Natural mycobacterium tuberculosis complex infection in a brown howler monkey (Alouatta guariba clamitans) in Brazil.

Neotropical primates rarely exhibit active tuberculosis. A brown howler monkey was found injured in an urban area. Histopathology revealed granulomatous inflammation in the lungs, lymph nodes, and liver. Immunohistochemistry and molecular analysis confirmed the presence of Mycobacterium tuberculosis complex. The findings highlight the importance of TB surveillance in nonhuman primates.

MYCOLICIBACTERIUM FORTUITUM INFECTION IN EX SITU EMERALD TREE BOA (Corallus batesii).

Emerald tree boas (Corallus batesii) are boids that in situ occurs in forested habitats in the Amazon Basin. The mycobacterial species can infect reptiles but the species Mycolicibacterium fortuitum was identified only in feces samples of ex situ Python regius and was isolated from granulomatous lesions of an ex situ Iguana iguana when was still part of the genus Mycobacterium. This article aims to report a mycobacteria infection case in a female Corallus batesii kept under human care. The animal presented apathy and 2 months of anorexia, being found dead. The necropsy revealed presence of tracheal and pulmonary nodules besides multifocal, bacterial, granulomatous pneumonia. After Fite-Faraco histochemical staining, immunohistochemistry, semi-nested polymerase chain reaction (PCR) and genetic sequencing the Mycolicibacterium fortuitum complex was diagnosed with 99.54% of nucleotide similarity. This mycobacterial species was already pointed out as an important nosocomial pathogen and more studies are necessary to explore their zoonotic potential.

The Complexity of Tobacco Smoke-Induced Mutagenesis in Head and Neck Cancer.

Tobacco smoke, alone or combined with alcohol, is the predominant cause of head and neck cancer (HNC). Here, we further explore how tobacco exposure contributes to cancer development by mutational signature analysis of 265 whole-genome sequenced HNC from eight countries. Six tobacco-associated mutational signatures were detected, including some not previously reported. Differences in HNC incidence between countries corresponded with differences in mutation burdens of tobacco-associated signatures, consistent with the dominant role of tobacco in HNC causation. Differences were found in the burden of tobacco-associated signatures between anatomical subsites, suggesting that tissue-specific factors modulate mutagenesis. We identified an association between tobacco smoking and three additional alcohol-related signatures indicating synergism between the two exposures. Tobacco smoking was associated with differences in the mutational spectra and repertoire of driver mutations in cancer genes, and in patterns of copy number change. Together, the results demonstrate the multiple pathways by which tobacco smoke can influence the evolution of cancer cell clones.

The Mutographs biorepository: A unique genomic resource to study cancer around the world.

Large-scale biorepositories and databases are essential to generate equitable, effective, and sustainable advances in cancer prevention, early detection, cancer therapy, cancer care, and surveillance. The Mutographs project has created a large genomic dataset and biorepository of over 7,800 cancer cases from 30 countries across five continents with extensive demographic, lifestyle, environmental, and clinical information. Whole-genome sequencing is being finalized for over 4,000 cases, with the primary goal of understanding the causes of cancer at eight anatomic sites. Genomic, exposure, and clinical data will be publicly available through the International Cancer Genome Consortium Accelerating Research in Genomic Oncology platform. The Mutographs sample and metadata biorepository constitutes a legacy resource for new projects and collaborations aiming to increase our current research efforts in cancer genomic epidemiology globally.

Unveiling the role of MGMT and DAPK hypermethylation in response to anti-EGFR agents: Molecular insights for advancing HNSCC treatment.

BACKGROUND: Epidermal growth factor receptor (EGFR) is frequently activated in head and neck squamous cell carcinoma (HNSCC) and serves as a valuable target for therapy. Despite the availability of the EGFR inhibitors Cetuximab, Afatinib, and Allitinib, there are limited predictive markers for their response. Understanding molecular aberrations in HNSCC could facilitate the identification of new strategies for patient clinical and biological classification, offering novel therapeutic avenues. METHODS: We assessed CCNA1, DCC, MGMT, CDKN2A/p16, and DAPK methylation status in HNSCC cell lines and their association with anti-EGFR treatment response. RESULTS: MGMT methylation status displayed high sensitivity and specificity in distinguishing sensitive and resistant HNSCC cell lines to Afatinib (AUC = 0.955) and Allitinib (AUC = 0.935). Moreover, DAPK methylation status predicted response to Allitinib with high accuracy (AUC = 0.852), indicating their putative predictive biomarker roles. CONCLUSION: These findings hold promise for the development of more personalized and effective treatment approaches for HNSCC patients.

