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Molecular Diversity of Midbrain Development in Mouse, Human, and Stem Cells

Understanding human embryonic ventral midbrain is of major interest for Parkinson's disease. However, the cell types, their gene expression dynamics, and their relationship to commonly used rodent models remain to be defined. We performed single-cell RNA sequencing to examine ventral midbrain development in human and mouse. We found 25 molecularly defined human cell types, including five subtypes

Statins are underused in recent-onset Parkinson's disease with increased vascular risk : findings from the UK Tracking Parkinson's and Oxford Parkinson's Disease Centre (OPDC) discovery cohorts

BACKGROUND: Cardiovascular disease (CVD) influences phenotypic variation in Parkinson's disease (PD), and is usually an indication for statin therapy. It is less clear whether cardiovascular risk factors influence PD phenotype, and if statins are prescribed appropriately.OBJECTIVES: To quantify vascular risk and statin use in recent-onset PD, and examine the relationship between vascular risk, PD

α-Synuclein pre-formed fibrils impair tight junction protein expression without affecting cerebral endothelial cell function

Recently it has been shown that there is impaired cerebral endothelial function in many chronic neurodegenerative disorders including Alzheimer's and Huntington's disease. Such problems have also been reported in Parkinson's disease, in which α-synuclein aggregation is the pathological hallmark. However, little is known about the relationship between misfolded α-synuclein and endothelial function.

A PBX1 transcriptional network controls dopaminergic neuron development and is impaired in Parkinson's disease

Pre-B-cell leukemia homeobox (PBX) transcription factors are known to regulate organogenesis, but their molecular targets and function in midbrain dopaminergic neurons (mDAn) as well as their role in neurodegenerative diseases are unknown. Here, we show that PBX1 controls a novel transcriptional network required for mDAn specification and survival, which is sufficient to generate mDAn from human s

Atomoxetine restores the response inhibition network in Parkinson's disease

Parkinson's disease impairs the inhibition of responses, and whilst impulsivity is mild for some patients, severe impulse control disorders affect ∼10% of cases. Based on preclinical models we proposed that noradrenergic denervation contributes to the impairment of response inhibition, via changes in the prefrontal cortex and its subcortical connections. Previous work in Parkinson's disease found

Vascular disease and vascular risk factors in relation to motor features and cognition in early Parkinson's disease

OBJECTIVE: The purpose of this study was to examine the relationship between vascular disease (and vascular risk factors), cognition and motor phenotype in Parkinson's disease (PD).METHODS: Recently diagnosed PD cases were enrolled in a multicenter prospective observational longitudinal cohort study. Montreal cognitive assessment (normal >23, mild cognitive impairment 22 to 23 or lower but without

Learning to be inflexible : Enhanced attentional biases in Parkinson's disease

Impaired attentional flexibility is considered to be one of the core cognitive deficits in Parkinson's disease (PD). However, the mechanisms that underlie this impairment are contested. Progress in resolving this dispute has also been hindered by the fact that cognitive deficits in PD are heterogeneous; therefore, it is unclear whether attentional impairments are only present in a subgroup of pati

Setting Global Standards for Stem Cell Research and Clinical Translation : The 2016 ISSCR Guidelines

The International Society for Stem Cell Research (ISSCR) presents its 2016 Guidelines for Stem Cell Research and Clinical Translation (ISSCR, 2016). The 2016 guidelines reflect the revision and extension of two past sets of guidelines (ISSCR, 2006; ISSCR, 2008) to address new and emerging areas of stem cell discovery and application and evolving ethical, social, and policy challenges. These guidel

Aberrant nigral diffusion in Parkinson's disease : A longitudinal diffusion tensor imaging study

BACKGROUND: Measuring microstructure alterations with diffusion tensor imaging in PD is potentially a valuable tool to use as a biomarker for early diagnosis and to track disease progression. Previous studies have reported a specific decrease of nigral fractional anisotropy in PD. However, to date the effect of disease progression on nigral or striatal diffusion indices has not been fully explored

