Multiple system atrophy (MSA) is a sporadic neurodegenerative disease clinically characterized by cerebellar signs, parkinsonism, and autonomic dysfunction. Pathologically, MSA is an ...α-synucleinopathy affecting striatonigral and olivopontocerebellar systems, while neocortical and limbic involvement is usually minimal. In this study, we describe four patients with atypical MSA with clinical features consistent with frontotemporal dementia (FTD), including two with corticobasal syndrome, one with progressive non-fluent aphasia, and one with behavioral variant FTD. None had autonomic dysfunction. All had frontotemporal atrophy and severe limbic α-synuclein neuronal pathology. The neuronal inclusions were heterogeneous, but included Pick body-like inclusions. The latter were strongly associated with neuronal loss in the hippocampus and amygdala. Unlike typical Pick bodies, the neuronal inclusions were positive on Gallyas silver stain and negative on tau immunohistochemistry. In comparison to 34 typical MSA cases, atypical MSA had significantly more neuronal inclusions in anteromedial temporal lobe and limbic structures. While uncommon, our findings suggest that MSA may present clinically and pathologically as a frontotemporal lobar degeneration (FTLD). We suggest that this may represent a novel subtype of FTLD associated with α-synuclein (FTLD-synuclein).
Varicella zoster virus (VZV) vasculopathy and cerebral amyloid angiopathy (CAA) have similar clinical presentations: both affect cerebrovasculature in the elderly, produce hemorrhage, and can have a ...protracted course of cognitive decline and other neurological deficits. The cause of CAA is unknown, but amyloid-beta (Aβ) is found within arterial walls. Recent studies show that VZV induces Aβ and amylin expression and an amyloid-promoting environment. Thus, we determined if VZV was present in CAA-affected arteries.
Two subjects with pathologically-verified CAA were identified postmortem and frontal lobes analyzed by immunohistochemistry for arteries containing VZV, Aβ, and amylin and H&E for pathological changes. VZV antigen detection was confirmed by PCR for VZV DNA in the same region.
In both CAA cases, sections with cerebral arteries containing VZV antigen with corresponding VZV DNA were identified; VZV antigen co-localized with Aβ in media of arteries with histological changes characteristic of CAA. Amylin was also seen in the intima of a VZV-positive artery in the diabetic subject. Not all Aβ-containing arteries had VZV, but all VZV-positive arteries contained Aβ.
VZV antigen co-localized with Aβ in some affected arteries from two CAA cases, suggesting a possible association between VZV infection and CAA.
•VZV vasculopathy and CAA have similar clinical presentations.•VZV vasculopathy and CAA cause cerebrovascular disease (hemorrhage).•VZV antigen and DNA co-localized with some CAA-affected arteries in two cases of CAA•VZV vasculopathy may contribute to CAA pathogenesis through induction of amyloid.
ABSTRACTThis study evaluated the impact of a 4-week mandatory Neurology-Physical Medicine and Rehabilitation (N-PM&R) advanced-core clerkship for fourth-year medical students. The combined clerkship ...encouraged an interdisciplinary and function-based approach to the management of common neurologic, musculoskeletal, and pain complaints. Seventy-three fourth-year medical students participated in the rotation over one year. A survey assessing knowledge and skill set topics was conducted before and after the clerkship. Qualitative feedback regarding the rotation was provided by the students and analyzed. Significant gaps in knowledge and skill sets were identified prior to the clerkship and successfully addressed by combined teaching modalities. These data demonstrate that an integrated N-PM&R clerkship can improve students’ confidence in multiple domains. Integrating PM&R into core clerkships at other medical schools may provide an avenue to address curriculum gaps.
Open data and digital morphology Davies, Thomas G.; Rahman, Imran A.; Lautenschlager, Stephan ...
