One week of bed rest leads to substantial muscle atrophy and induces whole-body insulin resistance in the absence of skeletal muscle lipid accumulation

Short ( < 10 days) periods of muscle disuse, often necessary for recovery from illness or injury, lead to various negative health consequences. The current study investigated mechanisms underlying disuse-induced insulin resistance, taking into account muscle atrophy. Ten healthy, young males (age: 23 ± 1 years; BMI: 23.0 ± 0.9 kg · m−2) were subjected to 1 week of strict bed rest. Prior to and after bed rest, lean body mass (dual-energy X-ray absorptiometry) and quadriceps cross-sectional area (CSA; computed tomography) were assessed, and peak oxygen uptake (VO2peak) and leg strength were determined. Whole-body insulin sensitivity was measured using a hyperinsulinemic-euglycemic clamp. Additionally, muscle biopsies were collected to assess muscle lipid (fraction) content and various markers of mitochondrial and vascular content. Bed rest resulted in 1.4 ± 0.2 kg lean tissue loss and a 3.2 ± 0.9% decline in quadriceps CSA (both P < 0.01). VO2peak and one-repetition maximum declined by 6.4 ± 2.3 (P < 0.05) and 6.9 ± 1.4% (P < 0.01), respectively. Bed rest induced a 29 ± 5% decrease in whole-body insulin sensitivity (P < 0.01). This was accompanied by a decline in muscle oxidative capacity, without alterations in skeletal muscle lipid content or saturation level, markers of oxidative stress, or capillary density. In conclusion, 1 week of bed rest substantially reduces skeletal muscle mass and lowers whole-body insulin sensitivity, without affecting mechanisms implicated in high-fat diet–induced insulin resistance

Encephalitis and cytokine storm secondary to respiratory viruses in children: Two case reports

Introduction Encephalitis is a syndrome characterized by brain damage secondary to an inflammatory process that is manifested by cognitive impairment and altered cerebral spinal fluid analysis; it may evolve with seizures and coma. Despite viral infections representing the main cause of encephalitis in children, respiratory syncytial virus (RSV) and parainfluenza virus are mostly associated with respiratory presentations. Uncommonly, the inflammatory phenomena from encephalitis secondary to viral agents may present with an exacerbated host response, the so-called cytokine storm. The link between these infectious agents and neurologic syndromes resulting in a cytokine storm is rare, and the underlying pathophysiology is still poorly understood. Case presentation A 5-year-old girl and a 2-year-old boy infected with parainfluenza and RSV, respectively, were identified through nasopharyngeal polymerase chain reaction. They were admitted into the pediatric intensive care unit due to encephalitis and multiple organ dysfunction manifested with seizures and hemodynamic instability. Magnetic resonance imaging findings from the first patient revealed a bilateral hypersignal on fluid-attenuated inversion recovery in the cerebral hemispheres, especially in the posterior parietal and occipital regions. The girl also had elevated IL-6 levels during the acute phase and evolved with a fast recovery of the clinical presentations. The second patient progressed with general systemic complications followed by cerebral edema and death. Conclusion Encephalitis secondary to respiratory viral infection might evolve with cytokine storm and multiorgan inflammatory response in children

Encephalitis and cytokine storm secondary to respiratory viruses in children: Two case reports

IntroductionEncephalitis is a syndrome characterized by brain damage secondary to an inflammatory process that is manifested by cognitive impairment and altered cerebral spinal fluid analysis; it may evolve with seizures and coma. Despite viral infections representing the main cause of encephalitis in children, respiratory syncytial virus (RSV) and parainfluenza virus are mostly associated with respiratory presentations. Uncommonly, the inflammatory phenomena from encephalitis secondary to viral agents may present with an exacerbated host response, the so-called cytokine storm. The link between these infectious agents and neurologic syndromes resulting in a cytokine storm is rare, and the underlying pathophysiology is still poorly understood.Case presentationA 5-year-old girl and a 2-year-old boy infected with parainfluenza and RSV, respectively, were identified through nasopharyngeal polymerase chain reaction. They were admitted into the pediatric intensive care unit due to encephalitis and multiple organ dysfunction manifested with seizures and hemodynamic instability. Magnetic resonance imaging findings from the first patient revealed a bilateral hypersignal on fluid-attenuated inversion recovery in the cerebral hemispheres, especially in the posterior parietal and occipital regions. The girl also had elevated IL-6 levels during the acute phase and evolved with a fast recovery of the clinical presentations. The second patient progressed with general systemic complications followed by cerebral edema and death.ConclusionEncephalitis secondary to respiratory viral infection might evolve with cytokine storm and multiorgan inflammatory response in children

