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Glucose metabolism modulates the islet β cell responses to diabetogenic stress, including inflammation. Here, we probed the metabolic mechanisms that underlie the protective effect of glucose in inflammation by interrogating the metabolite profiles of primary islets from human donors and identified de novo glutathione synthesis as a prominent glucose-driven pro-survival pathway. We find that pyruvate carboxylase is required for glutathione synthesis in islets and promotes their antioxidant capacity to counter inflammation and nitrosative stress. Loss- and gain-of-function studies indicate that pyruvate carboxylase is necessary and sufficient to mediate the metabolic input from glucose into glutathione synthesis and the oxidative stress response. Altered redox metabolism and cellular capacity to replenish glutathione pools are relevant in multiple pathologies beyond obesity and diabetes. Our findings reveal a direct interplay between glucose metabolism and glutathione biosynthesis via pyruvate carboxylase. This metabolic axis may also have implications in other settings where sustaining glutathione is essential., Competing Interests: Declarations of interests L.D.W. is a scientific co-founder and shareholder in Aileron Therapeutics. M.L.-R. is a co-founder and consultant of Enspire Bio. E.T.C. is a founder, board member, and equity holder in EoCys Therapeutics., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

In Europe, Puumala virus (PUUV) transmitted by the bank vole ( Myodes glareolus ) is the causative agent of nephropathia epidemica (NE), a mild form of haemorrhagic fever with renal syndrome. In France, very little is known about the spatial and temporal variability of the virus circulating within bank vole populations. The present study involved monitoring of bank vole population dynamics and PUUV microdiversity over a ten-year period (2000-2009) in two forests of the Ardennes region: Elan and Croix-Scaille. Ardennes region is characterised by different environmental conditions associated with different NE epidemiology. Bank vole density and population parameters were estimated using the capture/marking/recapture method, and blood samples were collected to monitor the overall seroprevalence of PUUV in rodent populations. Phylogenetic analyses of fifty-five sequences were performed to illustrate the genetic diversity of PUUV variants between forests. The pattern of the two forests differed clearly. In the Elan forest, the rodent survival was higher, and this limited turn-over resulted in a lower seroprevalence and diversity of PUUV sequences than in the Croix-Scaille forest. Uncovering the links between host dynamics and virus microevolution is improving our understanding of PUUV distribution in rodents and the NE risk.

Since the beginning of the 21st century five new coronaviruses inducing respiratory diseases in humans have been reported. These emergences has promoted research on coronaviruses in wildlife. We started the first eco-epidemiological study to screen the presence of coronaviruses circulating in mice and rats of four Canary Islands. Between 2015 and 2019, we obtained fecal samples of three rodent species (150 Mus musculus , 109 Rattus rattus and 1 Rattus norvegicus ) captured in urban and rural areas. Fecal samples were analyzed by nRT-PCR and the resulting sequences were compared to known diversity using Bayesian phylogenetic methods. We only found coronavirus RNA in house mice from El Hierro (10.53%), Tenerife (7.02%) and Lanzarote (5.26%) islands. All coronaviruses detected belong to the species Murine coronavirus belonging to the genus Betacoronavirus and subgenus Embecovirus , being all positive house mice captured in anthropogenic environment. The phylogenetic analysis shows that murine coronaviruses from the Canary Islands are related to European murine coronaviruses. Albeit data are still scarce in the region, the most probable origin of M. coronavirus present in the Canary Islands is continental Europe. According to temporal Bayesian phylogenetics, the differentiation between Canary and continental viruses seems to be quite recent. Moreover, murine coronaviruses from El Hierro, Tenerife and Lanzarote islands tend to segregate in different clades. This enlightens the potential role of rodents or other possibly invasive species in disseminating infectious diseases to remote places through exchanges with the continent. It is important to consider these aspects in the sanitary control of islands, for health and biodiversity preservation concerns., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Monastiri, Martín-Carrillo, Foronda, Izquierdo-Rodríguez, Feliu, López-Roig, Miquel, Ar Gouilh and Serra-Cobo.)

