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.

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.

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.

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.

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.

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.

Descriptive Epidemiology of Melanoma Diagnosed between 2010 and 2014 in a Colombian Cancer Registry and a Call for Improving Available Data on Melanoma in Latin America.

We aimed to improve the available information on morphology and stage for cutaneous melanoma in the population-based cancer registry of the Bucaramanga Metropolitan Area in Colombia. The incidence and survival rates and the distribution of melanoma patients by age, gender, anatomical subsite, and histological subtype were calculated. All 113 melanoma patients (median age 61) were followed up (median time 7.4 years). This exercise (filling in missing information in the registry by manual search of patient clinical record and other available information) yielded more identified invasive melanomas and cases with complete information on anatomical localization and stage. Age-standardized incidence and mortality rates were 1.86 and 1.08, being slightly higher for males. Most melanomas were localized on the lower limbs, followed by the trunk. For 35% of all melanomas, the morphological subtype remained unknown. Most of the remaining melanomas were nodular and acral lentiginous melanomas. Overall global and relative 5-year survival was 61.6% and 71.3%, respectively, with poorer survival for males than females. Melanomas on the head and neck and unspecified anatomical sites had the worst survival. Patients without stage information in their medical files had excellent survival, unlike patients for whom medical files were no longer available. This study shows the possibility of improving data availability and the importance of good quality population-based data.

Bioseguridad en ambientes quirúrgicos durante la COVID-19 / Biosafety in Surgical Environments during the COVID-19 Pandemic

Introducción: La COVID-19 significó un gran reto para los servicios de cirugía a nivel mundial, lo que trajo como consecuencia modificaciones, incluso la suspensión de la actividad quirúrgica en algunos casos con el objetivo de garantizar seguridad tanto para el paciente como para el personal de salud. Objetivo: Describir acciones que contribuyan a garantizar condiciones de bioseguridad en ambientes quirúrgicos durante la pandemia de COVID-19. Métodos: Se realizó una revisión bibliográfica para la cual se usaron 37 referencias bibliográficas en inglés y español. Se consultaron fuentes científicas como PubMed/Medline, SciELO, Scopus, ScienceDirect y fuentes oficiales como la Organización Mundial de la Salud. Desarrollo: Ante la reanudación de la cirugía electiva se crearon protocolos de actuación. Deben clasificarse los pacientes en 3 grupos según la posibilidad de padecer COVID-19: individuos sanos, portadores asintomáticos y pacientes con síntomas. Además, debe darse prioridad a los pacientes cuyos procedimientos fueron cancelados. Se preconiza crear circuitos independientes y separados para evitar el contacto de casos sospechosos o confirmados de COVID-19 con el resto de pacientes. Para garantizar mayor seguridad debe entrenarse al personal médico en la forma correcta de utilizar los medios de protección personal. La inducción anestésica de estos pacientes debe garantizar su seguridad y prevenir el contagio. Una vez concluida la cirugía, se llevará a cabo la recuperación inicial del paciente dentro del propio quirófano y este será higienizado estrictamente. Conclusiones: Los profesionales sanitarios deben estar adecuadamente entrenados y conocer las medidas de bioseguridad y protocolos sanitarios tanto del hospital como del país en que se encuentren(AU)

Introduction: COVID-19 posed a great challenge to surgical services worldwide, resulting in modifications, including the suspension of surgical activity in some cases with the aim of ensuring safety for both the patient and the health personnel. Objective: To describe actions that contribute to guarantee biosafety conditions in surgical environments during the COVID-19 pandemic. Methods: A bibliographic review was carried out using 37 bibliographic references in English and Spanish. Scientific sources, such as PubMed/Medline, SciELO, Scopus and ScienceDirect, were consulted; as well as official sources, such as the World Health Organization. Development: When elective surgery was resumed, action protocols were created. Patients should be classified into 3 groups, according to the possibility of having COVID-19: healthy individuals, asymptomatic carriers, and patients with symptoms. In addition, priority should be given to patients whose procedures have been cancelled. Independent and isolated wards are recommended to be created in order to avoid contact between suspected or confirmed COVID-19 cases and the rest of the patients. To ensure greater safety, the medical personnel should be trained in the correct use of personal protective equipment. The anesthetic induction of these patients should ensure their safety and prevent contagion. Once the surgery is over, the initial recovery of the patient will be carried out inside the operating room itself, which shall be strictly sanitized. Conclusions: Healthcare professionals must be adequately trained and be aware of the biosecurity measures and healthcare protocols of both the hospital and the country where they are located(AU)

