Large-Scale Conformational Changes of Trypanosoma cruzi Proline Racemase Predicted by Accelerated Molecular Dynamics Simulation

Chagas' disease, caused by the protozoan parasite Trypanosoma cruzi (T. cruzi), is a life-threatening illness affecting 11–18 million people. Currently available treatments are limited, with unacceptable efficacy and safety profiles. Recent studies have revealed an essential T. cruzi proline racemase enzyme (TcPR) as an attractive candidate for improved chemotherapeutic intervention. Conformational changes associated with substrate binding to TcPR are believed to expose critical residues that elicit a host mitogenic B-cell response, a process contributing to parasite persistence and immune system evasion. Characterization of the conformational states of TcPR requires access to long-time-scale motions that are currently inaccessible by standard molecular dynamics simulations. Here we describe advanced accelerated molecular dynamics that extend the effective simulation time and capture large-scale motions of functional relevance. Conservation and fragment mapping analyses identified potential conformational epitopes located in the vicinity of newly identified transient binding pockets. The newly identified open TcPR conformations revealed by this study along with knowledge of the closed to open interconversion mechanism advances our understanding of TcPR function. The results and the strategy adopted in this work constitute an important step toward the rationalization of the molecular basis behind the mitogenic B-cell response of TcPR and provide new insights for future structure-based drug discovery

Genetic parameters for faecal egg count, packed-cell volume and body-weight in Santa Inês lambs

Worm infection is one of the main factors responsible for economic losses in sheep breeding in Brazil. Random regression analysis was used to estimate genetic parameters for the factors faecal egg-count (FEC), packed-cell volume (PCV) and body weight (BW) in Santa Inês lambs. Data from 119 female, offspring of nine rams, were collected between December, 2005 and December, 2006, from the experimental flock of Embrapa Tabuleiros Costeiros, the Brazilian Agricultural Research Corporation located in Frei Paulo, SE, Brazil. After weaning, females were drenched until the faecal egg count had dropped to zero. Two natural challenges were undertaken. FEC heritability was extremely variable, this increasing from 0.04 to 0.27 in the first challenge and from 0.01 to 0.52 during the second. PCV heritability peaks were 0.31 and 0.12 in the first and second challenges, respectively. In the second challenge, BW heritability was close to 0.90. The genetic correlations among these traits did not differ from zero. There is the possibility of increasing parasite resistance in Santa Inês by selecting those animals with lower FEC. Selection to increase resistance will not adversely affect lamb-growth, although lambs with a slow growth-rate may be more susceptible to infection

Acidente ocupacional por material perfurocortante entre profissionais de saúde de um Centro Cirúrgico

O acidente ocupacional por material perfurocortante constitui uma preocupação para instituições e trabalhadores de saúde, devido à elevada frequência de procedimentos invasivos, e a dinâmica do trabalho. Objetivou-se identificar a incidência dos acidentes, dos materiais envolvidos, dos fatores contribuintes e das condutas tomadas pós-acidente. Participaram de um estudo transversal 127 funcionários do centro cirúrgico. Registraram-se 23,6% (30/127) acidentes com envolvimento de agulha (73,3%), lâmina de bisturi (6,7%) e eletrocautério (6,7%). Os fatores contribuintes para o acidente foram: falta de atenção (36,7%), más condições de trabalho (20,0%), descuido (13,3%), pressa (10%) e acaso/azar (6,7%). Somente 15,4% dos acidentes foram registrados. A subnotificação deveu-se à irrelevância do acidente, desconhecimento do protocolo de rotina, displicência e sobrecarga de trabalho. Os resultados alertam para a importância de se implementar estratégias para adoção/revisão de protocolos pós-acidentes, visando a redução dos acidentes e de sua subnotificação.El accidente laboral por elementos corto-punzantes constituye una preocupación para instituciones y trabajadores de la salud, debido a la elevada frecuencia con la que se realizan procedimientos invasivos y por la dinámica del trabajo. Se objetivó identificar la incidencia de los accidentes, los materiales involucrados, los factores contribuyentes y las conductas tomadas con posterioridad al accidente. Participaron de un estudio transversal 127 trabajadores de un centro quirúrgico. Sobre un porcentaje de accidentados del 23,6% (30/127), el 73,3% sufrió accidentes involucrando agujas, 6,7% se accidentó con hojas de bisturí y 6,7% se accidentó con electrocauterizador. Los factores que contribuyeron a los accidentes fueron: falta de atención (36,7%), malas condiciones de trabajo (20,0%), descuido (13,3%), prisa (10,0%) y casualidad / azar (6,7%). Sólo el 15,4% de los accidentes fueron registrados. La falta de notificación se debió a la irrelevancia del accidente, desconocimiento del protocolo de rutina, displicencia y sobrecarga de trabajo. Los resultados alertan sobre la importancia de implementar estrategias para adopción / revisión de protocolos post accidentes, apuntando a la reducción de la cantidad de accidentes y a evitar la ausencia de registro de los mismos.Occupational accidents involving piercing-cutting material are a concern for institutions and health workers due to the high frequency of invasive procedures and the dynamics involved in their practice. The objective of the present study was to identify the incidence of accidents, devices involved, contributing factors and post-accident behaviors. A cross-sectional study was conducted among 127 healthcare workers from the operating center. Of the total number of accidents reported, 23.6% (30/127) involved piercing-cutting materials, including needles (73.3%), scalpels (6.7%) and electrocautery (6.7%). The factors contributing to the accident were: lack of attention (36.7%), poor working conditions (20.0%), neglect (13.3%), rushing (10%) and accident/chance (6.7%). Only 15.4% of the accidents were recorded. Underreporting was due to: irrelevance of the accident, unaware of the protocol of routine, negligence and work overload. Results show the importance of implementing strategies for adopting/reviewing post-accident protocols aiming at reducing accidents and their underreporting