A Tropical Macroalga (Halimeda incrassata) Enhances Diversity and Abundance of Epifaunal Assemblages in Mediterranean Seagrass Meadows

The introduction and successful expansion of tropical species into temperate systems is being exacerbated by climate change, and it is particularly important to identify the impacts that those species may have, especially when habitat-forming species are involved. Seagrass meadows are key shallow coastal habitats that provide critical ecosystem services worldwide, and they are threatened by the arrival of non-native macroalgae. Here, we examined the effects of Halimeda incrassata, a tropical alga that has recently colonized the Mediterranean Sea, on epifaunal assemblages associated with Cymodocea nodosa seagrass meadows of Mallorca Island (Western Mediterranean Sea). This invasive macroalga is an ecological engineer and thus has a high potential of modifying native habitats. A seagrass meadow colonized by H. incrassata exhibited important changes on associated epifaunal assemblages, with an increase in abundance and diversity, particularly driven by higher abundances of Gammaridae, Polychaeta, Copepoda and Caprellidae. Given the key ecological contribution of epifauna to food webs, these alterations will likely have important implications for overall food web structure and ecosystem functioning of native ecosystems.En prens

Genetic landscape of 6089 inherited retinal dystrophies affected cases in Spain and their therapeutic and extended epidemiological implications

Inherited retinal diseases (IRDs), defined by dysfunction or progressive loss of photoreceptors, are disorders characterized by elevated heterogeneity, both at the clinical and genetic levels. Our main goal was to address the genetic landscape of IRD in the largest cohort of Spanish patients reported to date. A retrospective hospital-based cross-sectional study was carried out on 6089 IRD affected individuals (from 4403 unrelated families), referred for genetic testing from all the Spanish autonomous communities. Clinical, demographic and familiar data were collected from each patient, including family pedigree, age of appearance of visual symptoms, presence of any systemic findings and geographical origin. Genetic studies were performed to the 3951 families with available DNA using different molecular techniques. Overall, 53.2% (2100/3951) of the studied families were genetically characterized, and 1549 different likely causative variants in 142 genes were identified. The most common phenotype encountered is retinitis pigmentosa (RP) (55.6% of families, 2447/4403). The most recurrently mutated genes were PRPH2, ABCA4 and RS1 in autosomal dominant (AD), autosomal recessive (AR) and X-linked (XL) NON-RP cases, respectively; RHO, USH2A and RPGR in AD, AR and XL for non-syndromic RP; and USH2A and MYO7A in syndromic IRD. Pathogenic variants c.3386G > T (p.Arg1129Leu) in ABCA4 and c.2276G > T (p.Cys759Phe) in USH2A were the most frequent variants identified. Our study provides the general landscape for IRD in Spain, reporting the largest cohort ever presented. Our results have important implications for genetic diagnosis, counselling and new therapeutic strategies to both the Spanish population and other related populations.This work was supported by the Instituto de Salud Carlos III (ISCIII) of the Spanish Ministry of Health (FIS; PI16/00425 and PI19/00321), Centro de Investigación Biomédica en Red Enfermedades Raras (CIBERER, 06/07/0036), IIS-FJD BioBank (PT13/0010/0012), Comunidad de Madrid (CAM, RAREGenomics Project, B2017/BMD-3721), European Regional Development Fund (FEDER), the Organización Nacional de Ciegos Españoles (ONCE), Fundación Ramón Areces, Fundación Conchita Rábago and the University Chair UAM-IIS-FJD of Genomic Medicine. Irene Perea-Romero is supported by a PhD fellowship from the predoctoral Program from ISCIII (FI17/00192). Ionut F. Iancu is supported by a grant from the Comunidad de Madrid (CAM, PEJ-2017-AI/BMD7256). Marta del Pozo-Valero is supported by a PhD grant from the Fundación Conchita Rábago. Berta Almoguera is supported by a Juan Rodes program from ISCIII (JR17/00020). Pablo Minguez is supported by a Miguel Servet program from ISCIII (CP16/00116). Marta Corton is supported by a Miguel Servet program from ISCIII (CPII17/00006). The funders played no role in study design, data collection, data analysis, manuscript preparation and/or publication decisions

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Electrochemical Desorption of Thiolates and Sulfur from Nanoparticle and Planar Platinum Surfaces

