Evaluation of a point-of-care ultrasound curriculum and ocular phantom in residency training.

Specialized training in ocular ultrasound is not a focus for most emergency medicine residencies, despite the fact that it allows physicians to quickly and accurately identify ocular pathology and prioritize emergency ophthalmological consultations. Therefore, we tested the value of utilizing normal and pathologic ocular ultrasound phantoms as a training tool for residents. Twenty emergency medicine residents were given a pre-test including written and practical skills diagnosis of ocular phantom pathologies, a short video on common ocular pathologies, practice time with the phantoms and a post-test including written and scanning components. Residents were then asked to complete an overall evaluation of the learning activity. After didactic and hands-on training with phantoms, residents demonstrated a significant increase in knowledge, skills and preparedness for diagnosing real patients with ocular pathologies. Overall, the phantoms allowed residents an unrestricted opportunity to practice and refine their technique. This study provided a framework for teaching emergency medicine residents the basics of ocular US through a brief didactic and practical intervention using novel ocular pathology US phantoms. Our curriculum resulted in both objective and subjective improvement in residents' performance and understanding of ocular US.

Bone scintigraphy findings in calciphylaxis.

Calciphylaxis is a poorly understood condition involving vascular calcification and thrombosis that leads to skin necrosis. Unfortunately, a noninvasive definitive test for calciphylaxis does not currently exist, and diagnosis relies on clinical symptoms and risk factors. Imaging can help guide diagnosis of this rare disorder. We present a pathology-proven case of calciphylaxis and the corresponding imaging findings seen on bone scintigraphy.

Seeding of a high-grade papillary urothelial carcinoma of the bladder along a nephroureterostomy tract.

Percutaneous nephrostomy placement is a common treatment for obstructive uropathy of various causes. Although rare in the literature, tumor seeding along the nephrostomy tract is a potential risk of percutaneous nephrostomy in the treatment of obstructive symptoms secondary to urothelial carcinoma. In this case report, we present one such unusual outcome where urinary bladder urothelial cancer cells metastasized to the paravertebral soft tissues through apparent seeding along a nephroureterostomy tract.

Severe right hip pain.

While this patient had osteoporosis, she hadn't experienced any recent trauma or falls that would explain her pain.

Simultaneous duodenal stenosis and duodenal web in a newborn.

Failure of duodenal recanalization results in a spectrum of proximal bowel obstruction from stenosis to atresia. Associations between congenital duodenal obstruction and other congenital anomalies have been well documented although the coincidence of duodenal stenosis and duodenal web is incredibly rare, posing a unique diagnostic challenge. We report a case of a full-term 4-day-old female child presented with forceful, bilious emesis and poor oral intake with decreased frequency of urination, and stooling whose initial abdominal radiograph showed several loops of gas-filled bowel in the distal stomach and proximal duodenum mimicking the classic "double-bubble" sign. An upper gastrointestinal barium contrast study revealed distention of the duodenal bulb with an abrupt narrowing and subsequent dilation at the second portion of the duodenum raising the suggestion of multiple duodenal obstructions. Ladd's procedure was performed, and the stenotic and webbed segments were bypassed with a Kimura diamond-shaped duodenoduodenostomy.

Radiology's Emerging Role in 3-D Printing Applications in Health Care.

From its inception as a tool for prototype development in the early 1980s, three-dimensional (3-D) printing has made inroads into almost every sector of industry, including health care. Medical applications range from extra- and intracorporeal orthopedic devices to complex, temporal reconstructions of patient-specific anatomy that allow operative planning and education. In the contemporary climate of personalized medicine, the utility of tangible 3-D models extrapolated directly from patient imaging data seems boundless. The purpose of this review is to briefly outline the development of 3-D printing, discuss its applications across the many medical and surgical specialties, and attempt to address obstacles and opportunities facing radiology as this technology continues to be integrated into patient care.

Keloids and Hypertrophic Scars: A Spectrum of Clinical Challenges.

Since their earliest description, keloids and hypertrophic scars have beleaguered patients and clinicians alike. These scars can be aesthetically disfiguring, functionally debilitating, emotionally distressing, and psychologically damaging, culminating in a significant burden for patients. Our current understanding of keloid pathophysiology has grown and continues to advance while molecular biology, genetics, and technology provide ever-deepening insight into the nature of wound healing and the pathologic perturbations thereof. Greater understanding will lead to the development and application of refined therapeutic modalities. This article provides an overview of our current understanding of keloids, highlighting clinical characteristics and diagnostic criteria while providing a comprehensive summary of the many therapeutic modalities available. The proposed mechanism, application, adverse events, and reported efficacy of each modality is evaluated, and current recommendations are summarized.

An intracellular role for ABCG1-mediated cholesterol transport in the regulated secretory pathway of mouse pancreatic beta cells.

