Frailty is independently associated with increased hospitalisation days in patients on the liver transplant waitlist

AIM: To investigate the impact of physical frailty on risk of hospitalisation in cirrhotic patients on the liver transplant waitlist. METHODS: Cirrhotics listed for liver transplantation at a single centre underwent frailty assessments using the Fried Frailty Index, consisting of grip strength, gait speed, exhaustion, weight loss, and physical activity. Clinical and biochemical data including MELD score as collected at the time of assessment. The primary outcome was number of hospitalised days per year; secondary outcomes included incidence of infection. Univariable and multivariable analysis was performed using negative binomial regression to associate baseline parameters including frailty with clinical outcomes and estimated incidence rate ratios (IRR). RESULTS: Of 587 cirrhotics, 64% were male, median age (interquartile range) was 60 (53-64) years and MELD score was 15 (12-18). Median Fried Frailty Index was 2 (1-3); 31.6% were classified as frail (fried frailty ≥ 3). During 12 mo of follow-up, 43% required at least 1 hospitalisation; 38% of which involved major infection. 107/184 (58%) frail and 142/399 (36%) non-frail patients were hospitalised at least once (P < 0.001). In univariable analysis, Fried Frailty Index was associated with total hospitalisation days per year (IRR = 1.51, 95%CI: 1.28-1.77; P ≤ 0.001), which remained significant on multivariable analysis after adjustment for MELD, albumin, and gender (IRR for frailty of 1.21, 95%CI: 1.02-1.44; P = 0.03). Incidence of infection was not influenced by frailty. CONCLUSION: In cirrhotics on the liver transplant waitlist, physical frailty is a significant predictor of hospitalisation and total hospitalised days per year, independent of liver disease severity

Dynaflow ™ 48, a microfluidic chip solution for increasing throughput and data quality in patch-clamp-based drug screening

Ion channels are transm embrane proteins, found in virtually all cell types throughout the human body. Ion channels underlie neural communication, memory, behavior, every movement and heartbeat, and are as such prone to cause disease if malfunctioning. Therefore ion channels are very important targets in drug discovery. The gold standard technique for obtaining information on ion channel function with high information content and temporal resolution is patch-clamp. The technique measures the minute currents originating from the movement of ions across the cellular membrane, and enables determination of the potency and efficacy of a drug. However, patch-clamp suffers from serious throughput restrictions due to its laborious nature. To address the throughput problems we have developed a microfluidic chip containing 48 microchannels for an extremely rapid, sequential delivery of a large number of completely controlled solution environments to a lifted, patch-clamped cell. In this way, throughput is increased drastically compared to classical patch-clamp perfusion set-ups, with uncompromised data quality. The 48-microchannel chip has been used for the characterization of drugs affecting ligand-gated ion channels including agonists, antagonists and positive modulators with positive effects on both throughput and data quality.Zadanie pt. „Digitalizacja i udostępnienie w Cyfrowym Repozytorium Uniwersytetu Łódzkiego kolekcji czasopism naukowych wydawanych przez Uniwersytet Łódzki” nr 885/P-DUN/2014 dofinansowane zostało ze środków MNiSW w ramach działalności upowszechniającej naukę

The consequences of alcohol measure: psychometric evaluation of a new measure of positive and negative consequences of alcohol use

Alcohol is a widely used substance among university students. There are several measures that are used to assess the consequences of alcohol consumption. However, current instruments fail to capture several behavioural consequences established in literature. Negative consequences missing from existing measures are related to sexual behaviour, suicidal and non-suicidal selfinjury, and criminal and delinquent behaviour. In addition to negative consequences, positive consequences have been neglected from these measures. The goal of this research was to develop a new measure that addresses these gaps. In Study One, items from current and widely used measures in research and clinical applications, as well as newly developed items, were administered to a sample of undergraduate students. Factor analysis and item performance indices (e.g., item to total scale correlations, item variance, relationship to desirable responding) were used to construct a new scale. In Study Two, the new scale was administered to assess indices of reliability and validity. Although many of the new behavioural consequences (e.g., suicidality, eating behaviours, and aggression) were eliminated from the scale through empirical methods of item retention, the final scale was found to perform well across nearly all indices; there was strong evidence of construct, concurrent, and convergent validity. The final scale was comprised of positive and negative consequences, with an index for valence ratings

The impact of COVID-19 on the physical activity and sedentary behaviour levels of pregnant women with gestational diabetes

