Omega-3 polyunsaturated fatty acids and Parkinson's disease: A systematic review of animal studies.

Parkinson's disease (PD) is the second most common neurodegenerative disorder. The primary pathological features of PD include the presence of α-synuclein aggregates and Lewy bodies, mitochondrial dysfunction, oxidative stress, and neuroinflammation. Recently, omega-3 fatty acids (ω-3 PUFAs) have been under investigation as a preventive and/or therapeutic strategy for PD, primarily owing to their antioxidant and anti-inflammatory properties. Therefore, the objective of this study was to conduct a systematic review of the literature, focusing on studies that assessed the effects of ω-3 PUFAs in rodent models mimicking human PD. The search was performed using the terms "Parkinson's disease," "fish oil," "omega 3," "docosahexaenoic acid," and "eicosapentaenoic acid" across databases PUBMED, Web of Science, Science Direct, Scielo, and Google Scholar. Following analysis based on predefined inclusion and exclusion criteria, 39 studies were included. Considering behavioral parameters, pathological markers of the disease, quantification of ω-3 PUFAs in the brain, as well as anti-inflammatory, antioxidant, and anti-apoptotic effects, it can be observed that ω-3 PUFAs exhibit a potential neuroprotective effect in PD. In summary, this systematic review presents significant scientific evidence regarding the effects and mechanisms underlying the neuroprotective properties of ω-3 PUFAs, offering valuable insights for the development of future clinical investigations.

Self-inflicted burns in Brazil: systematic review and meta-analysis.

INTRODUCTION: burns represent a pivotal component of trauma in Brazil, accounting for 2 million incidents and 2,500 deaths annually. Self-intentional burns are associated with a worse prognosis, larger burned surface area, higher infection rates, and death. The lack of studies on the issue of self-immolation raises epidemiological questions regarding Brazilian victims. This study aimed to investigate the profile of burn events associated with self-injurious behavior among Brazilian victims. METHODS: this systematic review was performed according to PRISMA 2020 guidelines and evaluated the correlation between self-injurious behavior as a cause of burns in Brazilian victims and its epidemiological implications in the last 20 years (2003-2023). The MeSH terms "Burns", "Self-Injurious Behavior", "Epidemiology" and "Brazil" were queried in the PubMed/MEDLINE, SciELO, and Cochrane Library databases, and, after selection by inclusion/exclusion criteria, the most relevant studies were critically analyzed. RESULTS: From 1,077 pre-selected studies, 92 were potentially eligible, resulting in 7 manuscripts incorporated in this review. From 3,510 burned victims assembled in the pool of selected studies, 311 cases displayed self-injurious behavior. Burned patients who attempted to burn their lives have a higher risk of death (p<0.05; RR=5.1 [3.2-8.1]) and larger burned surface area (p<0.05; MD=19.2 [10-28.2]), compared to accidental cases. Moreover, the female gender was at a higher risk of attempting self-immolation (p<0.05; RR=4.01 [2.9-5.5]). CONCLUSION: our results show that self-inflicted burn cases were associated with a larger burned surface area and a higher risk of death, and the female gender was identified as a relevant risk factor in Brazil.

Alcohol consumption during pregnancy by women from southern Brazil: a cross-sectional study.

BACKGROUND: Some maternal characteristics are related to alcohol intake during pregnancy, which irreversibly compromises the maternal-fetal binomial integrity. OBJECTIVES: To identify the frequency, impact, and factors associated with alcohol consumption during pregnancy. DESIGN AND SETTING: A cross-sectional study was performed at the Hospital Materno Infantil Presidente Vargas (HMIPV) in Porto Alegre/RS between March and December 2016. METHODS: A structured questionnaire was administered along with a medical records review. They refer to the maternal sociodemographic and gestational status, alcohol consumption patterns, and characteristics of the fetus/newborn. In the statistical analysis, P values < 0.05 were considered significant. RESULTS: The frequency of alcohol intake was 37.3%; this was characterized by the consumption of fermented beverages (89.3%), especially during the first trimester (79.6%). Risky consumption (high and/or early) occurred for 30.2% of participants. Risk factors associated with maternal alcohol consumption during pregnancy were tobacco use (P < 0.001) and abortion attempt (P = 0.023). Living with a partner (P = 0.002) and planning pregnancy (P = 0.009) were protective factors. Risky consumption was related to all of the aforementioned variables as well as threatened abortion (P = 0.023). CONCLUSIONS: Alcohol intake during pregnancy is common and affects nearly one-third of pregnant women. Knowledge of the population at risk and protective factors is essential for the development of campaigns that seek to reduce consumption and, therefore, its consequences for the mother and fetus.

Dietary Salicornia ramosissima improves the European seabass (Dicentrarchus labrax) inflammatory response against Photobacterium damselae piscicida.

