The pathobiology of human fungal infections.

Human fungal infections are a historically neglected area of disease research, yet they cause more than 1.5 million deaths every year. Our understanding of the pathophysiology of these infections has increased considerably over the past decade, through major insights into both the host and pathogen factors that contribute to the phenotype and severity of these diseases. Recent studies are revealing multiple mechanisms by which fungi modify and manipulate the host, escape immune surveillance and generate complex comorbidities. Although the emergence of fungal strains that are less susceptible to antifungal drugs or that rapidly evolve drug resistance is posing new threats, greater understanding of immune mechanisms and host susceptibility factors is beginning to offer novel immunotherapeutic options for the future. In this Review, we provide a broad and comprehensive overview of the pathobiology of human fungal infections, focusing specifically on pathogens that can cause invasive life-threatening infections, highlighting recent discoveries from the pathogen, host and clinical perspectives. We conclude by discussing key future challenges including antifungal drug resistance, the emergence of new pathogens and new developments in modern medicine that are promoting susceptibility to infection.

Fear of the COVID-19 vaccine in a public healthcare system and university setting.

Despite the known benefits, some individuals remain apprehensive about receiving the COVID-19 vaccine, which hampers vaccination efforts and the achievement of herd immunity. Therefore, this cross-sectional study aimed to assess vaccination rates and identify factors influencing fear of the COVID-19 vaccine among individuals served by the public healthcare system (Family Health Strategy - FHS) and in a university community in Minas Gerais, Brazil. Surveys were conducted face-to-face with FHS participants and online with university members, employing a free sharing approach on social media. A total of 1896 and 312 responses were collected, respectively. The survey covered sociodemographic information, COVID-19 fear levels, and vaccination status for both individuals and their children Vaccination coverage was 83% among FHS participants and 99.1% in the university setting. Female respondents in both groups exhibited higher levels of COVID-19 fear (p<0.05), with FHS-assisted women reporting greater apprehension towards vaccination (p<0.05). Educated parents demonstrated better understanding of the importance of child vaccination, while younger parents expressed heightened concerns about vaccine side effects. Among FHS participants, women exhibited a 1.6 times higher fear of vaccination compared to men. Additionally, fear of vaccination increased by 1.10 times for each additional point on the COVID-19 Fear Scale (physiological domain). Effective communication strategies and dispelling misconceptions surrounding immunization could alleviate fear and promote vaccination acceptance.

Semisynthetic Glycoconjugate Vaccine Candidates against Cryptococcus neoformans.

Cryptococcus neoformans is a fungus classified by the World Health Organization as a critically important pathogen, which poses a significant threat to immunocompromised individuals. In this study, we present the chemical synthesis and evaluation of two semisynthetic vaccine candidates targeting the capsular polysaccharide glucuronoxylomannan (GXM) of C. neoformans. These semisynthetic glycoconjugate vaccines contain an identical synthetic decasaccharide (M2 motif) antigen. This antigen is present in serotype A strains, which constitute 95% of the clinical cryptococcosis cases. This synthetic oligosaccharide was conjugated to two proteins (CRM197 and Anthrax 63 kDa PA) and tested for immunogenicity in mice. The conjugates elicited a specific antibody response that bound to the M2 motif but also exhibited additional cross-reactivity toward M1 and M4 GXM motifs. Both glycoconjugates produced antibodies that bound to GXM in ELISA assays and to live fungal cells. Mice immunized with the CRM197 glycoconjugate produced weakly opsonic antibodies and displayed trends toward increased median survival relative to mice given a mock PBS injection (18 vs 15 days, p = 0.06). These findings indicate promise, achieving a successful vaccine demands further optimization of the glycoconjugate. This antigen could serve as a component in a multivalent GXM motif vaccine.

Assessing Phagocytosis of Cryptococcus neoformans Cells in Human Monocytes or the J774 Murine Macrophage Cell Line.

Monocyte/macrophage cells play a central role in innate immunity against C. neoformans and C. gattii, species known to cause human disease. Cryptococcus is the only fungal genus known to possess such a large extracellular polysaccharide capsule, which impacts interactions of innate cells with the yeast. This interaction results in different fates, such as phagocytosis and intracellular proliferation and, as the interaction progresses, vomocytosis, cell-to-cell transfer, lysis of macrophages, or yeast killing. Differentiating internalized versus external Cryptococcus cells is thus essential to evaluate monocyte-macrophage phagocytosis. We describe here a protocol that allows quantification of Cryptococcus spp. phagocytosis using quantitative flow cytometry in human monocytes and a murine macrophage cell line (J774).

Cryptococcus neoformans rapidly invades the murine brain by sequential breaching of airway and endothelial tissues barriers, followed by engulfment by microglia.

