Explore the vast range of titles available.

Background:There is evidence that ultra-endurance exercise causes myocardial injury. The extent and duration of these changes remains unresolved. Recent reports have speculated that structural adaptations to exercise, particularly of the right ventricle, may predispose to tachyarrhythmias and sudden cardiac death.Objective:To quantify the extent and duration of post-exercise cardiac injury with particular attention to right ventricular (RV) dysfunction.Methods:27 athletes (20 male, 7 female) were tested 1 week before, immediately after and 1 week after an ultra-endurance triathlon. Tests included cardiac troponin I (cTnI), B-type natriuretic peptide (BNP) and comprehensive echocardiographic assessment.Results:26 athletes completed the race and testing procedures. Post-race, cTnI was raised in 15 athletes (58%) and the mean value for the entire cohort increased (0.17 vs 0.49 μg/l, p<0.01). BNP rose in every athlete and the mean increased significantly (12.2 vs 42.5 ng/l, p<0.001). Left ventricular ejection fraction (LVEF) was unchanged (60.4% vs 57.5%, p = 0.09), but integrated systolic strain decreased (16.9% vs 15.1%, p<0.01). New regional wall motion abnormalities developed in seven athletes (27%) and LVEF was reduced in this subgroup (57.8% vs 45.9%, p<0.001). RV function was reduced in the entire cohort with decreases in fractional area change (0.47 vs 0.39, p<0.01) and tricuspid annular plane systolic excursion (21.8 vs 19.1 mm, p<0.01). At follow-up, all variables returned to baseline except in one athlete where RV dysfunction persisted.Conclusion:Myocardial damage occurs during intense ultra-endurance exercise and, in particular, there is a significant reduction in RV function. Almost all abnormalities resolve within 1 week.

Emotional distress as a trigger for acute myocardial infarction is beginning to gain credibility as it is recognised that traditional risk factors can account for only half of all myocardial infarctions. Here, three cases of myocardial infarction are presented in the setting of an acute emotional stressor, with coronary angiography showing only minimal coronary artery disease. In all cases striking wall motion abnormalities, mimicking a “tako-tsubo”, were noted with complete resolution within 30 days. This pattern suggests tako-tsubo-like transient left ventricular dysfunction.

ObjectiveTo measure cognition in patients before and after coronary angiography.DesignProspective observational cohort study.SettingUniversity teaching hospital.Patients56 patients presenting for elective coronary angiography.Main outcome measuresComputerised cognitive test battery administered before coronary angiography, before discharge from hospital and 7 days after discharge. A matched healthy control group was used as a comparator.ResultsWhen analysed by group, coronary angiography patients performed worse than matched controls at each time point. When the cognitive change was examined for each individual, of the 48 patients tested at discharge, 19 (39.6%) were classified as having a new cognitive dysfunction, and of 49 patients tested at day 7, six (12.2%) were classified as having a new cognitive dysfunction.ConclusionsThe results confirm that cognitive function is decreased in patients who have cardiovascular disease. Furthermore, coronary angiography may exacerbate this impaired cognition in some patients.

Background This paper presents a protocol for a randomised controlled trial of the Cardiac-Diabetes Transcare program which is a transitional care, multi-modal self-management program for patients with acute coronary syndrome comorbid with type 2 diabetes. Prior research has indicated people hospitalised with dual cardiac and diabetes diagnoses are at an elevated risk of hospital readmissions, morbidity and mortality. The primary aim of this study is to evaluate the effectiveness (and cost-effectiveness) of a Cardiac-Diabetes Transcare intervention program on 6-month readmission rate in comparison to usual care. Methods/Design A two-armed, randomised controlled trial with blinded outcome assessment will be conducted to evaluate the comparative effectiveness of two modes of care, including a Usual Care Group and a Cardiac-Diabetes Transcare Intervention (in addition to usual care) Group. The primary outcome is 6-month readmission rate, although a range of secondary outcomes will be collected (including self-efficacy) at baseline, 1, 3 and 6 month reassessments. The intervention group will receive in-hospital education tailored for people recovering from an acute coronary syndrome-related hospital admission who have comorbid diabetes, and they will also receive home visits and telephone follow-up by a trained Research Nurse to reinforce and facilitate disease-management-related behaviour change. Both groups will receive usual care interventions offered or referred from participating hospital facilities. A sample size of 432 participants from participating hospitals in the Australian states of Queensland and Victoria will be recruited for 90% power based on the most conservative scenarios modelled for sample size estimates. Discussion The study outlined in this protocol will provide valuable insight into the effectiveness of a transitional care intervention targeted for people admitted to hospital with cardiac-related presentations commencing in the inpatient hospital setting and transition to the home environment. The purpose of theory-based intervention comprising face-to-face sessions and telephone follow up for patients with acute coronary syndrome and type 2 diabetes is to increase self-efficacy to enhance self-management behaviours and thus improve health outcomes and reduce hospital readmissions. Trial registration This study has been registered with the Australian New Zealand Clinical Trials Registry dated 16/12/2014: ACTRN12614001317684 .

