Factors influencing the positivity of diagnostic tests for congenital syphilis.

OBJECTIVE: The objective of this study was to analyze the factors that influence the positivity of treponemal and non-treponemal tests in cases of congenital syphilis. METHODS: This cross-sectional and correlational study was carried out from the analysis of the database of Disease and Notification Information System (SINAN, in Portuguese) using the data obtained through the Epidemiological Surveillance Group 29, with 639 notifications of congenital syphilis between 2007 and 2018. The data were analyzed by a descriptive and inferential analysis from logistic regression with a significance level of 5% (p≤0.05). RESULTS: The positivity of the treponemal test was higher by 4.5 times in infants living in rural areas and 19.6 times among those whose mothers obtained the diagnosis of syphilis after birth. The treponemal test showed positivity 3.2 times higher for the variable "having been diagnosed between 2007 and 2015" and 5.5 times higher for the variable "having been diagnosed with maternal syphilis in the postpartum period." CONCLUSION: This study shows that testing during prenatal care is essential for early diagnosis and prevention of syphilis complications.

Renal control of life-threatening malarial anemia.

Iron recycling prevents the development of anemia under homeostatic conditions. Whether iron recycling was co-opted as a defense strategy to prevent the development of anemia in response to infection is unclear. We find that in severe Plasmodium falciparum malaria, the onset of life-threatening anemia is associated with acute kidney injury (AKI), irrespective of parasite load. Using a well-established experimental rodent model of malaria anemia, we identify a transcriptional response that endows renal proximal tubule epithelial cells (RPTECs) with the capacity to store and recycle iron during P. chabaudi chabaudi (Pcc) infection. This response encompasses the induction of ferroportin 1/SLC40A1, which exports iron from RPTECs and counteracts AKI while supporting compensatory erythropoiesis and preventing the onset of life-threatening malarial anemia. Iron recycling by myeloid cells is dispensable to this protective response, suggesting that RPTECs provide an iron-recycling salvage pathway that prevents the pathogenesis of life-threatening malarial anemia.

How to choose the appropriate cannulation technique for vascular access in hemodialysis patients.

The cannulation technique is important for the survival of the arteriovenous access. Choosing the appropriate technique is a complex decision. Such choice must be customized to patients, considering their characteristics, the type of arteriovenous access and the experience of the hemodialysis team. We describe seven items that can help nurses to identify the appropriate cannulation technique: type of arteriovenous access; drainage vein; hygienic self-care profile; experience of the nursing staff in the cannulation technique and nurse-to-patient ratio; hemodialysis treatment method; patient's condition; and patient's decision. Such items can help nurses in decision-making on the "ideal" cannulation technique for each patient.

Comparative analysis of oral and intravenous iron therapy in rat models of inflammatory anemia and iron deficiency.

Anemia is a major health issue and associated with increased morbidity. Iron deficiency anemia (IDA) is the most prevalent, followed by anemia of chronic disease (ACD). IDA and ACD often co-exist, challenging diagnosis and treatment. While iron supplementation is the first-line therapy for IDA, its optimal route of administration and the efficacy of different repletion strategies in ACD are elusive. Female Lewis rats were injected with group A streptococcal peptidoglycan-polysaccharide (PG-APS) to induce inflammatory arthritis with associated ACD and/or repeatedly phlebotomized and fed with a low iron diet to induce IDA, or a combination thereof (ACD/IDA). Iron was either supplemented by daily oral gavage of ferric maltol or by weekly intravenous (i.v.) injection of ferric carboxymaltose for up to 4 weeks. While both strategies reversed IDA, they remained ineffective to improve hemoglobin (Hb) levels in ACD, although oral iron showed slight amelioration of various erythropoiesis-associated parameters. In contrast, both iron treatments significantly increased Hb in ACD/IDA. In ACD and ACD/IDA animals, i.v. iron administration resulted in iron trapping in liver and splenic macrophages, induction of ferritin expression and increased circulating levels of the iron hormone hepcidin and the inflammatory cytokine interleukin-6, while oral iron supplementation reduced interleukin-6 levels. Thus, oral and i.v. iron resulted in divergent effects on systemic and tissue iron homeostasis and inflammation. Our results indicate that both iron supplements improve Hb in ACD/IDA, but are ineffective in ACD with pronounced inflammation, and that under the latter condition, i.v. iron is trapped in macrophages and may enhance inflammation.

