Rivastigmine in Chinese patients with subcortical vascular dementia

Vincent Mok1, Adrian Wong1, Simon Ho2, Thomas Leung1, Wynnie WM Lam2, Ka Sing Wong11Department of Medicine and Therapeutics; 2Department of Radiology and Organ Imaging, The Chinese University of Hong Kong, Shatin, Hong Kong, ChinaBackground: We explored the efficacy and tolerability of rivastigmine among Chinese patients with subcortical vascular dementia.Methods: Forty subjects were randomized to either placebo (n = 20) or rivastigmine (n = 20) in a double-blind 26-week trial. Outcome measures were cognition (mini-mental state examination, frontal assessment battery), neuropsychiatric inventory (NPI), instrumental activities of daily living, clinical dementia rating scale, and adverse events.Results: No statistical significant benefit could be observed in the active group in any of the efficacy measures. A trend favoring active group was observed only in the NPI subscore of irritability (p = 0.066) and aberrant motor behavior (p = 0.068). Withdrawal rate was 30% and 15% in the active and placebo group, respectively.Conclusion: Among Chinese subcortical vascular dementia patients, there was no apparent cognitive benefit associated with use of rivastigmine over the 6 months period. A trend favoring rivastigmine was observed in certain behavioral measures. Rivastigmine was associated with more withdrawals relative to placebo.Keywords: rivastigmine, subcortical vascular dementia, Chines

Hypomethylation of CYP2E1 and DUSP22 Promoters Associated With Disease Activity and Erosive Disease Among Rheumatoid Arthritis Patients.

OBJECTIVE:Epigenetic modifications have previously been associated with rheumatoid arthritis (RA). In this study, we aimed to determine whether differential DNA methylation in peripheral blood cell subpopulations is associated with any of 4 clinical outcomes among RA patients. METHODS:Peripheral blood samples were obtained from 63 patients in the University of California, San Francisco RA cohort (all satisfied the American College of Rheumatology classification criteria; 57 were seropositive for rheumatoid factor and/or anti-cyclic citrullinated protein). Fluorescence-activated cell sorting was used to separate the cells into 4 immune cell subpopulations (CD14+ monocytes, CD19+ B cells, CD4+ naive T cells, and CD4+ memory T cells) per individual, and 229 epigenome-wide DNA methylation profiles were generated using Illumina HumanMethylation450 BeadChips. Differentially methylated positions and regions associated with the Clinical Disease Activity Index score, erosive disease, RA Articular Damage score, Sharp score, medication at time of blood draw, smoking status, and disease duration were identified using robust regression models and empirical Bayes variance estimators. RESULTS:Differential methylation of CpG sites associated with clinical outcomes was observed in all 4 cell types. Hypomethylated regions in the CYP2E1 and DUSP22 gene promoters were associated with active and erosive disease, respectively. Pathway analyses suggested that the biologic mechanisms underlying each clinical outcome are cell type-specific. Evidence of independent effects on DNA methylation from smoking, medication use, and disease duration were also identified. CONCLUSION:Methylation signatures specific to RA clinical outcomes may have utility as biomarkers or predictors of exposure, disease progression, and disease severity

Prevalence and Treatments of Movement Disorders in Prion Diseases: A Longitudinal Cohort Study

BACKGROUND: Prion diseases cause a range of movement disorders involving the cortical, extrapyramidal, and cerebellar systems, and yet there are no large systematic studies of their prevalence, features, associations, and responses to commonly used treatments. OBJECTIVES: We sought to describe the natural history and pharmacological management of movement disorders in prion diseases. METHODS: We studied the serial examination findings, investigation results, and symptomatic treatment recorded for 700 patients with prion diseases and 51 mimics who had been enrolled onto the prospective longitudinal National Prion Monitoring Cohort study between 2008 and 2020. We performed an analysis to identify whether there were patterns of movement disorders associated with disease aetiology, PRNP codon 129 polymorphism, disease severity rating scales, magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) findings. RESULTS: Gait disturbances, myoclonus, and increased tone are the most frequently observed movement disorders in patients with prion diseases. The typical pattern of early motor dysfunction involves gait disturbance, limb ataxia, impaired smooth pursuit, myoclonus, tremor, and increased limb tone. Disturbances of gait, increased tone, and myoclonus become more prevalent and severe as the disease progresses. Chorea, alien limb phenomenon, and nystagmus were the least frequently observed movement disorders, with these symptoms showing spontaneous resolution in approximately half of symptomatic patients. Disease severity and PRNP codon 129 polymorphism were associated with different movement disorder phenotypes. Antiepileptics and benzodiazepines were found to be effective in treating myoclonus. CONCLUSIONS: We describe the prevalence, severity, evolution, treatment, and associated features of movement disorders in prion diseases based on a prospective cohort study. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Diagnosing Sporadic Creutzfeldt-Jakob Disease by the Detection of Abnormal Prion Protein in Patient Urine

