Kinase Inhibitor Profile For Human Nek1, Nek6, And Nek7 And Analysis Of The Structural Basis For Inhibitor Specificity.

Human Neks are a conserved protein kinase family related to cell cycle progression and cell division and are considered potential drug targets for the treatment of cancer and other pathologies. We screened the activation loop mutant kinases hNek1 and hNek2, wild-type hNek7, and five hNek6 variants in different activation/phosphorylation statesand compared them against 85 compounds using thermal shift denaturation. We identified three compounds with significant Tm shifts: JNK Inhibitor II for hNek1(Δ262-1258)-(T162A), Isogranulatimide for hNek6(S206A), andGSK-3 Inhibitor XIII for hNek7wt. Each one of these compounds was also validated by reducing the kinases activity by at least 25%. The binding sites for these compounds were identified by in silico docking at the ATP-binding site of the respective hNeks. Potential inhibitors were first screened by thermal shift assays, had their efficiency tested by a kinase assay, and were finally analyzed by molecular docking. Our findings corroborate the idea of ATP-competitive inhibition for hNek1 and hNek6 and suggest a novel non-competitive inhibition for hNek7 in regard to GSK-3 Inhibitor XIII. Our results demonstrate that our approach is useful for finding promising general and specific hNekscandidate inhibitors, which may also function as scaffolds to design more potent and selective inhibitors.

Análise do investimento em climatização para bovinos de leite em sistema de alojamento free-stall

The difficulty in adapting European dairy cows breeds in Brazil affect considerably the milk production sector. Brazilian climatic conditions are not totally favorable and the development of new tecnologies is needed for the animals express their genetic potential, as well as their best feed conversion. An economical analysis of the applied investment in the free-stall climatization equipment in dairy housing, for estimating studies related to profit, possibility of return investment as well as time for this return is necessary. The objective of this research was to evaluate the influence of climatization investment in the milk production process and analyze the economical aspect of this investment. There were used 470 high productive dairy cows with genetic and morphologic homogeneous characteristics, and analyzed in two similar periods. Investment calculations were done using Excell®. The results were satisfactory and the invested capital was proved to return to the producer in a short term, 57 days.

Gênero e estresse em trabalhadores de uma universidade pública do estado de São Paulo

The aim of this paper was to identify, according to gender, the indexes of Mental Health and the Psychosocial Risk Factors in workers at a state University. A sample of 400 was randomly selected, 253 female and 147 male. They were assessed by means of The Questionnaire SWS Survey (Self, Work and Social) (Ostermann & Gutiérrez, 1992), validated in Brazil by Guimarães and Macfadden (1999). Univariate, bivariate, multivariate statistics were assessed. Significant associations emerged from Mental Health and Gender, and Psychosocial Risk Factors and Gender. Women showed greater Psychosocial Risk Factors, Work and Social Stress, worst mental health than men (p < 0.05), which place them at greater risk for developing physical and/or mental illness.

COMPARAÇÃO DAS PROPRIEDADES REOLÓGICAS DA MASSA DE CACAU TORRADA CONVENCIONALMENTE E POR MICROONDAS

Two kinds of roasting cocoa system: conventional batch method in electrical oven, and by microwaves, in a continuous microwave rotary applicator (2450MHz), were compared with respect to viscosity. Cocoa was roasted in whole beans and in nibs. The variable used in the microwave treatment was the power density applied to the whole beans (254,45 to 290,80 Wh/kg) and to the nibs (227,27 to 262,23 Wh/kg), with a constant holding time of 10 minutes. The variable used in the conventional roasting process was the roasting time of the beans (40 to 44 min) and the nibs (34 to 38 min), with constant temperature in the jacket of electric oven (150°C). Viscosity was measured in a Brookfield rheometer (mod RV-DVIII) at 40°C. In general, the plastic viscosity of the microwaved samples was lower than that of the conventional roasted samples. Also the nibs showed lower viscosities than the whole beans when roasted in the electric oven. The viscosity of the samples roasted in the microwave oven was lower in the whole beans than in the nibs. The product was sensorially evaluated by three experts in cocoa flavour, and it was shown that the flavour of the microwave roasted products was similar to that of the conventionally roasted products, with the advantage of a reduction in process time.

