Abstract The TP53 3’UTR variant rs78378222 A>C has been detected in different tumor types as a somatic alteration that reduces p53 expression through modification of polyadenylation and miRNA regulation. Its prevalence is not yet known in all tumors. Herein, we examine tumor tissue prevalence of rs7837822 in Brazilian cohorts of patients from south and southeast regions diagnosed with lung adenocarcinoma (LUAD, n=586), sarcoma (SARC, n=188) and uterine leiomyoma (ULM, n=41). The minor allele (C) was identified in heterozygosity in 6/586 LUAD tumors (prevalence = 1.02 %) and none of the SARC and ULM samples. Additionally, next generation sequencing analysis revealed that all variant-positive tumors (n=4) with sample availability had additional pathogenic or likely pathogenic somatic variants in the TP53 coding regions. Among them, 3/4 (75 %) had the same pathogenic or likely pathogenic sequence variant (allele frequency <0.05 in tumor DNA) namely c.751A>C (p.Ile251Leu). Our results indicate a low somatic prevalence of rs78378222 in LUAD, ULM and SARC tumors from Brazilian patients, which suggests that no further analysis of this variant in the specific studied regions of Brazil is warranted. However, these findings should not exclude tumor molecular testing of this TP53 3’UTR functional variant for different populations.

ABSTRACT Objective: Evaluating the clinical results of bioactive glass S53P4 putty for the treatment of cavitary chronic osteomyelitis. Methods: Retrospective observational study, including patients of any age with clinical and radiological diagnosis of chronic osteomyelitis, who underwent surgical debridement and implantation of bioactive glass S53P4 putty (BonAlive® Putty, Turku, Finland). Patients who underwent any plastic surgery on the soft tissues of the affected site or had segmental bone lesions or septic arthritis were excluded. Statistical analysis was performed using Excel®. Demographic data, as well as data on the lesion, treatment, and follow-up, were collected. Outcomes were classified as “disease-free survival,” “failure,” or “indefinite.” Results: This study included 31 patients, of which 71% were men and had with a mean age of 53.6 years (SD ± 24.2). In total, 84% were followed-up for at least 12 months and 67.7% had comorbidities. We prescribed combination antibiotic therapy for 64.5% of patients. In 47.1%, Staphylococcus aureus was isolated. Finally, we classified 90.3% of cases as “disease-free survival” and 9.7% as “indefinite.” Conclusion: Bioactive glass S53P4 putty is safe and effective to treat cavitary chronic osteomyelitis, including infections by resistant pathogens, such as methicillin-resistant S. aureus. Level of Evidence IV, Case Series.

RESUMO Objetivo: Avaliar a atividade do vidro bioativo S53P4 em pasta no tratamento de osteomielite crônica. Métodos: Estudo observacional retrospectivo, com inclusão de indivíduos de qualquer idade com diagnóstico clínico e radiológico de osteomielite que realizaram tratamento cirúrgico com limpeza e desbridamento, seguido do preenchimento da cavidade com biovidro S53P4 em pasta (BonAlive ® Putty, Turku, Finland). Foram excluídos pacientes submetidos a procedimentos de cirurgia plástica nos tecidos moles do local afetado, com lesões ósseas segmentares e com presença de artrite séptica. A análise estatística foi realizada em Excel ® . Foram coletados dados demográficos, sobre a lesão, o tratamento e o acompanhamento. O desfecho foi classificado em “sobrevida livre de doença”, “falha” ou “indeterminado”. Resultados: Dos 31 pacientes analisados, 71% eram homens, com idade média de 53,6 anos (DP ± 24,26). Do total, 84% foram acompanhados por no mínimo 12 meses, e 67,7% apresentaram comorbidades. A terapia antibiótica combinada foi realizada em 64,5% dos pacientes, sendo o patógeno mais frequente o Staphylococcus aureus (47,1%). Ao final, 90,3% dos pacientes obtiveram “sobrevida livre de doenças” e 9,7% foram considerados “indeterminados”. Conclusão: O vidro bioativo S53P4 em pasta é seguro e eficaz no tratamento da osteomielite cavitária e de infecções por patógenos resistentes, incluindo o S. aureus multirresistente. Nível de Evidência IV, Série de Casos.