The purpose of this study is to evaluate the feasibility and patient acceptability of a novel artificial intelligence (AI)-based diabetic retinopathy (DR) screening model within endocrinology outpatient settings. Adults with diabetes were recruited from two urban endocrinology outpatient clinics and single-field, non-mydriatic fundus photographs were taken and graded for referable DR ( ≥ pre-proliferative DR). Each participant underwent; (1) automated screening model; where a deep learning algorithm (DLA) provided real-time reporting of results; and (2) manual model where retinal images were transferred to a retinal grading centre and manual grading outcomes were distributed to the patient within 2 weeks of assessment. Participants completed a questionnaire on the day of examination and 1-month following assessment to determine overall satisfaction and the preferred model of care. In total, 96 participants were screened for DR and the mean assessment time for automated screening was 6.9 minutes. Ninety-six percent of participants reported that they were either satisfied or very satisfied with the automated screening model and 78% reported that they preferred the automated model over manual. The sensitivity and specificity of the DLA for correct referral was 92.3% and 93.7%, respectively. AI-based DR screening in endocrinology outpatient settings appears to be feasible and well accepted by patients.

Background Type 1 diabetes (T1D) places an extraordinary burden on individuals and their families, as well as on the healthcare system. Despite recent advances in glucose sensors and insulin pump technology, only a minority of patients meet their glucose targets and face the risk of both acute and long-term complications, some of which are life-threatening. The JAK-STAT pathway is critical for the immune-mediated pancreatic beta cell destruction in T1D. Our pre-clinical data show that inhibitors of JAK1/JAK2 prevent diabetes and reverse newly diagnosed diabetes in the T1D non-obese diabetic mouse model. The goal of this study is to determine if the JAK1/JAK2 inhibitor baricitinib impairs type 1 diabetes autoimmunity and preserves beta cell function. Methods This will be as a multicentre, two-arm, double-blind, placebo-controlled randomized trial in individuals aged 10–30 years with recent-onset T1D. Eighty-three participants will be randomized in a 2:1 ratio within 100 days of diagnosis to receive either baricitinib 4mg/day or placebo for 48 weeks and then monitored for a further 48 weeks after stopping study drug. The primary outcome is the plasma C-peptide 2h area under the curve following ingestion of a mixed meal. Secondary outcomes include HbA1c, insulin dose, continuous glucose profile and adverse events. Mechanistic assessments will characterize general and diabetes-specific immune responses. Discussion This study will determine if baricitinib slows the progressive, immune-mediated loss of beta cell function that occurs after clinical presentation of T1D. Preservation of beta cell function would be expected to improve glucose control and prevent diabetes complications, and justify additional trials of baricitinib combined with other therapies and of its use in at-risk populations to prevent T1D. Trial registration ANZCTR ACTRN12620000239965 . Registered on 26 February 2020. ClinicalTrials.gov NCT04774224. Registered on 01 March 2021

The Great Lakes‐St Lawrence River basin is the world's most invaded freshwater system. Ballast water release from transoceanic shipping is deemed responsible for 65% of invasions in the basin since the modern St. Lawrence Seaway opened in 1959. Regulations requiring mid‐ocean exchange of ballast water applied in 1993 failed to stem ship‐mediated invasions because the procedure was not mandated for all ships. In 2006 and 2008, Canada and the United States, respectively, mandated that all transoceanic ships should conduct open ocean flushing to ensure that partially filled ballast tanks intended for discharge into the Great Lakes contained water of salinity ≥30 ppt before entering the Seaway. These regulations have been strictly enforced through record inspections and tests of ballast tank salinities of inbound ships. Before‐and‐after comparisons of total organismal abundance and species richness in ballast tanks revealed a substantial reduction in invasion risk from ships that conducted saltwater flushing. Since 2006, the rate of discovery of newly established non‐native species in the Great Lakes declined by 85% to its lowest level in two centuries. While multiple factors could plausibly contribute to this decline, empirical evidence supports the 2006/2008 ballast water regulation as the primary cause, highlighting the benefit of internationally coordinated vector control.

Infection of macrophages by the intracellular protozoan Leishmania leads to down-regulation of a number of macrophage innate host defense mechanisms, thereby allowing parasite survival and replication. The underlying molecular mechanisms involved remain largely unknown. In this study, we assessed epigenetic changes in macrophage DNA methylation in response to infection with L. donovani as a possible mechanism for Leishmania driven deactivation of host defense. We quantified and detected genome-wide changes of cytosine methylation status in the macrophage genome resulting from L. donovani infection. A high confidence set of 443 CpG sites was identified with changes in methylation that correlated with live L. donovani infection. These epigenetic changes affected genes that play a critical role in host defense such as the JAK/STAT signaling pathway and the MAPK signaling pathway. These results provide strong support for a new paradigm in host-pathogen responses, where upon infection the pathogen induces epigenetic changes in the host cell genome resulting in downregulation of innate immunity thereby enabling pathogen survival and replication. We therefore propose a model whereby Leishmania induced epigenetic changes result in permanent down regulation of host defense mechanisms to protect intracellular replication and survival of parasitic cells.