New Guidelines Of Cerebral Cardiopulmonary Resuscitation By The American Heart Association (2005 - 2006) [novas Diretrizes De Reanimação Cardiorrespiratória Cerebral Da Sociedade Americana De Cardiologia (2005 - 2006)]

No abstract available

Congenital eruption cyst: a case report

Congenital pathologies are those existing at or dating from birth. Occurrence of congenital cystic lesions in the oral cavity is uncommon in neonates. Eruption cyst (EC) is listed among these unusual lesions. It occurs within the mucosa overlying teeth that are about to erupt and, according to the current World Health Organization (WHO) classification of epithelial cysts of the jaws, EC is a separate entity. This paper presents a case of congenital EC successfully managed by close monitoring of the lesion, without any surgical procedure or tooth extraction. Eruption of the teeth involved, primary central incisors, occurred at the fourth month of age. During this time neither the child nor mother had any complication such as pain on sucking, refusal to feed, airway obstruction, or aspiration of fluids or teeth.

Management of a complex dentoalveolar trauma: a case report

This paper describes the case of a 12-year-old male patient who presented a severe lateral luxation of the maxillary central incisors due to a bicycle fall. Treatment involved suture of the soft tissues lacerations, and repositioning and splinting of the injured teeth, followed by endodontic treatment and periodontal surgery. After a 2-year follow-up, clinical and radiographic evaluation revealed that the incisors presented satisfactory esthetic and functional demands.

T-Bar clasp-retained removable partial denture as an alternative to implant-based prosthetic treatment

This article reports the case of a 55-year-old female patient who presented with unsatisfactory temporary crowns in the right mandibular premolars and molars, and a premolar-to-molar fixed partial denture in the left side. The clinical and radiographic examinations revealed a fracture of the left first premolar that was a retainer of the fixed partial denture and required extraction. Initially, the acrylic resin crowns were replaced by new ones, and a provisional RPD was made using acrylic resin and orthodontic wire clasps to resolve the problem arising from the loss of the fixed partial denture. Considering the patient's high esthetic demands, the treatment options for the definitive prosthetic treatment were discussed with her and rehabilitation with implant-supported dentures was proposed because the clinical conditions of the residual alveolar ridge were suitable for implant installation, and the patient's general health was excellent. However, the patient did not agree because she knew of a failed case of implant-retained denture in a diabetic individual and was concerned. The patient was fully informed that implant installation was the best indication for her case, but the arguments were not sufficient to change her decision. The treatment possibilities were presented and the patient opted for a clasp-retained removable partial denture (RPD) associated with the placement of crowns in the pillar teeth. The temporary RPD was replaced by the definitive RPD constructed subsequently. Although RPD was not the first choice, satisfactory esthetic and functional outcomes were achieved, overcaming the patient's expectations. This case report illustrates that the dentist must be prepared to deal with situations where, for reasons that cannot be managed, the patient does not accept the treatment considered as the most indicated for his/her case. Alternatives must be proposed and the functional and esthetic requirements must be fulfilled in the best possible manner.

Avaliação da prevalência do diabetes e da hiperglicemia de estresse no infarto agudo do miocárdio

OBJETIVOS: Determinar a prevalência do diabetes melito (DM) e da hiperglicemia de estresse (HE) em pacientes com infarto agudo do miocárdio (IAM) admitidos em unidade de emergência cardiológica. MÉTODOS: Análise retrospectiva de 2.262 pacientes com IAM, avaliando, além da prevalência de diabetes referido, o diagnosticado e a hiperglicemia de estresse. RESULTADOS: Apesar de referido em 12,1% dos pacientes (H: 10,7%, M: 15,8%), o DM ocorria efetivamente em 24,8% (H: 22,9%, M: 29,7%) e a HE em 13,6% (H: 14,3%, M: 11,7%) dos indivíduos dessa população. Portanto, alterações glicêmicas ocorreram em 37,4% dos indivíduos com IAM (H: 37,2%, M: 41,4%). Nos pacientes com DM, observou-se maior precocidade etária do IAM, maior prevalência de óbitos (DM: 20,7%, ND:13,8%, HE: 13,4%) e de procedimentos cirúrgicos (ND: 33,8%, HE: 18,0%, DM: 21,7%). CONCLUSÃO: A elevada prevalência de DM e hiperglicemia de estresse observada em nosso estudo indica que as alterações glicêmicas constituem um dos mais importantes fatores de risco para o IAM.

