Patients with severe mental illness (SMI) have been described at higher risk of cardiovascular disease (CVD). The aim of this systematic review and meta-analysis was to quantify prevalence, incidence, cross-sectional association and longitudinal increased risk of coronary heart disease (CHD), stroke, transient ischemic attack and cerebrovascular disease (CBVD), heart failure (HF), peripheral vascular disease (PVD), death due to CVD, and any CVD in patients with SMI. We included 92 studies, with a total population of 3,371,461 patients (BD = 241,226, MDD = 476,102, SCZ = 1,721,586, SMI = 932,547) and 113,925,577 controls. Pooled prevalence of any CVD in SMI was 9.9% (95% CI = 7.4–13.3) (33 studies, 360,144 patients). Compared to controls, after adjusting for a median of 7 confounders, SMI was associated with higher risk of CVD in cross-sectional studies, OR:1.53 (95% CI = 1.27–1.83) (11 studies), with CHD OR: 1.51 (95% CI = 1.47–1.55) (5 studies), with CBVD OR: 1.42 (95% CI = 1.21–1.66) (6 studies), and tended to be associated with HF OR: 1.28 (95% CI = 0.99–1.65) (4 studies). Cumulative incidence was 3.6 CVD events in a median follow-up period of 8.4 years (range: 1.76–30). After considering a median of 6 confounders, SMI was associated with higher longitudinal risk of CVD in longitudinal studies HR: 1.78 (95% CI = 1.6, 1.98) (31 studies), of CHD: HR: 1.54 (95% CI 1.30–1.82) (18 studies), of CBVD HR: 1.64 (95% CI 1.26–2.14) (11 studies), of HF HR:2.10 (95% CI 1.64–2.70) (2 studies), of PVD, unadjusted RR: 3.11 (95% CI 2.46–3.91) (3 studies), of death due to CVD, HR 1.85 (95% CI 1.53–2.24) (16 studies). In this meta-analysis, the association between SMI and CVD has been quantified in a world representative sample; we suggest prevention of CVD should be warranted as standard care in SMI.

OBJECTIVES/SPECIFIC AIMS: The objective of this study was to determine if trimethylamine N-oxide (TMAO) alone could acutely alter cardiac contractile function on a beat-to-beat basis. METHODS/STUDY POPULATION: CD1 adult mouse hearts were extracted, attached to a force transducer, oxygenated, and paced within an organ bath. Changes in contractility were measured after pipetting or reverse perfusing TMAO through the aorta via a modified Langendorff apparatus to facilitate TMAO delivery into the myocardium. To determine if our findings translated to the human heart, we performed contractility experiments using human right atrial appendage biopsy tissue retrieved during cardiopulmonary bypass procedures. To investigate whether TMAO alters contractile rate, in a separate series of experiments, the atria and sinoatrial node of isolated hearts were kept intact to allow for spontaneous beating without artificial pacing and were treated with TMAO or vehicle. In addition, intracellular calcium measurements were performed on spontaneously beating embryonic rat cardiomyocytes after TMAO or vehicle treatment. RESULTS/ANTICIPATED RESULTS: We found acute exposure to TMAO, diluted into the organ bath, increased average contraction amplitude 20% and 41% at 300 µM and 3000 µM, respectively (p<0.05, n=6). Langendorff reverse perfusion of mouse hearts ex vivo with 300 µM TMAO generated an even greater response than nonperfusion peripheral exposure and increased isometric force 32% (p<0.05, n=3). Consistent with what we observed in mouse hearts, incubation of human atrial muscle tissue with TMAO at 3000 µM increased isometric tension 31% compared with vehicle (p<0.05, n=4). TMAO treatment (3000 µM) also increased average beating frequency of ex vivo mouse hearts by 27% compared with vehicle (p<0.05, n=3) and increased the spontaneous beating frequency of primary rat cardiomyocytes by 13% compared with vehicle treatment (p<0.05, n=4). DISCUSSION/SIGNIFICANCE OF IMPACT: TMAO, at pathological concentrations, directly increases the force and rate of cardiac contractility. Initially, these inotropic and chronotropic effects may be adaptive during CKD; however, chronic increases in isometric tension and beating frequency can promote cardiac remodeling and heart failure. Further translational studies are needed to understand the intricate relationship between the microbiome, kidneys, and heart and to examine if TMAO represents a therapeutic target for reducing cardiovascular mortality in CKD patients.

