Sedentary Behavior and Cardiovascular Disease Risk: Mediating Mechanisms.

Sedentary behavior has a strong association with cardiovascular disease (CVD) risk, which may be independent of physical activity. To date, the mechanism(s) that mediate this relationship are poorly understood. We hypothesize that sedentary behavior modifies key hemodynamic, inflammatory, and metabolic processes resulting in impaired arterial health. Subsequently, these vascular impairments directly and indirectly contribute to the development of CVD

Depleted circulatory complement-lysis inhibitor (CLI) in childhood cerebral malaria returns to normal with convalescence

BACKGROUND: Cerebral malaria (CM), is a life-threatening childhood malaria syndrome with high mortality. CM is associated with impaired consciousness and neurological damage. It is not fully understood, as yet, why some children develop CM. Presented here is an observation from longitudinal studies on CM in a paediatric cohort of children from a large, densely-populated and malaria holoendemic, sub-Saharan, West African metropolis. METHODS: Plasma samples were collected from a cohort of children with CM, severe malarial anaemia (SMA), uncomplicated malaria (UM), non-malaria positive healthy community controls (CC), and coma and anemic patients without malaria, as disease controls (DC). Proteomic two-dimensional difference gel electrophoresis (2D-DIGE) and mass spectrometry were used in a discovery cohort to identify plasma proteins that might be discriminatory among these clinical groups. The circulatory levels of identified proteins of interest were quantified by ELISA in a prospective validation cohort. RESULTS: The proteome analysis revealed differential abundance of circulatory complement-lysis inhibitor (CLI), also known as Clusterin (CLU). CLI circulatory level was low at hospital admission in all children presenting with CM and recovered to normal level during convalescence (p < 0.0001). At acute onset, circulatory level of CLI in the CM group significantly discriminates CM from the UM, SMA, DC and CC groups. CONCLUSIONS: The CLI circulatory level is low in all patients in the CM group at admission, but recovers through convalescence. The level of CLI at acute onset may be a specific discriminatory marker of CM. This work suggests that CLI may play a role in the pathophysiology of CM and may be useful in the diagnosis and follow-up of children presenting with CM

Effect of different walking break strategies on superficial femoral artery endothelial function.

Breaking up prolonged sitting with physical activity (PA) breaks prevents conduit artery dysfunction. However, the optimal break strategy to achieve this, in terms of the frequency or duration of PA, is not known. This study assessed the effect of breaking up sitting with different PA break strategies on lower limb peripheral artery endothelial function. Fifteen participants (10 male, 35.8 ± 10.2 years, BMI: 25.5 ± 3.2 kg m-2 ) completed, on separate days, three 4-h conditions in a randomized order: (1) uninterrupted sitting (SIT), (2) sitting with 2-min light-intensity walking breaks every 30 min (2WALK), or (3) sitting with 8-min light-intensity walking breaks every 2 h (8WALK). At baseline and 4 h, superficial femoral artery function (flow-mediated dilation; FMD), blood flow, and shear rate (SR) were assessed using Doppler ultrasound. For each condition, the change in outcome variables was calculated and data were statistically analyzed using a linear mixed model. There was no significant main effect for the change in FMD (P = 0.564). A significant main effect was observed for the change in blood flow (P = 0.022), with post hoc analysis revealing a greater reduction during SIT (-42.7 ± 14.2 mL·min) compared to 8WALK (0.45 ± 17.7 mL·min; P = 0.012). There were no significant main effects for mean, antegrade, or retrograde SR (P > 0.05). Superficial femoral artery blood flow, but not FMD, was reduced following uninterrupted sitting. This decline in blood flow was prevented with longer duration, less frequent walking breaks rather than shorter, more frequent breaks suggesting the dose (duration and frequency) of PA may influence the prevention of sitting-induced decreases in blood flow

Cerebral and peripheral vascular differences between pre- and post-menopausal women

