Characterization of monocarboxylate transporters (MCTs) expression in soft tissue sarcomas: distinct prognostic impact of MCT1 sub-cellular localization

Background: Soft tissue sarcomas (STSs) are a group of neoplasms, which, despite current therapeutic advances, still confer a poor outcome to half of the patients. As other solid tumors, STSs exhibit high glucose consumption rates, associated with worse prognosis and therapeutic response. As highly glycolytic tumors, we hypothesized that sarcomas should present an increased expression of lactate transporters (MCTs).Methods: Immunohistochemical expression of MCT1, MCT2, MCT4 and CD147 was assessed in a series of 86 STSs and the expression profiles were associated with patients' clinical-pathological parameters.Results: MCT1, MCT4 and CD147 were mainly observed in the plasma membrane of cancer cells (around 60% for MCTs and 40% for CD147), while MCT2 was conspicuously found in the cytoplasm (94.2%). Importantly, we observed MCT1 nuclear expression (32.6%). MCT1 and MCT4, alone or co-expressed with CD147 in the plasma membrane, were associated with poor prognostic variables including high tumor grade, disease progression and shorter overall survival. Conversely, we found MCT1 nuclear expression to be associated with low grade tumors and longer overall survival.Conclusions: The present work represents the first report of MCTs characterization in STSs. We showed the original finding of MCT1 expression in the nucleus. Importantly, opposite biological roles should be behind the dual sub-cellular localization of MCT1, as plasma membrane expression of MCT1 is associated with worse patients' prognosis, while nuclear expression is associated with better prognosis.

The impact of the addition of iodoform on the physicochemical properties of an epoxy-based endodontic sealer

Due to the low radiopacity of Sealer 26, iodoform is frequently empirically added to this sealer. Thus, the interference of this procedure with the physicochemical properties of Sealer 26 must be evaluated. Objective: This study evaluated the influence of the addition of iodoform on setting time, flow, solubility, pH, and calcium release of an epoxy-based sealer. Material and Methods: The control group was pure Sealer 26, and the experimental groups were Sealer 26 added with 1.1 g, 0.55 g or 0.275 g of iodoform. Setting time evaluation was performed in accordance with the ASTM C266-03 speciflcation. The analysis of flow and solubility was in accordance with the ISO 6876-2001 speciflcation. For the evaluation of pH and calcium ion release, polyethylene tubes were filled with the materials and immersed in flasks with 10 ml of deionized water. After 24 h, 7, 14, 21, 28, and 45 days pH was measured. In 45 days, the calcium released was evaluated with an atomic absorption spectrophotometer. Results: The addition of iodoform increased setting time in comparison with pure sealer (P < 0.05). As for flow, solubility, and calcium release, the mixtures presented results similar to pure sealer (p > 0.05). In the 24 h period, the mixture with 1.1 g and 0.55 g of iodoform showed lower pH than pure sealer and than sealer added with 0.275 g of iodoform (P < 0.05). Conclusions: The iodoform added to Sealer 26 interferes with its setting time and solubility properties. Further studies are needed to address the clinical signiflcance of this interference.

Impact of gestational diabetes and lactational insulin replacement on structure and secretory function of offspring rat ventral prostate

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

The physiology and impact on fertility of the period of proestrus in lactating dairy cows

In cattle, proestrus begins with the initiation of luteolysis and ends with initiation of estrus and the GnRH/LH surge. This period is marked by a dramatic decrease in circulating progesterone (P4) that reaches a nadir by about 36-48 h in cows undergoing natural or prostaglandin F2 alpha (PGF)-induced luteolysis. Inadequate luteolysis is a cause of reduced fertility particularly in timed AI programs with small elevations in circulating P4 reducing fertility. Increasing circulating estradiol (E2) during proestrus is dependent on presence, size, and function of the dominant follicle and this varies during natural proestrus, due to whether animals have two or three follicular waves, and during PGF-induced proestrus, according to stage of the follicular wave at time of PGF treatment. Inadequate circulating E2 can limit fertility and increase pregnancy loss in some specific circumstances such as in cows with low BCS and in cows during heat stress. Thus, studies to optimize the length of proestrus and the concentrations of E2 and P4 during proestrus could produce substantial improvements in fertility and reductions in pregnancy loss.

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.

