Sedentary time play a moderator role in the relationship between physical fitness and brain-derived neurotrophic factor in children. A pilot study.

Aim: Despite some advances, there are many controversies concerning brain-derived neurotrophic factor (BDNF) and its relationships with variables related to physical fitness and sedentary time, especially in children. The aim of the study was to explore the moderating role of sedentary time on the association between physical fitness and BDNF. Therefore, this study will add to the perspective of understanding how much time children may spend being sedentary with no deleterious influence on the positive association between physical fitness and BDNF. Methods: This cross-sectional study included 44 children aged between 6 and 11 years (9.02 ± 1.43) from a public school in Porto Alegre, Brazil. Cardiorespiratory fitness (CRF) was determined by the 6-min walk/run test, and muscular strength was determined through the lower limb strength test (LLS). Sedentary time was assessed through accelerometers, and blood samples were collected to determine serum BDNF levels (z score). Moderation analysis was performed using the PROCESS macro adjusted for sex, age, somatic maturation, waist circumference, and socioeconomic level. Results: Sedentary time moderates the relationship between CRF and BDNF, such that children should spend less than 511 minutes per day sedentary to achieve the benefits of CRF in BDNF concentrations. Conclusion: Sedentary time plays a significant moderating role in the relationship between CRF and BDNF. Therefore, to promote brain health in children, both increasing physical fitness and reducing sedentary time might be encouraged.

MiR-193b promoter methylation accurately detects prostate cancer in urine sediments and miR-34b/c or miR-129-2 promoter methylation define subsets of clinically aggressive tumors.

BACKGROUND: Contemporary challenges of prostate cancer (PCa) include overdiagnosis and overtreatment, entailing the need for novel clinical tools to improve risk stratification and therapy selection. PCa diagnosis and prognostication might be perfected using epigenetic biomarkers, among which aberrant DNA methylation of microRNA promoters has not been systematically explored. Herein, we identified aberrantly methylated microRNAs promoters in PCa and assessed its diagnostic and prognostic biomarker potential. METHODS: Using HumanMethylation450 BeadChip-based analysis differentially methylated CpGs in microRNA promoters were identified. Promoter methylation of six microRNAs (miR-34b/c, miR-129-2, miR-152, miR-193b, miR-663a and miR-1258) was analyzed by qMSP in three sets (180 prostatectomies, 95 urine sediments and 74 prostate biopsies). Biomarkers' diagnostic (validity estimates) and prognostic [disease-free (DFS) and disease-specific survival (DSS)] performance was assessed. RESULTS: Significantly higher promoter methylation levels in PCa were confirmed for six candidate microRNAs. Except for miR-152, all displayed AUC values higher than 0.90, with miR-1258 and miR-193b disclosing the best performance (AUC = 0.99 and AUC = 0.96, respectively). In urine samples, miR-193b showed the best performance (91.6% sensitivity, 95.7% specificity, AUC = 0.96). Moreover, higher miR-129-2 independently predicted for shorter DSS and miR-34b/c methylation levels independently predicted for shorter DFS and DSS. CONCLUSIONS: Quantitative miR-193b, miR-129-2 and miR-34b/c promoter methylation might be clinically useful PCa biomarkers for non-invasive detection/diagnosis and prognostication, both in tissue and urine samples.

Identification of somatic TERT promoter mutations in familial nonmedullary thyroid carcinomas.

