Detection of Zika Virus in Aedes aegypti and Aedes albopictus Mosquitoes Collected in Urban Forest Fragments in the Brazilian Amazon.

Zika virus (ZIKV) is an RNA flavivirus (Flaviviridae family) endemic in tropical and subtropical regions that is transmitted to humans by Aedes (Stegomyia) species mosquitoes. The two main urban vectors of ZIKV are Aedes aegypti and Aedes albopictus, which can be found throughout Brazil. This study investigated ZIKV infection in mosquito species sampled from urban forest fragments in Manaus (Brazilian Amazon). A total of 905 non-engorged female Ae. aegypti (22 specimens) and Ae. albopictus (883 specimens) were collected using BG-Sentinel traps, entomological hand nets, and Prokopack aspirators during the rainy and dry seasons between 2018 and 2021. All pools were macerated and used to inoculate C6/36 culture cells. Overall, 3/20 (15%) Ae. aegypti and 5/241 (2%) Ae. albopictus pools screened using RT-qPCR were positive for ZIKV. No supernatants from Ae. aegypti were positive for ZIKV (0%), and 15 out of 241 (6.2%) Ae. albopictus pools were positive. In this study, we provide the first-ever evidence of Ae. albopictus naturally infected with ZIKV in the Amazon region.

Is zoonotic Plasmodium vivax malaria an obstacle for disease elimination?

BACKGROUND: The groundwork for malaria elimination does not currently consider the potential of Plasmodium zoonotic cycles that involve non-human primates (NHPs) in sylvatic environments. Since vivax malaria is less responsive to control measures, finding Plasmodium vivax infected NHPs adds even more concern. METHODS: Both Free-living monkeys in forest fragments inside the urban area and captive monkeys from a local zoo had blood samples tested for Plasmodium species. RESULTS: In this study, among the Neotropical monkeys tested, three (4.4%), one captive and two free-living, were found to be naturally infected by P. vivax. CONCLUSION: This important finding indicates that it is necessary to estimate the extent to which P. vivax NHP infection contributes to the maintenance of malaria transmission to humans. Therefore, the discussion on wildlife conservation and management must be incorporated into the malaria elimination agenda.

Subcutaneous Emphysema after a Dental Procedure.

Subcutaneous emphysema is the presence of air beneath the skin's soft tissues. It can result from medical conditions, trauma or iatrogenic causes. The occurrence of subcutaneous emphysema after a dental procedure is rare. Although it is mostly a benign and self-limiting complication, the consequences may be severe and life-threatening. We report the case of a 20-year-old man who presented to the emergency department with swelling of his face and neck after dental treatment. The diagnosis of subcutaneous emphysema and pneumomediastinum was made based on physical examination and a computerized tomography scan. LEARNING POINTS: Subcutaneous emphysema is a rare complication of dental procedures.It is mostly benign and self-limiting, although the consequences may be severe and potentially life-threatening.Early diagnosis and accurate treatment based on understanding its characteristics are important in the prognosis.

Mastodon footprints found to be water erosion in the Quebrada de Chalán (Licto, Ecuador).

The Chalan ravine is a deep bed creek that runs through Licto (Ecuador). It has been known since the 19th century for the abundance of paleontological remains of Pleiostocene fauna and megafauna in its profiles, where entire remains of mastodons were recovered. The abundance of these remains made one of the high areas, where marmites exist in different forms, was traditionally considered as mastodon footprints. Archaeological prospecting, geographic information system (GIS) technology, unmanned aerial vehicle (UAV), photogrammetry, and the geological study of the place, allowed us to determine that the mythical traces of mastodon were marmites made by the water erosion produced in the same ravine over time.

Hyperbaric oxygen as an adjuvant treatment for patients with COVID-19 severe hypoxaemia: a randomised controlled trial.

BACKGROUND: Hyperbaric oxygen (HBO2) therapy has been proposed to treat hypoxaemia and reduce inflammation in COVID-19. Our objective was to analyse safety and efficacy of HBO2 in treatment of hypoxaemia in patients with COVID-19 and evaluate time to hypoxaemia correction. METHODS: This was a multicentre, open-label randomised controlled trial conducted in Buenos Aires, Argentina, between July and November 2020. Patients with COVID-19 and severe hypoxaemia (SpO2 ≤90% despite oxygen supplementation) were assigned to receive either HBO2 treatment or the standard treatment for respiratory symptoms for 7 days. HBO2 treatment was planned for ≥5 sessions (1 /day) for 90 min at 1.45 atmosphere absolute (ATA). Outcomes were time to normalise oxygen requirement to SpO2 ≥93%, need for mechanical respiratory assistance, development of acute respiratory distress syndrome and mortality within 30 days. A sample size of 80 patients was estimated, with a planned interim analysis after determining outcomes on 50% of patients. RESULTS: The trial was stopped after the interim analysis. 40 patients were randomised, 20 in each group, age was 55.2±9.2 years. At admission, frequent symptoms were dyspnoea, fever and odynophagia; SpO2 was 85.1%±4.3% for the whole group. Patients in the treatment group received an average of 6.2±1.2 HBO2 sessions. Time to correct hypoxaemia was shorter in treatment group versus control group; median 3 days (IQR 1.0-4.5) versus median 9 days (IQR 5.5-12.5), respectively (p<0.010). OR for recovery from hypoxaemia in the HBO2 group at day 3 compared with the control group was 23.2 (95% CI 1.6 to 329.6; p=0.001) Treatment had no statistically significant effect on acute respiratory distress syndrome, mechanical ventilation or death within 30 days after admission. CONCLUSION: Our findings support the safety and efficacy of HBO2 in the treatment of COVID-19 and severe hypoxaemia. TRIAL REGISTRATION NUMBER: NCT04477954.

Adaptation of the stomatherapy service during the COVID-19 pandemic: an experience report.

