Repeated out-of-Africa expansions of Helicobacter pylori driven by replacement of deleterious mutations

Erratum in: Nat Commun. 2023 Mar 20;14(1):1539. doi: 10.1038/s41467-023-37302-5.Helicobacter pylori lives in the human stomach and has a population structure resembling that of its host. However, H. pylori fromEurope and the Middle East trace substantially more ancestry from modern African populations than the humans that carry them. Here, we use a collection of Afro-Eurasian H. pylori genomes to show that this African ancestry is due to at least three distinct admixture events. H. pylori from East Asia, which have undergone little admixture, have accumulated many more non-synonymous mutations than African strains. European and Middle Eastern bacteria have elevated African ancestry at the sites of these mutations, implying selection to remove them during admixture. Simulations show that population fitness can be restored after bottlenecks bymigration and subsequent admixture of small numbers of bacteria from non-bottlenecked populations. We conclude that recent spread of African DNA has been driven by deleterious mutations accumulated during the original out-of-Africa bottleneck.This work was supported by Sequencing Grants-in-aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology (MEXT) of Japan (221S0002, 18KK0266, 19H03473, 21H00346 and 22H02871) to Y.Y. F.F.V. is financed by FCT through Assistant Researcher grant CEECIND/03023/2017 and a project grant PTDC/BTM-TEC/3238/ 2020. I.K. studentship was funded by the National Strategic Reference Framework Operational Program “Competitiveness, Entrepreneurship and Innovation” (NSRF 2014-2020, project No. MIS5002486) and sequencing of strains was supported by the InfeNeutra Project (NSRF 2007-2013, project no. MIS450598) of the Ministry of Culture and Edu- cation, Greece. K.T. and the sequencing of KI isolates was supported by Erik Philip-Sörensen Foundation grant G2016-08, and Swedish Society for Medical research (SSMF). All primary bioinformatics and parts of the comparative genomics were performed on resources provided by Swedish National Infrastructure for Computing (SNIC) through Uppsala Multidisciplinary Center for Advanced Computational Science (UPPMAX) under projects snic2018-8-24 and uppstore2017270. Work by S.S. was supported by the German Research Foundation (DFG, project number 158 989 968–SFB 900/A1) and by the Bavarian Ministry of Sci- ence and the Arts in the framework of the Bavarian Research Network “New Strategies Against Multi-Resistant Pathogens by Means of Digital Networking—bayresq.net”. D.F. was supported by Shanghai Municipal Science and Technology Major Project No. 2019SHZDZX02.info:eu-repo/semantics/publishedVersio

Cardiovascular disease, chronic kidney disease, and diabetes mortality burden of cardiometabolic risk factors from 1980 to 2010: A comparative risk assessment

Background: High blood pressure, blood glucose, serum cholesterol, and BMI are risk factors for cardiovascular diseases and some of these factors also increase the risk of chronic kidney disease and diabetes. We estimated mortality from cardiovascular diseases, chronic kidney disease, and diabetes that was attributable to these four cardiometabolic risk factors for all countries and regions from 1980 to 2010. Methods: We used data for exposure to risk factors by country, age group, and sex from pooled analyses of population-based health surveys. We obtained relative risks for the effects of risk factors on cause-specific mortality from meta-analyses of large prospective studies. We calculated the population attributable fractions for each risk factor alone, and for the combination of all risk factors, accounting for multicausality and for mediation of the effects of BMI by the other three risks. We calculated attributable deaths by multiplying the cause-specific population attributable fractions by the number of disease-specific deaths. We obtained cause-specific mortality from the Global Burden of Diseases, Injuries, and Risk Factors 2010 Study. We propagated the uncertainties of all the inputs to the final estimates. Findings: In 2010, high blood pressure was the leading risk factor for deaths due to cardiovascular diseases, chronic kidney disease, and diabetes in every region, causing more than 40% of worldwide deaths from these diseases; high BMI and glucose were each responsible for about 15% of deaths, and high cholesterol for more than 10%. After accounting for multicausality, 63% (10·8 million deaths, 95% CI 10·1-11·5) of deaths from these diseases in 2010 were attributable to the combined effect of these four metabolic risk factors, compared with 67% (7·1 million deaths, 6·6-7·6) in 1980. The mortality burden of high BMI and glucose nearly doubled from 1980 to 2010. At the country level, age-standardised death rates from these diseases attributable to the combined effects of these four risk factors surpassed 925 deaths per 100 000 for men in Belarus, Kazakhstan, and Mongolia, but were less than 130 deaths per 100 000 for women and less than 200 for men in some high-income countries including Australia, Canada, France, Japan, the Netherlands, Singapore, South Korea, and Spain. Interpretation: The salient features of the cardiometabolic disease and risk factor epidemic at the beginning of the 21st century are high blood pressure and an increasing effect of obesity and diabetes. The mortality burden of cardiometabolic risk factors has shifted from high-income to low-income and middle-income countries. Lowering cardiometabolic risks through dietary, behavioural, and pharmacological interventions should be a part of the global response to non-communicable diseases. Funding: UK Medical Research Council, US National Institutes of Health. © 2014 Elsevier Ltd

