Preclinical evaluation of the efficacy and safety of AAV8-TNAP-D10 in Alpl-/- and AlplPrx1/Prx1 mouse models for the treatment of early and late-onset hypophosphatasia.

We previously documented successful resolution of skeletal and dental disease in the infantile and late-onset murine models of hypophosphatasia (HPP), with a single injection of an adeno-associated serotype 8 vector encoding mineral-targeted TNAP (AAV8-TNAP-D10). Here, we conducted dosing studies in both HPP mouse models. A single escalating dose from 4x108 up to 4x1010 (vg/b) was intramuscularly injected into 4-day-old Alpl-/- mice (an infantile HPP model) and a single dose from 4x106 up to 4x109 (vg/b) was administered to 8-week-old AlplPrx1/Prx1 mice (a late-onset HPP model).

High-Frequency Ultrasound for Detecting Periodontal Inflammation: A Preclinical Diagnostic Accuracy Study.

Aim: Ultrasonography (US) has shown accuracy in imaging healthy periodontium. This study aims to evaluate the feasibility and accuracy of US for estimating dimensions of inflamed periodontium induced by ligature and bacteria.

Methods: Periodontal tissues of maxillary as well as mandibular premolars and molars in six female mini pigs were treated with ligature and three strains of bacteria for 4-10 weeks.

Young, Empowered & strong (YES): a study protocol paper for a randomized controlled trial of an mHealth symptom monitoring and self-management intervention for adolescent and young adult (AYA) breast cancer survivors.

Background: Compared to older adults with breast cancer (BC), adolescents and young adults (AYAs) develop more aggressive disease necessitating more intensive therapy with curative intent, which is disruptive to planned life trajectories. The burden of unmet needs among AYA BC survivors exists in two domains: (1) symptoms (e.g.

Novel oral adjuvant to enhance cytotoxic memory like NK cell responses in HIV vaccine platform.

Natural killer (NK) cell-driven effector mechanisms, such as antibody-dependent cell-mediated cytotoxicity, emerged as a secondary correlate of protection in the RV144 HIV vaccine clinical trial, the only vaccine thus far demonstrating some efficacy in human trials. Therefore, leveraging NK cells with enhanced cytotoxic effector responses may bolster vaccine-induced protection against HIV. Here, we investigated the effect of orally administering indole-3-carbinol (I3C), an aryl hydrocarbon receptor (AHR) agonist, as an adjuvant to an RV144-like vaccine platform in a mouse model.

Benchmarking high-risk human papillomavirus testing against cytology and biopsy results in the detection of cervical dysplasia to inform clinical screening guidelines.

Introduction: The United States Preventive Services Task Force (USPSTF) recommendation for cervical cancer screening includes the option to screen with high-risk human papilloma virus (hrHPV) alone, but some studies have reported that hrHPV testing alone missed precancerous and cancerous lesions. In this study, we evaluated the test performance characteristics of hrHPV in detecting cervical dysplasia with cervical cytology and biopsy as comparators.

Materials And Methods: We conducted a retrospective analysis of Papanicolaou smears between January and December 2019 performed at our institution with concurrent hrHPV and cytology testing.

Default mode network functional connectivity as a transdiagnostic biomarker of cognitive function.

The default mode network (DMN) is intricately linked with processes such as self-referential thinking, episodic memory recall, goal-directed cognition, self-projection, and theory of mind. Over recent years, there has been a surge in examining its functional connectivity, particularly its relationship with frontoparietal networks (FPN) involved in top-down attention, executive function, and cognitive control. The fluidity in switching between these internal and external modes of processing-highlighted by anti-correlated functional connectivity-has been proposed as an indicator of cognitive health.

Critical Review: Considerations in Applying Avian Egg Injection Studies to Characterize Effects of Hydrophobic Organic Compounds on Wild Birds.

Egg injection has been used for decades to determine embryonic mortality and developmental effects of chemical exposures in birds. Specific egg injection methods affect how well these studies replicate the process of chemical delivery to the embryo via maternal deposition, yet few data are available to compare exposure-response relationships between egg injection and maternal transfer studies. This information gap creates uncertainty when considering egg injection studies for assessment of potential adverse effects in wild birds.

DNA-binding affinity and specificity determine the phenotypic diversity in BCL11B-related disorders.

BCL11B is a Cys2-His2 zinc-finger (C2H2-ZnF) domain-containing, DNA-binding, transcription factor with established roles in the development of various organs and tissues, primarily the immune and nervous systems. BCL11B germline variants have been associated with a variety of developmental syndromes. However, genotype-phenotype correlations along with pathophysiologic mechanisms of selected variants mostly remain elusive.

Evaluation of rapid evaporative ionization mass spectrometry (REIMS) for the prediction of slice shear force and quality grades in beef longissimus lumborum steaks.

Steak samples were collected from the longissimus lumborum muscles of beef carcasses (Canada AA, n = 1505; Canada AAA, n = 1363) over a 3-year period. Steaks were aged for 14 d, and tenderness was determined by slice shear force (SSF). Metabolomic profiling of beef samples was performed using rapid evaporative ionization mass spectrometry (REIMS) (N = 2853).

Phase-specific changes in hip joint loading during gait following sacroiliac joint fusion: Findings from a finite element analysis.