Objective: Menopause is associated with lower peripheral vascular function however cerebrovascular responses to this time-period are unclear. We aimed to describe peripheral vascular and cerebrovascular differences between pre- and post-menopausal women. Methods: Fifty pre- and post-menopausal women (N=100) underwent assessments of cerebral blood flow, cerebrovascular reactivity and autoregulation, carotid artery reactivity, brachial and femoral artery flow-mediated dilation and carotid, brachial and femoral artery intima-media thickness. Comparisons were made between pre- and post-menopausal women followed by a secondary-analysis (N=20) between late-pre-menopausal women and those within five years of menopause using a general linear model. Results: Cerebral blood flow (-11 [-17, -4 cm/s]; p=0.03) and carotid reactivity (-2.3 [-4.3, - 0.3%] p=0.03) were lower post-menopause compared to pre-menopause while cerebrovascular reactivity and autoregulation did not differ (p>0.05). Post-menopausal women had a larger carotid (0.16 [0.13, 0.20 mm] p<0.001), brachial (0.07 [0.03, 0.11mm] p=0.004) and femoral artery intima-media-thickness (0.09 [0.05, 0.14 mm] p=0.04), alongside lower brachial (-2.3 [-3.9, -0.7%] p=0.004) and femoral artery flow-mediated dilation (-3.0 [-4.3, - 1.8 %] p<0.001). In the secondary-analysis, early-post-menopausal women had a lower femoral artery flow-mediated dilation (-1.9 [-3.9, -0.0 %] p=0.05) and larger carotid intimamedia-thickness (0.07 [0.00, 0.14 mm] p=0.03) compared to late-pre-menopausal women. Conclusions: Cerebral blood flow, carotid artery reactivity, peripheral vascular function and structure are negatively affected by age. Preliminary data indicates that femoral artery function and carotid artery structure may be potentially impaired in early-post-menopause compared with late-pre-menopause. These findings suggest that conduit arteries susceptible to atherosclerosis may be important targets for lifestyle intervention in early menopause

Impact of green tea on the deleterious cardiometabolic effects of 7-days unhealthy lifestyle in young healthy males.

PURPOSE: The aim of this study was to examine if catechin-rich green tea abrogates the negative effects of 7-days of physical inactivity and excessive calorie-intake on insulin homeostasis and peripheral vascular function. METHODS: Using a randomized, double-blind, crossover design, twelve healthy men (29 ± 6 yrs) underwent 7-days unhealthy lifestyle (UL), including physical inactivity (-50% steps/day) and overfeeding (+50% kcal/day). This was combined with green tea consumption (UL-tea; 3 doses/day) or placebo (UL-placebo). Before and after each intervention, we examined postprandial blood glucose and insulin (3-h after a 1,202 kcal meal) and upper and lower limb vascular function (flow-mediated dilation (FMD%)) and carotid artery reactivity (CAR%). RESULTS: UL-placebo increased postprandial glucose and insulin, while UL-tea decreased postprandial glucose and insulin (Time*Intervention interaction effects: both p  0.05) for brachial FMD%. CONCLUSION: Seven days of physical inactivity and overfeeding impair insulin homeostasis and vascular function. These effects were mitigated by a daily intake of catechin-rich green tea

Standardisation of rates using logistic regression: a comparison with the direct method

<p>Abstract</p> <p>Background</p> <p>Standardisation of rates in health services research is generally undertaken using the direct and indirect arithmetic methods. These methods can produce unreliable estimates when the calculations are based on small numbers. Regression based methods are available but are rarely applied in practice. This study demonstrates the advantages of using logistic regression to obtain smoothed standardised estimates of the prevalence of rare disease in the presence of covariates.</p> <p>Methods</p> <p>Step by step worked examples of the logistic and direct methods are presented utilising data from BETS, an observational study designed to estimate the prevalence of subclinical thyroid disease in the elderly. Rates calculated by the direct method were standardised by sex and age categories, whereas rates by the logistic method were standardised by sex and age as a continuous variable.</p> <p>Results</p> <p>The two methods produce estimates of similar magnitude when standardising by age and sex. The standard errors produced by the logistic method were lower than the conventional direct method.</p> <p>Conclusion</p> <p>Regression based standardisation is a practical alternative to the direct method. It produces more reliable estimates than the direct or indirect method when the calculations are based on small numbers. It has greater flexibility in factor selection and allows standardisation by both continuous and categorical variables. It therefore allows standardisation to be performed in situations where the direct method would give unreliable results.</p

Conserved presence of G-quadruplex forming sequences in the Long Terminal Repeat Promoter of Lentiviruses