RESUMO Análises histológicas de amostras de Siderastrea stellata Verrill, 1868 branqueadas, doentes e com alteração no padrão de cloração, revelaram drásticas perturbações teciduais e celulares, como lise do epitélio externo, hiperplasia da mesogleia, apoptose das células epiteliais e das zooxantelas, e degradação dos filamentos mesentéricos e das células reprodutivas. Hifas fúngicas, diatomáceas e cianobactérias estavam presentes em amostras doentes e em tecidos de colônias com alteração no padrão de coloração. Além disso, amostras branqueadas e doentes apresentavam reduções significativas no número de zooxantelas por 100 µm2 da gastrodermis e, reduções significativas nos diâmetros e volumes dos oócitos de estágio V. Constatamos que eventos de branqueamento, doenças e colônias com alteração no padrão de cloração, promoveram degradação das células reprodutivas, resultando na consequente interrupção da reprodução do coral S. stellata, que é uma das espécies de corais brasileiro mais comuns. As implicações desses efeitos indiretos do branqueamento, doenças e das mudanças nos padrões de coloração dos corais na dinâmica populacional dos recifes brasileiros são discutidas.

ABSTRACT Histological analysis of bleached samples of Siderastrea stellata Verrill, 1868, with white plague disease and with alteration in the color pattern, revealed drastic tissue and cellular disturbances, such as lysis of the external epithelium, hyperplasia of gastrodermis, apoptosis of epithelial cells and zooxanthellae, and degradation of mesenteric filaments and reproductive cells. Fungal hyphae, diatoms, and cyanobacteria were present in diseased samples and colonies with alteration in the color pattern. Furthermore, bleached and diseased samples showed significant reductions in the number of zooxanthellae per 100 µm2 of gastrodermis and significant reductions in the diameters and volumes of stage V oocytes. We found that bleaching events, diseases, and colonies with alteration in the color pattern promoted degradation of reproductive cells, resulting in the consequent interruption of the reproduction of the coral S. stellata, which is one of the most common Brazilian coral species. The implications of these indirect effects of bleaching, disease, and changes in coral color patterns in the population dynamics of Brazilian reefs are discussed.

RESUMO Objetivo Correlacionar os achados de ressonância magnética (RNM) com o diagnóstico microbiológico e anatomopatológico de infecção na coluna vertebral. Métodos Estudo de coorte retrospectivo de revisão de prontuários online (laboratório, anatomopatológico e setor de diagnóstico por imagem) de pacientes com diagnóstico de espondilodiscite, submetidos ao exame de RNM da coluna vertebral e acompanhados pelo Departamento de Ortopedia e Traumatologia da Universidade Federal de São Paulo, entre janeiro de 2014 e julho de 2018. Resultados O agente etiológico mais comum encontrado foi o S. aureus (57%). A hemocultura mostrou-se positiva em 76% dos casos e 82% dos pacientes submetidos à biópsia apresentaram diagnóstico de espondilodiscite. A dor foi o achado clínico mais prevalente e a coluna lombossacra foi o sítio mais frequente de infecção. No exame de RNM, a presença de hipossinal em T1, hipersinal em T2/STIR e destruição das placas terminais foram identificados em quase todos os casos. Conclusões Não houve correlação direta dos achados na RNM com um agente etiológico específico na espondilodiscite. A hemocultura e a biópsia são ferramentas diagnósticas importantes que devem ser utilizadas para o diagnóstico preciso do agente infeccioso. Nível de evidência IV; Estudo diagnóstico.

