The Chilean exposome-based system for ecosystems (CHiESS): a framework for national data integration and analytics platform.

The double burden of diseases and scarce resources in developing countries highlight the need to change the conceptualization of health problems and translational research. Contrary to the traditional paradigm focused on genetics, the exposome paradigm proposed in 2005 that complements the genome is an innovative theory. It involves a holistic approach to understanding the complexity of the interactions between the human being's environment throughout their life and health. This paper outlines a scalable framework for exposome research, integrating diverse data sources for comprehensive public health surveillance and policy support. The Chilean exposome-based system for ecosystems (CHiESS) project proposes a conceptual model based on the ecological and One Health approaches, and the development of a technological dynamic platform for exposome research, which leverages available administrative data routinely collected by national agencies, in clinical records, and by biobanks. CHiESS considers a multilevel exposure for exposome operationalization, including the ecosystem, community, population, and individual levels. CHiESS will include four consecutive stages for development into an informatic platform: (1) environmental data integration and harmonization system, (2) clinical and omics data integration, (3) advanced analytical algorithm development, and (4) visualization interface development and targeted population-based cohort recruitment. The CHiESS platform aims to integrate and harmonize available secondary administrative data and provide a complete geospatial mapping of the external exposome. Additionally, it aims to analyze complex interactions between environmental stressors of the ecosystem and molecular processes of the human being and their effect on human health. Moreover, by identifying exposome-based hotspots, CHiESS allows the targeted and efficient recruitment of population-based cohorts for translational research and impact evaluation. Utilizing advanced technologies such as Artificial Intelligence (AI), Internet of Things (IoT), and blockchain, this framework enhances data security, real-time monitoring, and predictive analytics. The CHiESS model is adaptable for international use, promoting global health collaboration and supporting sustainable development goals.

Fractalkine in Health and Disease.

CX3CL1 is one of the 50 up-to-date identified and characterized chemokines. While other chemokines are produced as small, secreted proteins, CX3CL1 (fractalkine) is synthetized as a transmembrane protein which also leads to a soluble form produced as a result of proteolytic cleavage. The membrane-bound protein and the soluble forms exhibit different biological functions. While the role of the fractalkine/CX3CR1 signaling axis was described in the nervous system and was also related to the migration of leukocytes to sites of inflammation, its actions are controversial in cancer progression and anti-tumor immunity. In the present review, we first describe the known biology of fractalkine concerning its action through its cognate receptor, but also its role in the activation of different integrins. The second part of this review is dedicated to its role in cancer where we discuss its role in anti-cancer or procarcinogenic activities.

Acute activation of hemichannels by ethanol leads to Ca2+-dependent gliotransmitter release in astrocytes.

Multiple studies have demonstrated that acute ethanol consumption alters brain function and cognition. Nevertheless, the mechanisms underlying this phenomenon remain poorly understood. Astrocyte-mediated gliotransmission is crucial for hippocampal plasticity, and recently, the opening of hemichannels has been found to play a relevant role in this process. Hemichannels are plasma membrane channels composed of six connexins or seven pannexins, respectively, that oligomerize around a central pore. They serve as ionic and molecular exchange conduits between the cytoplasm and extracellular milieu, allowing the release of various paracrine substances, such as ATP, D-serine, and glutamate, and the entry of ions and other substances, such as Ca2+ and glucose. The persistent and exacerbated opening of hemichannels has been associated with the pathogenesis and progression of several brain diseases for at least three mechanisms. The uncontrolled activity of these channels could favor the collapse of ionic gradients and osmotic balance, the release of toxic levels of ATP or glutamate, cell swelling and plasma membrane breakdown and intracellular Ca2+ overload. Here, we evaluated whether acute ethanol exposure affects the activity of astrocyte hemichannels and the possible repercussions of this phenomenon on cytoplasmatic Ca2+ signaling and gliotransmitter release. Acute ethanol exposure triggered the rapid activation of connexin43 and pannexin1 hemichannels in astrocytes, as measured by time-lapse recordings of ethidium uptake. This heightened activity derived from a rapid rise in [Ca2+]i linked to extracellular Ca2+ influx and IP3-evoked Ca2+ release from intracellular Ca2+ stores. Relevantly, the acute ethanol-induced activation of hemichannels contributed to a persistent secondary increase in [Ca2+]i. The [Ca2+]i-dependent activation of hemichannels elicited by ethanol caused the increased release of ATP and glutamate in astroglial cultures and brain slices. Our findings offer fresh perspectives on the potential mechanisms behind acute alcohol-induced brain abnormalities and propose targeting connexin43 and pannexin1 hemichannels in astrocytes as a promising avenue to prevent deleterious consequences of alcohol consumption.

