Prioritization criteria in policies and manage- ment of human resources for health: a proposal for a validated methodology / Criterios para la asignación de prioridades en materia de políticas y gestión de recursos humanos para la salud: propuesta de una metodología validada / Critérios de priorização em políticas e gerenciamento de recursos humanos em saúde: proposta para uma metodologia validada

[ABSTRACT]. Objective. To create and validate criteria for prioritizing problems related to policies and management of the health workforce. Methods. This methodological study was divided into three stages. First, the criteria were elaborated by means of a systematized literature review. Second, the criteria were evaluated online by a committee of judges comprised of eight specialists. In the third stage, an evaluation was carried out by the target audience in a hybrid workshop. The participants evaluated the material using the Suitability Assessment of Materials instrument, adapted for the research. Results. Three prioritization criteria (relevance, window of opportunity and acceptability) and a scoring scale were developed based on the literature review. In the evaluation by the committee of judges, the approval percentage of the criteria and prioritization method was 84%. Modifications were made based on suggestions in relation to the material presented to the specialists. In the pre-test stage, the approval percentage varied by item, with six of them reaching a maximum approval of 100% (corresponding to approximately 46% of the items), four reaching 92% and three achieving 83% each, indicating positive results. Conclusions. The developed criteria were considered valid for use in the context of policies and management in the area of human resources for health.

[RESUMEN]. Objetivo. Crear y validar criterios para priorizar los problemas relacionados con las políticas y la gestión de los recursos humanos para la salud. Métodos. Este estudio metodológico se dividió en tres etapas. En la primera se elaboraron los criterios mediante una revisión sistematizada de la bibliografía. En la segunda un comité de ocho especialistas evaluó en línea los criterios. Y la tercera consistió en una evaluación por parte del público destinatario en un taller híbrido. Los participantes evaluaron el material utilizando el instrumento de evaluación de la idoneidad de los materiales, que fue adaptado para la investigación. Resultados. Sobre la base de la revisión de la bibliografía, se elaboraron tres criterios para la asignación de prioridades (relevancia, ventana de oportunidad y aceptabilidad) y una escala de puntuación. En la evaluación realizada por el comité de especialistas, el porcentaje de aprobación de los criterios y del método de asignación de prioridades fue del 84%. Se realizaron modificaciones basadas en sugerencias planteadas con respecto al material presentado a los especialistas. En la etapa posterior de prueba preliminar, el porcentaje de aprobación varió en los distintos puntos, de tal manera que en seis puntos (es decir, en aproximadamente el 46% de los puntos) se alcanzó una aprobación máxima del 100%, en cuatro una aprobación del 92% y en tres una aprobación del 83% en cada uno, lo que indica unos resultados positivos. Conclusiones. Se consideró que los criterios elaborados son válidos para su uso en el contexto de las políticas y la gestión en el ámbito de los recursos humanos para la salud.

[RESUMO]. Objetivo. Criar e validar critérios para priorizar problemas relacionados a políticas e gerenciamento da força de trabalho em saúde. Métodos. O presente estudo metodológico foi dividido em três fases. Primeiro, foram elaborados critérios por meio de revisão sistematizada da literatura. A seguir, os critérios foram avaliados on-line por uma comissão de juízes composta por oito especialistas. Na terceira fase, o público-alvo fez uma avaliação dos critérios em uma oficina de formato híbrido. Os participantes avaliaram o material usando o instrumento Suitability Assessment of Materials, adaptado para esta pesquisa. Resultados. Com base na revisão da literatura, foram elaborados três critérios de priorização (relevância, janela de oportunidade e aceitabilidade) e uma escala de pontuação. Na avaliação da comissão de juízes, a porcentagem de aprovação dos critérios e do método de priorização foi de 84%. Foram feitas alterações com base em sugestões relacionadas ao material apresentado aos especialistas. Na fase de pré-teste, a porcentagem de aprovação variou de acordo com o item. Seis deles (aproximadamente 46% dos itens) atingiram aprovação máxima de 100%, quatro atingiram 92% e três atingiram 83%, indicando resultados positivos. Conclusões. Os critérios desenvolvidos foram considerados válidos para uso no contexto de políticas e ger- enciamento na área de recursos humanos em saúde.

Effects of cancer-induced cachexia and administration of L-glutathione on the intestinal mucosa in rat.

Walker-256 tumor is an experimental model known to promote cachexia syndrome, oxidative stress, and systemic inflammation. This study evaluated the duodenal mucosa of rats with Walker-256 tumor administered with 1% L-glutathione, intending to evaluate the damage caused by cancer-associated cachexia in the gastrointestinal tract and the effects of antioxidant administration on mucosal protection. Twenty-four 55-day-old male Wistar rats were distributed into four groups: control (C); control administered with 1% L-glutathione (C-GSH); Walker-256 tumor (W) and Walker-256 tumor administered with 1% L-glutathione (W-GSH). After 14 days of treatment, the duodenum was harvested for morphometric analysis of the mucosa, proliferation, apoptosis, immunostaining of varicosities immunoreactive (IR) to vasoactive intestinal peptide (VIP) and 5-HT-IR cells, and quantification of mast cells and goblet cells. Walker-256 tumor-bearing rats showed cachexia syndrome, mucosal atrophy, reduced cell proliferation, reduced 5-HT-IR cells, and increased goblet cells and VIPergic varicosities, which were not reversed by L-glutathione. On the other hand, L-glutathione caused a reduction of cells in apoptosis and mast cell recruitment, demonstrating a partial recovery of the damage detected in the intestinal mucosa.

