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Introduction: Gabapentinoids are ligands of the α2-δ subunit of voltage-gated calcium channels (Cav) that have been associated with a risk of peripheral edema and acute heart failure in connection with a potentially dual mechanism, vascular and cardiac. Objectives & methods: All cases of peripheral edema or heart failure involving gabapentin or pregabalin reported to the French Pharmacovigilance Centers between January 1, 1994 and April 30, 2020 were included to describe their onset patterns (e.g., time to onset). Based on these data, we investigated the impact of gabapentinoids on the myogenic tone of rat third-order mesenteric arteries and on the electrophysiological properties of rat ventricular cardiomyocytes. Results: A total of 58 reports were included (gabapentin n = 5, pregabalin n = 53). The female-to-male ratio was 4:1 and the median age was 77 years (IQR 57–85, range 32–95). The median time to onset were 23 days (IQR 10–54) and 17 days (IQR 3–30) for non-cardiogenic edema and acute heart failure, respectively. Cardiogenic and non-cardiogenic peripheral edema occurred frequently after a dose escalation (27/45, 60%), and the course was rapidly favorable after discontinuation of gabapentinoid (median 7 days, IQR 5–13). On rat mesenteric arteries, gabapentinoids significantly decreased the myogenic tone to the same extent as verapamil and nifedipine. Acute application of gabapentinoids had no significant effect on Cav1.2 currents of ventricular cardiomyocytes. Conclusion: Gabapentinoids can cause concentration-dependent peripheral edema of early onset. The primary mechanism of non-cardiogenic peripheral edema is vasodilatory edema secondary to altered myogenic tone, independent of Cav1.2 blockade under the experimental conditions tested.

BACKGROUND: The lockdown linked to COVID-19 was shown to have negative effects on healthy behaviors in the general population, prompting the implementation of adapted public health measures. However, more vulnerable populations, such as pregnant women, were not specifically taken into account. At the time of writing this study, we know little about how the COVID-19 pandemic impacted the physical activity (PA) behavior of pregnant women in France. Given the many reports in the literature about women's low level of PA throughout pregnancy and the negative effects of the COVID-19 lockdown on behaviors in the general population; however, we might assume that their sedentary behaviors increased. The current study aimed to analyze the French recommendations and PA promotion among pregnant women. MATERIALS AND METHODS: A literature search was done using PubMed for the key terms “physical activity/physical activity promotion,” “pregnant women/pregnancy,”, and “French population/France.” All the relevant studies were included to support the argument for this narrative review. RESULTS: Efforts to promote PA for pregnant women often seem ineffective and even unrealistic, and many women become overweight or obese during pregnancy. Health professionals need evidence-based guidelines and continuous training and skills development in order to convincingly encourage women to be more active during pregnancy and the postpartum period. CONCLUSION: Health policies should strengthen PA promotion among pregnant women with detailed evidence-based guidelines on PA during postpartum.

Background and objective Warm exposure places high demands on thermoregulation mechanisms, which depend on the effectiveness of the microvascular function. The associations between the microcirculation and metabolism in warm environments have received little attention. The purpose of this study was to explore skin blood flow (SkBF) in response to food intake in a warm environment compared to control. Methods Thirty-two healthy, acclimated-to-warm-environment and physically active participants were recruited (20 females and 12 males). They participated in two sessions (warm environment: 31 °C and control: 20 °C, presented in randomized order). SkBF was measured before and after standardized food intake through the acquisition of perfusion signals by laser Doppler flowmetry (Periflux System 5000), following a local heating protocol. Results SkBF was affected by the environmental temperature, showing an increase in the warm environment compared to control (all p

Aims: The antenatal period provides an important opportunity for giving advice on healthy lifestyle choices. However, the prevalence of maternal obesity is increasing, and women report that they do not receive counseling. We investigated the information given to pregnant women on gestational weight gain, physical activity, and nutrition during pregnancy in relation with their initial weight status, current gestational weight gain and diagnoses of either pre-pregnancy overweight/obesity or excessive gestational weight gain.Methods: Cross-sectional survey using a questionnaire. Pregnant participants (n = 141) were recruited from a midwife center. They completed a structured questionnaire on the information they received during their pregnancy and we assessed its relationship with their weight.Results: We found that many pregnant women did not receive advice about physical activity, gestational weight gain and nutrition (37.5, 53.2, and 66.2%, respectively). Women with weight problems (pre-pregnancy overweight/obesity and excessive gestational weight gain) were less targeted for counseling, although more than 80% of the women viewed receiving information on these topics as positive. Also, being informed of a weight problem was associated with a greater chance of receiving information about physical activity, gestational weight gain and nutrition (all p < 0.05). However, verbalization of the weight problems was low (14.0% of women with pre-pregnancy overweight were informed of their status).Conclusion: Health professionals should dispense more information, especially on PA and particularly for women with weight problems. Verbalization of the weight problem seems associated with more frequent transmission of information.

