Pharmacologic Management of Heart Failure with Preserved Ejection Fraction (HFpEF) in Older Adults.

There are several pharmacologic agents that have been touted as guideline-directed medical therapy for heart failure with preserved ejection fraction (HFpEF). However, it is important to recognize that older adults with HFpEF also contend with an increased risk for adverse effects from medications due to age-related changes in pharmacokinetics and pharmacodynamics of medications, as well as the concurrence of geriatric conditions such as polypharmacy and frailty. With this review, we discuss the underlying evidence for the benefits of various treatments in HFpEF and incorporate key considerations for older adults, a subpopulation that may be at higher risk for adverse drug events.

Evaluation of UV-A and UV-B transmission through the windows of gas, hybrid, and electric vehicles.

UV-A exposure is a major risk factor for melanoma, nonmelanoma skin cancer, photoaging, and exacerbation of photodermatoses. Since people spend considerable time in cars daily, inadequate UV-A attenuation by car windows can significantly contribute to the onset or exacerbation of these skin diseases. Given recent market trends in the automobile industry and known impact of car windows on cumulative lifelong UV damage to the skin, there is a need to comparatively evaluate UV transmission across windows in electric vehicles (EV), hybrid vehicles (HV), and gas vehicles (GV) as well as variability based on year of manufacture and mileage to inform car manufacturers and consumers of the potential for UV exposure to the skin based on vehicle.

Reciprocal relationships between adolescent mental health difficulties and alcohol consumption.

The directionality of the relationship between adolescent alcohol consumption and mental health difficulties remains poorly understood. This study investigates the longitudinal relationship between alcohol use frequency, internalizing and externalizing symptoms from the ages of 11 to 17. We conducted a random-intercept cross-lagged panel model across three timepoints (ages: 11yrs, 14yrs, 17yrs; 50.

Comparison of the amyloid plaque proteome in Down syndrome, early-onset Alzheimer's disease, and late-onset Alzheimer's disease.

Down syndrome (DS) is strongly associated with Alzheimer's disease (AD) due to APP overexpression, exhibiting Amyloid-β (Aβ) and Tau pathology similar to early-onset (EOAD) and late-onset AD (LOAD). We evaluated the Aβ plaque proteome of DS, EOAD, and LOAD using unbiased localized proteomics on post-mortem paraffin-embedded tissues from four cohorts (n = 20/group): DS (59.8 ± 4.

Impact of Recent Translational and Therapeutic Developments on Clinical Course of BCR::ABL1-Positive and -Negative Myeloproliferative Neoplasms.

Despite the study of BCR::ABL1-positive and -negative myeloproliferative neoplasms (MPNs) providing seminal insights into cancer biology, tumor evolution and precision oncology over the past half century, significant challenges remain. MPNs are clonal hematopoietic stem cell-derived neoplasms with heterogenous clinical phenotypes and a clonal architecture which impacts the often-complex underlying genetics and microenvironment. The major driving molecular abnormalities have been well characterized, but debate on their role as disease-initiating molecular lesions continues.

Association of social determinants of health with first antiseizure medication prescription for patients with newly diagnosed epilepsy: A systematic review and meta-analysis.

Objective: To assess whether social determinants of health (SDOHs) are associated with the first antiseizure medication (ASM) prescribed for newly diagnosed epilepsy.

Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards were followed, and the protocol registered (CRD42023448998). Embase, Medline, and Web of Science were searched up to July 31, 2023.

Lineage-dependence of the neuroblastoma surfaceome defines tumor cell state-dependent and independent immunotherapeutic targets.

Background: Neuroblastoma is a heterogeneous disease with adrenergic (ADRN)- and therapy resistant mesenchymal (MES)-like cells driven by distinct transcription factor networks. Here, we investigate the expression of immunotherapeutic targets in each neuroblastoma subtype and propose pan-neuroblastoma and cell state specific targetable cell-surface proteins.

Methods: We characterized cell lines, patient-derived xenografts, and patient samples as ADRN-dominant or MES-dominant to define subtype-specific and pan-neuroblastoma gene sets.