The possible impacts of nano and microplastics on human health: lessons from experimental models across multiple organs.

The widespread production and use of plastics have resulted in accumulation of plastic debris in the environment, gradually breaking down into smaller particles over time. Nano-plastics (NPs) and microplastics (MPs), defined as particles smaller than 100 nanometers and 5 millimeters, respectively, raise concerns due to their ability to enter the human body through various pathways including ingestion, inhalation, and skin contact. Various investigators demonstrated that these particles may produce physical and chemical damage to human cells, tissues, and organs, disrupting cellular processes, triggering inflammation and oxidative stress, and impacting hormone and neurotransmitter balance. In addition, micro- and nano-plastics (MNPLs) may carry toxic chemicals and pathogens, exacerbating adverse effects on human health. The magnitude and nature of these effects are not yet fully understood, requiring further research for a comprehensive risk assessment. Nevertheless, evidence available suggests that accumulation of these particles in the environment and potential human uptake are causes for concern. Urgent measures to reduce plastic pollution and limit human exposure to MNPLs are necessary to safeguard human health and the environment. In this review, current knowledge regarding the influence of MNPLs on human health is summarized, including toxicity mechanisms, exposure pathways, and health outcomes across multiple organs. The critical need for additional research is also emphasized to comprehensively assess potential risks posed by degradation of MNPLs on human health and inform strategies for addressing this emerging environmental health challenge. Finally, new research directions are proposed including evaluation of gene regulation associated with MNPLs exposure.

Cancer-induced morphological changes in enteric glial cells in the jejunum of Walker-256 tumor-bearing rats.

Cancer-induced cachexia is associated with systemic inflammation and gastrointestinal dysfunction. How changes to cells of the enteric nervous system contribute to gut dysfunction in tumor development and cancer cachexia is unknown. Here, we tested the hypothesis that changes to enteric glia, a type of peripheral glia that surround enteric neurons and regulate gut homeostasis, are associated with tumor development and that supplementing with the antioxidant L-glutathione is protective against the changes induced. Immunohistochemistry for neurons, enteric glial cells and immune cells was performed in whole-mount preparations and frozen histological sections of the jejunum from 20 Wistar rats, distributed in 4 groups: control, tumor of Walker-256, control administered with 1 % L-glutathione, and tumor of Walker-256 administered with 1 % L-glutathione. Morphoquantitative analyses were made using Image-Pro® Plus 4.5 and ImageJ® 1.43° software. Tumor development significantly reduced neuronal and glial cell populations in the myenteric and submucosal plexuses and enlarged glial cell body area in the submucosal plexus. In contrast, tumors increased glia in the jejunal mucosa and this effect was accompanied by B-lymphocyte recruitment. GSH-supplemented diet was not sufficient to protect against changes to neurons and glia in the submucosal plexus but was partially protective in the myenteric plexus. L-glutathione had no effect on physiological parameters of cachexia but was sufficient to preserve enteric glial cell density in the myenteric plexus. These results suggest that changes to both enteric neurons and glia likely contribute to the gastrointestinal effects of tumor development and that oxidative stress contributes to these effects in the enteric nervous system.

[Respiratory changes in children exposed to dust from mining waste in Brumadinho, Minas Gerais State, Brazil: Bruminha Project]. / Alterações respiratórias em crianças expostas à poeira de resíduos de mineração em Brumadinho, Minas Gerais, Brasil: Projeto Bruminha.

This study aimed to investigate the occurrence of respiratory diseases in children exposed to dust from mining waste after the Brumadinho dam disaster, Minas Gerais State, Brazil. The study population included children aged 0-6 years, living in three communities exposed to mining waste dust (Córrego do Feijão, Parque da Cachoeira, and Tejuco) and one unexposed community (Aranha). Data were collected from July 19 to 30, 2021, using questionnaires that addressed sociodemographic information and a recall survey on signs, symptoms, and respiratory diseases. A total of 217 children were evaluated, 119 living in the exposed communities and 98 in the non-exposed community. The residents in the exposed communities reported an increase in the frequency of home cleaning (p = 0.04) and in vehicular traffic (p = 0.03). Among children aged four, a higher frequency of upper (p = 0.01) and lower (p = 0.01) airway disorders, as well as respiratory allergy (p = 0.05) was observed. The exposed group had 1.5 times more reports of respiratory allergy (75%; p = 0.02) compared to the non-exposed group (50.5%). Children living in communities exposed to waste dust were three times more likely (adjusted OR = 3.63; 95%CI: 1.37; 9.57) to have respiratory allergies than those not exposed. Two years and six months after the environmental disaster occurred, children living in the communities affected by waste from mining and remediation activities remained exposed to dust with harmful effects on respiratory health.

