The Prevalence of Gastric Atrophy in Western and Northern European Populations: A Systematic Review and Meta-Analysis

Aim Primary and secondary genetic clines in post‐glacial colonized regions have different implications for biogeographic distributions and the origin of species. Primary clines arisein situafter colonization as adaptive responses to environmental gradients, while secondary clines are caused by contact between vicariant lineages. Here we analyse primary versus secondary origin of a genetic cline in the tephritid flyUrophora carduiin Jutland, Denmark, in a post‐glacial landscape.Location Western Palaearctic.Methods Phylogeographic and demographic analyses ofU. carduibased on mitochondrial DNA (mtDNA) genealogies, hierarchical genetic variance tests based on allozymes and distribution analysis of a rare allele from the Jutland cline.Results There was no phylogeographic divergence between the Jutland population ofU. carduinorth of the cline and neighbouring western European regional populations, which all shared the common western European mtDNA haplotype H1. At nuclear loci, by contrast, the North Jutland population was diverged above the mean level of divergence among regional populations and had no loss of genetic variation. A rare allozyme allele that was frequent in the cline area (up to 45%) and was missing north of the cline also occurred at low frequency (0–14%) elsewhere in the sampling range. Shallow phylogeographic divergence was observed between Russian and western European populations and between English and continental populations.Main conclusions The genetic variation patterns support primary cline evolution and parapatric divergence in Jutland following a demographic expansion of a western European ancestral source population ofU. cardui, and suggest cryptic refugia and/or selection in other European population assemblages. The patterns of intra‐specific regional divergence are discussed with respect to the interpretation of cryptic refugia in Europe after the most recent ice age.

The determination of human leucocyte antigen (HLA)-A, HLA-B and HLA-DRB1 alleles in the routine procedure of a volunteer hematopoietic stem cell (HSC) donor's registration in the Croatian Bone Marrow Donor Registry (CBMDR) is performed to enhance the odds of finding a suitable HLA compatible donor for patients in need of a HSC transplantation worldwide. However, besides its original purpose, it also provides valuable information about the HLA polymorphism among Croats. The aim of the present study was to analyse the HLA allele and haplotype frequencies in a sample of 4000 donors from CBMDR. The distribution of HLA-A, HLA-B and HLA-DRB1 alleles did not demonstrate significant differences from the data reported for other European populations. The higher frequency of B*40:02 allele in comparison with B*40:01 and DRB1*11:04 in comparison with DRB1*11:01 is interesting because it represents a difference in comparison with the Western and Northern European populations which are a main source of donors for Croatian patients. The haplotype frequencies show a greater variation and difference in comparison with data from other registries and populations; however, due to a lack of high-resolution haplotype data, comparison was possible only with a very limited number of other populations.

A Summary of the 2020 Gastric Cancer Summit at Stanford University

The CHEK2 1100delC protein-truncating mutation has a carrier frequency of approximately 0.7% in Northern and Western European populations and confers an approximately 2-fold increased risk of breast cancer. It has also been suggested to increase risks of colorectal and prostate cancer, but its involvement with these or other types of cancer has not been confirmed. The incidence of cancer other than breast cancer in 11,116 individuals from 734 non-BRCA1/2 breast cancer families from the United Kingdom, Germany, Netherlands, and the United States was compared with that predicted by population rates. Relative risks (RR) to carriers and noncarriers were estimated by maximum likelihood, via the expectation-maximization algorithm to allow for unknown genotypes. Sixty-seven families contained at least one tested CHEK2 1100delC mutation carrier. There was evidence of underreporting of cancers in male relatives (422 cancers observed, 860 expected) but not in females (322 observed, 335 expected); hence, we focused on cancer risks in female carriers. The risk of cancers other than breast cancer in female carriers was not significantly elevated, although a modest increase in risk could not be excluded (RR, 1.18; 95% confidence interval, 0.64-2.17). The carrier risk was not significantly raised for any individual cancer site, including colorectal cancer (RR, 1.60; 95% confidence interval, 0.54-4.71). However, between ages 20 to 50 years, the risks of colorectal and lung cancer were both higher in female carriers than noncarriers (P = 0.041 and 0.0001, respectively). There was no evidence of a higher prostate cancer risk in carriers than noncarriers (P = 0.26), although underreporting of male cancers limited our power to detect such a difference. Our results suggest that the risk of cancer associated with CHEK2 1100delC mutations is restricted to breast cancer, although we cannot rule out a small increase in overall cancer risk.

