Enhancing quality of care for older adults: The age-friendly health system (4Ms framework) and the role of general medicine physicians as system-based complexologists.

The aging population presents critical challenges to global healthcare systems, with Japan expected to have 35% of its population aged 65 or older by 2040. Older adults often experience multimorbidity, cognitive impairments, and physical frailties, increasing healthcare utilization and costs. Traditional medical approaches that focus on organ-specific diagnoses are insufficient for addressing these multifaceted needs.

Relationship between physical activity and biomarkers of pathology and neuroinflammation in preclinical autosomal-dominant Alzheimer's disease.

Objective: Physical activity (PA) has been linked to reduced Alzheimer's disease (AD) risk. However, less is known about its effects in the AD preclinical stage. We aimed to investigate whether greater PA was associated with lower plasma biomarkers of AD pathology, neural injury, reactive astrocytes, and better cognition in individuals with autosomal-dominant AD due to the presenilin-1 E280A mutation who are virtually guaranteed to develop dementia.

Generalizability of consensus regarding standardized letters of evaluation competitiveness: A validity study in a national sample of emergency medicine faculty.

Background: Standardized letters of evaluation (SLOEs) are an important part of residency recruitment, particularly given the limited availability of other discerning factors in residency applications. While consensus regarding SLOE competitiveness has been studied within a small group of academic faculty, it remains unexplored how a more diverse group of letter readers interpret SLOEs in terms of competitiveness.

Methods: A sample of 50 real SLOEs in the new SLOE format (2022 eSLOE 2.

ChatG-PD? Comparing large language model artificial intelligence and faculty rankings of the competitiveness of standardized letters of evaluation.

Background: While faculty have previously been shown to have high levels of agreement about the competitiveness of emergency medicine (EM) standardized letters of evaluation (SLOEs), reviewing SLOEs remains a highly time-intensive process for faculty. Artificial intelligence large language models (LLMs) have shown promise for effectively analyzing large volumes of data across a variety of contexts, but their ability to interpret SLOEs is unknown.

Objective: The objective was to evaluate the ability of LLMs to rate EM SLOEs on competitiveness compared to faculty consensus and previously developed algorithms.

Endoscopic diagnosis of asymptomatic appendicitis in a pediatric patient.

Incidental diagnosis of asymptomatic appendicitis is exceptionally rare, even more so when identified endoscopically. This is among the first reported cases of appendicitis incidentally diagnosed during colonoscopy in a pediatric patient. Most notably, the identification of subclinical appendicitis allowed for early referral to pediatric surgery for management, which in turn may have prevented progression to acute symptomatic appendicitis.

A stretchable, electroconductive tissue adhesive for the treatment of neural injury.

Successful nerve repair using bioadhesive hydrogels demands minimizing tissue-material interfacial mechanical mismatch to reduce immune responses and scar tissue formation. Furthermore, it is crucial to maintain the bioelectrical stimulation-mediated cell-signaling mechanism to overcome communication barriers within injured nerve tissues. Therefore, engineering bioadhesives for neural tissue regeneration necessitates the integration of electroconductive properties with tissue-like biomechanics.

Quantitative pulmonary perfusion in acute pulmonary embolism and chronic thromboembolic pulmonary hypertension.

Current methods for quantifying perfusion from computed tomography pulmonary angiography (CTPA) often rely on semi-quantitative scoring systems and requires an experienced evaluator. Few studies report on absolute quantitative variables derived from the images, and the methods are varied with mixed results. Dual-energy CTPA (DE-CTPA) enables automatic quantification of lung and lobar perfusion with minimal user interaction by utilizing machine learning based software.

AAV-mouse DNase I sustains long-term DNase I expression in vivo and suppresses breast cancer metastasis.

Neutrophil extracellular traps (NETs) have been implicated in the pathology of various inflammatory conditions. In cancer, NETs have been demonstrated to induce systemic inflammation, impair peripheral vessel and organ function and promote metastasis. Here we show that the plasma level of NETs is significantly higher in patients with metastatic breast cancer compared to those with local disease, or those that were considered cured at a 5-year follow-up, confirming NETs as interesting therapeutic targets in metastatic breast cancer.

Faculty consensus on competitiveness for the new competency-based emergency medicine standardized letter of evaluation.

Background: Emergency medicine (EM) has introduced a new, competency-based standardized letter of evaluation (SLOE) template. While a previous version of the SLOE has been shown to promote a high degree of faculty consensus regarding competitiveness, this has not been shown for the new SLOE template.

Objective: The objective was to evaluate faculty consensus on competitiveness for the new EM SLOE 2.

Genetically proxied IL-6 signaling and risk of Alzheimer's disease and lobar intracerebral hemorrhage: A drug target Mendelian randomization study.

Introduction: Evidence suggests that higher C-reactive protein (CRP) is associated with lower risk of Alzheimer's disease (AD) and lobar intracerebral hemorrhage (ICH). Whether interleukin (IL)-6 signaling, an active pharmacological target upstream of CRP, is associated with these amyloid-related pathologies remains unknown.

Methods: We used 26 CRP-lowering variants near the IL-6 receptor gene to perform Mendelian randomization analyses for AD (111,326 cases, 677,663 controls) and ICH (1545 cases, 1481 controls).

