SPRY4 as a Potential Mediator of the Anti-Tumoral Role of Macrophages in Anaplastic Thyroid Cancer Cells.

Anaplastic thyroid carcinoma (ATC) is the most lethal subtype of thyroid cancer, with high invasive and metastatic potential, not responding to conventional treatments. Its aggressiveness may be influenced by macrophages, which are abundant cells in the tumor microenvironment. To investigate the role of macrophages in ATC aggressiveness, indirect co-cultures were established between ATC cell lines and THP-1-derived macrophages. Macrophages significantly increased both the migration and invasion of T235 cells (p < 0.01; p < 0.01), contrasting with a decrease in C3948 (p < 0.001; p < 0.05), with mild effects in T238 migration (p < 0.01) and C643 invasion (p < 0.05). Flow cytometry showed upregulation of CD80 (pro-inflammatory, anti-tumoral) and downregulation of CD163 (anti-inflammatory, pro-tumoral) in macrophages from co-culture with T235 (p < 0.05) and C3948 (p < 0.05), respectively. Accordingly, we found an upregulation of secreted pro-inflammatory mediators (e.g., GM-CSF, IL-1α; p < 0.05) in C3948-macrophage co-cultures. Proteomic analysis showed the upregulation of SPRY4, an inhibitor of the MAPK pathway, in C3948 cells from co-culture. SPRY4 silencing promoted cancer cell invasion, reverting the reduced invasion of C3948 caused by macrophages. Our findings support that macrophages play a role in ATC cell aggressiveness. SPRY4 is a possible modulator of macrophage-ATC cell communication, with a tumor suppressor role relevant for therapeutic purposes.

Clinical and molecular characterization of parathyroid carcinoma in multiple endocrine neoplasia type 1.

Nineteen cases of parathyroid carcinoma in patients with multiple endocrine neoplasia type 1 have been reported in the literature, of which 11 carry an inactivating germline mutation in the MEN1 gene. Somatic genetic abnormalities in these parathyroid carcinomas have never been detected. In this paper, we aimed to describe the clinical and molecular characterization of a parathyroid carcinoma identified in a patient with MEN1. A 60-year-old man was diagnosed with primary hyperparathyroidism during the postoperative period of lung carcinoid surgery. Serum calcium and parathyroid hormone levels were 15.0 mg/dL (8.4-10.2) and 472 pg/mL (12-65), respectively. The patient underwent parathyroid surgery, and histological findings were consistent with parathyroid carcinoma. Analysis of the MEN1 gene by next-generation sequencing (NGS) identified a novel germline heterozygous nonsense pathogenic variant (c.978C>A; p.(Tyr326*)), predicted to encode a truncated protein. Genetic analysis of the parathyroid carcinoma revealed a c.307del, p.(Leu103Cysfs*16) frameshift truncating somatic MEN1 variant in the MEN1 gene, which is consistent with MEN1 tumor-suppressor role, confirming its involvement in parathyroid carcinoma etiology. Genetic analysis of CDC73, GCM2, TP53, RB1, AKT1, MTOR, PIK3CA and CCND1 genes in the parathyroid carcinoma DNA did not detect any somatic mutations. To our knowledge, this is the first report of a PC case presenting both germline (first-hit) and somatic (second-hit) inactivation of the MEN1 gene.

Metastatic follicular thyroid cancer with a longstanding responsiveness to gemcitabine plus oxaliplatin.

Background: Treatment of advanced follicular thyroid carcinoma (FTC) is based primarily on indirect evidence obtained with multikinase inhibitors (MKI) in clinical trials in which papillary carcinomas represent the vast majority of cases. However, it should be noted that MKI have a non-negligible toxicity that may decrease the patient's quality of life. Conventional chemotherapy with GEMOX (gemcitabine plus oxaliplatin) is an off-label therapy, which seems to have some effectiveness in advanced differentiated thyroid carcinomas, with a good safety profile, although further studies are needed. Case report: We report a case of a metastatic FTC, resistant to several lines of therapy. However, with a durable response to GEMOX, the overall survival of our patient appears to have been extended significantly due to this chemotherapy. Conclusion: GEMOX may have a role in patients with thyroid cancer unresponsive to MKI.