<h3>Background and Importance</h3> Metamizole (dipyrone) is a non-opioid analgesic widely used for pain and fever. Although effective, its association with blood dyscrasias–particularly agranulocytosis–led to withdrawal in several countries. In Southern Europe, however, its safety remains widely accepted. Evidence suggests possible ethnic or genetic susceptibility, especially among Northern Europeans, but real-world data are scarce. Clarifying this risk is essential to improve pharmacovigilance, ensure patient safety, and guide appropriate analgesic use in diverse populations. <h3>Aim and Objectives</h3> This study aimed to estimate the incidence and relative risk of metamizole-induced agranulocytosis or neutropenia, comparing adults of Northern versus Southern European origin, and to identify possible ethnic differences in adverse reactions using hospital and outpatient real-world data. <h3>Material and Methods</h3> A retrospective observational study was conducted in five regional health departments with a high Northern European resident population. Data from 2016–2017 were obtained using the <i>Alumbra</i> platform, identifying hospital admissions in the CMBD database with ICD-10 codes for drug-induced neutropenia or agranulocytosis (D70.2, D70.8, D70.9, and related T39 codes). Patients &gt;45 years exposed to metamizole within one month before admission were included. Cases with neoplastic, haematologic, or infectious causes were excluded. Each case was reviewed individually. Incidence was expressed per 100,000 DDD and per 1,000 treated patients. <h3>Results</h3> A total of 555 hospitalisations were identified; 41 met inclusion criteria. Of these, 26 were of Northern European origin and 11 of Southern European origin. The incidence of agranulocytosis was 39.8 vs. 0.33 cases per 100,000 DDD (RR = 120.6). Nine deaths occurred, seven among Northern European patients. <h3>Conclusion and Relevance</h3> Real-world data revealed a significantly higher relative risk of agranulocytosis associated with metamizole in Northern European origin patients. Although the absolute incidence remains low, the findings support targeted pharmacovigilance, genetic susceptibility research, and cautious prescribing in susceptible populations. <h3>References and/or Acknowledgements</h3> 1. Ibáñez L, Vidal X, Ballarín E, Laporte JR. Agranulocytosis associated with metamizole. <i>Eur J Clin Pharmacol.</i> 2005;<b>60</b>:821–9. 2. Stammschulte T, Ludwig WD, Mühlbauer B, <i>et al.</i> Metamizole-associated agranulocytosis: analysis of spontaneous reports 1990-2012. <i>Eur J Clin Pharmacol.</i> 2015;<b>71</b>:1129–38. 3. Vlahov V, Bacracheva N, Tontcheva D, <i>et al</i>. Genetic factors and risk of agranulocytosis from metamizole. <i>Pharmacogenetics.</i> 1996;<b>6</b>:67–72. 4. Shah RR. Metamizole-induced agranulocytosis: does risk vary by ethnicity? <i>J Clin Pharm Ther.</i> 2018;<b>43</b>:556–64. <h3>Conflict of Interest</h3> No conflict of interest

