Public water without (public) financial mediation? Remunicipalizing water in Valladolid, Spain

We discuss the water remunicipalization process in the city of Valladolid (Spain), focusing specifically on its public financing model. Valladolid water remunicipalization has been a politically driven process, but implemented and managed in a technical way, through a public 100% municipality-owned company. As we show, it does not require the additional participation of financial intermediaries, public or private. The Valladolid remunicipalization process has been largely successful, with efficient financial and technical management, including some equity and environmental considerations, although it is not free from financial challenges that could cause it to totter in the future

Identification of an ASC oligomerization inhibitor for the treatment of inflammatory diseases

The ASC (apoptosis-associated speck-like protein containing a caspase recruitment domain (CARD)) protein is an scaffold component of different inflammasomes, intracellular multiprotein platforms of the innate immune system that are activated in response to pathogens or intracellular damage. The formation of ASC specks, initiated by different inflammasome receptors, promotes the recruitment and activation of procaspase-1, thereby triggering pyroptotic inflammatory cell death and pro-inflammatory cytokine release. Here we describe MM01 as the first-in-class small-molecule inhibitor of ASC that interferes with ASC speck formation. MM01 inhibition of ASC oligomerization prevents activation of procaspase-1 in vitro and inhibits the activation of different ASC-dependent inflammasomes in cell lines and primary cultures. Furthermore, MM01 inhibits inflammation in vivo in a mouse model of inflammasome-induced peritonitis. Overall, we highlight MM01 as a novel broad-spectrum inflammasome inhibitor for the potential treatment of multifactorial diseases involving the dysregulation of multiple inflammasomes

A Screen for Morphological Complexity Identifies Regulators of Switch-like Transitions between Discrete Cell Shapes

The way in which cells adopt different morphologies is not fully understood. Cell shape could be a continuous variable or restricted to a set of discrete forms. We developed quantitative methods to describe cell shape and show that Drosophila hemocytes in culture are a heterogeneous mixture of five discrete morphologies. In an RNAi screen of genes affecting the morphological complexity of heterogeneous populations, we found that most genes regulate the transition between discrete shapes rather than generating new morphologies. In particular, we identified a subset of genes, including the tumour suppressor PTEN, that decrease the heterogeneity of the population leading to populations enriched in rounded or elongated forms. We show that these genes have a highly conserved function as regulators of cell shape in both mouse and human metastatic melanoma cells

Smoking cessation improves clinical outcome in severe mental disorders and is modulated by genetic variability at CHRNA5 gene

Smoking has been traditionally tolerated for patients with mental disorders due to its hypothesized self-medication function (Schroeder and Morris, 2010).[...

Identifying potential areas of expansion for the endangered brown bear (Ursus arctos) population in the cantabrian mountains (NW Spain)

