Environmental conditions can modulate the links among oxidative stress, age, and longevity

Understanding the links between environmental conditions and longevity remains a major focus in biological research. We examined within-individual changes between early- and mid-adulthood in the circulating levels of four oxidative stress markers linked to ageing, using zebra finches (Taeniopygia guttata): a DNA damage product (8-hydroxy-2′-deoxyguanosine; 8-OHdG), protein carbonyls (PC), non-enzymatic antioxidant capacity (OXY), and superoxide dismutase activity (SOD). We further examined whether such within-individual changes differed among birds living under control (ad lib food) or more challenging environmental conditions (unpredictable food availability), having previously found that the latter increased corticosterone levels when food was absent but improved survival over a three year period. Our key findings were: (i) 8-OHdG and PC increased with age in both environments, with a higher increase in 8-OHdG in the challenging environment; (ii) SOD increased with age in the controls but not in the challenged birds, while the opposite was true for OXY; (iii) control birds with high levels of 8-OHdG died at a younger age, but this was not the case in challenged birds. Our data clearly show that while exposure to the potentially damaging effects of oxidative stress increases with age, environmental conditions can modulate the pace of this age–related change

Overcoming barriers to guideline implementation: the case of cardiac rehabilitation

Aims: This study explored the strategies used by cardiac rehabilitation (CR) coordinators to overcome the obstacles to implementation of the evidence-based Reducing Risk in Heart Disease guidelines. Methods: The study design used qualitative, semistructured in-depth interviews with 20 CR coordinators from New South Wales, Australia, to explore the strategies used to facilitate guideline implementation. Non-probability sampling was used torecruit CR coordinators to obtain a broad understandingof the issues. Interviews were transcribed and thematic content analysis was undertaken to identify common themes. Results: Coordinators addressed the barriers to implementing guidelines through their commitment tobest practice and striving to overcome the odds through providing opportunistic health education, alternate methods of secondary prevention, and partnering and engaging with local communities.Conclusions: Although CR coordinators face multiplebarriers to implementing evidence-based guidelines for patients with coronary heart disease, they use strategies such as harnessing community capacity and using available resources creatively. The development ofa more integrated, multifactorial and coordinated approach to improving use of guidelines in clinical practice to improve the treatment and secondary prevention of coronary heart disease is urgently needed

Development of a health-related lifestyle self-management intervention for patients with coronary heart disease

Risk-factor modification after an acute coronary event is imperative, and intervention strategies are continuously being developed to assist patients with behavioral change and, consequently, decreasing the risk of further coronary episodes. This article describes the development of the health-related lifestyle self-management (HeLM) intervention, which is a brief structured intervention embedded within the transtheoretical model of behavioral change. The HeLM intervention was developed by undertaking three discrete yet interrelated studies and consisted of the following components: goal-setting, the HeLM booklet, feedback regarding personal risk, team-building and communication with the patient's family physician, three supportive telephone calls, trained interviewers, a refrigerator magnet, and a health diary for self-monitoring. The HeLM intervention has been successfully implemented in 50 patients with acute coronary syndrome after discharge from hospital and has been demonstrated to be feasible and practical and could easily be delivered by health care professionals

Implementing Telerehabilitation Research For Stroke Rehabilitation With Community Dwelling Veterans: Lessons Learned

Telerehabilitation (TR) is the use of telehealth technologies to provide distance support, rehabilitation services and information exchange between people with disabilities and their clinical providers. This article discusses the barriers experienced when implementing a TR multi-site randomized controlled trial for stroke patients in their homes, and the lessons learned from conducting the study. The barriers are divided into two sections: those specific to TR and those pertinent to research overall. The TR specific barriers included the rapidly changing telecommunications and health care environment and inconsistent equipment functionality. The barriers applicable to research overall included the need for telehealth research to meet regulations in diverse departments and the rapidly expanding and changing research regulations. Solutions to the barriers included having various telehealth equipment available to allow for functionality with the currently diverse telecommunications infrastructure, rigorous pilot testing all equipment in different situations, and having biomedical engineering staff on-call and on-site

A pilot randomised controlled trial comparing a health-related lifestyle self-management intervention with standard cardiac rehabilitation following an acute cardiac event: Implications for a larger clinical trial

Summary. Purpose: This pilot study was to assess the feasibility of the health-related lifestyle self-management (HeLM) intervention as a strategy to decrease cardiovascular risk following acute coronary syndrome. Methods: Participants in this randomised controlled trial were recruited from a tertiary teaching hospital in metropolitan Sydney Australia. The multifaceted HeLM intervention, using the principles of the transtheoretical model, involved the use of bibliotherapy, a structured evidence-based approach to cardiovascular risk reduction, a communication strategy with general practitioners, three supportive telephone calls to participants and provision of behavioural prompts and a health record diary. Differences in behavioural and clinical outcomes between the HeLM intervention group (n=29) and the standard cardiac rehabilitation group (n=22) were assessed.Results: A total of 125 participants screened were eligible for participation in the study. Fifty-one participants, mean age 57 years (+8.78) were randomised. At the 8-week follow up, participants in the HeLM intervention group had a reduced systolic blood pressure compared to the standard care group (120.3 S.D.: 16.3 vs. 126.4 S.D.: 14.6). There were no significant differences in diastolic blood pressure and cholesterol levels between the two groups. Participants in both the intervention and control group had a reduction in waist circumference although when compared to baseline values, women in the HeLM intervention group had a greater reduction compared to those receiving standard care. Patients reported high levels of satisfaction with this intervention. Conclusions: Findings support the feasibility of implementing the health-related lifestyle self-management intervention for risk factor modification in patients with acute coronary syndrome. An adequately powered randomised controlled trial is required to test the impact of the intervention on cardiovascular risk reduction

