FORCE platform overcomes barriers of oligonucleotide delivery to muscle and corrects myotonic dystrophy features in preclinical models.

Background: We developed the FORCE platform to overcome limitations of oligonucleotide delivery to muscle and enable their applicability to neuromuscular disorders. The platform consists of an antigen-binding fragment, highly specific for the human transferrin receptor 1 (TfR1), conjugated to an oligonucleotide via a cleavable valine-citrulline linker. Myotonic dystrophy type 1 (DM1) is a neuromuscular disorder caused by expanded CUG triplets in the DMPK RNA, which sequester splicing proteins in the nucleus, lead to spliceopathy, and drive disease progression.

Lymphatic platelet thrombosis limits bone repair by precluding lymphatic transporting DAMPs.

In the musculoskeletal system, lymphatic vessels (LVs), which are interdigitated with blood vessels, travel and form an extensive transport network. Blood vessels in bone regulate osteogenesis and hematopoiesis, however, whether LVs in bone affect fracture healing is unclear. Here, we investigate the lymphatic draining function at the tibial fracture sites using near-infrared indocyanine green lymphatic imaging (NIR-ICG) and discover that lymphatic drainage insufficiency (LDI) starts on day one and persists for up to two weeks following the fracture in male mice.

Patient, Caregiver, and Provider Well-Being in Oncology.

Addressing various dimensions of well-being can help improve oncology patients' symptoms and their overall quality of life (QOL); similar strategies can be used to support caregivers of oncology patients to improve not only QOL of the caregiver, but the patient. Beyond patient and caregiver support, interventions focusing on dimensions of well-being can improve the culture of wellness, practice efficiency, and enhance personal resilience among oncology providers to mitigate burnout. Herein, the authors discuss multiple evidence-based strategies to improve well-being of oncology patients, caregivers, and providers.

Safety and Efficacy of Deutetrabenazine at High versus Lower Daily Dosages in the ARC-HD Study to Treat Chorea in Huntington Disease.

Background: Huntington disease (HD) is a progressive neurodegenerative disease that causes psychiatric and neurological symptoms, including involuntary and irregular muscle movements (chorea). Chorea can disrupt activities of daily living, pose safety issues, and may lead to social withdrawal. The vesicular monoamine transporter 2 inhibitors tetrabenazine, deutetrabenazine, and valbenazine are approved treatments that can reduce chorea.

Neutralizing antibody immune correlates in COVAIL trial recipients of an mRNA second COVID-19 vaccine boost.

Neutralizing antibody titer has been a surrogate endpoint for guiding COVID-19 vaccine approval and use, although the pandemic's evolution and the introduction of variant-adapted vaccine boosters raise questions as to this surrogate's contemporary performance. For 985 recipients of an mRNA second bivalent or monovalent booster containing various Spike inserts [Prototype (Ancestral), Beta, Delta, and/or Omicron BA.1 or BA.

Influence of edentulous areas on the accuracy of the maximum intercuspal position recorded by using different intraoral scanners or an artificial intelligence-based program.

Statement Of Problem: Intraoral scans can be articulated in maximum intercuspal position (MIP) by using an artificial intelligence (AI) based program; however, the impact of edentulous areas on the accuracy of the MIP located using this AI-based program is unknown.

Purpose: The purpose of this in vitro study was to assess the impact of edentulous areas (0, 1, 2, 3, and 4 posterior mandibular teeth) on the accuracy of the MIP located using 3 intraoral scanners (IOSs) and an AI-based program.

Material And Methods: Stone casts articulated in MIP in an articulator were digitized (T710).

Effect of nirmatrelvir/ritonavir (Paxlovid) on hospitalization among adults with COVID-19: An electronic health record-based target trial emulation from N3C.

Background: Nirmatrelvir with ritonavir (Paxlovid) is indicated for patients with Coronavirus Disease 2019 (COVID-19) who are at risk for progression to severe disease due to the presence of one or more risk factors. Millions of treatment courses have been prescribed in the United States alone. Paxlovid was highly effective at preventing hospitalization and death in clinical trials.

Engineering mechanisms of proton-coupled electron transfer to a titanium-substituted polyoxovanadate-alkoxide.

Metal oxides are promising catalysts for small molecule hydrogen chemistries, mediated by interfacial proton-coupled electron transfer (PCET) processes. Engineering the mechanism of PCET has been shown to control the selectivity of reduced products, providing an additional route for improving reductive catalysis with metal oxides. In this work, we present kinetic resolution of the rate determining proton-transfer step of PCET to a titanium-doped POV, TiVO(OCH) with 9,10-dihydrophenazine by monitoring the loss of the cationic radical intermediate using stopped-flow analysis.

Gestational exposure to PM, NO, and sex steroid hormones: Identifying critical windows of exposure in the Rochester UPSIDE Cohort.

Background: Sex steroid hormones are critical for maintaining pregnancy and optimal fetal development. Air pollutants are potential endocrine disruptors that may disturb sex steroidogenesis during pregnancy, potentially leading to adverse health outcomes.

Methods: In the Environmental influences on Child Health Outcomes Understanding Pregnancy Signals and Infant Development pregnancy cohort (Rochester, NY), sex steroid concentrations were collected at study visits in early-, mid-, and late-pregnancy in 299 participants.

Timing of Carpal Tunnel Syndrome Treatment Based on Social Deprivation.

Introduction: This study sought to investigate the impact of the area deprivation index (ADI) on the treatment timeline from carpal tunnel syndrome (CTS) to carpal tunnel release (CTR). We hypothesize that increased social deprivation will correlate with increased time between care milestones from presentation to surgery.

Methods: This is a retrospective review of patients diagnosed with CTS who underwent CTR at a single academic institution.

