Recent acquisition of Helicobacter pylori by Baka Pygmies

Both anatomically modern humans and the gastric pathogen Helicobacter pylori originated in Africa, and both species have been associated for at least 100,000 years. Seven geographically distinct H. pylori populations exist, three of which are indigenous to Africa: hpAfrica1, hpAfrica2, and hpNEAfrica. The oldest and most divergent population, hpAfrica2, evolved within San hunter-gatherers, who represent one of the deepest branches of the human population tree. Anticipating the presence of ancient H. pylori lineages within all hunter-gatherer populations, we investigated the prevalence and population structure of H. pylori within Baka Pygmies in Cameroon. Gastric biopsies were obtained by esophagogastroduodenoscopy from 77 Baka from two geographically separated populations, and from 101 non-Baka individuals from neighboring agriculturalist populations, and subsequently cultured for H. pylori. Unexpectedly, Baka Pygmies showed a significantly lower H. pylori infection rate (20.8%) than non-Baka (80.2%). We generated multilocus haplotypes for each H. pylori isolate by DNA sequencing, but were not able to identify Baka-specific lineages, and most isolates in our sample were assigned to hpNEAfrica or hpAfrica1. The population hpNEAfrica, a marker for the expansion of the Nilo-Saharan language family, was divided into East African and Central West African subpopulations. Similarly, a new hpAfrica1 subpopulation, identified mainly among Cameroonians, supports eastern and western expansions of Bantu languages. An age-structured transmission model shows that the low H. pylori prevalence among Baka Pygmies is achievable within the timeframe of a few hundred years and suggests that demographic factors such as small population size and unusually low life expectancy can lead to the eradication of H. pylori from individual human populations. The Baka were thus either H. pylori-free or lost their ancient lineages during past demographic fluctuations. Using coalescent simulations and phylogenetic inference, we show that Baka almost certainly acquired their extant H. pylori through secondary contact with their agriculturalist neighbors

Vascular CXCR4 Limits Atherosclerosis by Maintaining Arterial Integrity Evidence From Mouse and Human Studies

BACKGROUND: The CXCL12/CXCR4 chemokine ligand/receptor axis controls (progenitor) cell homeostasis and trafficking. So far, an atheroprotective role of CXCL12/CXCR4 has only been implied through pharmacological intervention, in particular, because the somatic deletion of the CXCR4 gene in mice is embryonically lethal. Moreover, cell-specific effects of CXCR4 in the arterial wall and underlying mechanisms remain elusive, prompting us to investigate the relevance of CXCR4 in vascular cell types for atheroprotection. METHODS: We examined the role of vascular CXCR4 in atherosclerosis and plaque composition by inducing an endothelial cell (BmxCreERT2-driven)-specific or smooth muscle cell (SMC, SmmhcCreERT2-or TaglnCre-driven)-specific deficiency of CXCR4 in an apolipoprotein E-deficient mouse model. To identify underlying mechanisms for effects of CXCR4, we studied endothelial permeability, intravital leukocyte adhesion, involvement of the Akt/WNT/beta-catenin signaling pathway and relevant phosphatases in VE-cadherin expression and function, vascular tone in aortic rings, cholesterol efflux from macrophages, and expression of SMC phenotypic markers. Finally, we analyzed associations of common genetic variants at the CXCR4 locus with the risk for coronary heart disease, along with CXCR4 transcript expression in human atherosclerotic plaques. RESULTS: The cell-specific deletion of CXCR4 in arterial endothelial cells (n=1215) or SMCs (n=13-24) markedly increased atherosclerotic lesion formation in hyperlipidemic mice. Endothelial barrier function was promoted by CXCL12/\CXCR4, which triggered Akt/WNT/beta-catenin signaling to drive VE-cadherin expression and stabilized junctional VE-cadherin complexes through associated phosphatases. Conversely, endothelial CXCR4 deficiency caused arterial leakage and inflammatory leukocyte recruitment during atherogenesis. In arterial SMCs, CXCR4 sustained normal vascular reactivity and contractile responses, whereas CXCR4 deficiency favored a synthetic phenotype, the occurrence of macrophage-like SMCs in the lesions, and impaired cholesterol efflux. Regression analyses in humans (n=259 796) identified the C-allele at rs2322864 within the CXCR4 locus to be associated with increased risk for coronary heart disease. In line, C/C risk genotype carriers showed reduced CXCR4 expression in carotid artery plaques (n=188), which was furthermore associated with symptomatic disease. CONCLUSIONS: Our data clearly establish that vascular CXCR4 limits atherosclerosis by maintaining arterial integrity, preserving endothelial barrier function, and a normal contractile SMC phenotype. Enhancing these beneficial functions of arterial CXCR4 by selective modulators might open novel therapeutic options in atherosclerosis

The scientific payload of the Ultraviolet Transient Astronomy Satellite (ULTRASAT)

