Adjuvant everolimus in high-risk diffuse large B-cell lymphoma: final results from the PILLAR-2 randomized phase III trial.

Background: Patients with diffuse large B-cell lymphoma (DLBCL) with an International Prognostic Index (IPI) ≥3 are at higher risk for relapse after a complete response (CR) to first-line rituximab-based chemotherapy (R-chemo). Everolimus has single-agent activity in lymphoma. PILLAR-2 aimed to improve disease-free survival (DFS) with 1 year of adjuvant everolimus. Patients and methods: Patients with high-risk (IPI ≥3) DLBCL and a positron emission tomography/computed tomography-confirmed CR to first-line R-chemo were randomized to 1 year of everolimus 10 mg/day or placebo. The primary end point was DFS; secondary end points were overall survival, lymphoma-specific survival, and safety. Results: Between August 2009 and December 2013, 742 patients were randomized to everolimus (n = 372) or placebo (n = 370). Median follow-up was 50.4 months (range 24.0-76.9). Overall, 47% of patients were ≥65 years, 50% were male, and 42% had an IPI of 4 or 5. 48% and 67% completed everolimus and placebo, respectively. Primary reasons for everolimus discontinuation versus placebo were adverse events (AEs; 30% versus 12%) and relapsed disease (6% versus 13%). Everolimus did not significantly improve DFS compared with placebo (hazard ratio 0.92; 95% CI 0.69-1.22; P = 0.276). Two-year DFS rate was 77.8% (95% CI 72.7-82.1) with everolimus and 77.0% (95% CI 72.1-81.1) with placebo. Common grade 3/4 AEs with everolimus were neutropenia, stomatitis, and decreased CD4 lymphocytes. Conclusions: Adjuvant everolimus did not improve DFS in patients already in PET/CT-confirmed CR. Future approaches should incorporate targeted agents such as everolimus with R-CHOP rather than as adjuvant therapy after CR has been obtained. ClinicalTrials.gov: NCT00790036.

Altering the time of the second gonadotropin-releasing hormone injection and artificial insemination (AI) during Ovsynch affects pregnancies per AI in lactating dairy cows.

Based on previous research, we hypothesized that Cosynch at 72 h [GnRH-7 d-PGF(2alpha)-72 h-GnRH + artificial insemination (AI)] would result in a greater number of pregnancies per AI (P/AI) than Cosynch at 48 h. Further, we hypothesized that P/AI would be improved to a greater extent when GnRH was administered at 56 h after PGF(2alpha) before AI at 72 h due to a more optimal interval between the LH surge and AI. Nine hundred twenty-seven lactating dairy cows (n = 1,507 AI) were blocked by pen, and pens rotated through treatments. All cows received GnRH followed 7 d later by PGF(2alpha) and then received one of the following: 1) GnRH + timed AI 48 h after PGF(2alpha) (Cosynch-48); 2) GnRH 56 h after PGF(2alpha) + timed AI 72 h after PGF(2alpha) (Ovsynch-56); or 3) GnRH + timed AI 72 h after PGF(2alpha) (Cosynch-72). Pregnancy diagnoses were performed by ultrasound at 31 to 33 d post-AI and again at 52 to 54 d post-AI. Overall P/AI were similar for the Cosynch-48 (29.2%) and Cosynch-72 (25.4%) groups. The Ovsynch-56 group had a greater P/AI (38.6%) than Cosynch-48 or Cosynch-72. Presynchronized first-service animals had greater P/AI than cows at later services in Cosynch-48 (36.2 vs. 23.0%) and Ovsynch-56 (44.8 vs. 32.7%) but not in Cosynch-72 (24.6 vs. 26.2%). Similarly, primiparous cows had greater P/AI than multiparous cows in Cosynch-48 (34.1 vs. 22.9%) and Ovsynch-56 (41.3 vs. 32.6%), but not Cosynch-72 (29.8 vs. 25.3%). In conclusion, we found no advantage to Cosynch at 72 h vs. 48 h. In contrast, we found a clear advantage to treating with GnRH at 56 h, 16 h before a 72-h AI, probably because of more-optimal timing of AI before ovulation.

