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Volunteers were exposed to four different environmental conditions [two hot environments: 30°C WBGT (1st: air temperature = 32.6°C; relative humidity = 30%; wind speed = 0.5 m/s; solar radiation = 800 W/m2 and 2nd. air temperature = 40.6°C; relative humidity = 30%; wind speed = 0.5 m/s; solar radiation = 0 W/m2) and two neutral environments: 20°C WBGT (1st: air temperature = 19.1°C; relative humidity = 30%; wind speed = 0.5 m/s; solar radiation = 800 W/m2 and 2nd. air temperature = 28.5°C; relative humidity = 30%; wind speed = 0.5 m/s; solar radiation = 0 W/m2], over an equal number of days. The aforementioned environmental scenarios were randomly allocated for each volunteer. To minimize participant bias, the true purpose of the study was hidden from the volunteers. Of course, once the data collection was completed, all volunteers were informed about the true purpose of the study and gave their permission to analyze and publish these data. During this blinded randomized controlled trial, all volunteers participated four times in an experimental protocol with a total duration of 03:20:00, following an hour of preparation and baseline tests. The protocol had three main time periods [rest (two hours), work (cycling) at 100 W (one hour), and recovery (twenty minutes)]. Anthropometrical data [age; body stature (Seca 213; seca GmbH & Co. KG; Hamburg, Germany); body mass (BC1000, Tanita corporation, Tokyo, Japan); body fat (DXA scan: Lunar DPX Madison, GE Healthcare, Wisconsin, USA); and lean mass (DXA scan: Lunar DPX Madison, GE Healthcare, Wisconsin, USA)] were collected two days prior to the experiments. Volunteers were euhydrated prior to the experiments. Hydration status was assessed using a handheld refractometer (ATAGO Ltd, Tokyo, Japan) and determined as either euhydrated (USG < 1.020) or dehydrated (USG ≥ 1.020) according to the current guidelines. Water consumption was restricted during the experimental protocol. The same clothing consisting of a light-blue t-shirt (100% cotton), a black exercise short pant (100% polyester), and a pair of medium-high socks (100% cotton) were used by volunteers throughout the experiments. A pair of sunglasses was mandatory to be worn throughout the experiments. Furthermore, experiments took place during the same hour of the day for each participant and an 8-hour fasting was ensured prior to the experiments. Furthermore, participants were requested to avoid caffeine and alcohol consumption for at least twelve hours before the experiments, as well as to avoid salt and sugar consumption eight hours before the experiments. During the study, continuous heart rate, core temperature, mean skin temperature, skin blood flow, and sweat rate were measured. Specifically, heart rate was collected using wireless heart rate monitors (Polar Team2. Polar Electro Oy, Kempele, Finland). Core temperature was collected using telemetric capsules (BodyCap, Caen, France). Skin temperature from four sites was measured using wireless thermistors (iButtons type DS1921H, Maxim/Dallas Semiconductor Corp., USA) and was expressed as mean skin temperature according to Ramanathan [mean skin temperature = 0.3(chest + arm) + 0.2(thigh + leg). Skin blood flow was measured with a laser Doppler flowmeter (PeriFlux 4000, Perimed, Stockholm, Sweden) at right forearm (brachioradialis) and leg (gastrocnemius). The probe (PROBE 413 Integrating Probe, Perimed, Stockhold, Sweden) was held in place with a plastic holder (PH 13, Perimed, Stockhold, Sweden). Sweat rate was measured at three regions [forehead, thigh (quadricep), and arm (bicep)] using ventilated capsule method. Thermal comfort (1 = comfortable; 5 = extremely uncomfortable), thermal sensation (-3 = cold; +3 = hot), and perceived exertion (6 = no exertion at all; 20 = maximal exertion), alongside cognitive performance (vigilance, divided attention, memory test, and reaction time) were assessed at baseline, pre work condition (01:40:00), and post work (03:00:00) conditions. Volunteers entered the chamber five minutes prior to the experiments to install data loggers and accompanied sensors on their body. Solar radiation is a physical phenomenon which interacts with any human being throughout its life on earth. This interaction is associated with numerous physiological functions, as well as a broad spectrum of deleterious effects on human health and wellbeing. The aim of this study is to elucidate the effects of solar radiation on human function and cognition in environmental conditions characterized by the same thermal stress.

Tiny molecules (hormones) are released from the bowels and other organs to the bloodstream in response to meals in order to orchestrate the metabolism. Oxyntomodulin, GLP-1 and glucagon are all known to regulate parameters such as appetite, food intake and induce weight loss. Therefore we want to investigate mechanistic relations between the three hormones.

