Increased Expression of the Δ133p53ß Isoform Enhances Brain Metastasis.

The Δ133p53ß isoform is increased in many primary tumors and has many tumor-promoting properties that contribute to increased proliferation, migration and inflammation. Here we investigated whether Δ133p53ß contributed to some of the most aggressive tumors that had metastasized to the brain. Δ133p53ß mRNA expression was measured in lung, breast, melanoma, colorectal metastases and, where available, the matched primary tumor. The presence of Δ133p53ß expression was associated with the time for the primary tumor to metastasize and overall survival once the tumor was detected in the brain. Δ133p53ß was present in over 50% of lung, breast, melanoma and colorectal metastases to the brain. It was also increased in the brain metastases compared with the matched primary tumor. Brain metastases with Δ133p53ß expressed were associated with a reduced time for the primary tumor to metastasize to the brain compared with tumors with no Δ133p53ß expression. In-vitro-based analyses in Δ133p53ß-expressing cells showed increased cancer-promoting proteins on the cell surface and increased downstream p-AKT and p-MAPK signaling. Δ133p53ß-expressing cells also invaded more readily across a mock blood-brain barrier. Together these data suggested that Δ133p53ß contributes to brain metastases by making cells more likely to invade the brain.

Disfunções sexuais em mulheres jovens universitárias: estudo transversal / Sexual dysfunctions in young university women: a cross-sectional study

OBJETIVO: Verificar a frequência e os fatores associados à disfunção sexual em mulheres jovens universitárias. MÉTODOS: Trata-se de um estudo descritivo analítico de corte transversal. Participaram deste estudo 111 mulheres, estudantes, heterossexuais do curso de fisioterapia da Universidade Federal da Bahia. Cada participante respondeu a dois questionários autoaplicáveis "Investigação de fatores associados" e "Quociente sexual ­ versão feminina", entre os meses de setembro e outubro de 2019. RESULTADOS: Foi encontrado nesta população prevalência de 8% de disfunção sexual. O sintoma de esforço evacuatório esteve associado a pior desempenho/satisfação sexual pelo score total do QS-F (p=0,03), e quando avaliado por agrupamento de questões, foi encontrada associação entre esforço evacuatório e pior excitação (p=0,01), esforço evacuatório e mais dor (p=0,04); urgência urinária e mais dor (p=0,04); violência e pior excitação (p=0,05) e violência e menos satisfação/orgasmo (p=0,02). CONCLUSÃO: Os resultados sugerem que há baixa prevalência de disfunção sexual na população estudada, mas há associação entre sintomas de disfunções do assoalho pélvico e disfunções sexuais em mulheres jovens.

OBJECTIVE: To estimate the prevalence of sexual dysfunction in young college women. METHODS: This is a descriptive-analytical cross-sectional study. A total of 111 heterosexual women students of the physiotherapy course from the Universidade Federal da Bahia participated in this study. Each participant answered two self-administered questionnaires, "Investigation of associated factors" and "Sex ratio - female version" between September and October 2019. RESULTS: A prevalence of 8% of sexual dysfunction was found in this population. The symptom of evacuatory effort was associated with worse performance / sexual satisfaction by the total SQ-F score (p=0.03), and when assessed by a grouping of questions, an association was found between evacuatory effort and worse arousal (p=0.01), evacuatory effort, and pain (p=0.04); urinary urgency and pain (p=0.04); violence and arousal (p=0.05); and violence and less satisfaction/orgasm (p=0.02). CONCLUSION: The results suggest a low prevalence of sexual dysfunction in the studied population, but there is an association between symptoms of pelvic floor dysfunction and sexual dysfunction in young women.

Role of atypical chemokine receptor ACKR2 in experimental oral squamous cell carcinogenesis.

