281 Lincoln St Med Staff Svcs
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Paraquat and psychological stressor interactions as pertains to Parkinsonian co-morbidity. - Neurobiology of stress
A number of epidemiological and experimental studies have implicated the non-selective herbicide, paraquat, in the development of sporadic Parkinson's disease (PD). While preclinical research has focused mainly on elucidating the nigrostriatal effects of paraquat, relatively little data are available concerning non-motor brain systems and inflammatory immune processes (which have been implicated in PD). Hence, in the present study, we sought to take a multi-system approach to characterize the influence of paraquat upon extra-nigrostriatal brain regions, as well ascertain whether the impact of the pesticide might be enhanced in the context of chronic intermittent stressor exposure. Our findings support the contention that paraquat itself acted as a systemic stressor, with the pesticide increasing plasma corticosterone, as well as altering neurochemical activity in the locus coeruleus, paraventricular nucleus of the hypothalamus, nucleus accumbens, dorsal striatum, and central amygdala. However, with the important exception striatal dopamine turnover, the stressor treatment did not further augment these effects. Additionally, paraquat altered inter-cytokine correlations and, to a lesser extent, circulating cytokine levels, and concomitant stress exposure modulated some of these effects. Finally, paraquat provoked significant (albeit modest) reductions of sucrose preference and weight gain, hinting at possible anhendonic-like or sickness responses. These data suggest that, in addition to being a well known oxidative stress generator, paraquat can act as a systemic stressor affecting hormonal and neurochemical activity, but largely not interacting with a concomitant stressor regimen.
The utility of automated measures of ocular metrics for detecting driver drowsiness during extended wakefulness. - Accident; analysis and prevention
Slowed eyelid closure coupled with increased duration and frequency of closure is associated with drowsiness. This study assessed the utility of two devices for automated measurement of slow eyelid closure in a standard poor performance condition (alcohol) and following 12-h sleep deprivation. Twenty-two healthy participants (mean age=20.8 (SD 1.9) years) with no history of sleep disorders participated in the study. Participants underwent one baseline and one counterbalanced session each over two weeks; one 24-hour period of sleep deprivation, and one daytime session during which alcohol was consumed after a normal night of sleep. Participants completed a test battery consisting of a 30-min simulated driving task, a 10-min Psychomotor Vigilance Task (PVT) and the Karolinska Sleepiness Scale (KSS) each in two baseline sessions, and in two randomised, counterbalanced experimental sessions; following sleep deprivation and following alcohol consumption. Eyelid closure was measured during both tasks using two automated devices (Copilot and Optalertâ„¢). There was an increase in the proportion of time with eyelids closed and the Johns Drowsiness Score (incorporating relative velocity of eyelid movements) following sleep deprivation using Optalert (p<0.05 for both). These measures correlated significantly with crashes, PVT lapses and subjective sleepiness (r-values 0.46-0.69, p<0.05). No difference between the two sessions for PERCLOS recorded during the PVT or the driving task as measured by the Copilot. The duration of eyelid closure predicted frequent lapses following sleep deprivation (which were equivalent to the average lapses at a blood alcohol concentration of 0.05% - area under curve for ROC curve 0.87, p<0.01). The duration of time with slow eyelid closure, assessed by the automated devices, increased following sleep deprivation and was associated with deterioration in psychomotor performance and subjective sleepiness. Comprehensive algorithms inclusive of ocular parameters may be a better indicator of performance impairment following sleep loss.Copyright Â© 2015 Elsevier Ltd. All rights reserved.
