Comprehensive population-wide analysis of Lynch syndrome in Iceland reveals founder mutations in MSH6 and PMS2.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked FilesLynch syndrome, caused by germline mutations in the mismatch repair genes, is associated with increased cancer risk. Here using a large whole-genome sequencing data bank, cancer registry and colorectal tumour bank we determine the prevalence of Lynch syndrome, associated cancer risks and pathogenicity of several variants in the Icelandic population. We use colorectal cancer samples from 1,182 patients diagnosed between 2000-2009. One-hundred and thirty-two (11.2%) tumours are mismatch repair deficient per immunohistochemistry. Twenty-one (1.8%) have Lynch syndrome while 106 (9.0%) have somatic hypermethylation or mutations in the mismatch repair genes. The population prevalence of Lynch syndrome is 0.442%. We discover a translocation disrupting MLH1 and three mutations in MSH6 and PMS2 that increase endometrial, colorectal, brain and ovarian cancer risk. We find thirteen mismatch repair variants of uncertain significance that are not associated with cancer risk. We find that founder mutations in MSH6 and PMS2 prevail in Iceland unlike most other populations.Ohio State University (OSU) Comprehensive Cancer Center OSU Colorectal Cancer Research fund Obrine-Weaver Fund Pelotonia Fellowship Award deCODE genetic

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe

Adolescents’ Experience of Parental Reactions and its Relations to Externalizing and Internalizing Problems

The present study examined 1336 twelve- and thirteen-year old Swedish adolescents’ experience of parents’ reactions to misbehavior and its relations to self-reported internalizing and externalizing problems. Parental reactions were measured as degree of experienced angry outbursts, coldness-rejection and attempted understanding from parents. Internalization and externalization were measured with the Strengths and Difficulties Questionnaire (SDQ). Our findings show that adolescents’ internalization and externalization were linked to parental reactions to misbehavior. Adolescents’ who reported more parental angry outbursts also reported more externalizing and internalizing problems. Coldness-rejection was similarly related to both problem-styles. Attempted understanding was related to less internalizing and externalizing in adolescents and seems to function as resilience against mental health problems. However, this effect was in turn mediated by attachment

Sjökaptensstudenters förhållningssätt till arbete med härdplaster

Härdplaster är en hälsovådlig produkt om den hanteras på ett felaktigt sätt. Sjömän tillhör en yrkesgrupp som använder denna produkt i sitt arbete ombord på olika fartyg. Det har visat sig från andra studier att andra yrkesgrupper inte tar nödvändiga skyddsåtgärder för att skydda sig mot härdplaster. Mot bakgrund till detta var syftet i denna studie att ta reda på hur sjökaptensstudenter förhåller sig till härdplaster och dess risker ombord. Undersökningen är baserad på åtta intervjuer bestående av avgångsstudenter från Sjökaptensprogrammet i Kalmar. Intervjuerna var strukturerade efter olika förvalda frågor inordnade efter olika temata samt med låg standardisering. Utfallet visade i stort sätt samma attityd bland respondenterna. Resultatet visade att rekommenderad personlig skyddsutrustning inte användes i någon större utsträckning vid hantering av härdplaster. Det framkom att den enskilt största faktorn till detta samt respondenternas attityd till det, påverkades av den övriga besättningens attityd och beteende. Respondenternas förhållningssätt förstärktes av att de önskade vara till lags och göra ett bra arbete. Övriga faktorer som påverkade var svårtillgänglighet till skyddsutrustning, attityd till riskerna med härdplaster, plats och exponeringstid.Thermosetting plastic is a toxic product if handled in a wrong way. Seaman belongs to a group of workers that use this product in their profession on board ships. It has been shown from other studies that workers from other professions do not take necessary safety precautions to protect themselves against thermosetting plastic. Therefore, the purpose of this study was to find out the attitude towards thermosetting plastic work and its risk involved. The study is based on eight interviews with graduating students from the Master Mariner Program in Kalmar. The structure of the interviews was organized after different predetermined questions with low standardization. The result showed basically the same attitude among the respondents. Also, the result showed that recommended personal protective equipment was generally not used consistently during thermosetting plastic work. The main reason for this was the influence from other crews’ attitude and behavior. It is likely that the respondents’ attitude were enhanced by their willingness to comply with procedures onboard. Other factors that influenced their behavior were the lack of easy access to equipment, attitude and perception towards the risks with thermosetting plastic, the location and length of exposure

Differential expression of CK20, β-catenin, and MUC2/5AC/6 in Lynch syndrome and familial colorectal cancer type X

Background: Hereditary non-polyposis colorectal cancer comprises Lynch syndrome and familial colorectal cancer type X (FCCTX). Differences in genetics, demographics and histopathology have been extensively studied. The purpose of this study is to characterize their immunoprofile of markers other than MMR proteins. Methods: We compared the expression patterns of cytokeratins (CK7 and CK20), mucins (MUC2/5 AC/6), CDX2 and β-catenin in Lynch syndrome and FCCTX. Results: Differences were identified for CK20 and nuclear β-catenin, which were significantly more often expressed in FCCTX than in Lynch syndrome (p < 0.001), whereas MUC2, MUC5AC and MUC6 were overexpressed in Lynch syndrome tumors compared with FCCTX tumors (p = 0.001, < 0.01, and < 0.001, respectively). We observed no differences in the expression patterns of CK7 and CDX2. Conclusions: In summary, we identified significant differences in the immunoprofiles of colorectal cancers linked to FCCTX and Lynch syndrome with a more sporadic-like profile in the former group and a more distinct profile with frequent MUC6 positivity in the latter group

Extracorporeal shock wave lithotripsy for pancreatic duct stones: an observational study.