Barriers to physical activity practice and associated factors in patients with hypertension / Barreiras para a prática de atividade física e fatores associados em pacientes com hipertensão arterial

Abstract The identification of barriers to regular physical activity (PA) is a form of an initial and effective strategy to encourage behavior modification and adherence to a more active lifestyle in hypertensive patients. This cross-sectional study aimed to identify the barriers to PA practice in patients with hypertension classified as physically inactive and to analyze the association of the number of these barriers with sociodemographic factors and health indicators. Two hundred one hypertensive patients of both sexes (61.7±12.7 years) answered an anamnesis with health information and sociodemographic data, a PA level questionnaire, and a barrier questionnaire for the practice of PA. Regarding the level of PA of the participants, 48.8% were classified as physically inactive and reported, on average, 6.1 (±3.8) barriers to PA practice, with the barrier "fear of falling or getting hurt" the most commonly reported. Furthermore, women and patients with low education, negative perception of health, and a greater presence of comorbidities reported a greater number of barriers to PA practice. PA practice as a non-pharmacological tool for the treatment of hypertension should focus on women and patients with low education, negative perception of health, and a greater presence of associated comorbidities.

Resumo A identificação de barreiras à atividade física regular (AF) é uma forma de estratégia inicial e eficaz para encorajar a modificação do comportamento e a adesão a um estilo de vida mais ativo em pacientes hipertensivos. Este estudo transversal visou identificar as barreiras à prática de AF em pacientes com hipertensão classificados como fisicamente inativos e analisar a associação do número destas barreiras com fatores sociodemográficos e indicadores de saúde. Duzentos e um pacientes hipertensos de ambos os sexos (61.7±12.7 anos) responderam a uma anamnese com informações de saúde e dados sociodemográficos, um questionário de nível de AF, e um questionário de barreira para a prática de AF. Relativamente ao nível de AF dos participantes, 48,8% foram classificados como fisicamente inativos e reportaram, em média, 6,1 (±3,8) barreiras à prática de AF, sendo a barreira "medo de cair ou de se magoar" a mais frequentemente reportada. Além disso, mulheres e pacientes com baixa educação, percepção negativa da saúde, e uma maior presença de comorbidades reportaram um maior número de barreiras à prática de AF. A prática de AF como ferramenta não farmacológica para o tratamento da hipertensão deve ter como foco mulheres e pacientes com baixa escolaridade, percepção negativa de saúde e maior presença de comorbidades associadas.

Overall Survival, BRAF, RAS, and MSI Status in Patients Who Underwent Cetuximab After Refractory Chemotherapy for Metastatic Colorectal Cancer.

PURPOSE: Evaluate overall survival (OS), RAS, BRAF, and MSI frequencies in patients with metastatic colorectal cancer (mCRC), refractory to chemotherapy, and finally treated with cetuximab. METHODS: A retrospective cohort study to evaluate 211 mCRC patients with wild-type KRAS treated with cetuximab. BRAF V600E, KRAS, NRAS gene mutations, and MSI status were identified using PCR techniques in a population of pre-treated patients who were refractory to fluoropyrimidines, oxaliplatin, and irinotecan. In addition, we evaluated the mutation frequency of the BRAF and NRAS genes and the MSI status of this population. Uni- and multivariate analyses were performed for independent prognostic factors of OS. RESULTS: The median OS was 10.4 months, 6.6 months for patients with right and 11.5 months for left colon cancers (p = 0.02). The frequencies of mutations were BRAF at 3.9% (median OS of 4.9 months), NRAS at 3.38% (median OS of 6.9 months), and MSI-High status at 3.3% (median OS of 4.6 months). The OS, NRAS, and MSI frequencies were similar to those found in other studies that evaluated cetuximab in poly-treated patients and were associated with lower survival rates in univariate analyses. The frequency of BRAF mutations was lower than that found in previous studies. The only variable that remained significant for OS in the multivariate model was tumour laterality, with patients with right colon cancer presenting a worse prognosis (HR = 2.81). CONCLUSION: Although BRAF, NRAS mutations, and MSI-High status were associated with shorter OS in univariate analyses, only tumour laterality remained an independent prognostic factor in the multivariate analysis.

miR-99a-5p as a biomarker for lymph node metastasis prediction in oral squamous cell carcinoma patients.

