Advances in ex vivo expansion of hematopoietic stem and progenitor cells for clinical applications.

As caretakers of the hematopoietic system, hematopoietic stem cells assure a lifelong supply of differentiated populations that are responsible for critical bodily functions, including oxygen transport, immunological protection and coagulation. Due to the far-reaching influence of the hematopoietic system, hematological disorders typically have a significant impact on the lives of individuals, even becoming fatal. Hematopoietic cell transplantation was the first effective therapeutic avenue to treat such hematological diseases. Since then, key use and manipulation of hematopoietic stem cells for treatments has been aspired to fully take advantage of such an important cell population. Limited knowledge on hematopoietic stem cell behavior has motivated in-depth research into their biology. Efforts were able to uncover their native environment and characteristics during development and adult stages. Several signaling pathways at a cellular level have been mapped, providing insight into their machinery. Important dynamics of hematopoietic stem cell maintenance were begun to be understood with improved comprehension of their metabolism and progressive aging. These advances have provided a solid platform for the development of innovative strategies for the manipulation of hematopoietic stem cells. Specifically, expansion of the hematopoietic stem cell pool has triggered immense interest, gaining momentum. A wide range of approaches have sprouted, leading to a variety of expansion systems, from simpler small molecule-based strategies to complex biomimetic scaffolds. The recent approval of Omisirge, the first expanded hematopoietic stem and progenitor cell product, whose expansion platform is one of the earliest, is predictive of further successes that might arise soon. In order to guarantee the quality of these ex vivo manipulated cells, robust assays that measure cell function or potency need to be developed. Whether targeting hematopoietic engraftment, immunological differentiation potential or malignancy clearance, hematopoietic stem cells and their derivatives need efficient scaling of their therapeutic potency. In this review, we comprehensively view hematopoietic stem cells as therapeutic assets, going from fundamental to translational.

A Contribution towards Sustainable Development in the Amazon Based on a Socioeconomic and Environmental Analysis of Visceral Leishmaniasis in the State of Pará, Brazil.

Human Visceral Leishmaniasis is an endemic public health problem in the Amazon. This article analyzed the spatial distribution of this disease and its relationship with socioeconomic, environmental and public health policy variables in four mesoregions of the state of Pará, from 2011 to 2022. This ecological study used secondary data obtained from official Brazilian agencies. Spatial analysis was performed using the Flow, Kernel and Global Moran bivariate techniques expressed in thematic maps. In the mesoregions studied, 2685 cases of the disease were confirmed, with the highest number of cases in Southeast Pará state. The epidemiological profile followed the national pattern of occurrence of the disease, with a higher number of cases in children below school age. Spatial dependence was observed between the prevalence of the disease and socio-economic indicators. The most intense movement of patients was towards the Belém Metropolitan mesoregion. The disease showed an inhomogeneous pattern of distribution of cases, with a direct relationship between areas with cases and deforestation associated with different anthropic activities. There is a socio-environmental production of the disease that goes beyond the border limits of the mesoregions, and its establishment is related to the unsustainable development model implemented in the region.

SNX27: A trans-species cognitive modulator with implications for anxiety and stress susceptibility.

Sorting Nexin 27 (SNX27) is a brain-enriched endosome-associated cargo adaptor that shapes excitatory control, being relevant for cognitive and reward processing, and for several neurological conditions. Despite this, SNX27's role in the nervous system remains poorly explored. To further understand SNX27 function, we performed an extensive behavioral characterization comprising motor, cognitive and emotional dimensions of SNX27+/- mice. Furthermore, attending on the recently described association between SNX27 function and cellular stress signaling mechanisms in vitro, we explored SNX27-stress interplay using a Caenorhabditis elegans Δsnx-27 mutant and wild-type (WT) rodents after stress exposure. SNX27+/- mice, as C. elegans Δsnx-27 mutants, present cognitive impairments, highlighting a conserved role for SNX27 in cognitive modulation across species. Interestingly, SNX27 downmodulation leads to anxiety-like behavior in mice evaluated in the Elevated Plus Maze (EPM). This anxious phenotype is associated with increased dendritic complexity of the bed nucleus of the stria terminalis (BNST) neurons, and increased complexity of the basolateral amygdala (BLA) pyramidal neurons. These findings highlight the still unknown role of SNX27 in anxiety regulation. Moreover, we uncovered a direct link between SNX27 dysfunction and stress susceptibility in C. elegans and found that stress-exposed rodents display decreased SNX27 levels in stress-susceptible brain regions. Altogether, we provided new insights on SNX27's relevance in anxiety-related behaviors and neuronal structure in stress-associated brain regions.