IMPORTANCE: Creutzfeldt-Jakob disease (CJD) is a fatal neurodegenerative disorder associated with the accumulation of infectious abnormal prion protein through a mechanism of templated misfolding. A recent report has described the detection of abnormal prion protein in the urine of patients with variant CJD (vCJD) using protein misfolding by cyclic amplification, which was apparently absent in the more common sporadic form of CJD (sCJD). A noninvasive diagnostic test could improve early diagnosis of sCJD and, by screening donations, mitigate the potential risks of prion transmission through human urine–derived pharmaceuticals. Here, we describe the adaptation of the direct detection assay, developed originally as a blood test for vCJD, for the detection of disease-associated prion protein in urine samples from patients with sCJD. OBJECTIVE: To determine the feasibility of sCJD diagnosis by adaptation of an established vCJD diagnostic blood test to urine. DESIGN, SETTINGS AND PARTICIPANTS: This retrospective, cross-sectional study included anonymized urine samples from healthy nonneurological control individuals (n = 91), patients with non-prion neurodegenerative diseases (n = 34), and patients with prion disease (n = 37) of which 20 had sCJD. Urine samples obtained during the Medical Research Council PRION-1 Trial, the National Prion Monitoring Cohort Study, and/or referred to the National Prion Clinic or Dementia Research Centre at the National Hospital for Neurology and Neurosurgery in the United Kingdom. MAIN OUTCOMES AND MEASURES: Presence of sCJD infection determined by an assay that captures, enriches, and detects disease-associated prion protein isoforms. RESULTS: A total of 162 samples were analyzed, composed of 91 normal control individuals (51 male, 33 female, and 7 not recorded), 34 neurological disease control individuals (19 male and 15 female), and 37 with prion disease (22 male and 15 female). The assay’s specificity for prion disease was 100% (95% CI, 97%-100%), with no false-positive reactions from 125 control individuals, including 34 from a range of neurodegenerative diseases. In contrast to a previous study, which used a different method, sensitivity to vCJD infection was low (7.7%; 95% CI, 0.2%-36%), with only 1 of 13 patients with positive test results, while sensitivity to sCJD was unexpectedly high at 40% (95% CI, 19%-64%). CONCLUSIONS AND RELEVANCE: We determined 40% of sCJD urine sample results as positive. To our knowledge, this is the first demonstration of an assay that can detect sCJD infection in urine or any target analyte outside of the central nervous system. Urine detection could allow the development of rapid, molecular diagnostics for sCJD and has implications for other neurodegenerative diseases where disease-related assemblies of misfolded proteins might also be present in urine

In vitro characterization of bionanocomposites with green silver nanoparticles: A step towards sustainable wound healing materials

This study investigated the characterization, antifungal activity, and biocompatibility of green agar/silver and collagen/silver bionanocomposite films for wound healing and cell growth scaffolds. Silver nanoparticles (AgNPs) are known for their antimicrobial properties, but their toxicity and harsh synthesis limit their applications. To address this, green‐synthesized AgNPs G‐AgNPs were incorporated into agar/collagen suspensions at specific concentrations and three different G‐AgNP‐agar and two different G‐AgNP‐col bionanocomposite films were produced. Nanoparticle homogeneity and film quality were characterized through SEM analysis. Mechanical properties were tested using a uniaxial tensile tester, revealing that the bioplastic control samples exhibited UTS of 3.86 MPa compared to 0.60 MPa for collagen, a 6‐fold improvement. Viable cell metabolic activity derived from MTT assay showed that Col‐4%AgNPs and Bio‐30%AgNPs had a 42.9% and 51.6% increase in net metabolic activity respectively compared to control on day 4. Fluorescence microscopy confirmed enhanced cell adhesion and proliferation in G‐AgNP‐incorporated samples. Antifungal properties were evaluated against Cladosporium spores, able to cause severe diseases when in contact with human skins, following ISO 16869:2008 standards. The demonstrated unique properties and tunability of G‐AgNPs bionanocomposites can be employed in a variety of specialties for wound‐healing applications, to improve rate and quality of healing while reducing the risk of infection

Use of Cannabis as a Harm Reduction Strategy Among People Who Use Drugs: A Cohort Study.

