Not all obstructive cardiac lesions are created equal: double-chamber right ventricle in pregnancy

Double-chambered right ventricle (DCRV) is a rare form of right ventricular outflow tract (RVOT) obstruction accounting for approximately 1% of patients with congenital heart disease. It consists of an anomalous muscle bundle that divides the right ventricle usually between the sinus (inlet) and the infundibulum (outlet). This division creates a proximal chamber with high pressure and a distal chamber with low pressure. The hemodynamic obstruction of the RVOT is usually an acquired phenomenon, however the substrate for the anomalous muscle bundle is likely congenital. The diagnosis of DCRV should be considered in the young patient with an elevated right ventricular systolic pressure and intracavitary gradient. Echocardiography and cardiac MRI are the principal diagnostic tools for the assessment of DCRV. This entity is often misdiagnosed as pulmonary hypertension in the young patient, and can often go overlooked and untreated for many years. Definitive therapy involves surgical resection of the muscle bundle. This can often be curative and if done in a timely fashion, may prevent right ventricular remodeling. We describe the unique diagnostic dilemma, the course and management of a young adult with DCRV during pregnancy.     

Corpus callosum area in children and adults with autism

Despite repeated findings of abnormal corpus callosum structure in autism, the developmental trajectories of corpus callosum growth in the disorder have not yet been reported. In this study, we examined corpus callosum size from a developmental perspective across a 30-year age range in a large cross-sectional sample of individuals with autism compared to a typically developing sample. Midsagittal corpus callosum area and the 7 Witelson subregions were examined in 68 males with autism (mean age 14.1 years; range 3–36 years) and 47 males with typical development (mean age 15.3 years; range 4–29 years). Controlling for total brain volume, increased variability in total corpus callosum area was found in autism. In autism, increased midsagittal areas were associated with reduced severity of autism behaviors, higher intelligence, and faster speed of processing (p = 0.003, p = 0.011, p = 0.013, respectively). A trend toward group differences in isthmus development was found (p = 0.029, uncorrected). These results suggest that individuals with autism benefit functionally from increased corpus callosum area. Our cross-sectional examination also shows potential maturational abnormalities in autism, a finding that should be examined further with longitudinal datasets.     

Solitary Extra-Hepatic Hilar Peribiliary Cyst Presenting with Obstructive Jaundice: A Case Report

Peribiliary cyst is a poorly recognized and under-reported clinico-pathologic entity around the biliary tree. Peribiliary cysts are cystic dilatations of obstructed peribiliary glands, which are normal elements of the biliary tract. They are generally asymptomatic and rarely cause biliary obstruction. They are usually discovered incidentally at autopsy or in explants following liver transplantation.

A 59-year-old male patient presenting with obstructive jaundice due to a large extra-hepatic hilar peribiliary cyst is reported here. We briefly discuss its differential diagnoses such as bile duct cyst, liver cyst or lymph cyst, and its management.

Radiological imaging demonstrated a solitary large (5 cm) well-defined, smooth, thin walled cystic lesion at the porta hepatis paralleling but not communicating with the bile duct. A wide cyst de-roofing was performed and histological examination of the cystic wall revealed an inflammatory cyst.

The patient made an uneventful recovery and remained asymptomatic with normal liver function tests 36 months post-operatively.     

Contribution of GPR30 for 1,25 dihydroxyvitamin D3 protection in EAE

Previous studies have demonstrated that vitamin D3-mediated protection in EAE occurs only in females and is dependent on the presence of diestrus levels of 17β-estradiol (E2). To evaluate the role of estrogen receptors in vitamin D3 treatment of EAE, we compared disease severity, CNS histopathology and immunological responses in vehicle and calcitrol (1,25 dihydroxyvitamin D₃) treated WT C57BL/6 mice vs. GPR30 membrane estrogen receptor (MER) knockout mice with MOG-35-55 peptide-induced EAE. Our results demonstrated that vitamin D₃-mediated prevention of clinical signs, CNS cellular lesions and demyelination observed in WT mice was abrogated in GPR30-KO mice with EAE. Regulatory effects of vitamin D₃ treatment that were MER dependent included increased levels of IL-10 and IL-6 secreted by MOG peptide-reactive splenocytes and increased expression of CCL5, CCR1 & CCR3 in spleen tissue. These results demonstrate for the first time that the MER is a key contributor to the E2-dependent effects of vitamin D₃-mediated protection in EAE.     