Culex quinquefasciatus vitellogenesis: morphological and biochemical aspects

The vitellogenic process in Culex quinquefasciatus, which is triggered by a blood meal, involves the synthesis, distribution and storage of the nutrients necessary for embryo development. The fat body of an adult female Cx. quinquefasciatus revealed two cell types: large trophocytes and small, eosinophilic, "oenocyte-like" cells, which show no morphological changes throughout the gonotrophic cycle. Trophocytes, which only begin to synthesise vitellogenin (Vg) 12 h post-blood meal (PBM), undergo a series of morphological changes following engorgement. These changes include the expansion of the rough endoplasmic reticulum (RER) and Golgi complex, which are later destroyed by autophagosomes. At 84 h PBM, trophocytes return to their pre-engorgement morphology. The ovarian follicles of non-blood-fed Cx. quinquefasciatus contain a cluster of eight undifferentiated cells surrounded by follicular epithelium. After engorgement, the oocyte membrane facing the perioocytic space increases its absorptive surface by microvilli development; large amounts of Vg and lipids are stored between 24 and 48 h PBM. Along with yolk storage in the oocyte, follicular cells exhibit the development of RER cisternae and electron-dense granules begin to fill the perioocytic space, possibly giving rise to endochorion. Later in the gonotrophic cycle, electron-dense vesicles, which are possible exochorion precursors, fuse at the apical membrane of follicular cells. This fusion is followed by follicular cell degeneration.

Desenvolvimento de capacidades e gestualidade espontânea

O objetivo deste artigo é apresentar e discutir, em uma interlocução com o pensamento winnicottiano, a potencialidade mutativa de uma modalidade de prática psicológica denominada Enquadre Clínico para Desenvolvimento de Capacidades; propõe, ainda, uma elaboração conceitual que distingue capacidades integradas e competências dissociadas. À luz de tal distinção, essa alternativa clínica pode ser compreendida como constituição de um ambiente facilitador que favorece tanto o desenvolvimento de capacidades incipientes como a integração de competências dissociadas, que passam a ser vividas transicionalmente como experiências criativas. Esse enquadre vem sendo utilizado produtivamente na forma de uma oficina voltada ao desenvolvimento da capacidade de escrever.

Influência de diferentes sistemas de solvente água-etanol sobre as propriedades físico-químicas e espectroscópicas dos compostos macrocíclicos feofitina e clorofila α

This work focus on the influence of solvent on the photophysical properties of chlorophyll α and pheophytin. Both compounds are related to the photosynthesis process and are considered prototypes of photosensitizers in Photodynamic Therapy. Fluorescence measurements were developed using water/ethanol mixtures at different compositions, since both solvents could be employed in biological applications. The spectroscopic properties of these compounds undergo profound changes depending on water content in the ethanol due to auto-aggregation processes. The major hydrophobicity and the lower dielectric constant of ethanol when compared with water precluded significantly the auto-aggregation process of these compounds.

Dispersal and survival of Nyssomyia intermedia and Nyssomyia neivai (Diptera: Psychodidae: Phlebotominae) in a cutaneous leishmaniasis endemic area of the speleological province of the Ribeira Valley, state of São Paulo, Brazil

The dispersal and survival of the phlebotomines Nyssomyia intermedia and Nyssomyia neivai (both implicated as vectors of the cutaneous leishmaniasis agent) in an endemic area was investigated using a capture-mark-release technique in five experiments from August-December 2003 in municipality of Iporanga, state of São Paulo, Brazil. A total of 1,749 males and 1,262 females of Ny. intermedia and 915 males and 411 females of Ny. neivai were marked and released during the five experiments. Recapture attempts were made using automatic light traps, aspiration in natural resting places and domestic animal shelters and Shannon traps. A total of 153 specimens (3.48%) were recaptured: 2.59% (78/3,011) for Ny. intermedia and 5.35% (71/1,326) for Ny. neivai. Both species were recaptured up to 144 h post-release, with the larger part of them recaptured within 48 h. The median dispersion distances for Ny. intermedia and Ny. neivai, respectively, were 109 m and 100 m. The greatest dispersal range of Ny. intermedia was 180 m, while for Ny. neivai one female was recaptured in a pasture at 250 m and another in a pigsty at 520 m, showing a tendency to disperse to more open areas. The daily survival rates calculated based on regressions of the numbers of marked insects recaptured on the six successive days after release were 0.746 for males and 0.575 for females of Ny. intermedia and 0.649 for both sexes of Ny. neivai. The size of the populations in the five months ranged from 8,332-725,085 for Ny. intermedia males, 2,193-104,490 for Ny. intermedia females, 1,687-350,122 for Ny. neivai males and 254-49,705 for Ny. neivai females.

