Is There an Interplay between Environmental Factors, Microbiota Imbalance, and Cancer Chemotherapy-Associated Intestinal Mucositis?

Interindividual variation in drug efficacy and toxicity is a significant problem, potentially leading to adverse clinical and economic public health outcomes. While pharmacogenetics and pharmacogenomics have long been considered the primary causes of such heterogeneous responses, pharmacomicrobiomics has recently gained attention. The microbiome, a community of microorganisms living in or on the human body, is a critical determinant of drug response and toxicity. Factors such as diet, lifestyle, exposure to xenobiotics, antibiotics use, illness, and genetics can influence the composition of the microbiota. Changes in the intestinal microbiota are particularly influential in drug responsiveness, especially in cancer chemotherapy. The microbiota can modulate an individual's response to a drug, affecting its bioavailability, clinical effect, and toxicity, affecting treatment outcomes and patient quality of life. For instance, the microbiota can convert drugs into active or toxic metabolites, influencing their efficacy and side effects. Alternatively, chemotherapy can also alter the microbiota, creating a bidirectional interplay. Probiotics have shown promise in modulating the microbiome and ameliorating chemotherapy side effects, highlighting the potential for microbiota-targeted interventions in improving cancer treatment outcomes. This opinion paper addresses how environmental factors and chemotherapy-induced dysbiosis impact cancer chemotherapy gastrointestinal toxicity.

Exploratory comparative transcriptomic analysis reveals potential gene targets associated with Cry1A.105 and Cry2Ab2 resistance in fall armyworm (Spodoptera frugiperda).

Genetically modified (GM) crops, expressing Bacillus thuringiensis (Bt) insecticidal toxins, have substantially transformed agriculture. Despite rapid adoption, their environmental and economic benefits face scrutiny due to unsustainable agricultural practices and the emergence of resistant pests like Spodoptera frugiperda, known as the fall armyworm (FAW). FAW's adaptation to Bt technology in corn and cotton compromises the long-term efficacy of Bt crops. To advance the understanding of the genetic foundations of resistance mechanisms, we conducted an exploratory comparative transcriptomic analysis of two divergent FAW populations. One population exhibited practical resistance to the Bt insecticidal proteins Cry1A.105 and Cry2Ab2, expressed in the genetically engineered MON-89Ø34 - 3 maize, while the other population remained susceptible to these proteins. Differential expression analysis supported that Cry1A.105 and Cry2Ab2 significantly affect the FAW physiology. A total of 247 and 254 differentially expressed genes were identified in the Cry-resistant and susceptible populations, respectively. By integrating our findings with established literature and databases, we underscored 53 gene targets potentially involved in FAW's resistance to Cry1A.105 and Cry2Ab2. In particular, we considered and discussed the potential roles of the differentially expressed genes encoding ABC transporters, G protein-coupled receptors, the P450 enzymatic system, and other Bt-related detoxification genes. Based on these findings, we emphasize the importance of exploratory transcriptomic analyses to uncover potential gene targets involved with Bt insecticidal proteins resistance, and to support the advantages of GM crops in the face of emerging challenges.

Socioeconomic factors increase the risk of teenage pregnancy: spatial and temporal analysis in a Brazilian municipality.

OBJECTIVE: To evaluate the distribution of the proportion of teenage mothers (PTM) in time and space and its relationship with socioeconomic indicators and social vulnerability. METHODS: An ecological study was carried out with teenage mothers living in 322 census tracts in Foz do Iguaçu (state of Paraná, Brazil) between 2013 and 2019. Spatial clusters of teenage mothers were identified by spatial scanning and grouped into strata with different prevalence. The association between these strata and the individual social vulnerability of the mothers was evaluated using the Pearson's Chi-square test. Linear regression models were adjusted to evaluate the association between PTM and socioeconomic factors by census tract and temporal trend in PTM in different strata. RESULTS: We identified five high prevalence clusters in peripheral regions and six with low prevalence in the central region of the municipality. Proportionally, there were more teenage mothers with a worse vulnerability index in the high prevalence stratum than in the low prevalence stratum. Places with worse socioeconomic conditions present higher PTM, a profile that did not change over time. For the increase of one unit in the Brazilian Deprivation Index and proportion of women responsible for the household, the PTM increased, respectively, by 3.8 (95%CI 3.1-4.4) and 0.086% (95%CI 0.03-0.14). There was a reduction in the global PTM in part of the period, which occurred later in the higher prevalence strata, but the proportions were stable again in the last years of study. CONCLUSION: Teenage pregnancy is concentrated in regions with worse socioeconomic conditions and greater maternal vulnerability and its behavior over time occurred differently in these areas.

Automatic mapping of high-risk urban areas for Aedes aegypti infestation based on building facade image analysis.

