Cytokine and T cell responses in post-chikungunya viral arthritis: A cross-sectional study.

OBJECTIVE: To define the relationship between chronic chikungunya post-viral arthritis disease severity, cytokine response and T cell subsets in order to identify potential targets for therapy. METHODS: Participants with chikungunya arthritis were recruited from Colombia from 2019-2021. Arthritis disease severity was quantified using the Disease Activity Score-28 and an Arthritis-Flare Questionnaire adapted for chikungunya arthritis. Plasma cytokine concentrations (interleukin (IL)-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, interferon-γ and tumor necrosis factor (TNF)) were measured using a Meso Scale Diagnostics assay. Peripheral blood T cell subsets were measured using flow cytometry. RESULTS: Among participants with chikungunya arthritis (N = 158), IL-2 levels and frequency of regulatory T cells (Tregs) were low. Increased arthritis disease activity was associated with higher levels of inflammatory cytokines (IL-6, TNF and CRP) and immunoregulatory cytokine IL-10 (p<0.05). Increased arthritis flare activity was associated with higher Treg frequencies (p<0.05) without affecting T effector (Teff) frequencies, Treg/Teff ratios and Treg subsets. Finally, elevated levels of IL-2 were correlated with increased Treg frequency, percent Tregs out of CD4+ T cells, and Treg subsets expressing immunosuppressive markers, while also correlating with an increased percent Teff out of live lymphocytes (p<0.05). CONCLUSION: Chikungunya arthritis is characterized by increased inflammatory cytokines and deficient IL-2 and Treg responses. Greater levels of IL-2 were associated with improved Treg numbers and immunosuppressive markers. Future research may consider targeting these pathways for therapy.

Reproductive benefits and reduced investment in parental care behavior associated with reproductive groups of males in Abudefduf troschelii.

Fishes of the family Pomacentridae present a wide diversity of mating systems, ranging from polygyny to promiscuity and from individual territorial defense to the establishment of reproductive colonies of males. The damselfish species Abudefduf troschelii has a reproductive colony mating system, in which males temporarily aggregate in reproductive areas to court and attract females. Males defend an individual territory where they receive eggs and perform paternal care behaviors for their offspring. The present study evaluated the advantages of the colonial mating system in A. troschelii. During an entire reproductive period, in a breeding colony within a rocky reef, we located, marked, geo-referenced, and measured the distances between the territories of all males. We quantified the variance among males in their patterns of paternal care investment, eggs acquired, hatching success, reproductive success, body size, and changes in body coloration. We found that males spatially distributed their nests in groups or independently (i.e., solitary nests). Nesting groups are formed by larger males that show intense nuptial coloration during the entire receptivity period. They are located centrally to the colony and consist of three to six males whose territories overlap. In contrast, small solitary males that fail to acquire or maintain nuptial coloration during the receptivity period establish their nests peripherally to the colony, away from the territories of other males. Our results highlight that the reproductive benefits of colonial nesting are unequal for males, as the spatial distribution of nests within the colony determines the reproductive success of males. Group nesting confers the highest reproductive benefits to males regarding eggs obtained, hatching success, and relative fitness and also enables males to reduce their parental investment in brood care behaviors. The preference of females for oviposition could be associated with greater intrasexual competitiveness, defense ability, body condition, or experience of group-nesting males located at the center of the colony or because their progeny will have a lower probability of predation than they would in solitary nests males.

Covid-19: Percepción de riesgo poblacional y cumplimiento de medidas de protección en La Habana / Covid-19: perception of population risk and compliance with protection measures in Havana

Introducción: En Cuba antes de registrarse casos de la Covid-19 se elaboró un Plan de Prevención y Control y se conformó un Grupo de Trabajo para asesorar al Gobierno en el enfrentamiento a la pandemia con una participación crucial y cohesionada de la comunidad, los trabajadores de la salud y la comunidad científica del país. Objetivo: Explorar la percepción de riesgo y las actitudes de personas residentes en La Habana en el cumplimiento de las medidas de protección durante la Covid-19. Material y Métodos: Entre los meses de mayo-julio de 2021 se realizó un estudio descriptivo trasversal para lo cual se aplicó una encuesta online en Google Forms que se mantuvo en línea durante tres meses; la misma fue respondida de forma voluntaria por 2 012 residentes en todos los municipios de La Habana, integrantes de grupos poblacionales de interés en Telegram®, WhatsApp y otras redes sociales. Resultados: Se evidenció baja percepción de riesgo e incumplimiento de las medidas de protección entre los encuestados. Conclusiones: La baja percepción de riesgo poblacional y el incumplimiento de las medidas de protección contribuyen a elevar la gravedad de la situación epidemiológica de La Habana y la expansión de la pandemia.