OBJECTIVE: To report the experience of adapting the stomatherapy service during the COVID-19 pandemic. METHOD: Experience report related to adaptations in the work routine in times of COVID-19 pandemic, from March to May 2020, in a specialized stomatherapy center in a city in the South of Brazil. RESULTS: The work routines were adapted to suit the protection measures for workers and users who used stomatherapy services. Some assistance processes were implemented to make users' access to care more flexible, and to modify routines to increase the safety of health professionals and users. CONCLUSION: The need to adapt the physical area, rethink the dynamics of care, use personal protective equipment, and guidance for servers and patients were of fundamental importance to continue attending the population safely in times of pandemic.

Automated analysis of bone-conduction cortical auditory evoked potential in normal-hearing neonates / Análise automática do potencial evocado auditivo cortical por via óssea em neonatos norma-ouvintes

Abstract Introduction The cortical auditory evoked potential allows the possibility of objectively evaluating the entire auditory system, which is desirable in the pediatric population. Bone conduction auditory stimulation is recommended in the differential diagnosis of conductive hearing loss. However, there are not many studies of cortical auditory evoked potential using bone conduction. Objective The aim of this study was to characterize the response of cortical auditory evoked potential through bone conduction in normal-hearing neonates using an automated response analysis equipment. Methods This study included 30 normal-hearing neonates, without risk factors for hearing loss. The equipment used was the HEARlab automated response analysis and the cortical responses were evaluated at the frequencies of 500-4000 Hz through bone conduction, at intensity ranging from 0 to 60 dBnHL. The latencies and amplitudes were manually marked by experienced judges. Results Cortical auditory evoked potential responses were detected in 100% of the evaluated subjects and there was no difference regarding the cortical response of the neonates in relation to the variables of gender, ear and masking use. At an intensity of 60 dBnHL for the frequencies of 500, 1000, 2000 and 4000 Hz the latencies were 234; 241; 239 and 253 ms and the amplitudes were 15.6; 8.4; 6.2; 6.3 µV. The mean thresholds were 23.6; 28; 31 and 33.1 dBnHL, respectively. Conclusion It was possible to measure the cortical auditory evoked potential response in the neonatal population using bone vibrator as sound transducer and to draw the profile of the cortical auditory evoked potential latencies and amplitudes by frequencies at the intensity of 60 dBnHL and at the threshold.

Resumo Introdução O potencial evocado auditivo cortical traz a possibilidade de avaliar de forma objetiva todo o sistema auditivo, o que é desejável na população infantil. A estimulação auditiva por condução óssea é recomendada no diagnóstico diferencial da perda auditiva condutiva. Entretanto, não há muitos estudos de potencial evocado auditivo cortical com o uso do vibrador ósseo. Objetivo Caracterizar a resposta do potencial evocado auditivo cortical por vibrador ósseo em neonatos normo-ouvintes com equipamento de análise automática de resposta. Metodologia A pesquisa incluiu 30 neonatos normo-ouvintes e sem fator de risco para deficiência auditiva. Foi usado o equipamento de análise automática de resposta HEARlab e foram avaliadas as repostas corticais na frequências de 500 a 4000 Hz por vibrador ósseo, na intensidade de 0 a 60 dBnNA. As latências e amplitudes foram marcadas manualmente por juízes experientes. Resultados Foram detectadas respostas de potencial evocado auditivo cortical em 100% dos sujeitos avaliados. Não houve diferença na resposta cortical dos neonatos para as variáveis: sexo, orelha e uso do mascaramento. Para as frequências de 500, 1000, 2000 e 4000 Hz foram observadas as latências de 234; 241; 239 e 253 ms, as amplitudes de 15,6; 8,4; 6,2; 6,3 µV, na intensidade de 60 dBnNA, e os limiares médios de 23,6; 28; 31 e 33,1 dBnNA, respectivamente. Conclusão Foi possível obter a resposta do potencial evocado auditivo cortical na população neonatal com vibrador ósseo como transdutor de som e traçar o perfil das latências e amplitudes dos potencial evocado auditivo cortical por frequência nas intensidades de 60 dBnNA e no limiar.

5-lipoxygenase- and Glucocorticoid-dependent eosinophilia in a novel surgical model in mice.

BACKGROUND: Subcutaneous implants of heat-coagulated egg white (egg white implants, EWI) induce intense local eosinophilia and prime for hyperreactivity following airway ovalbumin challenge. The roles of allergen sensitization, surgical trauma-induced glucocorticoids, and the 5-lipoxygenase (5-LO) pathway were hitherto unexplored in this model, in which quantitative recovery and large-scale purification of the eosinophils from the inflammatory site for functional and immunopharmacological studies are difficult to achieve. METHODS: We overcame this limitation by shifting the implantation site to the peritoneal cavity (EWIp), thereby enabling quantitative leukocyte retrieval. RESULTS: By day 7 post-surgery, eosinophil counts reached ~ 30% of all leukocytes recovered. Eosinophilia was prevented by: a) induction of allergen-specific oral tolerance to ovalbumin, the main allergen in egg white; b) inactivation of the 5-lipoxygenase pathway; c) blockade of endogenous glucocorticoid signaling by pretreatment with metirapone plus mifepristone before surgery. Highly purified eosinophils (~99% pure) could be obtained from the peritoneal exudate of EWIp-carrier mice in 2 simple, antibody-free steps. Preparative-scale yields, suitable for most biochemical, pharmacological, and molecular applications, were routinely obtained, and could be further enhanced through addition of pre-or post-surgery immunization steps (active or adoptive). The recovered eosinophils were fully functional in vivo, as demonstrated by the transfer of purified eosinophils into eosinophil-deficient Δdbl-GATA-1-KO mice, which upon subsequent challenge with eotaxin-1 present secondary accumulation of neutrophils, but not of mononuclear phagocytes. CONCLUSION: These findings document glucocorticoid-, allergen- and 5-lipoxygenase-dependent eosinophilia, which makes EWIp carriers an abundant source of pure, nontransgenic eosinophils for immunopharmacological studies.