ABSTRACT Objective To correlate magnetic resonance imaging (MRI) findings with the microbiological and anatomopathological diagnosis of spinal infection. Methods A retrospective, cohort review of online medical records (laboratory, anatomopathology and diagnostic imaging sector) of patients diagnosed with spondylodiscitis, who underwent a full spine MR scan between January 2014 and July 2018 at the Department of Orthopedics and Traumatology of the Universidade Federal de São Paulo. Results Staphylococcus aureus was the most commonly found etiological agent (57%). Blood culture was positive in 76% of cases and 82% of the patients who underwent biopsy had a spondylodiscitis diagnosis. Pain was the most prevalent clinical symptom and the lumbosacral spine was the most frequent site of infection. T1 hyposignal, T2/STIR hypersignal, and terminal plate destruction were verified in almost all MR scans. Conclusions No direct correlation was found between MR findings and any specific etiological agent. Blood culture and biopsy are important diagnostic tools that should be used for accurate diagnosis of the infectious agent . Level of evidence IV; Diagnostic Study.

RESUMEN Objetivo Correlacionar los hallazgos de resonancia magnética (RNM) con el diagnóstico microbiológico y anatomopatológico de infección de la columna vertebral. Métodos Un estudio de cohorte retrospectivo de revisión de prontuarios en línea (laboratorio, anatomopatológico y sector de diagnóstico por imagen) de pacientes con diagnóstico de espondilodiscitis, sometidos al examen de RNM de la columna vertebral y acompañados por el Departamento de Ortopedia y Traumatología de la Universidad Federal de São Paulo, entre enero de 2014 y julio de 2018. Resultados El agente etiológico más común encontrado fue el S. aureus (57%). El hemocultivo se mostró positivo en 76% de los casos y 82% de los pacientes sometidos a biopsia presentaron diagnóstico de espondilodiscitis. El dolor fue el hallazgo clínico más prevalente y la columna lumbosacra fue el sitio más frecuente de infección. En el examen de RNM, la presencia de hiposeñal en T1, hiperseñal en T2/STIR y destrucción de las placas terminales fueron identificadas en casi todos los casos. Conclusiones No hubo correlación directa de los hallazgos de la RNM con un agente etiológico específico en la espondilodiscitis. El hemocultivo y la biopsia son herramientas diagnósticas importantes, que deben ser utilizadas para el diagnóstico preciso del agente infeccioso. Nivel de evidencia IV; Estudio Diagnóstico.

ABSTRACT Stingless bee products such as honey, pollen, propolis, and geopropolis have been used for centuries in traditional medicine for the treatment of several illnesses. Investigation of the biological activity of stingless bee products, especially propolis and geopropolis, has revealed promising therapeutic properties. About 20% of total Neotropical stingless bees can be found in Brazil. Despite the species diversity, studies on their biological activity are scarce. The present review focuses on the antioxidant and antimicrobial activities of propolis and geopropolis from Brazilian stingless bees. In addition, the toxicity of these natural products was addressed. In order to provide new evidences for the toxic potential of propolis and geopropolis components, an in silico analysis was performed using the ADMET PredictorTM software. We observed that most of studies evaluated only crude ethanol extracts of a limited number of stingless bees species. Propolis and geopropolis displayed antioxidant capacity and antimicrobial activity. Concerning the toxic potential, the extracts of stingless bees propolis and geopropolis were considered safe. Nonetheless, in vitro and in vivo toxicological studies are still necessary.

Abstract Germline mutations in BRCA1 and BRCA2 (BRCA) genes confer high risk of developing cancer, especially breast and ovarian tumors. Since the cloning of these tumor suppressor genes over two decades ago, a significant amount of research has been done. Most recently, monoallelic loss-of-function mutations in PALB2 have also been shown to increase the risk of breast cancer. The identification of BRCA1, BRCA2 and PALB2 as proteins involved in DNA double-strand break repair by homologous recombination and of the impact of complete loss of BRCA1 or BRCA2 within tumors have allowed the development of novel therapeutic approaches for patients with germline or somatic mutations in said genes. Despite the advances, especially in the clinical use of PARP inhibitors, key gaps remain. Now, new roles for BRCA1 and BRCA2 are emerging and old concepts, such as the classical two-hit hypothesis for tumor suppression, have been questioned, at least for some BRCA functions. Here aspects regarding cancer predisposition, cellular functions, histological and genomic findings in BRCA and PALB2-related tumors will be presented, in addition to an up-to-date review of the evolution and challenges in the development and clinical use of PARP inhibitors.

