New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes

Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD

Restrictions for reimbursement of interferon-free direct-acting antiviral drugs for HCV infection in Europe

To access publisher's full text version of this article click on the hyperlink belowAll-oral direct-acting antiviral drugs (DAAs) for hepatitis C virus, which have response rates of 95% or more, represent a major clinical advance. However, the high list price of DAAs has led many governments to restrict their reimbursement. We reviewed the availability of, and national criteria for, interferon-free DAA reimbursement among countries in the European Union and European Economic Area, and Switzerland. Reimbursement documentation was reviewed between Nov 18, 2016, and Aug 1, 2017. Primary outcomes were fibrosis stage, drug or alcohol use, prescriber type, and HIV co-infection restrictions. Among the 35 European countries and jurisdictions included, the most commonly reimbursed DAA was ombitasvir, paritaprevir, and ritonavir, with dasabuvir, and with or without ribavirin (33 [94%] countries and jurisdictions). 16 (46%) countries and jurisdictions required patients to have fibrosis at stage F2 or higher, 29 (83%) had no listed restrictions based on drug or alcohol use, 33 (94%) required a specialist prescriber, and 34 (97%) had no additional restrictions for people co-infected with HIV and hepatitis C virus. These findings have implications for meeting WHO targets, with evidence of some countries not following the 2016 hepatitis C virus treatment guidelines by the European Association for the Study of Liver.UNSW (Sydney, Australia) CanHepC Trainee Program (Canada) National Health and Medical Research Council Australian Government Department of Healt

Meta-analysis of genome-wide association studies from the CHARGE consortium identifies common variants associated with carotid intima media thickness and plaque

Carotid intima media thickness (cIMT) and plaque determined by ultrasonography are established measures of subclinical atherosclerosis that each predicts future cardiovascular disease events. We conducted a meta-analysis of genome-wide association data in 31,211 participants of European ancestry from nine large studies in the setting of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. We then sought additional evidence to support our findings among 11,273 individuals using data from seven additional studies. In the combined meta-analysis, we identified three genomic regions associated with common carotid intima media thickness and two different regions associated with the presence of carotid plaque (P < 5 × 10 -8). The associated SNPs mapped in or near genes related to cellular signaling, lipid metabolism and blood pressure homeostasis, and two of the regions were associated with coronary artery disease (P < 0.006) in the Coronary Artery Disease Genome-Wide Replication and Meta-Analysis (CARDIoGRAM) consortium. Our findings may provide new insight into pathways leading to subclinical atherosclerosis and subsequent cardiovascular events

Mass conserved elementary kinetics is sufficient for the existence of a non-equilibrium steady state concentration

Living systems are forced away from thermodynamic equilibrium by exchange of mass and energy with their environment. In order to model a biochemical reaction network in a non-equilibrium state one requires a mathematical formulation to mimic this forcing. We provide a general formulation to force an arbitrary large kinetic model in a manner that is still consistent with the existence of a non-equilibrium steady state. We can guarantee the existence of a non-equilibrium steady state assuming only two conditions; that every reaction is mass balanced and that continuous kinetic reaction rate laws never lead to a negative molecule concentration. These conditions can be verified in polynomial time and are flexible enough to permit one to force a system away from equilibrium. In an expository biochemical example we show how a reversible, mass balanced perpetual reaction, with thermodynamically infeasible kinetic parameters, can be used to perpetually force a kinetic model of anaerobic glycolysis in a manner consistent with the existence of a steady state. Easily testable existence conditions are foundational for efforts to reliably compute non-equilibrium steady states in genome-scale biochemical kinetic models.Comment: 11 pages, 2 figures (v2 is now placed in proper context of the excellent 1962 paper by James Wei entitled "Axiomatic treatment of chemical reaction systems". In addition, section 4, on "Utility of steady state existence theorem" has been expanded.

