Village Midline Study: Rupandehi, Nepal

This report presents the findings from the village midline study conducted in Madhuri Village, the CCAFS benchmark site of Rupandehi district, Nepal between the 26th and the 30th of May 2019 . This document reports on the various changes which have occurred since the baseline was conducted in the same village. Changes in agricultural practices, sources of information, organizational and institutional development, climate change adaptation practices, and networks present in the community are assessed. During the village midline study, the participants identified 16 different organizations working closely with the community. These organizations provide support to households in the village in sectors such as agriculture, livestock, finance, saving and credits, infrastructural development, or irrigation. Special attention was paid to organizations which were working on food security and natural resource management. There have been significant changes in the federal government structure which has provided opportunities for the villagers. Women-led cooperatives were instrumental in uplifting the status of women and empowering them economically. Very few organizations working in the sector of natural resource management were cited by participants. Both groups identified that the information on seed selection and spacing, timing of fertilizers application along with information on irrigation have been received from cooperatives and agro-vets. Relatives and rural municipality played an important role in disseminating the information in the village. However, the frequency at which information was being spread was noted to be very low. Training on climate change and climate change adaptation, sustainable development, natural resource conservation and management, need to be the focus of future activities. Proper linkages and coordination mechanisms between both governmental and non –governmental organizations are necessary for the community to combat climate change’s negative impacts and increase resilience within the village

Chronic renal insufficiency among Asian Indians with type 2 diabetes: I. Role of RAAS gene polymorphisms

BACKGROUND: Renal failure in diabetes is mediated by multiple pathways. Experimental and clinical evidences suggest that renin-angiotensin-aldosterone system (RAAS) has a crucial role in diabetic kidney disease. A relationship between the RAAS genotypes and chronic renal insufficiency (CRI) among type 2 diabetes subjects has therefore been speculated. We investigated the contribution of selected RAAS gene polymorphisms to CRI among type 2 diabetic Asian Indian subjects. METHODS: Twelve single nucleotide polymorphisms (SNPs) from six genes namely-renin (REN), angiotensinogen (ATG), angiotensin converting enzyme I (ACE), angiotensin II type 1 receptor (AT1) and aldosterone synthase (CYP11B2) gene from the RAAS pathway and one from chymase pathway were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method and tested for their association with diabetic CRI using a case-control approach. Successive cases presenting to study centres with type 2 diabetes of ≥2 years duration and moderate CRI diagnosed by serum creatinine ≥3 mg/dl after exclusion of non-diabetic causes of CRI (n = 196) were compared with diabetes subjects with no evidence of renal disease (n = 225). Logistic regression analysis was carried out to correlate various clinical parameters with genotypes, and to study pair wise interactions between SNPs of different genes. RESULTS: Of the 12 SNPs genotyped, Glu53Stop in AGT and A>T (-777) in AT1 genes, were monomorphic and not included for further analysis. We observed a highly significant association of Met235Thr SNP in angiotensinogen gene with CRI (O.R. 2.68, 95%CI: 2.01–3.57 for Thr allele, O.R. 2.94, 95%CI: 1.88–4.59 for Thr/Thr genotype and O.R. 2.68, 95%CI: 1.97–3.64 for ACC haplotype). A significant allelic and genotypic association of T>C (-344) SNP in aldosterone synthase gene (O.R. 1.57, 95%CI: 1.16–2.14 and O.R. 1.81, 95%CI: 1.21–2.71 respectively), and genotypic association of GA genotype of G>A (-1903) in chymase gene (O.R. 2.06, 95%CI: 1.34–3.17) were also observed. CONCLUSION: SNPs Met235Thr in angiotensinogen, T>C (-344) in aldosterone synthase, and G>A (-1903) in chymase genes are significantly associated with diabetic chronic renal insufficiency in Indian patients and warrant replication in larger sample sets. Use of such markers for prediction of susceptibility to diabetes specific renal disease in the ethnically Indian population appears promising

Sarcopenia Exacerbates Obesity-Associated Insulin Resistance and Dysglycemia: Findings from the National Health and Nutrition Examination Survey III

