Vintherpenn2157

Hypertrophic cardiomyopathy is the most common genetically determined cardiac disease with a prevalence of 0.2-0.6%. The most important pathophysiological phenomenon is dynamic obstruction predominantly of the left ventricular outflow tract in 70% of the patients. Clinical symptoms (e.g. dyspnea, angina pectoris and syncope) are extremely variable depending on changes in preload and afterload and an increased risk of sudden cardiac death particularly in younger patients. The diagnostic measures should be carried out with respect to a prognostic and symptomatic treatment with implantation of an implantable cardioverter defibrillator (ICD) in cases of increased risk of sudden cardiac death. When medication treatment fails, first-line treatment consists of septal ablation and surgical myectomy as a supplementary measure, depending on the underlying morphology and experience of the surgeon.PURPOSE Bereavement is associated with increased morbidity and mortality, but few studies have examined the specific timing of depression onset. This study examines the risk of developing new-onset depression in adult children and partners by month, 1 year before and after death. METHODS Using population-based registers in Denmark, we assembled a cohort of 236,000 individuals who died a natural death (2010-2016). Partners and adult children of the deceased were identified and demographic and prescription data were collected. GEE logistic regression was used to model whether the bereaved received a new antidepressant prescription around the death of their loved one across 24 time intervals (12 months before and after death). RESULTS Male and female partners had an increase in receipt of new antidepressant prescriptions in the 11 months after the death of their partner, with a peak increase 2 or 3 months after death. Partners also increased new antidepressant prescription use 2 months before death. Characteristics of the decedents including cause of death were not associated with new antidepressant prescription in the surviving partner. Adult children did not have increased odds of being prescribed new antidepressants at any time. CONCLUSION Both male and female partners have increase in new antidepressant utilization before and after the death of their partner. Our work points to the importance of supporting partners not only after the death of their partner, but also in the period before death when families may be actively engaged in caregiving for the seriously ill.OBJECTIVES The purpose of this study is to analyse the effect of a community participation programme based on the ecosystem model on the incidence of dengue in urban communities. METHODS A randomized controlled field trial was conducted in the state of Colima, Mexico. The intervention consisted of a community participation programme focused on the ecosystem; simultaneously, the control groups were communities that only received the usual official prevention programs. The incidence of dengue was estimated in people of both groups due to the appearance of de novo IgM antibodies during the follow-up period. RESULTS The incidence of dengue in the intervened group was 2.58%/month (n = 818) and in control group 2.26%/month (n = 994), with a risk ratio of 1.14 (95% CI 0.89-1.45) and a PAF of 0.06 (95% CI - 0.056 to 0.16). The A. aegypti larval density (Breteau Index) was reduced in the treated group. CONCLUSIONS The implementation of a community participation programme in the cities of Colima, Mexico, showed a slightly counterproductive effect on the incidence of dengue. This happened even with a reduction in the A. aegypti index.Estragole, naturally occurring in a variety of herbs and spices, can form DNA adducts after bioactivation. Estragole DNA adduct formation and repair was studied in in vitro liver cell models, and a molecular dynamics simulation was used to investigate the conformation dependent (in)efficiency of N2-(trans-isoestragol-3'-yl)-2'-deoxyguanosine (E-3'-N2-dG) DNA adduct repair. HepG2, HepaRG cells, primary rat hepatocytes and CHO cells (including CHO wild-type and three NER-deficient mutants) were exposed to 50 μM estragole or 1'-hydroxyestragole and DNA adduct formation was quantified by LC-MS immediately following exposure and after a period of repair. Results obtained from CHO cell lines indicated that NER plays a role in repair of E-3'-N2-dG adducts, however, with limited efficiency since in the CHO wt cells 80% DNA adducts remained upon 24 h repair. Inefficiency of DNA repair was also found in HepaRG cells and primary rat hepatocytes. Changes in DNA structure resulting from E-3'-N2-dG adduct formation were investigated by molecular dynamics simulations. Results from molecular dynamics simulations revealed that conformational changes in double-stranded DNA by E-3'-N2-dG adduct formation are small, providing a possible explanation for the restrained repair, which may require larger distortions in the DNA structure. NER-mediated enzymatic repair of E-3'-N2-dG DNA adducts upon exposure to estragole will be limited, providing opportunities for accumulation of damage upon repeated daily exposure. The inability of this enzymatic repair is likely due to a limited distortion of the DNA double-stranded helix resulting in inefficient activation of nucleotide excision repair.P-glycoprotein (P-gp) is an ABC transporter exhibiting high pharmacotoxicological relevance by extruding a wide range of cytotoxic compounds out of the cells. Previously, we demonstrated that the phytoestrogen genistein (GNT) modulates P-gp expression in hepatocellular carcinoma in vitro. Although several beneficial effects (e.g., antioxidant, antimutagenic, anticancer) have been attributed to GNT, the molecular mechanisms have not been totally elucidated. Selleck SB-297006 In the present work, we evaluated the effect of GNT on P-gp expression in rat liver, kidney and ileum. We found that GNT (5 mg/kg daily s.c. 3 days) increased hepatic P-gp expression and also Mdr1a (one of the genes encoding P-gp) mRNA levels. Renal and intestinal P-gp remained unchanged after GNT treatment. Hepatic P-gp activity measured with rhodamine-123 and digoxin, both well-known P-gp substrates, was also increased. In vitro experiments using hepatocyte primary cell culture demonstrated that inhibition of ER-α with ICI182/780 did not prevent Mdr1a mRNA up-regulation by GNT (10 µM).