Chronic dermatomycoses of the foot as risk factors for acute bacterial cellulitis of the leg: A case-control study

Objective: To assess the role of foot dermatomycosis ( tinea pedis and onychomycosis) and other candidate risk factors in the development of acute bacterial cellulitis of the leg. Methods: A case-control study, including 243 patients ( cases) with acute bacterial cellulitis of the leg and 467 controls, 2 per case, individually matched for gender, age (+/-5 years), hospital and admission date (+/-2 months). Results: Overall, mycology-proven foot dermatomycosis was a significant risk factor for acute bacterial cellulitis (odds ratio, OR: 2.4; p < 0.001), as were tinea pedis interdigitalis (OR: 3.2; p < 0.001), tinea pedis plantaris (OR: 1.7; p = 0.005) and onychomycosis (OR: 2.2; p < 0.001) individually. Other risk factors included: disruption of the cutaneous barrier, history of bacterial cellulitis, chronic venous insufficiency and leg oedema. Conclusions: Tinea pedis and onychomycosis were found to be significant risk factors for acute bacterial cellulitis of the leg that are readily amenable to treatment with effective pharmacological therapy. Copyright (C) 2004 S. Karger AG, Basel

Attributable deaths and disability-adjusted life-years caused by infections with antibiotic-resistant bacteria in the EU and the European Economic Area in 2015: a population-level modelling analysis

Background: Infections due to antibiotic-resistant bacteria are threatening modern health care. However, estimating their incidence, complications, and attributable mortality is challenging. We aimed to estimate the burden of infections caused by antibiotic-resistant bacteria of public health concern in countries of the EU and European Economic Area (EEA) in 2015, measured in number of cases, attributable deaths, and disability-adjusted life-years (DALYs). Methods: We estimated the incidence of infections with 16 antibiotic resistance–bacterium combinations from European Antimicrobial Resistance Surveillance Network (EARS-Net) 2015 data that was country-corrected for population coverage. We multiplied the number of bloodstream infections (BSIs) by a conversion factor derived from the European Centre for Disease Prevention and Control point prevalence survey of health-care-associated infections in European acute care hospitals in 2011–12 to estimate the number of non-BSIs. We developed disease outcome models for five types of infection on the basis of systematic reviews of the literature. Findings: From EARS-Net data collected between Jan 1, 2015, and Dec 31, 2015, we estimated 671 689 (95% uncertainty interval [UI] 583 148–763 966) infections with antibiotic-resistant bacteria, of which 63·5% (426 277 of 671 689) were associated with health care. These infections accounted for an estimated 33 110 (28 480–38 430) attributable deaths and 874 541 (768 837–989 068) DALYs. The burden for the EU and EEA was highest in infants (aged <1 year) and people aged 65 years or older, had increased since 2007, and was highest in Italy and Greece. Interpretation: Our results present the health burden of five types of infection with antibiotic-resistant bacteria expressed, for the first time, in DALYs. The estimated burden of infections with antibiotic-resistant bacteria in the EU and EEA is substantial compared with that of other infectious diseases, and has increased since 2007. Our burden estimates provide useful information for public health decision-makers prioritising interventions for infectious diseases

Effective treatment of experimental acute otitis media by application of volatile fluids into the ear canal

To access publisher version of this article. Please click on the hyperlink in Additional Link fieldTo access full text version of this article. Please click on the hyperlink "View/Open" at the bottom of this pageEssential oils are volatile and can have good antimicrobial activity. We compared the effects of oil of basil (Ocimum basilicum) and essential oil components (thymol, carvacrol, and salicylaldehyde) to those of a placebo when placed in the ear canal of rats with experimental acute otitis media caused by pneumococci or Haemophilus influenzae. Progress was monitored by otomicroscopic examination and middle ear cultures. The treatment with oil of basil or essential oil components cured or healed 56%-81% of rats infected with H. influenzae and 6%-75% of rats infected with pneumococci, compared with 5.6%-6% of rats in the placebo group. Essential oils or their components placed in the ear canal can provide effective treatment of acute otitis media

