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Made available in DSpace on 2022-04-29T08:30:40Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-01-01 Background: Thyroid nodules diagnosed as 'atypia of undetermined significance/ follicular lesion of undetermined significance' (AUS/FLUS) or 'follicular neoplasm/ suspected follicular neoplasm' (FN/SFN), according to Bethesda’s classification, represena challenge in clinical practice. Computerized analysis of nuclear images (CANI) could be a useful tool for these cases. Our aim was to evaluate the ability of CANI to correctly classify AUS/FLUS and FN/SFN thyroid nodules for malignancy. Methods: We studied 101 nodules cytologically classified as AUS/FLUS (n = 68) or FN/SFN (n = 33) from 97 thyroidectomy patients. Slides with cytological material were submitted for manual selection and analysis of the follicular cell nuclei for morphometric and texture parameters using ImageJ software. The histologically benign and malignant lesions were compared for such parameters which were then evaluated for the capacity to predict malignancy using the classification and regression trees gini model. The intraclass coefficient of correlation was used to evaluate method reproducibility. Results: In AUS/FLUS nodule analysis, the benign and malignant nodules differed for entropy (P < 0.05), while the FN/SFN nodules differed for fractal analysis, coefficient of variation (CV) of roughness, and CV-entropy (P < 0.05). Considering the AUS/FLUS and FN/SFN nodules separately, it correctly classified 90.0 and 100.0% malignant nodules, with a correct global classification of 94.1 and 97%, respectively. We observed that reproducibility was substantially or nearly complete (0.61–0.93) in 10 of the 12 nuclear parameters evaluated. Conclusion: CANI demonstrated a high capacity for correctly classifying AUS/FLUS and FN/SFN thyroid nodules for malignancy. This could be a useful method to help increase diagnostic accuracy in the indeterminate thyroid cytology. Department of Internal Medicine Botucatu Medical School Sao Paulo State University (Unesp) Department of Pathology Botucatu Medical School Sao Paulo State University (Unesp) Department of Surgery and Orthopedics Botucatu Medical School Sao Paulo State University (Unesp) Department of Dermatology Botucatu Medical School Sao Paulo State University (Unesp) Department of Otolaryngology and Head and Neck Surgery Botucatu Medical School Sao Paulo State University (Unesp) Instituto de Investigação e Inovação em Saúde (i3S) Universidade do Porto Cancer Signaling and Metabolism Group Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP) Department of Pathology Medical Faculty of the University of Porto Department of Internal Medicine Botucatu Medical School Sao Paulo State University (Unesp) Department of Pathology Botucatu Medical School Sao Paulo State University (Unesp) Department of Surgery and Orthopedics Botucatu Medical School Sao Paulo State University (Unesp) Department of Dermatology Botucatu Medical School Sao Paulo State University (Unesp) Department of Otolaryngology and Head and Neck Surgery Botucatu Medical School Sao Paulo State University (Unesp)

Background: Calcifying pseudoneoplasm of the neuroaxis (CAPNON) is a very rare benign lesion that can be located anywhere in the nervous system, with only 59 intracranial cases described. The general lack of knowledge about this lesion hinders its preoperative diagnosis. Despite the consistent image findings, the final diagnosis is only established based on anatomopathological and immunohistochemical studies. The lesion is more commonly positive for epithelial membrane antigen (EMA) and vimentin, and negative for glial fibrillary acidic protein (GFAP) and S-100, suggesting a leptomeningeal origin. The opposite, however, may also occur, although very rarely (just two cases positive for GFAP and negative for EMA and vimentin reported this far). The treatment consists of total resection of the lesion, which yields a good prognosis. Case Presentation: We report the case of a 23-year-old female who presented with disperceptive focal seizures, sometimes evolving to bilateral tonic-clonic seizures, starting at age 9. She had a nodular calcified lesion in the left precuneus and inferior parietal lobe. The lesion was completely resected, and the immunohistochemical study revealed positivity for EMA, vimentin, GFAP, and S-100. No case hitherto published was positive for all four markers. This atypical immunohistochemical profile of the CAPNON may suggest a dual origin of this lesion, both parenchymal and leptomeningeal. Conclusion: The general lack of knowledge of CAPNON makes this lesion underdiagnosed. Therefore, in the face of a calcified lesion in the nervous system, one should consider the possibility of a CAPNON among the differential diagnoses. The immunohistochemistry is undoubtedly an important tool, but the anatomopathological study, associated with image findings, remain the gold standard for the diagnosis of CAPNON.

Background Primary cardiac tumors are extremely rare and are usually diagnosed late due to the nonspecific symptoms. Surgery is the main treatment option, and despite chemotherapy, the prognosis remains poor. Cardiac invasion by metastatic tumors, while more common, also entails an unsatisfactory outcome. The aim of this study was to review patients (P) with malignant cardiac tumors that were diagnosed by transthoracic echocardiogram (TTE) or transoesophageal echocardiogram (TOE) in a tertiary center between 1995 and 2020. Methods Retrospective analysis of clinical data, echocardiographic assessment of tumor location and morphology, histology results and survival outcomes. Results A total of 44 malignant cardiac tumors were diagnosed: 12 primary tumors (A) and 32 metastatic tumors (B). A: Regarding primary cardiac tumors, the most common types were angiosarcomas (6), undifferentiated pleomorphic sarcomas (2), fibrosarcomas (2), myxofibrosarcoma (1) and primary cardiac lymphoma (1). The mean age of P at time of diagnosis was 43±15 years, 50% male. The most frequent presentation was heart failure symptoms (50%) followed by arrhythmias (20%). 1 P presented with pruritus and polyarthralgias. On TTE, the most prevalent tumor location was in the right-heart chambers (70%) – mostly the right atrium (50%), with mean dimensions of 40±18x27±11 mm. 85% of P had preserved biventricular systolic function and there was severe pericardial effusion in 38%. The most frequent metastatic involvement at diagnosis was pulmonary (33%) and hepatic (33%). 50% of P were submitted to tumor resection and 40% to chemotherapy. Regarding angiosarcomas, the most common immunohistochemical markers were vimentin, CD31 and CD34. The authors found a mortality rate of 10P (83%) in P with primary cardiac tumors, with a median time to mortality of 5.5 (IQR 2–10) months (Figure 1), in a median follow-up of 6.2 (IQR 2.5–15) months (minimum of 20 days and maximum of 19 years). In the latter case, the P was submitted to heart transplantation after diagnosis of a fibrosarcoma and is still alive and well. B: Regarding secondary cardiac invasion, there was a diagnosis of the following primary tumor sites: 12 lung carcinomas, 7 thymomas, 4 lymphomas, 3 hepatocellular carcinomas, 2 bladder carcinomas, 1 parathyroid carcinoma, 1 soft tissue sarcoma, 1 uterine sarcoma and 1 melanoma. The mean age of P was 57±19 years, 57% male. On TTE/TOE the authors found a right-sided chambers predominance (12 P, 38%) vs left-sided chambers in (8 P, 25%), with pericardial metastasis also present in 13 P (41%). Cardiac tamponade occurred in 6P (19%). The mortality rate was 75% (24P), with a median time to mortality of 1.1 (IQR 0.6–3.8) months (minimum of 7 days, maximum of 44 months), in a median follow-up of 2.3 (IQR 0.8–14) months. Conclusion Cardiac malignant tumors generally present in a late stage with a dismal prognosis. When possible, heart transplantation can be an option with a favourable outcome. Funding Acknowledgement Type of funding sources: None. Figure 1. Kaplan-Meier analysis

Summary: The Met/hepatocyte growth factor (HGF) receptor tyrosine kinase (RTK) is deregulated in many cancers and is a recognized target for cancer therapies. Following HGF stimulation, the signaling output of Met is tightly controlled by receptor internalization and sorting for degradation or recycling. Here, we uncover a role for autophagy in selective degradation of Met and regulation of Met-dependent cell migration and invasion. Met engagement with the autophagic pathway is dependent on complex formation with the mammalian ATG8 family member MAP1LC3C. LC3C deletion abrogates Met entry into the autophagy-dependent degradative pathway, allowing identification of LC3C domains required for rescue. Cancer cells with low LC3C levels show enhanced Met stability, signaling, and cell invasion. These findings provide mechanistic insight into RTK recruitment to autophagosomes and establish distinct roles for ATG8 proteins in this process, supporting that differential expression of ATG8 proteins can shape the functional consequences of autophagy in cancer development and progression. : The Met RTK regulates migratory invasive responses during development and cancer. Bell et al. describe a mechanism whereby MAP1LC3C selectively targets ligand-activated Met for degradation upon starvation-induced autophagy. Loss of the VHL tumor suppressor decreases LC3C, thereby uncoupling Met from autophagic regulation and enhancing HGF-stimulated invasion in cancer. Keywords: MET, autophagy, RTK, LC3C, VHL, cell migration, cell signaling, membrane trafficking, membrane trafficking, endocytosis, cancer

Responses to COVID-19 have included top-down, command-and-control measures, laissez-faire approaches, and bottom-up, community-driven solidarity and support, reflecting long-standing contradictions around how people and populations are imagined in public health-as a 'problem' to be managed, as 'free agents' who make their own choices, or as a potential 'solution' to be engaged and empowered for comprehensive public health. In this rapid review, we examine community-engaged responses that move beyond risk communication and instead meaningfully integrate communities into decision-making and multi-sectoral action on various dimensions of the response to COVID-19. Based on a rapid, global review of 42 case studies of diverse forms of substantive community engagement in response to COVID-19, this paper identifies promising models of effective community-engaged responses and highlights the factors enabling or disabling these responses. The paper reflects on the ways in which these community-engaged responses contribute to comprehensive approaches and address social determinants and rights, within dynamics of relational power and inequality, and how they are sometimes able to take advantage of the ruptures and uncertainties of a new pandemic to refashion some of these dynamics.