OBJECTIVE: The genes causing familial nonmedullary thyroid carcinoma (FNMTC) identified to date are only involved in a small fraction of the families. Recently, somatic mutations in TERT promoter region and in EIF1AX gene were reported in thyroid tumours of undefined familial status. The aim of this study was to investigate the role of TERT and EIF1AX mutations in familial thyroid tumours. DESIGN: The promoter region of TERT was sequenced in leucocyte DNA of the probands from 75 FNMTC families. In thyroid tumours from 54 familial cases, we assessed somatic TERT promoter, RAS and BRAF hotspot mutations, and the whole EIF1AX gene. RESULTS: No potentially pathogenic germline variants were identified in TERT in the 75 FNMTC families' probands. In the 54 carcinomas, we identified five cases (9%) with hotspot somatic TERT promoter mutations. BRAF mutations were found in 41% of the tumours. All TERT-positive samples were also positive for BRAF p.Val600Glu, and this co-occurrence was found to be statistically significant (P=.008). RAS mutations were detected in four tumours wild-type for TERT (7%). Evaluation of tumour mutation data together with the patients' clinicopathological features revealed a significant correlation between TERT plus BRAF mutations and advanced tumour stage (T4) (P=.020). No mutations were identified in EIF1AX. CONCLUSIONS: The results of this study suggest that TERT promoter and EIF1AX mutations are not frequently involved in FNMTC aetiology. However, we show for the first time that TERT alterations are associated with familial thyroid tumour progression. Our data also suggest that TERT mutations are more often found in concomitance with BRAF mutations in advanced stages of FNMTC.

A validated dilute-and-shoot LC-MS-MS urine screening for the analysis of 95 illicit drugs and medicines: Insights from clinical and forensic Brazilian cases.

Urine toxicological analysis is a relevant tool in both clinical and forensic scenarios, enabling the diagnosis of acute poisonings, elucidation of deaths, verification of substance use in the workplace and identification of drug-facilitated crimes. For these analyses, the dilute-and-shoot technique associated with liquid chromatography coupled with tandem mass spectrometry (LC-MS-MS) is a promising alternative since it has demonstrated satisfactory results and broad applicability. This study developed and validated a comprehensive LC-MS-MS screening method to analyze 95 illicit drugs and medicines in urine samples and application to clinical and forensic Brazilian cases. The dilute-and-shoot protocol was defined through multivariate optimization studies and was set using 100 µL of sample and 300 µL of solvent. The total chromatographic run time was 7.5 min. The method was validated following the recommendations of the ANSI/ASB Standard 036 Guideline. The lower limits of quantification varied from 20 to 100 ng/mL. Within-run and between-run precision coefficient of variations% were <20%, and bias was within ± 20%. Only 4 of the 95 analytes presented significant ionization suppression or enhancement (>25%). As proof of applicability, 839 urine samples from in vivo and postmortem cases were analyzed. In total, 90.9% of the analyzed samples were positive for at least one substance, and 78 of the 95 analytes were detected. The most prevalent substances were lidocaine (40.2%), acetaminophen (38.0%) and benzoylecgonine (31.5%). The developed method proved to be an efficient and simplified alternative for analyzing 95 therapeutic and illicit drugs in urine samples. Additionally, the results obtained from sample analysis are essential for understanding the profile of Brazilian substance use, serving as a valuable database for the promotion of health and safety public policies.

First Case Report of Bilateral Parotid Lymphoepithelial Carcinoma.

Background/Aim: The parotid is the largest salivary gland and is located anteriorly to the sternocleidomastoid muscle and laterally to the ramus of the mandible. Neoplasms in this gland are relatively rare, with 80% being benign and 20% malignant, primarily represented by mucoepidermoid carcinoma. In the head and neck region, lymphoepithelial carcinoma (LEC) accounts for 0.4% of malignant salivary gland tumors. Case Report: A 35-year-old man with no previous comorbidities was admitted to a Head and Neck Surgery Specialty Service for a painless right cervical mass of uncertain growth. Extensive diagnostic investigation revealed involvement of the contralateral parotid, associated with systemic lymph node enlargement. Thus, adjuvant radiotherapy was decided by the treating team. Conclusion: This case confirms the heterogeneous features and distinctive behavior that the disease can present, as seen with bilateral parotid LEC.

Cork sheet as an efficient biosorbent for forensic toxicology: Application to vitreous humor analysis.

