Effect of Vitamin D and Docosahexaenoic Acid Co-Supplementation on Vitamin D Status,Body Composition,and Metabolic Markers in Obese Children: A Randomized,Double Blind,Controlled Study

Obese children are at high risk of developing vitamin D deficiency. Omega-3 polyunsaturated fatty acids and their derivatives might have a beneficial effect on vitamin D status of obese children, due to their anti-inflammatory action, and increasing its absorption. This multicenter, randomized, double-blind controlled study aims to investigate the effect of vitamin D and docosahexaenoic acid (DHA) co-supplementation for six months on vitamin D status, body composition, and metabolic markers of obese children with vitamin D deficiency. A total of 108 children were enrolled and 73 children completed the study: 33 were supplemented with an oral dose of 500 mg of DHA and 1200 IU/day of vitamin D3 and 41 were supplemented with 1200 IU/day of vitamin D3 + wheat germ oil. At the end of the study, more than 50% of the subjects improved their vitamin D status. However, co-supplementation was not more effective than vitamin D plus wheat germ oil. Fat mass percentage was significantly reduced, and body mass index improved in both groups, even if all the subjects were still obese at the end of the study. Children receiving both vitamin D and DHA presented a higher increase of DHA levels that could be relevant to prevent inflammatory-associated complications of obesity, but they had no effect on vitamin D levels.     

Noncoding RET variants explain the strong association with Hirschsprung disease in patients without rare coding sequence variant

The pathogenesis of Hirschsprung disease is complex. Although the RET proto-oncogene is the most frequently affected gene in Hirschsprung disease, rare coding sequence variants explain only a small part of Hirschsprung disease cases. We aimed to assess the genetic background of Hirschsprung disease using a genome-wide association analysis combined with sequencing all RET exons in samples from 105 Hirschsprung disease cases (30 familial and 75 sporadic) and 386 controls.As expected, variants in or near RET showed the strongest overall association with Hirschsprung disease and the most statistically significant association was observed when using a recessive genetic model (rs2435357, NC_000010.10:g.43582056T?>?C; genotype TT, OR?=?17.31, P?=?1.462?×?10^?21). Previously published associations in variants in SEMA (rs11766001, NC_000007.13:g.84145202A?>?C; allele C, OR?=?2.268, P?=?0.009533) and NRG1 (rs4541858, NC_000008.10:g.32410309A?>?G; allele G, OR?=?1.567, P?=?0.015; rs7835688, NC_000008.10:g.32411499G?>?C; allele C, OR?=?1.567, P?=?0.015) were also replicated in the genome-wide association analysis. Sequencing revealed a total of 12 exonic RET rare variants. Of these, eight amino acid changing rare variants and two frameshift variants caused or possibly caused Hirschsprung disease.Only a minority of the Hirschsprung disease cases (9/30 familial; 7/75 sporadic) carried one of the rare variants. Excluding the rare variant carriers from the genome-wide association analysis did not appreciably change the association of rs2435357 with Hirschsprung disease. We estimate that approximately two thirds of the sporadic cases may be statistically attributed to the recessive action of the common non-coding RET variants. Thus, even though most cases do not carry rare RET variants, combinations of rare variants and the common non-coding RET variant cause the majority of the cases in our population.     

Vitamin D and cardiovascular disease will it live up to its hype?

Substantial evidence suggests that a large portion of the population have suboptimal levels of vitamin D, which may adversely affect the cardiovascular (CV) system, including increasing levels of parathyroid hormone, activating the renin-angiotensin-aldosterone system, and increasing insulin resistance, thus leading to hypertension and left ventricular hypertrophy, metabolic syndrome/diabetes mellitus, systemic inflammation, and increased risk of atherosclerosis and CV disease events. We review the evidence that vitamin D deficiency is associated with incident CV disease events, as well as evidence that vitamin D supplementation is associated with reduction in CV diseases. Although the current evidence has created substantial hype, randomized controlled trials are needed to determine whether routine vitamin D assessment and supplementation will improve CV outcomes.     

Involvement of TSC genes and differential expression of other members of the mTOR signaling pathway in oral squamous cell carcinoma

Background  

Despite extensive research, the five-year survival rate of oral squamous cell carcinoma (OSCC) patients has not improved. Effective treatment of OSCC requires the identification of molecular targets and signaling pathways to design appropriate therapeutic strategies. Several genes from the mTOR signaling pathway are known to be dysregulated in a wide spectrum of cancers. However, not much is known about the involvement of this pathway in tumorigenesis of OSCC. We therefore investigated the role of the tumor suppressor genes, TSC1 and TSC2, and other members of this pathway in tumorigenesis of OSCC.