Germline mutations in cancer predisposition genes among pediatric patients with cancer and congenital anomalies.

BACKGROUND: Childhood cancer has a poorly known etiology, and investigating the underlying genetic background may provide novel insights. A recognized association exists between non-chromosomal birth defects and childhood cancer susceptibility. METHODS: We performed whole-exome sequencing and chromosomal microarray analysis in a cohort of childhood cancer (22 individuals, 50% with congenital anomalies) to unravel deleterious germline variants. RESULTS: A diagnostic yield of 14% was found, encompassing heterozygous variants in bona fide dominant Cancer Predisposition Genes (CPGs). Considering candidate and recessive CPGs harboring monoallelic variants, which were also deemed to play a role in the phenotype, the yield escalated to 45%. Most of the deleterious variants were mapped in genes not conventionally linked to the patient's tumor type. Relevant findings were detected in 55% of the syndromic individuals, mostly variants potentially underlying both phenotypes. CONCLUSION: We uncovered a remarkable prevalence of germline deleterious CPG variants, highlighting the significance of a comprehensive genetic analysis in pediatric cancer, especially when coupled with additional clinical signs. Moreover, our findings emphasized the potential for oligogenic inheritance, wherein multiple genes synergistically increase cancer risk. Lastly, our investigation unveiled potentially novel genotype-phenotype associations, such as SETD5 in neuroblastoma, KAT6A in gliomas, JAG1 in hepatoblastomas, and TNFRSF13B in Langerhans cell histiocytosis. IMPACT: Novel gene-phenotype associations and candidate genes for pediatric cancer were unraveled, such as KAT6A in gliomas, SETD5 in neuroblastoma, JAG1 in hepatoblastomas, and TNFRSF13B in Langerhans cell histiocytosis. Our analysis revealed a high frequency of deleterious germline variants, particularly in cases accompanied by additional clinical signs, highlighting the importance of a comprehensive genetic evaluation in childhood cancer. Our findings also underscored the potential for oligogenic inheritance in pediatric cancer risk. Understanding the cancer etiology is crucial for genetic counseling, often influencing therapeutic decisions and offering valuable insights into molecular targets for the development of oncological therapies.

Microbiological analysis of bacterial sealing of internal conical implants with different taper angles

Abstract The present study evaluated the effect of the taper angle of different internal conical connection implants and cyclic loading on the implant-abutment bacterial seal. A total of 96 implant-abutment sets were divided into eight groups. Four groups of different taper degrees with cyclic mechanical loading of 500,000 cycles per sample, with a 120-N load at 2 Hz before analysis [16DC (16-degree, cycled), 11.5DC (11.5-degree, cycled), 3DC (3- degree, cycled) and 4DC (4- degree, cycled)] were compared to four control groups without cyclic loading [16D (16-degree), 11.5D (11.5-degree), 3D (3-degree), and 4D (4-degree)]. Microbiological analysis was performed by immersing all samples in a suspension containing Escherichia coli and incubating them at 37°C. After 14 days, the presence of bacterial seals was evaluated. Fisher-Freeman-Halton exact tests and binomial tests were performed (5% significance level). The groups showed significant differences in bacterial seal, and mechanical load cycling improved the bacterial seal in the 3DC group. In all other groups, no significant differences in bacterial seal were found between cycled and uncycled samples. To conclude, the internal conical connection with a 3-degree taper angle showed better results than the other connection with different angles when subjected to load cycling. However, none of the angles tested were fully effective in sealing the implant-abutment interface.

Endoscopic submucosal dissection: a country dissemination experience and outcomes.

OBJECTIVE: An increasing use of endoscopic submucosal dissection (ESD) has been reported in Western countries, although some differences in training schemes and outcomes have been described. We aimed to report the training model, implementation, and outcomes of ESD in Portugal. METHODS: All endoscopists trained at our center from our country (n = 9) were invited to a survey regarding: (a) training period; (b) ESD outcomes and (c) implementation of ESD in each respective center. RESULTS: All endoscopists completed the survey. Learning ESD was centered on human ESD assistance in a high-volume center during a median time of 6 months and complemented mainly by hands-on courses (89%). During the surveyed period, a total of 1229 ESD were performed, mostly in gastric locations (74%). Median complete R0 and curative resection rate were 92% (IQR, 81-96.8) and 87% (IQR, 74-93.3), respectively, and median perforation rate was 0.89% (IQR, 0.25-6.22). The main limitations encountered during the implementation of ESD were related to the lack of initial mentoring or insufficient expertise to progress to more difficult lesions. CONCLUSION: Learning ESD through participation in hands-on courses and visiting high-volume centers seems to be adequate to achieve a good competence at the initial stage of ESD, which in fact is in consonance with the European Society of Gastrointestinal Endoscopy recommendations. However, mentoring is essential for technical progression, and this represents the fundamental barrier during the adoption of ESD, which may be overcome by increasing hands-on training in animal or artificial simulators, but preferably with the implementation of a structured training program.

Colorectal Screening Program in Northern Portugal: First Findings.

