International Migration, Refugees, and Spread of Tuberculosis in Brazil: Analysis of Clusters, Trends, and Associated Factors (2010-2021).

BACKGROUND: International migration is a global phenomenon with significant implications on the health-disease process due to exposures along transit routes and local/destination epidemiological indicators. We aimed to analyze the transmission and spread of tuberculosis among international migrants and refugees from a spatiotemporal perspective and the associated factors. METHOD: This was an ecological study of cases of tuberculosis in international migrants in Brazil, between 2010 and 2021. Annual incidence rates were calculated and spatiotemporal scan techniques were used to identify municipalities at risk. Multiple logistic regression was used to identify factors associated with tuberculosis in international migrants. RESULTS: A total of 4037 cases of tuberculosis were reported in Brazil in international migrants. Municipalities at risk for this event were identified using the spatiotemporal scan technique, and a cluster was identified with ITT: +52.01% and ETT: +25.60%. A higher probability of TB infection was identified in municipalities with a TB incidence rate >14.40 cases/100 inhabitants, population >11,042 inhabitants, Gini index >0.49, and illiteracy rate >13.12%. A lower probability was found in municipalities with average per capita household income >BRL 456.43. CONCLUSIONS: It is recommended that health authorities implement monitoring and rigorous follow-up in affected areas to ensure proper diagnosis and treatment completion for international migrants, preventing disease spread to other communities.

The genome and population genomics of allopolyploid Coffea arabica reveal the diversification history of modern coffee cultivars.

Coffea arabica, an allotetraploid hybrid of Coffea eugenioides and Coffea canephora, is the source of approximately 60% of coffee products worldwide, and its cultivated accessions have undergone several population bottlenecks. We present chromosome-level assemblies of a di-haploid C. arabica accession and modern representatives of its diploid progenitors, C. eugenioides and C. canephora. The three species exhibit largely conserved genome structures between diploid parents and descendant subgenomes, with no obvious global subgenome dominance. We find evidence for a founding polyploidy event 350,000-610,000 years ago, followed by several pre-domestication bottlenecks, resulting in narrow genetic variation. A split between wild accessions and cultivar progenitors occurred ~30.5 thousand years ago, followed by a period of migration between the two populations. Analysis of modern varieties, including lines historically introgressed with C. canephora, highlights their breeding histories and loci that may contribute to pathogen resistance, laying the groundwork for future genomics-based breeding of C. arabica.

Adhesive restorations in primary dentition: A retrospective analysis of survival rate and associated factors.

BACKGROUND: Several clinical and individual factors may play a role in the survival rate of dental restorations, such as characteristics related to the child's age and oral hygiene, and factors associated with the tooth, such as the type of material and number of surfaces to be restored. AIM: To analyse the survival rate of adhesive restorations on primary teeth and factors associated with restoration survival. DESIGN: The study included dental records of children aged 3-12 years having received adhesive restorations on primary teeth at a Brazilian dental school between 2009 and 2019. A Kaplan-Meier survival curve was used to plot survival rates using the log-rank test. A multivariate Cox regression model was run to identify individual and dental factors associated with restoration failure. RESULTS: The sample comprised 269 restored teeth in 111 children. Survival curves were similar for all materials (p = .20) and types of isolation (p = .05). The annual failure rate was 3.60% for glass ionomer cement, 1.23% for resin-modified glass ionomer cement and 0.40% for composite resin. The following variables were associated with more failures: Class II restoration compared with Class I (HR = 1.96; 95%CI: 1.28-2.99, p < .001), proportion of decayed teeth (HR = 11.89; 95%CI: 2.80-50.57, p < .001) and child's age (HR = 1.17; 95%CI: 1.06-1.29, p < .001). CONCLUSION: The different materials and types of isolation had similar survival rates. Children with more decayed teeth have an increased risk of restoration failure.

Impact of the COVID-19 pandemic on excess maternal deaths in Brazil: A two-year assessment.