BACKGROUND: Dengue, Zika, and chikungunya, whose viruses are transmitted mainly by Aedes aegypti, significantly impact human health worldwide. Despite the recent development of promising vaccines against the dengue virus, controlling these arbovirus diseases still depends on mosquito surveillance and control. Nonetheless, several studies have shown that these measures are not sufficiently effective or ineffective. Identifying higher-risk areas in a municipality and directing control efforts towards them could improve it. One tool for this is the premise condition index (PCI); however, its measure requires visiting all buildings. We propose a novel approach capable of predicting the PCI based on facade street-level images, which we call PCINet. METHODOLOGY: Our study was conducted in Campinas, a one million-inhabitant city in São Paulo, Brazil. We surveyed 200 blocks, visited their buildings, and measured the three traditional PCI components (building and backyard conditions and shading), the facade conditions (taking pictures of them), and other characteristics. We trained a deep neural network with the pictures taken, creating a computational model that can predict buildings' conditions based on the view of their facades. We evaluated PCINet in a scenario emulating a real large-scale situation, where the model could be deployed to automatically monitor four regions of Campinas to identify risk areas. PRINCIPAL FINDINGS: PCINet produced reasonable results in differentiating the facade condition into three levels, and it is a scalable strategy to triage large areas. The entire process can be automated through data collection from facade data sources and inferences through PCINet. The facade conditions correlated highly with the building and backyard conditions and reasonably well with shading and backyard conditions. The use of street-level images and PCINet could help to optimize Ae. aegypti surveillance and control, reducing the number of in-person visits necessary to identify buildings, blocks, and neighborhoods at higher risk from mosquito and arbovirus diseases.

Integrated transcriptomics uncovers an enhanced association between the prion protein gene expression and vesicle dynamics signatures in glioblastomas.

BACKGROUND: Glioblastoma (GBM) is an aggressive brain tumor that exhibits resistance to current treatment, making the identification of novel therapeutic targets essential. In this context, cellular prion protein (PrPC) stands out as a potential candidate for new therapies. Encoded by the PRNP gene, PrPC can present increased expression levels in GBM, impacting cell proliferation, growth, migration, invasion and stemness. Nevertheless, the exact molecular mechanisms through which PRNP/PrPC modulates key aspects of GBM biology remain elusive. METHODS: To elucidate the implications of PRNP/PrPC in the biology of this cancer, we analyzed publicly available RNA sequencing (RNA-seq) data of patient-derived GBMs from four independent studies. First, we ranked samples profiled by bulk RNA-seq as PRNPhigh and PRNPlow and compared their transcriptomic landscape. Then, we analyzed PRNP+ and PRNP- GBM cells profiled by single-cell RNA-seq to further understand the molecular context within which PRNP/PrPC might function in this tumor. We explored an additional proteomics dataset, applying similar comparative approaches, to corroborate our findings. RESULTS: Functional profiling revealed that vesicular dynamics signatures are strongly correlated with PRNP/PrPC levels in GBM. We found a panel of 73 genes, enriched in vesicle-related pathways, whose expression levels are increased in PRNPhigh/PRNP+ cells across all RNA-seq datasets. Vesicle-associated genes, ANXA1, RAB31, DSTN and SYPL1, were found to be upregulated in vitro in an in-house collection of patient-derived GBM. Moreover, proteome analysis of patient-derived samples reinforces the findings of enhanced vesicle biogenesis, processing and trafficking in PRNPhigh/PRNP+ GBM cells. CONCLUSIONS: Together, our findings shed light on a novel role for PrPC as a potential modulator of vesicle biology in GBM, which is pivotal for intercellular communication and cancer maintenance. We also introduce GBMdiscovery, a novel user-friendly tool that allows the investigation of specific genes in GBM biology.

Socioeconomic factors increase the risk of teenage pregnancy: spatial and temporal analysis in a Brazilian municipality / Fatores socioeconômicos aumentam o risco de gravidez na adolescência: análise espacial e temporal em um município brasileiro

ABSTRACT Objective: To evaluate the distribution of the proportion of teenage mothers (PTM) in time and space and its relationship with socioeconomic indicators and social vulnerability. Methods: An ecological study was carried out with teenage mothers living in 322 census tracts in Foz do Iguaçu (state of Paraná, Brazil) between 2013 and 2019. Spatial clusters of teenage mothers were identified by spatial scanning and grouped into strata with different prevalence. The association between these strata and the individual social vulnerability of the mothers was evaluated using the Pearson's Chi-square test. Linear regression models were adjusted to evaluate the association between PTM and socioeconomic factors by census tract and temporal trend in PTM in different strata. Results: We identified five high prevalence clusters in peripheral regions and six with low prevalence in the central region of the municipality. Proportionally, there were more teenage mothers with a worse vulnerability index in the high prevalence stratum than in the low prevalence stratum. Places with worse socioeconomic conditions present higher PTM, a profile that did not change over time. For the increase of one unit in the Brazilian Deprivation Index and proportion of women responsible for the household, the PTM increased, respectively, by 3.8 (95%CI 3.1-4.4) and 0.086% (95%CI 0.03-0.14). There was a reduction in the global PTM in part of the period, which occurred later in the higher prevalence strata, but the proportions were stable again in the last years of study. Conclusion: Teenage pregnancy is concentrated in regions with worse socioeconomic conditions and greater maternal vulnerability and its behavior over time occurred differently in these areas.