Cuidados de enfermagem na redução manual de prolapso de estomia / Nursing care in manual reduction of stoma prolapse / Atención de enfermería en la reducción manual del prolapso de ostomía

Objetivo: relatar um caso sobre a redução manual do prolapso em um estoma intestinal. Método: trata-se de um estudo descritivo, tipo relato de caso clínico, sobre a redução manual do prolapso em um estoma intestinal de um paciente. Relata-se que o cenário foi um centro de referência no atendimento ao estomizado. Avaliaram-se a efetividade das intervenções de Enfermagem com base na comparação dos resultados iniciais e finais do procedimento. Resultados: nota-se a presença de lesões e permeabilidade na presença de prolapso, realizando a manobra de redução digital, até a sua total regressão, facilitando a limpeza da pele e a colocação do equipamento coletor, observando as possíveis lesões periestomais e na mucosa. Conclusão: informa-se que os pacientes com prolapso em estoma intestinal têm um desconforto devido ao volume dentro do equipamento coletor e ao pouco espaço para conter as suas eliminações. Utiliza-se a técnica de redução manual para facilitar a troca do equipamento coletor, esta deverá ser realizada por enfermeiro estomaterapeuta ou enfermeiro capacitado. Salienta-se que os casos em que se afeta o desenvolvimento de atividades cotidianas merecem uma avaliação da equipe cirúrgica.(AU)

Objective: to report a case about manual reduction of prolapse in an intestinal stoma. Method: it is a descriptive, case report type study on the manual reduction of prolapse in a patient's intestinal stoma. It is reported that the scenario was a reference center in the care of the stoma. They evaluated the effectiveness of nursing interventions based on the comparison of the initial and final results of the procedure. Results: the presence of injuries and permeability in the presence of prolapse is noted, performing the digital reduction maneuver, until its total regression, facilitating the cleaning of the skin and the placement of the collector equipment, observing the possible periestomal and mucosal lesions. Conclusion: it is reported that patients with prolapse in the intestinal stoma have a discomfort due to the volume inside the collector equipment and the little space to contain their eliminations. The manual reduction technique is used to facilitate the exchange of the collector equipment, this should be performed by a stoma therapist or trained nurse. It is emphasized that the cases in which the development of daily activities is affected deserve an evaluation of the surgical team.(AU)

Objetivo: reportar un caso de reducción manual del prolapso en un estoma intestinal. Método: se trata de un estudio descriptivo, a modo de reporte de caso clínico, sobre la reducción manual del prolapso en el estoma intestinal de un paciente. Se informa que el escenario fue un centro de referencia en la atención de pacientes ostomizados. Evaluaron la efectividad de las intervenciones de Enfermería a partir de una comparación de los resultados iniciales y finales del procedimiento. Resultados: se observa la presencia de lesiones y permeabilidad en presencia de prolapso, realizando la maniobra de reducción digital, hasta su total regresión, facilitando la limpieza de la piel y la colocación del equipo colector, observando las posibles lesiones periestomales y mucosas. Conclusión: se informa que los pacientes con prolapso en estoma intestinal presentan molestias por el volumen dentro del equipo de recolección y el poco espacio para contener sus eliminaciones. La técnica de reducción manual se utiliza para facilitar el intercambio del equipo colector, esto debe ser realizado por un estomaterapeuta o enfermero capacitado. Cabe destacar que los casos en los que se ve afectado el desarrollo de las actividades diarias merecen una valoración por parte del equipo quirúrgico. (AU)

Automated analysis of bone-conduction cortical auditory evoked potential in normal-hearing neonates.

INTRODUCTION: The cortical auditory evoked potential allows the possibility of objectively evaluating the entire auditory system, which is desirable in the pediatric population. Bone conduction auditory stimulation is recommended in the differential diagnosis of conductive hearing loss. However, there are not many studies of cortical auditory evoked potential using bone conduction. OBJECTIVE: The aim of this study was to characterize the response of cortical auditory evoked potential through bone conduction in normal-hearing neonates using an automated response analysis equipment. METHODS: This study included 30 normal-hearing neonates, without risk factors for hearing loss. The equipment used was the HEARlab automated response analysis and the cortical responses were evaluated at the frequencies of 500-4000Hz through bone conduction, at intensity ranging from 0 to 60dBnHL. The latencies and amplitudes were manually marked by experienced judges. RESULTS: Cortical auditory evoked potential responses were detected in 100% of the evaluated subjects and there was no difference regarding the cortical response of the neonates in relation to the variables of gender, ear and masking use. At an intensity of 60 dBnHL for the frequencies of 500, 1000, 2000 and 4000Hz the latencies were 234; 241; 239 and 253ms and the amplitudes were 15.6; 8.4; 6.2; 6.3µV. The mean thresholds were 23.6; 28; 31 and 33.1dBnHL, respectively. CONCLUSION: It was possible to measure the cortical auditory evoked potential response in the neonatal population using bone vibrator as sound transducer and to draw the profile of the cortical auditory evoked potential latencies and amplitudes by frequencies at the intensity of 60dBnHL and at the threshold.

Adaptation of the stomatherapy service during the COVID-19 pandemic: an experience report / Adpatación del servicio de estomaterapia durante la pandemia Covid-19: informe de experiência / Adaptação do serviço de estomaterapia durante a pandemia do Covid-19: relato de experiência

ABSTRACT Objective To report the experience of adapting the stomatherapy service during the COVID-19 pandemic. Method Experience report related to adaptations in the work routine in times of COVID-19 pandemic, from March to May 2020, in a specialized stomatherapy center in a city in the South of Brazil. Results The work routines were adapted to suit the protection measures for workers and users who used stomatherapy services. Some assistance processes were implemented to make users' access to care more flexible, and to modify routines to increase the safety of health professionals and users. Conclusion The need to adapt the physical area, rethink the dynamics of care, use personal protective equipment, and guidance for servers and patients were of fundamental importance to continue attending the population safely in times of pandemic.