Proceedings of the Royal Society. B, Biological sciences,
04/2017, Letnik:
284, Številka:
1852
Journal Article
Recenzirano
Odprti dostop
Over the past two decades, the development of methods for visualizing and analysing specimens digitally, in three and even four dimensions, has transformed the study of living and fossil organisms. ...However, the initial promise that the widespread application of such methods would facilitate access to the underlying digital data has not been fully achieved. The underlying datasets for many published studies are not readily or freely available, introducing a barrier to verification and reproducibility, and the reuse of data. There is no current agreement or policy on the amount and type of data that should be made available alongside studies that use, and in some cases are wholly reliant on, digital morphology. Here, we propose a set of recommendations for minimum standards and additional best practice for three-dimensional digital data publication, and review the issues around data storage, management and accessibility.
Frontotemporal dementia (FTD) with inclusion body myopathy and Paget disease of bone (IBMPFD) is a rare, autosomal-dominant disorder caused by mutations in the valosin-containing protein (VCP) gene, ...a member of the AAA-ATPase gene superfamily. The neuropathology associated with sporadic FTD is heterogeneous and includes tauopathies and frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U). However, there is limited information on the neuropathology in IBMPFD. We performed a detailed, systematic analysis of the neuropathologic changes in 8 patients with VCP mutations. A novel pattern of ubiquitin pathology was identified in IBMPFD that was distinct from sporadic and familial FTLD-U without VCP gene mutations. This was characterized by ubiquitin-positive neuronal intranuclear inclusions and dystrophic neurites. In contrast to FTLD-U, only rare intracytoplasmic inclusions were identified. The ubiquitin pathology was abundant in the neocortex, less robust in limbic and subcortical nuclei, and absent in the dentate gyrus. Only rare inclusions were detected with antibodies to VCP and there was no biochemical alteration in the VCP protein. VCP is associated with a variety of cellular activities, including regulation of the ubiquitin-proteasome system. Our findings are consistent with the hypothesis that the pathology associated with VCP gene mutations is the result of impairment of ubiquitin-based degradation pathways.
Abstract Background and aims In previous analyses, we identified three dietary patterns from food frequency questionnaire data among a sample of Yup'ik Alaska Native people living in Southwest ...Alaska: a “subsistence foods” dietary pattern and two market-based dietary patterns “processed foods” and “fruits and vegetables”. In this analysis, we aimed to characterize the association between the dietary patterns and cardiometabolic (CM) risk factors (lipids, blood pressure, glucose, adiposity). Methods and results We used multilevel linear regression to estimate the mean of each CM risk factor, comparing participants in the 4th to the 1st quartile of each dietary pattern (n = 637). Models were adjusted for age, sex, past smoking, current smoking, and physical activity. Mean log triglyceride levels were significantly higher among participants in the 4th compared to the 1st quartile of the processed foods dietary pattern (β = 0.11). Mean HbA1c percent was significantly lower (β = −0.08) and mean diastolic blood pressure (DBP) mm Hg was significantly higher (β = 2.87) among participants in the 4th compared to the 1st quartile of the fruits and vegetables dietary pattern. Finally, mean log triglyceride levels and mean DBP mm Hg were significantly lower among participants in the 4th compared to the 1st quartile of the subsistence foods dietary pattern (β = −0.10 and β = −3.99 respectively). Conclusions We found increased CM risk, as reflected by increased triglycerides, associated with eating a greater frequency of processed foods, and reduced CM risk, as reflected by lower triglycerides and DBP, associated with eating a greater frequency of subsistence foods.