Motor learning may be enhanced when a single session of aerobic exercise is performed immediately before or after motor skill practice. Most research to date has focused on aerobically trained (AT) individuals, but it is unknown if aerobically untrained (AU) individuals would equally benefit. We aimed to: (a) replicate previous studies and determine the effect of rest (REST) versus exercise (EXE) on motor skill retention, and (b) explore the effect of aerobic fitness level (AU, AT), assessed by peak oxygen uptake (VO 2 peak), on motor skill retention after exercise. Forty-four participants (20-29 years) practiced a visuomotor tracking task (acquisition), immediately followed by 25-min of high-intensity cycling or rest. Twenty-four hours after acquisition, participants completed a motor skill retention test. REST and EXE groups significantly improved motor skill performance during acquisition [F(3.17, 133.22) = 269.13, P = 0.001], but had no group differences in motor skill retention across time. AU-exercise (VO 2 peak = 31.6 ± 4.2 ml kg -1  min -1 ) and AT-exercise (VO 2 peak = 51.5 ± 7.6 ml kg -1  min -1 ) groups significantly improved motor skill performance during acquisition [F(3.07, 61.44) = 155.95, P = 0.001], but had no group differences in motor skill retention across time. Therefore, exercise or aerobic fitness level did not modify motor skill retention.

We conducted a systematic review with meta-analysis to determine the evidence in support of exercise to improve sleep quality assessed subjectively and objectively in Parkinson's Disease (PD). Standardized mean differences (SMD) comparing the effects of exercise and control interventions on sleep quality with 95% confidence intervals (CI) were calculated. Data from 10 randomized and 2 non-randomized controlled trials, including a total of 690 persons with PD were included. Exercise had a significant positive effect on sleep quality assessed subjectively (SMD = 0.53; 95% CI = 0.16-0.90; p = 0.005). However, the methodological quality of the studies showing positive effects on sleep quality was significantly poorer than the studies showing no effects. Only one study assessed the impact of exercise on objective sleep quality, showing improvements in sleep efficiency assessed with polysomnography (SMD = 0.94; 95% CI = 0.38-1.50; p = 0.001). Exercise performed at moderate to maximal intensities (SMD = 0.46; 95% CI = 0.05-0.87; p = 0.03) had significant effects on subjective sleep quality. In contrast, exercise performed at mild to moderate intensities showed non-significant effects (SMD = 0.76; 95% CI = -0.24-1.76; p = 0.14). These results support the use of exercise to improve sleep quality in persons with PD and reinforce the importance of achieving vigorous exercise intensities. Biases, limitations, practice points and directions for future research are discussed., Competing Interests: Conflicts of interest None., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

More than 200 viruses have been detected in bats. Some unique bat characteristics can explain the roles played in the maintenance and transmission of viruses: long phylogenetic history can have originated coevolution processes, great number of species are adapted to live in different environments, big mobility, long lifespan and gregarious behaviour of many species.To analyse zoonoses long longitudinal studies are needed with a multidisciplinary approximation to obtain the following eco-epidemiological data: colony size, number of bats per species, population structure, behaviour of each species, degree of contact between bats, social structure, remaining time of bats in the colony, colony type, foraging area, turnover rate of individuals, shelter temperature, relationship with other colonies and co-infection processes. These data allows assessing the epidemiological risk and which preventive measures are necessary to take.The structure and functionality of ecosystems are changing worldwide at an unprecedented rate and can modify the interactions between humans and infected bats. There are more or less local factors that can affect the emergence and spread of diseases (environmental alterations, changes in land use, human population growth, changes in human socioeconomic behavior or social structure, people mobility increase, trade increase, forest fires, extreme weather events, wars, breakdown in public health infrastructure, etc.).Twenty-three percent of all bat species in the world are decreasing. How does the regression of bat species affect the dynamic of viruses? The dichotomy between health risk and bat preservation is compatible with a preventive task based on more information and training.

