Physical Activity and Sedentary Time: Association with Metabolic Health and Liver Fat.

INTRODUCTION/PURPOSE: To investigate whether a) lower levels of daily physical activity (PA) and greater sedentary time accounted for contrasting metabolic phenotypes (higher liver fat/presence of metabolic syndrome [MetS+] vs lower liver fat/absence of metabolic syndrome [MetS-]) in individuals of similar BMI and b) the association of sedentary time on metabolic health and liver fat. METHODS: Ninety-eight habitually active participants (53 female, 45 male; age 39±13 years; BMI 26.9±5.1 kg/m), underwent assessments of PA (SenseWear armband; wear time ~98%), cardio-respiratory fitness (V[Combining Dot Above]O2 peak), body composition (MRI and MRS) and multi-organ insulin sensitivity (OGTT). We undertook a) cross-sectional analysis comparing four groups: non-obese or obese, with and without metabolic syndrome (MetS+ vs MetS-) and b) univariate and multivariate regression for sedentary time and other levels of PA in relation to liver fat. RESULTS: Light, moderate and vigorous PA did not account for differences in metabolic health between individuals, whether non-obese or obese, although MetS+ individuals were more sedentary, with a higher number, and prolonged bouts (~1-2 hours). Overall, sedentary time, average daily METS and V[Combining Dot Above]O2 peak were each independently associated with liver fat percentage. Each additional hour of daily sedentary time was associated with a 1.15% (95% CI, 1.14-1.50%) higher liver fat content. CONCLUSIONS: Greater sedentary time, independent of other levels of PA, is associated with being metabolically unhealthy; even in habitually active people, lesser sedentary time, and higher cardio-respiratory fitness and average daily METS is associated with lower liver fat.This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Surfactant protein D modulates HIV infection of both T-cells and dendritic cells

Surfactant Protein D (SP-D) is an oligomerized C-type lectin molecule with immunomodulatory properties and involvement in lung surfactant homeostasis in the respiratory tract. SP-D binds to the enveloped viruses, influenza A virus and respiratory syncytial virus and inhibits their replication in vitro and in vivo. SP-D has been shown to bind to HIV via the HIV envelope protein gp120 and inhibit infectivity in vitro. Here we show that SP-D binds to different strains of HIV (BaL and IIIB) and the binding occurs at both pH 7.4 and 5.0 resembling physiological relevant pH values found in the body and the female urogenital tract, respectively. The binding of SP-D to HIV particles and gp120 was inhibited by the presence of several hexoses with mannose found to be the strongest inhibitor. Competition studies showed that soluble CD4 and CVN did not interfere with the interaction between SP-D and gp120. However, soluble recombinant DC-SIGN was shown to inhibit the binding between SP-D and gp120. SP-D agglutinated HIV and gp120 in a calcium dependent manner. SP-D inhibited the infectivity of HIV strains at both pH values of 7.4 and 5.0 in a concentration dependent manner. The inhibition of the infectivity was abolished by the presence of mannose. SP-D enhanced the binding of HIV to immature monocyte derived dendritic cells (iMDDCs) and was also found to enhance HIV capture and transfer to the T-cell like line PM1. These results suggest that SP-D can bind to and inhibit direct infection of T-cells by HIV but also enhance the transfer of infectious HIV particles from DCs to T-cells in vivo