O sexting no Brasil: a percepção sobre mensagens sexuais / Sexting en Brasil: la percepción sobre los mensajes sexuales / Sexting in Brazil: the perception about sexual messages

RESUMO. O sexting é uma prática cada vez mais frequente na sociedade atual, mas ainda há poucos estudos sobre como os brasileiros veem a troca de mensagens sexuais. O objetivo desse estudo foi investigar a percepção de brasileiros acerca do sexting e fornecer um panorama de como o fenômeno ocorre na realidade brasileira. Foi realizado um survey online com perguntas discursivas com 41 participantes sobre a dinâmica da prática e foi utilizada a análise de conteúdo para tratamento dos dados. Os resultados revelaram que algumas visões sociais são permeadas por estereótipos, como se observa em pesquisas de outros países. O sexting ainda é em muitos momentos confundido com diferentes formas de violência, apesar de estar sendo naturalizado no país e de já ser parte da experiência sexual cotidiana de muitas pessoas. Evidenciou-se que a educação sexual no contexto digital se faz necessária para que as pessoas compreendam seus direitos e reconheçam as diferenças entre sexting saudável e violências possivelmente atreladas à prática.

RESUMEN. El sexting es una práctica cada vez más frecuente en la sociedad actual, pero todavía hay pocos estudios sobre cómo algunos brasileños ven los mensajes sexuales. El objetivo de este estudio fue investigar la percepción de los brasileños sobre el sexting y proporcionar una visión general de cómo se produce el fenómeno en la realidad brasileña. Se realizó un survey online con preguntas discursivas con 41 participantes sobre la dinámica de la práctica y se utilizó el análisis de contenido para el tratamiento de datos. Los resultados revelaron que algunos puntos de vista sociales están impregnados de estereotipos, como se observó en investigaciones de otros países. El sexting aún se confunde con diferentes formas de violencia, a pesar de estar naturalizado en el país y ya es parte de la experiencia sexual diaria de muchas personas. Se hizo evidente que la educación sexual en el contexto digital es necesaria para que las personas entiendan sus derechos y reconozcan las diferencias entre el sexting saludable y la violencia posiblemente vinculada a la práctica.

ABSTRACT. Sexting is an increasingly frequent practice in today's society, but there are still few studies about the perceptions of Brazilians about sexual messages. The aim of this study was to investigate the perception of some Brazilians about sexting and provide an overview of the characteristics of the phenomenon in the Brazilian reality. An online survey was conducted with discursive questions with 41 participants about the dynamics of the practice and content analysis was used for data treatment. The results revealed that some social views are permeated by stereotypes, as observed in research from other countries. Sexting is still often confused with different forms of violence, despite being naturalized around the country and already being part of the daily sexual experience of many people. It became evident that sex education in the digital context is necessary for people to understand their rights and recognize the differences between healthy sexting practice and violence possibly linked to the messages.

Gestão unificada dos prontuários como ferramenta de gestão em Centro Pós-COVID / Unified management of medical records as a management tool in a post-COVID center / Gestión unificada de históriasclínicas como herramienta de gestión en un centro post-COVID

Objetivo: Relatar a experiência dos integrantes do PET-Saúde Gestão e Assistência na implantação da gestão unificada de prontuários em Centro Tratamento Pós-Covid no interior baiano. Método:Trata-se de um relato de experiência sobre a vivência do grupo tutorial GT05 do PET-Saúde da Universidade Estadual de Feira de Santana no centro especializado no período de agosto de 2022 a julho de 2023. Resultados:As atividades de organização e unificação dos prontuários ocorreram entre maio a julho de 2023, sendo organizados 1.481 fichas de atendimentos em pastas, com codificação numérica de A01 ao Z006, correspondente às letras alfabéticas de A a Z, não sendo possível a conclusão, pelo término das atividades do programa no cenário de prática. Os recepcionistas e coordenação do serviço acompanharam as atividades de codificação numérica das fichas para darem sequência à organização, sendo disponibilizado o arquivo com banco de dados dos usuários. Conclusão:A experiência da gestão unificada dos prontuários, possibilitou aos integrantes uma reflexão sobre as ferramentas de gestão e a importância do conhecimento do serviço para a implementação de propostas resolutivas que contribuam para a organização da gestão em saúde, facilitando o trabalho da equipe multidisciplinar e possibilitando a visão ampliada dos processos de trabalho

