Maternal obesity and long-term neuropsychiatric morbidity of the offspring

Archives of Gynecology and Obstetrics - To evaluate the long-term pediatric neuropsychiatric morbidity of children born to obese patients. A population-based cohort analysis was performed comparing...     

Over-expression of Aurora-A targets cytoplasmic polyadenylation element binding protein and promotes mRNA polyadenylation of Cdk1 and cyclin B1

Aurora-A is a centrosomal serine-threonine kinase that regulates mitosis. Over-expression of Aurora-A has been found in a wide range of tumors and has been implicated in oncogenic transformation. However, how Aurora-A over-expression contributes to promotion of carcinogenesis remains elusive. Immunohistochemical analysis of breast tumors revealed that over-expressed Aurora-A is not restricted to the centrosomes but is also found in the cytoplasm. This over-expressed Aurora-A appeared to be phosphorylated on Thr288, which is known to be required for its enzymatic activation. In analogy to Aurora-A's role in oocyte maturation and the early embryonic cell cycle, here we investigated whether ectopically over-expressed Aurora-A can similarly stimulate polyadenylation of mRNA in human somatic cultured cells by interacting with a human ortholog of cytoplasmic polyadenylation element binding protein, h-CPEB. In vitro experiments revealed that Aurora-A binds directly to, and phosphorylates, h-CPEB. We found that polyadenylation of mRNA tails of cyclin B1 and Cdk1 was synergistically stimulated when Aurora-A and h-CPEB were over-expressed, and they were further promoted in the presence of an Aurora-A activator Ajuba. Our results suggest a function of ectopically over-expressed Aurora-A that might be relevant for carcinogenesis.     

Using Time-delay to Improve Social Play Skills with Peers for Children with Autism

Interventions that teach social communication and play skills are crucial for the development of children with autism. The time delay procedure is effective in teaching language acquisition, social use of language, discrete behaviors, and chained activities to individuals with autism and developmental delays. In this study, three boys with autism, attending a non-public school, were taught play activities that combined a play sequence with requesting peer assistance, using a graduated time delay procedure. A multiple-baseline across subjects design demonstrated the success of this procedure to teach multiple-step social play sequences. Results indicated an additional gain of an increase in pretend play by one of the participants. Two also demonstrated a generalization of the skills learned through the time delay procedure.     

Intraneuronal amyloid β oligomers cause cell death via endoplasmic reticulum stress, endosomal/lysosomal leakage, and mitochondrial dysfunction in vivo

Intraneuronal accumulation of amyloid β (Aβ) is an early pathological change in Alzheimer's disease. Previously, we showed that the E693Δ mutation (referred to as the “Osaka” mutation) of amyloid precursor protein (APP) caused intracellular accumulation of Aβ oligomers and apoptosis in transfected COS‐7 cells. We also showed that transgenic mice expressing APP_E693Δ (APP_OSK) displayed both an age‐dependent accumulation of intraneuronal Aβ oligomers from 8 months of age and apparent neuronal loss in the hippocampus at 24 months of age. These findings indicate that intraneuronal Aβ oligomers cause cell death, but the mechanism of this process remains unclear. Accordingly, here we investigated the subcellular localization and toxicity of intraneuronal Aβ oligomers in APP_OSK‐transgenic mice. We found Aβ oligomer accumulation in the endoplasmic reticulum (ER), endosomes/lysosomes, and mitochondria in hippocampal neurons of 22‐month‐old mice. We also detected up‐regulation of Grp78 and HRD1 (an E3 ubiquitin ligase), leakage of cathepsin D from endosomes/lysosomes into cytoplasm, cytochrome c release from mitochondria, and activation of caspase‐3 in the hippocampi of 18‐month‐old mice. Collectively, our findings suggest that intraneuronal Aβ oligomers cause cell death by inducing ER stress, endosomal/lysosomal leakage, and mitochondrial dysfunction in vivo. © 2011 Wiley‐Liss, Inc.     

