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Genetic analyses can provide important insights into the demographic processes that underlie recovering populations of mammals of conservation concern such as felid species. To better understand the recent and rapid recovery of bobcats (Lynx rufus (Schreber, 1777)) in Ohio, we analyzed samples from four states in the lower Great Lakes Region using 12 microsatellite DNA loci and a portion of the mtDNA control region. Our results showed that a newly established population of bobcats in the eastern part of Ohio was genetically distinct from a multistate population distributed across Kentucky, southern Ohio, West Virginia, and western Pennsylvania. There was no direct genetic evidence of a bottleneck or inbreeding in this population. A lack of private alleles and only slightly lower levels of allelic richness and heterozygosity compared with its neighbors suggest that the eastern Ohio population likely originated from the migration of relatively large numbers of individuals from a source population rather than re-emerging from an undetected residual population. We recommend that a management plan should define the areas occupied by the two populations in Ohio as separate management units at least for the near future. Key words: Lynx rufus, bobcat, mtDNA, microsatellites, population bottleneck, conservation genetics, management units. Les analyses genetiques peuvent fournir d'importants renseignements sur les processus demographiques qui soustendent les populations en cours de retablissement de mammiferes dont la conservation est preoccupante, comme des especes de felides. Afin de mieux comprendre le retablissement recent et rapide des lynx roux (Lynx rufus (Schreber, 1777)) en Ohio, nous avons analyse des echantillons provenant de quatre Etats de la partie inferieure de la region des Grands Lacs en utilisant 12 sites d'ADN microsatellites et une portion de la region temoin d'ADNmt. Nos resultats montrent qu'une population de lynx roux nouvellement etablie dans la partie orientale de l'Ohio est differente sur le plan genetique d'une population repartie sur plusieurs Etats, dont le Kentucky, le sud de l'Ohio, la Virginie occidentale et l'ouest de la Pennsylvanie. Aucun indice genetique direct de la presence d'un goulot d'etranglement ou de consanguinite dans cette population n'a ete observe. L'absence d'alleles prives et des degres de richesse allelique et d'heterozygotie juste un peu plus faibles que ceux de ses voisins donnent a penser que la population de l'est de l'Ohio est vraisemblablement issue de la migration d'un assez grand nombre d'individus a partir d'une population source, plutot que de la reemergence d'une population residuelle non detectee. Nous recommandons qu'un plan d'amenagement devrait definir les aires occupees par les deux populations de l'Ohio comme representant deux unites d'amenagement distinctes, a tout le moins pour l'avenir rapproche. [Traduit par la Redaction] Mots-cles: Lynx rufus, lynx roux, ADNmt, microsatellites, goulot d'etranglement genetique, genetique de la conservation, unites d'amenagement., Introduction Conservation biologists use analyses of genetic data to gain demographic information about endangered species or species of concern that are hard to study using conventional census techniques (Nowell and [...]

Objective: To assess amantadine use and associated factors in the patients with Parkinson's disease (PD)., Background: Immediate-release amantadine is approved for the treatment of PD and is largely used in clinical practice to treat "levodopa-induced dyskinesia (LIDs). Its use varies according to countries and PD stages. The prospective NS-Park cohort collects features of PD patients followed by 26 French PD Expert Centres., Methods: Variables used for the analyses included demographics, motor and non-motor PD symptoms and motor complications [motor fluctuations (MFs), LIDs)], antiparkinsonian pharmacological classes and levodopa equivalent daily dose (LEDD). We evaluated: (i) prevalence of amantadine use and compared clinical features of amantadine users vs. non-users (cross-sectional analysis); (ii) factors associated with amantadine initiation (longitudinal analysis); (iii) amantadine effect on LIDs, MFs, apathy, impulse control disorders and freezing of gait (Fog) (longitudinal analysis)., Results: Amantadine use prevalence was 12.6% (1,585/12,542, median dose = 200 mg). Amantadine users were significantly younger, with longer and more severe PD symptoms, greater LEDD and more frequent use of device-aided/surgical treatment. Factors independently associated with amantadine initiation were younger age, longer PD duration, more frequent LIDs, MFs and FoG, higher LEDD and better cognitive function. 9 of the 658 patients on amantadine had stopped it at the following visit, after 12-18 months (1.3%). New users of amantadine presented a higher improvement in LIDs and MF compared to amantadine never users., Conclusions: About 12% of PD patients within the French NS-Park cohort used amantadine, mostly those with younger age and more severe PD. Amantadine initiation was associated with a subsequent reduction in LIDs and MFs., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Resilience in neuroscience generally refers to an individual's capacity to counteract the adverse effects of a neuropathological condition. While resilience mechanisms in Alzheimer's disease are well-investigated, knowledge regarding its quantification, neurobiological underpinnings, network adaptations, and long-term effects in Parkinson's disease is limited. Our study involved 151 Parkinson's patients from the Parkinson's Progression Marker Initiative Database with available Magnetic Resonance Imaging, Dopamine Transporter Single-Photon Emission Computed Tomography scans, and clinical information. We used an improved prediction model linking neuropathology to symptom severity to estimate individual resilience levels. Higher resilience levels were associated with a more active lifestyle, increased grey matter volume in motor-associated regions, a distinct structural connectivity network and maintenance of relative motor functioning for up to a decade. Overall, the results indicate that relative maintenance of motor function in Parkinson's patients may be associated with greater neuronal substrate, allowing higher tolerance against neurodegenerative processes through dynamic network restructuring., (© 2024. The Author(s).)