BACKGROUND: Metastatic lymph node involvement influences therapy decisions and serves as a prognostic indicator in oral squamous cell carcinoma (OSCC). However, many early-stage patients with clinically negative lymph nodes exhibit no metastasis upon surgical staging. This study aimed to identify differentially expressed miRNAs capable of distinguishing pathologically positive (pN+) from negative (pN0) nodes in OSCC patients without clinical evidence of lymph node metastases (cN0). METHODS: Expression levels of 798 miRNAs were assessed in tumor samples from 10 pN+ and 10 pN0 patients using the Nanostring nCounter platform. Validation was performed in an independent cohort of 15 pN+ and 24 pN0 patients through RT-qPCR. RESULTS: Eight miRNAs exhibited differential expression between pN0 and pN+ patients. Notably, hsa-miR-99a-5p demonstrated high sensitivity and specificity in predicting patients at higher risk of positive lymph nodes. CONCLUSIONS: These findings highlight hsa-miR-99a-5p as a potential biomarker for detecting lymph node metastasis in primary OSCC tumors.

Proteolytic inactivation of CXCL12 in the lungs and circulation of COVID-19 patients.

The human chemokine stromal cell-derived factor-1 (SDF-1) or CXCL12 is involved in several homeostatic processes and pathologies through interaction with its cognate G protein-coupled receptor CXCR4. Recent research has shown that CXCL12 is present in the lungs and circulation of patients with coronavirus disease 2019 (COVID-19). However, the question whether the detected CXCL12 is bioactive was not addressed. Indeed, the activity of CXCL12 is regulated by NH2- and COOH-terminal post-translational proteolysis, which significantly impairs its biological activity. The aim of the present study was to characterize proteolytic processing of CXCL12 in broncho-alveolar lavage (BAL) fluid and blood plasma samples from critically ill COVID-19 patients. Therefore, we optimized immunosorbent tandem mass spectrometry proteoform analysis (ISTAMPA) for detection of CXCL12 proteoforms. In patient samples, this approach uncovered that CXCL12 is rapidly processed by site-specific NH2- and COOH-terminal proteolysis and ultimately degraded. This proteolytic inactivation occurred more rapidly in COVID-19 plasma than in COVID-19 BAL fluids, whereas BAL fluid samples from stable lung transplantation patients and the non-affected lung of lung cancer patients (control groups) hardly induced any processing of CXCL12. In COVID-19 BAL fluids with high proteolytic activity, processing occurred exclusively NH2-terminally and was predominantly mediated by neutrophil elastase. In low proteolytic activity BAL fluid and plasma samples, NH2- and COOH-terminal proteolysis by CD26 and carboxypeptidases were observed. Finally, protease inhibitors already approved for clinical use such as sitagliptin and sivelestat prevented CXCL12 processing and may therefore be of pharmacological interest to prolong CXCL12 half-life and biological activity in vivo.

Canine distemper virus and canine adenovirus type 1 co-infection in a free-living hoary fox (Lycalopex vetulus) from Brazil.

The present case is the first description of a co-infection with canine distemper virus (CDV) and canine adenovirus type 1 (CAdV-1) in a free-living hoary fox pup from Brazil. The animal was found and rescued with poor body condition, dehydration, incoordination, ataxia, excessive vocalization, and "blue eyes" phenomenon. Despite the efforts, euthanasia was elected due to worsening clinical signs and poor prognosis. Pathologic examination revealed a mild, acute, random, necrotizing hepatitis, acute bronchopneumonia, hydrocephalus, corneal edema with epithelium degeneration, and acidophilic intracytoplasmatic inclusion bodies in different epithelial cells types with rare syncytial. Through immunohistochemistry, CDV antigen was observed in the tongue, trachea, lungs, liver, spleen, stomach, intestine and urinary bladder. Adenovirus antigen was identified in the nucleus of scattered hepatocytes. Polymerase chain reaction and sequencing demonstrated high similarity with CAdV-1 and wild-type strain of CDV close related to Brazilian viral lineages isolated from domestic dogs. Disease surveillance in wildlife animals is essential to assess possible conservation threats and consider the implementation of mitigation or control measures.