Adopción/Adaptación mediante Comentario para Argentina por intermedio de la Federación Iberopanamericana de Periodoncia (FIPP) de la Guía de Práctica Clínica (GPC) de nivel S3: Tratamiento de la periodontitis en los estadios I ­ III, de la Federación Europea de Periodoncia (EFP), traducida por la Sociedad Española de Periodoncia (SEPA) / Adoption/Adaptation by Comment, for Argentina through the Iberopanamerican Federation of Periodontology (FIPP) of the S3 Level Clinical Practice Guideline (CPG): Treatment of periodontitis in stages I ­ III, of the European Federation of Periodontology (EFP), translated by the Spanish Society of Periodontics (SEPA)

La Sociedad Argentina de Periodoncia ha formulado un Comentario, analizando los condicionantes del contexto na- cional, para determinar si las recomendaciones generadas en la Guía de Práctica Clínica de nivel S3 de la Federación Eu- ropea de Periodoncia para el tratamiento de la periodontitis en estadios I-III, podrían ser aplicadas para dar respuesta a la demanda de la población, en lo referido a la salud periodontal (AU)

The Argentine Society of Periodontics has formulated a Commentary, analyzing the determining factors of the nation- al context, to determine if the recommendations generated in the Level S3 Clinical Practice Guideline of the European Fed- eration of Periodontics for the treatment of periodontitis in stages I-III could be applied to respond to the demand of the population, regarding periodontal health (AU)

Health care experiences of Black cancer survivors: A qualitative study exploring drivers of low and high Consumer Assessment of Healthcare Providers and Systems global ratings of care.

BACKGROUND: The purpose of this study was to understand the experiences of Black patients with cancer in health care by comparing drivers of high and low ratings. METHODS: Semistructured in-depth interviews were conducted with 18 Black patients with cancer recruited from cancer survivorship support groups and Facebook between May 2019 and March 2020. Interviews were coded across all transcripts by using a thematic analysis approach before comparing low- and high-rating groups. RESULTS: There were three major themes that influenced whether patients rated their care as low or high, which included the patient-provider relationship, health care staff interactions, and cancer care coordination. For example, the high-rating group described good communication with the health care team as physicians listening to their needs, being responsive to their concerns, and providing recommendations on how to address side effects. In contrast, the low-rating group described poor communication with their health care team as their needs being dismissed and being excluded from decision-making processes. Additionally, there were two distinct themes that influenced patients' low ratings: insurance and financial toxicity issues and experiences of health care discrimination. CONCLUSIONS: In an effort to promote equitable cancer care experiences for Black patients, it is important that health systems work to prioritize patient interactions with health care providers and staff, comprehensive care management for patients with cancer, and reductions in the financial burden of caring for cancer.

Adopción/Adaptación mediante Comentario para Argentina por intermedio de la Federación Iberopanamericana de Periodoncia (FIPP) de la Guía de Práctica Clínica (GPC) de nivel S3: Tratamiento de la periodontitis en los estadios I - III, de la Federación Europea de Periodoncia (EFP), traducida por la Sociedad Española de Periodoncia (SEPA) / Adoption/Adaptation by Comment, for Argentina through the Iberopanamerican Federation of Periodontology (FIPP) of the S3 Level Clinical Practice Guideline (CPG): Treatment of periodontitis in stages I - III, of the European Federation of Periodontology (EFP), translated by the Spanish Society of Periodontics (SEPA)

Resumen La Sociedad Argentina de Periodoncia ha formulado un Comentario, analizando los condicionantes del contexto nacional, para determinar si las recomendaciones generadas en la Guía de Práctica Clínica de nivel S3 de la Federación Europea de Periodoncia para el tratamiento de la periodontitis en estadios I-III, podrían ser aplicadas para dar respuesta a la demanda de la población, en lo referido a la salud periodontal.

