Stochastic priming and spatial cues orchestrate heterogeneous clonal contribution to mouse pancreas organogenesis

The pancreas arises from a small population of cells but how individual cells contribute to organ formation is unclear. Here, the authors deconstruct pancreas organogenesis into clonal units, showing that single progenitors give rise to heterogeneous multi-lineage and endocrinogenic single-lineage clones

Evaluation of the impact of the Covid-19 pandemic on people and organisations in long-term care facilities of Catalonia and proposals for improving the care model: the resicovid-19 project

Background: During the first wave of the COVID-19 pandemic, it is estimated that around 25% of infected residents in Nursing Homes in Catalonia died, which accounted for more than 50% of total COVID-19 deaths in the region. This devastating impact not only highlights the structural deficits of the long-term care facilities system, but it also provides a unique opportunity to gather evidence to support a redesign of the health and social care models–a redesign that focuses on individuals and their singularities, and is equipped with the staff and infrastructure required to meet their needs. Methods: The ResiCOVID-19 project will include five work packages to assess the impact of the COVID-19 pandemic (from March 2020 to June 2022) on the individuals living in long-term care facilities in Catalonia, their family members, health care workers, and the organisations themselves. In this project, we will develop proposals for improvement and indicators for the long-term care model in Catalonia to better adapt to the current and future needs of people-centred care through conducting a rapid review, analysis of international experiences, retrospective analysis, and a cross-sectional study. The analysis will be conducted both from a quantitative and a qualitative perspective, measuring the impact at a system level as well as at a setting and individual level, including residents, families, professionals, and managers of longterm care facilities. Conclusions: The ResiCOVID-19 project is expected to have a significant impact at different dimensions, including the care model, social and organisational aspects (on professionals and facilities), systemic efforts (both for the healthcare and the social systems), and scientific contributions (providing evidence in a field of limited research in Catalonia)

Urinary incontinence and sedentary behaviour in nursing home residents in Osona, Catalonia: protocol for the OsoNaH project, a multicentre observational study

Introduction Several studies have shown that physical activity (PA) levels and sedentary behaviour (SB) are independent risk factors for many health-related issues. However, there is scarce evidence supporting the relationship between SB and urinary incontinence (UI) in community-dwelling older adults, and no information on any possible association in institutionalised older adults. Stage I of this project has the main objective of determining the prevalence of UI and its associated factors in nursing home (NH) residents, as well as analysing the association between UI (and its types) and SB. Stage II aims to investigate the incidence and predictive factors of functional and continence decline, falls, hospitalisations, mortality and the impact of the COVID-19 pandemic among NH residents.Methods and analysis Stage I is an observational, multicentre, cross-sectional study with mixed methodology that aims to explore the current status of several health-related outcomes in NH residents of Osona (Barcelona, Spain). The prevalence ratio will be used as an association measure and multivariate analysis will be undertaken using Poisson regression with robust variance. Stage II is a 2-year longitudinal study that aims to analyse functional and continence decline, incidence of falls, hospitalisations, mortality and the impact of the COVID-19 pandemic on these outcomes. A survival analysis using the actuarial method for functional decline and continence, evaluated every 6 months, and the Kaplan-Meier method for falls, hospitalisations and deaths, and Cox regression for multivariate analysis will be undertaken.Ethics and dissemination The study received the following approvals: University of Vic - Central University of Catalonia Ethics and Research Committee (92/2019 and 109/2020), Clinical Research Ethics Committee of the Osona Foundation for Health Research and Education (FORES) (code 2020118/PR249). Study results will be disseminated at conferences, meetings and through peer-reviewed journals.Trial registration number NCT04297904

Where Is More Important Than How in Coastal and Marine Ecosystems Restoration

Restoration is considered an effective strategy to accelerate the recovery of biological communities at local scale. However, the effects of restoration actions in the marine ecosystems are still unpredictable.We performed a global analysis of published literature to identify the factors increasing the probability of restoration success in coastal and marine systems. Our results confirm that the majority of active restoration initiatives are still concentrated in the northern hemisphere and that most of information gathered from restoration efforts derives from a relatively small subset of species. The analysis also indicates that many studies are still experimental in nature, covering small spatial and temporal scales. Despite the limits of assessing restoration effectiveness in absence of a standardized definition of success, the context (degree of human impact, ecosystem type, habitat) of where the restoration activity is undertaken is of greater relevance to a successful outcome than how (method) the restoration is carried out. Contrary to expectations, we found that restoration is not necessarily more successful closer to protected areas (PA) and in areas of moderate human impact. This result can be motivated by the limits in assessing the success of interventions and by the tendency of selecting areas in more obvious need of restoration, where the potential of actively restoring a degraded site is more evident. Restoration sites prioritization considering human uses and conservation status present in the region is of vital importance to obtain the intended outcomes and galvanize further actions

Accelerometer-measured sedentary and physical activity time and their correlates in European older adults: The SITLESS study

