Targeting Cathepsin K to Accelerate Diabetic Wound Healing.

: Elevated protease activity impairs wound healing. Cathepsin K is a cysteine protease with potent collagenolytic and elastolytic activity. This study examined the effects of odanacatib, a cathepsin K inhibitor, on wound healing in a diabetic porcine model.

Increased ROS and Persistent Pro-Inflammatory Responses in a Diabetic Wound Healing Model (db/db): Implications for Delayed Wound Healing.

Diabetes and its complications, including impaired wound healing, present a critical clinical challenge and burden for the U.S. healthcare system, with costs of over USD 13 billion annually.

Management of Pediatric Solid Organ Injuries.

Solid organ injury (SOI) is common in children who experience abdominal trauma, and the management of such injuries has evolved significantly over the past several decades. In 2000, the American Pediatric Surgical Association (APSA) published the first societal guidelines for the management of blunt spleen and/or liver injury (BLSI), advocating for optimized resource utilization while maintaining patient safety. Nonoperative management (NOM) has become the mainstay of treatment for SOI, and since the publication of the APSA guidelines, numerous groups have evaluated how invasive procedures, hospitalization, and activity restrictions may be safely minimized in children with SOI.

Targeting Inflammation and Oxidative Stress to Improve Outcomes in a TNBS Murine Crohn's Colitis Model.

Inflammation and oxidative stress are implicated in the pathogenesis of Crohn's disease. Cerium oxide nanoparticle (CNP) conjugated to microRNA 146a (miR146a) (CNP-miR146a) is a novel compound with anti-inflammatory and antioxidative properties. We hypothesized that local administration of CNP-miR146a would improve colitis in a 2,4,6-Trinitrobenzenesulfonic acid (TNBS) mouse model for Crohn's disease by decreasing colonic inflammation.

The Effect of Steroids on Prenatally Diagnosed Lung Lesions.

Background: Open fetal resection for large lung lesions has virtually been replaced by maternal steroid administration. Despite this paradigm shift, little is known about the effects steroids have on lung lesion growth in utero.

Methods: A 10-year retrospective review of all prenatally diagnosed lung lesions cared for at our fetal care center was performed.

Surgical Necrotizing Enterocolitis - Can We Predict the Need for Gastrostomy Tube Placement?

Introduction: Necrotizing enterocolitis (NEC) is a significant cause of morbidity and mortality among extremely premature infants. Approximately 50% of cases progress to surgery, frequently resulting in resection of necrotic bowel and ostomy creation. Premature neonates are at risk for bronchopulmonary dysplasia and feeding failure; surgery in these patients is higher risk.

Fetal lung volumes measured by MRI predict pulmonary morbidity among infants with giant omphaloceles.

Objective: Giant omphaloceles (GO) have associated pulmonary hypoplasia and respiratory complications. Total lung volumes (TLV) on fetal MRI can prognosticate congenital diaphragmatic hernia outcomes; however, its applicability to GO is unknown. We hypothesize that late gestation TLV and observed-to-expected TLV (O/E TLV) on fetal MRI correlate with postnatal pulmonary morbidity in GO.

CNP-miR146a Decreases Inflammation in Murine Acute Infectious Lung Injury.

Acute respiratory distress syndrome (ARDS) has approximately 40% in-hospital mortality, and treatment is limited to supportive care. Pneumonia is the underlying etiology in many cases with unrestrained inflammation central to the pathophysiology. We have previously shown that CNP-miR146a, a radical scavenging cerium oxide nanoparticle (CNP) conjugated to the anti-inflammatory microRNA(miR)-146a, reduces bleomycin- and endotoxin-induced acute lung injury (ALI) by decreasing inflammation.

Angiogenic and Inflammatory microRNA Regulation in a Mouse Model of Fetal Growth Restriction.

Introduction: Fetal growth restriction (FGR) is associated with impaired angiogenesis and chronic inflammation. MicroRNAs (miRs) are short noncoding RNAs that regulate gene expression at the post-transcriptional level by targeting messenger RNA (mRNA) for degradation or by suppressing translation. We hypothesize that dysregulation of miR-15b, an antiangiogenic miR, and miR-146a, an anti-inflammatory miR, are associated with the FGR's pathogenesis.

Quality Improvement Campaign Improved Utilization of Rapid Sequence MRI for Diagnosis of Pediatric Appendicitis.

Introduction: Appendicitis is the most common indication for emergency general surgery in the pediatric population. Computed tomography (CT) or magnetic resonance imaging (MRI) may be used for diagnosis when ultrasound findings are equivocal. However, CT involves unnecessary radiation exposure if MRI is available.

Effects of microRNAs on angiogenesis in diabetic wounds.

Diabetes mellitus is a morbid condition affecting a growing number of the world population, and approximately one third of diabetic patients are afflicted with diabetic foot ulcers (DFU), which are chronic non-healing wounds that frequently progress to require amputation. The treatments currently used for DFU focus on reducing pressure on the wound, staving off infection, and maintaining a moist environment, but the impaired wound healing that occurs in diabetes is a constant obstacle that must be faced. Aberrant angiogenesis is a major contributor to poor wound healing in diabetes and surgical intervention is often necessary to establish peripheral blood flow necessary for healing wounds.

Use of prehospital reverse shock index times Glasgow Coma Scale to identify children who require the most immediate trauma care.

Background: Appropriate prehospital trauma triage ensures transport of children to facilities that provide specialized trauma care. There are currently no objective and generalizable scoring tool for emergency medical services to facilitate such decisions. An abnormal reverse shock index times Glasgow Coma Scale (rSIG), which is calculated using readily available parameters, has been shown to be associated with severely injured children.