Angiotensin-converting enzyme 2 (ACE2), transmembrane serine 2 and serine 11A proteases (TMPRSS2, TMPRSS11A), and a cell surface cluster of differentiation 147 (CD147) might be a gene candidate that exerts the susceptibility to and mortality from coronavirus disease 19 (COVID-19). The aim of this study was to investigate the associations between ace2, tmprss2, tmprss11a, and cd147 polymorphic variants and the severity of COVID-19 in the Ukrainian population. The study population consisted of the Ukrainian population with COVID-19: patients without oxygen therapy (n=62), with non-invasive (n=92) and invasive (n=35) oxygen therapy, as well as control subjects (n=92). Allelic polymorphisms of ace2 rs4240157, tmprss2 rs12329760, and tmprss11a rs353163 were determined by real-time PCR, and cd147 rs8259 polymorphism was detected by PCR with subsequent restrictase analysis. We compared investigated polymorphisms distribution with other populations by meta-analysis. Our study is the first to obtain data about the distribution of investigated gene polymorphisms in the Ukrainian population: tmprss2 rs12329760 - CC 60.9%, CT 35.9%, TT 3.2%; tmprss11a rs353163 - CC 46.7%, CT 40.2%, TT 13.1%; ace2 rs4240157 - CC 7.6%, C 18.5%, CT 22.8%, TT 19.6%, T 31.5%; cd147 rs8259 - TT 60.9%, AT 32.6%, AA 6.5%. This distribution was similar to the Northern, Western and Southern European populations. There was a statistically significant difference in the frequency of tmprss2 polymorphic genotypes CC 57.1%, CT 28.6%, and TT 14.3% (P<0.05) in COVID-19 patients with invasive oxygen therapy in comparison with non-invasive oxygen therapy. This tmprss2 mutation occurs in the scavenger receptor cysteine-rich (SRCR) domain and might be important for protein-protein interaction in a calcium-dependent manner. Our study indicated the presence of an association between the tmprss2 rs12329760 polymorphism and the severity of COVID-19 in the Ukrainian population.

BackgroundSocio-economic inequalities in suicide remain substantial and persistent in most European countries. The mechanism driving these inequalities, however, remains obscure. Two causal mechanisms have been attributed varying degrees of importance:...

ABSTRACTIcelandic cattle is believed to have been brought from Norway during the settlement of Iceland around AD 870-930. Previous research on genetic relationships has indicated that Icelandic cattle is most related to northern Nordic indigenous breeds. Using single nucleotide polymorphism genotype data from Icelandic cattle and 29 Northern and Western European cattle breeds, we studied relationships and admixture among these breeds, and assessed population structure in Icelandic cattle. Population structure analysis through principal component analysis, estimation of ancestry, and analysis of patterns of population splitting and mixing revealed that Icelandic cattle are most related to three Finncattle breeds (Eastern, Northern and Western Finncattle), and Swedish Mountain cattle. Icelandic cattle has very low levels of admixture. We observed very limited population structure in Icelandic cattle. The observed structure was due to variable sire contributions. Over 1000 years of almost complete isolation has made Icelandic cattle highly genetically distinct from other cattle breeds.

Cost Analysis of Screening According to ECCO Guidelines for Prevention of Opportunistic Infections in Infliximab-Treated IBD Patients

IntroductionWe previously reported that our practice of screening for and prevention of opportunistic infections (OI's) in at risk IBD patients was not in line with ECCO recommendations.1 2 In this...

Noninvasively collected genetic data can be used to analyse large-scale connectivity patterns among populations of large predators without disturbing them, which may contribute to unravel the species' roles in natural ecosystems and their requirements for long-term survival. The demographic history of brown bears (Ursus arctos) in Northern Europe indicates several extinction and recolonization events, but little is known about present gene flow between populations of the east and west. We used 12 validated microsatellite markers to analyse 1580 hair and faecal samples collected during six consecutive years (2005-2010) in the Pasvik Valley at 70°N on the border of Norway, Finland and Russia. Our results showed an overall high correlation between the annual estimates of population size (N(c) ), density (D), effective size (N(e) ) and N(e) /N(c) ratio. Furthermore, we observed a genetic heterogeneity of ∼0.8 and high N(e) /N(c) ratios of ∼0.6, which suggests gene flow from the east. Thus, we expanded the population genetic study to include Karelia (Russia, Finland), Västerbotten (Sweden) and Troms (Norway) (477 individuals in total) and detected four distinct genetic clusters with low migration rates among the regions. More specifically, we found that differentiation was relatively low from the Pasvik Valley towards the south and east, whereas, in contrast, moderately high pairwise F(ST) values (0.91-0.12) were detected between the east and the west. Our results indicate ongoing limits to gene flow towards the west, and the existence of barriers to migration between eastern and western brown bear populations in Northern Europe.

