Methylation status of LDLR, PCSK9 and LDLRAP1 is associated with cardiovascular events in familial hypercholesterolemia.

Aim: Methylation of LDLR, PCSK9 and LDLRAP1 CpG sites was assessed in patients with familial hypercholesterolemia (FH). Methods: DNA methylation of was analyzed by pyrosequencing in 131 FH patients and 23 normolipidemic (NL) subjects. Results: LDLR, PCSK9 and LDLRP1 methylation was similar between FH patients positive (MD) and negative (non-MD) for pathogenic variants in FH-related genes. LDLR and PCSK9 methylation was higher in MD and non-MD groups than NL subjects (p < 0.05). LDLR, PCSK9 and LDLRAP1 methylation profiles were associated with clinical manifestations and cardiovascular events in FH patients (p < 0.05). Conclusion: Differential methylation of LDLR, PCSK9 and LDLRAP1 is associated with hypercholesterolemia and cardiovascular events. This methylation profile maybe useful as a biomarker and contribute to the management of FH.

[Box: see text].

Malaria in areas under mining activity in the Amazon: A review.

Deforestation and high human mobility due to mining activities have been key to the increase in malaria cases in the Americas. Here, we review the epidemiological and control aspects of malaria in the Amazon mining areas. Epidemiological evidence shows: 1) a positive correlation between illegal mining activity and malaria incidence, mostly in the Amazon region; 2) most Brazilian miners are males aged 15-29 years who move between states and even countries; 3) miners do not fear the disease and rely on medical care, diagnosis, and medication when they become ill; 4) illegal mining has emerged as the most reported anthropogenic activity within indigenous lands and is identified as a major cause of malaria outbreaks among indigenous people in the Amazon; and 5) because mining is largely illegal, most areas are not covered by any healthcare facilities or activities, leading to little assistance in the diagnosis and treatment of malaria. Our review identified five strategies for reducing the malaria incidence in areas with mining activities: 1) reviewing legislation to control deforestation and mining expansion, particularly in indigenous lands; 2) strengthening malaria surveillance by expanding the network of community health agents to support rapid diagnosis and treatment; 3) reinforcing vector control strategies, such as the use of insecticide-treated nets; 4) integrating deforestation alerts into the national malaria control program; and 5) implementing multi-sectoral activities and providing prompt assistance to indigenous populations. With this roadmap, we can expect a decrease in malaria incidence in the Amazonian mining areas in the future.

Effect of environmental variables on the abundance of Amblyomma ticks, potential vectors of Rickettsia parkeri in central Brazil.

Amblyomma ticks are vectors of both Rickettsia rickettsii and R. parkeri in the Americas, where capybaras (Hydrochoerus hydrochaeris) are the main hosts in urban areas, thus contributing to the transmission of spotted fever. Herein, we studied: (i) the seasonal dynamics and abundance of ticks in areas where capybaras live, (ii) the effect of environmental variables on tick abundance, and (iii) the presence of Rickettsia-infected ticks. Between September 2021 and September 2022, we sampled ticks using cloth-dragging at 194 sites on the shore of Lake Paranoá in Brasília, Brazil. We measured environmental data (season, vegetation type, canopy density, temperature, humidity, and presence or vestige of capybara) at each site. Nymphs and adults were morphologically identified to the species level, and a selected tick sample including larvae was subjected to genotypic identification. We investigated Rickettsia-infected ticks by PCR (gltA, htrA, ompB, and ompA genes) and associations between tick abundance and environmental variables using Generalized Linear Models. A total of 30,334 ticks (96% larvae) were captured. Ticks were identified as Amblyomma, with A. sculptum comprising 97% of the adult/nymphs. Genotype identification of a larval sample confirmed that 95% belonged to A. dubitatum. Seasonal variables showed significant effects on tick abundance. Most larvae and nymphs were captured during the early dry season, while the adults were more abundant during the wet season. Vegetation variables and the presence of capybaras showed no association with tick abundance. Rickettsia parkeri group and R. bellii were identified in A. dubitatum, while A. sculptum presented R. bellii. We conclude that: (i) Amblyomma ticks are widely distributed in Lake Paranoá throughout the year, especially larvae at the dry season, (ii) the abundance of Amblyomma ticks is explained more by climatic factors than by vegetation or presence of capybaras, and (iii) A. dubitatum ticks are potential vectors of R. parkeri in Brasília.

Dynamic shoreline alterations and their impacts on Olive Ridley Turtle (Lepidochelys olivacea) nesting sites in Gahirmatha Marine Wildlife Sanctuary, Odisha (India).