Telemedicine in HIV health care during the COVID-19 pandemic: An implementation research study in Buenos Aires, Argentina.

BACKGROUND: From October 2020 to October 2022, we conducted an implementation study to offer telemedicine (TM) across four HIV units of general public hospitals in Buenos Aires. The intervention used TM to provide a continuum of care to patients with HIV. METHODS AND SETTING: We used the RE-AIM framework to evaluate the strategy. The study started during a COVID-19 outbreak with strict lockdown policies and continued until return to normal practices. Implementation facilitation served as the core implementation strategy. RESULTS: We reached 4118 patients (58% of eligible individuals), and the main perceived benefits were the ability to avoid exposure to infectious diseases and reduced travel time and cost. After a median of 515 days of follow-up, 95.7% of participants with HIV were receiving antiretroviral therapy, and 87.8% were virally suppressed, with a median CD4+ count of 648 cells/µL. In total, 36.6% reported clinical events, and 20.4% presented with COVID-19 infection. The proportion of physicians adopting TM was 69.37%. After enrolment, 2406 of 5640 (43%) follow-up visits were conducted via TM. By the end of the study, 26.29% of appointments offered in the four centres were through TM, whereas 73.71% were in-person appointments. CONCLUSION: It was feasible to implement TM in the four centres in the public health sector in Buenos Aires, Argentina. It was acceptable for both patients and healthcare workers, and effectively reached a large proportion of the population served in these clinics. Both healthcare workers and patients consider it a model of care that will continue to be offered in the future.

Association between environmental gradient of anthropization and phenotypic plasticity in two species of triatomines.

BACKGROUND: Triatoma garciabesi and T. guasayana are considered secondary vectors of Trypanosoma cruzi and frequently invade rural houses in central Argentina. Wing and head structures determine the ability of triatomines to disperse. Environmental changes exert selective pressures on populations of both species, promoting changes in these structures that could have consequences for flight dispersal. The aim of this study was to investigate the relationship between a gradient of anthropization and phenotypic plasticity in flight-related traits. METHODS: The research was carried out in Cruz del Eje and Ischilín departments (Córdoba, Argentina) and included 423 individuals of the two species of triatomines. To measure the degree of anthropization, a thematic map was constructed using supervised classification, from which seven landscapes were selected, and nine landscape metrics were extracted and used in a hierarchical analysis. To determine the flight capacity and the invasion of dwellings at different levels of anthropization for both species, entomological indices were calculated. Digital images of the body, head and wings were used to measure linear and geometric morphometric variables related to flight dispersion. One-way ANOVA and canonical variate analysis (CVA) were used to analyze differences in size and shape between levels of anthropization. Procrustes variance of shape was calculated to analyze differences in phenotypic variation in heads and wings. RESULTS: Hierarchical analysis was used to classify the landscapes into three levels of anthropization: high, intermediate and low. The dispersal index for both species yielded similar results across the anthropization gradient. However, in less anthropized landscapes, the density index was higher for T. garciabesi. Additionally, in highly anthropized landscapes, females and males of both species exhibited reduced numbers. Regarding phenotypic changes, the size of body, head and wings of T. garciabesi captured in the most anthropized landscapes was greater than for those captured in less anthropized landscapes. No differences in body size were observed in T. guasayana collected in the different landscapes. However, males from highly anthropized landscapes had smaller heads and wings than those captured in less anthropized landscapes. Both wing and head shapes varied between less and more anthropogenic environments in both species. CONCLUSIONS: Results of the study indicate that the flight-dispersal characteristics of T. garciabesi and T. guasayana changed in response to varying degrees of anthropization.

Cx43 hemichannels and panx1 channels contribute to ethanol-induced astrocyte dysfunction and damage.

BACKGROUND: Alcohol, a widely abused drug, significantly diminishes life quality, causing chronic diseases and psychiatric issues, with severe health, societal, and economic repercussions. Previously, we demonstrated that non-voluntary alcohol consumption increases the opening of Cx43 hemichannels and Panx1 channels in astrocytes from adolescent rats. However, whether ethanol directly affects astroglial hemichannels and, if so, how this impacts the function and survival of astrocytes remains to be elucidated. RESULTS: Clinically relevant concentrations of ethanol boost the opening of Cx43 hemichannels and Panx1 channels in mouse cortical astrocytes, resulting in the release of ATP and glutamate. The activation of these large-pore channels is dependent on Toll-like receptor 4, P2X7 receptors, IL-1ß and TNF-α signaling, p38 mitogen-activated protein kinase, and inducible nitric oxide (NO) synthase. Notably, the ethanol-induced opening of Cx43 hemichannels and Panx1 channels leads to alterations in cytokine secretion, NO production, gliotransmitter release, and astrocyte reactivity, ultimately impacting survival. CONCLUSION: Our study reveals a new mechanism by which ethanol impairs astrocyte function, involving the sequential stimulation of inflammatory pathways that further increase the opening of Cx43 hemichannels and Panx1 channels. We hypothesize that targeting astroglial hemichannels could be a promising pharmacological approach to preserve astrocyte function and synaptic plasticity during the progression of various alcohol use disorders.

