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Résumé Objectif - Il a été démontré que le polymorphisme rs5963409 du gène codant l’Or­nithine TransCarbamylase (OTC) est associé à l’hypertension et à la vasomotricité coronaire dans les populations caucasiennes. Sur la base de ces résultats, nous avons choisi d’étudier l’association de deux polymorphismes rs5963409, localisé au niveau de la région 5’ du promoteur et rs1800321, localisé au niveau de l’exon 2, du gène OTC avec le risque de survenue d’infarctus du myocarde (IDM) et les valeurs de pres­sions artérielles systolique et diastolique. Population étudiée et Méthodes - Cette étude a été réalisée dans la population de l’étude ECTOR (Etude Cas Témoins sur l’Infarctus du myocarde en ORanie). La popu­lation étudiée est composée de deux groupes : 68 cas ayant survécu à un Infarctus Du Myocarde (IDM) et 67 sujets témoins ne souffrant d’aucune maladie apparente. La caractérisation génétique des deux polymorphismes a été réalisée par la technique PCR (Polymerase Chain Reaction) suivie d’une digestion enzymatique. Résultats - Les polymorphismes rs5963409 et rs1800321 ne sont pas associés ni à l’IDM ni aux variations des valeurs de pressions artérielles systolique et diastolique. Cependant, nous avons observé une interaction significative entre le polymorphisme rs5963409 et l’Indice de Masse Corporelle (IMC) sur le risque de survenue d’IDM. Conclusion - Nos résultats indiquent queles deux polymorphismes du gène de l’OTC ne sont pas associés à l’IDM dans la population Ouest-Algérienne. Abstract Objective - The polymorphism rs5963409 of the gene coding for Ornithine Trans­Carbamylase (OTC) has been shown to be associated with hypertension and co­ronary vasomotricity in Caucasian populations. On the basis of these results, we chose to study the association of two polymorphisms rs5963409, located at the 5 ‘region of the promoter and rs1800321, located at exon 2, of the OTC gene with the risk of The occurrence of myocardial infarction (MI) and the systolic and diastolic blood pressure values. Patients and methods- the SNPs were characterised in a case control study (70 cases vs 68 controls) based on the male population originating from Oran, Alge­ria ECTOR study. Genetic characterization of both polymorphisms was carried out using the Polymerase Chain Reaction (PCR) technique followed by enzymatic digestion. Results -The rs5963409 and rs1800321 polymorphisms are not associated with MI or changes in systolic and diastolic blood pressure values. However, we observed a significant interaction between the polymorphism rs5963409 and the Body Mass Index (BMI) on the risk of the occurrence of MI. Conclusion: Our results indicate that both polymorphisms of the OTC gene are not associated with MI in the West-Algerian population.

Summary: Background: Research in healthy young adults shows that characteristic patterns of brain activity define individual “brain-fingerprints” that are unique to each person. However, variability in these brain-fingerprints increases in individuals with neurological conditions, challenging the clinical relevance and potential impact of the approach. Our study shows that brain-fingerprints derived from neurophysiological brain activity are associated with pathophysiological and clinical traits of individual patients with Parkinson’s disease (PD). Methods: We created brain-fingerprints from task-free brain activity recorded through magnetoencephalography in 79 PD patients and compared them with those from two independent samples of age-matched healthy controls (N = 424 total). We decomposed brain activity into arrhythmic and rhythmic components, defining distinct brain-fingerprints for each type from recording durations of up to 4 min and as short as 30 s. Findings: The arrhythmic spectral components of cortical activity in patients with Parkinson’s disease are more variable over short periods, challenging the definition of a reliable brain-fingerprint. However, by isolating the rhythmic components of cortical activity, we derived brain-fingerprints that distinguished between patients and healthy controls with about 90% accuracy. The most prominent cortical features of the resulting Parkinson’s brain-fingerprint are mapped to polyrhythmic activity in unimodal sensorimotor regions. Leveraging these features, we also demonstrate that Parkinson’s symptom laterality can be decoded directly from cortical neurophysiological activity. Furthermore, our study reveals that the cortical topography of the Parkinson’s brain-fingerprint aligns with that of neurotransmitter systems affected by the disease’s pathophysiology. Interpretation: The increased moment-to-moment variability of arrhythmic brain-fingerprints challenges patient differentiation and explains previously published results. We outline patient-specific rhythmic brain signaling features that provide insights into both the neurophysiological signature and symptom laterality of Parkinson’s disease. Thus, the proposed definition of a rhythmic brain-fingerprint of Parkinson’s disease may contribute to novel, refined approaches to patient stratification. Symmetrically, we discuss how rhythmic brain-fingerprints may contribute to the improved identification and testing of therapeutic neurostimulation targets. Funding: Data collection and sharing for this project was provided by the Quebec Parkinson Network (QPN), the Pre-symptomatic Evaluation of Novel or Experimental Treatments for Alzheimer’s Disease (PREVENT-AD; release 6.0) program, the Cambridge Centre for Aging Neuroscience (Cam-CAN), and the Open MEG Archives (OMEGA). The QPN is funded by a grant from Fonds de Recherche du Québec - Santé (FRQS). PREVENT-AD was launched in 2011 as a $13.5 million, 7-year public-private partnership using funds provided by McGill University, the FRQS, an unrestricted research grant from Pfizer Canada, the Levesque Foundation, the Douglas Hospital Research Centre and Foundation, the Government of Canada, and the Canada Fund for Innovation. The Brainstorm project is supported by funding to SB from the NIH (R01-EB026299-05). Further funding to SB for this study included a Discovery grant from the Natural Sciences and Engineering Research Council of Canada of Canada (436355-13), and the CIHR Canada research Chair in Neural Dynamics of Brain Systems (CRC-2017-00311).

BackgroundLittle is known about the effect of combined exposure to different air pollutants on mortality in dialysis patients. This study aimed to investigate the association of multiple exposures to air pollutants with all-cause and cause-specific death in dialysis patients.Materials and methodsThis registry-based nationwide cohort study included 90,373 adult kidney failure patients initiating maintenance dialysis between 2012 and 2020 identified from the French REIN registry. Estimated mean annual municipality levels of PM2.5, PM10, and NO2 between 2009 and 2020 were combined in different composite air pollution scores to estimate each participant’s exposure at the residential place one to 3 years before dialysis initiation. Adjusted cause-specific Cox proportional hazard models were used to estimate hazard ratios (HRs) per interquartile range (IQR) greater air pollution score. Effect measure modification was assessed for age, sex, dialysis care model, and baseline comorbidities.ResultsHigher levels of the main air pollution score were associated with a greater rate of all-cause deaths (HR, 1.082 [95% confidence interval (CI), 1.057–1.104] per IQR increase), regardless of the exposure lag. This association was also confirmed in cause-specific analyses, most markedly for infectious mortality (HR, 1.686 [95% CI, 1.470–1.933]). Sensitivity analyses with alternative composite air pollution scores showed consistent findings. Subgroup analyses revealed a significantly stronger association among women and fewer comorbid patients.DiscussionLong-term multiple air pollutant exposure is associated with all-cause and cause-specific mortality among patients receiving maintenance dialysis, suggesting that air pollution may be a significant contributor to the increasing trend of CKD-attributable mortality worldwide.