There is an increasing number of people affected worldwide by mental health disorders, such as depression and anxiety. One of the main courses of treatment, along with psychotherapy, is the use of psychoactive medications, like antidepressants and benzodiazepines. Also, the unprescribed use of these substances is a concerning public health issue. Hence, the analysis of psychotropic medications is mandatory in postmortem toxicology and various biological samples can be used for this detection, among them the vitreous humor (VH) stands out. Also, there is a demand for more sustainable and more efficient extraction methodologies according to green chemistry. An example is solid phase microextraction techniques (SPME), which use a solid sorbent and small solvent amounts. Biosorbents are substances of natural origin with sorptive properties, and they have been successfully used in SPME in environmental toxicology for water analysis, mainly. This study aimed to develop a sustainable, fast, cheap and simple SPME methodology using cork sheet strips as a biosorbent, to extract antidepressants, benzodiazepines and others from VH samples by liquid chromatography coupled to tandem mass spectrometry. The extraction was conducted in a 96-well plate using 200 µL of VH and optimization of relevant parameters for extraction was performed. For solvent optimization, two simplex-centroid experiments were planned for extraction and desorption and to evaluate time and pH, a Doehlert design experiment was performed. The analytical method for the determination and quantification of 17 substances was validated. The quantification limits were 5 ng/mL for all analytes and the calibration curves were linear between 5 and 30 ng/mL. This study was able to develop an efficient, cheap, simple and fast microextraction method for 17 analytes in VH, using strips of cork sheet for extraction and a 96-well plate as a container. Furthermore, this approach system could be automated for routine toxicology laboratories.

Effects of resistance training on the glycemic control of people with type 1 diabetes: a systematic review and meta-analysis.

Resistance training has shown the potential to contribute to better glycemic control in people with Type 1 Diabetes (T1D), however, there are contradictory results in this regard and a need to clarify the effects of isolated resistance training on glycemic control in T1D. The aim was to verify the effects of resistance training on the glycemic control of people with T1D. Original articles were selected, randomized and non-randomized clinical trials that aimed to verify chronic responses, through the concentrations of glycated hemoglobin (HbA1c), to a structured program of resistance exercise in the glycemia of patients with T1D. The following databases were searched; MEDLINE, PubMed, Web of Science, Scopus, ScienceDirect, LILACS, and SciELO. Five studies were included in the review. A reduction in HbA1c was observed (SMD = -0.568 ± 0.165 [95% CI = -0.891 to -0.246]; p = 0.001; I2 = 82%) in patients undergoing resistance training, when compared to the control group (SMD = 1.006 ± 0.181 [95% CI = 0.653 to 1.360]; p <0.001). Two studies, with children and adolescents and longer interventions, demonstrated a significant reduction in HbA1c, increased strength, and an improved lipid profile. Resistance training was efficient for assisting in glycemic control in people with T1D and should be incorporated in treatment plans.

Bioanalytical method for simultaneous determination of benzodiazepines in vitreous humor using liquid chromatography-tandem mass spectrometry.

The use of vitreous humor (VH) in forensic casework has been growing in the last years due to numerous advantages. Several compounds can be evaluated in this matrix, including benzodiazepines whose determination is essential due to their great availability and potential of dependance and misuse. Postmortem toxicological analyses are required to determine the influence of benzodiazepines in deaths. However, most of the analytical methods which determine these drugs in VH are laborious and time consuming. This article describes a simple method based on protein precipitation for the determination of eight benzodiazepines in VH samples. Samples were prepared through a protein precipitation method and analyzed by liquid chromatography tandem mass spectrometry. Solvent choice and sample and solvent volumes for precipitation were optimized using chemometric approaches. The method was validated for selectivity, lower limit of quantification (LLOQ), linearity, carryover, precision, bias, matrix effect and dilution integrity. In order to verify the applicability, 62 vitreous humor samples were analyzed. LLOQs were 1 ng/mL and calibration curves were linear from 1 to 25 ng/mL (r2 > 0,99) for all analytes. Bias, precision and dilution integrity results were satisfactory according to proper guidelines. Ionization suppression was significant with values ranging from 8 to 37%. Two samples from real cases were positive for diazepam with the following concentrations: 6.80 ng/mL and 47.68 ng/mL, approximately 10 times lower than those found in peripheral blood. The procedure described here can be used as a straightforward and low cost method for the quantitation of multiple benzodiazepines in VH.

