Associations between the measures of physical function, risk of falls and the quality of life in haemodialysis patients : a cross-sectional study

Background Impaired physical function due to muscle weakness and exercise intolerance reduces the ability to perform activities of daily living in patients with end-stage kidney disease, and by consequence, Health-Related Quality of Life (HRQoL). Furthermore, the risk of falls is an aggregate of physical function and, therefore, could be associated with HRQoL as well. The present study examined the associations between objective and subjective measures of physical function, risk of falls and HRQoL in haemodialysis patients. Methods This cross-sectional multicentre study included patients on maintenance haemodialysis. Physical function (quadriceps force, handgrip force, Sit-to-Stand, and six-minute walking test), the risk of falls (Tinetti, FICSIT-4, and dialysis fall index) and HRQoL (PROMIS-29 and EQ-5D-3 L) were measured and analysed descriptively, by general linear models and logistic regression. Results Of the 113 haemodialysis patients (mean age 67.5 +/- 16.1, 57.5% male) enrolled, a majority had impaired quadriceps force (86.7%) and six-minute walking test (92%), and an increased risk of falls (73.5%). Whereas muscle strength and exercise capacity were associated with global HRQoL (R-2 = 0.32) and the risk of falls, the risk of falls itself was related to psycho-social domains (R-2 = 0.11) such as depression and social participation, rather than to the physical domains of HRQoL. Objective measures of physical function were not associated with subjective fatigue, nor with subjective appreciation of health status. Conclusions More than muscle strength, lack of coordination and balance as witnessed by the risk of falls contribute to social isolation and HRQoL of haemodialysis patients. Mental fatigue was less common than expected, whereas, subjective and objective physical function were decreased

Cohesin Releases DNA through Asymmetric ATPase-Driven Ring Opening

Cohesin stably holds together the sister chromatids from S phase until mitosis. To do so, cohesin must be protected against its cellular antagonist Wapl. Eco1 acetylates cohesin's Smc3 subunit, which locks together the sister DNAs. We used yeast genetics to dissect how Wapl drives cohesin from chromatin and identified mutants of cohesin that are impaired in ATPase activity but remarkably confer robust cohesion that bypasses the need for the cohesin protectors Eco1 in yeast and Sororin in human cells. We uncover a functional asymmetry within the heart of cohesin's highly conserved ABC-like ATPase machinery and find that both ATPase sites contribute to DNA loading, whereas DNA release is controlled specifically by one site. We propose that Smc3 acetylation locks cohesin rings around the sister chromatids by counteracting an activity associated with one of cohesin's two ATPase sites. Tight regulation of DNA entrapment and release by the cohesin complex is crucial for its multiple cellular functions. Elbatsh et al. find that cohesin's release from DNA requires an activity associated with one of its ATPase sites, whereas both sites control cohesin's loading onto DNA

Markers of protein-energy wasting and physical performance in haemodialysis patients: A cross-sectional study

info:eu-repo/semantics/publishe

Keanekaragaman genetik bakteri pendegradasi Dibenzofuran yang diisolasi dari tanah hutan bakau dengan dan tanpa melalui proses pengayaan