Simulation-based training for trauma resuscitation among ACS TQIP-Pediatric centers: Understanding prevalence of use,associated center characteristics,training factors,and implementation barriers

Background

Simulation-based training (SBT) for pediatric trauma resuscitation can improve team performance. The purpose of this study was to describe the nationwide trend in SBT use and barriers to SBT implementation.

Occurrence of ocular disease in traumatic brain injury in a selected sample: a retrospective analysis

Primary objective: To determine retrospectively the relative risk of ocular disease in a selected, visually-symptomatic sample of clinic patients having traumatic brain injury (TBI; n = 160) vs. cerebrovascular accident (CVA; n = 60), with all initially presenting at the clinic with symptoms and/or signs of vision dysfunction.

Methods and procedures: To review retrospectively 220 medical records of individuals with TBI (n = 160) vs. CVA (n = 60), as determined by a computer-based query spanning the years 2000-2003, to ascertain the frequency of occurrence of ocular disease in the two major sub-groups of acquired brain injury.

Main outcomes and results: Conditions with high relative risk unique to TBI included corneal abrasion, blepharitis, chalazion/hordeolum, dry eye, traumatic cataract, vitreal prolapse and optic atrophy. This is distinct from those ophthalmic conditions unique to CVA, which included sub-conjunctival haemorrhage and ptosis.

Conclusion: These new findings should alert clinicians to the potential increased frequency of occurrence of specific ocular diseases in a selected, visually-symptomatic population with TBI and their associated rehabilitative and quality-of-life implications.     

Resolution of epileptic encephalopathy following treatment with transdermal nicotine

We report resolution of an epileptic encephalopathy by administration of transdermal nicotine patches in an adolescent with severe nonlesional refractory frontal lobe epilepsy. The 18.5‐year‐old female patient had refractory epilepsy from the age of 11. Recurrent electroencephalography (EEG) recordings showed mostly generalized activity, albeit with right frontal predominance. Almost all antiepileptic medications failed to provide benefit. She developed an encephalopathic state with cognitive decline. The nonlesional frontal lobe epilepsy and a family history of a cousin with nocturnal epilepsy with frontal origin suggested genetic etiology. Transdermal nicotine patches brought complete resolution of the seizures, normalization of the EEG, and a significant improvement in her thinking process and speech organization. Sequencing of the CHRNB2 and CHRNA4 genes did not detect a mutation. Transdermal nicotine patches should be considered in severe pharmacoresistant frontal lobe epilepsy.     

General practitioners’ experiences and perceptions of mild moderate depression management and factors influencing effective service delivery in rural Australian communities: a qualitative study

Background

Rural communities in Australia face significant disadvantages relating to geographical isolation and limited access to mental health services. Documenting general practitioners’ (GP) experiences and perception of mental health services in rural Australia may be useful to gain insight into rural GP management of mild to moderate depression.

Aims

To explore GPs’ experience and views on which factors influence access to mental health services for mild to moderate depression.

Method

This qualitative study was conducted in 2014 in the Northern Rivers, NSW, Australia. Data were obtained from semi-structured in-depth face-to-face interviews with ten GPs, and analyses were performed using a general inductive method of thematic analysis.

Results

Most GPs believed that the current services for managing mild-moderate depression were adequate, however they also identified the need for better access and more services that were free for patients. GPs had a positive perception of management of depression in a rural setting, identifying advantages including better doctor-patient relationships, continuity of care and the proximity of services. However, GPs also identified several barriers to access to mental health services in a rural setting, including long waiting-times, inadequate patient rapport with referred professionals, cost of treatment, transportation, geographical location, stigma, and lack of education about available mental health services. As a result, GPs frequently self-managed patients in addition to referring them to other community mental health service providers where possible.

Conclusion

Overall, GPs appeared relatively satisfied with the resources available in their communities but also identified numerous barriers to access and room for improvement. Rural GPs often self-managed patients in addition to referring patients to other mental health services providers. This should be taken into account when designing mental health policies, developing new services or re-designing current services in rural communities.

