What are the main oral manifestations in heart transplant patients? A scoping review.

OBJECTIVE: The purpose of this scoping review is to evaluate the oral manifestations (OM) of heart transplant (HT) patients undergoing immunosuppressive therapy (IT). MATERIAL AND METHODS: A literature search was performed using keywords and MeSH terms related to OM and HT in the Medline/PubMed, Web of Science, Cochrane Library, Scopus, LILACS/BBO databases and in gray literature without language or date restrictions until June 2023. Studies that evaluated HT individuals who used any IT and who reported the occurrence of OM were considered eligible. The results from the search were imported to EndNote Web, and duplicates were removed followed by title/abstract and full-text analysis. RESULTS: A total of 402 nonduplicated studies were found and 13 fulfilled the criteria and were included in the present review: 10 cross-sectional, 2 cohorts, and 1 clinical trial. The most reported OM were periodontal diseases, including drug-induced gingival enlargement (DIGE), gingival bleeding, gingivitis, and periodontitis. Reported in a minority of studies are oral cancer, opportunistic infections (oral hairy leukoplakia and erythematous candidiasis), enamel defects, and burning mouth. CONCLUSION: Considering the methodological heterogeneity of the studies analyzed, DIGE is the most commonly observed oral manifestation in HT individuals.

CCL21-CCR7 signaling promotes microglia/macrophage recruitment and chemotherapy resistance in glioblastoma.

Glioblastoma (GBM) is the most common and fatal primary tumor of the central nervous system (CNS) and current treatments have limited success. Chemokine signaling regulates both malignant cells and stromal cells of the tumor microenvironment (TME), constituting a potential therapeutic target against brain cancers. Here, we investigated the C-C chemokine receptor type 7 (CCR7) and the chemokine (C-C-motif) ligand 21 (CCL21) for their expression and function in human GBM and then assessed their therapeutic potential in preclinical mouse GBM models. In GBM patients, CCR7 expression positively associated with a poor survival. CCL21-CCR7 signaling was shown to regulate tumor cell migration and proliferation while also controlling tumor associated microglia/macrophage recruitment and VEGF-A production, thereby controlling vascular dysmorphia. Inhibition of CCL21-CCR7 signaling led to an increased sensitivity to temozolomide-induced tumor cell death. Collectively, our data indicate that drug targeting of CCL21-CCR7 signaling in tumor and TME cells is a therapeutic option against GBM.

Action of Hyaluronic Acid as a Damage-Associated Molecular Pattern Molecule and Its Function on the Treatment of Temporomandibular Disorders.

The temporomandibular joint is responsible for fundamental functions. However, mechanical overload or microtraumas can cause temporomandibular disorders (TMD). In addition to external factors, it is known that these conditions are involved in complex biological mechanisms, such as activation of the immune system, activation of the inflammatory process, and degradation of extracellular matrix (ECM) components. The ECM is a non-cellular three-dimensional macromolecular network; its most studied components is hyaluronic acid (HA). HA is naturally found in many tissues, and most of it has a high molecular weight. HA has attributed an essential role in the viscoelastic properties of the synovial fluid and other tissues. Additionally, it has been shown that HA molecules can contribute to other mechanisms in the processes of injury and healing. It has been speculated that the degradation product of high molecular weight HA in healthy tissues during injury, a low molecular weight HA, may act as damage-associated molecular patterns (DAMPs). DAMPs are multifunctional and structurally diverse molecules that play critical intracellular roles in the absence of injury or infection. However, after cellular damage or stress, these molecules promote the activation of the immune response. Fragments from the degradation of HA can also act as immune response activators. Low molecular weight HA would have the ability to act as a pro-inflammatory marker, promoting the activation and maturation of dendritic cells, the release of pro-inflammatory cytokines such as interleukin 1 beta (IL-1ß), and tumor necrosis factor α (TNF-α). It also increases the expression of chemokines and cell proliferation. Many of the pro-inflammatory effects of low molecular weight HA are attributed to its interactions with the activation of toll-like receptors (TLRs 2 and 4). In contrast, the high molecular weight HA found in healthy tissues would act as an anti-inflammatory, inhibiting cell growth and differentiation, decreasing the production of inflammatory cytokines, and reducing phagocytosis by macrophages. These anti-inflammatory effects are mainly attributed to the interaction of high-weight HA with the CD44 receptor. In this study, we review the action of the HA as a DAMP and its functions on pain control, more specifically in orofacial origin (e.g., TMD).

GANT-61 Induces Autophagy and Apoptosis in Glioblastoma Cells despite their heterogeneity.

Glioblastoma (GBM) is the most common adult primary tumor of the CNS characterized by rapid growth and diffuse invasiveness into the brain parenchyma. The GBM resistance to chemotherapeutic drugs may be due to the presence of cancer stem cells (CSCs). The CSCs activate the same molecular pathways as healthy stem cells such as WNT, Sonic hedgehog (SHH), and Notch. Mutations or deregulations of those pathways play a key role in the proliferation and differentiation of their surrounding environment, leading to tumorigenesis. Here we investigated the effect of SHH signaling pathway inhibition in human GBM cells by using GANT-61, considering stem cell phenotype, cell proliferation, and cell death. Our results demonstrated that GANT-61 induces apoptosis and autophagy in GBM cells, by increasing the expression of LC3 II and cleaved caspase 3 and 9. Moreover, we observed that SHH signaling plays a crucial role in CSC phenotype maintenance, being also involved in the epithelial-mesenchymal transition (EMT) phenotype. We also noted that SHH pathway modulation can regulate cell proliferation as revealed through the analysis of Ki-67 and c-MYC expressions. We concluded that SHH signaling pathway inhibition may be a promising therapeutic approach to treat patients suffering from GBM refractory to traditional treatments.