Cryptococcus neoformans causes lethal meningitis and accounts for approximately 10%-15% of AIDS-associated deaths worldwide. There are major gaps in our understanding of how this fungus invades the mammalian brain. To investigate the dynamics of C. neoformans tissue invasion, we mapped fungal localization and host cell interactions in infected brain, lung, and upper airways using mouse models of systemic and airway infection. To enable this, we developed an in situ imaging pipeline capable of measuring large volumes of tissue while preserving anatomical and cellular information by combining thick tissue sections, tissue clarification, and confocal imaging. We confirm high fungal burden in mouse upper airway after nasal inoculation. Yeast in turbinates were frequently titan cells, with faster kinetics than reported in mouse lungs. Importantly, we observed one instance of fungal cells enmeshed in lamina propria of the upper airways, suggesting penetration of airway mucosa as a possible route of tissue invasion and dissemination to the bloodstream. We extend previous literature positing bloodstream dissemination of C. neoformans, by finding viable fungi in the bloodstream of mice a few days after intranasal infection. As early as 24 h post systemic infection, the majority of C. neoformans cells traversed the blood-brain barrier, and were engulfed or in close proximity to microglia. Our work presents a new method for investigating microbial invasion, establishes that C. neoformans can breach multiple tissue barriers within the first days of infection, and demonstrates microglia as the first cells responding to C. neoformans invasion of the brain.IMPORTANCECryptococcal meningitis causes 10%-15% of AIDS-associated deaths globally. Still, brain-specific immunity to cryptococci is a conundrum. By employing innovative imaging, this study reveals what occurs during the first days of infection in brain and in airways. We found that titan cells predominate in upper airways and that cryptococci breach the upper airway mucosa, which implies that, at least in mice, the upper airways are a site for fungal dissemination. This would signify that mucosal immunity of the upper airway needs to be better understood. Importantly, we also show that microglia, the brain-resident macrophages, are the first responders to infection, and microglia clusters are formed surrounding cryptococci. This study opens the field to detailed molecular investigations on airway immune response, how fungus traverses the blood-brain barrier, how microglia respond to infection, and ultimately how microglia monitor the blood-brain barrier to preserve brain function.

Semi-synthetic glycoconjugate vaccine candidate against Cryptococcus neoformans.

Cryptococcus neoformans is a fungus classified by the World Health Organization as a critically important pathogen, posing a significant threat to immunocompromised individuals. In this study, we present the chemical synthesis and evaluation of two semi-synthetic vaccine candidates targeting the capsular polysaccharide glucuronoxylomannan (GXM) of C. neoformans. These semi-synthetic glycoconjugate vaccines contain the identical synthetic decasaccharide (M2 motif) antigen. This motif is present in serotype A strains, which constitute 95% of clinical cryptococcosis cases. This synthetic oligosaccharide was conjugated to two proteins (CRM197 and Anthrax 63 kDa PA) and tested for immunogenicity in mice. The conjugates elicited a specific antibody response that bound to the M2 motif but also exhibited additional cross-reactivity towards M1 and M4 GXM motifs. Both glycoconjugates produced antibodies that bound to GXM in ELISA assays and to live fungal cells. Mice immunized with the CRM197 glycoconjugate produced opsonic antibodies and displayed trends toward increased median survival relative to mice given a mock PBS injection (18 vs 15 days, p = 0.06). While these findings indicate promise, achieving a successful vaccine demands further optimization of the glycoconjugate. It could serve as a component in a multi-valent GXM motif vaccine, enhancing both strength and breadth of immune responses.

Dynapenia and sarcopenia: association with the diagnosis, duration and complication of type 2 diabetes mellitus in ELSA-Brasil.

Sarcopenia (the loss of muscle mass, strength and skeletal muscle function) increases mortality and the risk of hospitalization in the older population. Although it is known that older adults with type 2 diabetes mellitus (T2DM) have a higher risk of dynapenia and sarcopenia, few studies have investigated these conditions in middle-aged populations. The objective of this study was to investigate whether T2DM, its duration, the presence of albuminuria, and glycemic control are associated with sarcopenia and its components in adults. The cross-sectional analysis was based on data from visit 2 of the Brazilian Longitudinal Study of Adult Health (2012-2014). The 2018 European Working Group on Sarcopenia in Older People criteria were used to define dynapenia, low appendicular muscle mass (LAMM), and sarcopenia (absent/probable/confirmed). The explanatory variables were: T2DM; duration of T2DM; T2DM according to the presence of albuminuria; and glycemic control (HbA1C < 7%) among people with T2DM. A total of 12,132 participants (mean age = 55.5, SD: 8.9 years) were included. The odds ratio for LAMM was greater among those with T2DM, T2DM duration from 5 to 10 years, and T2DM without albuminuria. Chances of dynapenia were higher among those with T2DM, T2DM duration > 10 years, and T2DM with and without albuminuria. The variables T2DM, T2DM ≥ 10 years, and T2DM with albuminuria increased the odds of probable sarcopenia, and T2DM duration from 5 to 10 years increased the odds of confirmed sarcopenia. The results support the importance of frequently monitoring the musculoskeletal mass and strength of individuals with T2DM to prevent sarcopenia and related outcomes.