Impact of patient training patterns on peritonitis rates in a large national cohort study

Background. Ideal training methods that could ensure best peritoneal dialysis (PD) outcome have not been defined in previous reports. The aim of the present study was to evaluate the impact of training characteristics on peritonitis rates in a large Brazilian cohort.Methods. Incident patients with valid data on training recruited in the Brazilian Peritoneal Dialysis Multicenter Study (BRAZPD II) from January 2008 to January 2011 were included. Peritonitis was diagnosed according to International Society for Peritoneal Dialysis guidelines; incidence rate of peritonitis (episodes/patient-months) and time to the first peritonitis were used as end points.Results. Two thousand two hundred and forty-three adult patients were included in the analysis: 59 +/- 16 years old, 51.8% female, 64.7% with <= 4 years of education. The median training time was 15 h (IQI 10-20 h). Patients were followed for a median of 11.2 months (range 3-36.5). The overall peritonitis rate was 0.29 per year at risk (1 episode/41 patient-months). The mean number of hours of training per day was 1.8 +/- 2.4. Less than 1 h of training/day was associated with higher incidence rate when compared with the intervals of 1-2 h/day (P = 0.03) and > 2 h/day (P = 0.02). Patients who received a cumulative training of > 15 h had significantly lower incidence of peritonitis compared with < 15 h (0.26 per year at risk versus 0.32 per year at risk, P = 0.01). The presence of a caregiver and the number of people trained were not significantly associated with peritonitis incidence rate. Training in the immediate 10 days after implantation of the catheter was associated with the highest peritonitis rate (0.32 per year), compared with training prior to catheter implantation (0.28 per year) or > 10 days after implantation (0.23 per year). More experienced centers had a lower risk for the first peritonitis (P = 0.003).Conclusions. This is the first study to analyze the association between training characteristics and outcomes in a large cohort of PD patients. Low training time (particularly < 15 h), smaller center size and the timing of training in relation to catheter implantation were associated with a higher incidence of peritonitis. These results support the recommendation of a minimum amount of training hours to reduce peritonitis incidence regardless of the number of hours trained per day.

Response to Chemotherapy in Overweight/Obese Patients With Low-Risk Gestational Trophoblastic Neoplasia

Objective Despite rising global obesity rates, the impact of obesity on gestational trophoblastic neoplasia (GTN) remains uninvestigated. This study aimed at investigating whether overweight/obesity relates to response to chemotherapy in low-risk GTN patients.Methods This nonconcurrent cohort study included 300 patients with International Federation of Gynecology and Obstetrics-defined postmolar low-risk GTN treated with a single-agent chemotherapymethotrexate or actinomycin-D (actD)between 1973 and 2012 at the New England Trophoblastic Disease Center. Chemotherapy dosing was based on actual body weight regardless of obesity status, except for 5-day courses or pulse regimens of actD. Patients were classified as overweight/obese (body mass index [BMI] 25 kg/m(2)) or non-overweight/obese (BMI <25 kg/m(2)). Information on patient characteristics and response to chemotherapy (need for second-line chemotherapy, reason for changing to an alternative chemotherapy, number of cycles, need for combination chemotherapy, and time to human chorionic gonadotropin remission) was obtained.Results Of 300 low-risk GTN patients, 81 (27%) were overweight/obese. Overweight/obese patients were older than the non-overweight/obese patients (median age: 30 vs 28 years, P = 0.004). First-line therapy using actD was more frequent in overweight/obese patients (6.2% vs 1.4%, P = 0.036). Resistance and toxicity were similar between groups. No significant difference in the number of chemotherapy cycles needed for remission or time required to achieve remission was found between groups.Conclusions No association between overweight/obesity and low-risk GTN outcomes was found. Current chemotherapy dosing using BMI seems to be appropriate for overweight/obese patients with low-risk GTN.

Induction of multiple ovulations in mares using low doses of GnRH agonist Deslorelin Acetate at 48 hours after luteolysis