Abstract Background Long Intergenic noncoding RNA predicting CARdiac remodeling (LIPCAR) is a long noncoding RNA identified in plasma of patients after myocardial infarction (MI) to be associated with left ventricle remodeling (LVR). LIPCAR was also shown to be a predictor of early death in heart failure (HF) patients. However, no information regarding the expression of LIPCAR and its function in heart as well as the mechanisms involved in its transport to the circulation is known. The aims of this study are (1) to characterize the transporter of LIPCAR from heart to circulation; (2) to determine whether LIPCAR levels in plasma isolated-extracellular vesicles (EVs) reflect the alteration of its expression in total plasma and could be used as biomarkers of LVR post-MI. Methods Since expression of LIPCAR is restricted to human species and the limitation of availability of cardiac biopsy samples, serum-free conditioned culture media from HeLa cells were first used to characterize the extracellular transporter of LIPCAR before validation in EVs isolated from human cardiac biopsies (non-failing and ischemic HF patients) and plasma samples (patients who develop or not LVR post-MI). Differential centrifugation at 20,000g and 100,000g were performed to isolate the large (lEVs) and small EVs (sEVs), respectively. Western blot and nanoparticle tracking (NTA) analysis were used to characterize the isolated EVs. qRT-PCR analysis was used to quantify LIPCAR in all samples. Results We showed that LIPCAR is present in both lEVs and sEVs isolated from all samples. The levels of LIPCAR are higher in lEVs compared to sEVs isolated from HeLa conditioned culture media and cardiac biopsies. No difference of LIPCAR expression was observed in tissue or EVs isolated from cardiac biopsies obtained from ischemic HF patients compared to non-failing patients. Interestingly, LIPCAR levels were increased in lEVs and sEVs isolated from MI patients who develop LVR compared to patients who did not develop LVR. Conclusion Our data showed that large EVs are the main extracellular vesicle transporter of LIPCAR from heart into the circulation independently of the status, non-failing or HF, in patients. The levels of LIPCAR in EVs isolated from plasma could be used as biomarkers of LVR in post-MI patients.

Abstract Objective To describe the proportions of subjects exposed to crystalline silica and the sectors of activity concerned between 1965 and 2010 in a sample of the general French population. Methods We included 2942 participants aged 40 to 65 years, recruited at random from electoral rolls, from the French general population in the cross-sectional ELISABET study between 2011 and 2013. The proportions of subjects exposed to crystalline silica and their sectors of activity were determined on the basis of their career history and the use of the Matgéné job-exposure matrix. Results In the total sample, occupational exposure to crystalline silica was found for 291 subjects (9.9%) between 1965 and 2010, with a predominance of men (20.2% of exposed subjects among men (282 out of 1394) versus 0.6% among women (9 out of 1548)). The highest proportion of participants exposed to crystalline silica was reached in 1980 with 6.1% and then decreases to 4.4% in 2010. Among men, the most frequently exposed sectors of activity were manufacture of basic metals (41.5% of exposed men (117 out of 282)), specialised construction activities (23.1% of exposed men (65 out of 282)) and construction of buildings (14.2% of exposed men (40 out of 282)). Conclusions Although the proportion of workers exposed to crystalline silica has been decreasing since the 1980s, it is still significant at least until 2010, particularly in the construction sector, and further research is needed to improve the monitoring of workers who are or have been exposed to crystalline silica.

In structural mechanics, the design of component assemblies is fundamental for ensuring structural integrity and durability. Fatigue, a common failure mode, particularly challenges the validation of welded joints' fatigue resistance. Various analytical and numerical methods estimate fatigue life but often involve costly processes requiring extensive parameter adjustments and software integration. This study applies machine learning (ML) for metamodeling of a complete finite element analysis and fatigue analysis workflow for estimating the fatigue life of welded joints, considering geometric characteristics, loading conditions, and weld classes. The comparison of the effect of learning database configuration for several regression estimators has led to a reduced model that provides design rules. Our findings demonstrate the significant potential of ML to streamline complex frameworks and accurately estimate the fatigue life of welded joints, advancing AI's application in mechanical engineering.

Abstract Human-animal pathogenic transmissions threaten both human and animal health, and the processes catalyzing zoonotic spillover and spillback are complex. Prior field studies offer partial insight into these processes but overlook animal ecologies and human perceptions and practices facilitating human-animal contact. Conducted in Cameroon and a European zoo, this integrative study elucidates these processes, incorporating metagenomic, historical, anthropological and great ape ecological analyses, and real-time evaluation of human-great ape contact types and frequencies. We find more enteric eukaryotic virome sharing between Cameroonian humans and great apes than in the zoo, virome convergence between Cameroonian humans and gorillas, and adenovirus and enterovirus taxa as most frequently shared between Cameroonian humans and great apes. Together with physical contact from hunting, meat handling and fecal exposure, overlapping human cultivation and gorilla pillaging in forest gardens help explain these findings. Our multidisciplinary study identifies environmental co-use as a complementary mechanism for viral sharing.

After over three decades of unsuccessful attempts, we report the first detection of molecular gas emission in Malin 1, the largest spiral galaxy observed to date, and one of the most iconic giant low surface brightness galaxies. Using Atacama Large Millimeter/submillimeter Array, we detect significant ^12 CO ( J = 1–0) emission in the galaxy’s central region and tentatively identify CO emission across three regions on the disk. These observations allow for a better estimate of the H _2 mass and molecular gas mass surface density, both of which are remarkably low given the galaxy’s scale. By integrating data on its H i mass, we derive a very low molecular-to-atomic gas mass ratio. Overall, our results highlight the minimal presence of molecular gas in Malin 1, contrasting sharply with its extensive, homogeneous atomic gas reservoir. For the first time, we position Malin 1 on the Kennicutt–Schmidt diagram, where it falls below the main sequence for normal spirals, consistent with previous upper limits but now with more accurate figures. These findings are crucial for constraining our understanding of star formation processes in environments characterized by extremely low molecular gas densities and for refining models of galaxy formation, thereby improving predictions concerning the formation, evolution, and distribution of these giant, elusive galaxies.