Este estudo teve como objetivo investigar a ocorrência de afecções respiratórias em crianças expostas à poeira de resíduos de mineração após o desastre do rompimento da barragem em Brumadinho, Minas Gerais, Brasil. A população de estudo incluiu crianças com idades entre 0 e 6 anos, residentes em três comunidades expostas à resíduos de poeira de mineração (Córrego do Feijão, Parque da Cachoeira e Tejuco) e uma comunidade não exposta (Aranha). A coleta de dados ocorreu entre 19 e 30 de julho de 2021, por meio de questionários que abordavam informações sociodemográficas e um inquérito recordatório sobre sinais, sintomas e doenças respiratórias. Foram avaliadas 217 crianças, sendo 119 das comunidades expostas e 98 da comunidade não exposta. Os residentes nas comunidades expostas relataram aumento na frequência de faxina em suas residências (p = 0,04) e no tráfego de veículos (p = 0,03). Entre as crianças de 4 anos, foi observada uma maior frequência de afecções das vias aéreas superiores (p = 0,01) e inferiores (p = 0,01), bem como de alergia respiratória (p = 0,05). O grupo exposto apresentou 1,5 vez mais relatos de alergia respiratória (75%; p = 0,02) em comparação com o não exposto (50,5%). Crianças que viviam nas comunidades expostas à poeira de resíduos apresentaram três vezes mais chance (OR ajustada = 3.63; IC95%: 1,37; 9,57) de ocorrência de alergia respiratória em comparação com as não expostas. Dois anos e seis meses após a ocorrência do desastre ambiental, as crianças das comunidades afetadas pelos resíduos das atividades de mineração e remediação permaneciam expostas à poeira com efeitos tóxicos sobre a saúde respiratória.

El objetivo de este estudio fue investigar la ocurrencia de enfermedades respiratorias en niños expuestos al polvo de residuos de la minería tras el desastre del colapso de la represa en Brumadinho, Minas Gerais, Brasil. La población de estudio incluyó niños que tenían entre 0 y 6 años, que viven en tres comunidades expuestas a residuos de polvo de la minería (Córrego do Feijão, Parque da Cachoeira y Tejuco) y una comunidad no expuesta (Aranha). Se recolectaron los datos entre el 19 y el 30 de julio de 2021, a través de cuestionarios que abordaban informaciones sociodemográficas y una encuesta recordatoria acerca de los señales, síntomas y enfermedades respiratorias. Se evaluaron 217 niños, de los cuales 119 viven en las comunidades expuestas y 98 viven en la comunidad no expuesta. Los residentes de las comunidades expuestas relataron un aumento en la frecuencia de limpieza de sus casas (p = 0,04) y en el tráfico de vehículos (p = 0,03). Entre los niños de 4 años, se observó una frecuencia más alta de enfermedades de las vías aéreas superiores (p = 0,01) e inferiores (p = 0,01), así como de alergia respiratoria (p = 0,05). El grupo expuesto presentó 1,5 veces más relatos de alergia respiratoria (el 75%; p = 0,02) en comparación con el grupo no expuesto (el 50,5%). Niños que vivían en las comunidades expuestas al polvo de residuos presentaron tres veces más probabilidad (OR ajustada = 3,63; IC95%: 1,37; 9,57) de ocurrencia de alergia respiratoria en comparación con los niños que no se expusieron. Dos años y seis meses tras el desastre ambiental, los niños que viven en las comunidades afectadas por los residuos de las actividades de minería y descontaminación permanecían expuestos al polvo con efectos tóxicos para la salud respiratoria.

Impacts for health and care workers of Covid-19 and other public health emergencies of international concern: living systematic review, meta-analysis and policy recommendations.

BACKGROUND: Health and care workers (HCW) faced the double burden of the SARS-CoV-2 pandemic: as members of a society affected by a public health emergency and as HWC who experienced fear of becoming infected and of infecting others, stigma, violence, increased workloads, changes in scope of practice, among others. To understand the short and long-term impacts in terms of the COVID-19 pandemic and other public health emergencies of international concern (PHEICs) on HCW and relevant interventions to address them, we designed and conducted a living systematic review (LSR). METHODS: We reviewed literature retrieved from MEDLINE-PubMed, Embase, SCOPUS, LILACS, the World Health Organization COVID-19 database, the ClinicalTrials.org and the ILO database, published from January 2000 until December 2021. We included quantitative observational studies, experimental studies, quasi-experimental, mixed methods or qualitative studies; addressing mental, physical health and well-being and quality of life. The review targeted HCW; and interventions and exposures, implemented during the COVID-19 pandemic or other PHEICs. To assess the risk of bias of included studies, we used the Johanna Briggs Institute (JBI) Critical Appraisal Tools. Data were qualitatively synthetized using meta-aggregation and meta-analysis was performed to estimate pooled prevalence of some of the outcomes. RESULTS: The 1013 studies included in the review were mainly quantitative research, cross-sectional, with medium risk of bias/quality, addressing at least one of the following: mental health issue, violence, physical health and well-being, and quality of life. Additionally, interventions to address short- and long-term impact of PHEICs on HCW included in the review, although scarce, were mainly behavioral and individual oriented, aimed at improving mental health through the development of individual interventions. A lack of interventions addressing organizational or systemic bottlenecks was noted. DISCUSSION: PHEICs impacted the mental and physical health of HCW with the greatest toll on mental health. The impact PHEICs are intricate and complex. The review revealed the consequences for health and care service delivery, with increased unplanned absenteeism, service disruption and occupation turnover that subvert the capacity to answer to the PHEICs, specifically challenging the resilience of health systems.

Testicular adrenal rest tumors - Epidemiology, diagnosis and treatment.