Objective: To report the experience of the members of the PET-Saúde Gestão e Assistência in the implementation of the unified management of medical records in a Post-Covid Treatment Center in the interior of Bahia. Method:This is an experience report on the experience of the tutorial group GT05 of PET-Saúde at the State University of Feira de Santana in the specialized center from August 2022 to July 2023. Results:The organization and unification activities of the medical records took place between May and July 2023, with 1.481 attendance sheets being organized in folders, with numerical coding from A01 to Z006, corresponding to the alphabetic letters from A to Z, and it was not possible to conclude, due to the end of the program's activities in the scenario of practice. The receptionists and service coordination followed the numerical coding activities of the forms to continue the organization, and the file with the users' database was made available. Conclusion: The experience of unified management of medical records allowed the membersto reflect on the management tools and the importance of knowledge of the service for the implementation of resolution proposals that contribute to the organization of health management, facilitating the work of the multidisciplinary team and enabling a broader view of work processes.

Objetivo: Informar la experiencia de los integrantes del PET-Saúde Gestão e Assistência en la implementación de la gestión unificada de registros médicos en un Centro de Tratamiento Post-Covid en el interior de Bahia. Método: Se trata de un relato de experiencia sobre la experiencia del grupo tutorial GT05 del PET-Saúde en la Universidad Estadual de Feira de Santana en el centro especializado de agosto de 2022 a julio de 2023. Resultados:Las actividades de organización y unificación de las historias clínicas tomaron lugar entre mayo y julio de 2023, con 1.481 hojas de asistencia organizadas en carpetas, con codificación numérica de A01 a Z006, correspondientes a las letras del alfabeto de la A a la Z, y no fue posible concluir, por la finalización de las actividades del programa en el escenario de la práctica. Las recepcionistas y la coordinación del servicio siguieron las actividades de codificación numérica de los formularios para continuar con la organización, y se dispuso el archivo con la base de datos de los usuarios. Conclusión:La experiencia de gestión unificada de prontuarios permitió a los integrantes reflexionar sobre las herramientas de gestión y la importancia del conocimiento del servicio para la implementación de propuestas de resolución que contribuyan a la organización de la gestión en salud, facilitando el trabajo del equipo multidisciplinario y permitiendo una visión más amplia de los procesos de trabajo.

Effects of drought on grassland phenology depend on functional types.

Shifts in flowering phenology are important indicators of climate change. However, the role of precipitation in driving phenology is far less understood compared with other environmental cues, such as temperature. We use a precipitation reduction gradient to test the direction and magnitude of effects on reproductive phenology and reproduction across 11 plant species in a temperate grassland, a moisture-limited ecosystem. Our experiment was conducted in a single, relatively wet year. We examine the effects of precipitation for species, functional types, and the community. Our results provide evidence that reduced precipitation shifts phenology, alters flower and fruit production, and that the magnitude and direction of the responses depend on functional type and species. For example, early-blooming species shift toward earlier flowering, whereas later-blooming species shift toward later flowering. Because of opposing species-level shifts, there is no overall shift in community-level phenology. This study provides experimental evidence that changes in rainfall can drive phenological shifts. Our results additionally highlight the importance of understanding how plant functional types govern responses to changing climate conditions, which is relevant for forecasting phenology and community-level changes. Specifically, the implications of divergent phenological shifts between early- and late-flowering species include resource scarcity for pollinators and seed dispersers and new temporal windows for invasion.

Mitochondrial Respiration in Response to Iron Deficiency Anemia: Comparison of Peripheral Blood Mononuclear Cells and Liver.

Iron is an essential component for metabolic processes, including oxygen transport within hemoglobin, tricarboxylic acid (TCA) cycle activity, and mitochondrial energy transformation. Iron deficiency can thus lead to metabolic dysfunction and eventually result in iron deficiency anemia (IDA), which affects approximately 1.5 billion people worldwide. Using a rat model of IDA induced by phlebotomy, we studied the effects of IDA on mitochondrial respiration in peripheral blood mononuclear cells (PBMCs) and the liver. Furthermore, we evaluated whether the mitochondrial function evaluated by high-resolution respirometry in PBMCs reflects corresponding alterations in the liver. Surprisingly, mitochondrial respiratory capacity was increased in PBMCs from rats with IDA compared to the controls. In contrast, mitochondrial respiration remained unaffected in livers from IDA rats. Of note, citrate synthase activity indicated an increased mitochondrial density in PBMCs, whereas it remained unchanged in the liver, partly explaining the different responses of mitochondrial respiration in PBMCs and the liver. Taken together, these results indicate that mitochondrial function determined in PBMCs cannot serve as a valid surrogate for respiration in the liver. Metabolic adaptions to iron deficiency resulted in different metabolic reprogramming in the blood cells and liver tissue.

