Algunos aspectos de la actividad eléctrica en el tejido cardiaco utilizando elementos finitos

En el siglo pasado fueron muchos los avances que se dieron en las ciencias biológicas, en particular, en la fisiología humana con la utilización de los modelos matemáticos para acercarnos a la comprensión de su fenomenología fisiológica, en especial con las ecuaciones diferenciales tanto las ordinarias como las parciales. Sólo por mencionar algunos de los principales investigadores en este campo tenemos a Hodkin y Huxley en (1952), [25, 26, 27, 29]; FitzHugh-Nagumo (1961), Hirota, Satsamo (1987), quienes han colaborado con una serie de modelos matemáticos de gran aplicabilidad en la fisiología humana, mostrando el acercamiento con otras disciplinas de las ciencias exactas para la interpretación y esclarecimiento del fenómeno afrontado. Los avances en la computación hacen posible simulaciones en tiempo real de los fenómenos y esclarecer los procesos óptimos que utiliza la fisiología para completar sus procesos funcionales [19].iv, 80 p.Contenido parcial: Fisiología del corazón -- La dinámica de las células excitables -- El modelo Hodgkin-Huxley -- La actividad eléctrica del tejido cardiaco -- El método de los elementos finitos

Reproducibility in the absence of selective reporting: An illustration from large‐scale brain asymmetry research

The problem of poor reproducibility of scientific findings has received much attention over recent years, in a variety of fields including psychology and neuroscience. The problem has been partly attributed to publication bias and unwanted practices such as p‐hacking. Low statistical power in individual studies is also understood to be an important factor. In a recent multisite collaborative study, we mapped brain anatomical left–right asymmetries for regional measures of surface area and cortical thickness, in 99 MRI datasets from around the world, for a total of over 17,000 participants. In the present study, we revisited these hemispheric effects from the perspective of reproducibility. Within each dataset, we considered that an effect had been reproduced when it matched the meta‐analytic effect from the 98 other datasets, in terms of effect direction and significance threshold. In this sense, the results within each dataset were viewed as coming from separate studies in an “ideal publishing environment,” that is, free from selective reporting and p hacking. We found an average reproducibility rate of 63.2% (SD = 22.9%, min = 22.2%, max = 97.0%). As expected, reproducibility was higher for larger effects and in larger datasets. Reproducibility was not obviously related to the age of participants, scanner field strength, FreeSurfer software version, cortical regional measurement reliability, or regional size. These findings constitute an empirical illustration of reproducibility in the absence of publication bias or p hacking, when assessing realistic biological effects in heterogeneous neuroscience data, and given typically‐used sample sizes

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

Global urban environmental change drives adaptation in white clover

Urbanization transforms environments in ways that alter biological evolution. We examined whether urban environmental change drives parallel evolution by sampling 110,019 white clover plants from 6169 populations in 160 cities globally. Plants were assayed for a Mendelian antiherbivore defense that also affects tolerance to abiotic stressors. Urban-rural gradients were associated with the evolution of clines in defense in 47% of cities throughout the world. Variation in the strength of clines was explained by environmental changes in drought stress and vegetation cover that varied among cities. Sequencing 2074 genomes from 26 cities revealed that the evolution of urban-rural clines was best explained by adaptive evolution, but the degree of parallel adaptation varied among cities. Our results demonstrate that urbanization leads to adaptation at a global scale

Niraparib in patients with metastatic castration-resistant prostate cancer and DNA repair gene defects (GALAHAD): a multicentre, open-label, phase 2 trial

