Changes in biomarker levels of Alzheimer's disease (AD) reflect underlying pathophysiological changes in the brain and can provide evidence of direct and downstream treatment effects linked to disease modification. Recent results from clinical trials of anti-amyloid β (Aβ) treatments have raised the question of how to best characterize the relationship between AD biomarkers and clinical endpoints. Consensus methodology for assessing such relationships is lacking, leading to inconsistent evaluation and reporting.
View Article and Find Full Text PDFIntroduction: Tau-positron emission tomography (PET) outcome data of patients with Alzheimer's disease (AD) cannot currently be meaningfully compared or combined when different tracers are used due to differences in tracer properties, instrumentation, and methods of analysis.
Methods: Using head-to-head data from five cohorts with tau PET radiotracers designed to target tau deposition in AD, we tested a joint propagation model (JPM) to harmonize quantification (units termed "CenTauR" [CTR]). JPM is a statistical model that simultaneously models the relationships between head-to-head and anchor point data.
Background And Objectives: Sensitive, reliable, and scalable biomarkers are needed to accelerate the development of therapies for Parkinson disease (PD). In this study, we evaluate the biomarkers of early PD diagnosis, disease progression, and treatment effect collected in the SPARK.
Methods: Cinpanemab is a human-derived monoclonal antibody binding preferentially to aggregated forms of extracellular α-synuclein.
J Opioid Manag
February 2024
Introduction: Although many drugs are implicated in the crisis, opioids and concomitant sedatives are associated with increased overdose risk in both rural and urban communities. Individuals in rural areas are up to 5-fold more likely to experience adverse outcomes related to opioids. The primary objective of this study was to evaluate concomitant use of opioid and benzodiazepine prescriptions in Texas, compare metropolitan and rural differences, and use these data to inform clinicians and to help develop harm reduction strategies.
View Article and Find Full Text PDFImportance: The biological processes that underlie the association of neighborhood environment with chronic diseases, such as cancer, remain poorly understood.
Objective: To determine whether differences in breast tissue DNA methylation are associated with neighborhood deprivation among Black and White women with breast cancer.
Design, Setting, And Participants: This cross-sectional study collected breast tissue from women undergoing surgery for breast cancer between January 1, 1993, and December 31, 2003.
Importance: Accumulation of hyperphosphorylated, tangled microtubule-associated protein tau (MAPT) is a pathological hallmark of Alzheimer disease (AD) associated with disease progression and cognitive decline.
Objective: To evaluate the effect of tau synthesis reduction on tau biomarkers in patients with mild AD.
Design, Setting, And Participants: This randomized clinical trial was a double-blind, placebo-controlled 36-week multiple-ascending dose (MAD) phase 1b trial (October 2017 to September 2020), followed by a 64- or 71-week open-label long-term extension (LTE) (October 2019 to May 2022).
Background: A large epidemic, such as that observed with SARS-CoV-2, seriously challenges available hospital capacity, and this would be augmented by infection of healthcare workers (HCW). Bacillus Calmette-Guérin (BCG) is a vaccine against tuberculosis, with protective non-specific effects against other respiratory tract infections in vitro and in vivo. Preliminary analyses suggest that regions of the world with existing BCG vaccination programs have lower incidence and mortality from COVID-19.
View Article and Find Full Text PDFPremise: Sample preparation in genomics is a critical step that is often overlooked in molecular workflows and impacts the success of downstream genetic applications. This study explores the use of a recently developed focused ultrasound extraction (FUSE) technique to enable the rapid release of DNA from plant tissues for genetic analysis.
Methods: FUSE generates a dense acoustic cavitation bubble cloud that pulverizes targeted tissue into acellular debris.
Tissue fragility, skin hyperextensibility and joint hypermobility are defining characteristics of Ehlers-Danlos syndrome (EDS). Human EDS is subclassified into fourteen types including dermatosparactic EDS, characterized by extreme skin fragility and caused by biallelic mutations. We report two novel, variants in DNA from EDS-affected dogs.
View Article and Find Full Text PDFBackground: Aggregated α-synuclein plays an important role in Parkinson's disease pathogenesis. Cinpanemab, a human-derived monoclonal antibody that binds to α-synuclein, is being evaluated as a disease-modifying treatment for Parkinson's disease.
Methods: In a 52-week, multicenter, double-blind, phase 2 trial, we randomly assigned, in a 2:1:2:2 ratio, participants with early Parkinson's disease to receive intravenous infusions of placebo (control) or cinpanemab at a dose of 250 mg, 1250 mg, or 3500 mg every 4 weeks, followed by an active-treatment dose-blinded extension period for up to 112 weeks.
Non-manifesting carriers (NMCs) of Parkinson's disease (PD)-related mutations such as LRRK2 and GBA are at an increased risk for developing PD. Dopamine transporter (DaT)-spectral positron emission computed tomography is widely used for capturing functional nigrostriatal dopaminergic activity. However, it does not reflect other ongoing neuronal processes; especially in the prodromal stages of the disease.
