Ecological sensitivity and vulnerability of fishing fleet landings to climate change across regions

The degree of exposure of fishing communities to environmental changes can be partially determined by the vulnerability of the target species and the landings composition. Hence, identifying the species that ecologically most contribute to the vulnerability of the landings are key steps to evaluate the risk posed by climate change. We analyse the temporal variability in intrinsic sensitivity and the ecological vulnerability of the Portuguese fisheries landings, considering the species proportions derived both from the weights and revenues. To account for the diversification of species of each fleet, we explored the species dependence of the fishery in combination with the vulnerability of them. The analyses were carried out separately for three fleet typologies and three regions. Opposite to what has been observed at a global scale, the ecological sensitivity of the fisheries landings between 1989 and 2015 did not display a decline across areas or fishing fleets. Considering each fleet independently, for trawling, where average vulnerability was lower than in the other fleets, the sensitivity of the landings increased since the 2000s. On the other hand, the high vulnerability found in multi-gear fleets was compensated by diversification of the species caught, while purse-seine fleets targeted low vulnerability species but presented a high fishery dependence on few species. The results highlight the importance of combining information on ecological vulnerability and diversification of fishing resources at a regional scale while providing a measure of the ecological exposure to climate change.info:eu-repo/semantics/publishedVersio

Predicting two-year mortality from discharge after acute coronary syndrome: An internationally-based risk score.

BACKGROUND: Long-term risk of post-discharge mortality associated with acute coronary syndrome remains a concern. The development of a model to reliably estimate two-year mortality risk from hospital discharge post-acute coronary syndrome will help guide treatment strategies. METHODS: EPICOR (long-tErm follow uP of antithrombotic management patterns In acute CORonary syndrome patients, NCT01171404) and EPICOR Asia (EPICOR Asia, NCT01361386) are prospective observational studies of 23,489 patients hospitalized for an acute coronary syndrome event, who survived to discharge and were then followed up for two years. Patients were enrolled from 28 countries across Europe, Latin America and Asia. Risk scoring for two-year all-cause mortality risk was developed using identified predictive variables and forward stepwise Cox regression. Goodness-of-fit and discriminatory power was estimated. RESULTS: Within two years of discharge 5.5% of patients died. We identified 17 independent mortality predictors: age, low ejection fraction, no coronary revascularization/thrombolysis, elevated serum creatinine, poor EQ-5D score, low haemoglobin, previous cardiac or chronic obstructive pulmonary disease, elevated blood glucose, on diuretics or an aldosterone inhibitor at discharge, male sex, low educational level, in-hospital cardiac complications, low body mass index, ST-segment elevation myocardial infarction diagnosis, and Killip class. Geographic variation in mortality risk was seen following adjustment for other predictive variables. The developed risk-scoring system provided excellent discrimination (c-statistic=0.80, 95% confidence interval=0.79-0.82) with a steep gradient in two-year mortality risk: >25% (top decile) vs. ~1% (bottom quintile). A simplified risk model with 11 predictors gave only slightly weaker discrimination (c-statistic=0.79, 95% confidence interval =0.78-0.81). CONCLUSIONS: This risk score for two-year post-discharge mortality in acute coronary syndrome patients ( www.acsrisk.org ) can facilitate identification of high-risk patients and help guide tailored secondary prevention measures

Trends in the Epidemiology of Leishmaniasis in the City of Barcelona (1996-2019)

Background: Leishmaniasis is a neglected zoonosis produced by 20 different flagellated parasites of the Leishmania genus, a protozoan transmitted to humans and other vertebrates by the bite of dipteran insects of the Phlebotominae subfamily. It is endemic in Mediterranean countries and the number of cases is expected to increase due to climate change and migration. Prioritizing public health interventions for prevention and control is essential. The objective was to characterize the epidemiology and temporal trends in the incidence of human leishmaniasis in the city of Barcelona, between the years 1996 and 2019. Methods: A population-based, analytical observational study among residents in the city of Barcelona was conducted of all the cases of leishmaniasis reported between 1996 and 2019 to the Public Health Agency. The epidemiological survey contains clinical, diagnostic, and epidemiological data, including contact with suspicious mammals or insects. Annual incidence-rates were calculated by sex, age, and country of origin. Chi-square tests were used to assess association between studied risk factors, periods of time and type of leishmaniasis. Results: During the study period a total of 177 cases of leishmaniasis were reported in Barcelona, being 74.6% (n = 132) of the total cases in Spanish born, although within the foreign-born population the incidence was higher. Median age was 34 years (IQR = 10-48) and 121 (66.8%) were male. The main type was cutaneous (46%) followed by visceral (35.1%). The cumulative incidence was 0.47 per 100,000 inhabitants, with the highest incidence found in 2017 (1.60 per 100,000 inhabitants). A higher incidence was observed in the 0-4-year-old group (1.73 per 100,000 inhabitants), but increased during the study period for all age groups. There was an increase of foreign origin cases, and a decrease in the number of cases associated to any immunosuppression. Conclusion: In Barcelona, leishmaniasis incidence continues to be higher in people under 5 years of age, and 25-64 years old males, but it has also increased in population from foreign country of birth. There is an increase of the cases since 2016, probably due to the changes in the notification system, increasing the diagnosis of cutaneous leishmaniasis. Improvements in the current surveillance system are needed. Notification of the disease, vector, and reservoir control activities are also essential for the control of the disease