Quantitative Pupillometry Predicts Neurologic Deterioration in Patients with Large Middle Cerebral Artery Stroke.

Objective: This study assesses whether longitudinal quantitative pupillometry predicts neurological deterioration after large middle cerebral artery (MCA) stroke and determines how early changes are detectable.

Methods: This prospective, single-center observational cohort study included patients with large MCA stroke admitted to Boston Medical Center's intensive care unit (2019-2024). Associations between time-to-neurologic deterioration and quantitative pupillometry, including Neurological Pupil Index (NPi), were assessed using Cox proportional hazards models with time-dependent covariates adjusted for age, sex, and Alberta Stroke Program Early CT Score.

Near-Infrared Spectroscopic Mapping of the Human Epicardium.

Epicardial catheter ablation is necessary to address ventricular tachycardia targets located far from the endocardium, but epicardial adipose tissue and coronary blood vessels can complicate ablation. We demonstrate that catheter-based near-infrared spectroscopy (NIRS) can identify these obstacles to guide ablation. Eighteen human ventricles were mapped ex vivo using NIRS catheters with optical source-detector separations (SDSs) of 0.

New onset refractory status epilepticus: Long-term outcomes beyond seizures.

We propose and prioritize important outcome domains that should be considered for future research investigating long-term outcomes (LTO) after new onset refractory status epilepticus (NORSE). The study was led by the international NORSE Institute LTO Working Group. First, literature describing the LTO of NORSE survivors was identified using a PubMed search and summarized to identify knowledge gaps.

Gender dysphoria in a Hispanic pregnant transgender man: Case report and review of literature.

There is limited research concerning the transgender population's health issues, such as gender dysphoria, and disparities within the healthcare system, especially in the Latino or Hispanic population. This study aimed to report the case of a Puerto Rican transgender man who achieved pregnancy without reproductive assistance after cessation of testosterone therapy for 3 months and who in the postpartum period experienced significant gender dysphoria. A narrative literature review was carried out to identify the role of gender dysphoria in pregnancy, lactation, health-related spaces, and mental health.

Response to neoadjuvant chemotherapy leads to better survival outcomes in upper tract urothelial carcinoma.

Objectives: To evaluate the benefit of neoadjuvant chemotherapy (NAC) for patients with high-risk upper tract urothelial carcinoma (UTUC) using a large, well-curated multi-institutional database.

Patients And Methods: This study was a multi-institutional retrospective analysis conducted by the UTUC Collaborative Network (UCAN), combining data from 2276 patients with UTUC who underwent radical nephroureterectomy at seven high-volume tertiary care centres in the United States. The UCAN data were analysed to evaluate the impact of response to NAC on survival outcomes in patients with UTUC.

Costs analysis of integrating group interpersonal therapy into HIV care services in Senegal.

Introduction: Group Interpersonal Therapy (IPT), an evidence-based treatment of depression recommended by the WHO mhGAP Intervention Guide, was implemented through a task-shifting approach in Senegal, as a treatment for depressed people living with HIV (PLWH). Since a description of the resources used and the implementation costs incurred is necessary to inform policymakers better, this study aimed to estimate the costs associated with its implementation.

Methods: Intervention costs were analyzed using an "ingredients-based costing approach" from the provider's perspective.

Meta-analyses of mouse and human prostate single-cell transcriptomes reveal widespread epithelial plasticity in tissue regression, regeneration, and cancer.

Background: Despite extensive analysis, the dynamic changes in prostate epithelial cell states during tissue homeostasis as well as tumor initiation and progression have been poorly characterized. However, recent advances in single-cell RNA-sequencing (scRNA-seq) technology have greatly facilitated studies of cell states and plasticity in tissue maintenance and cancer, including in the prostate.

Methods: We have performed meta-analyses of new and previously published scRNA-seq datasets for mouse and human prostate tissues to identify and compare cell populations across datasets in a uniform manner.

Enhancing prehospital decision-making: exploring user needs and design considerations for clinical decision support systems.

