Association of Autonomic Dysfunction With Disease Progression and Survival in Parkinson Disease.

Importance: Evidence suggests that development of autonomic dysfunction (AutD) may negatively affect disease course and survival in patients with synucleinopathies. However, the few available studies on Parkinson disease (PD) have conflicting results, comprise a small number of patients, have short follow-up periods, and lack pathologic confirmation of the diagnosis.

Objective: To examine the association of time of onset of AutD with disease progression and survival in PD.

Estimating the causal influence of body mass index on risk of Parkinson disease: A Mendelian randomisation study.

Background: Both positive and negative associations between higher body mass index (BMI) and Parkinson disease (PD) have been reported in observational studies, but it has been difficult to establish causality because of the possibility of residual confounding or reverse causation. To our knowledge, Mendelian randomisation (MR)-the use of genetic instrumental variables (IVs) to explore causal effects-has not previously been used to test the effect of BMI on PD.

Methods And Findings: Two-sample MR was undertaken using genome-wide association (GWA) study data.

The relationship between the First World War and neurology: 100 years of "Shell Shock".

The First World War was a global war, beginning on 28 July 1914, until 11 November 1918. Soon after the beginning of the war, there was an "epidemic" of neurological conversion symptoms. Soldiers on both sides started to present in large numbers with neurological symptoms, such as dizziness, tremor, paraplegia, tinnitus, amnesia, weakness, headache and mutism of psychosomatic origin.

Opicapone for the management of end-of-dose motor fluctuations in patients with Parkinson's disease treated with L-DOPA.

Opicapone is a third generation, highly potent and effective catechol O‑methyltransferase (COMT) inhibitor that optimizes the pharmacokinetics and bioavailability of L-DOPA therapy. Areas covered: In this review, the authors describe the preclinical and clinical development of opicapone. In PD patients with motor fluctuations, once daily opicapone administration was well-tolerated and consistently reduced OFF-time and increased ON-time without increasing the frequency of troublesome dyskinesia, and these benefits were maintained over at least a year of continued open-label therapy.

Development of a glycoconjugate vaccine to prevent invasive Salmonella Typhimurium infections in sub-Saharan Africa.

Invasive infections associated with non-typhoidal Salmonella (NTS) serovars Enteritidis (SE), Typhimurium (STm) and monophasic variant 1,4,[5],12:i:- are a major health problem in infants and young children in sub-Saharan Africa, and currently, there are no approved human NTS vaccines. NTS O-polysaccharides and flagellin proteins are protective antigens in animal models of invasive NTS infection. Conjugates of SE core and O-polysaccharide (COPS) chemically linked to SE flagellin have enhanced the anti-COPS immune response and protected mice against fatal challenge with a Malian SE blood isolate.

Viral hepatitis and Parkinson disease: A national record-linkage study.

Objective: To study associations between viral hepatitis and Parkinson disease (PD).

Methods: A retrospective cohort study was done by analyzing linked English National Hospital Episode Statistics and mortality data (1999-2011). Cohorts of individuals with hepatitis B, hepatitis C, autoimmune hepatitis, chronic active hepatitis, and HIV were constructed, and compared to a reference cohort for subsequent rates of PD.

Parkinson's disease - 200 years: the outstanding contribution of "Old Hubert".

Two hundred years after the publication, of "An Essay on the Shaking Palsy", this indisputable landmark in our understanding of the nature of Parkinson's disease still remains. What is frequently overlooked, however, is the originality of James Parkinson's ideas about how clinical observations could be segregated into diagnostic entities. Parkinson was a surgeon apothecary with wide ranging interests outside medicine including geology and paleontology.

Georges Simenon, Inspector Maigret and his relevance to the practice of Neurology.

Georges Simenon's work, including his famous 'romans durs' novels and the forensic investigations carried out by his artistic creation, Inspector Maigret, bear many similarities to some of the diagnostic methods of the founders of Neurology, particularly Jean-Martin Charcot.

Thermoregulation of the bovine scrotum 1: measurements of free-range animals in a paddock and pen.

The bull's scrotum and scrotal cord vasculature has traditionally been regarded as a thermoregulatory device for maintaining optimal testicular temperature for normal spermatogenesis. This assumption has mostly been derived from discrete measurements using thermocouples with limited data correlating continuous scrotal temperature (ST) to body temperature (BT). From mid-summer to early autumn, four Wagyu bulls (9-18 months) were surgically implanted with two data loggers (DL) logging at 30 min intervals: one on the right hand side flank and the other was attached to the visceral vaginal tunic of the mid-testis.

Identification of candidate cerebrospinal fluid biomarkers in parkinsonism using quantitative proteomics.

Introduction: Neurodegenerative parkinsonian syndromes have significant clinical and pathological overlap, making early diagnosis difficult. Cerebrospinal fluid (CSF) biomarkers may aid the differentiation of these disorders, but other than α-synuclein and neurofilament light chain protein, which have limited diagnostic power, specific protein biomarkers remain elusive.