Currently, sea turtle habitats are being altered by climate change and human activities, with habitat loss posing an urgent threat to Indian sea turtles. Thus, the objective of this study is to analyze the dynamic shoreline alterations and their impacts on Olive Ridley Sea Turtle (ORT) nesting sites in Gahirmatha Marine Wildlife Sanctuary from 1990 to 2022. Landsat satellite images served as input datasets to assess dynamic shoreline changes. This study assessed shoreline alterations and their rates across 929 transects divided into four zones using the Digital Shoreline Analysis System (DSAS) software. The results revealed a significant 14-km northward shift in the nesting site due to substantial coastal erosion, threatening the turtles' Arribada. This study underscores the need for conservation efforts to preserve nesting environments amidst changing coastal landscapes, offering novel insights into the interaction between coastal processes and marine turtle nesting behaviors.

Predicted deleterious variants in ABCA1, LPL, LPA and KIF6 are associated with statin response and adverse events in patients with familial hypercholesterolemia and disturb protein structure and stability.

OBJECTIVES: This study explored the association of deleterious variants in pharmacodynamics (PD) genes with statin response and adverse effects in patients with familial hypercholesterolemia (FH) and analyzed their potential effects on protein structure and stability. METHODS: Clinical and laboratory data were obtained from 144 adult FH patients treated with statins. A panel of 32 PD genes was analyzed by exon-targeted gene sequencing. Deleterious variants were identified using prediction algorithms and their structural effects were analyzed by molecular modeling studies. RESULTS: A total of 102 variants were predicted as deleterious (83 missense, 8 stop-gain, 4 frameshift, 1 indel, 6 splicing). The variants ABCA1 rs769705621 (indel), LPA rs41267807 (p.Tyr2023Cys) and KIF6 rs20455 (p.Trp719Arg) were associated with reduced low-density lipoprotein cholesterol (LDLc) response to statins, and the LPL rs1801177 (p.Asp36Asn) with increased LDLc response (P < 0.05). LPA rs3124784 (p.Arg2016Cys) was predicted to increase statin response (P = 0.022), and ABCA1 rs769705621 to increase the risk of statin-related adverse events (SRAE) (P = 0.027). LPA p.Arg2016Cys and LPL p.Asn36Asp maintained interactions with solvent, LPA p.Tyr2023Cys reduced intramolecular interaction with Gln1987, and KIF6 p.Trp719Arg did not affect intramolecular interactions. DDMut analysis showed that LPA p.Arg2016Cys and p.Tyr2023Cys and LPL p.Asp36Asn caused energetically favorable changes, and KIF6 p.Trp719Arg resulted in unfavorable energetic changes, affecting protein stability. CONCLUSION: Deleterious variants in ABCA1, LPA, LPL and KIF6 are associated with variability in LDLc response to statins, and ABCA1 rs769705621 is associated with SRAE risk in FH patients. Molecular modeling studies suggest that LPA p.Tyr2023Cys and KIF6 p.Trp719Arg disturb protein conformational structure and stability.

Contaminação pelo Covid-19 em profissionais de hospital de referência no Pará / Contamination by Covid-19 in professionals of a reference hospital in Para's state / Contaminación por Covid-19 en profesionales de un hospital de referencia del estado de Pará

A pandemia do novo coronavírus colocou em alerta os sistemas de saúde, estabelecendo sentimentos de instabilidade e de medo. O trabalho é e importante pilar para o traçado de políticas públicas. Objetivo: analisar a contaminação pelo COVID-19 em profissionais de hospital de referência no Pará. Metodologia: Trata-se de estudo retrospectivo, quantitativo, observacional, com aplicação de série temporal no período de março de 2020 a março de 2022. Foram incluídos todos os servidores atuantes durante a pandemia, que apresentaram atestados médicos com diagnóstico de COVID, e/ou testagem positiva, ou atestados por suspeita de contaminação. O perfil de servidores foi analisado, explorando as variáveis sexo, idade, convivência ou não com parceiros, grau de escolaridade, cargo e setor; juntamente com a incidência de casos confirmados e incidência total (suspeitos e confirmados). Resultados: O total de afastamentos do trabalho devido ao diagnóstico de COVID-19 foi de 1.420 casos, mais 839 casos suspeitos; sendo que 173 trabalhadores apresentaram reincidência. A incidência foi maior nos meses de maio de 2020, março de 2021 e janeiro de 2022. Houve predominância do sexo feminino e da categoria de enfermagem. Setores administrativos e financeiros apresentaram maior porcentagem de contaminados durante a pandemia (73,40%), proporcionalmente ao quantitativo de servidores atuantes na lotação. Entretanto, foram servidores da assistência direta ao paciente que apresentaram maior porcentagem de reinfecção. Conclusão: Foi possível visualizar três ondas na distribuição temporal dos casos de COVID-19, com destaque para elevação nos primeiros meses de 2022. O declínio no diagnóstico de casos novos no hospital estudado após dois anos de pandemia pode representar esforços individuais e coletivos em resistir às dificuldades da conjuntura. É importante observar o comportamento da pandemia em distintas regiões do Brasil para atualização de estratégias de enfrentamento como um todo.