Abstract The Argentine Society of Periodontics has formulated a Commentary, analyzing the determining factors of the national context, to determine if the recommendations generated in the Level S3 Clinical Practice Guideline of the European Federation of Periodontics for the treatment of periodontitis in stages I-III could be applied to respond to the demand of the population, regarding periodontal health.

Healthcare Experiences Are Associated with Colorectal Cancer Mortality but only for Specific Racial Groups: a SEER-CAHPS Study.

BACKGROUND: The objective of this study was to determine whether racial/ethnic disparities exist in patient-reported experiences with care after colorectal cancer diagnosis and whether they are associated with mortality. METHODS: We conducted a retrospective cohort study of colorectal cancer patients diagnosed from 1997 to 2011, ≥ 65 years, and completed a Consumer Assessment of Healthcare Providers and Systems (CAHPS) survey at least 6 months after a cancer diagnosis. We leverage the National Cancer Institute's SEER-CAHPS dataset of Medicare beneficiaries. CAHPS survey responses were used to generate four composite measures of patient experiences with 1) getting needed care, 2) getting needed prescription drugs, 3) getting care quickly, and 4) physician communication. We used multivariable linear regression models to examine racial differences in patient experiences with aspects of their care and multivariable Cox proportional hazards models to identify the risk of mortality associated with each composite score by racial group. RESULTS: Of the 5135 patients, 76.86% were non-Hispanic White, 7.58% non-Hispanic Black, 8.30% Hispanic, and 7.26% non-Hispanic Asian. Overall, patients reported the highest scores for composite measures regarding "getting all needed prescriptions" and the lowest score for "getting care quickly." In our adjusted models, we found that Hispanics, non-Hispanic Black, and non-Hispanic Asian patients reported significantly lower scores for getting needed prescription drugs (B = - 4.34, B = - 4.32, B = - 5.66; all p < 0.001) compared to non-Hispanic Whites. Moreover, non-Hispanic Black patients also reported lower scores for getting care quickly (B = - 3.44, p < 0.05). We only found one statistically significant association between composite scores of patient experience and mortality. For non-Hispanic Black patients, a 3-unit increase in getting needed care was associated with 0.97 times the hazard of mortality (p = 0.003). CONCLUSION: Our research underscores that CAHPS patient experiences with care are an important patient-centered quality-of-care metric that may be associated with cancer outcomes and that there may be differences in these relationships by race and ethnicity. Thus, highlighting how patients' perceptions of their healthcare experiences can contribute to disparities in colorectal cancer outcomes.

PRC2 disruption in cerebellar progenitors produces cerebellar hypoplasia and aberrant myoid differentiation without blocking medulloblastoma growth.

We show that Polycomb Repressive Complex-2 (PRC2) components EED and EZH2 maintain neural identity in cerebellar granule neuron progenitors (CGNPs) and SHH-driven medulloblastoma, a cancer of CGNPs. Proliferating CGNPs and medulloblastoma cells inherit neural fate commitment through epigenetic mechanisms. The PRC2 is an epigenetic regulator that has been proposed as a therapeutic target in medulloblastoma. To define PRC2 function in cerebellar development and medulloblastoma, we conditionally deleted PRC2 components Eed or Ezh2 in CGNPs and analyzed medulloblastomas induced in Eed-deleted and Ezh2-deleted CGNPs by expressing SmoM2, an oncogenic allele of Smo. Eed deletion destabilized the PRC2, depleting EED and EZH2 proteins, while Ezh2 deletion did not deplete EED. Eed-deleted cerebella were hypoplastic, with reduced proliferation, increased apoptosis, and inappropriate muscle-like differentiation. Ezh2-deleted cerebella showed similar, milder phenotypes, with fewer muscle-like cells and without reduced growth. Eed-deleted and Ezh2-deleted medulloblastomas both demonstrated myoid differentiation and progressed more rapidly than PRC2-intact controls. The PRC2 thus maintains neural commitment in CGNPs and medulloblastoma, but is not required for SHH medulloblastoma progression. Our data define a role for the PRC2 in preventing inappropriate, non-neural fates during postnatal neurogenesis, and caution that targeting the PRC2 in SHH medulloblastoma may not produce durable therapeutic effects.

