Visceral fat area and cardiometabolic risk: The Kardiovize study

BACKGROUND: Visceral fat is associated with adiposity-based complications. Bioimpedance measurement allows estimation of visceral fat area (VFA) in an easy manner. However, a validated cut-off value for VFA by bioimpedance associated with cardiometabolic risk is lacking in European population. AIM: To determine cut-off values of VFA measured via bioimpedance associated with cardiometabolic risk. METHODS: Random cross-sectional Czech population-based sample of 25-64 years old subjects. Receiver Operating Characteristic (ROC) curves were used and the area under the curve (AUC), sensitivity, and specificity were calculated. The Cardiometabolic Disease Staging System (CMDS) was used to classify cardiometabolic risk: Stage 1 - 1 or 2 metabolic syndrome (MetS) components, without impaired fasting glucose (IFG); Stage 2 - MetS or IFG; Stage 3 - MetS with IFG; Stage 4 - type 2 diabetes and/or cardiovascular disease. RESULTS: 2052 participants (54.5% females, median age 49 years) were included. Median VFA (inter-quartile range) were 82.2 cm2 (54.8) in men and 89.8 cm2 (55.6) in women. The best VFA cut-offs associated with Stage 1 in men and women were 71 cm2 (sensitivity = 0.654; specificity = 0.427) and 83 cm2 (sensitivity = 0.705; specificity = 0.556) ; Stage 2: 84 cm2 (sensitivity = 0.673; specificity = 0.551) and 98 cm2 (sensitivity = 0.702; specificity = 0.628) ; Stage 3: 90 cm2 (sensitivity = 0.886; specificity = 0.605) and 109 cm2 (sensitivity = 0.755; specificity = 0.704); Stage 4: 91 cm2 (sensitivity = 0.625; specificity = 0.611) and 81 cm2 (sensitivity = 0.695; specificity = 0.448), respectively. CONCLUSION: A cut-off value of VFA of 71 cm2 in men and 83 cm2 in women exhibited the earliest stage of cardiometabolic risk, and 90 cm2 in men and 109 cm2 in women showed the best performance to detect risk

Lateral Gene Expression in Drosophila Early Embryos Is Supported by Grainyhead-Mediated Activation and Tiers of Dorsally-Localized Repression

The general consensus in the field is that limiting amounts of the transcription factor Dorsal establish dorsal boundaries of genes expressed along the dorsal-ventral (DV) axis of early Drosophila embryos, while repressors establish ventral boundaries. Yet recent studies have provided evidence that repressors act to specify the dorsal boundary of intermediate neuroblasts defective (ind), a gene expressed in a stripe along the DV axis in lateral regions of the embryo. Here we show that a short 12 base pair sequence (“the A-box”) present twice within the ind CRM is both necessary and sufficient to support transcriptional repression in dorsal regions of embryos. To identify binding factors, we conducted affinity chromatography using the A-box element and found a number of DNA-binding proteins and chromatin-associated factors using mass spectroscopy. Only Grainyhead (Grh), a CP2 transcription factor with a unique DNA-binding domain, was found to bind the A-box sequence. Our results suggest that Grh acts as an activator to support expression of ind, which was surprising as we identified this factor using an element that mediates dorsally-localized repression. Grh and Dorsal both contribute to ind transcriptional activation. However, another recent study found that the repressor Capicua (Cic) also binds to the A-box sequence. While Cic was not identified through our A-box affinity chromatography, utilization of the same site, the A-box, by both factors Grh (activator) and Cic (repressor) may also support a “switch-like” response that helps to sharpen the ind dorsal boundary. Furthermore, our results also demonstrate that TGF-β signaling acts to refine ind CRM expression in an A-box independent manner in dorsal-most regions, suggesting that tiers of repression act in dorsal regions of the embryo

Leg length, skull circumference, and the incidence of dementia in Latin America and China: A 10/66 population-based cohort study