A Phase II Study of Venetoclax in Combination With Pomalidomide and Dexamethasone in Relapsed/Refractory Multiple Myeloma

© 2021 The Authors.[Background]: Venetoclax is a selective BCL-2 inhibitor with clinical activity in relapsed/refractory multiple myeloma (RRMM). Combinations of venetoclax with agents that have complementary mechanisms of action may improve venetoclax efficacy in RRMM. This study evaluated venetoclax with pomalidomide and dexamethasone (VenPd) in RRMM. [Patients and Methods]: This phase II open label study (NCT03567616) evaluated VenPd in patients with RRMM who had received ≥ 1 prior therapy and were refractory to lenalidomide. Venetoclax was administered orally daily for days 1 to 28, pomalidomide was administered orally daily for days 1 to 21, and dexamethasone was administered weekly for each 28-day cycle. The primary objective was to characterize the safety and tolerability of VenPd. The secondary objectives were to evaluate the efficacy and pharmacokinetics. The study was terminated early due to partial clinical hold and decision to pursue biomarker driven strategy. [Results]: Eight patients were enrolled. Patients had a median age of 67.5 years. All patients received 400 mg venetoclax; 4 patients experienced dose-limiting toxicities and the dose was not escalated. All patients had a grade ≥ 3 adverse event, and the most common was neutropenia (n = 6); cytopenias were the most prevalent adverse events. Five patients (63%) had a confirmed response, and the median duration of response was 12.9 months. The median progression-free survival was 10.5 months. [Conclusions]: Given the limited enrollment, no clear safety or efficacy conclusions about VenPd can be drawn. Preliminary safety data, particularly the occurrence of cytopenias, can be used to guide dosing strategies for future combinations of venetoclax with immunomodulatory agents.AbbVie Inc is a private corporation, and funding is not associated with a grant number. Funding information is correct as stated

FGFR1 amplification or overexpression and hormonal resistance in luminal breast cancer: rationale for a triple blockade of ER, CDK4/6, and FGFR1.

BACKGROUND: FGFR1 amplification, but not overexpression, has been related to adverse prognosis in hormone-positive breast cancer (HRPBC). Whether FGFR1 overexpression and amplification are correlated, what is their distribution among luminal A or B HRPBC, and if there is a potential different prognostic role for amplification and overexpression are currently unknown features. The role of FGFR1 inhibitors in HRPBC is also unclear. METHODS: FGFR1 amplification (FISH) and overexpression (RNAscope) were investigated in a N = 251 HRPBC patients cohort and the METABRIC cohort; effects on survival and FISH-RNAscope concordance were determined. We generated hormonal deprivation resistant (LTED-R) and FGFR1-overexpressing cell line variants of the ER+ MCF7 and T47-D and the ER+, FGFR1-amplified HCC1428 cell lines. The role of ER, CDK4/6, and/or FGFR1 blockade alone or in combinations in Rb phosphorylation, cell cycle, and survival were studied. RESULTS: FGFR1 overexpression and amplification was non-concordant in > 20% of the patients, but both were associated to a similar relapse risk (~ 2.5-fold; P < 0.05). FGFR1 amplification or overexpression occurred regardless of the luminal subtype, but the incidence was higher in luminal B (16.3%) than A (6.6%) tumors; P < 0.05. The Kappa index for overexpression and amplification was 0.69 (P < 0.001). Twenty-four per cent of the patients showed either amplification and/or overexpression of FGFR1, what was associated to a hazard ratio for relapse of 2.6 (95% CI 1.44-4.62, P < 0.001). In vitro, hormonal deprivation led to FGFR1 overexpression. Primary FGFR1 amplification, engineered mRNA overexpression, or LTED-R-acquired FGFR1 overexpression led to resistance against hormonotherapy alone or in combination with the CDK4/6 inhibitor palbociclib. Blocking FGFR1 with the kinase-inhibitor rogaratinib led to suppression of Rb phosphorylation, abrogation of the cell cycle, and resistance-reversion in all FGFR1 models. CONCLUSIONS: FGFR1 amplification and overexpression are associated to similar adverse prognosis in hormone-positive breast cancer. Capturing all the patients with adverse prognosis-linked FGFR1 aberrations requires assessing both features. Hormonal deprivation leads to FGFR1 overexpression, and FGFR1 overexpression and/or amplification are associated with resistance to hormonal monotherapy or in combination with palbociclib. Both resistances are reverted with triple ER, CDK4/6, and FGFR1 blockade

