As figurações da morte e da memória na poética de Manoel de Barros

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

The symbology of the sea in Lygia Bojunga Nunes's work: a reflection on utopian and dystopian framing

The ambivalent image of the sea is recurrent in Bojunga Nunes’s work. It receives a lot of symbolic meanings in her production, being sometimes a positive and sometimes a negative element. Thus, the sea is used in a utopic way, as a place for pleasure and leisure, and in a dystopic way, as scenery of a rite of passage, which includes the pain and suffering, part of the rite of passage that characterizes the bildungsromans. So, if in some texts the sea assumes a utopic character, being a place of snuggle, security, the ideal to reach, in others it is represented as dystopic, a place of distress, asphyxia and death. In this text we will study the hypothesis that, even in its dark symbolic meaning, in the author’s work the sea is an element of reflection and revelation. Thereby, it assumes metaphorically a sense of magnification of the reader’s expectative, being an element of emancipation. The objective of this text is to present a reflection on the sea’s symbolism on the mentioned texts and its importance for the reader’s formation.

Low serum potassium levels increase the infectious-caused mortality in peritoneal dialysis patients: a propensity-matched score study

Background and ObjectivesHypokalemia has been consistently associated with high mortality rate in peritoneal dialysis. However, studies investigating if hypokalemia is acting as a surrogate marker of comorbidities or has a direct effect in the risk for mortality have not been studied. Thus, the aim of this study was to analyze the effect of hypokalemia on overall and cause-specific mortality.Design, Setting, Participants and MeasurementsThis is an analysis of BRAZPD II, a nationwide prospective cohort study. All patients on PD for longer than 90 days with measured serum potassium levels were used to verify the association of hypokalemia with overall and cause-specific mortality using a propensity match score to reduce selection bias. In addition, competing risks were also taken into account for the analysis of cause-specific mortality.ResultsThere was a U-shaped relationship between time-averaged serum potassium and all-cause mortality of PD patients. Cardiovascular disease was the main cause of death in the normokalemic group with 133 events (41.8%) followed by PD-non related infections, n=105 (33.0%). Hypokalemia was associated with a 49% increased risk for CV mortality after adjustments for covariates and the presence of competing risks (SHR 1.49; CI95% 1.01-2.21). In contrast, in the group of patients with K < 3.5mEq/L, PD-non related infections were the main cause of death with 43 events (44.3%) followed by cardiovascular disease (n=36; 37.1%). For PD-non related infections the SHR was 2.19 (CI95% 1.52-3.14) while for peritonitis was SHR 1.09 (CI95% 0.47-2.49).ConclusionsHypokalemia had a significant impact on overall, cardiovascular and infectious mortality even after adjustments for competing risks. The causative nature of this association suggested by our study raises the need for intervention studies looking at the effect of potassium supplementation on clinical outcomes of PD patients.

Are metabolic syndrome and its components associated with 5-year mortality in chronic obstructive pupmonary disease patients?

The aim of this study was to evaluate the risk of mortality according to the presence of metabolic syndrome in chronic obstructive pulmonary disease (COPD) patients who were followed for 5 years. We did not establish the influence of metabolic syndrome on mortality rate. However, an increase of 100 mg of triglycerides was associated with a 39% increase in the probability of death in the period of the study (hazard ratio 1.39, 95% confidence interval 1.06-1.83).

Nanoparticles increase the efficacy of cancer chemopreventive agents in cells exposed to cigarette smoke condensate

Lung cancer is a leading cause of death in developed countries. Although smoking cessation is a primary strategy for preventing lung cancer, former smokers remain at high risk of cancer. Accordingly, there is a need to increase the efficacy of lung cancer prevention. Poor bioavailability is the main factor limiting the efficacy of chemopreventive agents. The aim of this study was to increase the efficacy of cancer chemopreventive agents by using lipid nanoparticles (NPs) as a carrier. This study evaluated the ability of lipid NPs to modify the pharmacodynamics of chemopreventive agents including N-acetyl-L-cysteine, phenethyl isothiocyanate and resveratrol (RES). The chemopreventive efficacy of these drugs was determined by evaluating their abilities to counteract cytotoxic damage (DNA fragmentation) induced by cigarette smoke condensate (CSC) and to activate protective apoptosis (annexin-V cytofluorimetric staining) in bronchial epithelial cells both in vitro and in ex vivo experiment in mice. NPs decreased the toxicity of RES and increased its ability to counteract CSC cytotoxicity. NPs significantly increased the ability of phenethyl isothiocyanate to attenuate CSC-induced DNA fragmentation at the highest tested dose. In contrast, this potentiating effect was observed at all tested doses of RES, NPs dramatically increasing RES-induced apoptosis in CSC-treated cells. These results provide evidence that NPs are highly effective at increasing the efficacy of lipophilic drugs (RES) but are not effective towards hydrophilic agents (N-acetyl-L-cysteine), which already possess remarkable bioavailability. Intermediate effects were observed for phenethyl isothiocyanate. These findings are relevant to the identification of cancer chemopreventive agents that would benefit from lipid NP delivery.

