A polymorphism at IGF1 locus is associated with anemia

In vitro and in vivo studies suggest that IGF-1 has a role in erythropoiesis. There is evidence that the rs35767 C/T polymorphism near IGF1 is associated with plasma IGF-1 levels. We investigated the effect of this polymorphism on hemoglobin (Hb) concentration and anemia. The study group comprised 3286 adult Whites. The rs35767 polymorphism was screened using a TaqMan allelic discrimination assay. The rs35767 polymorphism was not associated with age, gender, BMI, waist circumference, smoking, blood pressure, plasma glucose, HbA1c, type 2 diabetes, HOMA-IR, hsCRP, eGFR, and lipid profile. Erythrocyte sedimentation rate (ESR), fibrinogen, and fasting insulin levels were significantly lower in TT genotype carriers compared with C allele carriers. Hb concentration was significantly higher in carriers of the TT genotype compared with C allele carriers, and a lower proportion of TT carriers had anemia. As compared with TT genotype carriers, those bearing the CC genotype had a 2.4-fold higher risk of anemia (OR 2.40, 95%CI 1.19-4.82), and those with the CT genotype had a 2.0-fold higher risk of anemia (OR 2.06, 95%CI 1.04-4.11). The association remained significant when fasting insulin, eGFR, smoking, diabetes, ACE inhibitors, sartans or diuretics treatments, use of metformin and pioglitazone were added to the model, but its independence was not retained after inclusion of fibrinogen and ESR values into the model. In conclusion, rs35767 TT allele carriers exhibited significantly higher concentrations of Hb, and lower risk of anemia compared with C allele carriers supporting the idea that IGF-1 plays a role in erythropoiesis homeostasis

Elevated hemoglobin glycation index identify non-diabetic individuals at increased risk of kidney dysfunction

Hemoglobin glycation index (HGI), calculated as the difference between the observed value of HbA1 and the predicted HbA1c based on plasma glucose concentration, is a measure of the individual tendency toward non-enzymatic hemoglobin glycation which has been found to be positively associated with nephropathy in subjects with diabetes. In this cross-sectional study we aimed to evaluate whether higher HGI levels are associated with impaired kidney function also among nondiabetic individuals. The study group comprised 1505 White nondiabetic individuals stratified in quartiles according to HGI levels. Estimated glomerular filtration rate (eGFR) was calculated by using the MDRD equation. Individuals in the intermediate and high HGI groups exhibited a worse metabolic phenotype with increased levels of visceral obesity, total cholesterol, triglycerides, inflammatory biomarkers such as hsCRP and white blood cells count and lower values of HDL and insulin sensitivity assessed by Matsuda index in comparison to the lowest quartile of HGI. Subjects in the intermediate and high HGI groups displayed a graded decrease of eGFR levels in comparison with the lowest quartile of HGI. In a logistic regression analysis individuals in the highest quartile of HGI exhibited a significantly 3.6-fold increased risk of having chronic kidney disease (95% CI: 1.13-11.24, P = 0.03) and a significantly 1.6-fold increased risk of having a mildly reduced kidney function (95% CI: 1.19-2.28, P = 0.003) in comparison to individuals in the lowest HGI group. In conclusion HGI may be a useful tool to identify nondiabetic individuals with an increased risk of having kidney dysfunction

Farmers’ organizations and sustainable development: An introduction

This special issue features 14 new research papers investigating the role of farmers’ organizations (e.g., collective action, self-help groups, producer companies/organizations, and cooperatives) in supporting sustainable development. The key findings include: (1) farmer groups and cooperatives promote farmers’ adoption of good farm management practices, new agricultural technologies and sustainable farming practices, although not substantially improving farm yield; (2) outsourcing services provided by agricultural cooperatives help to increase the technical efficiency of crop production; (3) cooperative membership enhances members’ bargaining power and enables them to sell their products at higher prices; (4) cooperatives motivate rural laborers to work in off-farm sectors, while self-help groups empower rural women in decision-making; (5) internet use improves agricultural cooperatives’ economic, social, and innovative performances; (6) direct administrative intervention supporting cooperative development may lead to the emergence of shell cooperatives; (7) participation in forest farmer organizations enables wood value chain upgrading; (8) increasing the cooperative size in terms of income, equity, and assets increases the profitability of savings and credit cooperatives; and (9) creating cross-border cooperation between cooperatives generates benefits for all parties involved. These findings can inspire the design of policies aimed to support farmers’ organizations in achieving sustainable development goals