INTRODUCTION: Testicular adrenal rest tumors (TART) are common in males suffering from congenital adrenal hyperplasia (CAH). Correct and timely diagnosis is important for differential diagnosis with malignant testis tumors, related infertility and as TART may worsen in time, especially in the absence of adequate and continuous hormonal control. The rarity of the disease, predominance of small cohorts and case reports and research heterogeneity (concerning type of CAH, patients' age and specific focus of the paper) complicate the understanding of this condition. OBJECTIVES: To review epidemiological and clinical aspects of TART, including treatment and prognosis. METHODS: Non-systematic review of CAH-related TART research. RESULTS: TART's prevalence grows progressively over time, predominating after puberty, affecting a mean of 20-40 % of CAH males. There is no proof of more frequent proportional affection of specific CAH phenotypes or types of enzyme deficiency, but cases of TART among non-classic CAH patients have been rarely reported. Chronic undertreated are more frequently affected and present larger tumors. Systematic ultrasound screening of CAH males is the state-of-the art for diagnosis, but TART are still often diagnosed in CAH adults seeking infertility treatment. TART are usually asymptomatic and present normal testicular volume. Biopsies are not recommended, except when the differential diagnosis between TART and testicular tumors cannot be guaranteed. Abnormal semen analysis is common. Leydig cell tumors are the main differential diagnosis, due to histological similarities to TART. Misdiagnosis may lead to unnecessary orchiectomies. Preservation of gonadal functions is inversely proportional to the total tumor volume. Tumors tend to regress under adequate adrenal suppression with steroids. Surgery in not indicated to treat TART. DISCUSSION: The reported prevalence of TART depends on age, usage of systematic follow-up ultrasound, and adequate CAH control. Timely detection of the disease is important to avoid irreversible gonadal dysfunction (not clinically apparent, due to high serum levels of androgen) and infertility. The relationship between TART and specific CAH phenotypes/genotypes has not been proved, and some cases do not present abnormal serum ACTH levels. Knowledge about TART should be disseminated among non-experts, to avoid unnecessary orchiectomies and false diagnosis of malignant testis tumors. Infertility is frequent, but has not been not satisfactorily addressed by physicians, even among experts. Sperm cryopreservation should be early offered to CAH adult males, but there are offer problems related to high cost.

Alterações respiratórias em crianças expostas à poeira de resíduos de mineração em Brumadinho, Minas Gerais, Brasil: Projeto Bruminha / Respiratory changes in children exposed to dust from mining waste in Brumadinho, Minas Gerais State, Brazil: Bruminha Project / Alteraciones respiratorias en niños expuestos al polvo de residuos de la minería en Brumadinho, Minas Gerais, Brasil: Proyecto Bruminha

Este estudo teve como objetivo investigar a ocorrência de afecções respiratórias em crianças expostas à poeira de resíduos de mineração após o desastre do rompimento da barragem em Brumadinho, Minas Gerais, Brasil. A população de estudo incluiu crianças com idades entre 0 e 6 anos, residentes em três comunidades expostas à resíduos de poeira de mineração (Córrego do Feijão, Parque da Cachoeira e Tejuco) e uma comunidade não exposta (Aranha). A coleta de dados ocorreu entre 19 e 30 de julho de 2021, por meio de questionários que abordavam informações sociodemográficas e um inquérito recordatório sobre sinais, sintomas e doenças respiratórias. Foram avaliadas 217 crianças, sendo 119 das comunidades expostas e 98 da comunidade não exposta. Os residentes nas comunidades expostas relataram aumento na frequência de faxina em suas residências (p = 0,04) e no tráfego de veículos (p = 0,03). Entre as crianças de 4 anos, foi observada uma maior frequência de afecções das vias aéreas superiores (p = 0,01) e inferiores (p = 0,01), bem como de alergia respiratória (p = 0,05). O grupo exposto apresentou 1,5 vez mais relatos de alergia respiratória (75%; p = 0,02) em comparação com o não exposto (50,5%). Crianças que viviam nas comunidades expostas à poeira de resíduos apresentaram três vezes mais chance (OR ajustada = 3.63; IC95%: 1,37; 9,57) de ocorrência de alergia respiratória em comparação com as não expostas. Dois anos e seis meses após a ocorrência do desastre ambiental, as crianças das comunidades afetadas pelos resíduos das atividades de mineração e remediação permaneciam expostas à poeira com efeitos tóxicos sobre a saúde respiratória.

This study aimed to investigate the occurrence of respiratory diseases in children exposed to dust from mining waste after the Brumadinho dam disaster, Minas Gerais State, Brazil. The study population included children aged 0-6 years, living in three communities exposed to mining waste dust (Córrego do Feijão, Parque da Cachoeira, and Tejuco) and one unexposed community (Aranha). Data were collected from July 19 to 30, 2021, using questionnaires that addressed sociodemographic information and a recall survey on signs, symptoms, and respiratory diseases. A total of 217 children were evaluated, 119 living in the exposed communities and 98 in the non-exposed community. The residents in the exposed communities reported an increase in the frequency of home cleaning (p = 0.04) and in vehicular traffic (p = 0.03). Among children aged four, a higher frequency of upper (p = 0.01) and lower (p = 0.01) airway disorders, as well as respiratory allergy (p = 0.05) was observed. The exposed group had 1.5 times more reports of respiratory allergy (75%; p = 0.02) compared to the non-exposed group (50.5%). Children living in communities exposed to waste dust were three times more likely (adjusted OR = 3.63; 95%CI: 1.37; 9.57) to have respiratory allergies than those not exposed. Two years and six months after the environmental disaster occurred, children living in the communities affected by waste from mining and remediation activities remained exposed to dust with harmful effects on respiratory health.