BACKGROUND: Chemokines and chemokine receptors are critical in oral tumourigenesis. The atypical chemokine receptor ACKR2 is a scavenger of CC chemokines controlling the availability of these molecules at tumour sites, but the role of ACKR2 in the context of oral carcinogenesis is unexplored. METHODS: In this study, wild-type (WT) and ACKR2 deficient mice (ACKR2-/-) were treated with chemical carcinogen 4-nitroquinoline-1-oxide (4NQO) for induction of oral carcinogenesis. Tongues were collected for macro and microscopic analysis and to evaluate the expression of ACKRs, CC chemokines and its receptors, inflammatory cytokines, angiogenic factors, adhesion molecules and extracellular matrix components. RESULTS: An increased expression of ACKR2 in squamous cell carcinoma (SCC) lesions of 4NQO-treated WT mice was observed. No significant differences were seen in the ACKR1, ACKR3 and ACKR4 mRNA expression comparing SCC lesions from WT and ACKR2-/- treated mice. Significantly higher expression of CCL2, IL-6 and IL-17 was detected in ACKR2-/- treated mice. In contrast, the expression of other CC-chemokines, and receptors, angiogenic factors, adhesion molecules and extracellular matrix components were similarly increased in SCC lesions of both groups. Clinical and histopathological analysis revealed no differences in inflammatory cell recruitment and in the SCC incidence comparing WT and ACKR2-/- treated mice. CONCLUSION: The results suggest that ACKR2 expression regulates inflammation in tumour-microenvironment but the absence of ACKR2 does not impact chemically-induced oral carcinogenesis.

Efeitos da realidade virtual na função muscular em mulheres com incontinência urinária: relatos de caso / Effects of virtual reality exposure therapy in muscle function in women with urinary incontinence: case series

INTRODUÇÃO: A incontinência urinária (IU) é um dos mais constrangedores e estressantes sintomas urinários e a principal disfunção do assoalho pélvico. O tratamento através da realidade virtual tem o objetivo de aumentar a adesão das pacientes ao tratamento de forma lúdica e não invasiva, promovendo a capacidade de contração dos MAP durante as atividades físicas, com potenciais reflexos na melhora da incontinência. OBJETIVOS: Avaliar a função muscular do assoalho pélvico e perda de urina de mulheres incontinentes tratadas por meio de um protocolo específico de terapia por exposição à realidade virtual. MÉTODOS: Relato de casos, composto 02 casos de mulheres com diagnóstico médico de IU. Tratadas com realidade virtual através dos jogos do Nintendo Wii Fit PlusTM por 12 sessões de 50 minutos cada, três vezes por semana. Cada sessão compreendeu de 20 minutos de momento educativo, com orientações das ações durante os jogos e treinamento prévio para a contração dos músculos transverso do abdome e assoalho pélvico, seguido de 30 minutos de intervenção com o jogo. O protocolo foi dividido em duas fases de seis sessões cada de acordo com a dificuldade dos jogos, priorizando inicialmente aqueles que exploravam movimentos da pelve no plano frontal (Lotus FocusTM, Penguin SlideTM e Soccer HeadingTM) e, com a evolução, os que permitiam movimentos pélvicos mais globalizados (Penguin SlideTM, Table TiltTM e Balance BubbleTM). A função muscular do assoalho pélvico e a perda urinária foram avaliadas, respectivamente, através do Esquema PERFECT e do pad test de 1 hora, sendo os resultados sumarizados de forma descritiva em tabelas do Excel. RESULTADOS: Melhora da perda urinária através do pad test de 1 hora e da função muscular através da palpação digital associada ao Esquema PERFECT das participantes com incontinência urinária após intervenção. CONCLUSÃO: O tratamento dos MAP através da realidade virtual demonstrou-se efetivo na melhora da perda urinária e da função muscular do assoalho pélvico nas participantes deste estudo, porém fazem-se necessárias ensaios clínicos para comprovar sua eficácia. [AU]

