Gray Matter Pathology in MS: A 3-Year Longitudinal Study in a Pediatric Population

RESULTS: At T0, GMf did not differ between cMS and NC (P .18), while it was lower in patients with aMS compared with both NCs (P .001) and patients with cMS (P .001). The number of patients with CLs, as well as CL number and volume, were higher in patients with aMS than in those with cMS (P .001). At T3, -GMf was higher in both patients with cMS (1.6% 0.5%; range 0.7%–3.4%; P .001) and aMS (1.6% 0.6%; range 0.6%–3.4%; P .001) compared with NCs (0.7% 0.2%; range 0.4%–1.1%), whereas no difference was observed between patients with cMS and aMS (P .93). -GMf significantly correlated with increased CL volume (cMS: r 0.46; aMS: r 0.48) and with the appearance of new CLs (cMS: r 0.51; aMS: r 0.49). CONCLUSIONS: Our findings suggest that focal (CLs) and diffuse (atrophy) GM damage are strictly associated with the biologic onset of MS, and proceed linearly and partly independently of WM pathology. ABBREVIATIONS: aMS adult-onset multiple sclerosis; CL cortical lesion; cMS childhoodonset multiple sclerosis; EDSS Expanded Disability Status Scale; GM gray matter; GMf gray matter fraction; -GMf delta gray matter fraction; -GMf_1 delta gray matter fraction at T1; -GMf_2 delta gray matter fraction at T2; -GMf_3 delta gray matter fraction at T3; NC healthy control; T0 baseline; T2WMLV T2 white matter lesion volum

Life in harsh environments : carabid and spider trait types and functional diversity on a debris-covered glacier and along its foreland

1. Patterns of species richness and species assemblage composition of ground-dwelling arthropods in primary successions along glacier forelands are traditionally described using a taxonomic approach. On the other hand, the functional trait approach could ensure a better characterisation of their colonisation strategies in these types of habitat. 2. The functional trait approach was applied to investigate patterns of functional diversity and life-history traits of ground beetles and spiders on an alpine debris-covered glacier and along its forefield in order to describe their colonisation strategies. 3. Ground beetles and spiders were sampled at different successional stages, representing five stages of deglaciation. 4. The results show that the studied glacier hosts ground beetle and spider assemblages that are mainly characterised by the following traits: walking colonisers, ground hunters and small-sized species. These traits are typical of species living in cold, wet, and gravelly habitats. The diversity of functional traits in spiders increased along the succession, and in both carabids and spiders, life-history traits follow the \u2018addition and persistence model\u2019. Accordingly, there is no turnover but there is an addition of new traits and a variation in their proportion within each species assemblage along the succession. The distribution of ground beetles and spiders along the glacier foreland and on the glacier seems to be driven by dispersal ability and foraging strategy. 5. The proposed functional approach improves knowledge of the adaptive strategies of ground-dwelling arthropods colonising glacier surfaces and recently deglaciated terrains, which represent landforms quickly changing due to global warming

Development and Validation of Automated Magnetic Resonance Parkinsonism Index 2.0 to Distinguish Progressive Supranuclear Palsy-Parkinsonism From Parkinson's Disease