Introduction Obstructive Sleep Apnea Syndrome (OSAS) is a public health issue, due to its increasing prevalence and associated morbidity and mortality, worsened by the underestimated diagnosis of this entity in clinical practice. Objectives To correlate clinical, demographic and anthropometric indicators, and elaborate a predictive equation for OSAS severity and prevalence, in males and females. Methodology In this cross-sectional study, all the included patients performed a type I Polysomnography in ULSM – HPH Neurophysiology Laboratory, between July 2011 and December 2017. Patient’s weight, height, body mass index (BMI), waist circumference (WC) and neck circumference (NC) were assessed. Daytime excessive sleepiness was rated through the Epworth Sleepiness Scale (ESS). The apnea-hypopnea index and the snoring presence were obtained through the polygraphic recording. Demographic, anthropometric, clinical variables and ESS punctuation were correlated with the presence of OSAS and its severity through a multivariable regression model. Results The study included 472 patients (275 males and 197 females). OSAS prevalence was 65,7% (75,3% in males and 52,3% in females), being the males related to the most severe forms of OSAS (p < 0,001), the same happening with the age group 60-69 years. OSAS severity correlated directly with NC, WC, BMI and ESS increase. Snoring was present in 92,8% of the cases and did not correlate with OSAS severity. In females, severity correlated directly with age and BMI. Age and NC were identified as the strongest independent OSAS predictors (p-value=0,011 and p-value=0,006, respectively). Conclusion In this study, OSAS severity predictors were gender, age, NC, WC, BMI, snoring and ESS result (NC and age were the strongest independent predictors). These findings should be confirmed in more robust studies, to identify patients at risk of severe OSAS, to allow earlier diagnostic evaluation and therefore preventing OSAS associated complications.

Macroautophagy/autophagy is an evolutionarily conserved degradative process with a central role in maintaining cellular homeostasis under conditions of stress, and recent evidence suggests this may occur in part through direct modification of cell signaling. The MET/HGF receptor tyrosine kinase (RTK) signaling axis is an important mediator of cell motility and invasion in normal cell functions and in cancer. We discovered a role for autophagy in regulating ligand-activated MET signaling and cellular responses. When autophagy is induced by starvation, the HGF-activated and internalized MET RTK is selectively recruited for autophagic degradation through complex formation with the MAP1LC3C autophagy protein. Decreased LC3C expression in cancer results in loss of autophagic degradation of MET and enhanced HGF-stimulated cell invasion implicated in metastatic progression. This emerging role for autophagy in selectively regulating signaling proteins has implications for understanding cellular adaptations to stress and the functions of autophagy at different stages of cancer progression.

Objective Synovial fluid (SF) plays an important role in the maintenance of articular cartilage. SF is a dynamic reservoir of proteins derived from cartilage and synovial tissue; thus, its composition may serve as a biomarker that reflects the health and pathophysiological condition of the joint. The purpose of the current study was to evaluate the osteoarthritic synovial fluid (OASF) and transforming growth factor-β1 (TGF-β1) activity in articular chondrocytes catabolic and inflammatory responses. Design Chondrocytes were seeded at passage 2 and cultured for 72 hours under different conditions. Human chondrocytes were subjected to OASF while rat chondrocytes were subjected to either healthy synovial fluid (rSF) or TGF-β1 and then assigned for cell viability analysis. In addition, the effects of OASF and TGF-β1 on chondrocytes metalloprotease (MMP)-3 and MMP-13 and interleukin-18 (IL-18) expression were evaluated by immunocytochemistry, ELISA, and reverse transcriptase-polymerase chain reaction. Results SF from osteoarthritic patients significantly induced MMP-3, MMP-13, and IL-18 receptor expression in chondrocytes. To put in evidence the inflammatory activity of OASF, healthy chondrocytes from rat were cultured with TGF-β1. In the presence of TGF-β1 these cells started to express MMP-3, MMP-13, and IL-18 genes and attached to each other forming a chondrocyte aggregated structure. Healthy SF was able to maintain a typical monolayer of rounded chondrocytes with no inflammatory response. Conclusion In summary, these observations demonstrated that TGF-β1, one of the components of OASF, has a dual effect, acting in chondrocyte maintenance and also inducing inflammatory and catabolic properties of these cells.

Background: Computerized image analysis seems to represent a promising diagnostic possibility for thyroid tumors. Our aim was to evaluate the discriminatory diagnostic efficiency of computerized image analysis of cell nuclei from histological materials of follicular tumors. Methods: We studied paraffin-embedded materials from 42 follicular adenomas (FA), 47 follicular variants of papillary carcinomas (FVPC) and 20 follicular carcinomas (FC) by the software ImageJ. Based on the nuclear morphometry and chromatin texture, the samples were classified as FA, FC or FVPC using the Classification and Regression Trees method. Results: We observed high diagnostic sensitivity and specificity rates (FVPC: 89.4% and 100%; FC: 95.0% and 92.1%; FA: 90.5 and 95.5%, respectively). When the tumors were compared by pairs (FC vs FA, FVPC vs FA), 100% of the cases were classified correctly. Conclusion: The computerized image analysis of nuclear features showed to be a useful diagnostic support tool for the histological differentiation between follicular adenomas, follicular variants of papillary carcinomas and follicular carcinomas. This study received financial support from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP; process number 2014/10028-2), and PIBIC/PROPE-Unesp (process number 33347). The authors thank to Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP; process number 2014/10028-2), and PIBIC/PROPE-Unesp (process number 33347) for the research support and to Marcos Roberto Franchi and Luiz Fernando Franchi for the help in processing the histological material.

OBJECTIVES: Cardiac surgery has little effect on life expectancy in elderly patients. Thus, improving the quality of life should be the main factor affecting therapeutic decisions. Most studies on quality of life in elderly patients undergoing cardiac surgery report improvement but have limitations. Consequently, we assessed improvements in the quality of life of elderly patients undergoing elective cardiac surgery, identified influencing variables and established patterns of mental and physical health variations in the first year postoperatively. METHODS: We conducted a prospective study of patients aged 65 or older who underwent elective cardiac surgery between September 2011 and August 2013. The 36-item Short Form (SF-36) surveys were obtained preoperatively and at 3, 6 and 12 months postoperatively. RESULTS: The 430 preoperative patients with a mean age of 74 years (SD 5.5 years) comprised 220 men. Most physical health improvements occurred within 3 months and continued to improve significantly until 12 months. Predictive variables for patients showing less improvement were poor preoperative physical health, female sex, older age and longer length of hospital stay. Mental health improved significantly through the third postoperative month. The negative predictive variables were poor preoperative mental health and longer intensive care unit stay. CONCLUSIONS: Most patients improved both physically and mentally after surgery, and most of the improvement occurred within 3 months post-surgery. These improvement patterns should be taken into account when creating rehabilitation programmes, and patients should be counselled on what improvements can be expected during the first 12 months after surgery. info:eu-repo/semantics/publishedVersion

Summary Triple-negative breast cancers (TNBCs) display a complex spectrum of mutations and chromosomal aberrations. Chromosome 5q (5q) loss is detected in up to 70% of TNBCs, but little is known regarding the genetic drivers associated with this event. Here, we show somatic deletion of a region syntenic with human 5q33.2–35.3 in a mouse model of TNBC. Mechanistically, we identify KIBRA as a major factor contributing to the effects of 5q loss on tumor growth and metastatic progression. Re-expression of KIBRA impairs metastasis in vivo and inhibits tumorsphere formation by TNBC cells in vitro. KIBRA functions co-operatively with the protein tyrosine phosphatase PTPN14 to trigger mechanotransduction-regulated signals that inhibit the nuclear localization of oncogenic transcriptional co-activators YAP/TAZ. Our results argue that the selective advantage produced by 5q loss involves reduced dosage of KIBRA, promoting oncogenic functioning of YAP/TAZ in TNBC., Graphical Abstract, Highlights • Reduced KIBRA expression is associated with chr 5q loss in breast cancer • Restoring Kibra expression inhibits metastatic dissemination in mice • KIBRA impairs the self-renewal capacity of triple-negative breast cancer cells • KIBRA blocks mechanotransduction signals required for YAP/TAZ activation, Triple-negative breast cancers (TNBCs) frequently lose chromosome 5q. Using a TNBC mouse model with spontaneous loss of a syntenic region, Knight et al. identify KIBRA as a metastasis suppressor. Mechanistically, KIBRA suppresses RHOA activation, impairing nuclear translocation of the oncogenes YAP/TAZ, which drive metastatic and cancer stem cell-like behavior.

