The sensitivity to change of the cluster headache quality of life scale assessed before and after deep brain stimulation of the ventral tegmental area.

BACKGROUND: Cluster headache (CH) is a trigeminal autonomic cephalalgia (TAC) characterized by a highly disabling headache that negatively impacts quality of life and causes limitations in daily functioning as well as social functioning and family life. Since specific measures to assess the quality of life (QoL) in TACs are lacking, we recently developed and validated the cluster headache quality of life scale (CH-QoL). The sensitivity of CH-QoL to change after a medical intervention has not been evaluated yet. METHODS: This study aimed to test the sensitivity to change of the CH-QoL in CH. Specifically we aimed to (i) assess the sensitivity of CH-QoL to change before and following deep brain stimulation of the ventral tegmental area (VTA-DBS), (ii) evaluate the relationship of changes on CH-QoL with changes in other generic measures of quality of life, as well as indices of mood and pain. Ten consecutive CH patients completed the CH-QoL and underwent neuropsychological assessment before and after VTA-DBS. The patients were evaluated on headache frequency, severity, and load (HAL) as well as on tests of generic quality of life (Short Form-36 (SF-36)), mood (Beck Depression Inventory, Hospital Anxiety and Depression Rating Scale), and pain (McGill Pain Questionnaire, Headache Impact Test, Pain Behaviour Checklist). RESULTS: The CH-QoL total score was significantly reduced after compared to before VTA-DBS. Changes in the CH-QoL total score correlated significantly and negatively with changes in HAL, the SF-36, and positively and significantly with depression and the evaluative domain on the McGill Pain Questionnaire. CONCLUSIONS: Our findings demonstrate that changes after VTA-DBS in CH-QoL total scores are associated with the reduction of frequency, duration, and severity of headache attacks after surgery. Moreover, post VTA-DBS improvement in CH-QoL scores is associated with an amelioration in quality of life assessed with generic measures, a reduction of depressive symptoms, and evaluative pain experience after VTA-DBS. These results support the sensitivity to change of the CH-QoL and further demonstrate the validity and applicability of CH-QoL as a disease specific measure of quality of life for CH

Ventral tegmental area deep brain stimulation for chronic cluster headache: Effects on cognition, mood, pain report behaviour and quality of life

BACKGROUND: Deep brain stimulation in the ventral tegmental area (VTA-DBS) has provided remarkable therapeutic benefits in decreasing headache frequency and severity in patients with medically refractory chronic cluster headache (CH). However, to date the effects of VTA-DBS on cognition, mood and quality of life have not been examined in detail. METHODS: The aim of the present study was to do so in a case series of 18 consecutive patients with cluster headache who underwent implantation of deep brain stimulation electrodes in the ventral tegmental area. The patients were evaluated preoperatively and after a mean of 14 months of VTA-DBS on tests of global cognition (Mini Mental State Examination), intelligence (Wechsler Abbreviated Scale of Intelligence), verbal memory (California Verbal Learning Test-II), executive function (Delis-Kaplan Executive Function System), and attention (Paced Auditory Serial Addition Test). Depression (Beck Depression Inventory and Hospital Anxiety and Depression Rating Scale-D), anxiety (Hospital Anxiety and Depression Rating Scale-A), apathy (Starkstein Apathy Scale), and hopelessness (Beck Hopelessness Scale) were also assessed. Subjective pain experience (McGill Pain Questionnaire), behaviour (Pain Behaviour Checklist) and quality of life (Short Form-36) were also evaluated at the same time points. RESULTS: VTA-DBS resulted in significant improvement of headache frequency (from a mean of five to two attacks daily, p < .001) and severity (from mean Verbal Rating Scale [VRS] of 10 to 7, p < .001) which was associated with significant reduction of anxiety (from mean HADS-A of 11.94 to 8.00, p < .001) and help-seeking behaviours (from mean PBC of 4.00 to 2.61, p < .001). VTA-DBS did not produce any significant change to any tests of cognitive function and any other outcome measures (BDI, HADS-D, SAS, BHS, McGill Pain Questionnaire, Short Form-36). CONCLUSION: We confirm the efficacy of VTA-DBS in the treatment of medically refractory chronic cluster headache. The reduction of headache frequency and severity was associated with a significant reduction of anxiety. Furthermore, the result suggests that VTA-DBS for chronic cluster headache improves pain-related help-seeking behaviours and does not produce any change in cognition

Intuition: Myth or a Decision-making Tool?