El objetivo de este estudio fue investigar la ocurrencia de enfermedades respiratorias en niños expuestos al polvo de residuos de la minería tras el desastre del colapso de la represa en Brumadinho, Minas Gerais, Brasil. La población de estudio incluyó niños que tenían entre 0 y 6 años, que viven en tres comunidades expuestas a residuos de polvo de la minería (Córrego do Feijão, Parque da Cachoeira y Tejuco) y una comunidad no expuesta (Aranha). Se recolectaron los datos entre el 19 y el 30 de julio de 2021, a través de cuestionarios que abordaban informaciones sociodemográficas y una encuesta recordatoria acerca de los señales, síntomas y enfermedades respiratorias. Se evaluaron 217 niños, de los cuales 119 viven en las comunidades expuestas y 98 viven en la comunidad no expuesta. Los residentes de las comunidades expuestas relataron un aumento en la frecuencia de limpieza de sus casas (p = 0,04) y en el tráfico de vehículos (p = 0,03). Entre los niños de 4 años, se observó una frecuencia más alta de enfermedades de las vías aéreas superiores (p = 0,01) e inferiores (p = 0,01), así como de alergia respiratoria (p = 0,05). El grupo expuesto presentó 1,5 veces más relatos de alergia respiratoria (el 75%; p = 0,02) en comparación con el grupo no expuesto (el 50,5%). Niños que vivían en las comunidades expuestas al polvo de residuos presentaron tres veces más probabilidad (OR ajustada = 3,63; IC95%: 1,37; 9,57) de ocurrencia de alergia respiratoria en comparación con los niños que no se expusieron. Dos años y seis meses tras el desastre ambiental, los niños que viven en las comunidades afectadas por los residuos de las actividades de minería y descontaminación permanecían expuestos al polvo con efectos tóxicos para la salud respiratoria.

Severe Acute Liver Injury due to Secondary Hemophagocytic Lymphohistiocytosis: A Case Report.

Severe acute liver injury (ALI) is mostly triggered by viral infections and hepatotoxic drugs; however, it can also be seen in systemic diseases. Hemophagocytic lymphohistiocytosis (HLH) is a rare, immune-mediated syndrome that presents as a life-threatening inflammatory disorder affecting multiple organs. Secondary causes occur mainly in the set of malignancy, infection, and autoimmune disease, and are seldom triggered by vaccination. Although liver involvement is common, presentation as severe ALI is rare. We describe a case of a 65-year-old male with history of low-risk chronic lymphocytic leukemia and rheumatoid arthritis treated with prednisolone who presented with persistent fever and jaundice 1 week after COVID-19 vaccination. The diagnosis was challenging given the predominant liver impairment, characterized by hyperbilirubinemia, transaminases over 1,000 U/L, and prolonged INR, which prompted an extensive investigation and exclusion of autoimmune, toxic, and viral causes of hepatitis. Laboratory workup revealed bicytopenia, hyperferritinemia, which together with organ failure and evidence of hemophagocytosis in bone marrow suggested the diagnosis of HLH. After excluding infectious etiologies, flare of rheumatological disease, and the progression of hematological disease, HLH was diagnosed. He was successfully treated with etoposide and corticosteroids, with dramatic improvement of liver tests. After exclusion of other causes of secondary HLH, the recent vaccination for COVID-19 was the likely trigger. We report a case of double rarity of HLH, as it presented with severe liver dysfunction which was probably triggered by vaccination. In this case, the predominant liver involvement urged extensive investigation of liver disease, so a high index of suspicion was required to make an early diagnosis. Clinicians should consider HLH in patients with unexplained signs and symptoms of systemic inflammatory response and multiorgan involvement, including severe liver involvement as the first presentation.

A lesão hepática aguda (LHA) grave é desencadeada principalmente por infeções virais e hepatotóxicos; contudo, pode ocorrer em condições com envolvimento sistémico. A linfohistiocitose hemofagocítica (LHH) é uma síndrome inflamatória, rara, imunomediada, potencialmente fatal, que pode afetar múltiplos órgãos. A LHH secundária ocorre em contexto de neoplasias, infeções e doenças autoimunes, podendo raramente ser precipitada pela vacinação. Embora seja frequente o envolvimento hepático na LHH, a apresentação como LHA grave é rara. Os autores descrevem o caso de um homem de 65 anos com história de leucemia linfocítica crónica de baixo risco e artrite reumatóide sob prednisolona de 65 anos, que se apresentou com febre persistente e icterícia uma semana após a primeira dose da vacina COVID-19. O diagnóstico constituiu um desafio dado o envolvimento hepático predominante, caracterizado por hiperbilirrubinemia, transaminases acima de 1000 U/L e INR prolongado, o que condicionou uma extensa investigação e exclusão das causas autoimunes, tóxicas, e virais de doença hepática. A presença de bicitopenia e hiperferritinemia, conjuntamente com o desenvolvimento de falências de órgão e evidência de hemofagocitose na medula óssea sugeriram o diagnóstico de LHH. Após exclusão infeções, agudização da doença reumatológica e progressão da doença hematológica, foi feito o diagnóstico de LHH.O doente foi tratado com etoposido e corticosteróides com sucesso, verificando-se uma melhoria dramática das provas hepáticas. Após a exclusão de outras causas de LHH secundária, a recente vacinação foi assumida como provável fator desencadeante. Relatamos um caso raro de LHH, quer pela apresentação com lesão hepática grave, quer pela vacinação como presumível desencadeante. Neste caso, o envolvimento hepático predominante promoveu a uma investigação extensa da doença hepática, tendo sido necessário um elevado índice de suspeição para um diagnóstico atempado. Os médicos devem considerar o diagnóstico de LHH em doentes com sinais e sintomas de resposta inflamatória sistémica, inexplicados que se acompanham por disfunção multiorgânica, nomeadamente disfunção hepática grave como apresentação clínica.