Influence of sociodemographic and obstetric factors on maternal mortality in Brazil from 2011 to 2021.

BACKGROUND: Obstetric causes are classified as direct (complications of pregnancy, childbirth or the puerperium) or indirect (caused by pregnancy but not directly caused by it). This study aimed to analyze maternal mortality from obstetric causes in Brazil from 2011 to 2021. METHODS: This was an ecological study on mortality and live births. The outcomes were the specific risk of mortality from direct and indirect cause adjustment and death during pregnancy and the puerperium. Binary and multiple linear logistic regressions were used to assess the influence of sociodemographic factors and maternal and child health indicators on maternal mortality and time of death (pregnancy and puerperium). RESULTS: Regarding mortality during pregnancy and during the puerperium, increased (p = 0.003) and decreased (p = 0.004) mortality over the years, respectively; residing in the northern region was associated with lower (p < 0.05) and greater (p = 0.035) odds; and the Maternal Mortality Committee was the primary and least active source of investigation, respectively (p < 0.0001). The number of deaths from indirect causes increased with age (p < 0.001) and in the northern region (p = 0.011) and decreased in the white (< 0.05) and stable union (0.002) regions. Specifically, for mortality risk, the age group [women aged 15-19 years presented an increase in cesarean section (p < 0.001) was greater than that of women who had < 4 antenatal visits (p < 0.001)], education [women who completed high school (8 to 11 years) was greater when they had < 4 prenatal visits (p = 0.018)], and marital status [unmarried women had more than 4 antenatal visits (p < 0.001); cesarean birth (p = 0.010) and < 4 antenatal visits (p = 0.009) were predictors of marriage; and women in a stable union who had < 4 prenatal visits and live births to teenage mothers (p < 0.001) were predictors]. Women who had no education (p = 0.003), were divorced (p = 0.036), had cesarean deliveries (p < 0.012), or lived in the north or northeast (p < 0.008) had higher indirect specific mortality risk. CONCLUSIONS: Sociodemographic factors and maternal and child health indicators were related to different patterns of obstetric mortality. Obstetric mortality varied by region, marital status, race, delivery, prenatal care, and cause of death.

The role of mifepristone on first trimester miscarriage treatment - A double-blind randomized controlled trial - MiFirsT.

OBJECTIVES: To evaluate the efficacy of combined mifepristone and misoprostol compared to misoprostol alone in outpatient medical treatment of first trimester miscarriage. Additionally, the study intends to compare the rate of complications, adverse effects, and treatment acceptability between groups. STUDY DESIGN: Single-center double-blind randomized placebo-controlled trial including women with diagnosis of missed first trimester miscarriage up to 9 weeks of gestation. RESULTS: Between April 2019 and November 2021, 216 women diagnosed with first trimester miscarriage up to 9 weeks of gestation were randomly assigned to mifepristone group or to misoprostol-alone group. Data from 105 women in mifepristone group and 103 women in misoprostol-alone group were analyzed, with no differences in baseline characteristics. The median time between medications (oral mifepristone/placebo and vaginal misoprostol) was nearly 43 h in both groups (p = 0.906). The median time to first follow-up was 2.6 weeks (IQR 1.0) in mifepristone group and 2.4 weeks (IQR 1.0) in misoprostol-alone group (p = 0.855). The overall success rate of medical treatment was significantly higher in the mifepristone-group comparing to misoprostol-alone group (94.3% vs. 82.5%, RR 1.14, 95% CI, 1.03-1.26; p = 0.008). Accordingly, the rate of surgical treatment was significantly lower in the mifepristone-group (5.7% vs.14.6%, RR 0.39, 95% CI, 0.16-0.97; p = 0.034). The composite complication rate was similar and lower than 4% in both groups. No case of complicated pelvic infection, hemodynamic instability or inpatient supportive treatment was reported. There were no significant differences in the rates of adverse events, median score for vaginal bleeding intensity or analgesics use. Despite the same median value, the score of abdominal pain intensity was significantly higher in the mifepristone-group (p = 0.011). In both groups, more than 65% of the women classified the treatment as "good" and 92% would recommend it to a friend on the same clinical situation. CONCLUSION: The mifepristone plus vaginal misoprostol combined treatment for medical resolution of first trimester miscarriage resulted in significant higher success rate and lower rate of surgical uterine evacuation comparing to misoprostol-alone treatment, with no relevant differences in adverse events or treatment acceptability.

