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.

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.

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.

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)

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.

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)

Função urinária e sexual de mulheres puerperais que usaram o balão vaginal na preparação para o parto vaginal ­ um estudo transversal / Urinary and sexual function of puerperal women who used the vaginal balloon in preparation for vaginal birth ­ a cross sectional study

INTRODUÇÃO: O balão vaginal pode ser uma opção para preparar os músculos do assoalho pélvico para o parto vaginal. Suas implicações para as funções urinária e sexual precisam ser mais estudadas. OBJETIVO: Avaliar as implicações do balão vaginal na preparação para o parto vaginal nas funções sexual e urinária. METODOLOGIA: Estudo transversal realizado em Belém do Pará, com primíparas de partos vaginais, de 18 a 40 anos. Formouse dois grupos: o GE se constituiu de puérperas que usaram o balão vaginal durante a gravidez provenientes da Clínica Cafisio Mulher e o GC de puérperas que não fizeram uso do balão vaginal durante a gestação, provenientes do Centro de Saúde Escola do Marco. Utilizou-se uma ficha de avaliação sociodemográfica, um questionário com perguntas acerca dos eventos do trabalho de parto, o International Consultation on Incontinence Questionnaire Short Form e o Female Sexual Function Index. Foi utilizado o software Excel para entrada dos dados, confecção das tabelas e análise estatística descritiva das variáveis. RESULTADOS: Em ambos os grupos, a maioria das mulheres apresentou alguma perda urinária, com impactos diferentes na qualidade de vida. Quanto à função sexual, ambos os grupos estão abaixo do ponto de corte, o que indica disfunção sexual. No entanto, não foi possível estabelecer uma associação entre a função urinária e sexual entre os dois grupos devido às diferenças no tamanho da amostra entre os grupos. CONCLUSÃO: As funções urinária e sexual de ambos os grupos estavam alteradas.

INTRODUCTION: Vaginal balloon can be an option to prepare the pelvic floor muscles for vaginal birth. Its implications for urinary and sexual functions need to be further studied. OBJECTIVE: To evaluate the implications of the vaginal balloon in preparation for vaginal birth on sexual and urinary functions. METHODOLOGY: Cross-sectional study was carried out in Belém do Pará, with primiparous women from vaginal births, aged between 18 and 40 years. Two groups were formed: the EG consisted of postpartum women who used the vaginal balloon during pregnancy from the Clínica Cafisio Mulher and the CG of postpartum women who did not use the vaginal balloon during pregnancy, from the Centro de Saúde Escola do Marco. A sociodemographic evaluation form, a questionnaire with questions about labor events, the International Consultation on Incontinence Questionnaire Short Form, and the Female Sexual Function Index were used. Excel software was used for data entry, preparation of tables, and descriptive statistical analysis of the variables. RESULTS: Most women had some urinary loss in both groups, with different impacts on quality of life. As for sexual function, both groups are below the cutoff point, which indicates sexual dysfunction. However, it was impossible to establish an association between urinary and sexual function between the two groups due to differences in sample size. CONCLUSION: The urinary and sexual functions of both groups were altered.

Efeito da fisioterapia nos sintomas de síndrome da bexiga hiperativa decorrente do tratamento do câncer de colo de útero / Effect of physical therapy on symptoms of the hyperactive bladder arising from the treatment of cervical cancer

Introdução: A síndrome da bexiga hiperativa pode afetar as mulheres após o tratamento para câncer de colo do útero, interferindo diretamente a qualidade de vida e funcionalidade. Objetivo: Verificar os efeitos da Fisioterapia nos sintomas da síndrome da bexiga hiperativa em mulheres submetidas ao tratamento de câncer de colo do útero. Métodos: Trata-se de um ensaio clínico não controlado, com mulheres que realizaram o tratamento para câncer de colo do útero. Foi utilizada uma ficha de avaliação para verificar dados ginecológicos/obstétricos, assim como hábitos de vida das pacientes. Os sintomas da síndrome da bexiga hiperativa foram avaliados por meio do Incontinence Questionnaire Overactive Bladder. Para a intervenção fisioterapêutica foi utilizado o protocolo de Treinamento dos Músculos do Assoalho, Eletroestimulação Transcutânea do Nervo Tibial e Terapia Comportamental. Resultados: No pós-tratamento ocorreu decréscimo estatisticamente significativo na mediana dos sintomas da síndrome da bexiga hiperativa e no impacto da qualidade de vida em relação ao pré-tratamento, indicando melhora do quadro. Conclusão: Esta pesquisa concluiu que o protocolo fisioterapêutico utilizado apresentou eficácia na melhora dos sintomas da síndrome da bexiga hiperativa após tratamento para câncer de colo do útero. (AU)

