Effects of transcranial direct current stimulation on working memory and negative symptoms in schizophrenia: a phase II randomized sham-controlled trial

Background: The lack of efficacy of pharmacological treatments for cognitive and negative symptoms in schizophrenia highlights the need for new interventions. We investigated the effects of tDCS on working memory and negative symptoms in patients with schizophrenia. Method: Double-blinded, randomized, sham-controlled clinical trial, investigating the effects of 10 sessions of tDCS in schizophrenia subjects. Stimulation used 2 mA, for 20 min, with electrodes of 25 cm2 wrapped in cotton material soaked in saline solution. Anode was positioned over the left DLPFC and the cathode in the contralateral area. Twenty-four participants were assessed at baseline, after intervention and in a three-months follow-up. The primary outcome was the working memory score from MATRICS and the secondary outcome the negative score from PANSS. Data were analyzed using generalized estimating equations. Results: We did not find group ∗ time interaction for the working memory (p = 0.720) score or any other cognitive variable (p > 0.05). We found a significant group ∗ time interaction for PANSS negative (p < 0.001, d = 0.23, CI.95 = −0.59–1.02), general (p = 0.011) and total scores (p < 0.001). Exploratory analysis of PANSS 5 factors suggests tDCS effect on PANSS negative (p = 0.012), cognitive (p = 0.016) and depression factors (p = 0.029). Conclusion: The results from this trial highlight the therapeutic effects of tDCS for treatment of persistent symptoms in schizophrenia, with reduction of negative symptoms. We were not able to confirm the superiority of active tDCS over sham to improve working memory performance. Larger sample size studies are needed to confirm these findings

Pesquisas cooperativas entre universidades e institutos públicos no setor agropecuário brasileiro: um estudo na Embrapa

A presente pesquisa objetivou a caracterização das cooperações entre universidades e institutos de pesquisa (U-IP) no setor agropecuário. O referencial teórico aborda temas como tecnologia e inovação tecnológica, sistema nacional de inovação (SNI), cooperação interinstitucional para inovação tecnológica, transferência de tecnologia, além dos papéis de universidades e institutos de pesquisa dentro do SNI. Também aborda os temas de tipos de pesquisa e o contexto da pesquisa agropecuária brasileira. A revisão teórica foi fundamentada na cooperação entre universidades e empresas (U-E), dada a reduzida literatura a respeito da cooperação U-IP. A metodologia utilizada foi a de estudo de caso, de natureza exploratória e qualitativa, utilizando roteiros de entrevista semiestruturados, questionários semiestruturados, bem como análise documental. O caso estudado foi o da Empresa Brasileira de Pesquisa Agropecuária (Embrapa), onde foram coletados dados em três unidades de pesquisa, três universidades que cooperam com essas unidades e três unidades administrativas da Embrapa que apresentam contato com as universidades, totalizando nove entrevistas e questionários. Foi possível dessa forma identificar motivadores, tipos de ligações, barreiras, facilitadores e resultados percebidos nessas cooperações

Sistema de recomendação de fertilizantes e corretivos para a cultura do abacaxi - fertcalc-abacaxi Fertilizer and lime recommendation system for pineapple - fertcalc-abacaxi

