Hepatitis C virus (HCV) is one of the leading causes of chronic liver disease, cirrhosis, and hepatocellular carcinoma, resulting in major global public health concerns. The HCV infection is unevenly ...distributed worldwide, with variations in prevalence across and within countries. The studies on molecular epidemiology conducted in several countries provide an essential supplement for a comprehensive knowledge of HCV epidemiology, genotypes, and subtypes, along with providing information on the impact of current and earlier migratory flows. HCV is phylogenetically classified into 8 major genotypes and 57 subtypes. HCV genotype and subtype distribution differ according to geographic origin and transmission risk category. Unless people with HCV infection are detected and treated appropriately, the number of deaths due to the disease will continue to increase. In 2015, 1.75 million new viral infections were mostly due to unsafe healthcare procedures and drug use injections. In the same year, access to direct-acting antivirals was challenging and varied in developing and developed countries, affecting HCV cure rates based on their availability. The World Health Assembly, in 2016, approved a global strategy to achieve the elimination of the HCV public health threat by 2030 (by reducing new infections by 90% and deaths by 65%). Globally, countries are implementing policies and measures to eliminate HCV risk based on their distribution of genotypes and prevalence.
There have been no worldwide standardised surveys of prevalence and severity of asthma, rhinoconjunctivitis and eczema in school children for 15 years. The present study aims to provide this ...information.Following the exact International Study of Asthma and Allergies in Childhood (ISAAC) methodology (cross-sectional questionnaire-based survey) the Global Asthma Network (GAN) Phase I was carried out between 2015 and 2020 in many centres worldwide.The study included 157 784 adolescents (13-14 years of age) in 63 centres, in 25 countries; and 101 777 children (6-7 years of age) in 44 centres, in 16 countries. The current prevalence of symptoms, respectively, was: 11.0% and 9.1% for asthma; 13.3% and 7.7% for rhinoconjunctivitis; and 6.4% and 5.9% for eczema. For asthma ever, hay fever ever and eczema ever prevalence was 10.5% and 7.6%; 15.2% and 11.1%; and 10.6% and 13.4%. Centres in countries with low- or lower-middle- gross national income (LICs or L-MICs) had significantly lower prevalence of the three disease symptoms and diagnoses (except for hay fever). In children, the prevalence of asthma and rhinoconjunctivitis symptoms were higher in males, while the reverse occurred among adolescents. For eczema, while the prevalence among female adolescents was double that of males, there was no sex difference among children. Centre accounted for a non-negligible variability of all disease symptoms (10% to 20%).The burden of asthma, rhinoconjunctivitis and eczema vary widely among the limited number of countries studied. Although symptom prevalence is lower in LICs and L-MICs, it represents a considerable burden everywhere studied.
Asthma, hay fever and eczema are three common chronic conditions. There are no recent multi-country data on the burden of these three conditions in adults; the aims of this study are to fill this ...evidence gap.The Global Asthma Network (GAN) Phase I is a multi-country cross-sectional population-based study using the same core methodology as the International Study of Asthma and Allergies in Childhood (ISAAC) Phase III. It provides data on the burden of asthma, hay fever, and eczema not only in children and adolescents but also for the first time in their parents/guardians.Data were available from 193 912 adults (104 061 female; mean age 38 (sd 7.5)) in 43 centres in 17 countries. The overall prevalences (range) of symptoms of current wheeze, asthma ever, hay fever ever and eczema ever were 6.6% (0.9%-32.7%), 4.4%(0.9%-29.0%), 14.4%(2.8%-45.7%), and 9.9%(1.6%-29.5%), respectively. Centre prevalence varied considerably both between countries and within countries. There was a moderate correlation between hay fever ever and asthma ever, and between eczema ever and hay fever ever at the centre level. There were moderate to strong correlations between indicators of the burden of disease reported in adults and the two younger age groups.We found evidence for a substantial burden of asthma, hay fever ever and eczema ever in countries examined highlighting the major public health importance of these diseases. Prevention strategies and equitable access to effective and affordable treatments for these three conditions would help mitigate the avoidable morbidity they cause.
An electrical storm of Torsade de Pointes arrhythmias (TdP) can be reproducibly induced in the anesthetized chronic AV-block (CAVB) dog by infusion of the I
-blocker dofetilide. Earlier studies ...showed that these arrhythmias 1) arise from locations with high spatial dispersion in repolarization (SDR) and 2) can be suppressed by high-rate pacing. We examined whether suppression of TdP by high-rate pacing is established through a decrease in SDR in the CAVB dog.
Dofetilide (25 μg/kg in 5 min) was administered to 5 anesthetized CAVB dogs to induce TdP arrhythmias. During the experiments, animals were continuously paced from the right ventricular apex at 50 beats/minute (RVA50). Upon TdP occurrence and conversion, RVA pacing was consecutively set to 100, 80 and 60 beats/minute for 2 min, referred to as pacing blocks. To determine the additional anti-arrhythmic effects of HRP over defibrillation alone, the number of arrhythmic events and SDR at RVA100 were compared to data from three previously conducted experiments, in which dogs underwent the same experimental protocol but were paced at RVA60 upon TdP occurrence (RVA60
). In all experiments, recordings included surface electrocardiogram and mapping by 56 intramural needles, each recording four electrograms, evenly inserted into the ventricular walls and septum. For each pacing block, the number of ectopic beats (EB), and TdP severity were scored. SDR was quantified as the average difference in repolarization time within four squared needles (SDR
).