The decline of the European eel (Anguilla anguilla L., 1758) population throughout Europe has been partially attributed to pollution. As glass eel estuarine migration may represent a considerable threat, the impact of mercury (Hg) contamination at this stage was evaluated through an in situ experiment (7days). Total Hg (tHg) bioaccumulation was evaluated concomitantly with erythrocytic nuclear morphology alterations: erythrocytic nuclear abnormalities assay (ENA), frequency of immature erythrocytes (IE) and the erythrocytic maturity index (EMI). The ENA results suggested a genotoxic pressure at the most contaminated sites, in line with the tHg increase. The EMI data, together with IE frequency, showed that fish exposed to high levels of Hg exhibited alterations of haematological dynamics, translated into an erythropoiesis increment. Despite the presence of these compensatory mechanisms, the present findings suggest a harmful impact of Hg on genome integrity at this early development stage, potentially affecting eels' condition and ultimately the population sustainability.

Prenatal undernutrition impairs copulatory behavior and increases the tendency to become obese/overweight, which also reduces sexual behavior. Re-feeding rats prenatally undernourished with a normocaloric diet can restore their physiological conditions and copulatory behavior. Thus, the present study investigated whether a hypercaloric diet that is administered in rats during the juvenile period prevents sexual impairments that are caused by maternal food restriction and the tendency to become overweight/obese. Female rats were prenatally fed a 40% restricted diet from gestational day 2 to 18. The pups received a hypercaloric diet from postnatal day (PND) 23 to PND65 (food restricted hypercaloric [FRH] group) or laboratory chow (food restricted control [FRC] group). Pups from non-food-restricted dams received laboratory chow during the entire experiment (non-food-restricted [NFR] group). During the juvenile period and adulthood, body weight gain was evaluated weekly. The day of balanopreputial separation, sexual behavior, sexual organ weight, hypodermal adiposity, striatal dopamine and serotonin, serum testosterone, and tumor necrosis factor α (TNF-α) were evaluated. The FRH group exhibited an increase in body weight on PND58 and PND65. The FRC group exhibited an increase in the latency to the first mount and intromission and an increase in serum TNF-α levels but a reduction of dopaminergic activity. The hypercaloric diet reversed all of these effects but increased adiposity. We concluded that the hypercaloric diet administered during the juvenile period attenuated reproductive impairments that were induced by maternal food restriction through increases in the energy expenditure but not the tendency to become overweight/obese.

As a means of dealing with shortcomings in the coverage, quality and efficiency of the public health care sector, several municipalities in the state of São Paulo, Brazil, have started to contract pre-certified non-profit or non-governmental organizations to take part in the delivery of health care services. This paper explores the impact of introducing these contracts in the primary health care sector. Using data on the 645 municipalities in the state of São Paulo and difference-in-differences methods, we estimate the effect of contracting out in the primary health care sector on various dimensions of mortality and health care use. The results show that implementation of the contracting out strategy significantly increases the number of primary health care appointments by approximately one appointment per user of the national health care system per year. Point estimates indicate a reducing effect on hospitalization for preventable diseases.

Rationale: Although proposed as a clinical prompt to sepsis based on predictive validity for mortality, the Quick Sepsis-related Organ Failure Assessment (qSOFA) score is often used as a screening tool, which requires high sensitivity.Objectives: To assess the predictive accuracy of qSOFA for mortality in Brazil, focusing on sensitivity.Methods: We prospectively collected data from two cohorts of emergency department and ward patients. Cohort 1 included patients with suspected infection but without organ dysfunction or sepsis (22 hospitals: 3 public and 19 private). Cohort 2 included patients with sepsis (54 hospitals: 24 public and 28 private). The primary outcome was in-hospital mortality. The predictive accuracy of qSOFA was examined considering only the worst values before the suspicion of infection or sepsis.Measurements and Main Results: Cohort 1 contained 5,460 patients (mortality rate, 14.0%; 95% confidence interval [CI], 13.1-15.0), among whom 78.3% had a qSOFA score less than or equal to 1 (mortality rate, 8.3%; 95% CI, 7.5-9.1). The sensitivity of a qSOFA score greater than or equal to 2 for predicting mortality was 53.9% and the 95% CI was 50.3 to 57.5. The sensitivity was higher for a qSOFA greater than or equal to 1 (84.9%; 95% CI, 82.1-87.3), a qSOFA score greater than or equal to 1 or lactate greater than 2 mmol/L (91.3%; 95% CI, 89.0-93.2), and systemic inflammatory response syndrome plus organ dysfunction (68.7%; 95% CI, 65.2-71.9). Cohort 2 contained 4,711 patients, among whom 62.3% had a qSOFA score less than or equal to 1 (mortality rate, 17.3%; 95% CI, 15.9-18.7), whereas in public hospitals the mortality rate was 39.3% (95% CI, 35.5-43.3).Conclusions: A qSOFA score greater than or equal to 2 has low sensitivity for predicting death in patients with suspected infection in a developing country. Using a qSOFA score greater than or equal to 2 as a screening tool for sepsis may miss patients who ultimately die. Using a qSOFA score greater than or equal to 1 or adding lactate to a qSOFA score greater than or equal to 1 may improve sensitivity.Clinical trial registered with www.clinicaltrials.gov (NCT03158493).

Background Surgical mitral valve repair currently remains a good option in both organic or functional mitral valve regurgitation (MVR). However, a significant number of patients (P) have comorbidities that can contribute to adverse outcomes. Objective To determine clinical and echocardiographic predictors of adverse outcomes in P submitted to MV repair surgery in our center, notably MVR recurrence and new MV replacement surgery or all-cause mortality. Methods Retrospective analysis of 262 P who underwent MV repair surgery between 2008 and 2017, with a mean follow-up of 30 months. P were included with both organic or functional MV regurgitation. P who underwent simultaneous coronary artery bypass grafting (CABG), atrial fibrillation (AF) surgery and tricuspid valve repair were also included. However, P with simultaneous surgical aortic valve replacement or previous endocarditis were excluded and the remaining 204 P were analysed. We evaluated whether MVR etiology, simultaneous surgery (tricuspid valve repair, AF or CABG), body mass index (BMI), gender, chronic obstructive pulmonary disease (COPD), diabetes mellitus, renal dysfunction (measured by serum creatinine levels), baseline left ventricular ejection fraction (LVEF) and left ventricle end-diastolic diameter (LVED) were predictors of a composite endpoint (follow-up MV replacement surgery or all-cause mortality) and secondary endpoints: MV replacement surgery and all-cause mortality. Results 204 P who underwent MV repair surgery, 67.2% male, mean age of 62 ± 14 years. 80.4% had organic MVR and 19.6% functional MVR (mostly ischemic – 72.4%). 7P (3.4%) had rheumatic MVR. 16.8% underwent simultaneous CABG, 12.3% tricuspid valve repair and 7.8% AF ablation. 30-day mortality was 0%. The composite endpoint occurred in 40P (20%) and there was MVR recurrence with follow-up MV replacement surgery in 15P (7.5%) and all-cause mortality in 28P (13.7%). The authors found that elevated serum creatinine levels (OR 4.66; p = 0.003), COPD (OR 3.00; p = 0.035) and functional etiology (OR 2.22; p = 0.049) were predictors of the composite endpoint. Both COPD (OR 2.823; p = 0.024) and renal dysfunction (OR 6.901; p = 0.001) were also found to be independent predictors of all-cause mortality. Simultaneous CABG was a predictor of all-cause mortality (OR 2.82; p = 0.024). Female gender was a predictor of future MV replacement surgery (13.4% vs 4.7%, p = 0.023). However, echocardiographic variables (baseline LVEF and LVED) were not found to be significant predictors of adverse outcomes in MV repair surgery. Likewise, simultaneous AF or tricuspid valve surgery, rheumatic/ischemic etiology, high BMI or diabetes were not associated with poorer prognosis. Conclusion In P undergoing MV repair surgery, renal dysfunction and COPD were independent predictors of all-cause mortality. Functional etiology and simultaneous CABG surgery were also predictors of adverse outcomes. Baseline LVEF and LVED were not correlated with prognosis.