RESUMEN Objetivo Informar sobre la experiencia de adaptar el servicio de estomatoterapia durante la pandemia de Covid-19. Método Informe de experiencia relacionado con adaptaciones en la rutina laboral en tiempos de pandemia de Covid-19, de marzo a mayo de 2020 en un centro de referencia en estomaterapia en una ciudad en la región sur de Brasil. Resultados las rutinas de trabajo se adaptaron a las medidas de protección para trabajadores y usuarios que usaban servicios de estomatoterapia. Se implementó algunos procesos de asistencia para que el acceso de los usuarios a la atención fuera más flexible y para modificar las rutinas aumentando la seguridad de los profesionales y usuarios de la salud. Conclusión La necesidad de adaptar el área física, repensar la dinámica de la atención, el uso de equipos de protección personal, y las orientaciones para servidores y pacientes fueron de fundamental importancia para continuar ofreciendo el servicio a la población de manera segura en tiempos de pandemia.

RESUMO Objetivo Relatar a experiência das adaptações do serviço de estomaterapia durante a pandemia do Covid-19. Método Relato de experiência relacionado às adaptações na rotina de trabalho em tempos de pandemia do Covid-19, no período de março a maio de 2020 em um centro de referência em estomaterapia de uma cidade da região sul do Brasil. Resultados As rotinas de trabalho foram adaptadas para adequar às medidas de proteção para os servidores e usuários que utilizaram os serviços de estomaterapia. Foram implantados alguns processos assistências para a flexibilização do acesso de usuários para atendimento, e modificações de rotinas para o aumento da segurança dos profissionais da saúde e usuários. Conclusão A necessidade em adequar a área física, repensar a dinâmica do atendimento, uso de equipamentos de proteção individual, orientações para servidores e pacientes foi de fundamental importância para seguir o atendimento à população com segurança em tempos de pandemia.

Impact of clinical, sociodemographic and quality of life factors on dialysis patient survival: a nine-year follow-up cohort study.

Although renal replacement therapy has contributed to the survival of chronic kidney failure (CKF) patients, mortality remains a major concern. This study aimed to identify the factors associated with mortality in a prospective cohort of CKF patients. Sociodemographic, clinical, nutritional, lifestyle and quality of life data were collected from 712 patients. The instruments used were the Short-Form Health Survey (SF-36), Global Subjective Assessment (GSA) and Charlson Comorbidity Index (CCI) questionnaires. A total of 444 patients died during the study. After five years of follow-up, factors such as not being married (hazard ratio - HR = 1.289, 95%CI: 1.001; 1.660), a low frequency of leisure activities (HR = 1.321; 95%CI: 1.010; 1.727) and not being transplanted (HR = 7.246; 95%CI: 3.359; 15.630) remained independently associated with the risk of mortality. At the end of the follow-up period, factors such as not being married (HR = 1.337, 95%CI: 1.019; 1.756), not being transplanted (HR = 7.341, 95%CI: 3.829; 14.075) and having a worse nutritional status (HR = 1.363, 95%CI: 1.002; 1.853) remained independently associated with an increased risk of mortality, whereas a high schooling level (10 to 12 years, HR = 0.578, 95%CI: 0.344; 0.972; and over 12 years, HR = 0.561, 95%CI: 0.329; 0.956) and a better SF-36 physical functioning score (HR = 0.992, 95%CI: 0.987; 0.998) were protective factors associated with survival. The survival of patients with CKF is associated with factors not restricted to the clinical spectrum. The following factors were associated with high mortality: not being married, low schooling level, a limited social routine, a longer time on dialysis, worse nutritional status, and worse physical functioning.

[Costs attributable to obesity, hypertension, and diabetes in the Unified Health System, Brazil, 2018Costos atribuibles a la obesidad, la hipertensión y la diabetes en el Sistema Único de Salud de Brasil, 2018]. / Custos atribuíveis a obesidade, hipertensão e diabetes no Sistema Único de Saúde, Brasil, 2018.

OBJECTIVE: To estimate the cost attributable to arterial hypertension, diabetes and obesity in the Unified Health System of Brazil in 2018. METHOD: The study estimated the cost attributable to non-communicable chronic diseases based on relative risk and population prevalence of hypertension, diabetes, and obesity, considering the cost of hospitalizations, outpatient procedures, and medications distributed by the SUS to treat these diseases. Cost data were obtained from SUS information systems. The analysis explored the cost of disease according to sex and age in the adult population. RESULTS: The total cost of hypertension, diabetes, and obesity in the SUS reached R$ 3.45 billion (95%CI: 3.15-3.75) in 2018, that is, more than US$ 890 million. Of this amount, 59% referred to the treatment of hypertension, 30% to diabetes, and 11% to obesity. The age group from 30 to 69 years accounted for 72% of the total costs, and women accounted for 56%. When obesity was considered separately as a risk factor for hypertension and diabetes, the cost attributable to this diseases reached R$ 1.42 billion (95%CI: 0.98-1.87), i.e., 41% of the total cost. CONCLUSIONS: The estimates of costs attributable to the main chronic diseases associated with inadequate diet revealed a heavy economic burden of these disorders for the SUS. The data show the need to prioritize integrated and intersectoral policies for the prevention and control of hypertension, diabetes, and obesity, and may support the advocacy for interventions such as fiscal and regulatory measures to ensure that the objectives of the United Nations Decade of Action on Nutrition are met.

