Nanostructured gellan and xanthan hydrogel depot integrated within a baghdadite scaffold augments bone regeneration

Controlled delivery of biological cues through synthetic scaffolds to enhance the healing capacity of bone defects is yet to be realized clinically. The purpose of this study was development of a bioactive tissue‐engineered scaffold providing the sustained delivery of an osteoinductive drug, dexamethasone disodium phosphate (DXP), encapsulated within chitosan nanoparticles (CN). Porous baghdadite (BD; Ca₃ZrSi₂O₉) scaffolds, a zirconia‐modified calcium silicate ceramic, was coated with DXP‐encapsulated CN nanoparticles (DXP–CN) using nanostructured gellan and xanthan hydrogel (GX). Crosslinker and GX polymer concentrations were optimized to achieve a homogeneous distribution of hydrogel coating within BD scaffolds. Dynamic laser scattering indicated an average size of 521 ± 21 nm for the DXP–CN nanoparticles. In vitro drug‐release studies demonstrated that the developed DXP–CN–GX hydrogel‐coated BD scaffolds (DXP–CN–GX–BD) resulted in a sustained delivery of DXP over the 5 days (78 ± 6% of drug release) compared with burst release over 1 h, seen from free DXP loaded in uncoated BD scaffolds (92 ± 8% release in 1 h). To estimate the influence of controlled delivery of DXP from the developed scaffolds, the effect on MG 63 cells was evaluated using various bone differentiation assays. Cell culture within DXP–CN–GX–BD scaffolds demonstrated a significant increase in the expression of early and late osteogenic markers of alkaline phosphatase activity, collagen type 1 and osteocalcin, compared to the uncoated BD scaffold. The results suggest that the DXP‐releasing nanostructured hydrogel integrated within the BD scaffold caused sustained release of DXP, improving the potential for osteogenic differentiation. Copyright © 2015 John Wiley & Sons, Ltd.     

Cancer screening promotion among medically underserved Asian American women: integration of research and practice

Mammography and Pap smear tests are known to be effective early detection measures for breast and cervical cancers, respectively, but Asian Americans are reluctant to make visits for routine preventive care. Quantitative and qualitative research conducted by the Healthy Asian Americans Project (HAAP) between 1996 and 1999 indicated that Asian residents in southeastern Michigan, like the general Asian population in the US, underutilized early cancer screening programs due to cultural, psychosocial, linguistic, and economic barriers. This article reports how the HAAP's research findings guided the Michigan Breast and Cervical Cancer Control Program (BCCCP) promotion (conducted from 2000 to 2001 among medically underserved Asian women residing in southeastern Michigan), and how evaluation of the HAAP's BCCCP promotion will direct future research and health promotion programs. The article presents strategies used to improve access to cancer screening programs for diverse Asian sub-groups as well as outcomes of the 2-year HAAP's BCCCP promotion among the target population. Discussion regarding lessons and experiences gained from integration of research and practice has implications on design and implementation of the cancer screening promotion for the rapidly increasing Asian American population as well as other medically underserved minority populations in the US.     

Developmental cigarette smoke exposure: kidney proteome profile alterations in low birth weight pups

The Brenner hypothesis states that a congenital reduction in nephron number predisposes to adult-onset hypertension and renal failure. The reduction in nephron number induced by proportionally smaller kidney mass may predispose offspring to glomerular hyperfiltration with maturity onset obesity. Developmental cigarette smoke exposure (CSE) results in intrauterine growth retardation with a predisposition to obesity and cardiovascular disease at maturity. Utilizing a mouse model of 'active' developmental CSE (gestational day [GD] 1-postnatal day [PD] 21; cotinine>50 ng/mL) characterized by persistently smaller offspring with proportionally decreased kidney mass, the present study examined the impact of developmental CSE on the abundance of proteins associated with cellular metabolism in the kidney. Following cessation of CSE on PD21, kidney tissue was collected from CSE and Sham exposed pups for 2D-SDS-PAGE based proteome profiling with statistical analysis by partial least squares-discriminant analysis (PLS-DA) with affected molecular pathways identified by ingenuity pathway analysis. Proteins whose expression in the kidney were affected by developmental CSE belonged to the inflammatory disease, cell to cell signaling/interaction, lipid metabolism, small molecule biochemistry, cell cycle, respiratory disease, nucleic acid and carbohydrate metabolism networks. The present findings indicate that developmental CSE alters the kidney proteome. The companion paper details the liver proteome alterations in the same offspring.     

