Conflicting phylogenetic signals in the SlX1/Y1 gene in Silene

Background: Increasing evidence from DNA sequence data has revealed that phylogenies based on different genes may drastically differ from each other. This may be due to either inter- or intralineage processes, or to methodological or stochastic errors. Here we investigate a spectacular case where two parts of the same gene (SlX1/Y1) show conflicting phylogenies within Silene (Caryophyllaceae). SlX1 and SlY1 are sex-linked genes on the sex chromosomes of dioecious members of Silene sect. Elisanthe. Results: We sequenced the homologues of the SlX1/Y1 genes in several Sileneae species. We demonstrate that different parts of the SlX1/Y1 region give different phylogenetic signals. The major discrepancy is that Silene vulgaris and S. sect. Conoimorpha (S. conica and relatives) exchange positions. To determine whether gene duplication followed by recombination (an intralineage process) may explain the phylogenetic conflict in the Silene SlX1/Y1 gene, we use a novel probabilistic, multiple primer-pair PCR approach. We did not find any evidence supporting gene duplication/loss as explanation to the phylogenetic conflict. Conclusion: The phylogenetic conflict in the Silene SlX1/Y1 gene cannot be explained by paralogy or artefacts, such as in vitro recombination during PCR. The support for the conflict is strong enough to exclude methodological or stochastic errors as likely sources. Instead, the phylogenetic incongruence may have been caused by recombination of two divergent alleles following ancient interspecific hybridization or incomplete lineage sorting. These events probably took place several million years ago. This example clearly demonstrates that different parts of the genome may have different evolutionary histories and stresses the importance of using multiple genes in reconstruction of taxonomic relationships. </p

Effectiveness of Prophylactic Antibiotics in a Population-Based Cohort of Patients Undergoing Planned Cholecystectomy

In the absence of randomized controlled trials with sufficient power to assess the effectiveness of prophylactic antibiotics (PA), the best evidence is provided by large population-based register studies. The Swedish Register of Gallstone Surgery and ERCP (GallRiks) started in May 2005 and reached 75% national coverage in 2007. During 2006 and 2007, a total of 16,400 operations were registered in GallRiks. In the present study, all elective procedures performed in 2006-2007 in units performing at least 25 operations annually were included in an analysis of the risk for postoperative infectious complications Altogether 10,927 procedures were performed 2006-2007. Univariate logistic regression analysis revealed a paradoxical increase in postoperative infectious complications requiring antibiotic treatment and postoperative abscess if PA were given (p < 0.05). This increase disappeared in multivariate analysis with adjustment for age, gender, presence of cholecystitis, accidental gallbladder perforation, and presence of bile duct stones. No benefit from PA was seen in this study on elective cholecystectomy. Although a randomized controlled trial could possibly show a reduction in the risk for postoperative infectious complications not detected in this study, such a reduction must be weighed against the risk of promoting drug resistance by the widespread use of PA

Childhood bereavement and risk of type 1 diabetes : a Swedish population-based register study

Background and aims: Loss of a first-degree family member in childhood constitutes a major psychological stressor, and is associated both with subsequent psychiatric and somatic morbidity. The potential influence on type 1 diabetes risk has however not yet been fully elucidated. In this study we therefore aimed to investigate the impact of childhood bereavement on type 1 diabetes risk.Materials and methods: We conducted a population-based study in Sweden, encompassing 2,321,318 children born in Sweden January 1 1990 to December 31 2012. The follow up ended December 31 2013, at death of the child, type 1 diabetes diagnosis, emigration or when the child turned 19 years. All children were followed from the age of one, with exposure defined as death of a mother, father, or sibling. Type 1 diabetes diagnoses were extracted from the National Patient Register. We applied Cox proportional hazards models with attained age as time scale and loss of family member as a time varying variable, adjusting for potential confounders including parental type 1 diabetes, parental country of birth, and region of residence. We further categorized child age at bereavement as pre-school (1-6 years), school age (7-12 years) and teenage (13-18 years).Results: During follow-up (median 10.8 years), 50,253 (2.2%) children experienced loss of a family member. Median age at loss was 9.6 years, and 32% of all deaths were categorized as traumatic (accident, suicide, violence, or other sudden unnatural deaths). In total 10,965 children were diagnosed with type 1 diabetes during follow-up and median age at diagnosis was 8.5 years. We observed no overall association between childhood bereavement and type 1 diabetes risk (crude HR 1.00, 95% CI 0.86-1.18, adjusted HR 0.96, 95% CI 0.82 -1.13). The risk was not influenced by sex of the child, cause of death of family member, or familial relationship to the deceased. However, we noted an association when the exposure occurred during the teenage years (adjusted HR 1.67, 95% CI 1.15-2.43).Conclusion: Overall, childhood bereavement was not associated with the risk of type 1 diabetes, but the impact of childhood loss on type 1 diabetes may be modified by age at bereavement.</p

Associations of HbA1c and educational level with risk of cardiovascular events in 32871 drug-treated patients with Type2 diabetes: a cohort study in primary care