Weight calibration in the joint modelling of medical cost and mortality.

Joint modelling of longitudinal and time-to-event data is a method that recognizes the dependency between the two data types, and combines the two outcomes into a single model, which leads to more precise estimates. These models are applicable when individuals are followed over a period of time, generally to monitor the progression of a disease or a medical condition, and also when longitudinal covariates are available. Medical cost datasets are often also available in longitudinal scenarios, but these datasets usually arise from a complex sampling design rather than simple random sampling and such complex sampling design needs to be accounted for in the statistical analysis. Ignoring the sampling mechanism can lead to misleading conclusions. This article proposes a novel approach to the joint modelling of complex data by combining survey calibration with standard joint modelling. This is achieved by incorporating a new set of equations to calibrate the sampling weights for the survival model in a joint model setting. The proposed method is applied to data on anti-dementia medication costs and mortality in people with diagnosed dementia in New Zealand.

Relationship between genetic diversity and morpho-functional characteristics of flight-related traits in Triatoma garciabesi (Hemiptera: Reduviidae).

BACKGROUND: Triatoma garciabesi, a potential vector of the parasitic protozoan Trypanosoma cruzi, which is the causative agent of Chagas disease, is common in peridomestic and wild environments and found throughout northwestern and central Argentina, western Paraguay and the Bolivian Chaco. Genetic differentiation of a species across its range can help to understand dispersal patterns and connectivity between habitats. Dispersal by flight is considered to be the main active dispersal strategy used by triatomines. In particular, the morphological structure of the hemelytra is associated with their function. The aim of this study was to understand how genetic diversity is structured, how morphological variation of dispersal-related traits varies with genetic diversity and how the morphological characteristics of dispersal-related traits may explain the current distribution of genetic lineages in this species. METHODS: Males from 24 populations of T. garciabesi across its distribution range were examined. The cytochrome c oxidase I gene (coI) was used for genetic diversity analyses. A geometric morphometric method based on landmarks was used for morpho-functional analysis of the hemelytra. Centroid size (CS) and shape of the forewing, and contour of both parts of the forewing, the head and the pronotum were characterised. Length and area of the forewing were measured to estimate the aspect ratio. RESULTS: The morphometric and phylogenetic analysis identified two distinct lineages, namely the Eastern and Western lineages, which coincide with different ecological regions. The Eastern lineage is found exclusively in the eastern region of Argentina (Chaco and Formosa provinces), whereas the Western lineage is prevalent in the rest of the geographical range of the species. CS, shape and aspect ratio of the hemelytra differed between lineages. The stiff portion of the forewing was more developed in the Eastern lineage. The shape of both portions of the hemelytra were significantly different between lineages, and the shape of the head and pronotum differed between lineages. CONCLUSIONS: The results provide preliminary insights into the evolution and diversification of T. garciabesi. Variation in the forewing, pronotum and head is congruent with genetic divergence. Consistent with genetic divergence, morphometry variation was clustered according to lineages, with congruent variation in the size and shape of the forewing, pronotum and head.

Biocontrol activities of yeasts or lactic acid bacteria isolated from Robusta coffee against Aspergillus carbonarius growth and ochratoxin A production in vitro.

Biocontrol Agents (BCAs) can be an eco-friendly alternative to fungicides to reduce the contamination with mycotoxigenic fungi on coffee. In the present study, different strains of bacteria and yeasts were isolated from Ivorian Robusta coffee. Their ability to reduce fungal growth and Ochratoxin A (OTA) production during their confrontation against Aspergillus carbonarius was screened on solid media. Some strains were able to reduce growth and OTA production by 85 % and 90 % and were molecularly identified as two yeasts, Rhodosporidiobolus ruineniae and Meyerozyma caribbica. Subsequent tests on liquid media with A. carbonarius or solely with OTA revealed adhesion of R. ruineniae to the mycelium of A. carbonarius through Scanning Electron Microscopy, and an OTA adsorption efficiency of 50 %. For M. caribbica potential degradation of OTA after 24 h incubation was observed. Both yeasts could be potential BCAs good candidates for Ivorian Robusta coffee protection against A. carbonarius and OTA contamination.

Assessment of a Digital Health Coordination Program to Mitigate Telehealth Access Disparities.

