Whole-body heat stress and exercise stimulate the appearance of platelet microvesicles in plasma with limited influence of vascular shear stress

Intense, large muscle mass exercise increases circulating microvesicles, but our understanding of microvesicle dynamics and mechanisms inducing their release remains limited. However, increased vascular shear stress is generally thought to be involved. Here, we manipulated exercise-independent and exercise-dependent shear stress using systemic heat stress with localized single-leg cooling (low shear) followed by single-leg knee extensor exercise with the cooled or heated leg (Study 1, n = 8) and whole-body passive heat stress followed by cycling (Study 2, n = 8). We quantified femoral artery shear rates (SRs) and arterial and venous platelet microvesicles (PMV-CD41+) and endothelial microvesicles (EMV-CD62E+). In Study 1, mild passive heat stress while one leg remained cooled did not affect [microvesicle] (P ≥ 0.05). Single-leg knee extensor exercise increased active leg SRs by ~12-fold and increased arterial and venous [PMVs] by two- to threefold, even in the nonexercising contralateral leg (P < 0.05). In Study 2, moderate whole-body passive heat stress increased arterial [PMV] compared with baseline (mean±SE, from 19.9 ± 1.5 to 35.5 ± 5.4 PMV.μL-1.103, P < 0.05), and cycling with heat stress increased [PMV] further in the venous circulation (from 27.5 ± 2.2 at baseline to 57.5 ± 7.2 PMV.μL-1.103 during cycling with heat stress, P < 0.05), with a tendency for increased appearance of PMV across exercising limbs. Taken together, these findings demonstrate that whole-body heat stress may increase arterial [PMV], and intense exercise engaging either large or small muscle mass promote PMV formation locally and systemically, with no influence upon [EMV]. Local shear stress, however, does not appear to be the major stimulus modulating PMV formation in healthy humans

The Development of a Motion Sensing Device for Use in a Home Setting

Parkinson\u27s disease (PD) is the second most prevalent neurodegenerative disease, with over 10 million individuals diagnosed with PD world-wide. The most common symptom characterized by PD is tremor. Tremor is an involuntary oscillatory motion that most prominently occurs in upper limb, specifically in the hand and wrist that has a measurable frequency and amplitude. This thesis aims to evaluate the usability and functionality of a tremor sensing device designed to collect quantitative data on individuals with PD. The designed device uses 23 commercially-available inertial measuring units (IMUs) located between 21 joints: distal interphalangeal (DIP) joints, proximal interphalangeal (PIP) joints, Interphalangeal (IP) joint, metacarpophalangeal (MCP) joints, carpometacarpal (CMC) joint, trapeziometacarpal (TMC) joint, radiocarpal joint, and the elbow joint. The IMU sensors include a 3 degree of freedom (DOF) accelerometer and a 3 DOF gyroscope activated during data collection. In specific, this thesis evaluates the device with trials on healthy participants by collecting data in the time and frequency domain during activities of daily living (ADL) over 48 hours in a home setting. A total of 7 healthy participants were recruited to wear the device in a home setting over 2 days. The linear acceleration and angular velocity signals were captured, which were later used to analyze the data in the frequency domain, similar to if it were for tremor signals. If the voluntary motion signals in the time and frequency domain are close to the accepted values for voluntary motion, the battery life is sufficient, and data is collected effectively, the device functionality will be validated and can be used to capture tremor data

Dehydration accelerates reductions in cerebral blood flow during prolonged exercise in the heat without compromising brain metabolism

Dehydration hastens the decline in cerebral blood flow (CBF) during incremental exercise, while the cerebral metabolic rate for oxygen (CMRO2) is preserved. It remains unknown whether CMRO2 is also maintained during prolonged exercise in the heat and whether an eventual decline in CBF is coupled to fatigue. Two studies were undertaken. In study 1, ten male cyclists cycled in the heat for ~2 h with (control) and without fluid replacement (dehydration) while internal (ICA) and external (ECA) carotid artery blood flow and core and blood temperature were obtained. Arterial and internal jugular venous blood samples were assessed with dehydration to evaluate the CMRO2. In study 2 (8 males), middle cerebral artery blood velocity (MCA Vmean) was measured during prolonged exercise to exhaustion in both dehydrated and euhydrated states. After a rise at the onset of exercise, ICA flow declined to baseline with progressive dehydration (P < 0.05). However, cerebral metabolism remained stable through enhanced oxygen and glucose extraction (P < 0.05). ECA flow increased for one hour but declined prior to exhaustion. Fluid ingestion maintained cerebral and extra-cranial perfusion throughout non-fatiguing exercise. During exhaustive exercise, however, euhydration delayed but did not prevent the decline in cerebral perfusion. In conclusion, during prolonged exercise in the heat dehydration accelerates the decline in CBF without affecting CMRO2 and also restricts extra-cranial perfusion. Thus fatigue is related to reduction in CBF and extra-cranial perfusion rather than in CMRO2.The study was supported by a grant from the Gatorade Sports Science Institute, PepsiCo Inc, USA

