Body composition and body fat distribution are related to cardiac autonomic control in non-alcoholic fatty liver disease patients

BACKGROUND/OBJECTIVES: Heart rate recovery (HRR), a cardiac autonomic control marker, was shown to be related to body composition (BC), yet this was not tested in non-alcoholic fatty liver disease (NAFLD) patients. The aim of this study was to determine if, and to what extent, markers of BC and body fat (BF) distribution are related to cardiac autonomic control in NAFLD patients. SUBJECTS/METHODS: BC was assessed with dual-energy X-ray absorptiometry in 28 NAFLD patients (19 men, 51±13 years, and 9 women, 47±13 years). BF depots ratios were calculated to assess BF distribution. Subjects’ HRR was recorded 1 (HRR1) and 2 min (HRR2) immediately after a maximum graded exercise test. RESULTS: BC and BF distribution were related to HRR; particularly weight, trunk BF and trunk BF-to-appendicular BF ratio showed a negative relation with HRR1 (r 1⁄4 0.613, r 1⁄4 0.597 and r 1⁄4 0.547, respectively, Po0.01) and HRR2 (r 1⁄4 0.484, r 1⁄4 0.446, Po0.05, and r 1⁄4 0.590, Po0.01, respectively). Age seems to be related to both HRR1 and HRR2 except when controlled for BF distribution. The preferred model in multiple regression should include trunk BF-to-appendicular BF ratio and BF to predict HRR1 (r2 1⁄4 0.549; Po0.05), and trunk BF-to-appendicular BF ratio alone to predict HRR2 (r2 1⁄4 0.430; Po0.001). CONCLUSIONS: BC and BF distribution were related to HRR in NAFLD patients. Trunk BF-to-appendicular BF ratio was the best independent predictor of HRR and therefore may be best related to cardiovascular increased risk, and possibly act as a mediator in age-related cardiac autonomic control variation.info:eu-repo/semantics/publishedVersio

Stress-Induced Reinstatement of Drug Seeking: 20 Years of Progress

In human addicts, drug relapse and craving are often provoked by stress. Since 1995, this clinical scenario has been studied using a rat model of stress-induced reinstatement of drug seeking. Here, we first discuss the generality of stress-induced reinstatement to different drugs of abuse, different stressors, and different behavioral procedures. We also discuss neuropharmacological mechanisms, and brain areas and circuits controlling stress-induced reinstatement of drug seeking. We conclude by discussing results from translational human laboratory studies and clinical trials that were inspired by results from rat studies on stress-induced reinstatement. Our main conclusions are (1) The phenomenon of stress-induced reinstatement, first shown with an intermittent footshock stressor in rats trained to self-administer heroin, generalizes to other abused drugs, including cocaine, methamphetamine, nicotine, and alcohol, and is also observed in the conditioned place preference model in rats and mice. This phenomenon, however, is stressor specific and not all stressors induce reinstatement of drug seeking. (2) Neuropharmacological studies indicate the involvement of corticotropin-releasing factor (CRF), noradrenaline, dopamine, glutamate, kappa/dynorphin, and several other peptide and neurotransmitter systems in stress-induced reinstatement. Neuropharmacology and circuitry studies indicate the involvement of CRF and noradrenaline transmission in bed nucleus of stria terminalis and central amygdala, and dopamine, CRF, kappa/dynorphin, and glutamate transmission in other components of the mesocorticolimbic dopamine system (ventral tegmental area, medial prefrontal cortex, orbitofrontal cortex, and nucleus accumbens). (3) Translational human laboratory studies and a recent clinical trial study show the efficacy of alpha-2 adrenoceptor agonists in decreasing stress-induced drug craving and stress-induced initial heroin lapse

Height and timing of growth spurt during puberty in young people living with vertically acquired HIV in Europe and Thailand.

OBJECTIVE: The aim of this study was to describe growth during puberty in young people with vertically acquired HIV. DESIGN: Pooled data from 12 paediatric HIV cohorts in Europe and Thailand. METHODS: One thousand and ninety-four children initiating a nonnucleoside reverse transcriptase inhibitor or boosted protease inhibitor based regimen aged 1-10 years were included. Super Imposition by Translation And Rotation (SITAR) models described growth from age 8 years using three parameters (average height, timing and shape of the growth spurt), dependent on age and height-for-age z-score (HAZ) (WHO references) at antiretroviral therapy (ART) initiation. Multivariate regression explored characteristics associated with these three parameters. RESULTS: At ART initiation, median age and HAZ was 6.4 [interquartile range (IQR): 2.8, 9.0] years and -1.2 (IQR: -2.3 to -0.2), respectively. Median follow-up was 9.1 (IQR: 6.9, 11.4) years. In girls, older age and lower HAZ at ART initiation were independently associated with a growth spurt which occurred 0.41 (95% confidence interval 0.20-0.62) years later in children starting ART age 6 to 10 years compared with 1 to 2 years and 1.50 (1.21-1.78) years later in those starting with HAZ less than -3 compared with HAZ at least -1. Later growth spurts in girls resulted in continued height growth into later adolescence. In boys starting ART with HAZ less than -1, growth spurts were later in children starting ART in the oldest age group, but for HAZ at least -1, there was no association with age. Girls and boys who initiated ART with HAZ at least -1 maintained a similar height to the WHO reference mean. CONCLUSION: Stunting at ART initiation was associated with later growth spurts in girls. Children with HAZ at least -1 at ART initiation grew in height at the level expected in HIV negative children of a comparable age

TRY plant trait database - enhanced coverage and open access

Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

Mechanisms Establishing TLR4-Responsive Activation States of Inflammatory Response Genes

