Abnormal ECG Findings in Athletes: Clinical Evaluation and Considerations.

PURPOSE OF REVIEW: Pre-participation cardiovascular evaluation with electrocardiography is normal practice for most sporting bodies. Awareness about sudden cardiac death in athletes and recognizing how screening can help identify vulnerable athletes have empowered different sporting disciplines to invest in the wellbeing of their athletes. RECENT FINDINGS: Discerning physiological electrical alterations due to athletic training from those representing cardiac pathology may be challenging. The mode of investigation of affected athletes is dependent on the electrical anomaly and the disease(s) in question. This review will highlight specific pathological ECG patterns that warrant assessment and surveillance, together with an in-depth review of the recommended algorithm for evaluation

Guía práctica para la producción artesanal de semillas de cebolla para la agricultura familiar de la zona de la Norpatagonia

Esta publicación tiene como objetivo general constituirse en una guía de consulta permanente, incorporando una serie de conocimientos prácticos suficiente para aquellos agricultores familiares que deseen generar su propia simiente. De igual manera puede ser útil para que grupos de agricultores organizados se inicien en un programa de producción artesanal de semillas de cebolla a pequeña escala, con fines de autoabastecimiento para grupos o asociaciones de agricultores regionales, pudiendo generar además una fuente adicional de ingresos para su economía familiar. Está basado en experiencias realizadas en la chacra experimental de la Facultad de Ciencias Agrarias ubicada en la localidad de Cinco Saltos, Provincia de Río Negro (38° 50’ 41 21 S y 68° 04’ 04 88 O 287 m.s.n.m.). Sabemos que la información aquí presentada no le será totalmente desconocida; sino que a partir de conocimientos previos y experiencias podrán enriquecer y ampliar este material. Ahora bien, Porqué producir nuestras propias semillas? En realidad podemos producir nuestras propias semillas, pagar por ellas, o esperar que algún organismo estatal nos las entregue; son tres tipos de abastecimiento posibles. Pero entre la mayoría de los agricultores que constituyen por su escala de producción la agricultura familiar sin duda la primera es la única que genera un nivel de independencia y de control de lo que se está consumiendo que a mediano y largo plazo termina siendo la propuesta más provechosa. El hecho de multiplicar nuestras propias semillas nos permite sobre todas las cosas la posibilidad de contar en tiempo y forma con material genético conocido, además de tener la certeza de que se trata de variedades adaptadas a las condiciones agroecológicas de la zona. También nos da mayor tranquilidad el saber que partimos utilizando semillas frescas garantizándonos una mayor y mejor germinación. Las condiciones agroecológicas de la Norpatagonia para la producción de semillas de cebolla en lo referente al suelo, agua, temperatura y Humedad relativa ambiente son inmejorables.Fil: Verdile, Horacio. Universidad Nacional del Comahue. Facultad de Ciencias Agrarias; Argentina

Generation and quality control of lipidomics data for the alzheimers disease neuroimaging initiative cohort.

Alzheimers disease (AD) is a major public health priority with a large socioeconomic burden and complex etiology. The Alzheimer Disease Metabolomics Consortium (ADMC) and the Alzheimer Disease Neuroimaging Initiative (ADNI) aim to gain new biological insights in the disease etiology. We report here an untargeted lipidomics of serum specimens of 806 subjects within the ADNI1 cohort (188 AD, 392 mild cognitive impairment and 226 cognitively normal subjects) along with 83 quality control samples. Lipids were detected and measured using an ultra-high-performance liquid chromatography quadruple/time-of-flight mass spectrometry (UHPLC-QTOF MS) instrument operated in both negative and positive electrospray ionization modes. The dataset includes a total 513 unique lipid species out of which 341 are known lipids. For over 95% of the detected lipids, a relative standard deviation of better than 20% was achieved in the quality control samples, indicating high technical reproducibility. Association modeling of this dataset and available clinical, metabolomics and drug-use data will provide novel insights into the AD etiology. These datasets are available at the ADNI repository at http://adni.loni.usc.edu/

Evaluation of virtual screening strategies for the identification of γ-secretase inhibitors and modulators