Influência do local de nascimento e do transporte sobre a morbimortalidade de recém-nascidos prematuros

OBJETIVO: Verificar a influência do local de nascimento e do transporte sobre a morbimortalidade de recém-nascidos prematuros na Região Sul do Brasil. MÉTODOS: Estudo de coorte com recém-nascidos prematuros transferidos para a unidade de tratamento intensivo de referência (grupo transporte = 61), tendo sido acompanhados até a alta. Os dados sobre o atendimento no hospital de origem e transporte foram obtidos no momento da internação. Esse grupo foi comparado com neonatos da maternidade de referência, pareados por idade gestacional (grupo controle = 123), tendo como desfecho primário o óbito e desfechos secundários as alterações da glicemia, temperatura e saturação de oxigênio no momento da internação e a incidência de enterocolite necrosante, displasia broncopulmonar e sepses. Na associação entre as variáveis e o desfecho, foi utilizado o risco relativo. Foi adotado um nível de significância de α = 5% e β = 90%. RESULTADOS: A distância média percorrida foi de 91 km. A idade gestacional média foi de 34 semanas. Entre os recém-nascidos transferidos, 23% (n = 14) não tiveram atendimento pediátrico na sala de parto. No transporte, 33% dos recém-nascidos foram acompanhados por pediatra, e os equipamentos utilizados foram: incubadora (57%), bomba de infusão (13%), oxímetro (49%) e aparelho para aferição da glicemia (21%). O grupo transporte apresentou maior incidência de hiperglicemia, risco relativo (RR) = 3,2 (2,3-4,4), hipoglicemia, RR = 2,4 (1,4-4,0), hipertermia, RR = 2,5 (1,6-3,9), e hipoxemia, RR = 2,2 (1,6-3,0). Foram observados 18% de óbitos no grupo dos transferidos e 8,9% no grupo controle, RR = 2,0 (1,0-2,6). CONCLUSÕES: A pesquisa expõe deficiências no atendimento e transporte dos recém-nascidos, sendo necessária uma melhor organização do atendimento perinatal e do transporte na região nordeste do Rio Grande do Sul.

The expression of vulnerability through infant mortality in the municipality of Embu

CONTEXTO E OBJETIVO: A mortalidade infantil expressa uma conjunção de fatores relacionados às condições de vida, trabalho e acesso aos serviços de saúde, e a identificação desses fatores pode contribuir para definição de intervenções em saúde. O objetivo deste trabalho foi analisar a expressão da vulnerabilidade e conseqüentes diferenças de acesso aos serviços de saúde e na ocorrência de óbitos em menores de um ano no município do Embu. TIPO DE ESTUDO E LOCAL: Estudo descritivo, no município de Embu. MÉTODOS: Foram coletados dados secundários (declarações de óbitos) e primários (entrevistas a famílias de crianças residentes do município do Embu, falecidas nos anos de 1996 e 1997, antes de completarem um ano). Variáveis estudadas foram relacionadas às condições de vida, renda e trabalho, à assistência pré-natal, ao parto e à atenção à saúde da criança, as quais foram comparadas com resultados obtidos em estudo realizado no ano de 1996. RESULTADOS: Verificaram-se diferenças estatisticamente significantes quanto a renda, trabalho sem carteira assinada e acesso a plano privado de saúde entre famílias de crianças que foram ao óbito. Verificaram-se, também, diferenças quanto ao acesso e à qualidade da assistência pré-natal, à freqüência de baixo peso ao nascer e a intercorrências neonatais. CONCLUSÕES: A situação de emprego/desemprego foi decisiva na determinação da estabilidade familiar, conferindo maior vulnerabilidade para ocorrência de óbitos infantis, somada às condições de acesso e à qualidade dos serviços de saúde