L-glutathione 1% promotes neuroprotection of nitrergic neurons and reduces the oxidative stress in the jejunum of rats with Walker-256-bearing tumor.

AIMS: Our main goals were to investigate the effects of L-glutathione (1%) treatment in Walker-256 tumor-bearing rats by analyzing immunoreactive neurons (IR), responsive to the nNOS enzyme and 3-Nitrotyrosine, in their jejunum myenteric plexus. Moreover, the oxidative state and inflammatory process in these animals were investigated. METHODS: Four experimental groups were utilized: control (C), control treated with L-glutathione (CGT), Walker-256 tumor-bearing rats (TW), and Walker-256 tumor-bearing rats treated with L-glutathione (TWGT). After 14 days of tumor inoculation, the jejunum was collected for immunohistochemical techniques and assessment of oxidative status. Plasma was collected to evaluate oxidative status and measure cytokines. RESULTS: The TW group exhibited a decrease of reduced glutathione in their jejunum, which was prevented in the L-glutathione treated TWGT group. TW animals presented pronounced oxidative stress by increasing levels of lipoperoxidation in their jejunum and malondialdehyde in their plasma; however, the L-glutathione treatment in TWGT group was not able to avoid it. The total antioxidant capacity was altered in groups TW and TWGT, yet the last one had a better index in their plasma. The IL-10, and TNF-α levels increased in TWGT animals. The nNOS-IR neuron density decreased in the jejunum myenteric plexus of the TW group, which was avoided in the TWGT group. The nNOS +3-Nitrotyrosine neurons quantification did not show significative alterations. CONCLUSION: The treatment with L-glutathione (1%) imposed an important defense to some parameters of oxidative stress induced by TW-256, leading to neuroprotection to the loss in the nNOS-IR neuron density.

Severe Hypercholesterolemia Mediated by Lipoprotein X in an Immunosuppressed Patient: A Case Report.

Cholestatic liver diseases may be associated with increased plasmatic cholesterol due to an abnormal lipoprotein - lipoprotein X (LpX). Correcting the underlying cause of cholestasis is the critical treatment of LpX-associated hypercholesterolemia without any proven benefit from conventional lipid-lowering agents. In some situations, plasma exchange may apply to prevent associated complications, such as hyperviscosity syndrome. The authors present the case of a 44-year-old man with orbital inflammatory pseudotumor on prednisolone, admitted due to hepatocellular and cholestatic lesion and severe hypercholesterolemia. Laboratory investigation established that hepatitis E virus was responsible for liver injury and showed that LpX mediated the severe hypercholesterolemia. Reduction of the immunosuppressive load contributed to virus clearance. The consequent resolution of cholestasis and cholesterol removal by plasmapheresis allowed lipid profile normalization. The authors report the first case of LpX-associated hypercholesterolemia in a patient with hepatitis E-induced cholestasis and revisit the role of the liver in lipid metabolism.

As doenças hepáticas colestáticas podem associar-se a um aumento do colesterol à custa de uma lipoproteína anómala, a lipoproteína X (LpX). Os agentes hipolipemiantes convencionais não apresentam benefício nesta entidade, pelo que o tratamento da hipercolesterolemia associada de LpX baseia-se na correção da causa subjacente da colestase. A plasmaferese pode ser necessária para evitar complicações, como a síndrome de hiperviscosidade. Os autores apresentam o caso de um homem de 44 anos com antecedentes de pseudotumor inflamatório da órbita sob prednisolona, admitido por lesão hepatocelular e colestática e hipercolesterolemia grave. A investigação laboratorial permitiu estabelecer a hepatite E aguda como responsável da lesão hepática e mostrou que a hipercolesterolemia grave foi mediada pela LpX. A redução da carga imunossupressora facilitou a eliminação do vírus da hepatite E. A consequente resolução da colestase coadjuvada pela remoção de colesterol por plasmaferese, permitiu a normalização mantida do perfil lipídico. Os autores relatam o primeiro caso de hipercolesterolemia associada a LpX em contexto de colestase induzida pelo vírus da hepatite E, e revisitam a importância do fígado no metabolismo dos lípidos.

The Importance of Ultrasonography in the Evaluation of Mammary Tumors in Bitches.

The high incidence of mammary tumors in small animals is concerning. Patient history, clinical examination, physical evaluation, and imaging studies are important for clinical staging. Ultrasonography is commonly applied to investigate the presence of abdominal metastasis. However, it has been shown to provide important information regarding mammary tumors' architecture and advanced sonographic techniques can provide information regarding neovascularization, stiffness, and perfusion. Different techniques have been investigated to determine accuracy to predict the lesions' histological classification. This paper reviews the information regarding each sonographic technique in the evaluation of mammary tumors, describing the most common findings and their potential to accurately assess and predict malignancy. Even though the gold standard for the diagnosis of mammary lesions is the histopathological examination, some ultrasonographic features described can predict the potential of a lesion being malignant. Among the different sonographic techniques, elastography can be considered the most reliable modality to accurately differentiate benign from malignant tumors when malignant lesions present increased stiffness. However, the combination of all sonographic techniques can provide important information that can lead to a better therapeutic approach and clinical staging. Furthermore, the potential of the sonographic study, especially CEUS to monitor therapeutic progression, demonstrate the need of further studies.