OBJETIVO: Estimar los costos atribuibles a la hipertensión arterial, la diabetes y la obesidad en el Sistema Único de Salud (SUS) de Brasil en el 2018. MÉTODOS: Se estimaron los costos atribuibles a las enfermedades crónicas no transmisibles a partir de los riesgos relativos y de las tasas de prevalencia poblacional de hipertensión, diabetes y obesidad, teniendo en cuenta los costos de hospitalización, los procedimientos ambulatorios y los medicamentos distribuidos por el SUS para el tratamiento de esas enfermedades. Los datos de costos se obtuvieron en los sistemas de información de salud disponibles en el SUS. En el análisis se exploraron los costos de las enfermedades según el sexo y la edad de la población adulta. RESULTADOS: Los costos totales atribuibles a la hipertensión, la diabetes y la obesidad en el SUS alcanzaron R$ 3,450 milliones (IC 95%: de 3,15 a 3,75) en el 2018, o sea, más de US$ 890 millones. De esos costos, 59% correspondió al tratamiento de la hipertensión, 30% al de la diabetes y 11% al de la obesidad. En total, 72% de los costos correspondieron a personas de 30 a 69 años y 56%, a mujeres. Al considerarse por separado la obesidad como factor de riesgo de hipertensión y diabetes, los costos atribuibles a esa enfermedad alcanzaron R$ 1.420 millones (IC 95%: de 0,98 a 1,87), o sea, 41% del total. CONCLUSIONES: Las estimaciones de los costos atribuibles a las principales enfermedades crónicas relacionadas con la alimentación inadecuada ponen de manifiesto la pesada carga económica de esas enfermedades para el SUS. Los datos muestran la necesidad de priorizar políticas integradas e intersectoriales para la prevención y el control de la hipertensión, la diabetes y la obesidad, y permiten apoyar la defensa de intervenciones como medidas fiscales y regulatorias para alcanzar los objetivos del Decenio de las Naciones Unidas de Acción sobre la Nutrición.

Allergen challenge-induced changes in bone-marrow responses to leukotriene D4, nonsteroidal anti-inflammatory drugs and cytokines.

Context: In nonallergic (naive) mice, type I cysteinyl-leukotriene receptors (CysLT1R) mediate the stimulatory effects of cytokines (eotaxin/CCL11, interleukin[IL] - 13), and nonsteroidal anti-inflammatory drugs (NSAID; indomethacin, aspirin) on eosinophil production by IL-5-stimulated bone-marrow. In ovalbumin (OVA)-sensitized mice, airway challenge-induced bone-marrow eosinophilia and eosinopoiesis are prevented by pretreatment with blockers of adrenal glucocorticoid signaling (RU486, metyrapone) or cysteinyl-leukotriene (CysLT) signaling (montelukast).Objective: To define whether allergen challenge modifies subsequent bone-marrow responses to CysLT, NSAID, and cytokines which act through type 1 CysLT receptor (CysLT1R).Methods: We examined the effects of sensitization/challenge, and of in vivo blockade of endogenous glucocorticoid or CysLT signaling, on ex vivo responses to CysLT1R-dependent stimuli.Results and discussion: Challenge abolished the stimulatory ex vivo responses to CysLT1R-dependent agents in the eosinophil lineage. In cultured bone-marrow of naive, sensitized and sensitized/challenged mice, responses to leukotriene D4 (LTD4) in eosinophil differentiation ex vivo shifted from stimulatory (without challenge) to suppressive (following challenge). Both stimulatory and suppressive LTD4 effects were blocked by montelukast. The suppressive LTD4 effect was accounted for by accelerated maturation followed by apoptosis of eosinophils. RU486/metyrapone or montelukast pretreatments before challenge prevented the challenge-induced change in subsequent responses to all these agents. Hence, allergen challenge has two separate effects on bone-marrow: (a) it enhances eosinopoiesis in vivo and upregulates ex vivo responses to IL-5; (b) it promotes a faster, but self-limiting, response to LTD4 and CysLT1R-dependent stimuli.Conclusion: Allergen challenge modifies eosinopoiesis through systemic (glucocorticoid- and CysLT1R-dependent) mechanisms, increasing responses to IL-5 but restricting responses to subsequent CysLT1R stimulation.

Custos atribuíveis a obesidade, hipertensão e diabetes no Sistema Único de Saúde, Brasil, 2018 / Costs attributable to obesity, hypertension, and diabetes in the Unified Health System, Brazil, 2018 / Costos atribuibles a la obesidad, la hipertensión y la diabetes en el Sistema Único de Salud de Brasil, 2018

RESUMO Objetivo. Estimar os custos atribuíveis a hipertensão arterial, diabetes e obesidade no Sistema Único de Saúde (SUS) no Brasil em 2018. Métodos. Realizou-se uma estimativa dos custos atribuíveis a doenças crônicas não transmissíveis a partir dos riscos relativos e das prevalências populacionais de hipertensão, diabetes e obesidade, considerando custos de hospitalizações, procedimentos ambulatoriais e medicamentos distribuídos pelo SUS para tratamento dessas doenças. As informações de custo foram obtidas nos sistemas de informação em saúde disponíveis no SUS. A análise explorou os custos das doenças segundo sexo e idade na população adulta. Resultados. Os custos totais de hipertensão, diabetes e obesidade no SUS alcançaram 3,45 bilhões de reais (R$) (IC95%: 3,15 a 3,75) em 2018, ou seja, mais de 890 milhões de dólares (US$). Desses custos, 59% foram referentes ao tratamento da hipertensão, 30% ao do diabetes e 11% ao da obesidade. No total, 72% dos custos foram com indivíduos de 30 a 69 anos de idade e 56%, com mulheres. Considerando separadamente a obesidade como fator de risco para hipertensão e diabetes, os custos atribuíveis a essa doença chegaram a R$ 1,42 bilhão (IC95%: 0,98 a 1,87), ou seja, 41% dos custos totais. Conclusões. As estimativas dos custos atribuíveis às principais doenças crônicas associadas à alimentação inadequada evidenciam a grande carga econômica dessas doenças para o SUS. Os dados mostram a necessidade de priorizar políticas integradas e intersetoriais para a prevenção e o controle da hipertensão, do diabetes e da obesidade e podem apoiar a defesa de intervenções como medidas fiscais e regulatórias para alcançar os objetivos da Década de Ação das Nações Unidas sobre Nutrição.(AU)