Cholesterol is a critical component of cell membranes, and cellular cholesterol levels and distribution are tightly regulated in mammals. Recent evidence has revealed a critical role for pancreatic beta cell-specific cholesterol homeostasis in insulin secretion as well as in beta cell dysfunction in diabetes and the metabolic response to thiazolidinediones (TZDs), which are antidiabetic drugs. The ATP-binding cassette transporter G1 (ABCG1) has been shown to play a role in cholesterol efflux, but its role in beta cells is currently unknown. In other cell types, ABCG1 expression is downregulated in diabetes and upregulated by TZDs. Here we have demonstrated an intracellular role for ABCG1 in beta cells. Loss of ABCG1 expression impaired insulin secretion both in vivo and in vitro, but it had no effect on cellular cholesterol content or efflux. Subcellular localization studies showed the bulk of ABCG1 protein to be present in insulin granules. Loss of ABCG1 led to altered granule morphology and reduced granule cholesterol levels. Administration of exogenous cholesterol restored granule morphology and cholesterol content and rescued insulin secretion in ABCG1-deficient islets. These findings suggest that ABCG1 acts primarily to regulate subcellular cholesterol distribution in mouse beta cells. Furthermore, islet ABCG1 expression was reduced in diabetic mice and restored by TZDs, implicating a role for regulation of islet ABCG1 expression in diabetes pathogenesis and treatment.

The unique hypusine modification of eIF5A promotes islet beta cell inflammation and dysfunction in mice.

In both type 1 and type 2 diabetes, pancreatic islet dysfunction results in part from cytokine-mediated inflammation. The ubiquitous eukaryotic translation initiation factor 5A (eIF5A), which is the only protein to contain the amino acid hypusine, contributes to the production of proinflammatory cytokines. We therefore investigated whether eIF5A participates in the inflammatory cascade leading to islet dysfunction during the development of diabetes. As described herein, we found that eIF5A regulates iNOS levels and that eIF5A depletion as well as the inhibition of hypusination protects against glucose intolerance in inflammatory mouse models of diabetes. We observed that following knockdown of eIF5A expression, mice were resistant to beta cell loss and the development of hyperglycemia in the low-dose streptozotocin model of diabetes. The depletion of eIF5A led to impaired translation of iNOS-encoding mRNA within the islet. A role for the hypusine residue of eIF5A in islet inflammatory responses was suggested by the observation that inhibition of hypusine synthesis reduced translation of iNOS-encoding mRNA in rodent beta cells and human islets and protected mice against the development of glucose intolerance the low-dose streptozotocin model of diabetes. Further analysis revealed that hypusine is required in part for nuclear export of iNOS-encoding mRNA, a process that involved the export protein exportin1. These observations identify the hypusine modification of eIF5A as a potential therapeutic target for preserving islet function under inflammatory conditions.

AGI-1067, a novel antioxidant and anti-inflammatory agent, enhances insulin release and protects mouse islets.

The antioxidant and anti-inflammatory compound AGI-1067 (succinobucol) has potential as an oral anti-diabetic agent. AGI-1067 reduces H(b)A1c, improves fasting plasma glucose, and reduces new-onset diabetes. We investigated AGI-1067 for possible effects on mouse pancreatic islets in vitro. Pretreatment with 10 microM AGI-1067 increased glucose-stimulated insulin secretion (11 mM) without affecting secretion in basal (3 mM) glucose. AGI-1067 enhanced the intracellular calcium response to glucose stimulation in 7 mM and 11 mM glucose, but had no effect in 28 mM or basal glucose. AGI-1067-pretreated islets also showed enhanced calcium responses to methyl pyruvate and alpha-ketoisocaproate at low doses, but not high doses. The AGI-1067-mediated effects on glucose-stimulated calcium were maintained during continuous diazoxide exposure, suggesting effects on the K(ATP)-channel-independent pathway. AGI-1067 also reduced cytokine-induced islet cell death and expression of iNOS, a key component in cytokine signaling. This is the first report of direct stimulatory and protective effects of a first-in-class potential anti-diabetic agent on pancreatic islets.

Methyltransferase Set7/9 maintains transcription and euchromatin structure at islet-enriched genes.

OBJECTIVE: The activation of beta-cell genes, particularly of those encoding preproinsulin, requires an appropriate euchromatin (or "open") DNA template characterized by hypermethylation of Lys4 of histone H3. We hypothesized that this modification is maintained in islet beta-cells by the action of the histone methyltransferase Set7/9. RESEARCH DESIGN AND METHODS: To identify the role of Set7/9, we characterized its expression pattern and gene regulation and studied its function using RNA interference in both cell lines and primary mouse islets. RESULTS: Within the pancreas, Set7/9 protein shows striking specificity for islet cells, including alpha- and beta-cells, as well as occasional cells within ducts. Consistent with these findings, the Set7/9 gene promoter contained an islet-specific enhancer located between -5,768 and -6,030 base pairs (relative to the transcriptional start site) that exhibited Pdx1-responsive activation in beta-cells. To study Set7/9 function, we depleted insulinoma cells and primary mouse islets of Set7/9 protein using siRNA. Following siRNA treatment, we observed striking repression of genes involved in glucose-stimulated insulin secretion, including Ins1/2, Glut2, and MafA. These changes in transcription were accompanied by loss of dimethylated H3 Lys4 and RNA polymerase II recruitment, particularly at the Ins1/2 and Glut2 genes. Consistent with these data, depletion of Set7/9 in islets led to defects in glucose-stimulated Ca(2+) mobilization and insulin secretion. CONCLUSIONS: We conclude that Set7/9 is required for normal beta-cell function, likely through the maintenance of euchromatin structure at genes necessary for glucose-stimulated insulin secretion.