Introduction: Modern fish farming faces challenges in sourcing feed ingredients, most related with their prices, 21 availability, and specifically for plant protein sources, competition for the limited cultivation space for 22 vegetable crops. In that sense, halophytes have the added value of being rich in valuable bioactive compounds and salt tolerant. This study assessed the inclusion of non-food fractions of S. ramosissima in European seabass diets. Methods: Different levels (2.5%, 5%, and 10%) were incorporated into seabass diets, replacing wheat meal (diets ST2.5, ST5, and ST10) or without inclusion (CTRL). Experimental diets were administered to seabass juveniles (8.62 ± 0.63 g) for 34 and 62 days and subsequent inflammatory responses to a heat-inactivated Photobacterium damselae subsp. piscicida (Phdp) were evaluated in a time-course manner (4, 24, 48, and 72 h after the challenge). At each sampling point, seabass haematological profile, plasma immune parameters, and head-kidney immune-related gene expression were evaluated. Results: After both feeding periods, most parameters remained unaltered by S. ramosissima inclusion; nonetheless, seabass fed ST10 showed an upregulation of macrophage colony-stimulating factor 1 receptor 1 (mcsf1r1) and cluster of differentiation 8 (cd8ß) compared with those fed CTRL after 62 days of feeding. Regarding the inflammatory response, seabass fed ST10 showed lower plasma lysozyme levels than their counterparts fed ST2.5 and ST5 at 24 h following injection, while 4 h after the inflammatory stimulus, seabass fed ST10 presented higher numbers of peritoneal leucocytes than fish fed CTRL. Moreover, at 4 h, fish fed ST2.5, ST5, and ST10 showed a higher expression of interleukin 1ß (il1ß), while fish fed ST5 showed higher levels of ornithine decarboxylase (odc) than those fed CTRL. An upregulation of macrophage colony-stimulating factor 1 receptor 1 (mcsf1r1) and glutathione peroxidase (gpx) was also observed at 72 h in fish fed ST10 or ST5 and ST10 compared with CTRL, respectively. Discussion: In conclusion, incorporating up to 10% of the non-food fraction S. ramosissima in feed did not compromise seabass growth or immune status after 62 days, aligning with circular economy principles. However, S. ramosissima inclusion improved the leucocyte response and upregulated key immune-related genes in seabass challenged with an inactivated pathogen.

Renal vein thrombosis in the course of non-operative treatment of kidney trauma: A rare case report.

INTRODUCTION: Venous thromboembolism is widely recognized as a life-threatening complication in trauma, yet renal vein thrombosis (RVT) following trauma is particularly rare. PRESENTATION OF CASE: We report a case of a 67-year-old man who was brought to the emergency department after falling down a 14-step staircase at home which presented right kidney trauma (parenchyma laceration with a perirenal hematoma) on computed tomography, and hematuria. Considering the patient's hemodynamic stability, a non-operative treatment was initiated, and the patient was referred to the intensive care unit for close observation. On post-trauma day 3, a repeated CT revealed right renal vein thrombosis. After evaluation, it was decided to maintain prophylactic anticoagulation doses of enoxaparin (40 mg/day) due to the elevated risk of bleeding in high-grade renal trauma and planned an inferior vena cava (IVC) filter placement. In the following days, the hematuria resolved spontaneously and an IVC filter was placed. The patient progressed with no complaints, spontaneous diuresis, improvement in laboratory parameters, and cardiovascular stability, which led to his discharge on day 12 with rivaroxaban 10 mg/day. The patient was successfully treated with a non-operative approach, and the RVT disappeared after 35 days. DISCUSSION: Post-traumatic renal vein thrombosis is a rare occurrence, and due to the infrequent nature of these events, specific management guidelines are not fully established, particularly when thrombosis is confirmed in an acutely injured patient. CONCLUSION: Conservative therapy seems to play a meaningful role in trauma-related renal vein thrombosis treatment.

Development of a Smart Wireless Multisensor Platform for an Optogenetic Brain Implant.

Implantable cell replacement therapies promise to completely restore the function of neural structures, possibly changing how we currently perceive the onset of neurodegenerative diseases. One of the major clinical hurdles for the routine implementation of stem cell therapies is poor cell retention and survival, demanding the need to better understand these mechanisms while providing precise and scalable approaches to monitor these cell-based therapies in both pre-clinical and clinical scenarios. This poses significant multidisciplinary challenges regarding planning, defining the methodology and requirements, prototyping and different stages of testing. Aiming toward an optogenetic neural stem cell implant controlled by a smart wireless electronic frontend, we show how an iterative development methodology coupled with a modular design philosophy can mitigate some of these challenges. In this study, we present a miniaturized, wireless-controlled, modular multisensor platform with fully interfaced electronics featuring three different modules: an impedance analyzer, a potentiostat and an optical stimulator. We show the application of the platform for electrical impedance spectroscopy-based cell monitoring, optical stimulation to induce dopamine release from optogenetically modified neurons and a potentiostat for cyclic voltammetry and amperometric detection of dopamine release. The multisensor platform is designed to be used as an opto-electric headstage for future in vivo animal experiments.

