Whole-body galactose oxidation as a robust functional assay to assess the efficacy of gene-based therapies in a mouse model of Galactosemia.

Despite the implementation of lifesaving newborn screening programs and a galactose-restricted diet, many patients with classic galactosemia develop long-term debilitating neurological deficits and primary ovarian insufficiency. Previously, we showed that the administration of human mRNA predominantly expressed in the gene-trapped mouse liver augmented the expression of hepatic GALT activity, which decreased not only galactose-1 phosphate (gal-1P) in the liver but also peripheral tissues. Since each peripheral tissue requires distinct methods to examine the biomarker and/or GALT effect, this highlights the necessity for alternative strategies to evaluate the overall impact of therapies.

Challenges and Burdens in the Coronary Artery Disease Care Pathway for Patients Undergoing Percutaneous Coronary Intervention: A Contemporary Narrative Review.

Clinical and economic burdens exist within the coronary artery disease (CAD) care pathway despite advances in diagnosis and treatment and the increasing utilization of percutaneous coronary intervention (PCI). However, research presenting a comprehensive assessment of the challenges across this pathway is scarce. This contemporary review identifies relevant studies related to inefficiencies in the diagnosis, treatment, and management of CAD, including clinician, patient, and economic burdens.

Mitigating COVID-19 Vaccine Waste Through a Multidisciplinary Inpatient Vaccination Initiative.

A multidisciplinary team at a tertiary care Veterans Health Administration medical center created a standardized process to identify medically stable inpatients, to notify inpatient staff of available COVID-19 vaccine doses, and to coordinate inpatient vaccine administration. The team's goals were to mitigate vaccine waste while safely vaccinating as many patients as possible. Using a unique set of exclusion criteria and clinical judgment, a quality improvement team reviewed patients admitted to medicine teams to determine medical stability.

A potential widespread and important role for sleep-disordered breathing in pressure injury development and delayed healing among those with spinal cord injury.

Soft tissue pressure injuries commonly occur in those with spinal cord injury. They add an immeasurable medical, emotional, and social burden to those who suffer a spinal cord injury and ultimately can cause death due to sepsis when they ulcerate and become infected. Hence it is notable that (i) obstructive sleep apnea and other forms of sleep-disordered breathing are highly prevalent among those with spinal cord injury; (ii) several of the pathophysiologic consequences of sleep-disordered breathing, including hypoxemia, ischemia, oxidative stress, and endothelial dysfunction, would be expected to increase susceptibility to pressure injuries, worsen their severity, and slow or prevent their healing; and (iii) there is emerging clinical evidence that sleep-disordered breathing can have a significant role in the pathogenesis of other types of chronic wounds and that treatment of sleep-disordered breathing can aid in the healing of these wounds.

Fracture Resistance of Various Thickness e.max CAD Lithium Disilicate Crowns Cemented on Different Supporting Substrates: An In Vitro Study.

Purpose: To investigate the influence of abutment material properties on the fracture resistance and failure mode of lithium disilicate (IPS e.max) CAD/CAM (computer-aided design/manufacturing) crowns on traditionally and minimally prepared simulated tooth substrates.

Materials And Methods: Thirty lithium disilicate (IPS e.

The Diagnostic Accuracy of Incisional Biopsy in the Oral Cavity.

Purpose: To determine the accuracy of incisional biopsy examination to diagnose oral lesions.

Materials And Methods: This retrospective cohort study was performed to determine the concordance rate between incisional biopsy examination and definitive resection diagnosis for different oral lesions. The study sample was derived from the population of patients who presented to the Department of Oral and Maxillofacial Surgery, Massachusetts General Hospital (Boston, MA) from January 2005 through December 2012.

Shape and evolution of the fundamental niche in marine Vibrio.

Hutchinson's fundamental niche, defined by the physical and biological environments in which an organism can thrive in the absence of inter-species interactions, is an important theoretical concept in ecology. However, little is known about the overlap between the fundamental niche and the set of conditions species inhabit in nature, and about natural variation in fundamental niche shape and its change as species adapt to their environment. Here, we develop a custom-made dual gradient apparatus to map a cross-section of the fundamental niche for several marine bacterial species within the genus Vibrio based on their temperature and salinity tolerance, and compare tolerance limits to the environment where these species commonly occur.

Hedgehog signaling inhibition blocks growth of resistant tumors through effects on tumor microenvironment.

Hedgehog (Hh) signaling is implicated in bone development and cellular transformation. Here we show that inhibition of Hh pathway activity inhibits tumor growth through effects on the microenvironment. Pharmacologic inhibition of the Hh effector Smoothened (Smo) increased trabecular bone in vivo and inhibited osteoclastogenesis in vitro.

Quantification of factors influencing fluorescent protein expression using RMCE to generate an allelic series in the ROSA26 locus in mice.

Fluorescent proteins (FPs) have great utility in identifying specific cell populations and in studying cellular dynamics in the mouse. To quantify the factors that determine both the expression and relative brightness of FPs in mouse embryonic stem cells (mESCs) and in mice, we generated eight different FP-expressing ROSA26 alleles using recombinase-mediated cassette exchange (RMCE). These alleles enabled us to analyze the effects on FP expression of a translational enhancer and different 3'-intronic and/or polyadenylation sequences, as well as the relative brightness of five different FPs, without the confounding position and copy number effects that are typically associated with randomly inserted transgenes.

Initial clinical experience with contrast-enhanced digital breast tomosynthesis.

Rationale And Objectives: Contrast-enhanced digital mammography and digital breast tomosynthesis are two imaging techniques that attempt to increase malignant breast lesion conspicuity. The combination of these into a single technique, contrast-enhanced digital breast tomosynthesis (CE-DBT), could potentially integrate the strengths of both. The objectives of this study were to assess the clinical feasibility of CE-DBT as an adjunct to digital mammography, and to correlate lesion enhancement characteristics and morphology obtained with CE-DBT to digital mammography, ultrasound, and magnetic resonance (MR).

Fetal posterior fossa volume: assessment with MR imaging.

Purpose: To retrospectively determine the relationship between posterior fossa volume (PFV) and estimated gestational age (EGA) and/or femur length (FL) during pregnancy for the purpose of developing a normal growth curve.

Materials And Methods: Advance institutional review board approval was obtained for this HIPAA-compliant study, and the need for parent informed consent was waived. A cross-sectional retrospective study was performed to measure PFV on in vivo magnetic resonance (MR) images obtained in 76 fetuses of 18-36 weeks gestation who had a morphologically normal CNS.