Made available in DSpace on 2021-06-25T10:36:13Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-09-01 Objective: Follicular lesions of the thyroid with papillary carcinoma nuclear characteristics are classified as infiltrative follicular variant of papillary thyroid carcinoma-FVPTC (IFVPTC), encapsulated/ well demarcated FVPTC with tumour capsular invasion (IEFVPTC), and the newly described category “non-invasive follicular thyroid neoplasm with papillary-like nuclear features” (NIFTP) formerly known as non-invasive encapsulated FVPTC.This study evaluated whether computerized image analysis can detect nuclear differences between these three tumour subtypes. Materials and methods: Slides with histological material from 15 cases of NIFTP and 33 cases of FVPTC subtypes (22 IEFVPTC, and 11 IFVPTC) were analyzed using the Image J image processing program.Tumour cells were compared for both nuclear morphometry and chromatin textural characteristics. Results: Nuclei from NIFTP and IFVPTC tumours differed in terms of chromatin textural features (grey intensity): mean (92.37 ± 21.01 vs 72.99 ± 14.73, p = 0.02), median (84.93 ± 21.17 vs 65.18 ± 17.08, p = 0.02), standard deviation (47.77 ± 9.55 vs 39.39 ± 7.18; p = 0.02), and coefficient of variation of standard deviation (19.96 ± 4.01 vs 24.75 ± 3.31; p = 0.003). No differences were found in relation to IEFVPTC. Conclusion: Computerized image analysis revealed differences in nuclear texture between NIFTP and IFVPTC, but not for IEFVPTC. Departamento de Cirurgia e Ortopedia Faculdade de Medicina de Botucatu Universidade Estadual de São Paulo (Unesp) Departamento de Dermatologia Faculdade de Medicina de Botucatu Universidade Estadual de São Paulo (Unesp) Departamento de Medicina Interna Faculdade de Medicina de Botucatu Universidade Estadual de São Paulo (Unesp) Departamento de Patologia Faculdade de Medicina de Botucatu Universidade Estadual de São Paulo (Unesp) Departamento de Otorrinolaringologia e Cirurgia de Cabeça e Pescoço Faculdade de Medicina de Botucatu Universidade Estadual de São Paulo (Unesp) Instituto de Investigação e Inovação em Saúde (i3S) Universidade do Porto Grupo de Sinalização e Metabolismo do Câncer Instituto de Patologia Molecular e Imunologia da Universidade do Porto (IPATIMUP) Departamento de Patologia Faculdade de Medicina da Universidade do Porto Departamento de Cirurgia e Ortopedia Faculdade de Medicina de Botucatu Universidade Estadual de São Paulo (Unesp) Departamento de Dermatologia Faculdade de Medicina de Botucatu Universidade Estadual de São Paulo (Unesp) Departamento de Medicina Interna Faculdade de Medicina de Botucatu Universidade Estadual de São Paulo (Unesp) Departamento de Patologia Faculdade de Medicina de Botucatu Universidade Estadual de São Paulo (Unesp) Departamento de Otorrinolaringologia e Cirurgia de Cabeça e Pescoço Faculdade de Medicina de Botucatu Universidade Estadual de São Paulo (Unesp)

Background Mitral valve regurgitation (MVR) represents the second most frequent valvular heart disease. MV surgical repair is often the preferred treatment when MV anatomy is suitable. Purpose To characterize the population who underwent MV repair surgery and evaluate the outcomes of residual MVR, allcause mortality and functional classification. Methods Retrospective analysis of 262 patients (P) admitted between 2008 and 2017 for MV repair surgery. P who undergone simultaneous coronary artery bypass graft (CABG) surgery, atrial fibrillation (AF) surgery and tricuspid valve repair were also included. P with endocarditis, P who underwent simultaneous aortic valve replacement and P with rheumatic predominant MV stenosis were excluded, the remaining 204 P were analysed. Clinical and echocardiographic characteristics were evaluated in a mean follow-up of 30 months. Results 204 P, 67.2% male, mean age 62 + 14 years. The most frequent etiology was organic (80.4%), mostly of degenerative cause. Functional etiology was present in 19.6%, mostly ischemic (72.4%). 16.8% underwent simultaneous CABG, 12.3% tricuspid valve repair and 7.8% AF ablation. Hypertension was significantly associated with functional etiology (90% vs 72.8%, p = 0.022), as well as hypercholesterolemia (80% vs 48.2%, p 50% in 78.4%, reduced (30-50%) 18.1% and poor ( Functional etiology was significantly associated with LVEF 161P (78.9%) had MV prolapse: 120P (74.5%) posterior, 29P (18%) anterior and 7.4% (12P) of both leaflets. P2 was the most frequently involved scallop, in 92P (57.1%), followed by P3, in 41P (25.4%). There was MV chordae rupture in 94P (58.3%). Post-surgery echocardiography revealed that 93.8% had mild or no residual MVR. 30-day mortality rate was 0%. There was MVR recurrence with MV replacement surgery in 15P (7.5%), mean time 37.1 months. All-cause mortality was registered in 28P (13.7%), with a mean time of 43.7 months after MV surgery. Of the P without MVR recurrence or mortality, 111P (70%) were in NYHA class I, 41P (26%) in NYHA class II and 6P (4%) in NYHA class III. 6P were lost to follow-up. Upon echocardiographic revaluation there was no residual MVR in 53P (39%), mild MVR in 67P (49%) and moderate MVR in 16P (11.8%). Conclusion In P who underwent MV repair surgery, there was 7.5% recurrence rate with follow-up MV replacement surgery and an all-cause mortality of 13.7%. In a mean follow-up of 30 months, 70% of P were in NYHA I class and there was none or mild residual MVR in 88% of P.

Background Primary cardiac tumors are extremely rare and are usually diagnosed late due to the non-specific symptomatology. Surgery is the main treatment option and despite chemotherapy, the prognosis remains poor. Cardiac invasion by metastatic tumors, while more common, also entails an unsatisfactory outcome. Purpose To review patients (P) with malignant cardiac tumours that were diagnosed by transthoracic echocardiography (TTE) or by transesophageal echocardiogram (TEE) in a tertiary center between 1997 and 2019. Methods Retrospective analysis of clinical data from the digital files, echocardiographic assessment of tumor location and morphology, histology results and survival outcomes. Results A total of 33 malignant cardiac tumors were diagnosed: 12 primary tumors (A) and 21 metastatic tumors (B). A Regarding primary cardiac tumors, the most common types were angiosarcomas (6 cases), 2 undifferentiated pleomorphic sarcomas, 1 right ventricle (RV) sarcoma, 1 primary cardiac lymphoma, 1 myxofibrosarcoma and 1 fibrosarcoma. The mean age of the P at time of diagnosis was 43 ± 15 years, 50% female gender. The most frequent presentation was heart failure symptoms (50% of P) followed by arrhythmias (20%). One patient had a rare presentation with pruritus and polyarthralgias. On TTE, the most prevalent tumor location was in the right-heart chambers (70%) - mostly the right atrium (50%), with mean dimensions of 40 ± 18 mm x 27 ± 11 mm. 85% of patients had preserved systolic left ventricular function and there was moderate or severe pericardial effusion in 38%. The most frequent distant metastatic involvement of primary tumors at diagnosis was pulmonary (33%) and hepatic (33%). 50% of P were submitted to tumor resection and 40% were submitted to chemotherapy. In the case of angiosarcomas, the most common immunohistochemical markers were vimentin, CD31 and CD34. The authors found a mortality rate of 81% in P with primary cardiac tumors, with a median time of follow-up of 6 months (minimum of 20 days and maximum of 18 years). In the latter case, the P was submitted to heart transplantation after diagnosis of a sarcoma of the RV and is still alive and well. B Regarding secondary cardiac invasion, there was a diagnosis of the following primary tumor sites: 6 thymomas, 4 cases of lymphoma, 3 lung carcinomas, 3 hepatocellular carcinomas, 2 bladder carcinomas, 1 parathyroid carcinoma, 1 soft tissue sarcoma and 1 melanoma. The mean age of P with metastastic involvement of the heart was 57 ± 22 years, 65% male. On TTE/TEE the authors also found a right-sided chambers predominance (60%), with pericardial metastasis in 35%. As expected, the mortality rate was also extremely high (90%), with a median time of follow up of 1.5 months (minimum of one week, maximum of 44 months) Conclusion Cardiac malignant tumors generally present in a late stage with a dismal prognosis. When possible, heart transplantation can be an option with a good outcome.