Objective: Patients with digital disparity experience challenges with utilizing and accessing virtual care. This study implemented a digital coordination program for patients in outpatient psychiatry. Methods: Clinicians referred patients to a digital health coordinator who provided training to enhance virtual access. Outcomes were patient sociodemographics, barriers to digital health care utilization, change in completed video visits, and clinician satisfaction. Results: The patient cohort included 44 patients with a mean age of 59.8, 75% female, 73% Caucasian, and 84% non-Hispanic. The median household income was less than $25,000. The most common barrier to completing a video visit was difficulty using Zoom. The proportion of completed to scheduled video visits increased in 27% of patients. In such patients, the mean increase in completed visits was 32%. A majority of referring providers (64%) reported increased meaningfulness of work. Conclusion: This pilot proactively identified disparities in virtual care access and mitigated digital literacy barriers, boosting meaningfulness of work for clinicians.

The antiseizure medication valproate increases hemichannel activity found in brain cells, which could worsen disease outcomes.

Glial cells play relevant roles in neuroinflammation caused by epilepsy. Elevated hemichannel (HC) activity formed by connexins (Cxs) or pannexin1 (Panx1) largely explains brain dysfunctions commonly caused by neuroinflammation. Glia express HCs formed by Cxs 43, 30, or 26, while glia and neurons both express HCs formed by Panx1. Cx43 HCs allow for the influx of Ca2+, which promotes glial reactivity, enabling the release of the gliotransmitters that contribute to neuronal over-stimulation. Valproate (VPA), an antiseizure medication, has pleiotropic actions on neuronal molecular targets, and their action on glial cell HCs remains elusive. We used HeLa cells transfected with Cx43, Cx30, Cx26, or Panx1 to determine the effect of VPA on HC activity in the brain. VPA slightly increased HC activity under basal conditions, but significantly enhanced it in cells pre-exposed to conditions that promoted HC activity. Furthermore, VPA increased ATP release through Cx43 HCs. The increased HC activity caused by VPA was resistant to washout, being consistent with in silico studies, which predicted the binding site for VPA and Cx43, as well as for Panx1 HCs on the intracellular side, suggesting that VPA first enters through HCs, after which their activity increases.

Estimating the effects of vegetation and increased albedo on the urban heat island effect with spatial causal inference.

The urban heat island effect causes increased heat stress in urban areas. Cool roofs and urban greening have been promoted as mitigation strategies to reduce this effect. However, evaluating their efficacy remains a challenge, as potential temperature reductions depend on local characteristics. Existing methods to characterize their efficacy, such as computational fluid dynamics and urban canopy models, are computationally burdensome and require a high degree of expertise to employ. We propose a data-driven approach to overcome these hurdles, inspired by recent innovations in spatial causal inference. This approach allows for estimates of hypothetical interventions to reduce the urban heat island effect. We demonstrate this approach by modeling evening temperature in Durham, North Carolina, using readily retrieved air temperature, land cover, and satellite data. Hypothetical interventions such as lining streets with trees, cool roofs, and changing parking lots to green space are estimated to decrease evening temperatures by a maximum of 0.7-0.9   [Formula: see text], with reduced effects on temperature as a function of distance from the intervention. Because of the ease of data access, this approach may be applied to other cities in the U.S. to help them come up with city-specific solutions for reducing urban heat stress.

Vaccination impact: mortality and time shift to COVID-19 maximum severity in hospitalized patients. An Argentine multicenter registry.

INTRODUCTION: The COVID-19 vaccine became an effective instrument to prevent severe SARS-CoV-2 infections. However, 5% of vaccinated patients will have moderate or severe disease. OBJECTIVE: to compare mortality and days between the symptom onset to the peak disease severity, in vaccinated vs. unvaccinated COVID-19 hospitalized patients. METHODS: Retrospective observational study in 36 hospitals in Argentina. COVID-19 adults admitted to general wards between January 1, 2021, and May 31, 2022 were included. Days between symptoms onset to peak of severity were compared between vaccinated vs. unvaccinated patients with Cox regression, adjusted by Propensity Score Matching (PSM). Results in patients with one and two doses were also compared. RESULTS: A total of 3663 patients were included (3001 [81.9%] unvaccinated and 662 [18%] vaccinated). Time from symptom onset to peak severity was 7 days (IQR 4-12) vs. 7 days (IQR 4-11) in unvaccinated and vaccinated. In crude Cox regression analysis and matched population, no significant differences were observed. Regarding mortality, a Risk Ratio (RR) of 1.51 (IC95% 1.29-1.77) was observed in vaccinated patients, but in the PSM cohort, the RR was 0.73 (IC95% 0.60-0.88). RR in patients with one COVID-19 vaccine dose in PSM adjusted population was 0.7 (IC95% 0.45-1.03), and with two doses 0.6 (IC95% 0.46-0.79). DISCUSSION: The time elapsed between the onset of COVID-19 symptoms to the highest severity was similar in vaccinated and unvaccinated patients. However, hospitalized vaccinated patients had a lower risk of mortality than unvaccinated patients.