BACKGROUND: Accurate estimates of the COVID-19 pandemic's indirect impacts are crucial, especially in low- and middle-income countries. This study aims to update estimates of excess maternal deaths in Brazil during the first two years of the COVID-19 pandemic. METHODS: This was an exploratory mixed ecological study using the counterfactual approach. The observed maternal deaths were gathered from the Mortality Information System (SIM) for the period between March 2015 and February 2022. Expected deaths from March 2020 to February 2022 were estimated using quasipoisson generalized additive models, considering quadrimester, age group, and their interaction as predictor variables. Analyses were performed in R version 4.1.2, RStudio, version 2023.03.1+446 and carried out with support from the "mgcv" and "plot_model" libraries. RESULTS: A total of 5,040 maternal deaths were reported, with varying excess mortality across regions and age groups, resulting in 69% excess maternal mortality throughout Brazil during the first two years of the pandemic. The Southeast region had 50% excess mortality throughout the first two years and 76% excess in the second year. The North region had 69% excess mortality, increasing in the second year, particularly among women aged 20-34. The Northeast region showed 80% excess mortality, with a significant increase in the second year, especially among women aged 35-49. The Central-West region had 75% excess mortality, higher in the second year and statistically significant among women aged 35-49. The South region showed 117% excess mortality, reaching 203% in the second year among women aged 20-34, but no excess mortality in the 10-19 age category. CONCLUSIONS: Over two years, Brazil saw a significant impact on maternal excess deaths, regardless of region and pandemic year. The highest peak occurred between March and June 2021, emphasizing the importance of timely and effective epidemic responses to prevent avoidable deaths and prepare for new crises.

Impact of Extraction Methods and Transportation Conditions on Lipid Profiles of Bovine Oocytes.

Lipids play numerous pivotal physiological roles in mammalian reproduction, being indispensable for oocyte competence acquisition and post-fertilization embryonic development. Profiling lipids in minute samples, such as oocytes, presents challenges but has been accomplished through mass spectrometry technologies like Multiple Reaction Monitoring (MRM) profiling. With the dual objectives of simplifying workflow and examining the influence of preanalytical conditions, we assessed whether transportation at room temperature affects the lipid profile of bovine oocytes. To this end, samples were prepared using either monophasic (methanol only) or biphasic liquid extraction protocols (Bligh & Dyer method) and transported either on dry ice or at room temperature inside sealed-vacuum packages to prevent lipid oxidation. Subsequently, employing a comprehensive method, we screened a list of 316 MRMs from 10 different lipid subclasses in oocyte lipid extracts. Principal Component Analysis (PCA) revealed similar lipid profiles concerning temperature during transportation, whereas clear differentiation among samples was observed based on the lipid extraction method. Univariate analysis indicated that the one-phase methanol extraction resulted in higher relative abundances of phospholipids, except for phosphatidylserines. Conversely, the Bligh & Dyer extraction favored the detection of neutral intracellular lipids (triacylglycerols, free fatty acids, cholesteryl esters, and acyl-carnitines). Consequently, lipid recovery was directly correlated with the polarity of lipid class and the extraction method. Regarding transportation temperature, phosphatidylethanolamine, triacylglycerol, and free fatty acids exhibited lower abundances when samples were transported at room temperature. Based on multivariate and univariate analyses, we conclude that if samples undergo the same lipid extraction protocol and are transported in the same batch at room temperature inside vacuum-sealed bags, it is feasible to analyze lipid extracts of bovine oocytes and still obtain informative lipid profiling results.

Multiple-Digit Pigmented Bowen's Disease Induced by Human Papillomavirus in an Immunocompetent Child.

Introduction: Bowen's disease is a squamous cell carcinoma in situ, the most common malignancy of the nail unit. Presenting more frequently in the fingernails, common risk factors include ionizing radiation, oral exposure to arsenic or pesticides, dyskeratosis congenita, and quite commonly diverse subtypes of HPV. We report the first case of multiple periungual pigmented Bowen's disease in a pediatric patient. Case Presentation: A healthy 13-year-old boy presented with a 9-month history of a pigmented erythematous patch on the proximal nail fold of his 3rd right finger without associated symptoms. A punch biopsy was taken, and the diagnosis of Bowen's disease was made. The patient received photodynamic therapy and three cycles of imiquimod without response, and two new lesions appeared on the first and second right fingers. Surgical removal was performed on all lesions. A polymerase chain reaction detected an HPV type 16. Discussion/Conclusion: Multiple periungual Bowen's disease is rare, with the most frequent risk factors being HPV infection and chronic immunosuppression. Less than 10% of the cases present as longitudinal melanonychia. To date, there are no previous reports of multiple pigmented periungual Bowen's disease. HPV-induced Bowen's disease is usually present in adults aged between 22 and 89 years as persistent verrucae. In this case, koilocytosis and the fact that all lesions appeared on the right hand are suggestive of HPV infection.