Risk factors for delay in symptomatic presentation: a survey of cancer patients

Background: Delay in symptomatic presentation leading to advanced stage at diagnosis may contribute to poor cancer survival. To inform public health approaches to promoting early symptomatic presentation, we aimed to identify risk factors for delay in presentation across several cancers. Methods: We surveyed 2371 patients with 15 cancers about nature and duration of symptoms using a postal questionnaire. We calculated relative risks for delay in presentation (time from symptom onset to first presentation >3 months) by cancer, symptoms leading to diagnosis and reasons for putting off going to the doctor, controlling for age, sex and deprivation group. Results: Among 1999 cancer patients reporting symptoms, 21% delayed presentation for >3 months. Delay was associated with greater socioeconomic deprivation but not age or sex. Patients with prostate (44%) and rectal cancer (37%) were most likely to delay and patients with breast cancer least likely to delay (8%). Urinary difficulties, change of bowel habit, systemic symptoms (fatigue, weight loss and loss of appetite) and skin symptoms were all common and associated with delay. Overall, patients with bleeding symptoms were no more likely to delay presentation than patients who did not have bleeding symptoms. However, within the group of patients with bleeding symptoms, there were significant differences in risk of delay by source of bleeding: 35% of patients with rectal bleeding delayed presentation, but only 9% of patients with urinary bleeding. A lump was a common symptom but not associated with delay in presentation. Twenty-eight percent had not recognised their symptoms as serious and this was associated with a doubling in risk of delay. Embarrassment, worry about what the doctor might find, being too busy to go to the doctor and worry about wasting the doctor’s time were also strong risk factors for delay, but were much less commonly reported (<6%). Interpretation: Approaches to promote early presentation should aim to increase awareness of the significance of cancer symptoms and should be designed to work for people of the lowest socioeconomic status. In particular, awareness that rectal bleeding is a possible symptom of cancer should be raised

Increased ventral striatal volume in college-aged binge drinkers

BACKGROUND Binge drinking is a serious public health issue associated with cognitive, physiological, and anatomical differences from healthy individuals. No studies, however, have reported subcortical grey matter differences in this population. To address this, we compared the grey matter volumes of college-age binge drinkers and healthy controls, focusing on the ventral striatum, hippocampus and amygdala. METHOD T1-weighted images of 19 binge drinkers and 19 healthy volunteers were analyzed using voxel-based morphometry. Structural data were also covaried with Alcohol Use Disorders Identification Test (AUDIT) scores. Cluster-extent threshold and small volume corrections were both used to analyze imaging data. RESULTS Binge drinkers had significantly larger ventral striatal grey matter volumes compared to controls. There were no between group differences in hippocampal or amygdalar volume. Ventral striatal, amygdalar, and hippocampal volumes were also negatively related to AUDIT scores across groups. CONCLUSIONS Our findings stand in contrast to the lower ventral striatal volume previously observed in more severe forms of alcohol use disorders, suggesting that college-age binge drinkers may represent a distinct population from those groups. These findings may instead represent early sequelae, compensatory effects of repeated binge and withdrawal, or an endophenotypic risk factor

Reasons for non-participation in a primary care-based physical activity trial: a qualitative study.

OBJECTIVES: To explore reasons for non-participation in a primary care-based physical activity trial and understand how these may contribute to recruitment of non-representative research samples. We also aimed to elicit non-participants' own recommendations for enhancing trial uptake in primary care. DESIGN: Semistructured telephone interviews with non-participants to a randomised controlled trial of a very brief intervention for promoting physical activity conducted in primary care (the Very Brief Interventions trial), with thematic analysis of interview transcripts. SETTING: 5 general practice (GP) surgeries in the East of England, UK. PARTICIPANTS: Interviews were completed with 10 female and 6 male non-participants of white ethnicity and aged between 40 and 71 years. 13 of the 16 interviewees were either active or moderately active according to the GP Physical Activity Questionnaire (GPPAQ). RESULTS: Interviewees discussed a range of reasons for non-participation. These included beliefs surrounding the personal relevance of the trial based on preconceptions of intervention content. Many interviewees considered themselves either sufficiently active or too functionally limited to increase activity levels further, so rendering participation pointless in their view. Other identified barriers included a lack of free time, for trial participation and for increasing physical activity, and dissatisfaction with appointment scheduling systems in place at GP surgeries. Interviewees questioned the appropriateness of primary care as a context for delivering interventions to promote physical activity. In general, interviewees were positively disposed towards the idea of trial participation, especially if personal benefits are made salient, but suggested that interventions could be delivered in a different setting such as the internet. CONCLUSIONS: To increase participation in physical activity promotion trials conducted in primary care, the content of invitation materials and procedures for contacting potential participants require reconsideration. Specific recommendations include streamlining intervention materials and enhancing their relevance to the health concerns of invitees. TRIAL REGISTRATION NUMBER: ISRCTN72691150; Pre-results.The work was undertaken by the Centre for Diet and Activity Research (CEDAR), a UKCRC Public Health Research Centre of Excellence. Funding from the British Heart Foundation, Cancer Research UK, Economic and Social Research Council, Medical Research Council, the National Institute for Health Research, and the Wellcome Trust, under the auspices of the UK Clinical Research Collaboration, is gratefully acknowledged. This study was conducted on behalf of the Very Brief Interventions Programme Team. This work was funded by the National Institute for Health Research (NIHR) under its Programme Grants for Applied Research Programme (Grant Reference Number RP-PG-0608-10079). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health.This is the final version of the article. It first appeared from BMJ Group via https://doi.org/ 10.1136/bmjopen-2016-01157