Innovations in Curriculum Designs Do Not Guarantee Students' Patient-Centered Attitudes Running Title: Curricula and Patient-Centered Attitudes / Inovações no Desenho Curricular não Garantem Atitudes Centradas no Paciente entre os Estudantes

ABSTRACT Background Medical schools all around the world are engaged in curricular reforms aimed at fostering patient- and learner-centeredness, implementing curricular transformations in order to counterbalance the erosion of humanistic and professional values and the loss of idealism of recent graduate physicians. In Brazil, medical schools are facing the challenge of redesigning medical curricula towards more learner-centered and patient-centered approaches, stimulated by recent national medical education guidelines. However, desirable outcomes towards medical education have not been fully achieved. Aim To access medical students' attitudes and determine predictors of medical students' patient-centered attitudes among students from different curricular designs (traditional, innovative and advanced). Methods Medical students from 1st to 6th year from 21 Brazilian medical schools participating in the project for evaluating change and trends proposed by the Brazilian Association of Medical Education, with different stages of curricular designs (traditional, innovative and advanced), answered the Brazilian version of the Patient-Practitioner Orientation Scale (B-PPOS) and a questionnaire with curricular and sociodemographic variables. Results Brazilian medical students care more than they share information, power and responsibility (p < 0.001; d = 0.599). They are more concerned with the psychosocial context than with patient's perspective (p < 0.001; d = 0.797) and share more power and responsibility than understanding (p < 0.001, d = 0.455). Female gender (B = 0.180), students from public schools (B = 0.132), year of medical training (B = 0.021), preference for future medical practice in public services (B = 0.053) and extracurricular activities (B = 0.068) were predictors of patient-centered attitudes among medical students (p < 0.05). Meanwhile, the father's educational level and choice to study surgical specialties (p < 0.05) were predictors of less patient-centered attitudes among students. Different curricular designs were not associated with students' patient-centered attitudes (p > 0.05). Conclusion tant predictors of patient-centered attitudes among medical students. Further research should investigate the direct influence of faculty professionalism development programs on students' patient centered-attitudes.

Introdução Escolas médicas de todo o mundo estão engajadas em reformas curriculares com o objetivo de melhorar a centralidade do ensino no paciente e no aluno, implementando transformações curriculares a fim de contrabalançar a erosão dos valores humanísticos e profissionais, bem como a perda do idealismo de médicos recém-formados. Escolas médicas brasileiras encaram o desafio de redesenhar os currículos médicos em direção a abordagens mais centradas no paciente e no aluno, estimuladas pelas recentes diretrizes curriculares nacionais dos cursos de Medicina. Entretanto, os resultados desejados não têm sido totalmente alcançados. Objetivo Acessar as atitudes dos estudantes de Medicina e determinar preditores das atitudes mais centradas no paciente entre os estudantes de Medicina de diferentes desenhos de currículo (tradicional, inovador e avançado). Método Estudantes de Medicina do primeiro ao sexto ano de 21 escolas médicas brasileiras que participaram do projeto de avaliação de tendências de mudanças no curso de graduação nas escolas médicas brasileiras proposta pela Associação Brasileira de Educação Médica, com diferentes estágios de currículo (tradicional, inovador e avançado), responderam à versão brasileira da Escala de Orientação Médico-Paciente (EOMP) e a um questionário com variáveis sociodemográficas e curriculares. Resultados Estudantes de Medicina brasileiros cuidam mais do que compartilham informação, poder e responsabilidade (p < 0.001; d = 0.599). Cuidam mais do contexto psicossocial do que da perspectiva do paciente (p < 0.001; d = 0.797) e compartilham mais poder e responsabilidade do que entendimento (p < 0.001, d = 0.455). Gênero feminino (B = 0.180), estudantes de escolas médicas públicas (B = 0.132), ano de treinamento médico (B = 0.021), preferência por futura prática em serviços públicos (B = 0.053) e atividades extracurriculares (B = 0.068) foram preditores de atitudes mais centradas no paciente entre os estudantes de Medicina (p < 0.05). Diferentes desenhos curriculares não foram associados com atitudes mais centradas no paciente (p > 0.05). Conclusões Desenhos curriculares não predizem atitudes dos estudantes de Medicina. Ser mulher e frequentar uma escola médica pública foram importantes preditores de atitudes mais centradas no paciente entre os estudantes de Medicina.