Self-inflicted burns in Brazil: systematic review and meta-analysis / Queimaduras autoprovocadas no Brasil: revisão sistemática e meta-análise

ABSTRACT Introduction: burns represent a pivotal component of trauma in Brazil, accounting for 2 million incidents and 2,500 deaths annually. Self-intentional burns are associated with a worse prognosis, larger burned surface area, higher infection rates, and death. The lack of studies on the issue of self-immolation raises epidemiological questions regarding Brazilian victims. This study aimed to investigate the profile of burn events associated with self-injurious behavior among Brazilian victims. Methods: this systematic review was performed according to PRISMA 2020 guidelines and evaluated the correlation between self-injurious behavior as a cause of burns in Brazilian victims and its epidemiological implications in the last 20 years (2003-2023). The MeSH terms "Burns", "Self-Injurious Behavior", "Epidemiology" and "Brazil" were queried in the PubMed/MEDLINE, SciELO, and Cochrane Library databases, and, after selection by inclusion/exclusion criteria, the most relevant studies were critically analyzed. Results: From 1,077 pre-selected studies, 92 were potentially eligible, resulting in 7 manuscripts incorporated in this review. From 3,510 burned victims assembled in the pool of selected studies, 311 cases displayed self-injurious behavior. Burned patients who attempted to burn their lives have a higher risk of death (p<0.05; RR=5.1 [3.2-8.1]) and larger burned surface area (p<0.05; MD=19.2 [10-28.2]), compared to accidental cases. Moreover, the female gender was at a higher risk of attempting self-immolation (p<0.05; RR=4.01 [2.9-5.5]). Conclusion: our results show that self-inflicted burn cases were associated with a larger burned surface area and a higher risk of death, and the female gender was identified as a relevant risk factor in Brazil.

RESUMO Introdução: Queimaduras representam um componente fundamental do trauma no Brasil, sendo responsáveis por 2 milhões de incidentes e 2.500 mortes anualmente. Queimaduras autointencionais estão associadas a pior prognóstico, maior superfície corporal queimada, maiores taxas de infecção e morte. A falta de estudos sobre a problemática da autoimolação levanta questões epidemiológicas em relação às vítimas brasileiras. O estudo se objetivou investigar o perfil das queimaduras associados ao comportamento autolesivo entre vítimas brasileiras. Métodos: Esta revisão sistemática foi realizada de acordo com as diretrizes PRISMA 2020 e avaliou a correlação entre comportamento autolesivo como causa de queimaduras em vítimas brasileiras e suas implicações epidemiológicas nos últimos 20 anos (2003-2023). Os termos MeSH "Burns", "Self-Injurious Behavior", "Epidemiology" e "Brazil" foram elencados no PubMed/MEDLINE, SciELO e Cochrane Library e, após seleção por critérios de inclusão/exclusão, os estudos mais relevantes foram analisados criticamente. Resultados: Dos 1.077 estudos pré-selecionados, 92 foram potencialmente elegíveis, resultando em 7 manuscritos incorporados nesta revisão. Das 3.510 vítimas queimadas reunidas no conjunto de estudos selecionados, 311 casos apresentaram comportamento autolesivo. Pacientes que tentaram autoimolação apresentam maior risco de morte (p<0,05; RR=5,1 [3,2-8,1]) e maior superfície corporal queimada (p<0,05; MD=19,2 [10-28,2]), em comparação com casos acidentais. Ademais, o sexo feminino apresentou maior risco para tentativa de autoimolação (p<0,05; RR=4,01 [2,9-5,5]). Conclusão: Nossos resultados mostram que os casos de queimaduras autoprovocadas foram associados a uma maior área de superfície corporal queimada e a um maior risco de morte, e o sexo feminino foi identificado como um fator de risco relevante no Brasil.

