Associations of stunting in early childhood with cardiometabolic risk factors in adulthood

Abstract Early life stunting may have long-term effects on body composition, resulting in obesity-related comorbidities. We tested the hypothesis that individuals stunted in early childhood may be at higher cardiometabolic risk later in adulthood. 1753 men and 1781 women participating in the 1982 Pelotas (Brazil) birth cohort study had measurements of anthropometry, body composition, lipids, glucose, blood pressure, and other cardiometabolic traits at age 30 years. Early stunting was defined as height-for-age Z-score at age 2 years below -2 against the World Health Organization growth standards. Linear regression models were performed controlling for sex, maternal race/ethnicity, family income at birth, and birthweight. Analyses were stratified by sex when p-interaction<0.05. Stunted individuals were shorter (β=-0.71 s.d.; 95% CI: -0.78 to -0.64), had lower BMI (β=-0.14 s.d.; 95%CI: -0.25 to -0.03), fat mass (β=-0.28 s.d.; 95%CI: -0.38 to -0.17), SAFT (β=-0.16 s.d.; 95%CI: -0.26 to -0.06), systolic (β=-0.12 s.d.; 95%CI: -0.21 to -0.02) and diastolic blood pressure (β=-0.11 s.d.; 95%CI: -0.22 to -0.01), and higher VFT/SAFT ratio (β=0.15 s.d.; 95%CI: 0.06 to 0.24), in comparison with non-stunted individuals. In addition, early stunting was associated with lower fat free mass in both men (β=-0.39 s.d.; 95%CI: -0.47 to -0.31) and women (β=-0.37 s.d.; 95%CI: -0.46 to -0.29) after adjustment for potential confounders. Our results suggest that early stunting has implications on attained height, body composition and blood pressure. The apparent tendency of stunted individuals to accumulate less fat-free mass and subcutaneous fat might predispose them towards increased metabolic risks in later life.The last phase of the 1982 Pelotas (Brazil) birth cohort study was supported by the Wellcome Trust and the Fundação de Aparo à Pesquisa do Estado do Rio Grande do Sul; Brazil (Edital 04/2012 – PQG; Processo 12/2185-9). Earlier phases were funded by the International Development Research Centre (Canada), the WHO (Department of Child and Adolescent Health and Development and Human Reproduction Programme) to BLH, the Overseas Development Administration (currently the Department for International Development, United Kingdom), the European Union, the United Nations Development Fund for Women, the National Program for Centres of Excellence, the Pastorate of the Child (Brazil), the National Council for Scientific and Technological Development (CNPq; Brazil), and the Ministry of Health (Brazil). GVAF was supported by the Brazilian Coordination of Improvement of Higher Education Personnel (scholarship process BEX 5077/13-3). EDLR and KKO are supported by the Medical Research Council [Unit Programme number MC_UU_12015/2]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Accurate simultaneous quantification of liver steatosis and iron overload in diffuse liver diseases with MRI

Purpose: To evaluate the diagnostic performances of 3 Tesla multi-echo chemical shift-encoded gradient echo magnetic resonance (MECSE-MR) imaging to simultaneously quantify liver steatosis and iron overload in a wide spectrum of diffuse liver diseases having biopsy as reference standard. Methods: MECSE-MR-acquired images were used to calculate fat fraction and iron content in a single breath-hold in 109 adult patients. Proton density fat fraction (PDFF) was prospectively estimated using complex-based data reconstruction with multipeak fat modeling. Water R2* was used to estimate iron content. Biopsy was obtained in all cases, grading liver steatosis, siderosis, inflammation, and fibrosis. Differences in PDFF and R2* values across histopathological grades were analyzed, and ROC curves analyses evaluated the MR diagnostic performance. Results: Calculated fat fraction measurements showed significant differences (p < 0.001) among steatosis grades, being unaffected by the presence of inflammation or fibrosis (p ≥ 0.05). A strong correlation was found between fat fraction and steatosis grade (R S = 0.718, p < 0.001). Iron deposits did not affect fat fraction quantitation (p ≥ 0.05), except in cases with severe iron overload (grade 4). A strong positive correlation was also observed between R2* measurements and iron grades (R S = 0.704, p < 0.001). Calculated R2* values were not different across grades of steatosis, inflammation, and fibrosis (p ≥ 0.05). Conclusion: A MECSE-MR sequence simultaneously quantifies liver steatosis and siderosis, regardless coexisting liver inflammation or fibrosis, with high accuracy in a wide spectrum of diffuse liver disorders. This sequence can be acquired within a single breath-hold and can be implemented in the routine MR evaluation of the liver.This work was partially funded by a research grant from the Teaching and Research Department of Centro Hospitalar do Porto (DEFI:309/12(213-DEFI/251-CES)) and from a Spanish Ministry of Health and Carlos III Health Institute funding grant (PI12/01262). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Optimizing Trajectories for Cranial Laser Interstitial Thermal Therapy Using Computer-Assisted Planning: A Machine Learning Approach

