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Factors associated with lack of improvement in submaximal exercise capacity of patients with heart failure

Aims Improvement in exercise capacity is the primary goal of physical activity programmes for patients with heart failure (HF). Although activity programmes are effective for some patients, others do not benefit. Identifying factors related to a lack of improvement in submaximal exercise capacity may help us interpret findings and design new interventions. The aim of this study is to identify factors contributing to a lack of improvement in submaximal exercise capacity 3 months after physical activity advice or an exergame intervention in patients with HF. Additionally, we aimed to assess differences in lack of improvement in submaximal exercise capacity of patients whose baseline exercise capacity predicted a worse compared with better prognosis of HF.Methods and results This secondary analysis of the HF-Wii study analysed baseline and 3 month data of the 6 min walk test (6MWT) from 480 patients (mean age 67 years, 72% male). Data were analysed separately in patients with a pre-defined 6 min walking distance at baseline of <300 m (n = 79) and >= 300 m (n = 401). Among patients with a baseline 6MWT of >= 300 m, 18% had deteriorated submaximal exercise capacity. In the multiple logistic regression analysis, lower baseline levels of self-reported physical activity [odds ratio (OR) = 0.77, 95% confidence interval (CI) = 0.60-0.97], lower baseline levels of cognitive function (OR = 0.87, 95%CI = 0.79-0.96) were significantly associated with lack of improvement in exercise capacity at 3 months. Not randomized to exergaming (OR = 0.63, 95%CI = 0.37-1.09) was likely (P = 0.097) to be associated with lack of improvement in exercise capacity at 3 months. Among the 79 patients with baseline 6MWT of <300 m, 41% (n = 32) did not improve 6MWT distance at 3 months. Independent predictors for the lack of improvement for 6MWT were New York Heart Association class III/IV (OR = 4.68, 95%CI = 1.08-20.35), higher levels of serum creatinine (OR = 1.02, 95%CI = 1.003-1.03), lower cognitive function (OR = 0.86, 95%CI = 0.75-0.99), and fewer anxiety symptoms (OR = 0.84, 95%CI = 0.72-0.98).Conclusions Lower self-reported physical activity and cognitive impairment predict lack of improvement in submaximal exercise capacity in HF patients. Patients who have a worse prognosis (score <300 m at the 6MWT) are often frail and gain less in exercise capacity. These patients may need a more comprehensive approach to have an effect on exercise capacity, including an individually tailored exercise programme with aerobic exercise (if tolerated) and strength exercises

Effects of exergaming on exercise capacity in patients with heart failure: results of an international multicentre randomized controlled trial

Aims Exergaming is a new tool to increase physical activity. This study aimed to determine the effects of access to a home-based exergame (Nintendo Wii) in patients with heart failure (HF) on exercise capacity, self-reported physical activity and patient-reported outcome measures.Methods and results We enrolled 605 HF patients in New York Heart Association functional class I-IV, independent of ejection fraction, in an international multicentre randomized controlled trial. Patients were randomized to exergame (intervention) or motivational support (control). The primary endpoint was change in submaximal aerobic exercise capacity as measured by the distance walked in 6 min (6MWT) between baseline and 3 months. Secondary endpoints included long-term submaximal aerobic exercise capacity, muscle function, self-reported physical activity, exercise motivation, exercise self-efficacy at 3, 6 and 12months. At baseline, patients on average walked 403142m on the 6MWT. Patients in the exergame group walked further compared to controls at 3 months (454123 vs. 420 +/- 127m, P = 0.005), at 6 months (452 +/- 123 vs. 426 +/- 133m, P = 0.015) and 12months (456 +/- 122 vs. 420 +/- 135m, P = 0.004). However, correcting for baseline 6MWT values by means of a linear mixed-effects model revealed no main effect for the intervention on 6MWT. Small significant effects on muscle function were found. Statistically significant treatment effects were found for muscle function but after correction for baseline and confounders, only the treatment effect for the heel-rise left at 6 months was significant (P<0.05). No treatment effect was found for exercise motivation, exercise self-efficacy, or self-reported physical activity.ConclusionExergaming was safe and feasible in patients with HF with different profiles in different health care systems, cultures and climates. However, it was not effective in improving outcomes on submaximal aerobic exercise capacity. Subgroup analysis did not identify specific subgroups benefiting from the intervention.Clinical Trial Registration: Identifier: NCT01785121