Redescription of Hatschekia exigua Pearse, 1951 (Copepoda: Hatschekiidae), parasitic on the Squirrelfish Holocentrus adscensionis (Osbeck, 1765) (Actinopterygii: Holocentridae) off Ceará, Northeastern Brazil, with first description of the male.

The original description of Hatschekia exigua Pearse, 1951 neglected innumerous features of taxonomic value as well as morphometric data and illustrations. Posteriorly, other author tried to access the type material, but their poor state of preservation compromised a detailed redescription. Since then, this species is in need for new morphological data, mainly from fresh material. In the present work, three specimens of Holocentrus adscensionis from Mucuripe Bay, Fortaleza, State of Ceará, Northeastern Brazil, were parasitized by copepods on their gills. Parasites were fixed and preserved in 80% ethanol and cleared in 85% lactic acid for morphological observations using light microscopy. The females were identified as Hatschekia exigua by the cephalothorax representing about one-fourth of total body length, with lateral margins expanded into lateral lobes, first exopod with basal segment armed with one outer setae and terminal segment with three setae, first endopod with basal segment unarmed and terminal segment with five setae, leg 3 reduced to two setae and leg 4 reduced to single seta. Comparison with the type series revealed morphological differences in trunk and small appendages, which may be related to alterations in the specimens, caused by the mounting methodology and poor preservation. A detailed morphological analysis of the male revealed for the first time that they differ from their closest congeners by having five setae on the last endopodal segment of leg 1, by smooth intercoxal sclerites on legs 1 and 2 and by a proximolateral process on the third segment of antenna. Moreover, this work represents the first report of H. exigua in Brazil and the first hatschekiid copepod found off the coast of Ceará, highlighting that the diversity of Hatschekiidae in this oceanographic region still needs further investigation.

The Coiling Effect in Ether Ionic Liquids: Exploiting Acetate as a Probe for Transport Properties and Microenvironment Analysis.

The inherently high viscosity of ionic liquids (ILs) can limit their potential applications. One approach to address this drawback is to modify the cation side chain with ether groups. Herein, we assessed the structure-property relationship by focusing on acetate (OAc), a strongly coordinating anion, with 1,3-dialkylimidazolium cations with different side chains, including alkyl, ether, and hydroxyl functionalized, as well as their combinations. We evaluated their viscosity, thermal stabilities, and microstructure using Raman and infrared (IR) spectroscopies, allied to density functional theory (DFT) and ab initio molecular dynamics (AIMD) simulations. The viscosity data showed that the ether insertion significantly enhances the fluidity of the ILs, consistent with the coiling effect of the cation chain. Through a combined experimental and theoretical approach, we analyzed how the OAc anion interacts with ether ILs, revealing a characteristic bidentate coordination, particularly in hydroxyl functionalized ILs due to specific hydrogen bonding with the OH group. IR spectroscopy showed subtle shifts in the acidic hydrogens of imidazolium ring C(2)-H and C(4,5)-H, suggesting weaker interactions between OAc and the imidazolium ring in ether-functionalized ILs. Additionally, spatial distribution functions (SDF) and dihedral angle distribution obtained via AIMD confirmed the intramolecular hydrogen bonding due to the coiling effect of the ether side chain.

Camera trap surveys of Atlantic Forest mammals: A data set for analyses considering imperfect detection (2004-2020).