Molecular analyses of blood samples revealed infection with hemoplasmas in 97% of 31 cave bats captured in three caves in North-Eastern Spain. The characterization of 1250 bp of the 16S rRNA gene in 29 of the positive bats identified two different groups of sequences. Twenty-two Schreibers' bats (Miniopterus schreibersii) and one long-eared bat (Myotis capaccinii) shared one group, composed of seven closely related sequences. These sequences showed an identity of about 97% with "Candidatus Mycoplasma hemohominis" and the phylogenetic branch including bat and human sequences showed a 100% bootstrap value, supporting a close phylogenetic relationship between these hemoplasmas. The second group, representing a potentially novel species, was composed of a single sequence shared by six Schreibers' bats that had 91% identity with the recently reported hemoplasma from little brown bats in North America. Large bat aggregations in roosting caves probably benefits intra and inter-species transmission explaining the high observed prevalence., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

We have recently shown that a single bout of acute cardiovascular exercise improves motor skill learning through an optimization of long-term motor memory. Here we expand this previous finding, to explore potential exercise-related biomarkers and their association with measures of motor memory and skill acquisition. Thirty-two healthy young male subjects were randomly allocated into either an exercise or control group. Following either an intense bout of cycling or rest subjects practiced a visuomotor tracking task. Motor skill acquisition was assessed during practice and retention 1 h, 24 h and 7 days after practice. Plasma levels of brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF-1), epinephrine, norepinephrine, dopamine and lactate were analyzed at baseline, immediately after exercise or rest and during motor practice. The exercise group showed significantly better skill retention 24h and 7 days after acquisition. The concentration of all blood compounds increased significantly immediately after exercise and remained significantly elevated for 15 min following exercise except for BDNF and VEGF. Higher concentrations of norepinephrine and lactate immediately after exercise were associated with better acquisition. Higher concentrations of BDNF correlated with better retention 1 h and 7 days after practice. Similarly, higher concentrations of norepinephrine were associated with better retention 7 days after practice whereas lactate correlated with better retention 1h as well as 24 h and 7 days after practice. Thus, improvements in motor skill acquisition and retention induced by acute cardiovascular exercise are associated with increased concentrations of biomarkers involved in memory and learning processes. More mechanistic studies are required to elucidate the specific role of each biomarker in the formation of motor memory., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Declines in the ability to learn motor skills in older adults are commonly attributed to deficits in the encoding of sensorimotor information during motor practice. We investigated whether aging also impairs motor memory consolidation by assessing the susceptibility to memory interference and off-line gains in motor skill learning after practice in children, young, and older adults. Subjects performed a ballistic task (A) followed by an accuracy-tracking task (B) designed to disrupt the consolidation of A. Retention tests of A were performed immediately and 24 hours after B. Older adults showed greater susceptibility to memory interference and no off-line gains in motor skill learning. Performing B produced memory interference and reduced off-line gains only in the older group. However, older adults also showed deficits in memory consolidation independent of the interfering effects of B. Age-related declines in motor skill learning are not produced exclusively by deficits in the encoding of sensorimotor information during practice. Aging also increases the susceptibility to memory interference and reduces off-line gains in motor skill learning after practice., (Copyright © 2014 Elsevier Inc. All rights reserved.)

