Circadian-Related Sleep Disorders and Sleep Medication Use in the New Zealand Blind Population: An Observational Prevalence Survey

STUDY OBJECTIVES: To determine the prevalence of self-reported circadian-related sleep disorders, sleep medication and melatonin use in the New Zealand blind population. DESIGN: A telephone survey incorporating 62 questions on sleep habits and medication together with validated questionnaires on sleep quality, chronotype and seasonality. PARTICIPANTS: PARTICIPANTS WERE GROUPED INTO: (i) 157 with reduced conscious perception of light (RLP); (ii) 156 visually impaired with no reduction in light perception (LP) matched for age, sex and socioeconomic status, and (iii) 156 matched fully-sighted controls (FS). SLEEP HABITS AND DISTURBANCES: The incidence of sleep disorders, daytime somnolence, insomnia and sleep timing problems was significantly higher in RLP and LP compared to the FS controls (p<0.001). The RLP group had the highest incidence (55%) of sleep timing problems, and 26% showed drifting sleep patterns (vs. 4% FS). Odds ratios for unconventional sleep timing were 2.41 (RLP) and 1.63 (LP) compared to FS controls. For drifting sleep patterns, they were 7.3 (RLP) and 6.0 (LP). MEDICATION USE: Zopiclone was the most frequently prescribed sleep medication. Melatonin was used by only 4% in the RLP group and 2% in the LP group. CONCLUSIONS: Extrapolations from the current study suggest that 3,000 blind and visually impaired New Zealanders may suffer from circadian-related sleep problems, and that of these, fewer than 15% have been prescribed melatonin. This may represent a therapeutic gap in the treatment of circadian-related sleep disorders in New Zealand, findings that may generalize to other countries

Analysis Method and Experimental Conditions Affect Computed Circadian Phase from Melatonin Data

Accurate determination of circadian phase is necessary for research and clinical purposes because of the influence of the master circadian pacemaker on multiple physiologic functions. Melatonin is presently the most accurate marker of the activity of the human circadian pacemaker. Current methods of analyzing the plasma melatonin rhythm can be grouped into three categories: curve-fitting, threshold-based and physiologically-based linear differential equations. To determine which method provides the most accurate assessment of circadian phase, we compared the ability to fit the data and the variability of phase estimates for seventeen different markers of melatonin phase derived from these methodological categories. We used data from three experimental conditions under which circadian rhythms - and therefore calculated melatonin phase - were expected to remain constant or progress uniformly. Melatonin profiles from older subjects and subjects with lower melatonin amplitude were less likely to be fit by all analysis methods. When circadian drift over multiple study days was algebraically removed, there were no significant differences between analysis methods of melatonin onsets (P = 0.57), but there were significant differences between those of melatonin offsets (P<0.0001). For a subset of phase assessment methods, we also examined the effects of data loss on variability of phase estimates by systematically removing data in 2-hour segments. Data loss near onset of melatonin secretion differentially affected phase estimates from the methods, with some methods incorrectly assigning phases too early while other methods assigning phases too late; missing data at other times did not affect analyses of the melatonin profile. We conclude that melatonin data set characteristics, including amplitude and completeness of data collection, differentially affect the results depending on the melatonin analysis method used

Robot Wars: US Empire and geopolitics in the robotic age

How will the robot age transform warfare? What geopolitical futures are being imagined by the US military? This article constructs a robotic futurology to examine these crucial questions. Its central concern is how robots – driven by leaps in artificial intelligence and swarming – are rewiring the spaces and logics of US empire, warfare, and geopolitics. The article begins by building a more-than-human geopolitics to de-center the role of humans in conflict and foreground a worldly understanding of robots. The article then analyzes the idea of US empire, before speculating upon how and why robots are materializing new forms of proxy war. A three-part examination of the shifting spaces of US empire then follows: (1) Swarm Wars explores the implications of miniaturized drone swarming; (2) Roboworld investigates how robots are changing US military basing strategy and producing new topological spaces of violence; and (3) The Autogenic Battle-Site reveals how autonomous robots will produce emergent, technologically event-ful sites of security and violence – revolutionizing the battlespace. The conclusion reflects on the rise of a robotic US empire and its consequences for democracy

Validation of 2006 WHO Prediction Scores for True HIV Infection in Children Less than 18 Months with a Positive Serological HIV Test