An Observational Study to Determine the Prevalence of COVID-19 Among Hospitalized Patients With Multidrug-Resistant Enterobacterales Infections and Clinical Outcomes, 10 US Sites, 2020--2022.

Background: We investigated hospitalized carbapenem-resistant Enterobacterales (CRE) and extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) cases with and without COVID-19, as identified through Emerging Infections Program surveillance in 10 sites from 2020 to 2022.

Methods: We defined a CRE case as the first isolation of , complex, , , , or resistant to any carbapenem. We defined an ESBL-E case as the first isolation of , , or resistant to any third-generation cephalosporin and nonresistant to all carbapenems tested.

"Many old people taking care of old people": Experiences of older adults after Hurricane María in Puerto Rico.

The Puerto Rican population has presented demographic changes resulting in a greater proportion of older adults than almost any other country in the world, with an estimated 28% of the total population being over 60 years of age. A key public health issue in Puerto Rico (PR) is older adults' mental health and wellbeing. Located in the Caribbean, PR is prone to natural hazards such as hurricanes, which are a known threat to older adults' overall health and wellbeing.

Mode of Delivery and Subsequent Motor Function in Children With Myelomeningocele Without In Utero Repair.

Objective: To assess the association between mode of delivery and 2-year motor function in children with prenatal diagnosis of myelomeningocele.

Methods: A multisite retrospective cohort study of children with myelomeningocele across 14 NAFTNet (North American Fetal Therapy Network) centers born between 2007 and 2020 who had a physical examination available at 2 years of life. Exclusion criteria were in utero myelomeningocele repair, postnatal myelomeningocele diagnosis, missing data on fetal presentation at delivery, and contraindications to labor.

Post-Traumatic Hip Osteoarthritis after Pelvic Ring Injuries.

Objectives: While rates of post-traumatic osteoarthritis after acetabulum fracture have been thoroughly studied, there has been less emphasis on hip osteoarthritis after pelvic ring injuries. The objective of this study was to determine the frequency of post-traumatic hip osteoarthritis in pelvic ring injury patients. It was hypothesized that more severe pelvic ring injuries would be associated with greater rates of post-traumatic hip osteoarthritis.

Utilizing Simulated Telemedicine Encounters to Conduct Nationwide Studies of Physician Communication Practices.

High-quality communication and shared decision making (SDM) are crucial elements of effective patient care. SDM conversations are intimate and logistically challenging to capture. Evaluating alternative methods to effectively observe how physicians conduct these conversations may improve research efforts in this core discipline of medicine.

Pediatric Dialysis: Ethical Dilemmas Faced by Pediatric Intensive Care Nurses.

Whether pediatric dialysis is morally obligatory is an ethical issue. The study's aim was to understand neonatal and pediatric intensive care unit (ICU) nurses' beliefs regarding the ethical use of pediatric dialysis. A single center study was conducted using theoretical and case-based surveys.

Outer hair cells stir cochlear fluids.

We hypothesized that active outer hair cells drive cochlear fluid circulation. The hypothesis was tested by delivering the neurotoxin, kainic acid, to the intact round window of young gerbil cochleae while monitoring auditory responses in the cochlear nucleus. Sounds presented at a modest level significantly expedited kainic acid delivery.

Reevaluating Anti-Inflammatory Therapy: Targeting Senescence to Balance Anti-Cancer Efficacy and Vascular Disease.

Modulating immune function is a critical strategy in cancer and atherosclerosis treatments. For cancer, boosting or maintaining the immune system is crucial to prevent tumor growth. However, in vascular disease, mitigating immune responses can decrease inflammation and slow atherosclerosis progression.

Disseminated TB With IRIS Presenting as a Pancreatic Mass in Newly Diagnosed HIV: A Case Report.

Pancreatic tuberculosis (TB) is an uncommon extrapulmonary presentation of TB. Identification of coinfection with HIV may unmask not only disseminated TB but also immune reconstitution inflammatory syndrome (IRIS). We present the case of a 70-year-old Indian woman newly diagnosed with AIDS and pancreatic tuberculosis with miliary disseminated disease.

Feasibility of measuring magnetic resonance elastography-derived stiffness in human thoracic aorta and aortic dissection phantoms.

Type B aortic dissection (TBAD) represents a serious medical emergency with up to a 50% associated 5-year mortality caused by thoracic aorta, dissection-associated aneurysmal (DAA) degeneration, and rupture. Unfortunately, conventional size-related diagnostic methods cannot distinguish high-risk DAAs that benefit from surgical intervention from stable DAAs. Our goal is to use DAA stiffness measured with magnetic resonance elastography (MRE) as a biomarker to distinguish high-risk DAAs from stable DAAs.

Design concepts for advanced-technology intraocular lenses [Invited].

An intraocular lens (IOL) replaces the natural crystalline lens during cataract surgery, and although the vast majority of implants have simple optics, "advanced technology" IOLs have multifocal and extended depth of focus (EDOF) properties. Optical concepts are evaluated here, with image contrast, focal range, and unwanted visual phenomena being the primary concerns. Visual phenomena with earlier bifocal diffractive lenses led to alternative diffractive designs (trifocals, etc.

Military influences on the evolution of clinical trials throughout history.

Clinical trials of drugs, procedures, and other therapies play a crucial role in advancing medical science by evaluating the safety, efficacy, and optimal use of medical interventions. The design and implementation of these trials have evolved significantly over time, reflecting advancements in medicine, ethics, and methodology. Early historical examples, such as King Nebuchadnezzar II's and his captives' dietary experiment and Ambroise Paré's treatment of gunshot wounds, laid some foundational principles of trial design.