Prognostic factors associated with survival in patients with hepatocellular carcinoma undergoing transarterial chemoembolisation: an Australian multicenter cohort study

Aim: Transarterial chemoembolisation (TACE) is recommended therapy for intermediate-stage hepatocellular carcinoma (HCC). However, the wide variations in outcom...     

The buried canadian roots of community psychology

In the Canadian psychological literature, the term community psychology was used in 1951 by William Line to refer to the mainstream of psychology in Canada from the early 1900s to about 1950. This psychology stemmed from two even earlier trends—the philosophy of social purpose and the mental health movement as inspired by C. W. Beers and established by C. M. Hincks. The culmination of this development was the definition of health that G. B. Chisholm used as the cornerstone for the World Health Organization; i.e., that health is not just the absence of disease or infirmity but a complete state of physical, mental, social and economic well-being.     

Neuropathology of vascular cognitive impairment and vascular dementia

Understanding of vascular substrates of cognitive decline in the elderly is evolving to include a major emphasis on the impact of small vessel disease (SVD). While existing concepts of multi-infarct dementia and strategic infarct dementia remain valid, they present difficulty in generalizing clinicopathological correlations from patient to patient. The range and significance of lesions that should be included as manifestations of SVD are unresolved, as is their impact on, and association with, neurodegenerative changes. This mini-review summarizes the authors' views on SVD substrates leading to cognitive decline and proposes priorities for pathological investigations of human cerebrovascular mechanisms leading to cognitive decline.     

ENIGMA-DTI: Translating reproducible white matter deficits into personalized vulnerability metrics in cross-diagnostic psychiatric research

The ENIGMA-DTI (diffusion tensor imaging) workgroup supports analyses that examine the effects of psychiatric, neurological, and developmental disorders on the white matter pathways of the human brain, as well as the effects of normal variation and its genetic associations. The seven ENIGMA disorder-oriented working groups used the ENIGMA-DTI workflow to derive patterns of deficits using coherent and coordinated analyses that model the disease effects across cohorts worldwide. This yielded the largest studies detailing patterns of white matter deficits in schizophrenia spectrum disorder (SSD), bipolar disorder (BD), major depressive disorder (MDD), obsessive–compulsive disorder (OCD), posttraumatic stress disorder (PTSD), traumatic brain injury (TBI), and 22q11 deletion syndrome. These deficit patterns are informative of the underlying neurobiology and reproducible in independent cohorts. We reviewed these findings, demonstrated their reproducibility in independent cohorts, and compared the deficit patterns across illnesses. We discussed translating ENIGMA-defined deficit patterns on the level of individual subjects using a metric called the regional vulnerability index (RVI), a correlation of an individual's brain metrics with the expected pattern for a disorder. We discussed the similarity in white matter deficit patterns among SSD, BD, MDD, and OCD and provided a rationale for using this index in cross-diagnostic neuropsychiatric research. We also discussed the difference in deficit patterns between idiopathic schizophrenia and 22q11 deletion syndrome, which is used as a developmental and genetic model of schizophrenia. Together, these findings highlight the importance of collaborative large-scale research to provide robust and reproducible effects that offer insights into individual vulnerability and cross-diagnosis features.     

Long-term proliferation and dopaminergic differentiation of human mesencephalic neural precursor cells

We report on generation of dopamine neurons from long-term cultures of human fetal mesencephalic precursor cells. These CNS precursor cells were successfully expanded in vitro using the mitogens epidermal growth factor (EGF) and fibroblast growth factor-2 (FGF-2). Incubation of these cultures in 3% atmospheric oxygen resulted in higher cellular yields than room air. Following incubation in differentiation media containing interleukin (IL)-1b (IL-1b), IL-11, leukemia inhibitory factor (LIF), and glial cell line-derived neurotrophic factor (GDNF), up to 1% of the precursor cells converted into cells immunoreactive for tyrosine hydroxylase (TH), a marker for dopamine neurons. The TH immunoreactive cells exhibited morphological and functional properties characteristic of dopamine neurons in culture. These precursor cells might serve as a useful source of human dopamine neurons for studying the development and degeneration of human dopamine neurons and may further serve as a continuous, on-demand source of cells for therapeutic transplantation in patients with Parkinson's disease.     

Chronic mild stress-induced anhedonia: A realistic animal model of depression

Chronic sequential administration of a variety of mild stressors causes a decrease in responsiveness to rewards in rats, which is reversed by chronic administration of antidepressant drugs. This paper reviews the validity of chronic mild stress-induced anhedonia as an animal model of depression, and the evidence that changes in hedonic responsiveness in this model are mediated by changes in the sensitivity of dopamine D2 receptors in the nucleus accumbens. The review opens with an analysis of the design features of animal models of depression, and ends with a brief account of other animal models of anhedonia.     

Chronic stress in the adult dentate gyrus reduces cell proliferation near the vasculature and VEGF and Flk-1 protein expression

Recent evidence has shown that cell proliferation in the adult hippocampal dentate gyrus occurs in tight clusters located near the vasculature. Also, changes in neurogenesis often appear parallel to changes in angiogenesis. Moreover, both these processes share similar modulating factors, like vascular endothelial growth factor (VEGF) and its receptor Flk-1. In an earlier study we found that chronic stress decreased new cell proliferation in the adult dentate gyrus. We here questioned whether these effects of chronic stress are mediated through the vasculature and whether they involve an angiogenic-signaling pathway. We therefore measured the surface area covered by the vasculature, the proportion of vascular-associated newborn cells, and analysed VEGF and Flk-1 protein expression in the hippocampus of a control, chronically stressed and recovery group of rats. Our results show that 32% of the proliferating cells in the rat hippocampus is vascular associated. Chronic stress affected this population of newborn cells to a significantly larger extent than the non-associated cells. Interestingly, after 3 weeks of recovery, the decreased proliferation not associated with the vasculature was more effectively restored than vascular-associated proportion of proliferating cells. VEGF protein was expressed in high densities in GFAP-positive astrocytes located in the hilus, with VEGF-positive end feet extending into and often contacting the granule cells. After chronic stress, both VEGF and Flk-1 protein levels were significantly decreased in the granular cell layer, and again recovered after 3 weeks. This demonstrates that changes in angiogenic factors are implicated in the decreased adult proliferation found after chronic stress.     

Alan Gregg and the rise of general hospital psychiatry

The authors review the forces that encouraged the entry of psychiatry into the general hospital in the 1930s. Those forces, which included concern about increasing health care costs, pressure to reform medical and psychiatric education, and the growth of dynamic psychiatry and psychosomatic medicine, are described. The activities of Alan Gregg, Director of the Medical Sciences Division of the Rockefeller Foundation during that era are highlighted. Gregg encouraged research in neurobiologic correlates of psychiatric illness and funded psychiatric units in eight general hospitals in the United States. The authors suggest that the development of general hospital psychiatry was strongly influenced by Alan Gregg and his support for a medical model of psychiatric illness. In addition to other forces that spurred the growth of general hospital psychiatry, the authors suggest that Gregg's influence significantly aided psychiatry's entrance into the general hospital.