Expression of EMT-Related Genes CAMK2N1 and WNT5A is increased in Locally Invasive and Metastatic Prostate Cancer.

Purpose: Prostate cancer (PCa) varies clinically from very indolent, not requiring therapeutic intervention, to highly aggressive, entailing radical treatment. Currently, stratification of PCa aggressiveness is mostly based on Gleason score, serum PSA and TNM stage, but outcome prediction in an individual basis is suboptimal. Thus, perfecting pre-therapeutic discrimination between indolent and aggressive PCa, avoiding overtreatment is a major challenge. Epithelial to mesenchymal transition (EMT) allows epithelial cells to acquire mesenchymal properties, constituting a critical step in tumor invasion and metastization. Thus, we hypothesized that EMT-related markers might allow for improved assessment of PCa aggressiveness. Methods and Results: Using RealTime ready Custom Panel 384 assay, 93 EMT-related genes were assessed in normal prostate tissues (NPT, n=5), stage pT2a+b-PCa (n=5) and stage pT3b-PCa (n=5), from which CAMK2N1, CD44, KRT14, TGFß3 and WNT5A genes emerged as the most significantly altered. Expression levels were then evaluated in a larger series (16 NPT and 94 PCa) of frozen tissues using quantitative RT-PCR. Globally, CAMK2N1, CD44 and WNT5A displayed higher expression levels at higher stages and less differentiated PCa. CAMK2N1 and WNT5A immunoexpression analysis disclosed significantly lower expression in NPT and increasing proportion of high-expression cases from pT2a+b to pT3b and metastatic PCa. Furthermore, higher CAMK2N1 and WNT5A transcript levels associated with shorter disease-free and disease-specific survival. In multivariable analysis, a trend for WNT5A expression levels to independently predict DFS was disclosed (p=0.056). Conclusions: Globally, our findings suggest an association between PCa aggressiveness and increased expression of CAMK2N1 and WNT5A, reflecting the acquisition of effective EMT characteristics by PCa cells.

LOW-COST SIMULATOR ASSEMBLY FOR 3-DIMENSIONAL VIDEOSURGERY TRAINING.

BACKGROUND: Three-dimensional videosurgery is already a reality worldwide. The trainee program for this procedure should be done initially and preferably in simulators. AIM: Assemble low-cost simulator for three-dimensional videosurgery training. METHODS: The simulator presented here was mounted in two parts, base and glasses. After, several stations can be inserted into the simulator for skills training in videosurgery. RESULTS: It was possible to set up three dimensional (3D) video simulations with low cost. It has proved to be easy to assemble and allows the training surgeon of various video surgical skills. CONCLUSION: This equipment may be used in undergraduate programs and advanced courses for residents and surgeons. The acrylic box allows the visualization of the task executed by the tutor and even by other experienced students.

Assessment of Physical Therapy Strategies for Recovery of Urinary Continence after Prostatectomy

Introduction: Urinary incontinence is a complication of radical prostatectomy. Pelvic floor exercises can facilitate recovery of continence after surgery; however, there is not sufficient evidence that physical therapy with biofeedback training is effective, particularly with respect to providing a faster recovery. Objective: To analyze the application of physical therapy techniques in the recovery of urinary incontinence after prostatectomy. Methodology: A randomized clinical trial was conducted from April to October 2015 with patients undergoing radical prostatectomy up to three months after surgery at the Santa Casa de Misericordia in Northeastern Brazil. The physical therapy intervention consisted of up to eight individual sessions. Patients were randomized into the intervention group, which performed exercises and received biofeedback training, and the control group, which performed exercises alone. Participants were assessed before, during and after treatment. The initial assessment included a structured instrument addressing sociodemographic and urological data. Frequencies were calculated for all variables and comparisons were checked by the Mann-Whitney test and for correlation significance. Results: The study included 13 patients aged 54-74 years, the majority undergoing retropubic surgery with mild urinary incontinence [11 (84.6%)]. There was a significant difference in the outcome of the pad test before (p=0.070) and after (p=0.015) treatment between the groups, but the reduction of urinary loss and the time to recovery of continence were equivalent for both groups. Conclusion: Both interventions provided improvement in the degree of incontinence within two months of treatment.