The Ultraviolet Transient Astronomy Satellite (ULTRASAT) is a space-borne near UV telescope with an unprecedented large field of view (200 sq. deg.). The mission, led by the Weizmann Institute of Science and the Israel Space Agency in collaboration with DESY (Helmholtz association, Germany) and NASA (USA), is fully funded and expected to be launched to a geostationary transfer orbit in Q2/3 of 2025. With a grasp 300 times larger than GALEX, the most sensitive UV satellite to date, ULTRASAT will revolutionize our understanding of the hot transient universe, as well as of flaring galactic sources. We describe the mission payload, the optical design and the choice of materials allowing us to achieve a point spread function of ~10arcsec across the FoV, and the detector assembly. We detail the mitigation techniques implemented to suppress out-of-band flux and reduce stray light, detector properties including measured quantum efficiency of scout (prototype) detectors, and expected performance (limiting magnitude) for various objects.Comment: Presented in the SPIE Astronomical Telescopes + Instrumentation 202

The Human Phenotype Ontology in 2024: phenotypes around the world.

The Human Phenotype Ontology (HPO) is a widely used resource that comprehensively organizes and defines the phenotypic features of human disease, enabling computational inference and supporting genomic and phenotypic analyses through semantic similarity and machine learning algorithms. The HPO has widespread applications in clinical diagnostics and translational research, including genomic diagnostics, gene-disease discovery, and cohort analytics. In recent years, groups around the world have developed translations of the HPO from English to other languages, and the HPO browser has been internationalized, allowing users to view HPO term labels and in many cases synonyms and definitions in ten languages in addition to English. Since our last report, a total of 2239 new HPO terms and 49235 new HPO annotations were developed, many in collaboration with external groups in the fields of psychiatry, arthrogryposis, immunology and cardiology. The Medical Action Ontology (MAxO) is a new effort to model treatments and other measures taken for clinical management. Finally, the HPO consortium is contributing to efforts to integrate the HPO and the GA4GH Phenopacket Schema into electronic health records (EHRs) with the goal of more standardized and computable integration of rare disease data in EHRs

Post-Operative Functional Outcomes in Early Age Onset Rectal Cancer

Background: Impairment of bowel, urogenital and fertility-related function in patients treated for rectal cancer is common. While the rate of rectal cancer in the young (<50 years) is rising, there is little data on functional outcomes in this group. Methods: The REACCT international collaborative database was reviewed and data on eligible patients analysed. Inclusion criteria comprised patients with a histologically confirmed rectal cancer, <50 years of age at time of diagnosis and with documented follow-up including functional outcomes. Results: A total of 1428 (n=1428) patients met the eligibility criteria and were included in the final analysis. Metastatic disease was present at diagnosis in 13%. Of these, 40% received neoadjuvant therapy and 50% adjuvant chemotherapy. The incidence of post-operative major morbidity was 10%. A defunctioning stoma was placed for 621 patients (43%); 534 of these proceeded to elective restoration of bowel continuity. The median follow-up time was 42 months. Of this cohort, a total of 415 (29%) reported persistent impairment of functional outcomes, the most frequent of which was bowel dysfunction (16%), followed by bladder dysfunction (7%), sexual dysfunction (4.5%) and infertility (1%). Conclusion: A substantial proportion of patients with early-onset rectal cancer who undergo surgery report persistent impairment of functional status. Patients should be involved in the discussion regarding their treatment options and potential impact on quality of life. Functional outcomes should be routinely recorded as part of follow up alongside oncological parameters

Enhancing goal priming effects: an experimental study of the influences of diet reminders and activity equivalent labells on calories consumption reduction