Introduction: Before cases of Covid-19 were registered in Cuba, a prevention and control plan was developed and a working group was formed to advise the Government on the confrontation of the pandemic with a crucial and cohesive participation of the community, the health workers, and the scientific community of the country. Objective: to explore the risk perception and attitudes of people residing in Havana in compliance with protection measures during Covid-19. Material and Methods: A cross-sectional descriptive study was carried out between May and July 2021 applying an online survey in Google Forms that remained online for three months and was answered voluntarily by 2 012 residents in all the municipalities of Havana that were members of population groups of interest on Telegram®, WhatsApp, and other social networks. Results: Low risk perception and non-compliance with protection measures were evidenced among the respondents. Conclusions: The low perception of population risk and non-compliance with protection measures contribute to increasing the severity of the epidemiological situation in Havana and the spread of the pandemic.

Effect of intranasal administration of NeuroEPO in the histological structure of the olfactory mucosa of Wistar rats / Efecto de la administración intranasal de NeuroEPO en la estructura histológica de la mucosa olfatoria de ratas Wistar

Introduction: Strokes and neurodegenerative diseases are major global health problems, not only because they cause high mortality and disability, but due to the lack of effective therapies. NeuroEPO, a variant of recombinant human erythropoietin (rHu-EPO) with a low sialic acid content, has shown encouraging results as a potential neuroprotective agent when administered intranasally. Objective: To determine the effect of intranasal administration of NeuroEPO on the histological structure of the olfactory mucosa of Wistar rats. Materials and Methods: An experimental, prospective, and longitudinal study was conducted on Wistar rats. Ten healthy animals were randomly distributed into two groups of five each. The control group received a vehicle (0.3 μl/g/day) and the treated group received NeuroEPO (300 μg/kg/day). Both treatments were administered intranasally for 28 days. The histological characteristics of the olfactory mucosa were evaluated. The medians between the study groups were compared using the Mann-Whitney U test. Results: There were no alterations in the histological characteristics of the olfactory epithelium. However, slight hypertrophy and hyperplasia of the Bowman's glands were observed at the level of the lamina propria in the group treated with NeuroEPO. Conclusions: The administration of the nasal formulation of NeuroEPO did not induce histological alterations of the olfactory mucosa of Wistar rats under the experimental conditions of this research.

Introducción: Los accidentes cerebrovasculares y las enfermedades neurodegenerativas constituyen un importante problema de salud mundial. No solo porque causan una alta mortalidad y discapacidad, sino por la falta de terapias eficaces para tratarlos. La NeuroEPO, una variante de la eritropoyetina humana recombinante (rHu-EPO) con bajo contenido en ácido siálico, ha mostrado resultados alentadores como potencial agente neuroprotector al ser administrada por vía intranasal. Objetivo: Determinar el efecto de la administración intranasal de NeuroEPO en la estructura histológica de la mucosa olfatoria de ratas Wistar. Materiales y Métodos: Se realizó un estudio experimental, prospectivo y de corte longitudinal en ratas Wistar. Se utilizaron diez animales sanos distribuidos aleatoriamente en dos grupos de cinco cada uno. El grupo control recibió vehículo (0,3 μl/g/día) y el grupo tratado recibió NeuroEPO (300 μg/kg/día). Ambos tratamientos fueron administrados por vía intranasal durante 28 días. Fueron evaluadas las características histológicas de la mucosa olfatoria. Las medianas de los grupos del estudio fueron comparadas mediante la prueba U de Mann-Whitney. Resultados: No se evidenciaron alteraciones en las características histológicas del epitelio olfatorio. Sin embargo, a nivel de la lámina propia en el grupo tratado con NeuroEPO, se observó una ligera hipertrofia e hiperplasia de las glándulas de Bowman. Conclusiones: La administración de la formulación nasal de NeuroEPO no indujo alteraciones histopatológicas de la mucosa olfatoria de ratas Wistar en las condiciones experimentales de esta investigación.