The new coronavirus pandemic has put health systems on alert, establishing feelings of instability and fear. Working is an important pillar for the design of public policies. Objective: to analyze the contamination by COVID-19 in professionals of a reference hospital in Para's State. Methodology: This is a retrospective, quantitative, observational study, with the application of a time series from March 2020 to March 2022. All civil servants working during the pandemic, who presented medical certificates with a diagnosis of COVID, and/or or positive test, or attestations for suspected contamination. The servants' profile was analyzed, exploring the variables sex, age, living or not with partners, education level, position and sector; along with the incidence of confirmed cases and total incidence (suspected and confirmed). Results: The total number of absences from work due to the diagnosis of COVID-19 was 1,420 cases, plus 839 suspected cases; 173 workers presented recurrence. The incidence was higher in the months of May 2020, March 2021 and January 2022. There was a predominance of females and the nursing category. Administrative and financial sectors had a higher percentage of people infected during the pandemic (73.40%), proportionally to the number of servers working in the capacity. However, it was direct patient care workers who had the highest percentage of reinfection. Conclusion: It was possible to visualize three waves in the temporal distribution of COVID-19 cases, with emphasis on an increase in the first months of 2022. The decline in the diagnosis of new cases in the hospital studied after two years of the pandemic may represent individual and collective efforts to resist to the difficulties of the situation. It is important to observe the behavior of the pandemic in different regions of Brazil to update coping strategies in a general scenery.

La nueva pandemia de coronavirus ha puesto en alerta a los sistemas de salud, estableciendo sentimientos de inestabilidad y miedo. El trabajo es un pilar importante para el diseño de políticas públicas. Objetivo: analizar la contaminación por COVID-19 en profesionales de un hospital de referencia en el Estado de Pará. Metodología: Se trata de un estudio retrospectivo, cuantitativo, observacional, con la aplicación de una serie de tiempo de marzo de 2020 a marzo de 2022. Todos los funcionarios que trabajaron durante la pandemia, que presentaron certificados médicos con diagnóstico de COVID, y/o o test positivo, o atestados por sospecha de contaminación. Se analizó el perfil de los funcionarios, explorando las variables sexo, edad, convivencia o no con la pareja, nivel de escolaridad, cargo y sector; junto con la incidencia de casos confirmados y la incidencia total (sospechosos y confirmados). Resultados: El número total de bajas laborales por diagnóstico de COVID-19 fue de 1.420 casos, más 839 casos sospechosos; 173 trabajadores presentaron recurrencia. La incidencia fue mayor en los meses de mayo de 2020, marzo de 2021 y enero de 2022. Hubo predominio del sexo femenino y de la categoría de enfermería. Los sectores administrativo y financiero presentaron mayor porcentaje de infectados durante la pandemia (73,40%), proporcionalmente al número de servidores que trabajaban en esa función. Sin embargo, fueron los trabajadores de atención directa al paciente los que presentaron el mayor porcentaje de reinfección. Conclusiones: Fue posible visualizar tres olas en la distribución temporal de los casos de COVID-19, destacándose un aumento en los primeros meses de 2022. La disminución en el diagnóstico de nuevos casos en el hospital estudiado después de dos años de pandemia puede representar esfuerzos individuales y colectivos para resistir a las dificultades de la situación. Es importante observar el comportamiento de la pandemia en diferentes regiones de Brasil para actualizar las estrategias de afrontamiento en un escenario general.

Locally advanced breast cancer: breast-conserving surgery and other factors linked to overall survival after neoadjuvant treatment.