Precipitation effects on grassland plant performance are lessened by hay harvest.

Climate and human management, such as hay harvest, shape grasslands. With both disturbances co-occurring, understanding how these ecosystems respond to these combined drivers may aid in projecting future changes in grasslands. We used an experimental precipitation gradient combined with mimicked acute hay harvest (clipping once a year) to examine (1) whether hay harvest influences precipitation effects on plant performance (cover and height) and (2) the role of inter-specific responses in influencing plant performance. We found that hay harvest reduced the strength of precipitation effects on plant performance through changes in bare-ground soil cover. Species performance were mainly influenced by change in abiotic factors, often responding negatively, as hay harvest increased bare-ground amount. Conversely, altered precipitation without hay harvest promoted plant species performance through abiotic factors change first, followed by biotic. Most species, including the dominant grass Schizachyrium scoparium, increased their performance with greater leaf area index (proxy for canopy structure). Our experiment demonstrates that plant performance responds directly to abiotic factors with hay harvest, but indirectly without hay harvest. Positive effects of increasing precipitation were likely due to microhabitat amelioration and resource acquisition, thus inclusion of hay harvest as a disturbance lessens positive impacts of biotic variables on species performance to climate change.

Effects of demographic and clinical character on differences in self-care behavior levels with arteriovenous fistula by hemodialysis patients: An ordinal logistic regression approach.

INTRODUCTION: Hemodialysis (HD) patients should be trained to develop self-care behaviors in order to prevent and preserve their arteriovenous fistula (AVF). The aim of this study was identifying the factors that affect the levels of self-care behavior with AVF by HD patients. METHODS: A cross-sectional study was conducted involving 89 patients. RESULTS: Self-care levels were negatively affected by patients' location (Azores) and positively affected by marital status, education, employment, AVF duration, and absence of complications with the AVF. Concerning the management of signs and symptoms, self-care levels were negatively affected by patients' location. Regarding prevention of complications, self-care levels were negatively affected by age and marital status and positively affected by marital status, employment, chronic kidney disease etiology, AVF duration, and previous AVF. CONCLUSION: Further studies are required in order to confirm whether the considered factors affect levels of self-care behaviors with AVF, or whether other factors are needed as well.

Fire promotes functional plant diversity and modifies soil carbon dynamics in tropical savanna.

Fire is an evolutionary environmental filter in tropical savanna ecosystems altering functional diversity and associated C pools in the biosphere and fluxes between the atmosphere and biosphere. Therefore, alterations in fire regimes (e.g. fire exclusion) will strongly influence ecosystem processes and associated dynamics. In those ecosystems C dynamics and functions are underestimated by the fire-induced offset between C output and input. To determine how fire shapes ecosystem C pools and fluxes in an open savanna across recently burned and fire excluded areas, we measured the following metrics: (I) plant diversity including taxonomic (i.e. richness, evenness) and plant functional diversity (i.e. functional diversity, functional richness, functional dispersion and community weighted means); (II) structure (i.e. above- and below-ground biomass, litter accumulation); and (III) functions related to C balance (i.e. net ecosystem carbon dioxide (CO2) exchange (NEE), ecosystem transpiration (ET), soil respiration (soil CO2 efflux), ecosystem water use efficiency (eWUE) and total soil organic C (SOC). We found that fire promoted aboveground live and belowground biomass, including belowground organs, coarse and fine root biomass and contributed to higher biomass allocation belowground. Fire also increased both functional diversity and dispersion. NEE and total SOC were higher in burned plots compared to fire-excluded plots whereas soil respiration recorded lower values in burned areas. Both ET and eWUE were not affected by fire. Fire strongly favored functional diversity, fine root and belowground organ biomass in piecewise SEM models but the role of both functional diversity and ecosystem structure to mediate the effect of fire on ecosystem functions remain unclear. Fire regime will impact C balance, and fire exclusion may lead to lower C input in open savanna ecosystems.