Alcohol consumption during pregnancy by women from southern Brazil: a cross-sectional study

ABSTRACT BACKGROUND: Some maternal characteristics are related to alcohol intake during pregnancy, which irreversibly compromises the maternal-fetal binomial integrity. OBJECTIVES: To identify the frequency, impact, and factors associated with alcohol consumption during pregnancy. DESIGN AND SETTING: A cross-sectional study was performed at the Hospital Materno Infantil Presidente Vargas (HMIPV) in Porto Alegre/RS between March and December 2016. METHODS: A structured questionnaire was administered along with a medical records review. They refer to the maternal sociodemographic and gestational status, alcohol consumption patterns, and characteristics of the fetus/newborn. In the statistical analysis, P values < 0.05 were considered significant. RESULTS: The frequency of alcohol intake was 37.3%; this was characterized by the consumption of fermented beverages (89.3%), especially during the first trimester (79.6%). Risky consumption (high and/or early) occurred for 30.2% of participants. Risk factors associated with maternal alcohol consumption during pregnancy were tobacco use (P < 0.001) and abortion attempt (P = 0.023). Living with a partner (P = 0.002) and planning pregnancy (P = 0.009) were protective factors. Risky consumption was related to all of the aforementioned variables as well as threatened abortion (P = 0.023). CONCLUSIONS: Alcohol intake during pregnancy is common and affects nearly one-third of pregnant women. Knowledge of the population at risk and protective factors is essential for the development of campaigns that seek to reduce consumption and, therefore, its consequences for the mother and fetus.

Effects of the COVID-19 pandemic on delays in diagnosis-to-treatment initiation for breast cancer in Brazil: a nationwide study.

Background: Short period from diagnosis to breast cancer (BC) treatment initiation remains challenging for the public health system in Brazil, which may have been further affected by the coronavirus disease-2019 (COVID-19) pandemic. This study assessed BC diagnosis-to-treatment intervals (DTi) in Brazil and the possible effects of the COVID-19 outbreak on delays. Methods: The Painel de Monitoramento de Tratamento Oncológico database was queried to obtain the number of Brazilian patients with a BC confirmed diagnosis and initiating cancer treatment in the pre-COVID-19 (2013-2019) and during the COVID-19 (2020-2021) periods, adopting a 60-day limit as timely treatment. A p-value of <0.05 was considered significant. Results: A total of 315,951 cases were included (females: 99.3% and males: 0.7%), of which 251,667 and 64,284 records were computed before and during the COVID-19 years, respectively. Most patients failed to perform the first cancer treatment within 60 days (>60: 51.8%). We observed an upward trend in the number of BC treatments provided in the pre-COVID-19 years (r2 = 0.9575; p < 0.05), but the volume of treatments exhibited an average reduction of 24.6% yearly during the COVID-19 pandemic. The average DTi in days was 122.4, 122.5 and 122.3 in the total period studied, before and during the COVID-19 outbreak, respectively. The arrival of COVID-19 in Brazil increased the chances of treatment delay (OR = 1.043; p < 0.05) and inverted the proportion of early/advanced stages at BC diagnosis (55.8%/44.2%-48.4%/51.6%). Conclusion: COVID-19 has imposed changes in BC care in Brazil, reducing the number of treatments provided by the Brazilian public health system, increasing the chances of delayed treatment initiation despite no differences in DTi averages being identified, and raising the proportion of advanced-stage diagnoses.

Trends in the morbidity and mortality of coronavirus disease 2019 in different ethnic groups and gender in a large Brazilian city.

As the coronavirus disease 2019 (COVID-19) outbreak spread, evidence has emerged that gender and race would bear a disproportionate impact on the morbimortality of COVID-19. Here, we conducted a retrospective observational study using the TabNet/Departamento de informática do sistema único de saúde platform of the city of São Paulo. COVID-19 records from March 2020 through December 2021 were included, and we evaluated the temporal trends of confirmed cases and case fatality rate by gender and ethnicity. Statistical analysis was performed using the R-software and BioEstat-software, considering p < 0.05 significant. From March/2020 to December/2021, 1 315 160 COVID-19 confirmed cases were recorded (57.1% females), and 2973 deaths were due to COVID-19. Males presented higher median mortality (0.44% vs. 0.23%; p < 0.05) and intensive care unit (ICU) admission rates (0.34% vs. 0.20%; p < 0.05). Men were also associated with a higher risk of death (risk ratio [RR] = 1.28; p < 0.05) and a higher chance of requiring ICU care (RR = 1.29; p < 0.05). Black ethnicity was associated with a higher risk of death (RR = 1.19; p < 0.05). White patients were more likely to require ICU admission (RR = 1.13; p < 0.05), whereas Browns were associated with a protective effect (RR = 0.86; p < 0.05). Furthermore, men presented a higher chance of death than women across the three major ethnic groups: Whites (RR = 1.33; p < 0.05), Blacks (RR = 1.24; p < 0.05), and Browns (RR = 1.35; p < 0.05). In this study of COVID-19 in São Paulo, men were associated with worse outcomes, including in the three major ethnicities in the population. Blacks exhibited a higher risk of death, Whites were more likely to require intensive care, and Browns were at protection from ICU hospitalization.

Dissolving Kraft Pulp Production and Xylooligosaccharide Coproduction: Effect of Pre-Hydrolysis Conditions.