Insulin sensitivity, β-cell function, and incretin effect in individuals with elevated 1-hour postload plasma glucose levels

OBJECTIVE: Individuals with normal glucose tolerance (NGT), whose 1-h postload plasma glucose is ≥155 mg/dL (NGT 1h-high), have an increased risk of type 2 diabetes. The purpose of this study was to characterize their metabolic phenotype. RESEARCH DESIGN AND METHODS: A total of 305 nondiabetic offspring of type 2 diabetic patients was consecutively recruited. Insulin secretion was assessed using both indexes derived from oral glucose tolerance test (OGTT) and intravenous glucose tolerance test (IVGTT). Insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp. RESULTS: Compared with individuals with a 1-h postload plasma glucose <155 mg/dL (NGT 1h-low), NGT 1h-high individuals exhibited lower insulin sensitivity after adjustment for age, sex, and BMI. Insulin secretion estimated from the OGTT did not differ between the two groups of individuals. By contrast, compared with NGT 1h-low individuals, the acute insulin response during an IVGTT and the disposition index were significantly reduced in NGT 1h-high individuals after adjustment for age, sex, and BMI. Incretin effect, estimated as the ratio between total insulin responses during OGTT and IVGTT, was higher in NGT 1h-high individuals compared with NGT 1h-low individuals. CONCLUSIONS: NGT 1h-high individuals may represent an intermediate state of glucose intolerance between NGT and type 2 diabetes characterized by insulin resistance and reduced β-cell function, the two main pathophysiological defects responsible for the development of type 2 diabetes. Postload hyperglycemia is the result of an intrinsic β-cell defect rather than impaired incretin effec

Modulation of DNA topoisomerase II activity and expression in melanoma cells with acquired drug resistance

The role of DNA topoisomerases (Topo) IIα and IIβ was investigated in various drug-resistant melanoma cells. Melanoma cells resistant to etoposide, exhibited an up to tenfold reduced Topo II activity corresponding to an increasing degree of drug resistance indicating that modulation of Topo II activity contribute to the drug-resistant phenotype. The reduction of Topo II activity was reflected by decreased nuclear amounts of both Topo II isoforms. © 2000 Cancer Research Campaig

The Huntington's disease mutation impairs Huntingtin's role in the transport of NF-κB from the synapse to the nucleus

Expansion of a polyglutamine (polyQ) tract in the Huntingtin (Htt) protein causes Huntington's disease (HD), a fatal inherited neurodegenerative disorder. Loss of the normal function of Htt is thought to be an important pathogenetic component of HD. However, the function of wild-type Htt is not well defined. Htt is thought to be a multifunctional protein that plays distinct roles in several biological processes, including synaptic transmission, intracellular transport and neuronal transcription. Here, we show with biochemical and live cell imaging studies that wild-type Htt stimulates the transport of nuclear factor κ light-chain-enhancer of activated B cells (NF-κB) out of dendritic spines (where NF-κB is activated by excitatory synaptic input) and supports a high level of active NF-κB in neuronal nuclei (where NF-κB stimulates the transcription of target genes). We show that this novel function of Htt is impaired by the polyQ expansion and thus may contribute to the etiology of HD

Hypoglycemia Assessed by Continuous Glucose Monitoring Is Associated with Preclinical Atherosclerosis in Individuals with Impaired Glucose Tolerance