Assessing the health and development of ART-conceived young adults: A study of feasibility, parent recall, and acceptability

<p>Abstract</p> <p>Background</p> <p>Assisted reproductive technologies (ART) to treat infertility have been available for nearly three decades. There have been a number of systematic comparisons of the health and development of ART-conceived with spontaneously-conceived (SC) children. Data are equivocal, some finding no differences and others that there are more health and developmental problems in the ART group. It is agreed that perinatal mortality and morbidity are worse after assisted than spontaneous conception and the impact of the hormonally altered intrauterine environment on puberty and later fertility of offspring are unknown. To date however, there has been no investigation of the health and development of ART-conceived young adults, including from the world's few prospective cohorts of ART conceived children. Obtaining these data requires contact to be made with people at least twenty years after discharge from the treating service. Given the ethical difficulties of approaching families to participate in research up to two decades after cessation of treatment, the aim of this exploratory qualitative investigation was to assess the feasibility and acceptability of approaching mothers treated for infertility prior to 1988, and their recall of the health and development of their ART-conceived young adult children.</p> <p>Methods</p> <p>Mothers treated for infertility at the Royal Women's Hospital Reproductive Biology Unit in Melbourne, Australia prior to 1988 were approached by a senior clinician and invited to participate in individual semi-structured interviews which could include their partners and/or young adult children if they wished. Recruitment continued until theoretic saturation had been reached.</p> <p>Results</p> <p>Ten mothers, two of their husbands and five young adults participated in interviews, and the health and development of 15 ART-conceived young adults were described. The experience of conception, pregnancy, birth and the health and development of the children were recalled vividly and in detail. Families were pleased to have been approached and supported the need for systematic data collection. Mode of conception had been disclosed from childhood to all the offspring.</p> <p>Conclusion</p> <p>With careful and sensitive recruitment strategies it is feasible and acceptable to contact women treated for infertility at least two decades ago and their families, to assess the health and development of ART-conceived young adults.</p

International Guidelines for Veterinary Tumor Pathology: A Call to Action

Standardization of tumor assessment lays the foundation for validation of grading systems, permits reproducibility of oncologic studies among investigators, and increases confidence in the significance of study results. Currently, there is minimal methodological standardization for assessing tumors in veterinary medicine, with few attempts to validate published protocols and grading schemes. The current article attempts to address these shortcomings by providing standard guidelines for tumor assessment parameters and protocols for evaluating specific tumor types. More detailed information is available in the Supplemental Files, the intention of which is 2-fold: publication as part of this commentary, but more importantly, these will be available as “living documents” on a website (www.vetcancerprotocols.org), which will be updated as new information is presented in the peer-reviewed literature. Our hope is that veterinary pathologists will agree that this initiative is needed, and will contribute to and utilize this information for routine diagnostic work and oncologic studies. Journal editors and reviewers can utilize checklists to ensure publications include sufficient detail and standardized methods of tumor assessment. To maintain the relevance of the guidelines and protocols, it is critical that the information is periodically updated and revised as new studies are published and validated with the intent of providing a repository of this information. Our hope is that this initiative (a continuation of efforts published in this journal in 2011) will facilitate collaboration and reproducibility between pathologists and institutions, increase case numbers, and strengthen clinical research findings, thus ensuring continued progress in veterinary oncologic pathology and improving patient care

The discovery of Hepatocyte Growth Factor (HGF) and its significance for cell biology, life sciences and clinical medicine

It has been more than 25 years since HGF was discovered as a mitogen of hepatocytes. HGF is produced by stromal cells, and stimulates epithelial cell proliferation, motility, morphogenesis and angiogenesis in various organs via tyrosine phosphorylation of its receptor, c-Met. In fetal stages, HGF-neutralization, or c-Met gene destruction, leads to hypoplasia of many organs, indicating that HGF signals are essential for organ development. Endogenous HGF is required for self-repair of injured livers, kidneys, lungs and so on. In addition, HGF exerts protective effects on epithelial and non-epithelial organs (including the heart and brain) via anti-apoptotic and anti-inflammatory signals. During organ diseases, plasma HGF levels significantly increased, while anti-HGF antibody infusion accelerated tissue destruction in rodents. Thus, endogenous HGF is required for minimization of diseases, while insufficient production of HGF leads to organ failure. This is the reason why HGF supplementation produces therapeutic outcomes under pathological conditions. Moreover, emerging studies delineated key roles of HGF during tumor metastasis, while HGF-antagonism leads to anti-tumor outcomes. Taken together, HGF-based molecules, including HGF-variants, HGF-fragments and c-Met-binders are available as regenerative or anti-tumor drugs. Molecular analysis of the HGF-c-Met system could provide bridges between basic biology and clinical medicine