Peri-implant status in partially edentulous individuals subjected to dental implant rehabilitation

Objective:Oral rehabilitation with dental implants has become a daily routine in dental clinics. However, peri-implant diseases can affect the tissues around dental implants over time. The aim of this study was to evaluate peri-implant health status in partially edentulous individuals rehabilitated with dental implants in comparison with either periodontally healthy individuals or those with periodontitis. Methods: Study participants were subjected to anamnestic questionnaires and full periodontal/ peri-implant examination. Twenty-five dental implant carriers (45% women; mean age, 57.2 years), 35 periodontally healthy individuals (28.6% women; mean age, 24.1 years), and 25 subjects with periodontitis (20% women; mean age, 47.5 years) were included. Those in the healthy and periodontitis groups had no dental implants. Significant differences were analyzed by Wilcoxon, Chi-square, and Kruskal-Wallis tests. Results: The dental implant carriers had an average of 3.9 implants with an average time of 5.1 years since insertion. Peri-implant disease was detected in 75% of individuals in the Dental Implant Carriers group (70% had peri-implant mucositis). Dental implants presented probing depths and clinical attachment levels significantly higher when compared with those of unaffected teeth from the same individuals (pd"0.004), or with teeth from periodontally healthy individuals (p<0.0001). Although implants presented less dental biofilm, they presented higher percentages of bleeding on probing compared with unaffected teeth in the same individuals (p=0.002) and with teeth in periodontally healthy individuals (p<0.0001). The population studied had a relatively high prevalence of peri-implant disease. Conclusion: It is possible to verify that the clinical characteristics of the peri-implant tissues resembled those of individuals with periodontitis.

Objetivo: A reabilitação oral com o emprego de implantes dentários é uma rotina na clínica odontológica. Entretanto, as doenças peri-implantares podem se estabelecer ao redor dos implantes dentários com o passar do tempo. O objetivo deste estudo foi avaliar a saúde peri-implantar de indivíduos submetidos a tratamento com implantes dentários comparados a indivíduos com saúde periodontal e periodontite. Métodos : Os participantes do estudo foram submetidos a questionários anamnésicos e exame periodontal/ peri-implantar completo. Foram incluídos 20 indivíduos Portadores de Implantes Dentários (45% mulheres; idade média de 57,2 anos), 35 indivíduos com Saúde Periodontal (28,6% mulheres; idade média de 24,1 anos) e 25 indivíduos com Periodontite (20% mulheres; idade média de 47,5 anos). Estes últimos não possuíam implantes dentários. Diferenças significativas foram analisadas através dos testes Wilcoxon, Qui-quadrado e Kruskal- allis. Resultados : O grupo Portadores de Implantes Dentários possuía uma média de 3,9 implantes com tempo médio de instalação de 5,1 anos. Doença peri-implantar foi detectada em 75% dos indivíduos com implantes dentários, sendo 70% mucosite peri-implantar. Implantes dentários apresentaram profundidade de sondagem e nível clínico de inserção significativamente maior quando comparado a dentes dos mesmos indivíduos (p d" 0,004), ou de indivíduos com saúde periodontal (p < 0,0001). Apesar de implantes apresentarem menor acúmulo de biofilme dental, apresentaram maiores porcentuais de sangramento à sondagem comparado a dentes (nos mesmos indivíduos; p = 0,002) e a indivíduos com saúde periodontal (p < 0,0001). Conclusão : A população estudada apresenta uma relativamente alta prevalência de doença peri-implantar. Além disto, foi possível constatar que as características clínicas do tecido peri-implantar se assemelharam àquelas de indivíduos com periodontite.

MicroRNAs, Hypoxia and the Stem-Like State as Contributors to Cancer Aggressiveness.

MicroRNAs (miRNAs) are small non-coding RNA molecules that play key regulatory roles in cancer acting as both oncogenes and tumor suppressors. Due to their potential roles in improving cancer prognostic, predictive, diagnostic and therapeutic approaches, they have become an area of intense research focus in recent years. Several studies have demonstrated an altered expression of several miRNAs under hypoxic condition and even shown that the hypoxic microenvironment drives the selection of a more aggressive cancer cell population through cellular adaptations referred as the cancer stem-like cell. These minor fractions of cells are characterized by their self-renewal abilities and their ability to maintain the tumor mass, suggesting their crucial roles in cancer development. This review aims to highlight the interconnected role between miRNAs, hypoxia and the stem-like state in contributing to the cancer aggressiveness as opposed to their independent contributions, and it is based in four aggressive tumors, namely glioblastoma, cervical, prostate, and breast cancers.

Glioblastoma Therapy in the Age of Molecular Medicine.

Glioblastoma (GBM) is the most common and fatal primary malignant brain tumor. Despite advances in the understanding of the biology of gliomas, little has changed in the treatment of these tumors in the past decade. Phase III clinical trials showed no benefit for the use of bevacizumab in newly diagnosed patients, leading to a renewed search for new antiangiogenic drugs, as well as immunotherapeutic approaches, including checkpoint inhibitors, chimeric antigen receptor T cells, and intracerebral CpG-oligodeoxynucleotides. The emerging role of infiltrating microglia and macrophages, and of metabolic alterations, is also being taken into account in preclinical research and drug development. In this review, we discuss progress in the search for new therapeutic strategies, particularly approaches focusing on the tumor microenvironment.

In vitro and in silico validation of CA3 and FHL1 downregulation in oral cancer.