\ua9 2018 Prince et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background Adult leg length is influenced by nutrition in the first few years of life. Adult head circumference is an indicator of brain growth. Cross-sectional studies indicate inverse associations with dementia risk, but there have been few prospective studies. Methods Population-based cohort studies in urban sites in Cuba, Dominican Republic Puerto Rico and Venezuela, and rural and urban sites in Peru, Mexico and China. Sociodemographic and risk factor questionnaires were administered to all participants, and anthropometric measures taken, with ascertainment of incident dementia, and mortality, three to five years later. Results Of the original at risk cohort of 13,587 persons aged 65 years and over, 2,443 (18.0%) were lost to follow-up; 10,540 persons with skull circumference assessments were followed up for 40,466 person years, and 10,400 with leg length assessments were followed up for 39,954 person years. There were 1,009 cases of incident dementia, and 1,605 dementia free deaths. The fixed effect pooled meta-analysed adjusted subhazard ratio (ASHR) for leg length (highest vs. lowest quarter) was 0.80 (95% CI, 0.66–0.97) and for skull circumference was 1.02 (95% CI, 0.84–1.25), with no heterogeneity of effect between sites (I2 = 0%). Leg length measurements tended to be shorter at follow-up, particularly for those with baseline cognitive impairment and dementia. However, leg length change was not associated with dementia incidence (ASHR, per cm 1.006, 95% CI 0.992–1.020), and the effect of leg length was little altered after adjusting for baseline frailty (ASHR 0.82, 95% CI 0.67–0.99). A priori hypotheses regarding effect modification by gender or educational level were not supported. However, the effect of skull circumference was modified by gender (M vs F ASHR 0.86, 95% CI 0.75–0.98), but in the opposite direction to that hypothesized with a greater protective effect of larger skull dimensions in men. Conclusions Consistent findings across settings provide quite strong support for an association between adult leg length and dementia incidence in late-life. Leg length is a relatively stable marker of early life nutritional programming, which may confer brain reserve and protect against neu-rodegeneration in later life through mitigation of cardiometabolic risk. Further clarification of these associations could inform predictive models for future dementia incidence in the context of secular trends in adult height, and invigorate global efforts to improve childhood nutrition, growth and development

Using internet enabled mobile devices and social networking technologies to promote exercise as an intervention for young first episode psychosis patients

<p>Abstract</p> <p>Background</p> <p>Young people with first episode psychosis are at an increased risk for a range of poor health outcomes. In contrast to the growing body of evidence that suggests that exercise therapy may benefit the physical and mental health of people diagnosed with schizophrenia, there are no studies to date that have sought to extend the use of exercise therapy among patients with first episode psychosis. The aim of the study is to test the feasibility and acceptability of an exercise program that will be delivered via internet enabled mobile devices and social networking technologies among young people with first episode psychosis.</p> <p>Methods/Design</p> <p>This study is a qualitative pilot study being conducted at Orygen Youth Health Research Centre in Melbourne, Australia. Participants are young people aged 15-24 who are receiving clinical care at a specialist first episode psychosis treatment centre. Participants will also comprise young people from the general population. The exercise intervention is a 9-week running program, designed to gradually build a person's level of fitness to be able to run 5 kilometres (3 miles) towards the end of the program. The program will be delivered via an internet enabled mobile device. Participants will be asked to post messages about their running experiences on the social networking website, and will also be asked to attend three face-to-face interviews.</p> <p>Discussion</p> <p>This paper describes the development of a qualitative study to pilot a running program coupled with the use of internet enabled mobile devices among young people with first episode psychosis. If the program is found to be feasible and acceptable to patients, it is hoped that further rigorous evaluations will ultimately lead to the introduction of exercise therapy as part of an evidence-based, multidisciplinary approach in routine clinical care.</p

Conditional Facilitation of an Aphid Vector, Acyrthosiphon pisum, by the Plant Pathogen, Pea Enation Mosaic Virus