The Standardized Field Sobriety Tests (SFST) and measures of cognitive functioning. - Accident; analysis and prevention
The Standardized Field Sobriety Tests (SFST) are utilised widely to assess fitness to drive when law enforcement suspects a driver's ability to drive is impaired, whether by drugs or alcohol. The SFST ostensibly achieve this through assessment of the level of drivers' cognitive and psychomotor impairment, although no studies have explicitly assessed the relatedness of cognitive ability and performance on the SFST. The current study aimed to assess the relationship between the three components of the SFST with a well validated computerised cognitive battery.A sub-set of 61 placebo condition participants comprised the sample, with 33 females and 28 males (mean age 25.45 years). Correlations between the individual SFST subscales 'Horizontal Gaze Nystagmus' (HGN), the 'One Leg Stand' (OLS) and the 'Walk and Turn' test (WAT) and Cognitive Drug Research (CDR) sub-scales of 'Quality of Working Memory', 'Power of Attention' and 'Continuity of Attention' were analysed using point-biserial correlation.Sixty participants were included for analyses. A weak-moderate positive (five subscales) and a moderate-strong negative (two subscales) association was noted between seven of the nine individual CDR subscales and the SFST subscale of the WAT test (all p<0.05). Individually, a moderate positive association was noted between the sub-scale 'Nystagmus lack of smooth pursuit' and 'digit vigilance reaction time' and 'choice reaction time; reaction time' (both p<0.05) and 'Nystagmus head move and/or jerk' and 'simple reaction time' (p<0.001). When assessed as a partially composite factor, a comparable association was also noted between the composite score of the SFST subscale 'Nystagmus head move and/or jerk' and both (a) simple and (b) digit vigilance reaction time (both p<0.05). No association was noted between any of the individual cognitive variables and the SFST subscale 'OLS', or between composite cognitive scores 'Quality of Working Memory', 'Power of Attention' and 'Continuity of Attention' and total SFST scores.Variation in some aspects of cognitive performance was found to be moderately and positively correlated with some individual aspects of the SFST; particularly among tasks which assess reaction time. Impairment of these cognitive processes can also contribute to the completion of complex tasks such as driving or the SFST. Complex behavioural tasks such as driving are often severely impaired due to intoxication, and thus in a practical sense, the SFST can still be considered a useful screening tool to identify drug or alcohol impaired drivers.Copyright Â© 2015 Elsevier Ltd. All rights reserved.
Major Alterations of Phosphatidylcholine and Lysophosphotidylcholine Lipids in the Substantia Nigra Using an Early Stage Model of Parkinson's Disease. - International journal of molecular sciences
Parkinson's disease (PD) is a progressive neurodegenerative disease affecting the nigrostriatal pathway, where patients do not manifest motor symptoms until >50% of neurons are lost. Thus, it is of great importance to determine early neuronal changes that may contribute to disease progression. Recent attention has focused on lipids and their role in pro- and anti-apoptotic processes. However, information regarding the lipid alterations in animal models of PD is lacking. In this study, we utilized high performance liquid chromatography electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) and novel HPLC solvent methodology to profile phosphatidylcholines and sphingolipids within the substantia nigra. The ipsilateral substantia nigra pars compacta was collected from rats 21 days after an infusion of 6-hydroxydopamine (6-OHDA), or vehicle into the anterior dorsal striatum. We identified 115 lipid species from their mass/charge ratio using the LMAPS Lipid MS Predict Database. Of these, 19 lipid species (from phosphatidylcholine and lysophosphotidylcholine lipid classes) were significantly altered by 6-OHDA, with most being down-regulated. The two lipid species that were up-regulated were LPC (16:0) and LPC (18:1), which are important for neuroinflammatory signalling. These findings provide a first step in the characterization of lipid changes in early stages of PD-like pathology and could provide novel targets for early interventions in PD.