Association of social determinants with the severity of congenital heart disease.

BACKGROUND: Congenital heart diseases are the most prevalent congenital malformations and cause greater morbi-mortality in newborns and infants. The aim of this study was to analyze the social determinants in families with children with the severity of congenital heart disease. METHODS: Analytical cross-sectional study in 140 families of children with congenital heart disease to whom a structured survey was applied addressing topics related to family structure, health, economic conditions, exposure factors, and other social conditions relevant to the study, during 1 year. RESULTS: In all, 53.7% of the studied population belonged to low socioeconomic levels. No association was found between the severity of the heart disease and the presence of pathological antecedents in the parents. The families resided in urban areas. Also, 28.3% of the mothers had four or fewer prenatal controls during pregnancy. Only 22% of heart diseases were diagnosed during pregnancy. It was found that exposure to cigarette and wood smoke during pregnancy, in addition to low socioeconomic status, was associated with greater severity of heart disease (RACHS-1 and STS-Score), when evaluated by pathophysiological groups (cyanotic/non-cyanotic/single ventricle). CONCLUSIONS: Exposure to cigarette smoke, wood smoke during pregnancy, and low socioeconomic status turned out to be social determinants associated with the severity of heart disease analyzed by pathophysiological groups. IMPACT: The social component has not been well characterized as a cause of congenital heart disease, especially in countries like ours, where the existence of gaps and social inequities have a high impact. The findings of this study could have an impact on public health to the extent that policies are implemented to reduce exposure to cigarettes, especially during pregnancy. Knowledge of these changes and their measurement in this type of pathology could open the door to the creation of policies aimed at their prevention, focusing on the local risk factors found, which can impact the disease.

Ensayo controlado y aleatorizado del uso de Heberkinasa® en el derrame pleural paraneumónico en niños / Randomized Controlled Trial of the Use of Heberkinase® in Parapneumonic Pleural Effusion in Children

Introducción: El derrame pleural paraneumónico resulta la complicación más frecuente de la neumonía bacteriana, de manejo complejo y muchas veces quirúrgico. No existen publicaciones en Cuba provenientes de ensayos clínicos controlados y aleatorizados ni del uso de la estreptoquinasa recombinante (Heberkinasa®) en el derrame pleural. Objetivo: Evaluar la eficacia y la seguridad de la Heberkinasa® en el tratamiento del derrame pleural paraneumónico complicado complejo y el empiema en niños. Métodos: Ensayo clínico fase III, abierto, aleatorizado (2:1), en grupos paralelos y controlado. Se concluyó la inclusión prevista de 48 niños (1-18 años de edad), que cumplieron los criterios de selección. Los progenitores otorgaron el consentimiento informado. Los pacientes se distribuyeron en dos grupos: I- experimental: terapia estándar y administración intrapleural diaria de 200 000 UI de Heberkinasa® durante 3-5 días y II-control: tratamiento estándar. Las variables principales: necesidad de cirugía y la estadía hospitalaria. Se evaluaron los eventos adversos. Resultados: Ningún paciente del grupo I-experimental requirió cirugía, a diferencia del grupo II-control en el que 37,5 por ciento necesitó cirugía video-toracoscópica, con diferencia altamente significativa. Se redujo la estadía hospitalaria (en cuatro días), las complicaciones intratorácicas y las infecciones asociadas a la asistencia sanitaria en el grupo que recibió Heberkinasa®. No se presentaron eventos adversos graves atribuibles al producto. Conclusiones: La Heberkinasa® en el derrame pleural paraneumónico complicado complejo y empiema resultó eficaz y segura para la evacuación del foco séptico, con reducción de la necesidad de tratamiento quirúrgico, de la estadía hospitalaria y de las complicaciones, sin eventos adversos relacionados con su administración(AU)

