Lipodystrophy syndrome among HIV infected children on highly active antiretroviral therapy in northern India

Background: It is estimated that about 2.5 million people are living with HIV infection in India. Although antiretroviral drugs have been able to reduce the mortality, these drugs have serious side effects one of which is lipodystrophy syndrome. Most of the drugs used in HAART viz, protease inhibitors, stavudine and nevirapine are associated with lipodystrophy. Hence we conducted this study to assess the prevalence of lipodystrophy in HIV infected children on HAART and its associated risk factors.Materials and methods: A cross sectional study was conducted on 80 HIV infected children aged 2-18 years of age who were on stavudine based HAART for .2 years. These children were assessed for presence of lipodystrophy, its metabolic complications and associated risk factors.Results: Lipodystrophy was observed in 33.7% of children with lipoatrophy being the commonest subtype followed by lipohypertrophy. Older age, increased duration of treatment and dyslipidaemia were found to be associated in patients with lipodystrophy than those without. On further multivariate analysis of independent risk factors only increased duration of treatment was significantly associated with lipodystrophy. No association was found with insulin resistance.Conclusion: We observed that lipodystrophy is a common finding in HIV patients treated with HAART for long duration.Key Words: lipodystrophy syndrome, lipoatrophy, HAART, HI

Effect of vitamin D supplementation on serum sclerostin levels in chronic kidney disease.

Vitamin D deficiency, cardiovascular disease and abnormal bone mineral metabolism are common in chronic kidney disease (CKD). Abnormal bone mineral metabolism has been linked to vascular calcification in CKD. Sclerostin has emerged as an important messenger in cross talk between bone-vascular axis. We analyzed sclerostin in subjects who participated in the randomized, double blind, placebo controlled trial investigating the effect of cholecalciferol supplementation on vascular function in non-diabetic CKD stage G3-4 and vitamin D ≤20ng/ml [CTRI/2013/05/003648]. Patients were randomized (1:1) to receive either two directly observed oral doses of 300,000 IU of cholecalciferol or matching placebo at baseline and 8 weeks. Of the 120 subjects enrolled, 58 in the cholecalciferol group and 59 in the placebo group completed the study. At baseline, serum levels of sclerostin were similar in both groups (cholecalciferol - median;190pg/ml, IQR;140-260pg/ml and placebo - median;180pg/ml, IQR; 140-240pg/ml, p=0.67). 16 weeks after cholecalciferol supplementation, there was no change in level of sclerostin (mean change;1.10 pg/ml, 95%CI; -27.34 to 29.34 pg/ml, p=0.25). However, a significant decrease in sclerostin level was noted in the placebo group (mean change; -31.94pg/ml, 95%CI; -54.76 to -9.13 pg/ml, p=0.002). Change (Δ) in sclerostin level at 16 weeks correlated negatively with Δ eGFR (r=-0.20, p=0.03) and positively with Δuric acid (r=0.37, p<0.001) but not with Δ25(OH) D (r=0.06, p=0.54), Δ iPTH (r=-0.03, p=0.78) ΔFGF23 (r=-0.08, p=0.38) and Δ1,25 (OH)2 D (r=-0.04, p=0.65). In conclusion, high dose cholecalciferol supplementation did not change sclerostin levels in non-diabetic stage 3-4 CKD subjects

Coffin-Siris syndrome with Mayer-Rokitansky-Küster-Hauser syndrome: a case report

<p>Abstract</p> <p>Introduction</p> <p>We report the case of an unusual association of Coffin-Siris syndrome with Mayer-Rokitansky-Küster-Hauser syndrome. This association has never previously been reported in the medical literature.</p> <p>Case presentation</p> <p>A nine-year-old Indian girl was referred to our hospital for growth retardation, mental retardation, lax joints, generalized hypertrichosis, and hypoplastic fifth fingernails and toenails. A thorough medical examination and evaluation revealed she had phenotypic features of Coffin-Siris syndrome, with Mayer-Rokitansky-Küster-Hauser syndrome on radiological evaluation. The karyotype of our patient was normal.</p> <p>Conclusion</p> <p>In an unexplained case of mental retardation with facies suggestive of Coffin-Siris syndrome, association with Mayer-Rokitansky-Küster-Hauser syndrome should be considered and the patient should be evaluated for the same. Both of these syndromes may have a common pathogenesis, as yet unknown. This case report has broad implications, as similar cases in future may give insights into the pathogenesis of both these syndromes.</p

Vascular function and cholecalciferol supplementation in CKD: A self-controlled case series.