INTRODUCTION: In Portugal, a colorectal cancer screening program based on faecal immunochemical test followed by colonoscopy was shown to be cost-effective for individuals between 50 and 74 years old. We report the first findings of the implementation of a population-based program In Northern Portugal. MATERIAL AND METHODS: In the pilot phase, eligible subjects were allocated either to a direct mailing invitation or to primary care centers. In the first year of program implementation, we assessed the uptake rate, the faecal immunochemical test -positivity rate, the diagnostic yield of advanced neoplasia, and the quality parameters for post-faecal immunochemical test + colonoscopy. RESULTS: We invited 100 501 eligible subjects (49% male with a median age of 55 years). Of these, 5228 participated in the pilot phase and 95 273 participated in the first year of the program. In the first year of the program, the adherence was 29%, with a positivity rate of 5% and a 60% compliance to colonoscopy. The faecal immunochemical test-detection rate of advanced neoplasia was 0.35/1000 subjects, and the positive predictive value at post- faecal immunochemical test + colonoscopy was 44% and 2% for advanced adenoma and invasive cancer, respectively. No major adverse events were reported after colonoscopy. DISCUSSION: The suboptimal adherence to faecal immunochemical test and post-faecal immunochemical test + colonoscopy remains the most urgent step to be addressed. CONCLUSION: A centralized invitation system based on direct mailing was feasible and both colonoscopy quality and diagnostic yield were adequate antecipating the success of the programme.

Introdução: Em Portugal, foi demonstrado que o rastreio do cancro colo-rectal, baseado no teste imunoquímico fecal seguido de colonoscopia, seria custo-efetivo para indivíduos entre os 50 e 74 anos. Neste artigo reportamos os primeiros resultados da implementação do programa de base populacional na região Norte de Portugal. Material e Métodos: Na fase piloto, os sujeitos elegíveis foram alocados a dois métodos, por convite através do correio ou por meio de entrega direta nos centros de saúde. No primeiro ano de implementação do programa avaliámos a taxa de adesão, a taxa de positividade de teste imunoquímico fecal, o rendimento diagnóstico de neoplasia avançada e os parâmetros de qualidade da colonoscopia pós- teste imunoquímico fecal positivo. Resultados: Foram convidados 100 501 indivíduos elegíveis (49% do sexo masculino com idade mediana de 55 anos). Destes, 5228 participaram na fase piloto e 95 273 participaram no primeiro ano do programa. No primeiro ano do programa, a adesão foi de 29%, com taxa de positividade de 5% e adesão de 60% às colonoscopias. A taxa de deteção de teste imunoquímico fecal de neoplasia avançada foi de 0,35/1000 indivíduos, e o valor preditivo positivo na colonoscopia pós-teste imunoquímico fecal positivo foi de 44% e 2% para adenoma avançado e cancro invasivo, respetivamente. Não foi relatado nenhum evento adverso após colonoscopia. Discussão: A adesão subótima a teste imunoquímico fecal e colonoscopia pós-teste imunoquímico fecal continua a ser a etapa mais problemática. Conclusão: Um sistema de convite centralizado foi viável, a qualidade das colonoscopias realizadas e o rendimento diagnóstico adequados antecipando o sucesso do programa.

Rehabilitation of Atrophic Maxilla With Immediate Loading of Extrasinus Zygomatic Implant.

ABSTRACT: The aim of this case series was to evaluate the long-term success rate of immediate occlusal loading of extrasinus zygomatic dental implants after a 3-year follow-up. The sample consisted of 31 patients (mean age of 64 years) with atrophic maxillae rehabilitated with 1 to 4 extrasinus zygomatic implants, placed unilaterally or bilaterally. All the patients received complete implant-supported dental prostheses with immediate loading by associating zygomatic implants with conventional implants. None of the procedures were associated with bone grafts. During the 3-year period of follow-up in the present study, all the patients attended clinical sessions and underwent radiographic exams every 6 months. In total 55 zygomatic and 69 conventional implants were placed, where 1 zygomatic and 2 conventional implants were lost, representing success rates of 98.18% and 97.20%, respectively. None of the studied patients had signs of sinusitis or changes in the maxillary sinuses. All the patients showed occlusal contact on natural antagonist teeth or implant-supported dental prostheses. Therefore, it was concluded that the use of exteriorized zygomatic implants with immediate loading represented a feasible option with high success rates for the treatment of atrophic maxilla.

A novel MYT1L mutation in a boy with syndromic obesity: Case report and literature review.

BACKGROUND: Pathogenic variants involving the MYT1L gene lead to an autosomal dominant form of syndromic obesity, characterized by polyphagia, intellectual disability/developmental delay, and behavioral problems, and that a characteristic facial phenotype does not seem to be recognizable. METHODS: Trio whole exome sequencing was performed in a 10-year-old Brazilian male presenting polyphagia, severe early-onset obesity, intellectual disability, speech delay, macrocephaly, frontal bossing, telecanthus, strabismus, and hypogenitalism. Additionally, we performed a literature review of patients carrying non-copy number MYT1L variants. RESULTS: A de novo genetic variant not previously reported in MYT1L (NM_015025.4:c.2990C>A) was identified in the proband and classified as pathogenic. From a literature search, 22 further patients carrying non-copy number MYT1L variants were identified, evidencing that although the associated phenotype is quite variable, intellectual disability/developmental and speech delays are always present. Further, most patients have obesity or overweight due to polyphagia. Macrocephaly, strabismus, behavioral problems, and hand/feet malformations are also recurrent features. CONCLUSIONS: We described the first Brazilian case of MYT1L related syndrome and highlighted clinical characteristics based on the literature. Other syndromic forms of obesity such as Prader-Willi, Bardet-Biedl, Börjeson-Forssman-Lehmann, MORM, Cohen, Alstrom, and Kleefstra type 1 syndromes should be considered in the differential diagnosis. Further, although obesity is frequent, it is not an obligatory feature of all carriers of MYT1L mutations.