Alcohol use is associated with intracranial hemorrhage in older emergency department head trauma patients.

Objectives: Falls are common in adults aged 65 years and older and are the leading cause of traumatic brain injuries in this age group. Alcohol use may increase the risk of falls as well as the severity of resultant injuries. The aim of this study was to examine the association between self-reported alcohol use and the prevalence of intracranial hemorrhage (ICH) in this patient group.

Amyloid beta-independent sleep markers associated with early regional tau burden and cortical thinning.

Introduction: Sleep is crucial for memory consolidation and the clearance of toxic proteins associated with Alzheimer's disease (AD). We examined the association between sleep characteristics and imaging biomarkers of early amyloid beta (Aβ) and tau pathology as well as neurodegeneration in brain regions known to be affected in the incipient stages of AD.

Methods: Thirty-nine cognitively unimpaired (CU) participants of the Harvard Aging Brain Study underwent at-home polysomnography as well as tau positron emission tomography (flortaucipir-PET), amyloid PET (Pittsburgh compound B [PiB]-PET), and magnetic resonance imaging-derived assessment of cortical thickness (CT).

Trafficking through the blood-brain barrier is directed by core and outer surface components of layer-by-layer nanoparticles.

Drug-carrying nanoparticles are a promising strategy to deliver therapeutics into the brain, but their translation requires better characterization of interactions between nanomaterials and endothelial cells of the blood-brain barrier (BBB). Here, we use a library of 18 layer-by-layer electrostatically assembled nanoparticles (NPs) to independently assess the impact of NP core and surface materials on in vitro uptake, transport, and intracellular trafficking in brain endothelial cells. We demonstrate that NP core stiffness determines the magnitude of transport, while surface chemistry directs intracellular trafficking.

Pragmatism and feasibility: A qualitative study of experiences implementing and upgrading care in geriatric emergency departments.

Objectives: Implementation and sustainability of new care processes in emergency departments (EDs) is difficult. We describe experiences of implementing geriatric care processes in EDs that upgraded their accreditation level for the Geriatric Emergency Department Accreditation (GEDA) program. These EDs can provide a model for adopting and sustaining guidelines for evidence-based geriatric care.

Immune profiling of responses to influenza vaccination in patients with myeloproliferative neoplasms.

Myeloproliferative neoplasms (MPNs) are associated with immune dysregulation and increased susceptibility to infection, emphasizing the importance of vaccination for patients. This pilot study evaluated immune responses to influenza vaccination in MPN patients compared with healthy donors using mass cytometry and serology. We observed diminished CXCR5+ B-cell, CXCR3+ T-cell, activated CD127+ memory T-cell subsets, and a trend toward lower hemagglutinin inhibition titer in MPN patients.

"Right now, it's kind of haphazard"-Pediatric emergency care coordinators and quality of emergency care for children: A qualitative study.

Objectives: Pediatric readiness varies widely among emergency departments (EDs). The presence of a pediatric emergency care coordinator (PECC) has been associated with improved pediatric readiness and decreased mortality, but adoption of PECCs has been limited. Our objective was to understand factors associated with PECC implementation in general EDs.

Plasma NEDD9 is increased following SARS-CoV-2 infection and associates with indices of pulmonary vascular dysfunction.

Compared to healthy volunteers, participants with post-acute sequelae of SARS-CoV-2 infection (PASC) demonstrated increased plasma levels of the prothrombotic protein NEDD9, which associated inversely with indices of pulmonary vascular function. This suggests persistent pulmonary vascular dysfunction may play a role in the pathobiology of PASC.

Longitudinal associations of apathy and regional tau in mild cognitive impairment and dementia: Findings from the Alzheimer's Disease Neuroimaging Initiative.

Introduction: It is important to study apathy in Alzheimer's disease (AD) to better understand its underlying neurobiology and develop effective interventions. In the current study, we sought to examine the relationships between longitudinal apathy and regional tau burden in cognitively impaired older adults from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database.

Methods: Three hundred and nineteen ADNI participants with mild cognitive impairment (MCI) or AD dementia underwent flortaucipir (FTP) tau positron emission tomography (PET) imaging and clinical assessment with the Neuropsychiatric Inventory (NPI) annually.

Neurofilament light chain concentration mediates the association between regional medial temporal lobe structure and memory in adults with Down syndrome.

Introduction: Virtually all people with Down syndrome (DS) develop neuropathology associated with Alzheimer's disease (AD). Atrophy of the hippocampus and entorhinal cortex (EC), as well as elevated plasma concentrations of neurofilament light chain (NfL) protein, are markers of neurodegeneration associated with late-onset AD. We hypothesized that hippocampus and EC gray matter loss and increased plasma NfL concentrations are associated with memory in adults with DS.

Photoinduced charge separation and DNA self-repair depend on sequence directionality and stacking pattern.

Charge separation is one of the most common consequences of the absorption of UV light by DNA. Recently, it has been shown that this process can enable efficient self-repair of cyclobutane pyrimidine dimers (CPDs) in specific short DNA oligomers such as the GAT[double bond, length as m-dash]T sequence. The mechanism was characterized as sequential electron transfer through the nucleobase stack which is controlled by the redox potentials of nucleobases and their sequence.