Abstract Objective Eating behaviors play important roles in the development of obesity. A better knowledge of the psychological aspects of eating behaviors in individuals with and without obesity and their consequences on daily eating and lifestyle habits would be informative. The Three‐Factor Eating Questionnaire (TFEQ)‐R21 assesses the psychometrics of eating behavior. The objectives of the study were to establish which eating habits were or were not associated with TFEQ eating behaviors, and to quantify the extent to which those eating habits mediated the association between TFEQ eating behaviors and obesity risk. Methods Data were obtained from the Gene and Environment Case‐Control Obesity Study from northern France. It included 2237 individuals with obesity and 403 individuals without obesity. Eating behaviors were assessed according to the TFEQ‐R21. Two activity levels (physical activity and television watching) and six eating habits (e.g., plate size, having one serving or at least two servings of the main meal, …) were evaluated. Regression and mediation analyses were performed. Results Higher cognitive restraint, higher uncontrolled eating (UE) and higher emotional eating (EE) were associated with a higher risk of obesity, independently of each other and of age, sex, socio‐economic status and physical activity. Cognitive restraint was negatively associated with having at least two servings, while UE and EE were associated with several obesogenic habits such as eating in front of the television or eating at night. Each of these obesogenic habits mediated between 3% and 20% of the association between UE or EE and obesity. Conclusions Psychological eating behaviors were associated with several lifestyle and eating habits in both individuals with and without obesity. Moreover, some eating habits partially mediated (between 3% and 20%) the association between TFEQ eating behaviors and obesity risk. For clinicians, this study shows that simple, easy‐to‐ask questions on specific daily eating habits can provide essential information to better understand and manage patients with obesity.

Aortic distensibility is a risk factor for multiple cardiovascular events, but the genetic etiology is not well understood. Here, the authors identify genetic variants linked to aortic distensibility, highlighting mechanistic pathways and causal relationships between distensibility and both aortic aneurysms and brain small vessel disease.

The variations of oxygen abundance and ionization parameter in H ii regions are usually thought to be the dominant factors that produced variations seen in observed emission-line spectra. However, if and how these two quantities are physically related is hotly debated in the literature. Using emission line data of NGC 628 observed with SITELLE as part of the Star formation, Ionized Gas, and Nebular Abundances Legacy Survey (SIGNALS), we use a suite of photoionization models to constrain the abundance and ionization parameters for over 1500 H ii regions throughout its disk. We measure an anticorrelation between these two properties, consistent with expectations, although with considerable scatter. Secondary trends with dust extinction and star formation rate surface density potentially explain the large scatter observed. We raise concerns throughout regarding various modeling assumptions and their impact on the observed correlations presented in the literature.

Introduction: MicroRNAs are epigenetic regulatory factors capable of silencing the expression of target genes and might mediate the effects of air pollution on health. The objective of the present population-based study was to investigate the association between microRNA expression and long-term, residential exposure to atmospheric PM10 and NO2. Method: We included 998 non-smoking adult participants from the cross-sectional ELISABET survey (2010–2014) in the Lille urban area of France. The mean residential annual pollution levels were estimated with an atmospheric dispersion modelling system. Ten microRNAs were selected on the basis of the literature data, together with two housekeeping microRNAs (miR-93-5p and miR-191-5p) and were quantified with RT-qPCRs. Multivariate linear regression models were used to study the association between microRNAs and air pollution. The threshold for statistical significance (after correction for the FDR) was set to p

Summary: This study investigates the ability of high-throughput aptamer-based platform to identify circulating biomarkers able to predict occurrence of heart failure (HF), in blood samples collected during hospitalization of patients suffering from a first myocardial infarction (MI). REVE-1 (derivation) and REVE-2 (validation) cohorts included respectively 254 and 238 patients, followed up respectively 9 · 2 ± 4 · 8 and 7 · 6 ± 3 · 0 years. A blood sample collected during hospitalization was used for quantifying 4,668 proteins. Fifty proteins were significantly associated with long-term occurrence of HF with all-cause death as the competing event. k-means, an unsupervised clustering method, identified two groups of patients based on expression levels of the 50 proteins. Group 2 was significantly associated with a higher risk of HF in both cohorts. These results showed that a subset of 50 selected proteins quantified during hospitalization of MI patients is able to stratify and predict the long-term occurrence of HF.

Abstract Background Genetic variants within the APOE locus may modulate Alzheimer’s disease (AD) risk independently or in conjunction with APOE*2/3/4 genotypes. Identifying such variants and mechanisms would importantly advance our understanding of APOE pathophysiology and provide critical guidance for AD therapies aimed at APOE. The APOE locus however remains relatively poorly understood in AD, owing to multiple challenges that include its complex linkage structure and uncertainty in APOE*2/3/4 genotype quality. Here, we present a novel APOE*2/3/4 filtering approach and showcase its relevance on AD risk association analyses for the rs439401 variant, which is located 1801 base pairs downstream of APOE and has been associated with a potential regulatory effect on APOE. Methods We used thirty-two AD-related cohorts, with genetic data from various high-density single-nucleotide polymorphism microarrays, whole-genome sequencing, and whole-exome sequencing. Study participants were filtered to be ages 60 and older, non-Hispanic, of European ancestry, and diagnosed as cognitively normal or AD (n = 65,701). Primary analyses investigated AD risk in APOE*4/4 carriers. Additional supporting analyses were performed in APOE*3/4 and 3/3 strata. Outcomes were compared under two different APOE*2/3/4 filtering approaches. Results Using more conventional APOE*2/3/4 filtering criteria (approach 1), we showed that, when in-phase with APOE*4, rs439401 was variably associated with protective effects on AD case-control status. However, when applying a novel filter that increases the certainty of the APOE*2/3/4 genotypes by applying more stringent criteria for concordance between the provided APOE genotype and imputed APOE genotype (approach 2), we observed that all significant effects were lost. Conclusions We showed that careful consideration of APOE genotype and appropriate sample filtering were crucial to robustly interrogate the role of the APOE locus on AD risk. Our study presents a novel APOE filtering approach and provides important guidelines for research into the APOE locus, as well as for elucidating genetic interaction effects with APOE*2/3/4.

Abstract The Bridging Integrator 1 (BIN1) gene is a major susceptibility gene for Alzheimer’s disease (AD). Deciphering its pathophysiological role is challenging due to its numerous isoforms. Here we observed in Drosophila that human BIN1 isoform1 (BIN1iso1) overexpression, contrary to human BIN1 isoform8 (BIN1iso8) and human BIN1 isoform9 (BIN1iso9), induced an accumulation of endosomal vesicles and neurodegeneration. Systematic search for endosome regulators able to prevent BIN1iso1-induced neurodegeneration indicated that a defect at the early endosome level is responsible for the neurodegeneration. In human induced neurons (hiNs) and cerebral organoids, BIN1 knock-out resulted in the narrowing of early endosomes. This phenotype was rescued by BIN1iso1 but not BIN1iso9 expression. Finally, BIN1iso1 overexpression also led to an increase in the size of early endosomes and neurodegeneration in hiNs. Altogether, our data demonstrate that the AD susceptibility gene BIN1, and especially BIN1iso1, contributes to early-endosome size deregulation, which is an early pathophysiological hallmark of AD pathology.