Introduction: Paraneumonic pleural effusion is the most frequent complication of bacterial pneumonia, with complex and often surgical management. There are no publications in Cuba from randomized controlled clinical trials or the use of recombinant streptokinase (Heberkinase®) in pleural effusion. Objective: To evaluate the efficacy and safety of Heberkinase® in the treatment of complex complicated parapneumonic pleural effusion and empyema in children. Methods: Phase III, open-label, randomized (2:1), parallel-group, controlled clinical trial. The planned inclusion of 48 children (1-18 years of age), who met the selection criteria, was completed. Parents gave informed consent. The patients were divided into two groups: I-experimental: standard therapy and daily intrapleural administration of 200,000 IU of Heberkinase® for 3-5 days; and II-control: standard treatment. The main variables: need for surgery and hospital stay. Adverse events were evaluated. Results: No patient in group I-experimental required surgery, unlike group II-control in which 37.5 percent required video-assisted thoracoscopic surgery, with a highly significant difference. Hospital stay (to 4 days), intrathoracic complications and infections associated to healthcare in the group that received Heberkinase® was reduced. No serious adverse events attributable to the product occurred. Conclusions: Heberkinase® in complex complicated parapneumonic pleural effusion and empyema was effective and safe for the draining of the septic focus, with reduction of the need for surgical treatment, hospital stay and complications, with no adverse events related to its administration(AU)

Repercusión de la pandemia por SARS-COV-2 sobre las consultas en los Servicios de Emergencia Pediátrica en Uruguay / Consequences of the SARS-COV-2 pandemic on Pediatric Emergency Services in Uruguay / Repercussão da pandemia de SARS-COV-2 nas consultas nos Serviços de Emergência Pediátrica do Uruguai

En marzo de 2020 se confirma el primer caso de enfermedad por coronavirus en Uruguay, recomendándose un confinamiento social. La atención sanitaria se redujo a servicios de urgencia y emergencia (SE). Objetivo: analizar las características de las consultas pediátricas en los SE del subsector público y privado en Uruguay, durante los primeros 4 meses de la pandemia por SARS-CoV-2. Metodología: estudio descriptivo, retrospectivo, multicéntrico. Resultados: participaron 23 SE de todas las regiones del país. Período 1 prepandemia: 14/03/19-29.07.19, período 2: 14/03/20-29/07/20 Consultas: período 1 n=121.116, período 2 n=33.099 (desciende 73%). Hospitalizaciones desde el SE: período 1 n= .6649 (tasa 5,5%). Período 2: n=2.948 (tasa 9,5%). Diagnósticos período 1: infección respiratoria aguda (IRA) alta 39.892 (33%), IRA baja 86.56 (7%), trauma menor 8.651 (7%), gastroenteritis 8.044 (6,6%), crisis asmática/CBO 7.974 (6,5%), lesiones 4.389 (3,6%), dolor abdominal 3.528 (3%), problemas de salud mental 859 (0,7%), convulsiones 758 (0,7%), patología social 678 (0,5%). Diagnósticos 2020: IRA alta 5.168 (16%), trauma menor 2.759 (8%), lesiones 2.652 (8%), dolor abdominal 1.494 (4,5%), gastroenteritis 1.296 (4%), asma/CBO 1.095 (3,3%), IRA baja 700 (2,1%), patología social 522 (1,6%), problemas de salud mental 471 (1,4%), convulsiones 408 (1,2%). Conclusiones: en los primeros meses de la pandemia hubo una reducción sostenida y significativo de consultas pediátricas en los SE. No hubo aumento en frecuencia absoluta de ninguno de los diagnósticos. Se registró un descenso histórico de las IRA bajas y las hospitalizaciones por esta causa en todo el país. Mantener una vigilancia de las consultas en los SE permitiría identificar e intervenir oportunamente si se produjeran cambios o situaciones de riesgo hasta el momento no detectadas.