The First Brazilian Cardiovascular Registry of Atrial Fibrillation: Primary Results of the RECALL Study.

BACKGROUND: It is estimated that atrial fibrillation (AF) affects approximately 1.5 million people in Brazil; however, epidemiological data are limited. We sought to evaluate the characteristics, treatment patterns, and clinical outcomes in patients with AF in Brazil by creating the first nationwide prospective registry. METHODS: RECALL was a multicenter, prospective registry that included and followed for 1 year 4,585 patients with AF at 89 sites across Brazil from April 2012 to August 2019. Patient characteristics, concomitant medication use, and clinical outcomes were analyzed using descriptive statistics and multivariable models. RESULTS: Of 4,585 patients enrolled, the median age was 70 (61, 78) years, 46% were women, and 53.8% had permanent AF. Only 4.4% of patients had a history of previous AF ablation and 25.2% had a previous cardioversion. The mean (SD) CHA2DS2-VASc score was 3.2 (1.6); median HAS-BLED score was 2 (2, 3). At baseline, 22% were not on anticoagulants. Of those taking anticoagulants, 62.6% were taking vitamin K antagonists and 37.4% were taking direct oral anticoagulants. The primary reasons for not using an oral anticoagulant were physician judgment (24.6%) and difficulty in controlling (14.7%) or performing (9.9%) INR. Mean (SD) TTR for the study period was 49.5% (27.5). During follow-up, the use of anticoagulants and INR in the therapeutic range increased to 87.1% and 59.1%, respectively. The rates/100 patient-years of death, hospitalization due to AF, AF ablation, cardioversion, stroke, systemic embolism, and major bleeding were 5.76 (5.12-6.47), 15.8 (14.6-17.0), 5.0 (4.4-5.7), 1.8 (1.4-2.2), 2.77 (2.32-3.32), 1.01 (0.75-1.36), and 2.21 (1.81-2.70). Older age, permanent AF, New York Heart Association class III/IV, chronic kidney disease, peripheral arterial disease, stroke, chronic obstructive pulmonary disease, and dementia were independently associated with increased mortality while the use of anticoagulant was associated with lower risk of death. CONCLUSIONS: RECALL represents the largest prospective registry of patients with AF in Latin America. Our findings highlight important gaps in treatment, which can inform clinical practice and guide future interventions to improve the care of these patients.

Malaria and environmental, socioeconomics and public health conditions in the municipality of São Félix do Xingu, Pará, Eastern Amazon, Brazil: An ecological and cross-sectional study.