Cognitive decline and quality of life in incident Parkinson's disease : The role of attention

INTRODUCTION: Parkinson's disease dementia (PDD) is associated with poorer quality of life (QoL). Prior to the onset of PDD, many patients experience progressive cognitive impairment. There is a paucity of longitudinal studies investigating the effects of cognitive decline on QoL. This study aimed to determine the longitudinal impact of cognitive change on QoL in an incident PD cohort.METHODS: Rec

Time on timing : Dissociating premature responding from interval sensitivity in Parkinson's disease

BACKGROUND: Parkinson's disease (PD) can cause impulsivity with premature responses, but there are several potential mechanisms. We proposed a distinction between poor decision-making and the distortion of temporal perception. Both effects may be present and interact, but with different clinical and pharmacological correlates.OBJECTIVES: This study assessed premature responding during time percept

Deletions at 22q11.2 in idiopathic Parkinson's disease : a combined analysis of genome-wide association data

BACKGROUND: Parkinson's disease has been reported in a small number of patients with chromosome 22q11.2 deletion syndrome. In this study, we screened a series of large, independent Parkinson's disease case-control studies for deletions at 22q11.2.METHODS: We used data on deletions spanning the 22q11.2 locus from four independent case-control Parkinson's disease studies (UK Wellcome Trust Case Cont

Variation in Recent Onset Parkinson's Disease : Implications for Prodromal Detection

BACKGROUND: The detection of prodromal Parkinson's disease (PD) is desirable to test drugs with neuroprotective potential, but will be affected by known disease variations.OBJECTIVE: To assess the prevalence of four key non-motor prodromal PD markers, and evaluate the sensitivity of case detection when non-motor screening tools for prodromal PD are implemented in an early clinical PD cohort.METHOD

Determination of an antimicrobial activity of Weissella confusa, Lactobacillus fermentum, and Lactobacillus plantarum against clinical pathogenic strains of Escherichia coli and Staphylococcus aureus in co-culture

Lactic acid bacteria (LAB) have long been used to produce safe and high quality products as they are potential producers of a wide range of antimicrobial compounds that exert either narrow or wide spectrum antimicrobial activity towards spoilage or disease-causing organisms. The present investigation aimed to study the antimicrobial effect of three LAB strains, viz., Lactobacillus plantarum (86),

Serum immune markers and disease progression in an incident Parkinson's disease cohort (ICICLE-PD)

BACKGROUND: The immune system is a promising therapeutic target for disease modification in Parkinson's disease (PD), but appropriate immune-related biomarkers must be identified to allow patient stratification for trials and tracking of therapeutic effects. The objective of this study was to investigate whether immune markers in peripheral blood are candidate prognostic biomarkers through determi

Case management for older persons with multi-morbidity. Experiences of an intervention from the perspectives of older persons, family members, case managers and health and social care staff members

Complex health systems make it difficult to ensure a continuity of care for older persons with multi-morbidity, and risk fragmented care. Fragmented care could affect the quality and safety of the care provided. Case management could provide an approach to counteract this unfavourable situation. Case management is practised by case managers and aims to improve the coordination of healthcare and soComplex health systems make it difficult to ensure a continuity of care for older persons with multi-morbidity, and risk fragmented care. Fragmented care could affect the quality and safety of the care provided. Case management could provide an approach to counteract this unfavourable situation. Case management is practised by case managers and aims to improve the coordination of healthcare and so

Hypothalamic volume loss is associated with reduced melatonin output in Parkinson's disease

BACKGROUND: Recent studies have suggested that melatonin-a hormone produced by the pineal gland under circadian control-contributes to PD-related sleep dysfunction. We hypothesized that degenerative changes to the neural structures controlling pineal function (especially the suprachiasmatic nuclei of the anterior hypothalamus) may be responsible for reduced melatonin output in these patients. We c