Down syndrome with ambiguous genitalia: A rare association

Down syndrome (DS) is one of the most common chromosomal disorders. Although genitourinary anomalies, such as a cryptorchidism, micropenis, posterior urethral valves, and hypospadias, have been recognized as complications, the association of ambiguous genitalia with DS has been rarely reported. We report the case of a 1-year-old baby; assigned male sex at birth who was the first child born of a non-consanguineous marriage, by vaginal delivery at term with a birth weight of 2.2 kg. The baby had clinical features suggestive of DS with a micropenis, penoscrotal hypospadias, and incompletely fused labial-scrotal folds with palpable gonads. The external masculinization score was 3/12. The child was reared as a male and hormonal investigations were suggestive of androgen insensitivity. Karyotype was 47, XY, +21

Rare site of presentation of a rare manifestation of graves’ disease

Infiltrative dermopathy is an uncommon manifestation of Graves’ disease frequently involving the lower extremities. The pretibial area is most commonly involved. Rarely the fingers, hands, elbows, arms, or face are affected. Skin thickening is the characteristic abnormality. Localized myxedema is an autoimmune manifestation of Graves’ disease. Here, we report the case of a 45-year-old who presented with thyroid-associated orbitopathy and localized myxoedema over both the shoulders. In a patient who has long-standing hyperthyroidism, the diagnosis of infiltrative dermopathy is usually confirmed by the location, non-pitting nature, and distinct borders of the lesions. As most of these lesions are asymptomatic, no specific therapy is required

A Study On The Prevalence Of Vitamin B12 Deficiency In Eastern Indian Type 2 Diabetes Mellitus Patients With Peripheral Neuropathy On Metformin Presenting To A Tertiary Care Hospital

Introduction: The association between long-term metformin use in type 2 diabetes mellitus (T2DM) and low vitamin B12 levels has been proven and screening for the same is recommended by American Diabetes Association (ADA) guidelines. The potential of the deficiency to cause or worsen diabetic peripheral neuropathy (DPN) in T2DM patients has been investigated in previous studies. However, the prevalence estimates of vitamin B12 deficiency in T2DM patients treated with long term metformin and having established DPN is lacking in our country. The aim of our study was to estimate the prevalence of vitamin B12 deficiency in T2DM patients with DPN on metformin and find out the risk factors for vitamin B12 deficiency in these patients. Methods: This cross-sectional study was conducted in the department of endocrinology in a tertiary care hospital on T2DM patients with DPN on long term metformin therapy. Vitamin B12 levels were estimated in all the subjects and the prevalence and risk factors for Vitamin B12 deficiency were assessed. Results: The prevalence of vitamin B12 deficiency in our patients was 32%. Based on the correlation estimates, none of the factors studied were significantly associated with variations in Vitamin B12 levels. Conclusion: Our study found that a third of metformin treated T2DM patients with peripheral neuropathy had vitamin B12 deficiency with no specific clinical predictor for the same. We thereby recommend screening for vitamin B12 deficiency in T2DM patients on long-term metformin and with established DPN

Avascular necrosis of the hip: A unique presentation of pseudohypoparathyroidism

Pseudohypoparathyroidism is a rare, heterogeneous disorder characterized by parathyroid hormone resistance. Its association with avascular necrosis of the hip has been reported infrequently in the past. We report the case of a 27-year-old lady with pseudohypoparathyroidism Type 1 whose initial presentation was with avascular necrosis of bilateral hip. Apart from the common clinical features of pseudohypoparathyroidism, clinicians should also be aware of the rarer resentations such as avascular necrosis. A good clinical history and physical examination are warranted for early diagnosis in order to prevent serious morbidity in thesepatients

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Role of DnaK in In Vitro and In Vivo Expression of Virulence Factors of Vibrio cholerae

The dnaK gene of Vibrio cholerae was cloned, sequenced, and used to construct a dnaK insertion mutant which was then used to examine the role of DnaK in expression of the major virulence factors of this important human pathogen. The central regulator of several virulence genes of V. cholerae is ToxR, a transmembrane DNA binding protein. The V. cholerae dnaK mutant grown in standard laboratory medium exhibited phenotypes characteristic of cells deficient in ToxR activity. Using Northern blot analysis and toxR transcriptional fusions, we demonstrated a reduction in expression of the toxR gene in the dnaK mutant strain together with a concomitant increase in expression of a htpG-like heat shock gene that is located immediately upstream and is divergently transcribed from toxR. This may be due to increased heat shock induction in the dnaK mutant. In vivo, however, although expression from heat shock promoters in the dnaK mutant was similar to that observed in vitro, expression of both toxR and htpG was comparable to that by the parental strain. In both strains, in vivo expression of toxR was significantly higher than that observed in vitro, but no reciprocal decrease in htpG expression was observed. These results suggest that the modulation of toxR expression in vivo may be different from that observed in vitro

Competitive Growth Advantage of Nontoxigenic Mutants in the Stationary Phase in Archival Cultures of Pathogenic Vibrio cholerae Strains

Spontaneous nontoxigenic mutants of highly pathogenic Vibrio cholerae O1 strains accumulate in large numbers during long-term storage of the cultures in agar stabs. In these mutants, production of the transcriptional regulator ToxR was reduced due to the presence of a mutation in the ribosome-binding site immediately upstream of the toxR open reading frame. Consequently, the ToxR-dependent virulence regulon was turned off, with concomitant reduction in the expression of cholera toxin and toxin-coregulated pilus. An intriguing feature of these mutants is that they have a competitive fitness advantage when grown in competition with the parent strains in stationary-phase cocultures which is independent of RpoS, the only locus known to be primarily associated with acquisition of a growth advantage phenotype in bacteria