Objectives: SLC6A1 -related disorders encompass heterogeneous neuropsychiatric manifestations through GABAergic dysregulation, without any specific abnormalities on brain MRI, nor evidence of dopaminergic cell loss on I 123 -FP-β-CIT SPECT. We report here a case of globus pallidus lesions and dopaminergic denervation in a patient with a pathogenic SLC6A1 variant., Methods: A 26-year-old female patient with intellectual disability, behavioral, and psychiatric disorders treated by neuroleptics for many years developed a parkinsonian syndrome associated with mild hand dystonia and chorea. A 3T brain MRI and I 123 -FP-β-CIT SPECT were performed., Results: MRI of the brain found bilateral pallidal lesions consistent with neurodegeneration with iron accumulation. The I 123 -FP-β-CIT SPECT showed bilateral striatal presynaptic dopaminergic denervation. Whole-genome sequencing revealed a pathogenic SLC6A1 de novo variant. No additional variant was found in any of the genes responsible for Neurodegeneration with Brain Iron Accumulation (NBIA)., Discussion: This is a description of dopaminergic denervation and globus pallidus lesions with iron accumulation related to a SLC6A1 pathogenic variant. These findings expand the phenotype of SLC6A1 -related disorder and suggest that it could be considered as a differential diagnosis of NBIA., Competing Interests: The authors report no relevant disclosures. Go to Neurology.org/NG for full disclosures., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Postoperative apathy is a frequent symptom in Parkinson's disease patients who have undergone bilateral deep brain stimulation of the subthalamic nucleus. Two main hypotheses for postoperative apathy have been suggested: (i) dopaminergic withdrawal syndrome relative to postoperative dopaminergic drug tapering; and (ii) direct effect of chronic stimulation of the subthalamic nucleus. The primary objective of our study was to describe preoperative and 1-year postoperative apathy in Parkinson's disease patients who underwent chronic bilateral deep brain stimulation of the subthalamic nucleus. We also aimed to identify factors associated with 1-year postoperative apathy considering: (i) preoperative clinical phenotype; (ii) dopaminergic drug management; and (iii) volume of tissue activated within the subthalamic nucleus and the surrounding structures. We investigated a prospective clinical cohort of 367 patients before and 1 year after chronic bilateral deep brain stimulation of the subthalamic nucleus. We assessed apathy using the Lille Apathy Rating Scale and carried out a systematic evaluation of motor, cognitive and behavioural signs. We modelled the volume of tissue activated in 161 patients using the Lead-DBS toolbox and analysed overlaps within motor, cognitive and limbic parts of the subthalamic nucleus. Of the 367 patients, 94 (25.6%) exhibited 1-year postoperative apathy: 67 (18.2%) with 'de novo apathy' and 27 (7.4%) with 'sustained apathy'. We observed disappearance of preoperative apathy in 22 (6.0%) patients, who were classified as having 'reversed apathy'. Lastly, 251 (68.4%) patients had neither preoperative nor postoperative apathy and were classified as having 'no apathy'. We identified preoperative apathy score [odds ratio (OR) 1.16; 95% confidence interval (CI) 1.10, 1.22; P < 0.001], preoperative episodic memory free recall score (OR 0.93; 95% CI 0.88, 0.97; P = 0.003) and 1-year postoperative motor responsiveness (OR 0.98; 95% CI 0.96, 0.99; P = 0.009) as the main factors associated with postoperative apathy. We showed that neither dopaminergic dose reduction nor subthalamic stimulation were associated with postoperative apathy. Patients with 'sustained apathy' had poorer preoperative fronto-striatal cognitive status and a higher preoperative action initiation apathy subscore. In these patients, apathy score and cognitive status worsened postoperatively despite significantly lower reduction in dopamine agonists (P = 0.023), suggesting cognitive dopa-resistant apathy. Patients with 'reversed apathy' benefited from the psychostimulant effect of chronic stimulation of the limbic part of the left subthalamic nucleus (P = 0.043), suggesting motivational apathy. Our results highlight the need for careful preoperative assessment of motivational and cognitive components of apathy as well as executive functions in order to better prevent or manage postoperative apathy., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Impulsive-compulsive behaviour (ICB) is a frequently observed non-motor symptom in early Parkinson's disease after initiating dopamine replacement therapy. At the opposite end of the motivated behaviour spectrum, apathy occurs in early Parkinson's disease even before dopamine replacement is started. The co-occurrence of these behavioural conditions in Parkinson's disease raises questions about their relationship and underlying pathophysiological determinants. In previous imaging or genetic studies, both conditions have been associated with the limbic dopaminergic system. The risk variant of the Ser9Gly polymorphism of the dopamine receptor D3 (DRD3) is linked to increased dopamine affinity in the limbic striatum. With this in mind, we investigated how ICB expression is explained by apathy and DRD3 polymorphisms and their effects on grey matter volume and dopamine synthesis capacity. Fifty-four patients with early Parkinson's disease took part in anatomical T1-weighted MRI. Forty of them also underwent dynamic PET imaging using [18F]DOPA to measure striatal dopamine synthesis capacity. Further, Ser9Gly (rs6280) gene polymorphism influencing the DRD3 dopamine-binding affinity was determined in all patients. The severity of impulsive-compulsive behaviour and apathy was assessed using the Questionnaire for Impulsive-Compulsive Disorders Rating Scale and the Apathy Evaluation Scale. ICB and the severity of apathy were indeed positively correlated. Apathy and the DRD3 polymorphism were interactive risk factors for ICB severity. Apathy was significantly linked to atrophy of the bilateral putamen. Patients with the DRD3 risk type had reduced dopamine synthesis capacity in the putamen and limbic striatum, apathy was associated with reduced dopamine synthesis capacity in the limbic striatum. The results of [18F]DOPA reached only trend significance. Apathy in drug-naïve PD patients might be a consequence of impaired striatal dopaminergic tone. This may represent a predisposing factor for the development of ICB after the initiation of dopamine replacement therapy. The risk type of DRD3 could further amplify this predisposition due to its higher affinity to dopamine., (© 2023. The Author(s).)