BACKGROUND: Malaria is a parasitosis conditioned by several factors. This study sought to analyze the spatial distribution of malaria considering environmental, socioeconomic, and political variables in São Félix do Xingu, Pará, Brazil, from 2014 to 2020. METHODS: Epidemiological, cartographic, and environmental data were obtained from the Ministry of Health, Brazilian Geographical and Statistical Institute, and National Space Research Institute. Statistical and spatial distribution analyses were performed using chi-squared tests of expected equal proportions and the kernel and bivariate global Moran's techniques with Bioestat 5.0 and ArcGIS 10.5.1. RESULTS: The highest percentage of cases occurred in adult males with brown skin color, mainly placer miners, with a primary education level, living in rural areas, who were infected with Plasmodium vivax and with parasitemia of two or three crosses as diagnosed by the thick drop/smear test. The disease had a non-homogeneous distribution, with distinct annual parasite indices associated with administrative districts and clusters of cases in locations with deforestation, mining, and pastures close to Conservation Units and Indigenous Lands. Thus, a direct relationship between areas with cases and environmental degradation associated with land use was demonstrated, along with the precarious availability of health services. Pressure on protected areas and epidemiological silence in Indigenous Lands were also noted. CONCLUSIONS: Environmental and socioeconomic circuits were identified for development of diseases associated with precarious health services in the municipality. These findings highlight the need to intensify malaria surveillance and contribute to the systematic knowledge of malaria's epidemiology by considering the complexity of its conditioning factors.

COVID-19 in the Eastern Brazilian Amazon: Incidence, Clinical Management, and Mortality by Social Determinants of Health, Symptomatology, and Comorbidities in the Xingu Health Region.

This study aims to investigate the relationship between social determinants of health (SDH), incidence, and mortality to verify which sociodemographic factors, symptoms, and comorbidities predict clinical management; second, this study aims to conduct a survival analysis of individuals with COVID-19 in the Xingu Health Region. Consequently, this study adopted an ecological framework, employing secondary data of COVID-19-positive individuals from the Xingu Health Region, Pará State, Brazil. The data were obtained through the database of the State of Pará Public Health Secretary (SESPA) for the period from March 2020 to March 2021. The incidence and mortality were higher in Vitória do Xingu and Altamira. Municipalities with a higher percentage of citizens with health insurance and higher public health expenditure showed a higher incidence and mortality. A higher gross domestic product was associated with a higher incidence. Females were found to be associated with better clinical management. To live in Altamira was a risk factor for intensive care unit admission. The symptoms and comorbidities that predicted worse clinical management were dyspnea, fever, emesis, chills, diabetes, cardiac and renal diseases, obesity, and neurological diseases. There were higher incidence, mortality, and lower survival rates among the elderly. Thus, it can be concluded that SDH indicators, symptomatology, and comorbidities have implications for the incidence, mortality, and clinical management of COVID-19 in the Xingu Health Region of eastern Amazonia, Brazil.

Cellular Aging Secretes: a Comparison of Bone-Marrow-Derived and Induced Mesenchymal Stem Cells and Their Secretome Over Long-Term Culture.

Mesenchymal stem cells (MSCs) hold promising therapeutic potential in several clinical applications, mainly due to their paracrine activity. The implementation of future secretome-based therapeutic strategies requires the use of easily accessible MSCs sources that provide high numbers of cells with homogenous characteristics. MSCs obtained from induced pluripotent stem cells (iMSCs) have been put forward as an advantageous alternative to the gold-standard tissue sources, such as bone marrow (BM-MSCs). In this study, we aimed at comparing the secretome of BM-MSCs and iMSCs over long-term culture. For that, we performed a broad characterization of both sources regarding their identity, proteomic secretome analysis, as well as replicative senescence and associated phenotypes, including its effects on MSCs secretome composition and immunomodulatory action. Our results evidence a rejuvenated phenotype of iMSCs, which is translated into a superior proliferative capacity before the induction of replicative senescence. Despite this significant difference between iMSCs and BM-MSCs proliferation, both untargeted and targeted proteomic analysis revealed a similar secretome composition for both sources in pre-senescent and senescent states. These results suggest that shifting from the use of BM-MSCs to a more advantageous source, like iMSCs, may yield similar therapeutic effects as identified over the past years for this gold-standard MSC source.