Due to cotton's declining sustainability, more lignocellulosic materials are being used to produce dissolving pulp for textile applications. Pre-hydrolysis kraft is one of the main processes used to produce this material. Pre-hydrolysis under conventional conditions removes most of the hemicelluloses, but the majority end up as xylose and furfural, traditionally burned in a recovery boiler. The xylooligosaccharides (XOS), derived from hemicelluloses are a specialty product and can be recovered but requires adapted operative conditions. Thus, the objective was to recover XOS and evaluate the effect of pre-hydrolysis conditions on the final pulp characteristics. A flow-through reactor (FTR) was used to study the pre-hydrolysis, which allowed for modification of the retention time of the xylan in the free liquor after extraction from wood. The results have shown that by changing the fluid retention time in the pre-hydrolysis, the proportion of XOS/xylose/furfural recovered can be strongly changed. The hemicellulose content of the dissolving pulp decreased from 6.8% to about 2.6% using the FTR pretreatment.

Prostate-specific antigen response after Abiraterone treatment in mCRPC: PSA as a predictor of overall survival.

OBJECTIVES: Abiraterone Acetate (AA) is an important agent in the treatment of advanced prostate cancer. It was primarily approved for the treatment of metastatic castration-resistant prostate cancer (mCRPC) after failure of androgen deprivation therapy. There is still no available strong data regarding the impact of early decline of prostate-specific antigen (PSA) in the overall survival. The aim of this study was to evaluate the clinical efficacy of an early prostate-specific antigen response as a predictor of overall survival (OS) in metastatic castration-resistant prostate cancer when treated with Abiraterone Acetate. MATERIALS AND METHODS: A dual center, retrospective, cohort study on patients diagnosed with mCRPC treated with abiraterone between 2013 and 2020 was performed. Primary end-point was to demonstrate the efficacy of AA, with the analysis of PSA decline, and the correlation with overall survival. RESULTS: The cohort analysis consisted of 84 patients with a median age of 71 ± 9 years. A PSA response of > 30% and > 50% at 60 and 90 days was associated with improved OS. Multivariate analysis revealed that a 60 day PSA decline of > 30% was predictive of overall survival. Median OS of diag-nosed mCRPC patients was 28 months. Docetaxel pre-treatment was not associated with longer OS. The median duration of drug exposure for patients submitted to AA was found to be 14 months. CONCLUSIONS: Early PSA response rate can offer clinically meaningful information and can be considered a surrogate of longer OS. A > 30% or > 50% prostate-specific antigen decline at 60 and 90 days provided an important low-cost clinical tool to predict subsequent events in mCRPC patients treated with abiraterone.

A POPULATION STUDY ON GENDER AND ETHNICITY DIFFERENCES IN GALLBLADDER DISEASE IN BRAZIL.

AIM: Gallbladder diseases (GBD) are one of the most common medical conditions requiring surgical intervention, both electively and urgently. It is widely accepted that sex and ethnic characteristics mighty influence both prevalence and outcomes. This study aimed to evaluate the differences on distributions of gender and ethnicity related to the epidemiology of GBD in the Brazilian public health system. METHODS: DATASUS was used to retrieve patients' data recorded under the International Code of Diseases (ICD-10) - code K80 from January 2008 to December 2019. The number of admissions, modality of care, number of deaths, and in-hospital mortality rate were analyzed by gender and ethnic groups. RESULTS: Between 2008 and 2019, a total of 2,899,712 patients with cholelithiasis/cholecystitis (K80) were admitted to the hospitals of the Brazilian Unified Health System, of whom only 22.7% were males. Yet, the in-hospital mortality rate was significantly higher in males (15.9 per 1,000 male patients) than females (6.3 per 1,000 female patients) (p<0.05). Moreover, men presented a significantly higher risk of death (RR=2.5; p<0.05) and longer hospital stay (4.4 days vs. 3.3 days; p<0.05) than females. Compared to females, men presented a higher risk of death across all self-declared ethnic groups: whites (RR=2.4; p<0.05), blacks (RR=2.7; p<0.05), browns (RR=2.6; p<0.05), and Brazilian Indians (RR=2.13; p<0.05). CONCLUSION: In the years 2008-2019, women presented the highest prevalence of hospital admissions for GBD in Brazil, and men were associated with worse outcomes, including all ethnic groups.