Vitamin D deficiency is common and associated with mortality in chronic kidney disease (CKD) patients. Cardiovascular disease (CVD) is the commonest cause of mortality in CKD patients. In a randomized, double blind, placebo controlled trial, we have recently reported favorable effects of vitamin D supplementation on vascular & endothelial function and inflammatory biomarkers in vitamin D deficient patients with non-diabetic stage 3-4 CKD (J Am Soc Nephrol 28: 3100-3108, 2017). Subjects in the placebo group who had still not received vitamin D after completion of the trial received two oral doses 300000 IU of oral cholecalciferol at 8 weeks interval followed by flow mediated dilatation (FMD), pulse wave velocity (PWV), circulating endothelial and inflammatory markers (E-Selectin, vWF, hsCRP and IL-6), 1,25 (OH)2D, iPTH and iFGF-23 assessment at 16 weeks. 31 subjects completed this phase of the study. Last values recorded in the preceding clinical trial were taken as baseline values. Serum 25(OH)D and 1,25(OH)2D increased and FMD significantly improved after cholecalciferol supplementation [mean change in FMD%: 5.8% (95% CI: 4.0-7.5%, p<0.001]. Endothelium independent nitroglycerine mediated dilatation, PWV, iPTH, iFGF-23 and IL-6 also showed favorable changes. The data further cement the findings of beneficial effects of correction of vitamin D deficiency on vascular function

Antimicrobial resistance in neonates with suspected sepsis

SettingNobel Medical College and Teaching Hospital, Biratnagar, Nepal.ObjectiveTo determine the pattern of antimicrobial resistance and hospital exit outcomes in neonates with suspected sepsis in a tertiary neonatal intensive care unit (NICU).DesignThis hospital-based cohort study was conducted to follow patients from January to December 2019. All identified cases of suspected sepsis were enlisted from hospital records.ResultsSepsis was suspected in 177 (88%) of the 200 cases admitted in the NICU; 52 (29%) were culture-positive. Pseudomonas was the predominant organism isolated (n = 40; 78%), followed by coagulase negative staphylococcus (n = 12, 23%). Nine (17%) of the 52 isolates were resistant to the Access and Watch group of antibiotics, including some resistance to Reserve group drugs such as imipenem and linezolid. Most treated cases (n = 170, 96%) improved, although 7 (4%) left against medical advice.ConclusionMost of the pathogens were resistant to WHO Access and Watch antibiotics and occasional resistance was observed to Reserve group drugs. Most sepsis was caused by Gram-negative bacilli. Improving turnaround times for antibiotic sensitivity testing using point-of-care testing, and a greater yield of culture-positive results are needed to enhance the management of neonatal sepsis

Integrated Farming System: An ideal approach for developing more economically and environmentally sustainable farming systems for the Eastern Himalayan Region

The present work was carried out at Chandel Khullen village of Chandel hill district of Manipur during 2010-11 to 2012-13. The average holding size of the farmer was 1.33 ha in 2010-11, 1.96 ha in 2011-12 and 2.21 ha in 2012-13. The tribal farmer adopted seven components, i e crop production, vegetables, fruits, piggery, backyard poultry, fishery and water management as suggested by ICAR Manipur Centre. In 2010-11, the paddy yield was 3.5 tonnes/ha as compared to 4.79 tonnes/ha in 2012-13. It was mainly due to adoption of improved package and practices. The cabbage and onion yield increased by 103 and 54 per cent, respectively after adoption of improved cultivation methods under integrated farming system. Similarly, the papaya and banana production was increased by 275 and 270 per cent. There was marked increase in pork, chicken, egg and fish production. In 2012-13, this system also provided significantly higher Rs per Re invested than that of the other 2010-11. In Manipur, women’s participation is more in farming system rather than men. In the same way, this farming system also gives more opportunity to women to engage in agriculture farming. Thus integrated farming system provides new venture for employment and sustainable development of livelihood for North Eastern people. The overall result revealed that the improved practices with different crop and animal components are an excellent approach for sustainable production, income generation and employment opportunity for the small and marginal rural households of Manipur

Genetic risk factors for ischaemic stroke and its subtypes (the METASTROKE Collaboration): a meta-analysis of genome-wide association studies