BACKGROUND: Aberrant methylation is a frequent event in oral cancer. METHODS: In order to better characterize these alterations, a search for genes downregulated by aberrant methylation in oral squamous cell carcinoma (OSCC) was conducted through the mining of ORESTES dataset. Findings were further validated in OSCC cell lines and patients' samples and confirmed using TCGA data. Differentially expressed genes were identified in ORESTES libraries and validated in vitro using RT-PCR in HNSCC cell-lines and OSCC tumor samples. Further confirmation of these results was performed using mRNA expression and methylation data from The Cancer Genome Atlas (TCGA) data. RESULTS: From the set of genes selected for validation, CA3 and FHL1 were downregulated in 60% (12/20) and 75% (15/20) of OSCC samples, respectively, and in HNSCC cell lines. The treatment of cell lines JHU-13 and FaDu with the demethylating agent 5'-aza-dC was efficient in restoring CA3 and FHL1 expression. TCGA expression and methylation data on OSCC confirms the downregulation of these genes in OSCC samples and also suggests that expression of CA3 and FHL1 is probably regulated by methylation. The downregulation of CA3 and FHL1 observed in silico was validated in HNSCC cell lines and OSCC samples, showing the feasibility of integrating different datasets to select differentially expressed genes in silico. CONCLUSIONS: These results showed that the downregulation of CA3 and FHL1 data observed in the ORESTES libraries was validated in HNSCC cell lines and OSCC samples and in a large cohort of samples from the TCGA database. Moreover, it suggests that expression of CA3 and FHL1 could probably be regulated by methylation having an important role the oral carcinogenesis.

miRNAs: Important Targets for Oral Cancer Pain Research.

Pain is a symptom shared by an incredible number of diseases. It is also one of the primary conditions that prompt individuals to seek medical treatment. Head and neck squamous cell carcinoma (HNSCC) corresponds to a heterogeneous disease that may arise from many distinct structures of a large, highly complex, and intricate region. HNSCC affects a great number of patients worldwide and is directly associated with chronic pain, which is especially prominent during the advanced stages of oral squamous cell carcinoma (OSCC), an anatomical and clinical subtype that corresponds to the great majority oral cancers. Although the cellular and molecular bases of oral cancer pain have not been fully established yet, the results of recent studies suggest that different epigenetic mechanisms may contribute to this process. For instance, there is strong scientific evidence that microRNAs (miRNAs), small RNA molecules that do not encode proteins, might act by regulating the mechanisms underlying cancer-related pain. Among the miRNAs that could possibly interfere in pain-signaling pathways, miR-125b, miR-181, and miR-339 emerge as some of the most promising candidates. In fact, such molecules apparently contribute to inflammatory pain. Moreover, these molecules possibly influence the activity of endogenous pain control systems (e.g., opioidergic and serotonergic systems), which could ultimately result in peripheral and central sensitization, central nervous system (CNS) phenomena innately associated with chronic pain. This review paper focuses on the current scientific knowledge regarding the involvement of miRNAs in cancer pain, with special attention dedicated to OSCC-related pain.

Consumo de álcool entre pescadores: uma revisão integrativa / Consumo de alcohol entre los pescadores: una revisión integradora / Alcohol consumption among fishermen: an integrative review

Objective: to summarize the scientific literature regarding the consumption of alcohol among fishermen. Method: Integrative review performed by literature in CAPES databases, ScieLO and LILACS, through data collection in the period from March to April 2014. Results: Alcohol consumption was evidenced as an usual activity among fishermen, emphasizing its association with religion, long working hours, lack of maximum levels of weekly satisfactory consumption of alcohol, occupational accidents, cardiovascular and sexually transmitted diseases, and hyperlipidemia. Conclusion: The consumption of alcohol is a common practice among fishermen and despite all the studies pointing to this practice, there is no evidence of real alternatives related to promotion, prevention and healthcare of fishermen in relation to alcohol consumption.

Objetivo: sintetizar a produção científica quanto ao consumo de álcool entre pescadores. Método: Revisão integrativa realizada por meio de levantamento bibliográfico nas bases de dados CAPES, ScieLO e LILACS, com período de coleta de dados entre março e abril de 2014. Resultados: Evidenciou-se o consumo de álcool como atividade habitual entre pescadores, salientando a associação com religião, longas jornadas de trabalho, desconhecimento dos níveis máximos de consumo de álcool semanais satisfatórios, acidentes ocupacionais, doenças sexualmente transmissíveis e cardiovasculares, e hiperlipidemia. Conclusão: O consumo de álcool é uma prática comum entre os pescadores e apesar de todos os estudos apontarem para essa prática, não há evidências de alternativas reais relacionadas a promoção, prevenção e cuidado da saúde de pescadores no que tange ao consumo de álcool.

Objetivo: para resumir la literatura científica en relación con el consumo de alcohol entre los pescadores. Método: Revisión integrada realizada por la literatura en las bases de datos de la CAPES, SciELO y LILACS, con período de recolección de los datos de marzo a abril de 2014. Resultados: Se evidenció el consumo de alcohol como una actividad habitual entre los pescadores, haciendo hincapié en su asociación con la religión, largas horas de trabajo, la falta de niveles máximos de consumo de alcohol semanal satisfactorios, accidentes de trabajo, transmisibles y cardiovascular sexual, y la hiperlipidemia. Conclusión: El consumo de alcohol es una práctica común entre los pescadores y a pesar de todos los estudios que apuntana esta práctica, no hay pruebas de alternativas reales relacionados con los pescadores de promoción, prevención y atención de la salud en relación con el consumo de alcohol.