A demanda nutricional do abacaxizeiro é alta em relação à de outras culturas e depende do cultivar, do peso do fruto, do destino da produção, do sistema e da densidade de plantio, e a variação desses fatores nem sempre está contemplada nas tabelas de adubação. O objetivo deste trabalho foi propor um Sistema de Recomendação de Fertilizantes e Corretivos para a Cultura do Abacaxi (FERTCALC-Abacaxi), elaborado a partir da sistematização e modelagem de informações de literatura e do conhecimento atual sobre adubação e nutrição mineral da cultura. O FERTCALC-Abacaxi baseia-se no método do balanço nutricional e está subdividido em dois subsistemas: o subsistema requerimento, que contempla a demanda pela planta, considerando a eficiência de recuperação dos nutrientes aplicados e uma dose para atender o critério de "sustentabilidade", e o subsistema suprimento, que compreende a oferta de nutrientes pela calagem, pelo solo, pela matéria orgânica e pelos resíduos orgânicos. Simulações realizadas com o FERTCALC-Abacaxi mostraram que o Sistema recomenda maiores doses para o cultivar Pérola em relação ao Smooth Cayenne, para plantios mais adensados e para obtenção de frutos mais pesados. Diferentemente das tabelas, as doses variaram de forma contínua com a produtividade esperada e com o teor de nutrientes no solo, sendo maiores no primeiro em relação ao segundo cultivo. Por contemplar na sua estrutura maior número de fatores envolvidos na resposta da cultura à adubação, a exemplo da produtividade esperada, do cultivar, do peso do fruto, do sistema e da densidade de plantio, e considerar a contribuição dos resíduos orgânicos do cultivo anterior, o FERTCALC-Abacaxi constitui-se numa alternativa mais versátil para recomendar doses de fertilizantes e corretivos para o abacaxizeiro, embora precise ser aperfeiçoado em futuras versões e ter seu desempenho avaliado em condições práticas.<br>The nutritional demand of pineapple plants is higher than for other crops and IT depends on cultivar, fruit weight, production destination and planting density and cultivation system. However, the variation in these factors is not always taken into account in fertilization tables. The purpose of this study was to propose a fertilizer and lime recommendation system for pineapple designated FERTCALC-Abacaxi, based on systematization and modeling of literature data and the current knowledge concerning fertilization and mineral nutrition of the crop. FERTCALC-Abacaxi is based on the nutritional balance method and is divided into two subsystems: the requirement subsystem that contemplates the plant demand, considering the efficiency of recovery of the applied nutrients and a dose to meet the requirement "sustainability"; and the supply subsystem that comprises the nutrient supply by liming, soil, organic matter, and by organic residues. Simulations with FERTCALC-Abacaxi showed that the System recommends higher doses for the Pérola cv., than for Smooth Cayenne, for denser planting systems and to obtain heavier fruits; and differently from the tables, it varied continuously with the expected productivity and soil nutrient contents, being higher in the first than in the second growing cycle. In view of the higher number of factors taken into consideration that reflect the response of the crop to fertilization, for example the expected yield, cultivar, fruit weight, planting density and system, besides taking into account the contribution of organic residues from the previous cycle, the FERTCALC- Abacaxi represents a more versatile alternative for fertilizer and lime recommendation for the pineapple crop. However, improvements in future versions of the System as well as its validation under practical conditions are necessary

Margem de segurança do meloxicam em cães: efeitos deletérios nas células sangüíneas e trato gastrintestinal Margin of safety of meloxicam in dogs: deleterious effects on blood cells and gastrointestinal tract