Background Physical impairments are common in uraemia, as reflected by the high risk of falls of haemodialysis (HD) patients. Furthermore, these patients often suffer from malnutrition. Objective Up to now, it is unknown which aspects of physical performance are predominantly driven by malnutrition in HD patients. As this answer could steer different interventions, the aim of this study was to evaluate the cross-sectional relationship between nutritional status, muscle strength, exercise capacity and the risk of falls. Methods This study recruited HD patients between December 2016 and March 2018 from two hospital-based and five satellite dialysis units (registration number on clinicaltrial.gov: NCT03910426). The mini-nutritional assessment scale as well as objective measures of protein-energy wasting were obtained (total iron-binding capacity, total protein levels, and CRP). Physical assessment included muscle strength (quadriceps, handgrip force, and sit-to-stand test), exercise capacity (six-minute walking test) and the risk of falls (Tinetti, FICSIT, and dialysis fall index). Their interrelationship was analysed by ridge regression models. Results Out of 113 HD patients (mean age 67 years +/- 16.1, 57.5% male) 36.3% were malnourished according to the mini-nutritional assessment scale and a majority had impaired quadriceps force (86.7%), six-minute walking test (92%), and an increased risk of falls (73.5%). Total protein and CRP levels were identified as relevant nutritional factors in the association with physical performance. Nutritional parameters explained 9.2% of the variance in the risk of falls and 7.6% of the variance in exercise capacity. No conclusive association was found between nutritional status and muscle strength. Conclusion Protein-energy wasting is a determinant ofthe risk of fallsandexercise capacityin patients on HD. The association between malnutrition andmuscle weaknessremains inconclusive

The effects of aerobic exercise on eGFR, blood pressure and VO2peak in patients with chronic kidney disease stages 3-4: A systematic review and meta-analysis

info:eu-repo/semantics/publishe

The effects of aerobic exercise on eGFR, blood pressure and VO2peak in patients with chronic kidney disease stages 3-4: A systematic review and meta-analysis.

BACKGROUND:CKD is associated with several comorbidities, cardiovascular disease being the most significant. Aerobic training has a beneficial effect on cardiovascular health in healthy and some well-defined non-healthy populations. However, the effect of aerobic training on glomerular filtration rate in patients with CKD stages 3-4 is unclear. OBJECTIVE:To review the effects of aerobic exercise training on kidney and cardiovascular function in patients with chronic kidney disease (CKD) stages 3-4. METHODS:A random-effects meta-analysis was performed to analyse published randomized controlled trials through February 2018 on the effect of aerobic training on estimated glomerular filtration rate, blood pressure and exercise tolerance in patients with CKD stages 3-4. Web of Science, PubMed and Embase databases were searched for eligible studies. RESULTS:11 randomized controlled trials were selected including 362 participants in total. Favourable effects were observed on estimated glomerular filtration rate (+2.16 ml/min per 1.73m2; [0.18; 4.13]) and exercise tolerance (+2.39 ml/kg/min; [0.99; 3.79]) following an on average 35-week aerobic training program when compared to standard care. No difference in change in blood pressure was found. CONCLUSIONS:There is a small beneficial effect of aerobic training on estimated glomerular filtration rate and exercise tolerance, but not on blood pressure, in patients with CKD stages 3-4. However, data are limited and pooled findings were rated as of low to moderate quality

Integrating chemical and genetic silencing strategies to identify host kinase-phosphatase inhibitor networks that control bacterial infection

Every year three million people die as a result of bacterial infections, and this number may further increase due to resistance to current antibiotics. These antibiotics target almost all essential bacterial processes, leaving only a few new targets for manipulation. The host proteome has many more potential targets for manipulation in order to control bacterial infection, as exemplified by the observation that inhibiting the host kinase Akt supports the elimination of different intracellular bacteria including Salmonella and M. tuberculosis. If host kinases are involved in the control of bacterial infections, phosphatases could be as well. Here we present an integrated small interference RNA and small molecule screen to identify host phosphatase-inhibitor combinations that control bacterial infection. We define host phosphatases inhibiting intracellular growth of Salmonella and identify corresponding inhibitors for the dual specificity phosphatases DUSP11 and 27. Pathway analysis places many kinases and phosphatases controlling bacterial infection in an integrated pathway centered around Akt. This network controls host cell metabolism, survival, and growth and bacterial survival and reflect a natural host cell response to bacterial infection. Inhibiting two enzyme classes with opposite activities-kinases and phosphatases-may be a new strategy to overcome infections by antibiotic-resistant bacteria

The first step of peptide selection in antigen presentation by MHC class I molecules

Chemical Immunolog