Características da dor no joelho em idosos usuários da atenção primária à saúde, segundo aspectos sociodemográficos / Characteristics of knee pain among older adults users of primary health care, according to sociodemographic aspects

Dor no joelho é uma condição reconhecida pelo elevado impacto funcional na população idosa. O conhecimento sobre as características dessas demandas na Atenção Primária à Saúde (APS) é escasso, o que dificulta o planejamento de linhas de cuidados destinadas ao manejo da dor nessa população. O objetivo foi investigar características da dor no joelho em idosos usuários da atenção primária à saúde, segundo aspectos sociodemográficos. Foi realizado estudo transversal com 201 idosos em três unidades de saúde selecionadas aleatoriamente. Dor no joelho foi classificada em crônica (>três meses) e aguda (

Knee pain is a condition recognized for its high functional impact in the older population. Knowledge about the characteristics of these demands in Primary Health Care (PHC) is scarce, which makes it difficult to plan lines of care aimed at pain management in this population. The objective of this study was to investigate characteristics of knee pain among older adults users of primary health care, according to sociodemographic aspects. A cross-sectional study was carried out with 201 older adults in three randomly selected health units. Knee pain was classified as chronic (>3 months) and acute (<3 months). The Analog Pain Scale was applied to assess the intensity, scored from 0 to 10, and questions about the impact of pain on daily life and demand for health services. Gender, age, presence of a partner, and education were recorded. Chronic knee pain was reported by 39.8% of participants; 24.9% reported functional impact and 23.9% sought a health service. Presence of pain (p=0.021) and functional impact (p=0.016) were more frequent among those who did not have a partner and the search for health services was more frequent among those with higher education. Acute knee pain was reported by 37.8% of participants, mean pain intensity was 2.4 (SD:3.6), and was associated with higher education and not having a partner. The demand for care for older adults with knee pain in PHC is high and is characterized as being functionally impactful and stimulating the demand for health services, in addition to being unequal in terms of education and the presence of a partner.

Condições de saúde de mulheres e homens idosos com idade avançada: estudo longitudinal / Health status of older men and women: longitudinal study / Condiciones de salud de mujeres y hombres de edad avanzada: un estudio longitudinal

Objetivo: descrever as características sociodemográficas e de saúde de mulheres e homens com 75 anos ou mais de idade, no baseline e follow-up de quatro anos e verificar para mulheres e homens as mudanças nas condições de saúde. Métodos: estudo longitudinal com 109 idosos de 75 anos ou mais de idade de um município no Triângulo Mineiro. A coleta dos dados, realizada em dois momentos (2014-2018), ocorreu no domicílio com a aplicação de instrumentos validados no Brasil. Procederam-se às análises descritiva e teste t pareado (p<0,05). Os projetos foram aprovados pelo Comitê de Ética e Pesquisa com Seres Humanos. Resultados: verificaram-se, em ambos os sexos, aumento do número de morbidades e diminuição do escore total das atividades instrumentais da vida diária. Entre as mulheres observou-se, ainda, aumento do número de quedas e do escore de fragilidade. Conclusão: ao longo do seguimento houve piora nas condições de saúde dos idosos, sendo mais expressiva entre as mulheres.

Objective: to describe the sociodemographic and health characteristics of women and men aged 75 or over, at baseline and after four years of follow-up, and to ascertain changes in their health status. Methods: in this longitudinal study of 109 elderly people aged 75 or over from a city in the Triângulo Mineiro, data were collected at two points (2014 and 2018), at home, by applying instruments validated for use in Brazil. Descriptive analysis and paired t-tests were performed (p < 0.05). The projects were approved by the human research ethics committee. Results: in both genders, the number of morbidities increased and the total score for instrumental activities of daily living decreased. Among women, the number of falls and frailty score also increased. Conclusion: the older people's health status worsened over the course of follow-up, more so among the women.