ABSTRACT Objective. To estimate the cost attributable to arterial hypertension, diabetes and obesity in the Unified Health System of Brazil in 2018. Method. The study estimated the cost attributable to non-communicable chronic diseases based on relative risk and population prevalence of hypertension, diabetes, and obesity, considering the cost of hospitalizations, outpatient procedures, and medications distributed by the SUS to treat these diseases. Cost data were obtained from SUS information systems. The analysis explored the cost of disease according to sex and age in the adult population. Results. The total cost of hypertension, diabetes, and obesity in the SUS reached R$ 3.45 billion (95%CI: 3.15-3.75) in 2018, that is, more than US$ 890 million. Of this amount, 59% referred to the treatment of hypertension, 30% to diabetes, and 11% to obesity. The age group from 30 to 69 years accounted for 72% of the total costs, and women accounted for 56%. When obesity was considered separately as a risk factor for hypertension and diabetes, the cost attributable to this diseases reached R$ 1.42 billion (95%CI: 0.98-1.87), i.e., 41% of the total cost. Conclusions. The estimates of costs attributable to the main chronic diseases associated with inadequate diet revealed a heavy economic burden of these disorders for the SUS. The data show the need to prioritize integrated and intersectoral policies for the prevention and control of hypertension, diabetes, and obesity, and may support the advocacy for interventions such as fiscal and regulatory measures to ensure that the objectives of the United Nations Decade of Action on Nutrition are met.(AU)

RESUMEN Objetivo. Estimar los costos atribuibles a la hipertensión arterial, la diabetes y la obesidad en el Sistema Único de Salud (SUS) de Brasil en el 2018. Métodos. Se estimaron los costos atribuibles a las enfermedades crónicas no transmisibles a partir de los riesgos relativos y de las tasas de prevalencia poblacional de hipertensión, diabetes y obesidad, teniendo en cuenta los costos de hospitalización, los procedimientos ambulatorios y los medicamentos distribuidos por el SUS para el tratamiento de esas enfermedades. Los datos de costos se obtuvieron en los sistemas de información de salud disponibles en el SUS. En el análisis se exploraron los costos de las enfermedades según el sexo y la edad de la población adulta. Resultados. Los costos totales atribuibles a la hipertensión, la diabetes y la obesidad en el SUS alcanzaron R$ 3,450 milliones (IC 95%: de 3,15 a 3,75) en el 2018, o sea, más de US$ 890 millones. De esos costos, 59% correspondió al tratamiento de la hipertensión, 30% al de la diabetes y 11% al de la obesidad. En total, 72% de los costos correspondieron a personas de 30 a 69 años y 56%, a mujeres. Al considerarse por separado la obesidad como factor de riesgo de hipertensión y diabetes, los costos atribuibles a esa enfermedad alcanzaron R$ 1.420 millones (IC 95%: de 0,98 a 1,87), o sea, 41% del total. Conclusiones. Las estimaciones de los costos atribuibles a las principales enfermedades crónicas relacionadas con la alimentación inadecuada ponen de manifiesto la pesada carga económica de esas enfermedades para el SUS. Los datos muestran la necesidad de priorizar políticas integradas e intersectoriales para la prevención y el control de la hipertensión, la diabetes y la obesidad, y permiten apoyar la defensa de intervenciones como medidas fiscales y regulatorias para alcanzar los objetivos del Decenio de las Naciones Unidas de Acción sobre la Nutrición.(AU)

Mapping Alterations Induced by Long-Term Axenic Cultivation of Leishmania amazonensis Promastigotes With a Multiplatform Metabolomic Fingerprint Approach.

Leishmaniases are widespread neglected diseases with an incidence of 1.6 million new cases and 40 thousand deaths per year. Leishmania parasites may show distinct, species-specific patterns of virulence that lead to different clinical manifestations. It is well known that successive in vitro passages (SIVP) lead to the attenuation of virulence, but neither the metabolism nor the pathways involved in these processes are well understood. Herein, promastigotes of a virulent L. amazonensis strain recently isolated from mice was compared to SIVP derived and attenuated promastigotes, submitted to 10, 40, and 60 axenic passages and named R10, R40, and R60, respectively. In vitro assays and in vivo tests were performed to characterize and confirmed the attenuation profiles. A metabolomic fingerprint comparison of R0, R10, and R60 was performed by means of capillary electrophoresis, liquid and gas chromatography coupled to mass spectrometry. To validate the metabolomic data, qPCR for selected loci, flow cytometry to measure aPS exposure, sensitivity to antimony tartrate and ROS production assays were conducted. The 65 identified metabolites were clustered in biochemical categories and mapped in eight metabolic pathways: ABC transporters; fatty acid biosynthesis; glycine, serine and threonine metabolism; ß-alanine metabolism; glutathione metabolism; oxidative phosphorylation; glycerophospholipid metabolism and lysine degradation. The obtained metabolomic data correlated with previous proteomic findings of the SVIP parasites and the gene expression of 13 selected targets. Late SIVP cultures were more sensitive to SbIII produced more ROS and exposed less phosphatidylserine in their surface. The correspondent pathways were connected to build a biochemical map of the most significant alterations involved with the process of attenuation of L. amazonensis. Overall, the reported data pointed out to a very dynamic and continuous metabolic reprogramming process, accompanied by changes in energetic, lipid and redox metabolisms, membrane remodeling and reshaping of parasite-host cells interactions, causing impacts in chemotaxis, host inflammatory responses and infectivity at the early stages of infection.

Depression and anxiety among patients undergoing dialysis and kidney transplantation: a cross-sectional study.