A population study on gender and ethnicity differences in gallbladder disease in brazil / Estudo populacional sobre as diferenças de gênero e etnia na doença da vesícula biliar no brasil

ABSTRACT - BACKGROUND: Gallbladder diseases (GBD) are one of the most common medical conditions requiring surgical intervention, both electively and urgently. It is widely accepted that sex and ethnic characteristics mighty influence both prevalence and outcomes. AIM: This study aimed to evaluate the differences on distributions of gender and ethnicity related to the epidemiology of GBD in the Brazilian public health system. METHODS: DATASUS was used to retrieve patients' data recorded under the International Code of Diseases (ICD-10) - code K80 from January 2008 to December 2019. The number of admissions, modality of care, number of deaths, and in-hospital mortality rate were analyzed by gender and ethnic groups. RESULTS: Between 2008 and 2019, a total of 2,899,712 patients with cholelithiasis/cholecystitis (K80) were admitted to the hospitals of the Brazilian Unified Health System, of whom only 22.7% were males. Yet, the in-hospital mortality rate was significantly higher in males (15.9 per 1,000 male patients) than females (6.3 per 1,000 female patients) (p<0.05). Moreover, men presented a significantly higher risk of death (RR=2.5; p<0.05) and longer hospital stay (4.4 days vs. 3.3 days; p<0.05) than females. Compared to females, men presented a higher risk of death across all self-declared ethnic groups: whites (RR=2.4; p<0.05), blacks (RR=2.7; p<0.05), browns (RR=2.6; p<0.05), and Brazilian Indians (RR=2.13; p<0.05). CONCLUSION: In the years 2008-2019, women presented the highest prevalence of hospital admissions for GBD in Brazil, and men were associated with worse outcomes, including all ethnic groups.

RESUMO - RACIONAL: Doenças da vesícula biliar (DVB) são uma das condições médicas mais comuns que requerem intervenção cirúrgica, tanto eletiva como urgente. É amplamente aceito que o sexo e as características étnicas podem influenciar a prevalência e os desfechos. OBJETIVO: Avaliar as diferenças nas distribuições de gênero e etnia relacionados à epidemiologia da DVB no sistema público de saúde brasileiro. MÉTODOS: O DATASUS foi usado para elencar os dados de pacientes registrados no Código Internacional de Doenças (CID-10) sob o código K80, de janeiro de 2008 a dezembro de 2019. O número de admissões, caráter de atendimento, número de óbitos e taxa de mortalidade hospitalar foram analisados por gênero e por etnia. RESULTADO: Entre 2008 e 2019, 2.899.712 pacientes com colelitíase/colecistite (K80) foram admitidos em hospitais do Sistema Único de Saúde (SUS), dos quais apenas 22,7% eram do sexo masculino. Ainda assim, a taxa de mortalidade intra-hospitalar masculina (15,9:1.000 pacientes homens) foi significativamente maior do que a feminina (6,3:1.000 pacientes mulheres) (p<0,05). Ademais, homens apresentaram risco de morte significativamente maior em comparação às mulheres (RR=2,5; p<0,05) e maior tempo de internação hospitalar (4,4 dias versus 3,3 dias; p<0,05). Em comparação ao sexo feminino, homens apresentaram maior risco de morte em todos os grupos étnicos autodeclarados: brancos (RR=2,4; p<0,05), negros (RR=2,7; p<0,05), pardos (RR=2,6; p<0,05) e indígena (RR=2,13; p<0,05). CONCLUSÃO: Nos anos de 2008-2019, as mulheres apresentaram as maiores prevalências de internações hospitalares por DVB no Brasil, porém, os homens foram associados a piores desfechos, inclusive entre todos os grupos étnicos.

Myeloid cell subsets that express latency-associated peptide promote cancer growth by modulating T cells.

Myeloid suppressor cells promote tumor growth by a variety of mechanisms which are not fully characterized. We identified myeloid cells (MCs) expressing the latency-associated peptide (LAP) of TGF-ß on their surface and LAPHi MCs that stimulate Foxp3+ Tregs while inhibiting effector T cell proliferation and function. Blocking TGF-ß inhibits the tolerogenic ability of LAPHi MCs. Furthermore, adoptive transfer of LAPHi MCs promotes Treg accumulation and tumor growth in vivo. Conversely, anti-LAP antibody, which reduces LAPHi MCs, slows cancer progression. Single-cell RNA-Seq analysis on tumor-derived immune cells revealed LAPHi dominated cell subsets with distinct immunosuppressive signatures, including those with high levels of MHCII and PD-L1 genes. Analogous to mice, LAP is expressed on myeloid suppressor cells in humans, and these cells are increased in glioma patients. Thus, our results identify a previously unknown function by which LAPHi MCs promote tumor growth and offer therapeutic intervention to target these cells in cancer.

Targeting folate receptor beta on monocytes/macrophages renders rapid inflammation resolution independent of root causes.