Background: Sedentary behavior (SB) and physical activity (PA) are important determinants of health in older adults. This study aimed to describe the composition of accelerometer-measured SB and PA in older adults, to explore self-reported context-specific SB, and to assess socio-demographic and functional correlates of engaging in higher levels of SB in participants of a multi-center study including four European countries. Methods: 1360 community-dwelling older adults from the SITLESS study (61.8% women; 75.3±6.3 years) completed a self-reported SB questionnaire and wore an ActiGraph accelerometer for seven days. Accelerometer-determined compositional descriptive statistics were calculated. A fixed effects regression analysis was conducted to assess the socio-demographic (country, age, sex, civil status, education and medications) and functional (BMI and gait speed) correlates. Results: Older adults spent 78.8% of waking time in SB, 18.6% in light-intensity PA (LPA), and 2.6% in moderate to vigorous PA (MVPA). Accelerometry showed that women engaged in more LPA and walking and men engaged in higher amounts of MVPA. Watching television and reading accounted for 47.2% of waking time. Older age, being a man, single, taking more medications, being obese and overweight, and having a slower gait speed were statistically significant correlates of more sedentary time. Conclusions: The high amount of SB of our participants justifies the need to develop and evaluate interventions to reduce sitting time. A clinically relevant change in gait speed can decrease almost 0.45 percentage points of sedentary time. The distribution of context-specific sedentary activities by country and sex showed minor differences, albeit worth noting

Probiotic Sonicates Selectively Induce Mucosal Immune Cells Apoptosis through Ceramide Generation via Neutral Sphingomyelinase

This is an open-access article distributed under the terms of the Creative Commons Attribution License.-- et al.[Background]: Probiotics appear to be beneficial in inflammatory bowel disease, but their mechanism of action is incompletely understood. We investigated whether probiotic-derived sphingomyelinase mediates this beneficial effect. [Methodology/Principal Findings]: Neutral sphingomyelinase (NSMase) activity was measured in sonicates of the probiotic L. brevis (LB) and S. thermophilus (ST) and the non-probiotic E. coli (EC) and E. faecalis (EF). Lamina propria mononuclear cells (LPMC) were obtained from patients with Crohn's disease (CD) and Ulcerative Colitis (UC), and peripheral blood mononuclear cells (PBMC) from healthy volunteers, analysing LPMC and PBMC apoptosis susceptibility, reactive oxygen species (ROS) generation and JNK activation. In some experiments, sonicates were preincubated with GSH or GW4869, a specific NSMase inhibitor. NSMase activity of LB and ST was 10-fold that of EC and EF sonicates. LB and ST sonicates induced significantly more apoptosis of CD and UC than control LPMC, whereas EC and EF sonicates failed to induce apoptosis. Pre-stimulation with anti-CD3/CD28 induced a significant and time-dependent increase in LB-induced apoptosis of LPMC and PBMC. Exposure to LB sonicates resulted in JNK activation and ROS production by LPMC. NSMase activity of LB sonicates was completely abrogated by GW4869, causing a dose-dependent reduction of LB-induced apoptosis. LB and ST selectively induced immune cell apoptosis, an effect dependent on the degree of cell activation and mediated by bacterial NSMase. [Conclusions]: These results suggest that induction of immune cell apoptosis is a mechanism of action of some probiotics, and that NSMase-mediated ceramide generation contributes to the therapeutic effects of probiotics.The funding sources included grants from Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Ministerio de Ciencia e Innovación (SAF2005-00280 and SAF2008-03676 to MS, FIS2009-00056 to AM, SAF2009-11417 to JCF), Fundación Ramón Areces (to MS), the National Institutes of Health (DK30399 and DK50984 to CF) and the Research Center for Liver and Pancreatic Diseases funded by the United States National Institute for Alcohol Abuse and Alcoholism (P50 AA 11999 to JCF).Peer reviewe

The SITLESS project: Exercise referral schemes enhanced by self-management strategies to battle sedentary behaviour in older adults: Study protocol for a randomised controlled trial

Abstract Background Older adults are the fastest growing segment of the world‘s population. Recent evidence indicates that excessive sitting time is harmful to health, independent of meeting the recommended moderate to vigorous physical activity (PA) guidelines. The SITLESS project aims to determine whether exercise referral schemes (ERS) can be enhanced by self-management strategies (SMSs) to reduce sedentary behaviour (SB), increase PA and improve health, quality of life and function in the long term, as well as psychosocial outcomes in community-dwelling older European citizens from four countries, within a three-armed pragmatic randomised controlled trial, compared with ERS alone and also with general recommendations about PA. Methods A total of 1338 older adults will be included in this study, recruited from four European countries through different existing primary prevention pathways. Participants will be randomly allocated into an ERS of 16 weeks (32 sessions, 45–60 min per session), ERS enhanced by seven sessions of SMSs and four telephone prompts, or a control group. Outcomes will be assessed at baseline, month 4 (end of ERS intervention), month 16 (12 months post intervention) and month 22 (18 months post intervention). Primary outcomes will include measures of SB (time spent sedentary) and PA (counts per minute). Secondary outcomes will include muscle and physical function, health economics’ related outcomes, anthropometry, quality of life, social networks, anxiety and depressive symptoms, disability, fear of falling, executive function and fatigue. A process evaluation will be conducted throughout the trial. The full analysis set will follow an intention-to-treat principle and will include all randomised participants for whom a baseline assessment is conducted. The study hypothesis will be tested with mixed linear models with repeated measures, to assess changes in the main outcomes (SB and PA) over time (baseline to month 22) and between study arms. Discussion The findings of this study may help inform the design and implementation of more effective interventions to reduce SB and increase PA levels, and hence improve long-term health outcomes in the older adult population. SITLESS aims to support policy-makers in deciding how or whether ERS should be further implemented or restructured in order to increase its adherence, impact and cost-effectiveness. Trial registration ClinicalTrials.gov, NCT02629666 . Registered 19 November 2015

