A longitudinal study of child mental health and problem behaviours at 14 years of age following unplanned pregnancy

A substantial minority of children are born as a consequence of an unplanned pregnancy. Yet little is known about the impact of unplanned/unwanted pregnancy (UP) on long-term health outcomes for children. This study aimed to examine the association between UP and child mental health and behavioural problems at 14 years, and whether this association is confounded or mediated by other variables. Data were from a pre-birth prospective study that included 4765 mothers and their children (48.4% female and 51.6% male) followed up from pregnancy to 14 years of the child's age in Brisbane, Australia. Child anxiety/depression, aggression, delinquency, attention problems, withdrawal problems, somatic complaints, social problems, thought problems, internalizing, externalizing and total problems were measured using the Achenbach's Youth Self Report at 14 years. Child smoking and alcohol consumption were self-reported at 14 years. UP was prospectively assessed at the first antenatal visit of pregnancy. UP as reported by mothers at first antenatal visit predicted elevated levels of problem behaviours and increased substance use in children at 14 years. The impact of UP on child mental health and problem behaviours is partly due to the confounding effect of other variables, such as maternal socio-demographic status, mental health and substance use during pregnancy. Further research is needed to investigate the mechanism of association between UP and child aggression and early alcohol consumption at 14 years.     

Erythropoietin in neonatal brain protection: the past, the present and the future

Over the last decade, neuroprotective effects of erythropoietin (Epo) and its underlying mechanisms in terms of signal transduction pathways have been defined and there is a growing interest in the potential therapeutic use of Epo for neuroprotection. Several mechanisms by which Epo provides neuroprotection are recognized. In this review, we focused on the neuroprotective mechanisms of Epo and provide a short overview on both experimental and clinical studies, testing Epo as a neuroprotective agent in the neonatal brain injury, and the safety concerns with the clinical use of Epo treatment in neonates.     

The prevalence of neurological disorders in Saudi children: a community-based study

There are limited data on the pattern and prevalence of pediatric chronic neurologic conditions in the region. Therefore, the objective of this study was to establish the prevalence of these disorders in the Kingdom of Saudi Arabia. A multistage probability sampling design was used to select a random sample of Saudi households representative of the Saudi population. A total of 45 682 Saudi children were screened. Of these children, 313 had a chronic major neurologic disorder indicating a prevalence of 68.5 per 10 000 children, which was the highest among all chronic diseases in children. Mental retardation and cerebral palsy were the most common neurologic disorders among Saudi children with a prevalence rate of 26.3/10 000 and 23.4/10 000, respectively. The finding that major neurologic disorders are the most common pediatric chronic disorders in the Kingdom of Saudi Arabia indicates that priority should be given to research and education as well as health care planning.     

Proteomic CNS Profile of Delayed Cognitive Impairment in Mice Exposed to Gulf War Agents

Gulf War Illness (GWI) is a chronic multisymptom condition with a central nervous system (CNS) component, for which there is no treatment available. It is now believed that the combined exposure to Gulf War (GW) agents, including pyridostigmine bromide (PB) and pesticides, such as permethrin (PER), was a key contributor to the etiology of GWI. In this study, a proteomic approach was used to characterize the biomolecular disturbances that accompany neurobehavioral and neuropathological changes associated with combined exposure to PB and PER. Mice acutely exposed to PB and PER over 10 days showed an increase in anxiety-like behavior, psychomotor problems and delayed cognitive impairment compared to control mice that received vehicle only. Proteomic analysis showed changes in proteins associated with lipid metabolism and molecular transport in the brains of GW agent-exposed mice compared to controls. Proteins associated with the endocrine and immune systems were also altered, and dysfunction of these systems is a prominent feature of GWI. The presence of astrogliosis in the GW agent-exposed mice compared to control mice further suggests an immune system imbalance, as is observed in GWI. These studies provide a broad perspective of the molecular disturbances driving the late pathology of this complex illness. Evaluation of the potential role of these biological functions in GWI will be useful in identifying molecular pathways that can be targeted for the development of novel therapeutics against GWI.     