Cancer Stem Cells and Nucleolin as Drivers of Carcinogenesis.

Cancer, one of the most mortal diseases worldwide, is characterized by the gain of specific features and cellular heterogeneity. Clonal evolution is an established theory to explain heterogeneity, but the discovery of cancer stem cells expanded the concept to include the hierarchical growth and plasticity of cancer cells. The activation of epithelial-to-mesenchymal transition and its molecular players are widely correlated with the presence of cancer stem cells in tumors. Moreover, the acquisition of certain oncological features may be partially attributed to alterations in the levels, location or function of nucleolin, a multifunctional protein involved in several cellular processes. This review aims at integrating the established hallmarks of cancer with the plasticity of cancer cells as an emerging hallmark; responsible for tumor heterogeneity; therapy resistance and relapse. The discussion will contextualize the involvement of nucleolin in the establishment of cancer hallmarks and its application as a marker protein for targeted anticancer therapies.

Agricultura urbana em contextos de vulnerabilidade social na zona leste de São Paulo e em Lisboa, Portugal / Urban agriculture in contexts of social vulnerability in the East of São Paulo and in Lisbon, Portugal

Esta pesquisa investiga a produção da agricultura urbana (AU) em contextos de vulnerabilidade social em sete hortas localizadas na zona Leste de São Paulo e em dois Parques Hortícolas de bairros sociais de Lisboa, Portugal, em torno do seguinte questionamento: "Como se constrói a Agricultura Urbana em regiões de vulnerabilidade social na zona Leste de São Paulo e em Parques Hortícolas de Lisboa, Portugal e como os agentes presentes nessas localidades operam nesses processos?". O estudo é ancorado nas Ciências Sociais e Humanas, notadamente na Perspectiva Multinível, Transição para a Sustentabilidade e em estudos que fundamentam a Agricultura Urbana e Periurbana. Parte-se da hipótese que a AU pode viabilizar possibilidades de combate às desigualdades estruturais em contextos de vulnerabilidade social, propiciando: geração de renda; melhorias na qualidade de vida de agricultores (as) urbanos (as); ampliação na produção e acesso de alimentos adequados ao consumo humano; e preservação ambiental. Nessa direção, a pesquisa identifica e analisa os múltiplos agentes - poder público, empresas privadas e mistas, organizações da sociedade civil e agricultores (as) - e as dinâmicas instauradas entre eles que, em conjunto, produzem a agricultura urbana nas respectivas localidades. Trata-se de estudo qualitativo fundamentado na Observação Participante, metodologia que proporciona densa descrição dos dados, em interlocução com a literatura da área. Na zona Leste de São Paulo, os resultados mostram: (a) o crescente protagonismo feminino na AU agroecológica, associado ao empreendedorismo popular e à conscientização das injustiças que agricultoras enfrentam; (b) as disputas entre modelos de gestão de hortas e concepções de cultivo; (c) desafios das transições sociotécnicas no que se refere às regulamentações e operacionalização das hortas; (d) a necessidade de diversificação de fontes de financiamento; (e) garantias de acesso e permanência nos terrenos das hortas. Em Lisboa, os resultados mostram: (a) o caráter fortemente regulatório da AU materializado no projeto Parques Hortícolas; (b) o potencial inexplorado de mobilização e participação popular de agricultores (as) em bairros sociais e de inovação por parte da juventude. O estudo conclui, ainda, que a atividade da AU, nos contextos estudados, provoca ampla melhoria na qualidade de vida de agricultores (as); inicia ou amplia a produção local de alimentos adequados ao consumo humano por parte de populações vulneráveis; implementa práticas de AU associadas à preservação ambiental e promove conscientização ambiental através de práticas pedagógicas. Em suma, a AU - materializada tanto em atividades de caráter emancipatório, assistencialista ou regulatório - tem potencial para combater desigualdades estruturais enfrentadas por populações vulneráveis, contribuindo para transformações sociais e econômicas em grandes cidades.

This research investigates the production of urban agriculture (UA) in contexts of social vulnerability in seven community gardens located in the east of São Paulo and in two horticultural parks in social districts of Lisbon, Portugal, around the following question: "How is the construction of Urban Agriculture in regions of social vulnerability in the East of São Paulo and in Horticultural Parks of Lisbon, Portugal and how do the agents present in these locations operate in these processes?". The study is anchored in Social and Human Sciences, notably in the Multilevel Perspective Theory, Transition to Sustainability and in studies that underlie Urban and Peri-Urban Agriculture. It is based on the hypothesis that UA can enable possibilities to combat structural inequalities in contexts of social vulnerability, providing: income generation; improvements in the quality of life of urban farmers; expansion in the production and access of food suitable for human consumption; and environmental preservation. In this sense, the research identifies and analyzes the multiple agents - government, private and mixed companies, civil society organizations and farmers - and the dynamics established among them that, together, produce urban agriculture in the localities. This is a qualitative study based on Participant Observation, a methodology that provides a dense description of data, in dialogue with the literature of the field. In the East zone of São Paulo, the results show: (a) the growing female role in agroecological UA, associated with popular entrepreneurship and the awareness of the injustices that female urban farmers face; (b) disputes between community garden management models and cultivation concepts; (c) challenges of socio-technical transitions with regard to the regulations and operation of community gardens; (d) the need to diversify funding sources; (e) guarantees of access and permanence in the community gardens' grounds. In Lisbon, the results show: (a) the UA's highly regulatory nature materialized in the Horticultural Parks project; (b) the untapped potential for mobilization and popular participation of urban farmers in social neighborhoods and innovation led by the youth. The study concludes that the UA activity, in the studied contexts, causes wide improvement in the quality of life of urban farmers; initiates or expands local production of food suitable for human consumption by vulnerable populations; implements UA practices associated with environmental preservation and promotes environmental awareness through pedagogical practices. In short, UA - materialized in activities of an emancipatory, assistance or regulatory nature - has the potential to combat structural inequalities faced by vulnerable populations, contributing to social and economic transformations in large cities.