Blood Transfusion is Associated With Adverse Outcomes in Pediatric Solid Tumor Oncology Patients Following Tumor Resection.

Background: Packed red blood cell (PRBC) transfusion is a lifesaving intervention that also has proinflammatory and immunosuppressive effects. Adults with a malignancy who receive PRBC transfusion have increased rates of infection, tumor recurrence, and decreased survival. The effect of PRBC transfusion among children with solid tumors is unknown.

gastric perforation from combined duodenal and esophageal atresia without consistent polyhydramnios.

We present a case in which prenatal imaging at 21-weeks' gestation suggested duodenal atresia with a double-bubble sign and enlarged stomach. Fetal magnetic resonance imaging findings demonstrated dilation of the stomach and proximal duodenum favoring duodenal atresia but no indications of esophageal atresia. Subsequent prenatal imaging demonstrated interval spontaneous decompression of the stomach without the development of polyhydramnios, obscuring the diagnosis.

7T quantitative magnetization transfer (qMT) of cortical gray matter in multiple sclerosis correlates with cognitive impairment.

Cognitive impairment (CI) is a major manifestation of multiple sclerosis (MS) and is responsible for extensively hindering patient quality of life. Cortical gray matter (cGM) damage is a significant contributor to CI, but is poorly characterized by conventional MRI let alone with quantitative MRI, such as quantitative magnetization transfer (qMT). Here we employed high-resolution qMT at 7T via the selective inversion recovery (SIR) method, which provides tissue-specific indices of tissue macromolecular content, such as the pool size ratio (PSR) and the rate of MT exchange (kmf).

Glutamate-sensitive imaging and evaluation of cognitive impairment in multiple sclerosis.

Background: Cognitive impairment (CI) profoundly impacts quality of life for patients with multiple sclerosis (MS). Dysfunctional regulation of glutamate in gray matter (GM) has been implicated in the pathogenesis of MS by post-mortem pathological studies and in CI by in vivo magnetic resonance spectroscopy, yet GM pathology is subtle and difficult to detect using conventional T- and T-weighted magnetic resonance imaging (MRI). There is a need for high-resolution, clinically accessible imaging techniques that probe molecular changes in GM.

Quantitative characterization of optic nerve atrophy in patients with multiple sclerosis.

Background: Optic neuritis (ON) is one of the most common presentations of multiple sclerosis (MS). Magnetic resonance imaging (MRI) of the optic nerves is challenging because of retrobulbar motion, orbital fat and susceptibility artifacts from maxillary sinuses; therefore, axonal loss is investigated with the surrogate measure of a single heuristically defined point along the nerve as opposed to volumetric investigation.

Objective: The objective of this paper is to derive optic nerve volumetrics along the entire nerve length in patients with MS and healthy controls in vivo using high-resolution, clinically viable MRI.

Evaluating single-point quantitative magnetization transfer in the cervical spinal cord: Application to multiple sclerosis.

Spinal cord (SC) damage is linked to clinical deficits in patients with multiple sclerosis (MS), however, conventional MRI methods are not specific to the underlying macromolecular tissue changes that may precede overt lesion detection. Single-point quantitative magnetization transfer (qMT) is a method that can provide high-resolution indices sensitive to underlying macromolecular composition in a clinically feasible scan time by reducing the number of MT-weighted acquisitions and utilizing a two-pool model constrained by empirically determined constants. As the single-point qMT method relies on a priori constraints, it has not been employed extensively in patients, where these constraints may vary, and thus, the biases inherent in this model have not been evaluated in a patient cohort.

Amide proton transfer CEST of the cervical spinal cord in multiple sclerosis patients at 3T.

Purpose: The ability to evaluate pathological changes in the spinal cord in multiple sclerosis (MS) is limited because T - and T -w MRI imaging are not sensitive to biochemical changes in vivo. Amide proton transfer (APT) chemical exchange saturation transfer (CEST) can indirectly detect amide protons associated with proteins and peptides, potentially providing more pathological specificity. Here, we implement APT CEST in the cervical spinal cord of healthy and MS cohorts at 3T.

Quantifying the impact of underlying measurement error on cervical spinal cord diffusion tensor imaging at 3T.

Purpose: To empirically characterize and quantify the impact of gradient weighting schemes on the appearance and fidelity of diffusion tensor imaging of the human spinal cord in vivo in clinically relevant scan time equivalents (STE).

Materials And Methods: In five healthy controls at 3T, we evaluated test-retest reproducibility and performed voxelwise analysis of diffusion tensor imaging (DTI)-derived indices (fractional anisotropy [FA], mean [MD], axial [AD], and radial [RD] diffusivity) in the cervical spinal cord to assess spatial dependencies of measurement error and differences across three different sampling schemes (6, 15, and 32 directions) at STE of 4.5, 9, and 18 minutes.

Incorporating dixon multi-echo fat water separation for novel quantitative magnetization transfer of the human optic nerve in vivo.

Purpose: The optic nerve (ON) represents the sole pathway between the eyes and brain; consequently, diseases of the ON can have dramatic effects on vision. However, quantitative magnetization transfer (qMT) applications in the ON have been limited to ex vivo studies, in part because of the fatty connective tissue that surrounds the ON, confounding the magnetization transfer (MT) experiment. Therefore, the aim of this study was to implement a multi-echo Dixon fat-water separation approach to remove the fat component from MT images.

Magnetic resonance imaging of the cervical spinal cord in multiple sclerosis at 7T.

Background: The clinical course of multiple sclerosis (MS) is mainly attributable to cervical and upper thoracic spinal cord dysfunction. High-resolution, 7T anatomical imaging of the cervical spinal cord is presented. Image contrast between gray/white matter and lesions surpasses conventional, clinical T1- and T2-weighted sequences at lower field strengths.