Provoked by sterile/nonsterile insults, prolonged monocyte mobilization and uncontrolled monocyte/macrophage activation can pose imminent or impending harm to the affected organs. Curiously, folate receptor beta (FRß), with subnanomolar affinity for the vitamin folic acid (FA), is upregulated during immune activation in hematopoietic cells of the myeloid lineage. This phenomenon has inspired a strong interest in exploring FRß-directed diagnostics/therapeutics. Previously, we have reported that FA-targeted aminopterin (AMT) therapy can modulate macrophage function and effectively treat animal models of inflammation. Our current investigation of a lead compound (EC2319) leads to discovery of a highly FR-specific mechanism of action independent of the root causes against inflammatory monocytes. We further show that EC2319 suppresses interleukin-6/interleukin-1ß release by FRß+ monocytes in a triple co-culture leukemic model of cytokine release syndrome with anti-CD19 chimeric antigen receptor T cells. Because of its chemical stability and metabolically activated linker, EC2319 demonstrates favorable pharmacokinetic characteristics and cross-species translatability to support future pre-clinical and clinical development.

Comparison of outcomes and cost-effectiveness of laparoscopic and open appendectomies in public health services.

Acute appendicitis is the leading cause of abdominal emergency surgery worldwide and appendectomy continues to be the definitive treatment of choice. This cost-effectiveness analysis evaluates laparoscopic versus open appendectomies performed in public health services in the state of Bahia (Brazil). We conducted a retrospective observational study using the database from the Department of Informatics of the Unified Health System (DATASUS). Available data on appendectomies between 2008 and 2019 were included, and we evaluated the temporal trend of hospital admissions, procedure-related mortality rates, length of stay, and costs. Statistical analysis was performed using the R-software (R Foundation, v.4.0.3) and the BioEstat software (IMDS, v. 5.3), considering p<0.05 as significant. During 2008-2019, 53,024 appendectomies were performed in the public health services in Bahia, of which 94.9% were open surgeries. The open technique was associated with a higher mortality rate (4.9/1,000 procedures; p<0.05) and a higher risk of death (RR=4.5; p<0.05) compared to laparoscopy (1.1/1,000 procedures). Laparoscopic appendectomy (median of 2.7 days) had a shorter length of stay compared to laparotomy (median of 4.15 days) (p<0.05). There was no difference in the medians of costs nor hospital services, per procedure (p=0.08 and p=0.08, respectively). Laparoscopic professional median costs were higher by US$ 1.39 (p<0.05). Minimally invasive surgery for appendicitis is a safe and efficacious procedure in Brazilian public health care services, as it provides advantages over the open method (including lower procedure-related mortality rate and earlier discharges), and it did not imply higher expenses for public service budgets in the state of Bahia.

Breast cancer in Brazil: Screening program and surgical approach.

BACKGROUND: Screening mammography for breast cancer (BC) is a current strategy that reduces the mortality of BC by up to 30 %. Although mastectomy has been an important component of treatment for decades, conservative surgery (lumpectomy) has become the gold-standard approach for most cases, yet it depends on early detection of the BC. METHODS: This was an epidemiological study performed through DATASUS (2010-2018). We evaluated the temporal trend of screening mammograms, deaths from BC, and surgical procedures at national, regional and state levels. Statistical analysis was performed on VassarStat®-Website for Statistical Computation (Vassar College, New York, USA) and the R-software (R Foundation, v.4.0.3). RESULTS: During 2010-2018 there were 67,392 oncological mastectomies and 48,567 lumpectomies in Brazil's health system. Mastectomies decreased in the Northeast (-3.67 % ± 0.43 per year) and in Bahia state (-3.58 % ± 0.24 per year). Lumpectomies increased in Brazil (median 2.19 (-9.6 to 20.96)), the Northeast (median -12.07 (-25.8 to 9.43)) and Bahia (median 0.16 (-29.1 to 1.9)). Also, screening mammograms increased in Brazil (3.29 % ± 0.43), the Northeast (6.36 % ± 0.49) and Bahia (5.51 % ± 0.31), with 35,317,728 exams during this period. Deaths from BC increased annually in Brazil (+4.13 % ± 0.86), the Northeast (+4.76 % ± 1.45) and Bahia (+5.65 % ± 0.83). CONCLUSION: The number of mammograms related to the screening program increased in the years 2010-2018 in Brazil. Furthermore, we identified an increase in lumpectomies as opposed to mastectomies, and this approach is associated with a reduction in hospitalization days by almost a half, which in turn might result in a cost decrease and probably an earlier return to work.

Chemical Strategies towards the Synthesis of Betulinic Acid and Its More Potent Antiprotozoal Analogues.

