Role of oxidative stress on the etiology and pathophysiology of Amyotrophic Lateral Sclerosis (ALS) and its relation with the enteric nervous system

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting motor neurons in the spinal cord, cerebral cortex, and medulla oblongata. Most patients present a clinical phenotype of classic ALS—with predominant atrophy, muscle weakness, and fasciculations—and survival of 3 to 5 years following diagnosis. In the present review, we performed a literature search to provide an update on the etiology and pathophysiological mechanisms involved in ALS. There are two types of ALS: the familial form with genetic involvement, and the sporadic form with a multifactorial origin. ALS pathophysiology is characterized by involvement of multiple processes, including oxidative stress, glutamate excitotoxicity, and neuroinflammation. Moreover, it is proposed that conditioning risk factors affect ALS development, such as susceptibility to neurodegeneration in motor neurons, the intensity of performed physical activity, and intestinal dysbiosis with involvement of the enteric nervous system, which supports the existing theories of disease generation. To improve patients’ prognosis and survival, it is necessary to further deepen our understanding of the etiopathogenesis of ALS

Oxygen Consumption with High-Flow Nasal Oxygen versus Mechanical Ventilation— An International Multicenter Observational Study in COVID–19 Patients (PROXY–COVID)

Nasal oxygen; Mechanical ventilation; COVID-19Oxígeno nasal; Ventilación mecánica; COVID-19Oxigen nasal; Ventilació mecànica; COVID-19The COVID–19 pandemic led to local oxygen shortages worldwide. To gain a better understanding of oxygen consumption with different respiratory supportive therapies, we conducted an international multicenter observational study to determine the precise amount of oxygen consumption with high-flow nasal oxygen (HFNO) and with mechanical ventilation. A retrospective observational study was conducted in three intensive care units (ICUs) in the Netherlands and Spain. Patients were classified as HFNO patients or ventilated patients, according to the mode of oxygen supplementation with which a patient started. The primary endpoint was actual oxygen consumption; secondary endpoints were hourly and total oxygen consumption during the first two full calendar days. Of 275 patients, 147 started with HFNO and 128 with mechanical ventilation. Actual oxygen use was 4.9-fold higher in patients who started with HFNO than in patients who started with ventilation (median 14.2 [8.4–18.4] versus 2.9 [1.8–4.1] L/minute; mean difference = 11.3 [95% CI 11.0–11.6] L/minute; P < 0.01). Hourly and total oxygen consumption were 4.8-fold (P < 0.01) and 4.8-fold (P < 0.01) higher. Actual oxygen consumption, hourly oxygen consumption, and total oxygen consumption are substantially higher in patients that start with HFNO compared with patients that start with mechanical ventilation. This information may help hospitals and ICUs predicting oxygen needs during high-demand periods and could guide decisions regarding the source of distribution of medical oxygen

Strengthening research integrity: which topic areas should organisations focus on?

The widespread problems with scientific fraud, questionable research practices, and the reliability of scientific results have led to an increased focus on research integrity (RI). International organisations and networks have been established, declarations have been issued, and codes of conducts have been formed. The abstract principles of these documents are now also being translated into concrete topic areas that Research Performing organisations (RPOs) and Research Funding organisations (RFOs) should focus on. However, so far, we know very little about disciplinary differences in the need for RI support from RPOs and RFOs. The paper attempts to fill this knowledge gap. It reports on a comprehensive focus group study with 30 focus group interviews carried out in eight different countries across Europe focusing on the following research question: “Which RI topics would researchers and stakeholders from the four main areas of research (humanities, social science, natural science incl. technical science, and medical science incl. biomedicine) prioritise for RPOs and RFOs?” The paper reports on the results of these focus group interviews and gives an overview of the priorities of the four main areas of research. The paper ends with six policy recommendations and a reflection on how the results of the study can be used in RPOs and RFOs.Modern and Contemporary Studie

