Abnormal connectivity between the default mode and the visual system underlies the manifestation of visual hallucinations in Parkinson’s disease:A task-based fMRI study

Background: The neural substrates of visual hallucinations remain an enigma, due primarily to the difficulties associated with directly interrogating the brain during hallucinatory episodes. Aims: To delineate the functional patterns of brain network activity and connectivity underlying visual hallucinations in Parkinson’s disease. Methods: In this study, we combined functional magnetic resonance imaging (MRI) with a behavioral task capable of eliciting visual misperceptions, a confirmed surrogate for visual hallucinations, in 35 patients with idiopathic Parkinson’s disease. We then applied an independent component analysis to extract time series information for large-scale neuronal networks that have been previously implicated in the pathophysiology of visual hallucinations. These data were subjected to a task-based functional connectivity analysis, thus providing the first objective description of the neural activity and connectivity during visual hallucinations in patients with Parkinson’s disease. Results: Correct performance of the task was associated with increased activity in primary visual regions; however, during visual misperceptions, this same visual network became actively coupled with the default mode network (DMN). Further, the frequency of misperception errors on the task was positively correlated with the strength of connectivity between these two systems, as well as with decreased activity in the dorsal attention network (DAN), and with impaired connectivity between the DAN and the DMNs, and ventral attention networks. Finally, each of the network abnormalities identified in our analysis were significantly correlated with two independent clinical measures of hallucination severity. Conclusions: Together, these results provide evidence that visual hallucinations are due to increased engagement of the DMN with the primary visual system, and emphasize the role of dysfunctional engagement of attentional networks in the pathophysiology of hallucinations

Sex differences in plasma clozapine and norclozapine concentrations in clinical practice and in relation to body mass index and plasma glucose concentrations: a retrospective survey

Background Clozapine is widely prescribed and, although effective, can cause weight gain and dysglycemia. The dysmetabolic effects of clozapine are thought to be more prevalent in women with this gender on average attaining 17 % higher plasma clozapine concentrations than men. Methods We investigated the relationship between dose, body mass index (BMI), plasma glucose concentration, and plasma clozapine and N-desmethylclozapine (norclozapine) concentrations in 100 individuals with a severe enduring mental illness. Results Mean (10th/90th percentile) plasma clozapine concentrations were higher for women [0.49 (0.27–0.79) mg/L] compared with men [0.44 (0.26–0.70) mg/L] (F = 2.2; p = 0.035). There was no significant gender difference in the prescribed clozapine dose. BMI was significantly higher in women [mean (95 % CI) = 34.5 (26.0–45.3)] for females compared with 32.5 (25.2–41.0) for males. Overall, BMI increased by 0.7 kg/m 2 over a mean follow-up period of 210 days. A lower proportion, 41 % of women had a fasting blood glucose ≤6.0 mmol/L (<6.0 mmol/L is defined by the International Diabetes Federation as normal glucose handling), compared with 88 % of men (χ2  = 18.6, p < 0.0001). Conclusions We have shown that mean BMI and blood glucose concentrations are higher in women prescribed clozapine than in men. Women also tended to attain higher plasma clozapine concentrations than men. The higher BMI and blood glucose in women may relate to higher tissue exposure to clozapine, as a consequence of sex differences in drug metabolism

Measuring Anxiety in Lewy Body Disease – Which Scale to Choose?

Background: Anxiety is among the most prevalent mood disorders in Lewy Body Disease (LBD) (i.e., Parkinson’s disease (PD), Dementia with Lewy bodies DLB), and those at-risk for developing LBD (e.g. isolated REM Sleep Behaviour Disorder (iRBD)). Yet, there is little consensus on which clinical scale best evaluates anxiety across synuclein-based diseases. Objective: This study compared the convergent validity of commonly used anxiety scales across PD, DLB and iRBD patients. Methods: Anxiety was assessed using the Hospital Anxiety and Depression Scale (HADS-A), State-Trait Anxiety Inventory (STAI), MDS-UPDRS Anxiety item, and the Parkinson Anxiety Scale (PAS) in 57 participants (17 PD, 16 DLB, and 23 iRBD). Results: Across all groups, PAS total score was significantly associated with trait anxiety (STAI-Y2), whilst HADS-A was associated with PAS total score in the PD and iRBD group. In DLB patients, HADS-A was weakly associated with PAS total score, and significantly correlated with PAS episodic anxiety. Notably, the anxiety item from the MDS-UPDRS did not correlate with any of the other anxiety outcome measures in any group. Conclusions: PAS and STAI-Y2 are the most suitable scales to assess anxiety in synuclein-based diseases. HADS-A showed strong convergent validity in PD and iRBD, it had weaker convergent validity in DLB. The UPDRS anxiety item did not correlate with any of the other anxiety measures, and thus may not be sensitive at detecting anxiety symptoms. Future work should validate anxiety scales in all Lewy Body Disease groups if they are to be implemented in prospective longitudinal cohorts