Background: Impulse control disorders (ICDs) are frequently encountered in Parkinson's disease (PD)., Objectives: We aimed to assess whether clonidine, an α2-adrenergic receptor agonist, would improve ICDs., Methods: We conducted a multicentre trial in five movement disorder departments. Patients with PD and ICDs (n = 41) were enrolled in an 8-week, randomised (1:1), double-blind, placebo-controlled study of clonidine (75 μg twice a day). Randomisation and allocation to the trial group were carried out by a central computer system. The primary outcome was the change at 8 weeks in symptom severity using the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS) score. A reduction of the most elevated subscore of the QUIP-RS of more than 3 points without any increase in the other QUIP-RS dimension defined success., Results: Between 15 May 2019 and 10 September 2021, 19 patients in the clonidine group and 20 patients in the placebo group were enrolled. The proportion difference of success in reducing QUIP-RS at 8 weeks, was 7% (one-sided upper 90% CI 27%) with 42.1% of success in the clonidine group and 35.0% in the placebo group. Compared to patients in the placebo group, patients in the clonidine group experienced a greater reduction in the total QUIP-RS score at 8 weeks (11.0 points vs. 3.6)., Discussion: Clonidine was well tolerated but our study was not enough powerful to demonstrate significant superiority compared to placebo in reducing ICDs despite a greater reduction of total QUIP score at 8 weeks. A phase 3 study should be conducted., Trial Registration: The study was registered (NCT03552068) on clinicaltrials.gov on June 11, 2018., (© 2023. The Author(s).)

The limbic system describes a complex of brain structures central for memory, learning, as well as goal directed and emotional behavior. In addition to pathological studies, recent findings using in vivo structural and functional imaging of the brain pinpoint the vulnerability of limbic structures to neurodegeneration in Parkinson's disease (PD) throughout the disease course. Accordingly, dysfunction of the limbic system is critically related to the symptom complex which characterizes PD, including neuropsychiatric, vegetative, and motor symptoms, and their heterogeneity in patients with PD. The aim of this systematic review was to put the spotlight on neuroimaging of the limbic system in PD and to give an overview of the most important structures affected by the disease, their function, disease related alterations, and corresponding clinical manifestations. PubMed was searched in order to identify the most recent studies that investigate the limbic system in PD with the help of neuroimaging methods. First, PD related neuropathological changes and corresponding clinical symptoms of each limbic system region are reviewed, and, finally, a network integration of the limbic system within the complex of PD pathology is discussed.

In this one-year prospective study, Parkinson's disease (PD) patients with or without mania following STN-DBS were compared to investigate risk and etiological factors, clinical management and consequences. Eighteen (16.2%) out of 111 consecutive PD patients developed mania, of whom 17 were males. No preoperative risk factor was identified. Postoperative mania was related to ventral limbic subthalamic stimulation in 15 (83%) patients, and resolved as stimulation was relocated to the sensorimotor STN, besides discontinuation or reduction of dopamine agonists and use of low-dose clozapine in 12 patients, while motor and nonmotor outcomes were similar. These findings underpin the prominent role of limbic subthalamic stimulation in postoperative mania. ANN NEUROL 2022;92:411-417., (© 2022 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Neurodegenerative parkinsonian disorders are characterized by a great diversity of clinical symptoms and underlying neuropathology, yet differential diagnosis during lifetime remains probabilistic. Molecular imaging is a powerful method to detect pathological changes in vivo on a cellular and molecular level with high specificity. Thereby, molecular imaging enables to investigate functional changes and pathological hallmarks in neurodegenerative disorders, thus allowing to better differentiate between different forms of degenerative parkinsonism, improve the accuracy of the clinical diagnosis and disentangle the pathophysiology of disease-related symptoms. The past decade led to significant progress in the field of molecular imaging, including the development of multiple new and promising radioactive tracers for single photon emission computed tomography (SPECT) and positron emission tomography (PET) as well as novel analytical methods. Here, we review the most recent advances in molecular imaging for the diagnosis, prognosis, and mechanistic understanding of parkinsonian disorders. First, advances in imaging of neurotransmission abnormalities, metabolism, synaptic density, inflammation, and pathological protein aggregation are reviewed, highlighting our renewed understanding regarding the multiplicity of neurodegenerative processes involved in parkinsonian disorders. Consequently, we review the role of molecular imaging in the context of disease-modifying interventions to follow neurodegeneration, ensure stratification, and target engagement in clinical trials.