Objetivo: describir las características sociodemográficas y de salud de mujeres y hombres de 75 años o más, en la base de referencia y el seguimiento durante cuatro años, y verificar los cambios en las condiciones de salud de mujeres y hombres. Métodos: estudio longitudinal con 109 personas mayores, de 75 años o más, de un municipio del Triângulo Mineiro. La recolección de datos, realizada en dos momentos (2014-2018), se realizó en sus domicilios aplicando instrumentos validados en Brasil. Se realizaron análisis descriptivos y prueba t pareada (p <0.05). Los proyectos fueron aprobados por el Comité de Ética en Investigación con Humanos. Resultados: en ambos os sexos, hubo un aumento en el número de morbilidades y una disminución en la puntuación total de las actividades instrumentales de la vida diaria. Entre las mujeres, se observó asimismo un aumento en el número de caídas y la puntuación de fragilidad. Conclusión: a lo largo del seguimiento, las condiciones de salud de las personas mayores empeoraron, más expresivamente entre las mujeres.

Dietary Iron Overload and Hfe-/- Related Hemochromatosis Alter Hepatic Mitochondrial Function.

Iron is an essential co-factor for many cellular metabolic processes, and mitochondria are main sites of utilization. Iron accumulation promotes production of reactive oxygen species (ROS) via the catalytic activity of iron species. Herein, we investigated the consequences of dietary and genetic iron overload on mitochondrial function. C57BL/6N wildtype and Hfe-/- mice, the latter a genetic hemochromatosis model, received either normal diet (ND) or high iron diet (HI) for two weeks. Liver mitochondrial respiration was measured using high-resolution respirometry along with analysis of expression of specific proteins and ROS production. HI promoted tissue iron accumulation and slightly affected mitochondrial function in wildtype mice. Hepatic mitochondrial function was impaired in Hfe-/- mice on ND and HI. Compared to wildtype mice, Hfe-/- mice on ND showed increased mitochondrial respiratory capacity. Hfe-/- mice on HI showed very high liver iron levels, decreased mitochondrial respiratory capacity and increased ROS production associated with reduced mitochondrial aconitase activity. Although Hfe-/- resulted in increased mitochondrial iron loading, the concentration of metabolically reactive cytoplasmic iron and mitochondrial density remained unchanged. Our data show multiple effects of dietary and genetic iron loading on mitochondrial function and linked metabolic pathways, providing an explanation for fatigue in iron-overloaded hemochromatosis patients, and suggests iron reduction therapy for improvement of mitochondrial function.

Nursing supervised curricular internship in the Covid-19 pandemic: experience in the program Brasil Conta Comigo.

OBJECTIVE: To report the experience of the nursing supervised curricular internship in the program "O Brasil Conta Comigo" carried out in the Covid-19 pandemic. METHOD: Experience report of activities developed in Primary Health Care in a municipality in the southern region of the state of Goiás during the Covid-19 pandemic, from April to November 2020. RESULTS: The inclusion in the government program allowed the strengthening of the student's active role in the teaching-learning process and teaching-service approximation, with the student as the point of connection, which resulted in the implementation of actions for the fight against the pandemic in the municipality, such as elaboration, implementation, and evaluation of the service flowchart for people with suspected Covid-19. CONCLUSION: The experience was successful, as it consolidated knowledge regarding leadership and autonomy, integration between theory and practice, critical thinking, and evidence-based problem solving. The participation in the program allowed for contributions to assistance and management in the actions to combat the new coronavirus in the scope of primary care, as well as for the contribution to the training of the student tutored by nurses in the field and supervised by professors from the federal university of origin.

Outcomes of adults who received liver transplant as young children.

BACKGROUND: Patient and graft survival 20-years after pediatric liver transplantation (pLT) are excellent. In children, attainment of normal growth, education and social adaptation to be an independent adult are equally important. This is particularly relevant for children who receive liver transplant at a young age, where infantile-onset liver disease, surgery and immunosuppression can adversely affect growth and neurodevelopment. The aim of this study was to evaluate the long-term physical and psychosocial outcomes of pLT recipients with normal graft function. We coin the term 'meaningful survival'. METHODS: We performed a cross-sectional study of pLT recipients who received transplants between 1985 and 2004. A 20-year evaluation of physical health (growth, renal function), mental wellbeing and social outcomes (substance abuse, adherence, education, employment) was performed. All patients included were considered to have normal graft function. FINDINGS: Eighty-four patients met study criteria. Median age at transplantation was 1.3 years (IQR 0·7-3·3 years), with median duration of follow-up of 20.2 years (18·0-23·5). At median of 20-years, 19 patients (23%) had chronic renal dysfunction and 3 patients (4%) had a BMI of >30 (mean 20·4). Evaluation of long-term psychosocial outcomes demonstrated 22 patients (26%) with mental health disorders. Substance abuse was lower than national average. 62 patients (74%) were in education, employment or training. Overall, only 26% of our cohort achieved a composite outcome of 'meaningful survival'. INTERPRETATION: This is the largest reported long-term study of biopsychosocial outcomes of pLT recipients with normal liver biochemistry, with follow-up upon completion of physical growth and senior school education. Importantly, despite normal liver function, many patients did not demonstrate 'meaningful survival'. We must refocus our efforts towards better understanding the long-term outcomes of children. A 'meaningful survival' rather than mere survival should be our goal. FUNDING: None.