Introduction Papillary fibroelastomas are rare benign primary cardiac tumors that more frequently involve cardiac valves. They are frequently incidentally discovered by echocardiography but may also cause symptoms. Purpose The aim of this study was to characterize several features of histologically confirmed fibroelastomas. Methods Retrospective analysis of patients with echocardiographic suspicion of fibroelastoma between 2009 and 2019 in a single tertiary center. Echocardiography was compared with histology, and echocardiographic, surgical and pathological information about confirmed fibroelastomas was collected. Results 37 patients (P) (54.1% men) with an echocardiographic suspicion and/or histologically confirmed fibroelastoma were included, with a mean age of 58 +- 3 years (min 22, max 82). Echocardiographic report was analyzed in 34P (91.9%), with 32P (94.1%) reporting a likely fibroelastoma and 2P (5.9%) reporting a non-specified mass. 21P (56.8%) had surgery, with 12P (57.1%) having a surgical suspicion of a fibroelastoma, 2P (9.5%) of a mixoma, 1P (4.8%) of a non-specified mass and 6P (28.6%) with undefined suspicion. Of the 21P who had surgery, 66.7% (14P) had a histologically confirmed fibroelastoma, 1P (4.8%) had a mixoma, and 6P (28.6%) had other diagnoses. From the 14P with histologically confirmed fibroelastoma 64.3% had this suspicion by echocardiography and 35.7% had an echocardiogram reporting a non-specified. There was a global concordance between echocardiography and histology in 52.9%. The mean age of confirmed fibroelastoma P was 54 +-5years, and 50% were men. 7P (50%) were asymptomatic, 2 (14.3%) had a stroke, 2 (14.3%) had syncope, 1 (7.1%) had fatigue, 1 (7.1%) had palpitations and 1P had consciousness alteration. In echocardiography most P (71.4%) had only one mass but 1P had 4 different masses. The tumors had a longer axis between 6 and 25mm, with the majority (57.1%) measuring more than 10mm. 12P (85.7%) had valvular fibroelastomas, 50% of these in the aortic valve (3 in non-coronary cusp, 1 in right coronary cusp and 2 non-specified) and 50% in the mitral valve (all in sub-valvular apparatus, involving anterior leaflet, tendinous chord or papillary muscle). 1P had a left ventricular fibroelastoma (apical) and 1P had four masses in the left atrium. Macroscopically 4 lesions had a gelatinous consistency, 2 of them were membranous, 2 were elastic, 2 were friable, 1 was villainous and in 3 of them consistency was not described. The majority (57%) was white, 14% was translucent and in the rest the color was not specified. There was no described recurrence after surgery and there were no deaths registered. Conclusion In this population there was a reasonable concordance between echocardiography and histology, but in some cases the diagnosis was undefined or wrong. 50% of the patients were asymptomatic and the majority had valvular fibroelastomas, but a few had a different location.

Background and objectives The primary treatment for locally advanced cases of cervical cancer is chemoradiation followed by high-dose brachytherapy. When this treatment fails, pelvic exenteration (PE) is an option in some cases. This study aimed to develop recommendations for the best management of patients with cervical cancer undergoing salvage PE. Methods A questionnaire was administered to all members of the Brazilian Society of Surgical Oncology. Of them, 68 surgeons participated in the study and were divided into 10 working groups. A literature review of studies retrieved from the National Library of Medicine database was carried out on topics chosen by the participants. These topics were indications for curative and palliative PE, preoperative and intraoperative evaluation of tumor resectability, access routes and surgical techniques, PE classification, urinary, vaginal, intestinal, and pelvic floor reconstructions, and postoperative follow-up. To define the level of evidence and strength of each recommendation, an adapted version of the Infectious Diseases Society of America Health Service rating system was used. Results Most conducts and management strategies reviewed were strongly recommended by the participants. Conclusions Guidelines outlining strategies for PE in the treatment of persistent or relapsed cervical cancer were developed and are based on the best evidence available in the literature.

Background There is no consensus on the cutoff value of B-type natriuretic peptide (BNP) to rule in or rule out the diagnosis of heart failure (HF) in the community. For instance, the ESC guidelines propose a cutoff of 35 pg/mL and the Canadian Guidelines propose 50 pg/mL. Objectives To evaluate the performance of several BNP cutoffs to rule in or rule out the diagnosis of HF in the community. Methods A total of 633 randomly selected individuals, aged 45 to 99 years, of both sexes, enrolled in a primary care program in several regions of a medium-sized city with 487,562 inhabitants were evaluated. A cross-sectional study, in which one-day clinical data collection, laboratory tests, BNP tests and tissue Doppler echocardiogram (TDE) were performed. The final diagnosis of HF was adjudicated by two independent cardiologists. Sensitivity (SEN), specificity (SPE), negative predictive value (NPV) and positive predictive value (PPV) were evaluated for different BNP cutoffs. A ROC curve was used to determine the best cutoff value. Results The mean age was 59.6±10.4 years and 62% were women. The incidence for ACC/AHA HF stages Zero, A, B, C and D were, respectively, 11.8%, 36.3%, 42.6%, 9.3% and 0%. There was a predominance of HF with preserved versus reduced ejection fraction (59% vs 41%). For the identification of the 59 patients with symptomatic HF, the cutoff of 35pg/mL presented SEN 98%, SPE 87%, NPV 100% and PPV 44%. For cutoff of 50pg/mL these values were SEN 78%, SPE 94%, NPV 98% and PPV 58%. The best combination of SEN and SPE was with a cutoff of 42pg/mL (SEN 92% and SPE 91%). Only one patient with HF had BNP Conclusions The cutoff with higher specificity to rule in the diagnosis of HF was 50pg/mL. However, with this cutoff an expressive number of patients with HF would have been missed. For screening purpose in the community, the best cutoff to rule out HF was 35pg/mL, as proposed in the ESC guidelines

This paper aimed at evaluating the total mercury content in five common fish species from the western European Atlantic coastal waters, and the associated risk of consumption. Mercury concentrations in muscle of Atlantic mackerel (Scomber scombrus), Atlantic chub mackerel (Scomber colias), European anchovy (Engraulis encrasicolus), Atlantic horse mackerel (Trachurus trachurus) and European pilchard (Sardina pilchardus) ranged from 0.003 to 0.20 mg kg−1 wet weight, and no significant differences were observed between the average concentration in each species. A significant increasing trend in mercury content with fish size was observed for all species (except for European anchovy), suggesting mercury bioaccumulation throughout their life cycle. Still, the mercury content was far below the European Food Safety Authority and World Health Organization food safety thresholds in all species, highlighting the low risk to human health due to the ingestion of these species and the importance of consumer options for risk reduction.

Authors acknowledge the financial support of the Portuguese Foundation for the Science and Technology (FCT) through PhD grants to José Seco (SRFH/PD/BD/113487), Francesca Coppola (SFRH/BD/118582/2016) and Ângela Almeida (SFRH/BD/110218/2015), and the Portuguese Polar Program PROPOLAR. This study also benefited from the strategic program of MARE (Marine and Environmental Sciences Centre) financed by FCT (UIDB/04292/2020). João Pedro Coelho was funded by the Integrated Program of SR&TD ‘Smart Valorization of Endogenous Marine Biological Resources Under a Changing Climate’ (Centro-01-0145-FEDER-000018), co-funded by Centro 2020 program, Portugal 2020 and the European Regional Development Fund. Thanks are due for the financial support to CESAM (UIDB/50017/2020+UIDP/50017/2020) and REQUIMTE (UIDB/50006/2020). The Institut Universitaire de France (IUF) is acknowledged for its support to P. Bustamante as a Senior Member. RAS, SF, GS and GT were supported by the British Antarctic Surveys Ecosystem Programme, which is part of NERC and UKRI. Indicators of oxidative stress and metabolic capacity are key factors in understanding the fitness of wild populations. In the present study, these factors were evaluated in the pelagic Southern Ocean taxa Antarctic krill (Euphausia superba) and myctophid fish (Electrona antarctica, Gymnoscopelus braueri and G. nicholsi) to establish a baseline record for future studies. Mercury (Hg) concentrations were also analysed to evaluate its potential impacts on species biochemical performance. E. superba had higher metabolic activity than most of the myctophid species, which may explain the comparatively lower energy reserves found in the former. The activity of antioxidant enzymes showed, generally, a lower level in E. superba than in the myctophid species. The lack of any relationship between Hg concentrations and organisms' antioxidant and biotransformation defence mechanisms indicate that levels of Hg accumulated in the studied species were not high enough to affect their biochemical processes adversely. Postprint

Background The keratocystic odontogenic tumour (KCOT) is a benign intraosseous odontogenic lesion relatively frequent in the oral cavity. It has a locally aggressive behaviour and exhibits a high propensity to recur after treatment. All the singular characteristics of this pathology have originated controversy in the scientific community regarding the most appropriate surgical approaches for the successful treatment of this tumour. Objectives To analyse the optimal treatment choice for this tumour, ensuring high success rates of treatment, preventing future recurrences and allowing the maintenance of the patient's quality of life. Materials and methods A search was conducted in Cochrane – 1 result – and in PubMed – 756 results. The selection of articles was based on abstracts and inclusion and exclusion criteria. Three research studies were considered for the final analysis. Results One hundred and nineteen lesions were identified (73 males and 46 females). Twenty-nine tumours were found in the maxilla and 91 in the mandible; the applied therapeutic methods were: marsupialization/decompression, marsupialization followed by enucleation and adjunctive therapies (peripheral ostectomy and Carnoy's solution), solely enucleation, enucleation and Carnoy's solution, enucleation followed by peripheral ostectomy and Carnoy's solution and resection. Discussion and conclusions Treatment by enucleation, in combination with adjunctive measures, is associated with minor recurrence rates when compared with enucleation alone. The small number of KCOT that were treated with en bloc resection did not obtain statistically relevant results. Therefore, more studies with well-established criteria are necessary to enable an adequate analysis of recurrence rates associated with each treatment modality.

