Neuroimmune Dynamics in Alzheimer’s Disease Progression

Alzheimer’s disease (AD) is a neurodegenerative disease, the most common cause of dementia in senile population. According to the World Health Organization, AD represents around 12% of people over 65 worldwide. Due to its etiological agents, neurofibrillary tangles (NFT) and amyloid plaques (AP), several attempts to explain the genesis and progression of AD have been proposed. Pathological variants of tau protein, are the main precursor for AD onset, with a molecular mechanism based on neuroinflammatory processes in the context of the neuroimmunomodulation theory. Microglial cells play preponderant roles in innate immunity and are the main source of proinflammatory factors in the central nervous system (CNS), the links between microglia and neurons are the main focus on AD pathogenesis. Depending on these factors, either a neuroprotective or a proinflammatory effect could be triggered. In AD, a persistently active microglial condition generates neuronal damage and death, causing the release of pathological tau toward the extracellular environment. This causes the activation of microglia, promoting a feedback mechanism and generating a continuous cellular damage. After activation of microglia, generation of NF‐kB occurs, thus promoting the expression and release of proinflammatory cytokines. As a consequence, short‐lived cytotoxic factors, such as O2, NO and other reactive oxygen species, are released. In normal physiological conditions, tau’s kinases play a role in regulating normal tau functions in neurons. Glycogen synthase kinase 3‐beta (GSK3β)‐mediated tau phosphorylation promotes N‐methyl‐D aspartate receptor (NMDAr)‐mediated long‐term depression. The increase of proinflammatory cytokines during AD by microglia leads to an increase in kinase expression and activity of cyclin‐dependent kinase 5 (Cdk‐5) and GSK3‐β. On the other hand, TNF‐α and IL‐8 increase expression and activity of Cdk5, whereas IL‐1β hyperactivates GSK3‐β, leading to tau hyperphosphorylation and impairing its normal function. Tau hyperphosphorylation results in microtubule destabilization, impaired axonal transport, NMDAr‐mediated neurotoxicity, synaptic dysfunction and cell death. Finally, the previously summarized mechanisms could explain the onset and progression of AD, opening a new projection to focus research on therapeutic agents that could modulate the interactions between tau and microglial cells. The neuroimmunomodulation mechanism has been the conceptual framework for the search of therapeutic approaches for AD and other neurodegenerative disorders

Photofunctional Scope of Fluorescent Dithienylethene Conjugates with Aza-Heteroaromatic Cations

A series of dithienylethene (DTE) photoswitches with aza-heteroaromatic cationic moieties is synthesized. The switches are characterized regarding their photochemical and photophysical properties in acetonitrile and in water. The efficiency of the switching and the photostationary state composition depend on the degree of π-conjugation of the heteroaromatic systems. Thus, DTEs with acridinium-derived moieties have very low quantum yields for the ring-closing process, which is in contrast to switches with pyridinium and quinolinium moieties. All switches emit fluorescence in their open forms. The involved electronic transitions are traced back to an integrative picture including the DTE core and the cationic arms. The emission can be fine-tuned by the π-conjugation of the heteroaromatic cations, reaching the red spectral region for DTEs with acridinium moieties. On ring-closing of the DTEs the fluorescence is not observable anymore. Theoretical calculations point to rather low-lying energy levels of the highly conjugated ring-closed DTEs, which would originate near-infrared emission (> 1200 nm). The latter is predicted to be very weak due to the concurrent non-radiative deactivation, according to the energy-gap law. In essence, an ON-OFF fluorescence switching as the result of the electrocyclic ring-closing reaction is observed.The authors acknowledge the financial support by the Spanish Ministerio de Ciencia e Innovación (grant PID2020-119992GB-I00 for U.P., PID2019-104293GB-I00 for F.N., PID2019-108292RA-I00, EUR2020-112189 for A.J.M.-M.), the Consejería de Universidad, Investigación e Innovación/Junta de Andalucía (grant P18-FR-4080 for U.P.), the European Research and Development Fund (ERDF), and the Junta de Andalucía / University of Huelva (grant UHU-202070 for U.P.). A.J.M.-M. thanks the AEI Research State Agency for a Ramón y Cajal research contract (RYC-2017-21783). The authors are indebted to the Supercomputing and Bioinformatics Centre (SCBI) of the University of Málaga for making available the computer resources that were employed for the theoretical calculations

Desenlaces clínicos de los pacientes con diabetes e hiperglucemia de estrés que presentaron infección por SARS-CoV-2