BACKGROUND: Depression and anxiety are the most prevalent psychological disorders among end-stage renal disease patients and are associated with various conditions that result in poorer health outcomes, e.g. reduced quality of life and survival. We aimed to investigate the prevalences of depression and anxiety among patients undergoing renal replacement therapy. DESIGN AND SETTING: Cross-sectional study in Belo Horizonte, Brazil. METHODS: Patients' depression and anxiety levels were assessed using the Beck Inventory. The independent variables were the 36-Item Short-Form Health Survey (SF-36), Charlson Comorbidity Index and Global Subjective Assessment, along with sociodemographic and clinical characteristics. RESULTS: 205 patients were included. Depression and anxiety symptoms were detected in 41.7% and 32.3% of dialysis patients and 13.3% and 20.3% of transplantation patients, respectively. Lower SF-36 mental summary scores were associated with depression among transplantation patients (odds ratio, OR: 0.923; 95% confidence interval, CI: 0.85-0.99; P = 0.03) and dialysis patients (OR: 0.882; 95% CI: 0.83-0.93; P ≤ 0.001). Physical component summary was associated with depression among dialysis patients (OR: 0.906; 95% CI: 0.85-0.96; P = 0.001). Loss of vascular access (OR: 3.672; 95% CI: 1.05-12.78; P = 0.04), comorbidities (OR: 1.578; 95% CI: 1.09-2.27; P = 0.01) and poorer SF-36 mental (OR: 0.928; 95% CI: 0.88-0.97; P = 0.002) and physical (OR: 0.943; 95% CI: 0.89-0.99; P = 0.03) summary scores were associated with anxiety among -dialysis patients. CONCLUSIONS: Depression and anxiety symptoms occurred more frequently among patients undergoing dialysis. Quality of life, comorbidities and loss of vascular access were associated factors.

Qualidade de vida e sintomas de depressão e ansiedade de pacientes em terapia renal substitutiva em Belo Horizonte: uma coorte histórica / Qualidade de vida e sintomas de depressão e ansiedade de pacientes em terapia renal substitutiva em Belo Horizonte: uma coorte histórica

Introdução: depressão e ansiedade são os transtornos mentais mais prevalentes em pacientes com falência renal crônica. Eles interferem negativamente na qualidade de vida e sobrevida, sendo o tempo e o tipo de terapia renal substitutiva importantes fatores de risco. Objetivo: avaliar a qualidade de vida, os sintomas de depressão e ansiedade e a sobrevida em uma coorte de pacientes com falência renal crônica em diálise. Desenho do estudo: estudo longitudinal com análises de dados transversais. População: pacientes de 18 anos ou mais que iniciaram diálise entre 1º de janeiro de 2006 e 1º de janeiro de 2008 em dez serviços de diálise conveniados com o SUS em Belo Horizonte, Minas Gerais. Foram elegíveis para o estudo os pacientes com no mínimo três meses de tratamento, sem histórico de realização de transplante e que concordaram em participar da pesquisa. Métodos: a coleta de dados ocorreu em dois momentos: linha de base (tempo 1) e após dez anos de seguimento (tempo 2). Todos os pacientes incluídos no tempo 1 foram novamente convidados a participar das entrevistas no tempo 2. Aqueles que recusaram, recuperaram a função renal ou que foram transferidos para acompanhamento em outra cidade foram excluídos do seguimento. Em ambos os tempos, foram coletadas informações sociodemográficas, clínicas, nutricionais, de hábitos e qualidade de vida. Dados sobre depressão e ansiedade foram coletados apenas no tempo 2. Os instrumentos utilizados foram: 36 Item Short Form Health Survey (SF 36), Inventários Beck de Depressão e Ansiedade, Avaliação Global Subjetiva e Índice de Comorbidade de Charlson. Para a análise estatística foram utilizados modelos de regressão logística multivariada e regressão linear múltipla para avaliar os fatores de risco associados aos sintomas de depressão e ansiedade e à mudança da qualidade de vida entre os tempos 1 e 2, respectivamente. Também foram utilizados modelos de riscos proporcionais univariados e multivariados de Cox para avaliar aqueles associados à mortalidade. Resultados: 712 pacientes iniciaram o estudo e apenas 205 foram novamente entrevistados no tempo 2. A amostra total apresentou idade média de 53,9±15,2, tendo sido 301 (42,3%) pertencentes ao sexo feminino e 418 (59,1%) com nível fundamental de escolaridade. No tempo 2, foram detectados sintomas de depressão e ansiedade, respectivamente, em 77 (41,7%) e 41 (32,3%) dos pacientes em diálise, e em 10 (13,3%) e 15 (20,3%) dos pacientes transplantados. Menores escores no componente mental do SF--36 foram associados à depressão nos pacientes transplantados (p=0,03) e nos em diálise (p=0,001). Menores escores no componente físico foram associados à depressão apenas nos pacientes em diálise (p=0,001). As variáveis associadas à ansiedade em pacientes em diálise foram perda do acesso vascular (p=0,04), comorbidades (p=0,01) e piores escores nos componentes mental (p=0,001) e físico (p=0,02). A qualidade de vida dos 205 pacientes sobreviventes foi comparada segundo três grupos de acordo com as mudanças dos pacientes no seguimento: 113 (diálise--diálise), 75 (diálise--transplante) e 17 (diálise--transplante--diálise). No tempo 1, apenas a idade foi significativamente diferente entre os grupos. No tempo 2, os pacientes transplantados mantiveram maior participação social, retenção de emprego e melhora nos escores do SF--36. Os fatores associados à mudança na qualidade de vida foram maior tempo em diálise, que interferiu negativamente na capacidade funcional (p=0,002), limitações por aspectos físicos (p=0,002), estado geral de saúde (p=0,007), aspectos sociais (p=0,02), aspectos emocionais (p=0,003) e componente físico (p=0,002); a não participação em grupos sociais nos tempos 1 e 2, que reduziu os escores vitalidade (p=0,02); ter trabalho no tempo 2, que aumentou os escores de vitalidade (p=0,02) e saúde mental (p=0,02). Ao final dos 9 anos de seguimento, 444 (62,3%) pacientes morreram durante o estudo. Não ser casado ou não ter companheiro estável (p=0,04), baixa frequência em atividades de lazer (p=0,04) e não ser transplantado (p<0,001) permaneceram independentemente associados à mortalidade após cinco anos de seguimento. E não ser casado ou não ter companheiro estável (p=0.03), não ser transplantado (p<0,001) e pior estado nutricional (p=0,04) permaneceram independentemente associados ao aumento da mortalidade ao final de 9 anos de seguimento, enquanto alto nível de escolaridade (p=0,03) e melhores escores no domínio funcionamento físico do SF--36 (p=0,007) foram fatores protetivos associados à sobrevida. Conclusão: os sintomas de depressão e ansiedade foram mais frequentes em pacientes submetidos à diálise. A qualidade de vida mostrou--se dinâmica ao longo dos anos de terapia renal substitutiva, e, dentre os tratamentos, o transplante apresentou mais benefícios ao paciente. E a sobrevida do paciente com falência renal crônica foi associada a um amplo conjunto de fatores que não se limitam apenas ao espectro clínico, estando os hábitos, a qualidade de vida e as características sociais como fatores protetivos à saúde