Duration of untreated psychosis,ethnicity, educational level,and gender in a multiethnic South‐East Asian country: report from Malaysia schizophrenia registry

Introduction: Duration of untreated psychosis (DUP) determines the outcome of schizophrenia. Previously, there was no information about the DUP among patients in Malaysia with schizophrenia. The aim of the present study was to investigate the association between DUP and patients' demographic, social cultural background and clinical features. Method: This is a cross‐sectional study on patients who presented with first episode schizophrenia. Data from 74 primary care centers and hospitals between 1 January 2003 and 31 December 2007 were included in the analysis. All patients with first‐episode schizophrenia were enrolled in the study. Results: The mean DUP was 37.6 months. The indigenous community appeared to have the shortest DUP compared to the Malay, Chinese and Indian communities. Female, people with lower educational level, and comorbidity with medical illness during contact had longer DUP. Discussion: DUP in this multiethnicity country was found to be significantly short among the indigenous people, which may sugest that traditional values and strong family and community ties shorten the DUP. Educational level may need to be further investigated, because as upgrading the general educational level could lead to shorter DUP among the patients as well.     

Influence of apolipoprotein E ɛ4 on rates of cognitive and functional decline in mild cognitive impairment

BackgroundApolipoprotein E ?4 (APOE ?4) allele carrier status has been well established as a risk factor for developing Alzheimer's disease. However, the specific influence of APOE ?4 allele status on cognitive and functional rates of decline in mild cognitive impairment (MCI) is poorly understood. We examine the prospective association of APOE ?4 allele status on measures of cognitive and functional decline in subjects with amnestic MCI (aMCI).MethodsA total of 516 aMCI participants aged 55–90 years who received placebo or vitamin E from the Alzheimer's Disease Cooperative Study's MCI treatment trial were evaluated. During the 36-month study period, neurocognitive and functional measures were collected. These measures were assessed over time for change and association with APOE ?4 status. Generalized Estimating Equations were performed to model each outcome measure over the study period.ResultsAPOE ?4 status had a significant impact on cognitive and functional decline on multiple measures; those who were APOE ?4 positive had significantly more rapid decline in performance on all cognitive and functional measures except Number Cancellation and Maze tracing (P < .05). The greatest decline was seen in global measures of cognition and function including the Clinical Diagnostic Rating scale, followed by the Mini-Mental State Examination, Global Deterioration scale, and the Alzheimer's Disease Assessment Scale-Cognitive Subscale.ConclusionsThese findings demonstrate that APOE ?4 genotype is predictive of increased general rates of decline with global measures of cognition and function most affected. With accelerated declines in common clinical trial primary efficacy measures, APOE ?4 status needs to be accounted for in treatment trials of MCI.     

Engineering an artificial alveolar-capillary membrane: a novel continuously perfused model within microchannels

Introduction

Pulmonary hypoplasia is a condition of the newborn that is characterized by underdeveloped lungs and poor outcome. One strategy in the treatment of patients with hypoplasia is to augment underdeveloped lungs using biocompatible artificial lung tissue. However, one central challenge in current pulmonary tissue engineering efforts remains the development of a stable bio-mimetic alveolar-capillary membrane. Accordingly, we have built a series of bio-mimetic microfluidic devices that specifically model the alveolar-capillary membrane. Current designs include a single-layer microchip that exposes alveolar and endothelial cell types to controlled fluidic stimuli. A more advanced multi-layered device allows for alveolar cells to be cultured at an air interface while allowing constant media nourishment and waste removal, thus better mimicking the physiologic milieu of the alveolar-capillary interface. Both devices possess the benefit of parallel testing.

Material and methods

Microdevices were fabricated using soft lithography in a biocompatible transparent polymeric material, polydimethyl siloxane, sealed covalently to glass. The multistage microdevice also integrated a suspended polyethylene terephthalate membrane connected via microfluidic channels to constant media and air access. Pulmonary endothelial (HMEC-1) and alveolar epithelial (A549) cell lines, along with fetal pulmonary cells (FPC) harvested from Swiss Webster mice at day 18 gestational age, were studied under multiple hydrodynamic shear conditions and liquid-to-cell ratio regimes. Cultures were examined for cell viability, function and proliferation to confluent monolayers. A549 cells cultured at an air-interface in a microdevice was also tested for their ability to maintain cell phenotype and function.

Results

The single-layer differential flow microdevice allowed for a systematic determination of the optimal growth conditions of various lung-specific cell types in a microfluidic environment. Our device showed a greater surfactant based decrease in surface tension of the alveolar hypophase in A549 cultures exposed to air as compared to submerged cultures.

Conclusions

We have successfully developed biomimetic microfluidic devices that specifically allow stable alveolar cell growth at the air-liquid interface. This work serves prerequisite towards an implantable artificial alveolar membrane.