Abstract Germline mutations in the TP53 gene are associated with Li-Fraumeni and Li-Fraumeni-Like Syndromes, characterized by increased predisposition to early-onset cancers. In Brazil, the prevalence of the TP53-p.R337H germline mutation is exceedingly high in the general population and in cancer-affected patients, probably as result of a founder effect. Several genotyping methods are used for the molecular diagnosis of LFS/LFL, however Sanger sequencing is still considered the gold standard. We compared performance, cost and turnaround time of Sanger sequencing, PCR-RFLP, TaqMan-PCR and HRM in the p.R337H genotyping. The performance was determined by analysis of 95 genomic DNA samples and results were 100% concordant for all methods. Sequencing was the most expensive method followed by TaqMan-PCR, PCR-RFLP and HRM. The overall cost of HRM increased with the prevalence of positive samples, since confirmatory sequencing must be performed when a sample shows an abnormal melting profile, but remained lower than all other methods when the mutation prevalence was less than 2.5%. Sequencing had the highest throughput and the longest turnaround time, while TaqMan-PCR showed the lowest turnaround and hands-on times. All methodologies studied are suitable for the detection of p.R337H and the choice will depend on the application and clinical scenario.

INTRODUÇÃO: A doença cardíaca valvar é um grave problema de saúde pública, mais frequente em países em desenvolvimento, acometendo indivíduos em idade laboralmente produtiva. OBJETIVO: Avaliar o perfil socioeconômico e epidemiológico dos pacientes submetidos a cirurgia valvar e a sua relação com os tipos de próteses utilizadas em um centro de referência público de Salvador, BA, Brasil. MÉTODOS: Estudo de corte transversal descritivo de prevalência, no qual foram analisados retrospectivamente idade, sexo, procedência, tipo de valvopatia, cirurgia a qual o paciente foi submetido e o tipo de prótese utilizada em casos de trocas, em centro de referência público de cardiologia. RESULTADOS: Foram revisados 366 prontuários, de todos os pacientes submetidos a cirurgia de valva cardíaca, de janeiro de 2007 a dezembro de 2009. Em relação ao sexo, 52% dos pacientes eram do sexo feminino. A idade média ± DP foi de 41,70 ± 17,85 anos. Dentre os pacientes, 37,7% eram procedentes da capital e 62,3%, do interior do estado da Bahia (Brasil). A troca valvar foi realizada em 73% dos pacientes, enquanto que 7,38% realizaram plastia valvar e 18,3% realizaram tanto plastia quanto troca. Dos pacientes que realizaram troca valvar, 70% receberam bioprótese e 30% do tipo metálica, com predominância do uso bioprótese nas faixas etárias jovens (P<0,001). CONCLUSÃO: Próteses biológicas foram predominantemente usadas em jovens. Esse fato, possivelmente, pode ser atribuído ao baixo nível socioeconômico da população em questão, distância de centros urbanos, dificuldade de realização de exames para controle da anticoagulação e nível educacional ruim, inviabilizando o uso de valva metálica e a consequente terapia anticoagulante.

