and "vegetable" (P value=<0.0001) by 2004, there was a decreasing trend from 2004 to 2017, but the share of them in the total calorie consumption increased. The "dairy" (P value = 0.0002) consumption had a decreasing trend in recent years. Conclusions: Iranian household food basket, during these years, had significant changes that some of them (increase in the share of the vegetables and fruits in the total calorie intake) are positive and some of them are negative (decrease in the consumption of dairy). [ABSTRACT FROM AUTHOR]

Objectives: The 24-hour urine sodium (Na) test is the gold standard method for measuring salt intake in community studies. This study aimed to compare the results of a 24-hour urine Na test with those obtained from the salt taste sensitivity test (STST) in order to validate the STST as a possible substitute for the 24-hour urine Na test. Materials and Methods: Both tests were simultaneously performed on 30 individuals. The results were compared using correlation models. Results: STST results in the tolerance threshold had a strong and positive correlation with the results of the 24-hour urine Na (r=0.93, P < 0.001). In addition, the distance between the tolerance threshold and the recognition threshold scores was strongly correlated with the results of 24-hour urine Na (r=0.830, P < 0.001). Finally, there was no significant correlation between recognition threshold scores and 24-hour urine Na (r=0.087, P = 0.64). Conclusions: In general, the STST showed a promising potential to be replaced with the 24-hour urine Na test in community studies. [ABSTRACT FROM AUTHOR]