Camera traps became the main observational method of a myriad of species over large areas. Data sets from camera traps can be used to describe the patterns and monitor the occupancy, abundance, and richness of wildlife, essential information for conservation in times of rapid climate and land-cover changes. Habitat loss and poaching are responsible for historical population losses of mammals in the Atlantic Forest biodiversity hotspot, especially for medium to large-sized species. Here we present a data set from camera trap surveys of medium to large-sized native mammals (>1 kg) across the Atlantic Forest. We compiled data from 5380 ground-level camera trap deployments in 3046 locations, from 2004 to 2020, resulting in 43,068 records of 58 species. These data add to existing data sets of mammals in the Atlantic Forest by including dates of camera operation needed for analyses dealing with imperfect detection. We also included, when available, information on important predictors of detection, namely the camera brand and model, use of bait, and obstruction of camera viewshed that can be measured from example pictures at each camera location. Besides its application in studies on the patterns and mechanisms behind occupancy, relative abundance, richness, and detection, the data set presented here can be used to study species' daily activity patterns, activity levels, and spatiotemporal interactions between species. Moreover, data can be used combined with other data sources in the multiple and expanding uses of integrated population modeling. An R script is available to view summaries of the data set. We expect that this data set will be used to advance the knowledge of mammal assemblages and to inform evidence-based solutions for the conservation of the Atlantic Forest. The data are not copyright restricted; please cite this paper when using the data.

As armadilhas fotográficas tornaram­se o principal método de observação de muitas espécies em grandes áreas. Os dados obtidos com armadilhas fotográficas podem ser usados para descrever os padrões e monitorar a ocupação, abundância e riqueza da vida selvagem, informação essencial para a conservação em tempos de rápidas mudanças climáticas e de cobertura do solo. A perda de habitat e a caça furtiva são responsáveis pelas perdas populacionais históricas de mamíferos no hotspot de biodiversidade da Mata Atlântica, especialmente para espécies de médio e grande porte. Aqui apresentamos um conjunto de dados de levantamentos com armadilhas fotográficas de mamíferos de médio e grande porte (>1 kg) em toda a Mata Atlântica. Compilamos dados de 5.380 armadilhas fotográficas instaladas no nível do chão em 3.046 locais, de 2004 a 2020, resultando em 43.068 registros de 58 espécies. Esses dados acrescentam aos conjuntos de dados existentes de mamíferos na Mata Atlântica por incluir as datas de operação das câmeras, que são necessárias para análises que lidam com detecção imperfeita. Também incluímos, quando disponíveis, informações sobre importantes preditores de detecção, como marca e modelo da câmera, uso de isca e obstrução do visor da câmera que pode ser medido a partir de imagens de exemplo em cada local da câmera. Além de estudos sobre os padrões e mecanismos por trás da ocupação, abundância relativa, riqueza e detecção, o conjunto de dados aqui apresentado pode ser usado para estudar os padrões de atividade diária das espécies, nível de atividade e interações espaço­temporais entre as espécies. Além disso, os dados podem ser usados em combinação com outras fontes de dados em diversas análises com modelagem populacional integrada. Um script R está disponível para visualizar um resumo do conjunto de dados. Esperamos que este conjunto de dados seja usado para aumentar o conhecimento sobre as assembleias de mamíferos e usado para informar soluções baseadas em evidências para a conservação da Mata Atlântica. Os dados não são restritos por direitos autorais e, por favor, cite este documento ao usar os dados.

LEARNING CURVE IN PONSETI METHOD - EVOLUTION IN 5 YEAR-INTERVALS.

Objective: Evaluate whether the experience of the surgeon could reduce Ponseti treatment time, and a number of cast changes, and the evolution of the Pirani Score. Methods: 2 reference centers were evaluated. At Institution 1, 254 patients with idiopathic clubfoot (403 feet) were included, and at Institution 2, 32 patients (51 feet). At institution 1 (mentor), 3 intervals of 5 years each were analyzed. At the Institution 2 (trainee), 1 interval of 5 years was analyzed. Results: Patients treated by the mentor had fewer casts compared with the trainee (p < 0.001). At Institution 1, the three mentor intervals showed differences in the number of casts (p < 0.05). A statistically significant difference was observed only in the first mentor interval (2000 to 2005, average of 3.47 casts) compared with the 2 other intervals (2005 to 2010; average of 2.6 casts and 2011 to 2015; average of 2.79 casts; p < 0.0001). Pirani score decreases the most until the third clinic visit. Conclusion: The mentor's greater expertise was associated with fewer casts and shorter time to obtain correction in isolated clubfoot, especially right after the first 5 years of practice. Progression of the Pirani score in both institutions occurs between the first and the third casts. Level of Evidence III; Therapeutic Study, Retrospective Comparative Study.

