Basic Science and Pathogenesis.

Background: New methods developed to estimate when AD biomarkers became abnormal in individuals have shown considerable heterogeneity in amyloid and tau pathology onset age. This work used polygenic scores (PGS) generated from CSF Aβ and ptau GWAS, individual-level genetic data, and estimated tau onset age (ETOA) to identify genetic influences on tau onset beyond APOE.

Method: Participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) with genetic data, CSF biomarkers (Aβ and ptau), and longitudinal [F]Flortaucipir (FTP) tau PET were analyzed (N = 462).

Basic Science and Pathogenesis.

Background: "SuperAgers" are older adults (ages 80+) whose cognitive performance resembles that of adults in their 50s to mid-60s. Factors underlying their exemplary aging are underexplored in large, racially diverse cohorts. Using eight cohorts, we investigated the frequency of APOE genotypes in SuperAgers compared to middle-aged and older adults.

Basic Science and Pathogenesis.

Background: Cognitive decline is often influenced by Alzheimer's disease (AD) pathology (e.g., beta-amyloid burden) and other pathology (e.

Basic Science and Pathogenesis.

Background: DNA microarray-based studies report differentially methylated positions (DMPs) in blood between cognitively unimpaired persons (CU) and persons with late-onset dementia due to Alzheimer's disease (AD) or Mild Cognitive Impairment (MCI) but interrogate less than 4% of the human genome. Whole genome methylation sequencing (WGMS) quantifies DNA methylation levels across the entire human genome (>25 million CpG loci). Using WGMS, we previously reported 28,038 DMPs within 2,707 genes between persons with and without AD.

Clinical Manifestations.

Background: Sensitive screening for early Alzheimer's disease (AD)-related cognitive decline are needed. Prior research links high beta-amyloid (Aβ) levels to reduced proper name (PN) retrieval in individuals without cognitive impairment. We examined whether language-related regional tau from PET associated with Logical Memory (LM) proper name recall, accounting for LM covariates.

Clinical Manifestations.

Background: Mild behavioral impairment (MBI) is associated with all-cause dementia. Little is known about MBI's effects on cognitive function among individuals in earlier disease stages, particularly in racially diverse samples. We examined relationships between MBI and cognitive decline in a richly characterized sample of white and African American (AA) older-middle aged adults.

Clinical Manifestations.

Background: The Clinical Dementia Rating Scale (CDR) is a gold standard metric for staging the nature and severity of global cognitive and functional impairment in Alzheimer's disease (AD) and other dementias. Prior evidence from older and/or smaller samples suggests that The Quick Dementia Rating System (QDRS) informant questionnaire provides results comparable to the CDR and can be completed in just 3-5 minutes, sans a trained clinician or rater. This study aimed to: 1) investigate concordance between the QDRS-derived global CDR ("QDRS-global"; Galvin, 2015) and CDR-global scores; 2) examine item-level QDRS/CDR agreement; and (3) evaluate QDRS-global/CDR-global concordant/discordant groups against concurrent Preclinical Alzheimer's Cognitive Composite (PACC3) performance.

Clinical Manifestations.

Background: Frequent and remote cognitive assessment may improve sensitivity to subtle cognitive decline associated with preclinical Alzheimer's disease (AD). Our objective was to evaluate the feasibility, reliability, and construct validity of repeated remote memory assessment in late middle-aged and older adults.

Method: Participants were recruited from longitudinal aging cohorts to complete medial temporal lobe-based memory paradigms (Object-In-Room Recall [ORR], Mnemonic Discrimination for Objects and Scenes [MDT-OS], Complex Scene Recognition [CSR]) using the neotiv application on a smartphone or tablet at repeated intervals over one year.

Clinical Manifestations.

Background: Frequent and remote cognitive assessment may improve sensitivity to subtle cognitive decline associated with preclinical Alzheimer's disease (AD). However, repeated testing can result in unintended inflation of scores, due to practice effects. The objective of this study is to evaluate the extent of sessions with non-identical stimuli on performance and determine if study design or amyloid PET status moderates the impact of practice.

Clinical Manifestations.

Background: Each year, millions of Americans experience mild traumatic brain injury (mTBI). Current research on the long-term effects of mTBI vary considerably. Several mechanisms linking mTBI to dementia have been proposed including amyloid plaque formation and cerebrovascular injury following mTBI.

Clinical Manifestations.

Background: The Uniform Data Set (UDS) neuropsychological battery, administered across Alzheimer's Disease Centers (ADC), includes memory tests but lacks a list-learning paradigm. ADCs often supplement the UDS with their own preferred list-learning task. Given the importance of list-learning for characterizing memory, we aimed to develop a harmonized memory score that incorporates UDS memory tests while allowing centers to contribute differing list-learning tasks.

Clinical Manifestations.

Background: Older women accumulate more pathological tau than older men in the early stages of Alzheimer's disease (AD). However, the cognitive effects of early tau deposition may be obscured in women given their superior performance on verbal memory tests, which are commonly used in diagnosing AD. Visuospatial memory may more accurately reflect early tau burden in older women due to less apparent sex differences.

Motivations for obtaining advance provision of medication abortion in the United States: a qualitative study.

Background: Advance provision of medication abortion, or the prescription of mifepristone and misoprostol before pregnancy occurs, is an unexplored care model aimed at expanding abortion access. We examine motivations for obtaining advance provision from the online telemedicine service, Aid Access, which supports people in the United States.