Effects of different doses of ionizing radiation on alveolar bone repair in post-extraction tooth socket: an experimental study in rats.

OBJECTIVE: This study aimed to evaluate the dose-response effects of ionizing radiation (IR) on alveolar bone repair and bone strength after tooth extraction. MATERIALS AND METHODS: A total of 32 male Wistar rats were used in the study, 28 animals were included in the final analysis, and n = 7 for each experimental group. Mandibular first molars were extracted. After 7 days, the animals were randomly divided into four groups according to single-dose irradiation: NIr, control group; Ir15, irradiated at 15 Gy; Ir20, irradiated at 20 Gy; and Ir30, irradiated at 30 Gy. The tooth extraction sites were subjected to micro-computed tomography (micro-CT), histological, histomorphometric, and biomechanical analyses 14 days after extraction. Data were analyzed using one-way ANOVA followed by Tukey's post hoc test (α = 0.05). RESULTS: Micro-CT analysis revealed that IR led to lower values of bone volume (BV, in mm3) (0.68 ± 0.08, P < 0.001) and bone volume fraction, ratio of the segmented bone volume to the total volume of the region of interest (BV/TV, in %) (44.1 ± 8.3, P < 0.001) for the Ir30 group compared to the control group. A significantly lower amount of newly formed bone was observed in the Ir30 (P = 0.005) than in the Ir15 group. The histomorphometric results of quantification of bone matrix neoformation and the micro-CT were in agreement, demonstrating greater damage to the Ir30 group. IR30 cells showed a lower percentage of densely packed collagen than control cells. No significant differences were found in the biomechanical parameters. CONCLUSION: IR affects alveolar bone repair. A dose of 30 Gy reduced the bone healing process owing to a smaller amount of newly formed bone and a lower percentage of densely packed collagen. Therefore, a dose of 30 Gy can be used to successfully establish an animal model of an irradiated mandible that mimics the irradiated clinical conditions. CLINICAL RELEVANCE: Radiotherapy can lead to severe side effects and tooth extraction is a major risk factor. A proper understanding of the pathological mechanisms of radiation in alveolar bone repair requires the establishment of a suitable animal model of clinical conditions.

Policies and Management Interventions to Enhance Health and Care Workforce Capacity for Addressing the COVID-19 Pandemic: Protocol for a Living Systematic Review.

BACKGROUND: Countries and health systems have had to make challenging resource allocation and capacity-building decisions to promote proper patient care and ensure health and care workers' safety and well-being, so that they can effectively address the present COVID-19 pandemic as well as upcoming public health problems and natural catastrophes. As innovations are already in place and updated evidence is published daily, more information is required to inform the development and implementation of policies and interventions to improve health and care workforce capacity to address the COVID-19 pandemic response. OBJECTIVE: The objective of this protocol review is to identify countries' range of experiences with policies and management interventions that can improve health and care workers' capacity to address the COVID-19 pandemic response and synthesize evidence on the effectiveness of the interventions. METHODS: We will conduct a living systematic review of quantitative, qualitative, and mixed methods studies and gray literature (technical and political documents) published in English, French, Hindi, Portuguese, Italian, and Spanish between January 1, 2000, and March 1, 2022. The databases to be searched are MEDLINE (PubMed), Embase, SCOPUS, and Latin American and Caribbean Health Sciences Literature. In addition, the World Health Organization's COVID-19 Research Database and the websites of international organizations (International Labour Organization, Economic Co-operation and Development, and The Health System Response Monitor) will be searched for unpublished studies and gray literature. Data will be extracted from the selected documents using an electronic form adapted from the Joanna Briggs Institute quantitative and qualitative tools for data extraction. A convergent integrated approach to synthesis and integration will be used. The risk of bias will be assessed with Joanna Briggs Institute critical appraisal tools, and the certainty of the evidence in the presented outcomes will be assessed with the Grading of Recommendations, Assessment, Development and Evaluation. RESULTS: The database and gray literature search retrieved 3378 documents. Data are being analyzed by 2 independent reviewers. The study is expected to be published by the end of 2023 in a peer-reviewed journal. CONCLUSIONS: This review will allow us to identify and describe the policies and strategies implemented by countries and their effectiveness, as well as identify gaps in the evidence. TRIAL REGISTRATION: PROSPERO CRD42022327041; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=327041. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/50306.

Implementation of policy and management interventions to improve health and care workforce capacity to address the COVID-19 pandemic response: a systematic review.

BACKGROUND: The COVID-19 pandemic highlighted pre-existing weaknesses in health and care systems and services and shortages of health and care workers (HCWs). As a result, policymakers needed to adopt measures to improve the health and care workforce (HCWF) capacity. This review aims to identify countries' range of policies and management interventions implemented to improve HCWs' capacity to address the COVID-19 pandemic response, synthesize their evidence on effectiveness, and identify gaps in the evidence. METHODS: The literature was searched in PubMed, Embase, Scopus, LILACS-BVS, WHO's COVID-19 Research Database and the ILO, OECD and HSRM websites for literature and documents published between January 2020 and March 2022. Eligibility criteria were HCWs as participants and policy and management interventions aiming to improve HCWF capacity to address the COVID-19 pandemic response. Risk of bias was assessed with Joanna Briggs Institute (JBI) Critical Appraisal Tools (CAT) and certainty of the evidence in presented outcomes with GRADE. RESULTS: The searches retrieved 3378 documents. A total of 69 were included, but only 8 presented outcomes of interventions implemented. Most of the selected documents described at least one intervention implemented by countries at the organizational environment level to increase the flexibility and capacity of the HCWF to respond to the pandemic, followed by interventions to attract and retain HCWs in safe and decent working environments. There was a lack of studies addressing social protection, human resources for health information systems, and regarding the role of community health workers and other community-based providers. Regarding the risk of bias, most of documents were rated as medium or high quality (JBI's CAT), while the evidence presented for the outcomes of interventions was classified as mostly low-certainty evidence (GRADE). CONCLUSIONS: Countries have implemented various interventions, some innovative, in response to the pandemic, and others had their processes started earlier and accelerated by the pandemic. The evidence regarding the impact and efficacy of the strategies used by countries during the pandemic still requires further research.