Receptor for Advanced Glycation End Products (RAGE) and Implications for the Pathophysiology of Heart Failure

The receptor for advanced glycation end products (RAGE) is expressed in the heart in cardiomyocytes, vascular cells, fibroblasts, and in infiltrating inflammatory cells. Experiments in murine, rat, and swine models of injury suggest that RAGE and the ligands of RAGE are upregulated in key injuries to the heart, including ischemia/reperfusion injury, diabetes, and inflammation. Pharmacological antagonism of RAGE or genetic deletion of the receptor in mice is strikingly protective in models of these stresses. Data emerging from human studies suggest that measurement of levels of RAGE ligands or soluble RAGEs in plasma or serum may correlate with the degree of heart failure. Taken together, the ligand-RAGE axis is implicated in heart failure and we predict that therapeutic antagonism of RAGE might be a unique target for therapeutic intervention in this disorder.     

Nanofibrous structured biomimetic strategies for skin tissue regeneration

Mimicking porous topography of natural extracellular matrix is advantageous for successful regeneration of damaged tissues or organs. Nanotechnology being one of the most promising and growing technology today shows an extremely huge potential in the field of tissue engineering. Nanofibrous structures that mimic the native extracellular matrix and promote the adhesion of various cells are being developed as tissue‐engineered scaffolds for skin, bone, vasculature, heart, cornea, nervous system, and other tissues. A range of novel biocomposite materials has been developed to enhance the bioactive or therapeutic properties of these nanofibrous scaffolds via surface modifications, including the immobilization of functional cell‐adhesive ligands and bioactive molecules such as drugs, enzymes, and cytokines. In skin tissue engineering, usage of allogeneic skin is avoided to reestablish physiological continuity and also to address the challenge of curing acute and chronic wounds, which remains as the area of exploration with various biomimetic approaches. Two‐dimensional, three‐dimensional scaffolds and stem cells are presently used as dermal regeneration templates for the treatment of full‐thickness skin defects resulting from injuries and severe burns. The present review elaborates specifically on the fabrication of nanofibrous structured strategies for wound dressings, wound healing, and controlled release of growth factors for skin tissue regeneration.     

Metabolic effects of sleeve gastrectomy in female rat model of diet-induced obesity

BackgroundAlthough women disproportionately undergo bariatric surgery, the rodent models investigating the mechanisms of bariatric surgery have been limited to males. Female rodent models can also potentially allow us to understand the effects of surgical intervention on future generations of offspring. Sleeve gastrectomy is an attractive weight loss procedure for reproductive-age female patients because it avoids the malabsorption associated with intestinal bypass. We sought to evaluate the effect of sleeve gastrectomy on young female rats with diet-induced obesity at the University of California, Los Angeles, David Geffen School of Medicine.MethodsSprague-Dawley female rats were fed a 60% high-fat diet. At 12 weeks of age, the rats underwent either sleeve gastrectomy or sham surgery. The rats were killed 4 weeks after surgery. A chemistry panel was performed, and the serum adipokines and gut hormones were assayed. The homeostasis model assessment score was calculated. The liver histologic findings were graded for steatosis. The 2-sample t test was used to compare the results between the 2 groups.ResultsSleeve gastrectomy was associated with significant weight loss (5% ± 6% versus ?4% ± 6%; P < .001), lower leptin levels (1.3 ± 1.2 versus 3.5 ± 2.3 ng/mL; P < .01), and higher adiponectin levels (.43 ± .19 versus .17 ± .14 ng/mL; P < .004) compared with the sham-operated rats. No significant differences were found in the fasting ghrelin levels. Furthermore, we did not observe evidence of insulin resistance or steatohepatitis after 11 weeks of high-fat diet. Despite these limitations, additional gender-specific studies are warranted given that most bariatric surgeries are performed in women.ConclusionSleeve gastrectomy appears to result in weight loss and improvements in adiponectin and leptin by way of mechanisms independent of ghrelin levels in a female model of diet-induced obesity.