In 4 out of 5 animals, pacing at RVA100 suppressed TdP occurrence. One dog could not be converted by defibrillation after the initial TdP. Compared to RVA50, pacing at RVA100, but not RVA80 and RVA60, significantly reduced the TdP score (78 ± 33 vs
0 ± 0,
< 0.05 and vs
12.5 ± 25 and 25 ± 50, both
> 0.05). The reduction in TdP score was reflected by a significant decrease in SDR
(125 ± 46 ms before TdP vs
49 ± 18 ms during RVA100,
< 0.05), and SDR was smaller than in the RVA60
animals (101 ± 52 ms,
< 0.05 vs
RVA100).
In CAVB dogs, high-rate pacing effectively suppresses TdP, which, at least in part, results from a spatial homogenization of cardiac repolarization, as reflected by a decrease in SDR.
Torsade de pointes arrhythmias (TdP) in the chronic atrioventricular block (CAVB) dog model result from proarrhythmic factors, which trigger TdP and/or reinforce the arrhythmic substrate. This study ...investigated electrophysiological and arrhythmogenic consequences of severe bradycardia for TdP.
Dofetilide (25 μg/kg per 5 min) was administered to eight anesthetized, idioventricular rhythm (IVR) remodeled CAVB dogs in two serial experiments: once under 60 beats per minute (bpm), right ventricular apex paced (RVA60) conditions, once under more bradycardic IVR conditions. Recordings included surface electrocardiogram and short-term variability (STV) of repolarization from endocardial unipolar electrograms. TdP inducibility (three or more episodes within 10 min after start of dofetilide) and arrhythmic activity scores (AS) were established. Mapping experiments in 10 additional dogs determined the effect of lowering rate on STV and spatial dispersion of repolarization (SDR) in baseline.
IVR-tested animals had longer baseline RR-interval (1,403 ± 271 ms) and repolarization intervals than RVA60 animals. Dofetilide increased STV similarly under both rhythm strategies. Nevertheless, TdP inducibility and AS were higher under IVR conditions (6/8 and 37 ± 27 vs. 1/8 and 8 ± 12 in RVA60, respectively, both
0.05). Mapping: Pacing from high (128 ± 10 bpm) to middle (88 ± 10 bpm) to experimental rate (61 ± 3 bpm) increased all electrophysiological parameters, including interventricular dispersion, due to steeper left ventricular restitution curves, and intraventricular SDR: maximal cubic dispersion from 60 ± 14 (high) to 69 ± 17 (middle) to 84 ± 22 ms (
< 0.05 vs. high and middle rate).
In CAVB dogs, severe bradycardia increases the probability and severity of arrhythmic events by heterogeneously causing electrophysiological instability, which is mainly reflected in an increased spatial, and to a lesser extent temporal, dispersion of repolarization.
A comprehensive understanding of the interaction between triggers and electrical substrates leading to ventricular fibrillation (VF) and sudden cardiac arrest is lacking, and electrical substrates ...are difficult to detect and localize with current clinical tools. Here, we created repolarization time (RT) dispersion by regional drug infusion in perfused explanted human (
= 1) and porcine (
= 6) hearts and in a computational model of the human ventricle. Arrhythmia induction was tested with a single ventricular extrastimulus applied at the early or late RT region. Arrhythmias could only be induced from early RT regions. Vulnerability to VF increased with RT gradient steepness and with larger areas of early RT, but not with markers on the body-surface electrocardiogram. Noninvasive electrocardiographic imaging was performed in survivors of idiopathic VF (
= 11), patients with frequent premature ventricular complexes (PVCs) but no history of sudden cardiac arrest (
= 7), and controls (
= 10). In survivors of idiopathic VF, RT gradients were steeper than in controls, without differences in the clinical electrocardiogram, consistent with the ex vivo results. Patients with idiopathic VF also showed local myocardial regions with distinctly early-versus-late RT that were more balanced in size than in controls. Premature beats originated more often from the early RT regions in idiopathic VF survivors than in patients with frequent PVCs only. Thus, idiopathic VF emerges from the spatiotemporal interaction of a premature beat from an early-repolarization region with critical repolarization dispersion in that region. Electrocardiographic imaging can uncover the co-occurrence of these abnormalities.