Development of esthetic prosthesis for a patient with severe stigmatizing facial lesions due to cancer: a pilot study.

PURPOSE: Severe physical facial deformities due to surgical interventions can have significant psychosocial consequences to patient's relationships with friends and family and thus, has a considerable impact on their quality of life. We have developed a 3D prosthesis for a 56-year-old woman diagnosed with epidermoid carcinoma at the right hemiface, to improve her quality of life. METHODS: The patient started radiotherapy with modulated intensity. To deal with the advance of the process, a maxilectomy of supra structure with modified radical cervical emptying on the right hemiface was performed. Reconstruction of areas surgically affected by the displacement of islands of skin and muscle (flaps) from healthy regions was initiated. Although the procedure occurred without intercurrences, the patient developed necrosis and loss of the myocutaneous flap. After the removal of the flap, the esthetic result of the treatment was evident causing exposure of subcutaneous and granulation tissues. RESULTS: A computational model was used to develop a 3D structure of the affected area and then used to construct the prosthesis. The prosthesis was applied over the affected area, and the patient was able see her face on the mirror for the first time in years. The patient was grateful and hopeful. CONCLUSION: We have found that the application of this new technology greatly improves the social interaction of patients with deformities due to surgical interventions.

Polycystic Ovary Syndrome as a systemic disease with multiple molecular pathways: a narrative review.

Polycystic Ovary Syndrome (PCOS) is characterized by hyperandrogenism, amenorrhea, and polycystic ovaries. This endocrinopathy is associated with many metabolic disorders such as dyslipidemia and insulin resistance, with increased risk of type 2 diabetes mellitus, metabolic syndrome, and cardiovascular complications. Inflammation is likely to play an important role in the promoting these metabolic imbalances, while prothrombotic and pro-oxidative mechanisms further contribute to the cardiovascular risk of these patients. The etiology of PCOS is still not fully understood, but there is evidence of genetic and environmental components. This review aims to discuss some molecular pathways associated with PCOS that could contribute to the better understanding about this syndrome. Recent evidence suggests that intrauterine exposure of female mice to an excess of anti-Müllerian hormone may induce PCOS features in their post-natal life. High cytokine levels and cytokine gene polymorphisms also appear to be associated with the pathophysiology of PCOS. Furthermore, high levels of microparticles may contribute to the altered hemostasis and enhanced inflammation in PCOS. All these mechanisms may be relevant to clarify some aspects of PCOS pathogenesis and inspire new strategies to prevent the syndrome as well as treat its symptoms and mitigate the risk of long-term complications.

Efeito de diferentes doses de laser de baixa intensidade em células-tronco dentais cultivadas sobre arcabouços de ácido polilático / Effect of different doses of low intensity laser on dental stem cells cultured on polylactic acid scaffolds

As células-tronco mesenquimais dentais (dMSC) têm sido amplamente utilizadas na engenharia tecidual por sua capacidade de auto-renovação e potencial multilinhagem. Dentre as dMSCs, as células-tronco da polpa do dente decíduo esfoliado (SHEDs) destacam-se pela facilidade de coleta, capacidade proliferativa e tempo sobrevivência. O objetivo do estudo foi avaliar, através de experimentos in vitro, o efeito de diferentes doses do laser de baixa intensidade (LBI) na atividade biológica de SHEDs cultivadas sobre arcabouços de ácido polilático (PLA). Células previamente isoladas e caracterizadas foram cultivadas sobre filmes de PLA e foram irradiadas ou não (controle) com um laser diodo InGaAlP (660 nm, 30 mW, modo de ação contínuo) em um screening de doses (1, 4, 7.5, 15, 22.5 e 30 J/cm²). A proliferação e viabilidade celular foram analisadas nos intervalos de 24, 48 e 72 h, através dos ensaios do Alamar Blue e Live/Dead. A morfologia celular foi avaliada por MEV no intervalo de 72h. A avaliação do estresse oxidativo foi realizada através das dosagens de malondialdeído (MDA) e glutationa (GSH). Densidades de energia de 1 J/cm² e 4 J/cm² promoveram um efeito estimulador da proliferação celular nos três intervalos de tempo quando comparados ao grupo controle e aos demais grupos irradiados. Por outro lado, doses elevadas de irradiação (22.5 e 30 J/cm²) promoveram redução significativa das células. Verificou-se que a viabilidade celular foi afetada ao longo do experimento nos grupos L22.5 e L30, que apresentaram maior quantidade de células mortas no intervalo de 72h. Na análise por MEV evidenciou-se uma maior densidade celular nos grupos L1 e L4, contrapondo-se às SHEDs arranjadas mais dispersamente nos grupos L22.5 e L30. Em relação ao estresse oxidativo, nos grupos L1 e L4 houve elevação dos níveis de GSH e redução do MDA, de modo contrário, nos grupos L22.5 e L30 houve redução dos níveis de GSH e elevação do MDA. Conclui-se que doses baixas de LBI (1 e 4 J/cm²) promovem proliferação e tem efeito citoprotetor em SHEDs cultivadas sobre arcabouços de PLA, enquanto doses elevadas (22.5 e 30J/cm²) tem ação citotóxica e reduzindo a viabilidade e proliferação destas células (AU).