NS1 Specific CD8(+) T-Cells with Effector Function and TRBV11 Dominance in a Patient with Parvovirus B19 Associated Inflammatory Cardiomyopathy

Background: Parvovirus B19 (B19V) is the most commonly detected virus in endomyocardial biopsies (EMBs) from patients with inflammatory cardiomyopathy (DCMi). Despite the importance of T-cells in antiviral defense, little is known about the role of B19V specific T-cells in this entity. Methodology and Principal Findings: An exceptionally high B19V viral load in EMBs (115,091 viral copies/mg nucleic acids), peripheral blood mononuclear cells (PBMCs) and serum was measured in a DCMi patient at initial presentation, suggesting B19V viremia. The B19V viral load in EMBs had decreased substantially 6 and 12 months afterwards, and was not traceable in PBMCs and the serum at these times. Using pools of overlapping peptides spanning the whole B19V proteome, strong CD8(+) T-cell responses were elicited to the 10-amico-acid peptides SALKLAIYKA (19.7% of all CD8(+) cells) and QSALKLAIYK (10%) and additional weaker responses to GLCPHCINVG (0.71%) and LLHTDFEQVM (0.06%). Real-time RT-PCR of IFN gamma secretion-assay-enriched T-cells responding to the peptides, SALKLAIYKA and GLCPHCINVG, revealed a disproportionately high T-cell receptor Vbeta (TRBV) 11 expression in this population. Furthermore, dominant expression of type-1 (IFN gamma, IL2, IL27 and Tbet) and of cytotoxic T-cell markers (Perforin and Granzyme B) was found, whereas gene expression indicating type-2 (IL4, GATA3) and regulatory T-cells (FoxP3) was low. Conclusions: Our results indicate that B19V Ag-specific CD8(+) T-cells with effector function are involved in B19V associated DCMi. In particular, a dominant role of TRBV11 and type-1/CTL effector cells in the T-cell mediated antiviral immune response is suggested. The persistence of B19V in the endomyocardium is a likely antigen source for the maintenance of CD8(+) T-cell responses to the identified epitopes

Evidence for the role of EPHX2 gene variants in anorexia nervosa.

Anorexia nervosa (AN) and related eating disorders are complex, multifactorial neuropsychiatric conditions with likely rare and common genetic and environmental determinants. To identify genetic variants associated with AN, we pursued a series of sequencing and genotyping studies focusing on the coding regions and upstream sequence of 152 candidate genes in a total of 1205 AN cases and 1948 controls. We identified individual variant associations in the Estrogen Receptor-ß (ESR2) gene, as well as a set of rare and common variants in the Epoxide Hydrolase 2 (EPHX2) gene, in an initial sequencing study of 261 early-onset severe AN cases and 73 controls (P=0.0004). The association of EPHX2 variants was further delineated in: (1) a pooling-based replication study involving an additional 500 AN patients and 500 controls (replication set P=0.00000016); (2) single-locus studies in a cohort of 386 previously genotyped broadly defined AN cases and 295 female population controls from the Bogalusa Heart Study (BHS) and a cohort of 58 individuals with self-reported eating disturbances and 851 controls (combined smallest single locus P&lt;0.01). As EPHX2 is known to influence cholesterol metabolism, and AN is often associated with elevated cholesterol levels, we also investigated the association of EPHX2 variants and longitudinal body mass index (BMI) and cholesterol in BHS female and male subjects (N=229) and found evidence for a modifying effect of a subset of variants on the relationship between cholesterol and BMI (P&lt;0.01). These findings suggest a novel association of gene variants within EPHX2 to susceptibility to AN and provide a foundation for future study of this important yet poorly understood condition