Entrectinib in the neoadjuvant setting of anaplastic thyroid cancer: a case report.

Background: Anaplastic thyroid carcinoma (ATC) is one of the most aggressive solid tumors. ATC is frequently diagnosed at advanced stages with unresectable disease and palliative care is often indicated. Recently, several patient-tailored therapies for ATC are emerging due to advances in molecular profiling of these tumors. Entrectinib is a potent oral selective inhibitor of neutrotrophic tropomyosin receptor kinase (NTRK), ROS1, and anaplastic lymphoma kinase fusions. The experience regarding ATC and other thyroid carcinomas, particularly in the neoadjuvant setting, is minimal. Case report: We present a case of a 51-year-old female patient presenting with a bulky mass of the left thyroid lobe measuring 100 × 108 × 80 mm that was considered surgically unresectable. While waiting for next-generation sequence (NGS) profiling, lenvatinib was initiated. There was an initial clinical and imagiologic response; however, progression occurred after 12 weeks, and at this time NGS identified an ETV6-NTRK3 fusion and entrectinib was started. After 12 weeks, tumor diameters reduced to a minimum of 68×60×49 mm, and the patient underwent total thyroidectomy plus central lymphadenectomy. Histological diagnosis confirmed an ATC (pT4a R2 N1a). Adjuvant radiotherapy (RT) (60 Grays) with weekly paclitaxel (45 mg/m2) was then administered followed by maintenance entrectinib 600 mg daily. Fluorodeoxyglucose positron emission tomography performed 3 months after completion of RT showed only non-specific uptake in the posterior wall of the hypopharynx and larynx, suggestive of inflammation. Conclusion: We report the first case of an ATC with a dramatic response to neoadjuvant therapy with entrectinib, which enabled surgical resection of an ab initio unresectable tumor.

Avidity and Outcomes of Radioiodine Therapy for Distant Metastasis of Distinct Types of Differentiated Thyroid Cancer.

CONTEXT: The recommendations for radioactive-iodine treatment (RAIT) in metastatic differentiated thyroid cancer (DTC) are mostly based in the experience with papillary histotype and do not consider the differences within the distinct types of DTC, in terms of RAIT uptake and response. OBJECTIVE: This work aims to investigate the association between histology and RAIT avidity and response, and to evaluate whether histotype was an independent prognostic factor in progression-free survival (PFS) and disease-specific survival (DSS) after RAIT for distant metastatic disease. METHODS: A retrospective analysis was conducted of all DTC patients who underwent RAIT for distant metastatic disease, from 2001 to 2018, at a thyroid cancer referral center. We included 126 patients: 42 (33.3%) classical variant papillary thyroid cancer (cvPTC), 45 (35.7%) follicular variant PTC (fvPTC), 17 (13.5%) follicular thyroid cancer (FTC) and 22 (17.5%) Hürthle cell carcinoma. Main outcome measures included RAIT avidity and response. RESULTS: RAIT avidity was independently associated with histology (P < .001) and stimulated thyroglobulin (Tg) at first RAIT for distant lesions (P = .007). Avidity was lowest in HCC (13.6%), intermediate in cvPTC (21.4%), and highest in fvPTC (75.6%) and FTC (76.5%). Regarding RAIT response, HCC and FTC were not different; both showed significantly more often progression after RAIT than fvPTC and cvPTC. Histology influenced PFS (P = .014), but tumor type was not a significant prognostic factor in DSS. Instead, age at diagnosis, resection status, and stimulated Tg at the first RAIT were significantly associated with DSS. CONCLUSION: DTC histotype influenced RAIT avidity and PFS. It is crucial to better detect the metastatic patients that may benefit the most from RAIT.

Outcomes of Thyrotropin Alfa Versus Levothyroxine Withdrawal-Aided Radioiodine Therapy for Distant Metastasis of Papillary Thyroid Cancer.