Heterogeneous immunoassays (HI) are an invaluable tool for biomarker detection and remain an ideal candidate for microfluidic point-of-care diagnostics. However, automating and controlling sustained fluid flow from benchtop to microfluidics for the HI reaction during the extended sample incubation step, remains difficult to implement; this leads to challenges for assay integration and assay result interpretation. To address these issues, we investigated the liquid reciprocation process on a microfluidic centrifugal disc (CD) to generate continuous, bidirectional fluid flow using only a rotating motor. Large volumetric flow rates (μL s -1 ) through the HI reaction chamber were sustained for extended durations (up to 1 h). The CD liquid reciprocation operating behavior was characterized experimentally and simulated to determine fluid flow shear rates through our HI reaction chamber. We demonstrated the continuous CD liquid reciprocation for target molecule incubation for a microarray HI and that higher fluid shear rates negatively influenced our fluorescence intensity. We highlight the importance of proper fluid flow considerations when integrating HIs with microfluidics.

Background: De novo Parkinson's disease (PD) patients with apathy exhibit prominent limbic serotonergic dysfunction and microstructural disarray. Whether this distinctive lesion profile at diagnosis entails different prognosis remains unknown., Objectives: To investigate the progression of dopaminergic and serotonergic dysfunction and their relation to motor and nonmotor impairment in PD patients with or without apathy at diagnosis., Methods: Thirteen de novo apathetic and 13 nonapathetic PD patients were recruited in a longitudinal double-tracer positron emission tomography cohort study. We quantified the progression of presynaptic dopaminergic and serotonergic pathology using [ 11 C]PE2I for dopamine transporter and [ 11 C]DASB for serotonin transporter at baseline and 3 to 5 years later, using linear mixed-effect models and mediation analysis to compare the longitudinal evolution between groups for clinical impairment and region-of-interest-based analysis., Results: After the initiation of dopamine replacement therapy, apathy, depression, and anxiety improved at follow-up in patients with apathy at diagnosis (n = 10) to the level of patients without apathy (n = 11). Patients had similar progression of motor impairment, whereas mild impulsive behaviors developed in both groups. Striato-pallidal and mesocorticolimbic presynaptic dopaminergic loss progressed similarly in both groups, as did serotonergic pathology in the putamen, caudate nucleus, and pallidum. Contrastingly, serotonergic innervation selectively increased in the ventral striatum and anterior cingulate cortex in apathetic patients, contributing to the reversal of apathy besides dopamine replacement therapy., Conclusion: Patients suffering from apathy at diagnosis exhibit compensatory changes in limbic serotonergic innervation within 5 years of diagnosis, with promising evidence that serotonergic plasticity contributes to the reversal of apathy. The relationship between serotonergic plasticity and dopaminergic treatments warrants further longitudinal investigations. © 2022 International Parkinson and Movement Disorder Society., (© 2022 International Parkinson and Movement Disorder Society.)

Depression is one of the most frequent and burdensome non-motor symptoms in Parkinson's disease (PD), across all stages. Even when its severity is mild, PD depression has a great impact on quality of life for these patients and their caregivers. Accordingly, accurate diagnosis, supported by validated scales, identification of risk factors, and recognition of motor and non-motor symptoms comorbid to depression are critical to understanding the neurobiology of depression, which in turn determines the effectiveness of dopaminergic drugs, antidepressants and non-pharmacological interventions. Recent advances using in vivo functional and structural imaging demonstrate that PD depression is underpinned by dysfunction of limbic networks and monoaminergic systems, depending on the stage of PD and its associated symptoms, including apathy, anxiety, rapid eye movement sleep behavior disorder (RBD), cognitive impairment and dementia. In particular, the evolution of serotonergic, noradrenergic, and dopaminergic dysfunction and abnormalities of limbic circuits across time, involving the anterior cingulate and orbitofrontal cortices, amygdala, thalamus and ventral striatum, help to delineate the variable expression of depression in patients with prodromal, early and advanced PD. Evidence is accumulating to support the use of dual serotonin and noradrenaline reuptake inhibitors (desipramine, nortriptyline, venlafaxine) in patients with PD and moderate to severe depression, while selective serotonin reuptake inhibitors, repetitive transcranial magnetic stimulation and cognitive behavioral therapy may also be considered. In all patients, recent findings advocate that optimization of dopamine replacement therapy and evaluation of deep brain stimulation of the subthalamic nucleus to improve motor symptoms represents an important first step, in addition to physical activity. Overall, this review indicates that increasing understanding of neurobiological changes help to implement a roadmap of tailored interventions for patients with PD and depression, depending on the stage and comorbid symptoms underlying PD subtypes and their prognosis., (© 2022. The Author(s).)