Many large carnivore populations are expanding into human-modified landscapes and the subsequent increase in coexistence between humans and large carnivores may intensify various types of conflicts. A proactive management approach is critical to successful mitigation of such conflicts. The Cantabrian Mountains in Northern Spain are home to the last remaining native brown bear (Ursus arctos) population of the Iberian Peninsula, which is also amongst the most severely threatened European populations, with an important core group residing in the province of Asturias. There are indications that this small population is demographically expanding its range. The identification of the potential areas of brown bear range expansion is crucial to facilitate proactive conservation and management strategies towards promoting a further recovery of this small and isolated population. Here, we used a presence-only based maximum entropy (MaxEnt) approach to model habitat suitability and identify the areas in the Asturian portion of the Cantabrian Mountains that are likely to be occupied in the future by this endangered brown bear population following its range expansion. We used different spatial scales to identify brown bear range suitability according to different environmental, topographic, climatic and human impact variables. Our models mainly show that: (1) 4977 km2 are still available as suitable areas for bear range expansion, which represents nearly half of the territory of Asturias; (2) most of the suitable areas in the western part of the province are already occupied (77% of identified areas, 2820 km2), 41.4% of them occurring inside protected areas, which leaves relatively limited good areas for further expansion in this part of the province, although there might be more suitable areas in surrounding provinces; and (3) in the eastern sector of the Asturian Cantabrian Mountains, 62% (2155 km2) of the land was classified as suitable, and this part of the province hosts 44.3% of the total area identified as suitable areas for range expansion. Our results further highlight the importance of increasing: (a) the connectivity between the currently occupied western part of Asturias and the areas of potential range expansion in the eastern parts of the province; and (b) the protection of the eastern sector of the Cantabrian Mountains, where most of the future population expansion may be expected.S1 Fig. Brown bear occurrence data and location of the study area in Europe. https://doi.org/10.1371/journal.pone.0209972.s001S2 Fig. Evaluation metrics for 130 candidate models containing different levels of complexity defined by a range of five feature type combinations including linear (L), quadratic (Q), product (P), threshold (T) and hinge (H) features, each evaluated over a range of regularization multipliers ranging from 0 to 10, for (a) the coarse and (b) fine scales of the distribution of the Cantabrian brown bear in Asturias. Evaluation metrics include delta AICc, which is the difference in AICc (Akaikes Information Criterion corrected for small sample sizes, calculated as the sum of the log transformed raw output penalized by the number of model parameters), AUC test, which is the AUC (area Under the receiving operator characteristics Curve) score for the testing data set, AUC diff, which is the difference in AUC scores between the training and testing data sets, and OR min, which is a threshold dependent statistic corresponds to the proportion of testing localities that have MaxEnt output values lower than the value associated with the training locality with the lowest value. https://doi.org/10.1371/journal.pone.0209972.s002S3 Fig. Jacknife evaluations of variable contributions to the (a) coarse and (b) fine scale models. The variables with the highest gain when used in isolation are slope for the coarse scale (a) and forest cover foir the fine scale model (b). These variables therefore seem to have provided the most useful information by themselves for each scale. The variables that decreased the gain most when omitted, and thus possessed the greatest amount of information not present in the other variables, were slope for the coarse scale (a) and population density for the fine scale model (b). https://doi.org/10.1371/journal.pone.0209972.s003S4 Fig. Output of the coarse scale model with a 5 x 5 km resolution. The map presents a clog-log transformation of the raw MaxEnt output, which can be interpreted as a probability of brown bear range occurrence. https://doi.org/10.1371/journal.pone.0209972.s004S5 Fig. Schematic examples of incremental range expansion (a) out of an initial core area as well as (b) a patchy range expansion were no area is occupied two consecutive years, their nestedness values as well as the association matrices used to calculate nestedness. https://doi.org/10.1371/journal.pone.0209972.s005S6 Fig. Associations between predicted suitability estimated from the coarse scale model each of the included environmental predictors. https://doi.org/10.1371/journal.pone.0209972.s006S7 Fig. Associations between predicted suitability estimated from the fine scale model each of the included environmental predictors. https://doi.org/10.1371/journal.pone.0209972.s007S1 Table. Description, source and original format of the 25 environmental variables initially developed for the construction of the models. Variables marked with * are the ones not correlated and ultimately used in the modelling. https://doi.org/10.1371/journal.pone.0209972.s008S2 Table. Variable contribution to the construction of the coarse and fine scale models. https://doi.org/10.1371/journal.pone.0209972.s009S3 Table. Centre coordinates of the 5 x 5 km grids classed as bear home range used as bear occurrence data in the coarse scale model. https://doi.org/10.1371/journal.pone.0209972.s010S4 Table. Centre coordinates of the 1 x 1 km grids that contained a bear observation used as bear occurrence data in the fine scale model. https://doi.org/10.1371/journal.pone.0209972.s011The Gobierno del Principado de Asturias (with FEDER co-financing); the Spanish Ministry of Economy Industry and Competitiveness ((MINECO); the Agencia Estatal de Investigación (AEI) and the Fondo Europeo de Desarrollo Regional (FEDER, EU) as well as Ramon & Cajal research contracts from the Spanish Ministry of Economy, Industry and Competitiveness.http://www.plosone.org/pm2020Mammal Research InstituteZoology and Entomolog

A novel Nav1.5-dependent feedback mechanism driving glycolytic acidification in breast cancer metastasis

The authors wish to acknowledge the roles of the Breast Cancer Now Tissue Bank in collecting and making available the samples and data, and the patients who have generously donated their tissues and shared their data to be used in the generation of this publication. The authors also thank Prof. Miles Whittington (Hull-York Medical School, UK), Dr. John Davey and Dr. Katherine Newling (Technology Facility, University of York, UK), and Prof. Lýdia Vargová (Charles University, Czechia) for providing invaluable advice. For the purpose of open access, a Creative Commons Attribution (CC BY) licence is applied to any author accepted manuscript version arising from this submission.Peer reviewe

Distribution and genotype-phenotype correlation of GDAP1 mutations in Spain

Mutations in the GDAP1 gene can cause Charcot-Marie-Tooth disease. These mutations are quite rare in most Western countries but not so in certain regions of Spain or other Mediterranean countries. This cross-sectional retrospective multicenter study analyzed the clinical and genetic characteristics of patients with GDAP1 mutations across Spain. 99 patients were identified, which were distributed across most of Spain, but especially in the Northwest and Mediterranean regions. The most common genotypes were p.R120W (in 81% of patients with autosomal dominant inheritance) and p.Q163X (in 73% of autosomal recessive patients). Patients with recessively inherited mutations had a more severe phenotype, and certain clinical features, like dysphonia or respiratory dysfunction, were exclusively detected in this group. Dominantly inherited mutations had prominent clinical variability regarding severity, including 29% of patients who were asymptomatic. There were minor clinical differences between patients harboring specific mutations but not when grouped according to localization or type of mutation. This is the largest clinical series to date of patients with GDAP1 mutations, and it contributes to define the genetic distribution and genotype-phenotype correlation in this rare form of CMT