Assistência de enfermagem ao paciente oncológico hospitalizado: diagnósticos e intervenções relacionadas às necessidadespsicossociais e psicoespirituais / Nursing care in oncology hospitalized patients: diagnosis andinterventions related to psychosocial and psycospiritual needs / Asistencia de enfermería al paciente oncológico hospitalizado:diagnósticos e intervenciones relacionadas a las necesidades psicosocialesy psicoespirituales

Objective: This study aims at identifying the diagnosis and nursing interventions about psychosocial and psycospiritual needs of oncology patients. Method: Qualitative research, which setting was a care oncology unit. Carried out a collecting data through a structured instrument, from information contained in nursing records. Results: The diagnosis identified is concentrated in the domains of Self-perception, roles and relationship, total confrontation to stress, comfort and Principles of life. Nursing interventions carried out it has been highlighted the following: self-perception improvement, hope promoting, confrontation improvement, presence, self-esteem strengthen, family process maintenance, socialization improvement, safety increasing, emotional support, listing actively, spiritual support, body image improvement and painkillers administration. Conclusion: Is imperative to understand the impact caused by cancer, because such understanding enables the establishment of diagnosis, as well as, proper nursing interventions at the moment experienced.

Objetivo: Identificar os diagnósticos e intervenções de enfermagem acerca das necessidades psicossociais e psicoespirituais de pacientes oncológicos. Método: Pesquisa qualitativa, realizada em uma unidade de internação oncológica com dados de seis prontuários. A coleta dos dados ocorreu por meio de um instrumento estruturado, a partir das informações contidas nos registros de enfermagem. Resultados: Os diagnósticos identificados concentraram-se nos domínios de Autopercepção, Papéis e relacionamento, Enfrentamento total ao estresse, Conforto e Princípios da vida. Evidenciaram-se as intervenções de enfermagem: melhora da autopercepção, promoção de esperança, melhora do enfrentamento, presença, fortalecimento da autoestima, manutenção do processo familiar, melhora da socialização, aumento da segurança, apoio emocional, escutar ativamente, apoio espiritual, melhoria da imagem corporal e administração de analgésico. Conclusão: É imperativo compreender o impacto causado pelo câncer, pois tal entendimento possibilita o estabelecimento de diagnósticos e de intervenções de enfermagem adequadas ao momento vivido.

Objetivo: Identificar los diagnósticos e intervenciones de enfermería acerca de las necesidades psicosociales y psicoespirituales de pacientes oncológicos. Método: Investigación cualitativa, cuyo escenario fue una unidad de internación oncológica en seis prontuarios. La colecta de los datos ocurrió por medio de un instrumento estructurado, a partir de las informaciones contenidas en el registro de enfermería. Resultados:Los diagnósticos identificados se concentran en los dominios de Autopercepción, Papeles y relacionamiento, Enfrentamiento total al estrés, Conforto y Principios de la vida. Evidenciaron las intervenciones de enfermería: mejoría de la autopercepción, promoción de esperanza, mejoría del enfrentamiento, presencia, fortalecimiento de la autoestima, manutención del proceso familiar, mejoría de la socialización, aumento de la seguridad, apoyo emocional, escuchar activamente, apoyo espiritual, mejoría de la imagen corporal y administración de analgésico. Conclusión:Es imperativo comprender el impacto causado por el cáncer, pues tal entendimiento posibilita el establecimiento de diagnósticos, bien como, la realización de intervenciones de enfermería adecuadas al momento vivido.

Gliomas and the vascular fragility of the blood brain barrier.

Astrocytes, members of the glial family, interact through the exchange of soluble factors or by directly contacting neurons and other brain cells, such as microglia and endothelial cells. Astrocytic projections interact with vessels and act as additional elements of the Blood Brain Barrier (BBB). By mechanisms not fully understood, astrocytes can undergo oncogenic transformation and give rise to gliomas. The tumors take advantage of the BBB to ensure survival and continuous growth. A glioma can develop into a very aggressive tumor, the glioblastoma (GBM), characterized by a highly heterogeneous cell population (including tumor stem cells), extensive proliferation and migration. Nevertheless, gliomas can also give rise to slow growing tumors and in both cases, the afflux of blood, via BBB is crucial. Glioma cells migrate to different regions of the brain guided by the extension of blood vessels, colonizing the healthy adjacent tissue. In the clinical context, GBM can lead to tumor-derived seizures, which represent a challenge to patients and clinicians, since drugs used for its treatment must be able to cross the BBB. Uncontrolled and fast growth also leads to the disruption of the chimeric and fragile vessels in the tumor mass resulting in peritumoral edema. Although hormonal therapy is currently used to control the edema, it is not always efficient. In this review we comment the points cited above, considering the importance of the BBB and the concerns that arise when this barrier is affected.

Methylation pattern of IFNG in periapical granulomas and radicular cysts.