Hypoglycemia is associated with increased risk of cardiovascular adverse clinical outcomes. There is evidence that impaired glucose tolerance (IGT) is associated with cardiovascular morbidity and mortality. Whether IGT individuals have asymptomatic hypoglycemia under real-life conditions that are related to early atherosclerosis is unknown. To this aim, we measured episodes of hypoglycemia during continuous interstitial glucose monitoring (CGM) and evaluated their relationship with early manifestation of vascular atherosclerosis in glucose tolerant and intolerant individuals. An oral glucose tolerance test (OGTT) was performed in 79 non-diabetic subjects. Each individual underwent continuous glucose monitoring for 72 h. Cardiovascular risk factors and ultrasound measurement of carotid intima-media thickness (IMT) were evaluated. IGT individuals had a worse cardiovascular risk profile, including higher IMT, and spent significantly more time in hypoglycemia than glucose-tolerant individuals. IMT was significantly correlated with systolic (r = 0.22; P = 0.05) and diastolic blood pressure (r = 0.28; P = 0.01), total (r = 0.26; P = 0.02) and LDL cholesterol (r = 0.27; P = 0.01), 2-h glucose (r = 0.39; P<0.0001), insulin sensitivity (r = −0.26; P = 0.03), and minutes spent in hypoglycemia (r = 0.45; P<0.0001). In univariate analyses adjusted for gender, minutes spent in hypoglycemia were significantly correlated with age (r = 0.26; P = 0.01), waist circumference (r = 0.33; P = 0.003), 2-h glucose (r = 0.58; P<0.0001), and 2-h insulin (r = 0.27; P = 0.02). In a stepwise multivariate regression analysis, the variables significantly associated with IMT were minutes spent in hypoglycemia (r2 = 0.252; P<0.0001), and ISI index (r2 = 0.089; P = 0.004), accounting for 34.1% of the variation. Episodes of hypoglycemia may be considered as a new potential cardiovascular risk factor for IGT individuals

Evidence of multiple sorption modes in layered double hydroxides using Mo as structural probe

Layered double hydroxides (LDHs) have been considered as effective phases for the remediation of aquatic environments, to remove anionic contaminants mainly through anion exchange mechanisms. Here, a combination of batch isotherm experiments and X-ray techniques was used to examine molybdate (MoO ) sorption mechanisms on CaAl LDHs with increasing loadings of molybdate. Advanced modeling of aqueous data shows that the sorption isotherm can be interpreted by three retention mechanisms, including two types of edge sites complexes, interlayer anion exchange, and CaMoO precipitation. Meanwhile, Mo geometry evolves from tetrahedral to octahedral on the edge, and back to tetrahedral coordination at higher Mo loadings, indicated by Mo K-edge X-ray absorption spectra. Moreover, an anion exchange process on both CaAl LDHs was followed by in situ time-resolved synchrotron-based X-ray diffraction, remarkably agreeing with the sorption isotherm. This detailed molecular view shows that different uptake mechanisms - edge sorption, interfacial dissolution-reprecipitation - are at play and control anion uptake under environmentally relevant conditions, which is contrast to the classical view of anion exchange as the primary retention mechanism. This work puts all these mechanisms in perspective, offering a new insight into the complex interplay of anion uptake mechanisms by LDH phases, by using changes in Mo geometry as powerful molecular-scale probe.This work has been supported by a grant from Labex OSUG@2020 (Investissements d’avenir - ANR10 LABX56). B.M., A.F.-M., L.C., S.G. and F.C. thank the NEEDS program from the CNRS for funding support. B.M. also thanks the financial support from the China Scholarship Council (CSC)

Parenting behavior and the risk of becoming a victim and a bully/victim : a meta-analysis study

Objective: Being bullied has adverse effects on children's health. Children's family experiences and parenting behavior before entering school help shape their capacity to adapt and cope at school and have an impact on children's peer relationship, hence it is important to identify how parenting styles and parent–child relationship are related to victimization in order to develop intervention programs to prevent or mitigate victimization in childhood and adolescence. Methods: We conducted a systematic review of the published literature on parenting behavior and peer victimization using MEDLINE, PsychINFO, Eric and EMBASE from 1970 through the end of December 2012. We included prospective cohort studies and cross-sectional studies that investigated the association between parenting behavior and peer victimization. Results: Both victims and those who both bully and are victims (bully/victims) were more likely to be exposed to negative parenting behavior including abuse and neglect and maladaptive parenting. The effects were generally small to moderate for victims (Hedge's g range: 0.10–0.31) but moderate for bully/victims (0.13–0.68). Positive parenting behavior including good communication of parents with the child, warm and affectionate relationship, parental involvement and support, and parental supervision were protective against peer victimization. The protective effects were generally small to moderate for both victims (Hedge's g: range: −0.12 to −0.22) and bully/victims (−0.17 to −0.42). Conclusions: Negative parenting behavior is related to a moderate increase of risk for becoming a bully/victim and small to moderate effects on victim status at school. Intervention programs against bullying should extend their focus beyond schools to include families and start before children enter school