Approximately 11,000 Veterans present to a VAMC annually with an acute ischemic stroke or TIA. The cornerstone of secondary stroke/TIA prevention includes delivering timely, guideline-concordant vascular risk factor management. Over the past decade, OSA has been recognized as a potent, underdiagnosed, and inadequately treated cerebrovascular risk factor. OSA is very common among patients with stroke/TIA with a prevalence of 70-80%. Despite being highly prevalent, 70-80% of patients with OSA are neither diagnosed nor treated. Untreated OSA has been associated with poor outcomes among patients with cerebrovascular disease including higher mortality and worse functional status. The mainstay of OSA therapy is positive airway pressure (PAP). PAP reduces recurrent vascular events, improves neurological symptoms and functional status among stroke/TIA patients with OSA. The evidence favoring neurological recovery is strongest when interventions are applied early post-stroke/TIA. Guidelines recommend diagnosing and treating OSA for stroke and TIA patients; however, within VHA, very few stroke or TIA patients receive OSA screening. This guideline recommendation was informed in part by clinical trials utilizing an acute OSA assessment protocol developed and implemented by the investigators' group. To address the observed gap in care, the investigators propose a Hybrid Type I, randomized, stepped-wedge trial at 6 VAMCs to increase the rate of timely, guideline-concordant diagnosis and treatment of OSA among Veterans with ischemic stroke/TIA and thereby reduce recurrent vascular events and hospital readmissions. The investigators will identify matched control sites for each ASAP implementation site to examine temporal trends in outcomes among non-intervention sites. For example, the investigators will use administrative data to examine the use of polysomnography across stroke/TIA patients in the VA system and compare changes in matched controls versus the intervention sites on the diagnostic rate. The same adjustment approach will be used for ASAP intervention sites and for control sites. Effectively identifying and treating risk factors for ischemic stroke and transient ischemic attack (TIA) is important to patients, their family members, and healthcare systems. While obstructive sleep apnea (OSA) is a known risk factor for stroke and TIA that is present in more than 70% of stroke/TIA survivors, testing for OSA is infrequently performed for patients and within healthcare systems. The Addressing Sleep Apnea Post-Stroke/TIA (ASAP) study intends to improve rates of guideline-recommended OSA testing and treatment through local quality improvement initiatives (QI) conducted within and across 6 VA Medical Centers. ASAP will also determine the impact of these local QI initiatives on rates of OSA diagnosis, OSA treatment, treatment adherence, recurrent vascular events, and hospital readmissions.

Obesity continues to be a prevalent health concern affecting every race of the American population. According to data from the World Health Organization, 54% of U.S. adults are overweight (body mass index (BMI) >25 kg/m2 ) and 22% are obese (BMI >30 kg/m2) (1). In addition, 25% of U.S. children are overweight or obese (1). Studies show that obese children are likely to become obese adults (2-5). Also, recent studies report significant years of life lost due to the impact of being an obese adult (6, 7). Thus, insights into the pathogenesis of childhood obesity and preventative measures are needed to combat the inevitable increase in worldwide incidence of obesity and its associated co-morbidities. Recent studies have identified a new gastroenteric hormone, ghrelin, as a long-term regulator of energy balance in humans (12). Ghrelin is a 28 amino acid acylated peptide which is an endogenous ligand of the growth hormone secretagogue receptor (GHS-R), a hypothalamic G-protein-coupled receptor (13). Enteroendocrine cells (X/A-like cells) of the stomach are the major site of ghrelin synthesis, although a minor proportion of ghrelin synthesis occurs in other sites such as the hypothalamus, pituitary, duodenum, jejunum and lung (14) (15, 16). The hypothesis that hyperghrelinemia causes some of the features of PWS predicts that this disorder will be ameliorated (partially or completely) by lowering ghrelin levels. We have recently shown that the somatostatin agonist, octreotide, suppresses ghrelin levels in humans. If octreotide remains effective in longer term studies, the drug may become an adjuvant therapy, in addition to growth hormone, to control the insatiable appetite and morbid obesity seen in this condition. The purpose of this study is to investigate over a 6 month period the effect of octreotide therapy on food intake, sense of hunger, body weight, body composition, efficiency of burning calories, biomarkers of weight regulation and growth hormone markers in children and young Adults with Prader-Willi Syndrome(PWS).

The purpose of this study is to evaluate the safety and tolerability of the JAK2 inhibitor XL019 administered orally in adults with Polycythemia Vera.