Aims To explore the association of HbA1c and educational level with risk of cardiovascular events and mortality in patients with Type2 diabetes. Methods A cohort of 32871 patients with Type2 diabetes aged 35years and older identified by extracting data from electronic patient records for all patients who had a diagnosis of Type2 diabetes and had glucose-lowering agents prescribed between 1999 and 2009 at 84 primary care centres in Sweden. Associations of mean HbA1c levels and educational level with risks of cardiovascular events and all-cause mortality were analysed. Results The associations of HbA1c with risk of all-cause and cardiovascular mortality were J-shaped, with the lowest risk observed for cardiovascular mortality at an HbA1c level of 51mmol/mol (6.8%) for subjects on oral agents and 56mmol/mol (7.3%) in insulin-treated patients. The lowest risk observed for all-cause mortality was at an HbA1c level of 51mmol/mol (6.8%) for subjects on oral agents and 56mmol/mol (7.3%) in insulin-treated patients. There was an increased risk for cardiovascular death [hazard ratio1.6 (1.22.1), P=0.0008] at the lowest HbA1c decile for subjects in the low education category. For subjects with higher education there was no evident J curve for cardiovascular death [hazard ratio1.2 (0.81.6), P=0.3873]. Conclusions Our results lend support to the recent American Diabetes Association/ European Association for the Study of Diabetes position statement that emphasizes the importance of additional factors, including the propensity for hypoglycaemia, which should influence HbA1c targets and treatment choices for individual patients. (Clinical Trials Registry No; NCT 01121315

Changes in body mass index following newly diagnosed type 2 diabetes and risk of cardiovascular mortality: A cohort study of 8486 primary-care patients

Aims. - Elevated body mass index (BMI) is associated with an increased risk of type 2 diabetes and cardiovascular disease (CVD). This study explored the association between BMI changes in the first 18 months of newly diagnosed type 2 diabetes and the risk of long-term CVD mortality. Methods. - A total of 8486 patients with newly diagnosed type 2 diabetes and no previous history of CVD or cancer were identified from 84 primary-care centres in Sweden. During the first year after diagnosis, patients were grouped according to BMI change: 'Increase', or >= +1 BMI unit; 'unchanged', or between +1 and-1 BMI unit; and 'decrease', or <=-1 BMI unit. Associations between BMI change and CVD mortality, defined as death from stroke, myocardial infarction or sudden death, were estimated using adjusted Cox proportional hazards models (NCT 01121315). Results. - Baseline mean age was 60.0 years and mean BMI was 30.2 kg/m(2). Patients were followed for up to 9 years (median: 4.6 years). During the first 18 months, 53.4% had no change in their BMI, while 32.2% decreased and 14.4% increased. Compared with patients with unchanged BMI, those with an increased BMI had higher risks of CVD mortality (hazard ratio: 1.63, 95% CI: 1.11-2.39) and all-cause mortality (1.33, 1.01-1.76). BMI decreases had no association with these risks compared with unchanged BMI: 1.06 (0.76-1.48) and 1.06 (0.85-1.33), respectively. Conclusion. - Increased BMI within the first 18 months of type 2 diabetes diagnosis was associated with an increased long-term risk of CVD mortality. However, BMI decrease did not lower the long-term risk of mortality. (C) 2013 Elsevier Masson SAS. All rights reserved

2207Cardiovascular outcome in THEMIS -like type 2 diabetes patients in Sweden: a nationwide observational study

Abstract Background The THEMIS study (NCT01991795; in analysis phase; n=19,349) compares the effect of dual antiplatelet therapy (DAPT) vs ASA alone for the prevention of major cardiovascular (CV) events in type 2 diabetes (T2D) patients with coronary artery disease (CAD) at high CV risk, but without prior myocardial infarction (MI) or stroke. However, there is a lack of real-life data on CV risk in a THEMIS-like population compared to MI patients, where treatment with DAPT is guideline standard. The aim of this study was to investigate the CV risk in a THEMIS-like population vs an MI population Methods Patients invasively managed in Sweden (2006–2014) were identified using the SWEDEHEART registry and the National Patient Registry. Two populations were studied: a THEMIS-like population including patients with CAD and T2D, ≥1 vessel disease or elective percutaneous coronary intervention [PCI], and no prior stroke or MI), and a MI patient population alive at discharge. The cumulative incidence of the primary composite outcome (CV death (CVD)/MI/stroke) was estimated 3 years after index using the Kaplan-Meier method, and with probability plots adjusted for age, sex, atrial fibrillation, and heart failure. A 30 days blanking period for outcome was added to ensure capture of new events (index THEMIS-pop.: after angiography; index MI-pop.: after discharge). Results Overall, 6,534 THEMIS-like patients and 96,638 MI patients were included. At index, the THEMIS-like patients (CAD and T2D without previous MI/stroke) were aged 67.1 years (mean), 26.6% women, 9.2% AF, and 4.7% HF, while the MI patients were aged 67.3 years (mean), 30.7% women, 15.5% T2D, 17.9% previous MI, 5.2% stroke, 6.4% AF, and 4.8% HF. Three-year cumulative incidence for the composite outcome CVD/MI/stroke was 0.149 (95% CI 0.140, 0.158) for THEMIS-like patients, and 0.148 (95% CI 0.145, 0,15) for MI patients (p=0.88 log rank test) (Figure). Corresponding adjusted probably plots: 0.135 (95% CI 0.127, 0.143) and 0.131 (95% CI 0.128, 0.133). MI was the main risk driver with greatest cumulative incidence in both populations (0.091 vs 0.087) (Figure). Figure 1 Conclusions In this Swedish real-life setting, THEMIS-like patients, followed from 30 days after invasive intervention, had a similar long-term risk for CV events compared with MI patients surviving 30 days after discharge, with MI as the main risk driver, despite having no previous ischemic events. The present data indicate that long-term ischemic risk prevention should be a key strategy in coronary artery disease patients with diabetes requiring elective invasive intervention. Acknowledgement/Funding AstraZeneca </jats:sec