Circadian profiles in young people during the early stages of affective disorder

Although disturbances of the circadian system are strongly linked to affective disorders, no known studies have examined melatonin profiles in young people in early stages of illness. In this study, 44 patients with an affective disorder underwent clinical and neuropsychological assessments. They were then rated by a psychiatrist according to a clinical staging model and were categorized as having an ‘attenuated syndrome' or an ‘established disorder'. During the evening, salivary melatonin was sampled under dim light conditions over an 8-h interval and for each patient, the time of melatonin onset, total area under the curve and phase angle (difference between time of melatonin onset and time of habitual sleep onset) were computed. Results showed that there was no difference in the timing of melatonin onset across illness stages. However, area under the curve analyses showed that those patients with ‘established disorders' had markedly reduced levels of melatonin secretion, and shorter phase angles, relative to those with ‘attenuated syndromes'. These lower levels, in turn, were related to lower subjective sleepiness, and poorer performance on neuropsychological tests of verbal memory. Overall, these results suggest that for patients with established illness, dysfunction of the circadian system relates clearly to functional features and markers of underlying neurobiological change. Although the interpretation of these results would be greatly enhanced by control data, this work has important implications for the early delivery of chronobiological interventions in young people with affective disorders

Brain Responses to Violet, Blue, and Green Monochromatic Light Exposures in Humans: Prominent Role of Blue Light and the Brainstem

BACKGROUND: Relatively long duration retinal light exposure elicits nonvisual responses in humans, including modulation of alertness and cognition. These responses are thought to be mediated in part by melanopsin-expressing retinal ganglion cells which are more sensitive to blue light than violet or green light. The contribution of the melanopsin system and the brain mechanisms involved in the establishment of such responses to light remain to be established. METHODOLOGY/PRINCIPAL FINDINGS: We exposed 15 participants to short duration (50 s) monochromatic violet (430 nm), blue (473 nm), and green (527 nm) light exposures of equal photon flux (10(13)ph/cm(2)/s) while they were performing a working memory task in fMRI. At light onset, blue light, as compared to green light, increased activity in the left hippocampus, left thalamus, and right amygdala. During the task, blue light, as compared to violet light, increased activity in the left middle frontal gyrus, left thalamus and a bilateral area of the brainstem consistent with activation of the locus coeruleus. CONCLUSION/SIGNIFICANCE: These results support a prominent contribution of melanopsin-expressing retinal ganglion cells to brain responses to light within the very first seconds of an exposure. The results also demonstrate the implication of the brainstem in mediating these responses in humans and speak for a broad involvement of light in the regulation of brain function

Relationship between Exercise Capacity and Brain Size in Mammals

A great deal of experimental research supports strong associations between exercise, cognition, neurogenesis and neuroprotection in mammals. Much of this work has focused on neurogenesis in individual subjects in a limited number of species. However, no study to date has examined the relationship between exercise and neurobiology across a wide range of mammalian taxa. It is possible that exercise and neurobiology are related across evolutionary time. To test this hypothesis, this study examines the association between exercise and brain size across a wide range of mammals.Controlling for associations with body size, we examined the correlation between brain size and a proxy for exercise frequency and capacity, maximum metabolic rate (MMR; ml O(2) min(-1)). We collected brain sizes and MMRs from the literature and calculated residuals from the least-squares regression line describing the relationship between body mass and each variable of interest. We then analyzed the correlation between residual brain size and residual MMR both before and after controlling for phylogeny using phylogenetic independent contrasts. We found a significant positive correlation between maximum metabolic rate and brain size across a wide range of taxa.These results suggest a novel hypothesis that links brain size to the evolution of locomotor behaviors in a wide variety of mammalian species. In the end, we suggest that some portion of brain size in nonhuman mammals may have evolved in conjunction with increases in exercise capacity rather than solely in response to selection related to cognitive abilities

Hepatic stellate cells:central modulators of hepatic carcinogenesis

Hepatocellular carcinoma (HCC) represents the second most common cause of cancer-related death worldwide, and is increasing in incidence. Currently, our therapeutic repertoire for the treatment of HCC is severely limited, and therefore effective new therapies are urgently required. Recently, there has been increasing interest focusing on the cellular and molecular interactions between cancer cells and their microenvironment. HCC represents a unique opportunity to study the relationship between a diseased stroma and promotion of carcinogenesis, as 90 % of HCCs arise in a cirrhotic liver. Hepatic stellate cells (HSC) are the major source of extracellular proteins during fibrogenesis, and may directly, or via secreted products, contribute to tumour initiation and progression. In this review we explore the complex cellular and molecular interplay between HSC biology and hepatocarcinogenesis. We focus on the molecular mechanisms by which HSC modulate HCC growth, immune cell evasion and angiogenesis. This is followed by a discussion of recent progress in the field in understanding the mechanistic crosstalk between HSC and HCC, and the pathways that are potentially amenable to therapeutic intervention. Furthermore, we summarise the exciting recent developments in strategies to target HSC specifically, and novel techniques to deliver pharmaceutical agents directly to HSC, potentially allowing tailored, cell-specific therapy for HCC

Community-based infant hearing screening for early detection of permanent hearing loss in Lagos, Nigeria: a cross-sectional study

OBJECTIVE: To determine the feasibility and effectiveness of a community-based universal infant hearing screening programme for detecting permanent congenital and early-onset hearing loss (PCEHL) in Lagos, Nigeria. METHODS: This is a cross-sectional study in which all infants aged 3 months or under attending four bacille Calmette-Guérin (BCG) immunization clinics accounting for over 75% of the BCG coverage in the study location were screened by community health workers between July 2005 and April 2006. Screening followed a two-stage protocol involving transient evoked otoacoustic emissions and automated auditory brainstem responses. The main outcome measures were screening coverage, referral rates, return rates for second-stage screening and evaluation, yield and age at PCEHL diagnosis. FINDINGS: In total, 2003 (88%) of 2277 eligible infants attending the four BCG clinics were successfully screened between July 2005 and April 2006 at a mean age of 17.7 days, with no parent declining screening. The majority (55.2%) were born outside a hospital and, of such infants, 77% were born in traditional herbal maternity homes. The overall referral rate for diagnostic evaluation was 4.1%. Only 61% (50/82) of those referred returned for evaluation, and 45 of them were confirmed with PCEHL. Additionally, 11 infants who had previously passed the first screening stage were also found to have PCEHL, resulting in a yield of 28 per 1000 (56/2003). The mean age at diagnosis was 51 days. The sensitivity, specificity and positive predictive value of the first screening stage were 80.4%, 99.7% and 90.0%, respectively. The positive likelihood ratio was 268, while the negative likelihood ratio was 0.2. CONCLUSION: Routine hearing screening of infants attending BCG immunization clinics by community health workers was feasible and effective for the early detection of PCEHL in Lagos, Nigeria. However, an efficient tracking and follow-up system is needed to improve return rates for second-stage screening and diagnostic evaluation