Background: Thyrotropin alfa (rhTSH) is not currently approved by the Food and Drug Administration or European Medicines Agency for the preparation of radioactive iodine therapy (RAIT) in patients with distant metastatic papillary thyroid cancer (PTC). There are only a few studies comparing rhTSH with levothyroxine withdrawal (LTW) in this context. Our main aim was to compare the two methods of RAIT preparation in terms of avidity and structural/biochemical response in distant metastatic PTC. We also intended to evaluate whether the two methods of RAIT preparation represented independent prognostic factors for progression-free survival (PFS) and disease-specific survival (DSS) in this subset of patients. Methods: We performed a retrospective analysis of all patients with PTC treated with RAIT for distant metastatic disease between 2006 and 2018. We included 95 PTC patients-27 (28.4%) had LTW and 68 (71.6%) had rhTSH for RAIT. Results: The two groups presented similar clinicopathological characteristics, except for median age at PTC diagnosis, which was higher in the rhTSH group (p = 0.001), but the median age at first RAIT for distant metastatic disease was not different between the two methods of preparation, 63 years old (interquartile range [IQR] 23) in the LTW group versus 70 (IQR 26.75), p = 0.06. Avidity was similar between the two groups (p = 0.973). Median estimate PFS (p = 0.076) and DSS (p = 0.084) were also similar between LTW and rhTSH. Regarding RAIT-related side effects, only 1 (3.7%) patient and 5 (7.4%) patients in the LTW and rhTSH groups, respectively, reported sialadenitis (p = 0.670). Conclusions: There were no differences between the two methods of RAIT preparation regarding avidity and clinical response. rhTSH may be used as an alternative method of preparation for RAIT in patients with known distant lesions, as it presents similar clinical outcomes to LTW and a good safety profile.

A pathogenic variant in CHEK2 shows a founder effect in Portuguese Roma patients with thyroid cancer.

PURPOSE: Germline mutations in DNA repair-related genes have been recently reported in cases with familial non-medullary thyroid carcinoma (FNMTC). A Portuguese family from the Roma ethnic group with four members affected with papillary thyroid carcinoma (PTC), and three members with multinodular goiter (MNG) was identified. The aim of this study was to investigate the involvement of DNA repair-related genes in the etiology of FNMTC in this family and in the Roma ethnic group. METHODS: Ninety-four hereditary cancer predisposition genes were analyzed through next-generation sequencing. Sanger sequencing was used for variant confirmation and screening. Twelve polymorphic markers were genotyped for haplotype analysis in the CHEK2 locus. RESULTS: A germline pathogenic frameshift variant in the CHEK2 gene [c.596dupA, p.(Tyr199Ter)] was detected in homozygosity in the proband (PTC) and in his brother (MNG), being heterozygous in his mother (PTC), two sisters (PTC), and one nephew (MNG). This variant was absent in 100 general population controls. The screening of the CHEK2 variant was extended to other Roma individuals, being detected in 2/33 Roma patients with thyroid cancer, and in 1/15 Roma controls. Haplotype segregation analysis identified a common ancestral core haplotype (Hcac), covering 10 Mb in the CHEK2 locus, shared by affected CHEK2 variant carriers. Analysis of 62 individuals CHEK2 wild-type indicated that none presented the Hcac haplotype. The estimated age for this variant suggested that it was transmitted by a relatively recent common ancestor. CONCLUSIONS: We identified a founder CHEK2 pathogenic variant, which is likely to underlie thyroid cancer and other cancer manifestations in the Roma population.

Shelf life extension of mozzarella cheese packed in preserving liquid with calcium lactate and bergamot juice concentrate.

Traditional Mozzarella is a fresh cheese produced in Italian local market without additives that shows a short shelf life of about 5 d. This work tested the use of natural additives (bergamot juice concentrate-BJ and calcium lactate-CL) in preserving liquid for a Mozzarella cheese with the aim to extend its shelf life, regarding the microbial growth and overall cheese quality. Results of qualitative analyses showed that the preserving liquid with the mix of BJ and CL promoted an extension of mozzarella shelf life up to 20 d. A slightly reduced growth of Pseudomonas species was evidenced after 5 d of storage, whereas no inhibition of lactic acid bacteria was observed for the storage period. Moreover, mozzarella cheese packed in mixed preserving liquid possessed better textural properties, evidenced by the lowest proteolysis index measured after 13 d of storage, and a good antioxidant activity.