Geðheilbrigði á vinnustöðum : möguleikar til forvarna og ráðgjafar

Neðst á síðunni er hægt að nálgast greinina í heild sinni með því að smella á hlekkinn Skoða/Opna(view/open)Vinna í einu formi eða öðru er öllum nauðsynleg jafnt samfélagi sem einstaklingum. Markmið með vinnu er að skapa velmegun og vellíðan okkur sjálfum til handa, fjölskyldum okkar, fyrirtækjum sem við vinnum hjá og samfélagi því sem við búum í. E f vinnan skapar ekki velmegun og vellíðan, heldur veldur tapi og vanlíðan þá hættum við að stunda slíka vinnu og leitum verkefna sem uppfylla grundvallarmarkmið vinnu. Það er ekki skynsamlegt að gera ráð fyrir því að mikilvægi vinnu sé minna fyrir þá sem eru með geðraskanir eða aðra sjúkdóma en þá sem eru heilbrigðir. Það má gera sér í hugarlund að í raun sé mikilvægi hennar enn meira í þessum hópi. Vinnan rífur félagslega einangrun og setur skipulag á daginn jafnframt því sem hún örvar fólk til dáða. Að sama skapi eru slæm áhrif atvinnuleysis og atvinnuóöryggis á heilsu og félagslega velferð manna vel þekkt1. Beinn tollur á atvinnulífi vegna geðsjúkdóma er umtalsverður en þeir eru á meðal fimm algengustu ástæðna fyrir skammtíma fjarvistum frá vinnustöðum og talið er að um 25% starfsmanna hafa veruleg óþægindi af vinnutengdum geð- og streitu einkennum ár hvert í E vrópu2. Fjarvistir hvort sem er langtíma eða skammtíma eru ákaflega skýr merki um að veikindi starfsmanns séu að bitna á vinnu hans. V eikur í vinnu er hins vegar flestum framandi hugmynd því það að fara í vinnu er í hugum flestra merki um ákveðið heilbrigði. Á þessu þarf þó að hafa fyrirvara en skv. kanadískri rannsókn þá eru bein áhrif s.k. líkamlegra sjúkdóma á minnkun í framleiðni skýr og fremur auðgreinanleg. Hins vegar eru áhrif geðsjúkdóma á framleiðni meiri, og oftar dulin og tormetin t.d. vegna þess að starfsmaður mætir til vinnu en afköst hans eru skert3. Geðraskanir eru algengasta ástæða örorku á íslenskum vinnumarkaði og hafa aukist að umfangi hin síðari ár og eru nú um helmingur af meginorsök fyrir örorku4, 5. Þetta hefur gerst þrátt fyrir að algengi geðraskana á síðast liðnum tuttugu árum hefur ekki aukist í samfélaginu6

Hreyfing eða hreyfingarleysi barna í nútímanum

Neðst á síðunni er hægt að nálgast greinina í heild sinni með því að smella á hlekkinn View/OpenVandamálið offita og hreyfingarleysi barna er orðið að faraldri, að minnsta kosti í hinum vestræna heimi. Fjöldi feitra barna eykst stöðugt og afleiðingarnar eru sykursýki, hjartasjúkdómar, slitgigt og fleira. Íslenskar rannsóknir á þessu sviði eru enn af skornum skammti. Erlendar rannsóknir sýna hinsvegar að ná megi góðum árangri með offeit börn í átaksverkefnum þar sem útkoman er minni fituprósenta, aukið þol og betri matarvenjur. Það virðast helst vera þrír þættir sem skipta sköpum í baráttunni við þann vágest sem offitan er. Skipulag skólanna, skipulag bæjar- og sveitarfélaga og foreldrar sjálfir. Aðalnámsskrá skólanna segir að það sé ekki einungis hagur hvers nemanda að fá markvissa kennslu í íþróttum heldur getur það einnig ráðið miklu um heilbrigði þjóðarinnar. Sveitarfélög og Lýðheilsustöð hafa nú tekið höndum saman til að stuðla að aukinni hreyfingu og bættu mataræði barna. Framtíðarhugmynd er að samtvinna hreyfingu og hefðbundið skólastarf, í mun meiri mæli en gert er í dag. Bæjarog sveitarfélög mega ekki loka hreyfiþörf barna okkar inni með óbarnvænu skipulagi í bæjum og borgum. Foreldrar þurfa að taka sig á og muna að þeir eru sterkustu fyrirmyndir barna sinna