Improving the structural qualities of the new tissue that fills osteochondral defects is critical to enhance articular cartilage repair. Enamel matrix derivative (EMD) modulates chondrocyte proliferation and differentiation. In the present study, we assessed the effect of EMD on early chondrogenesis and bone repair in an osteochondral defect model in vivo. Standardized osteochondral defects were established in the trochlear groove of rabbits. EMD or the carrier substance without EMD activity was applied to the blood clot that was forming within the defect. After 3 weeks in vivo, the quality of articular cartilage repair was evaluated using a semiquantitative scoring system and biochemical assays for proteoglycan and DNA contents. The extent of formation of the subchondral bone within the original osteochondral defect was measured. Application of EMD resulted in an inferior histological articular cartilage repair. The total proteoglycan content of the repair tissue as well as the proteoglycan production standardized to the cell proliferative activities within the defects were reduced following treatment with EMD. Restoration of the subchondral bone within the osteochondral defect was delayed when EMD was applied. Significant changes of the synovial membrane were present, reflected in an increased villus thickening and changes in villus architecture. These data suggest that EMD inhibits the early repair of the osteochondral unit in vivo. Copyright © 2012 John Wiley & Sons, Ltd.

Objectives. Activity of neuropeptide Y (NPY), tyrosine hydroxylase (TH), corticoliberine (CRH), and oxytocin (OXY) producing cells was investigated in the ovariectomized (OVX) female C57BL/6 mice kept on the high fat diet for 16 weeks and their response to colchicine stress in selected brain areas, including the hypothalamic paraventricular (PVN), dorsomedial (DMN) and arcuate (ARC) nuclei, A1/C1 (in the ventrolateral medulla), and A2/C2 (in the nucleus of the solitarii tract, NTS) catecholaminergic cell groups.Methods. The OVX female C57BL/6 mice kept on high fat diet were sacrificed by transcardial perfusion with fixative 48 h after intracerebroventricular injection of colchicine (18 µg mice). Dual Fos/neuropeptide immunohistochemistry was employed to investigate Fos/neuropeptide colocalizations.Results. In the OVX saline-treated mice (sham control) with standard diet (St diet), no immunopositive CRH and NPY neurons were identified in the PVN and weak Fos immunostainig was visible in TH neurons in the DMN and ARC nuclei. Colchicine treatment in the OVX mice with St diet increased the number of CRH and OXY immunopositive neurons in the PVN as well as the number of NPY and TH neurons in DMN and ARC nuclei and NPY neurons in the middle NTS (mNTS) and A1/C1 cell group. Prolonged HF diet in OVX sham control mice moderately increased the number of Fos/TH neurons in the mNTS and commissural NTS (cNTS) in comparison with St diet mice. However, prolonged HF diet in OVX colchicines-treated mice reduced the number of Fos/NPY neurons in the anterior NTS (aNTS) and A1/C1 cell group in comparison with colchicines-treated animals with St diet as well as Fos-TH neurons in the mNTS and cNTS in comparison with saline-treated animals with HF diet.Conclusion. The data of this pilot study indicate that prolonged high fat diet might: 1) represent itself a light/moderate stimulus for activation of TH neurons in the NTS and A1/C1 cell group as well as NPY neurons in the A1/C1 cell group and 2) interfere with colchicines-induced and time-delayed Fos activation in the NPY and TH neurons in both the above mentioned brain nuclei.<strong></strong> Keywords: hypothalamic nuclei, Fos-immunohistochemistry, neuropeptide Y, tyrosine hydroxylase, corticoliberine, oxytocin, colchicine stress, female C57BL/6 mice.

ABSTRACT: BACKGROUND: Recommendations for acceptable emergency department (ED) length of stay (LOS) vary internationally with [less than or equal to] 8 h generally considered acceptable. Protracted ED LOS may place critically ill patients requiring mechanical ventilation at increased risk of adverse events as most EDs are not resourced for longitudinal delivery of critical care. Our objective was to quantify the ED LOS for mechanically ventilated patients (invasive and/or non-invasive ventilation [NIV]) and to explore patient and system level predictors of prolonged ED LOS. Additionally, we aimed to describe delivery and monitoring of ventilation in the ED. METHODS: Prospective observational study of ED LOS for all patients receiving mechanical ventilation at four metropolitan EDs in Toronto, Canada over two six-month periods in 2009 and 2010. RESULTS: We identified 618 mechanically ventilated patients which represented 0.5 %(95 % CI 0.4 %-0.5 %) of all ED visits. Of these, 484 (78.3 %) received invasive ventilation, 118 (19.1 %) received NIV; 16 received both during the ED stay. Median Kaplan-Meier estimated duration of ED stay for all patients was 6.4 h (IQR 2.8-14.6). Patients with trauma diagnoses had a shorter median (IQR) LOS, 2.5 h (1.3-5.1), compared to ventilated patients with non-trauma diagnoses, 8.5 h (3.3-14.0)(p <0.001). Patients requiring NIV had a longer ED stay (16.6 h, 8.2-27.9) compared to those receiving invasive ventilation exclusively (4.6 h, 2.2-11.1) and patients receiving both (15.4 h, 6.4-32.6)(p <0.001). Longer ED LOS was associated with ED site and lower priority triage scores. Shorter ED LOS was associated with intubation at another ED prior to transfer. CONCLUSIONS: While patients requiring mechanical ventilation represent a small proportion of overall ED visits these critically ill patients frequently experienced prolonged ED stay especially those treated with NIV, assigned lower priority triage scores at ED presentation, and non-trauma patients.