Background: depression and anxiety are the most prevalent disorders kideny failure chronic patients, providing a negative effect on morbidity and mortality, as well as quality of life and survival, leaving the time and type of renal replacement therapy as important risk factors. Objective: to evaluate the quality of life, depression, anxiety and survival in a cohort of patients with chronic kidney disease on dialysis. Study design: longitudinal study, with transversal data analysis. Population: the initial cohort included all patients aged 18 years or older, who started dialysis between January 1st, 2006 and January 1st, 2008, from ten dialysis services of the Brazilian public health system, in the city of Belo Horizonte, Minas Gerais, Brazil. The patients eligible for the study had least three months of treatment and no history of transplantation, and who agreed to participate in this research. Methods: the data collection in two distinct moments: baseline (time 1) and after 10 years of follow-up (time 2). All patients included in time 1 were again invited to participate in the interviews in time 2. Those who refused, recovered renal function or transferred to another city were excluded from follow-up. In both times, sociodemographic, clinical, nutritional, life habits and quality of life data were collected. Data on depression and anxiety were inserted only at time 2. The instruments used were: 36 Item Short-Form Health Survey (SF-36), Beck Inventories of Depression and Anxiety, Subjective Global Assessment, and Charlson Comorbidity Index. Results: 712 patients started the study and only 205 were interviewed again in time 2. The total sample had a mean age of 53.9 ± 15.2, of which 301 (42.3%) were females and 418 (59.1%) with only a fundamental level of schooling. In time 2, symptoms of depression were detected in 77 (41,7%) of dialysis patients and 10 (13,3%) of transplant patients, and anxiety was detected in 41 (32,3%) and 15 (20,3%) of dialysis and transplant patients, respectively. Lower SF-36 mental component scores were associated with depression in transplant (p=0,03) and dialysis patients (p=0,001), whereas physical component scores were associated with depression in dialysis patients only (p=0,001). Variables associated with anxiety in dialysis patients were loss of vascular access (p=0,04), comorbidities (p=0,01), and poorer SF-36 mental (p=0,001) and physical (p=0,02) component scores. For the evaluation of quality of life, the 205 surviving patients were allocated into three groups: 113 (dialysis-dialysis), 75 (dialysistransplantation) and 17 (dialysis-transplantation-dialysis). At time 1, only age was significantly different among groups; at time 2, transplant patients sustained greater social participation, job retention, and improvement in SF-36 scores. The factors associated with change in quality of life were more time on dialysis interfering negatively on physical functioning (P=0,002), role-physical limitations (p=0.002), general health (p=0,007), social functioning (p=0,02), role-emotional (p=0,003) and physical components (p=0,002); non-participation in social groups at times 1 and 2 reducing vitality (p=0,02) scores; and having work at time 2, increasing vitality (p=0,02) and mental health (p=0,02) scores. At the end of the 9- year follow-up, 444 (62.3%) patients died during the study. Not being married or not having a stable partner (p=0.04), low frequency in leisure activities (p=0.04) and not being transplanted (p

Potent stimulation of eosinopoiesis in murine bone-marrow by myriadenolide is mediated by cysteinyl-leukotriene signaling.

We describe the potent effect of myriadenolide (Myr), a naturally occurring labdane diterpene, in promoting the production of eosinophils in cultured bone-marrow from several inbred mouse strains. This enhancing effect is lineage-selective and requires the eosinophil growth factors, Interleukin(IL)-5 or GM-CSF. Myr acts over a very low concentration range (10-10-10-14 M), if added at the beginning of the cell cultivation. Its enhancing effect increases between 24 h and 10 days of culture. We used both pharmacological and genetical tools to analyze its mechanism of action. Several lines of evidence show that the enhancing effect of Myr requires functional integrity of the 5-lipoxygenase (5-LO) pathway, and of CysLT1 receptors, which transduce the effects of cysteinyl-leukotrienes generated through this pathway. Myr also protects developing eosinophils from apoptosis induced by exogenous prostaglandin E2 (PGE2), but not by NO, indicating that it acts upstream of NO in the PGE2-initiated proapoptotic pathway which requires iNOS and CD95. Exposure to NO concentrations insufficient to induce apoptosis abolished the ability of eosinophils to respond to Myr, suggesting the involvement of a NO-sensitive cellular target. Myr has potential as a chemically defined research tool, which can be used to generate large numbers of eosinophils, thereby overcoming current limitations in the biochemical and molecular biological study of murine eosinophils, which has so far depended on complex, labor-intensive and long-term culture protocols for in vitro expansion. SUMMARY: Potent enhancing effects of Myr on eosinophil production in bone marrow stimulated by GM-CSF and IL-5 are mediated by the 5-LO pathway.