Inspiratory muscle training in people with chronic obstructive pulmonary disease (COPD): a systematic review / Entrenamiento de los músculos inspiratorios en personas con enfermedad pulmonar obstructiva crónica (EPOC): una revisión sistemática / Treinamento muscular inspiratório em pessoas com doença pulmonar obstrutiva crônica (DPOC): uma revisão sistemática

ABSTRACT This systematic review aimed to demonstrate the effectiveness of inspiratory muscle training (IMT) in people with chronic obstructive pulmonary disease (COPD), analyzing the effects of IMT on inspiratory muscle strength and endurance, exercise tolerance and reduction of dyspnea. A systematic search was carried out in the PubMed, Cochrane and Lilacs databases, from August 2021 to February 2023, searching for studies published from 2016. The descriptors used for the search followed the description of the MeSH/DeCS terms, namely: "Pulmonary Disease, Chronic Obstructive," "Breathing Exercises," "Exercise Tolerance," "Dyspnea," and "Muscle strength," with the languages: English and Portuguese, using the Boolean operators "AND" and "OR." Ten studies met the inclusion criteria, including 733 patients. In all examined studies, there was a significant increase in inspiratory muscle strength and endurance compared to the control group; of the ten studies analyzed, four showed advances in reducing dyspnea and exercise tolerance. Notably, inspiratory muscle training is effective in improving dyspnea, exercise tolerance, and in increasing inspiratory muscle strength and endurance in people with moderate to severe COPD.

RESUMEN El objetivo de esta revisión sistemática fue evaluar la efectividad del entrenamiento muscular inspiratorio (EMI) en personas con enfermedad pulmonar obstructiva crónica (EPOC), analizando los efectos del EMI en la fuerza y resistencia muscular inspiratoria, en la tolerancia al ejercicio y en la reducción de la disnea. Se realizó una búsqueda sistemática en las bases de datos PubMed, Cochrane y LILACS, en el período de agosto de 2021 a febrero de 2023, en los estudios publicados desde 2016. Los descriptores utilizados en la búsqueda siguieron la descripción de los Medical Subject Headings (MeSH)/Descriptores en Ciencias de la Salud (DeCS), a saber: "pulmonary disease, chronic obstructive", "breathing exercises", "exercise tolerance", "dyspnea" y "muscle strength", en los idiomas inglés y portugués, y con los operadores booleanos "AND" y "OR". Diez estudios cumplieron los criterios de inclusión, en los cuales participaron 733 pacientes. En todos los estudios en análisis, se observó un significativo incremento de la fuerza muscular inspiratoria y de la resistencia en comparación con el grupo control. De los 10 estudios analizados, cuatro mostraron progreso en la reducción de la disnea y en la tolerancia al ejercicio. Cabe destacar que el entrenamiento muscular inspiratorio mostró ser eficaz en la mejora de la disnea, en la tolerancia al ejercicio y en el aumento de la fuerza y la resistencia muscular inspiratoria en personas con EPOC de moderada a grave.

RESUMO O objetivo desta revisão sistemática foi evidenciar a eficácia do treinamento muscular inspiratório (TMI) em pessoas com doença pulmonar obstrutiva crônica (DPOC), analisando os efeitos do TMI na força e resistência muscular inspiratória; na tolerância ao exercício; e na redução da dispneia. Realizou-se uma busca de forma sistemática nas bases de dados PubMed, Cochrane e LILACS, no período de agosto de 2021 a fevereiro 2023, por estudos publicados a partir de 2016. Os descritores utilizados para a busca seguiram a descrição dos Medical Subject Headings (MeSH)/Descritores em Ciências da Saúde (DeCS), sendo eles: "pulmonary disease, chronic obstructive", "breathing exercises", "exercise tolerance", "dyspnea" e "muscle strength", com o filtro dos idiomas inglês e português e os operadores booleanos "AND" e "OR". Dez estudos cumpriram os critérios de inclusão, envolvendo 733 pacientes. Em todos os estudos examinados, houve um aumento expressivo da força e da resistência muscular inspiratória em comparação ao grupo-controle. Ainda, dos 10 estudos analisados, quatro apresentaram progressos na diminuição da dispneia e na tolerância ao exercício. Ressalta-se que o treinamento muscular inspiratório é eficaz na melhora da dispneia, da tolerância ao exercício e do aumento da força e da resistência muscular inspiratória em pessoas com DPOC em estágios moderado a grave.

