Acceptability, Feasibility and Preliminary Evaluation of a Novel, Personalised, Home based Physical Activity Intervention for Chronic Heart Failure (Active-at-Home-HF)::A Pilot Study

Purpose: Less than 10% of heart failure patients in the UK participate in cardiac rehabilitation programmes. The present pilot study evaluated feasibility, acceptability and physiological effects of a novel, personalised, home-based physical activity intervention in chronic heart failure. Methods: Twenty patients (68±7 years old, 20% females) with stable chronic heart failure due to reduced left ventricular ejection fraction (31±8 %) participated in a single group, pilot study assessing the feasibility and acceptability of a 12-week personalised home-based physical activity intervention aiming to increase daily number of steps by 2000 from baseline (Active-at-Home-HF). Patients completed cardiopulmonary exercise testing with non-invasive gas exchange and haemodynamic measurements and quality of life questionnaire pre- and post-intervention. Patients were supported weekly via telephone and average weekly step count data collected using pedometers. Results: 43 patients were screened and 20 recruited into the study. Seventeen patients (85%) completed the intervention, and 15 (75%) achieved the target step count. Average step count per day increased significantly from baseline to 3 weeks by 2546 (5108±3064 to 7654±3849 P=0.03, n=17), and was maintained until week 12 (9022±3942). Following completion of the intervention, no adverse events were recorded, quality of life improved by 4 points (26±18 vs. 22±19). Peak exercise stroke volume increased by 19% (127±34 vs 151±34 m/beat, P=0.05), while cardiac index increased by 12% (6.8±1.5 vs. 7.6±2.0 L/min/m2, P=0.19). Workload and oxygen consumption at anaerobic threshold also increased by 16% (49±16 vs. 59±14 watts, P=0.01) and 10% (11.5±2.9 vs. 12.8±2.2 ml/kg/min, P=0.39). Conclusion: The Active-at-Home-HF intervention is feasible, acceptable and effective for increasing physical activity in CHF. It may lead to improvements in quality of life, exercise tolerance and haemodynamic function

KSHV gB associated RGD interactions promote attachment of cells by inhibiting the potential migratory signals induced by the disintegrin-like domain

Background: Kaposi's sarcoma-associated herpesvirus (KSHV) glycoprotein B (gB) is not only expressed on the envelope of mature virions but also on the surfaces of cells undergoing lytic replication. Among herpesviruses, KSHV gB is the only glycoprotein known to possess the RGD (Arg-Gly-Asp) binding integrin domain critical to mediating cell attachment. Recent studies described gB to also possess a disintegrin-like domain (DLD) said to interact with non-RGD binding integrins. We wanted to decipher the roles of two individually distinct integrin binding domains (RGD versus DLD) within KSHV gB in regulating attachment of cells over cell migration

The Pathogenic Potential of Campylobacter concisus Strains Associated with Chronic Intestinal Diseases

Campylobacter concisus has garnered increasing attention due to its association with intestinal disease, thus, the pathogenic potential of strains isolated from different intestinal diseases was investigated. A method to isolate C. concisus was developed and the ability of eight strains from chronic and acute intestinal diseases to adhere to and invade intestinal epithelial cells was determined. Features associated with bacterial invasion were investigated using comparative genomic analyses and the effect of C. concisus on host protein expression was examined using proteomics. Our isolation method from intestinal biopsies resulted in the isolation of three C. concisus strains from children with Crohn's disease or chronic gastroenteritis. Four C. concisus strains from patients with chronic intestinal diseases can attach to and invade host cells using mechanisms such as chemoattraction to mucin, aggregation, flagellum-mediated attachment, “membrane ruffling”, cell penetration and damage. C. concisus strains isolated from patients with chronic intestinal diseases have significantly higher invasive potential than those from acute intestinal diseases. Investigation of the cause of this increased pathogenic potential revealed a plasmid to be responsible. 78 and 47 proteins were upregulated and downregulated in cells infected with C. concisus, respectively. Functional analysis of these proteins showed that C. concisus infection regulated processes related to interleukin-12 production, proteasome activation and NF-κB activation. Infection with all eight C. concisus strains resulted in host cells producing high levels of interleukin-12, however, only strains capable of invading host cells resulted in interferon-γ production as confirmed by ELISA. These findings considerably support the emergence of C. concisus as an intestinal pathogen, but more significantly, provide novel insights into the host immune response and an explanation for the heterogeneity observed in the outcome of C. concisus infection. Moreover, response to infection with invasive strains has substantial similarities to that observed in the inflamed mucosa of Crohn's disease patients