Dental mesenchymal stem cells (dMSCs) have been widely used in tissue engineering for their capacity for self-renewal and multi-lineage potential. Among the dMSCs, the stem cells from human exfoliated deciduous teeth (SHEDs) are highlighted for their ease of collection, proliferative capacity and survival time. The aim of the study was to evaluate, through in vitro experiments, the effect of different doses of low intensity laser (LLLI) on the biological activity of SHEDs cultured on polylactic acid (PLA) scaffolds. Pre-isolated and characterized cells were cultured on PLA films and irradiated or not (control) with an InGaAlP diode laser (660 nm, 30 mW, continuous action mode) in a dose screening (1, 4, 7.5, 15, 22.5 and 30 J/cm²). Cell proliferation and viability were analyzed at 24, 48 and 72 hr using the Alamar Blue and Live/Dead assays. Cell morphology was evaluated by SEM at 72 h. The evaluation of oxidative stress was performed through the dosages of malondialdehyde (MDA) and glutathione (GSH). Energy densities of 1 J/cm² and 4 J/cm² promoted cell proliferation in all intervals when compared to the control group and the other irradiated groups. Contrarily, high doses of irradiation (22.5 and 30 J/cm²) promoted significant negative effect on cell proliferation. It was verified that cell viability was affected throughout the experiment in groups L22.5 and L30, which presented a higher number of dead cells in the interval of 72h. The SEM analysis showed a greater cell density in L1 and L4 groups, opposing the SHEDs arranged more sparsely in L22.5 and L30 groups. Regarding to oxidative stress, in L1 and L4 groups there was elevation of GSH levels and reduction of MDA, showing a cytoprotective effect of these doses. Conversely, in groups L22.5 and L30 there was a reduction of GSH levels and elevation of MDA, corroborating with the results of the aforementioned assays. It is concluded that low doses of LLLI (1 and 4 J/cm²) promote proliferation of SHEDs on PLA scaffolds, while high doses (22.5 and 30 J/cm²) promote cytotoxic and anti-proliferative action in these cells (AU).

Haptoglobin levels, but not Hp1-Hp2 polymorphism, are associated with polycystic ovary syndrome.

PURPOSE: Proteomic studies suggest an association between haptoglobin (Hp) and polycystic ovary syndrome (PCOS). Hp is a classic inflammatory marker and binds to the intravascular hemoglobin, avoiding the oxidative damages that can be caused by free hemoglobin. Inflammation and oxidative stress are important in the pathogenesis of the PCOS, one of the most frequent metabolic diseases in women. METHODS: To validate these proteomic studies, we developed a controlled cross-sectional study that aimed to evaluate the Hp levels and allelic and genotypic frequencies of Hp1-Hp2 polymorphism in Brazilian women with PCOS. We also investigated the correlation between Hp levels and several important parameters in PCOS as follows: body mass index (BMI), waist circumference (WC), fasting glucose, post-prandial glucose, homeostatic model assessment (HOMA), lipid accumulation product (LAP), C-reactive protein (CRP), and metabolization test of tetrazolium salts (MTTs-serum antioxidant capacity). RESULTS: Plasma Hp levels were higher in the PCOS group than in controls [8.20 (4.04) g/L; 7.98 (3.31) g/L; p = 0.018]. No significant difference was observed in the frequency of Hp1-Hp2 genotypes under additive, recessive, or dominant model of inheritance between the PCOS and the control groups. Plasma Hp levels did not differ according to the genotype. However, plasma Hp showed a negative correlation with MTT (r = - 0.383; p = 0.028), as well as a positive correlation with CRP (r = 0.361; p = 0.014) in the PCOS group. CONCLUSION: Hp1-Hp2 polymorphism is not associated with PCOS but plasma Hp could be a potential biomarker for PCOS and its complications.

Testicular Adrenal Rests Tumors and Testicular Microlithiasis in a Brazilian Case Series with Classic Congenital Adrenal Hyperplasia.

BACKGROUND: Testicular adrenal rest tumors are a benign condition characterized by the presence of remnants of adrenal tissue within the testes that can lead to infertility. Testicular microlithiasis are calculus deposits within the seminiferous tubules. Both are described in congenital adrenal hyperplasia. OBJECTIVES: Describe the frequency of testicular adrenal rest tumors and testicular microlithiasis in a Brazilian case series of patients with classic congenital adrenal hyperplasia and to also relate these changes to disease control and hypothalamic-pituitary-gonadal axis disorders. METHODS: Case series study. An ultrasound examination of the scrotum was performed on 12 patients between the ages of 5.33 to 22 (14.72 ± 5.26) years. Testicular adrenal rest tumors were classified according to the degree of testicular infiltration in stages by adapting the Grinten's classification, ranging from the absence of testicular adrenal rests visible by ultrasound (stage ≤ 1) to chronic obstruction of the testicular parenchyma with irreversible damage of the testicle (stage 5). RESULTS: Six patients (5 salt wasting and 1 simple virilizing) with an average age of 17.27 ± 3.09 years and have gone through puberty showed testicular adrenal rest tumors (Grinten stage ≥ 3). In 2 of the patients there was a coincidence with testicular microlithiasis. The frequency of testicular adrenal rest tumors did not relate with the levels of serum 17-hydroxyprogesterone and androstenedione. In 3 patients with testicular adrenal rest tumors, gonadotropin levels were suggestive of hypergonadotropic hypogonadism and one of hypogonadotropic hypogonadism. CONCLUSIONS: Testicular adrenal rest tumors were found in greater frequency during puberty and was not related to hormonal control in this group. Some of them happened with testicular microlithiasis.