RESUMO Objetivo: Avaliar a distribuição da proporção de mães adolescentes (PMA) no tempo e espaço e sua relação com indicadores socioeconômicos e vulnerabilidade social. Métodos: Realizou-se estudo ecológico com mães adolescentes residentes em 322 setores censitários de Foz do Iguaçu (PR) entre 2013 e 2019. Aglomerados espaciais de mães adolescentes foram identificados por varredura espacial e agrupados em estratos com diferentes prevalências. Avaliou-se a associação entre esses estratos e a vulnerabilidade social individual das mães pelo teste qui-quadrado de Pearson. Ajustaram-se modelos de regressão linear para avaliar associação entre a PMA e fatores socioeconômicos por setor censitário e tendência temporal da PMA nos diferentes estratos. Resultados: Identificaram-se cinco aglomerados de alta prevalência nas regiões periféricas e seis de baixa na região central do município. Proporcionalmente houve mais mães adolescentes com pior índice de vulnerabilidade no estrato de alta prevalência do que no de baixa. Locais com piores condições socioeconômicas apresentaram maior PMA, perfil que não mudou ao longo do tempo. Para o aumento de uma unidade do Índice Brasileiro de Privação e da proporção de mulheres responsáveis por domicílio, a PMA aumentou respectivamente 3,8 (IC95% 3,1-4,4) e 0,086% (IC95% 0,03-0,14). Houve uma redução na PMA global em parte do período, que ocorreu mais tardiamente nos estratos de maior prevalência, mas as proporções voltaram a ficar estáveis nos últimos anos de estudo. Conclusão: A gravidez na adolescência se concentra em regiões de pior condição socioeconômica e com maior vulnerabilidade materna e seu comportamento no tempo ocorreu, nessas áreas, de modo distinto.

Mapeamento da infestação por Aedes aegypti e Culex spp. adultos em Campinas (SP), Brasil / Mapping of Aedes aegypti and Culex spp. adults in Campinas (SP), Brazil

Introdução: Algumas arboviroses transmitidas por vetores como Aedes aegypti e Culex spp. são consideradas de grande importância epidemiológica, entre estas, destacam-se a dengue, Zika, chikungunya, febre amarela e febre do Nilo ocidental. A transmissão dos arbovírus ocorre enquanto as fêmeas infectadas realizam a hematofagia e as atuais medidas que visam a redução dessas arboviroses na população se dão principalmente com foco na redução da população de mosquitos. Índices de vigilância entomológica fazem parte das rotinas de programas de controle. Estudos recentes têm questionado a eficácia da utilização de índices de formas imaturas do vetor para predição do risco de transmissão de arboviroses e associação com incidência de casos. Isso indica que realizar a vigilância com a forma adulta dos vetores pode ser uma alternativa de maior eficácia. Objetivos: Estimar, predizer e mapear a infestação por Ae. aegypti e o Culex spp. associadas a variáveis de uso e ocupação do solo no município de Campinas/SP no período de verão entre os anos de 2021 a 2023. Material e Métodos: Trata-se de um estudo transversal realizado por meio de coletas mensais de mosquitos adultos realizadas em 200 armadilhas BG MosquititoTM distribuídas aleatoriamente na área urbana de Campinas. Foram realizadas regressões múltiplas em um contexto bayesiano e geoestatístico utilizando a abordagem de aproximações de Laplace aninhadas e integradas e equações diferenciais parciais estocásticas. Foram consideradas como covariáveis o Índice Brasileiro de Privação (IBP) e informações sobre uso e ocupação do solo obtidas de imagens de satélite. Resultados: O melhor modelo de regressão para o número de Ae. aegypti fêmeas encontrou associação positiva com o IBP, uma medida do nível socioeconômico, e árvores. Quanto aos machos, o melhor modelo mostrou associação positiva com cimento e telha de zinco. O melhor modelo para o total de mosquitos Ae. aegypti mostrou associação positiva com o IBP, cimento e árvore e o mesmo ocorreu para Culex spp. Foram elaborados mapas com a predição da quantidade de mosquitos para cada modelo considerando a distribuição das covariáveis presentes na área de estudo. Conclusões: Com esse estudo, foi possível modelar as quantidades de fêmeas, machos e total de Ae. aegypti e total de Culex spp., com base nas informações obtidas com a partir da instalação das armadilhas de adultos, e predizer os níveis de infestação para todos os locais da área de estudo. Variáveis socioeconômicas e de uso e ocupação do solo mostraram-se associadas aos números de mosquitos coletados, com exceção do nível socioeconômico para os machos de Ae. aegypti. Os resultados mostram que a utilização dessas covariáveis nas modelagens foram úteis para melhorar as predições nos locais não amostrados. Nosso estudo mostrou ser possível identificar áreas de maior risco para infestação de forma independente dos limites administrativos da área de estudo, quer sejam bairros ou distritos. Além disso, mostrou ser viável o uso de armadilhas de adultos para realização de vigilância entomológica.

Introduction: Some arboviruses transmitted by vectors such Aedes aegypti and Culex spp. are considered of great epidemiological importance, among which dengue, Zika and chikungunya, yellow fever and West Nile fever stand out. The transmission of arboviruses occurs while infected females are carrying out hematophagy, and current measures aimed at reducing these arboviruses in the population are mainly focused on reducing the mosquito population. Entomological surveillance indices are part of the routines of control programs. Recent studies have questioned the effectiveness of using indices of immature forms of the vector to predict the risk of arbovirus transmission and association with the incidence of cases. This indicates that carrying out surveillance with the adult form of the vectors may be a more effective alternative. Objectives: Estimate, predict and map the infestation of Ae. aegypti and Culex spp. associated with land use and occupation variables in the city of Campinas (SP) in the summer period between 2021 to 2023. Material and Methods: This is a cross-sectional study carried out through monthly collections of adult mosquitoes in 200 BG MosquititoTM traps randomly distributed in the urban area of Campinas. Multiple regressions were performed in a Bayesian and geostatistical context using the approach of nested and integrated Laplace approximations and stochastic partial differential equations. The Brazilian Deprivation Index (IBP) and information on land use and occupation obtained from satellite images were considered as covariates. Results: The best regression model for the number of female Ae. aegypti found a positive association with the IBP, a measure of socioeconomic status, and trees. As for males, the best model considered showed a positive association with cement and zinc tiles. The best model for the total number of Ae. aegypti showed a positive association with IBP, cement and trees, as the same occurred for Culex spp. Conclusions: With this study, it was possible to model the numbers of females, males and total Ae. aegypti and total Culex spp., based on the information obtained from the installation of adult traps, and to predict the infestation levels for all locations in the study area. Socioeconomic and land use and occupation variables were associated with the numbers of mosquitoes collected, with the exception of the socioeconomic level for males of Ae. aegypti. The results show that the use of these covariates in the models was useful to improve predictions in the non-sampled locations. Our study showed that it is possible to identify areas of greater risk for infestation independently of the administrative boundaries of the study area, whether they are neighborhoods, districts. Furthermore, it was shown to be feasible to use adult traps to carry out entomological surveillance.