Malaria and environmental, socioeconomics and public health conditions in the municipality of São Félix do Xingu, Pará, Eastern Amazon, Brazil: An ecological and cross-sectional study

ABSTRACT Background: Malaria is a parasitosis conditioned by several factors. This study sought to analyze the spatial distribution of malaria considering environmental, socioeconomic, and political variables in São Félix do Xingu, Pará, Brazil, from 2014 to 2020. Methods: Epidemiological, cartographic, and environmental data were obtained from the Ministry of Health, Brazilian Geographical and Statistical Institute, and National Space Research Institute. Statistical and spatial distribution analyses were performed using chi-squared tests of expected equal proportions and the kernel and bivariate global Moran's techniques with Bioestat 5.0 and ArcGIS 10.5.1. Results: The highest percentage of cases occurred in adult males with brown skin color, mainly placer miners, with a primary education level, living in rural areas, who were infected with Plasmodium vivax and with parasitemia of two or three crosses as diagnosed by the thick drop/smear test. The disease had a non-homogeneous distribution, with distinct annual parasite indices associated with administrative districts and clusters of cases in locations with deforestation, mining, and pastures close to Conservation Units and Indigenous Lands. Thus, a direct relationship between areas with cases and environmental degradation associated with land use was demonstrated, along with the precarious availability of health services. Pressure on protected areas and epidemiological silence in Indigenous Lands were also noted. Conclusions: Environmental and socioeconomic circuits were identified for development of diseases associated with precarious health services in the municipality. These findings highlight the need to intensify malaria surveillance and contribute to the systematic knowledge of malaria's epidemiology by considering the complexity of its conditioning factors.

Systems bioengineering approaches for developmental toxicology.

Developmental toxicology is the field of study that examines the effects of chemical and physical agents on developing organisms. By using principles of systems biology and bioengineering, a systems bioengineering approach could be applied to study the complex interactions between developing organisms, the environment, and toxic agents. This approach would result in a holistic understanding of the effects of toxic agents on organisms, by considering the interactions between different biological systems and the impacts of toxicants on those interactions. It would be useful in identifying key biological pathways and mechanisms affected by toxic agents, as well as in the development of predictive models to assess potential risks of exposure to toxicants during development. In this review, we discuss the relevance of systems bioengineering to the field of developmental toxicity and provide up-to-date examples that illustrate the use of engineering principles for this application.

Evaluación de la calidad de vida de personas mayores participantes de un centro diurno / Evaluation of quality of life of older people participating in an adult day care center

Objetivos: Evaluar los cambios en la calidad de vida de un grupo de personas mayores participantes de un centro de adultos mayores en Santiago, Chile. Metodología: Estudio longitudinal prospectivo con 2 aplicaciones, una al ingreso y otra al término de la participación en un centro de adultos mayores con 35 personas mayores de 60 años. La calidad de vida se midió con el instrumento de la Organización Mundial de la Salud en su versión abreviada. Para el análisis de los datos se utilizaron estadísticas descriptivas y el test de la t de Student. Resultados: Al alta, la calidad de vida mostró un aumento significativo (p < 0,05), es decir, las personas mayores reportan mejores puntuaciones de calidad de vida después de haber participado en las intervenciones que tiene el centro de adultos mayores. Conclusiones: La calidad de vida se debe considerar una medida clave para evaluar los resultados de las intervenciones realizadas en los centros de adultos mayores (AU)

Objectives: To examine the changes in the quality of life of a group of older people participating in an adult day care center in Santiago, Chile. Methodology: Longitudinal study with two applications, one at admission and the other at the end of participation in the adult day care center, among 35 older people over 60 years belonging to the adult day care centers in Santiago, Chile. Quality of life was measured with the World Health Organization BREF instrument. Descriptive and analytical statistics were used for data analysis (t Student test). Results: This study showed a significant increase in quality of life (p < 0.05); older people reported better scores for quality of life after having participated in the interventions that the adult day care center has. Conclusions: Quality of life should be considered a key outcome when evaluating the results of interventions in adult day care center (AU)

A Concise Review on Electrospun Scaffolds for Kidney Tissue Engineering.