Objective: Hot environments are associated with impaired glucose metabolism at rest in healthy humans. The purpose of this study was to explore the contribution of key glucoregulatory hormones and biomarkers to this altered glucose tolerance. Methods: The effects of ambient temperature on glucose tolerance and its determinants were assessed with a 3-hr oral glucose tolerance test (OGTT) administered to 19 healthy young men and women at 22 °C and 31 °C. Results: The glucose response amplitude was greater in warm environment (AUC 904 ± 151 vs. 721 ± 89 mmol/l·180 min at 31 °C and 22 °C, respectively, p .17). The cortisol response to the glucose load was reduced 30, 60, 90 and 120 minutes postload at 31 °C compared with 22 °C (p = .001). The interleukin-6 concentration was also lower in the session at 31 °C (p = .043). Conclusion: We conclude that the effects of environmental temperature on the glucoregulatory hormones and biomarkers reported in this study do not explain the exaggerated increase in blood glucose after a glucose load taken in a warm environmental temperature. Precis statement: This work demonstrates in healthy men and women that the ingestion of glucose elicits an exaggerated increase in blood glucose when the environmental temperature is warm.

Components of Earth system models (ESMs) usually use different numerical grids because of the different environments they represent. Therefore, a coupling field sent by a source model has to be regridded to be used by a target model. The regridding has to be accurate and, in some cases, conservative, in order to ensure the consistency of the coupled model. Here, we present work done to benchmark the quality of four regridding libraries currently used in ESMs, i.e., SCRIP, YAC, ESMF and XIOS. We evaluated five regridding algorithms with four different analytical functions for different combinations of six grids used in real ocean or atmosphere models. Four analytical functions were used to define the coupling fields to be regridded. This benchmark calculated some of the metrics proposed by the CANGA project, including the mean, maximum, RMS misfit, and global conservation. The results show that, besides a few very specific cases that present anomalous values, the regridding functionality in YAC, ESMF and XIOS can be considered of high quality and do not present the specific problems observed for the conservative SCRIP remapping. The evaluation of the computing performance of those libraries is not included in the current work but is planned to be performed in the coming months. This exercise shows that benchmarking can be a great opportunity to favour interactions between users and developers of regridding libraries.

Strategies for diets in chronic spontaneous urticaria (CSU) are controversial. This systematic review assessed the interest in diet for managing CSU. We searched for original reports in MEDLINE, EMBASE, CENTRAL and LILACS. Among the 278 reports screened, 20 were included, involving 1,734 patients. Reports described 3 types of systematic diet: pseudoallergen-free diet (n = 1,555 patients), low-histamine diet (n = 223) and diet without fish products (n = 47), which induced complete remission in 4.8%, 11.7% and 10.6% of patients, respectively, and partial remission in 37.0%, 43.9% and 4.3%. Eight reports described personalized exclusion diets (66 patients) adapted to symptoms/allergological test results and led to complete remission in 74.6% of patients, although the diagnosis of CSU was doubtful. No comparative randomized studies of diets were available. The only randomized studies were based on oral provocation tests with the suspected responsible diet. Population and outcomes were heterogeneous. In conclusion, there is evidence for the benefit of diets in CSU only in individual patients with clinical symptoms. However, the level of evidence is low for the benefit of systematic diets in CSU because systematic double-blind controlled trials of diet are lacking.