Electrochemical treatment of shrimp farming effluent: role of electrocatalytic material.

This study investigated the electrochemical oxidation of organic matter present in shrimp farming effluent using three types of electrocatalytic materials: Ti/Ru0.34Ti0.66O2, Ti/Pt, and boron-doped diamond (BDD). An electrochemical cell with 300 mL under stirring agitation was used by applying 20, 40, and 60 mA cm-2. A Ti/Ru0.34Ti0.66O2 anode showed a reduction of chemical oxygen demand (COD) about 84 % after 1 h of electrolysis, while at the same time, 71 % of COD decay was achieved at Ti/Pt. Conversely, only 71 % of COD was removed after 2 h with a BDD anode. Regarding the temperature effect, BDD showed better performances than those achieved for Ti/Ru0.34Ti0.66O2 and Ti/Pt anodes during an electrochemical treatment of a shrimp farming effluent, obtaining 72 % of COD removal by applying 20 mA cm-2 at 40 °C after 15 min. Energy consumption and cost were estimated in order to established the engineering applicability of this alternative process.

Risk factors for death among critically ill patients with acute renal failure.

CONTEXT AND OBJECTIVE: Acute renal failure is a common medical problem, with a high mortality rate. The aim of this work was to investigate the risk factors for death among critically ill patients with acute renal failure. DESIGN AND SETTING: Retrospective cohort at the intensive care unit of Hospital Universitário Walter Cantídio, Fortaleza. METHODS: Survivors and non-survivors were compared. Univariate and multivariate analyses were performed to establish risk factors for death. RESULTS: Acute renal failure occurred in 128 patients (33.5%), with mean age of 49 +/- 20 years (79 males; 62%). Death occurred in 80 (62.5%). The risk factors most frequently associated with death were hypotension, sepsis, nephrotoxic drug use, respiratory insufficiency, liver failure, hypovolemia, septic shock, multiple organ dysfunction, need for vasoactive drugs, need for mechanical ventilation, oliguria, hypoalbuminemia, metabolic acidosis and anemia. There were negative correlations between death and: prothrombin time, hematocrit, hemoglobin, systolic blood pressure, diastolic blood pressure, arterial pH, arterial bicarbonate and urine volume. From multivariate analysis, the independent risk factors for death were: need for mechanical ventilation (OR = 3.15; p = 0.03), hypotension (OR = 3.48; p = 0.02), liver failure (OR = 5.37; p = 0.02), low arterial bicarbonate (OR = 0.85; p = 0.005), oliguria (OR = 3.36; p = 0.009), vasopressor use (OR = 4.83; p = 0.004) and sepsis (OR = 6.14; p = 0.003). CONCLUSIONS: There are significant risk factors for death among patients with acute renal failure in intensive care units, which need to be identified at an early stage for early treatment.

Evaluation of the positioning of the tip of the Veress needle during creation of closed pneumoperitoneum in pigs.