Adherence to the Dietary Approaches to Stop Hypertension (DASH) and Serum Urate Concentrations: A Longitudinal Analysis from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

BACKGROUND: Increased serum urate (SU) and hyperuricemia (HU) are associated with chronic noncommunicable diseases and mortality. SU concentrations are affected by several factors, including diet, and are expected to rise with age. We investigated whether the Dietary Approaches to Stop Hypertension (DASH) diet alter this trend. OBJECTIVE: The objective was to assess whether adherence to the DASH diet predicts a longitudinal change in SU concentrations and risk of HU in 8 y of follow-up. METHODS: Longitudinal analyses using baseline (2008-2010, aged 35-74 y), second (2012-2014), and third (2016-2018) visits data from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). The inclusion criteria were having complete food frequency questionnaire (FFQ) and urinary sodium measurement, in addition to having SU measurement at the 1st visit and at least 1 of the 2 follow-up visits. For the HU incidence analyses, participants had also to be free from HU at baseline. The final samples included 12575 individuals for the SU change analyses and 10549 for the HU incidence analyses. Adherence to DASH diet was assessed as continuous value. HU was defined as SU>6.8 mg/dL and/or urate-lowering therapy use. Mixed-effect linear and Poisson regressions (incidence rate ratio [IRR] and 95% confidence interval [CI]) were used in the analyses, adjusted for confounders. RESULTS: The mean age was 51.4 (8.7) y, and 55.4% were females. SU means (standard deviation) were 5.4 (1.4) at 1st visit, 5.2 (1.4) at 2nd visit, and 5.1(1.3) mg/dL at 3rd visit. The HU incidence rate was 8.87 per 1000 person-y. Each additional point in adherence to the DASH diet accelerated SU decline (P< 0.01) and lowered the incidence of HU by 4.3% (IRR: 0.957; 95% CI: 0.938,0.977) in adjusted model. CONCLUSION: The present study findings reinforce the importance of encouraging the DASH diet as a healthy dietary pattern to control and reduce the SU concentrations and risk of HU.

Dynapenia and sarcopenia: association with the diagnosis, duration and complication of type 2 diabetes mellitus in ELSA-Brasil / Dinapenia e sarcopenia: associação com o diagnóstico, duração e complicações de diabetes mellitus tipo 2 no ELSA-Brasil / Dinapenia y sarcopenia: asociación con el diagnóstico, duración y complicaciones de la diabetes mellitus tipo 2 en ELSA-Brasil

Abstract: Sarcopenia (the loss of muscle mass, strength and skeletal muscle function) increases mortality and the risk of hospitalization in the older population. Although it is known that older adults with type 2 diabetes mellitus (T2DM) have a higher risk of dynapenia and sarcopenia, few studies have investigated these conditions in middle-aged populations. The objective of this study was to investigate whether T2DM, its duration, the presence of albuminuria, and glycemic control are associated with sarcopenia and its components in adults. The cross-sectional analysis was based on data from visit 2 of the Brazilian Longitudinal Study of Adult Health (2012-2014). The 2018 European Working Group on Sarcopenia in Older People criteria were used to define dynapenia, low appendicular muscle mass (LAMM), and sarcopenia (absent/probable/confirmed). The explanatory variables were: T2DM; duration of T2DM; T2DM according to the presence of albuminuria; and glycemic control (HbA1C < 7%) among people with T2DM. A total of 12,132 participants (mean age = 55.5, SD: 8.9 years) were included. The odds ratio for LAMM was greater among those with T2DM, T2DM duration from 5 to 10 years, and T2DM without albuminuria. Chances of dynapenia were higher among those with T2DM, T2DM duration > 10 years, and T2DM with and without albuminuria. The variables T2DM, T2DM ≥ 10 years, and T2DM with albuminuria increased the odds of probable sarcopenia, and T2DM duration from 5 to 10 years increased the odds of confirmed sarcopenia. The results support the importance of frequently monitoring the musculoskeletal mass and strength of individuals with T2DM to prevent sarcopenia and related outcomes.