Chronic hemolysis, enhanced oxidative stress, and decreased nitric oxide (NO) bioavailability promote vasculopathy in sickle cell anemia (SCA). Oxidative stress and NO are known to modulate eryptosis in healthy red blood cells (RBCs); however, their role in SCA eryptosis and their impact on the genesis of RBC-derived microparticles (RBC-MPs) remains poorly described. RBC-MPs could play a role in vascular dysfunction in SCA. The aims of this study were to evaluate the roles of oxidative stress and NO in eryptosis and RBC-MPs release, and to determine whether RBC-MPs could be involved in vascular dysfunction in SCA. Markers of eryptosis and oxidative stress, plasma RBC-MPs concentration and arterial stiffness were compared between SCA and healthy (AA) individuals. In-vitro experiments were performed to test: 1) the effects of oxidative stress (antioxidant: n-acetylcysteine (NAC); pro-oxidant: cumene hydroperoxide) and NO (NO donor: sodium nitroprusside (SNP); NO-synthase inhibitor (L-NIO)) on eryptosis, RBC deformability and RBC-MP genesis; 2) the effects of SCA/AA-RBC-MPs on human aortic endothelial cell (HAEC) inflammatory phenotype and TLR4 pathway. Eryptosis, RBC-MPs, oxidative stress and arterial stiffness were increased in SCA. NAC increased RBC deformability and decreased eryptosis and RBC-MPs release, while cumene did the opposite. SNP increased RBC deformability and limited eryptosis, but had no effect on RBC-MPs. L-NIO did not affect these parameters. Arterial stiffness was correlated with RBC-MPs concentration in SCA. RBC-MPs isolated directly from SCA blood increased adhesion molecules expression and the production of cytokines by HAEC compared to those isolated from AA blood. TLR4 inhibition alleviated these effects. Our data show that oxidative stress could promote eryptosis and the release of RBC-MPs that are potentially involved in macrovascular dysfunction in SCA.

Abstract Background Diabetes and myelodysplastic syndrome are two conditions that may coexist in a single patient, since both diseases are prevalent in the elderly. The pathophysiology of myelodysplastic syndrome involves recurrent genetic mutations, especially in genes controlling epigenetic regulation. Although the pathophysiology of diabetes is not well understood, several studies suggest a role of epigenetics in type 2 diabetes. Case presentation We report here for the first time the case of a 75-year-old Caucasian man who was treated for both diabetes and acute myeloid leukemia secondary to myelodysplastic syndrome, with a temporal association between glycemic dysregulation and the intake of 5-azacitidine. In fact, 2–3 days after starting each 7-day cycle of 5-azacitidine, he reported higher blood glucose levels, requiring an increased dose of self-administered insulin. Conclusion This observation could help to understand the pathophysiology of these two conditions and could encourage physicians to monitor blood glucose levels in patients under hypomethylating agent with a history of diabetes.

Blood viscosity is an important determinant of local flow characteristics, which exhibits shear thinning behavior: it decreases exponentially with increasing shear rates. Both hematocrit and plasma viscosity influence blood viscosity. The shear thinning property of blood is mainly attributed to red blood cell (RBC) rheological properties. RBC aggregation occurs at low shear rates, and increases blood viscosity and depends on both cellular (RBC aggregability) and plasma factors. Blood flow in the microcirculation is highly dependent on the ability of RBC to deform, but RBC deformability also affects blood flow in the macrocirculation since a loss of deformability causes a rise in blood viscosity. Indeed, any changes in one or several of these parameters may affect blood viscosity differently. Poiseuille’s Law predicts that any increase in blood viscosity should cause a rise in vascular resistance. However, blood viscosity, through its effects on wall shear stress, is a key modulator of nitric oxide (NO) production by the endothelial NO-synthase. Indeed, any increase in blood viscosity should promote vasodilation. This is the case in healthy individuals when vascular function is intact and able to adapt to blood rheological strains. However, in sickle cell disease (SCD) vascular function is impaired. In this context, any increase in blood viscosity can promote vaso-occlusive like events. We previously showed that sickle cell patients with high blood viscosity usually have more frequent vaso-occlusive crises than those with low blood viscosity. However, while the deformability of RBC decreases during acute vaso-occlusive events in SCD, patients with the highest RBC deformability at steady-state have a higher risk of developing frequent painful vaso-occlusive crises. This paradox seems to be due to the fact that in SCD RBC with the highest deformability are also the most adherent, which would trigger vaso-occlusion. While acute, intense exercise may increase blood viscosity in healthy individuals, recent works conducted in sickle cell patients have shown that light cycling exercise did not cause dramatic changes in blood rheology. Moreover, regular physical exercise has been shown to decrease blood viscosity in sickle cell mice, which could be beneficial for adequate blood flow and tissue perfusion.

Abstract Background Slow-flow superficial vascular malformations (VMs) are rare congenital anomalies that can be responsible for pain and functional impairment. Currently, we have no guidelines for their management, which can involve physical bandages, sclerotherapy, surgery, anti-inflammatory or anti-coagulation drugs or no treatment. The natural history is progressive and worsening. Mammalian target of rapamycin (mTOR) is a serine/threonine kinase that acts as a master switch in cell proliferation, apoptosis, metabolism and angio/lymphangiogenesis. Sirolimus directly inhibits the mTOR pathway, thereby inhibiting cell proliferation and angio/lymphangiogenesis. Case reports and series have reported successful use of sirolimus in children with different types of vascular anomalies, with heterogeneous outcomes. Objective The objective of this trial is to evaluate the efficacy and safety of sirolimus in children with complicated superficial slow-flow VMs. Methods/design This French multicenter randomized observational-phase, phase 2 trial aims to include 50 pediatric patients 6 to 18 years old who have slow-flow (lymphatic, venous or lymphatico-venous) voluminous complicated superficial VM. Patients will be followed up for 12 months. All patients will start with an observational period (no treatment). Then at a time randomly selected between month 4 and month 8, they will switch to the experimental period (switch time), when they will receive sirolimus until month 12. Each child will undergo MRI 3 times: at baseline, at the switch time, and at month 12. For both periods (observational and treatment), we will calculate the relative change in volume of the VM divided by the study period duration. This relative change weighted by the study period duration will constitute the primary endpoint. VM will be measured by MRI images, which will be centralized and interpreted by the same radiologist who will be blinded to the study period. Hence, each patient will be his/her own control. Secondary outcomes will include assessment of safety and efficacy by viewing standardized digital photographs and according to the physician, the patient or proxy; impact on quality of life; and evolution of biological makers (coagulation factors, vascular endothelial growth factor, tissue factor). Discussion The main benefit of the study will be to resolve uncertainty concerning the efficacy of sirolimus in reducing the volume of VMs and limiting related complications and the safety of the drug in children with slow-flow VMs. This trial design is interesting in these rare conditions because all included patients will have the opportunity to receive the drug and the physician can maintain it after the end of the protocol if is found efficient (which would not be the case in a classical cross-over study). Trial registration ClinicalTrials.gov Identifier: NCT02509468, first received: 28 July 2015. EU Clinical Trials Register EudraCT Number: 2015-001096-43.

To determine the relationships between limiting factors and neuromuscular activity during a self-paced 20-km cycling time trial and evaluate the effect of environmental conditions on fatigue indices. Methods: Ten endurance-trained and heat-acclimated athletes performed in three conditions (ambient temperature, relative humidity): HUMID (30 °C, 90%), DRY (35 °C, 46%) and NEUTRAL (22 °C, 55%). Voluntary muscular contractions and electromagnetic stimulations were recorded before and after the time trials to assess fatigue. The data on performance, temperature, heat storage, electromyogram, heart rate and rating of perceived exertion data were analyzed. Results: Performance was impaired in DRY and HUMID compared with NEUTRAL environment (p < 0.05). The force developed by the vastus lateral muscle during stimulation of the femoral nerve remained unchanged across conditions. The percentage of integrated electromyogram activity, normalized by the value attained during the pre-trial maximal voluntary contraction, decreased significantly throughout the trial only in HUMID condition (p < 0.01). Neuromuscular activity in peripheral skeletal muscle started to fall from the 11th km in HUMID and the 15th km in DRY condition, although core temperature did not reach critical values. Conclusions: These alterations suggest that afferences from core/skin temperature regulate the central neural motor drive, reducing the active muscle recruited during prolonged exercise in the heat in order to prevent the system from hyperthermia.

We described ceftriaxone-induced CNS adverse events through the largest case series of Adverse Drug Reactions (ADRs) reports, from 1995 to 2017, using the French Pharmacovigilance Database. In total, 152 cases of serious CNS ADRs were analyzed; 112 patients were hospitalized or had a prolonged hospitalization (73.7%), 12 dead (7.9%) and 16 exhibited life-threatening ADRs (10.5%). The median age was 74.5 years, mainly women (55.3%), with a median creatinine clearance of 35 mL/min. Patients mainly exhibited convulsions, status epilepticus, myoclonia (n = 75, 49.3%), encephalopathy (n = 45, 29.6%), confused state (n = 34, 22.4%) and hallucinations (n = 16, 10.5%). The median time of onset was 4 days, and the median duration was 4.5 days. The mean daily dose was 1.7 g mainly through an intravenous route (n = 106, 69.7%), and three patients received doses above maximal dose of Summary of Product Characteristics. Ceftriaxone plasma concentrations were recorded for 19 patients (12.5%), and 8 were above the toxicity threshold. Electroencephalograms (EEG) performed for 32.9% of the patients (n = 50) were abnormal for 74% (n = 37). We described the world’s biggest case series of ceftriaxone-induced serious CNS ADRs. Explorations (plasma concentrations, EEG) are contributive to confirm the ceftriaxone toxicity-induced. Clinicians may be cautious with the use of ceftriaxone, especially in the older age or renal impairment population.

The present study describes the assimilation of river water level observations and the resulting improvement in flood forecasting. The Kalman Filter algorithm was built on top of a one-dimensional hydraulic model which describes the Saint-Venant equations. The assimilation algorithm folds in two steps: the first one was based on the assumption that the upstream flow can be adjusted using a three-parameter correction; the second one consisted of directly correcting the hydraulic state. This procedure was applied using a four-day sliding window over the flood event. The background error covariances for water level and discharge were represented with anisotropic correlation functions where the correlation length upstream of the observation points is larger than the correlation length downstream of the observation points. This approach was motivated by the implementation of a Kalman Filter algorithm on top of a diffusive flood wave propagation model. The study was carried out on the Adour and the Marne Vallage (France) catchments. The correction of the upstream flow as well as the control of the hydraulic state during the flood event leads to a significant improvement in the water level and discharge in both analysis and forecast modes.

Understanding the regulation of human food intake in response to an acute exercise session is of importance for interventions with athletes and soldiers, as well as overweight individuals. However, the influence of hot and cold environments on this crucial function for the regulation of body mass and motor performance has not been summarized. The purpose of this review was to exhaustively search the literature on the effect of ambient temperature during an exercise session on the subsequent subjective feeling of appetite, energy intake (EI) and its regulation. In the absence of stress due to environmental temperature, exercise-induced energy expenditure is not compensated by EI during an ad libitum meal following the session, probably due to decreased acylated ghrelin and increased peptide tyrosine tyrosine (PYY), glucagon-like peptide 1 (GLP-1), and pancreatic polypeptide (PP) levels. No systematic analysis has been yet made for major alterations of relative EI in cold and hot environments. However, observed eating behaviors are altered (proportion of solid/liquid food, carbohydrate/fat) and physiological regulation appears also to be altered. Anorexigenic signals, particularly PYY, appear to further increase in hot environments than in those that are thermoneutral. Ghrelin and leptin may be involved in the observed increase in EI after exercise in the cold, in parallel with increased energy expenditure. The potential influence of ambient thermal environment on eating behaviors after an exercise session should not be neglected.

Over the last few years, a collaborative work between CERFACS, LNHE (EDF R&D), SCHAPI and CE-REMA resulted in the implementation of a Data Assimilation (DA) method on top of MASCARET in the framework of real-time forecasting. This prototype was based on a simplified Kalman filter where the description of the background error covariances is prescribed based on off-line climatology constant over time. This approach showed promising results on the Adour and Marne catchments as it improves the forecast skills of the hydraulic model using water level and discharge in-situ observations. An ensemble-based DA algorithm has recently been implemented to improve the modelling of the background error covariance matrix used to distribute the correction to the water level and discharge states when observations are assimilated from observation points to the entire state. It was demonstrated that the flow dependent description of the background error covariances with the EnKF algorithm leads to a more realistic correction of the hydraulic state with significant impact of the hydraulic network characteristics

The use of nutritional supplements among exercisers in gyms has been never investigated in the Middle East. The aim of the current study was to assess the prevalence intake of nutritional supplements and the potential influencing factors among people exercising in gyms in Beirut city. In this cross-sectional study, 512 exercisers, aged between 20 and 50 years, were randomly selected from gyms. The intake of nutritional supplements was reported among 36.3% (95% confidence interval 32.2–40.5) of participants, with a weak presence of medical supervision. Patterns of supplement use differed by gender and age. Men and younger exercisers were found to focus on supplements associated with performance enhancement and muscle building, while women and older exercisers were more concerned with health-promoting products such as vitamins, minerals, and herbal supplements. An appropriate dissemination of accurate and scientifically sound information regarding the benefits and side effects of nutritional supplements is highly recommended in the sports environment in Beirut city.