     

A neural mediator of human anxiety sensitivity

Advances in the neuroscientific understanding of bodily autonomic awareness, or interoception, have led to the hypothesis that human trait anxiety sensitivity (AS)—the fear of bodily autonomic arousal—is primarily mediated by the anterior insular cortex. Despite broad appeal, few experimental studies have comprehensively addressed this hypothesis. We recruited 55 individuals exhibiting a range of AS and assessed them with functional magnetic resonance imaging (fMRI) during aversive fear conditioning. For each participant, three primary measures of interest were derived: a trait Anxiety Sensitivity Index score; an in‐scanner rating of elevated bodily anxiety sensations during fear conditioning; and a corresponding estimate of whole‐brain functional activation to the conditioned versus nonconditioned stimuli. Using a voxel‐wise mediation analysis framework, we formally tested for ‘neural mediators’ of the predicted association between trait AS score and in‐scanner anxiety sensations during fear conditioning. Contrary to the anterior insular hypothesis, no evidence of significant mediation was observed for this brain region, which was instead linked to perceived anxiety sensations independently from AS. Evidence for significant mediation was obtained for the dorsal anterior cingulate cortex—a finding that we argue is more consistent with the hypothesized role of human cingulofrontal cortex in conscious threat appraisal processes, including threat‐overestimation. This study offers an important neurobiological validation of the AS construct and identifies a specific neural substrate that may underlie high AS clinical phenotypes, including but not limited to panic disorder. Hum Brain Mapp 36:3950–3958, 2015. © 2015 Wiley Periodicals, Inc.     

The effect of Lorenzo's oil on oxidative stress in X-linked adrenoleukodystrophy

X-linked adrenoleukodystrophy (X-ALD) is a peroxisomal disorder biochemically characterized by the accumulation of very long chain fatty acids (VLCFA), particularly hexacosanoic acid (C(26:0)) and tetracosanoic acid (C(24:0)), in tissues and biological fluids. Although patients affected by this disorder predominantly present central and peripheral demyelination as well as adrenal insufficiency, the mechanisms underlying the brain damage in X-ALD are poorly known. The current treatment of X-ALD with glyceroltrioleate (C(18:1))/glyceroltrierucate (C(22:1)) (Lorenzo's oil, LO) combined with a VLCFA-poor diet normalizes VLCFA concentrations, but the neurological symptoms persist or even progress in symptomatic patients. Considering that free radical generation is involved in various neurodegenerative disorders and that in a previous study we showed evidence that oxidative stress is probably involved in the pathophysiology of X-ALD symptomatic patients, in the present study we evaluated various oxidative stress parameters, namely thiobarbituric acid reactive species (TBA-RS) and total antioxidant reactivity (TAR) in plasma, as well as the activities of the antioxidant enzymes catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) in erythrocytes from symptomatic and asymptomatic X-ALD patients and verified whether LO treatment and a VLCFA restricted diet could change these parameters. We observed a significant increase of plasma TBA-RS in symptomatic and asymptomatic X-ALD patients, reflecting induction of lipid peroxidation even before the disease was manifested. In addition, LO treatment did not alter this profile. Furthermore, plasma TAR measurement of X-ALD patients was not different from that of controls. Similarly, the antioxidant enzyme activities CAT, SOD and GPx were not altered in erythrocyte from X-ALD patients as compared to controls. We also examined the in vitro effects of hexacosanoic acid (C(26:0)) and tetracosanoic acid (C(24:0)) alone or combined with oleic (C(18:1))/erucic (C(22:1)) acids on various oxidative stress parameters in cerebral cortex of young rats, namely chemiluminescence, TBA-RS, TAR, CAT, SOD and GPx in order to investigate whether those fatty acids were able to induce oxidative stress. We found that there was a significant increase of TBARS and of chemiluminescence in rat cerebral cortex exposed to C(26:0)/C(24:0), and that the addition of C(18:1)and C(22:1) to the assays did not prevent this effect. Furthermore, TAR measurement was not altered by C(26:0) and C(24:0) acids in rat cerebral cortex. Taken together, our results indicate that lipid peroxidation occurs in X-ALD and that LO treatment does not attenuate or prevent free radical generation in these patients. Therefore, it may be presumed that antioxidants should be considered as an adjuvant therapy for X-ALD patients.