INTRODUCTION: Urinary incontinence is one of the most embarrassing and stressful urinary symptoms and the main pelvic floor dysfunction. The treatment through virtual reality aims to increase the adherence of patients to treatment in a playful, non-invasive, promoting PFM contraction capacity during physical activities, with potential impacts on the improvement of this incontinence. OBJECTIVES: To evaluate the muscle function and loss of urine of the pelvic floor of women incontinent treated with a specific protocol of virtual reality exposure therapy. METHODS: Case report, composed of 02 cases of women with medical diagnosis of UI. Handled with virtual reality through Nintendo Wii Fit Plus ™ games for 12 50-minute sessions each, three times a week. Each session consisted of twenty minutes of educational time, with orientation of the actions during the games and previous training for the contraction of the transverse abdomen and pelvic floor muscles, followed by thirty minutes of intervention with the game. The protocol was divided into two phases of six sessions each according to the difficulty of the games, initially prioritizing those who explored movements of the pelvis in the frontal plane (Lotus FocusTM, Penguin SlideTM and Soccer HeadingTM) and, with evolution, those that allowed global movements (Penguin SlideTM, Table TiltTM and Balance BubbleTM). The pelvic floor muscle function and urinary loss were evaluated, respectively, through the PERFECT scheme and the pad test one hour and the results were descriptive summarized in Excel tables. RESULTS: Improved urinary loss through the pad test one hour and improve muscle function by digital palpation associated with the PERFECT scheme of the participants with urinary incontinence after intervention. CONCLUSION: The treatment of PFM through virtual reality proved to be effective in improving urinary loss and PF muscle function in this study, but clinical trials are required to prove their efficacy. [AU]

Avaliação da sinergia abdomino-pélvica durante atividades funcionais em mulheres nulíparas: série de caso / Evaluation of abdomino-pelvic synergy during functional activities in nulphary women: case series

Introdução: É relevante compreender que as disfunções do assoalho pélvico (DAP) feminino são condições clínicas que acometem um número crescente de mulheres a cada ano, constituindo um problema de saúde pública. DAP podem ter relação com o desequilíbrio entre a sobrecarga tensional dessa musculatura e a diminuição da capacidade desses músculos em suportar o aumento da pressão nessa região, uma vez que essa musculatura deve se contrair durante qualquer atividade que promova o aumento da pressão intra-abdominal favorecendo a manutenção da continência. Objetivo: analisar a presença desta sinergia em três voluntárias descrevendo o comportamento da atividade eletromiográfica de músculos localizados no assoalho pélvico e no abdome durante as atividades funcionais: andar, sentar/levantar, segurar peso, agachar, pular e tossir. Materiais e Métodos: Série de três casos, envolvendo voluntárias jovens universitárias nulíparas, sem queixas miccionais. Foi mensurado o registro da atividade eletromiográfica dos músculos do assoalho pélvico e o grupo muscular formado pelo transverso abdominal e oblíquo interno durante as atividades funcionais, utilizando a eletromiografia de superfície. Resultados: O sinal eletromiográfico aumentou em relação ao repouso durante as atividades funcionais de tossir, pular, agachar, sentar/levantar, segurar peso e andar em ambas as musculaturas analisadas. As maiores atividades eletromiográficas foram observadas durante as atividades de pular e agachar, e as menores ao segurar peso, andar e sentar/levantar. Conclusões: A partir da coleta eletromiográfica dos músculos transverso abdominal/ oblíquo interno e esfíncter anal externo em três voluntárias nulíparas foi possível observar sinergia destas musculaturas durante as atividades funcionais propostas. Estudos que envolvam grupos maiores de voluntárias, são necessários para podermos afirmar as respostas sobre a sinergia entre esses grupos musculares durante as atividades funcionais. [AU]

Introduction: It is relevant to understand that female pelvic floor dysfunctions (PFD) are clinical conditions that affect an increasing number of women each year, constituting a public health problem. PFD may be related to the imbalance between the tensional overload of this musculature and the decreased ability of these muscles to withstand increased pressure in this region, since this musculature must contract during any activity that promotes an increase in intra-abdominal pressure favoring the maintenance of continence. The present study aims to analyze the presence of this synergy in three volunteers describing the behavior of electromyographic activity of muscles located in the pelvic floor and abdomen during functional activities: walking, sitting rising, holding weight, crouching, jumping and coughing. Materials and Methods: A series of three cases, involving volunteer nulliparous university students, with no voiding complaints. The recording of electromyographic activity of pelvic floor muscles and muscular group formed by the transverse abdominal and oblique internal muscles during functional activities was measured using surface electromyography. Results: The electromyographic signal increased in relation to rest during functional activities of coughing, jumping, squatting, sitting rising, holding weight and walking in both musculature analyzed. The largest electromyographic activities were observed during jumping and crouching activities, and the lowest ones when holding weight, walking and sitting rising. Conclusion: From the electromyographic data collection of the transverse abdominal/internal oblique muscles and external anal sphincter in three nulliparous volunteers, it was possible to observe synergy of these muscles during the proposed functional activities. Studies involving larger groups of volunteers are needed to be able to state important details about the synergy between these muscle groups. [AU]

Arthritis-induced alveolar bone loss is associated with changes in the composition of oral microbiota.