Background: Recent data suggest that breast-conserving surgery (BCS) may positively impact overall survival (OS) in early breast cancer. However, the role of BCS in locally advanced breast cancer (LABC) following neoadjuvant therapy (NAT) remains uncertain. Methods: We conducted a retrospective cohort study involving 530 LABC patients who underwent surgery after NAT between 2010 and 2015. Outcomes examined included OS, distant recurrence rates (DRR), and loco-regional recurrence rates (LRRs). Results: Among the 927 breast cancer patients who received NAT, 530 were eligible for our study. Of these, 24.6% underwent BCS, while 75.4% underwent mastectomy (MS). The median follow-up duration was 79 months. BCS patients exhibited a higher pathological complete response (PCR) rate compared to those who underwent MS (22.3% vs. 10%, p < 0.001). The 6-year OS rates for BCS and MS were 81.5% and 62%, respectively (p < 0.000). In multivariate OS analysis, MS was associated with worse outcomes (OR 1.678; 95% CI 1.069-2.635; p = 0.024), as was body mass index (BMI) (OR 1.031; 95% CI 1.006-1.058; p = 0.017), and stage IIIB or IIIC (OR 2.450; 95% CI 1.561-3.846; p < 0.000). Conversely, PCR (OR 0.42; 95% CI 0.220-0.801; p = 0.008) was associated with improved survival. DRR was significantly lower in BCS (15.4%) compared to MS (36.8%) (OR 0.298; 95% CI 0.177-0.504). LRRs were comparable between BCS (9.2%) and MS (9.5%) (OR 0.693; 95% CI 0.347-1.383). Conclusion: Our findings suggest that BCS is oncologically safe, even for patients with large lesions, and is associated with superior OS rates compared to MS. Additionally, lower BMI, lower pretreatment stage, and achieving PCR were associated with improved survival outcomes.

Lipidomic analysis identified potential predictive biomarkers of statin response in subjects with Familial hypercholesterolemia.

Familial hypercholesterolemia (FH) is a disorder of lipid metabolism that causes elevated low-density lipoprotein cholesterol (LDL-c) and increased premature atherosclerosis risk. Statins inhibit endogenous cholesterol biosynthesis, which reduces LDL-c plasma levels and prevent from cardiovascular events. This study aimed to explore the effects of statin treatment on serum lipidomic profile and to identify biomarkers of response in subjects with FH. Seventeen adult FH patients underwent a 6-week washout followed by 4-week treatment with atorvastatin (80 mg/day) or rosuvastatin (40 mg/day). LDL-c response was considered good (40-70 % reduction, n = 9) or poor (3-33 % reduction, n = 8). Serum lipidomic profile was analyzed by ultra-high-performance liquid chromatography combined with electrospray ionization tandem time-of-flight mass spectrometry, and data were analyzed using MetaboAnalyst v5.0. Lipidomic analysis identified 353 lipids grouped into 16 classes. Statin treatment reduced drastically 8 of 13 lipid classes, generating a characteristic lipidomic profile with a significant contribution of phosphatidylinositols (PI) 16:0/18:2, 18:0/18:1 and 18:0/18:2; and triacylglycerols (TAG) 18:2x2/18:3, 18:1/18:2/18:3, 16:1/18:2x2, 16:1/18:2/18:3 and 16:1/18:2/Arachidonic acid (p-adjusted <0.05). Biomarker analysis implemented in MetaboAnalyst subsequently identified PI 16:1/18:0, 16:0/18:2 and 18:0/18:2 as predictors of statin response with and receiver operating characteristic (ROC) areas under the curve of 0.98, 0.94 and 0.91, respectively. In conclusion, statins extensively modulate the overall serum lipid composition of FH individuals and these findings suggest that phosphatidyl-inositol molecules are potential predictive biomarkers of statin response.

The toxic dinoflagellate Alexandrium catenella adversely affects early life stages of tehuelche scallop.

The effects of the toxic dinoflagellate Alexandrium catenella were investigated on growth, survival, and histopathology in larvae and spat of the Tehuelche scallop Aequipecten tehuelchus from Patagonia, Argentina. The study consisted of laboratory incubations of scallop larvae/spat with A. catenella, using environmentally realistic abundances of the dinoflagellate. Survival, growth, and histopathological effects were documented for scallop larvae/spat before, during, and after 7-day-long exposure to A. catenella. The scallops were grouped in flasks containing 0 (control), 20, 200, and 2000 cells mL-1 of A. catenella. The presence of A. catenella induced reduced larvae survival after 24 h, whereas a clear effect was observed after 3 days (survival of control larvae 95%, 72, and 79% for 20 and 200 cells mL-1, respectively, and 43% for 2000 cells mL-1). The growth rates of the control larvae and those exposed to 20 mL-1 cells were significantly different from zero. Histopathological effects (melanization, loss of connective tissue, necrosis, and inflammatory responses) were observed in spat exposed to A. catenella. These effects were more pronounced at the highest dinoflagellate concentration. Blooms of A. catenella frequently coincide with the reproductive season of A. tehuelchus, thus there is a need to further study the relationship between harmful algal blooms and the effect on scallops' natural populations in the region.