INTRODUCTION: Interferon-γ plays an important role in the pathogenesis of periapical lesions, and the methylation of IFNG has been associated with transcriptional inactivation. The purpose of the present study was to investigate IFNG promoter methylation in association with gene transcription and protein levels in periapical granulomas and radicular cysts. METHODS: Methylation-specific polymerase chain reaction was used to assess the DNA methylation pattern of the IFNG gene in 16 periapical granulomas and 13 radicular cyst samples. The transcription levels of IFNG mRNA were verified by quantitative real-time polymerase chain reaction, and protein expression was evaluated by immunohistochemistry. RESULTS: All the periapical lesion samples exhibited partial or total methylation of the IFNG gene. In addition, an increased methylation profile was found in radicular cysts compared with periapical granulomas. Increased IFNG mRNA expression was observed in the partially methylated periapical lesion samples relative to the samples that were completely methylated. CONCLUSIONS: The present study provides the first evidence of the possible impact of IFNG methylation on IFNG transcription in periapical lesions.

Assessment of TP53 mutations in benign and malignant salivary gland neoplasms.

Despite advances in the understanding of the pathogenesis of salivary gland neoplasms (SGN), the molecular pathways associated with enhanced tumor growth and cell survival remain to be established. The aim of the present study was to investigate whether TP53 mutations are relevant to SGN pathogenesis and if they impact on p53 protein expression. The study included 18 benign and 18 malignant SGN samples. Two polymorphic microsatellite markers at the TP53 genetic locus were chosen to assess loss of heterozygosity (LOH) in the samples that had matched normal DNA. The TP53 exons 2-11 were amplified by PCR, and all of the products were sequenced. Reverse transcription-PCR of the TP53 open reading frame (ORF) was carried out in the samples that had fresh tissue available, and immunohistochemistry for the p53 protein was performed in all samples. TP53 LOH was only found in two pleomorphic adenomas. We found two missense mutations in exon 7 (one in a pleomorphic adenoma and the other in a polymorphous low grade adenocarcinoma), another in exon 8 (in a carcinoma ex pleomorphic adenoma) and a fourth missense mutation in exon 10 (in a mucoepidermoid carcinoma). In addition, a nonsense mutation was found in exon 8 of an adenoid cystic carcinoma. Several intronic and exonic SNPs were detected. Although almost all of the malignant samples were immunopositive for p53, approximately 37% of the benign samples were positive, including the sample harboring the missense mutation and one of the samples that showed LOH. The complete TP53 ORF could be amplified in all samples analyzed, including the IHC negative samples, the samples showing LOH and one sample displaying a missense mutation. In summary, our results show that TP53 mutations are not a frequent event in SGN and that p53 immunopositivity might not be associated with sequence mutations in SGN.

Evaluation of MAGE A1 in oral squamous cell carcinoma.

MAGE A1 is a cancer testis antigen (CTA) described in a variety of human cancers. CTAs exhibit a highly restricted tissue expression and by virtue of their immunogenic potential, these genes are promising target molecules for cancer vaccines. DNA hypomethylation is associated with gene regulation in several types of tumours. The aim of this project was to identify the presence of MAGE A1 in oral squamous cell carcinoma (OSCC) samples and to investigate the hypomethylation profile of CpG islands situated in the promoter region of this gene. The expression of MAGE A1 in OSCC and healthy oral mucosal samples was determined by real-time quantitative and conventional endpoint PCR and also by immunohistochemistry staining. In addition, to investigate the hypomethylation profile of promoter MAGE A1 CpG islands, we performed bisulphite sequencing. Real-time quantitative and endpoint PCR assays demonstrated a lower level of MAGE A1 transcription. Endpoint PCR showed expression of MAGE A1 in 10% (2/20) of OSCCs. Sodium bisulphite sequencing analysis of MAGE A1 CpG islands did not reveal a difference between OSCC and normal oral mucosal samples. We further assessed MAGE A1 protein immunoexpression and found 80% (16/20) of immunopositivity in OSCCs. We did not observe a correlation between the presence of MAGE A1 protein and lower levels of transcripts. Identification of MAGE A1 protein in OSCCs and absence of immunoexpression in normal oral mucosa support the idea that this protein can be used as a biomarker for detection of OSCC; however, it is not associated with hypomethylation or high expression of the MAGE A1 gene.

Claudin-7 down-regulation is an important feature in oral squamous cell carcinoma.

AIMS: Claudins, a large family of essential tight junction (TJ) proteins, are abnormally regulated in human carcinomas, especially claudin-7. The aim of this study was to investigate claudin-7 expression and alterations in oral squamous cell carcinoma (OSCC). METHODS AND RESULTS: Expression of claudin-7 was analysed in 132 cases of OSCC organized in a tissue microarray. Claudin-7 mRNA transcript was evaluated using real-time polymerase chain reaction and the methylation status of the promoter was also assessed. Claudin-7 was negative in 58.3% of the cases. Loss of claudin-7 protein expression was associated with recurrence (P = 0.019), tumour size (P = 0.014), clinical stage of OSCC (P = 0.055) and disease-free survival (P = 0.015). Down-regulation of the claudin-7 mRNA transcripts was observed in 78% of the cases, in accordance with immunoexpression. Analysis of the methylation status of the promoter region of claudin-7 revealed that treatment of O28 cells (that did not express claudin-7 mRNA transcripts) with 5-Aza-2'-Deoxycytidine (5-Aza-dC) led to the re-expression of claudin-7 mRNA transcript. CONCLUSION: Loss of claudin-7 expression is associated with important subcellular processes in OSCC with impact on clinical parameters.

