Factors associated with SARS-CoV-2 infection in unvaccinated children and young adults.

BACKGROUND AND OBJECTIVES: Pediatric COVID-19 cases are often mild or asymptomatic, which has complicated estimations of disease burden using existing testing practices. We aimed to determine the age-specific population seropositivity and risk factors of SARS-CoV-2 seropositivity among children and young adults during the pandemic in British Columbia (BC). METHODS: We conducted two cross-sectional serosurveys: phase 1 enrolled children and adults < 25 years between November 2020-May 2021 and phase 2 enrolled children < 10 years between June 2021-May 2022 in BC. Participants completed electronic surveys and self-collected finger-prick dried blood spot (DBS) samples. Samples were tested for immunoglobulin G antibodies against ancestral spike protein (S). Descriptive statistics from survey data were reported and two multivariable analyses were conducted to evaluate factors associated with seropositivity. RESULTS: A total of 2864 participants were enrolled, of which 95/2167 (4.4%) participants were S-seropositive in phase 1 across all ages, and 61/697 (8.8%) unvaccinated children aged under ten years were S-seropositive in phase 2. Overall, South Asian participants had a higher seropositivity than other ethnicities (13.5% vs. 5.2%). Of 156 seropositive participants in both phases, 120 had no prior positive SARS-CoV-2 test. Young infants and young adults had the highest reported seropositivity rates (7.0% and 7.2% respectively vs. 3.0-5.6% across other age groups). CONCLUSIONS: SARS-CoV-2 seropositivity among unvaccinated children and young adults was low in May 2022, and South Asians were disproportionately infected. This work demonstrates the need for improved diagnostics and reporting strategies that account for age-specific differences in pandemic dynamics and acceptability of testing mechanisms.

Efecto de Dos Protocolos de Intervención para el Incremento de Ejercicio Físico: Estudio Longitudinal / The Effect of Two Intervention Protocols to Increase Physical Exercise: Longitudinal Study

Resumen El objetivo de este estudio fue conocer el impacto de la estrategia de autorregulación de Contraste Mental e Intenciones de Implementación (MCII) como complemento de una intervención con base en el Enfoque del Proceso de Acción en Salud (HAPA) para realizar ejercicio. Fueron reclutados 76 participantes con sobrepeso (índice de masa corporal [IMC]≥25) que querían perder peso (Medad =40 años; MIMC=29). Los participantes fueron asignados al azar a dos condiciones: HAPA (n=36) y HAPA+MCII (n=40). Las variables de interés (horas de ejercicio auto reportadas, medidas corporales y salud psicológica con DASS-21 e IWQOL-Lite) se midieron al inicio, en la semana 6 y en la 12. Encontramos un aumento significativo en las horas de ejercicio y disminución significativa del IMC y IWQOL-Lite Estado Físico y Autoestima al comparar las ocasiones de medición para la muestra total. Se observaron mayores efectos del protocolo HAPA+MCII que del HAPA en las variables de estudio, con excepción de las variables Ansiedad del DASS-21 y Vida sexual del IWQOL-Lite. Sin embargo, en ningún caso las diferencias resultaron estadísticamente significativas. El estudio indica el papel fundamental que desempeñan la autoeficacia y su operacionalización en el logro de una intervención exitosa. Al combinar dos protocolos, se recomienda considerar el efecto de techo que se puede obtener con un solo protocolo.

Abstrac The objective of this study was to understand the impact of the Mental Contrasting and Implementation Intentions (MCII) self-regulation technique as a complement to an intervention based on the Health Action Process Approach (HAPA) to perform exercise. Seventy-six participants with body mass index (BMI) ≥25 who wanted to lose weight (Mage =40 years; MBMI =29) were recruited. Participants were randomized into two conditions: HAPA (n=36) and HAPA + MCII (n=40). The variables of interest (self-reported hours of exercise, body measurements and psychological health with DASS-21 and IWQOL-Lite) were measured at the beginning, in week 6 and in 12. We found a significant increase in the hours of exercise and significant decrease in BMI and IWQOL-Lite Physical Functioning and Self-esteem when comparing the occasions of measurement for the total sample. Greater effects of the HAPA + MCII protocol were observed than of the HAPA for the study variables, with the exception of the DASS-21 Anxiety and the IWQOL-Lite Sexual life. However, the differences were not statistically significant. The study indicates the important role of self-efficacy and its operationalization for a successful intervention. When combining two protocols, the ceiling effect that can be obtained with a single protocol should be considered.

Naturally acquired antibody against Haemophilus influenzae type a in pediatric saliva.

We developed a salivary assay for the detection of naturally acquired IgA antibody against Haemophilus influenzae type a (Hia) capsular polysaccharide in healthy Indigenous children from Northwestern Ontario, Canada. Hia-specific IgA antibody was detected in the saliva of 93% of Indigenous children aged 2-7 years.

Dependence of Heart Rate Variability Indices on the Mean Heart Rate in Women with Well-Controlled Type 2 Diabetes.

Heart rate variability (HRV) is a method used to evaluate the presence of cardiac autonomic neuropathy (CAN) because it is usually attributed to oscillations in cardiac autonomic nerve activity. Recent studies in other pathologies suggest that HRV indices are strongly related to mean heart rate, and this does not depend on autonomic activity only. This study aimed to evaluate the correlation between the mean heart rate and the HRV indices in women patients with well-controlled T2DM and a control group. HRV was evaluated in 19 T2DM women and 44 healthy women during basal supine position and two maneuvers: active standing and rhythmic breathing. Time-domain (SDNN, RMSSD, pNN20) and frequency-domain (LF, HF, LF/HF) indices were obtained. Our results show that meanNN, age, and the maneuvers are the main predictors of most HRV indices, while the diabetic condition was a predictor only for pNN20. Given the known reduced HRV in patients with T2DM, it is clinically important that much of the HRV indices are dependent on heart rate irrespective of the presence of T2DM. Moreover, the multiple regression analyses evidenced the multifactorial etiology of HRV.

Metabolic Physiological Networks: The Impact of Age.

Metabolic homeostasis emerges from the interplay between several feedback systems that regulate the physiological variables related to energy expenditure and energy availability, maintaining them within a certain range. Although it is well known how each individual physiological system functions, there is little research focused on how the integration and adjustment of multiple systems results in the generation of metabolic health. The aim here was to generate an integrative model of metabolism, seen as a physiological network, and study how it changes across the human lifespan. We used data from a transverse, community-based study of an ethnically and educationally diverse sample of 2572 adults. Each participant answered an extensive questionnaire and underwent anthropometric measurements (height, weight, and waist), fasting blood tests (glucose, HbA1c, basal insulin, cholesterol HDL, LDL, triglycerides, uric acid, urea, and creatinine), along with vital signs (axillar temperature, systolic, and diastolic blood pressure). The sample was divided into 6 groups of increasing age, beginning with less than 25 years and increasing by decades up to more than 65 years. In order to model metabolic homeostasis as a network, we used these 15 physiological variables as nodes and modeled the links between them, either as a continuous association of those variables, or as a dichotomic association of their corresponding pathological states. Weight and overweight emerged as the most influential nodes in both types of networks, while high betweenness parameters, such as triglycerides, uric acid and insulin, were shown to act as gatekeepers between the affected physiological systems. As age increases, the loss of metabolic homeostasis is revealed by changes in the network's topology that reflect changes in the system-wide interactions that, in turn, expose underlying health stages. Hence, specific structural properties of the network, such as weighted transitivity, i.e., the density of triangles in the network, can provide topological indicators of health that assess the whole state of the system. Overall, our findings show the importance of visualizing health as a network of organs and/or systems, and highlight the importance of triglycerides, insulin, uric acid and glucose as key biomarkers in the prevention of the development of metabolic disorders.

Comparative evaluation of urban versus agricultural nitrate sources and sinks in an unconfined aquifer by isotopic and multivariate analyses.

Nitrate (NO3-) is one of the most widespread contaminants in groundwater primarily due to agricultural activities utilizing N-containing fertilizers and the presence of animal wastes. Hydrochemical and nitrate isotope data (δ15N-NO3- and δ18O-NO3-) from the unconfined aquifer in the urban area of Del Campillo city and its surrounding rural area with different land-use types, i.e. individual sanitation systems, agricultural areas and livestock breeding facilities, were generated to investigate the impact of nitrogen pollution sources and to assess N-biogeochemical processes. The Principal Component Analysis of hydrochemical and isotopic data were used to compare the factors that control the groundwater quality and particularly the nitrate concentrations in the urban and the rural area. The results showed that nitrate pollution in the urban area of Del Campillo city originated mainly from the on-site sanitation systems and/or animal domestic wastes, whereas in the rural area nitrate pollution was mostly attributed to a combination of urea-based fertilizers and manure from livestock breeding activities. The aquifer is under oxic to suboxic conditions in the rural area and becomes suboxic in the urban area where the higher supply of organic matter consumes oxygen. As a result, denitrification was more significant in the urban area compared to the rural area, as evidenced by the higher N and O isotope enrichment factor (ε). This work will be used to benchmark the current nitrate contamination status in the region and evaluate effective planning of environmental measures and remediation strategies.

Epidemiology of Burkholderia Infections in People with Cystic Fibrosis in Canada between 2000 and 2017.

Rationale: Infections by Burkholderia species bacteria in cystic fibrosis (CF) may be transmissible, necessitating infection control measures, and remain a serious cause of morbidity and mortality. The last major study of Burkholderia epidemiology in Canada included cases up until July 2000 and was marked by the dominance of a limited number of epidemic clones of Burkholderia cenocepacia.Objectives: Describe the nationwide epidemiology of Burkholderia species infections in people with cystic fibrosis in Canada over the 17-year period since 2000.Methods: Isolates were collected from across Canada between August 2000 and July 2017 and identified to the species and, for isolates between 2015 and 2017, strain level.Results: We analyzed 1,362 Burkholderia isolates from at least 396 people with CF. Forty-nine percent (n = 666) of all isolates and 47% (n = 179) of new incident infections were identified as B. multivorans. The incidence of Burkholderia infection in the Canadian CF population did not change between 2000 and 2017 at 6 cases per 1,000 annually. Multilocus sequence typing analysis suggested minimal sharing of clones in Canada.Conclusions: The epidemiology of Burkholderia in CF in Canada has shifted from limited numbers of epidemic strains of B. cenocepacia to largely nonclonal isolates of B. multivorans, B. cenocepacia, and other species. Despite widespread infection control, however, Burkholderia species bacteria continue to be acquired by people with CF at an unchanged rate, posing a continued hazard.

The Impact of Education and Age on Metabolic Disorders.

Metabolic disorders, such as obesity, elevated blood pressure, dyslipidemias, insulin resistance, hyperglycemia, and hyperuricemia have all been identified as risk factors for an epidemic of important and widespread chronic-degenerative diseases, such as type 2 diabetes and cardiovascular disease, that constitute some of the world's most important public health challenges. Their increasing prevalence can be associated with an aging population and to lifestyles within an obesogenic environment. Taking educational level as a proxy for lifestyle, and using both logistic and linear regressions, we study the relation between a wide set of metabolic biomarkers, and educational level, body mass index (BMI), age, and sex as correlates, in a population of 1,073 students, academic and non-academic staff at Mexico's largest university (UNAM). Controlling for BMI and sex, we consider educational level and age as complementary measures-degree and duration-of exposure to metabolic insults. Analyzing the role of education across a wide spectrum of educational levels (from primary school to doctoral degree), we show that higher education correlates to significantly better metabolic health when compared to lower levels, and is associated with significantly less risk for waist circumference, systolic blood pressure, glucose, glycosylated hemoglobin, triglycerides, high density lipoprotein and metabolic syndrome (all p < 0.05); but not for diastolic blood pressure, basal insulin, uric acid, low density lipoprotein, and total cholesterol. We classify each biomarker, and corresponding metabolic disorder, by its associated set of statistically significant correlates. Differences among the sets of significant correlates indicate various aetiologies and the need for targeted population-specific interventions. Thus, variables strongly linked to educational level are candidates for lifestyle change interventions. Hence, public policy efforts should be focused on those metabolic biomarkers strongly linked to education, while adopting a different approach for those biomarkers not linked as they may be poor targets for educational campaigns.

Application of isotope techniques to enhance the conceptual hydrogeological model and to assess groundwater sustainability in the Pampean plain in Córdoba, Argentina.

The objective of this work is to enhance the conceptual hydrogeological model in the Río Cuarto River basin by using isotope and hydrochemical techniques. The precipitation pattern, as reflected in the average values of δ 2H and δ 18O in stations located in the plains and in the mountains, showed an isotope depletion from the East to the West, attributed to continental and altitude effects. Groundwater quality is mainly the result of two controlling factors: lithology and flow distances from recharge. The aquifers show fresh calcium/sodium bicarbonate water in the upper and medium basin (coarse fluvial sediments) which evolve to sodium sulphate and chloride waters in the low basin (mainly loess and fine alluvial sediments). The confined aquifer systems in the lower basin (C and D systems) averaged more negative stable isotope values, indicating that groundwater recharged during colder climatic conditions (Pleistocene period). Groundwater dating with 14C confirmed that groundwater ages range from modern to 45,000 years BP showing that as the water flows towards deeper layers and farther from the mountainous recharge area, groundwater age increases. The confined aquifers can potentially be exploited in order to partly cover different water needs but they should be managed in a sustainable way.

Synergy between Cell Surface Glycosidases and Glycan-Binding Proteins Dictates the Utilization of Specific Beta(1,3)-Glucans by Human Gut Bacteroides.

The human gut microbiota (HGM) has far-reaching impacts on human health and nutrition, which are fueled primarily by the metabolism of otherwise indigestible complex carbohydrates commonly known as dietary fiber. However, the molecular basis of the ability of individual taxa of the HGM to address specific dietary glycan structures remains largely unclear. In particular, the utilization of ß(1,3)-glucans, which are widespread in the human diet as yeast, seaweed, and plant cell walls, had not previously been resolved. Through a systems-based approach, here we show that the symbiont Bacteroides uniformis deploys a single, exemplar polysaccharide utilization locus (PUL) to access yeast ß(1,3)-glucan, brown seaweed ß(1,3)-glucan (laminarin), and cereal mixed-linkage ß(1,3)/ß(1,4)-glucan. Combined biochemical, enzymatic, and structural analysis of PUL-encoded glycoside hydrolases (GHs) and surface glycan-binding proteins (SGBPs) illuminates a concerted molecular system by which B. uniformis recognizes and saccharifies these distinct ß-glucans. Strikingly, the functional characterization of homologous ß(1,3)-glucan utilization loci (1,3GUL) in other Bacteroides further demonstrated that the ability of individual taxa to utilize ß(1,3)-glucan variants and/or ß(1,3)/ß(1,4)-glucans arises combinatorially from the individual specificities of SGBPs and GHs at the cell surface, which feed corresponding signals to periplasmic hybrid two-component sensors (HTCSs) via TonB-dependent transporters (TBDTs). These data reveal the importance of cooperativity in the adaptive evolution of GH and SGBP cohorts to address individual polysaccharide structures. We anticipate that this fine-grained knowledge of PUL function will inform metabolic network analysis and proactive manipulation of the HGM. Indeed, a survey of 2,441 public human metagenomes revealed the international, yet individual-specific, distribution of each 1,3GUL.IMPORTANCEBacteroidetes are a dominant phylum of the human gut microbiota (HGM) that target otherwise indigestible dietary fiber with an arsenal of polysaccharide utilization loci (PULs), each of which is dedicated to the utilization of a specific complex carbohydrate. Here, we provide novel insight into this paradigm through functional characterization of homologous PULs from three autochthonous Bacteroides species, which target the family of dietary ß(1,3)-glucans. Through detailed biochemical and protein structural analysis, we observed an unexpected diversity in the substrate specificity of PUL glycosidases and glycan-binding proteins with regard to ß(1,3)-glucan linkage and branching patterns. In combination, these individual enzyme and protein specificities support taxon-specific growth on individual ß(1,3)-glucans. This detailed metabolic insight, together with a comprehensive survey of individual 1,3GULs across human populations, further expands the fundamental roadmap of the HGM, with potential application to the future development of microbial intervention therapies.

Evaluation of group concept mapping during advanced pharmacy practice experiences.

BACKGROUND AND PURPOSE: Concept mapping is an active learning tool associated with meaningful learning. In the pharmacy education literature, most evaluations of concept mapping focused solely on students' perceptions of mapping without evaluating its effectiveness on students' ability to apply the information learned. This article describes an evaluation of the effectiveness of group concept mapping during advanced pharmacy practice experiences (APPEs) by evaluating both application of the knowledge gained and students' reflections on the process. EDUCATIONAL ACTIVITY AND SETTING: Ambulatory care APPE students created group concept maps on pain management based on provided focus questions during a single session. Students completed pre-session and post-session tests comprised of the same multiple-choice questions that were derived from chapters on pain within licensure exam preparatory books. Additionally, students completed a survey after the group concept mapping session that assessed their thoughts on concept mapping. FINDINGS: Most students (92%) reported that concept mapping was an effective approach to learning, though there was not a statistically significant improvement in scores on the multiple-choice test. More than half (55%) of the students indicated the greatest gain in individual learning when actively discussing pain treatment related concepts amongst their group during concept map creation. Over 40% of students identified misconceptions related to pain management. SUMMARY: Using group concept mapping as a framework for discussions led to student integration of both concrete and abstract patient care concepts with individualized awareness of learning.

Terapias Celulares y Productos de Ingeniería de Tejidos para el Tratamiento de Lesiones Condrales de Rodilla / Cell Therapy and Tissue Engineering Products for Chondral Knee Injuries

RESUMEN El cartílago articular es un tejido vulnerable a las lesiones de diferente etiología; siendo uno de los más afectados, el cartílago de la rodilla. Aunque la mayoría de los tratamientos convencionales reducen los síntomas, generalmente conducen a la formación de fibrocartílago; el cual, posee características diferentes a las del cartílago hialino de las articulaciones. Son pocas las aproximaciones terapéuticas que promueven el reemplazo del tejido dañado por cartílago hialino funcional; las más exitosas son las denominadas terapias avanzadas, que aplican células y productos de ingeniería de tejidos con el fin de estimular la regeneración del cartílago. La mayoría de ellas se basan en colocar soportes hechos con biomateriales de diferente origen, que sembrados o no con células exógenas o endógenas, reemplazan al cartílago dañado y promueven su regeneración. Este trabajo revisa algunas de las aproximaciones terapéuticas enfocadas en la regeneración del cartílago articular de rodilla; así como, los biomateriales más empleados en la elaboración de soportes para terapia celular e ingeniería de tejido cartilaginoso.

ABSTRACT The articular cartilage is prone to suffer lesions of different etiology, being the articular cartilage lesions of the knee the most common. Although most conventional treatments reduce symptoms they lead to the production of fibrocartilage, which has different characteristics than the hyaline cartilage of the joint. There are few therapeutic approaches that promote the replacement of damaged tissue by functional hyaline cartilage. Among them are the so-called advanced therapies, which use cells and tissue engineering products to promote cartilage regeneration. Most of them are based on scaffolds made of different biomaterials, which seeded or not with endogenous or exogenous cells, can be used as cartilage artificial replacement to improve joint function. This paper reviews some therapeutic approaches focused on the regeneration of articular cartilage of the knee and the biomaterials used to develop scaffolds for cell therapy and tissue engineering of cartilage.

Relación entre condiciones sociodemográficas y conocimiento sobre riesgo preconcepcional en mujeres en edad fértil / Relationship between socio-demographic conditions and knowledge about the pre-conception risk in women in childbearing age

Fundamento: la disminución de la mortalidad materno-infantil es una de las prioridades del Ecuador, de ahí la importancia del control de los factores de riesgo preconcepcional.Objetivo: determinar la relación entre condiciones sociodemográficas y conocimiento sobre riesgo preconcepcional en mujeres en edad fértil.Métodos: estudio descriptivo, correlacional, realizado desde enero a junio de 2016, que incluyó 50 mujeres en edad fértil del Barrio Lourdes, Riobamba, Ecuador. Se aplicó una entrevista estructurada, validada por expertos, que midió condiciones  sociodemográficas y conocimiento en las siguientes  dimensiones: edad adecuada para embarazarse, antecedentes obstétricos desfavorables; edad intergenésica, uso de anticonceptivos, concepto de riesgo preconcepcional, peso ideal, enfermedades crónicas y embarazo, hábitos tóxicos  y embarazo. Se utilizó la prueba estadística de Fisher y Chi cuadrado para determinar la relación entre las variables con un nivel de significado de p<0,05.Resultados: el 52 % de las mujeres estaba entre 25-34 años, 82 % son mestizas; 40 % casadas; 50 % alcanzó el bachillerato; 50 % eran amas de casa y 72 % poseía nivel socioeconómico regular. Predominó el conocimiento no satisfactorio (76 %); mostraron correlación la dimensión concepto de riesgo preconcepcional  y etnia (p= 0,03), el estado civil y  la ocupación con el  conocimiento de la  dimensión hábitos tóxicos (p = 0,018) y con nivel económico (p= 0,001). Además existió relación entre dimensión peso ideal y edad (p=0,019).Conclusiones: la etnia fue la condición socioeconómica que más influyó en el bajo conocimiento sobre riesgo preconcepcional; el estado civil, ocupación, nivel económico y la edad influyeron en el conocimiento sobre  factores de riesgo.

Foundation: decreasing infant and maternal mortality in one of priorities in Ecuador,   therefore controlling pre conception risk factors are of great importance. Objective: to determine the relationship between the socio-demographic conditions and the knowledge about the pre conception risks in women at childbearing age.Methods: descriptive, correlational study, conducted from January to June 2016, which included 50 women of childbearing age from Barrio Lourdes, Riobamba, Ecuador. A structured interview was applied, validated by experts, who measured socio-demographic conditions and knowledge in the following dimensions: adequate age to get pregnant, unfavorable obstetric history; intergenesic age, use of contraceptives, concept of pre-conception risk, ideal weight, chronic diseases and pregnancy, toxic habits and pregnancy. Fisher's statistical test and Chi square were used to determine the relationship between the variables with a significance level of p <0.05.Results: 52% of the women were between 25-34 years old, 82% are mestizas; 40% married; 50% reached the baccalaureate; 50% were housewives and 72% had a regular socioeconomic level. Unsatisfactory knowledge predominated (76%); the concept dimension of pre-conception risk and ethnicity (p = 0.03), marital status and occupation with the knowledge of the toxic habits dimension (p = 0.018) and economic level (p = 0.001) were correlated. In addition, there was a relationship between the ideal weight and age dimension (p = 0.019).Conclusions: ethnicity was the socioeconomic condition that most influenced the low knowledge about pre conception risk; marital status, occupation, economic level and age influenced knowledge about risk factors.

Vaxchora: A Single-Dose Oral Cholera Vaccine.

OBJECTIVE: To review trials evaluating the efficacy and safety of Vaxchora, a reformulated, single-dose, oral, lyophilized Vibrio cholerae CVD 103-HgR vaccine for the prevention of travel-related cholera caused by V cholerae serogroup O1. DATA SOURCES: A literature search was conducted using MEDLINE (1946 to January week 3, 2017) and EMBASE (1996 to 2017 week 3). Keywords included oral cholera vaccine, single-dose, Vaxchora, and CVD 103-HgR. Limits included human, clinical trials published in English since 2010. ClinicalTrials.gov was used as a source for unpublished data. Additional data sources were obtained through bibliographic review of selected articles. STUDY SELECTION AND DATA EXTRACTION: Studies that addressed the safety and efficacy of Vaxchora, the reformulated, single-dose oral CVD 103-HgR cholera vaccine, were selected for analysis. DATA SYNTHESIS: Approval of Vaxchora, was based on efficacy of the vaccine in human trials demonstrating 90.3% protection among those challenged with V cholerae 10 days after vaccination and in immunogenicity studies with 90% systemic vibriocidal antibody conversion at 6 months after a single-dose of vaccine. Tolerability was acceptable, with the most common adverse effects reported to be fatigue, headache, and abdominal pain. CONCLUSION: Vaxchora is the only FDA-approved, single-dose oral vaccine for the prevention of cholera caused by V cholerae serogroup O1 in adult travelers from the United States going to cholera-affected areas. Safety and efficacy has not been established in children, immunocompromised persons, and pregnant or breastfeeding women or those living in cholera-endemic areas.

Heart Rate and Systolic Blood Pressure Variability in the Time Domain in Patients with Recent and Long-Standing Diabetes Mellitus.

Diabetes Mellitus (DM) affects the cardiovascular response of patients. To study this effect, interbeat intervals (IBI) and beat-to-beat systolic blood pressure (SBP) variability of patients during supine, standing and controlled breathing tests were analyzed in the time domain. Simultaneous noninvasive measurements of IBI and SBP for 30 recently diagnosed and 15 long-standing DM patients were compared with the results for 30 rigorously screened healthy subjects (control). A statistically significant distinction between control and diabetic subjects was provided by the standard deviation and the higher moments of the distributions (skewness, and kurtosis) with respect to the median. To compare IBI and SBP for different populations, we define a parameter, α, that combines the variability of the heart rate and the blood pressure, as the ratio of the radius of the moments for IBI and the same radius for SBP. As diabetes evolves, α decreases, standard deviation of the IBI detrended signal diminishes (heart rate signal becomes more "rigid"), skewness with respect to the median approaches zero (signal fluctuations gain symmetry), and kurtosis increases (fluctuations concentrate around the median). Diabetes produces not only a rigid heart rate, but also increases symmetry and has leptokurtic distributions. SBP time series exhibit the most variable behavior for recently diagnosed DM with platykurtic distributions. Under controlled breathing, SBP has symmetric distributions for DM patients, while control subjects have non-zero skewness. This may be due to a progressive decrease of parasympathetic and sympathetic activity to the heart and blood vessels as diabetes evolves.

Heart Rate and Systolic Blood Pressure Variability on Recently Diagnosed Diabetics / Variabilidade da Frequência Cardíaca e da Pressão Arterial Sistólica em Diabéticos com Diagnóstico Recente

Background:Diabetes affects approximately 250 million people in the world. Cardiovascular autonomic neuropathy is a common complication of diabetes that leads to severe postural hypotension, exercise intolerance, and increased incidence of silent myocardial infarction.Objective:To determine the variability of heart rate (HR) and systolic blood pressure (SBP) in recently diagnosed diabetic patients.Methods:The study included 30 patients with a diagnosis of type 2 diabetes of less than 2 years and 30 healthy controls. We used a Finapres® device to measure during five minutes beat-to-beat HR and blood pressure in three experimental conditions: supine position, standing position, and rhythmic breathing at 0.1 Hz. The results were analyzed in the time and frequency domains.Results:In the HR analysis, statistically significant differences were found in the time domain, specifically on short-term values such as standard deviation of NN intervals (SDNN), root mean square of successive differences (RMSSD), and number of pairs of successive NNs that differ by more than 50 ms (pNN50). In the BP analysis, there were no significant differences, but there was a sympathetic dominance in all three conditions. The baroreflex sensitivity (BRS) decreased in patients with early diabetes compared with healthy subjects during the standing maneuver.Conclusions:There is a decrease in HR variability in patients with early type 2 diabetes. No changes were observed in the BP analysis in the supine position, but there were changes in BRS with the standing maneuver, probably due to sympathetic hyperactivity.

