Loss of function,missense, and intronic variants in NOTCH1 confer different risks for left ventricular outflow tract obstructive heart defects in two European cohorts

Loss of function variants in NOTCH1 cause left ventricular outflow tract obstructive defects (LVOTO). However, the risk conferred by rare and noncoding variants in NOTCH1 for LVOTO remains largely uncharacterized. In a cohort of 49 families affected by hypoplastic left heart syndrome, a severe form of LVOTO, we discovered predicted loss of function NOTCH1 variants in 6% of individuals. Rare or low-frequency missense variants were found in 16% of families. To make a quantitative estimate of the genetic risk posed by variants in NOTCH1 for LVOTO, we studied associations of 400 coding and noncoding variants in NOTCH1 in 1,085 cases and 332,788 controls from the UK Biobank. Two rare intronic variants in strong linkage disequilibrium displayed significant association with risk for LVOTO amongst European-ancestry individuals. This result was replicated in an independent analysis of 210 cases and 68,762 controls of non-European and mixed ancestry. In conclusion, carrying rare predicted loss of function variants in NOTCH1 confer significant risk for LVOTO. In addition, the two intronic variants seem to be associated with an increased risk for these defects. Our approach demonstrates the utility of population-based data sets in quantifying the specific risk of individual variants for disease-related phenotypes.     

Success of Maternal and Child Health Pipeline Training Programs: Alumni Survey Results

Maternal and Child Health Journal - The Maternal and Child Health (MCH) Pipeline Training Program, promotes development of a diverse health workforce by training undergraduate students from...     

Sex-Dependent Effects of 7,8-Dihydroxyflavone on Metabolic Health Are Associated with Alterations in the Host Gut Microbiome

7,8-Dihydroxyflavone (DHF) is a naturally occurring flavonoid that has been reported to protect against a variety of pathologies. Chronic administration of DHF prevents high-fat diet (HFD)-induced obesity in female, but not male, mice. However, the mechanisms underlying this sexual dimorphism have not been elucidated. We have discovered that oral DHF supplementation significantly attenuates fat mass, hepatic lipid accumulation, and adipose tissue inflammation in female mice. In contrast, male mice were not protected from adiposity, and had a paradoxical worsening of hepatic lipid accumulation and adipose tissue inflammation upon DHF supplementation. Consistent with these sexually dimorphic effects on body weight and metabolic health, 7,8-DHF induced early and stable remodeling of the female intestinal microbiome. DHF supplementation significantly increased gut microbial diversity, and suppressed potentially detrimental bacteria, particularly Desulfovibrionaceae, which are pro-inflammatory and positively associated with obesity and inflammation. Changes in the female gut microbiome preceded alterations in body weights, and in silico analyses indicated that these early microbial changes were highly predictive of subsequent weight gain in female mice. While some alterations in the intestinal microbiome were also observed in male DHF-supplemented mice, these changes were distinct from those in females and, importantly, were not predictive of subsequent body weight changes in male animals. The temporality of microbial changes preceding alterations in body weight in female mice suggests a role for the gut microbiome in mediating the sexually dimorphic effects of DHF on body weight. Given the significant clinical interest in this flavonoid across a wide range of pathologies, further elucidation of these sexually dimorphic effects will aid the development of effective clinical therapies.     

A case report of an unusual presentation of ocular rhinosporidiosis as a conjunctival cystic mass

Ocular involvement of rhinosporidiosis is seen in about 15% of cases and clinically appears as a freely mobile, granular, pink, fleshy sessile or pedunculated mass. The conjunctiva is the most common site of origin. A 25-year-old male presented with a painless mass in the lower part of the left eye for 6 months which was gradually progressive. Examination revealed a pedunculated mass of 15 mm x 15 mm arising from the lower palpebrae of the left eye retracting the lower lid. It appeared to be vascular with few white spots at the apex. Rest of the ocular examinations was within the normal limit. The presentations of ocular rhinosporidiosis vary. Though the conjunctival origin is very common, it may not have a classic pink fleshy appearance at all times. A vascular/cystic painless conjunctival mass should also be considered as a case of rhinosporidiosis in prone areas.     

Rare occurrence of fatal Candida haemulonii peritonitis in a diabetic CAPD patient

A 68-year-old diabetic chronic kidney disease patient on continuous ambulatory peritoneal dialysis for two years developed Candida haemulonii peritonitis without any predisposing factors. There is no effective treatment for this fungus. A peritoneal biopsy showed morphological changes of acute inflammation and chronicity.     

Brain activation during the voiding phase of micturition in healthy adults: A meta‐analysis of neuroimaging studies

Several studies have used a variety of neuroimaging techniques to measure brain activity during the voiding phase of micturition. However, there is a lack of consensus on which regions of the brain are activated during voiding. The aim of this meta‐analysis is to identify the brain regions that are consistently activated during voiding in healthy adults across different studies. We searched the literature for neuroimaging studies that reported brain co‐ordinates that were activated during voiding. We excluded studies that reported co‐ordinates only for bladder filling, during pelvic floor contraction only, and studies that focused on abnormal bladder states such as the neurogenic bladder. We used the activation‐likelihood estimation (ALE) approach to create a statistical map of the brain and identify the brain co‐ordinates that were activated across different studies. We identified nine studies that reported brain activation during the task of voiding in 91 healthy subjects. Together, these studies reported 117 foci for ALE analysis. Our ALE map yielded six clusters of activation in the pons, cerebellum, insula, anterior cingulate cortex (ACC), thalamus, and the inferior frontal gyrus. Regions of the brain involved in executive control (frontal cortex), interoception (ACC, insula), motor control (cerebellum, thalamus), and brainstem (pons) are involved in micturition. This analysis provides insight into the supraspinal control of voiding in healthy adults and provides a framework to understand dysfunctional voiding. Clin. Anat., 2018. © 2018 Wiley Periodicals, Inc.     

Pellagra in a child–A rare entity

This case has been presented as pellagra, which is very rare in children. Pellagra is due dietary deficiency of niacin. Usually seen in alcoholics, malabsorption syndromes occur very rarely in children. A 11-y-old girl presented with well-defined, hyperpigmented, hyperkeratotic, symmetrical, thick scaly plaques surrounded by erythema on the dorsum of the hands, arms, feet, legs up to knees, and along the sides of the neck. The child was given 100 mg of Nicotinamide. Skin lesions resolved rapidly with the treatment and the child improved.