Plant pathogens can induce symptoms that affect the performance of insect herbivores utilizing the same host plant. Previous studies examining the effects of infection of tic bean, Vicia faba L. (Fabales: Fabaceae), by pea enation mosaic virus (PEMV), an important disease of legume crops, indicated there were no changes in the growth and reproductive rate of its primary vector the pea aphid, Acyrthosiphon pisum (Harris) (Hemiptera: Aphididae). Here, we report the results of laboratory experiments investigating how A. pisum responded to PEMV infection of a different host plant, Pisum sativum L., at different stages of symptom development. Aphid growth rate was negatively related to the age of the host plant, but when they were introduced onto older plants with well-developed PEMV symptoms they exhibited a higher growth rate compared to those developing on uninfected plants of the same age. In choice tests using leaf discs A. pisum showed a strong preference for discs from PEMV-infected peas, probably in response to visual cues from the yellowed and mottled infected leaves. When adults were crowded onto leaves using clip-cages they produced more winged progeny on PEMV-infected plants. The results indicate that PEMV produces symptoms in the host plant that can enhance the performance of A. pisum as a vector, modify the production of winged progeny and affect their spatial distribution. The findings provide further evidence that some insect vector/plant pathogen interactions could be regarded as mutualistic rather than commensal when certain conditions regarding the age, stage of infection and species of host plant are met

Analysis of IL28B Variants in an Egyptian Population Defines the 20 Kilobases Minimal Region Involved in Spontaneous Clearance of Hepatitis C Virus

Spontaneous clearance of hepatitis C virus (HCV) occurs in ∼30% of acute infections. Host genetics play a major role in HCV clearance, with a strong effect of single nucleotide polymorphisms (SNPs) of the IL28B gene already found in different populations, mostly infected with viral genotypes 1 and 3. Egypt has the highest prevalence of HCV infection in the world, which is mostly due to viral genotype 4. We investigated the role of several IL28B SNPs in HCV spontaneous clearance in an Egyptian population. We selected nine SNPs within the IL28B genomic region covering the linkage disequilibrium (LD) block known to be associated with HCV clearance in European populations. These SNPs were genotyped in 261 HCV-infected Egyptian subjects (130 with spontaneous clearance and 131 with chronic infection). The most associated SNPs were rs12979860 (P = 1.6×10−7) and the non-synonymous IL28B SNP, rs8103142 (P = 1.6×10−7). Interestingly, three SNPs at the two bounds of the region were monomorphic, reducing the size of the LD block in which the causal variants are potentially located to ∼20 kilobases. HCV clearance in Egypt was associated with a region of IL28B smaller than that identified in European populations, and involved the non-synonymous IL28B SNP, rs8103142

Intensive care unit course of infants and children after cranial vault reconstruction for craniosynostosis

<p>Abstract</p> <p>Background</p> <p>Craniosynostosis (CSS) results from the premature closure of one or more cranial sutures, leading to deformed calvaria at birth. It is a common finding in children with an incidence of one in 2000 births. Surgery is required in order to release the synostotic constraint and promote normal calvaria growth. Cranial vault remodeling is the surgical approach to CSS repair at our institution and it involves excision of the frontal, parietal, and occipital bones. The purpose of this article is to describe the post-operative course of infants and children admitted to our PICU after undergoing cranial vault remodeling for primary CSS.</p> <p>Findings</p> <p>Complete data was available for analyses in only 82 patients, 44 males (M) and 38 females (F); M: F ratio was 1:1.2. Patients (pts) age in months (mo) ranged from 2 mo to 132 mo, mean 18.2 ±-24.9 mo and weights (wt) ranged from 4.7 kg to 31.4 kg, mean 10.24 ± 5.5 Kg.. Duration of surgery (DOS) ranged from 70 minutes to 573 minutes mean 331.6 ± 89.0 minutes. No significant correlation exist between duration of surgery, suture category, patient's age or use of blood products (P > 0.05). IOP blood loss was higher in older pts (P < 0.05) and it correlates with body temperature in the PICU (P < .0001). Post-op use of FFP correlated with intra-operative PRBC transfusion (P < 0.0001). More PRBC was transfused within 12 hrs-24 hrs in PICU compared to other time periods (P < 0.05). LOS in PICU was < 3 days in 68% and > 3 days in 32%. Pts with fever had prolonged LOS (P < 0. 05); re-intubation rate was 2.4% and MVD were 1.83 days. Repeat operation for poor cosmetic results occurred in 9.7% of pts.</p> <p>Conclusions</p> <p>Post-op morbidities from increased use of blood products can be minimized if cranial vault remodeling is done at a younger age in patients with primary CSS. PICU length of stay is determined in part by post-op pyrexia and it can be reduced if extensive evaluations of post-op fever are avoided.</p