BACKGROUND: Valvar heart disease is an important public health problem, more common in developing countries, especially in younger. OBJECTIVE: To evaluate the epidemiological features of patients and its influence on the prosthesis type choice used on patients who underwent valve surgery. METHODS: Cross-sectional. Data such as age, sex, provenance, surgery procedure and prosthesis type were retrospectively analyzed. We reviewed 366 charts of all patients submitted to heart valve surgery during three years in a public health cardiovascular treatment center. RESULTS: 52% of patients were female. The age range was from 5 to 82, the median was 41 years old. In regards 37.7% of patients came from Salvador (Bahia, Brazil) and 62.3% from countryside. Valve replacement was performed in 73% of patients, whereas 7.38% underwent valvuloplasty and 18.3% underwent valve repair and replacement. Regarding type of prosthesis, 70.0% received bioprosthesis and 30.0% received metal prosthesis. On note bioprosthesis were more used in younger (P<0,001). CONCLUSION: Biological prostheses were used predominantly in younger. This might be possible due to a low social-economic status, avoiding metal valve implantation and the consequent anticoagulation therapy.

As neoplasias nasais são bastante raras. Os tumores mais observados na cavidade nasal são papilomas epiteliais, angiomas, carcinoma de células transicionais, carcinoma pavimentoso e adenocarcinoma. O adenoma pleomórfico pertence ao grupo de tumores que aparecem com menor freqüência na fossa nasal, e é o tumor benigno glandular mais comum originado na cabeça e pescoço. A apresentação clínica típica dos pacientes com adenoma pleomórfico do septo nasal é de obstrução nasal unilateral, epistaxe e massa indolor na cavidade nasal. Em vista da raridade da apresentação clínica do adenoma pleomórfico nesta localização, os autores descrevem um caso de adenoma pleomórfico nasal em um paciente do sexo masculino, com 69 anos de idade, onde relatam os achados clínicos, critérios diagnósticos, tratamento, prognóstico e revisão da literatura.

Nasal tumours are very rare. The neoplasms most frequently seen in the nasal cavity are epithelial papillomas, angiomas, transitional cells carcinoma, pavement carcinoma and adenocarcinoma. The pleomorphic adenoma belongs to the group of tumours less commonly observed in the nasal cavity, and is the most common head and neck benign glandular tumour. The typical clinical presentation of the nasal pleomorphic adenoma is of unilateral nasal obstruction, epistaxis and a painless mass in the nasal cavity. The authors reported an adenoma pleomorphic case that highlights itself by its unusual nasal presentation in the nasal septum of a 45-year-old male patient who was submitted to surgical treatment, and discuss the clinical findings, diagnostic criteria, treatment, prognosis and literature review.

Os autores descrevem sua experiência em recanalização tubária videolaparoscópica pós-laqueadura em 10 pacientes, tratadas no período de junho de 1994 a fevereiro de 1996. A duração da 1ª cirurgia foi de 4 horas e 30 minutos e da última foi de 2 horas e 30 minutos. A metade das recanalizações foi ístmo-ístmica. O tamanho mínimo das tubas restantes foi de 4 cm de cada lado e os fios utilizados para a sutura foram o 7-0 e 6-0 monofilamentares, derivados do ácido poliglicólico. A permeabilidade tubária foi verificada pela histerossalpingografia 3 meses após a cirurgia e, como resultado, 88, 8% das tubas operadas estavam permeáveis. Quatro das pacientes consideradas aptas para engravidar ficaram grávidas durante o período de seguimento. O tempo médio de permanência hospitalar foi de 24 horas. Não houve complicações cirúrgicas ou anestésicas.

The authors describe their experience with videolaparoscopic tubal anastomosis in 10 selected patients operated from June 1994 to February 1996. The time of the first surgery was 4 hours and 30 minutes and the last , 2 hours and 30 minutes. The time was different according to the change of auxiliary team. Half of the reanastomoses were isthmic- isthmic. The minimum size of the remaining tubes was 5cm on each side. We used 7-0 and 6-0 polyglycolic acid monofilament for suture. The tube patency was tested by hysterosalpingogram 3 months after surgery, and it was shown that 88.8% of the operated tubes were free. The patients considered able to become pregnant were followed up for a short period of time and 4 of them became pregnant. The hospitalization lasted 24 hours and there were no surgical or anesthetic complications.