All infants born to HIV-positive mothers have maternal HIV antibodies, sometimes persistent for 18 months. When Polymerase Chain Reaction (PCR) is not available, August 2006 World Health Organization (WHO) recommendations suggest that clinical criteria may be used for starting antiretroviral treatment (ART) in HIV seropositive children <18 months. Predictors are at least two out of sepsis, severe pneumonia and thrush, or any stage 4 defining clinical finding according to the WHO staging system.From January 2005 to October 2006, we conducted a prospective study on 236 hospitalized children <18 months old with a positive HIV serological test at the national reference hospital in Kigali. The following data were collected: PCR, clinical signs and CD4 cell count. Current proposed clinical criteria were present in 148 of 236 children (62.7%) and in 95 of 124 infected children, resulting in 76.6% sensitivity and 52.7% specificity. For 87 children (59.0%), clinical diagnosis was made based on severe unexplained malnutrition (stage 4 clinical WHO classification), of whom only 44 (50.5%) were PCR positive. Low CD4 count had a sensitivity of 55.6% and a specificity of 78.5%.As PCR is not yet widely available, clinical diagnosis is often necessary, but these criteria have poor specificity and therefore have limited use for HIV diagnosis. Unexplained malnutrition is not clearly enough defined in WHO recommendations. Extra pulmonary tuberculosis (TB), almost impossible to prove in young children, may often be the cause of malnutrition, especially in HIV-affected families more often exposed to TB. Food supplementation and TB treatment should be initiated before starting ART in children who are staged based only on severe malnutrition

Alterations of brain and cerebellar proteomes linked to Aβ and tau pathology in a female triple-transgenic murine model of Alzheimer's disease

The triple-transgenic Alzheimer (3 × Tg-AD) mouse expresses mutant PS1M146V, APPswe, and tauP301L transgenes and progressively develops plaques and neurofibrillary tangles with a temporal- and region-specific profile that resembles the neuropathological progression of Alzheimer's disease (AD). In this study, we used proteomic approaches such as two-dimensional gel electrophoresis and mass spectrometry to investigate the alterations in protein expression occurring in the brain and cerebellum of 3 × Tg-AD and presenilin-1 (PS1) knock-in mice (animals that do not develop Aβ- or tau-dependent pathology nor cognitive decline and were used as control). Finally, using the Ingenuity Pathway Analysis we evaluated novel networks and molecular pathways involved in this AD model. We identified several differentially expressed spots and analysis of 3 × Tg-AD brains showed a significant downregulation of synaptic proteins that are involved in neurotransmitter synthesis, storage and release, as well as a set of proteins that are associated with cytoskeleton assembly and energy metabolism. Interestingly, in the cerebellum, a structure not affected by AD, we found an upregulation of proteins involved in carbohydrate metabolism and protein catabolism. Our findings help to unravel the pathogenic brain mechanisms set in motion by mutant amyloid precursor protein (APP) and hyperphosphorylated tau. These data also reveal cerebellar pathways that may be important to counteract the pathogenic actions of Aβ and tau, and ultimately offer novel targets for therapeutic intervention

Swimming with Predators and Pesticides: How Environmental Stressors Affect the Thermal Physiology of Tadpoles

To forecast biological responses to changing environments, we need to understand how a species’s physiology varies through space and time and assess how changes in physiological function due to environmental changes may interact with phenotypic changes caused by other types of environmental variation. Amphibian larvae are well known for expressing environmentally induced phenotypes, but relatively little is known about how these responses might interact with changing temperatures and their thermal physiology. To address this question, we studied the thermal physiology of grey treefrog tadpoles (Hyla versicolor) by determining whether exposures to predator cues and an herbicide (Roundup) can alter their critical maximum temperature (CTmax) and their swimming speed across a range of temperatures, which provides estimates of optimal temperature (Topt) for swimming speed and the shape of the thermal performance curve (TPC). We discovered that predator cues induced a 0.4uC higher CTmax value, whereas the herbicide had no effect. Tadpoles exposed to predator cues or the herbicide swam faster than control tadpoles and the increase in burst speed was higher near Topt. In regard to the shape of the TPC, exposure to predator cues increased Topt by 1.5uC, while exposure to the herbicide marginally lowered Topt by 0.4uC. Combining predator cues and the herbicide produced an intermediate Topt that was 0.5uC higher than the control. To our knowledge this is the first study to demonstrate a predator altering the thermal physiology of amphibian larvae (prey) by increasing CTmax, increasing the optimum temperature, and producing changes in the thermal performance curves. Furthermore, these plastic responses of CTmax and TPC to different inducing environments should be considered when forecasting biological responses to global warming.Peer reviewe

Differential contributions of peripheral and central mechanisms to pain in a rodent model of osteoarthritis