Symptoms of Depression and Difficulty Initiating Sleep from Early Adolescence to Early Adulthood: A Longitudinal Study. - Sleep
To assess the direction of the relationship and degree of shared associations between symptoms of depression and difficulty initiating sleep (DIS) from early adolescence to early adulthood.Cross-sectional and longitudinal assessment of the symptoms of depression-DIS association from early adolescence (age 13 y) to early adulthood (age 23 y).Hordaland, Norway.There were 1,105 individuals (55% male) who took part in the Norwegian Longitudinal Health Behaviour Study (NLHB) and participated at least once across seven data collection waves during the years 1990-2000.N/A.Characteristic data were obtained during the first assessment. Symptoms of depression and instances of DIS were assessed during each data collection wave. Symptoms of depression and DIS were associated in all data waves, and one-step cross-lagged bivariate correlations were significant and comparatively high for both factors. Structural equation modelling indicated that DIS and symptoms of depression at wave 1 remain relatively stable across waves (all P < 0.001), and a significant and consistent unidirectional cross-lagged effect was noted running from symptoms of depression to DIS from early adolescence to early adulthood. DIS is only marginally and inconsistently associated with the lagged symptoms of depression score across waves.These results suggest that symptoms of depression established in early adolescence are a moderate predictor of difficulty initiating sleep (DIS) in early adulthood, whereas the reverse association of DIS predicting depression was not convincingly supported. These findings are in contrast to previous findings that suggest sleep problems as a risk factor for the later development of depression.Â© 2015 Associated Professional Sleep Societies, LLC.
Hematopoietic cytokines as therapeutic players in early stages Parkinson's disease. - Frontiers in aging neuroscience
Parkinson's disease (PD) is a devastating age related neurodegenerative disease that is believed to have a lengthy prodromal state. It is critical to find methods to harness compensatory recovery processes in order to slow or prevent the eventual progression of clinical symptoms. The current perspective paper argues that immune system signaling molecules represent such a promising therapeutic approach. Two cytokines of interest are granulocyte macrophage-colony stimulating factor (GM-CSF) and erythropoietin (EPO). These hematopoietic cytokines have been protective in models of stroke, neuronal injury, and more recently PD. It is our belief that these trophic cytokines can be used not only for cell protection but also regeneration. However, success is likely dependent on early intervention. This paper will outline our perspective on the development of novel trophic recovery treatments for PD. In particular, we present new data from our lab suggesting that EPO and GM-CSF can foster neural re-innervation in a "mild" or partial lesion PD model that could be envisioned as reflecting the early stages of the disease.
Trajectories and stability of self-reported short sleep duration from adolescence to adulthood. - Journal of sleep research
The trajectories and stability of self-reported sleep duration recorded at ages 13, 15, and 23 years on reported sleep duration at age 30 years among 1105 students (55% male) who participated in the Norwegian Longitudinal Health and Behaviour Study were examined. Questionnaire data were used to obtain demographic and sleep variables. Dichotomised short sleep duration was based on normative values and set as â‰¤ 8.5 h (age 13 years), â‰¤ 8 h (age 15 years) and â‰¤ 7 h (ages 23 and 30 years). Results indicated a significant overall reduction in total sleep duration (h per night) across age groups. Sleep duration (continuous) at age 15 and 23 years (whole group) was moderately but positively correlated with sleep duration at age 30 years (P < 0.01). When split by sex, at age 15 years, this association was present among females only (P < 0.01); however, at age 23 years, this association was present in both male and females (both P < 0.001). Categorical short sleep at age 23 years (whole group) was associated with short sleep at age 30 years (unadjusted odds ratio = 3.67, 95% confidence interval 2.36-5.69). Following sex stratification, this effect was significant for both males (unadjusted odds ratio = 3.77, 95% confidence interval: 2.22-6.42) and females (unadjusted odds ratio = 2.71, 95% confidence interval: 1.46-5.04). No associations were noted for categorical short sleep at ages 13 or 15 years, and subsequent short sleep at 30 years. Habitual short sleep duration during middle adulthood is not sustained from the time of early adolescence. Rather, these trends appear to be formed during early adulthood.Â© 2015 European Sleep Research Society.