Quality improvement in the implementation science paradigm in professional programs: scoping review / Mejora de la calidad en el paradigma de la ciencia de la implementación en programas profesionales: revisión del alcance / Melhoria de qualidade no paradigma da ciência da implementação em programas profissionais: revisão de escopo

ABSTRACT Objective: To map knowledge regarding Quality Improvement in the implementation science paradigm in graduate nursing education in professional programs. Method: This is a scoping review, conducted from October to December 2021, following the assumptions established by the Joanna Briggs Institute and the PRISMA-ScR protocol. Results: 18 studies were selected. Being, 7 articles (38.8%) about the implementation strategies and development of Quality Improvement projects for graduate nursing students. The included studies emphasize Quality Improvement as a methodological strategy capable of capturing a problem in practice, to be solved without losing scientific rigor, and emphasize the importance of obtaining Quality Improvement skills in professional programs. Conclusion: Implementation science and Quality Improvement projects advance professional programs to improve and develop quality health care.

RESUMEN Objetivo: Mapear el conocimiento sobre Mejora de la Calidad en el paradigma de la ciencia de la implementación, en la formación de posgrado en enfermería en programas profesionales. Método: Se trata de una revisión de alcance, realizada de octubre a diciembre de 2021, siguiendo los supuestos establecidos por el Instituto Joanna Briggs y el protocolo PRISMA-ScR. Resultados: Se seleccionaron 18 estudios. Siendo, 7 artículos (38,8%) sobre las estrategias de implementación y desarrollo de proyectos de Mejora de la Calidad para estudiantes de posgrado en enfermería. Los estudios incluidos enfatizan la Mejora de la Calidad como una estrategia metodológica capaz de capturar un problema en la práctica, para ser resuelto sin perder el rigor científico, y resaltan la importancia de obtener habilidades de Mejora de la Calidad en los programas profesionales. Conclusión: La ciencia de la implementación y los proyectos de mejora de la calidad avanzan en los programas profesionales para mejorar y desarrollar una atención médica de calidad.

RESUMO Objetivo: Mapear o conhecimento referente a Melhoria de Qualidade no paradigma da ciência da implementação na educação de pós-graduação em enfermagem de programas profissionais. Método: Trata-se de revisão de escopo, realizada de outubro a dezembro de 2021, seguindo os pressupostos estabelecidos pelo Joanna Briggs Institute e pelo protocolo PRISMA-ScR. Resultados: Foram selecionados 18 estudos. Sendo, 7 artigos (38,8 %) sobre as estratégias de implementação e de desenvolvimento de projetos de Melhoria de Qualidade para estudantes de pós-graduação em enfermagem.Os estudos incluídos fazem ênfase à Melhoria de Qualidade como estratégia metodológica capaz de captar uma problemática da prática, a ser resolvida sem perder o rigor científico e destaca a importância de obter habilidades de Melhoria de Qualidade nos programas profissionais. Conclusão: A ciência da implementação e os projetos de Melhoria da Qualidade avançam nos programas profissionais, para aprimorar e desenvolver os cuidados de saúde com qualidade.

Seroprevalence of SARS-CoV-2 antibodies in schoolchildren in the city of São Paulo, 2020 / Soroprevalência de anticorpos do vírus SARS-CoV-2 em escolares no município de São Paulo, 2020