Acute kidney injury in septic patients admitted to emergency clinical room: risk factors and outcome

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Sepsis and AKI in clinical emergency room patients: the role of urinary NGAL

Few studies have investigated the predictive properties of urinary (u) NGAL as an AKI marker in septic population. This study evaluated the efficacy of uNGAL as predictor of AKI and death in septic patients admitted to the clinical emergency room (ER). We prospectively studied patients with sepsis admitted to the ER. Urine was analyzed for NGAL within the first 24 hours after admission (classified as NGAL1), between 24 and 48 h (NGAL2), and at moment of AKI diagnosis (NGAL3). Among 168 septic patients admitted to ER, 72% developed AKI. The uNGAL and its relationship with creatinine (Cr) were high in septic patients but statistically higher in those with sepsis and AKI. The uNGAL1 and uNGAL2, as well as uNGAL1/uCr1 and uNGAL2/uCr2, were good predictors for AKI (AUC-ROC 0.73, 0.70, 0.77, and 0.84, resp.). The uNGAL1 and uNGAL1/uCr1 were poor predictors for death (AUC-ROC 0.66 and 0.68, resp.), whereas uNGAL2 and uNGAL2/uCr2 were better predictors (AUC-ROC 0.70 and 0.81, resp.). The uNGAL is highly sensitive but nonspecific predictor of AKI and death in septic patients admitted into ER.

Comparative analysis of the replication of bovine herpesvirus 1 (BHV1) and BHV5 in bovine derived-neuron-like cells

Members of the subfamily Alphaherpesvirinae use the epithelium of the upper respiratory and/or genital tract as preferential sites for primary replication. However, bovine herpesvirus 5 (BoHV5) is neurotropic and neuroinvasive and responsible for meningoencephalitis in cattle and in animal models. A related virus, BoHV1 has also been occasionally implicated in natural cases of neurological infection and disease in cattle. The aim of the present study was to assess the in vitro effects of BoHV1 and BoHV5 replication in neuron-like cells. Overall, cytopathic effects, consisting of floating rounded cells, giant cells and monolayer lysis, induced by both viruses at 48 h postinfection (p.i.) resulted in a loss of cell viability and high virus titres (r = 0.978). The BoHV1 Cooper strain produced the lowest titres in neuron-like cells, although viral DNA was detected in infected cells during all experiments. Virus replication in infected cells was demonstrated by immunocytochemistry, flow cytometry and qPCR assays. BoHV antigens were better visualized at 48 h p.i. and flow cytometry analysis showed that SV56/90 and Los Angeles antigens were present at higher levels. In spite of the fact that BoHV titres dropped at 48 h p.i, viral DNA remained detectable until 120 h p.i. Sensitive TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling) and annexin V assays were used to identify apoptosis. BoHV5 induced death in approximately 50 % of cells within 24 h p.i., similar to what has been observed for BoHV1 Los Angeles. Infection with the BoHV1 Cooper strain resulted in 26.37 % of cells being in the early stages of apoptosis; 63.69 % of infected cells were considered viable. Modulation of mitochondrial function, as measured by mitochondrial membrane depolarization, was synchronous with the virus replication cycle, cell viability and virus titres at 48 h p.i. Our results indicate that apoptosis plays an important role in preventing neuronal death and provides a bovine-derived in vitro system to study herpesvirus-neuron interactions.

