Investigating the neurodevelopmental mediators of aggression in children with a history of child maltreatment:An exploratory field study.

Maltreatment of children is a chronic community problem that increases the risk of future aggression. Despite several decades of research highlighting this relationship, few studies have explored the potential neuropsychological deficits that are likely to mediate it. This exploratory study aimed to examine how child maltreatment may be associated with aggression via impairment in the developing prefrontal-limbic-autonomic pathways that are implicated in neuropsychological models of aggression. Furthermore, it aimed to investigate the relationship between child maltreatment and both reactive and proactive aggression subtypes. To investigate this non-invasively in an at-risk population, children with a documented protective care history (n = 20) and a community control group (n = 30), aged between 6 and 12 years, were compared on measures of cardiovascular functioning, affect regulation and cognitive functioning aligned with this neuropsychological model. Whilst no group differences were found on cardiovascular functioning (i.e., resting heart rate, heart rate reactivity, heart rate variability), the protective care group performed significantly worse on measures of affect regulation and cognitive functioning (i.e., global intelligence, executive functioning, smell identification and social cognition). The relationship between child maltreatment and aggression was mediated by executive dysfunction and affect dysregulation but not global IQ, social cognition or olfactory identification. The results suggest that interventions targeting aggression in maltreated children will benefit from clinical assessment and psychological strategies that address the executive dysfunction and affect dysregulation that has been associated with this clinical outcome.

Silent information regulator 1 mediates hippocampal plasticity through presenilin1.

Silent information regulator 1 (SIRT1) is a nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase directly implicated in protecting a wide range of organisms against internal and external metabolic insults. However, the identification of SIRT1-specific DNA targets that confer such protection have remained elusive. Using human cells, we show that SIRT1 binds to, and transcriptionally regulates, a gene locus encoding presenilin1 (PSEN1), a protein intrinsically involved in the function of the γ-secretase protein complex. We also demonstrate that rats fed with resveratrol exhibit a significant increase in sirt1 and psen1 expression. Finally, dietary consumption of resveratrol also leads to an enhanced proliferative state of neuronal stem cells in the rat hippocampus. Our findings reveal a strong link between resveratrol-dependent SIRT1 signaling and hippocampal plasticity in the mammalian brain.

Olfactory identification dysfunction, aggression and impulsivity in war veterans with post-traumatic stress disorder.

BACKGROUND: Due to neuropsychological conceptualizations of orbitoprefrontal cortex (OFC) dysfunction underpinning impulsive aggression and the incidence of such behaviour in post-traumatic stress disorder (PTSD), this study aimed to explore olfactory identification (OI) ability in war veterans with PTSD as a probe of putative OFC dysfunction; and to explore the utility of OI ability in predicting aggressive and impulsive behavior in this clinical population. METHOD: Participants comprised 31 out-patient male war veterans with PTSD (mean=58.23 years, s.d.=2.56) recruited from a Melbourne Veterans Psychiatry Unit, and 31 healthy age- and gender-matched controls (mean=56.84 years, s.d.=7.24). All participants were assessed on clinical measures of PTSD, depression, anxiety, and alcohol misuse; olfactory identification; neurocognitive measures of dorsolateral prefrontal, lateral prefrontal and mesial temporal functioning; and self-report measures of aggression and impulsivity. RESULTS: War veterans with PTSD exhibited significant OI deficits (OIDs) compared to controls, despite uncompromised performance on cognitive measures. OIDs remained after covaring for IQ, anxiety, depression and alcohol misuse, and were significant predictors of aggression and impulsivity. CONCLUSIONS: This research contributes to emerging evidence of orbitoprefrontal dysfunction in the pathophysiology underlying PTSD. This is the first study to report OIDs as a predictor of aggression and impulsivity in this clinical population. It prompts further exploration of the potential diagnostic utility of OIDs in the assessment of PTSD. Such measures may help delineate the clinical complexity of PTSD, and support more targeted interventions for individuals with a greater susceptibility to aggressive and impulsive behaviors.

Efficient in vivo gene transfer by PCR amplified fragment with reduced inflammatory activity.

There are many problems associated with plasmid DNA that may limit its use in systemic gene transfer. These problems could be solved by the use of synthetic genes. As a model to test the feasibility of using synthetic genes for gene therapy, we PCR-amplified a fragment containing the CMV promoter, the luciferase gene and a polyadenylation signal. The in vivo expression efficiency of the PCR fragment was determined by using two different methods, a hydrodynamics-based gene transfer of naked DNA to the liver and LPD (a lipid-based vector) mediated gene transfer to the lung. Our results show that linear fragments are at least as active as plasmid DNA following systemic delivery by LPD. However, PCR fragments are much less inflammatory than plasmid DNA as shown by a three-fold reduction in serum levels of both TNF-alpha and IL-12. Our results also showed that PCR fragments are highly efficient in liver gene transfer following systemic administration in a large volume. Thus, these results support the idea of using synthetic genes for gene therapy. Since gene sequence can be easily obtained as a PCR fragment, our results also imply that it may provide a useful and convenient method for determining the physiologic function of a putative gene in intact animals.

A technique to retrieve stents dislodged in the coronary artery followed by fixation in the iliac artery by means of balloon angioplasty and peripheral stent deployment.

An unwelcome complication of the increasingly applied technique of coronary stenting is stent dislodgment, which may cause arterial occlusion or distal embolization, both with potentially adverse sequel. Stent dislodgment tends to occur when negotiating a tortuous artery with a balloon-mounted stent, especially if the artery is irregularly calcified or when applying a rigid stent. We have successfully applied in several patients at our laboratory a technique to retrieve a dislodged stent from the coronary artery, tow it to the iliac artery, and then deploy it locally by a peripheral balloon when retrieval through the vascular sheath seems impossible. Finally, the retrieved stent is secured by local anchoring with a peripheral stent. This technique was found to be useful and may prevent further complications and more costly interventions and hence result in a more benign clinical course. Cathet. Cardiovasc. Intervent. 49:77-81, 2000.