Evaluation of Genistein as a Mitochondrial Modulator and Its Effects on Sperm Quality.

Phytoestrogens, such as isoflavones, are bioactive compounds found in plants with defense and protection functions. In the human body, they simulate the behavior of the hormone estradiol and can modulate the function of the male hypothalamic-pituitary-gonadal axis. This study aims to describe the effects of genistein on sperm quality of Wistar rats (male/adult) after a short oral administration protocol (50 mg/day, for 5 days), focusing on mitochondrial function. No signs of toxicity were observed in the animals during the period. The testicular mass of rats from the genistein-treated group was lower than that from the control group. Isoflavone increased the number of viable Leydig and Sertoli cells, spermatogonia, and primary spermatocytes in the treated group. The rounded spermatid count was similar to the control group, and a decrease in elongated spermatids was observed in the treated group. Genistein treatment increased plasma testosterone levels in the treated group. To the best of our knowledge, this is the first report of an in vivo short protocol demonstrating that genistein administration stimulates the overall oxygen consumption in rat seminal samples. Therefore, genistein induced a pro-spermatogenesis effect, enhanced plasma testosterone levels, and increased oxygen consumption, improving sperm mitochondrial efficiency. Similar protocols can be explored in animal and human infertility issues.

Cost-effectiveness of nivolumab and ipilimumab versus pembrolizumab and axitinib in advanced renal cell carcinoma with intermediate or poor prognostic risk: a Brazilian private healthcare system perspective.

OBJECTIVE: Nivolumab plus ipilimumab (NIVO + IPI) and pembrolizumab plus axitinib (PEM + AXI) have demonstrated significant clinical benefits as first-line (1 L) treatments for intermediate/poor-risk advanced renal cell carcinoma (aRCC) patients. This study aimed to assess the cost-effectiveness of NIVO + IPI versus PEM + AXI from a Brazilian private healthcare system perspective, utilizing a novel approach to estimate comparative efficacy between the treatments. METHODS: A three-state partitioned survival model (progression-free, progressed, and death) was developed to estimate costs, life-years (LYs), quality-adjusted LYs (QALYs), and the incremental cost-utility ratio (ICUR) over a 40-year time horizon. In the absence of head-to-head comparisons between NIVO + IPI and PEM + AXI, clinical data for NIVO + IPI was obtained from CheckMate 214 (NCT02231749) and for PEM + AXI from KEYNOTE-426 (NCT02853331). A matching-adjusted indirect comparison was conducted to account for the imbalance of treatment effect modifiers between the trials. Patient characteristics, resource use, health state utilities, and costs were based on Brazilian-specific sources. Costs and health outcomes were both discounted by 5% annually in line with Brazilian guidelines. The robustness of the results was evaluated through extensive sensitivity analysis and scenario analyses. RESULTS: When comparing the matched versus unmatched OS, PFS, and TTD curves there was no noteworthy difference. NIVO + IPI was associated with cost savings (R$ 350,232), higher LYs (5.54 vs. 4.61), and QALYs (4.74 vs. 3.76) versus PEM + AXI, resulting in NIVO + IPI dominating PEM + AXI. Key model drivers were the treatment duration for PEM, NIVO, and AXI. NIVO + IPI remained dominant in all scenario analyses, which indicated that model results were robust to alternative modelling inputs or assumptions. CONCLUSIONS: This analysis shows that NIVO + IPI is estimated to be a life-extending and potentially cost-saving 1 L treatment option when compared with PEM + AXI for intermediate/poor-risk a RCC patients in the Brazilian private healthcare system.

Development of a Proposal for a Program to Promote Positive Mental Health Literacy among Adolescents: A Focus Group Study.

Over the last years, there have been several studies that have shown insufficient levels of adolescents' mental health literacy (MHL). Knowledge about intervention programs that promote positive mental health literacy (PMeHL) among adolescents is still very scarce. In this sense, we defined as objectives to identify and describe the necessary components to design a program proposal that promotes adolescents' PMeHL. We conducted an exploratory, descriptive, qualitative study using two focus groups in July and September 2022 with an intentional non-probability sample of eleven participants (nine professional experts and two adolescents). Data were analyzed using content analysis, using NVivo® 12 software (version 12, QRS International: Daresbury Cheshire, UK). We obtained a total of four categories and eighteen subcategories: structure (context; format; contents; length and frequency; pedagogical methods; pedagogical techniques; resources; denomination), participants (target group; program facilitators), assessment (timing; evaluation instruments), other components (planning, articulation and adaptation; involvement; training; special situations; partnerships; referral). The perspectives of the professional experts and of the adolescents that we obtained from this study contributed to the design of a proposal for a program to promote adolescents' PMeHL.