Sudden cardiac death is often caused by ventricular arrhythmias driven by reentry. Comprehensive characterization of the potential triggers and substrate in survivors of sudden cardiac arrest has ...provided insights into the trigger-substrate interaction leading to reentry. Previously, a "Triangle of Arrhythmogenesis", reflecting interactions between substrate, trigger and modulating factors, has been proposed to reason about arrhythmia initiation. Here, we expand upon this concept by separating the trigger and substrate characteristics in their spatial and temporal components. This yields four key elements that are required for the initiation of reentry: local dispersion of excitability (e.g., the presence of steep repolarization time gradients), a critical relative size of the region of excitability and the region of inexcitability (e.g., a sufficiently large region with early repolarization), a trigger that originates at a time when some tissue is excitable and other tissue is inexcitable (e.g., an early premature complex), and which occurs from an excitable region (e.g., from a region with early repolarization). We discuss how these findings yield a new mechanistic framework for reasoning about reentry initiation, the "Circle of Reentry." In a patient case of unexplained ventricular fibrillation, we then illustrate how a comprehensive clinical investigation of these trigger-substrate characteristics may help to understand the associated arrhythmia mechanism. We will also discuss how this reentry initiation concept may help to identify patients at risk, and how similar reasoning may apply to other reentrant arrhythmias.
Resumen La transformación genética de plantas es una herramienta biotecnológica de alto impacto en el mejoramiento vegetal que brinda la posibilidad de obtener nuevos cultivos que se adapten a las ...demandas de producción y de consumo. Actualmente la estrategia de transformación más utilizada en papa se basa en la incorporación de genes completos vía Agrobacterium tumefaciens. El objetivo del presente trabajo fue desarrollar el primer protocolo de transformación para Solanum tuberosum cv. Spunta mediado por Agrobacterium tumefaciens utilizando el antibiótico higromicina como agente de selección. Para ello se transformaron explantes de papa cv. Spunta utilizando A. tumefaciens con un vector binario que contenía el gen hpt que confiere resistencia al antibiótico higromicina. Se realizaron determinaciones moleculares y fenotípicas para validar tanto la eficiencia del protocolo de transformación como la acción del antibiótico higromicina como agente de selección. Se obtuvieron 62 ápices regenerados de los explantes inoculados con A. tumefaciens (62% de regeneración) de las cuales 30 plantas fueron positivas para el gen hpt. Considerando como eficiencia de transformación el número de plantas transgénicas/el número de explantes inoculados, obtuvimos un 30% de eficiencia. El presente trabajo permitió desarrollar un protocolo sencillo y eficiente de transformación genética de papa cv. Spunta mediante A. tumefaciens utilizando higromicina como agente selectivo.
Antimicrobial peptides have been developed based on plant-derived molecular scaffolds for the treatment of infectious diseases. Chenopodin is an abundant seed storage protein in quinoa, an Andean ...plant with high nutritional and therapeutic properties. Here, we used computer- and physicochemical-based strategies and designed four peptides derived from the primary structure of Chenopodin. Two peptides reproduce natural fragments of 14 amino acids from Chenopodin, named Chen1 and Chen2, and two engineered peptides of the same length were designed based on the Chen1 sequence. The two amino acids of Chen1 containing amide side chains were replaced by arginine (ChenR) or tryptophan (ChenW) to generate engineered cationic and hydrophobic peptides. The evaluation of these 14-mer peptides on
and
showed that Chen1 does not have antibacterial activity up to 512 µM against these strains, while other peptides exhibited antibacterial effects at lower concentrations. The chemical substitutions of glutamine and asparagine by amino acids with cationic or aromatic side chains significantly favoured their antibacterial effects. These peptides did not show significant hemolytic activity. The fluorescence microscopy analysis highlighted the membranolytic nature of Chenopodin-derived peptides. Using molecular dynamic simulations, we found that a pore is formed when multiple peptides are assembled in the membrane. Whereas, some of them form secondary structures when interacting with the membrane, allowing water translocations during the simulations. Finally, Chen2 and ChenR significantly reduced SARS-CoV-2 infection. These findings demonstrate that Chenopodin is a highly useful template for the design, engineering, and manufacturing of non-toxic, antibacterial, and antiviral peptides.
The studies about the quality of groundwater resources are scarce in Mexico, and often they do not consider indicators of geogenic background and anthropogenic pollution. So, we examined the quality ...of groundwater from five wells of the Apan aquifer (Hidalgo, Mexico). Four of these wells were taken as reference samples, while the Santa Cruz well was considered as the study site because it is locally recognized as a problem due to the geogenic presence of manganese. In all the sites, variables related to mineralization processes were analyzed, and a quality index (MWQI, from
mineralization
-
based water quality index
) was calculated. In the study site samples, we also determined several indicators of geogenic background (arsenic, manganese, and other heavy metals) and anthropogenic pollution (as organic matter, nutrients, and several microbial indicators), from which another quality index (GAWQI, from
geogenic background and anthropogenic pollution
-
based water quality index
) was calculated. The MWQI values classified the groundwater from all the sites, even that from the Santa Cruz well, as “excellent for drinking.” When the GAWQI was computed for the Santa Cruz site, this groundwater was found “unsuitable for drinking” due to its extremely high manganese content. We conclude that the GAWQI could represent a valuable communication tool to inform the population and the authorities about the quality of the groundwater resources.
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