Background: Differentiating progressive supranuclear palsy-parkinsonism (PSP-P) from Parkinson's disease (PD) is clinically challenging. Objective: This study aimed to develop an automated Magnetic Resonance Parkinsonism Index 2.0 (MRPI 2.0) algorithm to distinguish PSP-P from PD and to validate its diagnostic performance in two large independent cohorts. Methods: We enrolled 676 participants: a training cohort (n = 346; 43 PSP-P, 194 PD, and 109 control subjects) from our center and an independent testing cohort (n = 330; 62 PSP-P, 171 PD, and 97 control subjects) from an international research group. We developed a new in-house algorithm for MRPI 2.0 calculation and assessed its performance in distinguishing PSP-P from PD and control subjects in both cohorts using receiver operating characteristic curves. Results: The automated MRPI 2.0 showed excellent performance in differentiating patients with PSP-P from patients with PD and control subjects both in the training cohort (area under the receiver operating characteristic curve [AUC] = 0.93 [95% confidence interval, 0.89–0.98] and AUC = 0.97 [0.93–1.00], respectively) and in the international testing cohort (PSP-P versus PD, AUC = 0.92 [0.87–0.97]; PSP-P versus controls, AUC = 0.94 [0.90–0.98]), suggesting the generalizability of the results. The automated MRPI 2.0 also accurately distinguished between PSP-P and PD in the early stage of the diseases (AUC = 0.91 [0.84–0.97]). A strong correlation (r = 0.91, P < 0.001) was found between automated and manual MRPI 2.0 values. Conclusions: Our study provides an automated, validated, and generalizable magnetic resonance biomarker to distinguish PSP-P from PD. The use of the automated MRPI 2.0 algorithm rather than manual measurements could be important to standardize measures in patients with PSP-P across centers, with a positive impact on multicenter studies and clinical trials involving patients from different geographic regions. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Do Underwriters Matter? The Impact of the Near Loss of an Equity Underwriter

The financial crisis provides a natural experiment for testing theoretical predictions of the equity underwriter's role following an initial public offering. Clients of Bear Stearns, Lehman Brothers, Merrill Lynch, and Wachovia saw their stock prices fall almost 5 percent, on average, on the day it appeared that their equity underwriter might collapse. Representing a loss in equity value of more than $3 billion, the decline was more than 1 percent lower than the conditional return predicted by a market model. The price impact was worse for companies with more opaque operations and fewer monitors, suggesting that underwriters play an important role in monitoring newly public companies. There is no evidence that the abnormal price decrease was related to the role of the underwriter as market maker or lender

Protocol of a prospective study on the diagnostic value of transcranial duplex scanning of the substantia nigra in patients with parkinsonian symptoms

<p>Abstract</p> <p>Background</p> <p>Parkinson's disease (PD) is the second most common neurodegenerative disorder. As there is no definitive diagnostic test, its diagnosis is based on clinical criteria. Recently transcranial duplex scanning (TCD) of the substantia nigra in the brainstem has been proposed as an instrument to diagnose PD. We and others have found that TCD scanning of substantia nigra duplex is a relatively accurate diagnostic instrument in patients with parkinsonian symptoms. However, all studies on TCD so far have involved well-defined, later-stage PD patients, which will obviously lead to an overestimate of the diagnostic accuracy of TCD.</p> <p>We have therefore set out to conduct a prospective study testing the diagnostic accuracy of TCD in patients with a parkinsonism of unclear origin.</p> <p>Methods/Design</p> <p>We will enrol 250 consecutive patients, who are referred to neurology outpatient clinics of two teaching hospitals, for analysis of clinically unclear parkinsonism. Patients, whose parkinsonism is clearly diagnosable at the first visit, will be excluded from the study. All patients will undergo a TCD of the substantia nigra. As a surrogate gold standard we will use the consensus clinical diagnosis reached by two independent, blinded, movement disorder specialist neurologists after 2 years follow-up. At the time of TCD, patients will also undergo a SPECT scan of the brain.</p> <p>Discussion</p> <p>As this prospective trial enrols only patients with an early-stage parkinsonism, it will yield data on the diagnostic accuracy of TCD that is relevant to daily clinical practice: The neurologist needs a diagnostic tool that provides additional information in patients with a clinically indefinable parkinsonian syndrome. The above described observational longitudinal study was designed to explicitly study this aspect in the diagnostic process.</p> <p>Trial registration</p> <p><b>(ITRSCC) NCT00368199</b></p

Potential of Macrostomum lignano to recover from γ-ray irradiation

Stem cells are the only proliferating cells in flatworms and can be eliminated by irradiation with no damage to differentiated cells. We investigated the effect of fractionated irradiation schemes on Macrostomum lignano, namely, on survival, gene expression, morphology and regeneration. Proliferating cells were almost undetectable during the first week post-treatment. Cell proliferation and gene expression were restored within 1 month in a dose-dependent manner following exposure to up to 150 Gy irradiation. During recovery, stem cells did not cross the midline but were restricted within lateral compartments. An accumulated dose of 210 Gy resulted in a lethal phenotype. Our findings demonstrate that M. lignano represents a suitable model system for elucidating the effect of irradiation on the stem cell system in flatworms and for improving our understanding of the recovery potential of severely damaged stem-cell systems