Sheep reproductive management

Objetive: Describe some reproductive management programs that have made it possible to increase the productive efficiency of sheep. Desing/methodology/approach: Description of the main hormones and their application in sheep reproductive management protocols. The topics are addressed from academic references and use in sheep reproductive protocols in the Reproduction Laboratory for Sheep and Goat of the Colegio de Postgraduados, Mexico. Results: The use of hormones, socio-sexual strategies, reproductive protocols and techniques are tools that improve the reproductive efficiency of sheep during the reproductive and seasonal anestrus season. Study limitations/implications: The basic techniques of reproductive management and protocols in sheep are mostly available, however they still have a wide margin for improvement, which requires multiple efforts that involve all participating sectors, such as the primary sector, institutions public and private. Findings/conclusions: Reproductive management is a pillar of great importance in animal production, which is why it is essential to implement it to improve the reproductive and productive efficiency of the herd.Objective: To describe some reproductive management programs that allow increasing the productive efficiency of ewes. Design/methodology/approach: Description of the main hormones and their application in sheep reproductive management protocols. The subjects are reviewed based on academic references as well as on their use in sheep reproductive protocols at the Sheep and Goat Reproduction Laboratory of the Colegio de Postgraduados, Mexico. Results: Hormones, socio-sexual strategies, reproductive protocols and techniques are tools that improve the reproductive efficiency of ewes during the reproductive season and seasonal anestrus. Study limitations/implications: The basic techniques of reproductive management and protocols in sheep are mostly available, however, they still have room for improvement, therefore, multiple efforts involving all participants, such as the primary sector, public and private institutions, are required. Findings/conclusions: Reproductive management is an important pillar for animal production; thus its implementation is fundamental to improve the reproductive and productive efficiency of a her

GenSeed-HMM: A tool for progressive assembly using profile HMMs as seeds and its application in Alpavirinae viral discovery from metagenomic data

This work reports the development of GenSeed-HMM, a program that implements seed-driven progressive assembly, an approach to reconstruct specific sequences from unassembled data, starting from short nucleotide or protein seed sequences or profile Hidden Markov Models (HMM). The program can use any one of a number of sequence assemblers. Assembly is performed in multiple steps and relatively few reads are used in each cycle, consequently the program demands low computational resources. As a proof-of-concept and to demonstrate the power of HMM-driven progressive assemblies, GenSeed-HMM was applied to metagenomic datasets in the search for diverse ssDNA bacteriophages from the recently described Alpavirinae subfamily. Profile HMMs were built using Alpavirinae-specific regions from multiple sequence alignments using either the viral protein 1 (VP1) (major capsid protein) or VP4 (genome replication initiation protein). These profile HMMs were used by GenSeed-HMM (running Newbler assembler) as seeds to reconstruct viral genomes from sequencing datasets of human fecal samples. All contigs obtained were annotated and taxonomically classified using similarity searches and phylogenetic analyses. The most specific profile HMM seed enabled the reconstruction of 45 partial or complete Alpavirinae genomic sequences. A comparison with conventional (global) assembly of the same original dataset, using Newbler in a standalone execution, revealed that GenSeed-HMM outperformed global genomic assembly in several metrics employed. This approach is capable of detecting organisms that have not been used in the construction of the profile HMM, which opens up the possibility of diagnosing novel viruses, without previous specific information, constituting a de novo diagnosis. Additional applications include, but are not limited to, the specific assembly of extrachromosomal elements such as plastid and mitochondrial genomes from metagenomic data. Profile HMM seeds can also be used to reconstruct specific protein coding genes for gene diversity studies, and to determine all possible gene variants present in a metagenomic sample. Such surveys could be useful to detect the emergence of drug-resistance variants in sensitive environments such as hospitals and animal production facilities, where antibiotics are regularly used. Finally, GenSeed-HMM can be used as an adjunct for gap closure on assembly finishing projects, by using multiple contig ends as anchored seeds

Education and training policies for research integrity: insights from a focus group study

Education is important for fostering research integrity (RI). Although RI training is increasingly provided, there is little knowledge on how research stakeholders view institutional RI education and training policies. Following a constructivist approach, we present insights about research stakeholders’ views and experiences regarding how research institutions can develop and implement RI education and training policies. We conducted thirty focus groups, engaging 147 participants in eight European countries. Using a mixed deductive-inductive thematic analysis, we identified five themes: (1) RI education should be available to all; (2) education and training approaches and goals should be tailored; (3) motivating trainees is essential; (4) both formal and informal educational formats are necessary; and (5) institutions should take into account various individual, institutional, and system-of-science factors when implementing RI education. Our findings suggest that institutions should make RI education attractive for all and tailor training to disciplinary-specific contexts.Horizon 2020(H2020)824481Merit, Expertise and Measuremen

INDCOR white paper on the Design of Complexity IDNs

This white paper was written by the members of the Work Group focusing on design practices of the COST Action 18230 - Interactive Narrative Design for Complexity Representation (INDCOR, WG1). It presents an overview of Interactive Digital Narratives (IDNs) design for complexity representations through IDN workflows and methodologies, IDN authoring tools and applications. It provides definitions of the central elements of the IDN alongside its best practices, designs and methods. Finally, it describes complexity as a feature of IDN, with related examples. In summary, this white paper serves as an orienting map for the field of IDN design, understanding where we are in the contemporary panorama while charting the grounds of their promising futures