PURPOSE: Erroneous punctures and insufflations are frequent with the use of the Veress needle. Mistaken injections of gas in the preperitoneal space are not rare. The purpose of this research is to evaluate the correct positioning of the tip of the needle during creation of pneumoperitoneum. METHODS: The needle was inserted into the peritoneal cavity. Tests to assess the positioning of the needle tip were carried out. Pressure, flow rate and volume were periodically recorded and the needle was removed, being immediately reinserted into the right hypochondrium and placed in the preperitoneal space. RESULTS: The liquid flow test was always positive in the peritoneal cavity. No resistance to saline injection into the peritoneal cavity was observed, but increased resistance to saline injection into the preperitoneal space was observed in 45.5% of the cases. Some saline was recovered in 63.5% of the cases in the peritoneal cavity, and in 54.5% in the preperitoneal space. Saline drop test was positive in 66.6% of the cases in the peritoneal cavity and in 45.5% in the preperitoneal space. In the peritoneal cavity, initial pressure lower than 5 mm Hg was observed, and this pressure gradually increased during 123 seconds until reaching 15 mm Hg. In the preperitoneal space, initial pressure was 15 mm Hg. CONCLUSIONS: Aspiration, liquid flow and saline drop tests are important, whereas recovery test is inconclusive. Initial pressure of approximately 5 mm Hg indicates that the tip of the needle is in the peritoneal cavity. The peritoneal cavity should hold ten times as much volume of gas as the preperitoneal space. The increase in pressure and volume in the peritoneal cavity can be predicted by statistics.

TOTAL COST OF HOSPITALIZATION OF PATIENTS UNDERGOING ELECTIVE LAPAROSCOPIC CHOLECYSTECTOMY RELATED TO NUTRITIONAL STATUS.

BACKGROUND: In the Western world, the population developed an overweight profile. The morbidly obese generate higher cost to the health system. However, there is a gap in this approach with regard to individuals above the eutrofic pattern, who are not considered as morbidly obese. AIM: To correlate nutritional status according to BMI with the costs of laparoscopic cholecystectomy in a public hospital. METHOD: Data were collected from medical records about: nutritional risk assessment, nutricional state and hospital cost in patients undergoing elective laparoscopic cholecystectomy. RESULTS: Were enrolled 814 procedures. Average age was 39.15 (±12.16) years; 47 subjects (78.3%) were women. The cost was on average R$ 6,167.32 (±1830.85) to 4.06 (±2.76) days of hospitalization; 41 (68.4%) presented some degree of overweight; mean BMI was 28.07 (±5.41) kg/m²; six (10%) individuals presented nutritional risk ≥3. There was a weak correlation (r=0.2) and not significant (p <0.08) between the cost of hospitalization of the sample and length of stay; however, in individuals with normal BMI, the correlation was strong (r=0,57) and significant (p<0.01). CONCLUSION: Overweight showed no correlation between cost and length of stay. However, overweight individuals had higher cost of hospitalization than those who had no complications, but with no correlation with nutritional status. Compared to those with normal BMI, there was a strong and statistically significant correlation with the cost of hospital stay, stressing that there is normal distribution involving adequate nutritional status and success of the surgical procedure with the consequent impact on the cost of hospitalization.

RACIONAL: No mundo ocidental, a população desenvolveu um perfil de excesso de peso corporal. Os obesos mórbidos geram custo mais alto para o sistema de saúde. Entretanto, observa-se um hiato no tocante aos indivíduos acima do eutrofismo, mas não considerados obesos mórbidos. OBJETIVO: Correlacionar estado nutricional, segundo o IMC, com custo de internação de colecistectomias videolaparoscópicas. MÉTODO: Coleta de dados dos prontuários sobre: avaliação de risco nutricional, estado nutricional e custo de internação de pacientes submetidos à colecistectomia videolaparoscópica eletiva no período de janeiro de 2012 a dezembro de 2014. RESULTADOS: Foram analisados 814 procedimentos. A idade média foi de 39,15 (±12,16) anos; 47 (78,3%) eram mulheres. O custo de internação foi, em média, de R$ 6.167,32 (±1.830,85) para 4,06 (±2,76) dias de internação. Quarenta e um (68,4%) pacientes apresentavam algum grau de sobrepeso; o IMC médio foi 28,07 (±5,41) kg/m²; seis (10%) indivíduos apresentavam risco nutricional ≥3. Houve correlação fraca (r=0,2) e não significativa (p<0,08) entre o custo de hospitalização e o tempo de permanência. No entanto, em indivíduos com IMC normal, a correlação foi forte (r=0,57) e significante (p<0,01). CONCLUSÃO: Sobrepeso não demonstrou correlação entre custo e tempo de internação. Entretanto, os indivíduos com sobrepeso apresentaram custo maior de internação em relação aos que não tiveram intercorrência, mas sem correlação com o estado nutricional. Em relação aos com IMC normal, houve correlação forte e estatisticamente significante com o custo para tempo de internação, reforçando que há provável distribuição normal envolvendo estado nutricional adequado e sucesso do procedimento cirúrgico com consequente impacto no custo de internação.