Protective effect of NeuroEPO on the reproduction of diabetic rats / Efecto protector de la NeuroEPO en la reproducción de ratas diabéticas

Introduction: Pregestational diabetes constitutes a reproductive risk which requires new treatment strategies. NeuroEPO, a variant of the recombinant human erythropoietin produced in Cuba, has neuroprotective and hypoglycemic effects which can be considered for the treatment of this entity. Objective: To evaluate the protective effect of NeuroEPO on the reproduction of diabetic rats. Material and Methods: Four groups of adult female Wistar rats with streptozotocin-induced diabetes were used. During pregnancy, one group received the vehicle and the rest of the groups received different doses of NeuroEPO (0,5 mg/kg, 0,75 mg/kg, and 1 mg/kg) subcutaneously, on alternate days, for a total of six applications. A group of non-diabetic rats was used as a control group. Glycemia and reproductive variables were evaluated. For comparisons, Analysis of Variance and Fisher's Exact Test were used. There were significant differences with p-values less than 0,05. Results: The group with vehicle presented maintained hyperglycemia, fewer implantations, and embryos, and increased gestational losses. In the group receiving 0,5 mg/kg of NeuroEPO, glycemia decreased significantly and the results of the reproductive variables were similar to the group of non-diabetic rats. With higher doses of NeuroEPO, gestational losses were increased. No congenital malformations were identified in either group. Conclusions: The repeated administration of 0,5 mg/kg of NeuroEPO has a beneficial effect on the reproduction of diabetic rats, which may be associated with the reduction of hyperglycemia. Other cytoprotective mechanisms of NeuroEPO should be evaluated in future studies(AU)

Introducción: la diabetes pre-gestacional constituye un riesgo reproductivo, lo que requiere nuevas estrategias de tratamiento. Teniendo en cuenta que la NeuroEPO, una variante de la eritropoyetina recombinante humana producida en Cuba, tiene efectos neuroprotectores e hipoglicemiantes. Objetivo: evaluar el efecto protector de la NeuroEPO en la reproducción de ratas diabéticas. Material y Métodos: se utilizaron cuatro grupos de ratas Wistar hembras adultas, con diabetes inducida por estreptozotocina. Durante la gestación, un grupo recibió el vehículo y el resto diferentes dosis de NeuroEPO (0,5 mg/kg, 0,75 mg/kg y 1 mg/kg), por vía subcutánea, en días alternos, para un total de seis aplicaciones. Se empleó un grupo de ratas no-diabéticas como control. Se evaluó la glicemia y variables reproductivas. Para las comparaciones se empleó el Análisis de Varianza y la Prueba Exacta de Fisher. Las diferencias se consideraron significativas con valores de p menores que 0,05. Resultados: el grupo con vehículo presentó hiperglicemia mantenida, menor número de implantaciones y embriones, e incremento de las pérdidas gestacionales. En el grupo que recibió 0,5 mg/kg de NeuroEPO, la glicemia disminuyó de forma significativa y los resultados de las variables reproductivas fueron similares al grupo de ratas no-diabéticas. Con las dosis superiores de NeuroEPO se incrementaron las pérdidas gestacionales. No se identificaron malformaciones congénitas en ninguno de los grupos. Conclusiones: la administración reiterada de 0,5 mg/kg de NeuroEPO tiene efecto beneficioso en la reproducción de ratas diabéticas, que puede estar asociado a la reducción de la hiperglicemia. Otros mecanismos citoprotectores de la NeuroEPO deben ser evaluados en futuros estudios(AU)

Early Left Ventricular Thrombus Following Ventricular Fibrillation/Ventricular Tachycardia Electrical Storm.

