The HOPE4MCI study: AGB101 treatment slows progression of entorhinal cortex atrophy in ε4 non-carriers with mild cognitive impairment due to Alzheimer's disease.

Introduction: Hippocampal hyperactivity is a hallmark of prodromal Alzheimer's disease (AD) that predicts progression in patients with amnestic mild cognitive impairment (aMCI). AGB101 is an extended-release formulation of levetiracetam in the dose range previously demonstrated to normalize hippocampal activity and improve cognitive performance in aMCI. The HOPE4MCI study was a 78-week trial to assess the progression of MCI due to AD.

Piezoelectric stimulation enhances bone regeneration in alveolar bone defects through metabolic reprogramming of macrophages.

Immunomodulation has emerged as a promising strategy for promoting bone regeneration. However, designing osteoimmunomodulatory biomaterial that can respond to mechanical stress in the unique microenvironment of alveolar bone under continuous occlusal stress remains a significant challenge. Herein, a wireless piezoelectric stimulation system, namely, piezoelectric hydrogel incorporating BaTiO nanoparticles (BTO NPs), is successfully developed to generate piezoelectric potentials for modulating macrophage reprogramming.

Benign paroxysmal positional vertigo: A case report in which four wrongs made a right.

Repositioning maneuvers for benign paroxysmal positional vertigo (BPPV) designed to induce otoconial movement in one canal can trigger and sometimes unwittingly treat BPPV in other canals. Patients with BPPV are best managed by precisely diagnosing the canal variant and using correctly performed, standardized testing and treatment maneuvers.

Relevance of antinuclear antibody in diagnosis and characteristics of multiple sclerosis.

Background: Criteria for multiple sclerosis (MS) diagnosis rely upon clinical and paraclinical data that are supportive of MS in the absence of a better explanation. Patients referred for consideration of a MS diagnosis often undergo an extensive serologic workup including antinuclear antibody (ANA) testing, even when an individual already meets diagnostic criteria for MS. It is unclear whether ANA serostatus is associated with clinical outcomes in MS.

The HOPE4MCI study: A randomized double-blind assessment of AGB101 for the treatment of MCI due to AD.

Introduction: In addition to the accumulation of amyloid plaques and neurofibrillary tangles, the presence of excess neural activity is a pathological hallmark of Alzheimer's disease (AD) and a prognostic indicator for progression of AD pathology and clinical/cognitive worsening in mild cognitive impairment due to Alzheimer's disease (MCI due to AD). The HOPE4MCI clinical study tested the efficacy of a therapeutic with demonstrated ability to normalize heightened neural activity in the hippocampus in a randomized controlled trial of 78 weeks duration in patients with MCI due to AD.

Methods: One hundred and sixty-four participants were randomized to placebo ( = 83) or AGB101 ( = 81), an extended-release formulation of low dose (220 mg) levetiracetam.

Quantifying Induced Nystagmus Using a Smartphone Eye Tracking Application (EyePhone).

Background: There are ≈5 million annual dizziness visits to US emergency departments, of which vestibular strokes account for over 250 000. The head impulse, nystagmus, and test of skew eye examination can accurately distinguish vestibular strokes from peripheral dizziness. However, the eye-movement signs are subtle, and lack of familiarity and difficulty with recognition of abnormal eye movements are significant barriers to widespread emergency department use.

Rationale and Design of the mTECH-Rehab Randomized Controlled Trial: Impact of a Mobile Technology Enabled Corrie Cardiac Rehabilitation Program on Functional Status and Cardiovascular Health.

Background: Cardiac rehabilitation (CR) is an evidence-based, guideline-recommended intervention for patients recovering from a cardiac event, surgery or procedure that improves morbidity, mortality, and functional status. CR is traditionally provided in-center, which limits access and engagement, most notably among underrepresented racial and ethnic groups due to barriers including cost, scheduling, and transportation access. This study is designed to evaluate the Corrie Hybrid CR, a technology-based, multicomponent health equity-focused intervention as an alternative to traditional in-center CR among patients recovering from a cardiac event, surgery, or procedure compared with usual care alone.