The mechanisms underlying the transition from acute nociceptive pain to centrally maintained chronic pain are not clear. We have studied the contributions of the peripheral and central nervous systems during the development of osteoarthritis (OA) pain. Male Sprague-Dawley rats received unilateral intra-articular injections of monosodium iodoacetate (MIA 1mg) or saline, and weight bearing (WB) asymmetry and distal allodynia measured. Subgroups of rats received intra-articular injections of, QX-314 (membrane impermeable local anaesthetic)+capsaicin, QX-314, capsaicin or vehicle on days 7, 14 or 28 post-MIA and WB and PWT remeasured. On days 7&14 post-MIA, but not day 28, QX-314+capsaicin signfcantly attenuated changes in WB induced by MIA, illustrating a crucial role for TRPV1 expressing nociceptors in early OA pain. The role of top-down control of spinal excitability was investigated. The mu-opioid receptor agonist DAMGO was microinjected into the rostroventral medulla, to activate endogenous pain modulatory systems, in MIA and control rats and refex excitability measured using electromyography. DAMGO (3ng) had a signifcantly larger inhibitory effect in MIA treated rats than in controls. These data show distinct temporal contribtuions of TRPV1 expressing nociceptors and opioidergic pain control systems at later timepoints

Sphingomimetic multiple sclerosis drug FTY720 activates vesicular synaptobrevin and augments neuroendocrine secretion

Neurotransmission and secretion of hormones involve a sequence of protein/lipid interactions with lipid turnover impacting on vesicle trafficking and ultimately fusion of secretory vesicles with the plasma membrane. We previously demonstrated that sphingosine, a sphingolipid metabolite, promotes formation of the SNARE complex required for membrane fusion and also increases the rate of exocytosis in isolated nerve terminals, neuromuscular junctions, neuroendocrine cells and in hippocampal neurons. Recently a fungi-derived sphingosine homologue, FTY720, has been approved for treatment of multiple sclerosis. In its non-phosphorylated form FTY720 accumulates in the central nervous system, reaching high levels which could affect neuronal function. Considering close structural similarity of sphingosine and FTY720 we investigated whether FTY720 has an effect on regulated exocytosis. Our data demonstrate that FTY720 can activate vesicular synaptobrevin for SNARE complex formation and enhance exocytosis in neuroendocrine cells and neurons

The influence of behavioural and health problems on alcohol and drug use in late adolescence - a follow up study of 2 399 young Norwegians

<p>Abstract</p> <p>Background</p> <p>Both early alcohol debut, behavioural and health problems are reported to enhance adolescence substance use. This prospective study investigate the influence of behavioural and health problems on adolescents' alcohol and drug use.</p> <p>Method</p> <p>Prospective population based cohort study of 2 399 adolescents attending the Young-HUNT study, aged 13-15 at baseline in 1995/97, and 17-19 at follow-up 4 years later. Exposure variables were self reported conduct problems, attention problems, anxiety and depressive symptoms, and muscular pain and tension. Outcome variables at follow-up were frequent alcohol use and initiation of drug use. Associations were estimated by logistic regression models, influence of gender and drinking status at baseline were controlled for by stratification.</p> <p>Results</p> <p>At follow-up 19% of the students drank alcohol once a week or more frequently. Baseline conduct problems (OR 2.2, CI 1.7-3.0) and attention problems (OR 1.5, CI 1.2-2.0) increased the risk for frequent alcohol use at follow-up in the total population. Girls who had experienced alcohol-intoxications at baseline showed strong association between baseline problems and frequent alcohol use at follow-up. Conduct problems (OR 2.5, CI 1.3-4.8), attention problems (OR 2.1, CI 1.2-3.4), anxiety/depressive symptoms (OR 1.9, CI 1.1-3.1) and muscular pain and tension (OR 1.7, CI 1.0-2.9) all were associated with frequent alcohol use among early intoxicated girls.</p> <p>14% of the students had tried cannabis or other drugs at follow-up. Conduct problems at baseline increased the odds for drug use (OR 2.6, CI 1.9-3.6). Any alcohol intoxications at baseline, predicted both frequent alcohol use (boys OR 3.6, CI 2.4-5.2; girls OR 2.8, CI 1.9-4.1), and illegal drug use (boys OR 4.7; CI 3.2-7.0, girls OR 7.7, CI 5.2-11.5) within follow-up.</p> <p>Conclusions</p> <p>Conduct problems in high-school more than doubles the risk for both frequent alcohol use and initiation of drug use later in adolescence. The combination of health problems and alcohol intoxication in early adolescence was closely associated with more frequent drinking later in adolescence among girls.</p> <p>Overall, early alcohol intoxication was closely associated with both frequent alcohol use and drug use at follow up in both genders</p