Low-cost simulator for intra-abdominal bleeding.

BACKGROUND: training in critical surgical situations is crucial for a safe outcome. The use of simulators is well established, although many are quite expensive, requiring the search for financially viable solutions for training centers. METHODS: we built a low-cost simulator for intra-abdominal bleeding with inexpensive materials, such as a manikin chest, latex tubes, silicone rubber, and waterproof fabric, seeking to mimic the abdominal viscera and vessels and their anatomical correlations. An IV infusion set allowed simulated blood to flow under pressure, and the blood flowed freely during simulation. After obtaining a functional model, we selected general surgeons to validate the simulator and its use in teaching surgery. We used the content validity index (CVI), with a cutoff of 0.9. RESULTS: the cost of building the prototype was US$71,00 in 2021, accounting for the purchase of the various necessary materials. Twelve raters participated in the validation tests. The results obtained from the feedback survey showed a good evaluation of all items, especially the recognition of the injured vessel, access to the vascular injury, hemostasis by manual compression, and hemostatic suturing. CONCLUSION: the proposed simulator obtained good results in scenarios of intra-abdominal bleeding from large vessels, as well as for hemostasis by manual compression and suturing. It proved to be a useful tool for training in critical intra- abdominal bleeding situations, while maintaining a low cost of building.

Repouso eletromiográfico dos músculos mastigatórios de pacientes com disfunção temporomandibular antes e após intervenção fonoaudiológica com e sem bandagem elástica / Electromyographic rest of the masticatory muscles of patients with temporomandibular disorders before and after speech therapy with and without elastic bandage / Resto electromiográfico de los músculos masticatorios de pacientes con trastornos temporomandibulares antes y después de logopedia con y sin venda elástica

Objetivo: A pesquisa tem por objetivo verificar os limiares de repouso eletromiográfico dos músculos masseter e temporal em pacientes com disfunção temporomandibular (DTM) antes e após intervenção fonoaudiológica com e sem a utilização de bandagem elástica terapêutica. Métodos: A coleta contou com 14 participantes do sexo feminino, com idade entre 18 e 40 anos, com diagnóstico de DTM muscular ou mista. As pacientes foram divididas entre dois grupos classificados em: pacientes com bandagem associada à terapia tradicional (CB) e grupo de terapia tradicional (SB). As pacientes inicialmente foram avaliadas pelo exame de eletromiografia de superfície nas situações de contração voluntária máxima e repouso, e após quatro semanas de intervenção, foi realizada nova avaliação com os mesmos instrumentos. A análise dos dados ocorreu de forma quantitativa e qualitativa. Resultados:No grupo SB o músculo masseter direito apresentou aumento dos valores de repouso com significância, foi observado que o mesmo ocorreu para todos os músculos deste grupo, influenciando no equilíbrio da musculatura ipsilateral e contralateral, no entanto sem evidência estatística. O grupo CB não demonstrou valores estatísticos significativos, porém qualitativamente os valores de repouso muscular diminuíram e equilibraram-se de forma contralateral. Conclusão: Não foram observadas mudanças estatisticamente significantes nos limiares eletromiográficos durante repouso dos músculos masseter e temporal em ambos os grupos. Qualitativamente houve aumento dos valores eletromiográficos após terapia manual tradicional em todos os músculos do grupo SB. Com relação ao grupo CB, houve diminuição dos valores do repouso eletromiográfico após terapia, embora sem evidências estatísticas. (AU)

Purpose: Objective: The research aims to verify the electromyographic rest thresholds of the masseter and temporal muscles in patients with temporomandibular disorders (TMD) before and after speech therapy intervention with and without the use of therapeutic elastic bandage. Methods: The collection included 14 female participants, aged between 18 and 40 years, who had a diagnosis of muscular or mixed TMD. The patients were divided into two groups: with traditional therapy (CB) bandage and traditional therapy (SB) only group. The patients underwent initial evaluation, as well as surface electromyography in situations of maximum voluntary contraction and rest and at the end of the four weeks of intervention, a new evaluation was performed with the same instruments. Data analysis occurred quantitatively and qualitatively. Results: In the SB group, the right masseter muscle showed a significant increase in resting values. It was observed that the same occurred for all muscles in this group, influencing the balance of the ipsilateral and contralateral muscles, although without statistical evidence. The CB group did not show statistically significant values, but qualitatively the muscle rest values decreased and balanced in a contralateral way. Conclusion: No statistically significant changes were observed in the resting electromyographic thresholds of the masseter and temporalis muscles in both groups. Qualitatively, there was an increase in electromyographic values after traditional manual therapy in all muscles in the SB group. Regarding the CB group, there was a decrease in electromyographic resting values after therapy, although without statistical evidence. (AU)

