Transplantation of bioengineered elastic cartilage is considered to be a promising approach for patients with craniofacial defects. We have previously shown that human ear perichondrium harbors a population of cartilage progenitor cells (CPCs). The aim of this study was to examine the use of a rotating wall vessel (RWV) bioreactor for CPCs to engineer 3-D elastic cartilage in vitro. Human CPCs isolated from ear perichondrium were expanded and differentiated into chondrocytes under 2-D culture conditions. Fully differentiated CPCs were seeded into recently developed pC-HAp/ChS (porous material consisted of collagen, hydroxyapatite, and chondroitinsulfate) scaffolds and 3-D cultivated utilizing a RWV bioreactor. 3-D engineered constructs appeared shiny with a yellowish, cartilage-like morphology. The shape of the molded scaffold was maintained after RWV cultivation. Hematoxylin and eosin staining showed engraftment of CPCs inside pC-HAp/ChS. Alcian blue and Elastica Van Gieson staining showed of proteoglycan and elastic fibers, which are unique extracellular matrices of elastic cartilage. Thus, human CPCs formed elastic cartilage-like tissue after 3-D cultivation in a RWV bioreactor. These techniques may assist future efforts to reconstruct complicate structures composed of elastic cartilage in vitro.

This study reported detailed clinical effects of bovine lactoferrin on two canine littermates (1 female and 1 male) with familial neutrophil dysfunction and an investigation of their genetic background. Clinical signs caused by severe upper respiratory bacterial infections were observed in these dogs. Oral administration of bovine lactoferrin for a long duration improved their clinical signs (severe uveitis in the female dog and coughing from pneumonia in the male dog). Their backcross dogs that have the same father didn't show clinical signs of bacterial infection. Neutrophil function tests revealed that the backcross dogs didn't have any disorders. It is likely that abnormal clinical signs are associated with neutrophil dysfunction in the colony and the mother dog of these cases might be the genetic carrier of this dysfunction.

Hyperglycemia is linked to increased heart failure among diabetic patients. However, the mechanisms that mediate hyperglycemia-induced cardiac damage remain poorly understood. Autophagy is a cellular degradation pathway that plays important roles in cellular homeostasis. Autophagic activity is altered in the diabetic heart, but its functional role has been unclear. In this study, we determined if mimicking hyperglycemia in cultured cardiomyocytes from neonatal rats and adult mice could affect autophagic activity and myocyte viability. High glucose (17 or 30 mM) reduced autophagic flux compared with normal glucose (5.5 mM) as indicated by the difference in protein levels of LC3-II (microtubule-associated protein 1 light chain 3 form II) or the changes of punctate fluorescence patterns of GFP-LC3 and mRFP-LC3 in the absence and presence of the lysosomal inhibitor bafilomycin A 1. Unexpectedly, the inhibited autophagy turned out to be an adaptive response that functioned to limit high glucose cardiotoxicity. Indeed, suppression of autophagy by 3-methyladenine or short hairpin RNA-mediated silencing of the Becn1 or Atg7 gene attenuated high glucose-induced cardiomyocyte death. Conversely, upregulation of autophagy with rapamycin or overexpression of Becn1 or Atg7 predisposed cardiomyocytes to high glucose toxicity. Mechanistically, the high glucose-induced inhibition of autophagy was mediated at least partly by increased mTOR signaling that likely inactivated ULK1 through phosphorylation at serine 467. Together, these findings demonstrate that high glucose inhibits autophagy, which is a beneficial adaptive response that protects cardiomyocytes against high glucose toxicity. Future studies are warranted to determine if autophagy plays a similar role in diabetic heart in vivo.

Granulocytes were collected by the bag separation method and stored in whole blood for up to 72h. We evaluated the expressions of various surface antigens: CD62L, CD11b, CD18, CD64, CD16b, and CD95. Apoptosis was assessed both by flow cytometry and by light microscopy. Expression levels of all the surface antigens were shown to be maintained during storage for up to 72h. Approximately 80% of granulocytes were annexin V negative until 72h after collection. The storage of granulocyte concentrates collected by the bag separation method may maintain granulocyte surface antigens and lack an apoptotic marker.

PURPOSE This study seeks to investigate doctors' desire to change the hospital where they work to sustain higher quality care. DESIGN/METHODOLOGY/APPROACH Self-administered questionnaires were sent to doctors in Aichi Prefecture, Japan. Data were analyzed using univariate and logistic regression analysis and recursive partitioning. FINDINGS Factors related to doctors' desire to change hospitals, according to logistic regression, were interaction between working hours and satisfaction with the hospital, evaluation, local government hospitals versus private ones, small vs large hospitals, ophthalmology versus internal medicine, desire to continue working as a hospital doctor and age. Additionally, working hours were also found to be related, based on recursive partitioning. RESEARCH LIMITATIONS/IMPLICATIONS The response rate was low and sampling bias was observed--therefore results need careful interpretation. Also, because this was a cross-sectional study, causal relationships could not be identified. Desire to change hospitals, but not actual behavior, was measured. PRACTICAL IMPLICATIONS Efforts to prevent doctors from changing hospitals should include considering job satisfaction and workload, doctor evaluation methods, support for career progression and organizational management. ORIGINALITY/VALUE As the hospital doctor shortage in rural areas becomes more serious, exploring doctors' desire to leave their current hospital is meaningful for Japanese hospital managers and hospitals worldwide aiming to provide sustainable and higher quality care.