Alzheimer’s disease (AD) is the most prevalent cause of dementia in the elderly, characterized by the presence of amyloid-beta (Aβ) plaques, neurofibrillary tangles, neuroinflammation, synapse loss and neurodegeneration in the brain. The amyloid cascade hypothesis postulates that deposition of Aβ peptides is the causative agent of AD pathology, but we still lack comprehensive understanding of the molecular mechanisms connecting Aβ peptides to neuronal dysfunctions in AD. In this work, we investigate the early effects of Aβ peptide accumulation on the functional properties and gene expression profiles of human-induced neurons (hiNs). We show that hiNs acutely exposed to low concentrations of both cell-secreted Aβ peptides or synthetic Aβ1–42 exhibit alterations in the frequency of calcium transients suggestive of increased neuronal excitability. Using single-cell RNA sequencing, we also show that cell-secreted Aβ up-regulates the expression of several synapse-related genes and down-regulates the expression of genes associated with metabolic stress mainly in glutamatergic neurons and, to a lesser degree, in GABAergic neurons and astrocytes. These neuronal alterations correlate with activation of the SEMA5, EPHA and NECTIN signaling pathways, which are important regulators of synaptic plasticity. Altogether, our findings indicate that slight elevations in Aβ concentrations are sufficient to elicit transcriptional changes in human neurons, which can contribute to early alterations in neural network activity.

Fibromuscular dysplasia is a cardiovascular disease affecting mostly women with a mostly unknown genetic basis. Here the authors have performed a genome-wide association meta-analysis of Fibromuscular dysplasia to identify genetic loci, some of which are shared with common cardiovascular disease and traits.

Known genetic loci account for only a fraction of the genetic contribution to Alzheimer’s disease. Here, the authors have performed a large genome-wide meta-analysis comprising 409,435 individuals to discover 6 new loci and demonstrate the efficacy of an Alzheimer’s disease polygenic risk score.

Abstract Post-translational modifications of cardiac proteins could participate to left contractile dysfunction resulting in heart failure. Using a rat model of ischemic heart failure, we showed an accumulation of phosphorylated desmin leading to toxic aggregates in cardiomyocytes, but the cellular mechanisms are unknown. The same rat model was used to decipher the kinases involved in desmin phosphorylation and the proteolytic systems present in rat and human failing hearts. We used primary cultures of neonate rat cardiomyocytes for testing specific inhibitors of kinases and for characterizing the autophagic processes able to clear desmin aggregates. We found a significant increase of active PKCζ, no modulation of ubitiquitin-proteasome system, a defect in macroautophagy, and an activation of chaperone-mediated autophagy in heart failure rats. We validated in vitro that PKCζ inhibition induced a significant decrease of GSK3β and of soluble desmin. In vitro activation of ubiquitination of proteins and of chaperone-mediated autophagy is able to decrease soluble and insoluble forms of desmin in cardiomyocytes. These data demonstrate a novel signaling pathway implicating activation of PKCζ in desmin phosphorylation associated with a defect of proteolytic systems in ischemic heart failure, leading to desmin aggrephagy. Our in vitro data demonstrated that ubiquitination of proteins and chaperone-mediated autophagy are required for eliminating desmin aggregates with the contribution of its chaperone protein, α-crystallin Β-chain. Modulation of the kinases involved under pathological conditions may help preserving desmin intermediate filaments structure and thus protect the structural integrity of contractile apparatus of cardiomyocytes by limiting desmin aggregates formation.

Abstract Background Fruit abscission depends on cell separation that occurs within specialized cell layers that constitute an abscission zone (AZ). To determine the mechanisms of fleshy fruit abscission of the monocot oil palm (Elaeis guineensis Jacq.) compared with other abscission systems, we performed multi-scale comparative transcriptome analyses on fruit targeting the developing primary AZ and adjacent tissues. Results Combining between-tissue developmental comparisons with exogenous ethylene treatments, and naturally occurring abscission in the field, RNAseq analysis revealed a robust core set of 168 genes with differentially regulated expression, spatially associated with the ripe fruit AZ, and temporally restricted to the abscission timing. The expression of a set of candidate genes was validated by qRT-PCR in the fruit AZ of a natural oil palm variant with blocked fruit abscission, which provides evidence for their functions during abscission. Our results substantiate the conservation of gene function between dicot dry fruit dehiscence and monocot fleshy fruit abscission. The study also revealed major metabolic transitions occur in the AZ during abscission, including key senescence marker genes and transcriptional regulators, in addition to genes involved in nutrient recycling and reallocation, alternative routes for energy supply and adaptation to oxidative stress. Conclusions The study provides the first reference transcriptome of a monocot fleshy fruit abscission zone and provides insight into the mechanisms underlying abscission by identifying key genes with functional roles and processes, including metabolic transitions, cell wall modifications, signalling, stress adaptations and transcriptional regulation, that occur during ripe fruit abscission of the monocot oil palm. The transcriptome data comprises an original reference and resource useful towards understanding the evolutionary basis of this fundamental plant process.

Abstract Background There are limited data on Coronavirus disease 2019 (COVID-19) in solid organ transplant patients, especially in heart transplant recipients, with only a few case reports and case series described so far. Heart transplant recipients may be at particular high risk due to their comorbidities and immunosuppressed state. Case presentation This report describes the clinical course and the challenging management of early COVID-19 infection in two heart transplant recipients who tested positive for the SARS-CoV-2 virus in the perioperative period of the transplant procedure. The two patients developed a severe form of the disease and ultimately died despite the initiation of an antiviral monotherapy with hydroxychloroquine coupled with the interruption of mycophenolate mofetil. Conclusions These two cases illustrate the severity and poor prognosis of COVID-19 in the perioperative period of a heart transplant. Thorough screening of donors and recipients is mandatory, and the issue of asymptomatic carriers needs to be addressed.

White matter hyperintensities (WMH) are a common brain-imaging feature of cerebral small vessel disease. Here, the authors carry out a GWAS and followup analyses for WMH-volume, implicating several variants with potential for risk stratification and drug targeting.

Cortex morphology varies with age, cognitive function, and in neurological and psychiatric diseases. Here the authors report 160 genome-wide significant associations with thickness, surface area and volume of the total cortex and 34 cortical regions from a GWAS meta-analysis in 22,824 adults.