Laser interstitial thermal therapy (LITT) is an alternative to open surgery for drug-resistant focal mesial temporal lobe epilepsy (MTLE). Studies suggest maximal ablation of the mesial hippocampal head and amygdalohippocampal complex (AHC) improves seizure freedom rates while better neuropsychological outcomes are associated with sparing of the parahippocampal gyrus (PHG). Optimal trajectories avoid sulci and CSF cavities and maximize distance from vasculature. Computer-assisted planning (CAP) improves these metrics, but the combination of entry and target zones has yet to be determined to maximize ablation of the AHC while sparing the PHG. We apply a machine learning approach to predict entry and target parameters and utilize these for CAP. Ten patients with hippocampal sclerosis were identified from a prospectively managed database. CAP LITT trajectories were generated using entry regions that include the inferior occipital, middle occipital, inferior temporal, and middle temporal gyri. Target points were varied by sequential AHC erosions and transformations of the centroid of the amygdala. A total of 7600 trajectories were generated, and ablation volumes of the AHC and PHG were calculated. Two machine learning approaches (random forest and linear regression) were investigated to predict composite ablation scores and determine entry and target point combinations that maximize ablation of the AHC while sparing the PHG. Random forest and linear regression predictions had a high correlation with the calculated values in the test set (ρ = 0.7) for both methods. Maximal composite ablation scores were associated with entry points around the junction of the inferior occipital, middle occipital, and middle temporal gyri. The optimal target point was the anteromesial amygdala. These parameters were then used with CAP to generate clinically feasible trajectories that optimize safety metrics. Machine learning techniques accurately predict composite ablation score. Prospective studies are required to determine if this improves seizure-free outcome while reducing neuropsychological morbidity following LITT for MTLE

Evaluation of fibrosis and inflammation in diffuse liver diseases using intravoxel incoherent motion diffusion-weighted MR imaging

Purpose: The purpose of the study was to evaluate the role of intravoxel incoherent motion (IVIM) diffusion model for the assessment of liver fibrosis and inflammation in diffuse liver disorders, also considering the presence of liver steatosis and iron deposits. Methods: Seventy-four patients were included, with liver biopsy and a 3 Tesla abdominal magnetic resonance imaging examination, with an IVIM diffusion-weighted sequence (single-shot spin-echo echo-planar sequence, with gradient reversal fat suppression; 6 b-values: 0, 50, 200, 400, 600, and 800 s/mm2). Histological evaluation comprised the Ishak modified scale, for grading inflammation and fibrosis, plus steatosis and iron loading classification. The liver apparent diffusion coefficient (ADC) and IVIM parameters (D, D*, f) were calculated from the IVIM images. The relationship between IVIM parameters and histopathological scores were evaluated by ANOVA and Spearman correlation tests. A test-retest experiment assessed reproducibility and repeatability in 10 healthy volunteers and 10 randomly selected patient studies. Results: ADC and f values were lower with higher fibrosis stages (p = 0.009, p = 0.006, respectively) and also with higher necro-inflammatory activity grades (p = 0.02, p = 0.017, respectively). Considered together, only fibrosis presented a significant effect on ADC and f measurements (p 0.05). A mild correlation was found between ADC and f with fibrosis (R S = -0.32 and R S = -0.38; p < 0.05) and inflammation (R S = -0.31 and R S = -0.32, p < 0.05; respectively). The AUROC for ADC and f measurements with the different dichotomizations between fibrosis or inflammation grades were only fair (0.670 to 0.749, p < 0.05). Neither D nor D* values were significantly different between liver fibrosis or inflammation grades. D measurements were significantly different across histologic grades of steatosis (p < 0.001) and iron overload (p < 0.001), whereas f measurements showed significant differences across histologic steatosis grades (p = 0.005). There was an excellent agreement between the different readers for ADC, f, and D. Conclusions: Although fibrosis presented a significant effect on ADC and f, IVIM measurements are not accurate enough to stage liver fibrosis or necro-inflammatory activity in diffuse liver diseases. D values were influenced by steatosis and iron overload.This work was partially funded by a research Grant from the Teaching and Research Department of Centro Hospitalar do Porto (DEFI:309/12(213-DEFI/251-CES)) and from a Spanish Ministry of Health and Carlos III Health Institute funding grant (PI12/01262). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Comparative cytogenetic analysis of two grasshopper species of the tribe Abracrini (Ommatolampinae, Acrididae)