Caracterização dos partos e nascidos vivos de mães residentes no município de Sairé/PE, 2008 / Characteristics of births and live births of mothers resident in the municipality of Sairé / PE, 2008

O Sistema de Informação sobre Nascidos Vivos (SINASC) é um instrumento que contém importantes informações que orienta a tomada de decisão para gestores municipais. Neste sentido, essa pesquisa teve como objetivo caracterizar os partos e nascidos vivos de mães residentes em Sairé/PE, 2008. A população do estudo foi constituída de 179 partos de nascidos vivos das mães residentes no município de Sairé-PE no ano de 2008. Tratou-se de um estudo epidemiológico de corte transversal. As vaiáveis relacionadas ao parto foram tipo e local do parto e as relacionadas ao nascido vivo foram tipo e duração da gestação, peso ao nascer, apgar no 1º e 5º minuto e anomalias congênitas. Os principais resultados encontrados foram: 77 por cento dos partos ocorreram fora do município, 55,9 por cento do total de partos foram vaginais, 8,9 por cento apresentaram baixo peso ao nascer, o apgar se manteve baixo em 1,6 por cento dos casos e 0,5 por cento dos recém nascidos apresentaram anomalias congênitas. Conclui-se dessa forma que os partos ocorridos fora do município de residência da mãe em grande parte das vezes não apresentam situação de risco elevado para a criança e que poderiam ter ocorrido no nível local, chamando a atenção a responsabilidade dos gestores para a garantia de acesso oportuno, referenciando quando necessário e respeitando o processo de regionalização.

Identificação de genes epigeneticamentente inativados em carcinoma epidermóide de cavidade oral / Identification of epigenetically inactivated genes in oral carcinoma

O câncer oral está entre os dez sítios mais acometidos por neoplasia maligna na população brasileira. Muitos casos são diagnosticados em fase avançada, resultando no aumento da morbidade e na diminuição da sobrevida. Esforços intensos foram empregados ao longo dos anos, objetivando esclarecer seu comportamento clínico e biológico. No entanto, apesar das inúmeras pesquisas realizadas no campo da biologia molecular, os mecanismos genéticos e epigenéticos envolvidos no câncer oral, ainda não foram completamente elucidados. Recentemente, os eventos epigenéticos passaram a receber uma atenção especial por sua relação com a expressão gênica. Na carcinogênese oral, a metilação (o evento epigenético mais freqüente) tem sido bastante descrita, presente na região promotora de importantes genes supressores tumorais. Este projeto tem como principal objetivo a identificação de genes com expressão gênica reduzida em virtude de eventos epigenéticos em amostras de CE da cavidade oral (baseado nos dados de ORESTES), com o intuito de auxiliar a compreensão dos eventos biológicos envolvidos nessa doença. Para identificar genes com expressão alterada entre os tumores da região da cabeça e pescoço e os seus correspondentes normais, foram analisados os dados disponíveis no NCBI gerados a partir de bibliotecas de ORESTES, oriundas destes tecidos. Cerca de quatorze genes que se apresentaram hipoexpressos através de análise de bioinformática foram selecionados. A expressão gênica foi avaliada através de RT-PCR nos dez primeiros genes, utilizando linhagens celulares tumorais de cabeça e pescoço. Dois deles apresentaram-se hipoexpressos: o gene CA3 na linhagem O13 e o gene FHL1 na linhagem FaDu. O tratamento dessas duas linhagens tumorais (O13 e FaDu) com o 5' aza dC, um conhecido agente desmetilante, foi capaz de promover a reexpressão destes dois genes. Estes genes foram então selecionados para ter sua expressão diferencial avaliada por meio de PCR em tempo real, em 20 amostras de pacientes portadores de CE primário de cavidade oral. Observou-se que o CA3 e o FHL1 apresentaram uma diminuição da expressão em 60% (12/20) e 75% (15/20) das amostras estudadas respectivamente, em relação às amostras normais. Durante as análises de seqüenciamento pós-tratamento com bissulfito de sódio do DNA de três linhagens celulares tumorais (O13, FaDu e O28) foi observado que o gene CA3 exibiu altos níveis de metilação na ilha CpG, presente em sua região promotora, tanto na linhagem na qual se encontrava hipoexpresso, quanto na linhagem onde apresentava expressão normal. O gene FHL1 nesta mesma análise apresentou a maioria dos dinucleotídeos CpGs presentes em sua ilha CpG, desmetilada. Este trabalho permitiu demonstrar que a estratégia de escolha de genes a partir a análise das bibliotecas de ORESTES foi adequada, pois genes selecionados para validação, apresentaram uma diminuição de expressão nas linhagens celulares e amostras tumorais analisadas. Apesar do 5´-aza-dC ter sido capaz de promover o aumento de expressão do CA3 e do FHL1, não foi possível estabelecer uma correlação entre a redução no nível de expressão destes genes e a presença de hipermetilação em suas regiões promotoras.