Biochemical studies on leukocyte and fibroblast human beta-galactosidase.

OBJECTIVES: Some biochemical characteristics of the human leukocyte and fibroblast beta-galactosidase were studied. DESIGN AND METHODS: Leukocyte and fibroblast enzyme activity was determined fluorometricaly using 4-methylumbelliferyl-beta-D-galactoside as artificial substrate. Optimum pH, Km, Vmax and thermostability of the enzyme at 42 degrees C were determined. RESULTS: The leukocyte and fibroblast enzyme has an optimum pH at 4.2, which is in agreement with the lysosomal origin of the enzyme. The Km of the enzyme was 0.62 in leukocytes and 0.67 in fibroblasts, and Vmax was 289.9 nmol/h/mg of protein and 1779.2 nmol/h/mg of protein in the two tissues, respectively. When fibroblast or leukocyte beta-galactosidase was pre-incubated at 42 degrees C, it did not retain its activity because the residual activity after 80 minutes of pre-incubation at this temperature was lower than 30% of the initial activity both in leukocytes and fibroblasts. CONCLUSIONS: This was the first study of Km, Vmax and thermostability of beta-galactosidase performed on leukocytes and provided data for a better characterization of the enzyme beta-galactosidase, allowing the improvement of the analytical conditions.

Central nervous system effects of the crude extract of Erythrina velutina on rodents.

The aqueous extract (AE) of Erythrina velutina prolonged the sleep duration induced by sodium pentobarbital (control: 6.4 +/- 1.2 min; extract 10 mg/kg, 47.1 +/- 3.9 min; extract 100 mg/kg, 109.4 +/- 7.2 min; F = 243, P < 0.001). In the open field, the extract at the doses of 10 and 50 mg/kg did not changed the number of crossings, rearings nor groomings. On the other hand, at the dose of 200 mg/kg it reduced the number of crossings (q = 6.25, P < 0.05) and groomings (q = 3.91, P < 0.05). When exposed during three consecutive days to the open field, the control animals showed habituation for crossings (F = 17.56, P < 0.001) and rearings (F = 14.01, P < 0.001). The same was not true for animals treated with 10 mg/kg of the extract (crossings: F = 3.59, P > 0.05; rearings: F = 3.62, P > 0.05). At the same dose, the extract blocked the acquisition of foot shock memory (P = 0.9219) when compared to the control values (P = 0.0078). Our data showed that the crude extract of Erythrina velutina at lower doses interferes with mnemonic process for different tasks, while at higher doses, the sedative and neuromuscular blocking actions are the main effects.

Vivências do familiar frente ao diagnóstico de diabetes mellitus na criança/adolescente / Family experiences in the diagnosis of diabetes mellitus in children/adolescents

Objetivo: identificar as vivências do familiar frente ao diagnóstico de Diabetes Mellitus na criança/adolescente. Métodos: pesquisa qualitativa, realizada com 15 familiares de crianças/adolescentes do Centro Integrado de Diabetes de um Hospital Universitário do sul do Brasil. Coletou-se os dados no primeiro semestre de 2014 por entrevistas semiestruturadas, tratadas pela análise de Conteúdo. Resultados: os familiares identificam os sinais/sintomas, mas não associados com diabetes ou confundidos com outras patologias. O diagnóstico ocorre em consultas de rotina ou quando ocorre o agravamento da situação. Os sentimentos comuns são culpa e medo, por não saber como agir. Primeiro ocorre a negação e depois a busca por conhecimento acerca da doença. Considerações Finais: ao conhecer esse processo, os profissionais de enfermagem podem contribuir para diminuir o impacto do diagnóstico, apoiando a família e criança/adolescente no enfrentamento de mudanças.