The role of high-field magnetic resonance imaging in parkinsonian disorders: Pushing the boundaries forward

Historically, magnetic resonance imaging (MRI) has contributed little to the study of Parkinson's disease (PD), but modern MRI approaches have unveiled several complementary markers that are useful for research and clinical applications. Iron- and neuromelanin-sensitive MRI detect qualitative changes in the substantia nigra. Quantitative MRI markers can be derived from diffusion weighted and iron-sensitive imaging or volumetry. Functional brain alterations at rest or during task performance have been captured with functional and arterial spin labeling perfusion MRI. These markers are useful for the diagnosis of PD and atypical parkinsonism, to track disease progression from the premotor stages of these diseases and to better understand the neurobiological basis of clinical deficits. A current research goal using MRI is to generate time-dependent models of the evolution of PD biomarkers that can help understand neurodegeneration and provide reliable markers for therapeutic trials. This article reviews recent advances in MRI biomarker research at high-field (3T) and ultra high field-imaging (7T) in PD and atypical parkinsonism.For information regarding funding, please visit the publisher's website

COPPADIS-2015 (COhort of Patients with PArkinson's DIsease in Spain, 2015), a global--clinical evaluations, serum biomarkers, genetic studies and neuroimaging--prospective, multicenter, non-interventional, long-term study on Parkinson's disease progressio

Background: Parkinson?s disease (PD) is a progressive neurodegenerative disorder causing motor and non-motor symptoms that can affect independence, social adjustment and the quality of life (QoL) of both patients and caregivers. Studies designed to find diagnostic and/or progression biomarkers of PD are needed. We describe here the study protocol of COPPADIS-2015 (COhort of Patients with PArkinson?s DIsease in Spain, 2015), an integral PD project based on four aspects/concepts: 1) PD as a global disease (motor and non-motor symptoms); 2) QoL and caregiver issues; 3) Biomarkers; 4) Disease progression.Methods/design: Observational, descriptive, non-interventional, 5-year follow-up, national (Spain), multicenter (45 centers from 15 autonomous communities), evaluation study. Specific goals: (1) detailed study (clinical evaluations, serum biomarkers, genetic studies and neuroimaging) of a population of PD patients from different areas of Spain, (2) comparison with a control group and (3) follow-up for 5 years. COPPADIS-2015 has been specifically designed to assess 17 proposed objectives. Study population: approximately 800 non-dementia PD patients, 600 principal caregivers and 400 control subjects. Study evaluations: (1) baseline includes motor assessment (e.g., Unified Parkinson?s Disease Rating Scale part III), non-motor symptoms (e.g., Non-Motor Symptoms Scale), cognition (e.g., Parkinson?s Disease Cognitive Rating Scale), mood and neuropsychiatric symptoms (e.g., Neuropsychiatric Inventory), disability, QoL (e.g., 39-item Parkinson?s disease Quality of Life Questionnaire Summary-Index) and caregiver status (e.g., Zarit Caregiver Burden Inventory); (2) follow-up includes annual (patients) or biannual (caregivers and controls) evaluations. Serum biomarkers (S-100b protein, TNF-?, IL-1, IL-2, IL-6, vitamin B12, methylmalonic acid, homocysteine, uric acid, C-reactive protein, ferritin, iron) and brain MRI (volumetry, tractography and MTAi [Medial Temporal Atrophy Index]), at baseline and at the end of follow-up, and genetic studies (DNA and RNA) at baseline will be performed in a subgroup of subjects (300 PD patients and 100 control subjects). Study periods: (1) recruitment period, from November, 2015 to February, 2017 (basal assessment); (2) follow-up period, 5 years; (3) closing date of clinical follow-up, May, 2022. Funding: Public/Private. Discussion: COPPADIS-2015 is a challenging initiative. This project will provide important information on the natural history of PD and the value of various biomarkers