ABSTRACT OBJECTIVE To estimate seroprevalence of SARS-CoV-2 antibodies in schoolchildren aged 4 to 14 years living in the city of São Paulo, according to clinical, demographic, epidemiological, and social variables, during the school closure period as a measure against covid-19 spread. METHODS A serological survey was made in September 2020 with a random sample stratified by school system (municipal public, state public and private) type. A venous blood sample was collected using the Wondfo SARS-CoV-2 Antibody Test (lateral flow method) for detection of total SARS-CoV-2 virus antibodies. Semi-structured questionnaires were applied to collect clinical, demographic, social, and epidemiological data. RESULTS Seroprevalence of SARS-CoV-2 antibodies in schoolchildren was of 16.6% (95%CI 15.4-17.8). The study found higher seroprevalence in the municipal (18.5%; 95%CI 16.6-20.6) and state (16.2%; 95%CI 14.4-18.2) public school systems compared to the private school system (11.7; 95%CI 10.0-13.7), among black and brown students (18.4%; 95%CI 16.8-20.2) and in the most vulnerable social stratum (18.5 %;95%CI 16.9-20.2). Lower seroprevalence was identified in schoolchildren who reported following the recommended protective measures against covid-19. CONCLUSION Seroprevalence of SARS-CoV-2 antibodies is found mainly in the most socially vulnerable schoolchildren. This study can contribute to support public policies that reinforce the importance of suspending face-to-face classes and developing strategies aimed at protective measures and monitoring of the serological status of those who have not yet been included in the vaccination schedule.

RESUMO OBJETIVO Estimar a soroprevalência de anticorpos do vírus SARS-CoV-2 em escolares de quatro a 14 anos de idade residentes no município de São Paulo, segundo variáveis clínicas, demográficas, epidemiológicas e sociais, durante o período de fechamento das escolas como medida de controle da covid-19. MÉTODOS Realizou-se um inquérito sorológico em setembro de 2020 com amostra aleatória estratificada por tipo de rede de ensino (pública municipal, pública estadual e privada). Foi coletada amostra de sangue venoso utilizando-se o teste de imunoensaio de fluxo lateral da fabricante Wondfo para detecção de anticorpos totais contra o vírus SARS-CoV-2. Aplicaram-se questionários semiestruturados para o levantamento de dados clínicos, demográficos, sociais e epidemiológicos. RESULTADOS A soroprevalência de anticorpos do vírus SARS-CoV-2 em escolares foi de 16,6% (IC95% 15,4-17,8). O estudo encontrou soroprevalências mais elevadas na rede pública municipal (18,5%; IC95% 16,6-20,6) e estadual (16,2%; IC95% 14,4-18,2) em relação à rede privada (11,7; IC95% 10,0-13,7) e entre escolares da raça/cor preta e parda (18,4%; IC95% 16,8-20,2) e no estrato social mais vulnerável (18,5%; IC95% 16,9-20,2). A pesquisa identificou menores soroprevalências nos escolares que relataram seguir as medidas recomendadas de proteção contra a covid-19. CONCLUSÃO A soroprevalência de anticorpos contra o vírus SARS-CoV-2 atinge principalmente os escolares socialmente mais vulneráveis. Este estudo pode contribuir para embasar políticas públicas que reforcem a importância da suspensão das aulas presenciais e da necessidade de estratégias de medidas de proteção e acompanhamento do status sorológico daqueles que ainda não foram contemplados no calendário vacinal.

Diagnosis and successful treatment of Brazillian porcupine poxvirus infection in a free-ranging hairy dwarf porcupine (Coendu spinosus).

Brazilian porcupine poxvirus (BPoPV) is a new poxvirus recently described in porcupines (Coendou prehensilis) from Brazil. Herein, we described a free-ranging adult male Coendou (Sphiggurus) spinosus rescued after being found lethargic on the ground in a rural area. The animal presented crusty, edematous, and suppurative skin lesions on the face, tail, and perineum, and yellowish ocular secretion. The diagnosis was performed by histopathology, transmission electron microscopy (TEM), PCR, and sequencing. Microscopically, proliferative and necrotizing dermatitis, subacute, multifocal with ballooning degeneration, and eosinophilic intracytoplasmic viral inclusion bodies were observed. TEM confirmed large brick-shaped virions inside the keratinocyte cytoplasm, measuring about 200-280 × 120-180 nm. Partial fragment of intracellular mature virion membrane protein gene and putative metalloproteinase gene was successfully amplified and sequenced, and the strain herein denoted IAL/21 V-102 was classified as BPoPV, showing 99.4% of nucleotide identity to the reference strain UFU/USP001. Enrofloxacin 10% (10 mg/kg) was administered every 24 h through intramuscular injection for 10 days, dipyrone/metamizole (25 mg/kg) every 24 h orally (PO) for 3 days, 0.5 ml (mL) of thymomodulin every 24 h PO for 30 days, and each 48 h for another 15 days. The lesions were cleaned and debrided every 15 days. Seventy-five days after the beginning of the treatment, the cutaneous lesions regressed, the animal gained weight, and was clinically stable. After treatment, the skin biopsy showed only mild epidermal acanthosis, intra-cellular edema, and mild lymphoplasmacytic perivascular dermatitis. No viral particles were observed by TEM and no poxviral DNA was amplified by PCR. This study documents the first case of confirmed and treated BPoPV infection in a hairy dwarf porcupine. The implemented therapeutic plan eliminated the infection and improved the general state of the animal.