Trends in the epidemiology of catheter-related bloodstream infections; towards a paradigm shift, Spain, 2007 to 2019

Altres ajuts: Departament de Salut. Generalitat de Catalunya ("Pla estratègic de recerca i innovació en salut (PERIS) 2019-2021"); Ministerio de Asuntos Económicos y Transformación Digital; Red Española de Investigación en Patología Infecciosa (REIPI).Background: Catheter-related bloodstream infections (CRBSI) are frequent healthcare-associated infections and an important cause of death. Aim: To analyse changes in CRBSI epidemiology observed by the Infection Control Catalan Programme (VINCat). Methods: A cohort study including all hospital-acquired CRBSI episodes diagnosed at 55 hospitals (2007-2019) in Catalonia, Spain, was prospectively conducted. CRBSI incidence rates were adjusted per 1,000patientdays. To assess the CRBSI rate trend per year, negative binomial models were used, with the number of events as the dependent variable, and the year as the main independent variable. From each model, the annual rate of CRBSI diagnosed per 1,000patientdays and the incidence rate ratio (IRR) with its 95% confidence intervals (CI) were reported. Results: During the study, 9,290 CRBSI episodes were diagnosed (mean annual incidence rate:0.20episodes/1,000patientdays). Patients' median age was 64.1years; 36.6% (3,403/9,290) were female. In total, 73.7% (n=6,845) of CRBSI occurred in non-intensive care unit (ICU) wards, 62.7% (n=5,822) were related to central venous catheter (CVC), 24.1% (n=2,236) to peripheral venous catheters (PVC) and 13.3% (n=1,232) to peripherally-inserted central venous catheters (PICVC). Incidence rate fell over the study period (IRR:0.94;95%CI:0.93-0.96), especially in the ICU (IRR:0.88;95%CI:0.87-0.89). As a whole, while episodes of CVC CRBSI fell significantly (IRR:0.88;95%CI:0.87-0.91), peripherally-inserted catheter CRBSI (PVC and PICVC) rose, especially in medical wards (IRR PICVC:1.08;95%CI:1.05-1.11; IRR PVC: 1.03; 95% 1.00-1.05). Conclusions: Over the study, CRBSIs associated with CVC and diagnosed in ICUs decreased while episodes in conventional wards involving peripherally-inserted catheters increased. Hospitals should implement preventive measures in conventional wards

The evolution of the ventilatory ratio is a prognostic factor in mechanically ventilated COVID-19 ARDS patients

Background: Mortality due to COVID-19 is high, especially in patients requiring mechanical ventilation. The purpose of the study is to investigate associations between mortality and variables measured during the first three days of mechanical ventilation in patients with COVID-19 intubated at ICU admission. Methods: Multicenter, observational, cohort study includes consecutive patients with COVID-19 admitted to 44 Spanish ICUs between February 25 and July 31, 2020, who required intubation at ICU admission and mechanical ventilation for more than three days. We collected demographic and clinical data prior to admission; information about clinical evolution at days 1 and 3 of mechanical ventilation; and outcomes. Results: Of the 2,095 patients with COVID-19 admitted to the ICU, 1,118 (53.3%) were intubated at day 1 and remained under mechanical ventilation at day three. From days 1 to 3, PaO2/FiO2 increased from 115.6 [80.0-171.2] to 180.0 [135.4-227.9] mmHg and the ventilatory ratio from 1.73 [1.33-2.25] to 1.96 [1.61-2.40]. In-hospital mortality was 38.7%. A higher increase between ICU admission and day 3 in the ventilatory ratio (OR 1.04 [CI 1.01-1.07], p = 0.030) and creatinine levels (OR 1.05 [CI 1.01-1.09], p = 0.005) and a lower increase in platelet counts (OR 0.96 [CI 0.93-1.00], p = 0.037) were independently associated with a higher risk of death. No association between mortality and the PaO2/FiO2 variation was observed (OR 0.99 [CI 0.95 to 1.02], p = 0.47). Conclusions: Higher ventilatory ratio and its increase at day 3 is associated with mortality in patients with COVID-19 receiving mechanical ventilation at ICU admission. No association was found in the PaO2/FiO2 variation

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant