CD4+ T cell immunity is dependent on an intrinsic stem-like program.

CD4+ T cells are central to various immune responses, but the molecular programs that drive and maintain CD4+ T cell immunity are not entirely clear. Here we identify a stem-like program that governs the CD4+ T cell response in transplantation models. Single-cell-transcriptomic analysis revealed that naive alloantigen-specific CD4+ T cells develop into TCF1hi effector precursor (TEP) cells and TCF1-CXCR6+ effectors in transplant recipients. The TCF1-CXCR6+CD4+ effectors lose proliferation capacity and do not reject allografts upon adoptive transfer into secondary hosts. By contrast, the TCF1hiCD4+ TEP cells have dual features of self-renewal and effector differentiation potential, and allograft rejection depends on continuous replenishment of TCF1-CXCR6+ effectors from TCF1hiCD4+ TEP cells. Mechanistically, TCF1 sustains the CD4+ TEP cell population, whereas the transcription factor IRF4 and the glycolytic enzyme LDHA govern the effector differentiation potential of CD4+ TEP cells. Deletion of IRF4 or LDHA in T cells induces transplant acceptance. These findings unravel a stem-like program that controls the self-renewal capacity and effector differentiation potential of CD4+ TEP cells and have implications for T cell-related immunotherapies.

Treatment of textile wastewater using the Co(II)/NaHCO3/H2O2 oxidation system.

Textile wastewater (TWW) is one of the most hazardous wastewaters for ecosystems when it is discharged directly into water streams without adequate treatment. Some organic pollutants, such as dyes in TWW, are considered refractory compounds that are difficult to degrade using conventional chemical and biological methods. The bicarbonate-activated peroxide (BAP) system is an advanced oxidation process (AOP) based on applying H2O2, which has been demonstrated to be a clean and efficient technology for dye degradation, with the advantage of operating under slightly alkaline pH conditions. In this study, response surface methodology (RSM) based on a central composite design (CCD) was used to optimize the degradation of TWW contaminated with the azo dye Acid Black 194 using the BAP system catalyzed with cobalt ions in solution (Co2+). The analysis of variance (ANOVA) technique was applied to identify significant variables and their individual and interactive effects on the degradation of TWW. The optimum reagent concentrations for degrading TWW at 25 °C and with 45 µM Co2+ were 787.61 and 183.34 mM for H2O2 and NaHCO3, respectively. Under these conditions, complete decolorization (≥99.40), 32.20 % mineralization, and 52.02 % chemical oxygen demand removal were achieved. Additionally, the acute toxicity of textile wastewater before and after oxidation was evaluated with guppy fish (Poecilia reticulata), showing a total reduction in mortality after treatment with the Co2+-BAP system. The Co2+-BAP oxidation system is a potential method for textile wastewater treatment, which, in addition to achieving complete decolorization and partial mineralization, improves biodegradability and reduces the toxicity of the treated water.

Prevention and control of COVID-19 outbreak in a hemodialysis center.

BACKGROUND: The prevention and control of SARS-CoV-2 infection in hemodialysis (HD) units is challenging. AIM: To describe the clinical characteristics and outcome of patients with chronic kidney disease (CKD) on HD with COVID-19, between March 2020 and January 28, 2021, attending a single HD unit in Bogotá, Colombia. MATERIAL AND METHODS: In this prospective observational study, incidence, prevalence, and case-fatality rate were estimated, including screening results with RT-PCR and anti-SARS-CoV-2 IgG and IgM antibodies in all patients and health personnel in the HD unit. RESULTS: Among patients and health workers, 55 and 9 cases of COVID-19 were identified, respectively. The median age of patients was 63 years (84% males). Fifty five percent of patients were symptomatic, with fever, cough and/or myalgia. The most common comorbidities were hypertension, type 2 diabetes mellitus, and coronary heart disease. The cumulative incidence of infection was 30.2%, population seroprevalence was 24.9%, and fatality was 9.1%. CONCLUSIONS: The incidence of SARS-CoV-2 infection in this HD unit was high. Strict biosafety protocols are required to prevent outbreaks.

Autosomal dominant polycystic kidney disease in Colombia.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic cause of chronic kidney disease (CKD) that requires dialysis. Knowing geographical clusters can be critical for early diagnosis, progression control, and genetic counseling. The objective was to establish the prevalence, geographic location, and ethnic groups of patients with ADPKD who underwent dialysis or kidney transplant in Colombia between 2015 and 2019. METHODS: We did a cross-sectional study with data from the National Registry of Chronic Kidney Disease (NRCKD) managed by the High-Cost Diseases Fund (Cuenta de Alto Costo [CAC] in Spanish) between July 1, 2015, and June 30, 2019. We included Colombian population with CKD with or without renal replacement therapy (RRT) due to ADPKD. Crude and adjusted prevalence rates were estimated by state and city. RESULTS: 3,339 patients with ADPKD were included, period prevalence was 9.81 per 100,000 population; there were 4.35 cases of RRT per 100,000 population, mean age of 52.58 years (± 13.21), and 52.78% women. Seventy-six patients were Afro-Colombians, six were indigenous, and one Roma people. A total of 46.07% began scheduled dialysis. The highest adjusted prevalence rate was in Valle del Cauca (6.55 cases per 100,000 population), followed by Risaralda, and La Guajira. Regarding cities, Cali had the highest prevalence rate (9.38 cases per 100,000 population), followed by Pasto, Medellin, and Bucaramanga. CONCLUSIONS: ADPKD prevalence is lower compared to Europe and US; some states with higher prevalence could be objective to genetic prevalence study.

Prevention and control of COVID-19 outbreak in a hemodialysis center / Prevención y control de un brote de COVID-19 en una unidad de hemodiálisis

BACKGROUND: The prevention and control of SARS-CoV-2 infection in hemodialysis (HD) units is challenging. AIM: To describe the clinical characteristics and outcome of patients with chronic kidney disease (CKD) on HD with COVID-19, between March 2020 and January 28, 2021, attending a single HD unit in Bogotá, Colombia. MATERIAL AND METHODS: In this prospective observational study, incidence, prevalence, and case-fatality rate were estimated, including screening results with RT-PCR and anti-SARS-CoV-2 IgG and IgM antibodies in all patients and health personnel in the HD unit. RESULTS: Among patients and health workers, 55 and 9 cases of COVID-19 were identified, respectively. The median age of patients was 63 years (84% males). Fifty five percent of patients were symptomatic, with fever, cough and/or myalgia. The most common comorbidities were hypertension, type 2 diabetes mellitus, and coronary heart disease. The cumulative incidence of infection was 30.2%, population seroprevalence was 24.9%, and fatality was 9.1%. CONCLUSIONS: The incidence of SARS-CoV-2 infection in this HD unit was high. Strict biosafety protocols are required to prevent outbreaks.

INTRODUCCIÓN: La prevención y el control de la infección por SARS-CoV-2 en las unidades de hemodiálisis (HD) es un desafío. OBJETIVO: Describir las características clínicas y la evolución de los pacientes con enfermedad renal crónica (ERC) en HD con COVID-19, entre marzo de 2020 y el 28 de enero de 2021, que acudieron a una unidad de HD en Bogotá, Colombia. MATERIAL Y MÉTODOS: Estudio observacional prospectivo con estimación de incidencia, prevalencia y letalidad, incluyendo los resultados del cribado con RT-PCR y anticuerpos IgG e IgM anti-SARS-CoV-2 en todos los pacientes y personal sanitario de la unidad de HD. RESULTADOS: Se identificaron 55 casos de pacientes en HD y 9 casos de trabajadores de salud con COVID-19. La mediana de edad de los pacientes fue de 63 años y 84% eran hombres. Cincuenta y cinco por ciento de los pacientes eran sintomáticos, con fiebre, tos y/o mialgia. Las comorbilidades más frecuentes fueron hipertensión arterial, diabetes mellitus tipo 2 y enfermedad coronaria. La incidencia acumulada de infección fue del 30,2%, la seroprevalencia poblacional del 24,9% y la letalidad del 9,1%. CONCLUSIONES: La incidencia de infección por SARS-CoV-2 en esta unidad de HD fue alta. Se requieren de protocolos estrictos de bioseguridad para evitar brotes.

Uso de técnicas no farmacológicas para favorecer el estado emocional durante la aplicación del método Ponseti en pacientes pediátricos con pie equino varo congénito en Bogotá, Colombia / Non-pharmacological techniques to improve emotional state while using the Ponseti method in pediatric patients with congenital talipes equinovarus in Bogotá, Colombia

Introducción. Durante la aplicación del método Ponseti (MP), el niño puede mostrar incomodidad, tensión muscular o movimientos corporales que hacen del procedimiento una experiencia desagradable y estresante para pacientes, familiares y personal de salud.Objetivos. Describir los desenlaces de la aplicación de técnicas no farmacológicas (TNF) para el favorecer el estado emocional durante la atención estándar de pacientes con pie equino varo congénito (PEVC) tratados con el MP, el nivel de satisfacción del paciente y su familia con la atención recibida y la calidad de la atención en salud, y evaluar los posibles factores asociados al éxito de la aplicación de las TNF. Metodología. Estudio observacional descriptivo realizado en una cohorte de 21 niños atendidos en una clínica Ponseti de Bogotá (Colombia) entre febrero y noviembre de 2021. Las TNF se aplicaron en dos esquemas diferenciados por los sentidos estimulados. Los datos se describen usando medidas de tendencia central y de dispersión (prueba de Shapiro-Wilk), y la asociación exploratoria entre tener éxito en los esquemas de TNF y las variables se determinó con la prueba de chi-cuadrado (p≥0,05).Resultados. La mediana de edad fue 4,5 meses y el primer esquema de TNF fue exitoso en el 66,67% de los pacientes (97 consultas). El nivel de satisfacción de los cuidadores fue alto (86,07%). El equipo sanitario reportó que el procedimiento fue "extremadamente fácil" o "muy fácil" (86,07%-88,52%). Se identificaron como posibles factores asociados explor-atoriamente al éxito del primer esquema de TNF el sexo, antecedente de tratamiento con MP, y nivel de satisfacción del cuidador con la atención recibida.Conclusión. Las TNF mejoran el estado psicoemocional del niño, facilitando la aplicación del MP y aumentando la satisfacción del cuidador y del equipo sanitario con las sesiones de tratamiento

Introduction: Children may show discomfort, muscle tension or body movements while using the Ponseti method (PM), making the procedure an unpleasant and stressful experience for patients, family members, and health care personnel. Objectives: To describe the outcomes achieved following the use of non-pharmacological techniques (NPT) for emotional support when providing standard care to patients with congenital talipes equinovarus (CTEV) treated with the PM, as well as the level of patient and family satisfaction with the care received and the quality of health care, and to evaluate the possible factors associated with the success of the use of NPT.Methodology: Descriptive observational study conducted in a cohort of 21 children treated in a Ponseti clinic in Bogotá (Colombia) between February and November 2021. NPT were implemented in two schemes differentiated by the senses stimulated. Data are described using measures of central tendency and dispersion (Shapiro-Wilk test), and the exploratory association between having success with the NPT schemes and the variables was determined using the chi-square test (p≥0.05). Results: The median age was 4.5 months, and the first NPT scheme was successful in 66.67% of patients (97 consultations). The level of caregiver satisfaction was high (86.07%). The healthcare team reported that the procedure was "extremely easy" or "very easy" (86.07%-88.52%). Possible factors exploratorily associated with the success of the first NPT scheme were identified as gender, history of treatment with the PM, and level of caregiver satisfaction with the care received.Conclusion: NPT improve the psychoemotional state of the child, facilitating PM implementation, and increasing caregiver and healthcare team satisfaction with the treatment sessions

Recomendaciones sobre la vacunación contra SARS-CoV-2 en pacientes en diálisis y lista de espera de trasplante renal

Contexto las personas con diálisis se consideran una población de alto riesgo de infección por SARS-CoV-2, complicaciones y muerte. En Colombia, cerca del 44 % de la población en diálisis es menor de 60 años, adicionalmente, por los mismos retos que ha impuesto la pandemia a los programas de trasplantes, se ha incrementado notoriamente la población joven que debe seguir en diálisis al no tener opción a corto plazo de un trasplante renal, por lo tanto, las limitaciones en el acceso temprano a la vacunación contra SARS-CoV-2 agudizarían los problemas de esta población, provocando pérdidas considerables en años de vida que la vacuna podría salvar. Objetivo el objetivo del presente documento es sintetizar los principales motivos por los que se recomienda la priorización de la vacunación de los pacientes en diálisis crónica y lista de espera para trasplante renal. Metodología se realizó una búsqueda rápida de información sobre la vacunación en pacientes con ERC en diálisis o en espera de trasplante renal. La información resultante fue analizada críticamente por expertos en nefrología para la formulación de recomendaciones. Los resultados de la búsqueda se presentan a manera de síntesis narrativa. Resultados a partir de la información revisada y discutida por los expertos en nefrología se proponen 4 recomendaciones para la vacunación contra el virus SARS-Cov-2. Conclusiones la Asociación Colombiana de Nefrología e Hipertensión Arterial, la Asociación Colombiana de Nefrología Pediátrica y la Asociación Colombiana de Trasplante de Órganos, comprometidos con la salud de los pacientes con enfermedad renal en diálisis y listas de espera de trasplantes en Colombia, se unen a la solicitud mundial de generar recomendaciones para la vacunación contra SARS-CoV-2.

Background People on dialysis are considered a high-risk population for SARS-CoV-2 infection, complications, and death. In Colombia, about 44% of the population on dialysis is under 60 years of age. In addition, due to the same challenges that the pandemic has imposed on transplant programs, the young population that must continue on dialysis has increased markedly, as they have no option in the short term of a kidney transplant, therefore, the limitations in early access to vaccination against SARS-CoV-2 would exacerbate the problems of this population, causing considerable losses in years of life that the vaccine could save. Purpose The objective of this document is to summarize the main reasons why the prioritization of vaccination of patients on chronic dialysis and on the kidney transplant waiting list is recommended. Methodology A rapid search for information on vaccination in patients with CKD on dialysis or awaiting kidney transplantation was performed. The resulting information was critically analyzed by experts in nephrology for the formulation of recommendations. The search results are presented as a narrative synthesis. Results Based on the information reviewed and discussed by nephrology experts, 4 recommendations are proposed for vaccination against the SARS-Cov-2 virus. Conclusions The Colombian Association of Nephrology and Arterial Hypertension (ASOCOLNEF), the Colombian Association of Pediatric Nephrology (ACONEPE) and the Colombian Association of Organ Transplantation (ACTO), committed to the health of patients with kidney disease on dialysis and transplant waiting lists in Colombia, join to generate recommendations for prioritization and vaccination against SARS-CoV-2.

Vegetable fermentations brined with low salt for reclaiming food waste.

Fermentation of eight vegetables was studied as an alternative for reclamation of surplus volumes. Fermentation performance was predicted by comparing the amounts of acid that could be produced from the intrinsic sugar content with that buffered by the fresh vegetable matrices prior to reaching an inhibitory pH for fermentative microbes (3.30). Native fermentations were brined with 345.0 mM sodium chloride, 40.0 mM calcium chloride, 6.0 mM potassium sorbate, and vinegar to adjust the initial pH to 4.70. High-performance liquid chromatography analysis, pH, and carbon dioxide measurements and spiral plating on selective media were employed to monitor the progress of fermentations. The average colony counts for yeast and/or molds and Enterobacteriaceae declined to undetectable levels from 3.6 ± 1.5 log CFU/ml within 7 days of fermentation. The fermentation of sugars produced lactic, acetic, succinic, and/or malic acids, and ethanol. As predicted, the fermentation of vegetables with low sugar content, such as broccoli, green leaf lettuce, and green pea proceeded to completion. The fermentation of vegetables with a moderate sugar content, such as green bell pepper, red ripened tomato, and green bean were incomplete at pH 3.1 ± 0.2. The fermentation of high sugar vegetables including sweet potato and corn were expected and observed to be incomplete. It is concluded that the intrinsic sugar content and buffer capacity of surplus vegetables are relevant parameters in obtaining complete fermentations. PRACTICAL APPLICATION: Vegetables are the second most wasted commodity in the United States and a substantial constituent of the global food waste. Development of fermentation to reclaim surplus vegetables from farms, grocery stores, and farmer's markets offers opportunities to ameliorate economic losses and environmental impact and add value to waste. The research described here suggests that a fraction of vegetables could be fermented in cover brines while others, with high sugar content, need specialized handling. Evidently, optimization of vegetable fermentation with starter cultures and added buffers represent an opportunity to stimulate complete bioconversions useful for reclaiming surplus volumes.

Research Trends on Pillared Interlayered Clays (PILCs) Used as Catalysts in Environmental and Chemical Processes: Bibliometric Analysis.

Over the last four decades, a large number of studies have been published on pillared interlayered clays (PILCs) used as adsorbent materials and catalysts or supports for transition metals in heterogeneous catalysis. Particularly, PILCs have been used for water treatment through advanced oxidation processes (AOPs) to remove organic pollutants. They have also been studied in various chemical and environmental processes. Because of the growing interest in PILCs, this article is focused on analyzing scientific publications such as research/review articles and book chapters from the last four decades (from 1980 to 2019) through a bibliometric analysis (BA) to visualize and describe research trends on PILCs. By narrowing the bibliographic search to titles, keywords, and abstracts of publications related to PILCs, using Scopus and Web of Science (WoS) (the two scientific databases), a total of 3425 documents have been retrieved. The bibliometric dataset was analyzed by VantagePoint®. The main research trends identified in the last four decades were the use of PILCs in environmental processes (34.4% of total publications) along with chemical processes (petrochemical reactions 17.5%, SCR NOx 10.8%, and decomposition 8.2%). In environmental processes, PILCs have been used in photo-oxidation (32%), CWPO (21.1%), and heterogeneous catalysis (19.4%). Phenols, dyes, and VOCs have been the main pollutants studied using PILCs as catalysts. Fe, Ti, Zr, Cu, and Co are the most supported active phases in PILCs. Other research trends grouped by characterization techniques, countries, research areas, institutes, scientific journals that have published the most on this topic, number of publications per 5-year period, and most frequently used keywords through the last four decades have been identified. It was determined that the number of publications on PILCs has increased since 1980 and the countries with the highest number of publications are China, Spain, and The United States of America.

A Comprehensive Immune Cell Atlas of Cystic Kidney Disease Reveals the Involvement of Adaptive Immune Cells in Injury-Mediated Cyst Progression in Mice.

BACKGROUND: Inducible disruption of cilia-related genes in adult mice results in slowly progressive cystic disease, which can be greatly accelerated by renal injury. METHODS: To identify in an unbiased manner modifier cells that may be influencing the differential rate of cyst growth in injured versus non-injured cilia mutant kidneys at a time of similar cyst severity, we generated a single-cell atlas of cystic kidney disease. We conducted RNA-seq on 79,355 cells from control mice and adult-induced conditional Ift88 mice (hereafter referred to as cilia mutant mice) that were harvested approximately 7 months post-induction or 8 weeks post 30-minute unilateral ischemia reperfusion injury. RESULTS: Analyses of single-cell RNA-seq data of CD45+ immune cells revealed that adaptive immune cells differed more in cluster composition, cell proportion, and gene expression than cells of myeloid origin when comparing cystic models with one another and with non-cystic controls. Surprisingly, genetic deletion of adaptive immune cells significantly reduced injury-accelerated cystic disease but had no effect on cyst growth in non-injured cilia mutant mice, independent of the rate of cyst growth or underlying genetic mutation. Using NicheNet, we identified a list of candidate cell types and ligands that were enriched in injured cilia mutant mice compared with aged cilia mutant mice and non-cystic controls that may be responsible for the observed dependence on adaptive immune cells during injury-accelerated cystic disease. CONCLUSIONS: Collectively, these data highlight the diversity of immune cell involvement in cystic kidney disease.

[Ocular manifestations associated to CD4+ in patients with human immunodeficiency virus]. / Manifestaciones oculares asociadas a CD4+ en pacientes con virus de inmunodeficiencia humana.

BACKGROUND: Since the first cases of human immunodeficiency virus (HIV), ocular manifestations secondary to infection have been known and these have been related to the CD4+ lymphocyte count. OBJECTIVE: To describe the correlation between ocular manifestations in patients with HIV and the CD4+ lymphocyte count. MATERIAL AND METHODS: Analytical cross-sectional study of patients with HIV whose CD4+ count was correlated with the presence of ophthalmological manifestations. RESULTS: 21 patients between 26 and 67 years were studied. Only 3 patients were not on antiretroviral therapy. 67% of the patients presented some type of ocular manifestation, 42% presented non-infection related manifestations, 47% related manifestations and 24% both. Conjunctival microangiopathy was the most frequent ocular manifestation (35.7%). There was a statistically significant correlation (r = 0.76, p = 0.0001) between eye manifestations related to infection and CD4+ lymphocyte count. CONCLUSIONS: Patients with HIV frequently present ocular manifestations, the majority related to infection; there is a correlation between the presence of these with the CD4+ count. However, a similar number of manifestations not related to infection occurred without correlation with the count; therefore, HIV patients should have periodic ophthalmological examinations, independently of CD4+ count.

INTRODUCCIÓN: desde los primeros casos de virus de inmunodeficiencia humana (VIH), se conocen manifestaciones oculares secundarias a la infección y estas se han relacionado con el conteo de linfocitos CD4+. OBJETIVO: describir la correlación entre las manifestaciones oculares en pacientes con VIH y el conteo de linfocitos CD4+. MATERIAL Y MÉTODOS: estudio transversal analítico de pacientes con VIH, en quienes se analizó la correlación entre conteo de CD4+ y manifestaciones oftalmológicas. RESULTADOS: se incluyeron 21 pacientes entre 26 y 67 años de edad. Solo tres no se encontraban en terapia antirretroviral. El 67% presentó algún tipo de manifestación ocular, 42% presentó manifestaciones no relacionadas con la infección, 47% manifestaciones relacionadas y 24% ambas. La microangiopatía de la conjuntiva fue la manifestación ocular más frecuente (35.7%). Hubo una correlación estadísticamente significativa (r = 0.76, p = 0.0001) entre las manifestaciones oculares relacionadas con la infección y el conteo de linfocitos CD4+. CONCLUSIONES: los pacientes con VIH presentan con frecuencia manifestaciones oculares, la mayoría asociadas a la infección. Existe correlación entre la presencia de estas con el conteo de CD4+; sin embargo, un número similar de manifestaciones no asociadas a la infección se presentaron sin correlación con el conteo, por lo que los pacientes con VIH deberían tener revisiones oftalmológicas periódicas, independientemente del conteo de CD4+.

Clinical course, biomarkers, management and outcomes of patients hospitalised due to COVID-19 in Colombia / Curso clínico, biomarcadores, manejo y desenlaces de pacientes hospitalizados por COVID-19 en Colombia

Abstract Objective: To analyse the clinic characteristics, risk factors and evolution of the first cohort of hospitalised patients with confirmed infection by COVID-19 in 5 Colombian institutions. Materials and methods: Is a retrospective observational study of consecutive hospitalized patients with a diagnosis of COVID-19 confirmed from March 01 to May 30, 2020 in Colombia. Results: A total of 44 patients were included. The median age was 62 years. 43.2% had a history of smoking, while 69.8% were overweight or obese. 88.6% had at least one comorbidity and 52.3% had three or more comorbidities. Hypertension and dyslipidaemia were the most frequent comorbidities (40.9% and 34.1%, respectively). The 30-day mortality rate was 47.7% with a median of 11 days. The composite outcome occurred in the 36.4%. The biomarkers associated with mor tality risk included troponin higher than 14 ng/L (RR: 5.25; 95% CI 1.37-20.1, p = 0.004) and D-dimer higher than 1000 ng/ml (RR: 3.0; 95% CI 1.4-6.3, p = 0.008). Conclusions: The clinical course of SARS-CoV-2 infection in hospitalized Colombian was characterised by a more advanced stage of the infection.

Resumen Objetivo: Analizar las características, clínicas, factores de riesgo, y la evolución de pacientes hospitalizados con infección confirmada por COVID-19 en 5 Institu ciones de Colombia. Material y método: Es un estudio observacional retrospectivo de pacientes consecutivos hospitalizados con diagnóstico de COVID-19 confirmado entre 01 de Febrero de 2020 y 30 de Mayo de 2020 en Colombia. Resultados: Un total de 44 pacientes fueron incluidos. La mediana de edad fue de 62 años y la mayoría del sexo masculino. El 43.2% tenían historia de tabaquismo, mientras que el 69.8% tenían sobrepeso u obesidad. El 88.6% tenían al menos una comorbilidad y el 52.3% tenían tres o más comorbilidades. La hipertensión arterial fue la comorbilidad más frecuente (40.9%), seguido de la dislipidemia (34.1%). La tasa de letalidad a 30 días fue de 47.7% y ocurrió con una mediana de 11 días. El 36.4% presentó el desenlace compuesto. Los biomarcadores asociados con el riesgo de muerte fue troponina > 14 ng/mL (RR:5.25, IC95% 1.37-20.1, p=0.004) y dímero D mayor a 1000 mg/dL (RR: 3.0, IC95% 1.4-6.3, p=0.008). Conclusiones: El curso clínico de la infección por SARS-CoV-2 en colombianos hospitalizados fue un estadio más avanzado de la infección.

[Mental Health Care of Health Workers During Covid-19: Recommendations Based on Evidence and Expert Consensus]. / Cuidado de la salud mental del personal de salud durante COVID-19: recomendaciones basadas en evidencia y consenso de expertos.

INTRODUCTION: The crisis situation generated by COVID-19 and the measures adopted have generated social changes in the normal dynamics of the general population and especially for health workers, who find themselves caring for patients with suspected or confirmed infection. Recent studies have detected in them depression and anxiety symptoms and burnout syndrome, with personal and social conditions impacting their response capacity during the health emergency. Our aim was to generate recommendations for the promotion and protection of the mental health of health workers and teams in the first line of care in the health emergency due to COVID-19. METHODS: A rapid literature search was carried out in PubMed and Google Scholar, and an iterative expert consensus and through electronic consultation, with 13 participants from the areas of psychology, psychiatry and medicine; the grading of its strength and directionality was carried out according to the international standards of the Joanna Briggs Institute. RESULTS: Thirty-one recommendations were generated on self-care of health workers, community care among health teams, screening for alarm signs in mental health and for health institutions. CONCLUSIONS: The promotion and protection activities in mental health to face the health emergency generated by COVID-19 worldwide can include coordinated actions between workers, health teams and health institutions as part of a comprehensive, community care, co-responsible and sustained over time.

Manifestaciones oculares asociadas a CD4+ en pacientes con virus de inmunodeficiencia humana / Ocular manifestations associated to CD4+ in patients with human immunodeficiency virus

Introducción: desde los primeros casos de virus de inmunodeficiencia humana (VIH), se conocen manifestaciones oculares secundarias a la infección y estas se han relacionado con el conteo de linfocitos CD4+. Objetivo: describir la correlación entre las manifestaciones oculares en pacientes con VIH y el conteo de linfocitos CD4+. Material y métodos: estudio transversal analítico de pacientes con VIH, en quienes se analizó la correlación entre conteo de CD4+ y manifestaciones oftalmológicas. Resultados: se incluyeron 21 pacientes entre 26 y 67 años de edad. Solo tres no se encontraban en terapia antirretroviral. El 67% presentó algún tipo de manifestación ocular, 42% presentó manifestaciones no relacionadas con la infección, 47% manifestaciones relacionadas y 24% ambas. La microangiopatía de la conjuntiva fue la manifestación ocular más frecuente (35.7%). Hubo una correlación estadísticamente significativa (r = 0.76, p = 0.0001) entre las manifestaciones oculares relacionadas con la infección y el conteo de linfocitos CD4+. Conclusiones: los pacientes con VIH presentan con frecuencia manifestaciones oculares, la mayoría asociadas a la infección. Existe correlación entre la presencia de estas con el conteo de CD4+; sin embargo, un número similar de manifestaciones no asociadas a la infección se presentaron sin correlación con el conteo, por lo que los pacientes con VIH deberían tener revisiones oftalmológicas periódicas, independientemente del conteo de CD4+.

Background: Since the first cases of human immunodeficiency virus (HIV), ocular manifestations secondary to infection have been known and these have been related to the CD4+ lymphocyte count. Objective: To describe the correlation between ocular manifestations in patients with HIV and the CD4+ lymphocyte count. Material and methods: Analytical cross-sectional study of patients with HIV whose CD4+ count was correlated with the presence of ophthalmological manifestations. Results: 21 patients between 26 and 67 years were studied. Only 3 patients were not on antiretroviral therapy. 67% of the patients presented some type of ocular manifestation, 42% presented non-infection related manifestations, 47% related manifestations and 24% both. Conjunctival microangiopathy was the most frequent ocular manifestation (35.7%). There was a statistically significant correlation (r = 0.76, p = 0.0001) between eye manifestations related to infection and CD4+ lymphocyte count. Conclusions: Patients with HIV frequently present ocular manifestations, the majority related to infection; there is a correlation between the presence of these with the CD4+ count. However, a similar number of manifestations not related to infection occurred without correlation with the count; therefore, HIV patients should have periodic ophthalmological examinations, independently of CD4+ count.

Adult-onset CNS myelin sulfatide deficiency is sufficient to cause Alzheimer's disease-like neuroinflammation and cognitive impairment.

BACKGROUND: Human genetic association studies point to immune response and lipid metabolism, in addition to amyloid-beta (Aß) and tau, as major pathways in Alzheimer's disease (AD) etiology. Accumulating evidence suggests that chronic neuroinflammation, mainly mediated by microglia and astrocytes, plays a causative role in neurodegeneration in AD. Our group and others have reported early and dramatic losses of brain sulfatide in AD cases and animal models that are mediated by ApoE in an isoform-dependent manner and accelerated by Aß accumulation. To date, it remains unclear if changes in specific brain lipids are sufficient to drive AD-related pathology. METHODS: To study the consequences of CNS sulfatide deficiency and gain insights into the underlying mechanisms, we developed a novel mouse model of adult-onset myelin sulfatide deficiency, i.e., tamoxifen-inducible myelinating glia-specific cerebroside sulfotransferase (CST) conditional knockout mice (CSTfl/fl/Plp1-CreERT), took advantage of constitutive CST knockout mice (CST-/-), and generated CST/ApoE double knockout mice (CST-/-/ApoE-/-), and assessed these mice using a broad range of methodologies including lipidomics, RNA profiling, behavioral testing, PLX3397-mediated microglia depletion, mass spectrometry (MS) imaging, immunofluorescence, electron microscopy, and Western blot. RESULTS: We found that mild central nervous system (CNS) sulfatide losses within myelinating cells are sufficient to activate disease-associated microglia and astrocytes, and to increase the expression of AD risk genes (e.g., Apoe, Trem2, Cd33, and Mmp12), as well as previously established causal regulators of the immune/microglia network in late-onset AD (e.g., Tyrobp, Dock, and Fcerg1), leading to chronic AD-like neuroinflammation and mild cognitive impairment. Notably, neuroinflammation and mild cognitive impairment showed gender differences, being more pronounced in females than males. Subsequent mechanistic studies demonstrated that although CNS sulfatide losses led to ApoE upregulation, genetically-induced myelin sulfatide deficiency led to neuroinflammation independently of ApoE. These results, together with our previous studies (sulfatide deficiency in the context of AD is mediated by ApoE and accelerated by Aß accumulation) placed both Aß and ApoE upstream of sulfatide deficiency-induced neuroinflammation, and suggested a positive feedback loop where sulfatide losses may be amplified by increased ApoE expression. We also demonstrated that CNS sulfatide deficiency-induced astrogliosis and ApoE upregulation are not secondary to microgliosis, and that astrogliosis and microgliosis seem to be driven by activation of STAT3 and PU.1/Spi1 transcription factors, respectively. CONCLUSION: Our results strongly suggest that sulfatide deficiency is an important contributor and driver of neuroinflammation and mild cognitive impairment in AD pathology.

Mental health care of health workers during Covid-19: Recommendations based on evidence and expert consensus.

INTRODUCTION: The crisis situation generated by COVID-19 and the measures adopted have generated social changes in the normal dynamics of the general population and especially for health workers, who find themselves caring for patients with suspected or confirmed infection. Recent studies have detected in them depression and anxiety symptoms and burnout syndrome, with personal and social conditions impacting their response capacity during the health emergency. Our aim was to generate recommendations for the promotion and protection of the mental health of health workers and teams in the first line of care in the health emergency due to COVID-19. METHODS: A rapid literature search was carried out in PubMed and Google Scholar, and an iterative expert consensus and through electronic consultation, with 13 participants from the areas of psychology, psychiatry and medicine; the grading of its strength and directionality was carried out according to the international standards of the Joanna Briggs Institute. RESULTS: Thirty-one recommendations were generated on self-care of health workers, community care among health teams, screening for alarm signs in mental health and for health institutions. CONCLUSIONS: The promotion and protection activities in mental health to face the health emergency generated by COVID-19 worldwide can include coordinated actions between workers, health teams and health institutions as part of a comprehensive, community care, co-responsible and sustained over time.

Schrödinger's T Cells: Molecular Insights Into Stemness and Exhaustion.

T cell stemness and exhaustion coexist as two key contrasting phenomena during chronic antigen stimulation, such as infection, transplant, cancer, and autoimmunity. T cell exhaustion refers to the progressive loss of effector function caused by chronic antigen exposure. Exhausted T (TEX) cells highly express multiple inhibitory receptors and exhibit severe defects in cell proliferation and cytokine production. The term T cell stemness describes the stem cell-like behaviors of T cells, including self-renewal, multipotency, and functional persistence. It is well accepted that naïve and some memory T cell subsets have stem cell-like properties. When investigating the exhaustive differentiation of T cells in chronic infection and cancer, recent studies highlighted the stemness of "precursors of exhausted" T (TPEX) cells prior to their terminal differentiation to TEX cells. Clinically successful checkpoint blockades for cancer treatment appear to invigorate antitumor TPEX cells but not TEX cells. Here we discuss the transcriptional and epigenetic regulations of T cell stemness and exhaustion, with a focus on how systems immunology was and will be utilized to define the molecular basis underlying the transition of TPEX to TEX cells. We suggest a "stepwise model" of T cell stemness and exhaustion, in which loss of stemness and exhaustion progression are gradual multi-step processes. We provide perspectives on the research needed to define T cell stemness and exhaustion in the transplantation setting, in which allogenic T cells are also chronically exposed to alloantigens. A better understanding of T cell stemness and exhaustion will shed light on developing novel strategies for immunotherapies.