In Vitro Safety Evaluation of Caffeic Acid

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Occluded Tunneled Venous Catheter in Hemodialysis Patients: Risk Factors and Efficacy of Alteplase

Thrombosis of tunneled central venous catheters (CVC) in hemodialysis (HD) patients is common and it can lead to the elimination of vascular sites. This study aimed to evaluate the incidence of thrombotic obstruction of tunneled CVC in HD patients and the efficacy of occlusion treatment with alteplase use, and identify factors associated with thrombotic occlusion. It was a prospective cohort study performed in two centers which evaluated the diagnosis and treatment of thrombotic occlusion of CVC in HD patients for 24 consecutive months. The catheter occlusion was defined as the difficulty infusing or withdrawing fluid from their paths. Alteplase dose was infused to fill the lumen of the occluded catheter and remained for 50 min. As there was no obstruction of the catheter, the procedure was repeated. Three hundred and thirty-nine CVC in 247 patients were evaluated and followed, totalling 67 244 CVC-days. One hundred fifty-seven patients had only one CVC, 88 patients had two CVC during the study, and two patients had three CVC. The median age was 58 (47–66) years, patients were predominantly men (54%), with diabetic nephropathy as the main cause of chronic kidney disease (44%), the internal jugular vein as the main site of implantation (82%), and duration of dialysis before CVC implantation of 119 (41.5 to 585.5) days. Eight hundred and fifteen occlusion episodes were diagnosed (12 episodes/1000 CVC-days), with primary success with alteplase in 596 episodes (77%) and secondary in 81 cases (10%). In 99 episodes (13%), success was not achieved after the second dose of alteplase. Two hundred and thirty CVC were removed during the study and the removal causes were arteriovenous fistula use in 88 patients (38.3%), infectious and mechanical complications in 89 (38.7%) and 21 (9.1%), respectively, and others (transplantation, transfer, or death) in 32 patients (13.9%). Adverse effects were also not observed. In the multivariate analysis, we identified the greatest number of days with CVC (OR = 1.02, CI = 1.01–1.04, P = 0.004), the presence of diabetes (OR = 1.560, CI = 1.351–1.894, P = 0.015), and exit site infection (ESI) (OR = 1.567 CI = 1347–1926, P = 0.023) as factors associated with obstruction. Thrombotic occlusion showed frequent mechanical complication in CVC of HD patients. We observed 12 episodes of obstruction per 1000 CVC-days, with a high success rate after alteplase use (87%). In the multivariate analysis, the time with CVC, the presence of diabetes, and ESI were identified as variables associated with thrombotic obstruction.

Evaluation of quality of life related to i-131 therapy in patients with well-differentiated thyroid cancer and emphasis in salivary morbidity: a follow up study after treatment

To evaluate the impact of iodine-131 therapy received during childhood and adolescence and correlate it with the quality of life in these patients. Methods: We studied 19 patients diagnosed with cancer in childhood or adolescence who underwent thyroidectomy and supplemental therapy with I-131. We also recruited a control group of healthy subjects with the same demographic parameters. All patients were subjected to a scintigraphy examination of the salivary glands, and were also asked to complete a questionnaire in order to assess their overall quality of life. In addition, a more specific questionnaire for patients with head and neck cancer was also given to all study participants. Results: The quantitative and qualitative analyses of the salivary glands showed functional deficits with greater involvement of the parotid gland for volume, concentration and excretion. The right submandibular gland showed significant changes for volume in the patient group. The questionnaires made it possible to observe significant differences between the patient and control groups for symptoms such as thick saliva, dry mouth and speech problems. Conclusion: In spite of being very effective and widely used, iodine radionuclide therapy is correlated with a lower quality of life in young people.

Relationship between bone ageand pubertal breast stage to bone biomarkers and bone mineral density in healthy brazilian female adolescents

Background and Aims Bone metabolism involves understanding many factors, especially during puberty, when bone turnover is significant and the bone mass peak must be achieved as a protective factor of future bone health. The objective was to evaluate the behavior of formation and resorption bone biomarkers (BB) in function of biological maturation in female adolescents.Methods Evaluation of formation and resorption BB, osteocalcin (OC), bone alkaline phosphatase (BAP) and carboxyterminal telopeptide (S-CTx) by correlating them with bone mineralization, bone age and pubertal development in healthy female adolescents. Seventy-two volunteers were subdivided into groups according to chronological age/bone age (BA): 10 11 years (n=12), 12 13 years (n=16), 14 15 years (n=15) and 16 19 years (n=29). The following were evaluated: weight (kg), height (m), BMI (kg/m2), calcium intake (3-day 24h food recalls (mg/day), puberty events (Tanner stages), serum OC (ng/mL), BAP (U/L), S-CTx (ng/mL) and bone mineral density (BMD) as calculated by DXA (g/cm2) in the spine (L1-L4), proximal femur and whole body. The project was approved by the UNESP Ethics Committee.Results BB showed similar behaviors, with higher mean values for 10 12 years and when adolescents were in the B2-B3 Pubertal Maturation Stage (B2: BAP=110.16 U/L, OC=33.81ng/mL, S-CTx=1.66 ng/mL and B3: BAP=136.50 U/L, OC=39.15ng/mL and S-CTx=1.88 ng/mL; p<0.001). Mean BB values decreased with advancing BA and pubertal maturity.Conclusions BB values showed parallelism with peak height velocity and significant negative correlation with BMD in the different evaluated sites, with chronological and BA ; higher BMD values correlated with lower bone biomarker values.