Introduction: A hyperactive bladder syndrome can affect women after treatment for cervical cancer, directly interfering with quality of life and functionality. Objective: To verify the effects of physical therapy on the symptoms of hyperactive bladder syndrome in women undergoing treatment for cervical cancer. Methods: This is an uncontrolled clinical trial, with women who underwent treatment for cervical cancer. An evaluation form was used to check gynecological/obstetric data, as well as the patients' lifestyle. The symptoms of the hyperactive bladder syndrome were obtained through the hyperactive bladder questionnaire. For the physiotherapeutic intervention, the floor muscle training, transcutaneous electrostimulation of the tibial nerve and behavioral therapy protocol was used. Results: In the post-treatment there was a statistically significant decrease in the median of the symptoms of the hyperactive bladder syndrome and no impact on the quality of life in relation to the pre-treatment, an improvement indicated in the condition. Conclusion: This research concluded that the physical therapy protocol used showed improvement of symptoms of overactive bladder syndrome after treatment for cervical cancer. (AU)

Intra-abdominal resection of the umbilical vein and urachus of bovine fetuses using laparoscopy and celiotomy: surgical time and feasibility (cadaveric study).

Surgical intervention for umbilical diseases in calves, when indicated, is a complementary and indispensable therapeutic resource for the treatment of umbilical conditions and is commonly performed using celiotomy. However, laparoscopy has demonstrated feasibility in many diagnostic and therapeutic procedures. The aim of this study was to assess the feasibility of the techniques and the surgical time of laparoscopy and celiotomy used in intra-abdominal resection of the umbilical vein and urachus of bovine fetuses (cadavers). Resection of the umbilical vein and urachus using laparoscopy and celiotomy was performed in 26 anatomical specimens (bovine fetuses obtained from an official slaughterhouse). Resection of umbilical structures was feasible with both techniques, but shorter surgical time and minimal tissue damage were achieved using laparoscopy. Laparoscopy requires specialized training and appropriate instruments and is an important tool for diagnostic and therapeutic exploration of the umbilical structures, liver, bladder, and associated/adjacent structures.

Retinoids delay cell cycle progression and promote differentiation of intestinal epithelial cells exposed to nutrient deprivation.

OBJECTIVE: Vitamin A is commonly recommended as a treatment for diarrhea and undernutrition; however, little is known about the underlying cellular mechanisms. The aim of this study was to investigate the modulation of cell cycle by vitamin A derivatives (retinyl palmitate or retinol) in undernourished intestinal epithelial crypts (IEC-6). METHODS: IEC-6 cells were exposed to nutrient deprivation (no serum and no glutamine) and supplemented with retinyl palmitate or retinol at a range of 2 to 20 µM. Proliferation, apoptosis/necrosis, cell cycle process, and gene transcription were assessed. RESULTS: Nutrient deprivation for 6, 12, 24, or 48 h decreased cell proliferation, and retinyl palmitate further decreased it after 24 and 48 h. Apoptosis rates were reduced by undernourishment and further reduced by retinyl palmitate after 48 h; whereas necrosis rates were unaltered. Undernourishment induced overall cell quiescence, increased percentage of cells in G0/G1 phase and decreased percentage of cells in S phase after 12 h and in G2/M phases at 6, 12, and 24 h after treatment. Both retinoids also showed cell quiescence induction with less cells in G2/M phases after 48 h, whereas only retinol showed significant modulation of G0/G1 and S phases. Both retinoids also increased markers of cell differentiation Fabp and Iap gene transcriptions in about fivefold rates after 42 h. Furthermore, specific gene transcriptions related to MAP kinase signaling pathway regulation of cell differentiation and cell cycle regulation were triggered by retinoids in undernourished IEC-6, with higher levels of expression for Atf2 and C-jun genes. CONCLUSIONS: These findings indicated that both vitamin A derivatives induce further survival mechanisms in undernourished intestinal epithelial crypt cells. These mechanisms include increased cell quiescence, decreased apoptosis, increased cell differentiation, and transcription of genes related to MAP kinase signaling pathway.

Multifaceted WNT Signaling at the Crossroads Between Epithelial-Mesenchymal Transition and Autophagy in Glioblastoma.

Tumor cells can employ epithelial-mesenchymal transition (EMT) or autophagy in reaction to microenvironmental stress. Importantly, EMT and autophagy negatively regulate each other, are able to interconvert, and both have been shown to contribute to drug-resistance in glioblastoma (GBM). EMT has been considered one of the mechanisms that confer invasive properties to GBM cells. Autophagy, on the other hand, may show dual roles as either a GBM-promoter or GBM-suppressor, depending on microenvironmental cues. The Wingless (WNT) signaling pathway regulates a plethora of developmental and biological processes such as cellular proliferation, adhesion and motility. As such, GBM demonstrates deregulation of WNT signaling in favor of tumor initiation, proliferation and invasion. In EMT, WNT signaling promotes induction and stabilization of different EMT activators. WNT activity also represses autophagy, while nutrient deprivation induces ß-catenin degradation via autophagic machinery. Due to the importance of the WNT pathway to GBM, and the role of WNT signaling in EMT and autophagy, in this review we highlight the effects of the WNT signaling in the regulation of both processes in GBM, and discuss how the crosstalk between EMT and autophagy may ultimately affect tumor biology.