Precise control of the innate immune response is required for resistance to microbial infections and maintenance of normal tissue homeostasis. Because this response involves coordinate regulation of hundreds of genes, it provides a powerful biological system to elucidate the molecular strategies that underlie signal- and time-dependent transitions of gene expression. Comprehensive genome-wide analysis of the epigenetic and transcription status of the TLR4-induced transcriptional program in macrophages suggests that Toll-like receptor 4 (TLR4)-dependent activation of nearly all immediate/early- (I/E) and late-response genes results from a sequential process in which signal-independent factors initially establish basal levels of gene expression that are then amplified by signal-dependent transcription factors. Promoters of I/E genes are distinguished from those of late genes by encoding a distinct set of signal-dependent transcription factor elements, including TATA boxes, which lead to preferential binding of TBP and basal enrichment for RNA polymerase II immediately downstream of transcriptional start sites. Global nuclear run-on (GRO) sequencing and total RNA sequencing further indicates that TLR4 signaling markedly increases the overall rates of both transcriptional initiation and the efficiency of transcriptional elongation of nearly all I/E genes, while RNA splicing is largely unaffected. Collectively, these findings reveal broadly utilized mechanisms underlying temporally distinct patterns of TLR4-dependent gene activation required for homeostasis and effective immune responses

Alterations in Epithelial and Mesenchymal Intestinal Gene Expression During Doxorubicin-Induced Mucositis in Mice

In the current study we aimed to gain insight into epithelial-mesenchymal cross-talk and progenitor compartment modulation during doxorubicin (DOX)-induced mucositis in mice. Intestinal segments were collected on various days after DOX treatment. DOX-induced damage at day 1–2 was characterized by increased epithelial proliferation and apoptosis and a decrease in the expression of epithelial differentiation markers. Concurrently, T-cell factor-4 (TCF4) levels increased and the epithelial differentiation enhancing factor, bone morphogenic protein-4 (BMP4), decreased. During severe damage (day 3), BMP4 levels were significantly increased, which inversely correlated with epithelial proliferation. At the same time, the expression of the epithelial differentiation markers was increasing again. At day 7, BMP4 levels were down-regulated, while the levels of the epithelial differentiation markers and TCF4 were normalized again. These data suggest that in response to DOX-induced damage, BMP4 and TCF4 are modulated in such a way that homeostasis of the progenitor compartment is partly preserved

Preoperative Behavioural Intervention versus standard care to Reduce Drinking before elective orthopaedic Surgery (PRE-OP BIRDS):Protocol for a multicentre pilot randomised controlled trial

Background Evidence suggests that increased preoperative alcohol consumption increases the risk of postoperative complications; therefore, a reduction or cessation in alcohol intake before surgery may reduce perioperative risk. Preoperative assessment presents an opportunity to intervene to optimise patients for surgery. This multicentre, two-arm, parallel group, individually randomised controlled trial will investigate whether a definitive trial of a brief behavioural intervention aimed at reducing preoperative alcohol consumption is feasible and acceptable to healthcare professionals responsible for its delivery and the preoperative elective orthopaedic patient population. Methods Screening will be conducted by trained healthcare professionals at three hospitals in the North East of England. Eligible patients (those aged 18 or over, listed for elective hip or knee arthroplasty surgery and scoring 5 or more or reporting consumption of six or more units on a single occasion at least weekly on the alcohol screening tool) who enrol in the trial will be randomised on a one-to-one non-blinded basis to either treatment as usual or brief behavioural intervention delivered in the pre-assessment clinic. Patients will be followed up 1–2 days pre-surgery, 1–5 days post-surgery (as an in-patient), 6 weeks post-surgery, and 6 months post intervention. Feasibility will be assessed through rates of screening, eligibility, recruitment, and retention to 6-month follow-up. An embedded qualitative study will explore the acceptability of study methods to patients and staff. Discussion This pilot randomised controlled trial will establish the feasibility and acceptability of trial procedures reducing uncertainties ahead of a definitive randomised controlled trial to establish the effectiveness of brief behavioural intervention to reduce alcohol consumption in the preoperative period and the potential impact on perioperative complications

HisAK70: Progress towards a vaccine against different forms of leishmaniosis

Background: Leishmania major and Leishmania infantum are among the main species that are responsible for cutaneous leishmaniosis (CL) and visceral leishmaniosis (VL), respectively. The leishmanioses represent the second-largest parasitic killer in the world after malaria. Recently, we succeeded in generating a plasmid DNA (pCMV-HISA70m2A) and demonstrated that immunized mice were protected against L. major challenge. The efficacy of the DNA-vaccine was further enhanced by the inclusion of KMP-11 antigen into the antibiotic-free plasmid pVAX1-asd. Methods: Here, we describe the use of a HisAK70 DNA-vaccine encoding seven Leishmania genes (H2A, H2B, H3, H4, A2, KMP11 and HSP70) for vaccination of mice to assess the induction of a resistant phenotype against VL and CL. Results: HisAK70 was successful in vaccinated mice, resulting in a high amount of efficient sterile hepatic granulomas associated with a hepatic parasite burden fully resolved in the VL model; and resulting in 100 % inhibition of parasite visceralization in the CL model. Conclusions: The results suggest that immunization with the HisAK70 DNA-vaccine may provide a rapid, suitable, and efficient vaccination strategy to confer cross-protective immunity against VL and CL.This work was partially supported by grants from the Spanish Ministry of Economy and Competitiveness (AGL2010-17394 and AGL2013-44100R) and PLATESA (P2013/ABI-2906) from the Comunidad de Madrid (Spain).Peer Reviewe