Introduction. Diabetes and stress hyperglycemia (SH) have been related with poorer clinical outcomes in patients infected by SARS-CoV-2 and at risk for severe disease.Objective. To evaluate clinical outcomes in three groups of patients (with diabetes, without diabetes and stress hyperglycemia [SH]) with SARS-CoV-2 infection.Materials and methods. A retrospective cohort study was conducted in Cali-Colombia. Patients aged ≥18 years with a diagnosis of SARS-CoV-2 infection managed in the emergency room, hospitalization or intensive care unit (ICU) between March 2020 and December 2021 were included. Immunocompromised patients and pregnant women were excluded. Patients were classified in three groups: without diabetes, with diabetes and SH. A comparison between the groups was performed. Results. A total of 945 patients were included (59.6% without diabetes, 27% with diabetes and 13.4% with SH). Fifty-five-point three percent required ICU management, with a higher need in patients with SH (89.8%) and diabetes (67.1%), with no difference between these groups (p=0.249). A higher chance of death was seen in SH vs. without diabetes (adjOR= 8.12, 95% CI 5.12-12.88, p<0.01). Frequency of acute respiratory distress syndrome, need for invasive mechanical ventilation, use of vasopressors and inotropes, the need for de novo renal replacement therapy and mortality was higher in patients with metabolic alterations (diabetes and SH). Conclusions. Diabetes and SH are associated to worse clinical outcomes and mortality in patients with COVID-19. These patients should be identified early and considered as high risk at moment of COVID-19 diagnosis that allow to mitigate adverse outcomes.Introducción. La diabetes y la hiperglucemia de estrés (HE) se han relacionado con peores desenlaces clínicos en pacientes infectados por SARS-CoV-2 y con riesgo de enfermedad grave. Objetivo. Evaluar los resultados clínicos en tres grupos de pacientes (con diabetes, sin diabetes e hiperglucemia de estrés [SH]) con infección por SARS-CoV-2.Materiales y métodos. Se realizó un estudio de cohorte retrospectivo en Cali-Colombia. Se incluyeron pacientes ≥18 años con diagnóstico de infección por SARS-CoV-2 atendidos en urgencias, hospitalización o unidad de cuidados intensivos (UCI) entre marzo de 2020 y diciembre de 2021. Se excluyeron pacientes inmunocomprometidos y mujeres embarazadas. Los pacientes fueron clasificados en tres grupos: sin diabetes, con diabetes e HE. Se realizó una comparación entre los grupos.Resultados. Se incluyeron un total de 945 pacientes (59,6% sin diabetes, 27% con diabetes y 13,4% con HE). El 55,3% requirió manejo en UCI, con mayor necesidad en pacientes con HE (89,8%) y diabetes (67,1%), sin diferencia entre estos grupos (p=0,249). Se observó una mayor probabilidad de muerte en HE vs. sin diabetes (adjOR= 8,12, 95% IC 5,12-12,88, p<0,01). La frecuencia de síndrome de distrés respiratorio agudo, necesidad de ventilación mecánica invasiva, uso de vasopresores e inotrópicos, necesidad de terapia de reemplazo renal de novo y la mortalidad fue mayor en pacientes con alteraciones metabólicas (diabetes e HE).Conclusiones. La diabetes y la HE se asociaron a peores resultados clínicos y mortalidad en pacientes con COVID-19. Estos pacientes deben ser identificados tempranamente y considerados de alto riesgo al momento del diagnóstico de COVID-19 que permitan mitigar los desenlaces adversos

What makes Input-Output Tables of Trade of Raw Material Goods Peculiar Networks? The World and Mexican Cases

This paper examines several peculiarities of Input-Output Tables (IOTs) of trade of raw material goods when treated as networks. Methodology: two IOTs of trade of raw material goods (World and Mexico) are compared with a network with a scale free distribution and hierarchical organization (an email database) by using distinct centralities and statistics from graph theory. Results: IOTs are a very particular type of graph due to their idiosyncrasies, for which standard graph measures cannot provide satisfactory results, and which have to be adapted to give a fragmented picture of the whole network. Recommendations: analytical tools of network theory applied to IOTs substantially improve the understanding of trade of raw material goods, both at the national and the global level, which is useful in the design of trade policy. Limitations: this research does not include random walk centrality and regime switching from external shocks. Originality: this is a novel research that enlightens the particularities of the IOTs, seen as networks, for the Mexican case. Conclusions: this investigation finds important particularities of IOTs when compared with other networks

Monitor de área pasivo para neutrones

La relevancia de la presencia de neutrones en los LINACs para radioterapia ha sido establecida en los reportes 79 y 102 de la NCRP1. La medición de la contribución de la dosis y su distribución en el paciente es importante para evaluar el riesgo de la inducción de tumores secundarios2. Para medir el espectro de neutrones o cualquier magnitud dosimétrica asociada, dentro de las salas de radioterapia con LINACs se debe usar un sistema pasivo3. En este trabajo se presenta el diseño de un monitor de área para neutrones con detector pasivo, así como su desempeño en un LINAC de 15 MV

Effect of β-Glucans in Diets on Growth, Survival, Digestive Enzyme Activity, and Immune System and Intestinal Barrier Gene Expression for Tropical Gar (Atractosteus tropicus) Juveniles