Sialic Acid Glycobiology Unveils Trypanosoma cruzi Trypomastigote Membrane Physiology.

Trypanosoma cruzi, the flagellate protozoan agent of Chagas disease or American trypanosomiasis, is unable to synthesize sialic acids de novo. Mucins and trans-sialidase (TS) are substrate and enzyme, respectively, of the glycobiological system that scavenges sialic acid from the host in a crucial interplay for T. cruzi life cycle. The acquisition of the sialyl residue allows the parasite to avoid lysis by serum factors and to interact with the host cell. A major drawback to studying the sialylation kinetics and turnover of the trypomastigote glycoconjugates is the difficulty to identify and follow the recently acquired sialyl residues. To tackle this issue, we followed an unnatural sugar approach as bioorthogonal chemical reporters, where the use of azidosialyl residues allowed identifying the acquired sugar. Advanced microscopy techniques, together with biochemical methods, were used to study the trypomastigote membrane from its glycobiological perspective. Main sialyl acceptors were identified as mucins by biochemical procedures and protein markers. Together with determining their shedding and turnover rates, we also report that several membrane proteins, including TS and its substrates, both glycosylphosphatidylinositol-anchored proteins, are separately distributed on parasite surface and contained in different and highly stable membrane microdomains. Notably, labeling for α(1,3)Galactosyl residues only partially colocalize with sialylated mucins, indicating that two species of glycosylated mucins do exist, which are segregated at the parasite surface. Moreover, sialylated mucins were included in lipid-raft-domains, whereas TS molecules are not. The location of the surface-anchored TS resulted too far off as to be capable to sialylate mucins, a role played by the shed TS instead. Phosphatidylinositol-phospholipase-C activity is actually not present in trypomastigotes. Therefore, shedding of TS occurs via microvesicles instead of as a fully soluble form

Agreement between chromogenic in situ hybridisation (CISH) and FISH in the determination of HER2 status in breast cancer

Determination of the HER2/neu (HER2) status in breast carcinoma has become necessary for the selection of breast cancer patients for trastuzumab therapy. Amplification of the gene analysed by fluorescence in situ hybridisation (FISH) or overexpression of the protein determined by immunohistochemistry (IHC) are the two major methods to establish this status. A strong correlation has been previously demonstrated between these two methods. However, FISH is not always feasible in routine practice and weakly positive IHC tumours (2+) do not always correspond to a gene amplification. Our study was performed in order to evaluate the contribution of chromogenic in situ hybridisation (CISH), which enables detection of the gene copies through an immunoperoxidase reaction. CISH was performed in 79 breast carcinomas for which the HER2 status was previously determined by IHC and FISH. The results of IHC, FISH and CISH were compared for each tumour. CISH procedures were successful in 95% of our cases. Whatever the IHC results, we found a very good concordance (96%) between CISH and FISH. Our study confirms that CISH may be an alternative to FISH for the determination of the gene amplification status in 2+ tumours. Our results allow us to think that, in many laboratories, CISH may also be an excellent method to calibrate the IHC procedures or, as a quality control test, to check regularly that the IHC signal is in agreement with the gene statu