Objetivo: La investigación tiene como objetivo verificar los umbrales electromiográficos de reposo de los músculos masetero y temporal en pacientes con trastornos temporomandibulares (TMD) antes y después de la terapia del habla con y sin el uso de venda elástica terapéutica. Métodos: La colección incluyó a 14 participantes mujeres, con edades entre 18 y 40 años, diagnosticadas con TTM muscular o mixta. Los pacientes fueron divididos en dos grupos clasificados en: pacientes con vendaje asociado a terapia tradicional (CB) y grupo de terapia tradicional (SB). Los pacientes fueron inicialmente evaluados mediante electromiografía de superficie en situaciones de máxima contracción voluntaria y reposo, luego de cuatro semanas de intervención se realizó una nueva evaluación con los mismos instrumentos. El análisis de datos se llevó a cabo cuantitativa y cualitativamente. Resultados: En el grupo SB, el músculo masetero derecho presentó un aumento significativo en los valores de reposo, se observó que lo mismo ocurrió para todos los músculos de este grupo, influyendo en el equilibrio de los músculos ipsilaterales y contralaterales, sin embargo, sin evidencia estadística. El grupo CB no mostró valores estadísticamente significativos, pero cualitativamente los valores de descanso muscular disminuyeron y se equilibraron contralateralmente. Conclusión: No se observaron cambios estadísticamente significativos en los umbrales electromiográficos en reposo de los músculos masetero y temporal en ambos grupos. Cualitativamente, hubo un aumento de los valores electromiográficos después de la terapia manual tradicional en todos los músculos del grupo SB. En cuanto al grupo CB, hubo una disminución de los valores electromiográficos de reposo después de la terapia, aunque sin evidencia estadística. (AU)

Prognostic Value of the Platelet-lymphocyte Ratio for Glioblastoma: A Systematic Review.

BACKGROUND: Glioblastoma is the most common type of malignant glioma and is 1 of the most frequent primary tumors during adult life. The platelet-lymphocyte ratio (PLR) has been studied as an inflammatory marker associated with the prognosis of glioblastoma in previous studies. Considering the morbidity associated with this condition, it is important that there are other ways of assessing the prognosis that do not require invasive methods. Therefore, we performed this systematic review in order to determine the prognostic value of the PLR. METHODS: We conducted an English language, literature-based search for papers published from 2012 to 2022, using the PubMed, Cochrane, Biblioteca Virtual em Saúde and Biomed Central Journal. We use the Preferred Reporting Items for Systematic Reviews and Meta-analyses recommendations. Titles and abstracts were evaluated independently by 2 authors, after which articles were selected for final analysis based on application of inclusion criteria (patients diagnosed with glioblastoma; address the use of PLR as a prognostic factor; hazard ratio; adults; clinical trials and observational studies) and exclusion criteria (inclusion of pediatric or animals, case reports, letters, conference abstracts, meta-analysis, and nonclinical studies or did not include hazard ratio) during full text screen. Each included article was then assessed for quality using Newcastle-Ottawa scale and relevant variables were extracted for synthesis. RESULTS: Of 127 results, 11 articles were included for final analysis. There were 7 studies from China, 1 from Italy, 1 from Portugal, 1 from Turkey, and 1 from India. The years of publications were between 2015 and 2022. All the studies used PLR from the preoperative blood sample. Among the studies that analyzed the relationship between PLR and overall survival, 7 found a predictive relationship, 3 found no association, and 1 found an association between PLR and progression free survival in patients with glioblastoma. CONCLUSIONS: Studies have shown that PLR can be a useful marker to aid in the prognosis of glioblastoma. Due to the ease of obtaining, rapid analysis and low cost, the PLR can be particularly beneficial in health centers with limited financial resources.

Extracellular vesicles throughout development: A potential roadmap for emerging glioblastoma therapies.

Extracellular vesicles (EVs) are membrane-delimited vesicular bodies carrying different molecules, classified according to their size, density, cargo, and origin. Research on this topic has been actively growing through the years, as EVs are associated with critical pathological processes such as neurodegenerative diseases and cancer. Despite that, studies exploring the physiological functions of EVs are sparse, with particular emphasis on their role in organismal development, initial cell differentiation, and morphogenesis. In this review, we explore the topic of EVs from a developmental perspective, discussing their role in the earliest cell-fate decisions and neural tissue morphogenesis. We focus on the function of EVs through development to highlight possible conserved or novel processes that can impact disease progression. Specifically, we take advantage of what was learned about their role in development so far to discuss EVs impact on glioblastoma, a particular brain tumor of stem-cell origin and poor prognosis, and how their function can be hijacked to improve current therapies.

Low-cost simulator for intra-abdominal bleeding / Simulador de baixo custo para sangramento intra-abdominal

ABSTRACT Background: training in critical surgical situations is crucial for a safe outcome. The use of simulators is well established, although many are quite expensive, requiring the search for financially viable solutions for training centers. Methods: we built a low-cost simulator for intra-abdominal bleeding with inexpensive materials, such as a manikin chest, latex tubes, silicone rubber, and waterproof fabric, seeking to mimic the abdominal viscera and vessels and their anatomical correlations. An IV infusion set allowed simulated blood to flow under pressure, and the blood flowed freely during simulation. After obtaining a functional model, we selected general surgeons to validate the simulator and its use in teaching surgery. We used the content validity index (CVI), with a cutoff of 0.9. Results: the cost of building the prototype was US$71,00 in 2021, accounting for the purchase of the various necessary materials. Twelve raters participated in the validation tests. The results obtained from the feedback survey showed a good evaluation of all items, especially the recognition of the injured vessel, access to the vascular injury, hemostasis by manual compression, and hemostatic suturing. Conclusion: the proposed simulator obtained good results in scenarios of intra-abdominal bleeding from large vessels, as well as for hemostasis by manual compression and suturing. It proved to be a useful tool for training in critical intra- abdominal bleeding situations, while maintaining a low cost of building.