In this work the aim of study was the synthesis and evaluation of in vitro anti-Mycobacterium tuberculosis activity as well as the cytotoxicity in VERO cells of a series of 17 novel thiosemicarbazones derived from the natural monoterpene (-)-camphene by REMA and MTT methods. Overall, the majority of tested compounds exhibited considerable inhibitory effects on the growth of M. tuberculosis H37Rv, especially the derivatives 3, 4a–c, 4f, 4i, 4k, 5 and 6a–b. MIC values of 20 tested compounds ranged from 3.9 to > 250 μg/mL. It was found that when inserting new nitrogenous groups to the (-)-camphene increased the anti-M. tuberculosis activity of some compounds. The SI was calculated for all compounds that showed highly potent anti-M. tuberculosis activity and the best SI values were 21.36, 26.92 and 31.62 (4b, 6a and 6b), and may be considered potential candidates for future antituberculosis drugs.

Made available in DSpace on 2019-10-06T16:14:10Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-01-01. Added 1 bitstream(s) on 2021-07-15T15:23:41Z : No. of bitstreams: 1 S2523-31062018000100232.pdf: 638750 bytes, checksum: d03516198ab48aaabcf480e267ba8b66 (MD5) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Objective: To evaluate autoimmune hepatitis (AIH) in a multicenter cohort of childhood-onset systemic lupus erythematosus (cSLE) patients. Methods: This retrospective multicenter study included 847 patients with cSLE, performed in 10 Pediatric Rheumatology services of São Paulo state, Brazil. AIH was defined according to the International Autoimmune Hepatitis Group criteria (IAHGC). The statistical analysis was performed using the Bonferroni's correction (p < 0.0033). Results: AIH in cSLE patients confirmed by biopsy was observed in 7/847 (0.8%) and all were diagnosed during adolescence. The majority occurred before or at cSLE diagnosis [5/7 (71%)]. Antinuclear antibodies were a universal finding, 43% had concomitantly anti-smooth muscle antibodies and all were seronegative for anti-liver kidney microsomal antibodies. All patients with follow-up ≥18 months (4/7) had complete response to therapy according to IAHGC. None had severe hepatic manifestations such as hepatic failure, portal hypertension and cirrhosis at presentation or follow-up. Further comparison of 7 cSLE patients with AIH and 28 without this complication with same disease duration [0 (0-8.5) vs. 0.12 (0-8.5) years, p = 0.06] revealed that the frequency of hepatomegaly was significantly higher in cSLE patients in the former group (71% vs. 11%, p = 0.003) with a similar median SLEDAI-2 K score [6 (0-26) vs. 7 (0-41), p = 0.755]. No differences were evidenced regarding constitutional involvement, splenomegaly, serositis, musculoskeletal, neuropsychiatric and renal involvements, and treatments in cSLE patients with and without AIH (p > 0.0033). Conclusions: Overlap of AIH and cSLE was rarely observed in this large multicenter study and hepatomegaly was the distinctive clinical feature of these patients. AIH occurred during adolescence, mainly at the first years of lupus and it was associated with mild liver manifestations. Pediatric Rheumatology Unit Children's Institute3 Hospital das Clinicas HCFMUSP Faculdade de Medicina Universidade de Sao Paulo Division of Rheumatology Hospital das Clinicas HCFMUSP Faculdade de Medicina Universidade de Sao Paulo Pediatric Rheumatology Unit Universidade Federal de São Paulo Pediatric Rheumatology Unit São Paulo State University (UNESP) Faculdade de Medicina de Botucatu Pediatric Rheumatology Unit Ribeirão Preto Medical School University of São Paulo Pediatric Rheumatology Unit São Paulo State University (UNESP) Faculdade de Medicina de Botucatu FAPESP: 2015/ 03756-4 CNPq: CNPq 303422/2015-7

Introdução: O objetivo da cirurgia de substituição valvular aórtica é o aumento da esperança de vida e a melhoria da qualidade de vida relacionada com a saúde. Existem vários estudos que evidenciam melhoria da qualidade de vida relacionada com a saúde nestes doentes, mas não aplicados à população portuguesa. O objetivo deste estudo é avaliar a qualidade de vida relacionada com a saúde pós-implantação de prótese aórtica e comparar com a qualidade de vida relacionada com a saúde pré-operatória e da população em geral. Material e Métodos: Foi feito um estudo retrospetivo de doentes eletivos submetidos a implantação de prótese aórtica entre agosto de 2011 e abril de 2016. A qualidade de vida relacionada com a saúde foi avaliada com o Short Form 36 Health Survey Instrument e com o Short Form 6 Health Survey Instrument no pré-operatório e aos 3, 6 e 12 meses pós-cirurgia. Foram realizadas análises descritivas e inferenciais para analisar globalmente a amostra e para comparar a qualidade de vida relacionada com a saúde pré-operatória com a pós-operatória e com as normas da população portuguesa. Resultados: Foram incluídos 506 doentes, com idade média de 70,6 anos, sendo 53,6% do sexo masculino. Os resultados do pósoperatório evidenciam uma melhoria estatisticamente significativa quando comparados com o pré-operatório nas oito dimensões do Short Form 36 Health Survey Instrument. Comparando com a população Portuguesa em geral, a qualidade de vida relacionada com a saúde dos doentes é inferior no pré-operatório, melhorando no pós-operatório, atingindo níveis de qualidade de vida relacionada com a saúde superiores nalguns subgrupos de doentes e em algumas dimensões. Os resultados do Short Form 6 Health Survey Instrument revelam maior intensidade de problemas no pré-operatório quando comparados com a população em geral, aproximando-se dos valores população em geral ao final de um ano pós-cirurgia. Discussão: Este é o primeiro estudo realizado em Portugal que compara a qualidade de vida relacionada com a saúde, usando uma escala validada, antes e depois da cirurgia de implantação de prótese aórtica. Os resultados demonstram a existência de uma melhoria significativa em todas as dimensões, o que não acontece consistentemente noutros estudos publicados. Conclusão: A implantação de prótese aórtica melhora a qualidade de vida relacionada com a saúde dos doentes, permitindo que esta se aproxime dos resultados da população em geral. info:eu-repo/semantics/publishedVersion

This study describes the behavior of health inequalities in Brazil between 1980 and 2010 and revisit theoretical and methodological difficulties on researching this topic. The behavior of infant mortality and life expectancy in Brazil’s municipalities was investigated, attempting to identify the relationship between these indicators, on the one hand, and income, income inequality, supply of public health services and basic sanitation, and education, on the other. Over the course of that period, considerable improvements were recorded in both infant mortality rates and life expectancy at birth as well as in reducing the inequalities in these indicators among Brazil’s regions, states, and municipalities. A robust and statistically significant association was found between health indicators and mean income in the municipalities. That association was also positive for women’s level of education. Contrary to expectations, no association was found between expansion of public health care service supply and improvement in health indicators. An exercise to deepen the analysis, considering health inequalities between socioeconomic and racial groups, was made by calculating mortality rates directly, which yielded unsubstantial results. Improvement in Brazil’s vital statistics recording systems will make it possible – beyond the reach of this study – to examine the contribution made by the Brazilian public health system, the SUS, to improving health conditions and reducing health inequalities.

Brazil relies on the Sistema Unico de Saude (SUS), a public health-care system used by nearly 65 per cent of the population. This article analyses the role played by accountability mechanisms in expanding access to primary health care in the municipality of Sao Paulo, Brazil’s largest city. Two accountability mechanisms are described and discussed: political competition and outsourcing. The article shows that from 2001 to 2016 the supply of primary care grew and the disparities in access to public health services decreased across the city areas with both the best and worst indices of income, education, and health. These distributive results are striking given how difficult it is to reverse inequalities, as attested by the findings of a number of studies in different parts of the world which indicate that the richest populations tend to persistently benefit more than the poorest from public spending on health.