Chitosan feasibility to retain retinal stem cell phenotype and slow proliferation for retinal transplantation

Retinal stem cells (RSCs) are promising in cell replacement strategies for retinal diseases. RSCs can migrate, differentiate, and integrate into retina. However, RSCs transplantation needs an adequate support; chitosan membrane (ChM) could be one, which can carry RSCs with high feasibility to support their integration into retina. RSCs were isolated, evaluated for phenotype, and subsequently grown on sterilized ChM and polystyrene surface for 8 hours, 1, 4, and 11 days for analysing cell adhesion, proliferation, viability, and phenotype. Isolated RSCs expressed GFAP, PKC, isolectin, recoverin, RPE65, PAX-6, cytokeratin 8/18, and nestin proteins. They adhered (28 ± 16%, 8 hours) and proliferated (40 ± 20 cells/field, day 1 and 244 ± 100 cells/field, day 4) significantly low on ChM. However, they maintained similar viability (>95%) and phenotype (cytokeratin 8/18, PAX6, and nestin proteins expression, day 11) on both surfaces (ChM and polystyrene). RSCs did not express alpha-SMA protein on both surfaces. RSCs express proteins belonging to epithelial, glial, and neural cells, confirming that they need further stimulus to reach a final destination of differentiation that could be provided in in vivo condition. ChM does not alternate RSCs behaviour and therefore can be used as a cell carrier so that slow proliferating RSCs can migrate and integrate into retina

Quantitative thresholds enable accurate identification of clostridium difficile infection by the luminex xTAG gastrointestinal pathogen panel

Clostridium difficile colonizes the gastrointestinal (GI) tract, resulting in either asymptomatic carriage or a spectrum of diarrheal illness. If clinical suspicion for C. difficile is low, stool samples are often submitted for analysis by multiplex molecular assays capable of detecting multiple GI pathogens, and some institutions do not report this organism due to concerns for high false-positive rates. Since clinical disease correlates with organism burden and molecular assays yield quantitative data, we hypothesized that numerical cutoffs could be utilized to improve the specificity of the Luminex xTAG GI pathogen panel (GPP) for C. difficile infection. Analysis of cotested liquid stool samples (n 1,105) identified a GPP median fluorescence intensity (MFI) value cutoff of 1,200 to be predictive of two-step algorithm (2-SA; 96.4% concordance) and toxin enzyme immunoassay (EIA) positivity. Application of this cutoff to a second cotested data set (n 1,428) yielded 96.5% concordance. To determine test performance characteristics, concordant results were deemed positive or negative, and discordant results were adjudicated via chart review. Test performance characteristics for the MFI cutoff of 150 (standard), MFI cutoff of 1,200, and 2-SA were as follows (respectively): concordance, 95, 96, and 97%; sensitivity, 93, 78, and 90%; specificity, 95, 98, and 98%; positive predictive value, 67, 82, and 81%;, and negative predictive value, 99, 98, and 99%. To capture the high sensitivity for organism detection (MFI of 150) and high specificity for active infection (MFI of 1,200), we developed and applied a reporting algorithm to interpret GPP data from patients (n 563) with clinician orders only for syndromic panel testing, thus enabling accurate reporting of C. difficile for 95% of samples (514 negative and 5 true positives) irrespective of initial clinical suspicion and without the need for additional testing

Covalent and noncovalent hybrids of di-amino porphyrin functionalized graphene oxide and their interaction with gold nanoparticles