Introducción: A pesar de la eficacia de la vacuna contra el COVID-19 el 5% de los pacientes vacunados presentaran una enfermedad moderada o grave. El objetivo del presente estudio fue comparar los días entre el inicio de los síntomas y la gravedad máxima de la enfermedad, en pacientes con COVID-19 vacunados vs. no vacunados. Métodos: Estudio observacional retrospectivo en 36 hospitales de Argentina. Se incluyeron adultos con COVID-19 hospitalizados entre el 1/01/2021 y 31/5/2022. Se recolectaron datos demográficos, comorbilidades y progresión clínica de la enfermedad. Se compararon los días entre el inicio de los síntomas y el pico de gravedad entre vacunados y no vacunados mediante regresión de Cox, ajustada por emparejamiento por Propensity Score Matching (PSM). En un análisis de subgrupos, se compararon los resultados en pacientes con una y dos dosis de vacuna. Resultados: Se incluyeron 3663 pacientes (3001 [81.9%] no vacunados y 662 [18%] vacunados). El tiempo transcurrido desde el inicio de los síntomas hasta el pico de gravedad fue de 7 días (IQR 4 - 12) en no vacunados, y de 7 días (IQR 4-11) en vacunados. Tanto en el análisis de regresión de Cox crudo como en el ajustado, no se observaron diferencias significativas entre ambos grupos (HR ajustado 1.08 [IC 95% 0.82-1.4; p = 0.56]). En cuanto a la mortalidad, el Riesgo Relativo (RR) fue 1.51 (IC95% 1.29-1.77) en los pacientes vacunados, pero en la cohorte ajustada por Propensity Score, el RR fue de 0.73 (IC95% 0.60-0.88). El RR en el grupo con una dosis de vacuna COVID-19 en el análisis PSM fue 0.7 (IC95% 0.45-1.03), y con dos dosis 0.6 (IC95% 0.46-0.79). Discusión: El tiempo entre el inicio de los síntomas de COVID-19 y el pico de severidad fue igual en vacunados y no vacunados. Sin embargo, los pacientes vacunados hospitalizados presentaron menor mortalidad tras el ajuste por confundidores.

Nativity differences in socioeconomic barriers and healthcare delays among cancer survivors in the All of Us cohort.

PURPOSE: We aimed to assess whether nativity differences in socioeconomic (SES) barriers and health literacy were associated with healthcare delays among US cancer survivors. METHODS: "All of Us" survey data were analyzed among adult participants ever diagnosed with cancer. A binary measure of healthcare delay (1+ delays versus no delays) was created. Health literacy was assessed using the Brief Health Literacy Screen. A composite measure of SES barriers (education, employment, housing, income, and insurance statuses) was created as 0, 1, 2, or 3+. Multivariable logistic regression model tested the associations of (1) SES barriers and health literacy with healthcare delays, and (2) whether nativity modified this relationship. RESULTS: Median participant age was 64 years (n = 10,020), with 8% foreign-born and 18% ethnic minorities. Compared to survivors with no SES barriers, those with 3+ had higher likelihood of experiencing healthcare delays (OR 2.18, 95% CI 1.84, 2.58). For every additional barrier, the odds of healthcare delays were greater among foreign-born (1.72, 1.43, 2.08) than US-born (1.27, 1.21, 1.34). For every 1-unit increase in health literacy among US-born, the odds of healthcare delay decreased by 9% (0.91, 0.89, 0.94). CONCLUSION: We found that SES barriers to healthcare delays have a greater impact among foreign-born than US-born cancer survivors. Higher health literacy may mitigate healthcare delays among US cancer survivors. Healthcare providers, systems and policymakers should assess and address social determinants of health and promote health literacy as a way to minimize healthcare delays among both foreign- and US-born cancer survivors.

Alcohol and illicit drugs:prevalence of alcohol and illicit drug use and their predictors in young people from Argentina,Bulgaria,Chile and Romania / 《全球健康杂志（英文）》

Background:Alcohol and illicit drugs(AID)continue to be a major global health concern.Although preventable,AID is linked to millions of deaths annually worldwide.The situation is particularly grave for young people,with AID being a major direct risk factor for disability-adjusted youth life-years lost and death.It further contributes to assaults,road crashes,accidental poisoning,and suicide,leading to long-term issues and public health concerns. Objective:This study aimed at disclosing current AID prevalence data for Argentinian,Bulgarian,Chilean and Romanian youth.It shed light on the predictors of AID in young people from those countries. Method:The study used an online survey to gather data from people aged 18 to 25(n=1,297).The survey was underpinned by the theory of planned behaviour(TPB).Predictors were investigated separately for drinking alcohol and using illicit drugs. Results:Our data revealed that across the four target countries,49％to 90％of the participants drank alcohol,and 8％to 35％used illicit drugs in the past three months.Between 20％and 91％of them intended to drink,and between 8％and 31％intended to use illicit drugs in the following three months.Our TPB model predicted statistically significant(P＜0.001)amounts of variance in drinking alcohol(between 61％and 72％)and using il-licit drugs(between 20.3％and 74.4％).Intention was consistent in significantly predicting both behaviours.Evidence around the predictive validity of self-efficacy,age and gender was mixed across the investigated countries. Conclusion:This research provided an update on the scarce AID epidemiological data.It also supplied evidence about what theoretically-informed measures might be useful targets of interventions in the case of Argentina,Bulgaria,Chile and Romania.This new knowledge of understanding substance abuse determinants and prevalence may help researchers and practitioners better meet young people's health prevention needs.

Falls Risk in Long-Term Care Residents With Cognitive Impairment: Effects of COVID-19 Pandemic.

OBJECTIVES: The aim of this study was to investigate the impact of the COVID-19 pandemic on falls rates in long-term care residents with cognitive impairment. DESIGN: An observational study using routinely collected national interRAI data. SETTING AND PARTICIPANTS: Participants were from long-term care residents (age ≥60 years) who received an interRAI Long Term Care Facility assessment anywhere in New Zealand between August 17, 2018, and August 16, 2022. METHODS: The primary outcome was "At least 1 fall in the last 30 days." Based on the Cognitive Performance Scale (CPS), cognitive impairment was categorized into 3 levels: intact or borderline intact (0-1), mild to moderate impairment (2-3), and moderately to very severe impairment (4-6). The COVID-19 pandemic was divided into 3 periods (First wave: March 21, 2020, to June 8, 2020; Varying level of community outbreaks: June 9, 2020 to August 16, 2021; and Delta-Omicron wave: August 17, 2021, to August 16, 2021) and compared to a pre-COVID-19 period (August 17, 2018, to March 20, 2020). Cox regression modeling was used to study falls and interactions between CPS and COVID-19 pandemic periods, along with other established falls risk factors in the literature. RESULTS: A total of 282,518 interRAI-LTCF assessments from 75,132 unique residents were included. Interactions between CPS and COVID-19 pandemic periods found that cognitive impairment was associated with a higher hazard ratio (ranged from 1.22 to 1.37) in each of the 3 COVID-19 pandemic periods. We also found unstable health, unsteady gait, wandering, and moderate to severe ADL dependency were the strongest risk factors for falls. CONCLUSIONS AND IMPLICATIONS: Cognitively impaired long-term care residents had an increased risk for falls during the COVID-19 pandemic. This risk was influenced by several factors. In future pandemic or infection control related isolation, residents who are most at risk can be identified for targeted falls prevention programs.

Vaccination impact: mortality and time shift to Covid-19 maximum severity in hospitalized patients - An Argentine multicenter registry / Mortalidad y tiempo entre el inicio y máxima gravedad de COVID-19, en pacientes hospitalizados vacunados y no vacunados. Registro multicéntrico argentino

Abstract Introduction : The COVID-19 vaccine became an effec tive instrument to prevent severe SARS-CoV-2 infections. However, 5% of vaccinated patients will have moderate or severe disease. Objective: to compare mortality and days between the symptom onset to the peak disease severity, in vaccinated vs. unvaccinated COVID-19 hos pitalized patients. Methods : Retrospective observational study in 36 hospitals in Argentina. COVID-19 adults admitted to general wards between January 1, 2021, and May 31, 2022 were included. Days between symptoms onset to peak of severity were compared between vaccinated vs. unvaccinated patients with Cox regression, adjusted by Propensity Score Matching (PSM). Results in patients with one and two doses were also compared. Results : A total of 3663 patients were included (3001 [81.9%] unvaccinated and 662 [18%] vaccinated). Time from symptom onset to peak severity was 7 days (IQR 4-12) vs. 7 days (IQR 4-11) in unvaccinated and vacci nated. In crude Cox regression analysis and matched population, no significant differences were observed. Regarding mortality, a Risk Ratio (RR) of 1.51 (IC95% 1.29-1.77) was observed in vaccinated patients, but in the PSM cohort, the RR was 0.73 (IC95% 0.60-0.88). RR in patients with one COVID-19 vaccine dose in PSM adjusted population was 0.7 (IC95% 0.45-1.03), and with two doses 0.6 (IC95% 0.46-0.79). Discussion : The time elapsed between the onset of COVID-19 symptoms to the highest severity was simi lar in vaccinated and unvaccinated patients. However, hospitalized vaccinated patients had a lower risk of mortality than unvaccinated patients.