Excessive daytime sleepiness and falls among older men and women: cross-sectional examination of a population-based sample. - BMC geriatrics
Excessive daytime sleepiness (EDS) has been associated with an increased risk for falls among clinical samples of older adults. However, there is little detailed information among population-representative samples. The current study aimed to assess the relationship between EDS and falls among a cohort of population-based older adults.This study assessed 367 women aged 60-93 years (median 72, interquartile range 65-79) and 451 men aged 60-92 years (median 73, interquartile range 66-80) who participated in the Geelong Osteoporosis Study between the years 2001 and 2008. Falls during the prior year were documented via self-report, and for men, falls risk score was obtained using an Elderly Fall Screening Test (EFST). Sleepiness was assessed using the Epworth Sleepiness Scale (ESS), and scores of â€‰â‰¥â€‰10 indicated EDS. Differences among those with and without EDS in regard to falls were tested using logistic regression models.Among women, 50 (13.6%) individuals reported EDS. Women with EDS were more likely to report a fall, and were more likely to report the fall occurring outside. EDS was similarly associated with an increased risk of a fall following adjustment for use of a walking aid, cases of nocturia and antidepressant medication use (adjusted ORâ€‰=â€‰2.54, 95% CI 1.24-5.21). Multivariate modelling revealed antidepressant use (current) as an effect modifier (pâ€‰<â€‰.001 for the interaction term). After stratifying the data by antidepressant medication use, the association between EDS and falls was sustained following adjustment for nocturia among antidepressant non-users (adjusted ORâ€‰=â€‰2.63, 95% CI 1.31-5.30). Among men, 72 (16.0%) individuals reported EDS. No differences were detected for men with and without EDS in regard to reported falls, and a trend towards significance was noted between EDS and a high falls risk as assessed by the EFST (pâ€‰=â€‰0.06), however, age explained this relationship (age adjusted ORâ€‰=â€‰2.20, 95% CI 1.03-1.10).For women, EDS is independently associated with at least one fall during the previous year, and this is more likely to occur whilst located outside. Amelioration of EDS may assist in improving functional outcomes among these individuals by reducing the risk for falls.
Slow eyelid closure as a measure of driver drowsiness and its relationship to performance. - Traffic injury prevention
Slow eyelid closure is recognized as an indicator of sleepiness in sleep-deprived individuals, although automated ocular devices are not well validated. This study aimed to determine whether changes in eyelid closure are evident following acute sleep deprivation as assessed by an automated device and how ocular parameters relate to performance after sleep deprivation.Twelve healthy professional drivers (45.58 Â± 10.93 years) completed 2 randomized sessions: After a normal night of sleep and after 24 h of total sleep deprivation. Slow eye closure (PERCLOS) was measured while drivers performed a simulated driving task.Following sleep deprivation, drivers displayed significantly more eyelid closure (P < .05), greater variation in lane position (P < .01) and more attentional lapses (P < .05) compared to after normal sleep. PERCLOS was moderately associated with variability in both vigilance performance (r = 0.68, P < .05) and variation in lane position on the driving task (r = 0.61, P < .05).Automated ocular measurement appears to be an effective means of detecting impairment due to sleep loss in the laboratory.
Gender and brain regions specific differences in brain derived neurotrophic factor protein levels of depressed individuals who died through suicide. - Neuroscience letters
Considerable evidence supports the view that depressive illness and suicidal behaviour stem from perturbations of neuroplasticity. Presently, we assessed whether depressed individuals who died by suicide displayed brain region-specific changes in brain derived neurotrophic factor (BDNF) and whether such effects varied by gender. Using postmortem samples from non-psychiatric controls and depressed individuals who died by suicide, BDNF protein levels were assessed within the hippocampus and frontopolar prefrontal cortex using Western blot. As expected, BDNF levels were reduced within the frontopolar prefrontal cortex among female depressed suicides; however, males showed no such effect. Contrastingly, within the hippocampus, depressed male but not female suicides displayed significant reductions of BDNF protein levels. Although the mechanisms driving the gender and brain region specific BDNF changes are unclear, our data do support the notion that complex alterations of neuroplasticity may be fundamentally involved in the illness.Copyright Â© 2015 Elsevier Ireland Ltd. All rights reserved.
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