Background: Low back pain affects over 80 % of adults, with sacroiliac joint dysfunction accounting for 15-30 % of these cases. Sacroiliac fusion is a surgical procedure for refractory joint pain. While the biomechanics of the joint and its fusion relative to the spinal column are well-known, the hip-spine relationship post-fusion remains unclear.

Long-Term Safety and Efficacy of Bimekizumab in Axial Spondyloarthritis: 2-Year Results from Two Phase 3 Studies.

Objectives: Bimekizumab, a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)‑17F in addition to IL-17A, previously demonstrated efficacy and was well tolerated to 1 year in patients with non-radiographic (nr-) and radiographic (r-) axial spondyloarthritis (axSpA). Here, we report bimekizumab safety and efficacy to 2 years.

Methods: Patients completing week 52 in the phase 3 studies BE MOBILE 1 (nr-axSpA; NCT03928704) and 2 (r‑axSpA; NCT03928743) were eligible for an ongoing open‑label extension (OLE; NCT04436640).

Safety of accessing brachial veins for large-bore upper extremity venous thrombectomy using ClotTriever Thrombectomy System.

Purpose: To evaluate access site adverse events following ClotTriever-mediated large-bore mechanical thrombectomy via small upper extremity deep veins (< 6-mm).

Materials And Methods: Twenty patients, including 24 upper extremity venous access sites, underwent ClotTriever-mediated large-bore thrombectomy of the upper extremity and thoracic central veins for symptomatic deep vein obstruction unresponsive to anticoagulation. Patients without follow-up venous duplex examinations (n = 3) were excluded.

The Last Decade in Cardiac Amyloidosis: Advances in Understanding Pathophysiology, Diagnosis and Quantification, Prognosis, Treatment Strategies, and Monitoring Response.

Cardiac amyloidosis represents a unique disease process characterized by amyloid fibril deposition within the myocardial extracellular space. Advances in multimodality cardiac imaging enable accurate diagnosis and facilitate prompt initiation of disease-modifying therapies. Furthermore, rapid advances in multimodality imaging have enriched understanding of the underlying pathogenesis, enhanced prognostication, and resulted in the development of imaging-based markers that reflect the amyloid burden, which is of increasing importance when assessing the response to treatment.

Transcatheter Left Ventricular Reconstruction in Heart Failure Patients With Prior Anterior Myocardial Infarction: The Prospective ALIVE Trial.

Background: Left ventricular (LV) dilatation and extensive scar portend a poor prognosis in heart failure (HF). The Revivent TC system (BioVentrix Inc) is used either during a hybrid transcatheter-surgical or a surgical-only procedure to exclude transmural scar and reduce LV dimensions.

Objectives: The purpose of this study was to examine the safety and efficacy of the Revivent TC® anchor system in patients with HF.

Digital Solutions for the Optimization of Pharmacologic Therapy for Heart Failure.

Data from large-scale, randomized, controlled trials demonstrate that contemporary treatments for heart failure (HF) can substantially improve morbidity and mortality. Despite this, observed outcomes for patients living with HF are poor, and they have not improved over time. The are many potential reasons for this important problem, but inadequate use of optimal medical therapy for patients with HF, an important component of guideline-directed medical therapy, in routine practice is a principal and modifiable contributor.

Gentamicin ointment effect on hard-to-heal wounds: a case series.

Objective: The presence of microorganisms in a wound may lead to the development of pathologically extensive inflammation, and either delay or prevent the healing of hard-to-heal (chronic) wounds. The aim of this case series is to explore the use of topical gentamicin ointment, an aminoglycoside with activity against aerobic Gram-negative bacteria, as an option to address hard-to-heal wounds.

Method: We present a retrospective case series of patients with hard-to-heal wounds of varying pathophysiologies treated with topical gentamicin.

Investigation of stakeholder perceptions of the wheelchair service delivery process.

The wheelchair service delivery process (SDP) is a large complex system and therefore has many potential points of failure; determining priorities for improvement is challenging. The complexities introduce several barriers to accessing and maintaining wheelchairs for individuals with mobility impairments. Given the breadth and depth of the barriers, it is important to know in which areas to focus future policy reform efforts.

Protein thermal stability in the undergraduate biochemistry laboratory: Exploring protein thermal stability with yeast alcohol dehydrogenase.

We created a novel laboratory experience where undergraduate students explore the techniques used to study protein misfolding, unfolding, and aggregation. Despite the importance of protein misfolding and aggregation diseases, protein unfolding is not typically explored in undergraduate biochemistry laboratory classes. Yeast alcohol dehydrogenase (YADH) is used in the undergraduate biochemistry laboratory course at Miami University as the model system to explore protein overexpression and purification, bioinformatics, and enzyme characterization.

On fostering employee participation in voluntary corporate-sponsored wellness programs.

As organizations are increasingly turning to voluntary wellness programs to improve employee well-being, the majority of studies in literature have focused on corporate-level benefits of wellness programs, such as productivity. However, there is a scarcity of studies that examine the intrinsic motivators that influence employee participation in such programs. In this study, we use a unique secondary dataset from a voluntary corporate wellness program and propose a novel theoretical framework based on motivational and behavioral theories to examine and understand the participants' behavior.