Benzodiazepines are widely prescribed to manage sleep disorders, anxiety and muscular tension. While providing short-term relief, continued use induces tolerance and withdrawal, and in older users, increases the risk of falls. However, long-term prescription remains common, and effective interventions are not widely available. This study developed a self-managed cognitive behaviour therapy package for cessation of benzodiazepine use delivered to participants via mail (M-CBT) and trialled its effectiveness as an adjunct to a general practitioner (GP)-managed dose reduction schedule. In the pilot trial, participants were randomly assigned to GP management with immediate or delayed M-CBT. Significant recruitment and engagement problems were experienced, and only three participants were allocated to each condition. After immediate M-CBT, two participants ceased use, while none receiving delayed treatment reduced daily intake by more than 50%. Across the sample, doses at 12 months remained significantly lower than baseline, and qualitative feedback from participants was positive. While M-CBT may have promise, improved engagement of GPs and participants is needed for this approach to substantially impact on community-wide benzodiazepine use.

Fiber diffraction data have been obtained from Narcissus mosaic virus, a potexvirus from the family Flexiviridae, and soybean mosaic virus (SMV), a potyvirus from the family Potyviridae. Analysis of the data in conjunction with cryo-electron microscopy data allowed us to determine the symmetry of the viruses and to make reconstructions of SMV at 19 Å resolution and of another potexvirus, papaya mosaic virus, at 18 Å resolution. These data include the first well-ordered data ever obtained for the potyviruses and the best-ordered data from the potexviruses, and offer the promise of eventual high resolution structure determinations.

A historic debate with great implications for theology has resurfaced in New Testament circles; however, it has not received the attention it should by theologians. It concerns how to translate and interpret approximately ten instances of the Greek phrase pistis Christou and its near equivalents in the letters of Paul. This phrase occurs within theologically crucial sections of Romans and Galatians, which have provided the foundation for the Reformation understanding of ‘justification by grace through faith’. The question is whether ‘faith’ in these phrases refers principally to the believer's ‘faith in Christ’, as traditionally understood, or should be translated and understood as ‘the faith of Christ’. In this article, I hope to introduce theologians to this debate and make a contribution to it from a theological angle, by describing the two primary ‘patterns of soteriology’ which are in play, and then examining how easily these different patterns of soteriology can be read onto what Paul writes concerning three crucial issues in his letters: salvation, the Law and the ‘righteousness of God’. I argue that the overall theological vision which includes three facets – a christologically centred understanding of the pistis Christou passages, a broader understanding of pistis, and the centring of soteriology around the concept of ‘participation in Christ’ – provides the most convincing interpretational matrix for reading Paul. I also point out implications this has for contemporary theology.

In the summer of 1980 four members of the University of London Natural History Society went to Lake Alyki in Macedonia to study a population of tortoises Testudo hermanni. Such studies are urgently needed because very little is known about the ecology of Mediterranean tortoises, which are declining seriously, due mainly to habitat loss and collecting for the pet trade. The expedition chose Alyki after an expedition by the same society in 1979 had reported an exceptionally rich wildlife there including a large tortoise population. A new holiday village nearby did not appear to threaten the main wildlife areas, and a commercial salt works only operated at the north end of the lake from which access to the heath was not easy. However, unknown to the four members, the 1980 expedition had walked into an explosive situation. The following account is quoted from their report.