Resumo: A sarcopenia (perda de massa muscular, força e função muscular esquelética) aumenta a mortalidade e o risco de hospitalização em idosos. Idosos com diabetes mellitus tipo 2 (DMT2) apresentam risco elevado de desenvolver dinapenia e sarcopenia, mas poucos estudos investigaram populações de meia-idade. O objetivo foi investigar se DMT2, sua duração, a presença de albuminúria e o controle glicêmico estão associados à sarcopenia e seus componentes em adultos. Análise transversal baseada nos dados da segunda visita do Estudo Longitudinal de Saúde do Adulto (2012-2014). Os critérios do European Working Group on Sarcopenia in Older People [Grupo de Trabalho Europeu sobre Sarcopenia em Pessoas Idosas] de 2018 foram usados para definir dinapenia, baixa massa muscular apendicular e sarcopenia (ausente/provável/confirmada). As variáveis explicativas foram: DMT2; duração do DMT2; DMT2 de acordo com a presença de albuminúria; e controle glicêmico (HbA1c < 7%) entre pessoas com DMT2. Foram incluídos 12.132 participantes (idade média de 55,5; DP: 8,9 anos). A razão de chances para baixa massa muscular apendicular foi maior entre pessoas com DMT2, duração do DMT2 entre 5 e 10 anos e DMT2 sem albuminúria. As chances de dinapenia foram maiores entre pessoas com DMT2, duração do DMT2 > 10 anos e DMT2 com e sem albuminúria. DMT2, DMT2 ≥ 10 anos e DMT2 com albuminúria aumentaram as chances de sarcopenia provável e duração do DMT2 entre 5 e 10 anos aumentaram as chances de sarcopenia confirmada. Os resultados reforçam a importância do monitoramento frequente da massa e da força muscular em indivíduos com DMT2 para prevenir a sarcopenia e desfechos relacionados.

Resumen: La sarcopenia (pérdida de masa muscular, fuerza y función muscular esquelética) aumenta la mortalidad y el riesgo de hospitalización en ancianos. Los ancianos con diabetes mellitus tipo 2 (DMT2) presentan un mayor riesgo de sufrir dinapenia y sarcopenia, pero pocos estudios han investigado poblaciones de mediana edad. El objetivo fue investigar si la DMT2, su duración, la presencia de albuminuria y el control glucémico están asociados con la sarcopenia y sus componentes en adultos. Análisis transversal basado en los datos de la visita 2 del Estudio Longitudinal de Salud del Adulto en Brasil (2012-2014). Se utilizaron los criterios del European Working Group on Sarcopenia in Older People [Grupo de Trabajo Europeo sobre Sarcopenia en Personas Mayores] del 2018 para definir dinapenia, baja masa muscular apendicular y sarcopenia (ausente/probable/confirmada). Las variables explicativas fueron las siguientes: DMT2; duración de la DMT2; DMT2 según la presencia de albuminuria; y control glucémico (HbA1c < 7%) entre personas con DMT2. Se incluyeron 12.132 participantes (edad media = 55,5, DE: 8,9 años). La razón de probabilidades de masa muscular apendicular baja fue mayor entre personas con DMT2, duración de la DMT2 entre 5 y 10 años y DMT2 sin albuminuria. Las probabilidades de dinapenia fueron mayores entre las personas con DMT2, duración de la DMT2 > 10 años y DMT2 con y sin albuminuria. Las condiciones de DMT2, DMT2 ≥ 10 años y DMT2 con albuminuria aumentaron las probabilidades de sarcopenia probable y la duración de la DMT2 entre 5 y 10 años las probabilidades de sarcopenia confirmada. Los resultados refuerzan la importancia del monitoreo frecuente de la masa y de la fuerza musculoesquelética en individuos con DMT2 para prevenir la sarcopenia y los desenlaces relacionados.

Cryptococcus neoformans rapidly invades the murine brain by sequential breaching of airway and endothelial tissues barriers, followed by engulfment by microglia.

The fungus Cryptococcus neoformans causes lethal meningitis in humans with weakened immune systems and is estimated to account for 10-15% of AIDS-associated deaths worldwide. There are major gaps in our understanding of how this environmental fungus evades the immune system and invades the mammalian brain before the onset of overt symptoms. To investigate the dynamics of C. neoformans tissue invasion, we mapped early fungal localisation and host cell interactions at early times in infected brain, lung, and upper airways using mouse models of systemic and airway infection. To enable this, we developed an in situ imaging pipeline capable of measuring large volumes of tissue while preserving anatomical and cellular information by combining thick tissue sections, tissue clarification, and confocal imaging. Made possible by these techniques, we confirm high fungal burden in mouse upper airway turbinates after nasal inoculation. Surprisingly, most yeasts in turbinates were titan cells, indicating this microenvironment enables titan cell formation with faster kinetics than reported in mouse lungs. Importantly, we observed one instance of fungal cells enmeshed in lamina propria of upper airways, suggesting penetration of airway mucosa as a possible route of tissue invasion and dissemination to the bloodstream. We extend previous literature positing bloodstream dissemination of C. neoformans, via imaging C. neoformans within blood vessels of mouse lungs and finding viable fungi in the bloodstream of mice a few days after intranasal infection, suggesting that bloodstream access can occur via lung alveoli. In a model of systemic cryptococcosis, we show that as early as 24 h post infection, majority of C. neoformans cells traversed the blood-brain barrier, and are engulfed or in close proximity to microglia. Our work establishes that C. neoformans can breach multiple tissue barriers within the first days of infection. This work presents a new method for investigating cryptococcal invasion mechanisms and demonstrates microglia as the primary cells responding to C. neoformans invasion.