Chronic kidney disease is one of the deadliest diseases globally and treatment methods are still insufficient, relying mostly on transplantation and dialysis. Engineering of kidney tissues in vitro from induced pluripotent stem cells (iPSCs) could provide a solution to this medical need by restoring the function of damaged kidneys. However, implementation of such approaches is still challenging to achieve due to the complexity of mature kidneys in vivo. Several strategies have been defined to obtain kidney progenitor endothelial and epithelial cells that could form nephrons and proximal tube cells, but these lack tissue maturity and vascularisation to be further implemented. Electrospinning is a technique that has shown promise in the development of physiological microenvironments of several tissues and could be applied in the engineering of kidney tissues. Synthetic polymers such as polycaprolactone, polylactic acid, and poly(vinyl alcohol) have been explored in the manufacturing of fibres that align and promote the proliferation and cell-to-cell interactions of kidney cells. Natural polymers including silk fibroin and decellularised extracellular matrix have also been explored alone and in combination with synthetic polymers promoting the differentiation of podocytes and tubular-specific cells. Despite these attempts, further work is still required to advance the applications of electrospun fibres in kidney tissue engineering and explore this technique in combination with other manufacturing methods such as bioprinting to develop more organised, mature and reproducible kidney organoids.

Visceral Leishmaniasis and Land Use and Cover in the Carajás Integration Region, Eastern Amazon, Brazil.

Human visceral leishmaniasis is a major public health problem in the Amazon. Thus, we analyzed the spatial distribution of this disease and its relationship with epidemiological, socioeconomic, and environmental variables in the Carajás Integration Region, Pará state, from 2011 to 2020. Epidemiological data for this ecological study were obtained from the State Public Health Secretariat, environmental data were obtained from the National Space Research Institute, and socioeconomic data were obtained from the Brazilian Geography and Statistics Institute. ArcGIS 10.5.1 software was used for classifying land use and cover and for the Kernel and Moran spatial analyses. It was observed in 685 confirmed cases that the epidemiological profile followed the national pattern of the disease occurrence, with a high prevalence in children who were not school-aged. The disease had a non-homogeneous distribution with clusters related to different human activities, such as urbanization, ranching, and mining. A spatial dependence between the disease prevalence and socioeconomic indicators was observed. The municipalities presented gradients of case densities associated with a direct relationship between areas with cases and deforestation. The disease is developing due to risk factors such as establishment and maintenance related to the non-sustainable development model implemented in the region, pointing to the need for its revision.

Vasoactive Biomarkers in Patients With Vasovagal Syncope During Head-Up Tilt Test: A Case-Control Study.

Background: Vasovagal syncope (VVS) is the most common cause of syncope. Some stages of its pathophysiological mechanisms remain unclear. Vasoactive substances such as nitric oxide metabolites (NOx) and endothelin (ET) may be involved during acute orthostatic stress. Objective: To analyze plasma changes in NOx and ET and heart rate variability (HRV) in the supine positions (T1) and during the head-up tilt test (HUTT) (T2), in patients with VVS (case group) and control group. Methods: Thirty-seven patients (17 in the case group and 20 in the control group), matched for age and sex (mean aged 31.8 years) underwent HUTT with simultaneous HRV recording and venipuncture. Blood samples were collected during phases T1 and T2 and the analysis was performed without knowledge of the HUTT result. Results: In the total sample, there was an increase in NOx values (P = .014), however there was no increase in ET values from phase T1 to phase T2. Patients with VVS tended to increase plasma NOx values (P = .057) and had significantly higher plasma values compared to ET (P = .033) between phases T1 to T2. In the control group, there was no significant change in the values of these vasoactive substances. Regarding HRV, there were a decrease in the component HF (high frequency) and increased of the LF (low frequency)/HF ratio during HUTT. Conclusions: There was an increase in ET during HUTT occurred only in the case group. These patients are more likely to have an imbalance between antagonistic vasoactive biomarkers during orthostatic stress.