Background: In prehospital emergency care, providers face significant challenges in making informed decisions due to factors such as limited cognitive support, high-stress environments, and lack of experience with certain patient conditions. Effective Clinical Decision Support Systems (CDSS) have great potential to alleviate these challenges. However, such systems have not yet been widely adopted in real-world practice and have been found to cause workflow disruptions and usability issues.

The Impact of COVID-19 on the Division of Household Labor Among Women Physicians and Advanced Practice Providers.

Background: COVID-19 increased the burden of childcare on parents, leaving women vulnerable to increased disparities in the division of domestic labor. Women healthcare workers may be at heightened risk of worsening gender parity in the workplace as a result.

Objective: To examine the impact of the COVID-19 pandemic on gender parity in the division of household responsibilities among women healthcare workers.

Tucatinib and trastuzumab in HER2-mutated metastatic breast cancer: a phase 2 basket trial.

Human epidermal growth factor receptor 2 (HER2, also known as ERBB2) signaling promotes cell growth and differentiation, and is overexpressed in several tumor types, including breast, gastric and colorectal cancer. HER2-targeted therapies have shown clinical activity against these tumor types, resulting in regulatory approvals. However, the efficacy of HER2 therapies in tumors with HER2 mutations has not been widely investigated.

Explainable deep learning and virtual evolution identifies antimicrobial peptides with activity against multidrug-resistant human pathogens.

Artificial intelligence (AI) is a promising approach to identify new antimicrobial compounds in diverse microbial species. Here we developed an AI-based, explainable deep learning model, EvoGradient, that predicts the potency of antimicrobial peptides (AMPs) and virtually modifies peptide sequences to produce more potent AMPs, akin to in silico directed evolution. We applied this model to peptides encoded in low-abundance human oral bacteria, resulting in the virtual evolution of 32 peptides into potent AMPs.

Acoustic features of instrumental movie soundtracks elicit distinct and mostly non-overlapping extra-musical meanings in the mind of the listener.

Music can evoke powerful emotions in listeners. However, the role that instrumental music (music without any vocal part) plays in conveying extra-musical meaning, above and beyond emotions, is still a debated question. We conducted a study wherein participants (N = 121) listened to twenty 15-second-long excerpts of polyphonic instrumental soundtrack music and reported (i) perceived emotions (e.

Epicardial adipose tissue, cardiac damage, and mortality in patients undergoing TAVR for aortic stenosis.

Computed tomography (CT)-derived Epicardial Adipose Tissue (EAT) is linked to cardiovascular disease outcomes. However, its role in patients undergoing Transcatheter Aortic Valve Replacement (TAVR) and the interplay with aortic stenosis (AS) cardiac damage (CD) remains unexplored. We aim to investigate the relationship between EAT characteristics, AS CD, and all-cause mortality.

Microfluidic mixing probe: generating multiple concentration-varying flow dipoles.

This study advances microfluidic probe (MFP) technology through the development of a 3D-printed Microfluidic Mixing Probe (MMP), which integrates a built-in pre-mixer network of channels and features a lined array of paired injection and aspiration apertures. By combining the concepts of hydrodynamic flow confinements (HFCs) and "Christmas-tree" concentration gradient generation, the MMP can produce multiple concentration-varying flow dipoles, ranging from 0 to 100%, within an open microfluidic environment. This innovation overcomes previous limitations of MFPs, which only produced homogeneous bioreagents, by utilizing the pre-mixer to create distinct concentration of injected biochemicals.

Management of Vascular Complications from Button Battery Ingestions.

Purpose: To propose a gastrointestinal bleeding management algorithm that incorporates an endoscopic and imaging scoring system and specifies management of vascular complication from button battery ingestion.

Recent Findings: Button batteries (BB) are found in many electronic devices and ingestions are associated with serious complications especially in cases of unwitnessed ingestions, prolonged impaction, and in children less than 5 years of age. Gastrointestinal bleeding from BB related vascular injury is rare but often rapidly fatal, with a mortality rate as high as 81%.