In March 2020 the first case of coronavirus disease was confirmed in Uruguay, and lockdown was recommended. Health care services were reduced to Urgency and Emergency Services (ES). Objectives: to analyze the epidemiological characteristics of pediatric visits to the ES of the public and private subsector in Uruguay, during the first 4 months of the SARS-CoV-2 pandemic. Methods: descriptive, retrospective. Results: 23 institutions participated. 2 periods were considered: 1) pre-pandemic, 03/14/19 to 07/29/19, 2) 03/14/20 to 07/29/20. Visits: period 1: n=121,116 (< 15 years), period 2: n=33.099 (73% decrease). Hospital admissions: period 1: n=6,649 (rate 5.5). Period 2: n=2.948 (rate 9,5). Diagnoses period 1: High acute respiratory infection 39,892 (33%), low acute respiratory infection 8,656 (7%), minor trauma 8,651 (7%), gastroenteritis 8,044 (6,6%), asthmatic crisis/CBO 7.974 (6,5%), injuries 4,389 (3,6%), abdominal pain (3,528) 3%, mental health problems 859 (0.7%), seizures 758 (0.7%), social pathology 678 (0.5% ). 2020 diagnoses: high acute respiratory infection 5.168 (16%), minor trauma 2,759 (8%), injuries 2,652 (8%), abdominal pain 1,494 (4.5%), gastroenteritis 1,296 (4%), asthma/CBO 1,095 (3,3%), low acute respiratory infection 700 (2,1%), social pathology 522 (1,6%), mental health problems 471 (1,4%), seizures 408 (1,2%). Conclusions: in the first months of the pandemic there was a sustained and significant reduction in pediatric consultations in ES. There was no increase in absolute frequency of any of the diagnoses. There was a historical decrease in low respiratory infections and hospitalizations due to this cause in the whole country. Maintaining a surveillance of the visits in the ES would enable practitioners to identify and take action in case of changes or previously undetected risk situations.

Em março de 2020, foi confirmado o primeiro caso de doença por coronavírus no Uruguai, recomendando o confinamento. A assistência à saúde foi reduzida a serviços de urgência e emergência (SE). Objetivo: analisar as características das consultas pediátricas no SE do subsetor público e privado no Uruguai, durante os primeiros 4 meses da pandemia de SARS-CoV-2. Metodologia: estudo descritivo, retrospectivo, multicêntrico. Resultados: participaram 23 SEs de todas as regiões do país. Período pré-pandemia 1: 14/03/19-29/07/19, período 2: 14/03/20-29/07/20 Consultas: período 1 n=121.116, período 2 n=33.099 (redução de 73%) . Internações da SE: período 1 n= 0,6649 (taxa 5,5%). Período 2: n=2.948 (taxa de 9,5%). Diagnósticos do período 1: infecção respiratória aguda alta (IRA) 39.892 (33%), LRA baixa 86,56 (7%), trauma menor 8.651 (7%), gastroenterite 8.044 (6,6%), crise asmática/CBO 7.974 (6, 5% ), lesões 4.389 (3,6%), dor abdominal 3.528 (3%), problemas de saúde mental 859 (0,7%), convulsões 758 (0,7%), patologia social 678 (0,5%). Diagnósticos 2020: IRA alta 5.168 (16%), trauma leve 2.759 (8%), lesões 2.652 (8%), dor abdominal 1.494 (4,5%), gastroenterite 1.296 (4%), asma/CBO 1.095 (3, 3%), IRA baixa 700 (2,1%), patologia social 522 (1,6%), problemas de saúde mental 471 (1,4%), convulsões 408 (1,2%). Conclusões: nos primeiros meses da pandemia houve uma redução sustentada e significativa das consultas pediátricas no SE. Não houve aumento na frequência absoluta de nenhum dos diagnósticos. Foi registrado um decréscimo histórico de IRAs baixas e internações por essa causa em todo o país. A manutenção de uma vigilância das consultas no SE permitiria identificar e intervir atempadamente nos casos de alterações ou situações de risco que até agora não tinham sido detectadas.

Presentación cutánea atípica de histoplasmosis diseminada en paciente con VIH/sida / Atypical cutaneous presentation of disseminated

La histoplasmosis diseminada es una infección oportunista frecuente en los pacientes VIH/sida. Frecuentemente se encuentra compromiso cutáneo, siendo las formas clínicas más comunes el aspecto moluscoide, variceliforme y papulonecrótico.Se presenta el caso de una paciente con una forma cutánea atípica de histoplasmosis diseminada similar a pioderma gangrenoso cuyo diagnóstico fue realizado mediante escarificación.Es importante mantener la sospecha clínica en estas presentaciones atípicas y reforzar la utilidad de la escarificación de lesiones cutáneas como método rápido y efectivo para su diagnóstico.