Variants in the Mannose-binding Lectin Gene MBL2 do not Associate With Sepsis Susceptibility or Survival in a Large European Cohort

We use a large cohort of immune competent adults to analyze the influence of MBL2 genetic variants on sepsis susceptibility and survival. We find no significant associations with the 4 main functional single nucleotide polymorphisms in MBL2, or any combination of genotype

Identifying future models for delivering genetic services: a nominal group study in primary care

BACKGROUND: To enable primary care medical practitioners to generate a range of possible service delivery models for genetic counselling services and critically assess their suitability. METHODS: Modified nominal group technique using in primary care professional development workshops. RESULTS: 37 general practitioners in Wales, United Kingdom too part in the nominal group process. The practitioners who attended did not believe current systems were sufficient to meet anticipated demand for genetic services. A wide range of different service models was proposed, although no single option emerged as a clear preference. No argument was put forward for genetic assessment and counselling being central to family practice, neither was there a voice for the view that the family doctor should become skilled at advising patients about predictive genetic testing and be able to counsel patients about the wider implications of genetic testing for patients and their family members, even for areas such as common cancers. Nevertheless, all the preferred models put a high priority on providing the service in the community, and often co-located in primary care, by clinicians who had developed expertise. CONCLUSION: There is a need for a wider debate about how healthcare systems address individual concerns about genetic concerns and risk, especially given the increasing commercial marketing of genetic tests

Incorporation of Omega-3 Fatty Acids Into Human Skeletal Muscle Sarcolemmal and Mitochondrial Membranes Following 12 Weeks of Fish Oil Supplementation

Fish oil (FO) supplementation in humans results in the incorporation of omega-3 fatty acids (FAs) eicosapentaenoic acid (EPA; C20:5) and docosahexaenoic acid (DHA; C20:6) into skeletal muscle membranes. However, despite the importance of membrane composition in structure–function relationships, a paucity of information exists regarding how different muscle membranes/organelles respond to FO supplementation. Therefore, the purpose of the present study was to determine the effects 12 weeks of FO supplementation (3g EPA/2g DHA daily) on the phospholipid composition of sarcolemmal and mitochondrial fractions, as well as whole muscle responses, in healthy young males. FO supplementation increased the total phospholipid content in whole muscle (57%; p &lt; 0.05) and the sarcolemma (38%; p = 0.05), but did not alter the content in mitochondria. The content of omega-3 FAs, EPA and DHA, were increased (+3-fold) in whole muscle, and mitochondrial membranes, and as a result the omega-6/omega-3 ratios were dramatically decreased (-3-fold), while conversely the unsaturation indexes were increased. Intriguingly, before supplementation the unsaturation index (UI) of sarcolemmal membranes was ∼3 times lower (p &lt; 0.001) than either whole muscle or mitochondrial membranes. While supplementation also increased DHA within sarcolemmal membranes, EPA was not altered, and as a result the omega-6/omega-3 ratio and UI of these membranes were not altered. All together, these data revealed that mitochondrial and sarcolemmal membranes display unique phospholipid compositions and responses to FO supplementation

In Vivo, Fatty Acid Translocase (CD36) Critically Regulates Skeletal Muscle Fuel Selection, Exercise Performance, and Training-induced Adaptation of Fatty Acid Oxidation

For ∼40 years it has been widely accepted that (i) the exercise-induced increase in muscle fatty acid oxidation (FAO) is dependent on the increased delivery of circulating fatty acids, and (ii) exercise training-induced FAO up-regulation is largely attributable to muscle mitochondrial biogenesis. These long standing concepts were developed prior to the recent recognition that fatty acid entry into muscle occurs via a regulatable sarcolemmal CD36-mediated mechanism. We examined the role of CD36 in muscle fuel selection under basal conditions, during a metabolic challenge (exercise), and after exercise training. We also investigated whether CD36 overexpression, independent of mitochondrial changes, mimicked exercise training-induced FAO up-regulation. Under basal conditions CD36-KO versus WT mice displayed reduced fatty acid transport (−21%) and oxidation (−25%), intramuscular lipids (less than or equal to −31%), and hepatic glycogen (−20%); but muscle glycogen, VO(2max), and mitochondrial content and enzymes did not differ. In acutely exercised (78% VO(2max)) CD36-KO mice, fatty acid transport (−41%), oxidation (−37%), and exercise duration (−44%) were reduced, whereas muscle and hepatic glycogen depletions were accelerated by 27–55%, revealing 2-fold greater carbohydrate use. Exercise training increased mtDNA and β-hydroxyacyl-CoA dehydrogenase similarly in WT and CD36-KO muscles, but FAO was increased only in WT muscle (+90%). Comparable CD36 increases, induced by exercise training (+44%) or by CD36 overexpression (+41%), increased FAO similarly (84–90%), either when mitochondrial biogenesis and FAO enzymes were up-regulated (exercise training) or when these were unaltered (CD36 overexpression). Thus, sarcolemmal CD36 has a key role in muscle fuel selection, exercise performance, and training-induced muscle FAO adaptation, challenging long held views of mechanisms involved in acute and adaptive regulation of muscle FAO