Objetivo: Avaliar se a experiência no Método Ponseti pode reduzir o tempo de tratamento e o número de gessos. Métodos: Na instituição 1 foram incluídos 254 pacientes com pé torto idiopático (403 pés) e na instituição 2, 32 pacientes (51 pés). Na instituição 1 (mentora) foram analisados 3 intervalos de 5 anos. Na instituição 2 (estagiária), foi analisado 1 intervalo de 5 anos. Resultados: Os pacientes tratados pelo mentor tiveram menos gessos em comparação aos tratados pelo estagiário (p < 0,001). Na Instituição 1, os três intervalos de mentores apresentaram diferenças no número de gessos até a correção dos pés (p < 0,05). Diferença estatisticamente significativa foi observada no primeiro intervalo do mentor (2000 a 2005, média 3,47 gessos) em comparação com os outros 2 intervalos (2005 a 2010; média 2,6 gessos e 2011 a 2015; média 2,79 gessos; p < 0,0001). O escore de Pirani diminui mais até a terceira consulta clínica. Conclusão: A maior expertise do mentor no Método Ponseti esteve associada ao menor número de gessos e ao menor tempo para correção do pé torto, principalmente logo após os primeiros 5 anos. A maior progressão do score de Pirani ocorre entre o primeiro e o terceiro gesso. Nível de Evidência III; Estudo Terapêutico, Estudo Comparativo Retrospectivo.

Reproducibility of arterial spin labeling cerebral blood flow image processing: A report of the ISMRM open science initiative for perfusion imaging (OSIPI)_and the ASL MRI challenge.

PURPOSE: Arterial spin labeling (ASL) is a widely used contrast-free MRI method for assessing cerebral blood flow (CBF). Despite the generally adopted ASL acquisition guidelines, there is still wide variability in ASL analysis. We explored this variability through the ISMRM-OSIPI ASL-MRI Challenge, aiming to establish best practices for more reproducible ASL analysis. METHODS: Eight teams analyzed the challenge data, which included a high-resolution T1-weighted anatomical image and 10 pseudo-continuous ASL datasets simulated using a digital reference object to generate ground-truth CBF values in normal and pathological states. We compared the accuracy of CBF quantification from each team's analysis to the ground truth across all voxels and within predefined brain regions. Reproducibility of CBF across analysis pipelines was assessed using the intra-class correlation coefficient (ICC), limits of agreement (LOA), and replicability of generating similar CBF estimates from different processing approaches. RESULTS: Absolute errors in CBF estimates compared to ground-truth synthetic data ranged from 18.36 to 48.12 mL/100 g/min. Realistic motion incorporated into three datasets produced the largest absolute error and variability between teams, with the least agreement (ICC and LOA) with ground-truth results. Fifty percent of the submissions were replicated, and one produced three times larger CBF errors (46.59 mL/100 g/min) compared to submitted results. CONCLUSIONS: Variability in CBF measurements, influenced by differences in image processing, especially to compensate for motion, highlights the significance of standardizing ASL analysis workflows. We provide a recommendation for ASL processing based on top-performing approaches as a step toward ASL standardization.

Integrated Proteomics Characterization of NLRP3 Inflammasome Inhibitor MCC950 in Monocytic Cell Line Confirms Direct MCC950 Engagement with Endogenous NLRP3.

Inhibition of the NLRP3 inflammasome is a promising strategy for the development of new treatments for inflammatory diseases. MCC950 is a potent and selective small-molecule inhibitor of the NLRP3 pathway and has been validated in numerous species and disease models. Although the capacity of MCC950 to block NLRP3 signaling is well-established, it is still critical to identify the mechanism of action and molecular targets of MCC950 to inform and derisk drug development. Quantitative proteomics performed in disease-relevant systems provides a powerful method to study both direct and indirect pharmacological responses to small molecules to elucidate the mechanism of action and confirm target engagement. A comprehensive target deconvolution campaign requires the use of complementary chemical biology techniques. Here we applied two orthogonal chemical biology techniques: compressed Cellular Thermal Shift Assay (CETSA) and photoaffinity labeling chemoproteomics, performed under biologically relevant conditions with LPS-primed THP-1 cells, thereby deconvoluting, for the first time, the molecular targets of MCC950 using chemical biology techniques. In-cell chemoproteomics with inlysate CETSA confirmed the suspected mechanism as the disruption of inflammasome formation via NLRP3. Further cCETSA (c indicates compressed) in live cells mapped the stabilization of NLRP3 inflammasome pathway proteins, highlighting modulation of the targeted pathway. This is the first evidence of direct MCC950 engagement with endogenous NLRP3 in a human macrophage cellular system using discovery proteomics chemical biology techniques, providing critical information for inflammasome studies.