Background and Aims: This study aims at evaluating the ease of use of the new calorimeter for the measurement of energy expenditure (EE) in intensive care unit (ICU) patients. EE in ICU patients is highly variable depending on the severity of the disease and treatments. Clinicians need to measure EE by indirect calorimetry (IC) to optimize nutritional support for the better clinical outcome. However, indirect calorimeters available on the market have insufficient accuracy for clinical and research use. Difficulties of handling and interpretation of results often limit IC in ICU patients. An accurate, easy-to-use calorimeter has been developed to meet these needs. The Study Device: The new calorimeter (Quark RMR 2.0, COSMED) is capable of IC measurements in mechanically ventilated patients without warm-up and limited calibration. The disposable in-line pneumotach flow meter and direct sampling of respiratory gas from the ventilator circuit enables the accurate measurement of oxygen consumption volume (VO2) and CO2 production volume (VCO2) to derive the energy expenditure. The software interface to manage the device and the collected data provides easy-to-use, user-friendly interface. This calorimeter bears an European Commission (EC) Conformity Mark, and will be used in the way it is intended to be used as described in the instruction manual. Currently used indirect calorimeters at each study center will be used as the comparator. This study will evaluate the ease of use of the new calorimeter (Quark RMR 2.0 (COSMED, Italy)) in intensive care unit (ICU) patients compared to currently used calorimeters (i.e. Quark RMR 1.0(COSMED, Italy) or Deltatrac Metabolic Monitor (Datex, Finland)), as well as the stability and the feasibility of the measurements in various clinically relevant situations. Time needed to prepare and start indirect calorimetry (IC) measurement will be compared as the measure of the ease of use of the calorimeter.

The prevalence of type 1 diabetes has been steadily increasing for about 20 years. Despite therapeutic progress, between 20 and 65% of people with diabetes develop diabetic neuropathy, resulting in increased morbidity and mortality. Diabetic neuropathy is not limited to sensitive pain in the lower limbs. It also affects the fibres of the autonomic nervous system (ANS), which results in systemic complications, often disabling (erectile dysfunction, dysidrosis, gastroparesis, orthostatism, etc.) and a probable alteration in the body's thermogenic capacities, although this possibility has not been studied in humans. In rodents, it is possible to activate induced thermogenesis via central stimulation of the ANS or to inactivate it, which promotes the development of obesity and greater insulin resistance. This knowledge is based on cellular and animal models that have identified the bio-molecular mechanisms that give brown adipose tissue (BAT) the ability to dissipate energy in the form of heat. Induced thermogenesis is mediated by decoupling proteins 1 (DCS-1) located on the mitochondrial inner membrane of the TAB. DCS-1 decouple oxidative phosphorylation from ATP production, dissipating the proton gradient. The activation of UCP1 is particularly influenced by the sympathetic system and more particularly by catecholamines which will bind to ß3 adrenergic receptors (Rß3). In humans, the persistence of active areas of TAB has recently been demonstrated by positron emission tomography (PET) imaging using a glucose analogue radiotracer, 18F-Fluoro-Deoxy-Glucose (18F-FDG), coupled with the scanner (CT). Recently, it has been shown that the use of 18F-FDG PET coupled with magnetic resonance (MRI) is equally effective in differentiating TAB from white fat tissue with less patient irradiation. The activity of the TAB is estimated using the measurement of SUV (standard uptake value) which represents the total glycolytic activity of the tissue and is also commonly referred to as the total metabolic volume. It has been shown in humans that TAB activity is inversely correlated with body mass index and age and positively correlated with exposure to cold and stress levels[6]. Among diabetics, the data are disparate but the spontaneous prevalence of TAB appears to be reduced compared to the general population (1.1% vs 7.5%). To date, no studies have investigated a possible link between the decrease in TAB activity observed in diabetics and the presence of autonomic neuropathy, which is a common and often under-diagnosed complication of diabetes. The main purpose of this study is to evaluate whether the activity and distribution of TAB in patients with diabetes is influenced by the presence of diabetic neuropathy. On the other hand, if the existence of diabetic neuropathy influences energy expenditure in the event of exposure to cold. Finally, whether any differences in the activity and distribution of TAB could be related to changes in the central nervous system. The investigators plan to include a total of 24 patients with type 1 diabetes and separate them into 2 groups: group A; no neuropathic complications and group B; presence of neuropathy. All patients will be characterized in terms of clinical, metabolic and energy expenditure. The activity of the TAB will be evaluated through the use of 18F-FDG PET/IRM imaging, after a cold stimulation protocol (refrigerated jacket) in order to activate the TAB in a homogeneous manner among the participants. Influence of diabetic neuropathy on cold induced brown adipose tissue in type 1 diabetic patients.

A total of 170 participants were initially enrolled in the comprehensive behavioral weight loss intervention.In this study, investigators will conduct a follow-up visit 3 years after the completion of the intervention. Only participants who completed the behavioral weight loss intervention will be enrolled in this study. Participants will undergo testing of body weight, body composition, physical activity patterns, energy intake patterns, sleep patterns, resting metabolic rate, and total daily energy expenditure. This study is designed as an observational trial. The objective of this study is to follow-up with participants 3 years after completion of an 18-month comprehensive behavioral weight loss intervention. Outcomes of interest include change in body weight, body composition, physical activity, energy intake, and sleep. In addition, investigators will explore the associations between current physical activity, sleep, and energy intake patterns and body weight regulation.

Music has been consistently shown to reduce stress and increase weight gain in premature infants. The mechanism of this presumed improved metabolic efficiency is unknown. We aim to test the hypothesis that music by Mozart reduces energy expenditure in growing healthy preterm infants.