Faced with today’s ill-structured business environment of fast-paced change and rising uncertainty, organizations have been searching for management tools that will perform satisfactorily under such ambiguous conditions. In the arena of managerial decision making, one of the approaches being assessed is the use of intuition. Based on our definition of intuition as a non-sequential information-processing mode, which comprises both cognitive and affective elements and results in direct knowing without any use of conscious reasoning, we develop a testable model of integrated analytical and intuitive decision making and propose ways to measure the use of intuition

The Effect of Short Pulse Width Settings on the Therapeutic Window in Subthalamic Nucleus Deep Brain Stimulation for Parkinson's disease

Background: Subthalamic nucleus deep brain stimulation (STN-DBS) is an established treatment for selected Parkinson’s disease (PD) patients, but therapy is often limited by side effects. Previous studies indicate an inverse relationship of the therapeutic window (TW) to pulse width (PW) settings down to 60μs, but there is limited data available on the effect of shorter PWs. Objective: To define the TW of STN-DBS in PD at PW of 30μs (PW30) relative to standard PW settings at 60μs (PW60), and to compare speed of gait and speech intelligibility on the two PW conditions. Methods: Monopolar review data of 15 consecutive PD patients who had screening of contacts performed at PW60 and PW30 was used to calculate the TW at each contact. We compared the TWs of the most efficacious contact per STN, and a secondary analysis was performed comparing all contacts. Speed of gait with a timed 10 metre walk test, speech intelligibility, and perceptual characteristics of speech were also compared at the efficacy thresholds for PW60 and PW30. Results: The TW was significantly greater at PW30 [3.8±1.6mA] than at PW60 [1.7±1.1mA]. In the secondary analysis, 110 TWs could be calculated and these remained significantly higher at PW30. The timed 10 metre walk at PW30 was faster than at PW60, and perceptual rating scores of speech were significantly improved at PW30. Conclusions: STN-DBS in PD patients using a PW of 30μs significantly increases the TW compared to standard PW settings, and this effect is consistent across all contacts of an electrode. Speed of gait and perceptual speech scores are also improved at 30μs settings

Bioavailability in soils

The consumption of locally-produced vegetables by humans may be an important exposure pathway for soil contaminants in many urban settings and for agricultural land use. Hence, prediction of metal and metalloid uptake by vegetables from contaminated soils is an important part of the Human Health Risk Assessment procedure. The behaviour of metals (cadmium, chromium, cobalt, copper, mercury, molybdenum, nickel, lead and zinc) and metalloids (arsenic, boron and selenium) in contaminated soils depends to a large extent on the intrinsic charge, valence and speciation of the contaminant ion, and soil properties such as pH, redox status and contents of clay and/or organic matter. However, chemistry and behaviour of the contaminant in soil alone cannot predict soil-to-plant transfer. Root uptake, root selectivity, ion interactions, rhizosphere processes, leaf uptake from the atmosphere, and plant partitioning are important processes that ultimately govern the accumulation ofmetals and metalloids in edible vegetable tissues. Mechanistic models to accurately describe all these processes have not yet been developed, let alone validated under field conditions. Hence, to estimate risks by vegetable consumption, empirical models have been used to correlate concentrations of metals and metalloids in contaminated soils, soil physico-chemical characteristics, and concentrations of elements in vegetable tissues. These models should only be used within the bounds of their calibration, and often need to be re-calibrated or validated using local soil and environmental conditions on a regional or site-specific basis.Mike J. McLaughlin, Erik Smolders, Fien Degryse, and Rene Rietr

Differential Ly-6C expression identifies the recruited macrophage phenotype, which orchestrates the regression of murine liver fibrosis

Although macrophages are widely recognized to have a profibrotic role in inflammation, we have used a highly tractable CCl(4)-induced model of reversible hepatic fibrosis to identify and characterize the macrophage phenotype responsible for tissue remodeling: the hitherto elusive restorative macrophage. This CD11B(hi) F4/80(int) Ly-6C(lo) macrophage subset was most abundant in livers during maximal fibrosis resolution and represented the principle matrix metalloproteinase (MMP) -expressing subset. Depletion of this population in CD11B promoter–diphtheria toxin receptor (CD11B-DTR) transgenic mice caused a failure of scar remodeling. Adoptive transfer and in situ labeling experiments showed that these restorative macrophages derive from recruited Ly-6C(hi) monocytes, a common origin with profibrotic Ly-6C(hi) macrophages, indicative of a phenotypic switch in vivo conferring proresolution properties. Microarray profiling of the Ly-6C(lo) subset, compared with Ly-6C(hi) macrophages, showed a phenotype outside the M1/M2 classification, with increased expression of MMPs, growth factors, and phagocytosis-related genes, including Mmp9, Mmp12, insulin-like growth factor 1 (Igf1), and Glycoprotein (transmembrane) nmb (Gpnmb). Confocal microscopy confirmed the postphagocytic nature of restorative macrophages. Furthermore, the restorative macrophage phenotype was recapitulated in vitro by the phagocytosis of cellular debris with associated activation of the ERK signaling cascade. Critically, induced phagocytic behavior in vivo, through administration of liposomes, increased restorative macrophage number and accelerated fibrosis resolution, offering a therapeutic strategy to this orphan pathological process

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