Impulse oscillometry in patients with pulmonary arterial hypertension: an exploratory study.

INTRODUCTION: Studies suggest peripheral airway abnormalities in Pulmonary Arterial Hypertension (PAH). Impulse Oscillometry (IOS) is a noninvasive and sensitive technique for assessing the small airways. It evaluates the impedance of the respiratory system ‒ Resistance (R) and reactance (X) ‒ to a pulse of sound waves sent to the lungs, in a range of frequencies (5‒20 Hz). METHOD: Resistance variables: R5, R20, R5-R20 and reactance variables: AX (reactance area) and Fres (resonance frequency). The aim is to evaluate R and X in patients with idiopathic PAH (IPAH) and to investigate whether there is a correlation between IOS and spirometry. RESULTS: Thirteen IPAH patients and 11 healthy subjects matched for sex and age underwent IOS and spirometry. IPAH patients had lower FVC and FEV1 values (p < 0.001), VEF1/CVF (p = 0.049) and FEF 25-75 (p = 0.006) than healthy patients. At IOS, IPAH patients showed lower tidal volumes and higher AX (p < 0.05) compared to healthy individuals, and 53.8 of patients had R5-R20 values ≥ 0.07 kPa/L/s. Correlation analysis: X5, AX, R5-R20 and Fres showed moderate correlation with FVC (p = 0.036 r = 0.585, p = 0.001 r = -0.687, p = 0.005 r = -0.726 and p = 0.027 r = -0.610); Fres (p = 0.012 r = -0.669) and AX (p = 0.006 r = -0.711) correlated with FEV1; [R5 and R20, (R5-R20)] also correlated with FEV1 (p < 0.001 r = -0.573, p = 0.020 r = -0.634 and p = 0.010 r = -0.683, respectively) in the IPAH group. There were also moderate correlations of FEF 25-75 % with Z5 (p = 0.041), R5 (p = 0.018), Fres (p = 0.043) and AX (p = 0.023). DISCUSSION: Patients showed changes suggestive of increased resistance and reactance in the IOS compared to healthy individuals, and the IOS findings showed a good correlation with spirometry variables.

cirCodAn: A GHMM-based tool for accurate prediction of coding regions in circRNA.

Studies focusing on characterizing circRNAs with the potential to translate into peptides are quickly advancing. It is helping to elucidate the roles played by circRNAs in several biological processes, especially in the emergence and development of diseases. While various tools are accessible for predicting coding regions within linear sequences, none have demonstrated accurate open reading frame detection in circular sequences, such as circRNAs. Here, we present cirCodAn, a novel tool designed to predict coding regions in circRNAs. We evaluated the performance of cirCodAn using datasets of circRNAs with strong translation evidence and showed that cirCodAn outperformed the other tools available to perform a similar task. Our findings demonstrate the applicability of cirCodAn to identify coding regions in circRNAs, which reveals the potential of use of cirCodAn in future research focusing on elucidating the biological roles of circRNAs and their encoded proteins. cirCodAn is freely available at https://github.com/denilsonfbar/cirCodAn.

Oncopig bladder cancer cells recapitulate human bladder cancer treatment responses in vitro.

Introduction: Bladder cancer is a common neoplasia of the urinary tract that holds the highest cost of lifelong treatment per patient, highlighting the need for a continuous search for new therapies for the disease. Current bladder cancer models are either imperfect in their ability to translate results to clinical practice (mouse models), or rare and not inducible (canine models). Swine models are an attractive alternative to model the disease due to their similarities with humans on several levels. The Oncopig Cancer Model has been shown to develop tumors that closely resemble human tumors. However, urothelial carcinoma has not yet been studied in this platform. Methods: We aimed to develop novel Oncopig bladder cancer cell line (BCCL) and investigate whether these urothelial swine cells mimic human bladder cancer cell line (5637 and T24) treatment-responses to cisplatin, doxorubicin, and gemcitabine in vitro. Results: Results demonstrated consistent treatment responses between Oncopig and human cells in most concentrations tested (p>0.05). Overall, Oncopig cells were more predictive of T24 than 5637 cell therapeutic responses. Microarray analysis also demonstrated similar alterations in expression of apoptotic (GADD45B and TP53INP1) and cytoskeleton-related genes (ZMYM6 and RND1) following gemcitabine exposure between 5637 (human) and Oncopig BCCL cells, indicating apoptosis may be triggered through similar signaling pathways. Molecular docking results indicated that swine and humans had similar Dg values between the chemotherapeutics and their target proteins. Discussion: Taken together, these results suggest the Oncopig could be an attractive animal to model urothelial carcinoma due to similarities in in vitro therapeutic responses compared to human cells.