Rheumatoid arthritis (RA) and periodontitis (PD) are chronic inflammatory disorders that cause bone loss. PD tends to be more prevalent and severe in RA patients. Previous experimental studies demonstrated that RA triggers alveolar bone loss similarly to PD. The aim of this study was to investigate if arthritis-induced alveolar bone loss is associated with modification in the oral microbiota. Checkerboard DNA-DNA hybridization was employed to analyze forty oral bacterial species in 3 groups of C57BL/6 mice: control (n = 12; without any challenge); Y4 (n = 8; received oral inoculation of Aggregatibacter Actinomycetemcomitans strain FDC Y4) and AIA group (n = 12; chronic antigen-induced arthritis). The results showed that AIA and Y4 group exhibited similar patterns of bone loss. The AIA group exhibited higher counts of most bacterial species analyzed with predominance of Gram-negative species similarly to infection-induced PD. Prevotella nigrescens and Treponema denticola were detected only in the Y4 group whereas Campylobacter showae, Streptococcus mitis and Streptococcus oralis were only found in the AIA group. Counts of Parvimonas micra, Selenomonas Noxia and Veillonella parvula were greater in the AIA group whereas Actinomyces viscosus and Neisseira mucosa were in large proportion in Y4 group. In conclusion, AIA is associated with changes in the composition of the oral microbiota, which might account for the alveolar bone loss observed in AIA mice.

Hepatic DNA deposition drives drug-induced liver injury and inflammation in mice.

UNLABELLED: Drug-induced liver injury (DILI) is an important cause of acute liver failure, with limited therapeutic options. During DILI, oncotic necrosis with concomitant release and recognition of intracellular content amplifies liver inflammation and injury. Among these molecules, self-DNA has been widely shown to trigger inflammatory and autoimmune diseases; however, whether DNA released from damaged hepatocytes accumulates into necrotic liver and the impact of its recognition by the immune system remains elusive. Here we show that treatment with two different hepatotoxic compounds (acetaminophen and thioacetamide) caused DNA release into the hepatocyte cytoplasm, which occurred in parallel with cell death in vitro. Administration of these compounds in vivo caused massive DNA deposition within liver necrotic areas, together with an intravascular DNA coating. Using confocal intravital microscopy, we revealed that liver injury due to acetaminophen overdose led to a directional migration of neutrophils to DNA-rich areas, where they exhibit an active patrolling behavior. DNA removal by intravenous DNASE1 injection or ablation of Toll-like receptor 9 (TLR9)-mediated sensing significantly reduced systemic inflammation, liver neutrophil recruitment, and hepatotoxicity. Analysis of liver leukocytes by flow cytometry revealed that emigrated neutrophils up-regulated TLR9 expression during acetaminophen-mediated necrosis, and these cells sensed and reacted to extracellular DNA by activating the TLR9/NF-κB pathway. Likewise, adoptive transfer of wild-type neutrophils to TLR9(-/-) mice reversed the hepatoprotective phenotype otherwise observed in TLR9 absence. CONCLUSION: Hepatic DNA accumulation is a novel feature of DILI pathogenesis. Blockage of DNA recognition by the innate immune system may constitute a promising therapeutic venue.

Hypermethylation and low transcription of TLR2 gene in chronic periodontitis.