To access publisher's full text version of this article click on the hyperlink belowPrevious studies suggest that fragmentation of pancreatic duct stones (PDS) using extracorporeal shock wave lithotripsy (ESWL) is associated with pain relief. However, the treatment may not be effective in certain subgroups. To evaluate predictors of pain relief after ESWL in patients with chronic pancreatitis and PDS. Retrospective study including patients with chronic pancreatitis undergoing ESWL for painful PDS. Analgesic use before and after the ESWL procedure was registered. We defined adequate pain relief after ESWL as 'pain-free without analgesics or with use of weak analgesics as needed'. The study was approved by the Danish Data Protection Agency (approval number: AHH-2017-048). We included 81 patients (median age 58 years; 63% men; 68% alcoholic pancreatitis). Patients underwent one to seven ESWL procedures (mean 1.7). A concurrent ERCP was performed in 17%. All patients used analgesics before the ESWL procedure (68 used opioids). After ESWL, 43 still used opioids. Thirty-two patients achieved adequate pain relief. Univariable regression analysis showed that older age predicted adequate pain relief (OR 1.09;1.03-1.16; p = .002) as did location of the stone in the head or neck (OR 2.59;1.04-6.45; p = .041). In multivariable analysis, we found that the only two predictors of adequate pain relief were age (p = .002) and the location of the stones (p = .039)

Direct observation of grain boundaries in graphene through vapor hydrofluoric acid (VHF) exposure

The shape and density of grain boundary defects in graphene strongly influence its electrical, mechanical, and chemical properties. However, it is difficult and elaborate to gain information about the large-area distribution of grain boundary defects in graphene. An approach is presented that allows fast visualization of the large-area distribution of grain boundary–based line defects in chemical vapor deposition graphene after transferring graphene from the original copper substrate to a silicon dioxide surface. The approach is based on exposing graphene to vapor hydrofluoric acid (VHF), causing partial etching of the silicon dioxide underneath the graphene as VHF diffuses through graphene defects. The defects can then be identified using optical microscopy, scanning electron microscopy, or Raman spectroscopy. The methodology enables simple evaluation of the grain sizes in polycrystalline graphene and can therefore be a valuable procedure for optimizing graphene synthesis processes.QC 20180604European Research Council through the Starting Grants M&M’s (277879)Swedish Research Council (GEMS, 2015-05112)European Research Council through the Starting Grants InteGraDe (307311)China Scholarship CouncilGerman Federal Ministry for Education and Research (NanoGraM, BMBF, 03XP0006C)German Research Foundation (DFG; LE 2440/1-2)German Research Council (DFG) through the Priority Program SPP 1459 Graphen

Impact of the COVID-19 pandemic on the management of gallstone surgery : A Swedish population-based study

BACKGROUND: The SARS-CoV-2 pandemic has had a significant impact on healthcare delivery. As resources are reallocated, surgery for benign conditions such as gallstone disease is often given low priority. We do not know how this has affected the risk of patients with uncomplicated gallstone disease to develop acute cholecystitis, biliary pancreatitis, or obstructive jaundice. METHODS: The study was based on the population-based Swedish Register of Gallstone Surgery and Endoscopic Retrograde Cholangiopancreatography. The period prior to the first cases of COVID-19 in Sweden, that is, April 2015-March 2020, was compared to the period April 2020-March 2021 during the pandemic. Stratification was made for factors potentially related to priority decisions. RESULTS: Altogether, 78,211 procedures were performed during the period of the study. The ratio of procedures performed during April 2020-March 2021 in the previous 5 years was 0.960 (p = 0.113). The ratio of procedures on patients aged &lt;65 years was 0.945 (p = 0.008), on patients aged 65-80 years was 0.964 (p = 0.423), on patients aged &gt;80 years was 1.336 (p = 0.025), on men was 1.001 (p = 0.841), on women was 0.934 (p = 0.006), on procedures completed laparoscopically was 0.964 (p = 0.190), on procedures completed with open approach was 0.659 (p = 0.044), on acute procedures was 1.218 (p = 0.016), on planned procedures was 0.791 (p &lt; 0.001), on procedures performed for biliary colic was 0.808 (p &lt; 0.001), on procedures performed for acute cholecystitis was 1.274 (p = 0.012), for biliary pancreatitis was 1.192 (p = 0.037), and for obstructive jaundice was 1.366 (p = 0.008). CONCLUSIONS: The COVID-19 has had a great impact on how gallstone surgery has been organized over the last 2 years. The decreased number of planned procedures probably reflects the reallocation of resources during the pandemic. However, whether the increasing number of acute procedures is the result of postponed planned surgery or a continuation of a long-term trend toward more acute surgery remains unanswered. Further studies are needed to assess and evaluate how this has affected public health and health economics