Uncovering the effects of Giardia duodenalis on the balance of DNA viruses and bacteria in children's gut microbiota.

The neglected parasitosis giardiasis is one of the most common intestinal infections worldwide, affecting mainly infants and young children. Giardia duodenalis may disturb the local microbiome, leading to intestinal ecosystem disorders, and altering different processes in the host, such as the immune response. Nevertheless, the alterations promoted by G. duodenalis on the human gut microbiome have not been thoroughly investigated. Here, we characterized the gut microbiota of G. duodenalis-infected children and determine the main alterations promoted by the parasite. To do so, fecal samples of 26 infected and four uninfected children aged 2 to 6 years old were processed for High Efficiency Microarray analysis, in order to describe their bacterial and viral profiles. Then, we quantified the total bacterial population by qPCR and assessed fecal calprotectin levels, which are closely related with gut inflammation. A total of 286 bacteria's species and 17 viruses' strains were identified. Our results revealed no statistically significant differences between G. duodenalis positive and negative groups in the taxa's phyla and families. However, bacterial species diversity was increased in children infected with G. duodenalis (p < 0.05), while the total number of bacteria was decreased (p < 0.05). Considering the virome analysis, 17 different strains were identified, 88% being bacteriophages. The correlation analysis revealed an important disruption in the balance of DNA virus and bacteria within the intestinal microbiota of Giardia-positive children. Our findings constitute the first description of the gut virome of Giardia-infected children and suggest that G. duodenalis infection exerts a modulatory effect on the gut microbiome, promoting local inflammation and altering the equilibrium of the parasite-microbiota-host triad. This highlights the importance of considering polymicrobial associations and understanding the broader context of giardiasis. Overall, our study provides new insights into the complex interactions between intestinal parasites and the microbiota, which may have implications for the development of novel therapeutic interventions in the future.

LDLR and PCSK9 3´UTR variants and their putative effects on microRNA molecular interactions in familial hypercholesterolemia: a computational approach.

BACKGROUND: Familial hypercholesterolemia (FH) is caused by pathogenic variants in low-density lipoprotein (LDL) receptor (LDLR) or its associated genes, including apolipoprotein B (APOB), proprotein convertase subtilisin/kexin type 9 (PCSK9), and LDLR adaptor protein 1 (LDLRAP1). However, approximately 40% of the FH patients clinically diagnosed (based on FH phenotypes) may not carry a causal variant in a FH-related gene. Variants located at 3' untranslated region (UTR) of FH-related genes could elucidate mechanisms involved in FH pathogenesis. This study used a computational approach to assess the effects of 3'UTR variants in FH-related genes on miRNAs molecular interactions and to explore the association of these variants with molecular diagnosis of FH. METHODS AND RESULTS: Exons and regulatory regions of FH-related genes were sequenced in 83 FH patients using an exon-target gene sequencing strategy. In silico prediction tools were used to study the effects of 3´UTR variants on interactions between miRNAs and target mRNAs. Pathogenic variants in FH-related genes (molecular diagnosis) were detected in 44.6% FH patients. Among 59 3'UTR variants identified, LDLR rs5742911 and PCSK9 rs17111557 were associated with molecular diagnosis of FH, whereas LDLR rs7258146 and rs7254521 and LDLRAP1 rs397860393 had an opposite effect (p < 0.05). 3´UTR variants in LDLR (rs5742911, rs7258146, rs7254521) and PCSK9 (rs17111557) disrupt interactions with several miRNAs, and more stable bindings were found with LDLR (miR-4435, miR-509-3 and miR-502) and PCSK9 (miR-4796). CONCLUSION: LDLR and PCSK9 3´UTR variants disturb miRNA:mRNA interactions that could affect gene expression and are potentially associated with molecular diagnosis of FH.

Characteristics and prognosis of young breast cancer patients treated in a public comprehensive cancer centre in Brazil: A retrospective cohort study.