Sepsis-induced myopathy is characterized by muscle fiber atrophy, mitochondrial dysfunction, and worsened outcomes. Whether whole-body energy deficit participates in the early alteration of skeletal muscle metabolism has never been investigated. Three groups were studied: “Sepsis” mice, fed ad libitum with a spontaneous decrease in caloric intake (n = 17), and “Sham” mice fed ad libitum (Sham fed (SF), n = 13) or subjected to pair-feeding (Sham pair fed (SPF), n = 12). Sepsis was induced by the intraperitoneal injection of cecal slurry in resuscitated C57BL6/J mice. The feeding of the SPF mice was restricted according to the food intake of the Sepsis mice. Energy balance was evaluated by indirect calorimetry over 24 h. The tibialis anterior cross-sectional area (TA CSA), mitochondrial function (high-resolution respirometry), and mitochondrial quality control pathways (RTqPCR and Western blot) were assessed 24 h after sepsis induction. The energy balance was positive in the SF group and negative in both the SPF and Sepsis groups. The TA CSA did not differ between the SF and SPF groups, but was reduced by 17% in the Sepsis group compared with the SPF group (p < 0.05). The complex-I-linked respiration in permeabilized soleus fibers was higher in the SPF group than the SF group (p < 0.05) and lower in the Sepsis group than the SPF group (p < 0.01). Pgc1α protein expression increased 3.9-fold in the SPF mice compared with the SF mice (p < 0.05) and remained unchanged in the Sepsis mice compared with the SPF mice; the Pgc1α mRNA expression decreased in the Sepsis compared with the SPF mice (p < 0.05). Thus, the sepsis-like energy deficit did not explain the early sepsis-induced muscle fiber atrophy and mitochondrial dysfunction, but led to specific metabolic adaptations not observed in sepsis.

Background Recurrence is common after an acute coronary syndrome (ACS). In order to better assess the prognosis for patients with ACS, we compared clinical profiles, treatments, and case fatality rates for incident vs. recurrent ACS. Methods We enrolled 1,459 men and women (age: 35–74) living in three geographical areas covered by French MONICA registries and who had been admitted to hospital for an ACS in 2015/2016. We recorded and compared the clinical characteristics and medical care for patients with an incident vs. a recurrent ACS. Results Overall, 431 (30%) had a recurrent ACS. Relative to patients with an incident ACS, patients with recurrence were older (pConclusion Compared with incident patients, recurrent cases were more likely to have co-morbidities and to have suboptimal treatments prior to hospital stay, reinforcing the need for secondary prevention.

Abstract Background Participation in randomized controlled trials (RCTs) may be quite demanding and could represent an important burden for patients. We aimed to explore this research burden (i.e., the psychological, physical, and financial burdens) experienced by patients through their participation in a RCT. Methods We conducted a systematic review of qualitative studies exploring adult patients’ experiences with RCT participation. We searched MEDLINE (PubMed), CINAHL, PSYCHINFO, and Embase (search date March 2018) for eligible reports. Qualitative data coding and indexing were assisted by NVivo. The quality of reports was assessed by using the Critical Appraisal Skills Program (CASP) tool. Results We included 45 qualitative studies that involved 1732 RCT participants. Important psychological burdens were identified at every stage of the trial process. Participants reported feeling anxiety and being afraid of “being a ‘guinea pig’” and described undergoing randomization and allocation to a placebo as particularly difficult resulting in disappointment, anger, and depression. Patients’ follow-up and trial closure were also responsible for a wide range of psychological, physical, and financial burdens. Furthermore, factors related to burdensome impacts and consequences were discerned. These factors involved trial information, poorly organized and too-demanding follow-up, and lack of appropriate management when the patient’s participation ended. Trial participation was also associated with beneficial effects such as the satisfaction of feeling “useful,” gaining “a sense of control,” and receiving special attention. Conclusions Our finding provides a detailed description of research burden across the whole RCT process. Many of the burdens described could be anticipated, and some avoided in a movement toward minimally disruptive clinical research. Such an approach could improve trial recruitment and retention. Review registration PROSPERO CRD42018098994

Christina M. Lill, who contributed to analysis of data, was inadvertently omitted from the author list in the originally published version of this article. This has now been corrected in both the PDF and HTML versions of the article.

It has long been recognised that the role of soils is critical to the understanding of the way catchments store and release water. This study aimed to gain an understanding of the hydropedological characteristics and flow dynamics of the soils of three mountain catchment areas. Digital soil maps of the hydropedological characteristics of the catchments were interpreted and a conceptual response of these watersheds to precipitation was formed. This conceptual response was then tested with the use of site-specific precipitation and streamflow data. Furthermore, piezometers were installed in soils classified as the interflow hydropedological soil group as well as the saturated responsive hydropedological soil group and water table depth data for the three catchments were analysed. Climatic data indicated that there is a lag time effect in the quantity of precipitation that falls in the catchment and the corresponding rise in streamflow value. This lag time effect coupled with data obtained from the piezometers show that the various hydropedological soil groups play a pivotal role in the flow dynamics. Of importance is the unique influence of different wetland systems on the streamflow dynamics of the catchments. The drying and wetting cycles of individual wetland systems influenced both the baseflow connectivity and the overland flow during wetter periods. They are the key focus in understanding the connectivity between the hydropedological flow paths and the contribution of soil water to the stream networks of the three catchments.

Abstract Objective To assess the feasibility of delivering extracorporeal cardiopulmonary resuscitation (ECPR) in refractory out‐of‐hospital cardiac arrests (OHCA) by low volume extracorporeal membrane oxygenation (ECMO) centers and to explore pre‐ECPR predictors of survival. Methods Between 2016 and 2020, we studied 21 ECPR patients admitted in 2 tertiary ECMO centers in Liège, Belgium. Our ECPR protocol was based on 6 prehospital criteria (no flow 15 mmHg, age

Lysine acetylation is a highly conserved mechanism that affects several biological processes such as cell growth, metabolism, enzymatic activity, subcellular localization of proteins, gene transcription or chromatin structure. This post-translational modification, mainly regulated by lysine acetyltransferase (KAT) and lysine deacetylase (KDAC) enzymes, can occur on histone or non-histone proteins. Several studies have demonstrated that dysregulated acetylation is involved in cardiac dysfunction, associated with metabolic disorder or heart failure. Since the prevalence of obesity, type 2 diabetes or heart failure rises and represents a major cause of cardiovascular morbidity and mortality worldwide, cardiac acetylation may constitute a crucial pathway that could contribute to disease development. In this review, we summarize the mechanisms involved in the regulation of cardiac acetylation and its roles in physiological conditions. In addition, we highlight the effects of cardiac acetylation in physiopathology, with a focus on obesity, type 2 diabetes and heart failure. This review sheds light on the major role of acetylation in cardiovascular diseases and emphasizes KATs and KDACs as potential therapeutic targets for heart failure.