Evaluation of different salted governing liquids on shelf life extension of lacto-fermented mozzarella cheese.

The effect of different governing liquids on qualitative parameters of lacto-fermented mozzarella cheeses were studied. 0.6% calcium lactate solution maintained the quality of mozzarella cheese for microbial, color and textural properties and prolonged its shelf life up to 18 days, also improving its antioxidant activity by Trolox equivalent antioxidant capacity and Oxygen radical absorbance capacity assays.

Qualidade de vida relacionada à saúde de pacientes com câncer de próstata em tratamento de radioterapia: revisão integrativa de literatura / Quality of life of prostate cancer patients undergoing radiation treatment: an integrative literature review

O presente estudo objetiva analisar as publicações científicas de alto impacto que avaliaram a qualidade de vida relacionada à saúde de pacientes com câncer de próstata em tratamento radioterápico. Para tanto, ancora-se num estudo exploratório, de revisão integrativa da literatura, utilizando as bases de dados PubMed, Web of Science, Scopus e Lilacs, com os descritores: Quality of life, Prostatic neoplasms e Radiotherapy, usando o operador booleano AND. Do total de 1418 artigos localizados, foram excluídos 1403 após o uso dos filtros adotados como critérios de inclusão e exclusão, de acordo com cada base de dados, e leitura dos respectivos resumos, resultando em 15 artigos. Os resultados evidenciaram que o tratamento de radioterapia causa impacto na qualidade de vida relacionada à saúde dos pacientes, com manifestações de sinais e sintomas de intensidade variada, principalmente nas funções urinária, sexual e intestinal. Mesmo havendo declínio na qualidade de vida relacionada à saúde durante o tratamento, os efeitos negativos foram limitados e temporários, podendo melhorar com o passar do tempo. Ainda que os estudos tenham sido realizados em momentos e países diferentes, com amostras, modalidades de radiação e instrumentos distintos, os resultados contribuíram para o planejamento, a execução e avaliação do tratamento radioterápico no cotidiano dos serviços oncológicos, considerando a realidade de cada um. Recomenda-se a realização de novas pesquisas de modo a possibilitar a identificação dos efeitos dos diferentes tipos de radiação e suas consequências na vida dos pacientes, com vistas à escolha de medidas terapêuticas menos impactantes.

This paper has the aim of reviewing evidence on quality of life aspects related to the health of prostate cancer patients undergoing radiotherapy. An exploratory study was developed with an integrative literature review using the PubMed, Web of Science, Scopus, and Lilacs websites with the key words: Quality of life, Prostatic neoplasms, and Radiotherapy, using the Boolean AND operator. From the total 1418 articles found, 1403 were excluded after the use of filters adopted as inclusion and exclusion criteria, according to each database, and the reading of the abstracts, resulting in 15 articles. The results showed that the radiotherapy treatment has impact on the quality of life related to the health of patients with signs of manifestations and symptoms of varying intensity, especially in the urinary, sexual and bowel functions. Even though there is a decline in the quality of life related to health during the treatment, the negative effects were limited and temporary, meaning they may improve over time. Although the studies were carried out at different times and in different countries, with different number of samples, radiation modes and instruments, the results contributed to the planning, implementation and assessment of radiotherapy treatment in the routine of cancer services, considering their realities. Further research is recommended to enable the identification of the effects of different types of radiation therapy and their consequences in the lives of patients, with a view to choosing less impactful therapeutic measures.

Qualidade de vida relacionada à saúde de pacientes com câncer de próstata / Quality of life related to the health of patients with prostate cancer / Calidad de vida relacionada con la salud de los pacientes con cáncer de próstata