Background Metastatic castration-resistant prostate cancers are enriched for DNA repair gene defects (DRDs) that can be susceptible to synthetic lethality through inhibition of PARP proteins. We evaluated the anti-tumour activity and safety of the PARP inhibitor niraparib in patients with metastatic castration-resistant prostate cancers and DRDs who progressed on previous treatment with an androgen signalling inhibitor and a taxane. Methods In this multicentre, open-label, single-arm, phase 2 study, patients aged at least 18 years with histologically confirmed metastatic castration-resistant prostate cancer (mixed histology accepted, with the exception of the small cell pure phenotype) and DRDs (assessed in blood, tumour tissue, or saliva), with progression on a previous next-generation androgen signalling inhibitor and a taxane per Response Evaluation Criteria in Solid Tumors 1.1 or Prostate Cancer Working Group 3 criteria and an Eastern Cooperative Oncology Group performance status of 0–2, were eligible. Enrolled patients received niraparib 300 mg orally once daily until treatment discontinuation, death, or study termination. For the final study analysis, all patients who received at least one dose of study drug were included in the safety analysis population; patients with germline pathogenic or somatic biallelic pathogenic alterations in BRCA1 or BRCA2 (BRCA cohort) or biallelic alterations in other prespecified DRDs (non-BRCA cohort) were included in the efficacy analysis population. The primary endpoint was objective response rate in patients with BRCA alterations and measurable disease (measurable BRCA cohort). This study is registered with ClinicalTrials.gov, NCT02854436. Findings Between Sept 28, 2016, and June 26, 2020, 289 patients were enrolled, of whom 182 (63%) had received three or more systemic therapies for prostate cancer. 223 (77%) of 289 patients were included in the overall efficacy analysis population, which included BRCA (n=142) and non-BRCA (n=81) cohorts. At final analysis, with a median follow-up of 10·0 months (IQR 6·6–13·3), the objective response rate in the measurable BRCA cohort (n=76) was 34·2% (95% CI 23·7–46·0). In the safety analysis population, the most common treatment-emergent adverse events of any grade were nausea (169 [58%] of 289), anaemia (156 [54%]), and vomiting (111 [38%]); the most common grade 3 or worse events were haematological (anaemia in 95 [33%] of 289; thrombocytopenia in 47 [16%]; and neutropenia in 28 [10%]). Of 134 (46%) of 289 patients with at least one serious treatment-emergent adverse event, the most common were also haematological (thrombocytopenia in 17 [6%] and anaemia in 13 [4%]). Two adverse events with fatal outcome (one patient with urosepsis in the BRCA cohort and one patient with sepsis in the non-BRCA cohort) were deemed possibly related to niraparib treatment. Interpretation Niraparib is tolerable and shows anti-tumour activity in heavily pretreated patients with metastatic castration-resistant prostate cancer and DRDs, particularly in those with BRCA alterations

Centrality evolution of the charged-particle pseudorapidity density over a broad pseudorapidity range in Pb-Pb collisions at root s(NN)=2.76TeV

Peer reviewe

Estudio cualitativo de levaduras indígenas para su potencial uso como cultivos iniciadores en fermentaciones de aceitunas de mesa

Estudio cualitativo de levaduras indígenas para su potencial uso como cultivos iniciadores en fermentaciones de aceitunas de mesa.Fil: Pesce, V. M.. Universidad Nacional de San Juan. Facultad de Ingeniería. Instituto de Biotecnología; ArgentinaFil: Muñoz, M. A.. Universidad Nacional de San Juan. Facultad de Ingeniería. Instituto de Biotecnología; ArgentinaFil: Guerra, G. B.. Universidad Nacional de San Juan. Facultad de Ingeniería. Instituto de Biotecnología; ArgentinaFil: Carrizo, G.. Universidad Nacional de San Juan. Facultad de Ingeniería. Instituto de Biotecnología; ArgentinaFil: Nally, M. C.. Universidad Nacional de San Juan. Facultad de Ingeniería. Instituto de Biotecnología; ArgentinaFil: Toro, Maria Eugenia. Universidad Nacional de San Juan. Facultad de Ingeniería. Instituto de Biotecnología; ArgentinaFil: Castellanos, Lucia Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Planta Piloto de Procesos Industriales Microbiológicos; ArgentinaFil: Vazquez, Fabio. Universidad Nacional de San Juan. Facultad de Ingeniería. Instituto de Biotecnología; ArgentinaXI Congreso Latinoamericano de Microbiología e Higiene de AlimentosBuenos AiresArgentinaSociedad Latinoamericana de Microbiologí

Influencia de la inoculacion mixta de cepas Saccharomyces y no-Saccharomyces sobre la composición odorante de vinos Pedro Ximénez