BACKGROUND: The incidence of breast cancer among women under 41 years old varies worldwide, with higher rates observed in developing countries. These young women often face later-stage diagnoses. In this study, we examine a cohort of young women who were treated for breast cancer in São Paulo, Brazil. METHODS: We conducted a retrospective cohort study involving women under 41 years old. Our objective was to describe patient and treatment characteristics, with the main outcomes being overall and disease-free survival. Our analysis explored the associations between age of menarche, history of breastfeeding, use of hormonal contraceptives, and age at diagnosis. RESULTS: Our study included 493 patients with a mean follow-up of 62.8 months. The mean age of the patients was 34.6 (SD=4.19). Of the patients, 68% presented with locally advanced disease, and 19.27% were metastatic at the time of diagnosis. We observed significant associations between age of menarche and age at diagnosis (p = 0.0096), as well as age at diagnosis and breastfeeding (p = 0.0232). Chemotherapy was administered to 92.91% of the patients as part of their treatment, while 27.2% were eligible for breast-conserving surgery. During the follow-up period, 153 patients died, with disease progression being the cause of death in 73.2% of cases. The median survival time for the entire cohort is still under review, while the metastatic patients at diagnosis had a median survival time of 28.64 months (95%CI 20.21-40.89). CONCLUSION: Our findings highlight significant associations between late-stage diagnosis and overall and disease-free survival in this patient age group. Given that the majority of patients present with locally advanced breast cancer, it is crucial to implement strategies that promote early-stage diagnosis and improve survival rates.

Parasite Detection in Visceral Leishmaniasis Samples by Dye-Based qPCR Using New Gene Targets of Leishmania infantum and Crithidia.

Visceral leishmaniasis (VL) is a neglected disease considered a serious public health problem, especially in endemic countries. Several studies have discovered monoxenous trypanosomatids (Leptomonas and Crithidia) in patients with VL. In different situations of leishmaniasis, investigations have examined cases of co-infection between Leishmania spp. and Crithidia spp. These coinfections have been observed in a wide range of vertebrate hosts, indicating that they are not rare. Diagnostic techniques require improvements and more robust tools to accurately detect the causative agent of VL. This study aimed to develop a real-time quantitative dye-based PCR (qPCR) assay capable of distinguishing Leishmania infantum from Crithidia-related species and to estimate the parasite load in samples of VL from humans and animals. The primer LinJ31_2420 targets an exclusive phosphatase of L. infantum; the primer Catalase_LVH60-12060_1F targets the catalase gene of Crithidia. Therefore, primers were designed to detect L. infantum and Crithidia sp. LVH60A (a novel trypanosomatid isolated from VL patients in Brazil), in samples related to VL. These primers were considered species-specific, based on sequence analysis using genome data retrieved from the TriTryp database and the genome assembling of Crithidia sp. LVH60A strain, in addition to experimental and clinical data presented herein. This novel qPCR assay was highly accurate in identifying and quantifying L. infantum and Crithidia sp. LVH60A in samples obtained experimentally (in vitro and in vivo) or collected from hosts (humans, dogs, cats, and vectors). Importantly, the screening of 62 cultured isolates from VL patients using these primers surprisingly revealed that 51 parasite cultures were PCR+ for Crithidia sp. In addition, qPCR assays identified the co-infection of L. infantum with Crithidia sp. LVH60A in two new VL cases in Brazil, confirming the suspicion of co-infection in a previously reported case of fatal VL. We believe that the species-specific genes targeted in this study can be helpful for the molecular diagnosis of VL, as well as for elucidating suspected co-infections with monoxenous-like trypanosomatids, which is a neglected fact of a neglected disease.

First Evaluation of the Brazilian Advanced Life Support Training (TECA A)

Abstract Background Cardiac arrest (CA) is a common condition associated with high mortality. The Brazilian advanced life support training TECA A (Treinamento em Emergências Cardiovasculares Avançado — Advanced Cardiovascular Emergency Training) was created to train healthcare professionals in the management of CA. However, there are no studies evaluating the effectiveness of TECA A. Objective To assess the impact of TECA A on the management of CA using a simulated CA situation. Methods Fifty-six students underwent a simulated case of CA in a manikin. The students' performance in the management of CA was assessed for the time to first chest compression and defibrillation and for a global assessment score using a structured tool. These items were assessed and compared before and after the TECA A. Exclusion criteria were previous participation in CA trainings and absence from class. Categorical variables were compared using the McNemar test and quantitative variables using the Wilcoxon test. All tests were two-tailed, and statistical significance was set at p < 0.05. Results Compared with before TECA A, median global assessment scores were higher after TECA A (pre-training: 4.0 points [2.0-5.0] vs. 10 points [9.0-10.0]; p<0.001), the time to start chest compressions was shorter (pre-training: 25 seconds [15-34] vs. 19 seconds [16.2-23.0]; p=0.002) and so was the time to defibrillation (pre-training: 82.5 seconds [65.0-108.0] vs. 48 seconds [39.0-53.0]; p<0.001). Conclusions The TECA A promoted a higher adherence to cardiopulmonary resuscitation (CPR) guidelines and a reduction in the time elapsed from CA to first chest compression and defibrillation.