Objective: to identify the experiences of the relative in the diagnosis of Diabetes Mellitus in the child/adolescent. Methods: qualitative research, carried out with 15 family members of children/adolescents from the Integrated Diabetes Center of a University Hospital in southern Brazil. Data was collected in the first half of 2014 through semi-structured interviews, handled by Content analysis. Results: family members identify the signs/symptoms, but they do not associate it with diabetes, or they are confused with other pathologies. The diagnosis occurs in routine consultations or when the situation worsens. Common feelings are guilt and fear, for not knowing how to act. First there is denial and then the search for knowledge about the disease. Final considerations: by knowing this process, nursing professionals can contribute to decrease the impact of diagnosis, supporting the family and child/adolescent in coping with changes.

Simultaneous removal of 2-chlorophenol, phenol, p-cresol and p-hydroxybenzaldehyde under nitrifying conditions: kinetic study.

The kinetic behavior of a stable nitrifying consortium exposed to 2-chlorophenol (2-CP), phenol, p-cresol and p-hydroxybenzaldehyde (p-OHB) was evaluated in batch assays. Phenolic compounds were evaluated either individually or in mixture. In individual assays, 2-CP inhibited stronger the nitrification, diminishing the ammonium consumption efficiency (16%) and the nitrate production rate (at 91%). Nonetheless, the consumption efficiencies for all phenolics were of 100%. On the other hand, in mixture, the inhibitory effect of 2-CP diminished significantly, since ammonium consumption efficiency and nitrate production rate were improved. Consumption efficiencies for most of the phenolic compounds were high. Furthermore, the kinetic of 2-CP oxidation was 2.4-fold-faster than the individual assays. Finally, the experimental results showed the potential of nitrifying consortium for removing 2-CP, phenol, p-cresol and p-OHB. This is the first work showing the simultaneous removal of these pollutants and also this information might be useful for treating wastewaters of chemical complexity.

p-Cresol biotransformation by a nitrifying consortium.

The oxidizing ability of a nitrifying consortium exposed to p-cresol (25 mg CL(-1)) was evaluated in batch cultures. Biotransformation of the phenolic compound was investigated by identifying the different intermediates formed. p-Cresol inhibited the ammonia-oxidizing process with a decrease of 83% in the specific rate of ammonium consumption. After 48 h, ammonium consumption efficiency was 96+/-9% while nitrate yield reached 0.95+/-0.06 g NO(3)(-)-Ng(-1)NH(4)(+)-N consumed. High value for nitrate production yield showed that the nitrifying metabolic pathway was only affected at the specific rate level being nitrate the main end product. The consortium was able to totally oxidize p-cresol at a specific rate of 0.17+/-0.06 mg p-cresol-Cmg(-1) microbial protein h(-1). p-Cresol was first transformed to p-hydroxybenzaldehyde and p-hydroxybenzoate, which were later completely mineralized. In the presence of allylthiourea, a specific inhibitor of ammonia monooxygenase (AMO), p-cresol was oxidized to the same intermediates and in a similar pattern as obtained without the AMO inhibitor. AMO seemed not to be involved in the p-cresol oxidation process. When p-hydroxybenzaldehyde was added (25 mg CL(-1)), the nitrifying process was inhibited in the same way as observed with p-cresol, indicating that p-hydroxybenzaldehyde could be the main compound responsible for nitrification inhibition. p-Hydroxybenzaldehyde was accumulated during 15 h before complete consumption at a specific rate value eight times lower than the p-cresol consumption rate. Results showed that p-hydroxybenzaldehyde oxidation was the limiting step in p-cresol mineralization by the nitrifying consortium.

Acetylcholinesterase activities in marine snail (Cronia contracta) as a biomarker of neurotoxic contaminants along the Goa coast, West coast of India.