Purpose: Several small studies have reported that acute exacerbation (AE) of idiopathic interstitial pneumonia (IIP) can occur after lung resection for patients with non-small cell lung cancer, though the incidence rate is unclear. Methods: We examined our institutional data and performed a search of the MEDLINE database for publications regarding AE of IIP following surgery for lung cancer. Studies reporting the incidence rates of IIP and AE were included. Results: Eleven studies including our institutional data were determined to be eligible. Seven studies designated the incidence of IIP. Of 4749 patients (from 7 studies) who underwent lung resection for NSCLC, 277 had IIP, for an incidence rate of 5.8%(range 1.1%-11.7%). Eleven studies designated the incidence of AE from IIP patient, 67 (15.8%) of 424 IIP patients (from 11 studies) developed AE after surgery, of whom 38 (56.7%) died during the postoperative course. Conclusion: Coexistent IIP in patients with lung cancer increases the risk of lung cancer surgery. Furthermore, AE of IIP may be a major cause of operation-related death.

We previously demonstrated that a deficiency in core fucosylation by the genetic disruption of α 1, 6- fucosyltransferase ((#)Fut8) leads to lethal abnormalities and the development of emphysematous lesions in the lung by attenuation of TGF-β1 receptor signaling. Herein, we investigated the physiological relevance of core fucosylation in the pathogenesis of emphysema using viable heterozygous knockout mice (Fut8(+/-)) that were exposed to cigarette smoke (CS). The Fut8(+/-) mice exhibited a marked decrease in FUT8 activity and matrix metalloproteinase (MMP)-9 activities were elevated in the lung at an early stage of exposure. Emphysema developed after a three-month-CS-exposure, accompanied by the recruitment of large numbers of macrophages to the lung. CS exposure substantially and persistently elevated expression level of Smad7, resulting in a significant reduction of Smad2 phosphorylation that controls MMP-9 expression, in Fut8(+/-) mice and Fut8 deficient embryonic fibroblast cells. The present in vivo and in vitro studies show that an impaired core fucosylation enhanced the susceptibility to CS and constitutes, at least a part of the disease process of emphysema, in which TGF-β-Smad signaling is impaired and the MMP-mediated destruction of lung parenchyma was upregulated.

Ms1/STARS is a novel muscle specific actin-binding protein that specifically modulates the MRTF-SRF regulatory axis within striated muscle. This ms1/STARS dependent regulatory axis is of central importance within the cardiac gene regulatory network and has been implicated in cardiac development and post-natal cardiac function/homeostasis. Dysregulation of ms1/STARS is associated with and causative of pathological cardiac phenotypes, including cardiac hypertrophy and cardiomyopathy. In order to gain an understanding of the mechanisms governing ms1/STARS expression in the heart, we have coupled a comparative genomic in silico analysis with reporter,-gain and -loss of function approaches. Through this integrated analysis we have identified three evolutionary conserved regions (ECRs) α, SINA and DINA that act as cis-regulatory modules and confer differential cardiac specific activity. Two of these ECRs, α and DINA, displayed distinct regulatory sensitivity to the core cardiac transcription factor GATA4. Overall our results demonstrate that within the embryonic, neonatal and adult heart, GATA4 represses ms1/STARS expression with pathologically associated depletion of GATA4 (Type -1/-2 diabetic models) resulting in ms1/STARS up-regulation. This GATA4 dependent repression of ms1/STARS expression has major implications for MRTF-SRF signalling in the context of cardiac development and disease.

BACKGROUND AND OBJECTIVES: Gastroparesis, a gastrointestinal autonomic neuropathy, is a common adverse reaction in chronic hepatitis C (CHC) patients receiving interferon therapy. Current therapeutic options are limited. We evaluated the efficacy of mosapride for IFN-induced gastroparesis. METHODS: Twenty-four consecutive CHC patients were randomly assigned to either the control group, which received pegylated interferon α-2b at 1.5 μg/kg/week and ribavirin at 600-1,000 mg/day, depending on body weight (PegIFN/RBV), or the mosapride group, which received PegIFN/RBV plus mosapride at 15 mg/person/day. The solid-phase gastric emptying half-times (T1/2) of the total, proximal, and distal stomach (scintigraphy) and digestive symptoms (questionnaire) were measured within one week before and four weeks after initiation of the assigned therapy. The test meal comprised a 200-g pancake containing Tc-99m diethylenetriamine pentaacetic acid. RESULTS: In the control group, after PegIFN/RBV initiation, a significant increase was observed in the total T1/2 (before: 84.0 ± 22.1 min versus after: 100.8 ± 28.9 min, P = 0.03), the distal T1/2 (before: 95.3 ± 32.2 min versus after: 115.3 ± 41.4 min, P = 0.03), and digestive symptom score (before: 3.2 ± 1.4 versus after: 8.1 ± 4.8, P = 0.02); proximal T1/2 change was not significant. In the mosapride group, no significant delays were observed in the total, proximal, and distal T1/2 values; the change in symptom scores was not significant. CONCLUSIONS: Mosapride improved total and distal gastric motility in IFN-induced gastroparesis, and consequently relieved symptoms.