PS-042c is low-dose combined oral contraceptives use associated to lower bone mineral content variation in adolescents over a one-year period?

Background Low dose combined oral contraceptives (COC) can interfere in bone mass acquisition during adolescence. To evaluate bone mineral density (BMD) and bone mineral content (BMC) in female adolescents taking a standard low-dose (EE 20 µg/Desogestrel 150 µg) combination oral contraceptive (COC) over a one-year period and compare with healthy adolescents from the same age group not taking COCs.Methods A non-randomised parallel control study with one-year follow-up. Sixty-seven adolescents from 12 to 20 years of age, divided into COC users (n = 41) taking 20 µg EE/150 µg Desogestrel and non-user controls (n = 26), were evaluated through bone densitometry examinations at baseline and 12 months later. Comparisons between groups at study start was done through the Mann-Whitney test with significance level fixed at 5% or corresponding p value; comparisons between groups at study start and 12 months later used variations in median percentages for bone mass variables.Results COC users presented low bone mass acquisition in the lumbar spine and BMD and BMC median variations between baseline and at 12 months of 2.07% and +1.57% respectively whereas the control group presented variations of +12.16% and +16.84% for BMD and BMC, respectively, over the same period. The total body BMD and BMC presented similar evolution during the study in both groups. Statistical significance (pConclusion The use of a low COC dose (EE 20 µg/Desogestrel 150 µg) was associated to lower bone mass acquisition in adolescents during the study period.Trial registration: (Register Number):RBR-5 h9b3c

Modeling spatial distribution of cancer incidence in Cordoba, Argentina

Background: Cancer is the second leading cause of death in Argentina, and there is little knowledge about its incidence. The first study based on population-based cancer registry described spatial incidence and indicated that there existed at least county-level aggregation. The aim of the present work is to model the incidence patterns for the most incidence cancer in Córdoba Province, Argentina, using information from the Córdoba Cancer Registry by performing multilevel mixed model approach to deal with dependence and unobserved heterogeneity coming from the geo-reference cancer occurrence. Methods: Standardized incidence rates (world standard population) (SIR) by sex based on 5-year age groups were calculated for 109 districts nested on 26 counties for the most incidence cancers in Cordoba using 2004 database. A Poisson twolevel random effect model representing unobserved heterogeneity between first level-districts and second level-counties was fitted to assess the spatial distribution of the overall and site specific cancer incidence rates. Results: SIR cancer at Córdoba province shown an average of 263.53±138.34 and 200.45±98.30 for men and women, respectively. Considering the ratio site specific mean SIR to the total mean, breast cancer ratio was 0.25±0.19, prostate cancer ratio was 0.12±0.10 and lower values for lung and colon cancer for both sexes. The Poisson two-level random intercepts model fitted for SIR data distributed with overdispersion shown significant hierarchical structure for the cancer incidence distribution. Conclusions: a strong spatial-nested effect for the cancer incidence in Córdoba was observed and will help to begin the study of the factors associated with it.

FGFR4 Profile as a Prognostic Marker in Squamous Cell Carcinoma of the Mouth and Oropharynx

Background: Fibroblast growth factor receptor 4 (FGFR4) is a member of a receptor tyrosine kinase family of enzymes involved in cell cycle control and proliferation. A common single nucleotide polymorphism (SNP) Gly388Arg variant has been associated with increased tumor cell motility and progression of breast cancer, head and neck cancer and soft tissue sarcomas. The present study evaluated the prognostic significance of FGFR4 in oral and oropharynx carcinomas, finding an association of FGFR4 expression and Gly388Arg genotype with tumor onset and prognosis. Patients and Methods: DNA from peripheral blood of 122 patients with oral and oropharyngeal squamous cell carcinomas was used to determine FGFR4 genotype by PCR-RFLP. Protein expression was assessed by immunohistochemistry (IHC) on paraffin-embedded tissue microarrays. Results: Presence of allele Arg388 was associated with lymphatic embolization and with disease related premature death. In addition, FGFR4 low expression was related with lymph node positivity and premature relapse of disease, as well as disease related death. Conclusion: Our results propose FGFR4 profile, measured by the Gly388Arg genotype and expression, as a novel marker of prognosis in squamous cell carcinoma of the mouth and oropharynx.