Educational inequalities in cause-specific mortality in middle-aged and older men and women in eight western European populations

In recent years, a significant amount of scientific materials has been accumulated on the low intake and insufficient status of vitamin D among population in various countries. Optimal vitamin D intake and levels are important not only for bone health and calcium-phosphate metabolism, but also for overall health and well-being. Vitamin D deficiency and insufficiency as a global health problem are likely to increase the risk of a wide spectrum of acute and chronic illnesses. Vitamin D deficiency is common in Europe and the Middle East. It occurs in &lt;20% of the population in Northern Europe, in 30-60% of the population in Western, Southern and Eastern Europe and in up to 80% of the population in Middle East countries. Pregnant women are a special risk group for vitamin D deficiency. A global systematic review conducted in 2016 found that the prevalence of 25(OH)D &lt;= 50 nmol/L in pregnant women by WHO region was Americas (64%), Europe (57%), Eastern Mediterranean (46%), South-East Asia (87%) and Western Pacific (83%). Vitamin D plays an important role in epigenetic modifications in the fetus and in the processes of fetal programming. Vitamin D deficiency during pregnancy has been associated with several adverse outcomes for the mother and developing foetus gestational diabetes, preeclampsia and preterm birth. In addition, vitamin D deficiency in pregnant women has been associated with a higher risk of low birth weight, which can have long-term health consequences for the infant. A large number of epidemiological studies demonstrate associations between vitamin D deficiency and a variety of common disorders, including musculoskeletal, metabolic, cardiovascular, malignant, autoimmune, and infectious diseases. The majority of the human body’s vitamin D requirement is met through biosynthesis of this vitamin in the skin upon exposure to sunlight, with less than 30% of the daily requirement of vitamin D is obtained from dietary sources. Dietary intake of vitamin D is irregular, as some foods contain very little of the vitamin. The main dietary sources of this vitamin are oily fish, eggs, liver, and butter. Vitamin D deficiency can result from decreased endogenous synthesis and low dietary intake. High BMI and obesity can be risk factors for vitamin D deficiency. Creams, clothing, dust, smog, hypokinesia, and age can be other contributing factors. Endocrine Society Clinical Practice Guideline suggests empiric vitamin D (“empiric supplementation” as vitamin D intake that exceeds the Dietary Reference Intakes and is implemented without testing for 25(OH) D) for those aged 1 to 18 years and adults over 75 years of age, those who are pregnant, and those with high-risk prediabetes. Due to the scarcity of natural food sources rich in vitamin D, empiric supplementation can be achieved through a combination of fortified foods and supplements that contain vitamin D.

BackgroundThe European mink (Mustela lutreola, L. 1761) is a critically endangered mustelid, which inhabits several main river drainages in Europe. Here, we assess the genetic variation of existing populations of this species, including new sampling sites and additional molecular markers (newly developed microsatellite loci specific to European mink) as compared to previous studies. Probabilistic analyses were used to examine genetic structure within and between existing populations, and to infer phylogeographic processes and past demography.ResultsAccording to both mitochondrial and nuclear microsatellite markers, Northeastern (Russia, Estonia and Belarus) and Southeastern (Romania) European populations showed the highest intraspecific diversity. In contrast, Western European (France and Spain) populations were the least polymorphic, featuring a unique mitochondrial DNA haplotype. The high differentiation values detected between Eastern and Western European populations could be the result of genetic drift in the latter due to population isolation and reduction. Genetic differences among populations were further supported by Bayesian clustering and two main groups were confirmed (Eastern vs. Western Europe) along with two contained subgroups at a more local scale (Northeastern vs. Southeastern Europe; France vs. Spain).ConclusionsGenetic data and performed analyses support a historical scenario of stable European mink populations, not affected by Quaternary climate oscillations in the Late Pleistocene, and posterior expansion events following river connections in both North- and Southeastern European populations. This suggests an eastern refuge during glacial maxima (as already proposed for boreal and continental species). In contrast, Western Europe was colonised more recently following either natural expansions or putative human introductions. Low levels of genetic diversity observed within each studied population suggest recent bottleneck events and stress the urgent need for conservation measures to counteract the demographic decline experienced by the European mink.Electronic supplementary materialThe online version of this article (doi:10.1186/s12862-015-0427-9) contains supplementary material, which is available to authorized users.

Hereditary Diffuse Gastric Cancer: Surveillance Endoscopy is Not Enough to Save Lives