Getaway car: Fungal HscA steers human phagosomal p11 into an escape route.

In this issue of Cell Host & Microbe, Jia and colleagues discover how the human p11 (s100A10)-Anxa2 heterodimer drives sorting of microbial phagosomes into recycling versus degradative pathways. In a remarkable evolutionary arms race, the Aspergillus fumigatus protein HscA latches to p11 to steer its phagosome away from fungal killing.

Ultra-processed foods: Cross-sectional and longitudinal association with uric acid and hyperuricemia in ELSA-Brasil.

BACKGROUND AND AIMS: Food intake influences uric acid (UA) levels and hyperuricemia (HU), but evidence on the role of ultra-processed foods (UPFs) are scarce. The association between UPFs consumption and (1) HU prevalence and UA levels; (2) HU cumulative incidence; and (3) UA level change over a 4-year period was investigated. METHODS AND RESULTS: Cross-sectional and longitudinal analyses were performed using baseline (2008-2010, aged 35-74 years) and second visit (2012-2014) data from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Participants with glomerular filtration rate <60 mL/min/1.73 m2, bariatric surgery, implausible caloric intake, and using urate-lowering therapy (ULT) at baseline were excluded (all analyses). Participants with HU at baseline were excluded from longitudinal analyses. UPFs consumption was assessed using a food frequency questionnaire (FFQ) and categorized by the NOVA classification system (100 g/day). HU was defined as UA≥6.8 mg/dL. Linear, logistic, and mixed-effect linear regressions investigated the associations between UPFs consumption and UA/HU, adjusted for covariates. The final samples included 13,923 (cross-sectional) and 10,517 (longitudinal) individuals. The prevalence of HU was 18.7%, and the cumulative incidence was 4.9%. Greater UPFs consumption was associated with a greater prevalence of HU (OR:1.025 95%CI: 1.006; 1.044) and higher UA levels (ß:0.024 95%CI: 0.016; 0.032). Every additional consumption of 100 g/day of UPFs raised the 4-year cumulative incidence of HU by 5.6% (95%CI: 1.021; 1.092). However, UPFs were not associated with the pace of UA level changes during the study period. CONCLUSION: The present study shows that greater UPFs consumption is associated with another deleterious health consequence: higher UA levels and the risk of having HU.

Birth weight is related with bone mineral content in adulthood: results of ELSA-Brasil.

OBJECTIVE: To investigate the association between birth weight and bone mineral content (BMC), and whether this relationship differs between men and women. METHODS: A total of 10,159 participants from the ELSA-Brasil cohort were eligible for this analysis. The outcome was the z-score of the ratio BMC (kg)/height (m). The exposure was the low birth weight (< 2.5kg). The magnitude of the associations was estimated by mean differences and their respective 95% confidence intervals (95%CI) using linear regression. All analyses were presented for the total population and stratified by sex. RESULTS: Most were women (54.98%), and the mean age was 52.72 years (SD ± 6.6). In the crude model, we observed that low birth weight was associated with a lower mean BMC/height z-score, compared to adequate birth weight (mean difference: -0.30; 95%CI: -0.39 to -0.21), and this effect was stronger in men (mean difference: -0.43; 95%CI: -0.56 to -0.30) than in women (mean difference: -0.31; 95%CI: -0.44 to -0.19). After adjusting for age, sex per total population, race/skin color, maternal education, individual education, and current weight, there was a considerable reduction in the magnitude of the association (total population: -0.10; 95%CI: -0.14 to -0.06; men: -0.13; 95%CI: -0.21 to -0.06; women: -0.13; 95%CI: -0.21 to -0.05). CONCLUSION: Low birth weight is related to BMC/height z-score in both sexes with no indication of differences by sex. The magnitude of the associations was attenuated after adjustment for the current weight.