Thiolate-protected platinum nanoparticles have become promising for applications in heterogeneous catalysis and the fabrication of new materials for hydrogen storage. Once nanoparticles have been synthesized and conveniently grafted onto a particular support, thiol removal might be required before its use. Here, thiolate and sulfur electrodesorption from nanoparticle and planar platinum surfaces are comparatively studied by combining ex-situ X-ray photoelectron spectroscopy (XPS) and electrochemical techniques. We show that alkanethiolates and sulfur adsorbed on Pt surfaces are more stable against reductive desorption than these species on Au substrates. Furthermore, for short-chain thiol-capped platinum nanoparticles we observe complete removal of sulfur-containing species. Hence, these results make this procedure suitable for its use in electrocatalysis. As an example, we demonstrate that 2 nm thiomalic acid-protected platinum nanoparticles markedly improve the performance of a hydrogen storage alloy material, with no additional steps in the preparation of the electrodes.Fil: Floridia Addato, María Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicaciones; ArgentinaFil: Rubert, Aldo Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicaciones; ArgentinaFil: Benitez, Guillermo Alfredo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicaciones; ArgentinaFil: Zelaya, Maria Eugenia. Comisión Nacional de Energía Atómica. Gerencia del Área Investigaciones y Aplicaciones No Nucleares. Gerencia de Física (cab). Grupo de Fisica de Metales; ArgentinaFil: Cabello, Gema. Consejo Superior de Investigaciones Cientificas. Instituto de Quimica Fisica; ArgentinaFil: Cuesta, Angel. Consejo Superior de Investigaciones Cientificas. Instituto de Quimica Fisica; ArgentinaFil: Thomas, Jorge Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicaciones; ArgentinaFil: Arnaldo Visintín. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicaciones; ArgentinaFil: Salvarezza, Roberto Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicaciones; ArgentinaFil: Fonticelli, Mariano Hernan. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicaciones; Argentin

Seagrass Cymodocea nodosa across biogeographical regions and times: Differences in abundance, meadow structure and sexual reproduction

Seagrasses are key habitat-forming species of coastal areas. While previous research has demonstrated considerable small-scale variation in seagrass abundance and structure, studies teasing apart local from large-scale variation are scarce. We determined how different biogeographic scenarios, under varying environmental and genetic variation, explained variation in the abundance and structure (morphology and biomass allocation), epiphytes and sexual reproduction intensity of the seagrass Cymodocea nodosa. Regional and local-scale variation, including their temporal variability, contributed to differentially explain variation in seagrass attributes. Structural, in particular morphological, attributes of the seagrass leaf canopy, most evidenced regional seasonal variation. Allocation to belowground tissues was, however, mainly driven by local-scale variation. High seed densities were observed in meadows of large genetic diversity, indicative of sexual success, which likely resulted from the different evolutionary histories undergone by the seagrass at each region. Our results highlight that phenotypic plasticity to local and regional environments need to be considered to better manage and preserve seagrass meadows.This research was supported by a Doctoral fellowship from Universidad de Los Lagos (Chile) to Julia Máñez-Crespo and the work was funded by a project (RESIGRASS, CGL 2014-58829) supported by the Secretaría de Estado de Investigación, Desarrollo e Innovación (MINECO, Government of Spain) to F. Tomas and F. Tuya

Effect of SGLT2 Inhibitors on Stroke and Atrial Fibrillation in Diabetic Kidney Disease: Results From the CREDENCE Trial and Meta-Analysis