Background: Parkinson's disease (PD) is characterized by heterogeneous motor and nonmotor manifestations related to alterations in monoaminergic neurotransmission systems. Nevertheless, the characterization of concomitant dopaminergic and serotonergic dysfunction after different durations of Parkinson's disease, as well as their respective involvement in the expression and severity of neuropsychiatric signs, has gained little attention so far., Methods: To fill this gap, we conducted a cross-sectional study combining clinical and dual-tracer positron emission tomography (PET) neuroimaging approaches, using radioligands of dopamine ([ 11 C]-N-(3-iodoprop-2E-enyl)-2-beta-carbomethoxy-3-beta-(4-methylphenyl)-nortropane) ([ 11 C]PE2I) and serotonin ([ 11 C]-N,N-dimethyl-2-(-2-amino-4-cyanophenylthio)-benzylamine) ([ 11 C]DASB) reuptake, after different durations of Parkinson's disease (ie, in short-disease duration drug-naive de novo (n = 27, 0-2 years-duration), suffering from apathy (n = 14) or not (n = 13); intermediate-disease duration (n = 15, 4-7 years-duration) and long-disease duration, non-demented (n = 15, 8-10 years-duration) patients). Fifteen age-matched healthy subjects were also enrolled., Results: The main findings are threefold: (1) both dopaminergic and serotonergic lesions worsen with the duration of Parkinson's disease, spreading from midbrain/subcortical to cortical regions; (2) the presence of apathy at PD onset is associated with more severe cortical and subcortical serotonergic and dopaminergic disruption, similar to the denervation pattern observed in intermediate-disease duration patients; and (3) the severity of parkinsonian apathy, depression, and trait-anxiety appears primarily related to serotonergic alteration within corticostriatal limbic areas., Conclusions: Altogether, these findings highlight the prominent role of serotonergic degeneration in the expression of several neuropsychiatric symptoms occurring after different durations of Parkinson's disease. © 2021 International Parkinson and Movement Disorder Society., (© 2021 International Parkinson and Movement Disorder Society.)

Terrestrial carnivores are among the most imperiled species worldwide, yet some species are resilient and are recovering in human-dominated landscapes after decades or centuries of absence. Bobcat ( Lynx rufus ) populations were extirpated from much of Midwestern US in the mid-1800's, and are currently expanding and recolonizing their former range. In this study, we investigated multi-scale habitat selection for Ohio's expanding bobcat population, and examined habitat connectivity in order to evaluate the conduits for dispersal statewide. We used citizen observations collected between 1978 and 2019 and logistic regression to evaluate population-level habitat selection, and GPS telemetry data for 20 individuals collected between 2012 and 2014 and a distribution-weighted exponential Resource Selection Function to evaluate individual-level habitat selection within home ranges. At the population level, bobcats selected for higher amounts of forest and pasture (at a 50 km 2 scale) and herbaceous vegetation (at 15-50 50 km 2 scales), thus overall heterogeneous forested habitat. At individual (home range) level, bobcats selected for forested habitats with low road density and farther away from high traffic roads; they also showed weak selection for open habitat at the home range level. Male home ranges were significantly greater than female home ranges. Lastly, we used the population-level spatial outputs ( i.e . habitat suitability map) to parameterize habitat connectivity models using circuit theory in the program Circuitscape. We tested three relationships between habitat suitability and resistance to movement and used a subset of data on potential dispersing individuals to evaluate which relationship performed best. All three relationships performed almost equally well, and we calculated a weighted averaged connectivity map as our final map. Habitat was highly permeable to movements between core areas of two genetically distinct subpopulations located in southeastern Ohio. We also identified potential dispersal corridors from the core areas to other regions of Ohio dominated by agriculture and suburban development via forested riparian corridors. Overall, our analysis offers new information on habitat selection and connectivity in a rebounding felid population and offers important ecological information for wildlife management strategies. We recommend that the suitability and connectivity models should be periodically updated until the population reaches an equilibrium, and be integrated with data from neighboring states for a comprehensive assessment of a conservation success story., Competing Interests: The authors declare that they have no competing interests., (© 2021 Popescu et al.)

Background: Whether structural alterations underpin apathy and depression in de novo parkinsonian patients is unknown. The objectives of this study were to investigate whether apathy and depression in de novo parkinsonian patients are related to structural alterations and how structural abnormalities relate to serotonergic or dopaminergic dysfunction., Methods: We compared the morphological and microstructural architecture in gray matter using voxel-based morphometry and diffusion tensor imaging coupled with white matter tract-based spatial statistics in a multimodal imaging case-control study enrolling 14 apathetic and 13 nonapathetic patients with de novo Parkinson's disease and 15 age-matched healthy controls, paired with PET imaging of the presynaptic dopaminergic and serotonergic systems., Results: De novo parkinsonian patients with apathy had bilateral microstructural alterations in the medial corticostriatal limbic system, exhibiting decreased fractional anisotropy and increased mean diffusivity in the anterior striatum and pregenual anterior cingulate cortex in conjunction with serotonergic dysfunction. Furthermore, microstructural alterations extended to the medial frontal cortex, the subgenual anterior cingulate cortex and subcallosal gyrus, the medial thalamus, and the caudal midbrain, suggesting disruption of long-range nondopaminergic projections originating in the brainstem, in addition to microstructural alterations in callosal interhemispheric connections and frontostriatal association tracts early in the disease course. In addition, microstructural abnormalities related to depressive symptoms in apathetic and nonapathetic patients revealed a distinct, mainly right-sided limbic subnetwork involving limbic and frontal association tracts., Conclusions: Early limbic microstructural alterations specifically related to apathy and depression emphasize the role of early disruption of ascending nondopaminergic projections and related corticocortical and corticosubcortical networks which underpin the variable expression of nonmotor and neuropsychiatric symptoms in Parkinson's disease. © 2019 International Parkinson and Movement Disorder Society., (© 2019 International Parkinson and Movement Disorder Society.)

