Proteasome activity modulates amyloid toxicity.

Alzheimer's disease (AD) is responsible for 60%-80% of identified cases of dementia. While the generation and accumulation of amyloid precursor protein (APP) fragments is accepted as a key step in AD pathogenesis, the precise role of these fragments remains poorly understood. To overcome this deficit, we induced the expression of the soluble C-terminal fragment of APP (C99), the rate-limiting peptide for the generation of amyloid fragments, in yeast that contain thermosensitive mutations in genes encoding proteasome subunits. Our previous work with this system demonstrated that these proteasome-deficient yeast cells, expressing C99 when proteasome activity was blunted, generated amyloid fragments similar to those observed in AD patients. We now report the phenotypic repercussions of inducing C99 expression in proteasome-deficient cells. We show increased levels of protein aggregates, cellular stress and chaperone expression, electron-dense accumulations in the nuclear envelope/ER, abnormal DNA condensation, and an induction of apoptosis. Taken together, these findings suggest that the generation of C99 and its associated fragments in yeast cells with compromised proteasomal activity results in phenotypes that may be relevant to the neuropathological processes observed in AD patients. These data also suggest that this yeast model should be useful for testing therapeutics that target AD-associated amyloid, since it allows for the assessment of the reversal of the perturbed cellular physiology observed when degradation pathways are dysfunctional.

Theobroma cacao L. cultivar CCN 51: a comprehensive review on origin, genetics, sensory properties, production dynamics, and physiological aspects.

Many decades of improvement in cacao have aided to obtain cultivars with characteristics of tolerance to diseases, adaptability to different edaphoclimatic conditions, and higher yields. In Ecuador, as a result of several breeding programs, the clone CCN 51 was obtained, which gradually expanded through the cacao-production regions of Ecuador, Colombia, Brazil and Peru. Recognized for its high yield and adaptability to different regions and environments, it has become one of the most popular clones for breeding programs and cultivation around the world. This review aims to summarize the current evidence on the origin, genetics, morphological, volatile compounds, and organoleptic characteristics of this clone. Physiological evidence, production dynamics, and floral biology are also included to explain the high yield of CCN 51. Thus, characteristics such as osmotic adjustment, long pollen longevity, and fruit formation are further discussed and associated with high production at the end of the dry period. Finally, the impact of this popular clone on the current and future cacao industry will be discussed highlighting the major challenges for flavor enhancement and its relevance as a platform for the identification of novel genetic markers for cultivar improvement in breeding programs.

An integrated fuzzy sustainable supplier evaluation and selection framework for green supply chains in reverse logistics.

Green supply chain management considers the environmental effects of all activities related to the supply chain, from obtaining raw materials to the final delivery of finished goods. Selecting the right supplier is a critical decision in green supply chain management. We propose a fuzzy green supplier selection model for sustainable supply chains in reverse logistics. We define a novel hierarchical fuzzy best-worst method (HFBWM) to determine the importance weights of the green criteria and sub-criteria selected. The fuzzy extension of Shannon's entropy, a more complex evaluation method, is also used to determine the criteria weights, providing a reference comparison benchmark. Several hybrid models integrating both weighting techniques with fuzzy versions of complex proportional assessment (COPRAS), multi-objective optimization by ratio analysis plus the full multiplicative form (MULTIMOORA), and the technique for order of preference by similarity to ideal solution (TOPSIS) are designed to rank the suppliers based on their ability to recycle in reverse logistics. We aggregate these methods' ranking results through a consensus ranking model and illustrate the capacity of relatively simple methods such as fuzzy COPRAS and fuzzy MOORA to provide robust rankings highly correlated with those delivered by more complex techniques such as fuzzy MULTIMOORA. We also find that the ranking results obtained by these hybrid models are more consistent when HFBWM determines the weights. A case study in the asphalt manufacturing industry is presented to demonstrate the proposed methods' applicability and efficacy.

A hybrid data envelopment analysis-artificial neural network prediction model for COVID-19 severity in transplant recipients.

In an overwhelming demand scenario, such as the SARS-CoV-2 pandemic, pressure over health systems may outburst their predicted capacity to deal with such extreme situations. Therefore, in order to successfully face a health emergency, scientific evidence and validated models are needed to provide real-time information that could be applied by any health center, especially for high-risk populations, such as transplant recipients. We have developed a hybrid prediction model whose accuracy relative to several alternative configurations has been validated through a battery of clustering techniques. Using hospital admission data from a cohort of hospitalized transplant patients, our hybrid Data Envelopment Analysis (DEA)-Artificial Neural Network (ANN) model extrapolates the progression towards severe COVID-19 disease with an accuracy of 96.3%, outperforming any competing model, such as logistic regression (65.5%) and random forest (44.8%). In this regard, DEA-ANN allows us to categorize the evolution of patients through the values of the analyses performed at hospital admission. Our prediction model may help guiding COVID-19 management through the identification of key predictors that permit a sustainable management of resources in a patient-centered model. Supplementary Information: The online version contains supplementary material available at 10.1007/s10462-021-10008-0.