INTRODUÇÃO: O diagnóstico e o tratamento do câncer de próstata podem provocar modificações significativas na vida dos homens, alterando a sua qualidade de vida. O objetivo deste estudo foi avaliar a qualidade de vida relacionada à saúde de pacientes com câncer de próstata em tratamento de hormonioterapia e radioterapia. MATERIAIS E MÉTODOS: Estudo descritivo, transversal, com dados sociodemográficos, clínicos e de avaliação da qualidade de vida de 213 pacientes, obtidos por roteiro de entrevista e pelo questionário Expanded Prostate Cancer Index Composite. Utilizou-se estatística descritiva. RESULTADOS: Houve predominância de homens acima de 50 anos, brancos, casados, com baixa escolaridade e aposentados, com diagnóstico inicial obtido pelas alterações no exame de Antígeno Prostático Específico e estadiamento II. As médias dos escores obtidos no domínio da função sexual indicaram queda na qualidade de vida, para ambos os tratamentos. DISCUSSÃO: Tanto a hormonioterapia como a radioterapia podem causar algum tipo de efeito na função sexual, diretamente relacionado a um significativo impacto na qualidade de vida relacionada à saúde para muitos homens. CONCLUSÕES: Ainda que os resultados tenham sido obtidos e analisados pela primeira vez no hospital do estudo, oferecem subsídios para o conhecimento da realidade local e corroboram com os achados de outros estudos realizados em locais e realidades diferentes.

INTRODUCTION: The diagnosis and treatment of prostate cancer can cause significant modifications in the lives of men, altering their quality of life. The aim of this study was to assess the health-related quality of life of patients with prostate cancer in hormone therapy and radiotherapy treatment. MATERIALS AND METHODS: Descriptive, cross-sectional study with sociodemographic, clinical data and quality of life evaluation of 213 patients, obtained from the interview script and through the questionnaire Expanded Prostate Cancer Index Composite. Descriptive statistics were used. RESULTS: There was a predominance of white men over 50 years of age, married, with low schooling, and retirees with initial diagnosis obtained by alterations on the specific prostatic antigen test and stage II. The mean scores obtained in the sexual function domain indicated a decrease in quality of life for both treatments. DISCUSSION: Hormone therapy and radiotherapy can cause some type of type of effect on the sexual function, directly related to a significant impact on the quality of life related to health for many men. CONCLUSIONS: Although the results were obtained and analyzed for the first time in the study hospital, they offer subsidies for the knowledge of the local reality and corroborate with findings from other studies carried out in different places and realities.

INTRODUCCIÓN: El diagnóstico y el tratamiento del cáncer de próstata pueden provocar cambios significativos en la vida de los hombres, alterando su calidad de vida. El objetivo de este estudio fue evaluar la calidad de vida relacionada con la salud de pacientes con cáncer de próstata en tratamiento de hormonioterapia y radioterapia. MATERIALES Y MÉTODOS: Estudio descriptivo, transversal, con datos sociodemográficos, clínicos y de evaluación de la calidad de vida de 213 pacientes, obtenidos por un guión de entrevista y por el cuestionario Expanded Prostate Cancer Index Composite. Se utilizó estadística descriptiva. RESULTADOS: Hubo predominio de hombres mayores de 50 anos, blancos, casados, con baja escolaridad y jubilados, con diagnóstico inicial obtenido por las alteraciones en el examen de Antígeno Prostático Específico y estadio II. Las medias de las puntuaciones obtenidas en el dominio de la función sexual indicaron caída en la calidad de vida, para ambos tratamientos. DISCUSIÓN: Tanto la hormonioterapia como la radioterapia pueden causar algún tipo de efecto en la función sexual, directamente relacionado con un significativo impacto en la calidad de vida relacionada con la salud para muchos hombres. CONCLUSIONES: Aunque los resultados han sido obtenidos y analizados por primera vez en el hospital del estudio, ofrecen subsidios para el conocimiento de la realidad local y corroboran los resultados con otros estudios realizados en locales y realidades diferentes.

Câncer de próstata: retrato de uma realidade de pacientes em tratamento / Prostate cancer: picture of a reality of patients in treatment

Objetivo: descrever os dados sociodemográficos e clínicos e as possíveis dúvidas, dificuldades e limitações enfrentadas pelos pacientes em tratamento de câncer de próstata. Método: estudo descritivo, transversal, de abordagem quantitativa, realizado com 213 homens em tratamento de câncer de próstata. Os dados foram obtidos através de um formulário de entrevista e analisado com auxílio do programa SPSS. Resultados: amostra composta por homens predominantemente acima dos 50 anos, brancos, casados, aposentados, com ensino fundamental completo. O diagnóstico inicial foi através de alterações no PSA e/ou toque retal, pelo SUS, com estadiamento II. Das dificuldades e limitações sobressaíram as manifestações de alterações na função sexual e urinária. Conclusão: o conhecimento das características e opiniões dos participantes diante do diagnóstico e tratamento poderão contribuir para o planejamento da assistência prestada visando estabelecer medidas preventivas, terapêuticas e outras ações voltadas para melhor assistência.