Roadways pose challenges for conserving wide-ranging animal species. As bobcat (Lynx rufus) populations recover in Ohio, an accurate evaluation of population metrics is critical to understanding future population trajectories. In this study, we integrated multiple datasets to examine overall road mortality rates in Ohio. First, we utilized a long-term vehicle-strike dataset (1978-2017) to determine landscape and local predictors of road mortality. We found that bobcats were killed at higher rates on interstates regardless of surrounding landscape composition, but that landscape variables were useful at predicting mortality on lower-traffic roads. To explore road avoidance behaviors, we used GPS telemetry data from 18 individuals to compare road crossings along trajectory paths with random road crossings simulated using Correlated Random Walks. Bobcats exhibited avoidance of certain route types (county, municipal, and US routes). Finally, by integrating traffic volume data, road crossing behavior, and accounting for the proportion of each route type present in the study area, we estimated that a minimum of 6% and up to 18% of the bobcat population in Ohio is lost to vehicle-strikes annually. To fully understand the population level impacts of this mortality, we recommend further monitoring of age structure and sex of roadkill animals. Our results identify potential areas for mitigation of vehicle-strikes and emphasize the importance of accounting for road mortality when making management decisions for Ohio's recovering bobcat population.

Purpose of Review: To review the advances in structural imaging for the diagnosis, prognosis, and treatment of Parkinson's disease (PD) during the last 5 years., Recent Findings: Structural imaging using high-field MRI (≥ 3 T) and new MR sequences sensitive to iron and nigral pigments have achieved to assess in vivo pathological surrogates useful for PD diagnosis (notably decreased nigral neuromelanin and loss of dorsal nigral hyperintensity, increased nigral iron content, diffusivity, and free-water), prodromal diagnosis (decreased neuromelanin signal in the locus coeruleus), and PD progression (with increasing nigral iron content (increasing R2* rate) and nigral damage (increasing free-water)). Additionally, evaluation of atrophy in small monoaminergic nuclei is useful for prognosis, including cholinergic basal forebrain nuclei atrophy for cognitive impairment. New advances in multimodal structural imaging improve diagnosis, prognosis, and prediction of invasive treatment outcome in PD, and may further benefit from machine learning and large scale longitudinal studies to better identify prognostic subtypes.

The diagnosis of a parkinsonian syndrome based on clinical criteria remains sometimes difficult, especially at disease onset. Brain or heart molecular imaging techniques (SPECT or PET) can provide a major help to improve and speed up diagnosis, influencing treatment strategies. Presynaptic dopaminergic imaging using either [ 18 F]-Dopa PET or 123 I -2β-Carbomethoxy-3β-(4-Iodophenyl)- N-(3-Fluoropropyl) Nortropane ([ 123 I]-Ioflupane)SPECT demonstrates or rules out the presence of a dopaminergic degenerative process. This allows to distinguish Parkinson's disease, Parkinson "plus" syndromes and dementia with Lewy bodies (reduced radiotracers binding) from essential tremor, psychogenic, post-neuroleptic or vascular parkinsonisms, dopa-responsive dystonia and Alzheimer's disease (normal radiotracers binding). For differential diagnosis between Parkinson's disease and Parkinson "plus" syndromes, brain molecular imaging with [ 18 F]-Fluorodeoxyglucose ([ 18 F]-FDG) PET or 99m Tc-HMPAO SPECT can provide useful information, whereas [ 18 F]-Dopa PET or [ 123 I]-Ioflupane does not separate these entities. Finally, sympathetic cardiac [ 123 I]-Metaiodobenzylguanidine ([ 123 I]-MIBG) scintigraphy or SPECT can help distinguishing Parkinson's disease and dementia with Lew bodies (decreased binding) from multiple system atrophy and progressive supranuclear palsy (normal binding). New radiotracers notably those targeting the pathological process itself such as Tau aggregates are under development and may provide interesting informations to delineate the different Parkinson "plus" syndromes., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objective: To determine the time course of hazard for motor and nonmotor milestones of Parkinson disease (PD) in the long term and to investigate whether risk scales nonlinearly with time is instrumental in identifying changes in pathological processes and evaluating disease-modifying therapies in PD., Methods: Outpatients with PD at the Lyon University Movement Disorders Center were evaluated for 7 clinical milestones in this retrospective cohort study, encompassing 4 domains of PD progression: (1) motor (motor fluctuations, dyskinesias); (2) axial (postural instability and falls, freezing of gait); (3) neuropsychiatric (impulse control disorders, hallucinations); and (4) cognitive (dementia) complications. For each complication, we estimated the outcome-specific hazard using parsimonious smooth parametric Poisson regression models allowing for nonlinear scaling over disease duration, age at diagnosis, current age, and their interaction., Results: A total of 1,232 patients with PD experienced 1,527 disease-related complications in up to 12 years of follow-up. Specific to each complication, hazard rates increased dramatically starting from diagnosis and were highest for motor fluctuations and lowest for dementia up to 6 years after diagnosis in patients aged 65 years at diagnosis. Nonlinear patterns indicated dramatic changes in the course of PD after 5 years and predicted more severe axial prognosis after 70 years and for motor fluctuations, dyskinesias, and impulse control disorders before 60 years at diagnosis., Conclusion: Time course of motor and nonmotor milestones in PD is determined by disease duration and age at diagnosis in nonlinear patterns and their interaction. This indicates disease- and age-specific thresholds across the multiple neurodegenerative processes accumulating in PD at different paces., (© 2018 American Academy of Neurology.)