γ-Secretase is an intramembrane aspartyl protease that is important in regulating normal cell physiology via cleavage of over 100 transmembrane proteins, including Amyloid Precursor Protein (APP) and Notch family receptors. However, aberrant proteolysis of substrates has implications in the progression of disease pathologies, including Alzheimer’s disease (AD), cancers, and skin disorders. While several γ-secretase inhibitors have been identified, there has been toxicity observed in clinical trials associated with non-selective enzyme inhibition. To address this, γ-secretase modulators have been identified and pursued as more selective agents. Recent structural evidence has provided an insight into how γ-secretase inhibitors and modulators are recognized by γ-secretase, providing a platform for rational drug design targeting this protease. In this study, docking-and pharmacophore-based screening approaches were evaluated for their ability to identify, from libraries of known inhibitors and modulators with decoys with similar physicochemical properties, γ-secretase inhibitors and modulators. Using these libraries, we defined strategies for identifying both γ-secretase inhibitors and modulators incorporating an initial pharmacophore-based screen followed by a docking-based screen, with each strategy employing distinct γ-secretase structures. Furthermore, known γ-secretase inhibitors and modulators were able to be identified from an external set of bioactive molecules following application of the derived screening strategies. The approaches described herein will inform the discovery of novel small molecules targeting γ-secretase

International criteria for electrocardiographic interpretation in athletes: Consensus statement.

Sudden cardiac death (SCD) is the leading cause of mortality in athletes during sport. A variety of mostly hereditary, structural or electrical cardiac disorders are associated with SCD in young athletes, the majority of which can be identified or suggested by abnormalities on a resting 12-lead electrocardiogram (ECG). Whether used for diagnostic or screening purposes, physicians responsible for the cardiovascular care of athletes should be knowledgeable and competent in ECG interpretation in athletes. However, in most countries a shortage of physician expertise limits wider application of the ECG in the care of the athlete. A critical need exists for physician education in modern ECG interpretation that distinguishes normal physiological adaptations in athletes from distinctly abnormal findings suggestive of underlying pathology. Since the original 2010 European Society of Cardiology recommendations for ECG interpretation in athletes, ECG standards have evolved quickly, advanced by a growing body of scientific data and investigations that both examine proposed criteria sets and establish new evidence to guide refinements. On 26-27 February 2015, an international group of experts in sports cardiology, inherited cardiac disease, and sports medicine convened in Seattle, Washington (USA), to update contemporary standards for ECG interpretation in athletes. The objective of the meeting was to define and revise ECG interpretation standards based on new and emerging research and to develop a clear guide to the proper evaluation of ECG abnormalities in athletes. This statement represents an international consensus for ECG interpretation in athletes and provides expert opinion-based recommendations linking specific ECG abnormalities and the secondary evaluation for conditions associated with SCD

A Zebrafish melanophore model of Amyloid (beta) toxicity

Reliable animal models are required to facilitate the understanding of neurodegenerative pathways in Alzheimer’s disease. Animal models can also be employed to search for disease-modifying drugs. The embryos and larvae of zebrafish are particularly advantageous for this purpose. For Alzheimer’s disease, drugs that can ameliorate amyloidb (Ab) toxicity have therapeutic and=or prophylactic potential. We attempted to generate a zebrafish model of Ab toxicity that would be viable and fertile but have a highly visible pigmentation phenotype in larvae. The larvae could then be arrayed in microtiter plates to screen compound libraries for drugs acting to reduce Ab toxicity. We used the promoter of the zebrafish mitfa (nacre) gene to drive expression of the pathological 42 amino acid species of human Ab, Ab42, specifically in the highly visible melanophores (melanocytes) of transgenic zebrafish. However, the transgenic fish only showed an aberrant pigment phenotype in adults at the advanced age of 16 months. Nevertheless, our results show that alteration of zebrafish pigment pattern may be useful for analysis of toxic peptide action

A Detailed Study of Rainbow Trout (Onchorhynchus mykiss) Intestine Revealed That Digestive and Absorptive Functions Are Not Linearly Distributed along Its Length