This study was aimed to test low doses of a GnRH agonist, deslorelin acetate (DA), for induction of multiple ovulations in mares and to determine its impact upon their reproductive efficiency. Seven mares aging from 8-20 years were used in three consecutive reproductive cycles. Mares were initially monitored by ultrasound irrespectively of cycle stage, inseminated and submitted to embryo collection (EC) (T1). Immediately after, mares received 7.5 mg dinoprost tromothamine (DT) and were monitored by ultrasound twice a day until larger follicle reached 23-25mm and the second >18mm (T2). At this time point, mares received 100 mu g DA and ovulation was induced with 1000 mu g DA and 1000IU hCG when largest follicle reached 33-35mm in diameter, followed by EC. Mares were further allocated to T3 when received 7.5 mg DT after EC on 12 and 100 mu g DA 48 h later. DA treatment was performed until dominant follicle reached 34 +/- 1 mm or 6 days of application. All EC were performed 8 days after ovulation. Mares with multiple ovulations in T1, T2 and T3 were 14.28% (1/7), 100.00% (7/7) and 0.00% (0/7), respectively, and averaged 0.43 +/- 0.53 in T1, 0.86 +/- 0.38 in T2 and 0.00 in T3 embryos per donor, respectively. Embryo recovery rate was 43.00% in T1, 85.71% in T2 and 0.00% T3. In conclusion, use of DA in mares with follicles larger than 25mm enhanced dominant and co-dominant follicle growth, that ultimately increased the incidence of multiple ovulations and embryo recovery rate.

Search for displaced supersymmetry in events with an electron and a muon with large impact parameters

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Impact of the temperament of Nellore cows on the quality of handling and pregnancy rates in fixed-time artificial insemination

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

First insight on the impact of an osteoblastic layer on the bio-tribocorrosion performance of Ti6Al4V hip implants

In uncemented Ti6Al4V hip implants, the bone-stem interface is subjected to cyclic loading motion driven by the daily activities of the patients, which may lead to the complete failure of the implant in the long term. It may also compromise the proliferation and differentiation processes of osteoblastic cells (bone-forming cells). The main objective of this work is to approach for the first time the role of these organic materials on the bio-tribocorrosion mechanisms of cultured Ti6Al4V alloys. The colonized materials with MG63 osteoblastic-like cells were characterized through cell viability/proliferation and enzymatic activity. Tribocorrosion tests were performed under a reciprocating sliding configuration and low contact pressure. Electrochemical techniques were used to measure the corrosion kinetics of the system, under free potential conditions. All tests were performed at a controlled atmosphere. The morphology and topography of the wear scar were evaluated. The results showed that the presence of an osteoblastic cell layer on the implant surface significantly influences the tribocorrosion behavior of Ti6Al4V alloy. It was concluded that the cellular material was able to form an extra protective layer that inhibits further wear degradation of the alloy and decreases its corrosion tendency.

Selenium and vitamin A and E in the nutrition of very low-birth weight preterm infants

Deficient antioxidant defenses in preterm infants have been implicated in diseases such as bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis, periventricular leukomalacia, and intraventricular hemorrhage. The antioxidant properties of selenium, vitamin A, and vitamin E make these elements important in the nutrition of Very Low-Birth Weight (VLBW) infants. Selenium is a component of glutathione peroxidase, an enzyme that prevents the production of free radicals. The decrease in plasma selenium in VLBW infants in the first month after birth makes evident that preterm infants have low selenium store and require supplementation by parenteral and enteral nutrition. A meta-analysis, with only three trials, showed that selenium supplementation did not affect mortality, and the incidence of neonatal chronic lung disease or retinopathy of prematurity, but was associated with a reduction in lateonset sepsis. Most VLBW infants and extremely Low-Birth Weight Infants (ELBW) are born with low vitamin A stores and need vitamin A supplementation by intramuscular or enteral route. Low plasma retinol concentrations increase the risk of chronic lung disease/bronchopulmonary dysplasia and long-term respiratory disabilities in preterm infants. There is evidence that vitamin A supplementation decreases the mortality or oxygen requirement at one month of age, and oxygen requirement at 36 weeks’ postmenstrual age. Vitamin E blocks natural peroxidation of polyunsaturated fatty acids from lipid layers of cell membranes. VLBW infants have a decrease in plasma concentrations in the first month after birth suggesting the need of vitamin E supplementation. A meta-analysis on vitamin E supplementation concluded that vitamin E did not affect mortality, risk of bronchopulmonary dysplasia, and necrotizing enterocolitis but reduced the risk of intraventricular hemorrhage and increased the risk of sepsis. Serum vitamin E concentrations higher than 3.5 mg/dL are associated with a decrease in the risk of severe retinopathy of prematurity, and blindness, but also with an increase in neonatal sepsis. Caution is recommended with the supplementation of high doses of parenteral vitamin E and supplementation that increases serum levels above 3.5 mg/dL. In conclusion: although it is known that preterm infants are deficient in selenium, vitamin A and E, more studies are required to determine the best way to supplement and the impact of supplementation on neonatal outcome.