Somatic targeted mutation profiling of colorectal cancer precursor lesions.

BACKGROUND: Most colorectal cancers (CRC) arise from precursor lesions. This study aimed to characterize the mutation profile of colorectal cancer precursor lesions in a Brazilian population. METHODS: In total, 90 formalin-fixed paraffin-embedded colorectal precursor lesions, including 67 adenomas, 7 sessile serrated lesions, and 16 hyperplastic polyps, were analyzed by next-generation sequencing using a panel of 50 oncogenes and tumor suppressor genes. The genetic ancestry of the patients was estimated. RESULTS: Somatic driver mutations were identified in 66.7% of cases, including alterations in APC (32.2%), TP53 (20.0%), KRAS (18.9%), BRAF (13.3%) and EGFR (7.8%). Adenomas displayed a higher number of mutations, mainly in APC, compared to serrated polyps (73.1% vs. 47.8%, p = 0.026). Advanced adenomas had a significantly higher frequency of mutation in KRAS and a high overall mutation rate than early adenomas (92.9% vs. 59%, p = 0.006). A high degree of ancestry admixture was observed in the population studied, with a predominance of European components (mean of 73%) followed by African (mean of 11.3%). No association between genetic ancestry and type of lesions was found. The mutation profile of Brazilian colorectal precursor lesions exhibits alteration in APC, KRAS, TP53, and BRAF at different frequencies according to lesion type. CONCLUSIONS: These results bestow the knowledge of CRC's biologic history and support the potential of these biomarkers for precursor lesions detection in CRC screening of the Brazilian population.

Evaluation of olfactory function in patients undergoing endoscopic skull base surgery with nasoseptal flap / Avaliação da função olfatória nos pacientes submetidos à cirurgia endoscópica da base do crânio com realização de retalho nasosseptal

Abstract Introduction Endoscopic transnasal access to the skull base, both for treatment and reconstruction, can cause olfactory morbidity. Knowing the main consequences of this intervention is essential to have objective criteria for decision-making regarding the appropriate surgical technique. Objectives The aim of this study is to determine the impact on olfactory function of the endonasal endoscopic access to the skull base with the creation of the nasoseptal flap. Methods A prospective research was carried out in which 22 patients who underwent endoscopic transnasal surgery at the skull base, with the creation of a nasoseptal flap. The Connecticut Chemosensory Clinical Research Center test was applied before and at the 1st, 3rd and 6th postoperative months. Results The results showed that only in the first month of follow-up the mean patient classification was statistically worse than at the other evaluation moments (p < 0.05), but there was no mean difference in the Connecticut score classification between the other moments (p > 0.05); that is, patients showed worsening in the 1st month and returned to the preoperative mean after the 3rd month of follow-up. Conclusion The present study showed that the postoperative decrease in olfaction is transient, since the patient's sense of smell returns to pre-surgical values in the 3rd postoperative month.