Validation of GPM IMERG extreme precipitation in the Maritime Continent by station and radar data

The Maritime Continent (MC) is a region subject to high impact weather (HIW) events, which are still poorly predicted by numerical weather prediction (NWP) models. To improve predictability of such events, NWP need to be evaluated against accurate measures of extreme precipitation across the whole MC. With its global spatial coverage at high spatio-temporal resolution, the Global Precipitation Measurement (GPM) dataset is a suitable candidate. Here we evaluate extreme precipitation in the Integrated Multi-Satellite Retrieval for GPM (IMERG) V06B product against station data from the Global Historical Climatology Network (GHCN) in Malaysia and the Philippines. We find that the high intra-grid spatial variability of precipitation extremes results in large spatial sampling errors when each IMERG gridbox is compared with individual co-located precipitation measurements, a result that may explain discrepancies found in earlier studies in the MC. Overall, IMERG daily precipitation is similar to station precipitation between the 85th and 95th percentile, but tends to overestimate above the 95th. IMERG data were also compared with radar data in western Peninsular Malaysia for sub-daily timescales. Allowing for uncertainties in radar data, the analysis suggests that the 95th percentile is still suitable for NWP evaluation of extreme sub-daily precipitation, but that the rainfall rates diverge at higher percentiles. Hence, our overall recommendation is that the 95th percentile be used to evaluate NWP forecasts of HIW on daily and sub-daily time scales against IMERG data, but that higher percentiles (i.e., more extreme precipitation) be treated with caution

Validation of GPM IMERG extreme precipitation in the peninsular Malaysia and Philippines by station and radar data

Abstract: Extreme precipitation is ubiquitous in the Maritime Continent (MC) but poorly predicted numerical weather prediction (NWP) models. NWP evaluation against accurate measures of heavy precipitation is essential to improve their forecasting skill. Here we examine the potential utility of the Global Precipitation Measurement (GPM) Integrated Multi-Satellite Retrieval for GPM (IMERG) for NWP evaluation of extreme precipitation in the MC. For that purpose, we use radar data in Subang (Malaysia) and station data from the Global Historical Climatology Network (GHCN) in Malaysia and the Philippines. We find that earlier studies may have underestimated IMERG performances in the MC due to large spatial sampling errors of ground precipitation measurements, especially during extreme precipitation conditions. We recommend using the 95th percentile for NWP evaluation of extreme daily and sub-daily precipitation against IMERG. At higher percentiles, the IMERG rainfall rates tend to diverge from ground observation and may therefore be treated with caution

Sea-breeze dynamics and convection initiation: the influence of convective parameterization in weather and climate model biases

There are some long-established biases in atmospheric models that originate from the representation of tropical convection. Previously, it has been difficult to separate cause and effect because errors are often the result of a number of interacting biases. Recently, researchers have gained the ability to run multiyear global climate model simulations with grid spacings small enough to switch the convective parameterization off, which permits the convection to develop explicitly. There are clear improvements to the initiation of convective storms and the diurnal cycle of rainfall in the convection-permitting simulations, which enables a new process-study approach to model bias identification. In this study, multiyear global atmosphere-only climate simulations with and without convective parameterization are undertaken with the Met Office Unified Model and are analyzed over the Maritime Continent region, where convergence from sea-breeze circulations is key for convection initiation. The analysis shows that, although the simulation with parameterized convection is able to reproduce the key rain-forming sea-breeze circulation, the parameterization is not able to respond realistically to the circulation. A feedback of errors also occurs: the convective parameterization causes rain to fall in the early morning, which cools and wets the boundary layer, reducing the land–sea temperature contrast and weakening the sea breeze. This is, however, an effect of the convective bias, rather than a cause of it. Improvements to how and when convection schemes trigger convection will improve both the timing and location of tropical rainfall and representation of sea-breeze circulations