RESUMO Introdução: o treinamento em situações críticas em Cirurgia é determinante para o desfecho seguro. O uso de simuladores é bastante consolidado, embora muitos apresentem custos muito elevados, sendo necessária a busca de soluções financeiramente viáveis para os centros de treinamento. Métodos: construímos um simulador de sangramento intra-abdominal de baixo custo com materiais simples como tronco de manequim, tubos de látex, borracha de silicone e tecido impermeável, buscando representar vísceras abdominais e vasos e suas correlações anatômicas. Um sistema de tubos e equipos de soro permitiu o fluxo, sob pressão, de sangue simulado, que vertia livremente durante a simulação. Após a obtenção de modelo funcional, selecionamos cirurgiões gerais para a validação do simulador e seu uso no ensino de Cirurgia. Utilizamos o Índice de Validação de Concordância (IVC), com corte de 0,9. Resultados: a construção do protótipo resultou em gasto de US$71,00 em valores de 2021, destinados à aquisição dos diversos materiais necessários. Doze avaliadores participaram dos testes de validação. Os resultados obtidos dos questionários demonstraram uma boa avaliação em todos os itens, destacando-se o reconhecimento do vaso traumatizado, o acesso à lesão vascular, o controle hemostático por pressão direta assim como por sutura direta da lesão. Conclusão: o simulador proposto obteve bons resultados em cenários de sangramento abdominal de grandes vasos, assim como o controle hemostático do mesmo por pressão direta e sutura. Mostrou-se ferramenta útil para a adaptação a situações de estresse no treinamento em sangramentos intra-abdominais, além de manter baixo custo de construção.

Effects of Starch Overload and Cecal Buffering on Fecal Microbiota of Horses.

Starch overload in horses causes gastrointestinal and metabolic disorders that are associated with microbiota changes. Therefore, we identified the fecal microbiota and hypothesized that intracecal injection of alkaline solution (buffer; Mg(OH)2 + Al(OH)3) could stabilize these microbiota and clinical changes in horses submitted to corn starch overload. Ten crossbred horses (females and geldings) were allocated to group I (water−saline and starch−buffer treatments) and group II (water−buffer and starch−saline treatments). Clinical signs, gross analysis of the feces, and fecal microbiota were evaluated through 72 h (T0; T8; T12; T24; T48; T72). Corn starch or water were administrated by nasogastric tube at T0, and the buffer injected into the cecum at T8 in starch−buffer and water−buffer treatments. Starch overload reduced the richness (p < 0.001) and diversity (p = 0.001) of the fecal microbiota. However, the starch−buffer treatment showed greater increase in amylolytic bacteria (Bifidobacterium 0.0% to 5.6%; Lactobacillus 0.1% to 7.4%; p < 0.05) and decrease in fibrolytic bacteria (Lachnospiraceae 10.2% to 5.0%; Ruminococcaceae 11.7% to 4.2%; p < 0.05) than starch−saline treatment. Additionally, animals that received starch−buffer treatment showed more signs of abdominal discomfort and lameness associated with dysbiosis (amylolytic r > 0.5; fribolytic r < 0.1; p < 0.05), showing that cecal infusion of buffer did not prevent, but intensified intestinal disturbances and the risk of laminitis.

Laparoscopy assisted abomasal cannulation in cadavers of bovine fetuses.

BACKGROUND: Due to the complexity of ruminant digestion, cannulation of organs of the digestive tract has been carried out in order to advance the understanding of digestive physiology, nutrient degradability, gastrointestinal diseases and biotechnological research. The abomasal cannulation is interesting for nutritional studies, especially in suckling calves, to obtain fluid and abomasal content, evaluation of abomasal flow and function, and infusion of nutrients and drugs when it is intended to reach high concentrations in the organ. Conventionally, access and cannulation of digestive organs of ruminants has been performed by laparotomy, a method often criticized and classified as cruel by some sectors related to ethics and animal welfare. The aim of this present study is to describe and standardize a minimally invasive by laparoscopy assisted abomasal cannulation in bovine fetuses (cadavers), which had been previously slaughtered by accident and would be discarded in local slaughterhouses. RESULTS: The abomasal cannulation technique was feasible, simple and did not present major difficulties. The surgical time for cannulation of the abomasum, from the insertion of the trocars to the completion of the technique with fixation of the organ to the abdominal wall, ranged from 9 to 27 min, with an average of 15.5 ± 6.62 min. CONCLUSIONS: The Laproscopic assisted abomasal cannulation in bovine fetuses was feasible and safe with minimal tissue injury to the abdominal wall and with short surgical time. More studies in the clinical routine related to minimally invasive abomasal content collection, abomasopexy and abomasotomy are required in order to demonstrate its impact and importance in bovine clinic.

Unconventional Protein Secretion in Brain Tumors Biology: Enlightening the Mechanisms for Tumor Survival and Progression.