&lt;p&gt;Background - Various genome-wide association studies (GWAS) have been done in ischaemic stroke, identifying a few loci associated with the disease, but sample sizes have been 3500 cases or less. We established the METASTROKE collaboration with the aim of validating associations from previous GWAS and identifying novel genetic associations through meta-analysis of GWAS datasets for ischaemic stroke and its subtypes.&lt;/p&gt; &lt;p&gt;Methods - We meta-analysed data from 15 ischaemic stroke cohorts with a total of 12 389 individuals with ischaemic stroke and 62 004 controls, all of European ancestry. For the associations reaching genome-wide significance in METASTROKE, we did a further analysis, conditioning on the lead single nucleotide polymorphism in every associated region. Replication of novel suggestive signals was done in 13 347 cases and 29 083 controls.&lt;/p&gt; &lt;p&gt;Findings - We verified previous associations for cardioembolic stroke near PITX2 (p=2·8×10−16) and ZFHX3 (p=2·28×10−8), and for large-vessel stroke at a 9p21 locus (p=3·32×10−5) and HDAC9 (p=2·03×10−12). Additionally, we verified that all associations were subtype specific. Conditional analysis in the three regions for which the associations reached genome-wide significance (PITX2, ZFHX3, and HDAC9) indicated that all the signal in each region could be attributed to one risk haplotype. We also identified 12 potentially novel loci at p&#60;5×10−6. However, we were unable to replicate any of these novel associations in the replication cohort.&lt;/p&gt; &lt;p&gt;Interpretation - Our results show that, although genetic variants can be detected in patients with ischaemic stroke when compared with controls, all associations we were able to confirm are specific to a stroke subtype. This finding has two implications. First, to maximise success of genetic studies in ischaemic stroke, detailed stroke subtyping is required. Second, different genetic pathophysiological mechanisms seem to be associated with different stroke subtypes.&lt;/p&gt

Experimental investigation on the effect of wear flat inclination on the cutting response of a blunt tool in rock cutting

A vast majority of experimental researches focuses on the cutting action of a sharp cutter, while there has been limited experimental work devoted to the study of the contact process at the wear flat-rock interface. The specific objective of this study is to determine the effect of the wear flat inclination angle ( β ) with respect to the cutter velocity vector ( vv ) on both the contact stress ( σ ) and friction coefficient ( μ ) mobilized at the wear flat-rock interface. An extensive and comprehensive set of cutting experiments was carried out on thirteen different sedimentary quarry rock samples using a state-of-the-art rock cutting equipment. A unique cutter holder was purposely designed and manufactured along with a precise experimental protocol implemented in order to change the back rake angle and therefore the inclination β by steps of 0.10∘ . The experimental observations confirm the existence of three regimes of frictional contact (identified as elastic, elasto-plastic and plastic) for all rock samples. Further, the results suggest that the scaled contact stress is predominantly controlled by a dimensionless number η=E∗tanβq with E∗ the plane strain elastic modulus and q the rock strength

An AP-MS- and BioID-compatible MAC-tag enables comprehensive mapping of protein interactions and subcellular localizations

Protein-protein interactions govern almost all cellular functions. These complex networks of stable and transient associations can be mapped by affinity purification mass spectrometry (AP-MS) and complementary proximity-based labeling methods such as BioID. To exploit the advantages of both strategies, we here design and optimize an integrated approach combining AP-MS and BioID in a single construct, which we term MAC-tag. We systematically apply the MAC-tag approach to 18 subcellular and 3 sub-organelle localization markers, generating a molecular context database, which can be used to define a protein's molecular location. In addition, we show that combining the AP-MS and BioID results makes it possible to obtain interaction distances within a protein complex. Taken together, our integrated strategy enables the comprehensive mapping of the physical and functional interactions of proteins, defining their molecular context and improving our understanding of the cellular interactome.Peer reviewe

Analysis of the genome and transcriptome of Cryptococcus neoformans var. grubii reveals complex RNA expression and microevolution leading to virulence attenuation.

Cryptococcus neoformans is a pathogenic basidiomycetous yeast responsible for more than 600,000 deaths each year. It occurs as two serotypes (A and D) representing two varieties (i.e. grubii and neoformans, respectively). Here, we sequenced the genome and performed an RNA-Seq-based analysis of the C. neoformans var. grubii transcriptome structure. We determined the chromosomal locations, analyzed the sequence/structural features of the centromeres, and identified origins of replication. The genome was annotated based on automated and manual curation. More than 40,000 introns populating more than 99% of the expressed genes were identified. Although most of these introns are located in the coding DNA sequences (CDS), over 2,000 introns in the untranslated regions (UTRs) were also identified. Poly(A)-containing reads were employed to locate the polyadenylation sites of more than 80% of the genes. Examination of the sequences around these sites revealed a new poly(A)-site-associated motif (AUGHAH). In addition, 1,197 miscRNAs were identified. These miscRNAs can be spliced and/or polyadenylated, but do not appear to have obvious coding capacities. Finally, this genome sequence enabled a comparative analysis of strain H99 variants obtained after laboratory passage. The spectrum of mutations identified provides insights into the genetics underlying the micro-evolution of a laboratory strain, and identifies mutations involved in stress responses, mating efficiency, and virulence