Introduction: While substance use contributes to a substantial burden of disease, access to evidence-based harm reduction interventions remains limited or inaccessible. Preliminary research suggests that some individuals use cannabis to reduce the harms associated with their use of other substances, including opioids and stimulants. This study examines factors associated with the self-reported use of cannabis for harm reduction among people who use drugs (PWUD). Methods: We drew data from three prospective, community-recruited cohorts of PWUD in Vancouver, Canada, between June 2016 and May 2018. Multivariable generalized linear mixed-effects modeling was used to examine factors associated with the primary outcome of use of cannabis for harm reduction, defined as self-reported use of cannabis to substitute for other substances, treat withdrawal, or come down off other drugs. Results: One thousand nine hundred thirty-six participants contributed 5706 observations. In adjusted analyses, daily methamphetamine use (adjusted odds ratio [AOR]=1.43, 95% confidence interval [CI]: 1.09-1.89), experiencing barriers to accessing addiction treatment (AOR=1.92, 95% CI: 1.21-3.03), and enrollment in addiction treatment modalities other than opioid agonist therapy (AOR=1.64, 95% CI: 1.17-2.29) were positively associated with using cannabis for harm reduction. Older age was negatively associated (AOR=0.97, 95% CI: 0.95-0.98). Among 1281 (66.2%) participants who use cannabis, daily cannabis use and obtaining cannabis from unregulated dispensaries were also independent correlates of using cannabis for harm reduction. Discussion and Conclusions: Individuals who were more likely to use cannabis for harm reduction reported difficulty accessing addiction treatment or used substances, such as methamphetamines, where effective treatments are limited. These findings highlight the need to better understand the potential harm-reducing impacts of cannabis among PWUD in these scenarios

Reflectance anisotropy of Gd5Si2Ge2 and Tb5Si2.2Ge1.8

Reflectance difference (RD) spectra for the a–b plane of the single crystals of Gd5Si2Ge2and b–c planes of Gd5Si2Ge2 and Tb5Si2.2Ge1.8 were obtained in the photon energy range of 1.5–5.5 eV. Several peaks were observed for these crystals in the measured spectrum range. Similar features were observed in the RD spectra for the b–c planes ofGd5Si2Ge2 and Tb5Si2.2Ge1.8, while different features were observed for the a–b plane and b–c plane of Gd5Si2Ge2. The RD spectra for the crystals arise not only from the surface anisotropy but also from the bulk anisotropy due to the monoclinic structure of the bulk crystal

Spectroscopic ellipsometry study of optical anisotropy in Gd5Si2Ge2 and comparison with reflectance difference spectra

The complex dielectric functions of single crystals of Gd5Si2Ge2 were obtained using spectroscopic ellipsometry (SE) in the photon energy range of 1.5–5.0 eV at room temperature. Reflectance difference (RD) spectra for the a‐b and b‐c planes of single crystals of Gd5Si2Ge2 were derived from these dielectric functions and compared to those obtained from reflectance difference spectroscopy (RDS) at near-normal incidence. The two experimental RD spectra from SE and RDS agreed well. The in-plane optical anisotropy of the sample is mainly due to intrinsic bulk properties because of its larger magnitude (4×10−2) compared to surface-induced optical anisotropies, with a magnitude of only about 10−3 for a typical cubic material

Reliability and Validity of the Monitored Functional Task Evaluation (MFTE) for Patients with Chronic Obstructive Pulmonary Disease (COPD)

This article describes the development of a new functional measure — the Monitored Functional Task Evaluation (MFTE) — a symptom-limited evaluation that is used to measure the functional performance of an individual with chronic obstructive pulmonary disease (COPD), and to document a client's physiological changes through repeated testing. Stage I of the study included developing the content validity of the instrument. Stage II consisted of establishing the performance profile, test-retest and inter-rater reliability using a convenience sample of 27 inpatients and outpatients who had COPD. In stage III, the criterion-related and discriminative validity of the instrument was verified in a retrospective sample of 124 inpatients and day patients who had COPD. Results indicated that there was high intra- and inter-rater reliability for the total score of MFTE. Significant correlation of the MFTE was found with parameters such as Moser's Activities of Daily Living (ADL) class, COPD disability class, 6-minute walking distance, work capacity in terms the ratio of the metabolic rate associated with a given activity to the resting metabolic rate, and the fatigue dimension of the Chronic Respiratory Disease Questionnaire. In addition, prediction of group membership to Moser's ADL class revealed that 52.4% of the original grouped cases could be correctly classified by the MFTE alone. In conclusion, the MFTE is a useful measure to evaluate functional performance as well as document physiological changes in patients with moderate-to-severe COPD from both conceptual and empirical perspectives