Janus kinase (JAK) inhibitors, including baricitinib, block cytokine signaling and are effective disease-modifying treatments for several autoimmune diseases. Whether baricitinib preserves β-cell function in type 1 diabetes is unclear. In this phase 2, double-blind, randomized, placebo-controlled trial, we assigned patients with type 1 diabetes diagnosed during the previous 100 days to receive baricitinib (4 mg once per day) or matched placebo orally for 48 weeks. The primary outcome was the mean C-peptide level, determined from the area under the concentration-time curve, during a 2-hour mixed-meal tolerance test at week 48. Secondary outcomes included the change from baseline in the glycated hemoglobin level, the daily insulin dose, and measures of glycemic control assessed with the use of continuous glucose monitoring. A total of 91 patients received baricitinib (60 patients) or placebo (31 patients). The median of the mixed-meal-stimulated mean C-peptide level at week 48 was 0.65 nmol per liter per minute (interquartile range, 0.31 to 0.82) in the baricitinib group and 0.43 nmol per liter per minute (interquartile range, 0.13 to 0.63) in the placebo group (P = 0.001). The mean daily insulin dose at 48 weeks was 0.41 U per kilogram of body weight per day (95% confidence interval [CI], 0.35 to 0.48) in the baricitinib group and 0.52 U per kilogram per day (95% CI, 0.44 to 0.60) in the placebo group. The levels of glycated hemoglobin were similar in the two trial groups. However, the mean coefficient of variation of the glucose level at 48 weeks, as measured by continuous glucose monitoring, was 29.6% (95% CI, 27.8 to 31.3) in the baricitinib group and 33.8% (95% CI, 31.5 to 36.2) in the placebo group. The frequency and severity of adverse events were similar in the two trial groups, and no serious adverse events were attributed to baricitinib or placebo. In patients with type 1 diabetes of recent onset, daily treatment with baricitinib over 48 weeks appeared to preserve β-cell function as estimated by the mixed-meal-stimulated mean C-peptide level. (Funded by JDRF International and others; BANDIT Australian New Zealand Clinical Trials Registry number, ACTRN12620000239965.).

Background The reasons for reduced exercise capacity in diabetes mellitus (DM) remains incompletely understood, although diastolic dysfunction and diabetic cardiomyopathy are often favored explanations. However, there is a paucity of literature detailing cardiac function and reserve during incremental exercise to evaluate its significance and contribution. We sought to determine associations between comprehensive measures of cardiac function during exercise and maximal oxygen consumption ( V ˙ O 2 peak), with the hypothesis that the reduction in exercise capacity and cardiac function would be associated with co-morbidities and sedentary behavior rather than diabetes itself. Methods This case–control study involved 60 subjects [20 with type 1 DM (T1DM), 20 T2DM, and 10 healthy controls age/sex-matched to each diabetes subtype] performing cardiopulmonary exercise testing and bicycle ergometer echocardiography studies. Measures of biventricular function were assessed during incremental exercise to maximal intensity. Results T2DM subjects were middle-aged (52 ± 11 years) with a mean T2DM diagnosis of 12 ± 7 years and modest glycemic control (HbA 1c 57 ± 12 mmol/mol). T1DM participants were younger (35 ± 8 years), with a 19 ± 10 year history of T1DM and suboptimal glycemic control (HbA 1c 65 ± 16 mmol/mol). Participants with T2DM were heavier than their controls (body mass index 29.3 ± 3.4 kg/m 2 vs. 24.7 ± 2.9, P = 0.001), performed less exercise (10 ± 12 vs. 28 ± 30 MET hours/week, P = 0.031) and had lower exercise capacity ( V ˙ O 2 peak = 26 ± 6 vs. 38 ± 8 ml/min/kg, P < 0.0001). These differences were not associated with biventricular systolic or left ventricular (LV) diastolic dysfunction at rest or during exercise. There was no difference in weight, exercise participation or V ˙ O 2 peak in T1DM subjects as compared to their controls. After accounting for age, sex and body surface area in a multivariate analysis, significant positive predictors of V ˙ O 2 peak were cardiac size (LV end-diastolic volume, LVEDV) and estimated MET-hours, while T2DM was a negative predictor. These combined factors accounted for 80% of the variance in V ˙ O 2 peak (P < 0.0001). Conclusions Exercise capacity is reduced in T2DM subjects relative to matched controls, whereas exercise capacity is preserved in T1DM. There was no evidence of sub-clinical cardiac dysfunction but, rather, there was an association between impaired exercise capacity, small LV volumes and sedentary behavior.