Visualization of Glutamine Transporter Activities in Living Cells Using Genetically Encoded Glutamine Sensors

Glutamine plays a central role in the metabolism of critical biological molecules such as amino acids, proteins, neurotransmitters, and glutathione. Since glutamine metabolism is regulated through multiple enzymes and transporters, the cellular glutamine concentration is expected to be temporally dynamic. Moreover, differentiation in glutamine metabolism between cell types in the same tissue (e.g. neuronal and glial cells) is often crucial for the proper function of the tissue as a whole, yet assessing cell-type specific activities of transporters and enzymes in such heterogenic tissue by physical fractionation is extremely challenging. Therefore, a method of reporting glutamine dynamics at the cellular level is highly desirable. Genetically encoded sensors can be targeted to a specific cell type, hence addressing this knowledge gap. Here we report the development of Föster Resonance Energy Transfer (FRET) glutamine sensors based on improved cyan and yellow fluorescent proteins, monomeric Teal Fluorescent Protein (mTFP)1 and venus. These sensors were found to be specific to glutamine, and stable to pH-changes within a physiological range. Using cos7 cells expressing the human glutamine transporter ASCT2 as a model, we demonstrate that the properties of the glutamine transporter can easily be analyzed with these sensors. The range of glutamine concentration change in a given cell can also be estimated using sensors with different affinities. Moreover, the mTFP1-venus FRET pair can be duplexed with another FRET pair, mAmetrine and tdTomato, opening up the possibility for real-time imaging of another molecule. These novel glutamine sensors will be useful tools to analyze specificities of glutamine metabolism at the single-cell level

Increased masticatory activity and quality of life in elderly persons with dementia-a longitudinal matched cluster randomized single-blind multicenter intervention study.

Background: Worldwide, millions of people are suffering from dementia and this number is rising. An index of quality of life (QoL) can describe the impact a disease or treatment has on a person's wellbeing. QoL comprises many variables, including physical health and function, and mental health and function. QoL is related to masticatory ability and physical activity. Animal studies show that disruption of mastication due to loss of teeth or a soft diet leads to memory loss and learning problems. Since these are common complaints in dementia, it is hypothesized that improvement of masticatory function and normalization of diet consistency can increase QoL in elderly persons suffering from dementia. Therefore, the goal of the present study is to examine whether an increase in masticatory activity, achieved by increased food consistency and enhancement of masticatory function through improved oral health care has a positive effect on QoL, including cognition, mood, activities of daily living (ADL), and circadian rhythm in elderly persons with dementia.Methods and design: The described study is a prospective longitudinal matched cluster randomized single-blind multicenter study. Participants are elderly persons living in the Netherlands, suffering from dementia and receiving psychogeriatric care. An intervention group will receive improved oral health care and a diet of increased consistency. A control group receives care as usual. Participants will be assessed four times; outcome variables besides QoL are cognition, mood, independence, rest-activity rhythm, blood pressure, and masticatory function.Discussion: This research protocol investigates the effect of an intervention executed by daily caregivers. The intervention will increase masticatory activity, which is achieved by three different actions, (providing oral health care, increasing food consistency, or a combination of both). There is a certain amount of variety in the nature of the interventions due to local differences in nursing homes. This might be a scientific weakness in the study design; however, a practical implementation of any findings will be subject to the same factors, making this study design clinically relevant.Trial registration: NTR1561. © 2013 Weijenberg et al.; licensee BioMed Central Ltd

The importance of organizational characteristics for improving outcomes in patients with chronic disease: a systematic review of congestive heart failure