Sex-Specific Ventricular Arrhythmias and Mortality in Cardiac Resynchronization Therapy Recipients.

OBJECTIVES: The study goal was to examine whether there are sex-related differences in the incidence of ventricular arrhythmias and mortality in CRT-defibrillator (CRT-D) recipients. BACKGROUND: Few studies have evaluated sex-related benefits of cardiac resynchronization therapy (CRT). Moreover, data on sex-related differences in the occurrence of ventricular tachyarrhythmias in this population are limited. METHODS: A multicenter retrospective study was conducted in 460 patients (355 male subjects and 105 female subjects) from the UMBRELLA (Incidence of Arrhythmia in Spanish Population With a Medtronic Implantable Cardiac Defibrillator Implant) national registry. Patients were followed up through remote monitoring after the first implantation of a CRT-D during a median follow-up of 2.2 ± 1.0 years. Sex differences were analyzed in terms of ventricular arrhythmia-treated incidence and death during the follow-up period, with a particular focus on primary prevention patients. RESULTS: Baseline New York Heart Association functional class was worse in women compared with that in men (67.0% of women in New York Heart Association functional class III vs. 49.7% of men; p = 0.003), whereas women had less ischemic cardiac disease (20.8% vs. 41.7%; p < 0.001). Female sex was an independent predictor of ventricular arrhythmias (hazard ratio: 0.40; 95% confidence interval: 0.19 to 0.86; p = 0.020), as well as left ventricular ejection fraction and nonischemic cardiomyopathy. Mortality in women was one-half that of men, although events were scarce and without significant differences (2.9% vs. 5.6%; p = 0.25). CONCLUSIONS: Women with left bundle branch block and implanted CRT have a lower rate of ventricular tachyarrhythmias than men. All-cause mortality in patients is, at least, similar between female and male subjects.

Modeling patients as decision making units: evaluating the efficiency of kidney transplantation through data envelopment analysis.

The main applications of Data Envelopment Analysis (DEA) to medicine focus on evaluating the efficiency of different health structures, hospitals and departments within them. The evolution of patients after undergoing a medical procedure or their response to a given treatment are not generally studied through this programming technique. In addition to the difficulty inherent to the collection of this type of data, the use of a technique that is mainly applied to evaluate the efficiency of decision making units representing industrial and production structures to analyze the evolution of human patients may seem inappropriate. In the current paper, we illustrate how this is not actually the case and implement a decision engineering approach to model kidney transplantation patients as decision making units. As such, patients undergo three different phases, each composed by specific as well as interrelated variables, determining the potential success of the transplantation process. DEA is applied to a set of 12 input and 6 output variables - retrieved over a 10-year period - describing the evolution of 485 patients undergoing kidney transplantation from living donors. The resulting analysis allows us to classify the set of patients in terms of the efficiency of the transplantation process and identify the specific characteristics across which potential improvements could be defined on a per patient basis.

Atrial myxoma in a patient with patent foramen ovale: evaluation with multimodal imaging. Case report / Mixoma auricular en un paciente con foramen oval permeable: evaluación con imágenes multimodales. Reporte de un caso

Abstract: Primary cardiac tumors in adults are rare and mostly benign, approximately 75%, being the myxoma the most frequent in half of that percentage. One-fourth of the primary cardiac tumors are malignant and 95% of the cases are sarcomas. Metastases are more frequent than primary tumors. Cardiac surgery is indicated specially in benign masses and therapies such as chemotherapy and/or radiotherapy should be reserved for unresectable or metastatic malignancies. Hence the importance of a diagnostic approach, which leads to the best therapeutic conduct and in many cases, a multimodal image approach is necessary, as it is exposed in our case.(AU)

Resumen: Los tumores cardiacos primarios en adultos son raros y en su mayoría benignos, aproximadamente el 75%, siendo el mixoma el más frecuente en la mitad de ese porcentaje. Un cuarto de los tumores cardiacos primarios son malignos y el 95% de los casos son sarcomas. Las metástasis son más frecuentes que los tumores primarios. La cirugía cardiaca está indicada especialmente en masas benignas y las terapias como la quimioterapia y/o la radioterapia deben reservarse para tumores malignos o metástasis irresecables. De ahí la importancia de un enfoque de diagnóstico, que conduzca a la mejor conducta terapéutica y, en muchos casos, es necesario un enfoque de imagen multimodal, como está expuesto en nuestro caso.(AU)