Peptic ulcer disease in an adult population : the Kalixanda study : a population-based endoscopic study

Introduction: The pattern of symptoms and perception of disease among patients seeking care does, due to health care seeking behaviour, most probably not reflect the true health status in the general population. Upper esophagogastroduodenoscopy (EGD) is considered to be gold standard for upper gastrointestinal (GI) disease assessment, but is seldom used in epidemiological studies. We aimed to explore whether the EG13 affects symptom reporting and sampling among volunteers and to clarify the prevalence of peptic ulcer disease (PUD) and its risk factors in a general adult population. Methods: A random sample of 3,000 adults aged 20-80 years (mean age 50.4), from two Swedish municipalities (n=21,610) was surveyed using a validated postal abdominal symptom questionnaire. A random sub-sample of the responders (n=1,001) was invited, in random order, to undergo an upper endoscopy with biopsies and repeated symptom reporting with the same questionnaire, as well as for blood samples for Helicobacter pylori (H. pylori) serology and other biomarkers, medical history taking, measuring and weighing the subjects. Results: The response rate to the initial questionnaire was 74.2% and the participation rate for those eligible for the upper endoscopy was 73.3% (n=1,001, mean age 54.0 years, 48.8% male). No major social or symptom sampling error was encountered from the selection process, except for an excess of symptom reporters among the youngest subjects (< 35 years). The prevalence of gastroesophageal reflux symptoms (GERS), dyspepsia and the Irritable Bowel Syndrome (IBS) was 40%, 37.6% and 29.6%, respectively. The prevalence of peptic ulcer was 4.1 % (gastric ulcers (GU) n=20; duodenal ulcers (DU) n=21). Nausea and GERS, but not epigastric pain/discomfort, were significant predictors of PUD. Six individuals with GU and two with DU were asymptomatic (in all 20%). Eight DU subjects (38%) lacked evidence of current H. pylori infection. Five (25%) of the GU and four (19%) of the DU were idiopathic (no aspirin/NSAID use, no H. pylori infection and normal Gastrin-17). Smoking, aspirin and obesity were risk factors for GU; smoking, low dose aspirin (¡Ü 160 mg) and H. pylori infection were risk factors for DU. There were more endoscopic findings in obese subjects than in normal weight subjects, but the differences were not significant except for esophagitis and GU; the prevalence of reflux esophagitis in obesity was 26.5% versus 9.3% in normal weight subjects and the corresponding figures for GU were 5.6% and 1.4% respectively. Different types of tobacco use do not seem to have uniform health risks. While smoking increases the risk for PUD, smokeless tobacco use does not, or might even contribute to a lower risk. Use of smokeless tobacco is a significant risk for higher prevalence of reflux esophagitis and for intestinal metaplasia in the antrum (a preneoplastic marker). Conclusions: Valid epidemiology through upper endoscopy is possible. Smoking, aspirin and obesity are risk factors for GU; smoking, low dose aspirin (¡Ül60 mg) and H. pylori infection for DU. Smokeless tobacco is not a risk factor for PUD but most probably not harmless anyhow. Idiopathic ulcer may be more common than anticipated. PUD is often asymptomatic or coexists with atypical symptoms

Sub-Aggregator as a key enabler in harnessing demand response potential of electric vehicles

The necessary balance between power consumption and production is at risk due to the diminishing amount of controllable resources in the grid. Demand response has the ability to provide the needed ancillary services for the power system management and create a new stream of revenue for the flexible resource owner. The increasing amount of electric vehicles contain a huge balancing power potential due to their ability to store the electrical energy flexibly from the grid in times of long term parking. Sub-aggregator is an actor who possesses capabilities to monitor and control distributed energy resources. In the case of electric vehicles, Sub-aggregator plans and coordinates the smart charging of vehicles to create additional value for all participants. This paper presents a business model for aggregating distributed energy resources in a cost-efficient manner that is based on minimum investments needed.acceptedVersionPeer reviewe