Musculoskeletal disorders and stress among footwear industry workers.

BACKGROUND: Manufacturing footwear requires intense manual labor and high repetitions with low variability in function that may lead to musculoskeletal disorders (MSD) symptoms and psychological stress. OBJECTIVE: To evaluate a potential association between musculoskeletal disorders (MSD) and perceived stress among footwear industry workers. METHODS: The Nordic General Questionnaire (NGQ) and the Perceived Stress Scale (PSS-10) were completed by 357 footwear industry workers. The association between MSD and perceived stress was evaluated using the Chi-Square test and Odds Ratios along with their 95% Confidence Interval (95% CI) were calculated. RESULTS: The twelve-month prevalence of MSD symptoms among the respondents was 66% (n = 236) and the symptoms were significantly associated with perceived stress (p = 0.002, OR: 10, 95% CI: 1.7 to 60.6). The seven-day prevalence of MSD symptoms was 33% and the symptoms were also significantly associated with perceived stress (p = 0.001, OR: 2.7, 95% CI:0.8 to 9.3). The association between perceived stress and MSD symptoms indicates a strong association between MSD symptoms and perceived stress levels. CONCLUSION: Considering that these problems are important determinants of worker's health, a combined approach to reduce both stress and MSD symptoms is necessary for prevention and health promotion in the footwear industry.

N-Myc overexpression increases cisplatin resistance in neuroblastoma via deregulation of mitochondrial dynamics.

N-Myc is a global transcription factor that regulates the expression of genes involved in a number of essential cellular processes including: ribosome biogenesis, cell cycle and apoptosis. Upon deregulation, N-Myc can drive pathologic expression of many of these genes, which ultimately defines its oncogenic potential. Overexpression of N-Myc has been demonstrated to contribute to tumorigenesis, most notably for the pediatric tumor, neuroblastoma. Herein, we provide evidence that deregulated N-Myc alters the expression of proteins involved in mitochondrial dynamics. We found that N-Myc overexpression leads to increased fusion of the mitochondrial reticulum secondary to changes in protein expression due to aberrant transcriptional and post-translational regulation. We believe the structural changes in the mitochondrial network in response to N-Myc amplification in neuroblastoma contributes to two important aspects of tumor development and maintenance-bioenergetic alterations and apoptotic resistance. Specifically, we found that N-Myc overexpressing cells are resistant to programmed cell death in response to exposure to low doses of cisplatin, and demonstrated that this was dependent on increased mitochondrial fusion. We speculate that these changes in mitochondrial structure and function may contribute significantly to the aggressive clinical ph9enotype of N-Myc amplified neuroblastoma.

Toll-like receptor 4-mediated lymphocyte influx induces neonatal necrotizing enterocolitis.

The nature and role of the intestinal leukocytes in necrotizing enterocolitis (NEC), a severe disease affecting premature infants, remain unknown. We now show that the intestine in mouse and human NEC is rich in lymphocytes that are required for NEC development, as recombination activating gene 1­deficient (Rag1­/­) mice were protected from NEC and transfer of intestinal lymphocytes from NEC mice into naive mice induced intestinal inflammation. The intestinal expression of the lipopolysaccharide receptor TLR4, which is higher in the premature compared with full-term human and mouse intestine, is required for lymphocyte influx through TLR4-mediated upregulation of CCR9/CCL25 signaling. TLR4 also mediates a STAT3-dependent polarization toward increased proinflammatory CD3+CD4+IL-17+ and reduced tolerogenic Foxp3+ Treg lymphocytes (Tregs). Th17 lymphocytes were required for NEC development, as inhibition of STAT3 or IL-17 receptor signaling attenuated NEC in mice, while IL-17 release impaired enterocyte tight junctions, increased enterocyte apoptosis, and reduced enterocyte proliferation, leading to NEC. Importantly, TLR4-dependent Th17 polarization could be reversed by the enteral administration of retinoic acid, which induced Tregs and decreased NEC severity. These findings identify an important role for proinflammatory lymphocytes in NEC development via intestinal epithelial TLR4 that could be reversed through dietary modification.