Metformin reduces total microparticles and microparticles-expressing tissue factor in women with polycystic ovary syndrome.

PURPOSE: The objective of this study was to evaluate the levels of total microparticles (MPs) and microparticles-expressing tissue factor (TFMPs) in women with polycystic ovarian syndrome (PCOS) who use metformin comparing to those who do not take metformin. METHODS: We quantified total MPs and TFMPs in the plasma of 50 patients with PCOS-13 of these women used metformin (850 mg 2×/day during at least 6 months) and the other 37 did not. For this purpose, the microparticles (MPs) were purified by differential centrifugation of the plasma and, subsequently, by flow cytometry, using annexin-V and CD142 as markers. RESULTS: Total MPs levels were lower in treated patients (59.58 ± 28.43 MPs/µL) when compared to untreated group (97.32 ± 59.42; p = 0.033). Plasma levels of TFMPs were also significantly lower in the group of patients who used metformin (1.10 ± 0.94 MPs/µL) when compared to untreated patients (2.20 ± 1.42 MPs/µL) (p = 0.003). CONCLUSIONS: Considering that metformin reduced the levels of total MPs and TFMPs, our results suggest that this mechanism could be involved in the antithrombotic metformin effect, corroborating with the indication of this drug in the PCOS treatment.

Speech perception in noise in the elderly: interactions between cognitive performance, depressive symptoms, and education / Reconhecimento de fala no ruído de idosos: interações entre desempenho cognitivo, sintomatologia depressiva e escolaridade

Abstract Introduction: The difficulty the elderly experience in understanding speech may be related to several factors including cognitive and perceptual performance. Objective: To evaluate the influence of cognitive performance, depressive symptoms, and education on speech perception in noise of elderly hearing aids users. Methods: The sample consisted of 25 elderly hearing aids users in bilateral adaptation, both sexes, mean age 69.7 years. Subjects underwent cognitive assessment using the Mini-Mental State Examination and the Alzheimer's Disease Assessment Scale-cognitive and depressive symptoms evaluation using the Geriatric Depression Scale. The assessment of speech perception in noise (S/N ratio) was performed in free field using the Portuguese Sentence List test. Statistical analysis included the Spearman correlation calculation and multiple linear regression model, with 95% confidence level and 0.05 significance level. Results: In the study of speech perception in noise (S/N ratio), there was statistically significant correlation between education scores (p = 0.018), as well as with the Mini-Mental State Examination (p = 0.002), Alzheimer's Disease Assessment Scale-cognitive (p = 0.003), and Geriatric Depression Scale (p = 0.022) scores. We found that for a one-unit increase in Alzheimer's Disease Assessment Scale-cognitive score, the S/N ratio increased on average 0.15 dB, and for an increase of one year in education, the S/N ratio decreased on average 0.40 dB. Conclusion: Level of education, cognitive performance, and depressive symptoms influence the speech perception in noise of elderly hearing aids users. The better the cognitive level and the higher the education, the better is the elderly communicative performance in noise.

Resumo Introdução: A dificuldade na compreensão de fala dos idosos pode estar relacionada a vários fatores, como o desempenho cognitivo e perceptual. Objetivo: Avaliar a influência do desempenho cognitivo, sintomas depressivos e escolaridade no reconhecimento de fala no ruído de idosos usuários de próteses auditivas. Método: A amostra constituiu-se de 25 idosos usuários de próteses auditivas em adaptação bilateral, de ambos os sexos e média de 69,7 anos. Os indivíduos foram submetidos à avaliação cognitiva por meio do miniexame do estado mental (MEEM) e a escala de avaliação da doença de Alzheimer-cognitiva (ADAS-Cog) e avaliação de sintomatologia depressiva por meio da escala de depressão geriátrica (EDG). Já a pesquisa do reconhecimento de fala no ruído (relação S/R) foi feita, em campo livre, por meio do teste lista de sentenças no português (LSP). A análise estatística incluiu o cálculo de correlação de Spearman e modelo de regressão linear múltiplo, foram adotados coeficiente de confiança de 95% e nível de significância de 0,05. Resultados: No estudo do reconhecimento de sentenças no ruído (relação S/R) houve correlação, com significância estatística, entre a escolaridade (p = 0,018); assim como com os escores dos testes MEEM (p = 0,002), o Adas-Cog (p = 0,003) e o EDG (p = 0,022). Observou-se que, para um aumento de uma unidade no escore do Adas-Cog, a relação S/R aumenta, em média, 0,15 dB e para um aumento de um ano na escolaridade, a relação S/R diminui, em média, 0,40 dB. Conclusão: O nível de escolaridade, o desempenho cognitivo e sintomas depressivos influenciam o reconhecimento de fala no ruído de idosos usuários de prótese auditiva. Quanto melhor o nível cognitivo e maior a escolaridade, melhor é o desempenho comunicativo do idoso no ruído.