Baseline iron status and presence of anaemia determine the course of systemic Salmonella infection following oral iron supplementation in mice.

BACKGROUND: Iron deficiency anaemia (IDA) is a major health concern. However, preventive iron supplementation in regions with high burden of infectious diseases resulted in an increase of infection related morbidity and mortality. METHODS: We fed male C57BL/6N mice with either an iron deficient or an iron adequate diet. Next, they received oral iron supplementation or placebo followed by intraperitoneal infection with Salmonella Typhimurium (S.Tm). FINDINGS: We found that mice with IDA had a poorer clinical outcome than mice on an iron adequate diet. Interestingly, iron supplementation of IDA mice resulted in higher bacterial burden in organs and shortened survival. Increased transferrin saturation and non-transferrin bound iron in the circulation together with low expression of ferroportin facilitated the access of the pathogen to iron and promoted bacterial growth. Anaemia, independent of iron supplementation, was correlated with reduced neutrophil counts and cytotoxic T cells. With iron supplementation, anaemia additionally correlated with increased splenic levels of the cytokine IL-10, which is suggestive for a weakened immune control to S.Tm infection. INTERPRETATION: Supplementing iron to anaemic mice worsens the clinical course of bacterial infection. This can be traced back to increased iron delivery to bacteria along with an impaired anti-microbial immune response. Our findings may have important implications for iron supplementation strategies in areas with high endemic burden of infections, putting those individuals, who potentially profit most from iron supplementation for anaemia, at the highest risk for infections. FUNDING: Financial support by the Christian Doppler Laboratory for Iron Metabolism and Anemia Research.

Desempenho físico e força de preensão manual como preditores de qualidade de vida de idosos / Physical performance and handgrip strength as predictors of quality of life in the elderly

Objetivo: Verificar a influência do desempenho físico e da força de preensão manual na qualidade de vida de idosos. Método: Pesquisa quantitativa, longitudinal, do tipo inquérito domiciliar conduzida com 322 idosos residentes no interior de Minas Gerais. Os dados foram coletados em 2014 e 2017/2018 por meio dos instrumentos: Mini Exame do Estado Mental; questionários com dados sociodemográficos/econômico e clínico; Short Physical Performance Battery, dinamometria, World Health Organization Quality of Life-Bref e World Health Organization Quality of Life-Olders. Procedeu-se a análise descritiva, bivariada e regressão linear múltipla (p≤0,05). Resultados: Entre as duas coletas houve alteração do maior percentual do estado conjugal, com esposo(a) ou companheiro(a) na baseline para viúvos(as) no follow-up, além do aumento percentual de 5 ou mais morbidades. O menor desempenho físico foi preditor de piores escores de qualidade de vida nos domínios: físico (p<0,001) e relações sociais (p= 0,012); e nas facetas: autonomia (p= 0,001); atividades passadas, presentes e futuras (p= 0,005) e participação social (p<0,001). A menor força de preensão manual foi preditora de menor escore de qualidade de vida no domínio físico (p= 0,009). Conclusão: O menor desempenho físico e a menor força de preensão manual associaram-se com pior escore de qualidade de vida entre idosos da comunidade.