O desenvolvimento da atenção voluntária: contribuições da educação escolar / The development of voluntary attention: contributions of school education / El desarrollo de la atención voluntaria: contribuciones de la educación escolar

Este artigo propõe-se a apresentar aspectos essenciais das análises construídas a partir de uma pesquisa teórica que teve o objetivo de analisar as contribuições que a Pedagogia Histórico-crítica e a Psicologia Histórico-cultural apresentam em relação às potencialidades e possibilidades de que o ensino escolar e a atividade de ensino do professor promovam o desenvolvimento da atenção voluntária dos estudantes. Dessa forma, assumiu-se como objeto de estudo o desenvolvimento dessa função psicológica em sua dimensão cultural. As análises buscaram mostrar, nas produções da Psicologia Histórico-cultural e da Pedagogia Histórico-crítica, elementos acerca do desenvolvimento da atenção que possam auxiliar na concretização do objetivo apresentado por esta investigação, destacando a necessidade de considerar o materialismo histórico-dialético como perspectiva teórico-metodológica orientadora das teorias analisadas e também das análises propostas por este trabalho. O material empírico da investigação consistiu em artigos, teses e livros que discorrem sobre o desenvolvimento da atenção e o papel do ensino para tal desenvolvimento. Como síntese das dimensões essenciais identificadas por meio da análise das obras destaca-se a necessidade de compreender que o desenvolvimento das funções psicológicas humanas não se esgota em um processo de maturação biológica, mas articula e submete esta dimensão aos aspectos culturais, históricos e sociais do desenvolvimento humano, sendo que a adoção da Psicologia Histórico-cultural, como perspectiva teórico-metodológica para a organização do ensino e da atividade docente, mostra ser uma importante ferramenta para o enfrentamento da lógica medicalizante. (AU)

This article proposes to present essential aspects of the analyzes constructed from a theoretical research that had the objective of analyzing the contributions that Historical-Critical Pedagogy and Historical-Cultural Psychology present in relation to the potentialities and possibilities that the school education and the teaching activity promote the development of voluntary attention of the students. Thus, the development of this psychological function in its cultural dimension was assumed as the object of study. The analyzes sought to highlight elements of the development of attention in the productions of Historical-Cultural Psychology and of Historical-Critical Pedagogy that may assist in the achievement of the objective presented by this research, highlighting the need to consider historical-dialectical materialism as a theoretical perspective -methodological guide of the theories analyzed. The empirical material of the research consisted of articles, theses and books that discuss the development of attention and the role of teaching for such development. As a synthesis of the essential dimensions identified through the analysis of the works it is necessary to understand that the development of human psychological functions is not exclusively in a process of biological maturation, but rather it articulates and submits this dimension to the cultural, historical and social aspects of human development. The adoption of Historical-Cultural Psychology as a theoretical-methodological perspective for the organization of teaching and teaching activity, proves to be an important tool for confronting the medical logic. (AU)

Este artículo presenta los aspectos esenciales de las discusiones realizadas a partir de una investigación teórica que tuvo el objetivo de analizar las contribuciones que la Pedagogía Histórico-Crítica y la Psicología Histórico-Cultural direccionan a la enseñanza escolar y la actividad del profesor en la promoción del desarrollo de la atención voluntaria de los estudiantes. Así, se asumió como objeto de estudio el desarrollo de esa función psicológica en su dimensión cultural. Los análisis buscaron evidenciar, en las producciones de la Psicología Histórico-Cultural y de la Pedagogía HistóricoCrítica, elementos acerca del desarrollo de la atención que puedan auxiliar en la concreción del objetivo presentado por esta investigación, destacando la necesidad de considerar el materialismo histórico-dialéctico como perspectiva teórica-metodológica orientadora de las teorías analizadas y también de los análisis propuestos por este trabajo. El material empírico de la investigación consistió en artículos, tesis y libros que discurren sobre el desarrollo de la atención y el papel de la enseñanza para eso proceso. Como síntesis de las dimensiones esenciales identificadas por medio del análisis de las obras se destaca la necesidad de comprender que el desarrollo de las funciones psicológicas humanas no se agota en un proceso de maduración biológica sino que articula y somete esta dimensión a los aspectos culturales, históricos y sociales del desarrollo humano, siendo que la adopción de la Psicología Histórico-Cultural, como perspectiva teóricometodológica para la organización de la enseñanza y la actividad docente, demuestra ser una importante herramienta para el enfrentamiento de la lógica de la medicalización de la educació. (AU)

Cryptococcus neoformans releases proteins during intracellular residence that affect the outcome of the fungal-macrophage interaction.

Cryptococcus neoformans is a facultative intracellular pathogen that can replicate and disseminate in mammalian macrophages. In this study, we analyzed fungal proteins identified in murine macrophage-like cells after infection with C. neoformans. To accomplish this, we developed a protocol to identify proteins released from cryptococcal cells inside macrophage-like cells; we identified 127 proteins of fungal origin in infected macrophage-like cells. Among the proteins identified was urease, a known virulence factor, and others such as transaldolase and phospholipase D, which have catalytic activities that could contribute to virulence. This method provides a straightforward methodology to study host-pathogen interactions. We chose to study further Yeast Oligomycin Resistance (Yor1), a relatively uncharacterized protein belonging to the large family of ATP binding cassette transporter (ABC transporters). These transporters belong to a large and ancient protein family found in all extant phyla. While ABC transporters have an enormous diversity of functions across varied species, in pathogenic fungi they are better studied as drug efflux pumps. Analysis of C. neoformans yor1Δ strains revealed defects in nonlytic exocytosis, capsule size, and dimensions of extracellular vesicles, when compared to wild-type strains. We detected no difference in growth rates and cell body size. Our results indicate that C. neoformans releases a large suite of proteins during macrophage infection, some of which can modulate fungal virulence and are likely to affect the fungal-macrophage interaction.