Background: Cardiac disease is an important life-threatening complication during pregnancy. It is frequently seen in pregnant women living in resource-limited areas and often results in premature death. Aim: The aim of this hospital-based longitudinal study was to identify factors related to adverse maternal and neonatal outcomes in pregnant women with cardiac disease in low-resource settings. Methods: The study enrolled 91 pregnant women with congenital or acquired cardiac disease over a period of 2 years in Kenya. Results: Maternal and early neonatal deaths occurred in 12.2% and 12.6% of cases, respectively. The risk of adverse outcomes was significantly increased in those with pulmonary oedema (OR 11, 95% CI [2.3–52]; p=0.002) and arrhythmias (OR 16.9, 95% CI [2.5–113]; p=0.004). Limited access to care was significantly associated with adverse maternal outcomes (p≤0.001). Conclusion: Many factors contribute to adverse maternal and neonatal outcomes in pregnant women with cardiac disease. Access to comprehensive specialised care may help reduce cardiac-related complications during pregnancy.

Heart failure, mostly associated with cardiac hypertrophy, is a major cause of illness and death. Oxidative stress causes accumulation of reactive oxygen species (ROS), leading to mitochondrial dysfunction, suggesting that mitochondria-targeted therapies could be effective in this context. The purpose of this work was to determine whether mitochondria-targeted therapies could improve cardiac hypertrophy induced by mitochondrial ROS. We used neonatal (NCMs) and adult (ACMs) rat cardiomyocytes hypertrophied by isoproterenol (Iso) to induce mitochondrial ROS. A decreased interaction between sirtuin 3 and superoxide dismutase 2 (SOD2) induced SOD2 acetylation on lysine 68 and inactivation, leading to mitochondrial oxidative stress and dysfunction and hypertrophy after 24 h of Iso treatment. To counteract these mechanisms, we evaluated the impact of the mitochondria-targeted antioxidant mitoquinone (MitoQ). MitoQ decreased mitochondrial ROS and hypertrophy in Iso-treated NCMs and ACMs but altered mitochondrial structure and function by decreasing mitochondrial respiration and mitophagy. The same decrease in mitophagy was found in human cardiomyocytes but not in fibroblasts, suggesting a cardiomyocyte-specific deleterious effect of MitoQ. Our data showed the importance of mitochondrial oxidative stress in the development of cardiomyocyte hypertrophy. We observed that targeting mitochondria by MitoQ in cardiomyocytes impaired the metabolism through defective mitophagy, leading to accumulation of deficient mitochondria.

Introduction: Air pollution impacts health by increasing mortality and the incidence of acute events in unhealthy individuals. In contrast, the acute effects of pollution in healthy individuals are less obvious. The present study was designed to evaluate the associations between short-term exposure to air pollution on one hand and lung function, and inflammatory markers on the other in middle-aged, non-smoking adults with no respiratory disease, in two urban areas in northern France. Methods: A sample of 1506 non-smoking adults (aged from 40 to 65) with no respiratory disease was selected from the participants in the 2011–2013 cross-sectional Enquête Littoral Souffle Air Biologie Environnement (ELISABET) survey in two urban areas in the northern France. We evaluated the associations between (i) mean levels of particulate matter with aerodynamic diameter

Carotid intima-media thickness (cIMT) and plaque are associated with subclinical atherosclerosis and coronary heart disease (CHD). Here, the authors identify and prioritize genetic loci for cIMT and plaque by GWAS and colocalization approaches and further demonstrate genetic correlation with CHD and stroke.

Abstract Background Progressive supranuclear palsy (PSP) is a rare neurodegenerative disease for which the genetic contribution is incompletely understood. Methods We conducted a joint analysis of 5,523,934 imputed SNPs in two newly-genotyped progressive supranuclear palsy cohorts, primarily derived from two clinical trials (Allon davunetide and NNIPPS riluzole trials in PSP) and a previously published genome-wide association study (GWAS), in total comprising 1646 cases and 10,662 controls of European ancestry. Results We identified 5 associated loci at a genome-wide significance threshold P

Cognitive function is associated with health and important life outcomes. Here, the authors perform a genome-wide association study for general cognitive function in 300,486 individuals and identify genetic loci that implicate neural and cell developmental pathways in this trait.

Abstract Although several risk factors such as infarct size have been identified, the progression of heart failure (HF) remains difficult to predict in clinical practice. Using an experimental rat model of post-myocardial infarction (MI), we previously identified 45 proteins differentially modulated during HF by proteomic analysis. This study sought to identify microRNAs (miRNAs) able to regulate these proteins and to test their relevance as biomarkers for HF. In silico bioinformatical analysis selected 13 miRNAs related to the 45 proteins previously identified. These miRNAs were analyzed in the rat and in cohorts of patients phenotyped for left ventricular remodeling (LVR). We identified that 3 miRNAs, miR-21-5p, miR-23a-3p and miR-222-3p, and their target Mn superoxide dismutase (SOD2) were significantly increased in LV and plasma of HF-rats. We found by luciferase activity a direct interaction of miR-222-3p with 3′UTR of SOD2. Transfection of human cardiomyocytes with miR-222-3p mimic or inhibitor induced respectively a decrease and an increase of SOD2 expression. Circulating levels of the 3 miRNAs and their target SOD2 were associated with high LVR post-MI in REVE-2 patients. We demonstrated for the first time the potential of microRNAs regulating SOD2 as new circulating biomarkers of HF.

Domestication and human selection have formed diverse goat breeds with characteristic phenotypes. This process correlated with the fixation of causative genetic variants controlling breed-specific traits within regions of reduced genetic diversity, so called selection signatures or selective sweeps. Using whole genome sequencing of DNA pools (pool-seq) from 20 genetically diverse modern goat breeds and bezoars, we identified 2,239 putative selection signatures. In two Pakistani goat breeds, Pak Angora and Barbari, we found selection signatures in a region harboring KIT, a gene involved in melanoblast development, migration, and survival. The search for candidate causative variants responsible for these selective sweeps revealed two different copy number variants (CNVs) downstream of KIT that were exclusively present in white Pak Angora and white-spotted Barbari goats. Several Swiss goat breeds selected for specific coat colors showed selection signatures at the ASIP locus encoding the agouti signaling protein. Analysis of these selective sweeps revealed four different CNVs associated with the white or tan (AWt), Swiss markings (Asm), badgerface (Ab), and the newly proposed peacock (Apc) allele. RNA-seq analyses on skin samples from goats with the different CNV alleles suggest that the identified structural variants lead to an altered expression of ASIP between eumelanistic and pheomelanistic body areas. Our study yields novel insights into the genetic control of pigmentation by identifying six functionally relevant CNVs. It illustrates how structural changes of the genome have contributed to phenotypic evolution in domestic goats.