Objective: To verify the influence of physical performance and handgrip strength on the quality of life of the elderly. Method: Quantitative, longitudinal, household survey type survey conducted with 322 elderly people living in the interior of Minas Gerais. Data were collected in 2014 and 2017/2018 using the instruments: Mini Mental State Examination; questionnaires with sociodemographic/economic and clinical data; Short Physical Performance Battery, dynamometry, World Health Organization Quality of Life-Bref and World Health Organization Quality of Life-Olders. Descriptive, bivariate analysis and multiple linear regression (p≤0.05) were performed. Results: Between the two collections there was a change in the highest percentage of marital status, with husband or partner in the baseline for widowers at follow-up, in addition to the percentage increase of 5 or more morbidities. The lowest physical performance was a predictor of worse quality of life scores in the domains: physical (p <0.001) and social relationships (p= 0.012); and in the facets: autonomy (p= 0.001); past, present and future activities (p= 0.005) and social participation (p <0.001). The lower handgrip strength was a predictor of a lower quality of life score in the physical domain (p= 0.009). Conclusion: Lower physical performance and lower handgrip strength were associated with a worse quality of life score among elderly people in the community.

Cytokine-Mediated Regulation of ARG1 in Macrophages and Its Impact on the Control of Salmonella enterica Serovar Typhimurium Infection.

Arginase 1 (ARG1) is a cytosolic enzyme that cleaves L-arginine, the substrate of inducible nitric oxide synthase (iNOS), and thereby impairs the control of various intracellular pathogens. Herein, we investigated the role of ARG1 during infection with Salmonella enterica serovar Typhimurium (S.tm). To study the impact of ARG1 on Salmonella infections in vitro, bone marrow-derived macrophages (BMDM) from C57BL/6N wild-type, ARG1-deficient Tie2Cre+/-ARG1fl/fl and NRAMPG169 C57BL/6N mice were infected with S.tm. In wild-type BMDM, ARG1 was induced by S.tm and further upregulated by the addition of interleukin (IL)-4, whereas interferon-γ had an inhibitory effect. Deletion of ARG1 did not result in a reduction in bacterial numbers. In vivo, Arg1 mRNA was upregulated in the spleen, but not in the liver of C57BL/6N mice following intraperitoneal S.tm infection. The genetic deletion of ARG1 (Tie2Cre+/-ARG1fl/fl) or its pharmacological inhibition with CB-1158 neither affected the numbers of S.tm in spleen, liver and blood nor the expression of host response genes such as iNOS, IL-6 or tumour necrosis factor (TNF). Furthermore, ARG1 was dispensable for pathogen control irrespective of the presence or absence of the phagolysosomal natural resistance-associated macrophage protein 1 (NRAMP1). Thus, unlike the detrimental function of ARG1 seen during infections with other intraphagosomal microorganisms, ARG1 did not support bacterial survival in systemic salmonellosis, indicating differential roles of arginine metabolism for host immune response and microbe persistence depending on the type of pathogen.

Pharmacological Targeting of BMP6-SMAD Mediated Hepcidin Expression Does Not Improve the Outcome of Systemic Infections With Intra-Or Extracellular Gram-Negative Bacteria in Mice.

Introduction: Hepcidin is the systemic master regulator of iron metabolism as it degrades the cellular iron exporter ferroportin. In bacterial infections, hepcidin is upregulated to limit circulating iron for pathogens, thereby increasing iron retention in macrophages. This mechanism withholds iron from extracellular bacteria but could be of disadvantage in infections with intracellular bacteria. We aimed to understand the role of hepcidin in infections with intra- or extracellular bacteria using different hepcidin inhibitors. Methods: For the experiments LDN-193189 and oversulfated heparins were used, which interact with the BMP6-SMAD pathway thereby inhibiting hepcidin expression. We infected male C57BL/6N mice with either the intracellular bacterium Salmonella Typhimurium or the extracellular bacterium Escherichia coli and treated these mice with the different hepcidin inhibitors. Results: Both inhibitors effectively reduced hepcidin levels in vitro under steady state conditions and upon stimulation with the inflammatory signals interleukin-6 or lipopolysaccharide. The inhibitors also reduced hepcidin levels and increased circulating iron concentration in uninfected mice. However, both compounds failed to decrease liver- and circulating hepcidin levels in infected mice and did not affect ferroportin expression in the spleen or impact on serum iron levels. Accordingly, both BMP-SMAD signaling inhibitors did not influence bacterial numbers in different organs in the course of E.coli or S.Tm sepsis. Conclusion: These data indicate that targeting the BMP receptor or the BMP-SMAD pathway is not sufficient to suppress hepcidin expression in the course of infection with both intra- or extracellular bacteria. This suggests that upon pharmacological inhibition of the central SMAD-BMP pathways during infection, other signaling cascades are compensatorily induced to ensure sufficient hepcidin formation and iron restriction to circulating microbes.