The Clinical Variability of Maternally Inherited Diabetes and Deafness Is Associated with the Degree of Heteroplasmy in Blood Leukocytes

Context: Maternally inherited diabetes and deafness (MIDD) is a rare form of diabetes with a matrilineal transmission, sensorineural hearing loss, and macular pattern dystrophy due to an A to G transition at position 3243 of mitochondrial DNA (mtDNA) (m.3243A>G). The phenotypic heterogeneity of MIDD may be the consequence of different levels of mutated mtDNA among mitochondria in a given tissue. Objective: The aim of the present study was thus to ascertain the correlation between the severity of the phenotype in patients with MIDD and the level of heteroplasmy in the blood leukocytes. Participants: The GEDIAM prospective multicenter register was initiated in 1995. Eighty-nine Europid patients from this register, with MIDD and the mtDNA 3243A>G mutation, were included. Patients with MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) or with mitochondrial diabetes related to other mutations or to deletions of mtDNA were excluded. Results: A significant negative correlation was found between levels of heteroplasmy and age of the patients at the time of sampling for molecular analysis, age at the diagnosis of diabetes, and body mass index. After adjustment for age at sampling for molecular study and gender, the correlation between heteroplasmy levels and age at the diagnosis of diabetes was no more significant. The two other correlations remained significant. A significant positive correlation between levels of heteroplasmy and HbA1c was also found and remained significant after adjustment for age at molecular sampling and gender. Conclusions: These results support the hypothesis that heteroplasmy levels are at least one of the determinants of the severity of the phenotype in MIDD. Heteroplasmy levels are at least one of the determinants of the severity of the phenotype of maternally inherited diabetes and deafness

Polycystic ovary syndrome

The document attached has been archived with permission from the editor of the Medical Journal of Australia. An external link to the publisher’s copy is included.Polycystic ovary syndrome (PCOS) affects 5-20% of women of reproductive age worldwide. The condition is characterized by hyperandrogenism, ovulatory dysfunction and polycystic ovarian morphology (PCOM) - with excessive androgen production by the ovaries being a key feature of PCOS. Metabolic dysfunction characterized by insulin resistance and compensatory hyperinsulinaemia is evident in the vast majority of affected individuals. PCOS increases the risk for type 2 diabetes mellitus, gestational diabetes and other pregnancy-related complications, venous thromboembolism, cerebrovascular and cardiovascular events and endometrial cancer. PCOS is a diagnosis of exclusion, based primarily on the presence of hyperandrogenism, ovulatory dysfunction and PCOM. Treatment should be tailored to the complaints and needs of the patient and involves targeting metabolic abnormalities through lifestyle changes, medication and potentially surgery for the prevention and management of excess weight, androgen suppression and/or blockade, endometrial protection, reproductive therapy and the detection and treatment of psychological features. This Primer summarizes the current state of knowledge regarding the epidemiology, mechanisms and pathophysiology, diagnosis, screening and prevention, management and future investigational directions of the disorder.Robert J Norman, Ruijin Wu and Marcin T Stankiewic

Investigation of Genetic Variation Underlying Central Obesity amongst South Asians

The LOLIPOP study is supported by the National Institute for Health Research (NIHR) Comprehensive Biomedical Research Centre Imperial College Healthcare NHS Trust, the British Heart Foundation (SP/04/002), the Medical Research Council (G0601966,G0700931), the Wellcome Trust (084723/Z/08/Z), and the NIHR (RP-PG-0407-10371). The work was carried out in part at the NIHR/Wellcome Trust Imperial Clinical Research Facility. The Sikh Diabetes Study is supported by National Institute of Health grants KO1TW006087, funded by the Fogarty International Center, R01DK082766, funded by National Institute of Diabetes and Digestive and Kidney Diseases, and a seed grant from University of Oklahoma Health Sciences Center, Oklahoma City, USA. The Mauritius Family Study is supported by the Mauritius Ministry of Health and Quality of Life, Australian Government National Health and Medical Research Council NHMRC project grant numbers 1020285 and 1037916, the Victorian Government’s OIS Program, and partly funded by US National Institutes of Health Grant DK-25446. We thank the participants and research staff who made the study possible.South Asians are 1/4 of the world’s population and have increased susceptibility to central obesity and related cardiometabolic disease. Knowledge of genetic variants affecting risk of central obesity is largely based on genome-wide association studies of common SNPs in Europeans. To evaluate the contribution of DNA sequence variation to the higher levels of central obesity (defined as waist hip ratio adjusted for body mass index, WHR) among South Asians compared to Europeans we carried out: i) a genome-wide association analysis of >6M genetic variants in 10,318 South Asians with focused analysis of population-specific SNPs; ii) an exome-wide association analysis of ~250K SNPs in protein-coding regions in 2,637 South Asians; iii) a comparison of risk allele frequencies and effect sizes of 48 known WHR SNPs in 12,240 South Asians compared to Europeans. In genome-wide analyses, we found no novel associations between common genetic variants and WHR in South Asians at P<5x10-8; variants showing equivocal association with WHR (P<1x10-5) did not replicate at P<0.05 in an independent cohort of South Asians (N = 1,922) or in published, predominantly European meta-analysis data. In the targeted analyses of 122,391 population-specific SNPs we also found no associations with WHR in South Asians at P<0.05 after multiple testing correction. Exome-wide analyses showed no new associations between genetic variants and WHR in South Asians, either individually at P<1.5x10-6 or grouped by gene locus at P<2.5x10−6. At known WHR loci, risk allele frequencies were not higher in South Asians compared to Europeans (P = 0.77), while effect sizes were unexpectedly smaller in South Asians than Europeans (P<5.0x10-8). Our findings argue against an important contribution for population-specific or cosmopolitan genetic variants underlying the increased risk of central obesity in South Asians compared to Europeans.Yeshttp://www.plosone.org/static/editorial#pee