Apathy, depression, and anxiety are among the most important non-motor signs of Parkinson's disease (PD). This may be encountered at early stages of illness and represent a major source of burden. Understanding their pathophysiology is a major prerequisite for efficient therapeutic strategies. Anatomical and metabolic imaging studies have enabled a breakthrough by demonstrating that widespread abnormalities within the limbic circuits notably the orbitofrontal and anterior cingulate cortices, amygdala, thalamus, and ventral striatum are involved in the pathophysiology of depression, anxiety, and apathy in PD. Functional imaging has further shown that mesolimbic dopaminergic but also serotonergic lesions play a major role in the mechanisms of these three neuropsychiatric manifestations, which has direct therapeutic implications.

Role of brain imaging for Parkinsonism T brain MRI is normal in Pakinson's disease. Brain MRI is useless when clinical presentation is typical of idiopathic Parkinson's disease. Brain MRI is the exam of choice for differentiating idiopathic Parkinson's disease and atypical parkinsonism. DATscan* confirms or rules out dopaminergic degeneration but does not separate idiopathic Parkinson's disease from Parkinson "plus" syndromes. FDG PET is helpful to separate idiopathic Parkinson's disease from Parkinson "plus" syndromes., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Mammals often use latrine sites for defecation, yet little is known about patterns of latrine use in many common species such as raccoons (Procyon lotor). Because raccoon latrines are important foci for the transmission of raccoon roundworm (Baylisascaris procyonis), documenting metrics of raccoon latrine use may have public health implications. Although some studies have provided evidence that multiple raccoons visit single latrine sites, exact latrine visitation patterns of raccoons have never been documented. We monitored raccoon latrine usage using proximity-logging collars placed at 15 latrine sites. We found that latrine sites were visited by multiple raccoons (range 1-7), and raccoons visited as many as six latrines during a 2-wk period. No sex differences were found in the number of latrines visited or time spent during visits. We posit that the use of multiple latrine sites by raccoons may lead to the pattern that rates of B. procyonis infection at latrines are greater than infection rates found in individual raccoon fecal samples. This in turn could lead to greater transmission of B. procyonis to paratenic hosts. Our results support the conclusion that raccoon latrines can be major foci for the infection and spread of B. procyonis.

Raccoons are an important vector of rabies and other pathogens. The degree to which these pathogens can spread through a raccoon population should be closely linked to association rates between individual raccoons. Most studies of raccoon sociality have found patterns consistent with low levels of social connectivity within populations, thus the likelihood of direct pathogen transmission between raccoons is theoretically low. We used proximity detecting collars and social network metrics to calculate the degree of social connectivity in an urban raccoon population for purposes of estimating potential pathogen spread. In contrast to previous assumptions, raccoon social association networks were highly connected, and all individuals were connected to one large social network during 15 out of 18 months of study. However, these metrics may overestimate the potential for a pathogen to spread through a population, as many of the social connections were based on relatively short contact periods. To more closely reflect varying probabilities of pathogen spread, we censored the raccoon social networks based on the total amount of time spent in close proximity between two individuals per month. As this time criteria for censoring the social networks increased from one to thirty minutes, corresponding measures of network connectivity declined. These findings demonstrate that raccoon populations are much more tightly connected than would have been predicted based on previous studies, but also point out that additional research is needed to calculate more precise transmission probabilities by infected individuals, and determine how disease infection changes normal social behaviors.

Cytauxzoon felis, a protozoan parasite of wild and domestic felids, is the causative agent of cytauxzoonosis in domestic and some exotic felids in the United States. The bobcat (Lynx rufus) is the natural reservoir for this parasite, but other felids such as Florida panthers (Puma concolor coryii) and domestic cats may maintain long-term parasitemias and serve as reservoirs. Experimentally, two tick species, Dermacentor variabilis and Amblyomma americanum, have demonstrated the ability to transmit C. felis. These two tick species have overlapping distributions throughout much of the southeastern United States. The objective of the current study was to determine the distribution and prevalence of C. felis in free-ranging bobcat populations from 13 states including California, Colorado, Florida, Georgia, Kansas, Kentucky, Missouri, North Carolina, North Dakota, Ohio, Oklahoma, South Carolina, and West Virginia. These states were selected because of differential vector presence; D. variabilis is present in each of these states except for the region of Colorado sampled and A. americanum is currently known to be present only in a subset of these states. Blood or spleen samples from 696 bobcats were tested for C. felis infection by a polymerase chain reaction (PCR) assay which targeted the first ribosomal internal transcribed spacer region (ITS-1). Significantly higher prevalences of C. felis were detected from Missouri (79%, n=39), North Carolina (63%, n=8), Oklahoma (60%, n=20), South Carolina (57%, n=7), Kentucky (55%, n=74), Florida (44%, n=45), and Kansas (27%, n=41) compared with Georgia (9%, n=159), North Dakota (2.4%, n=124), Ohio (0%, n=19), West Virginia (0%, n=37), California (0%, n=26), and Colorado (0%, n=67). In addition to bobcats, seven cougars (Puma concolor) from Georgia, Louisiana, and North Dakota and one serval (Leptailurus serval) from Louisiana were tested for C. felis. Only one cougar from Louisiana was PCR positive, which represents the first report of an infected cougar outside of the Florida panther population. These data also indicate that C. felis is present in North Dakota where infection has not been reported in domestic cats. Based on a nonparametric analysis, prevalence rates were significantly higher in states where there are established populations of A. americanum, which supports recent data on the experimental transmission of C. felis by A. americanum and the fact that domestic cat clinical cases are temporally associated with A. americanum activity. Collectively, these data confirm that bobcats are a common reservoir for C. felis and that A. americanum is likely an epidemiologically important vector., (Copyright © 2010 Elsevier B.V. All rights reserved.)