The grasshopper species Orthoscapheus rufipes and Eujivarus fusiformis were analyzed using several cytogenetic techniques. The karyotype of O. rufipes, described here for the first time, had a diploid number of 2n = 23, whereas E. fusiformis had a karyotype with 2n = 21. The two species showed the same mechanism of sex determination (XO type) but differed in chromosome morphology. Pericentromeric blocks of constitutive heterochromatin (CH) were detected in the chromosome complement of both species. CMA3/DA/DAPI staining revealed CMA3-positive blocks in CH regions in four autosomal bivalents of O. rufipes and in two of E. fusiformis. The location of active NORs differed between the two species, occurring in bivalents M6 and S9 of O. rufipes and M6 and M7 of E. fusiformsi. The rDNA sites revealed by FISH coincided with the number and position of the active NORs detected by AgNO3 staining. The variability in chromosomal markers accounted for the karyotype differentiation observed in the tribe Abracrini

Peer substance use overestimation among French university students: a cross-sectional survey

<p>Abstract</p> <p>Background</p> <p>Normative misperceptions have been widely documented for alcohol use among U.S. college students. There is less research on other substances or European cultural contexts. This study explores which factors are associated with alcohol, tobacco and cannabis use misperceptions among French college students, focusing on substance use.</p> <p>Methods</p> <p>12 classes of second-year college students (n = 731) in sociology, medicine, nursing or foreign language estimated the proportion of tobacco, cannabis, alcohol use and heavy episodic drinking among their peers and reported their own use.</p> <p>Results</p> <p>Peer substance use overestimation frequency was 84% for tobacco, 55% for cannabis, 37% for alcohol and 56% for heavy episodic drinking. Cannabis users (p = 0.006), alcohol (p = 0.003) and heavy episodic drinkers (p = 0.002), are more likely to overestimate the prevalence of use of these consumptions. Tobacco users are less likely to overestimate peer prevalence of smoking (p = 0.044). Women are more likely to overestimate tobacco (p < 0.001) and heavy episodic drinking (p = 0.007) prevalence. Students having already completed another substance use questionnaire were more likely to overestimate alcohol use prevalence (p = 0.012). Students exposed to cannabis prevention campaigns were more likely to overestimate cannabis (p = 0.018) and tobacco use (p = 0.022) prevalence. Other identified factors are class-level use prevalences and academic discipline.</p> <p>Conclusions</p> <p>Local interventions that focus on creating realistic perceptions of substance use prevalence could be considered for cannabis and alcohol prevention in French campuses.</p

Enhanced ERbeta immunoexpression and apoptosis in the germ cells of cimetidine-treated rats

<p>Abstract</p> <p>Background</p> <p>Cimetidine, refereed as antiandrogenic drug, causes hormonal changes in male patients such as increased testosterone and FSH levels. In the rat testis, structural alterations in the seminiferous tubules have been related to germ cell loss and Sertoli cell death by apoptosis. Regarding the important role of Sertoli cells in the conversion of testosterone into estrogen, via aromatase, the immunoexpression of estrogen receptors-beta (ERbeta) was evaluated in the germ cells of untreated and treated rats with cimetidine. A relationship between ERbeta immunoreactivity and apoptosis was also investigated in the germ cells of damaged tubules.</p> <p>Methods</p> <p>Immunohistochemistry for detection of ERbeta and TUNEL method were performed in testicular sections of adult male rats treated with 50 mg/Kg of cimetidine (CmG) or saline solution (CG) for 52 days.</p> <p>Results</p> <p>In CG, a cytoplasmic immunoexpression for ERbeta was observed in spermatogonia, primary spermatocytes and spermatids. An evident ERbeta immunoreactivity was always observed in the flagellum and residual bodies of late spermatids. In CmG, the cytoplasm or cytoplasm and nuclei of germ cells of the damaged tubules by cimetidine showed enhanced ERbeta immunostaining. TUNEL-labeling was usually observed in the same germ cell types exhibiting enhanced ERbeta immunoreactivity.</p> <p>Conclusion</p> <p>The presence of ERbeta immunolabeling in the flagellum and residual bodies of spermatids reinforces the role of estrogen in spermiogenesis. The overexpression of ERbeta in the germ cells of CmG could be related to a possible interference of cimetidine on tubular androgenization and/or on the intratubular aromatase due to Sertoli cell damage. The parallelism between ERbeta overexpression and apoptosis indicates a participation of ERbeta on germ cell death.</p