Lipocalin-2 does not influence EAE clinical score but it increases inflammation in central nervous system.

The contribution of lipocalin-2 (LCN2) to multiple sclerosis (MS) is controversial. Herein, we induced experimental autoimmune encephalomyelitis (EAE) in LCN2-null and wild-type (Wt) mice. While we did not find differences between genotypes regarding clinical score, LCN2-null EAE mice presented decreased expression of interferon gamma and diminished demyelination in the cerebellum. Both genotypes presented similar alterations in the thymocyte and splenocyte populations. In MS patients, higher LCN2 CSF levels at diagnosis could be associated with faster disease progression, however further studies are needed to confirm these results, since this association was lost after controlling for the patients age, presence of oligoclonal bands and gender. Overall, our results support a harmful role for LCN2 in the disease context.

A Dynamic 3D Aggregate-Based System for the Successful Expansion and Neural Induction of Human Pluripotent Stem Cells.

The demand for large cell numbers for cellular therapies and drug screening applications requires the development of scalable platforms capable of generating high-quality populations of tissue-specific cells derived from human pluripotent stem cells (hPSCs). Here, we studied the ability of Gibco StemScale PSC Suspension Medium to promote the efficient expansion of hPSC cultures as aggregates grown in suspension. We tested human induced pluripotent stem cell (hiPSC) growth in 6-well plates (on orbital shaker platforms) and single-use vertical-wheel bioreactors for a total of three consecutive passages. Up to a 9-fold increase in cell number was observed over 5 days per passage, with a cumulative fold change up to 600 in 15 days. Additionally, we compared neural induction of hiPSCs by using a dual SMAD inhibition protocol with a commercially available neural induction medium, which can potentially yield more than a 30-fold change, including neural progenitor induction and expansion. This system can also be adapted toward the generation of floor plate progenitors, which yields up to an 80-fold change in cell number and generates FOXA2-positive populations. In summary, we developed platforms for hiPSC expansion and neural induction into different brain regions that provide scalability toward producing clinically relevant cell numbers.

Spatial distribution of malaria and primary healthcare in Cametá and Tucuruí, Pará state, Brazil.

INTRODUCTION: Malaria cases in Brazil are concentrated in the Amazon region. In the state of Pará, malaria is considered an endemic disease, and the population has different levels of exposure, which contributes to different types of occurrence in the municipalities. METHODOLOGY: A descriptive, cross-sectional, and ecological study was conducted using data from the Malaria Epidemiological Surveillance System of the municipalities of Cametá and Tucuruí, PA, Brazil, from 2014 to 2018; the Brazilian Institute of Geography and Statistics; and the National Registry of Health Institutions of the Ministry of Health. Statistical and spatial analyses of epidemiological, laboratory and public health service coverage variables were performed using the Bioestat 5.0 and ArcGis 10.5 software. RESULTS: 11,381 Malaria cases were reported in the two municipalities. The highest percentage of case notifications was reported in brown-skinned men aged from 19 and 59 years, and who had primary education levels. The predominant occupations were farming and livestock in Cametá and domestic activity in Tucuruí. The most common diagnostic examination used was a thick blood smear, and Plasmodium vivax was the species most often encountered. The percentage of primary care coverage increased during the study period. The spatial distribution of the disease was not homogeneous, and there were clusters of cases with different densities in Cametá and Tucuruí. CONCLUSIONS: Malaria is a public health problem in the municipalities of Cametá and Tucuruí, because of its transmission dynamics and variable spatial distribution as well as the coexistence of factors that favor the exposure of resident populations to epidemiological situations, thus reflecting health inequities.