Fluid/solid transition in a hard-core system

We prove that a system of particles in the plane, interacting only with a certain hard-core constraint, undergoes a fluid/solid phase transition

ATR-FTIR Spectroscopic Studies of Polymer-Based Identification Cards

Counterfeit production of polymer identity cards poses a significant economic cost to society and a threat to national security. Identifying these counterfeits is a challenge for ‘frontline’ personnel who lack training in specialised document examination. This study investigates the use of attenuated total reflectance Fourier Transform infrared (ATR-FTIR) spectroscopy with chemometrics as a potential approach to assessing polymer card authenticity. In situ analysis of several cards found that differentiation could be achieved based on the core polymer composition. A chemometric model was thus built for three driver’s licence series produced in Western Australia and tested using a separate set of seven licences. The majority of test samples were correctly matched to the series of issue, with atypical samples recognisable based on their discriminant values. Synchrotron FTIR imaging revealed that differentiation between each series was possibly related to the adhesive used between the core layers. The approach presented in this work has the potential to be developed as a rapid screening method to identify suspect polymer cards warranting further examination

Melatonin for rapid eye movement sleep behavior disorder in Parkinson's disease : a randomised controlled trial

Background Melatonin may reduce REM-sleep behavior disorder (RBD) symptoms in Parkinson's disease (PD), though robust clinical trials are lacking. Objective To assess the efficacy of prolonged-release (PR) melatonin for RBD in PD. Methods Randomized, double-blind, placebo-controlled, parallel-group trial with an 8-week intervention and 4-week observation pre- and postintervention (ACTRN12613000648729). Thirty PD patients with rapid eye movement sleep behavior disorder were randomized to 4 mg of prolonged-release melatonin (Circadin) or matched placebo, ingested orally once-daily before bedtime. Primary outcome was the aggregate of rapid eye movement sleep behavior disorder incidents averaged over weeks 5 to 8 of treatment captured by a weekly diary. Data were included in a mixed-model analysis of variance (n = 15 per group). Results No differences between groups at the primary endpoint (3.4 events/week melatonin vs. 3.6 placebo; difference, 0.2; 95% confidence interval = -3.2 to 3.6; P = 0.92). Adverse events included mild headaches, fatigue, and morning sleepiness (n = 4 melatonin; n = 5 placebo). Conclusion Prolonged-release melatonin 4 mg did not reduce rapid eye movement sleep behavior disorder in PD. (c) 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society

The dryas iulia genome supports multiple gains of a W chromosome from a B chromosome in butterflies

In butterflies and moths, which exhibit highly variable sex determination mechanisms, the homogametic Z chromosome is deeply conserved and is featured in many genome assemblies. The evolution and origin of the female W sex chromosome, however, remains mostly unknown. Previous studies have proposed that a ZZ/Z0 sex determination system is ancestral to Lepidoptera, and that W chromosomes may originate from sex-linked B chromosomes. Here, we sequence and assemble the female Dryas iulia genome into 32 highly contiguous ordered and oriented chromosomes, including the Z and W sex chromosomes. We then use sex-specific Hi-C, ATAC-seq, PRO-seq, and whole-genome DNA sequence data sets to test if features of the D. iulia W chromosome are consistent with a hypothesized B chromosome origin. We show that the putative W chromosome displays female-associated DNA sequence, gene expression, and chromatin accessibility to confirm the sex-linked function of the W sequence. In contrast with expectations from studies of homologous sex chromosomes, highly repetitive DNA content on the W chromosome, the sole presence of domesticated repetitive elements in functional DNA, and lack of sequence homology with the Z chromosome or autosomes is most consistent with a B chromosome origin for the W, although it remains challenging to rule out extensive sequence divergence. Synteny analysis of the D. iulia W chromosome with other female lepidopteran genome assemblies shows no homology between W chromosomes and suggests multiple, independent origins of the W chromosome from a B chromosome likely occurred in butterflies

Mild Cognitive Impairment in Parkinson’s Disease: A Review of Current Concepts

Mild Cognitive Impairment in Parkinson's Disease (PD-MCI) is common and may be associated with accelerated progression to dementia. Considering the importance of this emerging entity, new diagnostic criteria have recently been proposed. Early recognition and accurate classification of PD-MCI could offer opportunities for novel therapeutic interventions. This review discusses current definitions for PD-MCI, the screening tools used, the pattern of cognitive deficits observed, and the predictors of cognitive decline and transition to Parkinson's Disease Dementia. Emerging biomarkers, which may aid diagnosis, are also explored and the role of novel treatment options is considered