Summary: Background: To help adapt cardiovascular disease risk prediction approaches to low-income and middle-income countries, WHO has convened an effort to develop, evaluate, and illustrate revised risk models. Here, we report the derivation, validation, and illustration of the revised WHO cardiovascular disease risk prediction charts that have been adapted to the circumstances of 21 global regions. Methods: In this model revision initiative, we derived 10-year risk prediction models for fatal and non-fatal cardiovascular disease (ie, myocardial infarction and stroke) using individual participant data from the Emerging Risk Factors Collaboration. Models included information on age, smoking status, systolic blood pressure, history of diabetes, and total cholesterol. For derivation, we included participants aged 40–80 years without a known baseline history of cardiovascular disease, who were followed up until the first myocardial infarction, fatal coronary heart disease, or stroke event. We recalibrated models using age-specific and sex-specific incidences and risk factor values available from 21 global regions. For external validation, we analysed individual participant data from studies distinct from those used in model derivation. We illustrated models by analysing data on a further 123 743 individuals from surveys in 79 countries collected with the WHO STEPwise Approach to Surveillance. Findings: Our risk model derivation involved 376 177 individuals from 85 cohorts, and 19 333 incident cardiovascular events recorded during 10 years of follow-up. The derived risk prediction models discriminated well in external validation cohorts (19 cohorts, 1 096 061 individuals, 25 950 cardiovascular disease events), with Harrell's C indices ranging from 0·685 (95% CI 0·629–0·741) to 0·833 (0·783–0·882). For a given risk factor profile, we found substantial variation across global regions in the estimated 10-year predicted risk. For example, estimated cardiovascular disease risk for a 60-year-old male smoker without diabetes and with systolic blood pressure of 140 mm Hg and total cholesterol of 5 mmol/L ranged from 11% in Andean Latin America to 30% in central Asia. When applied to data from 79 countries (mostly low-income and middle-income countries), the proportion of individuals aged 40–64 years estimated to be at greater than 20% risk ranged from less than 1% in Uganda to more than 16% in Egypt. Interpretation: We have derived, calibrated, and validated new WHO risk prediction models to estimate cardiovascular disease risk in 21 Global Burden of Disease regions. The widespread use of these models could enhance the accuracy, practicability, and sustainability of efforts to reduce the burden of cardiovascular disease worldwide. Funding: World Health Organization, British Heart Foundation (BHF), BHF Cambridge Centre for Research Excellence, UK Medical Research Council, and National Institute for Health Research.

The hippocampus in mammalian brain varies in size across individuals. Here, Hibar and colleagues perform a genome-wide association meta-analysis to find six genetic loci with significant association to hippocampus volume.

Although several ADAMs (A disintegrin-like and metalloproteases) have been shown to contribute to the amyloid precursor protein (APP) metabolism, the full spectrum of metalloproteases involved in this metabolism remains to be established. Transcriptomic analyses centred on metalloprotease genes unraveled a 50% decrease in ADAM30 expression that inversely correlates with amyloid load in Alzheimer's disease brains. Accordingly, in vitro down- or up-regulation of ADAM30 expression triggered an increase/decrease in Aβ peptides levels whereas expression of a biologically inactive ADAM30 (ADAM30mut) did not affect Aβ secretion. Proteomics/cell-based experiments showed that ADAM30-dependent regulation of APP metabolism required both cathepsin D (CTSD) activation and APP sorting to lysosomes. Accordingly, in Alzheimer-like transgenic mice, neuronal ADAM30 over-expression lowered Aβ42 secretion in neuron primary cultures, soluble Aβ42 and amyloid plaque load levels in the brain and concomitantly enhanced CTSD activity and finally rescued long term potentiation alterations. Our data thus indicate that lowering ADAM30 expression may favor Aβ production, thereby contributing to Alzheimer's disease development.

Late onset Alzheimer's disease is the most common form of dementia for which about 30 susceptibility loci have been reported. The aim of the current study is to identify novel genes associated with Alzheimer's disease using the largest up-to-date reference single nucleotide polymorphism (SNP) panel, the most accurate imputation software and a novel gene-based analysis approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 million genotypes from 17,008 Alzheimer's cases and 37,154 controls. In addition to earlier reported genes, we detected three novel gene-wide significant loci PPARGC1A (p = 2.2 × 10-6), RORA (p = 7.4 × 10-7) and ZNF423 (p = 2.1 × 10-6). PPARGC1A and RORA are involved in circadian rhythm; circadian disturbances are one of the earliest symptoms of Alzheimer's disease. PPARGC1A is additionally linked to energy metabolism and the generation of amyloid beta plaques. RORA is involved in a variety of functions apart from circadian rhythm, such as cholesterol metabolism and inflammation. The ZNF423 gene resides in an Alzheimer's disease-specific protein network and is likely involved with centrosomes and DNA damage repair.

Emerging infectious diseases of zoonotic origin constitute a recurrent threat to global health. Nonhuman primates (NHPs) occupy an important place in zoonotic spillovers (pathogenic transmissions from animals to humans), serving as reservoirs or amplifiers of multiple neglected tropical diseases, including viral hemorrhagic fevers and arboviruses, parasites and bacteria, as well as retroviruses (simian foamy virus, PTLV) that are pathogenic in human beings. Hunting and butchering studies in Africa characterize at-risk human social groups, but overlook critical factors of contact heterogeneity and frequency, NHP species differences, and meat processing practices. In southeastern Cameroon, a region with a history of zoonotic emergence and high risk of future spillovers, we conducted a novel mixed-method field study of human physical exposure to multiple NHP species, incorporating participant-based and ecological methodologies, and qualitative interviews (n = 25). We find frequent physical contact across adult human populations, greater physical contact with monkeys than apes, especially for meat handling practices, and positive correlation of human exposure with NHP species abundance and proximity to human settlement. These fine-grained results encourage reconsideration of the likely dynamics of human-NHP contact in past and future NTD emergence events. Multidisciplinary social science and ecological approaches should be mobilized to generate more effective human and animal surveillance and risk communications around neglected tropical diseases. At a moment when the WHO has included "Disease X", a presumably zoonotic pathogen with pandemic potential, on its list of blueprint priority diseases as, new field-based tools for investigating zoonotic disease emergence, both known and unknown, are of critical importance.