Socioeconomic indicators of health inequalities and female mortality: a nested cohort study within the United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS)

Evidence is mounting that area-level socioeconomic indicators are important tools for predicting health outcomes. However, few studies have examined these alongside individual-level education. This nested cohort study within the control arm of the United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) assesses the association of mutually adjusted individual (education) and area-level (Index of Multiple Deprivation-IMD 2007) socioeconomic status indicators and all-cause female mortality

Circulation characteristics of a monsoon depression during BOBMEX-99 using high-resolution analysis

The skill and efficiency of a numerical model mostly varies with the quality of initial values, accuracy on parameterization of physical processes and horizontal and vertical resolution of the model. Commonly used low-resolution reanalyses are hardly able to capture the prominent features associated with organized convective processes in a monsoon depression. The objective is to prepare improved high-resolution analysis by the use of MM5 modelling system developed by the Pennsylvania State University/National Center for Atmospheric Research (PSU/NCAR). It requires the objective comparison of high and low-resolution analysis datasets in assessing the specific convective features of a monsoon depression. For this purpose, reanalysis datasets of NCAR/NCEP (National Center for Atmospheric Research/National Centers for Environmental Prediction) at a horizontal resolution of 2.5° (latitude/longitude) have been used as first guess in the objective analysis scheme. The additional asynoptic datasets obtained during BOBMEX-99 are utilized within the assimilation process. Cloud Motion Wind (CMW) data of METEOSAT satellite and SSM/I surface wind data are included for the improvement of derived analysis. The multiquadric (MQD) interpolation technique is selected and applied for meteorological objective analysis at a horizontal resolution of 30 km. After a successful inclusion of additional data, the resulting reanalysis is able to produce the structure of convective organization as well as prominent synoptic features associated with monsoon depression. Comparison and error verifications have been done with the help of available upper-air station data. The objective verification reveals the efficiency of the analysis scheme

Fructose transport-deficient Staphylococcus aureus reveals important role of epithelial glucose transporters in limiting sugar-driven bacterial growth in airway surface liquid.

Hyperglycaemia as a result of diabetes mellitus or acute illness is associated with increased susceptibility to respiratory infection with Staphylococcus aureus. Hyperglycaemia increases the concentration of glucose in airway surface liquid (ASL) and promotes the growth of S. aureus in vitro and in vivo. Whether elevation of other sugars in the blood, such as fructose, also results in increased concentrations in ASL is unknown and whether sugars in ASL are directly utilised by S. aureus for growth has not been investigated. We obtained mutant S. aureus JE2 strains with transposon disrupted sugar transport genes. NE768(fruA) exhibited restricted growth in 10 mM fructose. In H441 airway epithelial-bacterial co-culture, elevation of basolateral sugar concentration (5-20 mM) increased the apical growth of JE2. However, sugar-induced growth of NE768(fruA) was significantly less when basolateral fructose rather than glucose was elevated. This is the first experimental evidence to show that S. aureus directly utilises sugars present in the ASL for growth. Interestingly, JE2 growth was promoted less by glucose than fructose. Net transepithelial flux of D-glucose was lower than D-fructose. However, uptake of D-glucose was higher than D-fructose across both apical and basolateral membranes consistent with the presence of GLUT1/10 in the airway epithelium. Therefore, we propose that the preferential uptake of glucose (compared to fructose) limits its accumulation in ASL. Pre-treatment with metformin increased transepithelial resistance and reduced the sugar-dependent growth of S. aureus. Thus, epithelial paracellular permeability and glucose transport mechanisms are vital to maintain low glucose concentration in ASL and limit bacterial nutrient sources as a defence against infection

Increased airway glucose increases airway bacterial load in hyperglycaemia.