Utilidad de una estrategia educativa activo-participativa en el desarrollo del razonamiento clínico en pregrado / Usefulness of active participatory educational strategy for the development of clinical reasoning in undergraduate education

Introducción: algunas escuelas de Medicina, enfrentan hoy en día la dificultad que presentan los alumnos de pregrado al enfrentarse a problemas clínicos en los diferentes escenarios clínicos, situación que revela la visión de la educación médica, donde claramente predomina un enfoque pasivo en la construcción del conocimiento. Objetivo: comparar el grado de desarrollo del razonamiento clínico en los alumnos de la carrera de Medicina que reciben el curso de Ginecobstetricia utilizando una modalidad educativa activo-participativa, en comparación con los que utilizan el método tradicional. Métodos: estudio de intervención, comparativo y prospectivo en dos grupos de alumnos del 7mo. semestre de la carrera de Medicina. El grupo experimental incluyó a 16 alumnos y el grupo control a 22. Las modalidades educativas comparadas fueron: activo-participativa en la que los alumnos utilizan guías de lectura estructuradas para construir el conocimiento y la tradicional o expositiva. La variable dependiente en este estudio fue el grado de desarrollo del razonamiento clínico. Para el análisis de los resultados se utilizó estadística descriptiva y paramétrica. Resultados: el promedio de calificación en la posevaluación del total de participantes en este estudio, fue de 78,7 en los hombres y de 86,7 en las mujeres (p: NS). La diferencia del avance en el desarrollo del razonamiento clínico, fue mayor en la posevaluación a favor del grupo experimental (14,7 vs 33,2 puntos). Conclusiones: el desarrollo del razonamiento clínico es mayor con la estrategia educativa activo participativa que con la estrategia tradicional(AU)

Introduction: at present, some medical schools face the difficulties that their undergraduate students have when addressing clinical problems at various clinical settings, a situation that shows the vision of medical education in which a passive approach to the construction of knowledge clearly predominates. Objective: to compare the level of development of the clinical reasoning achieved by medical students who are in the gynecobstetrics course by using an active participatory educational modality and the traditional method. Methods: prospective, comparative and interventional study conducted in two 7th semester groups of medical students. The experimental group comprised 16 individuals and the control group 22. The educational modalities under comparison were active participatory where the students use structured reading guidelines to construct their knowledge and the traditional or expositional one. The depending variable was the level of development of the clinical reasoning. Results: the scoring of all the participating students post-evaluation was 78.7 for men and 86.7 for females. The differences in the development of clinical reasoning attained by students was higher in the experimental group after evaluation (14.7 vs 33.2) Conclusions: the development of the clinical reasoning was greater with the active participatory educational strategy than in the traditional method(AU)

Leukemia in children and youths of the Azuay province, Ecuador: 2000-2010.

We mapped leukemia risk among children and youths in the Azuay province, Rio Paute river basin, Ecuador, in 2000-2010, using a Bayesian disease mapping model. We assessed the comprehensiveness of the list of leukemia cases from the Sociedad de Lucha contra el Càncer en el Ecuador (SOLCA) Hospital in Cuenca, the only referral center for oncology in the whole Rio Paute area, by comparison to the Quito cancer registry. Risk of leukemia did not vary significantly by canton within the Azuay province. However, a moderate increase in risk of borderline statistical significance was observed in the city of Cuenca and particularly among males in a heavily industrialized parish, who had an almost eight-fold excess (95% CI 3.03, 20.39, p = 0.01) of AML. Analytical studies are warranted to properly address specific etiological factor of leukemia among children and youths of the Azuay province of Ecuador.

Incontinencia urinaria de esfuerzo: Manejo quirúrgico / Urinary stress incontinence: Surgical management

Se estudiaron 98 pacientes operadas por incontinencia urinaria de esfuerzo y se analizaron los factores de riesgo: edad, peso, talla, paridad, edad de menopausia y antecedentes médico quirúrgicos. Se dividieron en dos grupos; el grupo I, formado por pacientes operadas con la técnica de Kelly-Kennedy, (35), y el grupo II, pacientes operadas con la técnica de Burch (63). No se encontraron diferencias entre las características de las pacientes en ambos grupos; la patología agregada más frecuente fueron las distopias; las complicaciones se presentaron en 17.1 y 33.3%, respectivamente. Se corroboró la eficacia de la operación de Burch para manejar este padecimiento, siendo superior a la operación vaginal (p< - 0.05).(au)