Objectives: To study disease mechanisms and identify possible CSF diagnostic biomarkers through discovery proteomics, which discriminate parkinsonian syndromes from healthy controls.

Mixed pathologies including chronic traumatic encephalopathy account for dementia in retired association football (soccer) players.

In retired professional association football (soccer) players with a past history of repetitive head impacts, chronic traumatic encephalopathy (CTE) is a potential neurodegenerative cause of dementia and motor impairments. From 1980 to 2010, 14 retired footballers with dementia were followed up regularly until death. Their clinical data, playing career, and concussion history were prospectively collected.

Blood-based NfL: A biomarker for differential diagnosis of parkinsonian disorder.

Objective: To determine if blood neurofilament light chain (NfL) protein can discriminate between Parkinson disease (PD) and atypical parkinsonian disorders (APD) with equally high diagnostic accuracy as CSF NfL, and can therefore improve the diagnostic workup of parkinsonian disorders.

Methods: The study included 3 independent prospective cohorts: the Lund (n = 278) and London (n = 117) cohorts, comprising healthy controls and patients with PD, progressive supranuclear palsy (PSP), corticobasal syndrome (CBS), and multiple system atrophy (MSA), as well as an early disease cohort (n = 109) of patients with PD, PSP, MSA, or CBS with disease duration ≤3 years. Blood NfL concentration was measured using an ultrasensitive single molecule array (Simoa) method, and the diagnostic accuracy to distinguish PD from APD was investigated.

Wilson's disease: the 60th anniversary of Walshe's article on treatment with penicillamine.

This historical review describes Professor Walshe's seminal contribution to the treatment of Wilson's disease on the 60th anniversary of his pioneering article on penicillamine, the first effective treatment for the condition.

PREDICT-PD: An online approach to prospectively identify risk indicators of Parkinson's disease.

Background: A number of early features can precede the diagnosis of Parkinson's disease (PD).

Objective: To test an online, evidence-based algorithm to identify risk indicators of PD in the UK population.

Methods: Participants aged 60 to 80 years without PD completed an online survey and keyboard-tapping task annually over 3 years, and underwent smell tests and genotyping for glucocerebrosidase (GBA) and leucine-rich repeat kinase 2 (LRRK2) mutations.

Opicapone as Adjunct to Levodopa Therapy in Patients With Parkinson Disease and Motor Fluctuations: A Randomized Clinical Trial.

Importance: Catechol O-methyltransferase (COMT) inhibitors are an established treatment for end-of-dose motor fluctuations associated with levodopa therapy in patients with Parkinson disease (PD). Current COMT inhibitors carry a high risk for toxic effects to hepatic cells or show moderate improvement. Opicapone was designed to be effective without the adverse effects.

Subtle motor disturbances in PREDICT-PD participants.

Objective: The PREDICT-PD study aims to identify increased risk of Parkinson''s disease (PD) using online assessments of previously identified risk and early features of PD and an evidence-based scoring algorithm. We sought to determine whether higher risk participants (defined as those above the 15th centile of risk estimates) were more likely to have mild parkinsonian signs compared with lower risk participants.

Methods: Video recordings of neurological examinations, including the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III, of 208 individuals who had previously completed an online risk assessment were scored blindly and independently by two movement-disorders experts.

9.4 T MR microscopy of the substantia nigra with pathological validation in controls and disease.

Background: The anatomy of the substantia nigra on conventional MRI is controversial. Even using histological techniques it is difficult to delineate with certainty from surrounding structures. We sought to define the anatomy of the SN using high field spin-echo MRI of pathological material in which we could study the anatomy in detail to corroborate our MRI findings in controls and Parkinson's disease and progressive supranuclear palsy.

Using avian functional traits to assess the impact of land-cover change on ecosystem processes linked to resilience in tropical forests.

Vertebrates perform key roles in ecosystem processes via trophic interactions with plants and insects, but the response of these interactions to environmental change is difficult to quantify in complex systems, such as tropical forests. Here, we use the functional trait structure of Amazonian forest bird assemblages to explore the impacts of land-cover change on two ecosystem processes: seed dispersal and insect predation. We show that trait structure in assemblages of frugivorous and insectivorous birds remained stable after primary forests were subjected to logging and fire events, but that further intensification of human land use substantially reduced the functional diversity and dispersion of traits, and resulted in communities that occupied a different region of trait space.

A genome-wide association study in multiple system atrophy.

Objective: To identify genetic variants that play a role in the pathogenesis of multiple system atrophy (MSA), we undertook a genome-wide association study (GWAS).

Methods: We performed a GWAS with >5 million genotyped and imputed single nucleotide polymorphisms (SNPs) in 918 patients with MSA of European ancestry and 3,864 controls. MSA cases were collected from North American and European centers, one third of which were neuropathologically confirmed.