Resumo Introdução O acesso transnasal endoscópico à base do crânio, tanto no tratamento quanto na reconstrução, pode ocasionar morbidade olfatória. Conhecer as principais consequências dessa intervenção é fundamental para se dispor de elementos objetivos para a decisão da técnica cirúrgica adequada. Objetivo Determinar o impacto na função olfatória do acesso endoscópico endonasal à base do crânio com confecção do retalho nasosseptal. Método Foi feita pesquisa prospectiva na qual foram incluídos 22 pacientes submetidos à cirurgia endoscópica transnasal à base do crânio com confecção de retalho nasosseptal. Foi aplicado o teste Connecticut chemosensory clinical research center antes e após o 1°, 3° e 6° meses da cirurgia. Resultados Os resultados evidenciaram que apenas no 1° mês de seguimento a classificação média dos pacientes foi estatisticamente pior do que nos demais momentos de avaliação (p < 0,05), mas entre os demais momentos não houve diferença média na classificação do escore de Connecticut (p >0,05), ou seja, os pacientes pioraram no 1° mês e voltaram à média pré-operatória a partir do 3° mês de seguimento. Conclusão No presente estudo, demonstramos que a diminuição do olfato pós-operatória é transitória, já que, no 3° mês depois da cirurgia, o olfato do paciente retorna aos valores pré-cirúrgicos.

Accuracy and Clinical Relevance of Intra-Tumoral Fusobacterium nucleatum Detection in Formalin-Fixed Paraffin-Embedded (FFPE) Tissue by Droplet Digital PCR (ddPCR) in Colorectal Cancer.

The use of droplet digital PCR (ddPCR) to identify and quantify low-abundance targets is a significant advantage for accurately detecting potentially oncogenic bacteria. Fusobacterium nucleatum (Fn) is implicated in colorectal cancer (CRC) tumorigenesis and is becoming an important prognostic biomarker. We evaluated the detection accuracy and clinical relevance of Fn DNA by ddPCR in a molecularly characterized, formalin-fixed, paraffin-embedded (FFPE) CRC cohort previously analyzed by qPCR for Fn levels. Following a ddPCR assay optimization and an analytical evaluation, Fn DNA were measured in 139 CRC FFPE cases. The measures of accuracy for Fn status compared to the prior results generated by qPCR and the association with clinicopathological and molecular patients' features were also evaluated. The ddPCR-based Fn assay was sensitive and specific to positive controls. Fn DNA were detected in 20.1% of cases and further classified as Fn-high and Fn-low/negative, according to the median amount of Fn DNA that were detected in all cases and associated with the patient's worst prognosis. There was a low agreement between the Fn status determined by ddPCR and qPCR (Cohen's Kappa = 0.210). Our findings show that ddPCR can detect and quantify Fn in FFPE tumor tissues and highlights its clinical relevance in Fn detection in a routine CRC setting.

Evaluation of olfactory function in patients undergoing endoscopic skull base surgery with nasoseptal flap.

INTRODUCTION: Endoscopic transnasal access to the skull base, both for treatment and reconstruction, can cause olfactory morbidity. Knowing the main consequences of this intervention is essential to have objective criteria for decision-making regarding the appropriate surgical technique. OBJECTIVES: The aim of this study is to determine the impact on olfactory function of the endonasal endoscopic access to the skull base with the creation of the nasoseptal flap. METHODS: A prospective research was carried out in which 22 patients who underwent endoscopic transnasal surgery at the skull base, with the creation of a nasoseptal flap. The Connecticut Chemosensory Clinical Research Center test was applied before and at the 1st, 3rd and 6th postoperative months. RESULTS: The results showed that only in the first month of follow-up the mean patient classification was statistically worse than at the other evaluation moments (p<0.05), but there was no mean difference in the Connecticut score classification between the other moments (p>0.05); that is, patients showed worsening in the 1st month and returned to the preoperative mean after the 3rd month of follow-up. CONCLUSION: The present study showed that the postoperative decrease in olfaction is transient, since the patient's sense of smell returns to pre-surgical values in the 3rd postoperative month.

Contenção ambiental de idosos nas instituições de longa permanência em tempos de Covid-19: reflexão teórica / Contención ambiental de ancianos en las instituciones de larga permanencia en tiempos de Covid-19: reflexión teórica / Environmental restraint of the elderly in long-term care facilities in times of Covid-19: theoretical reflection

Estudo teórico de cunho reflexivo que aborda o fenômeno da contenção ambiental em instituições de longa permanência para idosos, apresentando o tema à luz dos direitos humanos e da legislação em vigor, que pregam boas práticas de cuidado aos idosos institucionalizados, inclusive frente ao cenário de enfrentamento à Covid-19. Considerando os impactos negativos da contenção ambiental na saúde física e mental dos idosos, sugere-se maior capacitação da equipe técnica das instituições de longa permanência para idosos e prospecção do fenômeno para garantia de condições mais dignas e que respeitem a liberdade dos idosos. (AU)

