Germline mosaicism in a family with MBD5 haploinsufficiency.

Haploinsufficiency of the methyl-CpG-binding domain protein 5 (MBD5) gene causes a neurodevelopmental disorder that includes intellectual disability, developmental delay, speech impairment, seizures, sleep disturbances, and behavioral difficulties. Microdeletion of 2q23.1 is the most common cause of haploinsufficiency, although MBD5 haploinsufficiency may also cause this genetic disorder. We report a family harboring a heterozygous loss-of-function variant in MBD5 (NM_018328.5:c.728delC; p.Pro243Hisfs*26), which includes three affected siblings with varying phenotypic features. Both parents were phenotypically normal but deep coverage sequencing of the parents showed germline mosaicism in the mother.

Trends in snakebite deaths in India from 2000 to 2019 in a nationally representative mortality study.

The World Health Organization call to halve global snakebite deaths by 2030 will require substantial progress in India. We analyzed 2833 snakebite deaths from 611,483 verbal autopsies in the nationally representative Indian Million Death Study from 2001 to 2014, and conducted a systematic literature review from 2000 to 2019 covering 87,590 snakebites. We estimate that India had 1.2 million snakebite deaths (average 58,000/year) from 2000 to 2019. Nearly half occurred at ages 30-69 years and over a quarter in children < 15 years. Most occurred at home in the rural areas. About 70% occurred in eight higher burden states and half during the rainy season and at low altitude. The risk of an Indian dying from snakebite before age 70 is about 1 in 250, but notably higher in some areas. More crudely, we estimate 1.11-1.77 million bites in 2015, of which 70% showed symptoms of envenomation. Prevention and treatment strategies might substantially reduce snakebite mortality in India.

Comparative evaluation of three noninvasive gingival displacement systems: An in vivo study.

AIM: An attempt is made to investigate clinical efficacy of cord, paste system, and a strip gingival retractile materials. This study aims to evaluate and compare the gingival retraction efficacy of retraction strip along with conventional retraction cord and paste system. MATERIAL AND METHODS: This in vivo experimental study was carried out on 30 patients. Three different gingival retraction systems were used to evaluate the amount of vertical and lateral displacement.Based on selection criteria, 30 individuals requiring fixed dental prosthesis with respect to mandibular first molar were selected. Tooth preparation for metal ceramic restoration with subgingival finish line was performed. Gingival displacement was accomplished with ultrapak cord, merocel strip, and magic foam cord immediately, 7 and 14 days after the tooth preparation, respectively. The amount of gingival displacement in vertical and lateral directions was measured at mesiobuccal, midbuccal, and distobuccal regions of the prepared tooth. The vertical retraction was measured intraorally by using digital vernier caliper, and postgingival displacement impression was used to measure lateral gingival retraction. Stereomicroscopic images of impression under ×10 resolution were transferred to image analyzer to measure the lateral displacement. The obtained data analyzed in one-way ANOVA and Bonferroni test were used to determine the significant difference at P < 0.05 level. RESULTS: ANOVA test showed the significant difference between the materials tested with respect to the mean vertical and lateral gingival retraction (P = 0.001). Multiple comparisons by Bonferroni test revealed a significant difference in vertical and lateral displacement among the materials tested. CONCLUSIONS: Merocel strip provided the maximum amount of vertical and lateral tissue displacement, followed by ultrapak cord and least with magic foam cord which was statistically significant.

Effects of body mass index, tobacco smoking, alcohol drinking and solid fuel use on the risk of asthma: Individual Participant Data (IPD) meta-analysis of 175†000 individuals from 51 nationally representative surveys.

BACKGROUND: We assessed the relationship of body mass index (BMI), smoking, drinking and solid fuel use (r; SFU), and the individual and combined effects of these factors on wheezing symptoms (WS) and on diagnosed asthma (DA). METHODS: We analysed 175 000 individuals from 51 nationally representative surveys, using self-reports of WS and DA as the measures of asthma. The fixed-effects and random-effects estimates of the pooled ORs between asthma and underweight (BMI <18.5 kg/m(2)), obesity (BMI ≥30 kg/m(2)), smoking, drinking and SFU were reported. RESULTS: The pooled risks of all individual risk factors were significantly associated with WS and DA (with the exception of current smoking with DA in women and SFU with DA in both genders). Stronger dose-response relationships were seen in women for smoking amounts and duration; BMI showed stronger quadratic relationships. The combined risks were generally larger in women than in men, with significant risks for underweight (OR=2.73) as well as obese (OR=2.00) smokers for WS (OR=2.13 and OR=1.58 for DA, respectively). The magnitude of the combined effects from low/high BMI, smoking and drinking were also consistently higher among women than among men in WS and DA. SFU among underweight smokers also had positive association with WS (men and women) and DA (women). CONCLUSIONS: BMI, smoking, drinking and SFU-in combination-are associated with double or triple the risk of development of asthma. These risk factors might help explain the wide variation in asthma burden across countries.

Exposure to second-hand smoke and the risk of tuberculosis in children and adults: a systematic review and meta-analysis of 18 observational studies.

BACKGROUND: According to WHO Global Health Estimates, tuberculosis (TB) is among the top ten causes of global mortality and ranks second after cardiovascular disease in most high-burden regions. In this systematic review and meta-analysis, we investigated the role of second-hand smoke (SHS) exposure as a risk factor for TB among children and adults. METHODS AND FINDINGS: We performed a systematic literature search of PubMed, Embase, Scopus, Web of Science, and Google Scholar up to August 31, 2014. Our a priori inclusion criteria encompassed only original studies where latent TB infection (LTBI) and active TB disease were diagnosed microbiologically, clinically, histologically, or radiologically. Effect estimates were pooled using fixed- and random-effects models. We identified 18 eligible studies, with 30,757 children and 44,432 adult non-smokers, containing SHS exposure and TB outcome data for inclusion in the meta-analysis. Twelve studies assessed children and eight studies assessed adult non-smokers; two studies assessed both populations. Summary relative risk (RR) of LTBI associated with SHS exposure in children was similar to the overall effect size, with high heterogeneity (pooled RR 1.64, 95% CI 1.00-2.83). Children showed a more than 3-fold increased risk of SHS-associated active TB (pooled RR 3.41, 95% CI 1.81-6.45), which was higher than the risk in adults exposed to SHS (summary RR 1.32, 95% CI 1.04-1.68). Positive and significant exposure-response relationships were observed among children under 5 y (RR 5.88, 95% CI 2.09-16.54), children exposed to SHS through any parent (RR 4.20, 95% CI 1.92-9.20), and children living under the most crowded household conditions (RR 5.53, 95% CI 2.36-12.98). Associations for LTBI and active TB disease remained significant after adjustment for age, biomass fuel (BMF) use, and presence of a TB patient in the household, although the meta-analysis was limited to a subset of studies that adjusted for these variables. There was a loss of association with increased risk of LTBI (but not active TB) after adjustment for socioeconomic status (SES) and study quality. The major limitation of this analysis is the high heterogeneity in outcomes among studies of pediatric cases of LTBI and TB disease. CONCLUSIONS: We found that SHS exposure is associated with an increase in the relative risk of LTBI and active TB after controlling for age, BMF use, and contact with a TB patient, and there was no significant association of SHS exposure with LTBI after adjustment for SES and study quality. Given the high heterogeneity among the primary studies, our analysis may not show sufficient evidence to confirm an association. In addition, considering that the TB burden is highest in countries with increasing SHS exposure, it is important to confirm these results with higher quality studies. Research in this area may have important implications for TB and tobacco control programs, especially for children in settings with high SHS exposure and TB burden.