G-quadruplexes (G4s) are secondary structures of nucleic acids that epigenetically regulate cellular processes. In the human immunodeficiency lentivirus 1 (HIV-1), dynamic G4s are located in the unique viral LTR promoter. Folding of HIV-1 LTR G4s inhibits viral transcription; stabilization by G4 ligands intensifies this effect. Cellular proteins modulate viral transcription by inducing/unfolding LTR G4s. We here expanded our investigation on the presence of LTR G4s to all lentiviruses. G4s in the 5'-LTR U3 region were completely conserved in primate lentiviruses. A G4 was also present in a cattle-infecting lentivirus. All other non-primate lentiviruses displayed hints of less stable G4s. In primate lentiviruses, the possibility to fold into G4s was highly conserved among strains. LTR G4 sequences were very similar among phylogenetically related primate viruses, while they increasingly differed in viruses that diverged early from a common ancestor. A strong correlation between primate lentivirus LTR G4s and Sp1/NF\u3baB binding sites was found. All LTR G4s folded: their complexity was assessed by polymerase stop assay. Our data support a role of the lentiviruses 5'-LTR G4 region as control centre of viral transcription, where folding/unfolding of G4s and multiple recruitment of factors based on both sequence and structure may take place

'Getting people on board': Discursive leadership for consensus building in team meetings

Meetings are increasingly seen as sites where organizing and strategic change take place, but the role of specific discursive strategies and related linguistic-pragmatic and argumentative devices, employed by meeting chairs, is little understood. The purpose of this article is to address the range of behaviours of chairs in business organizations by comparing strategies employed by the same chief executive officer (CEO) in two key meeting genres: regular management team meetings and ‘away-days’. While drawing on research from organization studies on the role of leadership in meetings and studies of language in the workplace from (socio)linguistics and discourse studies, we abductively identified five salient discursive strategies which meeting chairs employ in driving decision making: (1) Bonding; (2) Encouraging; (3) Directing; (4) Modulating; and (5) Re/Committing. We investigate the leadership styles of the CEO in both meeting genres via a multi-level approach using empirical data drawn from meetings of a single management team in a multinational defence corporation. Our key findings are, first, that the chair of the meetings (and leading manager) influences the outcome of the meetings in both negative and positive ways, through the choice of discursive strategies. Second, it becomes apparent that the specific context and related meeting genre mediate participation and the ability of the chair to control interactions within the team. Third, a more hierarchical authoritarian or a more interpersonal egalitarian leadership style can be identified via specific combinations of these five discursive strategies. The article concludes that the egalitarian leadership style increases the likelihood of achieving a durable consensus. Several related avenues for research are outlined

Formation of the Food Vacuole in Plasmodium falciparum: A Potential Role for the 19 kDa Fragment of Merozoite Surface Protein 1 (MSP119)

Plasmodium falciparum Merozoite Surface Protein 1 (MSP1) is synthesized during schizogony as a 195-kDa precursor that is processed into four fragments on the parasite surface. Following a second proteolytic cleavage during merozoite invasion of the red blood cell, most of the protein is shed from the surface except for the C-terminal 19-kDa fragment (MSP119), which is still attached to the merozoite via its GPI-anchor. We have examined the fate of MSP119 during the parasite's subsequent intracellular development using immunochemical analysis of metabolically labeled MSP119, fluorescence imaging, and immuno-electronmicroscopy. Our data show that MSP119 remains intact and persists to the end of the intracellular cycle. This protein is the first marker for the biogenesis of the food vacuole; it is rapidly endocytosed into small vacuoles in the ring stage, which coalesce to form the single food vacuole containing hemozoin, and persists into the discarded residual body. The food vacuole is marked by the presence of both MSP119 and the chloroquine resistance transporter (CRT) as components of the vacuolar membrane. Newly synthesized MSP1 is excluded from the vacuole. This behavior indicates that MSP119 does not simply follow a classical lysosome-like clearance pathway, instead, it may play a significant role in the biogenesis and function of the food vacuole throughout the intra-erythrocytic phase

The Formation and Evolution of the First Massive Black Holes

The first massive astrophysical black holes likely formed at high redshifts (z>10) at the centers of low mass (~10^6 Msun) dark matter concentrations. These black holes grow by mergers and gas accretion, evolve into the population of bright quasars observed at lower redshifts, and eventually leave the supermassive black hole remnants that are ubiquitous at the centers of galaxies in the nearby universe. The astrophysical processes responsible for the formation of the earliest seed black holes are poorly understood. The purpose of this review is threefold: (1) to describe theoretical expectations for the formation and growth of the earliest black holes within the general paradigm of hierarchical cold dark matter cosmologies, (2) to summarize several relevant recent observations that have implications for the formation of the earliest black holes, and (3) to look into the future and assess the power of forthcoming observations to probe the physics of the first active galactic nuclei.Comment: 39 pages, review for "Supermassive Black Holes in the Distant Universe", Ed. A. J. Barger, Kluwer Academic Publisher