Fundamento:O diabetes afeta aproximadamente 250 milhões de pessoas no mundo. A neuropatia autonômica cardiovascular é uma complicação comum do diabetes que leva à hipotensão postural grave, intolerância ao exercício e aumento na incidência de infarto do miocárdio silencioso.Objetivo:Determinar a variabilidade da frequência cardíaca (FC) e da pressão arterial sistólica (PAS) em pacientes diabéticos com diagnóstico recente.Métodos:O estudo incluiu 30 pacientes com diabetes tipo 2 diagnosticado há menos de 2 anos e 30 controles saudáveis. Nós utilizamos o dispositivo Finapres® para medir durante cinco minutos a FC batimento-a-batimento e a pressão arterial (PA) em três condições experimentais: posição supina, em pé e durante respiração rítmica na frequência de 0,1 Hz. Os resultados foram analisados nos domínios do tempo e da frequência.Resultados:Em relação à FC, foram encontradas diferenças estatisticamente significativas nos valores da análise do domínio do tempo, especificamente em valores determinados a curto prazo, tais como o desvio-padrão dos intervalos NN (DPNN), a raiz quadrada da média das diferenças sucessivas (RQMDS) para a FC e o número de pares de NNs sucessivos que diferem em mais de 50 ms (pNN50). Não houve diferença significativa na análise da PA, mas houve uma dominância simpática nas três condições. A sensibilidade do barorreflexo (SBR) esteve diminuída em pacientes com diabetes de início recente, em comparação aos indivíduos saudáveis durante execução da manobra na posição ortostática.Conclusões:Há uma diminuição na variabilidade da FC em pacientes com diabetes tipo 2 de início recente. Não foram observadas alterações na análise da PA na posição supina, mas a SBR apresentou mudança com a manobra em pé provavelmente causada por hiperatividade simpática.

Heart rate and systolic blood pressure variability on recently diagnosed diabetics.

BACKGROUND: Diabetes affects approximately 250 million people in the world. Cardiovascular autonomic neuropathy is a common complication of diabetes that leads to severe postural hypotension, exercise intolerance, and increased incidence of silent myocardial infarction. OBJECTIVE: To determine the variability of heart rate (HR) and systolic blood pressure (SBP) in recently diagnosed diabetic patients. METHODS: The study included 30 patients with a diagnosis of type 2 diabetes of less than 2 years and 30 healthy controls. We used a Finapres® device to measure during five minutes beat-to-beat HR and blood pressure in three experimental conditions: supine position, standing position, and rhythmic breathing at 0.1 Hz. The results were analyzed in the time and frequency domains. RESULTS: In the HR analysis, statistically significant differences were found in the time domain, specifically on short-term values such as standard deviation of NN intervals (SDNN), root mean square of successive differences (RMSSD), and number of pairs of successive NNs that differ by more than 50 ms (pNN50). In the BP analysis, there were no significant differences, but there was a sympathetic dominance in all three conditions. The baroreflex sensitivity (BRS) decreased in patients with early diabetes compared with healthy subjects during the standing maneuver. CONCLUSIONS: There is a decrease in HR variability in patients with early type 2 diabetes. No changes were observed in the BP analysis in the supine position, but there were changes in BRS with the standing maneuver, probably due to sympathetic hyperactivity.

[The cardiovagal, cardiosympathetic and vasosympathetic arterial baroreflexes and the neural control of short-term blood pressure]. / Los barorreflejos arteriales cardiovagal, cardiosimpatico y vasosimpatico y el control neural de la presion arterial a corto plazo.

INTRODUCTION: The factors that control the blood pressure are punctually regulated to keep it in reference values. These are maintained through autoregulatory mechanisms, humoral, nervous and endothelial-related. The humoral mechanisms are complex and modify the long-term blood pressure, in the other hand, the neurogenic mechanisms, are reflexive and can be observed in beat-to-beat changes of blood pressure. DEVELOPMENT: The nervous cardiovascular reflexes are mediated by high-pressure and low-pressure baroreceptors, as cardiovagal, cardiosympathetic and vasosympathetic. The arterial baroreceptor are stimulated when the blood volume-ejected by the ventricle distend the arterial walls. The neural discharge travels to the autonomic centers in the brain stem and the result is the modification of the heart rate and the vascular smooth muscle tone. This sudden modification is the responsible of the beat-to-beat (short-term) blood pressure variability. CONCLUSION: A review was made on the history of the physiology and experiments of the cardiovagal, cardiosympathetic and vasosympathetic baroreflexes and its influence in the short-term blood pressure variability.