Sarcopenia often co-exists with obesity, and may have additive effects on insulin resistance. Sarcopenic obese individuals could be at increased risk for type 2 diabetes. We performed a study to determine whether sarcopenia is associated with impairment in insulin sensitivity and glucose homeostasis in obese and non-obese individuals.We performed a cross-sectional analysis of National Health and Nutrition Examination Survey III data utilizing subjects of 20 years or older, non-pregnant (N = 14,528). Sarcopenia was identified from bioelectrical impedance measurement of muscle mass. Obesity was identified from body mass index. Outcomes were homeostasis model assessment of insulin resistance (HOMA IR), glycosylated hemoglobin level (HbA1C), and prevalence of pre-diabetes (6.0≤ HbA1C<6.5 and not on medication) and type 2 diabetes. Covariates in multiple regression were age, educational level, ethnicity and sex.Sarcopenia was associated with insulin resistance in non-obese (HOMA IR ratio 1.39, 95% confidence interval (CI) 1.26 to 1.52) and obese individuals (HOMA-IR ratio 1.16, 95% CI 1.12 to 1.18). Sarcopenia was associated with dysglycemia in obese individuals (HbA1C ratio 1.021, 95% CI 1.011 to 1.043) but not in non-obese individuals. Associations were stronger in those under 60 years of age. We acknowledge that the cross-sectional study design limits our ability to draw causal inferences.Sarcopenia, independent of obesity, is associated with adverse glucose metabolism, and the association is strongest in individuals under 60 years of age, which suggests that low muscle mass may be an early predictor of diabetes susceptibility. Given the increasing prevalence of obesity, further research is urgently needed to develop interventions to prevent sarcopenic obesity and its metabolic consequences

Search for intermediate mass black hole binaries in the first and second observing runs of the Advanced LIGO and Virgo network

Gravitational-wave astronomy has been firmly established with the detection of gravitational waves from the merger of ten stellar-mass binary black holes and a neutron star binary. This paper reports on the all-sky search for gravitational waves from intermediate mass black hole binaries in the first and second observing runs of the Advanced LIGO and Virgo network. The search uses three independent algorithms: two based on matched filtering of the data with waveform templates of gravitational-wave signals from compact binaries, and a third, model-independent algorithm that employs no signal model for the incoming signal. No intermediate mass black hole binary event is detected in this search. Consequently, we place upper limits on the merger rate density for a family of intermediate mass black hole binaries. In particular, we choose sources with total masses M=m1+m2ϵ[120,800] M and mass ratios q=m2/m1ϵ[0.1,1.0]. For the first time, this calculation is done using numerical relativity waveforms (which include higher modes) as models of the real emitted signal. We place a most stringent upper limit of 0.20 Gpc-3 yr-1 (in comoving units at the 90% confidence level) for equal-mass binaries with individual masses m1,2=100 M and dimensionless spins χ1,2=0.8 aligned with the orbital angular momentum of the binary. This improves by a factor of ∼5 that reported after Advanced LIGO's first observing run

Association of TGFβ1, TNFα, CCR2 and CCR5 gene polymorphisms in type-2 diabetes and renal insufficiency among Asian Indians

BACKGROUND: Cytokines play an important role in the development of diabetic chronic renal insufficiency (CRI). Transforming growth factor β1 (TGF β1) induces renal hypertrophy and fibrosis, and cytokines like tumor necrosis factor-alpha (TNFα), chemoattractant protein-1 (MCP-1), and regulated upon activation and normal T cell expressed and secreted (RANTES) mediate macrophage infiltration into kidney. Over expression of these chemokines leads to glomerulosclerosis and interstitial fibrosis. The effect of MCP-1 and RANTES on kidney is conferred by their receptors i.e., chemokine receptor (CCR)-2 and CCR-5 respectively. We tested association of nine single nucleotide polymorphisms (SNPs) from TGFβ1, TNFα, CCR2 and CCR5 genes among individuals with type-2 diabetes with and without renal insufficiency. METHODS: Type-2 diabetes subjects with chronic renal insufficiency (serum creatinine ≥ 3.0 mg/dl) constituted the cases, and matched individuals with diabetes of duration ≥ 10 years and normoalbuminuria were evaluated as controls from four centres in India. Allelic and genotypic contributions of nine SNPs from TGFβ1, TNFα, CCR2 and CCR5 genes to diabetic CRI were tested by computing odds ratio (OR) and 95% confidence intervals (CI). Sub-analysis of CRI cases diabetic retinopathy status as dependent variable and SNP genotypes as independent variable in a univariate logistic regression was also performed. RESULTS: SNPs Tyr81His and Thr263Ile in TGF β1 gene were monomorphic, and Arg25Pro in TGF β1 gene and Δ32 polymorphism in CCR5 gene were minor variants (minor allele frequency <0.05) and therefore were not considered for case-control analysis. A significant allelic association of 59029G>A SNP of CCR5 gene has been observed and the allele 59029A seems to confer predisposition to development of diabetic CRI (OR 1.39; CI 1.04–1.84). In CRI subjects a compound group of genotypes "GA and AA" of SNP G>A -800 was found to confer predisposition for proliferative retinopathy (OR 3.03; CI 1.08–8.50, p = 0.035). CONCLUSION: Of the various cytokine gene polymorphisms tested, allele 59029A of CCR5 gene is significantly associated with diabetic renal insufficiency among Asian Indians. Result obtained for 59029G>A SNP of CCR5 gene is in conformity with reports from a Japanese population but due to sub-optimal power of the sample, replication in larger sample set is warranted