Mucocutaneous Kaposi's sarcoma in an HIV-positive patient: diagnosis and treatment / Sarcoma de Kaposi mucocutâneo em paciente HIV positivo: diagnóstico e tratamento

ABSTRACT Kaposi's sarcoma (KS) is an endothelial neoplasia caused by infection with the human herpesvirus 8 (HHV-8), and the type associated with the human immunodeficiency virus (HIV) is considered the most aggressive and frequent. This paper reports a case of mucocutaneous KS in a patient not formerly aware of being an HIV bearer. A 38-year-old male patient has sought treatment with multiple oral lesions and one in the skin. Serology was positive for HIV and incisional biopsy diagnosed KS. After 11 months of chemotherapy and antiretroviral therapy, there was complete remission of the skin KS and partial remission of oral lesions.

RESUMO Sarcoma de Kaposi (SK) é uma neoplasia endotelial causada pelo herpes vírus humano tipo 8 (HHV-8), e o tipo associado ao vírus da imunodeficiência humana (HIV) é considerado o mais agressivo e frequente. Relata-se um caso de SK mucocutâneo em indivíduo não anteriormente ciente de ser portador de HIV. Paciente do sexo masculino, 38 anos, procurou atendimento com queixa de múltiplas lesões orais e uma lesão em pele. A sorologia foi positiva para HIV, e a biópsia incisional das lesões teve como diagnóstico SK. Após 11 meses de terapia antirretroviral e quimioterapia, houve remissão completa do SK cutâneo e parcial das lesões orais.

Controle do tabaco: uma análise sobre paternalismo e liberdade / Tobacco control: an analysis on paternalism and liberty

O presente trabalho tem o objetivo de verificar se as medidas adotadas no Brasil para o controle do tabaco são paternalistas e se elas de alguma forma restringem liberdades individuais. Primeiramente, serão analisadas as correntes teóricas a respeito do paternalismo e sua relação com a liberdade, com especial atenção à corrente do Paternalismo Libertário. Em seguida, analisar-se-ão as medidas adotadas no controle do tabaco em outros países e no Brasil. Por fim, analisar-se-á cada uma das medidas adotadas, buscando-se definir se elas restringem a liberdade e se há medidas alternativas menos restritivas. Chega-se, assim, à conclusão de que as medidas adotadas no Brasil, embora sejam majoritariamente paternalistas, não retiram necessariamente a liberdade dos indivíduos...

This paper aims at verifying if the measures adopted in Brazil for tobacco control are paternalistic and if they, in any way, restrict individual liberties. Firstly, some of the theories on paternalism and their relation to liberty will be analyzed, focusing on the Libertarian Paternalism doctrine. Then, measures for tobacco control adopted in other countries and in Brazil will be discussed. Finally, each measure adopted in Brazil will be thoroughly analyzed, in order to verify if it restricts liberty and if there are less restrictive measures available. The conclusion is that the measures adopted in Brazil, even though they are predominantly paternalistic, do not necessarily restrict individual liberties...

Unmet needs of people with severe multiple sclerosis and their carers: qualitative findings for a home-based intervention.

BACKGROUND: Few data on services for people with severe multiple sclerosis (MS) are available. The Palliative Network for Severely Affected Adults with MS in Italy (PeNSAMI) developed a home palliative care program for MS patients and carers, preceded by a literature review and qualitative study (here reported). OBJECTIVE: To identify unmet needs of people with severe MS living at home by qualitative research involving key stakeholders, and theorize broad areas of intervention to meet those needs. METHOD: Data were collected from: at least 10 personal interviews with adults with severe MS (primary/secondary progressive, EDSS≥8.0); three focus group meetings (FGs) of carers of people with severe MS; and two FGs of health professionals (HPs). Grounded theory guided the analysis of interview and FG transcripts, from which the areas of intervention were theorized. RESULTS: Between October 2012 and May 2013, 22 MS patients, 30 carers and 18 HPs participated. Forty-eight needs themes were identified, grouped into 14 categories and four domains. Seven, highly interdependent intervention areas were theorized. Patients had difficulties expressing needs; experiences of burden and loneliness were prominent, chiefly in dysfunctional, less affluent families, and among parent carers. Needs differed across Italy with requirements for information and access to services highest in the South. All participants voiced a strong need for qualified personnel and care coordination in day-to-day home care. Personal hygiene emerged as crucial, as did the need for a supportive network and preservation of patient/carer roles within family and community. CONCLUSIONS: Unmet needs transcended medical issues and embraced organizational and psychosocial themes, as well as health policies. The high interdependence of the seven intervention areas theorized is in line with the multifaceted approach of palliative care. At variance with typical palliative contexts, coping with disability rather than end-of-life was a major concern of patients and carers.