Phase transitions of choline dihydrogen phosphate: A vibrational spectroscopy and periodic DFT study.

Choline dihydrogen phosphate, [Chol][H2PO4], is a proton-conducting ionic plastic crystal exhibiting a complicated sequence of phase transitions. Here, we address the argument in the literature around the thermal properties of [Chol][H2PO4] using Raman and infrared microspectroscopy. The known structure of the low-temperature crystal, which contains the anti-conformer of [Chol]+ and hydrogen-bonded dimers of anions, was used to do periodic density functional theory calculations of the vibrational frequencies. Raman spectra indicate that the solid-solid transition at 20 °C is linked to a conformational change to the gauche [Chol] conformer with a concurrent local rearrangement of the anions. The distinct bands of lattice modes in the low-frequency range of the Raman spectra vanish at the 20 °C transition. Given the ease with which metastable crystals can be produced, Raman mappings demonstrate that a sample of [Chol][H2PO4] at ambient temperature can contain a combination of anti- and gauche conformers. Heating to 120 °C causes continuous changes in the local environment of anions rather than melting as suggested by a recent calorimetric investigation of [Chol][H2PO4]. The monotonic change in vibrational spectra is consistent with earlier observations of a very small entropy of fusion and no abrupt jump in the temperature dependence of ionic conductivity along the phase transitions of [Chol][H2PO4].

Comparison of energy expenditure of individuals with Duchenne muscular dystrophy in the sitting posture on the ground and in water.

Duchenne Muscular Dystrophy (DMD) is one of the most frequent childhood dystrophies, affecting cardiopulmonary functions and walking ability. One of the main symptoms is fatigue, which is caused by altered muscle metabolism related to energy expenditure (EE). Aquatic physiotherapy is a therapeutic modality that facilitates the maintenance of this posture because of immersion on the body. This cross-sectional observational study aimed to compare the EE on the ground and water of individuals with DMD through oxygen consumption in the maintenance of sitting posture. The individuals were in a sitting position on the ground and in the water for 20 min for the assessments. The variables peripheral oxygen saturation, heart rate, maximum expiratory pressure, maximum inspiratory pressure, forced vital capacity, respiratory quotient (RQ), and oxygen consumption per kilogram of body weight (VO2 /kg) were compared, adopting a significance of 5 %. No difference was found between medians and quartiles of RQ when comparing the two environments. The same was observed for VO2 /Kg values on the ground and in water. The data from this study demonstrate that the EE of individuals with DMD did not change when maintaining a sitting posture on the ground and in water.

The landscape of biomedical research funding in Brazil: a current overview.

OBJECTIVE: The objective of this narrative review is to discuss the current state of research funding in Brazil. MATERIALS AND METHODS: This study is based on the most recent edition of the course Funding for Research and Innovation in the University of Sao Paulo School of Medicine which was a three-day course with 12 hours of instruction. The course brought together leading experts in the field to comprehensively discuss the current state of research funding in Brazil. Each speaker provided a presentation on a specific topic related to research funding. After the workshop, speakers assembled relevant topics in this manuscript. RESULTS: collaborative research is critical for securing research funding. It optimizes proposal competitiveness, amplifies societal impact, and manages risks effectively. As such, fostering and supporting these collaborations is paramount for both researchers and funding agencies. To maintain the highest integrity in research, investigators involved in these collaborations must disclose any relationships that could potentially influence the outcomes or interpretation of their projects. CONCLUSIONS: In Brazil, the mainstay of research funding stems from public entities, with agencies such as CNPq, CAPES, and state bodies like FAPESP, FAPERJ, FAPEMIG and others at the forefront. Concurrently, industry funding offers viable pathways, especially through industry-sponsored studies, investigator-led projects, and collaborative initiatives. The Brazilian funding landscape is further enriched by innovative platforms, including crowdfunding and the contributions of institutions like the Serrapilheira Institute. Internationally, esteemed organizations such as the National Institutes of Health (NIH) and the Bill & Melinda Gates Foundation stand out as potential funders.