A força da ausência. A falta dos homens e do "Estado" na vida de mulheres moradoras de favela / La fuerza de la ausencia. La falta de los hombres y del "Estado" en la vida de mujeres que viven en favelas / The strength of absence. The lack of men and "State" in the lives of women living in favelas

Resumo Com base no trabalho de campo realizado em um complexo de favelas do Rio de Janeiro, analiso as condições de precariedade produzidas por ausências ativas masculinas, quer seja exercida pelas administrações de Estado ou por ausências masculinas na vida de mães e mulheres pobres. A partir das discussões antropológicas sobre gênero e Estado, o campo destas ausências é analisado enquanto um conjunto de forças sistemáticas e cotidianas. Essas forças se revelam de diferentes formas: seja por não receber "ajuda nenhuma do pai da criança", por não conseguir "uma vaga na creche", por "ter que se virar" para cuidar dos filhos sozinha e por ter que lidar com a política de invasões, tiroteios e extermínio exercida nos territórios de favelas. A ausência ativa de Estado também se materializa na ação das casas destinadas a "tomar conta" de crianças e das creches públicas, espaços voltados ao atendimento das famílias pobres. Na tentativa de refletir sobre este campo múltiplo de "faltas", procuro relacionar de que modo estas ausências estão associadas a dinâmicas de "violência" que incidem sobre comportamentos femininos apontados como "nervosos", "agressivos" ou "negligentes".

Resumen A partir del trabajo de campo realizado en un complejo de favelas de Río de Janeiro, analizo las precarias condiciones que producen las ausencias activas masculinas, ya sean ejercidas por las administraciones estatales o por ausencias masculinas en la vida de madres y mujeres pobres. A partir de las discusiones antropológicas sobre género y Estado, se analiza el campo de estas ausencias como un conjunto de fuerzas sistemáticas y cotidianas. Estas fuerzas se manifiestan de diferentes formas: ya sea por no recibir "ninguna ayuda del padre del niño", por no poder "conseguir una plaza en la guardería", se por la política de invasiones, fusilamientos y exterminio ejercida en los territorios de favelas. La ausencia activa del Estado también se materializa en la acción de las casas para "cuidar" a los niños y en las guarderías públicas, espacios destinados a atender a las familias pobres. En un intento de reflexionar sobre este campo múltiple de "ausencias", trato de relatar cómo estas ausencias se asocian con dinámicas de "violencia", que afectan los comportamientos femeninos identificados como "nerviosos", "agresivos" o "negligentes".

Abstract Based on the fieldwork carried out in a complex of favelas in Rio de Janeiro, I analyze the precarious conditions produced by active male absences, whether exercised by state administrations or by male absences in the lives of poor mothers and women. Based on the anthropological discussions about gender and State, these absences are analyzed as a set of systematic and daily forces. These forces are revealed in different ways: be it for not receiving "any help from the child's father", for not obtaining "a place in the daycare center", for "hav ing to manage" to take care of the children alone and for having to deal with a State policy of invasions, shootings and extermination exercised in the favelas territories. The active absence of the State also materializes in the action of the houses that "take in" children and in public daycare centers, spaces aimed at serving poor families. To reflect on this multiple fields of "absences", they are associated with dynamics of "violence", which affect female behaviors identified as "nervous", "aggressive" or "negligent".

Prion Protein at the Leading Edge: Its Role in Cell Motility.

Cell motility is a central process involved in fundamental biological phenomena during embryonic development, wound healing, immune surveillance, and cancer spreading. Cell movement is complex and dynamic and requires the coordinated activity of cytoskeletal, membrane, adhesion and extracellular proteins. Cellular prion protein (PrPC) has been implicated in distinct aspects of cell motility, including axonal growth, transendothelial migration, epithelial-mesenchymal transition, formation of lamellipodia, and tumor migration and invasion. The preferential location of PrPC on cell membrane favors its function as a pivotal molecule in cell motile phenotype, being able to serve as a scaffold protein for extracellular matrix proteins, cell surface receptors, and cytoskeletal multiprotein complexes to modulate their activities in cellular movement. Evidence points to PrPC mediating interactions of multiple key elements of cell motility at the intra- and extracellular levels, such as integrins and matrix proteins, also regulating cell adhesion molecule stability and cell adhesion cytoskeleton dynamics. Understanding the molecular mechanisms that govern cell motility is critical for tissue homeostasis, since uncontrolled cell movement results in pathological conditions such as developmental diseases and tumor dissemination. In this review, we discuss the relevant contribution of PrPC in several aspects of cell motility, unveiling new insights into both PrPC function and mechanism in a multifaceted manner either in physiological or pathological contexts.