Identification of pathogenic variants in the Brazilian cohort with Familial hypercholesterolemia using exon-targeted gene sequencing.

Familial hypercholesterolemia (FH) is a monogenic disease characterized by high plasma low-density lipoprotein cholesterol (LDL-c) levels and increased risk of premature atherosclerotic cardiovascular disease. Mutations in FH-related genes account for 40% of FH cases worldwide. In this study, we aimed to assess the pathogenic variants in FH-related genes in the Brazilian FH cohort FHBGEP using exon-targeted gene sequencing (ETGS) strategy. FH patients (n = 210) were enrolled at five clinical sites and peripheral blood samples were obtained for laboratory testing and genomic DNA extraction. ETGS was performed using MiSeq platform (Illumina). To identify deleterious variants in LDLR, APOB, PCSK9, and LDLRAP1, the long-reads were subjected to Burrows-Wheeler Aligner (BWA) for alignment and mapping, followed by variant calling using Genome Analysis Toolkit (GATK) and ANNOVAR for variant annotation. The variants were further filtered using in-house custom scripts and classified according to the American College Medical Genetics and Genomics (ACMG) guidelines. A total of 174 variants were identified including 85 missense, 3 stop-gain, 9 splice-site, 6 InDel, and 71 in regulatory regions (3'UTR and 5'UTR). Fifty-two patients (24.7%) had 30 known pathogenic or likely pathogenic variants in FH-related genes according to the American College Medical and Genetics and Genomics guidelines. Fifty-three known variants were classified as benign, or likely benign and 87 known variants have shown uncertain significance. Four novel variants were discovered and classified as such due to their absence in existing databases. In conclusion, ETGS and in silico prediction studies are useful tools for screening deleterious variants and identification of novel variants in FH-related genes, they also contribute to the molecular diagnosis in the FHBGEP cohort.

Prenatal repair of gastroschisis using partial carbon dioxide insufflation fetoscopy: lessons learned.

We report the long-term outcomes of a case of prenatal gastroschisis repair using a fully percutaneous fetoscopic approach with partial carbon dioxide insufflation. Surgery was performed as an experimental procedure before the scheduled elective birth. The fetal intestines were successfully returned to the abdominal cavity without any fetal or maternal complications. Ultrasonography performed 24 hours later revealed bowel peristalsis and no signs of fetal distress. After 48 hours, partial extrusion of the small bowel was observed, and the fetus was delivered. Gastroschisis repair was immediately performed upon delivery using the EXIT-like procedure as per our institutional protocol. The newborn did not require assisted mechanical ventilation, was discharged at 14 days of age and was then exclusively breastfed. At 3-year follow-up, the patient had no associated gastroschisis-related complications. This is the first case of prenatal repair of gastroschisis, which provides baseline knowledge for future researchers on the potential hurdles and management of prenatal repair.

Potentialities and limitations of Interprofessional Education during graduation: a systematic review and thematic synthesis of qualitative studies.

BACKGROUND: Rapid demographic, epidemiological, technological, cultural/behavioural, and educational transitions, as they become more complex, demand new integrated and complementary professional skills and abilities. Interprofessional Education (IPE) is a promising alternative to deal with these changes, especially in courses in the health area. This systematic review was to explore the potentialities and limitations of IPE, from the perspective of undergraduate students, through a thematic synthesis of qualitative studies. METHODS: A thematic synthesis of qualitative studies was conducted. The question elaborated for this review was: "What is the impact of interprofessional education on the teaching and learning of students in the health area inserted in Higher Education Institutions?". The search strategy was performed in the electronic databases PubMed, Latin American and Caribbean Literature in Health Sciences (LILACS), Cochrane Library, and Scientific Electronic Library Online (SciELO). In addition, searches were carried out in grey literature on the ERIC platforms, ProQuest Disserts and Theses, and Academic Google. The assessment of the quality of the studies was carried out using the Critical Appraisal Skills Programme tool. Data were summarized through thematic synthesis. From the databases, 8,793 studies were identified. After standardized filters procedures, critical summaries, and assessment of relevance to the eligibility criteria, 14 articles were included. RESULTS: The synthesis of the studies revealed the potential of this teaching approach, arranged in three analytical themes: learning from each other and about them; the value of education and interprofessional practice; patient-centred health care. On the other hand, some limitations were also identified, such as barriers related to EIP; the difficulties related to teaching methodologies. CONCLUSION: Overcoming the identified limitations can enhance the results of the IPE, in view of its impact on the education of students and on the health care of the population.