IgA Vasculitis involving four systems / Vasculitis IgA que afecta a cuatro sistemas

Henoch-Schonlein Purpura (HSP) is a systemic vasculitis now called IgA vasculitis, that infrequently occurs in adults. While rheumatological andgastrointestinal complications are common, lung involvement is a rare complication. We report the case of a 70 year-old female that presented tothe hospital with purpuric lesions on her legs and ileitis. During her hospital stay she developed respiratory distress, and the computed tomography (CT scan) showed evidence of Diffuse Alveolar Hemorrhage (DAH). She also had renal dysfunction, and the renal biopsy confirmed the presence of leukocytoclastic vasculitis on histology, consistent with HSP. The patient was initiated on corticosteroid therapy and cyclophosphamide,in addition to supportive management, leading to the resolution of her symptoms.This case is unique, as it presents a rare complication of HSP, with pulmonary disease, causing DAH. Furthermore, adult onset HSP is also anuncommon occurrence.It is very important to recognize DAH early in HSP, as it holds a high mortality rate. (AU)

Mortality attributed to sickle cell disease in children and adolescents in Brazil, 2000-2019.

OBJECTIVE: Estimate rates and describe mortality trends attributed to sickle cell disease in children and adolescents in Brazil from 2000 to 2019. METHODS: This is an ecological study of the time-trend of mortality rates that used the autoregressive method, proposed by Prais-Winsten, to evaluate trends in the estimated rates of sickle cell disease deaths in children and adolescents in Brazil. Deaths with code D57 were obtained from the Mortality Information System, considering age groups (0-4, 5-9, 10-14, 15-19 years) and were used to estimate age-specific and standardized rates by gender and age. RESULTS: From 2000 to 2019, Brazil had 2,422 deaths from sickle cell disease in people under 20 years of age, with higher frequency in the Northeast (40.46%), followed by the Southeast (39.02%), Midwest (9.58%), North (7.84%), and South (3.10%). The main victims were people of Black skin/race (78.73%). In Brazil, the global standardized average rate was 0.20/100,000 people-year, with an elevation trend (annual percentage change - APC = 5.44%; confidence interval - 95%CI: 2.57-8.39). The pattern was repeated in males (APC = 4.38%; 95%CI: 2.17-6.64) and females (APC = 6.96%; 95%CI: 3.05-11.01). Elaborating age-specific rates showed that the range up to four years experienced the highest rates, without distinction by region. The age group of 15 and 19 years was the second most affected in Brazil and in the Northeast, Southeast, and Midwest regions. CONCLUSION: Deaths due to sickle cell disorders showed an elevation trend in children and adolescents. Considering that the magnitude of deaths was more evident in the first years (0-4) and late adolescence (15-19), the study suggests that age-specific approaches may impact the control of fatal outcomes caused by sickle cell disease in Brazil.

Body fat distribution and its risk for cardiovascular events in 10 years: Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

Body fat distribution seems to have different effects in cardiovascular diseases (CVD). We aimed to estimate the associations between lower limbs and trunk fat ratio and the 10-year CVD risk, and isolated risk factors in men and women. A total of 10,917 participants from ELSA-Brasil were eligible for this cross-sectional study. Associations between lower limb/trunk fat ratio with the percentage of 10-year CVD risk - according to the Framingham Risk Score - and its risk factors (systolic blood pressure, total cholesterol and HDL-cholesterol, diabetes, and use of antihypertensive medication) were performed using generalized linear models, linear and logistic regressions. All analyses were stratified by gender and adjustments were made by age, self-reported skin color, educational attainment, alcohol consumption, leisure physical activity, hypolipidemic drug use and, for women, menopausal status. In this study, 55.91% were women, with a mean age of 52.68 (SD = 6.57) years. A higher lower limb/trunk fat ratio was related to lower 10-year CVD risk, as well as a reduction in systolic blood pressure, total cholesterol, and antihypertensive drug use, also an increasing HDL-cholesterol in both genders, but this relationship was stronger in women. Besides, a protective relationship to diabetes was observed in women. Higher fat accumulation in the lower body, when compared to the trunk, seems to have a lower risk of CVD and associated risk factors - even in the presence of fat in the abdominal region - with women presenting lower risks than men.

Racism and racial iniquities in poor self-rated health: the role of intergenerational social mobility in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). / Racismo e iniquidade racial na autoavaliação de saúde ruim: o papel da mobilidade social intergeracional no Estudo Longitudinal de Saúde do Adulto (ELSA-Brasil).