Há consenso que a presença abundante de alimentos altamente calóricos contribui para o aumento do sobrepeso e obesidade nas populações. Considerada uma epidemia pela Organização Mundial da Saúde (OMS), este problema de saúde pública tem atraído a atenção de governos, gerando metas globais para combater o problema. O sobrepeso e obesidade não somente representam um problema social, como também afetam o bem-estar do próprio indivíduo. Pesquisas multidisciplinares nas áreas de psicologia, comportamento do consumidor, nutrição, medicina, e outros campos de interesse, desenvolveram teorias na tentativa de explicar as razões pelas quais os indivíduos - mesmo cientes dos malefícios - falham no controle de peso em certas ocasiões. Baseado na teoria do conflito de objetivos no comportamento alimentar e goal priming, estudos mostram relativo sucesso no uso de diet reminders como intervenção situacional, reativando os objetivos de redução de peso e suprimindo o prazer do consumo imediato para indivíduos em restrição calórica. Em outra iniciativa, seguindo nesta mesma linha, a britânica Royal Society for Public Health promoveu recentemente uma larga discussão na mídia sobre a inserção de activity equivalent labels nos rótulos de alimentos para mostrar aos consumidores o quanto devem se exercitar para compensar o ganho calórico. Entretanto, estas duas iniciativas recentes ainda apresentam pouco suporte empírico, e pesquisadores da área clamam por mais estudos. Um estudo experimental utilizando ambos os métodos e promovendo o avanço do conhecimento nesta área, foi aplicado em laboratório, simulando escolhas reais por meio do menu de uma conhecida rede de fast-food. Quatro tipos de estímulos (nenhuma informação, somente calorias, diet reminders e activity equivalent label) foram testadas em mais de quinhentos indivíduos. Utilizando-se primordialmente análises de covariâncias (ANCOVAs) para reduzir a interferência de outros efeitos, os resultados sugerem significativa redução de calorias devido ao efeito de goal priming. Adicionalmente, um achado inédito sugere que os efeitos do activity equivalent label podem potencializar a redução do consumo em indivíduos que praticam atividades físicas regulares. Este é o primeiro estudo experimental que une e compara estes dois tipos de intervenção - diet reminders e activity equivalent label-, contribuindo para o avanço teórico sobre o uso do goal priming como incentivo aos comportamentos alimentares saudáveis. Além disso, o estudo traz relevante contribuição gerencial, principalmente no auxílio da tomada de decisão envolvendo políticas públicas.There is a common understanding that ample availability of high caloric food contributes to an increase in excessive weight and obesity among populations. Considered an epidemic by the World Health Organization (WHO), this health issue has caught the attention of governments and led to the creation of global aims to fight the problem. Excessive weight and obesity not only represent social issues, but also affect individual well-being. Multidisciplinary research in psychology, consumer behavior, nutrition, medicine, and other fields of interest have posited theories trying to explain why individuals-even those aware of the harm-fail to control their weight in certain instances. Based on the theories of goal conflict model of eating behavior and of goal priming, studies have suggested relative success using diet-reminders as a useful situational intervention in reactivating weight-loss goal, as well as suppressing thoughts associated with food pleasure right at the time of consumption for restrained eaters. In another initiative studying the same issue, the British Royal Society for Public Health promoted ample discussion on media regarding the adoption of activity-equivalent labels on food-packaging in order to show consumers how much exercise they needed to burn intaken calories. However, both initiatives have gathered little empirical evidence of their efficiency and researchers are now claiming for more studies on the issue. An experiment using both methods and further advancing knowledge in this field, has been conducted in a laboratory simulating the real set of menu choices available at a well-known fast-food chain. Four experimental types of stimulus (no information given, amount of calories, diet reminders, and activity equivalent labels) were defined and tested on more than five hundred individuals. Using analysis of covariances (ANCOVAs) to reduce the noise of other variables, results have suggested a significant reduction on the amount of calories ordered from the menu due to goal priming effects. Additionally, a new finding suggests activity equivalent labels may potentialize a reduction of calorie-intake in restrained eaters who also exercise regularly. This is the first experiment combining and comparing both types of intervention - diet reminders and activity equivalent labels -, and advancing knowledge regarding the use of goal priming to promote healthy eating behaviors. Furthermore, this study has managerial implications, especially in the form of an insight for public policies regarding decision-behavior

Design and baseline data of a pediatric study with rosuvastatin in familial hypercholesterolemia

BACKGROUND: Statin therapy is recommended for children with familial hypercholesterolemia (FH), but most children do not reach treatment targets. OBJECTIVE: Here we present the design and results at baseline of the ongoing CHARON study, to evaluate the safety and efficacy of rosuvastatin. METHODS: This study comprises an international 2-year open label, titration-to-goal study in 198 children with heterozygous FH aged 6 to 18 years, with rosuvastatin in a maximum dose of 10 mg (<10 years of age) or 20 mg (older children). In addition, 64 unaffected siblings were enrolled as controls. The primary efficacy outcome is the change from baseline in low-density lipoprotein cholesterol, and the secondary outcome is the change in carotid intima-media thickness (c-IMT) in patients with FH compared with their siblings. The primary safety outcomes are growth and sexual maturation; secondary outcomes are the change in other lipoprotein levels and the incidence of adverse events, discontinuation rates, and abnormal laboratory values. RESULTS: At baseline, mean age of patients with FH was 12.1 ± 3.3 years, 44% were boys, and mean low-density lipoprotein cholesterol levels were 6.1 ± 1.3 mmol/L (235.9 ± 48.7 mg/dL). Mean c-IMT was 0.399 mm (95% CI, 0.392-0.406 mm) in children with FH versus 0.377 (95% CI, 0.366-0.388 mm) in unaffected siblings (P = .001). CONCLUSIONS: At baseline, as expected according to on previous observations, children with FH proved to have a greater c-IMT than their healthy siblings. These differences had already occurred at a very young age, which emphasizes the importance of considering early statin initiation in this high-risk population.status: publishe