Perinatal asphyxia: current status and approaches towards neuroprotective strategies, with focus on sentinel proteins

Delivery is a stressful and risky event menacing the newborn. The mother-dependent respiration has to be replaced by autonomous pulmonary breathing immediately after delivery. If delayed, it may lead to deficient oxygen supply compromising survival and development of the central nervous system. Lack of oxygen availability gives rise to depletion of NAD+ tissue stores, decrease of ATP formation, weakening of the electron transport pump and anaerobic metabolism and acidosis, leading necessarily to death if oxygenation is not promptly re-established. Re-oxygenation triggers a cascade of compensatory biochemical events to restore function, which may be accompanied by improper homeostasis and oxidative stress. Consequences may be incomplete recovery, or excess reactions that worsen the biological outcome by disturbed metabolism and/or imbalance produced by over-expression of alternative metabolic pathways. Perinatal asphyxia has been associated with severe neurological and psychiatric sequelae with delayed clinical onset. No specific treatments have yet been established. In the clinical setting, after resuscitation of an infant with birth asphyxia, the emphasis is on supportive therapy. Several interventions have been proposed to attenuate secondary neuronal injuries elicited by asphyxia, including hypothermia. Although promising, the clinical efficacy of hypothermia has not been fully demonstrated. It is evident that new approaches are warranted. The purpose of this review is to discuss the concept of sentinel proteins as targets for neuroprotection. Several sentinel proteins have been described to protect the integrity of the genome (e.g. PARP-1; XRCC1; DNA ligase IIIα; DNA polymerase β, ERCC2, DNA-dependent protein kinases). They act by eliciting metabolic cascades leading to (i) activation of cell survival and neurotrophic pathways; (ii) early and delayed programmed cell death, and (iii) promotion of cell proliferation, differentiation, neuritogenesis and synaptogenesis. It is proposed that sentinel proteins can be used as markers for characterising long-term effects of perinatal asphyxia, and as targets for novel therapeutic development and innovative strategies for neonatal care

A review of hybrid integral transform solutions in fluid flow problems with heat or mass transfer and under Navier-Stokes equations formulation

The Generalized Integral Transform Technique (GITT) is reviewed as a hybrid numerical–analytical approach for fluid flow problems, with or without heat and mass transfer, here with emphasis on the literature related to flow problems formulated through the full Navier–Stokes equations. A brief overview of the integral transform methodology is first provided for a general nonlinear convection–diffusion problem. Then, different alternatives of eigenfunction expansion strategies are discussed in the integral transformation of problems for which the fluid flow model is either based on the primitive variables or the streamfunction-only formulations, as applied to both steady and transient states. Representative test cases are selected to illustrate the different eigenfunction expansion approaches, with convergence being analyzed for each situation. In addition, fully converged integral transform results are critically compared to previously reported simulations obtained from traditional purely discrete methods

Mortes perinatais e avaliação da assistência ao parto em maternidades do Sistema Único de Saúde em Belo Horizonte, Minas Gerais, Brasil, 1999 Perinatal deaths and childbirth healthcare evaluation in maternity hospitals of the Brazilian Unified Health System in Belo Horizonte, Minas Gerais, Brazil, 1999

Este trabalho analisa a associação entre a morte perinatal e o processo de assistência hospitalar ao parto, considerando-se que grande parte das mortes perinatais pode ser prevenível pela atenção qualificada de saúde e que a avaliação da qualidade da assistência perinatal ao parto é necessária para a redução da morbi-mortalidade perinatal. Realizou-se estudo caso-controle de base populacional dos óbitos perinatais (n = 118) e nascimentos (n = 492), ocorridos em maternidades do Sistema Único de Saúde (SUS) de Belo Horizonte, Minas Gerais, Brasil. Sexo masculino, prematuridade, doenças na gravidez, baixo peso ao nascer, doenças do recém-nascido, não realização de pré-natal, não utilização de partograma e menos de uma avaliação fetal por hora durante o trabalho de parto apresentaram associação estatisticamente significativa com o óbito perinatal. No modelo de regressão logística múltipla, não utilização do partograma durante o trabalho de parto e tipo de maternidade apresentaram-se como fatores de risco independentes para a morte perinatal. O estudo indica que é deficiente a qualidade da assistência hospitalar ao parto e que aspectos da estrutura dos serviços e do processo de assistência relacionam-se com a mortalidade perinatal por causas evitáveis.<br>This paper analyzes the association between perinatal mortality and factors related to hospital care during labor, considering that healthcare assessment is needed in order to reduce perinatal mortality. A population-based case-control study was conducted with 118 perinatal deaths (cases) and 492 births (controls) that took place in maternity hospitals of the Brazilian Unified Health System (SUS) in Belo Horizonte, Minas Gerais, Brazil. Male sex, prematurity, diseases during pregnancy, low birth weight, newborn diseases, lack of prenatal care, lack of partograph use during labor, and less than one fetus assessment per hour during labor were significantly associated with perinatal deaths. In the multiple regression analysis, lack of partograph use during labor and type of hospital were associated with perinatal deaths. These results indicate inadequate quality of care in maternity hospitals and show that health services structure and health care process are related to perinatal mortality due to preventable causes