BackgroundThe aim of this study was to understand how physical activity and sedentary behaviour levels of pregnant women with gestational diabetes in the UK have been affected by COVID-19.MethodsAn online survey exploring physical activity and sedentary behaviour levels of pregnant women with gestational diabetes during COVID-19 was distributed through social media platforms. Women who had been pregnant during the COVID-19 outbreak and had gestational diabetes, were resident in the UK, were 18 years old or over and could understand written English were invited to take part.ResultsA total of 724 women accessed the survey, 553 of these met the eligibility criteria and took part in the survey. Sedentary time increased for 79% of the women during the pandemic. Almost half of the women (47%) were meeting the physical activity guidelines pre COVID-19 during their pregnancy, this dropped to 23% during the COVID-19 pandemic. Fear of leaving the house due to COVID-19 was the most commonly reported reason for the decline. Significant associations were found between meeting the physical activity guidelines during COVID-19 and educational attainment, fitness equipment ownership and knowledge of how to exercise safely in pregnancy.Conclusions and implicationsThese results show the impact of COVID-19 on physical activity and sedentary behaviour levels and highlight the need for targeted public health initiatives as the pandemic continues and for future lockdowns. Women with gestational diabetes need to know how it is safe and beneficial to them to engage in physical activity and ways to do this from their homes if fear of leaving the house due to COVID-19 is a barrier for them. Online physical activity classes provided by certified trainers in physical activity for pregnant women may help them remain active when face-to-face appointments are reduced and limited additional resources are available

Reducing the Decline in Physical Activity during Pregnancy: A Systematic Review of Behaviour Change Interventions

Purpose: Physical activity (PA) typically declines throughout pregnancy. Low levels of PA are associated with excessive weight gain and subsequently increase risk of pre-eclampsia, gestational diabetes mellitus, hypertension disorders, delivery by caesarean section and stillbirth. Systematic reviews on PA during pregnancy have not explored the efficacy of behaviour change techniques or related theory in altering PA behaviour. This systematic review evaluated the content of PA interventions to reduce the decline of PA in pregnant women with a specific emphasis on the behaviour change techniques employed to elicit this change. Search and Review Methodology: Literature searches were conducted in eight databases. Strict inclusion and exclusion criteria were employed. Two reviewers independently evaluated each intervention using the behaviour change techniques (BCT) taxonomy to identify the specific behaviour change techniques employed. Two reviewers independently assessed the risk of bias using the guidelines from the Cochrane Collaboration. Overall quality was determined using the GRADE approach. Findings: A total of 1140 potentially eligible papers were identified from which 14 studies were selected for inclusion. Interventions included counselling (n = 6), structured exercise (n = 6) and education (n = 2). Common behaviour change techniques employed in these studies were goal setting and planning, feedback, repetition and substitution, shaping knowledge and comparison of behaviours. Regular face-to-face meetings were also commonly employed. PA change over time in intervention groups ranged from increases of 28% to decreases of 25%. In 8 out of 10 studies, which provided adequate data, participants in the intervention group were more physically active post intervention than controls. Conclusions and Implications: Physical activity interventions incorporating behaviour change techniques help reduce the decline in PA throughout pregnancy. Range of behaviour change techniques can be implemented to reduce this decline including goals and planning, shaping knowledge and comparison of outcomes. A lack of high quality interventions hampers conclusions of intervention effectiveness

Tumor Necrosis Factor-Alpha Signaling May Contribute to Chronic West Nile Virus Post-Infectious Proinflammatory State

Background: West Nile virus (WNV) causes a spectrum of human disease ranging from a febrile illness (WNV fever) to severe neuroinvasive disease (meningitis, encephalitis, acute flaccid paralysis). Since WNV gained entry into North America in 1999, clinicians caring for WNV survivors have observed persistent neurological symptoms occurring long-after the production of neutralizing antibodies and clearance of the virus. Accordingly, alternative pathogeneses other than direct viral invasion have been hypothesized to explain these post-infectious symptoms. The dominant hypothesis is that antiviral inflammatory responses triggered initially to clear WNV may persist to promote a post-infectious proinflammatory state. Methods: In 4 serologically-confirmed WNV patients with persistent post-infectious symptoms (3 WNV fever, 1 neuroinvasive disease), we ordered a comprehensive cytokine panel at weeks 8, 10, 12, and 36 months post-onset of illness, respectively, to better understand the pathophysiology of the protracted symptoms. Results: All patients had abnormally elevated tumor necrosis factor alpha (TNF-α), a major molecule triggering antiviral cytokines and chronic inflammation in many human autoimmune diseases, but heretofore not reported to be upregulated in human WNV infection. Three patients also had elevations of other proinflammatory proteins. Major symptoms included fatigue, arthralgias, myalgias, generalized or multifocal pain or weakness, imbalance, headaches, cognitive problems, and symptoms of dysautonomia. Conclusion: The findings provide support for an extended post-infectious proinflammatory state that may contribute to chronic inflammation and long-term morbidity in some WNV survivors and further suggest that TNF-α may play a pathogenic role in initiating this inflammatory environment. Clinical trials may be warranted to determine if TNF-α inhibitors or other immunosuppressive agents can improve patient outcomes