Left ventricular thrombus (LVT) formation is a serious clinical complication of low-flow states that may be seen in an ischaemic, arrhythmic heart. While LVT formation has a poor prognosis, in the setting of myocardial infarction it is usually a result of post-infarct sequelae such as left ventricle aneurysms, and inflammatory changes from damaged tissue, with the LVT taking several days to form. Arrythmias such as ventricular tachycardia (VT) or ventricular fibrillation (VF) may also lead to thrombus formation, as they contribute to stasis due to decreased cardiac output. Large anterolateral myocardial infarctions can cause electrical or arrhythmic storm, characterized by more than three episodes of VT or VF in a 24-hour period. This prolonged state of dyskinesis further increases the risk of thrombosis, creating a compounding effect. Here, we report the case of a patient who had a VF cardiac arrest with electrical storm secondary to anterolateral myocardial infarction complicated with LVT formation found on echocardiogram after the cardiac arrest, which was absent on presentation. This thrombus formation occurred particularly early during the course of the patient's arrest, possibly due to the compounding factors increasing the risk of thrombosis. Herein, we discuss in detail the risk factors for LVT formation, its mechanism and management options. A review of the literature also shows that LVT formation in the acute phase of arrest, as seen in our patient, is rare. LEARNING POINTS: Left ventricular thrombus (LVT) formation occurs 3-14 days after myocardial infarction, but in the setting of concomitant ventricular fibrillation arrest, may occur within the first 24 hours.Risk factors for LVT formation include a large infarct, anterior/anterior apical infarction, decreased ejection fraction (particularly <30-35%), left ventricular aneurysm, and delayed time to revascularization.Although diagnosis is generally made on transthoracic echocardiography with intravenous contrast, cardiac MRI with contrast has better sensitivity and specificity.Treatment consists of anticoagulation with a vitamin K antagonist or heparin for 3-6 months with a repeat echocardiogram to confirm the thrombus has organized or resolved. Further trials are needed to assess the efficacy of direct oral anticoagulants.

A Rare Presentation of Recurrent Diverticulitis in a Patient with Ulcerative Colitis.

Diverticulitis and ulcerative colitis (UC) are two separate colonic pathologies with different underlying mechanisms. Diverticulosis involves herniation of mucosal and submucosal tissue through muscular tissue in response to increased intraluminal pressure. In contrast, it is believed that the muscular tone in patients with UC is reduced due to chronic inflammatory changes. Thus, it has been reported that there may be an inverse relationship between the presence of diverticulosis in patients with UC, in that UC may possibly be protective against developing diverticular disease. Consequently, the co-presence of both pathologies is uncommon. Here we present a case in which a woman with a history of UC and recurrent diverticulitis after elective partial colectomy was admitted for recurrent acute diverticulitis. It is quite challenging to diagnose diverticulitis in ulcerative colitis patients given the usually similar presentation with abdominal pain, diarrhoea and hematochezia. A level of high suspicion is required for diagnosis. LEARNING POINTS: Colonic diverticulitis is not commonly associated with ulcerative colitis.The diagnosis of colonic diverticulitis in the setting of ulcerative colitis is challenging and requires a high level of suspicion.

Efecto hipoglicemiante de la NeuroEPO en ratas con y sin diabetes mellitus / Hypoglycemic effect of NeuroEPO in diabetic and non-diabetic rats

RESUMEN Introducción: La NeuroEPO es una variante no-hematopoyética de la eritropoyetina recombinante humana, que pudiera tener efecto hipoglicemiante. Objetivo: Evaluar la influencia de la NeuroEPO sobre la glicemia de ratas con diabetes mellitus y ratas no-diabéticas. Material y Métodos: Se realizaron experimentos en ratas Wistar con diabetes inducida por estreptozotocina, con y sin tratamiento con insulina, y en ratas no-diabéticas con una sobrecarga de glucosa. En cada experimento, un grupo recibió una inyección subcutánea de NeuroEPO (0,5 mg/kg) y otro el vehículo, y se determinó la glicemia durante 120 minutos. Se realizaron comparaciones mediante análisis de varianza de una y dos vías, seguidas por la prueba de Bonferroni. Las diferencias se consideraron significativas con valores de p < 0,05. Resultados: En las ratas diabéticas sin tratamiento con insulina, los niveles de glicemia del grupo con NeuroEPO disminuyeron de forma significativa. En las ratas no-diabéticas que recibieron NeuroEPO y una sobrecarga de glucosa, la glicemia fue similar al grupo control. En las ratas diabéticas que recibieron NeuroEPO e insulina la reducción de la glicemia fue mayor que en el grupo que solo recibió insulina. Conclusiones: La NeuroEPO tiene un efecto hipoglicemiante en ratas diabéticas, por un mecanismo insulinotrópico que muestra sinergismo con la insulina en el tratamiento de la hiperglicemia. Sin embargo, la NeuroEPO no influye en la tolerancia a la glucosa de ratas no-diabéticas, al menos de forma inmediata. Es necesario profundizar en los mecanismos mediante los cuales la NeuroEPO puede reducir la hiperglicemia, y la influencia de esta sustancia en condiciones de normoglicemia.