The oral cavity is among the ten most common sites for malignant neoplasm in the Brazilian population. Most cases are diagnosed at advanced stage, resulting in increase of morbidity and decrease of overall survival. Many efforts have been made during the years, to understand its clinical and biological behavior. However, despite extensive research in the molecular biology field, genetic and epigenetic mechanisms involved in oral cancer carcinogenesis, have not yet been completely elucidated. Recentely, epigenetic events have received special attention due to their correlation with gene expression. In oral carcinogenesis, methylation (the main epigenetic event) has been described as present at the promoter region of important tumour suppressor genes. The aim of this project is to identify genes showing downregulation by epigenetic events in oral cancer samples (based on ORESTES data), and improve understanding of biological events involved in this disease. To identify genes with alterated expression in head and neck tumours, data available at NCBI (generated by ORESTES library derived from these tissues) were analyzed and compared to their normal counterparts. Fourteen genes that showed hypoexpression by bioinformatics analysis were selected. Gene expression was evaluated by RT-PCR in the first ten genes in head and neck tumour cell lines. Two of these showed hypoexpression: CA3 in O13 cell line and FHL1 in Fadu cell line. Treatment of these two tumour cell lines with 5'-aza-dC, a known demethylant agent, was capable of promoting reexpression of these two genes. Subsequently, these two genes were selected for a differential expression evaluation by real time PCR in 20 primary OSCC patient samples. CA3 and FHL1 were found to be underexpressed in 60% (12/20) and 75% (15/20) of the samples analyzed, respectively, compared to normal samples. Sodium bisulfite sequencing analysis of three tumour cell lines (FaDu, O13 e O28) demonstrated high levels of methylation in CpG island situated at promotor site of CA3 gene, in both hypoexpressed and normally expressed cell lines. In this same analysis FHL1 showed most of CpGs situated in its CpG island were demethylated. This research demonstrated that the strategy to choose genes from ORESTES library was adequate, because the genes selected for validation showed low expression levels in cell lines and tumour oral samples. Although 5´-aza-dC was able to promote a CA3 and FHL1 expression increase, it was not possible to establish a correlation between expression level decrease of these genes and the presence of hypermethylation in their promoter sites

A participação do enfermeiro na implantação do Programa de Saúde da Família em Belo Horizonte / The nurse's participation in implementing the Family Health Program (PSF) in Belo Horizonte / La participación del enfermero en la implantación del Programa de Salud de la Familia (PSF) en Belo Horizonte

Este estudo analisa a participação do enfermeiro na implantação do Programa de Saúde da Família (PSF) em Belo Horizonte, visando a compreender sua inserção e expectativas como agente na organização dos serviços de saúde e superação dos problemas encontrados na implantação do programa em uma grande metrópole. Utiliza uma abordagem qualitativa, com base no Materialismo Histórico Dialético. Onze enfermeiras, inseridas no PSF, foram os sujeitos da pesquisa. Os dados foram coletados através de entrevista semi-estruturada e submetidos ao tratamento da Análise do Discurso. Os resultados demonstram que o enfermeiro está envolvido com a Saúde da Família e desempenha um papel significativo desde a implantação do Programa de Agentes Comunitários de Saúde, e que sua inserção no PSF é favorecida tanto por sua formação generalista como por sua experiência no planejamento, execução e avaliação das ações de saúde. Fatores relacionados às condições de trabalho do enfermeiro, como inadequação do ambiente, salário e tratamento diferenciado em relação ao médico nas atividades de equipe e sobrecarga de tarefas e responsabilidades, destacam-se como dificultadores na implantação do PSF em Belo Horizonte.

This study analyzes the nurse's participation in implementing the Family Health Program (PSF) in Belo Horizonte and aims at understanding their inclusion and expectations as an agent in the organization of health services and in overcoming problems found in the implementation of the program in a large city. A qualitative approach is used based on dialectic historic materialism. Eleven nurses participating in the PSF were the subjects of the research. Data was collected by means of a semi-structured interview and submitted to a discourse analysis treatment. The results demonstrate that the nurse has been involved with family health and playing a significant role ever since the implementation of the Community Health Agents Program (PACS) and that their inclusion in the PSF is favored both by their generalist background and their experience in planning, executing and evaluating health actions. Factors related to the nurse's work conditions, such as inadequacy of the environment, differentiated salary and treatment in relation to the doctor in team activities and the overload of tasks and responsibilities stand out as difficulty factors in implementing the PSF in Belo Horizonte.

Este estudio analiza la participación del enfermero en la implantación del programa de salud de la familia (psf) en Belo Horizonte buscando entender su inserción y expectativas como agente que contribuya para la organización de los servicios de salud y para la superación de los problemas y de las contradicciones encontrados en la implantación del psf en una gran metrópoli. Se utiliza abordaje cualitativo basado en el materialismo histórico dialéctico. Once enfermeras de las unidades básicas de la salud fueron los sujetos de la investigación. Se colectaron los datos a través de entrevistas semiestructuradas y se los sometió al tratamiento del análisis del discurso. Los resultados demuestran que el enfermero está involucrado con la salud de la familia y desempeña un papel significativo desde la implantación del programa de agentes comunitarios de la salud (pacs), y que su inserción en el psd se favorece tanto por su formación generalista como por su experiencia en el planeamiento, ejecución y evaluación de las acciones de la salud. Factores relacionados a las condiciones de trabajo del enfermero, como falta de adecuación del ambiente, sueldo y tratamiento diferenciado con relación al médico en las actividades de equipo y sobrecarga de tareas y responsabilidades, se destacan como dificultadores en la implantación del psf en Belo Horizonte.