The prognostic and predictive power of redox rotein expression for anthracycline-based chemotherapy response in locally advanced breast cancer

Neoadjuvant chemotherapy has become the standard of care for locally advanced primary breast cancer. Anthracycline-based regimens have proven to be one of the most effective treatments in this setting. As certain cytotoxic antineoplastic agents, such as anthracyclines, generate reactive oxygen species as a by-product of their mechanism of action, we examined whether redox protein expression was involved in the response to anthracycline-based chemotherapy and with clinical outcome. Pre treatment needle core biopsy and postanthracycline treatment tumour sections were analysed from 98 cases. In all, 32 individuals had a complete clinical response and 17 had a complete pathological response. Immunohistochemical staining was performed for eight redox proteins: thioredoxin, thioredoxin reductase thioredoxin interacting protein (TxNIP), glutathione S-transferase (GST) p, h and a, catalase and manganese superoxide dismutase. GST p (P¼0.05) and catalase (P¼0.045) were associated with pathological complete response in pre-chemotherapy samples. TxNIP (P¼0.017) and thioredoxin reductase (P¼0.022) were independent prognostic factors for distant metastasis free survival and TxNIP for overall survival (P¼0.014). In oestrogen receptor negative patients that are known to have a poor overall survival, a considerably worse prognosis was seen in cases that exhibited low expression of TxNIP (P¼0.000003), stratifying patients into more defined groups. This study indicates the importance of redox regulation in determining breast cancer response to anthracycline-based chemotherapy and provides ways of further stratifying pre-chemotherapy patients to potentially allow more tailored treatments

Association analysis of ADPRT1, AKR1B1, RAGE, GFPT2 and PAI-1 gene polymorphisms with chronic renal insufficiency among Asian Indians with type-2 diabetes

<p>Abstract</p> <p>Background</p> <p>To determine association of nine single nucleotide polymorphisms (SNPs) in ADP ribosyltransferase-1 (ADPRT1), aldo-keto reductase family 1 member B1 (AKR1B1), receptor for advanced glycation end-products (RAGE), glutamine:fructose-6-phosphate amidotransferase-2 (GFPT2), and plasminogen activator inhibitor-1 (PAI-1) genes with chronic renal insufficiency (CRI) among Asian Indians with type 2 diabetes; and to identify epistatic interactionss between genes from the present study and those from renin-angiotensin-aldosterone system (RAAS), and chemokine-cytokine, dopaminergic and oxidative stress pathways (previously investigated using the same sample set).</p> <p>Methods</p> <p>Type 2 diabetes subjects with CRI (serum creatinine ≥3.0 mg/dl) constituted the cases (n = 196), and ethnicity and age matched individuals with diabetes for a duration of ≥ 10 years, normal renal functions and normoalbuminuria recruited as controls (n = 225). Allelic and genotypic constitution of 10 polymorphisms (SNPs) from five genes namely- <it>ADPRT1</it>, <it>AKR1B1, RAGE, GFPT2 </it>and <it>PAI-1 </it>with diabetic CRI was investigated. The genetic associations were evaluated by computation of odds ratio and 95% confidence interval. Multiple logistic regression analysis was carried out to correlate various clinical parameters with genotypes, and to study epistatic interactions between SNPs in different genes.</p> <p>Results</p> <p>Single nucleotide polymorphisms -429 T>C in <it>RAGE </it>and rs7725 C>T SNP in 3' UTR in <it>GFPT2 </it>gene showed a trend towards association with diabetic CRI. Investigation using miRBase statistical tool revealed that rs7725 in <it>GFPT2 </it>was a perfect target for predicted miRNA (hsa miR-378) suggesting the presence of the variant 'T' allele may result in an upregulation of GFPT2 contributing to diabetic renal complication. Epistatic interaction between SNPs in transforming growth factor <it>TGF-β1 </it>(investigated using the same sample set and reported elsewhere) and <it>GFPT2 </it>genotype was observed.</p> <p>Conclusions</p> <p>Association of SNPs in <it>RAGE </it>and <it>GFPT2 </it>suggest that the genes involved in modulation of oxidative pathway could be major contributor to diabetic chronic renal insufficiency. In addition, GFPT2 mediated overproduction of TGF-β1 leading to endothelial expansion and thereby CRI seems likely, suggested by our observation of a significant interaction between GFPT2 with TGF-β1 genes. Further, identification of predicted miRNA targets spanning the associated SNP in <it>GFPT2 </it>implicates the rs7725 SNP in transcriptional regulation of the gene, and suggests <it>GFPT2 </it>could be a relevant target for pharmacological intervention. Larger replication studies are needed to confirm these observations.</p