View Article and Find Full Text PDFBackground: Dopamine transporter single-photon emission computed tomography (DaT-SPECT) can quantify the functional integrity of the dopaminergic nerve terminals and has been suggested as an imaging modality to verify the clinical diagnosis of Parkinson's disease (PD). Depending on the stage of progression, approximately 5-15% of participants clinically diagnosed with idiopathic PD have been observed in previous studies to have normal DaT-SPECT patterns. However, the utility of DaT-SPECT in enhancing early PD participant selection in a global, multicenter clinical trial of a potentially disease-modifying therapy is not well understood.
View Article and Find Full Text PDFMyelofibrosis (MF) is the deadliest form of myeloproliferative neoplasm (MPN). The JAK inhibitor Ruxolitinib can reduce constitutional symptoms but it does not substantially improve bone marrow fibrosis. Pim1 expression is significantly elevated in MPN/MF hematopoietic progenitors.
View Article and Find Full Text PDFObjective: T1-weighted MRI images are commonly used for volumetric assessment of brain structures. Magnetization prepared 2 rapid gradient echo (MP2RAGE) sequence offers superior gray (GM) and white matter (WM) contrast. This study aimed to quantitatively assess the agreement of whole brain tissue and deep GM (DGM) volumes obtained from MP2RAGE compared to the widely used MP-RAGE sequence.
View Article and Find Full Text PDFCancer is the second leading cause of death worldwide despite major advancements in diagnosis and therapy over the past century. One of the most debilitating aspects of cancer is the burden brought on by metastatic disease. Therefore, an ideal treatment protocol would address not only debulking larger primary tumors but also circulating tumor cells and distant metastases.
View Article and Find Full Text PDFBackground And Purpose: A prior study found a link between post-stroke blood-brain barrier disruption and functional outcomes. The current study aimed to replicate this finding in a cohort of patients recruited in the context of a randomized clinical trial.
Methods: The ACTION trial was a study of natalizumab in acute stroke patients.
Background: Development of reliable and accurate imaging biomarkers of dopaminergic cell neurodegeneration is necessary to facilitate therapeutic drug trials in Parkinson's disease (PD). Neuromelanin-sensitive MRI techniques have been effective in detecting neurodegeneration in the substantia nigra pars compacta (SNpc). The objective of the current study was to investigate longitudinal neuromelanin signal changes in the SNpc in PD patients.
View Article and Find Full Text PDFChanges in resting-state functional connectivity (rs-FC) under general anesthesia have been widely studied with the goal of identifying neural signatures of consciousness. This work has commonly revealed an apparent fragmentation of whole-brain network structure during unconsciousness, which has been interpreted as reflecting a break-down in connectivity and a disruption of the brain's ability to integrate information. Here we show, by studying rs-FC under varying depths of isoflurane-induced anesthesia in nonhuman primates, that this apparent fragmentation, rather than reflecting an actual change in network structure, can be simply explained as the result of a global reduction in FC.
View Article and Find Full Text PDFPurpose: The opioid crisis is devastating rural America, but findings of opioid utilization vary among previous studies. Previous studies were focused on misuse behaviors or overdose issues. This study will focus on the number of pills and prescriptions that rural and urban adults received.
View Article and Find Full Text PDFBackground: Clinical series have been published using the configuration of 2 intercarpal Kirschner wires (K-wires) adjacent to the fracture being connected, but biomechanical analysis is lacking. The objective of this pilot biomechanical study was to model and compare the effects of externally connecting 2 intermetacarpal K-wires for the stabilization of transverse metacarpal shaft fractures. Our research hypothesis was that the connected constructs would be stiffer than the unconnected K-wires.
View Article and Find Full Text PDFPurpose: This study (i) investigates the effect of recovery power (Prec) and duration (trec) on the recovery of the curvature constant (W') of the power-duration relationship, (ii) compares the experimentally measured W' balance to that predicted (W'bal) by two models (SK2 and BAR), and (iii) presents a case of real-time performance optimization using the critical power (CP) concept.
Methods: Seven competitive amateur cyclists performed a ramp test to determine their V˙O2peak and gas exchange threshold, two to four 3-min all-out tests to determine CP and W', and nine intermittent cycling tests to investigate W' recovery. The intermittent cycling tests involved a 2-min constant work-rate interval above CP, followed by a constant work-rate recovery interval below CP (Prec and trec were varied), followed by a 3-min all-out interval.
General anesthetics are routinely used to induce unconsciousness, and much is known about their effects on receptor function and single neuron activity. Much less is known about how these local effects are manifest at the whole-brain level nor how they influence network dynamics, especially past the point of induced unconsciousness. Using resting-state functional magnetic resonance imaging (fMRI) with nonhuman primates, we investigated the dose-dependent effects of anesthesia on whole-brain temporal modular structure, following loss of consciousness.
View Article and Find Full Text PDFJ Clin Orthop Trauma
September 2019
Background: Fractures of lateral condyle of humerus are very common in children. While the management of acute displaced and rotated lateral condyle fracture of humerus with early open reduction and internal fixation yields good results, the results of late treatment are less clear. We conducted this study to analyse the results of operative treatment of late presenting fractures and see if it is dependent on the patient's age, fracture type, or the time until treatment.
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