BACKGROUND AND PURPOSE: Chronic kidney disease with reduced estimated glomerular filtration rate or elevated albuminuria increases risk for ischemic and hemorrhagic stroke. This study assessed the effects of sodium glucose cotransporter 2 inhibitors (SGLT2i) on stroke and atrial fibrillation/flutter (AF/AFL) from CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) and a meta-analysis of large cardiovascular outcome trials (CVOTs) of SGLT2i in type 2 diabetes mellitus.METHODS: CREDENCE randomized 4401 participants with type 2 diabetes mellitus and chronic kidney disease to canagliflozin or placebo. Post hoc, we estimated effects on fatal or nonfatal stroke, stroke subtypes, and intermediate markers of stroke risk including AF/AFL. Stroke and AF/AFL data from 3 other completed large CVOTs and CREDENCE were pooled using random-effects meta-analysis.RESULTS: In CREDENCE, 142 participants experienced a stroke during follow-up (10.9/1000 patient-years with canagliflozin, 14.2/1000 patient-years with placebo; hazard ratio [HR], 0.77 [95% CI, 0.55-1.08]). Effects by stroke subtypes were: ischemic (HR, 0.88 [95% CI, 0.61-1.28]; n=111), hemorrhagic (HR, 0.50 [95% CI, 0.19-1.32]; n=18), and undetermined (HR, 0.54 [95% CI, 0.20-1.46]; n=17). There was no clear effect on AF/AFL (HR, 0.76 [95% CI, 0.53-1.10]; n=115). The overall effects in the 4 CVOTs combined were: total stroke (HRpooled, 0.96 [95% CI, 0.82-1.12]), ischemic stroke (HRpooled, 1.01 [95% CI, 0.89-1.14]), hemorrhagic stroke (HRpooled, 0.50 [95% CI, 0.30-0.83]), undetermined stroke (HRpooled, 0.86 [95% CI, 0.49-1.51]), and AF/AFL (HRpooled, 0.81 [95% CI, 0.71-0.93]). There was evidence that SGLT2i effects on total stroke varied by baseline estimated glomerular filtration rate (P=0.01), with protection in the lowest estimated glomerular filtration rate (<45 mL/min/1.73 m2]) subgroup (HRpooled, 0.50 [95% CI, 0.31-0.79]).CONCLUSIONS: Although we found no clear effect of SGLT2i on total stroke in CREDENCE or across trials combined, there was some evidence of benefit in preventing hemorrhagic stroke and AF/AFL, as well as total stroke for those with lowest estimated glomerular filtration rate. Future research should focus on confirming these data and exploring potential mechanisms. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02065791

Kidney and Cardiovascular Effects of Canagliflozin According to Age and Sex: A Post Hoc Analysis of the CREDENCE Randomized Clinical Trial

Rationale & Objective: It is unclear whether the effect of canagliflozin on adverse kidney and cardiovascular events in those with diabetic kid-ney disease varies by age and sex. We assessed the effects of canagliflozin among age group categories and between sexes in the Canagli-flozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) study.Study Design: Secondary analysis of a random-ized controlled trial. Setting & Participants: Participants in the CREDENCE trial. Intervention: Participants were randomly assigned to receive canagliflozin 100 mg/d or placebo.Outcomes: Primary composite outcome of kid-ney failure, doubling of serum creatinine con-centration, or death due to kidney or cardiovascular disease. Prespecified secondary and safety outcomes were also analyzed. Out-comes were evaluated by age at baseline (<60, 60-69, and >_70 years) and sex in the intention-to-treat population using Cox regression models.Results: The mean age of the cohort was 63.0 & PLUSMN; 9.2 years, and 34% were female. Older age and female sex were independently associ-ated with a lower risk of the composite of adverse kidney outcomes. There was no evidence that the effect of canagliflozin on the primary outcome (acomposite of kidney failure, a doubling of serum creatinine concentration, or death from kidney or cardiovascular causes) differed between age groups (HRs, 0.67 [95% CI, 0.52-0.87], 0.63 [0.4 8-0.82], and 0.89 [0.61-1.29] for ages <60, 60-69, and >_70 years, respectively; P = 0.3 for interaction) or sexes (HRs, 0.71 [95% CI, 0.5 4-0.95] and 0.69 [0.56-0.8 4] in women and men, respectively; P = 0.8 for interaction). No differences in safety outcomes by age group or sex were observed.Limitations: This was a post hoc analysis with multiple comparisons.Conclusions: Canagliflozin consistently reduced the relative risk of kidney events in people with diabetic kidney disease in both sexes and across age subgroups. As a result of greater background risk, the absolute reduction in adverse kidney outcomes was greater in younger participants.Funding: This post hoc analysis of the CREDENCE trial was not funded. The CREDENCE study was sponsored by Janssen Research and Development and was conducted collaboratively by the sponsor, an academic-led steering committee, and an academic research organization, George Clinical.Trial Registration: The original CREDENCE trial was registered at ClinicalTrials.gov with study number NCT02065791