Resumen Introducción : A pesar de la eficacia de la vacuna contra el COVID-19 el 5% de los pacientes vacunados presentaran una enfermedad moderada o grave. El ob jetivo del presente estudio fue comparar los días entre el inicio de los síntomas y la gravedad máxima de la enfermedad, en pacientes con COVID-19 vacunados vs. no vacunados. Métodos : Estudio observacional retrospectivo en 36 hospitales de Argentina. Se incluyeron adultos con CO VID-19 hospitalizados entre el 1/01/2021 y 31/5/2022. Se recolectaron datos demográficos, comorbilidades y progresión clínica de la enfermedad. Se compararon los días entre el inicio de los síntomas y el pico de gravedad entre vacunados y no vacunados mediante regresión de Cox, ajustada por emparejamiento por Propensity Score Matching (PSM). En un análisis de subgrupos, se compararon los resultados en pacientes con una y dos dosis de vacuna. Resultados : Se incluyeron 3663 pacientes (3001 [81.9%] no vacunados y 662 [18%] vacunados). El tiempo transcurrido desde el inicio de los síntomas hasta el pico de gravedad fue de 7 días (IQR 4 - 12) en no vacunados, y de 7 días (IQR 4-11) en vacunados. Tanto en el análisis de regresión de Cox crudo como en el ajustado, no se observaron diferencias significativas entre ambos grupos (HR ajustado 1.08 [IC 95% 0.82-1.4; p = 0.56]). En cuanto a la mortalidad, el Riesgo Relativo (RR) fue 1.51 (IC95% 1.29-1.77) en los pacientes vacunados, pero en la cohorte ajustada por Propensity Score, el RR fue de 0.73 (IC95% 0.60-0.88). El RR en el grupo con una dosis de vacuna COVID-19 en el análisis PSM fue 0.7 (IC95% 0.45-1.03), y con dos dosis 0.6 (IC95% 0.46-0.79). Discusión : El tiempo entre el inicio de los síntomas de COVID-19 y el pico de severidad fue igual en vacu nados y no vacunados. Sin embargo, los pacientes va cunados hospitalizados presentaron menor mortalidad tras el ajuste por confundidores.

Cx43 hemichannels and panx1 channels contribute to ethanol-induced astrocyte dysfunction and damage

Background Alcohol, a widely abused drug, significantly diminishes life quality, causing chronic diseases and psychiatric issues, with severe health, societal, and economic repercussions. Previously, we demonstrated that non-voluntary alcohol consumption increases the opening of Cx43 hemichannels and Panx1 channels in astrocytes from adolescent rats. However, whether ethanol directly affects astroglial hemichannels and, if so, how this impacts the function and survival of astrocytes remains to be elucidated. Results Clinically relevant concentrations of ethanol boost the opening of Cx43 hemichannels and Panx1 channels in mouse cortical astrocytes, resulting in the release of ATP and glutamate. The activation of these large-pore channels is dependent on Toll-like receptor 4, P2X7 receptors, IL-1β and TNF-α signaling, p38 mitogen-activated protein kinase, and inducible nitric oxide (NO) synthase. Notably, the ethanol-induced opening of Cx43 hemichannels and Panx1 channels leads to alterations in cytokine secretion, NO production, gliotransmitter release, and astrocyte reactivity, ultimately impacting survival. Conclusion Our study reveals a new mechanism by which ethanol impairs astrocyte function, involving the sequential stimulation of inflammatory pathways that further increase the opening of Cx43 hemichannels and Panx1 channels. We hypothesize that targeting astroglial hemichannels could be a promising pharmacological approach to preserve astrocyte function and synaptic plasticity during the progression of various alcohol use disorders.

Consultas tardías en los servicios de emergencias pediátricas durante la pandemia por COVID-19 en Uruguay, entre el 13 de marzo y el 29 de julio de 2020 / Delayed visits to Pediatric Emergency Departments during the COVID-19 pandemic in Uruguay between March 13 and July 29, 2020 / Consultas tardias nos Serviços de Emergência Pediátrica durante a pandemia de COVID-19 no Uruguai entre 13 de março e 29 de julho de 2020