Disseminated histoplasmosis is a frequent opportunistic infection in HIV/AIDS patients. Cutaneous manifestations are common, the most frequent are molluscum contagio-sum-like lesions, varicelliform eruption and papulo-necro-tic lesions.We present a case of an atypical disseminated cutaneous histoplasmosis with pyoderma gangrenosum-like ulcers, diagnosed by direct examination of tissue smear.It is important to have a high clinical suspicion of this atypical presentation and to emphasize the usefulness of skin smear as a simple and effective test to establish its diagnosis

Actividades ligninolíticas y producción de basidiomas de Ganoderma lucidum en cultivo sólido suplementado con manganeso / Ligninolytic activities and production of Ganoderma lucidum basidiomes in solid culture supplemented with manganese

RESUMEN Ganoderma lucidum es un basidiomiceto de pudrición blanca estudiado especialmente por sus atributos medicinales. No obstante, la información sobre la suplementación de los medios de cultivo con metales como Zn, Li, Mn, Cu es escasa aun conociendo que la presencia de metales en los sustratos mejora las características de los basidiomas obtenidos e incrementa su productividad. El objetivo fue evaluar las actividades enzimáticas lacasa (Lc) y manganeso peroxidasa (MnP), la fructificación y eficiencia biológica (EB) de G. lucidum en cultivos sólidos formulados con residuos agroindustriales (aserrín de roble, cascarilla de café, salvado de maíz) suplementados con dos niveles de sal de manganeso II (0,05 % y 0,1 % p/p) y una formulación sin adición de la sal de manganeso. Las actividades enzimáticas se determinaron durante 98 días del ciclo productivo, con toma de muestras semanales. El tratamiento uno (0,05 % p/p de MnSO4H2O) suministró la mayor EB del cultivo con 25,90 ± 2,12 % y los mayores títulos de actividades ligninolíticas en el tiempo con 0,7299 UE/g s.s. de MnP a los 35 días de fermentación y 4,1 760 UE/g s.s para la actividad de Lc a los 42 días de proceso con relación a los tratamientos dos y control. Asimismo, hubo una disminución del ciclo de cultivo del hongo para los tratamientos uno (83 días) y dos (95 días) en comparación con el tratamiento control (117 días). Los resultados de este trabajo son promisorios para cultivadores industriales de G. lucidum, ya que la suplementación de los sustratos con Mn incrementa la productividad de los cultivos.

ABSTRACT Ganoderma lucidum is a white rot basidiomycete specially studied for its medicinal attributes. However, the information on the supplementation of the substrate with metals such as Zn, Li, Mn, Cu and others is scarce. Even knowing that the presence of metals in the substrates improves the characteristics of the basidiomes produced and increases their productivity. The objective was to evaluate the enzymatic activities laccase (Lc) and manganese peroxidase (MnP). The fructification and biological efficiency (BE) of G. lucidum in solid culture formulated with agroindustrial residues, (oak sawdust, coffee husk, bran corn) supplemented with two levels of manganese II salt, (0.05 % and 0.1 % w/ w) and a formulation without addition of manganese II salt. Enzymatic activities were determined during 98 days of the production cycle, with weekly sampling. Treatment one (0.05 % w/w MnSO4.H2O) provided the highest BE of the culture with 25.90 ± 0.54% and the highest titers of ligninolytic activities, in the time with 0.7299 EU/g d.s for MnP at 35 days of fermentation and 4.1760 EU/g d.s for Lc activity at 42 days of process, in relation to treatments two and control. Likewise, there was a decrease in the fungus culture cycle for treatments one (83 days) and two (95 days) compared to the control treatment (117 days). The results of this work are promising for industrial growers of G. lucidum, since the supplementation of the substrates with Mn increase the productivity of the cultures.