Avaliação histopatológica e histoquímica das células claras em lesões odontogênicas císticas / Análisis histopatológico y histoquímico de células claras en lesiones quísticas odontogénicas / Histopathological and histochemical analysis of clear cells in odontogenic cystic lesions

Alterações degenerativas e metaplásicas são usualmente observadas no revestimento epitelial dos cistos odontogênicos. Nos tumores odontogênicos estes processos são considerados mais raros. Objetivo: demonstrar a presença de células claras no revestimento epitelial de uma série de lesões odontogênicas císticas. Métodos: realizou-se um estudo descritivo, em uma amostra de 22 lâminas histológicas, do total de lesões odontogênicas císticas procedentes do Laboratório de Patologia Bucal da Universidade Federal da Paraíba. As lâminas foram examinadas por dois avaliadores previamente calibrados e os blocos parafinados correspondentes às lesões em que se observaram células claras, foram novamente processados, e as lâminas foram coradas pela técnica do Ácido Periódico de Schiff após digestão pela diástase e avaliadas quanto à presença de células mucosas. Resultados: células contendo mucina estavam presentes em 12 (54,5 porcento) das lesões coradas pelo Ácido Periódico de Schiff com diástase. Células mucosas foram observadas em 5 (41,66 porcento) dos 12 casos de cistos radiculares, 1 (50 porcento) dos 2 casos de tumores odontogênicos ceratocísticos, nos 4 (100 porcento) casos de cistos dentígeros e em 2 (100 porcento) casos de ameloblastomas unicísticos. Células claras foram muitas vezes observadas em áreas de inflamação. Conclusão: na amostra estudada, células mucosas puderam ser evidenciadas ocasionalmente no epitélio de lesões odontogênicas císticas(AU)

Cambios metaplásicos y degenerativas se observan generalmente en el revestimiento epitelial de los quistes odontogénicos. En tumores odontogénicos estos procesos son considerados raros. Objetivo: demostrar la presencia de células claras en el epitelio de revestimiento de una serie de lesiones quísticas odontogénicas. Métodos: se realizó un estudio descriptivo, en una muestra de 22 cortes histológicos, del total de lesiones quísticas odontogénicas procedentes del Laboratorio de Patología Oral de la Universidad Federal de La Paraiba. Los cortes fueron examinados por dos examinadores calibrados previamente y los bloques de parafina correspondientes a las lesiones que se observaron con células claras se volvieran a procesar y los cortes fueron teñidos por el Ácido Periódico de Schiff después de la digestión por la diastasa y evaluados para la presencia de células mucosas. Resultados: células contiendo mucina estaban presentes en 12(54,5 por ciento) de las lesiones teñidas por el Ácido Periódico de Schiff con diastasa. Células mucosas fueran observadas en 5(41,66 por ciento) de los 12 casos de quistes radiculares, 1 (50 por ciento) de los 2 casos de tumores odontogénicos queratoquísticos, en los 4 (100 %) casos de quistes dentígeros y en los 2(100 por ciento) casos de ameloblastomas uniquísticos. Células claras fueron muchas veces observadas en zonas de inflamación. Conclusión: En la muestra estudiada, las células mucosas pudieron ser encontradas ocasionalmente en el epitelio de lesiones quísticas odontogénicas(AU)

Metaplastic and degenerative changes are usually observed in the epithelial lining of odontogenic cysts. These processes are considered rare in Odontogenic tumors. Objective: to demonstrate the presence of clear cells in the epithelial lining of a series of odontogenic cystic lesions. Methods: a descriptive study was done, in a sample of 22 histological slides of the total odontogenic cystic lesions originating from the Oral Pathology Laboratory at the Federal University of Paraiba. The slides were examined by two calibrated examiners and the paraffin blocks, corresponding to the lesions, where clear cells were observed, were re-processed and the slides were stained by the Periodic Acid-Schiff technique after digestion by diastase and evaluated for the presence of mucous cells. Results: mucin-containing cells were present in 12 (54,5 percent) of the stained lesions by Periodic Acid-Schiff technique with diastase. Mucous cells were observed in 5 (41.66 percent) of 12 root cysts cases, 1 (50 percent) of 2 keratocystic odontogenic tumors, in 4 (100 percent) cases of dentigerous cysts and in 2 (100 percent) cases of unicystic ameloblastomas. Clear cells were often observed in inflammation areas. Conclusion: In the study sample mucous cells could be evidenced occasionally in the epithelium of cystic odontogenic lesions(AU)

Pediatric fibromatosis involving mandible: case reportand a five-year post-operative follow-up / Fibromatose pediátrica em mandíbula: relato de caso e avaliação pós-operatória de cinco anos

Extra-abdominal fibromatosis is a benign fibrous neoplasm of locally aggressive behavior. Surgical excision with a wide margin is the treatment of choice. The aim of the present work is to report the case of fibromatosis in an 11-year-old melanodermic patient, who showed swelling in the area of the right mandible. Conservative surgery was performed based on the initial histopathological diagnosis of benign lesion suggestive of neural origin. The new anatomopathological examination of the surgical specimen was compatible with fibromatosis. The patient is still under periodic observation as part of the five-year surgical follow-up, showing no signs of recurrence.

Fibromatose extra-abdominal é uma neoplasia fibrosa benigna, caracterizada por comportamento agressivo local. Geralmente, o tratamento de escolha consiste na excisão cirúrgica com ampla margem de segurança. O objetivo deste trabalho é relatar um caso de fibromatose em uma paciente de 11 anos, melanoderma, que apresenta aumento de volume na mandíbula do lado direito. A partir do diagnóstico histopatológico inicial sugestivo de lesão benigna de origem neural, foi realizado tratamento cirúrgico conservador. Um novo exame anatomopatológico da peça cirúrgica foi compatível com fibromatose. A paciente encontra-se sob controle periódico de cinco anos da cirurgia, não havendo recorrência clínica da lesão.