Non-canonical secretion pathways, collectively known as unconventional protein secretion (UPS), are alternative secretory mechanisms usually associated with stress-inducing conditions. UPS allows proteins that lack a signal peptide to be secreted, avoiding the conventional endoplasmic reticulum-Golgi complex secretory pathway. Molecules that generally rely on the canonical pathway to be secreted may also use the Golgi bypass, one of the unconventional routes, to reach the extracellular space. UPS studies have been increasingly growing in the literature, including its implication in the biology of several diseases. Intercellular communication between brain tumor cells and the tumor microenvironment is orchestrated by various molecules, including canonical and non-canonical secreted proteins that modulate tumor growth, proliferation, and invasion. Adult brain tumors such as gliomas, which are aggressive and fatal cancers with a dismal prognosis, could exploit UPS mechanisms to communicate with their microenvironment. Herein, we provide functional insights into the UPS machinery in the context of tumor biology, with a particular focus on the secreted proteins by alternative routes as key regulators in the maintenance of brain tumors.

Preparação cognitiva comportamental do assoalho pélvico com balão vaginal para o parto / Behavioral cognitive preparation of the pelvic floor with vaginal balloon for childbirth

Introdução: Para aliviar ou prevenir as disfunções dos músculos do assoalho pélvico é necessário sejam treinados seus parâmetros funcionais: coordenação, força, potência, resistência e pré-contração, bem como tenham capacidade de alongamento suficiente durante a passagem do bebê, a fim de evitar lacerações e outras lesões. Objetivo: Avaliar a percepção de puérperas acerca do uso do balão vaginal, em termos cognitivo-comportamental, na preparação para o parto vaginal. Métodos: Estudo descritivo do tipo transversal e qualitativo, realizado com puérperas primíparas de parto vaginal que fizeram ou não o uso do balão vaginal durante a gestação, avaliadas por meio de uma ficha de avaliação sociodemográfica e obstétrica e da aplicação dos questionários sobre os eventos do trabalho de parto e de percepção do uso Epi-No. Resultados: Participaram do estudo 20 puérperas. Não houve diferença entre as puérperas quanto a presença de lacerações vaginais e o tempo de trabalho de parto. Todas as mulheres do grupo que utilizaram o balão vaginal perceberam influência positiva no trabalho de parto. Conclusão: O treinamento dos músculos do assoalho pélvico para o parto com balão vaginal exerceu efeito positivo na preparação cognitivo-comportamental da amostra estudada, o que facilitou o trabalho de parto.

Diagnostic challenges in hypophosphatasia in adult patients / Desafios do diagnóstico da hipofosfatasia em adultos

Introdução: Hipofosfatasia é um distúrbio metabólico que afeta a mineralização óssea e dentária, causada por mutações no gene ALPL, levando à deficiência enzimática da fosfatase alcalina tecido não-específica. A forma adulta caracteriza-se por fraturas atípicas do fêmur, osteomalácia, osteoporose, grave osteoartropatia, condrocalcinose e artralgia. Objetivo: Demonstrar desafios diagnósticos relacionados à hipofosfatasia através do relato de dois casos. Paciente 1: feminino, 59 anos, encaminhada para avaliação clínica devido às fraturas patológicas de difícil consolidação e osteoporose generalizada de causa genética. Relata perda dentária precoce da arcada superior, fraturas na coluna, em ombro esquerdo e no fêmur. Atualmente, queixa-se de dor crônica intensa, com uso de múltiplos medicamentos. Achados clínicos, laboratoriais e radiológicos foram compatíveis com o diagnóstico de hipofosfatasia. Paciente 2: masculino, 31 anos, filho da paciente 1, encaminhado para avaliação clínica por fratura patológica precoce em fêmur esquerdo e osteoporose não esclarecida. Atualmente relata dor e claudicação importante em membro inferior esquerdo, associado à lombalgia crônica. Confirmação do diagnóstico de hipofosfatasia por exames laboratoriais e radiológicos e sequenciamento do gene ALPL, aliados ao diagnóstico da sua genitora. Discussão: Hipofosfatasia é uma doença rara de herança autossômica dominante e recessiva. Pacientes acometidos apresentam fraturas constantes, densidade mineral óssea baixa, cicatrização óssea deficitária. É comum a hipofosfatasia ser diagnosticada erroneamente como osteopenia e/ou osteoporose primária, acarretando prejuízos ao paciente. Ressalta-se a importância da história clínica completa e dos antecedentes familiares a fim de se obter um diagnóstico precoce, garantindo, por sua vez, o adequado acompanhamento e manejo terapêutico (AU)

Introduction: hypophosphatasia is a metabolic disorder affecting bone and tooth mineralization, caused by mutations in the ALPL gene leading to enzymatic deficiency of tissue non-specific alkaline phosphatase. The adult form is characterized by atypical femur fractures, osteomalacia, osteoporosis, severe osteoarthropathy, chondrocalcinosis, and arthralgia. Objective: to demonstrate diagnostic challenges related to hypophosphatasia through the report of two cases. Patient 1: female, 59 years old, referred for clinical evaluation due to pathological fractures of difficult consolidation and generalized osteoporosis of genetic cause. She reports early tooth loss in the upper arch, fractures in the spine, left shoulder and femur. Currently, he complains of severe chronic pain, with use of multiple medications. Clinical, laboratory, and radiological findings were compatible with the diagnosis of hypophosphatasia. Patient 2:male, 31 years old, son of patient 1, referred for clinical evaluation due to an early pathological fracture in the left femur and unclear osteoporosis. He currently reports pain and significant claudication in the left lower limb, associated with chronic low back pain. Confirmation of the diagnosis of hypophasatasia by laboratory and radiological tests and sequencing of the ALPL gene combined with the diagnosis of his mother. Discussion: hypophosphatasia is a rare disease of autosomal dominant and recessive inheritance. Affected patients have constant fractures, low bone mineral density, and impaired bone healing. It is common for hypophosphatasia to be misdiagnosed as osteopenia and/or primary osteoporosis, which can be harmful to the patient. The importance of a complete clinical history and family history is emphasized in order to obtain an early diagnosis, ensuring adequate follow-up and therapeutic management (AU)

Percutaneous ruminostomy guided by rumenoscopy: study in an experimental model in bovine fetus.