IMPORTANCE: An oral treatment for neovascular age-related macular degeneration would be less burdensome than repeated intravitreous injections. X-82 is an oral tyrosine kinase inhibitor active ...against vascular endothelial growth factor (VEGF) and platelet-derived growth factor. OBJECTIVE: To undertake safety testing of oral X-82 administered for the treatment of neovascular AMD. DESIGN, SETTING, AND PARTICIPANTS: Phase 1, open-label, uncontrolled, dose-escalation study at 5 US retinal clinics between November 2012 and March 2015 (Retina-Vitreous Associates Medical Group, Beverly Hills, California; Blanton Eye Institute, Houston Methodist Hospital, Retina Consultants of Houston, Houston, Texas; New England Retina Associates, Guilford, Connecticut; Elman Retina Group, Baltimore, Maryland; and Retina Research Institute of Texas, Abilene). Thirty-five participants with neovascular age-related macular degeneration, 7 of whom were treatment naive. INTERVENTIONS: Participants received oral X-82 for 24 weeks at 50 mg alternate days (n = 3), 50 mg daily (n = 8), 100 mg alternate days (n = 4), 100 mg daily (n = 10), 200 mg daily (n = 7), and 300 mg daily (n = 3), with intravitreous anti-VEGF therapy using predefined retreatment criteria. Every 4 weeks, participants underwent best-corrected visual acuity measurement, fundus examination, and spectral-domain optical coherence tomography. MAIN OUTCOMES AND MEASURES: The main outcome was adverse events. Other outcomes included visual acuity, central subfield retinal thickness, and number of anti-VEGF injections. RESULTS: Of the 35 participants, the mean age was 76.8 years, 16 were men and 19 were women, and 33 were white and 2 were nonwhite. Of 25 participants (71%) who completed the 24 weeks of X-82 treatment, all except 1 maintained or improved their visual acuity (mean SD, +3.8 9.6 letters). Fifteen participants (60%) required no anti-VEGF injections (mean, 0.68). Mean SD central subfield thickness reduced by −50 97 μm, with 8 participants (all receiving at least 100 mg daily) demonstrating sustained reductions despite no anti-VEGF injections. The most common adverse events attributed to X-82 were diarrhea (n = 6), nausea (n = 5), fatigue (n = 5), and transaminase elevation (n = 4). A dose relationship to the transaminase elevations was not identified; all normalized when X-82 was discontinued. All but 1 were asymptomatic. Ten participants withdrew consent or discontinued prematurely, 6 owing to adverse events attributed to X-82 including leg cramps (n = 2), elevated alanine aminotransferase (n = 2), diarrhea (n = 1), and nausea/anorexia (n = 1). CONCLUSIONS AND RELEVANCE: X-82 can be associated with reversible, elevated liver enzymes; hence, liver function testing is needed to identify those unsuited to treatment. Although 17% of participants discontinued X-82 owing to AEs, those who completed the study had lower than expected anti-VEGF injection rates. Further studies appear justified, with a phase 2 randomized clinical study under way.
Process evaluations can help to optimise the implementation of school-based physical activity interventions. The purpose of this paper is to describe the process evaluation of a school-based ...high-intensity interval training (HIIT) program for older adolescent students, known as Burn 2 Learn (B2L). B2L was evaluated via a cluster randomised controlled trial in 20 secondary schools (10 intervention, 10 control) in New South Wales, Australia. Teachers (
= 22 (55% female)) from the 10 intervention schools, delivered the program over three phases (Phases 1 and 2, 6 months; Phase 3, 6 months) to older adolescent students (
= 337 (50% female); mean ± standard deviation (SD) age = 16.0 ± 0.4 years). Process evaluation data were collected across the 12-month study period. Teachers delivered 2.0 ± 0.8 and 1.7 ± 0.6 sessions/week in Phases 1 and 2 respectively (mean total 25.9 ± 5.2), but only 0.6 ± 0.7 sessions/week in Phase 3. Observational data showed that session quality was high, however heart rate (HR) data indicated that only half of the students reached the prescribed threshold of ≥85% predicted HR
during sessions. Over 80% of teachers reported they intended to deliver the B2L program to future student cohorts. Almost 70% of students indicated they intended to participate in HIIT in the future. Teachers considered the program to be adaptable, and both students and teachers were satisfied with the intervention. B2L was implemented with moderate-to-high fidelity in Phases 1 and 2, but low in Phase 3. Our findings add to the relatively scant process evaluation literature focused on the delivery of school-based physical activity programs.
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