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Together, these findings reveal insight into the role of macrophages as indispensable mediators of lymphatic growth during the development of the mammalian cardiac vasculature.Microtubules (MTs) regulate numerous cellular processes, but their roles in brain morphogenesis are not well known. Here, we show that CAMSAP3, a non-centrosomal microtubule regulator, is important for shaping the lateral ventricles. In differentiating ependymal cells, CAMSAP3 became concentrated at the apical domains, serving to generate MT networks at these sites. Camsap3-mutated mice showed abnormally narrow lateral ventricles, in which excessive stenosis or fusion was induced, leading to a decrease of neural stem cells at the ventricular and subventricular zones. This defect was ascribed at least in part to a failure of neocortical ependymal cells to broaden their apical domain, a process necessary for expanding the ventricular cavities. mTORC1 was required for ependymal cell growth but its activity was downregulated in mutant cells. Lysosomes, which mediate mTORC1 activation, tended to be reduced at the apical regions of the mutant cells, along with disorganized apical MT networks at the corresponding sites. These findings suggest that CAMSAP3 supports mTORC1 signaling required for ependymal cell growth via MT network regulation, and, in turn, shaping of the lateral ventricles.Formation of a zygote is coupled with extensive epigenetic reprogramming to enable appropriate inheritance of histone methylation and prevent developmental delays. In Caenorhabditis elegans, this reprogramming is mediated by the H3K4me2 demethylase SPR-5 and the H3K9 methyltransferase, MET-2. In contrast, the H3K36 methyltransferase MES-4 maintains H3K36me2/3 at germline genes between generations to facilitate re-establishment of the germline. To determine whether the MES-4 germline inheritance pathway antagonizes spr-5; met-2 reprogramming, we examined the interaction between these two pathways. We found that the developmental delay of spr-5; met-2 mutant progeny is associated with ectopic H3K36me3 and the ectopic expression of MES-4-targeted germline genes in somatic tissues. Furthermore, the developmental delay is dependent upon MES-4 and the H3K4 methyltransferase, SET-2. We propose that MES-4 prevents crucial germline genes from being repressed by antagonizing maternal spr-5; met-2 reprogramming. Thus, the balance of inherited histone modifications is necessary to distinguish germline versus soma and prevent developmental delay.This article has an associated 'The people behind the papers' interview.Rab11 family-interacting protein 5 (Rab11fip5) is an adaptor protein that binds to the small GTPase Rab11, which has an important function in endosome recycling and trafficking of cellular proteins to the plasma membrane. Rab11fip5 is involved in many cellular processes, such as cytoskeleton rearrangement, iron uptake and exocytosis in neuroendocrine cells, and is also known as a candidate gene for autism-spectrum disorder. However, the role of Rab11fip5 during early embryonic development is not clearly understood. In this study, we identified Rab11fip5 as a protein that interacts with ephrinB1, a transmembrane ligand for Eph receptors. The PDZ binding motif in ephrinB1 and the Rab-binding domain in Rab11fip5 are necessary for their interaction in a complex. learn more EphrinB1 and Rab11fip5 display overlapping expression in the telencephalon of developing amphibian embryos. The loss of Rab11fip5 function causes a reduction in telencephalon size and a decrease in the expression level of ephrinB1. Moreover, morpholino oligonucleotide-mediated knockdown of Rab11fip5 decreases cell proliferation in the telencephalon. The overexpression of ephrinB1 rescues these defects, suggesting that ephrinB1 recycling by the Rab11/Rab11fip5 complex is crucial for proper telencephalon development.

Numerous studies have highlighted the burden of hypertension by estimating its prevalence. However, information regarding quantum and characteristics of persons whose blood pressure converts to hypertension range from their previous state of prehypertension or normal blood pressure is crucial for any public health programme. We aimed to estimate incidence rate of hypertension and to identify risk factors for the same, so that it is useful for programme implementation.

We established a cohort of adults residing in urban slums of Bhopal, who were registered in a baseline cardiovascular risk assessment survey, which was performed between November 2017 and March 2018. Blood pressure assessment was done at least three times at baseline for diagnosis of hypertension, which was defined as systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg on two occasions. Participants who did not have a diagnosis of hypertension were followed up during April-June 2019.

Of the 5673 participants assessed aem, driven by efforts of community health workers.

We found that incidence of hypertension in urban slums of central India is higher with increasing age and in men. Illiteracy, lower Wealth Index and prehypertension are other determinants. We also demonstrate feasibility of establishing a cohort within the public health delivery system, driven by efforts of community health workers.

Coronary microvascular dysfunction (CMD) is considered to cause angina pectoris in a large proportion of women with no obstructive coronary artery disease (CAD). However, data supporting a relation between angina pectoris and CMD are limited. We compared CMD in women with angina with asymptomatic women and evaluated the relation between presence of CMD, angina characteristics, cardiovascular risk factors and results of stress testing.