Porphyrin functionalization of graphene oxide (GO) influenced the plasmonic effect of gold nanoparticles (AuNP). The former was achieved by modification of GO with 5,10-bis(4-aminophenyl)-15,20-diphenylpor-phyrin, P(NH2)2,adj, by noncovalent interactions as well as by covalent association, following standard chemis-try. The success of the chemical functionalization of GO with P(NH2)2,adj, was confirmed by FTIR. Steady-state and time-resolved fluorescence showed a strong fluorescence quenching of porphyrin in the presence of GO, indicative of a photoinduced electron transfer process from porphyrin units to GO, which acts as an electron acceptor. The surface plasmon coupling effect promoted by the AuNP@GO hybrids, proved to be effective only in the case of the noncovalent hybrid, detected through the decrease of the porphyrin fluorescence lifetime and increase in the emission intensity in solution, in good agreement with FLIM results on deposited samples.info:eu-repo/semantics/publishedVersio

Climate change vulnerability assessment of the main marine commercial fish and invertebrates of Portugal

This is the first attempt to apply an expert-based ecological vulnerability assessment of the effects of climate change on the main marine resources of Portugal. The vulnerability, exposure, sensitivity, adaptive capacity, and expected directional effects of 74 species of fish and invertebrates of commercial interest is estimated based on criteria related to their life-history and level of conservation or exploitation. This analysis is performed separately for three regions of Portugal and two scenarios of climate change (RCP 4.5 and RCP 8.5). To do that, the fourth assessment report IPCC framework for vulnerability assessments was coupled to the outputs of a physical-biogeochemical model allowing to weight the exposure of the species by the expected variability of the environmental variables in the future. The highest vulnerabilities were found for some migratory and elasmobranch species, although overall vulnerability scores were low probably due to the high adaptive capacity of species from temperate ecosystems. Among regions, the highest average vulnerability was estimated for the species in the Central region while higher vulnerabilities were identified under climate change scenario RCP 8.5 in the three regions, due to higher expected climatic variability. This work establishes the basis for the assessment of the vulnerability of the human activities relying on marine resources in the context of climate change.FCT: UIDB/04326/2020/ UIDP/50017/2020+UIDB/50017/2020; MAR2020-FEAMP through project CLIMA-PESCA: MAR-01.03.02-FEAMP-0052/ n2/SAICT/2017-SAICT/ SAICT-45-2017-02/ ALG-01-0145-FEDER-028518/ PTDC/ASP-PES/28518/2017info:eu-repo/semantics/publishedVersio

Reiterative infusions of MSCs improve pediatric osteogenesis imperfecta eliciting a pro-osteogenic paracrine response: TERCELOI clinical trial

Background Osteogenesis imperfecta (OI) is a rare genetic disease characterized by bone fragility, with a wide range in the severity of clinical manifestations. The majority of cases are due to mutations in the COL1A1 or COL1A2 genes, which encode type I collagen. Mesenchymal stem cells (MSCs), as the progenitors of the osteoblasts, the main type I collagen secreting cell type in the bone, have been proposed and tested as an innovative therapy for OI with promising but transient outcomes. Methods To overcome the short-term effect of MSCs therapy, we performed a phase I clinical trial based on reiterative infusions of histocompatible MSCs, administered in a 2.5-year period, in two pediatric patients affected by severe and moderate OI. The aim of this study was to assess the safety and effectiveness of this cell therapy in nonimmunosuppressed OI patients. The host response to MSCs was studied by analyzing the sera from OI patients, collected before, during, and after the cell therapy. Results We first demonstrated that the sequential administration of MSCs was safe and improved the bone parameters and quality of life of OI patients along the cell treatment plus 2-year follow-up period. Moreover, the study of the mechanism of action indicated that MSCs therapy elicited a pro-osteogenic paracrine response in patients, especially noticeable in the patient affected by severe OI. Conclusions Our results demonstrate the feasibility and potential of reiterative MSCs infusion for two pediatric OI and highlight the paracrine response shown by patients as a consequence of MSCs treatment.We are grateful to the patients affected by OI and their families, and to the AHUCE Foundation, especially to its director Ms Julia Piniella, for the support during the clinical trial. We also thank Dr ME Fernandez-Santos (GM-Cell Production Unit, IiSGM) for her expertise in the cell production, Jose Ignacio Pijoan Zubizarreta (Clinical Epidemiology Unit of Cruces University Hospital) for the overall support provided to the project, and Natale Imaz (Biocruces Bizkaia Health Research Institute) for providing the data and safety monitoring of the clinical trial. We are indebted to all the health professionals from Cruces University Hospital, especially to the Pediatric Intensive Care Unit for their participation. This study was funded by the Spanish Ministry of Health through the call for independent clinical trials projects "EC10-219," Instituto de Salud Carlos III through the project "PI15/00820" (Co-funded by European Regional Development Fund; "A way to make Europe"), Bioef-EiTB maratoia (BIO14/TP/007), and the AHUCE Foundation