We reviewed the evidence for the use of cardiovascular exercise to improve memory and explored potential mechanisms. Data from 29 and 21 studies including acute and long-term cardiovascular interventions were retrieved. Meta-analyses revealed that acute exercise had moderate (SMD=0.26; 95% CI=0.03, 0.49; p=0.03; N=22) whereas long-term had small (SMD=0.15; 95% CI=0.02, 0.27; p=0.02; N=37) effects on short-term memory. In contrast, acute exercise showed moderate to large (SMD=0.52; 95% CI=0.28, 0.75; p<0.0001; N=20) whereas long-term exercise had insignificant effects (SMD=0.07; 95% CI=-0.13, 0.26; p=0.51; N=22) on long-term memory. We argue that acute and long-term cardiovascular exercise represent two distinct but complementary strategies to improve memory. Acute exercise improves memory in a time-dependent fashion by priming the molecular processes involved in the encoding and consolidation of newly acquired information. Long-term exercise, in contrast, has negligible effects on memory but provides the necessary stimuli to optimize the responses of the molecular machinery responsible for memory processing. Strategically combined, acute and long-term interventions could maximize the benefits of cardiovascular exercise on memory., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Objective: To identify the 100 top-cited articles ever published in rehabilitation journals and to analyze their characteristics as a quantitative approach to investigating the quality and evolution of rehabilitation research., Data Sources: The Institute for Scientific Information Web of Knowledge Database and the 2007 and 2008 Journal Citation Report Science Editions were used to retrieve the 100 top-cited articles from 30 rehabilitation dedicated journals., Study Selection: The 100 top-cited articles included randomized controlled trials, case-control studies, case series studies, case reports, methodologic studies, systematic reviews, narrative reviews, and expert opinions., Data Extraction: Two independent reviewers performed data extraction from the retrieved articles and compared their results. The Sackett's initial rules of evidence were used to categorize the type of study design as well as to evaluate the level of evidence provided by the results of the 100 top-cited articles., Data Synthesis: Among the 45,700 articles published in these journals, the 100 top-cited articles were published between 1959 and 2002 with an average of 200 citations an article (range, 131-1109). Top-cited articles were all English-language, primarily from North America (United States=67%; Canada=11%) and published in 11 journals led by the Archives of Physical Medicine and Rehabilitation. Eighty-four percent of the articles were original publications and were most commonly prospective (76%) case series studies (67%) that used human subjects (96%) providing level 4 evidence. Neurorehabilitation (41%), disability (19%), and biomechanics (18%) were the most common fields of study., Conclusions: We demonstrated that methodologic observational studies performed in North America and published in English have had the highest citations in rehabilitation journals.

Chronic obstructive pulmonary disease (COPD) is a respiratory disease that results in airflow limitation and respiratory distress. The effects of COPD, however, are not exclusively limited to respiratory function and people with COPD face many non-respiratory manifestations that affect both function and mobility. Deficits in function and mobility have been associated with an increased risk for falling in older adults. The purpose of this study was to provide a theoretical framework to identify risks factors for falls in people with COPD. We have analyzed the literature to identify possible relationships between pathophysiological changes observed in COPD and common risk factors for falls. Well-established fall risk factors in people with COPD include lower limb muscle weakness and impaired activities of daily living. Other intrinsic risk factors such as gait and balance deficits, nutritional depletion, malnutrition, depression, cognitive impairments and medications are possible risk factors that need to be confirmed with more studies. There is no evidence that visual deficits are common in COPD. The role that precipitating factors such as syncope and postural hypotension may have on fall risk is unclear. Exacerbations and dyspnea do not have a precipitating effect on fall risk but they contribute to the progressive physical deterioration that may theoretically increase the risk for falls. While these results suggest that people with COPD might have an increased susceptibility to fall compared to their healthy peers, further research is needed to determine the prevalence of falls and specific risk factors for falls in people living with COPD.

Background: Chronic obstructive pulmonary disease (COPD) can lead to peripheral muscle atrophy and weakness. Electrical stimulation (ES) is commonly used to improve muscle function and structure. The purpose of this systematic review is to determine the effect of ES on muscle function, muscle size, fibre characteristics and exercise performance in patients with COPD., Methods: A search was performed in seven electronic databases (Cochrane Controlled Trials Register, Pubmed, CINAHL, Embase, SPORTDiscus, Web of Science, PEDro). Inclusion criteria were: (1) randomized controlled trials (RCTs), (2) on COPD patients, (3) investigating a defined protocol of ES applied to the lower extremities, (4) analysing at least one main outcome, (5) full text available. Two reviewers extracted the data and evaluated the methodological quality of the studies using the PEDro scale., Results: The initial search yielded 167 abstracts, of which five RCTs met the inclusion criteria. The mean (SD) methodological quality of the studies was 6.2+1.3 out of 10. Meta-analyses of three studies showed significant increases in muscle torque and walk distance in the ES groups compared to values in the control, sham or other treatment groups. Measures of muscle size revealed equivocal evidence. Patients with less severe COPD tended to show less improvement., Conclusions: The modest effect sizes after ES, small n, and small number of studies provide weak evidence for the effectiveness of ES to improve lower limb muscle function in COPD patients. Further study should elucidate the optimal parameters for ES protocols and selection criteria for responders and non-responders.