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Aims: Multiple sclerosis (MS) is a chronic neurological disease that currently lacks effective curative treatments. There is a need to find effective therapies, especially to reverse the progressive demyelination and neuronal damage. Oligodendrocytes form the myelin sheath around axons in the central nervous system (CNS) and oligodendrocyte precursor cells (OPCs) undergo mechanisms that enable spontaneously the partial repair of damaged lesions. The aim of this study was to discover small molecules with potential effects in demyelinating diseases, including (re)myelinating properties. Methods: Recently, it has been shown how LRRK2 inhibition promotes oligodendrogliogenesis and therefore an efficient repair or myelin damaged lesions. Here we explored small molecules inhibiting LRRK2 as potential enhancers of primary OPCs proliferation and differentiation, and their potential impact on the clinical score of experimental autoimmune encephalomyelitys (EAE) mice, a validated model of the most frequent clinical form of MS, relapsing–remitting MS. Results: One of the LRRK2 inhibitors presented in this study promoted the proliferation and differentiation of OPC primary cultures. When tested in the EAE murine model of MS, it exerted a statistically significant reduction of the clinical burden of the animals, and histological evidence revealed how the treated animals presented a reduced lesion area in the spinal cord. Conclusions: For the first time, a small molecule with LRRK2 inhibition properties presented (re)myelinating properties in primary OPCs cultures and potentially in the in vivo murine model. This study provides an in vivo proof of concept for a LRRK2 inhibitor, confirming its potential for the treatment of MS. [ABSTRACT FROM AUTHOR]

Patients with chronic obstructive pulmonary disease (COPD) accumulate low levels of physical activity. How environmental factors affect their physical activity in the short-term is uncertain. Aim: to assess the short-term effects of air pollution and weather on physical activity levels in COPD patients. This multi-center panel study assessed 408 COPD patients from Catalonia (Spain). Daily physical activity (i.e., steps, time in moderate-to-vigorous physical activity (MVPA), locomotion intensity, and sedentary time) was recorded in two 7-day periods, one year apart, using the Dynaport MoveMonitor. Air pollution (nitrogen dioxide (NO 2), particulate matter below 10 μm (PM 10) and a marker of black carbon (absorbance of PM 2.5 : PM 2.5ABS), and weather (average and maximum temperature, and rainfall) were estimated the same day (lag zero) and up to 5 days prior to each assessment (lags 1–5). Mixed-effect distributed lag linear regression models were adjusted for age, sex, weekday, public holidays, greenness, season, and social class, with patient and city as random effects. Patients (85% male) were on average (mean ± SD) 68 ± 9 years old with a post-bronchodilator forced expiratory volume in 1 s (FEV 1) of 57 ± 18% predicted. Higher NO 2 , PM 10 and PM 2.5ABS levels at lag four were associated with fewer steps, less time in MVPA, reduced locomotion intensity, and longer sedentary time (e.g., coefficient (95% CI) of −60 (−105, −15) steps per 10 μg/m3 increase in NO 2). Higher average and maximum temperatures at lag zero were related to more steps and time in MVPA, and less sedentary time (e.g., +85 (15, 154) steps per degree Celsius). Higher rainfall at lag zero was related to fewer steps and more sedentary time. Air pollution affects the amount and intensity of physical activity performed on the following days in COPD patients, whereas weather affects the amount of physical activity performed on the same day. • Higher air pollution relates to low physical activity in COPD up to four days later. • High temperature relates to high physical activity in COPD only on the same day. • Greater rainfall relates to low physical activity in COPD only on the same day. • Urban and transport planning policy should consider people with chronic conditions. • Research on physical activity in COPD should collect data on environmental factors. [ABSTRACT FROM AUTHOR]

This paper reports results of laboratory and 3D numerical modeled pull-out tests with steel ladders and polymeric strip reinforcements. These types of reinforcement are commonly used in reinforced soil walls constructed with concrete facing elements. Laboratory pull-out tests are required to determine accurate and realistic pull-out strength values considering the interaction of specific reinforcement and backfill materials under different confining pressures (i.e., trying to simulate the different reinforcement layer arrangements and load conditions in actual reinforced soil walls). International design Codes for reinforced soil walls provide default values for pull-out strength. However, in many cases, default values are too conservative and/or are not strictly specified for particular reinforcement types. Pull-out tests can be difficult and expensive to perform, thus not being common nor worth for the vast majority of reinforced soil wall projects. Consequently, calibrated numerical models can be useful to predict pull-out response under site-specific conditions, and provide further understanding of the mechanisms involved in the soil-reinforcement interaction. Details of the numerical approach, including relevant aspects of the soil-reinforcement interfaces, are described. Examples of calibrated numerical predictions for pull-out loads, displacements, and soil-dilatancy effects are presented. The influence of reinforcement, soil and interface stiffnesses is shown. Numerical results provide useful insight for future modelling works of the complex interaction between type-specific backfill materials and reinforcement element, relevant for investigation and/or practical design of reinforced soil walls. [ABSTRACT FROM AUTHOR]

Background: Congestion is an essential issue in patients with heart failure (HF). Standard treatments do not usually achieve decongestion, and various strategies have been proposed to guide treatment, such as determination of natriuresis. After starting treatment with loop diuretics, we postulate that initial natriuresis might help treatment titration, decongestion, and improve prognosis. Methods: It was a prospective and observational study. Patients admitted with the diagnosis of HF decompensation were eligible. An assessment of congestion was performed during the first 48 h. Results: A total of 113 patients were included. A poor diuretic response was observed in 39.8%. After the first 48 h, patients with a greater diuretic response on admission (NaU > 80 mmol/L) showed fewer pulmonary b lines (12 vs. 15; p = 0.084), a lower IVC diameter (18 mm vs. 22 mm; p = 0.009), and lower IAP figures (11 mmHg vs. 13 mmHg; p = 0.041). Survival analysis tests demonstrated significant differences showing a higher proportion of all-cause mortality (ACM) and HF rehospitalization in the poor-diuretic-response group (log-rank test = 0.020). Conclusions: Up to 40% of the patients presented a poorer diuretic response at baseline, translating into worse outcomes. Patients with an optimal diuretic response showed significantly higher abdominal decongestion at 48 h and a better prognosis regarding ACM and/or HF rehospitalizations. [ABSTRACT FROM AUTHOR]