Background and purposePolymorphisms in coagulation genes have been associated with early-onset ischemic stroke. Here we pursue an a priori hypothesis that genetic variation in the endothelial-based receptors of the thrombomodulin-protein C system (THBD and PROCR) may similarly be associated with early-onset ischemic stroke. We explored this hypothesis utilizing a multi-stage design of discovery and replication.MethodsDiscovery was performed in the Genetics-of-Early-Onset Stroke (GEOS) Study, a biracial population-based case-control study of ischemic stroke among men and women aged 15-49 including 829 cases of first ischemic stroke (42.2% African-American) and 850 age-comparable stroke-free controls (38.1% African-American). Twenty-four single-nucleotide-polymorphisms (SNPs) in THBD and 22 SNPs in PROCR were evaluated. Following LD pruning (r2≥0.8), we advanced uncorrelated SNPs forward for association analyses. Associated SNPs were evaluated for replication in an early-onset ischemic stroke population (onset-ageResultsAmong GEOS Caucasians, PROCR rs9574, which was in strong LD with 8 other SNPs, and one additional independent SNP rs2069951, were significantly associated with ischemic stroke (rs9574, OR = 1.33, p = 0.003; rs2069951, OR = 1.80, p = 0.006) using an additive-model adjusting for age, gender and population-structure. Adjusting for risk factors did not change the associations; however, associations were strengthened among those without risk factors. PROCR rs9574 also associated with early-onset ischemic stroke in the replication sample (OR = 1.08, p = 0.015), but not older-onset stroke. There were no PROCR associations in African-Americans, nor were there any THBD associations in either ethnicity.ConclusionPROCR polymorphisms are associated with early-onset ischemic stroke in Caucasians.

BackgroundThe aim of this study was to investigate whether the association between baseline cardiovascular health (CVH) and incident cardiovascular disease differs according to coronary heart disease (CHD) and stroke subtypes, and to assess the mediating effect of inflammatory and hemostatic blood biomarkers. Methods and ResultsThe association of ideal CVH with outcomes was derived in 9312 middle‐aged men from Northern Ireland and France (whole cohort) in multivariable Cox proportional hazards regression analysis. The mediating effect of baseline inflammatory and hemostatic blood biomarkers was evaluated in a case–control study nested within the cohort after 10 years of follow‐up. After a median follow‐up of 10 years, 614 first CHD events and 117 first stroke events were adjudicated. Compared with those with poor CVH, those with an ideal CVH profile at baseline had a 72% lower risk of CHD (hazard ratio=0.28; 95% confidence interval, 0.17; 0.46) and a 76% lower risk of stroke (hazard ratio =0.24; 95% confidence interval, 0.06; 0.98). The magnitude of the risk reductions was similar for incident angina and myocardial infarction, but was lower for ischemic stroke. In the controls, the mean concentrations of high‐sensitivity C‐reactive protein, IL‐6, and fibrinogen decreased with higher CVH status. Furthermore, the association of behavioral CVH with incident CHD was partly mediated by high‐sensitivity C‐reactive protein (16.69%), IL‐6 (8.52%), and fibrinogen (7.30%) ConclusionsOur study shows no clear heterogeneity in the association of baseline CVH with the main subtypes of cardiovascular disease. This supports a universal promotion of ideal CVH for all cardiovascular disease subtypes. Furthermore, our mediation analysis suggests that the lower risk of CHD associated with ideal CVH is partly mediated by lower inflammatory and hemostatic blood biomarkers.

Objective - The polymorphism rs5963409 of the gene coding for Ornithine Trans- Carbamylase (OTC) has been shown to be associated with hypertension and coronary vasomotricity in Caucasian populations. On the basis of these results, we chose to study the association of two polymorphisms rs5963409, located at the 5 ‘region of the promoter and rs1800321, located at exon 2, of the OTC gene with the risk of The occurrence of myocardial infarction (MI) and the systolic and diastolic blood pressure values. Patients and methods- the SNPs were characterised in a case control study (70 cases vs 68 controls) based on the male population originating from Oran, Algeria ECTOR study. Genetic characterization of both polymorphisms was carried out using the Polymerase Chain Reaction (PCR) technique followed by enzymatic digestion. Results -The rs5963409 and rs1800321 polymorphisms are not associated with MI or changes in systolic and diastolic blood pressure values. However, we observed a significant interaction between the polymorphism rs5963409 and the Body Mass Index (BMI) on the risk of the occurrence of MI. Conclusion: Our results indicate that both polymorphisms of the OTC gene are not associated with MI in the West-Algerian population.

Background . The indigenous Nenets reindeer herders in northern Russia annually migrate several hundred kilometers between summer and winter pastures. In the warming climate, ice-rich permafrost and glaciers are being significantly reduced and will eventually disappear from parts of the Arctic. The emergent changes in hydrological cycles have already led to substantial increases in open water that stays unfrozen for longer periods of time. This environmental change has been reported to compromise the nomadic Nenets’ traditional way of life because the presence of new water in the tundra reduces the Nenets’ ability to travel by foot, sled, or motor vehicle from the summer transitory tundra campsites in order to access healthcare centers in villages. New water can also impede their access to family and community at other herder camps and in the villages. Although regional and global models predicting hydrologic changes due to climate changes exist, the spatial resolution of these models is too coarse for studying how increases in open water affect health and livelihoods. To anticipate the full health impact of hydrologic changes, the current gap between globally forecasted scenarios and locally forecasted hydrologic scenarios needs to be bridged. Objectives . We studied the effects of the autumn temperature anomalies and increases in open water on health care access and transmigration of reindeer herders on the Kanin Peninsula. Design . Correlational and time series analyses were completed. Methods . The study population consisted of 370 full-time, nomadic reindeer herders. We utilized clinical visit records, studied surface temperature anomalies during autumn migrations, and used remotely sensed imagery to detect water bodies. Spearman correlation was used to measure the relationship between temperature anomalies and the annual arrival of the herders at the Nes clinic for preventive and primary care. Piecewise regression was used to model change in mean autumnal temperature anomalies over time. We also created a water body product to detect inter-annual changes in water area. Results . Correlation between arrivals to the Nes clinic and temperature anomalies during the fall transmigration (1979–2011) was r = 0.64, p = 0.0004; 95% CI (0.31; 0.82). Regression analysis estimated that mean temperature anomalies during the fall migration in September–December were stochastically stationary pre-1991 and have been rising significantly (p

A new C47 polyoxygenated acetylenic acid, nepheliosyne B (2), along with the previously described nepheliosyne A (1), have been isolated from the New Caledonian marine sponge Niphates sp. Their structures have been elucidated on the basis of extensive spectroscopic analyses. These metabolites exhibited a moderate cytotoxicity against K562, U266, SKM1, and Kasumi cancer cell lines.