Advancing Cardiovascular Health Equity Globally Through Digital Technologies.

Cardiovascular diseases (CVDs) remain the leading cause of death and disability worldwide. Digital health technologies are important public health interventions for addressing the burden of cardiovascular disease. In this article, we discuss the importance of translating digital innovations in research-funded projects to low-resource settings globally to advance global cardiovascular health equity.

An Empirical Comparison of Commonly Used Universal Rating Scales for Dystonia.

Background: There are several widely used clinical rating scales for documenting the severity and distribution of various types of dystonia.

Objectives: The goal of this study was to evaluate the performance of the most commonly used scales in a large group of adults with the most common types of isolated dystonia.

Methods: Global Dystonia Rating Scale (GDRS) and the Burke-Fahn-Marsden Dystonia Rating Scale (BFM) scores were obtained for 3067 participants.

Toward a human brain extracellular vesicle atlas: Characteristics of extracellular vesicles from different brain regions, including small RNA and protein profiles.

Extracellular vesicles (EVs) are released from different cell types in the central nervous system (CNS) and play roles in regulating physiological and pathological functions. Although brain-derived EVs (bdEVs) have been successfully collected from brain tissue, there is not yet a "bdEV Atlas" of EVs from different brain regions. To address this gap, we separated EVs from eight anatomical brain regions of a single individual and subsequently characterized them by count, size, morphology, and protein and RNA content.

Acoustic Noise Levels in High-field Magnetic Resonance Imaging Scanners.

7-Tesla (T) magnetic resonance imaging may allow for higher resolution images but may produce greater acoustic noise than 1.5- and 3-T scanners. We sought to characterize the intensity of acoustic noise from 7- versus 3-T scanners.

Timing of cognitive effects on afterdischarge termination.

Objective: We previously studied efficacy of cognitive tasks on afterdischarge termination in patients undergoing cortical stimulation and found that diffuse wavelet cross-coherence changes on electrocorticography were associated with termination efficacy. We now report wavelet cross-coherence findings during different time segments of trials during which afterdischarges ended.

Methods: For 12 patients with implanted subdural electrodes, we compared wavelet cross-coherence findings among several 1-second portions of cognitive tasks, reflecting task presentation, patient replies, and afterdischarge termination.

Vitamin D status and latitude predict brain lesions in adrenoleukodystrophy.

Objectives: Approximately 40% of boys with X-linked adrenoleukodystrophy (ALD) develop inflammatory demyelinating brain lesions (cerebral ALD, cALD) and are at risk for death or severe disability. Risk factors for cALD are poorly understood. Our objective was to evaluate whether vitamin D status, which influences immune function, is associated with risk for cALD.

An exploratory study of sleep quality and quantity in children with causal variants in SYNGAP1, an autism risk gene.

Study Objectives: Sleep disturbances are reported in 62% of children with SYNGAP1-Intellectual Disability (SYNGAP1-ID), a rare neurodevelopmental disorder characterized by intellectual disability, epilepsy, autism spectrum disorder (ASD), sensory and behavioral challenges. Although Children's Sleep Habits Questionnaire (CSHQ) scores are elevated in children with SYNGAP1-ID factors that predict sleep disturbance are not well understood. The goal of this study is to identify predictors of sleep problems.

Longitudinal CSF Alzheimer's disease biomarker changes from middle age to late adulthood.

Introduction: We examined longitudinal cerebrospinal fluid (CSF) Alzheimer's disease (AD) biomarker changes among cognitively normal individuals with 10.7 years follow-up, on average.

Methods: Analyses included 278 participants ( age = 57.

Large-scale production of extracellular vesicles: Report on the "massivEVs" ISEV workshop.

Extracellular vesicles (EVs) large-scale production is a crucial point for the translation of EVs from discovery to application of EV-based products. In October 2021, the International Society for Extracellular Vesicles (ISEV), along with support by the FET-OPEN projects, "The Extracellular Vesicle Foundry" (evFOUNDRY) and "Extracellular vesicles from a natural source for tailor-made nanomaterials" (VES4US), organized a workshop entitled "massivEVs" to discuss the potential challenges for translation of EV-based products. This report gives an overview of the topics discussed during "massivEVs", the most important points raised, and the points of consensus reached after discussion among academia and industry representatives.