BACKGROUND: Endosurgery is a surgical subspecialty that has been widely used in production animals, because it enables good visualization of abdominal organs and the diagnosis and treatment of several conditions in a minimally invasive manner, while preserving the animal's well-being and causing a lower impact on animal production. Rumenostomy is one of the most common surgical procedures in ruminants. This procedure is used to allow access to the rumen for various purposes, especially nutritional and therapeutic studies, and it can be performed either in a conventional way or in a minimally invasive video-assisted manner. Another possibility of access to ruminants is through the rumenoscopy technique. The objective of this study is to describe a minimally invasive technique for rumenostomy using an endoscope, working on a bovine fetal corpse as an experimental model. RESULTS: The execution of the endoscopy-guided rumenostomy technique was simple and did not present major difficulties. The endoscope, its lighting and air pump, and the decubitus used provided a good anatomical visualization of the rumen, and it was possible to evaluate several regions of the organ. The mean duration of the procedure was 11.15 min. CONCLUSIONS: The endoscopic rumenostomy technique using anatomical pieces of calves was shown to be feasible. It was performed in a simple and efficient way, particularly regarding the premise of preserving the animal's well-being, due to its minimally invasive nature.

Desafios do diagnóstico da hipofosfatasia em adultos / Diagnostic challenges in hypophosphatasia in adult patients

RESUMO:Introdução: Hipofosfatasia é um distúrbio metabólico que afeta a mineralização óssea e dentária, causada por mutações no gene ALPL, levando à deficiência enzimática da fosfatase alcalina tecido não-específica. A forma adulta caracteriza-se por fraturas atípicas do fêmur, osteomalácia, osteoporose, grave osteoartropatia, condrocalcinose e artralgia. Objetivo: Demonstrar desafios diagnósticos relacionados à hipofosfatasia através do relato de dois casos. Paciente 1: feminino, 59 anos, encaminhada para avaliação clínica devido às fraturas patológicas de difícil consolidação e osteoporose generalizada de causa genética. Relata perda dentária precoce da arcada superior, fraturas na coluna, em ombro esquerdo e no fêmur. Atualmente, queixa-se de dor crônica intensa, com uso de múltiplos medicamentos. Achados clínicos, laboratoriais e radiológicos foram compatíveis com o diagnóstico de hipofosfatasia. Paciente 2: masculino, 31 anos, filho da paciente 1, encaminhado para avaliação clínica por fratura patológica precoce em fêmur esquerdo e osteoporose não esclarecida. Atualmente relata dor e claudicação importante em membro inferior esquerdo, associado à lombalgia crônica. Confirmação do diagnóstico de hipofosfatasia por exames laboratoriais e radiológicos e sequenciamento do gene ALPL, aliados ao diagnóstico da sua genitora. Discussão: Hipofosfatasia é uma doença rara de herança autossômica dominante e recessiva. Pacientes acometidos apresentam fraturas constantes, densidade mineral óssea baixa, cicatrização óssea deficitária. É comum a hipofosfatasia ser diagnosticada erroneamente como osteopenia e/ou osteoporose primária, acarretando prejuízos ao paciente. Ressalta-se a importância da história clínica completa e dos antecedentes familiares a fim de se obter um diagnóstico precoce, garantindo, por sua vez, o adequado acompanhamento e manejo terapêutico. (AU)

ABSTRACT: Introduction: hypophosphatasia is a metabolic disorder affecting bone and tooth mineralization, caused by mutations in the ALPL gene leading to enzymatic deficiency of tissue non-specific alkaline phosphatase. The adult form is characterized by atypical femur fractures, osteomalacia, osteoporosis, severe osteoarthropathy, chondrocalcinosis, and arthralgia. Objective: to demonstrate diagnostic challenges related to hypophosphatasia through the report of two cases. Patient 1: female, 59 years old, referred for clinical evaluation due to pathological fractures of difficult consolidation and generalized osteoporosis of genetic cause. She reports early tooth loss in the upper arch, fractures in the spine, left shoulder and femur. Currently, he complains of severe chronic pain, with use of multiple medications. Clinical, laboratory, and radiological findings were compatible with the diagnosis of hypophosphatasia. Patient 2:male, 31 years old, son of patient 1, referred for clinical evaluation due to an early pathological fracture in the left femur and unclear osteoporosis. He currently reports pain and significant claudication in the left lower limb, associated with chronic low back pain. Confirmation of the diagnosis of hypophasatasia by laboratory and radiological tests and sequencing of the ALPL gene combined with the diagnosis of his mother. Discussion: hypophosphatasia is a rare disease of autosomal dominant and recessive inheritance. Affected patients have constant fractures, low bone mineral density, and impaired bone healing. It is common for hypophosphatasia to be misdiagnosed as osteopenia and/or primary osteoporosis, which can be harmful to the patient. The importance of a complete clinical history and family history is emphasized in order to obtain an early diagnosis, ensuring adequate follow-up and therapeutic management. (AU)