Glucagon is a hyperglycemic pancreatic hormone that has been shown to provide a beneficial effect against asthmatic bronchospasm. We investigated the role of this hormone on airway smooth muscle contraction and lung inflammation using bothin vitroandin vivoapproaches. The action of glucagon on mouse cholinergic tracheal contraction was studied in a conventional organ bath system, and its effect on airway obstruction was also investigated using the whole-body pletysmographic technique in mice. We also tested the effect of glucagon on lipopolysaccharide (LPS)-induced airway hyperreactivity (AHR) and inflammation. The expression of glucagon receptor (GcgR), CREB, phospho-CREB, nitric oxide synthase (NOS)-3, pNOS-3 and cyclooxygenase (COX)-1 was evaluated by western blot, while prostaglandin E2(PGE2) and tumour necrosis factor-α were quantified by enzyme-linked immunoassay and ELISA respectively. Glucagon partially inhibited carbachol-induced tracheal contraction in a mechanism clearly sensitive to des-His1-[Glu9]-glucagon amide, a GcgR antagonist. Remarkably, GcgR was more expressed in the lung and trachea with intact epithelium than in the epithelium-denuded trachea. In addition, the glucagon-mediated impairment of carbachol-induced contraction was prevented by either removing epithelial cells or blocking NOS (l-NAME), COX (indomethacin) or COX-1 (SC-560). In contrast, inhibitors of either heme oxygenase or COX-2 were inactive. Intranasal instillation of glucagon inhibited methacholine-induced airway obstruction by a mechanism sensitive to pretreatment withl-NAME, indomethacin and SC-560. Glucagon induced CREB and NOS-3 phosphorylation and increased PGE2levels in the lung tissue without altering COX-1 expression. Glucagon also inhibited LPS-induced AHR and bronchoalveolar inflammation. These findings suggest that glucagon possesses airway-relaxing properties that are mediated by epithelium-NOS-3-NO- and COX-1-PGE2-dependent mechanisms.

Mast cell tumors represent the most common malignant skin tumor in the dog. This review outlines the incidence, etiology and clinical signs of mast cell tumors. Diagnostic tests, staging and treatments are also discussed. This study was performed by the Veterinary Oncology and Pathology of UNESP, Jaboticabal and the Service of Pathology Veterinary, of UNESP-Botucatu with the support of the Brazilian Association of Veterinary Oncology and the Brazilian Association of Veterinary Pathology.

Throughout the world, people’s diet is generally quite restricted regarding the variety of plants used in their daily regime. The Unconventional Food Plant (UFP) Lactuca canadensis L. is an edible species of wild lettuce sparsely described in literature and considered to be native from the eastern and central parts of North America. To valorize this species as potential alternative food, an analysis of its nutritional, chemical, and bioactive properties was performed. The results specify the occurrence of organic acids, mainly quinic acid (127.9 ± 0.6 g/kg dry weight (dw)), polyunsaturated fatty acids (65.3%), among which are linolenic acid (44.4 ± 0.4 %), and tocopherols, mostly α-tocopherol (61.2 ± 0.7 mg/kg dw). Additionally, eight phenolic compounds were also identified, among which luteolin-O-glucuronide was found in larger amounts in both infusion and hydroethanolic extracts (5.46 ± 0.09 and 4.6 ± 0.1 mg/g dw, respectively). Carbohydrates and proteins were the main macronutrients (603 ± 1 and 177.5 ± 0.3 g/kg dw, respectively), followed by ashes (166.5 ± 0.9), indicative of a great amount of minerals. Additionally, good antioxidant and antibacterial activities were detected in the analyzed extracts. In general, our results contribute to extend the range of different, unexploited, and nutritionally balanced plant foods, such as Lactuca canadensis, that can and should be included in the daily diet. The authors are grateful to the Foundation for Science and Technology (FCT, Portugal) for financial support by national funds FCT/MCTES to CIMO (UIDB/00690/2020) and national funding by FCT, P.I., through the institutional scientific employment program-contract for L.B., A.F. and M.I.D., and through the individual scientific employment program-contract for J.P. (CEECIND/01011/2018). The authors are also grateful to the project TRANSCoLAB (0612_TRANS_CO_LAB_2_P), to the European Regional Development Fund (ERDF) through the Regional Operational Program North 2020, within the scope of Project GreenHealth, Norte-01-0145-FEDER-000042. The authors C.T.P.C. and V.G.P.S. are grateful to the international mobility departments of the Federal University of Goiás and the Polytechnic Institute of Bragança for the opportunity for student exchange of C.T.P.C. and developing of the research with L. canadensis species. info:eu-repo/semantics/publishedVersion

Aims The effects of maternal food restriction during gestation in F0 generation followed by hypercaloric diet (HD) during puberty in F1 generation (F1HD) were investigated on astrocyte behavior of F2 generation. Also, the astrocyte behavior, after an immune challenge, was examined by the immunohistochemical expression of glial fibrillary acidic protein (GFAP) in several brain areas. Methods The body weight gain (BW) during development and in postnatal day (PND) 90–95, the retroperitoneal fat weight (RPF), and the size of larger and smaller adipocytes in the F1 generation were assessed to observe the effects of HD in female rats. The BW, RPF weight and size of smaller and larger adipocytes was also measured to evaluate the transgenerational effects of F0 and F1 diets on F2 generation, treated or not with lipopolysaccharide (LPS). Key findings The F1HD group exhibited a higher BW gain than the F1 treated with normocaloric diet (ND, group F1ND), from weaning to PND65. In the frontal/parietal cortex, nucleus accumbens, hypothalamic arcuate/periventricular nuclei, molecular/granular layers of the cerebellum areas, excepting the pons, GFAP expression was greater in F1HD group relative to F1ND group. A reduced GFAP expression was observed in both groups born from F1 generation fed with HD (groups F2HDS and F2HDLPS) in relation to F2 generation born from dams fed with ND (groups F2NDS and F2NDLPS), independently of LPS challenge. Significance These data show an attenuation of LPS effect on GFAP expression, probably by a transgenerational effect of both maternal food deprivation in F0 generation and HD in F1 generation.

Degree of unsaturation of fatty acids, which is influenced by lipid source and level of metabolism in the rumen, is a major determinant in how dietary lipids affect genes that regulate beef marbling. A total of 28 Red Norte bulls with an initial live weight of 361±32 kg (P>0.05) were used in a completely randomized experimental design to analyze the expression of genes that are involved in lipid metabolism in the longissimus dorsi (LD) when diets contained soybean grain or rumen-protected fat, with or without monensin. Treatments were arranged as a 2×2 factorial, with 4 treatments and 7 replicates per treatment. Half of the animals that received soybean or rumen-protected fat were supplemented with 230 mg head(-1) d(-1) of monensin. Gene expression was analyzed by reverse-transcription quantitative PCR (RT-qPCR). Expression of sterol regulatory element-binding protein-1c (SREBP-1c) in the LD muscle was not affected by lipid source or monensin (P>0.05). There was an interaction effect (P

The aim of this study was to evaluate the concentration of cefazolin in adipose tissue of patients undergoing bariatric surgery.Eighteen patients undergoing bariatric surgery were evaluated during the period from October 2011 to May 2012. All patients had a dosage schedule of antibiotic prophylaxis with cefazolin administered as follows: first, 2 g in anesthetic induction, followed by continuous infusion of 1 g diluted in 250 ml of saline solution. Adipose samples, collected soon after the incision (initial) and before the skin synthesis (final), were analyzed using reverse phase high-pressure liquid chromatography. The level of significance adopted was 5 %.The cefazolin concentration in the adipose tissue samples at the beginning of surgery was an average of 6.66 ± 2.56 ug/ml. The mean concentration before the skin synthesis was 7.93 ± 2.54 ug/ml. Patients with BMI 40 kg/m(2) had higher initial and final sample concentrations of cefazolin than patients with BMI ≥ 40 kg/m(2). There was no surgical site infection (SSI) in any of the patients.In bariatric surgeries, addition of a 1 g increase of cefazolin, administered through continuous intravenous infusion, to the currently recommended dose of 2 g administered in anesthetic induction provided a concentration in the adipose tissue above the minimum inhibitory concentration (MIC) of the main causal agents of SSI. An inverse correlation between BMI and concentration of cefazolin in adipose tissue was observed.

A lipid nanoemulsion (LDE) resembling low-density lipoprotein can target malignant tumours. In in vivo and clinical studies, association of chemotherapeutic agents to LDE decreased their toxicity and increased pharmacological action. Here, safety of LDE as carmustine carrier (50 mg m(-2) , intravenous) combined with vincristine and prednisone for the treatment of dogs with lymphoma was tested and compared with commercial carmustine with vincristine and prednisone. In five dogs from LDE-carmustine and six from commercial carmustine, complete remission was achieved (P > 0.05). Partial remission occurred in two dogs from each group. In both groups, the median progression-free intervals (119 and 199 days) and overall survival times (207 and 247 days) were equal. Neutropenia was observed in both groups, but no other major toxicities occurred. Therefore, no difference was observed between the treatments. LDE-carmustine was shown to be safe and effective in a drug combination protocol, which encourages larger studies to investigate the use of this novel formulation to treat canine lymphomas.