Periodontitis is an inflammatory disorder characterized by interactions between periodontal pathogens and host's immune response. Epigenetic may contribute to disease development and outcome by influencing the expression of genes involved in the immune response. It has been shown that Toll-like receptors (TLR) play an important role in the response to periodontopathic bacteria. The aim of study was to evaluate the methylation status and the expression of TLR2 gene in gingival samples from individuals with and without periodontitis. DNA was analyzed using the Methyl Profiler DNA Methylation qPCR assay. DNA methylation and transcript levels were evaluated by real-time polymerase chain reaction. The periodontitis group showed a hypermethylated profile and a low expression of gene. Positive correlation between the TLR2 methylation frequency and probing depth was observed. This study gives the first evidence of methylation frequency in inflamed periodontal tissues and of the possible participation of methylation in the development of periodontitis.

Transcription factor STAT1 gene polymorphism is associated with the development of severe forms of periodontal disease.

INTRODUCTION: Periodontal disease (PD) is one of the most common inflammatory diseases, affecting about 10 % of the world population. The establishment of PD is influenced by polymorphisms in genes involved with the inflammatory response. Signal Transducer and Activator of Transcription (STAT)-1 is a transcription factor that plays a key role in the intracellular signaling triggered by cytokines and, thus, its activation is critical in inflammatory diseases. AIM AND METHODS: We aim to evaluate the occurrence of association between STAT-1 (rs3771300) polymorphism and distinct clinical forms and severity of PD; we genotyped 180 subjects using realtime PCR. RESULTS AND CONCLUSION: We observed that the presence of the G allele for STAT-1 was associated with twice as high of a chance to develop aggressive periodontitis, and the most severe form of the disease.

Evaluation of IL17A expression and of IL17A, IL17F and IL23R gene polymorphisms in Brazilian individuals with periodontitis.

The IL23/Th17 axis plays an important role in the pathogenesis of cell-mediated tissue damage caused either by autoimmunity or immune responses against bacterial infection. Single nucleotide polymorphisms in the IL17A, IL17F and IL23R genes have been associated with several inflammatory diseases. However, these polymorphisms have not yet been studied in periodontitis. The aim of present study was to evaluate the expression of IL17A and occurrence of the IL17A (rs2275913), IL17F (rs763780) and IL23R (rs11209026) gene polymorphisms in different clinical forms or severity of periodontitis in a sample of Brazilian individuals. Peripheral blood was obtained from 30 non-smoker individuals and analyzed by flow cytometry to determine IL-17 expression. Genomic DNA was obtained from oral swabs in 180 individuals and analyzed by Real-time PCR. The study group was composed by individuals without periodontitis (control), with aggressive periodontitis (AP) and with chronic periodontitis (CP). Higher frequency of IL17A+CD4+ T cells was observed in control group. The A+ genotype from IL17A (rs2275913) was associated with lack of disease. No association was found considering the IL17F and IL23R polymorphisms. Our data suggest that IL17A and the presence of IL17A (rs2275913) A allele are associated with the absence of periodontal disease.

Fluido crevicular gengival: marcadores bioquímicos da doença periodontal / Gingival crevicular fluid: biochemical markers of periodontal disease

A periodontite (DP) é uma doença caracterizada pela perda de tecido de suporte. O diagnóstico atual é baseado em parâmetros clínicos como profundidade de sondagem, perda de inserção, sangramento a sondagem e exames radiográficos. A meta da Periodontia é o estabelecimento de novos métodos que possibilitem o diagnóstico, a identificação precoce da doença e predizer uma futura perda de inserção. O fluido crevicular gengival (FCG) é composto de uma gama de biomarcadores celulares e moleculares. A coleta do FCG é uma técnica fácil e não invasiva, o que o torna um método diagnóstico promissor. O objetivo do presente trabalho foi realizar uma revisão da literatura crítica sobre a análise do FCG como ferramenta para o estabelecimento do diagnóstico precoce, bem como o monitoramento da evolução da doença. Na literatura é possível encontrar inúmeros estudos de possíveis biomarcadores da DP no FCG como fosfatase alcalina, citocinas, aspartato aminotransferase, oncostatina M, Rank/Rankl/OPG, catepsina B, catepsina K, osteocalcina, osteopontina, metaloproteinases e leucotrieno B4. As pesquisas apontam alguns biomarcadores promissores para o diagnóstico da DP, entretanto, não há ainda um marcador que possa predizer a futura perda de inserção ou a susceptibilidade à DP. São necessários estudos longitudinais para melhor entendimento do papel de biomarcadores do FCG.