Promoção da saúde e tuberculose / Health promotion and tuberculosis

A tuberculose (TB) é uma doença antiga que acompanha a humanidade há milênios. Apesar dos vários esforços para seu controle e eliminação os indicadores da doença são altos, especialmente nos países com precárias condições de vida. Objetivando realizar uma revisão sistemática da literatura para identificar pesquisas que associem algum indicador epidemiológico da tuberculose com as condições de vida da população, foram realizadas buscas eletrônicas em publicações nos bancos de dados Scientific Electronic Library Online (SCIELO) e na Biblioteca Regional de Medicina (BIREME). Das publicações selecionadas 9 (52,9%) foram estudos ecológicos com representação espacial, 6 (35,3%) utilizaram como método a pesquisa qualitativa com utilização de entrevistas e 2 (11,8%) foram estudos epidemiológicos descritivos. Os aspectos socioeconômicos como índice de desenvolvimento humano, renda, emprego/ocupação, condições de moradia, quantidade de pessoas por residência e o acesso aos serviços de saúde foram os mais frequentemente utilizados. Após décadas de tentativas de controle e eliminação da doença, o país vive uma fase de estagnação da qual dependem estratégias e políticas mais amplas voltadas à promoção da saúde, para superar não só os altos indicadores epidemiológicos da tuberculose, como de várias doenças.

Tuberculosis (TB) is an ancient disease that accompanies humankind for millennia. Despite various efforts for its control and elimination, the disease indicators are high, especially in countries with poor living conditions. Aiming at performing a systematic review of the literature to identify studies involving tuberculosis epidemiological indicator related to the population living conditions, electronic searches were conducted in publications in the databases of Scientific Electronic Library Online (SciELO) and the Regional Library of Medicine (BIREME). From the publications selected, nine (52.9%) were ecological studies with spatial representation, six (35.3%) used a qualitative research as their method with the use of interviews, and two (11.8%) were descriptive epidemiological studies. The socio-economic aspects such as the human development index, income, employment/occupation, housing conditions, number of people per household and access to health services were the most frequent aspects used. After decades of attempts to control and eliminate the disease, the country is experiencing a period of stagnation that depends on broader strategies and policies aimed at promoting health, in order to overcome not only the high epidemiological indicators of tuberculosis, but also various other diseases.

Qualidade de vida de trabalhadores informais da mineração / Quality of life of informal mining workers / Calidad de vida de los trabajadores informales de minería

Objetivo:avaliar a qualidade de vida de trabalhadores informais da mineração. Método:estudo descritivo, transversal-analítico, realizado na área territorialparaibana denominada de Província Pegmatítica da Borborema com 371 trabalhadores informais da mineração da região do Seridó paraibano. Para a coleta de dados foi utilizado o Medical Outcomes Study 36-Item Short-Form Health Survey(SF-36), analisado a partir de métodos de estatística descritiva e inferencial (nível de significância igual a 5%). O projeto de pesquisa recebeu parecer favorável do Comitê de Ética em Pesquisa, CAAE 07052613.8.0000.5495. Resultados: a média geral para qualidade de vida dos trabalhadores foi de 80,17+11,89. Entre os domínios avaliados, o maior escore foi obtido para acapacidade funcional (92,03+15,75), e o menor para a vitalidade (69,26+16,13). Conclusão: este estudo vem demonstrar que a forma de trabalho informal apresenta poucocomprometimento com a qualidade de vida dos trabalhadores.(AU)

Objective: evaluation of the quality of life of informal mining workers in Seridó, a region of the State of Paraíba.Method: adescriptive, transversal and analytical study conducted in a territorial area in Paraiba denominated the Province Pegmatítica da Borborema with 371 informal mining workers. For the data collection it was used the Medical Outcomes Study 36-item Short-Form Health Survey (SF-36), analyzed from descriptive and inferential statistical methods (significance level of 5%). The research project was approved by the University of Franca Research Ethics Committee, CAAE 07052613.8.0000.5495. Results: the general average for the quality of life presented was of 80,17+11,89 points. Considering the domains, the highest score was of the functional capacity (92,03 ±15,75 points) and the worst averages were for the vitality (69,26±16,13 points). Conclusion: this study demonstrates that informal work presented little commitment with the quality of life of the workers.(AU)