ABSTRACT Introduction: NeuroEPO is a non-hematopoietic variant of human recombinant erythropoietin, which may have a hypoglycemic effect. Objectives: To evaluate the influence of NeuroEPO on glycemia in diabetic and non-diabetic rats. Material and Methods: The experiments were conducted in Wistar rats with streptozotocin-induced diabetes with and without insulin treatment, and in non-diabetic rats with glucose overload. In each experiment, one group received a subcutaneous injection of NeuroEPO (0.5 mg/kg) and the other group received a vehicle. Glycemia was determined in 120 min. Comparisons were made using one-and two-way analysis of variance, followed by the Bonferroni test. The differences were considered significant with p values < 0,05. Results: In diabetic rats without insulin treatment, glycemic levels decreased significantly in the group that received NeuroEPO. In nondiabetic rats that received NeuroEPO and a glucose overload, glycemia was similar to that in the control group. In diabetic rats that received NeuroEPO and insulin, the glycemia reduction was greater than in the group that only received insulin. Conclusions: NeuroEPO has a hypoglycemic effect in diabetic rats due to an insulinotropic mechanism that shows synergism with insulin in the treatment of hyperglycemia. However, NeuroEPO does not influence the glucose tolerance in non-diabetic rats, at least immediately. It is necessary to delve into the mechanisms by which NeuroEPO can reduce hyperglycemia and the influence of this substance under conditions of normoglycemia.

Actitudes y percepciones de la población de La Habana sobre la COVID-19

RESUMEN Introducción: Cualquier estrategia diseñada para aumentar la percepción de riesgo involucra procesos de cambio o modificación de las actitudes subyacentes. Objetivo: Explorar las actitudes y percepciones de la población de La Habana sobre la COVID-19. Métodos: Estudio descriptivo transversal en una población de 2012 habaneros que, de forma anónima y voluntaria, respondieron un cuestionario en línea distribuido en redes sociales entre mayo y junio de 2021. Se emplearon variables sobre la caracterización demográfica y las relacionadas con el objeto de estudio agrupadas en causas a las que atribuyen la situación epidemiológica actual: sociales, estatales y externas. Se utilizó la prueba estadística ji cuadrado y el modelo de los residuos corregidos. Resultados: Los participantes de los municipios de Playa (14,1 %), Plaza de la Revolución (13,2 %) y Diez de Octubre (12,7 %) fueron los más frecuentes. Las 3 causas predominantes según más del 80 % fueron "Violación del distanciamiento social", "Resquebrajamiento de la disciplina social" y "Celebración y festividades". De la dimensión estatal se destacaron, violaciones del distanciamiento social, apertura de los aeropuertos y eliminación de las pesquisas activas. El 43,5 % de las respuestas a 14 de las 32 señaladas por los encuestados, están relacionadas con la baja percepción de riesgo de la población. Conclusiones: No es posible atribuir la situación epidemiológica por la COVID-19 en La Habana, solo a la baja percepción de riesgo de la sociedad; este es un fenómeno multicausal con causas atribuidas a la acción/ inacción estatal y al comportamiento social.

ABSTRACT Introduction: Any strategy designed to increase the perception of risk involves processes of change or modification of the underlying attitudes. Objective: To explore the attitudes and perceptions of the population of Havana about COVID-19. Methods: Cross-sectional descriptive study was carried out in a population of 2012 citizens of Havana who, anonymously and voluntarily, answered an online questionnaire distributed on social networks between May and June 2021. Variables on demographic characterization and those related to the object of study were used grouped into causes to which they attribute the current epidemiological situation: social, state and external. The chi-square statistical test and the corrected residuals model were used. Results: Participants from the municipalities of "Playa" (14.1%), "Plaza de la Revolución" (13.2%) and "Diez de Octubre" (12.7%) were the most frequent. The 3 predominant causes according to more than 80 % were "Violation of social distancing", "Breakdown of social discipline" and "Celebration and festivities". Of the state dimension, violations of social distancing, opening of airports and elimination of active investigations stood out. 43.5 % of the responses to 14 of the 32 indicated by those surveyed are related to the population's low perception of risk. Conclusions: It is not possible to attribute the epidemiological situation due to COVID-19 in Havana, only to the low perception of risk in society; This is a multicausal phenomenon with causes attributed to state action / inaction and social behavior.