Diabetes is associated with increased frequency of hospitalization due to bacterial lung infection. We hypothesize that increased airway glucose caused by hyperglycaemia leads to increased bacterial loads. In critical care patients, we observed that respiratory tract bacterial colonisation is significantly more likely when blood glucose is high. We engineered mutants in genes affecting glucose uptake and metabolism (oprB, gltK, gtrS and glk) in Pseudomonas aeruginosa, strain PAO1. These mutants displayed attenuated growth in minimal medium supplemented with glucose as the sole carbon source. The effect of glucose on growth in vivo was tested using streptozocin-induced, hyperglycaemic mice, which have significantly greater airway glucose. Bacterial burden in hyperglycaemic animals was greater than control animals when infected with wild type but not mutant PAO1. Metformin pre-treatment of hyperglycaemic animals reduced both airway glucose and bacterial load. These data support airway glucose as a critical determinant of increased bacterial load during diabetes

Important synoptic features during INDOEX IFP-99

INDOEX IFP-99 was undertaken as part of the international experiment in the Indian Ocean to take observations pertaining to aerosols, radiation, cloud physics and other related meteorological parameters. The important-aim of the INDOEX was to quantify radiative forcing due to natural and anthropogenic aerosols and their feedback on regional and global climate systems. Since prevailing circulation features transports aerosols, it is essential that important synoptic patterns during the expedition phase, i.e. 20 January to 10 March 1999 be examined. Based on the synoptic features it was noticed that crossequatorial flow in lower levels from western Arabian Sea to southern Indian Ocean was significantly higher than the eastern Arabian Sea. Two cyclonic storms, one in the south Bay of Bengal during 1-3 February and another in the south Indian Ocean during 4-13 March were observed. Significant changes in the cross-equatorial flow in the lower/upper tropospheric levels and ITCZ locations were noticed

Temperature-dependent release of ATP from human erythrocytes: Mechanism for the control of local tissue perfusion

Copyright @ 2012 The AuthorsThis article has been made available through the Brunel Open Access Publishing Fund.Human limb muscle and skin blood flow increases significantly with elevations in temperature, possibly through physiological processes that involve temperature-sensitive regulatory mechanisms. Here we tested the hypothesis that the release of the vasodilator ATP from human erythrocytes is sensitive to physiological increases in temperature both in vitro and in vivo, and examined potential channel/transporters involved. To investigate the source of ATP release, whole blood, red blood cells (RBCs), plasma and serum were heated in vitro to 33, 36, 39 and 42°C. In vitro heating augmented plasma or ‘bathing solution’ ATP in whole blood and RBC samples, but not in either isolated plasma or serum samples. Heat-induced ATP release was blocked by niflumic acid and glibenclamide, but was not affected by inhibitors of nucleoside transport or anion exchange. Heating blood to 42°C enhanced (P < 0.05) membrane protein abundance of cystic fibrosis transmembrane conductance regulator (CFTR) in RBCs. In a parallel in vivo study in humans exposed to whole-body heating at rest and during exercise, increases in muscle temperature from 35 to 40°C correlated strongly with elevations in arterial plasma ATP (r2 = 0.91; P = 0.0001), but not with femoral venous plasma ATP (r2 = 0.61; P = 0.14). In vitro, however, the increase in ATP release from RBCs was similar in arterial and venous samples heated to 39°C. Our findings demonstrate that erythrocyte ATP release is sensitive to physiological increases in temperature, possibly via activation of CFTR-like channels, and suggest that temperature-dependent release of ATP from erythrocytes might be an important mechanism regulating human limb muscle and skin perfusion in conditions that alter blood and tissue temperature.This article is made available through the Brunel Open Access Publishing Fund

Diabetes UK evidence-based nutrition guidelines for the prevention and management of diabetes

A summary of the latest evidence‐based nutrition guidelines for the prevention and management of diabetes is presented. These guidelines are based on existing recommendations last published in 2011, and were formulated by an expert panel of specialist dietitians after a literature review of recent evidence. Recommendations have been made in terms of foods rather than nutrients wherever possible. Guidelines for education and care delivery, prevention of Type 2 diabetes, glycaemic control for Type 1 and Type 2 diabetes, cardiovascular disease risk management, management of diabetes‐related complications, other considerations including comorbidities, nutrition support, pregnancy and lactation, eating disorders, micronutrients, food supplements, functional foods, commercial diabetic foods and nutritive and non‐nutritive sweeteners are included. The sections on pregnancy and prevention of Type 2 diabetes have been enlarged and the weight management section modified to include considerations of remission of Type 2 diabetes. A section evaluating detailed considerations in ethnic minorities has been included as a new topic. The guidelines were graded using adapted ‘GRADE’ methodology and, where strong evidence was lacking, grading was not allocated. These 2018 guidelines emphasize a flexible, individualized approach to diabetes management and weight loss and highlight the emerging evidence for remission of Type 2 diabetes. The full guideline document is available at www.diabetes.org.uk/nutrition-guidelines