The application of β-1,3/1,6-glucan derived from yeast at five concentrations (0%, 0.5%, 1.0%, 1.5%, and 2.0%) in formulated diets was evaluated in juveniles for its effects on the growth, survival, digestive enzymatic activity, and expression of genes associated with the immune system (interlukin-10 (IL-10), transforming growth factor (TGF), occludin (OCC), mucin2 (MUC2), lysozyme (LYS), and nucleotide-binding and oligomerization domain 2 (NOD2)) in tropical gar (Atractosteus tropicus). For the experiment, three replicates of 30 fish per experimental unit (70 L) were cultivated for 62 days. The growth results showed no statistically significant differences in relation to weight and total length between treatments. The activity of digestive enzymes (alkaline proteases, trypsin, leucine aminopeptidase, and amylase) did not show significant differences between treatments, except for chymotrypsin activity, where fish fed 1.0% and 1.5% of β-glucans showed higher activities compared with the rest of the treatments. On the other hand, the analysis of gene expression did not show significant differences between treatments, although a tendency of increase in the expression of IL-10, TGF, MUC2, and OCC was observed with an addition of 1.5% of the prebiotic, but there was a decrease in the fish fed with 2% of the prebiotic. It is possible to include concentrations of between 0.5% and 1.5% of β-glucans in the diets for A. tropicus, with no detectable adverse effects on growth, survival, digestive enzyme activity, or specific gene expression. β-glucan 1,3/1,6 added at 1.0% and 1.5% in the diet significantly increases chymotrypsin activity.info:eu-repo/semantics/publishedVersio

Causes of Morbidity in Wild Raptor Populations Admitted at a Wildlife Rehabilitation Centre in Spain from 1995-2007: A Long Term Retrospective Study

Background: Morbidity studies complement the understanding of hazards to raptors by identifying natural or anthropogenic factors. Descriptive epidemiological studies of wildlife have become an important source of information about hazards to wildlife populations. On the other hand, data referenced to the overall wild population could provide a more accurate assessment of the potential impact of the morbidity/mortality causes in populations of wild birds. Methodology/Principal Findings: The present study described the morbidity causes of hospitalized wild raptors and their incidence in the wild populations, through a long term retrospective study conducted at a wildlife rehabilitation centre of Catalonia (1995-2007). Importantly, Seasonal Cumulative Incidences (SCI) were calculated considering estimations of the wild population in the region and trend analyses were applied among the different years. A total of 7021 birds were analysed: 7 species of Strigiformes (n = 3521) and 23 of Falconiformes (n = 3500). The main causes of morbidity were trauma (49.5%), mostly in the Falconiformes, and orphaned/young birds (32.2%) mainly in the Strigiformes. During wintering periods, the largest morbidity incidence was observed in Accipiter gentillis due to gunshot wounds and in Tyto alba due to vehicle trauma. Within the breeding season, Falco tinnunculus (orphaned/young category) and Bubo bubo (electrocution and metabolic disorders) represented the most affected species. Cases due to orphaned/young, infectious/parasitic diseases, electrocution and unknown trauma tended to increase among years. By contrast, cases by undetermined cause, vehicle trauma and captivity decreased throughout the study period. Interestingly, gunshot injuries remained constant during the study period. Conclusions/Significance: Frequencies of morbidity causes calculated as the proportion of each cause referred to the total number of admitted cases, allowed a qualitative assessment of hazards for the studied populations. However, cumulative incidences based on estimated wild raptor population provided a more accurate approach to the potential ecological impact of the morbidity causes in the wild populations

VAMOS: a Pathfinder for the HAWC Gamma-Ray Observatory

VAMOS was a prototype detector built in 2011 at an altitude of 4100m a.s.l. in the state of Puebla, Mexico. The aim of VAMOS was to finalize the design, construction techniques and data acquisition system of the HAWC observatory. HAWC is an air-shower array currently under construction at the same site of VAMOS with the purpose to study the TeV sky. The VAMOS setup included six water Cherenkov detectors and two different data acquisition systems. It was in operation between October 2011 and May 2012 with an average live time of 30%. Besides the scientific verification purposes, the eight months of data were used to obtain the results presented in this paper: the detector response to the Forbush decrease of March 2012, and the analysis of possible emission, at energies above 30 GeV, for long gamma-ray bursts GRB111016B and GRB120328B.Comment: Accepted for pubblication in Astroparticle Physics Journal (20 pages, 10 figures). Corresponding authors: A.Marinelli and D.Zaboro

Leucaena leucocephala (Lam) de Wit and Moringa oleífera Lam: Especies con alto valor proteico para la liberación de péptidos bioactivos

Leucaena y Moringa son leguminosas con un alto valor nutricional (proteínas), por lo que pueden ser utilizadas como fuente de proteína para la producción de concentrados, aislados o hidrolizados proteicos. Estos materiales, ricos en proteína, pueden además ser sustrato para la producción de péptidos bioactivos, que son secuencias de aminoácidos presentes en las proteínas que al ser liberados por digestión gastrointestinal o proteólisis in vitro con diferentes enzimas, presentan algunas actividades biológicas, como la antioxidante y anticancerígena, además de propiedades funcionales. Los diferentes estudios realizados de estas semillas hasta el momento proveen información que sugiere que pueden dar lugar a fragmentos susceptibles para la liberación de pépticos con diversas actividades, lo que podría ser una estrategia adecuada para la producción de péptidos bioactivos con actividad bio-funcional. Sin embargo, se requiere de mayor investigación sobre las características de los fragmentos liberados para determinar los mecanismos y propiedades de las secuencias responsables de las diversas actividades