The measurement of acetylcholinesterase (AChE) activity is used worldwide as a biomarker of environmental contamination due to neurotoxic substances. In the present study the AChE activities was measured in marine snails (Cronia contracta) collected seasonally from six sampling sites (viz. Arambol, Anjuna, Dona Paula, Vasco, Velsao and Palolem) along the Goa coast during the pre-monsoon (April, 2004), monsoon (September, 2004) and post-monsoon (November, 2004) periods. The AChE activities in C. contracta showed wide variation along the Goa coast. It was found to be quite high at the reference site, Palolem (23.97, 21.72 and 24.85) throughout the sampling period (April-November, 2004). The AChE activities in C. contracta decreased significantly at Vasco (44.6-52.4% reduction) followed by Dona Paula (24.9-36.2% reduction), Velasao (10.8-35.9% reduction), Arambol (12.6-37.3% reduction) and Anjuna (0-12.7% reduction). Such a significant variation of AChE activities in the marine snail along the Goa coast can be attributed to neurotoxic substances prevalent in those regions. The high concentration of different neurotoxic metals (lead, cadmium, copper, manganese and iron) and petroleum hydrocarbons in the tissues of the marine snails at Dona Paula, Vasco and Velsao clearly substantiate reduction of AChE activities in C. contracta. The in vitro studies on the inhibition of AChE by different metals and PHC indicated that lead, cadmium and copper are the most predominant inhibitor. Based on the AChE activities in C. contracta the sampling sites along the Goa coast can be classified into three major clusters such as highly contaminated sites (Dona Paula, Vasco and Velsao), moderately contaminated sites (Arambol, Anjuna) and least contaminated site (Palolem).

Ocorrência de neoplasias em cães e gatos da mesorregião metropolitana de Belém, PA entre 2005 e 2010 / Occurrence of neoplasms in canine and feline from the Metropolitan Mesoregion of Belém, PA from 2005 to 2010

Data on the occurrence of cancers in dogs and cats from the Metropolitan Mesoregion of Belém are not available in the literature. This paper describes the occurrence of neoplasms in these species from 2005 to 2010. The canine cutaneous system was the most affected in this study (47 percent), followed by the mammary gland (39 percent), reproductive system (4 percent), oral cavity (4 percent), bones and joints (2 percent), ocular system (1.5 percent), digestive system (1.5 percent) and urinary tract (1 percent). In feline species, the mammary gland accounted for 87.8 percent, followed by the cutaneous system (6 percent), respiratory system (3 percent) and oral cavity (3 percent).

Avaliação do equilibrio estatico em individuos amputados de membros inferiores atraves da biofotogrametria computadorizada / Evaluation of the static balance lower limb amputers by means of computerized biophotogrammetry

Para que sejam realizadas atividades funcionais da vida diaria e primordial a manutencao do equilibrio estatico, possibilitando posturas, movimentos e respostas adequadas. Objetivos O presente trabalho teve como finalidade avaliar e comparar, atraves do teste de Romberg adaptado, as oscilacoes do equilibrio estatico de amputados protetizados de membros inferiores com individuos nao amputados. metodos Foram avaliados 33 individuoes do sexo masculino com idade media de 33,38 anos, divididos em tres diferentes grupos. O grupo A foi composto por 12 individuos amputados que utilizavam protese transfemural. O grupo B foi formado por 9 individuos amputados transtibias. O grupo C continua 12 individuos nao amputados. cada individuo foi filmado nos planos frontal e sagital, avaliado quadro a quadro para a selecao de momentos de maiores oscilacoes. As imagens selecionadas foram quantificadas atraves da Biofotogrametria computadorizada, utilizando-se o programa AL Cimage 2.1. Resultados Os resultados mostram diferencas significativas entre as oscilacoes anteriores para o grupo A (transfemural) e entre as oscilacoes para o lado esquerdo no grupo B. Conclusao A partir destes resultados, conclui-se que amputados de membros inferiores apresentam uma tendencia de oscilacao mais significativa em direcao anterior e para o lado contra-lateral a protese. com o avanco da idade, nota-se uma menor tendencia a oscilacao posterior