Luci K. Leykum, Jacqueline Pugh, Valerie Lawrence, and Polly H. Noel are with the South Texas Veterans Health Care System and Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio TX, 78229, USA -- Michael Parchman is with the South Texas Veterans Health Care System and Department of Family and Community Medicine, University of Texas Health Science Center at San Antonio, San Antonio TX, 78229, USA -- Reuben R. McDaniel Jr. is with the McComb's School of Business, University of Texas at Austin, Austin TX, USABackground: Despite applications of models of care and organizational or system-level interventions to improve patient outcomes for chronic disease, consistent improvements have not been achieved. This may reflect a mismatch between the interventions and the nature of the settings in which they are attempted. The application of complex adaptive systems (CAS) framework to understand clinical systems and inform efforts to improve them may lead to more successful interventions. We performed a systematic review of interventions to improve outcomes of patients with congestive heart failure (CHF) to examine whether interventions consistent with CAS are more likely to be effective. We then examine differences between interventions that are most effective for improving outcomes for patients with CHF versus previously published data for type 2 diabetes to explore the potential impact of the nature of the disease on the types of interventions that are more likely to be effective. Methods: We conducted a systematic review of the literature between 1998 and 2008 of organizational interventions to improve care of patients with CHF. Two independent reviewers independently assessed studies that met inclusion criteria to determine whether each reported intervention reflected one or more CAS characteristics. The effectiveness of interventions was rated as either 0 (no effect), 0.5 (mixed effect), or 1.0 (effective) based on the type, number, and significance of reported outcomes. Fisher's exact test was used to examine the association between CAS characteristics and intervention effectiveness. Specific CAS characteristics associated with intervention effectiveness for CHF were contrasted with previously published data for type 2 diabetes. Results and discussion: Forty-four studies describing 46 interventions met eligibility criteria. All interventions utilized at least one CAS characteristic, and 85% were either 'mixed effect' or 'effective' in terms of outcomes. The number of CAS characteristics present in each intervention was associated with effectiveness (p < 0.001), supporting the idea that interventions consistent with CAS are more likely to be effective. The individual CAS characteristics associated with CHF intervention effectiveness were learning, self-organization, and co-evolution, a finding different from our previously published analysis of interventions for diabetes. We suggest this difference may be related to the degree of uncertainty involved in caring for patients with diabetes versus CHF. Conclusion: These results suggest that for interventions to be effective, they must be consistent with the CAS nature of clinical systems. The difference in specific CAS characteristics associated with intervention effectiveness for CHF and diabetes suggests that interventions must also take into account attributes of the disease.McCombs School of [email protected]

Transcriptomic analysis of the temporal host response to skin infestation with the ectoparasitic mite Psoroptes ovis

<p>Abstract</p> <p>Background</p> <p>Infestation of ovine skin with the ectoparasitic mite <it>Psoroptes ovis </it>results in a rapid cutaneous immune response, leading to the crusted skin lesions characteristic of sheep scab. Little is known regarding the mechanisms by which such a profound inflammatory response is instigated and to identify novel vaccine and drug targets a better understanding of the host-parasite relationship is essential. The main objective of this study was to perform a combined network and pathway analysis of the <it>in vivo </it>skin response to infestation with <it>P. ovis </it>to gain a clearer understanding of the mechanisms and signalling pathways involved.</p> <p>Results</p> <p>Infestation with <it>P. </it>ovis resulted in differential expression of 1,552 genes over a 24 hour time course. Clustering by peak gene expression enabled classification of genes into temporally related groupings. Network and pathway analysis of clusters identified key signalling pathways involved in the host response to infestation. The analysis implicated a number of genes with roles in allergy and inflammation, including pro-inflammatory cytokines (<it>IL1A, IL1B, IL6, IL8 </it>and <it>TNF</it>) and factors involved in immune cell activation and recruitment (<it>SELE, SELL, SELP, ICAM1, CSF2, CSF3, CCL2 </it>and <it>CXCL2</it>). The analysis also highlighted the influence of the transcription factors NF-kB and AP-1 in the early pro-inflammatory response, and demonstrated a bias towards a Th2 type immune response.</p> <p>Conclusions</p> <p>This study has provided novel insights into the signalling mechanisms leading to the development of a pro-inflammatory response in sheep scab, whilst providing crucial information regarding the nature of mite factors that may trigger this response. It has enabled the elucidation of the temporal patterns by which the immune system is regulated following exposure to <it>P. ovis</it>, providing novel insights into the mechanisms underlying lesion development. This study has improved our existing knowledge of the host response to <it>P. ovis</it>, including the identification of key parallels between sheep scab and other inflammatory skin disorders and the identification of potential targets for disease control.</p