En diciembre de 2019, en Wuhan, China, se detectaron los primeros casos de SARS-CoV-2. En Uruguay, desde el 16 de marzo de 2020 se suspendieron las actividades de enseñanza, deportivas y espectáculos públicos. Varios países reportaron una marcada disminución de las visitas a urgencias. Algunos niños presentaron enfermedades ocasionales o descompensaciones de enfermedades crónicas, consultando en forma tardía con el riesgo que ello implica. El objetivo de este trabajo es realizar una descripción de las consultas tardías durante la pandemia. Se realizó un estudio multicéntrico y descriptivo entre el 13 de marzo y el 29 de julio de 2020. Se definió consulta tardía como los ingresos por injurias agudas con más de 6 horas de evolución, fiebre mayor a 72 horas de evolución, dificultad respiratoria con más de 12 horas de evolución, síntomas agudos, como dolor abdominal, de más de 24 horas de evolución, síntomas de más de 12 horas de evolución en niños con enfermedades crónicas que determinaron descompensación e ingreso. Se incluyeron 27 centros. Se registraron un total de 34.260 consultas en urgencia, se incluyeron 189 niños para el estudio. El promedio de edad fue de 6 años; 17 pacientes requirieron ingreso a unidad de cuidados intensivos (UCI). Predominó la apendicitis entre los diagnósticos al alta. Esta investigación puso en evidencia la existencia de consultas tardías en nuestro país. Esto contribuye a ponderar el impacto negativo de la pandemia en la población pediátrica.

In December 2019, the first cases of SARS-CoV-2 were detected in Wuhan. In Uruguay, since March 16, teaching, sports and public entertainment activities were suspended. Several countries reported a marked decrease in emergency room visits. Some children presented occasional illnesses or decompensations from chronic illnesses, consulting late with the risk that this implies. The objective of the work is to make a description of late consultations during the pandemic. A multicenter and descriptive study was carried out between March 13 and July 29, 2020. "Late consultation" was defined as admissions for: Acute injuries with more than 6 hours of evolution, fever greater than 72 hours of evolution, difficulty respiratory disease with more than 12 hours of evolution, acute symptoms such as abdominal pain of more than 24 hours of evolution, symptoms of more than 12 hours of evolution in children with chronic diseases that determined decompensation and admission. 27 centers were included. A total of 34260 emergency consultations were registered, 189 children were included for the study. The average age was 6 years. 17 patients required admission to the ICU. Appendicitis predominated among the diagnoses at discharge. This research revealed the existence of late consultations in our country. This helps to weigh the negative impact of the pandemic on the pediatric population.

Em dezembro de 2019, em Wuhan, foram detectados os primeiros casos de SARS-CoV-2. No Uruguai, desde 16 de março, as atividades de ensino, esporte e entretenimento público foram suspensas. Vários países relataram uma diminuição acentuada nas visitas ao pronto-socorro. Algumas crianças apresentavam doenças ocasionais ou descompensações de doenças crônicas, consultando tardiamente os riscos que isso implica. O objetivo do trabalho é fazer uma descrição das consultas tardias durante a pandemia. Um estudo multicêntrico e descritivo foi realizado entre 13 de março e 29 de julho de 2020. Consulta tardia foi definida como internações por: Lesões agudas com mais de 6 horas de evolução, febre maior que 72 horas de evolução, dificuldade respiratória com mais de 12 horas de evolução, sintomas agudos como dor abdominal com mais de 24 horas de evolução, sintomas com mais de 12 horas de evolução em crianças com doenças crônicas que determinaram descompensação e internação. 26 centros foram incluídos. Um total de 34.260 consultas de emergência foram registradas, 189 crianças foram incluídas no estudo. A idade média era de 6 anos. 17 pacientes necessitaram de internação na UTI. Apendicite predominou entre os diagnósticos na alta. Esta pesquisa revelou a existência de consultas tardias em nosso país. Isso ajuda a pesar o impacto negativo da pandemia na população pediátrica.

Bladder Cancer and Probiotics: What Do We Know So Far?

Bladder cancer is around the 10th most diagnosed cancer, although has a considerable mortality. Recent research and new methodologies have discarded the historical dogma that the bladder (and urine) was sterile under normal conditions. Specifically, only a few studies have reported a detailed analysis of the urinary microbiota in patients with bladder cancer, thus exhibiting a remarkable variability due to the low biomass of the urinary microbiota and the influence of many factors. Nevertheless, this research shows us signals that urinary microbiota is a factor to be considered in the pathophysiology of bladder cancer. More importantly, probiotics could be useful as an adjuvant therapy to reduce the recurrence rate or increase the disease-free period after surgery. In vitro studies and animal assays have shown promising results, but the research in this context has also been scarce, and only a few studies have been conducted in humans. In summary, there is little evidence of the possible beneficial effect of probiotics in controlling the overgrowth of genera that could be involved in the carcinogenesis of bladder cancer. This narrative review aims to compile all the evidence to date on the therapeutic potential of probiotics injected directly into the bladder or orally administered.