Objetivo: evaluar la calidad de vida de los trabajadores informales de minería en la región minera de Paraíba, Seridó. Método: este es unestudio descriptivo, transversal analítico conducido en Paraíba en el ámbito territorial llamado Provincia Pegmatítica da Borborema con 371 trabajadores mineros informales. Para recoger los datos se utilizó el Medical Outcomes Study 36-item Short-FormHealth Survey(SF-36) y se analizaron utilizando métodos de estadística descriptiva e inferencial (nivel de significación de 5%). El proyecto de investigación ha recibido un dictamen favorable del Comité de Ética en la Investigación de la Universidad de Franca, CAAE 07052613.8.0000.5495. Resultados:la media general de la calidad de vida de los trabajadores fue de 80,17+11,89. Entre las áreas evaluadas, la puntuación más alta se obtuvo para la capacidad funcional (92,03+15,75) y la más baja para la vitalidad (69,26+16,13). Conclusión: este estudio demuestra que el trabajo informal muestra poco compromiso con la calidad de vida de los trabajadores.(AU)

Synthesis of anti-inflammatory α-and ß-linked acetamidopyranosides as inhibitors of toll-like receptor 4 (TLR4).

The low-molecular weight isopropyl 2-acetamido-α-glucoside 16 (C34) inhibits toll-like receptor 4 (TLR4) in enterocytes and macrophages in vitro, and reduces systemic inflammation in mouse models of endotoxemia and necrotizing enterocolitis. We used a copper(II)-mediated solvolysis of anomeric oxazolines and an acid-mediated conversion of ß-glucosamine and ß-galactosamine pentaacetates to generate analogs of 16 at the anomeric carbon and at C-4 of the pyranose ring. These compounds were evaluated for their influence on TLR4-mediated inflammatory signaling in cultured enterocytes and monocytes. Their efficacy was confirmed using a NF-kB-luciferase reporter mouse, thus establishing the first structure-activity relationship (SAR) study in this series and identifying the more efficacious isopropyl 2-acetamido-α-galactoside 17.

Identification of a novel germline FOXE1 variant in patients with familial non-medullary thyroid carcinoma (FNMTC).

The familial forms of non-medullary thyroid carcinoma (FNMTC) represent approximately 5 % of thyroid neoplasms. Nine FNMTC susceptibility loci have been mapped; however, only the DICER1 and SRGAP1 susceptibility genes have been identified. The transcription factors NKX2-1, FOXE1, PAX8, and HHEX are involved in the morphogenesis and differentiation of the thyroid. Recent studies have identified NKX2-1 germline mutations in FNMTC families. However, the role of high-penetrant FOXE1 variants in FNMTC etiology remains unclear. The aim of this study was to investigate the role of FOXE1 germline mutations in the pathogenesis of FNMTC. We searched for molecular changes in the FOXE1 gene in the probands from 60 Portuguese families with FNMTC. In this series, we identified nine polymorphisms and one variant (c.743C>G, p.A248G) which was not previously described. This variant, which involved an amino acid residue conserved in evolution, segregated with disease in one family, and was also detected in an apparently unrelated case of sporadic NMTC. Functional studies were performed using rat normal thyroid cells (PCCL3) clones and human papillary thyroid carcinoma cell line (TPC-1) pools, expressing the wild type and mutant (p.A248G) forms of FOXE1. In these experiments, we observed that the p.A248G variant promoted cell proliferation and migration, suggesting that it may be involved in thyroid tumorigenesis. Additionally, somatic p.V600E BRAF mutations were also detected in the thyroid tumors of two members of the family carrying the p.A248G variant. This study represents the first evidence of involvement of a germline FOXE1 rare variant in FNMTC etiology and suggests that mutations in MAPK pathway-related genes may contribute to tumor development in these familial cases.