Male breast cancer: Looking for better prognostic subgroups.

PURPOSE: Male Breast Cancer (MBC) remains a poor understood disease. Prognostic factors are not well established and specific prognostic subgroups are warranted. PATIENTS/METHODS: Retrospectively revision of 111 cases treated in the same Cancer Center. Blinded-central pathological revision with immunohistochemical (IHQ) analysis for estrogen (ER), progesterone (PR) and androgen (AR) receptors, HER2, ki67 and p53 was done. Cox regression model was used for uni/multivariate survival analysis. Two classifications of Female Breast Cancer (FBC) subgroups (based in ER, PR, HER2, 2000 classification, and in ER, PR, HER2, ki67, 2013 classification) were used to achieve their prognostic value in MBC patients. Hierarchical clustering was performed to define subgroups based on the six-IHQ panel. RESULTS: According to FBC classifications, the majority of tumors were luminal: A (89.2%; 60.0%) and B (7.2%; 35.8%). Triple negative phenotype was infrequent (2.7%; 3.2%) and HER2 enriched, non-luminal, was rare (≤1% in both). In multivariate analysis the poor prognostic factors were: size >2 cm (HR:1.8; 95%CI:1.0-3.4 years, p = 0.049), absence of ER (HR:4.9; 95%CI:1.7-14.3 years, p = 0.004) and presence of distant metastasis (HR:5.3; 95%CI:2.2-3.1 years, p < 0.001). FBC subtypes were independent prognostic factors (p = 0.009, p = 0.046), but when analyzed only luminal groups, prognosis did not differ regardless the classification used (p > 0.20). Clustering defined different subgroups, that have prognostic value in multivariate analysis (p = 0.005), with better survival in ER/PR+, AR-, HER2-and ki67/p53 low group (median: 11.5 years; 95%CI: 6.2-16.8 years) and worst in PR-group (median:4.5 years; 95%CI: 1.6-7.8 years). CONCLUSION: FBC subtypes do not give the same prognostic information in MBC even in luminal groups. Two subgroups with distinct prognosis were identified in a common six-IHQ panel. Future studies must achieve their real prognostic value in these patients.

Familial vs sporadic papillary thyroid carcinoma: a matched-case comparative study showing similar clinical/prognostic behaviour.

OBJECTIVE: Familial non-medullary thyroid cancer has been proposed as an aggressive clinical entity. Our aim in this study is to investigate potential distinguishing features as well as the biological and clinical aggressiveness of familial vs sporadic papillary thyroid carcinoma (PTC). We assessed clinicopathological characteristics, outcome measures and DNA ploidy. DESIGN: A matched-case comparative study. METHODS: A series of patients with familial PTC (n=107) and two subgroups, one with three or more affected elements (n=32) and another including index cases only (n=61), were compared with patients with sporadic PTC (n=107), matched by age, gender, pTNM disease extension and approximate follow-up duration. Histological variant, extrathyroidal extension, vascular invasion, tumour multifocality and bilateral growth were evaluated. Ploidy pattern was analysed in available samples by DNA flow cytometry. The probabilities of disease-free survival (DFS) and overall survival (OS) were estimated according to the Kaplan-Meier (K-M) method. RESULTS: No patient with familial PTC died of disease during follow-up (median, 72 months), contrarily to five patients (4.7%) (P=0.06) with sporadic PTC (median, 90 months). There was a significantly higher tumour multifocality in familial PTC (index cases subgroup) vs sporadic PTC (P=0.035), and a trend, in the familial PTC cohort with three or more affected elements, to show extrathyroidal extension (P=0.054) more frequently. No difference was observed in DNA ploidy status. The K-M analyses showed no significant differences between both entities in relation to DFS or OS. CONCLUSION: Apart from multifocality, familial PTC appears to have similar clinical/prognostic behaviour when compared with sporadic forms of the disease.