Evaluating the persistence of malachite green residues in tilapia and pacu fish.

Although banned in food-producing animals, residues of malachite green (MG) and its primary metabolite, leucomalachite green (LMG), have been found in fish due to illegal use in aquaculture and the release of industrial wastewater, which represent a serious risk to food and environmental securities. This study aimed to investigate the residue depletion profile of MG and LMG in edible tissues of Nile tilapia (Oreochromis niloticus) and pacu (Piaractus mesopotamicus) cultured simultaneously under the same environmental conditions to support control measures in case of abuse. An analytical method involving QuEChERS sample preparation and liquid chromatography coupled to tandem mass spectrometry was developed, validated, and applied to quantify MG and LMG residues in fish fillets from two depletion experiments after treatment by immersion bath (MG at 0.10 mg L-1 for 60 min). During the experiment, the average water temperature was 30 ºC, while the pH was 6.9. The method is selective, precise (CV = 0.4 - 22%) and accurate (recovery 92 - 114%). The limits of detection and quantification are 0.15 and 0.5 ng g-1, respectively. In both species, the sum of MG and LMG residues were quantified up to the 32nd day post-exposure, and the concentrations were significantly higher in the pacu fillets (up to 3284 ng g-1) than in Nile tilapia (up to 432 ng g-1). The sums of MG and LMG residues were below 2 ng g-1 at 44 days and 342 days for Nile tilapia and pacu, respectively - the Minimum Required Performance Limit (MRPL) for analytical methods intended to monitor forbidden substances in food according to old European Commission guidelines. The persistence of MG residues in pacu may be attributed to its higher lipid content, which favors the accumulation of the non-polar metabolite LMG. These results provide insights into the concern about human, animal, and environmental health risks resulting from unauthorized use or aquatic contamination by industrial wastewater containing MG residues.

Unsuccessful tuberculosis treatment outcomes across Brazil's geographical landscape before and during the COVID-19 pandemic: are we truly advancing toward the sustainable development/end TB goal?

BACKGROUND: Tuberculosis is one of the most significant infectious diseases for global public health. The reallocation of healthcare resources and the restrictions imposed by the COVID-19 pandemic have hindered access to TB diagnosis and treatment. Increases in unfavorable outcomes of the disease have been observed in Brazil. The objective of this study was to analyze the spatial distribution of unfavorable TB treatment outcomes in Brazil before and during the pandemic. METHODS: An ecological study with spatial analysis was conducted with all 5569 municipalities in Brazil. All reported cases of tuberculosis between January 2010 and December 2021, as well as reported cases of COVID-19 from February 2020 to December 2021, were included. The outcomes studied encompass loss to follow-up, drug-resistant tuberculosis, and death. The Getis Ord GI* technique was employed to assess spatial association, and the Kernel density estimator was used to identify areas with concentrated increases or decreases in outcomes. Bivariate Local Moran's I was used to examine the spatial association between outcomes and COVID-19 incidence. The study was approved by the Research Ethics Committee of Ribeirão Preto Nursing School, University of São Paulo. RESULTS: There were 134,394 cases of loss to follow-up, 10,270 cases of drug resistance, and 37,863 deaths. Clusters of high and low values were identified for all three outcomes, indicating significant changes in the spatial distribution patterns. Increases in concentrations were observed for lost to follow-up cases in the Southeast, while reductions occurred in the Northeast, South, and Midwest. Drug-resistant tuberculosis experienced an increase in the Southern and Southeastern regions and a decrease in the Northeast and South. TB-related deaths showed notable concentrations in the Midwest, Northeast, South, and Southeast. There was an increase in high occurrence clusters for deaths after 2020 and 2021 in the Northeast. CONCLUSIONS: The pandemic has brought additional challenges, emphasizing the importance of enhancing efforts and disease control strategies, prioritizing early identification, treatment adherence, and follow-up. This commitment is vital for achieving the goal of tuberculosis elimination.