In a cross-sectional study, we included 1684 women with angina and <50% coronary artery stenosis on invasive angiography. Asymptomatic women from the community-based Copenhagen City Heart Study served as reference group (n=102). link2 Coronary microvascular function was determined by coronary flow velocity reserve (CFVR) assessed by transthoracic Doppler stress echocardiography. CFVR < 2 was defined as CMD. Symptoms were obtained from standardised angina questionnaires and results of stress testing from health records.

Median CFVR was 2.33 (IQR 2.00-2.75) in symptomatic wong and increased heart rate. Neither a positive bicycle test, single photon emission CT stress test nor chest pain characteristics identify women with impaired CFVR among women with angina and no obstructive CAD. Results may question the concept of microvascular angina as currently defined.

To validate a multivariable risk prediction model (Cohorts for Heart and Aging Research in Genomic Epidemiology model for atrial fibrillation (CHARGE-AF)) for 5-year risk of atrial fibrillation (AF) in routinely collected primary care data and to assess CHARGE-AF's potential for automated, low-cost selection of patients at high risk for AF based on routine primary care data.

We included patients aged ≥40 years, free of AF and with complete CHARGE-AF variables at baseline, 1 January 2014, in a representative, nationwide routine primary care database in the Netherlands (Nivel-PCD). We validated CHARGE-AF for 5-year observed AF incidence using the C-statistic for discrimination, and calibration plot and stratified Kaplan-Meier plot for calibration. We compared CHARGE-AF with other predictors and assessed implications of using different CHARGE-AF cut-offs to select high-risk patients.

Among 111 475 patients free of AF and with complete CHARGE-AF variables at baseline (17.2% of all patients aged ≥40 years anine Dutch primary care, CHARGE-AF accurately assessed AF risk among older primary care patients, outperformed both CHA

DS

-VASc and age alone as predictors for AF and showed potential for automated, low-cost patient selection in AF screening.

In patients with complete baseline CHARGE-AF data through routine Dutch primary care, CHARGE-AF accurately assessed AF risk among older primary care patients, outperformed both CHA2DS2-VASc and age alone as predictors for AF and showed potential for automated, low-cost patient selection in AF screening.

In patients with chronic coronary syndrome, percutaneous coronary intervention targets haemodynamically significant stenoses, that is, those thought to cause ischaemia. Intracoronary ECG (icECG) detects ischaemia directly where it occurs. Thus, the goal of this study was to test the accuracy of icECG during pharmacological inotropic stress to determine functional coronary lesion severity in comparison to the structural parameter of quantitative angiographic per cent diameter stenosis (%S), as well as to the haemodynamic indices of fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR).

The primary study endpoint of this prospective trial was the maximal change in icECG ST-segment shift during pharmacological inotropic stress induced by dobutamine plus atropine obtained within 1 min after reaching maximal heart rate(=220 - age). IcECG was acquired by attaching an alligator clamp to the angioplasty guidewire positioned downstream of the stenosis. For the pressure-derived stenosis severity ratemic icECG ST-segment shift detects structurally relevant coronary stenotic lesions with high sensitivity, while they are identified highly specific by FFR and iFR.Sport specialisation is becoming increasingly common among youth and adolescent athletes in the USA and many have raised concern about this trend. Although research on sport specialisation has grown significantly, numerous pressing questions remain pertaining to short-term and long-term effects of specialisation on the health and well-being of youth, including the increased risk of overuse injury and burnout. Many current elite athletes did not specialise at an early age. link3 Methodological and study design limitations impact the quality of current literature, and researchers need to prioritise pressing research questions to promote safe and healthy youth sport participation. The American Medical Society for Sports Medicine hosted a Youth Early Sport Specialization Summit in April 2019 with the goal of synthesising and reviewing current scientific knowledge and developing a research agenda to guide future research in the field based on the identified gaps in knowledge. This statement provides a broad summary of the existing literature, gaps and limitations in current evidence and identifies key research priorities to help guide researchers conducting research on youth sport specialisation. Our goals are to help improve the quality and relevance of research on youth sport specialisation and to ultimately assure that opportunities for healthy and safe sport participation continue for all youth.

Only international studies can provide the full variability of built environments and accurately estimate effect sizes of relations between contrasting environments and health-related outcomes. The aims of the International Physical Activity and Environment Study of Adolescents (IPEN Adolescent) are to estimate the strength, shape and generalisability of associations of the community environment (geographic information systems (GIS)-based and self-reported) with physical activity and sedentary behaviour (accelerometer-measured and self-reported) and weight status (normal/overweight/obese).

The IPEN Adolescent observational, cross-sectional, multicountry study involves recruiting adolescent participants (ages 11-19 years) and one parent/guardian from neighbourhoods selected to ensure wide variations in walkability and socioeconomic status using common protocols and measures. Fifteen geographically, economically and culturally diverse countries, from six continents, participated Australia, Bangladesh, Belgium, Brazil, Czech Republic, Denmark, Hong Kong SAR, India, Israel, Malaysia, New Zealand, Nigeria, Portugal, Spain and USA.