Maternal blood cadmium, lead and arsenic levels, nutrient combinations, and offspring birthweight

Abstract Background Cadmium (Cd), lead (Pb) and arsenic (As) are common environmental contaminants that have been associated with lower birthweight. Although some essential metals may mitigate exposure, data are inconsistent. This study sought to evaluate the relationship between toxic metals, nutrient combinations and birthweight among 275 mother-child pairs. Methods Non-essential metals, Cd, Pb, As, and essential metals, iron (Fe), zinc (Zn), selenium (Se), copper (Cu), calcium (Ca), magnesium (Mg), and manganese (Mn) were measured in maternal whole blood obtained during the first trimester using inductively coupled plasma mass spectrometry. Folate concentrations were measured by microbial assay. Birthweight was obtained from medical records. We used quantile regression to evaluate the association between toxic metals and nutrients due to their underlying wedge-shaped relationship. Ordinary linear regression was used to evaluate associations between birth weight and toxic metals. Results After multivariate adjustment, the negative association between Pb or Cd and a combination of Fe, Se, Ca and folate was robust, persistent and dose-dependent (p < 0.05). However, a combination of Zn, Cu, Mn and Mg was positively associated with Pb and Cd levels. While prenatal blood Cd and Pb were also associated with lower birthweight. Fe, Se, Ca and folate did not modify these associations. Conclusion Small sample size and cross-sectional design notwithstanding, the robust and persistent negative associations between some, but not all, nutrient combinations with these ubiquitous environmental contaminants suggest that only some recommended nutrient combinations may mitigate toxic metal exposure in chronically exposed populations. Larger longitudinal studies are required to confirm these findings

Silver-Gold Alloys Prepared by Pulse Plating: Modeling of the Chemical Composition

International audienceThe individual and simultaneous deposition of silver and gold from low cyanide concentration solutions showed two regions in the potentiodynamical j‐E curves. At low overpotentials, these processes take place through adsorbed species while at high overpotentials the normal diffusional region is observed. Then, when pure silver and gold deposits are prepared by galvanostatic pulse plating, the presence of adsorbed species cannot be disregarded. This phenomenon prevails and has an important effect when silver and gold are simultaneously deposited by pulse plating. Therefore, the chemical composition of the alloys is described by a model in the activation region while another model was deduced for the diffusional region. The models take into account typical parameters of pulse plating and were developed by application of the statistical experimental design methodology

Initial stages of the electrocrystallization of copper from non-cyanide alkaline bath containing glycine

International audienceAn electrochemical study on the initial stages of copper electrodeposition onto nickel substrate from non-cyanide alkaline bath containing glycine as complexing agent is presented in this work. The studied parameters were copper concentration, glycine concentration, and deposition potential. Upon scanning in the negative direction, one cathodic peak was observed, which is associated to copper electrodeposition from CuL2 complex at pH 10.0 (where L− is the anion form of glycine). Analysis of the chronoamperograms indicates time-dependent nucleation mechanisms. A progressive nucleation mechanism without overlap of diffusion zones, which involved an electron transfer reaction (at short times) and a progressive nucleation mechanism with overlap of diffusion zones (at long times). Non-linear fitting methods were applied to obtain the growth and nucleation kinetic parameters from theoretical equations proposed to describe this system

Precipitation variance analysis of the Taboão river watershed (RS)

O objetivo deste trabalho foi determinar a distribuição de probabilidade que melhor se ajuste à variância da série histórica de precipitações diárias em seis estações na bacia hidrográfica do rio Taboão, região noroeste do Estado do Rio Grande do Sul, durante um período de sete anos, distribuídos nos intervalos de 05/05/03 a 09/05/06 e 01/07/07 a 04/06/11. Para isso, foram determinados os padrões de agrupamento, em relação à variância. Na comparação do ajustamento das distribuições observadas da variável variância com as distribuições teóricas, foi utilizado o teste de ajustamento de Shapiro-Wilk. Determinadas as distribuições Log Pearson e Gama, realizou-se o agrupamento das estações de acordo com sua variância pela distância Euclidiana através do método de Ward. Os agrupamentos propostos foram verificados através da ANOVA e teste de Tukey, resultando que os agrupamentos propostos não se sustentavam, demonstrando a homogeneidade entre a média das variâncias das séries históricas das estações analisadas. Os resultados obtidos permitem concluir que a precipitação na bacia do rio Taboão é homogênea.The objective of this paper was to determine the probabilistic distribution that fits the variance of the precipitation data obtained in six stations located at Taboão river watershed, northwestern region of Rio Grande do Sul State, during a seven years period from 5/May/2003 to 9/May/2006 and from 1/July/2007 to 4/June/2011. Group patterns were determined in relation to the variance. The Shapiro-Wilk test was used for a comparison between the observed and theoretical distributions of the variance. After determining the Log Pearson and Gama distribution, the grouping of stations was performed based on theirs variances by the Euclidean distance using the Ward’s method. The evaluation with the ANOVA and Tukey’s test showed that the proposed groupings were not sustainable, which implies the homogeneity among the mean values of the historical series variances from the six analyzed precipitation stations. The obtained results permit to conclude that the precipitation is homogeneous in the Taboão river watershed