Association of Vascular Properties With the Brain White Matter Hyperintensity in Middle-Aged Population.

Background The periventricular white matter is more sensitive to the systemic hemodynamic alterations than the deep white matter because of differences in its vascular structure and systemic circulation relationship. We hypothesize that periventricular white matter hyperintensity (PVWMH) volume shows greater association than deep white matter hyperintensity (DWMH) volume with vascular properties (VPs) reflecting arterial stiffness and cardiovascular remodeling, indicators of the systemic circulation. Methods and Results A total of 426 participants (age, 59.

Current Guidelines for Classifying and Diagnosing Cervical Dystonia: Empirical Evidence and Recommendations.

Background: The dystonias are phenotypically and etiologically heterogenous disorders. Many proposals and a consensus recommendation have been provided for the diagnosis and classification of the dystonias, but these recommendations serve only as general guidelines. Current diagnosis and classification may still depend on clinical judgment causing different opinions.

Characterization of extracellular vesicles and synthetic nanoparticles with four orthogonal single-particle analysis platforms.

We compared four orthogonal technologies for sizing, counting, and phenotyping of extracellular vesicles (EVs) and synthetic particles. The platforms were: single-particle interferometric reflectance imaging sensing (SP-IRIS) with fluorescence, nanoparticle tracking analysis (NTA) with fluorescence, microfluidic resistive pulse sensing (MRPS), and nanoflow cytometry measurement (NFCM). EVs from the human T lymphocyte line H9 (high CD81, low CD63) and the promonocytic line U937 (low CD81, high CD63) were separated from culture conditioned medium (CCM) by differential ultracentrifugation (dUC) or a combination of ultrafiltration (UF) and size exclusion chromatography (SEC) and characterized by transmission electron microscopy (TEM) and Western blot (WB).

Uniform data set language measures for bvFTD and PPA diagnosis and monitoring.

Introduction: The Frontotemporal Lobar Degeneration Module (FTLD-MOD) includes a neuropsychological battery designed to assess the clinical features of FTLD, although much is unknown about its utility. We investigated FTLD-MOD and Uniform Data Set 3.0 (UDS) language tests for differential diagnosis and disease monitoring.

Common Medications and Intracerebral Hemorrhage: The ARIC Study.

Background Antiplatelets, anticoagulants, and statins are commonly prescribed for various indications. The associations between these medications and the risk of intracerebral hemorrhage (ICH) and cerebral microbleeds (CMBs) are unclear. Methods and Results We performed a retrospective study of the ARIC (Atherosclerosis Risk in Communities) study cohort, recruited from 4 US communities in 1987 to 1989 with follow-up.

Comprehensive evaluation of methods for small extracellular vesicles separation from human plasma, urine and cell culture medium.

One of the challenges that restricts the evolving extracellular vesicle (EV) research field is the lack of a consensus method for EV separation. This may also explain the diversity of the experimental results, as co-separated soluble proteins and lipoproteins may impede the interpretation of experimental findings. In this study, we comprehensively evaluated the EV yields and sample purities of three most popular EV separation methods, ultracentrifugation, precipitation and size exclusion chromatography combined with ultrafiltration, along with a microfluidic tangential flow filtration device, Exodisc, in three commonly used biological samples, cell culture medium, human urine and plasma.

Apathy and Anxiety in De Novo Parkinson's Disease Predict the Severity of Motor Complications.

Background: Neuropsychiatric and affective symptoms are prevalent in prodromal and clinical Parkinson's disease (PD). Some evidence suggests that they may also signify risk for motor complications (motor fluctuations and dyskinesias) of dopamine replacement therapy (DRT).

Objective: To determine whether neuropsychiatric symptoms present in de novo PD (ie, before DRT initiation) predict the severity of eventual motor complications of DRT.