Este trabalho investigou a margem de segurança do inibidor COX-2, meloxicam, em cães, enfocando seus efeitos deletérios nas células sangüíneas e no trato gastrintestinal. Para tanto, após uma avaliação clínico-laboratorial, os cães foram distribuídos nos seguintes grupos: I (placebo; n= 3), II (piroxicam; 1,0mg kg-1; n= 5), III (meloxicam; 0,2mg kg-1; n= 5), IV (meloxicam;1,0mg kg-1; n= 5) e V (meloxicam; 2,0mg kg-1; n= 5). Os fármacos foram usados, por via oral, por 16 dias. No 17&ordm; dia, repetiu-se o hemograma completo e, então, procedeu-se a eutanásia seguida pela necrópsia. No grupo I, não houve alterações dignas de nota. No grupo II, todos os cães apresentaram episódios moderados de vômito e diarréia. O perfil celular sangüíneo não foi significativamente modificado. Em dois cães, houve redução no hematócrito e na hemoglobina. Na necropsia, observaram-se focos hemorrágicos e lesões gastriduodenais moderadas. A análise microscópica revelou a presença de gastrite e enterite ulcerativa. No grupo III, quatro cães (80%) apresentaram vômito e diarréia, sem alteração no perfil celular sangüíneo. Na análise macroscópica, observaram-se lesões brandas na mucosa gástrica e focos hemorrágicos no duodeno em quatro cães. Na histopatologia, observaram-se lesões sugestivas de discreta gastroenterite. No grupo IV, os cinco cães tiveram vômito e diarréia sanguinolenta. Quatro deles (80%) apresentaram anemia (p < 0,05). Quatro e cinco cães apresentaram redução no hematócrito e hemoglobina, respectivamente. Ocorreram, ainda, leucocitose, neutrofilia e linfopenia significantes (p < 0,05), em 60% dos cães. Na necrópsia, evidenciaram-se hiperemia, hemorragia e úlceras gástricas severas em 100% dos animais. Verificou-se na microscopia um quadro de gastroenterite ulcerativa nos cinco cães. No grupo V, todos os cães apresentaram sérios episódios de vômito, diarréia e melena. Os quatro (80%) cães que suportaram o tratamento apresentaram anemia e leucocitose com neutrofilia e linfopenia significativas (p< 0,05). Houve, ainda, uma redução no hematócrito e hemoglobina desses cães. Na necropsia, foram visualizadas hemorragias e graves ulcerações gastroduodenais. À histopatologia, evidenciou-se severa gastroenterite. Conclui-se que o meloxicam, mesmo sendo COX-2 seletivo, induz efeitos deletérios no trato gastrintestinal e células sangüíneas de cães, quando administrado em concentrações cinco e dez vezes a dose terapêutica, que demonstram sua estreita margem de segurança nesta espécie.<br>This study investigated the margin of safety of the COX-2e inhibitor, meloxicam on blood cells and gastrointestinal tract of dogs. After a clinical and laboratorial examination, the dogs were distributed in the following groups: I (placebo; n=3), II (piroxicam: 1.0mg kg-1; n=5), III (meloxicam: 0.2mg kg-1; n=5), IV (meloxican: 1.0mg kg-1; n=5) and V (meloxican: 2.0mg kg-1; n=5). The drugs were given orally for 16 days. On the 17th day the complete hemogram was repeated and the euthanasia and necropsy were then accomplished. In group I there were no significative alterations. In group II, all the dogs showed moderate episodes of vomit and diarrhea. The blood-cell profile was not modified. Two dogs had hematocrit and hemoglobin reduction. In the necropsy, hemorrhagic spots and moderate gastroduodenal lesions were seen. The microscopic analysis revealed the presence of gastritis and ulcerative enteritis. In group III, four dogs (80%) showed vomit and diarrhea, without alteration in blood-cell profile. The microscopic analysis showed mild lesions in the gastric mucosa and hemorrhagic spots in the duodenum of four dogs. Histology showed lesions suggesting mild gastroenteritis. In group IV, all the dogs (n=5) showed vomit and blood diarrhea. Four of them showed anemia (p <0.05). Four and five dogs, respectively, had hematocrit and hemoglobin reduction. In addition, there was a significant (p<0.05) leukocytosis, neutrophilia and linfopenia in 60% of the dogs. The necropsy showed hiperemia, hemorrhage and severe gastric ulcers in all the dogs. In the microscopic analyses, gastroenteritis ulcerative was present in all the animals. In group V, the dogs (n=5) had serious vomit, diarrhea and melena episodes. The dogs that bore the treatment (n=4) had anemia and leukocytosis with neutrophilia and linfopenia significatives (p<0.05). All the dogs had hematocrit and hemoglobin reduction. In the necropsy, hemorrhages and severe gastroduodenal ulceration were seen. The microscopic analysis showed severe gastroenteritis. It can be concluded that, although meloxicam is a COX-2 selective inhibitor, it induces deleterious effects on gastrointestinal tract and blood cells of dogs, when given five or ten times the therapeutic dose, which demonstrate its low margin of safety in this animal specie

A consensus on the diagnosis and treatment of acromegaly comorbidities: an update

Objective: The aim of the Acromegaly Consensus Group was to revise and update the consensus on diagnosis and treatment of acromegaly comorbidities last published in 2013.Participants: The Consensus Group, convened by 11 Steering Committee members, consisted of 45 experts in the medical and surgical management of acromegaly. The authors received no corporate funding or remuneration.Evidence: This evidence-based consensus was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe both the strength of recommendations and the quality of evidence following critical discussion of the current literature on the diagnosis and treatment of acromegaly comorbidities.Consensus Process: Acromegaly Consensus Group participants conducted comprehensive literature searches for English-language papers on selected topics, reviewed brief presentations on each topic, and discussed current practice and recommendations in breakout groups. Consensus recommendations were developed based on all presentations and discussions. Members of the Scientific Committee graded the quality of the supporting evidence and the consensus recommendations using the GRADE system.Conclusions: Evidence-based approach consensus recommendations address important clinical issues regarding multidisciplinary management of acromegaly-related cardiovascular, endocrine, metabolic, and oncologic comorbidities, sleep apnea, and bone and joint disorders and their sequelae, as well as their effects on quality of life and mortality

Treatment-Resistant Schizophrenia: Treatment Response and Resistance in Psychosis (TRRIP) Working Group Consensus Guidelines on Diagnosis and Terminology

Objective: Research and clinical translation in schizophrenia is limited by inconsistent definitions of treatment resistance and response. To address this issue, the authors evaluated current approaches and then developed consensus criteria and guidelines. Method: A systematic review of randomized antipsychotic clinical trials in treatment-resistant schizophrenia was performed, and definitions of treatment resistance were extracted. Subsequently, consensus operationalized criteria were developed through 1) a multiphase, mixed methods approach, 2) identification of key criteria via an online survey, and 3) meetings to achieve consensus. Results: Of 2,808 studies identified, 42 met inclusion criteria. Of thes