Background A significant percentage of antibiotics worldwide are prescribed inappropriately (context, dosage and duration), especially the use of quinolones, carbapenems and anti-MRSA agents. In order to optimise interventions in a paper-free hospital, a platform has been developed locally allowing prescription monitoring and registration of multidisciplinary interventions under the platform that supports antimicrobial prescription (PAPA), complementing automatically generated email notifications when prescribing conditioned antibiotics or outside the local guidelines. Interventions are made by physician and pharmacist members of the Prevention and Control of Infection and Antimicrobial Resistance Group (GCL-PPCIRA) in real time. Purpose To characterise hospital prescriptions for quinolones, carbapenems and anti-MRSA agents in March 2016, using the platform. Material and methods This was a pilot prospective analysis on the use of a PAPA platform, which integrates data relating to the prescriber, scope and characteristics of the prescription, initial GCL-PPCIRA interventions, follow-up by pharmacists, medical acceptance and registration of clinical and laboratory variables. Results The analysis involved 220 conditioned prescriptions, automatically generated by the prescription system and introduced into platform. Of these, 48% required GCL-PPCIRA interventions. 47.2% of the suggested interventions were accepted. In only 6.6% of non-accepted interventions was there an automatic justification and in 46.2% there was no given justification. Most suggested interventions (41.5%) included antibiotic exchange, suspension (26.4%), duration of therapy (12.3%), change of dosage (4.7%) and addition of another antibiotic (1.9%). Most interventions made were for carbapenems (34.9%), followed by quinolones (13.2%) and anti-MRSA agents (9.4%), with an acceptance profile, respectively, of 17/6/4 cases. 34.9% of interventions were made in the emergency department. Conclusion In order to reduce the emergence of resistances, conducting interventions under a PAPA should be complemented by evaluation of prescription quality and adequacy of interventions, requiring tools that integrate information and enable real time interventions by multiple professionals. This analysis concluded that the rate of interventions in total prescriptions generated meets the estimated international values, which translates into a good robustness. The data analysis related to the reasons for interventions and acceptance rate, and other data not mentioned in this analysis, makes it possible to define improvement strategies for good antibiotic prescribing practices, particularly in the conditioned antibiotics from the prescriber to the institutional level. No conflict of interest

The Paris Agreement signed by 195 countries in 2015 sets out a global action plan to avoid dangerous climate change by limiting global warming to remain below 2 degrees C. Under that premise, in situ experiments were run to test the effects of 2 degrees C temperature increase on the benthic communities in a seagrass bed and adjacent bare sediment, from a temperate European estuary. Temperature was artificially increased in situ and diversity and ecosystem functioning components measured after 10 and 30 days. Despite some warmness effects on the analysed components, significant impacts were not verified on macro and microfauna structure, bioturbation or in the fluxes of nutrients. The effect of site/ habitat seemed more important than the effects of the warmness, with the seagrass habitat providing more homogenous results and being less impacted by warmness than the adjacent bare sediment. The results reinforce that most ecological responses to global changes are context dependent and that ecosystem stability depends not only on biological diversity but also on the availability of different habitats and niches, highlighting the role of coastal wetlands. In the context of the Paris Agreement it seems that estuarine benthic ecosystems will be able to cope if global warming remains below 2 degrees C., The authors would like to thank P. Cardoso, S. Leston e M. D'Ambrosio who helped in field and laboratorial work. This research was supported by FCT (Portuguese Foundation for Science and Technology), through the grants attributed to D Crespo (SFRH/BD/80252/2011), T F Grilo (SFRH/BPD/98590/2013), J P Coelho (SFRH/BPD/102870/2014), I Fernandes (SFRH/BPD/97656/2013), to Investigador FCT programme attributed to M. Dolbeth (IF/00919/2015) and BIOCHANGED project (PTDC/MAR/111901/2009), subsidized by the European Social Fund and MCTES (Portuguese Ministry of Science, Technology and Higher Education), through the POPH (Human Potential Operational Programme), QREN (National Strategic Reference Framework) and COMPETE (Programa Operacional Factores de Competitividade). Thanks are also due, for the financial support to CESAM (UID/AMB/50017/2013), to FCT/MEC through national funds, and the co-funding by the FEDER, within the PT2020 Partnership Agreement and Compete 2020., info:eu-repo/semantics/publishedVersion

Chronic kidney disease (CKD) is frequently observed in cats and it is characterized as a multisystemic illness, caused by several underlying metabolic changes, and secondary renal hyperparathyroidism (SRHPT) is relatively common; usually it is associated with the progression of renal disease and poor prognosis. This study aimed at determining the frequency of SRHPT, and discussing possible mechanisms that could contribute to the development of SRHPT in cats at different stages of CKD through the evaluation of calcium and phosphorus metabolism, as well as acid-base status. Forty owned cats with CKD were included and divided into three groups, according to the stages of the disease, classified according to the International Renal Interest Society (IRIS) as Stage II (n=12), Stage III (n=22) and Stage IV (n=6). Control group was composed of 21 clinically healthy cats. Increased serum intact parathyroid hormone (iPTH) concentrations were observed in most CKD cats in all stages, and mainly in Stage IV, which hyperphosphatemia and ionized hypocalcemia were detected and associated to the cause for the development of SRHPT. In Stages II and III, however, ionized hypercalcemia was noticed suggesting that the development of SRHPT might be associated with other factors, and metabolic acidosis could be involved to the increase of serum ionized calcium. Therefore, causes for the development of SRHPT seem to be multifactorial and they must be further investigated, mainly in the early stages of CKD in cats, as hyperphosphatemia and ionized hypocalcemia could not be the only factors involved. A doença renal crônica (DRC) em gatos é frequentemente observada e caracteriza-se como alteração multissistêmica, causada por alterações metabólicas, e o hiperparatireoidismo secundário renal (HPTSR) seria o mais comum e usualmente está associada com progressão da doença renal e mau prognóstico. Esse estudo teve como objetivo determinar a frequência do HPTSR, e discutir os possíveis mecanismos que podem contribuir para o desenvolvimento de SRHPT em gatos em diferentes estágios de DRC, pela avaliação do metabolismo do cálcio e fósforo, bem como do equilíbrio ácido-base. Quarenta gatos com DRC foram divididos em três subgrupos, de acordo com a classificação proposta pela International Renal Interest Society (IRIS), Estágio II (n=12), Estágio III (n=22) e Estágio IV (n=6). O grupo-controle foi composto por 21 gatos clinicamente saudáveis. O aumento das concentrações séricas de paratormônio intacto (PTHi) foi observado na maioria dos casos, mas principalmente no Estágio IV, no qual a hiperfosfatemia e a hipocalcemia ionizada parecem estar associadas ao desenvolvimento do HPTSR. No entanto, nos Estágios II e III, observou-se hipercalcemia ionizada, sugerindo que, nestes estágios, o desenvolvimento do HPTSR possa estar associado a outros fatores, e a acidose metabólica pode estar envolvida com o desenvolvimento de hipercalcemia ionizada. Assim, outros fatores, além da hiperfosfatemia e da hipocalcemia ionizada, possam estar envolvidos com o desenvolvimento do HPTSR, principalmente nos estágios iniciais da DRC. Futuros estudos são necessários para uma melhor compreensão da fisiopatologia do HPTSR em gatos.

Background: In lung cancer (LC) patients an early detection and surgical resection offers the highest likelihood of cure, however, patients in extremes of age may fail to benefit maximally from these interventions. Aim: Characterize symptoms, comorbidities and stage in younger and older groups of patients with LC. Methods: Review of medical records of 323 patients with LC diagnosed between 2013-15 in our hospital. Patients were selected by age as 80 years. Results: 80 group: 24 patients (83% male), with mean age of 84 years (80-90). 71% were current or ex-smokers. The most frequent histological type was ADC (54%). 63% had PS 0-2, 88% had respiratory ou cardiovascular comorbidities. The stage at presentation was: 4% in stage I, 13% II, 21% III and 58% IV. In 13% a curative approach was intended, 1 patient had surgery. 50% were treated with BSC. Overall survival was 9,1 months. Conclusion: The paucity of symptoms in younger patients can influence an early diagnosis and the presence of multiple comorbidities in older patients can have impact on surgical possibility. Studies on large population are needed.

The aim of this study was to investigate the correspondence between the coronary arterial anatomy and the supplied myocardium based on the proposed American Heart Association (AHA) 17-segment model. Six human cadaveric hearts without signs of infarct were selectively injected with colored contrasted gelatin in the three major coronary arteries. After injection, the hearts were scanned by computed tomography (64-detector scanner LightSpeed VCT, GE Healthcare) with a collimation of 64 × 0.625 mm. Reconstructed image data were analyzed in order to evaluate the blood supply of each myocardial segment. Coronary artery territory varies due to anatomy variations. Left anterior descending coronary artery (LAD) was the main vessel responsible for the myocardium blood supply in 11 segments. LAD contributed to the blood supply of all apical segments. Left circumflex (LCx) was the main coronary artery for the infero-anterior wall. Right coronary artery (RCA) contributed in all hearts for the blood supply of infero-septal segments. There was an important overlap between LAD and RCA territories at the infero-septal region and between LAD and LCx territories at the antero-lateral region. In our experiment, LAD territory was larger than the AHA-proposed 17-segment model. The most specific segments were located at the anterior wall and supplied exclusively by LAD. No specific segment could be exclusively attributed to RCA or to LCx. Sometimes, LCx can be the most important artery for the blood supply of the inferior wall even if the origin of the posterior descending artery is the RCA.