Associations between age and sleep apnea risk among newborn infants

ObjectiveAmong older children, sleep‐disordered breathing (SDB) is associated with measurable neurocognitive consequences. However, diagnostic SDB thresholds are lacking for infants < 12 months. We sought to evaluate the relationship between SDB indices, gestational age (GA), and postmenstrual age (PMA) for infants who underwent clinically‐indicated polysomnograms at a tertiary care center.MethodsEvery infant < 3‐months chronological age whose first clinically‐indicated polysomnogram was between 2/2012 and 2/2017 was included. Linear regression was used to evaluate associations between apnea‐hypopnea index (AHI), obstructive‐apnea index (OAI), and GA and PMA for infants with and without obvious clinical risk factors for SDB (eg, micrognathia and cleft palate).ResultsFor 53 infants without obvious SDB risk factors (GA 35.6 ± 4.5 weeks; PMA 41.2 ± 4.0 weeks), mean AHI was 27 ± 18 and OAI 2.9 ± 4.5. There was a weak inverse relationship between AHI and PMA (r2 = 0.12, P = 0.01), but AHI was not predicted by GA (r2 = 0.04, P = 0.13). Conversely, OAI was more strongly associated with GA (r2 = 0.33, P < 0.0001) than PMA (r2 = 0.08, P = 0.036). For 28 infants with congenital structural anomalies that predispose to SDB (GA 38.0 ± 3.1 weeks, PMA 43.1 ± 3.3 weeks, AHI 37.7 ± 30, OAI 8.2 ± 11.8), neither AHI nor OAI were related to PMA or GA.ConclusionsAmong infants who received clinically‐indicated polysomnograms but did not have obvious structural risk for SDB, AHI declined with advancing PMA, but obstructive‐apnea was best predicted by prematurity. In contrast, the SDB risk did not improve with increasing GA or PMA for infants with congenital structural risk factors; such infants may not outgrow their risk for SDB.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/150552/1/ppul24354_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150552/2/ppul24354.pd

Metabolic syndrome is associated with reduced flow mediated dilation independent of obesity status.

Background: Data suggest that metabolic health status, incorporating components of metabolic syndrome (MetS), predicts cardiovascular disease (CVD) risk better than BMI. This study explored the association of MetS and obesity with endothelial function, a prognostic risk factor for incident CVD. Methods: Forty-four participants were phenotyped according to BMI as non-obese vs obese (30 kg/m2) and according to the International Diabetes Federation criteria of MetS: ≤2 criteria MetS (MetS-) vs ≥3 criteria MetS (MetS+); (1.)non-obese MetS- vs (2.) non-obese MetS+ and (3.) obese MetS- vs (4.) obese MetS+. Flow-mediated dilation (FMD), body composition including liver fat (MRI and spectroscopy), dietary intake, intensities of habitual physical activity and cardio-respiratory fitness were determined. Variables were analysed using a one-factor between-groups ANOVA and linear regression; mean (95% CI) are presented. Results: Individuals with MetS+ displayed lower FMD than those with MetS-. For non-obese individuals mean difference between MetS+ and MetS- was 4.1% ((1.0, 7.3); P = 0.004) and obese individuals had a mean difference between MetS+ and MetS- of 6.2% ((3.1, 9.2); P < 0.001). Although there was no association between BMI and FMD (P = 0.27), an increased number of MetS components was associated with a lower FMD (P = 0.005), and after adjustment for age and sex, 19.7% of the variance of FMD was explained by MetS, whereas only 1.1% was explained by BMI. Conclusions: In this study cohort, components of MetS, rather than obesity per se, contribute to reduced FMD, which suggests a reduced bioavailability of nitric oxide and thus increased risk of CVD