Study protocol: home-based telehealth stroke care: a randomized trial for veterans

<p>Abstract</p> <p>Background</p> <p>Stroke is one of the most disabling and costly impairments of adulthood in the United States. Stroke patients clearly benefit from intensive inpatient care, but due to the high cost, there is considerable interest in implementing interventions to reduce hospital lengths of stay. Early discharge rehabilitation programs require coordinated, well-organized home-based rehabilitation, yet lack of sufficient information about the home setting impedes successful rehabilitation. This trial examines a multifaceted telerehabilitation (TR) intervention that uses telehealth technology to simultaneously evaluate the home environment, assess the patient's mobility skills, initiate rehabilitative treatment, prescribe exercises tailored for stroke patients and provide periodic goal oriented reassessment, feedback and encouragement.</p> <p>Methods</p> <p>We describe an ongoing Phase II, 2-arm, 3-site randomized controlled trial (RCT) that determines primarily the effect of TR on physical function and secondarily the effect on disability, falls-related self-efficacy, and patient satisfaction. Fifty participants with a diagnosis of ischemic or hemorrhagic stroke will be randomly assigned to one of two groups: (a) TR; or (b) Usual Care. The TR intervention uses a combination of three videotaped visits and five telephone calls, an in-home messaging device, and additional telephonic contact as needed over a 3-month study period, to provide a progressive rehabilitative intervention with a treatment goal of safe functional mobility of the individual within an accessible home environment. Dependent variables will be measured at baseline, 3-, and 6-months and analyzed with a linear mixed-effects model across all time points.</p> <p>Discussion</p> <p>For patients recovering from stroke, the use of TR to provide home assessments and follow-up training in prescribed equipment has the potential to effectively supplement existing home health services, assist transition to home and increase efficiency. This may be particularly relevant when patients live in remote locations, as is the case for many veterans.</p> <p>Trial Registration</p> <p>Clinical Trials.gov Identifier: NCT00384748</p

A Novel Chemically Differentiated Mouse Embryonic Stem Cell-Based Model to Study Liver Stages of Plasmodium berghei.

Asymptomatic and obligatory liver stage (LS) infection of Plasmodium parasites presents an attractive target for antimalarial vaccine and drug development. Lack of robust cellular models to study LS infection has hindered the discovery and validation of host genes essential for intrahepatic parasite development. Here, we present a chemically differentiated mouse embryonic stem cell (ESC)-based LS model, which supports complete development of Plasmodium berghei exoerythrocytic forms (EEFs) and can be used to define new host-parasite interactions. Using our model, we established that host Pnpla2, coding for adipose triglyceride lipase, is dispensable for P. berghei EEF development. In addition, we also evaluated in-vitro-differentiated human hepatocyte-like cells (iHLCs) to study LS of P. berghei and found it to be a sub-optimal infection model. Overall, our results present a new mouse ESC-based P. berghei LS infection model that can be utilized to study the impact of host genetic variation on parasite development

A Novel Chemically Differentiated Mouse Embryonic Stem Cell-Based Model to Study Liver Stages of Plasmodium berghei.

Asymptomatic and obligatory liver stage (LS) infection of Plasmodium parasites presents an attractive target for antimalarial vaccine and drug development. Lack of robust cellular models to study LS infection has hindered the discovery and validation of host genes essential for intrahepatic parasite development. Here, we present a chemically differentiated mouse embryonic stem cell (ESC)-based LS model, which supports complete development of Plasmodium berghei exoerythrocytic forms (EEFs) and can be used to define new host-parasite interactions. Using our model, we established that host Pnpla2, coding for adipose triglyceride lipase, is dispensable for P. berghei EEF development. In addition, we also evaluated in-vitro-differentiated human hepatocyte-like cells (iHLCs) to study LS of P. berghei and found it to be a sub-optimal infection model. Overall, our results present a new mouse ESC-based P. berghei LS infection model that can be utilized to study the impact of host genetic variation on parasite development

BMP-9 induced endothelial cell tubule formation and inhibition of migration involves Smad1 driven endothelin-1 production.

BACKGROUND: Bone morphogenetic proteins (BMPs) and their receptors, such as bone morphogenetic protein receptor (BMPR) II, have been implicated in a wide variety of disorders including pulmonary arterial hypertension (PAH). Similarly, endothelin-1 (ET-1), a mitogen and vasoconstrictor, is upregulated in PAH and endothelin receptor antagonists are used in its treatment. We sought to determine whether there is crosstalk between BMP signalling and the ET-1 axis in human pulmonary artery endothelial cells (HPAECs), possible mechanisms involved in such crosstalk and functional consequences thereof. METHODOLOGY/PRINCIPAL FINDING: Using western blot, real time RT-PCR, ELISA and small RNA interference methods we provide evidence that in HPAECs BMP-9, but not BMP-2, -4 and -6 significantly stimulated ET-1 release under physiological concentrations. This release is mediated by both Smad1 and p38 MAPK and is independent of the canonical Smad4 pathway. Moreover, knocking down the ALK1 receptor or BMPR II attenuates BMP-9 stimulated ET-1 release, whilst causing a significant increase in prepro ET-1 mRNA transcription and mature peptide release. Finally, BMP-9 induced ET-1 release is involved in both inhibition of endothelial cell migration and promotion of tubule formation. CONCLUSIONS/SIGNIFICANCE: Although our data does not support an important role for BMP-9 as a source of increased endothelial ET-1 production seen in human PAH, BMP-9 stimulated ET-1 production is likely to be important in angiogenesis and vascular stability. However, increased ET-1 production by endothelial cells as a consequence of BMPR II dysfunction may be clinically relevant in the pathogenesis of PAH