TITLE: Los barorreflejos arteriales cardiovagal, cardiosimpatico y vasosimpatico y el control neural de la presion arterial a corto plazo.Introduccion. Los factores que modulan la presion arterial a corto plazo se encuentran puntualmente regulados para mantenerla dentro de valores de referencia. Esto se logra gracias a la existencia de mecanismos de autorregulacion, tanto humorales como nerviosos. Los mecanismos neurogenicos son reflejos y su resultado se observa en cambios de presion arterial de forma inmediata, latido a latido. Desarrollo. Los reflejos nerviosos cardiovasculares se encuentran mediados por los barorreceptores arteriales, a traves de los efectores cardiovagal, cardiosimpatico y vasosimpatico. El barorreceptor es estimulado cuando el volumen de sangre eyectado por el ventriculo distiende las paredes arteriales del seno carotideo y la aorta proximal y estimula los mecanorreceptores situados en la adventicia de estos vasos. El estimulo aferente viaja hasta el nucleo del haz solitario en el bulbo raquideo y otras areas en el puente donde se integran estos reflejos y la parte eferente genera cambios compensatorios en la frecuencia cardiaca y el tono del musculo liso vascular. Esta modificacion subita es la responsable de la variabilidad de la presion arterial latido a latido (corto plazo). Conclusion. Se realiza una revision sobre la historia, la fisiologia y los experimentos de los barorreflejos cardiovagal, cardiosimpatico y vasosimpatico y su influencia en la variabilidad de la presion arterial a corto plazo.

Aedes aegypti Mos20 cells internalizes cry toxins by endocytosis, and actin has a role in the defense against Cry11Aa toxin.

Bacillus thuringiensis (Bt) Cry toxins are used to control Aedes aegypti, an important vector of dengue fever and yellow fever. Bt Cry toxin forms pores in the gut cells, provoking larvae death by osmotic shock. Little is known, however, about the endocytic and/or degradative cell processes that may counteract the toxin action at low doses. The purpose of this work is to describe the mechanisms of internalization and detoxification of Cry toxins, at low doses, into Mos20 cells from A. aegypti, following endocytotic and cytoskeletal markers or specific chemical inhibitors. Here, we show that both clathrin-dependent and clathrin-independent endocytosis are involved in the internalization into Mos20 cells of Cry11Aa, a toxin specific for Dipteran, and Cry1Ab, a toxin specific for Lepidoptera. Cry11Aa and Cry1Ab are not directed to secretory lysosomes. Instead, Mos20 cells use the Rab5 and Rab11 pathways as a common mechanism, most probably for the expulsion of Cry11Aa and Cry1Ab toxins. In conclusion, we propose that endocytosis is a mechanism induced by Cry toxins independently of specificity, probably as part of a basal immune response. We found, however, that actin is necessary for defense-specific response to Cry11Aa, because actin-silenced Mos20 cells become more sensitive to the toxic action of Cry11A toxin. Cry toxin internalization analysis in insect cell lines may contribute to a better understanding to Cry resistance in mosquitoes.

[Cortical spreading depolarization: a new pathophysiological mechanism in neurological diseases]. / Despolarización cortical extendida: un nuevo mecanismo fisiopatológico en las enfermedades neurológicas.

Cortical spreading depolarization is a wave of almost complete depolarization of the neuronal and glial cells that occurs in different neurological diseases such as migraine with aura, subarachnoid hemorrhage, intracerebral hemorrhage, head trauma and stroke. These depolarization waves are characterized by a change in the negative potential with an amplitude between -10 and -30mV, duration of ∼1min and changes in the ion homeostasis between the intra- and extracellular space. This results in neuronal edema and dendritic distortion. Under pathologic states of hypoperfusion, cortical spreading depolarization can produce oxidative stress, worsen hypoxia and induce neuronal death. This is due to intense arterial vasoconstriction produced by an inverse response called spreading ischemia. Only in the last years there has been an electrophysiological confirmation of cortical spreading depolarization in human brains. Occurrence of cortical spreading depolarization has been associated with worse outcome in patients. Currently, increased knowledge regarding the pathophysiologic mechanisms supports the hypothetical correlation of cortical spreading depolarization with brain damage in humans. There are diverse therapeutic alternatives that promise inhibition of cortical spreading depolarization and subsequent better outcomes.