To increase the sustainability of trout farming,the industry requires alternatives to \ufb01sh-based meals that do not compromise animal health and growth performances. To develop new feeds, detailed knowledge of intestinal morphology and physiology is required. We performed histological, histochemical, immunohistochemical and morphometric analysis at typical time points of in vivo feeding trials (50, 150 and 500 g). Only minor changes occurred during growth whereas di\ufb00erences characterized two compartments, not linearly distributed along the intestine. The \ufb01rst included the pyloric caeca, the basal part of the complex folds and the villi of the distal intestine. This was characterized by a signi\ufb01cantly smaller number of goblet cells with smaller mucus vacuoles, higher proliferation and higher apoptotic rate but a smaller extension of fully di\ufb00erentiated epithelial cells and by the presence of numerous pinocytotic vacuolization. The second compartment was formed by the proximal intestine and the apical part of the posterior intestine complex folds. Here we observed more abundant goblet cells with bigger vacuoles, low proliferation rate, few round apoptotic cells, a more extended area of fully di\ufb00erentiated cells and no pinocytotic vacuoles. Our results suggest that rainbow trout intestine is physiologically arranged to mingle digestive and absorptive functions along its lengt

The Guinea Pig as a model for sporadic Alzheimer's Disease (AD): the impact of cholesterol intake on expression of AD-related genes

Extent: 12p.We investigated the guinea pig, Cavia porcellus, as a model for Alzheimer’s disease (AD), both in terms of the conservation of genes involved in AD and the regulatory responses of these to a known AD risk factor - high cholesterol intake. Unlike rats and mice, guinea pigs possess an Aβ peptide sequence identical to human Aβ. Consistent with the commonality between cardiovascular and AD risk factors in humans, we saw that a high cholesterol diet leads to up-regulation of BACE1 (β-secretase) transcription and down-regulation of ADAM10 (α-secretase) transcription which should increase release of Aβ from APP. Significantly, guinea pigs possess isoforms of AD-related genes found in humans but not present in mice or rats. For example, we discovered that the truncated PS2V isoform of human PSEN2, that is found at raised levels in AD brains and that increases γ-secretase activity and Aβ synthesis, is not uniquely human or aberrant as previously believed. We show that PS2V formation is up-regulated by hypoxia and a high-cholesterol diet while, consistent with observations in humans, Aβ concentrations are raised in some brain regions but not others. Also like humans, but unlike mice, the guinea pig gene encoding tau, MAPT, encodes isoforms with both three and four microtubule binding domains, and cholesterol alters the ratio of these isoforms. We conclude that AD-related genes are highly conserved and more similar to human than the rat or mouse. Guinea pigs represent a superior rodent model for analysis of the impact of dietary factors such as cholesterol on the regulation of AD-related genes.Mathew J. Sharman, Seyyed H. Moussavi Nik, Mengqi M. Chen, Daniel Ong, Linda Wijaya, Simon M. Laws, Kevin Taddei, Morgan Newman, Michael Lardelli, Ralph N. Martins, Giuseppe Verdil

Aberrant Phase Transitions: Side Effects and Novel Therapeutic Strategies in Human Disease

Phase separation is a physiological process occurring spontaneously when single-phase molecular complexes separate in two phases, a concentrated phase and a more diluted one. Eukaryotic cells employ phase transition strategies to promote the formation of intracellular territories not delimited by membranes with increased local RNA concentration, such as nucleolus, paraspeckles, P granules, Cajal bodies, P-bodies, and stress granules. These organelles contain both proteins and coding and non-coding RNAs and play important roles in different steps of the regulation of gene expression and in cellular signaling. Recently, it has been shown that most human RNA-binding proteins (RBPs) contain at least one low-complexity domain, called prion-like domain (PrLD), because proteins harboring them display aggregation properties like prion proteins. PrLDs support RBP function and contribute to liquid–liquid phase transitions that drive ribonucleoprotein granule assembly, but also render RBPs prone to misfolding by promoting the formation of pathological aggregates that lead to toxicity in specific cell types. Protein–protein and protein-RNA interactions within the separated phase can enhance the transition of RBPs into solid aberrant aggregates, thus causing diseases. In this review, we highlight the role of phase transition in human disease such as amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and in cancer. Moreover, we discuss novel therapeutic strategies focused to control phase transitions by preventing the conversion into aberrant aggregates. In this regard, the stimulation of chaperone machinery to disassemble membrane-less organelles, the induction of pathways that could inhibit aberrant phase separation, and the development of antisense oligonucleotides (ASOs) to knockdown RNAs could be evaluated as novel therapeutic strategies for the treatment of those human diseases characterized by aberrant phase transition aggregates