Methods: Between May and November 2023, we conducted semi-structured, in-depth interviews with 39 people who obtained advance provision between January 2022 and April 2023.

Current Trends in Remote and Flexible Work Options in Radiology and Perception of Impact on Radiologist Well-being.

Objective: This study aims to assess the current trends in remote and flexible work models in radiology, evaluate their perceived impact on radiologists' well-being, and explore the importance of these options in shaping employment decisions.

Methods: A voluntary, anonymous survey was sent to 981 members of the Association of Academic Radiologists (AAR) in April 2024. Descriptive statistics were used to analyze demographics and trends in remote and flexible work participation.

Do the provisional PRINTO Enthesitis/Spondylitis-Related JIA criteria capture youth with axial spondyloarthritis?

Background: The Paediatric Rheumatology International Trials Organisation (PRINTO) recently undertook an effort to better harmonize the pediatric and adult arthritis criteria. These provisional criteria are being refined for optimal performance. We aimed to investigate differences between patients who did and did not fulfill these PRINTO criteria amongst youth diagnosed with juvenile spondyloarthritis (SpA) that met axial juvenile SpA (axJSpA) classification criteria.

Performance of study partner reports in a non-demented at-risk sample.

Introduction: The Clinical Dementia Rating (CDR) Scale is a gold standard for staging impairment in Alzheimer's disease and other dementias (ADRD). The Quick Dementia Rating System (QDRS) offers similar results in 3 to 5 minutes without a trained clinician. This study aimed to (1) investigate concordance between comparably derived QDRS and CDR global scores, (2) examine item-level QDRS/CDR agreement, and (3) compare sample characteristics and cognitive performance across QDRS/CDR global concordant/discordant groups.

Multicohort Analysis of Bronchial Epithelial Cell Expression in Healthy Subjects and Patients with Asthma Reveals Four Clinically Distinct Clusters.

Asthma is a heterogeneous disease with variable presentation and characteristics. There is a critical need to identify underlying molecular endotypes of asthma. We performed the largest transcriptomic analysis of 808 bronchial epithelial cell (BEC) samples across 11 independent cohorts, including 3 cohorts from the Severe Asthma Research Program (SARP).

Female Pelvic Conditions: Interstitial Cystitis/Bladder Pain Syndrome.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a likely underdiagnosed chronic pain syndrome consisting of pelvic pain lasting longer than 6 weeks plus lower urinary tract symptoms in the absence of infection or other identifiable cause. It is more common after 40 years of age. The etiology is unclear, but some patients have inflammatory findings in the bladder known as Hunner lesions.

Female Pelvic Conditions: Sexually Transmitted Infections.

Sexually transmitted infection rates are increasing in the United States, with significant increases in the rates of syphilis among patients of reproductive age and, subsequently, congenital syphilis. Syphilis screening is recommended in sexually active patients 15 to 44 years of age in communities with high syphilis rates and in all pregnant patients at the time of diagnosis or prenatal intake, in the third trimester, and at delivery. Screening for chlamydia and gonorrhea is currently recommended in asymptomatic, sexually active patients younger than 25 years, as well as in older patients with risk factors.

Female Pelvic Conditions: Dyspareunia and Vulvodynia.

Genito-pelvic pain/penetration disorder is a relatively new term encompassing both dyspareunia (recurrent pain with intercourse) and vaginismus (involuntary contraction of the pelvic floor with attempted penetration). Symptoms are often multifactorial. Thus, a detailed history and sensitive patient-centered examination are essential to identify and treat the underlying cause(s).

Non-conventional toxin WTX and its disulfide-fixed synthetic fragments: Interaction with nicotinic acetylcholine receptors and reduction of blood pressure.

Non-conventional snake venom toxins, such as WTX from the cobra Naja kaouthia, are three-finger proteins containing a fifth disulfide bond in the N-terminal polypeptide loop I and inhibiting α7 and muscle-type nicotinic acetylcholine receptors (nAChRs). Because the central polypeptide loop II of non-conventional toxins plays an important role in their biological activity, we synthesized several WTX loop II fragments with two cysteine residues added at the N- and C-termini and oxidized to form a disulfide bond. The inhibition by peptides of several nAChRs subtypes was investigated using different methods and the effects of peptides on the rat arterial pressure and heart rate were analyzed.

Comparison of Race-neutral Versus Race-specific Spirometry Equations for Evaluation of Child Asthma.

Rationale: Race-based estimates of pulmonary function in children could influence the evaluation of asthma in children from racial and ethnic minoritized backgrounds.

Objectives: To determine if race-neutral (GLI-Global) versus race-specific (GLI-Race-Specific) reference equations differentially impact spirometry evaluation of childhood asthma.

Methods: The analysis included 8,719 children aged 5 to <12 years from 27 cohorts across the United States grouped by parent-reported race and ethnicity.

Estimation of Cancer Deaths Averted From Prevention, Screening, and Treatment Efforts, 1975-2020.

Importance: Cancer mortality has decreased over time, but the contributions of different interventions across the cancer control continuum to averting cancer deaths have not been systematically evaluated across major cancer sites.

Objective: To quantify the contributions of prevention, screening (to remove precursors [interception] or early detection), and treatment to cumulative number of cancer deaths averted from 1975 to 2020 for breast, cervical, colorectal, lung, and prostate cancers.

Design, Setting, And Participants: In this model-based study using population-level cancer mortality data, outputs from published models developed by the Cancer Intervention and Surveillance Modeling Network were extended to quantify cancer deaths averted through 2020.