Estudio teórico de cuño reflexivo que aborda el fenómeno de la contención ambiental en instituciones de larga permanencia para ancianos, presentando el tema a la luz de los derechos humanos y de la legislación en vigor que proponen buenas prácticas de cuidado para los ancianos institucionalizados, incluso ante el escenario del enfrentamiento a la Covid-19. Considerando los impactos negativos de la contención ambiental en la salud física y mental de los ancianos, se sugiere mayor capacitación del equipo técnico de las instituciones de larga permanencia para ancianos y prospección del fenómeno para garantía de condiciones más dignas y que respeten la libertad de los ancianos. (AU)

A theoretical and reflexive study addressing the phenomenon of environmental restraint in long-term care facilities for the elderly, presenting the topic under the light of human rights and the legislation in force, which postulate good care practices to institutionalized elderly even in the face of the Covid-19 situation. By considering the negative impacts of environmental restraint on the physical and mental health of the elderly, it is suggested that the technical team of long-term care institutions for the elderly should be better trained, and that the phenomenon needs to be explored to guarantee more dignified conditions that respect the freedom of the elderly. (AU)

Profile of esophageal squamous cell carcinoma mutations in Brazilian patients.

Esophageal cancer is an aggressive tumor that has a high rate of incidence and mortality worldwide. It is the 10th most frequent type in Brazil, being squamous cell carcinoma (ESCC) the predominant subtype. There is currently an incessant search to identify the frequently altered genes associated with esophageal squamous cell carcinoma biology that could be druggable. This study aimed to analyze the somatic mutation profile of a large panel of cancer-related genes in Brazilian ESCC. In a series of 46 ESCC diagnoses at Barretos Cancer Hospital, DNA isolated from paired fresh-frozen and blood tissue, a panel of 150 cancer-related genes was analyzed by next-generation sequencing. The genes with the highest frequency of mutations were TP53 (39/46, 84.8%), followed by NOTCH1 (7/46, 15.2%), NFE2L2 (5/46, 10.8%), RB1 (3/46, 6.5%), PTEN (3/46, 6.5%), CDKN2A (3/46, 6.5%), PTCH1 (2/46, 4.3%) and PIK3CA (2/46, 4.3%). There was no significant association between molecular and patients' clinicopathological features. Applying an evolutionary action score of p53 (EAp53), we observed that 14 (35.9%) TP53 mutations were classified as high-risk, yet no association with overall survival was observed. Concluding, this the largest mutation profile of Brazilian ESCC patients, which helps in the elucidation of the major cancer-related genes in this population.

DNA Methylation Markers from Negative Surgical Margins Can Predict Recurrence of Oral Squamous Cell Carcinoma.

The identification of molecular markers in negative surgical margins of oral squamous cell carcinoma (OSCC) might help in identifying residual molecular aberrations, and potentially improve the prediction of prognosis. We performed an Infinium MethylationEPIC BeadChip array on 32 negative surgical margins stratified based on the status of tumor recurrence in order to identify recurrence-specific aberrant DNA methylation (DNAme) markers. We identified 2512 recurrence-associated Differentially Methylated Positions (DMPs) and 392 Differentially Methylated Regions (DMRs) which were enriched in cell signaling and cancer-related pathways. A set of 14-CpG markers was able to discriminate recurrent and non-recurrent cases with high specificity and sensitivity rates (AUC 0.98, p = 3 × 10-6; CI: 0.95-1). A risk score based on the 14-CpG marker panel was applied, with cases classified within higher risk scores exhibiting poorer survival. The results were replicated using tumor-adjacent normal HNSCC samples from The Cancer Genome Atlas (TCGA). We identified residual DNAme aberrations in the negative surgical margins of OSCC patients, which could be informative for patient management by improving therapeutic intervention. This study proposes a novel DNAme-based 14-CpG marker panel as a promising predictor for tumor recurrence, which might contribute to improved decision-making for the personalized treatment of OSCC cases.