MHC class III genes are important in immune regulation and inflammation, and the gene products of this region are well conserved between species. Their role in diabetes is, however, unknown. We used islets from NOD mice that lacked expression of both MHC class I and class II molecules to test the effect of class III differences on the injury of transplanted NOD islets. Loss of islet MHC class I was highly protective, while deletion of MHC class II had no benefit on islet survival. However the combined absence of both MHC class I and class II expression by NOD islets resulted in a delayed form of injury, when islets were transplanted to NOD mice. As neither MHC class I or II molecules were expressed by donor islet tissue, these results suggest a previously unrecognized and important contribution of MHC class III differences on islet injury following transplantation.

Aim: The posture of school children was examined in order to establish whether possible differences in clinically normal and insufficient posture can be detected by means of ultrasound topometry., Method: 105 healthy school children (56 female, 49 male) with an average age of 8 years (+/- 0.9) were examined. To classify the children as having sufficient or insufficient posture the Matthiass posture test was used. While the child stood in a relaxed position, the profile of the spine was measured with a topometric digitiser, recording each spinal processus from C7 to L5., Results: 42 children (22 female, 20 male) showed an insufficient posture during the Matthiass test. The topometrically measured angles of kyphosis and lordosis were significantly smaller in these children, corresponding to a clinically greater thoracic kyphosis and lumbar lordosis. No significant differences in the lateral and anterior-posterior trunk deviation, nor in the range of trunk sway in the relaxed standing position could be observed., Conclusion: Using ultrasound topometry, the posture of children with sufficient and insufficient posture can be differentiated by measuring, the angles of kyphosis and lordosis. This quantification could be used for objective monitoring of the posture.

The injury of transplanted islets may occur by both autoimmune and alloimmune processes directed against MHC targets. To examine the role of MHC class I in islet graft injury, we transplanted syngeneic and allogeneic beta2-microglobulin-deficient islets into diabetic nonobese diabetic (NOD) mice. Loss of graft function was observed within 14 days using allogeneic C57BL/6 and BALB/c MHC class I deficient as well as wild-type MHC class I-bearing NOD donor islets. However, islets isolated from MHC class I-deficient NOD mice (NOD-B2 m-/-) survived indefinitely when transplanted under the kidney capsule of diabetic NOD recipients. Transplanted NOD-B2 m-/- islets were surrounded by a nondestructive periinsular infiltrate that expressed interleukin-4 in addition to interferon-gamma. These studies demonstrate the primary role of MHC class I molecules in causing autoimmune destruction or recurrent diabetes in transplanted islets.

Aim: The anteflexion of the spine in normal schoolchildren was examined by 3D real-time ultrasound topometry to see if differences in the form of restrictions of anteflexion could be detected., Methods: 102 schoolchildren at the age of 7 to 9 years volunteered to the study. We measured the spinal anteflexion by recording the row of the spines (C7-L5) in a maximally flexed position with a topometric digitiser. By computer-aided data analysis the curvature of the spinal line was reproduced by lined up radii., Results: In the sagittal plane the spinal line in anteflexed position showed a single curvature in 8 cases. In 94 cases the spinal line was subdivided into three curvatures (X1, X2, X3) with less mobility of the region from the middle to the lower thoracic segments. For these less mobile segments we calculated a mean relative anteflexion (X2/[(X1 + X3)/2]) of 0.36 (+/- 0.18). In seven children (6.8%) with clinically indirect signs of scoliosis the anteflexion was reduced and in 4 cases out of the standard deviation. For the relative anteflexion the Pearson's correlation coefficient of the measurement 1 and the direct control-measurement was 0.86 (p < 0.001)., Conclusion: By ultrasound topometric measurement of the spinal anteflexion in schoolchildren we are able to identify cases with less ability of anteflexion. Because a restriction of anteflexion is discussed in the pathogenesis of idiopathic scoliosis, a follow up of these children seems to be usefully.

Recently there has been increased demand for chemical sensors measuring in-line the concentration of selected substances in complex liquids in order to guarantee a high product quality in the process industry. At present there is a great interest in acoustic sensor systems for concentration measurements. This article presents a new ultrasonic sensor system consisting of a miniaturized multi-sensor arrangement for the comprehensive acoustic characterization of liquid mixtures. The sensor system measures sound velocity, impedance coefficient, attenuation coefficient and temperature.