Betulinic acid (BA, 3ß-hydroxy-lup-20(29)-en-28-oic acid) is a pentacyclic triterpene acid present predominantly in Betula ssp. (Betulaceae) and is also widely spread in many species belonging to different plant families. BA presents a wide spectrum of remarkable pharmacological properties, such as cytotoxic, anti-HIV, anti-inflammatory, antidiabetic and antimicrobial activities, including antiprotozoal effects. The present review first describes the sources of BA and discusses the chemical strategies to produce this molecule starting from betulin, its natural precursor. Next, the antiprotozoal properties of BA are briefly discussed and the chemical strategies for the synthesis of analogues displaying antiplasmodial, antileishmanial and antitrypanosomal activities are systematically presented. The antiplasmodial activity described for BA was moderate, nevertheless, some C-3 position acylated analogues showed an improvement of this activity and the hybrid models-with artesunic acid-showed the most interesting properties. Some analogues also presented more intense antileishmanial activities compared with BA, and, in addition to these, heterocycles fused to C-2/C-3 positions and amide derivatives were the most promising analogues. Regarding the antitrypanosomal activity, some interesting antitrypanosomal derivatives were prepared by amide formation at the C-28 carboxylic group of the lupane skeleton. Considering that BA can be produced either by isolation of different plant extracts or by chemical transformation of betulin, easily obtained from Betula ssp., it could be said that BA is a molecule of great interest as a starting material for the synthesis of novel antiprotozoal agents.

In-hospital mortality in patients with acute limb ischemia over a 12-year period in the Brazilian public health-care system.

BACKGROUND: Arterial diseases represent a severe public health problem in the 21st century. Although men have a higher overall prevalence, reports have suggested that women may exhibit atypical manifestations, be asymptomatic, and have hormonal peculiarities, resulting in worse outcomes and severe emergencies, such as acute limb ischemia (ALI). OBJECTIVES: To analyze the morbidity and mortality profile of ALI emergencies in Brazil between 2008 and 2019. METHODS: An ecological study was carried out with secondary data from SIH/SUS, using ICD-10 code I.74 The proportions of emergency hospital admissions and in-hospital mortality rates (HMR) by gender, ethnicity, and age were extracted from the overall figures. P<0.05 was considered significant. RESULTS: From 2008 to 2019, there were 195,567 urgent hospitalizations due to ALI in Brazil, 111,145 (56.8%) of which were of men. Women had a higher HMR (112:1,000 hospitalizations) than men (85:1,000 hospitalizations) (p<0.05), and a higher chance of death (OR=1.36; p<0.05). Furthermore, mean survival was significantly higher among men (8,483/year versus 6,254/year; p<0.05). Stratified by ethnicity, women who self-identified as white (OR=1.44; p<0.05), black (OR=1.33; p<0.05), and brown (RR=1.25; p <0.05) had greater chances of death than men in the same ethnicity categories. Moreover, women over the age of 50 years had a higher chance of death, with a progressive increment in risk as age increased. CONCLUSIONS: There was a trend to worse prognosis in ALI emergencies associated with women, especially in older groups. The literature shows that the reasons for these differences are still poorly investigated and more robust studies of this relevant disease in the area of vascular surgery are encouraged.

CONTEXTO: Doenças arteriais representam um grave problema de saúde pública no século XXI. Apesar de homens apresentarem maior prevalência geral, estudos sugerem que mulheres podem cursar com quadros assintomáticos, clínica atípica e particularidades hormonais, que resultam em desfechos desfavoráveis e urgências graves, como oclusões arteriais aguda (OAA). OBJETIVOS: Analisar o perfil de morbimortalidade das urgências em OAA no Brasil entre 2008 e 2019. MÉTODOS: Realizou-se estudo ecológico com dados secundários do Sistema de Informações Hospitalares/Sistema Único de Saúde, utilizando-se o código I.74 do Código Internacional de Doenças-10. Dos números absolutos, obteve-se proporções de internamentos de urgência e taxa de mortalidade intra-hospitalar (TMH) por gênero, etnia e idade. Considerou-se p < 0,05 significativo. RESULTADOS: Entre 2008 e 2019, houve 195.567 internamentos de urgência por OAA no Brasil, dos quais 111.145 (56,8%) eram homens. Mulheres tiveram maior TMH (112:1.000 hospitalizações) em comparação a homens (85:1.000 hospitalizações) (p < 0,05), assim como maior chance de morte (odds ratio [OR] = 1,36; p < 0,05). Ademais, a média de sobrevida anual foi maior entre homens do que entre mulheres (8.483/ano vs. 6.254/ano, respectivamente; p < 0,05). Estratificando por etnia, mulheres apresentaram maior chance de óbitos entre brancas (OR = 1,44; p < 0,05), pretas (OR = 1,33; p < 0,05) e pardas (razão de risco [RR] = 1,25; p < 0,05), comparadas a homens das mesmas etnias. Nas análises etárias, mulheres com mais de 50 anos apresentaram maior chance de óbito, com aumento progressivo do risco com o envelhecimento. CONCLUSÕES: Nossas análises comparativas evidenciaram tendência de pior prognóstico nas urgências em OAA associadas a mulheres, sobretudo em grupos de idade avançada. A literatura evidencia que as razões para essas diferenças ainda são pouco estudadas, estimulando investigações mais robustas sobre essa importante casuística da cirurgia vascular.