Deregulated expression of selected histone methylases and demethylases in prostate carcinoma.

Prostate cancer (PCa), a leading cause of cancer-related morbidity and mortality, arises through the acquisition of genetic and epigenetic alterations. Deregulation of histone methyltransferases (HMTs) or demethylases (HDMs) has been associated with PCa development and progression. However, the precise influence of altered HMTs or HDMs expression and respective histone marks in PCa onset and progression remains largely unknown. To clarify the role of HMTs and HDMs in prostate carcinogenesis, expression levels of 37 HMTs and 20 HDMs were assessed in normal prostate and PCa tissue samples by RT-qPCR. SMYD3, SUV39H2, PRMT6, KDM5A, and KDM6A were upregulated, whereas KMT2A-E (MLL1-5) and KDM4B were downregulated in PCa, compared with normal prostate tissues. Remarkably, PRMT6 was the histone modifier that best discriminated normal from tumorous tissue samples. Interestingly, EZH2 and SMYD3 expression levels significantly correlated with less differentiated and more aggressive tumors. Remarkably, SMYD3 expression levels were of independent prognostic value for the prediction of disease-specific survival of PCa patients with clinically localized disease submitted to radical prostatectomy. We concluded that expression profiling of HMTs and HDMs, especially SMYD3, might be of clinical usefulness for the assessment of PCa patients and assist in pre-therapeutic decision-making.

Estratégia Saúde da Família rural: uma análise a partir da visão dos movimentos populares do Ceará / Rural Family Health Strategy: an analysis from the perspective of popular movements in Ceará

RESUMO A conquista do direito constitucional à saúde não se efetivou em diversos cenários. A partir dessa realidade, em 2011, foi publicada a Política Nacional de Saúde Integral das Populações do Campo, da Floresta e das Águas (PNSIPCFA). Este artigo objetiva analisar as práticas da Estratégia Saúde da Família (ESF) em territórios rurais no Ceará. Trata-se de estudo qualitativo, descritivo, realizado com 5 movimentos populares, sendo 3 entrevistados de cada um deles, totalizando 15 participantes. Utilizaram-se entrevista semiestruturada e análise do discurso. Os movimentos apontaram que houve expansão da ESF no campo, com avanços no acesso à saúde, apesar de existirem limitações. O Programa Mais Médicos destacou-se como marco relevante. Os movimentos têm o desafio de se apropriarem da PNSIPCFA, e contribuir, juntamente com ESF, para a ampliação da participação popular em saúde e reconhecimento dos saberes e práticas populares, considerando a determinação social da saúde.

ABSTRACT The conquest of the constitutional right to health has not been enforced in various scenarios. Considering this reality, in 2011 the National Policy for Integral Health of Countryside, Forest and Water Populations (PNSIPCFA) was published. This article aims to analyze the practices of the Family Health Strategy (FHS) in agricultural territories in Ceará. This is a qualitative, descriptive study, conducted with five popular movements, with 3 respondents from each movement, totaling 15 participants. Semi-structured interview and discourse analysis were used. The movements pointed out that there was an expansion of the FHS in the Countryside, with advances in access to health, despite some restrictions. The More Doctors Program stood out as a relevant milestone. The movements have the challenge of seizing the PNSIPCFA and contribute, along with the FHS, to the expansion of popular participation in health and recognition of popular knowledge and practices, considering the social determination of health.