Introducción: la fermentación vínica es el producto de la acción de un cultivo mixto de microorganismos que involucra tanto a levaduras del género Saccharomyces, como a otros géneros no–Saccharomyces [1]. Como producto de su metabolismo secundario, se encuentran en el vino compuestos odorantes que representan cuantitativamente la mayor parte de los constituyentes del aroma [2]. Actualmente, se re- evalúa la función de las levaduras no- Saccharomyces, dado que con cultivos mixtos se podrían obtener vinos de complejidad superior [4, 5]. Estas levaduras producen ciertas enzimas que pueden mejorar el proceso de elaboración del vino y estimular su calidad promoviendo el carácter varietal [3]. El objetivo del presente trabajo fue evaluar el efecto de la inoculación de cultivos puros y mixtos de cepas Saccharomyces y no-Saccharomyces sobre la composición odorante de vinos Pedro Ximénez. Metodología: se llevaron a cabo vinificaciones a escala de laboratorio con mosto sin prensar perteneciente al varietal "Pedro Ximénez" (3 litros en envases de 5 litros de capacidad), los mismos fueron cerrados con tapones provistos de válvulas de Müller. Se emplearon las cepas BSc562-04 (Saccharomyces cerevisiae), BDv566-04 (Debaryomyces vanrijiae) y BCs403-04 (Candida sake) en condiciones puras y mixtas Saccharomyces / no-Saccharomyces: 1-99% (M1 y M3) y 10-90% (M2 y M4). Los compuestos odorantes se extrajeron por microextracción en fase sólida en espacio de cabeza (HS-SPME) y se analizaron por Cromatografía de Gases - Espectrometría de Masas. Resultados: se identificaron y cuantificaron 84 compuestos odorantes. Se clasificaron como ácidos, ésteres, alcoholes, terpenos, norisoprenoides, aldehídos y cetonas. Se evaluó el contenido total de estos grupos de compuestos. Cuando se compararon los valores de aromas de las condiciones puras de S. cerevisiae, D. vanrijiae y C. sake con sus correspondientes mixtas (M1-M3 y M2- M4 respectivamente) no se encontraron diferencias estadísticamente significativas en el contenido total de ácidos y alcoholes (Duncan, p<0,05). Sin embargo, se observaron diferencias estadísticamente significativas en el contenido total de terpenos y norisoprenoides, ambos de origen varietal; en cuya liberación está involucrada la acción de la β-glucosidasa producida por las levaduras, y ésteres. Estos tres grupos de compuestos se presentaron en todas las muestras analizadas. En todos los ensayos no se detectaron aldehídos. Las muestras “Control” (mosto sin fermentar) fueron las únicas en las que se identificaron cetonas (2-heptanona, 2- nonanona y 2-undecanona). Conclusión: este ensayo permitió observar diferencias estadísticamente significativas en la composición odorante de vinos inoculados con cultivos puros y cultivos mixtos sugiriendo la influencia de esta modalidad de inoculación en las características finales del producto.Fil: Maturano, Yolanda Paola. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de San Juan. Facultad de Ingeniería. Instituto de Biotecnología; ArgentinaFil: Rodríguez Assaf, Leticia Anahí. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de San Juan. Facultad de Ingeniería. Instituto de Biotecnología; Argentina. Universidad Nacional de San Juan. Facultad de Ciencias Exactas, Físicas y Naturales; ArgentinaFil: Castellanos, Lucia Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Planta Piloto de Procesos Industriales Microbiológicos; Argentina. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia; ArgentinaFil: Toro, Maria Eugenia. Universidad Nacional de San Juan. Facultad de Ingeniería. Instituto de Biotecnología; ArgentinaFil: Vazquez, Fabio. Universidad Nacional de San Juan. Facultad de Ingeniería. Instituto de Biotecnología; ArgentinaFil: Assof, M.. Instituto Nacional de Tecnologia Agropecuaria. Centro Regional Mendoza-san Juan. Estacion Experimental Agropecuaria Mendoza. Agencia de Extension Rural Lujan de Cuyo.; ArgentinaFil: Jofre, V.. Instituto Nacional de Tecnologia Agropecuaria. Centro Regional Mendoza-san Juan. Estacion Experimental Agropecuaria Mendoza. Agencia de Extension Rural Lujan de Cuyo.; ArgentinaXII Congreso Internacional de Viticultura y EnologíaMontevideoUruguayAsociación de Enólogos de Urugua

Almiramide D, cytotoxic peptide from the marine cyanobacterium Oscillatoria nigroviridis

Marine benthic cyanobacteria are widely known as a source of toxic and potentially useful compounds. These microorganisms have been studied from many Caribbean locations, which recently include locations in the Colombian Caribbean Sea. In the present study, six lipopeptides named almiramides D to H, together with the known almiramide B are identified from a mat characterized as Oscillatoria nigroviridis collected at the Island of Providence (Colombia, S.W. Caribbean Sea). The most abundant compounds, almiramides B and D were characterized by NMR and HRESIMS, while the structures of the minor compounds almiramides E to H were proposed by the analysis of their HRESIMS and MS2 spectra. Almiramides B and D were tested against six human cell lines including a gingival fibroblast cell line and five human tumor cell lines (A549, MDA-MB231, MCF-7, HeLa and PC3) showing a strong but not selective toxicity