Novel SOX2 partner-factor domain mutation in a four-generation family

Anophthalmia (no eye), microphthalmia (small eye) and associated ocular developmental anomalies cause significant visual handicap. In most cases the underlying genetic cause is unknown, but mutations in some genes, such as SOX2, cause ocular developmental defects, particularly anophthalmia, in a subset of patients. Here, we describe a four-generation family with a p.Asp123Gly mutation in the highly conserved partner-factor interaction region of the SOX2 protein, which is important for cell-specific actions of SOX2. The proband in this family has bilateral anophthalmia and several other family members have milder ocular phenotypes, including typical optic fissure coloboma. Expression studies indicate that Sox2 is expressed in the eye at the site of closure of the optic fissure during development. The SOX2 mutation in this family implicates the partner-factor interaction region of SOX2 in contributing to the specificity of SOX2 action in optic fissure closure. Our findings indicate that investigation of SOX2 in a broad range of eye anomaly patients aids in the determination of particular functions of SOX2 in development.     

Chylothorax following innominate vein thrombosis--a rare complication of transvenous pacemaker implantation

A case of chylothorax following innominate vein thrombosis which developed as a late complication of transvenous pacemaker implantation is discussed. A 78-year-old man presented with a refractory left-sided pleural effusion, which turned out to be a chylothorax. He had undergone a transvenous pacemaker implantation 6 years earlier for sick sinus syndrome. Aetiological work-up showed occlusion of the innominate vein as the cause for the chylothorax. The chylothorax resolved following pleurodesis with talc slurry, and the innominate vein was recanalized by angioplasty. To our knowledge, this is the first report of a case of this nature.     

Ameliorative effects of tinospora cordifolia root extract on histopathological and biochemical changes induced by aflatoxin-b(1) in mice kidney

The present study was planned to investigate the ability of the Tinospora cordifolia to scavenge free radicals generated during aflatoxicosis. A total no. of 48 male Swiss albino mice (30 ± 5 g) were exposed to Aflatoxin B(1)(AFB(1)) (2 μg/30 g b.wt, orally) either individually or in combination with T. cordifolia (50, 100, 200 mg/kg, orally) once daily for 25 days. AFB(1) exposure led to significant rise in thiobarbituric acid reactive substances (TBARS) and fall in superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), glutathione-S-transferase (GST), glutathione peroxidase (GPx), glutathione reductase (GR), ascorbic acid, and protein content. T. cordifolia was found to show protective effect by lowering down the content of TBARS and enhancing the GSH, ascorbic acid, protein, and the activities of antioxidant enzymes viz., SOD, CAT, glutathione peroxidase, GST, and GR in kidney. Histopathological analysis of kidney samples also confirmed the protective values and antioxidant activity of ethanolic extract of herb. T. cordifolia showed protection against aflatoxin-induced nephrotoxicity due to the presence of alkaloids such as a choline, tinosporin, isocolumbin, palmatine, tetrahydropalmatine, and magnoflorine.     

Pulmonary complications of hemoglobinopathies

Hemoglobinopathies are diseases caused by genetic mutations that result in abnormal, dysfunctional hemoglobin molecules or lower levels of normal hemoglobin molecules. The most common hemoglobinopathies are sickle cell disease (SCD) and the thalassemias. In SCD, an abnormal hemoglobin alters the erythrocyte, causing a chronic hemolytic anemia, which can lead to pulmonary parenchymal damage and impaired vascular function. Pulmonary complications of SCD include the acute chest syndrome (ACS), reactive airways disease, pulmonary hypertension (PH), and pulmonary fibrosis. Episodes of ACS and the development of PH both increase the risk of death in patients with SCD. Both α and β thalassemia are characterized by impaired production of hemoglobin subunits, and severity of disease varies widely. Although screening studies suggest that PH is a common complication for patients with thalassemia, its impact on survival is unknown. Understanding the pathogenesis, diagnostic options, and prevention and treatment strategies for such complications is critical for clinicians who care for these patients. In this review, we discuss the mechanisms and clinical presentation of pulmonary complications associated with hemoglobinopathies, with a focus on recent advances in pathogenesis and treatment.     

Dectin-1 Fc targeting of aspergillus fumigatus beta-glucans augments innate defense against invasive pulmonary aspergillosis

Invasive pulmonary aspergillosis (IPA) has significantly increased over the last decade. Here, a fusion protein consisting of the Dectin-1 extracellular domain linked to the Fc portion of murine immunoglobulin G1 augmented alveolar macrophage killing of Aspergillus fumigatus and shifted mortality associated with IPA via attenuation of A. fumigatus growth in the lung.     

Large retroperitoneal schwannoma mimicking a cystic ovarian mass in a patient with Hansen's disease

We present a rare case of retroperitoneal cystic schwannoma of the pelvis in a patient with Hansen's disease that mimicked an ovarian cyst. Due to economic constraints and because the lesion was assumed to be of ovarian origin, the patient did not undergo any cross-sectional imaging other than sonography. Sonographically guided fine needle aspiration of the cystic lesion was inconclusive. A cystic schwannoma was diagnosed at laparotomy.