Influenza vaccine effectiveness in reducing severe outcomes over six influenza seasons, a case-case analysis, Spain, 2010/11 to 2015/16

When influenza vaccination is ineffective in preventing influenza virus infection, it may still reduce the severity of influenza-associated disease. Here, we estimate the effect of influenza vaccination in preventing severe outcomes e.g. intensive care unit (ICU) admission and death, even thougHospital it did not prevent influenza virus infection and subsequent hospitalisation. An observational case-case epidemiological study was carried out in 12 sentinel hospitals in Catalonia (Spain) over six influenza seasons 2010/11-2015/16. Cases were individuals witHospital severe laboratory-confirmed influenza virus infection and aged 18 years and older. For eacHospital reported case we collected demographic, virological and clinical characteristics. Logistic regression was used to estimate the crude, adjusted odd ratios (aOR) and 95% confidence intervals (CI). Of 1,727 hospital-ised patients included in the study, 799 were female (46.7%), 591 (34.2%) were admitted to the ICU and 223 (12.9%) died. Influenza vaccination uptake was lower in cases that required ICU admission or died (21.2% vs 29.7%, p < 0.001). The adjusted influenza vaccination effectiveness in preventing ICU admission or deatHospital was 23% (95% CI: 1 to 40). In an analysis restricted to sex, age group and antiviral treatment, influenza vaccination had a positive effect on disease severity in all age groups and categories. We found that influenza vaccination reduced the severity of disease even in cases where it did not prevent infection and influenza-associated hospitalisation. Therefore, increased vaccination uptake may reduce complications, ICU admission and death

Long-Term Real-World Effectiveness and Safety of Ustekinumab in Crohn’s Disease Patients: The SUSTAIN Study

Background Large real-world-evidence studies are required to confirm the durability of response, effectiveness, and safety of ustekinumab in Crohn’s disease (CD) patients in real-world clinical practice. Methods A retrospective, multicentre study was conducted in Spain in patients with active CD who had received ≥1 intravenous dose of ustekinumab for ≥6 months. Primary outcome was ustekinumab retention rate; secondary outcomes were to identify predictive factors for drug retention, short-term remission (week 16), loss of response and predictive factors for short-term efficacy and loss of response, and ustekinumab safety. Results A total of 463 patients were included. Mean baseline Harvey-Bradshaw Index was 8.4. A total of 447 (96.5%) patients had received prior biologic therapy, 141 (30.5%) of whom had received ≥3 agents. In addition, 35.2% received concomitant immunosuppressants, and 47.1% had ≥1 abdominal surgery. At week 16, 56% had remission, 70% had response, and 26.1% required dose escalation or intensification; of these, 24.8% did not subsequently reduce dose. After a median follow-up of 15 months, 356 (77%) patients continued treatment. The incidence rate of ustekinumab discontinuation was 18% per patient-year of follow-up. Previous intestinal surgery and concomitant steroid treatment were associated with higher risk of ustekinumab discontinuation, while a maintenance schedule every 12 weeks had a lower risk; neither concomitant immunosuppressants nor the number of previous biologics were associated with ustekinumab discontinuation risk. Fifty adverse events were reported in 39 (8.4%) patients; 4 of them were severe (2 infections, 1 malignancy, and 1 fever). Conclusions Ustekinumab is effective and safe as short- and long-term treatment in a refractory cohort of CD patients in real-world clinical practice

The impact of SARS-CoV-2 in dementia across Latin America : A call for an urgent regional plan and coordinated response

The SARS-CoV-2 global pandemic will disproportionately impact countries with weak economies and vulnerable populations including people with dementia. Latin American and Caribbean countries (LACs) are burdened with unstable economic development, fragile health systems, massive economic disparities, and a high prevalence of dementia. Here, we underscore the selective impact of SARS-CoV-2 on dementia among LACs, the specific strain on health systems devoted to dementia, and the subsequent effect of increasing inequalities among those with dementia in the region. Implementation of best practices for mitigation and containment faces particularly steep challenges in LACs. Based upon our consideration of these issues, we urgently call for a coordinated action plan, including the development of inexpensive mass testing and multilevel regional coordination for dementia care and related actions. Brain health diplomacy should lead to a shared and escalated response across the region, coordinating leadership, and triangulation between governments and international multilateral networks