Impact of COVID-19 on Portuguese Dental Students: A Cohort Study.

INTRODUCTION: The goal of this study was to assess the impact of COVID-19 on Portuguese dental students on their depression, anxiety, temporomandibular dysfunction, academic degree, and oral behaviors. METHODS: The target of this population study was to enroll third-, fourth-, and fifth-year students of the Integrated Master's degree in Dental Medicine at the Universidade Católica Portuguesa-Faculty of Dental Medicine (Viseu, Portugal) in the academic year 2021-2022. Temporomandibular disorders (TMD) symptoms, oral behaviors, anxiety, and depression were assessed using validated questionnaires. The variables under study were (a) age, gender, marital status, academic level, academic degree, medication, and any existing pathologies; (b) questions related to taste changes or thoughts that would indicate (or not) worsening psychological conditions (anxiety and depression). After data collection (Google Forms®), data were transferred to an Excel file and entered into SPSS® software. A chi-square test allowed the independence between ordinal or nominal variables. The Spearman correlation test was used to analyze the relationship between variables in the study (significant if p ≤ 0.05). RESULTS: 98.2% of the students answered the questionnaire. TMD had a prevalence of 35%, and anxiety and depression a prevalence of 29% and 24%, respectively. The results showed that the female gender was the most affected by psychological and temporomandibular disorders. Statistically significant correlations were identified between variables, such as gender and anxiety, TDM, and depression (respectively, p = 0.0001, p = 0.014, and p = 0.026); between TDM and anxiety and depression (respectively, p = 0.001 and p < 0.001); and between performing oral behaviors and TMD, anxiety, and depression (respectively, p = 0.0001, p = 0.0001, and p = 0.006). The variables, such as age and academic degree, did not establish a statistically significant relationship with TMD, oral behaviors, and the two psychological conditions. CONCLUSIONS: It was possible to conclude that there was a moderate prevalence of TMD, anxiety, and depression in the period studied. Moreover, a statistically significant relationship was found between TMD, anxiety, and depression with gender and frequency of OBs; however, no significant association was found for TMD, anxiety, and depression with the age of students and with the academic degree.

Effects of preoperative magnetic resonance image on survival rates and surgical planning in breast cancer conservative surgery: randomized controlled trial (BREAST-MRI trial).

BACKGROUND: Breast magnetic resonance imaging (MRI) has high sensitivity in detecting invasive neoplasms. Controversy remains about its impact on the preoperative staging of breast cancer surgery. This study evaluated survival and surgical outcomes of preoperative MRI in conservative breast cancer surgery. METHODS: A phase III, randomized, open-label, single-center trial including female breast cancer participants, stage 0-III disease, and eligible for breast-conserving surgery. We compared the role of including MRI in preoperative evaluation versus radiologic exam routine with mammography and ultrasound in breast cancer conservative candidates. The primary outcome was local relapse-free survival (LRFS), and secondary outcomes were overall survival (OS), mastectomy rate, and reoperation rate. RESULTS: 524 were randomized to preoperative MRI group (n = 257) or control group (n = 267). The survival analysis showed a 5.9-years LRFS of 99.2% in MRI group versus 98.9% in control group (HR = 0.72; 95% CI 0.12-4.28; p = 0.7) and an OS of 95.3% in the MRI group versus 96.3% in the control group (HR = 1.37 95% CI 0.59-3.19; p = 0.8). Surgical management changed in 21 ipsilateral breasts in the MRI group; 21 (8.3%) had mastectomies versus one in the control group. No difference was found in reoperation rates, 22 (8.7%) in the MRI group versus 23 (8.7%) in the control group (RR = 1.002; 95% CI 0.57-1.75; p = 0.85). CONCLUSION: Preoperative MRI increased the mastectomy rates by 8%. The use of preoperative MRI did not influence local relapse-free survival, overall survival, or reoperation rates.