Blacks and Browns have major health disadvantages, are less likely to rise in the social hierarchy throughout the course of life, and pertain to lower socioeconomic levels than Whites as a result of structural racism. However, little is known about the mediating role of intergenerational mobility in the association between race/skin color and health. The aim of the present study was to investigate the association between racism and self-rated health and to verify to what extent intergenerational social mobility mediates this association. This was a cross-sectional study conducted with data from 14,386 participants from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) baseline (2008-2010). Maternal education, education of the participant, socio-occupational class of the head of household, and socio-occupational class of the participant were used in the indicators of intergenerational social mobility (educational and socio-occupational). Logistic regression models were used. The prevalence of poor self-rated health was 15%, 24%, and 28% among Whites, Browns, and Blacks, respectively. After adjustments for age, sex, and research center, greater chances of poor self-rated health were found among Blacks (OR = 2.15; 95%CI: 1.92-2.41) and Browns (OR = 1.82; 95%CI: 1.64-2.01) when compared to Whites. Intergenerational educational and socio-occupational mobility mediated, respectively, 66% and 53% of the association between race/color and poor self-rated health in Blacks, and 61% and 51% in Browns, respectively. Results confirm racial iniquity in self-rated health and point out that unfavorable intergenerational social mobility is an important mechanism to explain this iniquity.

Pretos e pardos apresentam grandes desvantagens de saúde, possuem menores chances de ascensão na hierarquia social no curso de vida e menores níveis socioeconômicos do que brancos como resultado do racismo estrutural. Entretanto, pouco se sabe sobre o papel mediador da mobilidade intergeracional na associação entre racismo e saúde. O objetivo do presente estudo foi investigar a associação entre racismo e a autoavaliação de saúde, e verificar em que medida a mobilidade social intergeracional media essa associação. Estudo transversal realizado com dados de 14.386 participantes da linha de base (2008-2010) do Estudo Longitudinal de Saúde do Adulto (ELSA-Brasil). Escolaridade materna, escolaridade do participante, classe sócio-ocupacional do chefe de família e classe sócio-ocupacional do participante compuseram os indicadores de mobilidade social intergeracional (educacional e sócio-ocupacional). Modelos de regressão logística foram utilizados. A prevalência de autoavaliação de saúde ruim foi de 15%, 24% e 28% entre brancos, pardos e pretos, respectivamente. Após ajustes por idade, sexo e centro de investigação foram encontradas maiores chances de autoavaliação de saúde ruim entre pretos (OR = 2,15; IC95%: 1,92-2,41) e pardos (OR = 1,82; IC95%: 1,64-2,01) quando comparados aos brancos. A mobilidade educacional e sócio-ocupacional intergeracional mediaram, respectivamente, 66% e 53% da associação entre a raça/cor e autoavaliação de saúde ruim em pretos, e 61% e 51% em pardos, respectivamente. Resultados confirmam a iniquidade racial na autoavaliação de saúde e apontam que a mobilidade social intergeracional desfavorável é um importante mecanismo para explicar essa iniquidade.

Negros y mulatos presentan grandes desventajas de salud, poseen menores oportunidades de ascensión en la jerarquía social en el trascurso de su vida, y menores niveles socioeconómicos que los blancos, como resultado del racismo estructural. No obstante, poco se sabe sobre el papel mediador de la movilidad intergeneracional en la asociación entre racismo y salud. El objetivo de este estudio fue investigar la asociación entre racismo y autoevaluación de salud, así como verificar en qué medida la movilidad social intergeneracional interfiere en esa asociación. Se trata de un estudio transversal, realizado con datos de 14.386 participantes de la base de referencia (2008-2010) del Estudio Longitudinal de Salud de Adultos (ELSA-Brasil). La escolaridad materna, del participante, clase socio-ocupacional del jefe de familia y clase socio-ocupacional del participante compusieron los indicadores de movilidad social intergeneracional (educacional y socio-ocupacional). Se utilizaron modelos de regresión logística. La prevalencia de autoevaluación de mala salud fue de 15%, 24% y 28% entre blancos, mulatos/mestizos y negros, respectivamente. Tras los ajustes por edad, sexo y centro de investigación, se encontraron mayores oportunidades de autoevaluación de mala salud entre negros (OR = 2,15; IC95%: 1,92-2,41) y mulatos/mestizos (OR = 1,82; IC95%: 1,64-2,01), cuando se compara con los blancos. La movilidad educacional y socio-ocupacional intergeneracional mediaron, respectivamente, 66% y 53% de la asociación entre raza/color y autoevaluación de mala salud en negros, y 61% y 51% en mulatos/mestizos, respectivamente. Los resultados confirman la inequidad racial en la autoevaluación de salud y apuntan que la movilidad social intergeneracional desfavorable es un importante mecanismo para explicar esa inequidad.