Genetic studies indicate high number of potential factors related to asthma. Based on earlier linkage analyses we selected the 11q13 and 14q22 asthma susceptibility regions, for which we designed a partial genome screening study using 145 SNPs in 1201 individuals (436 asthmatic children and 765 controls). The results were evaluated with traditional frequentist methods and we applied a new statistical method, called Bayesian network based Bayesian multilevel analysis of relevance (BN-BMLA). This method uses Bayesian network representation to provide detailed characterization of the relevance of factors, such as joint significance, the type of dependency, and multi-target aspects. We estimated posteriors for these relations within the Bayesian statistical framework, in order to estimate the posteriors whether a variable is directly relevant or its association is only mediated.With frequentist methods one SNP (rs3751464 in the FRMD6 gene) provided evidence for an association with asthma (OR = 1.43(1.2-1.8); p = 3×10(-4)). The possible role of the FRMD6 gene in asthma was also confirmed in an animal model and human asthmatics.In the BN-BMLA analysis altogether 5 SNPs in 4 genes were found relevant in connection with asthma phenotype: PRPF19 on chromosome 11, and FRMD6, PTGER2 and PTGDR on chromosome 14. In a subsequent step a partial dataset containing rhinitis and further clinical parameters was used, which allowed the analysis of relevance of SNPs for asthma and multiple targets. These analyses suggested that SNPs in the AHNAK and MS4A2 genes were indirectly associated with asthma. This paper indicates that BN-BMLA explores the relevant factors more comprehensively than traditional statistical methods and extends the scope of strong relevance based methods to include partial relevance, global characterization of relevance and multi-target relevance.

BACKGROUND: The excellent prognosis of human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinomas (SCCs) against severe chemoradiotherapy (CRT) toxicities has opened discussion of deintensification trials. The purpose of this study was to describe the perspective of patients with HPV-positive and HPV-negative disease toward such studies. METHODS: Fifty-one patients with oropharyngeal SCC (post-CRT) underwent semistructured interviews contrasting toxicities of radiotherapy (RT) alone and CRT. Patients were asked what potential difference in cancer survival was acceptable to prefer RT over CRT. Initially, survival rate was the same for both treatments, then the RT rate was reduced until the preference switched. Treatment experience and preference for deintensified CRT were collected. RESULTS: Ninety-percent of patients initially selected RT, but 69% switched to CRT after 0% to 5% reduction in survival. Patients that rated their treatment experience as mild would accept lower survival versus severe treatment (p =.02). Eighty-one percent of patients (33 of 40) indicated they preferred reduced chemotherapy in CRT. CONCLUSION: Patients accept little difference in survival between treatments to avoid toxicity. © 2012 Wiley Periodicals, Inc. Head Neck, 2012.

The dominant nicotine acetylcholine receptor (nAChR) subtype in the brain is the pentameric receptor containing both α4 and β2 subunits (α4β2). Due to the lack of selective agonists it has not been ruled out what neuronal circuits that are stimulated after systemic administration with nicotine. We used the novel and selective α4β2 receptor agonist ispronicline (10 and 30mg/kg s.c.) to localise the activated neurons in the rat forebrain using c-Fos-immunoreactivity as a marker of immediate neuronal activity. In the hypothalamic paraventricular nucleus, a large increase of c-Fos-positive cells was found only within its medial part. In addition, an increased number of c-Fos-immunoreactive cells were observed in the central nucleus of the amygdala, and the dorsolateral part of the bed nucleus of the stria terminalis. The restricted distribution of c-Fos to these areas, all of which are directly or indirectly involved in acute stress regulation after a single dose of ispronicline, supports earlier studies that the α4β2 receptors are strongly involved in nicotine-dependent activation of the hypothalamo-pituitary adrenocortical axis.

Korompay A, Borka K, Lotz G, Somorácz Á, Törzsök P, Erdélyi-Belle B, Kenessey I, Baranyai Z, Zsoldos F, Kupcsulik P, Bodoky G, Schaff Z & Kiss A (2012) Histopathology Tricellulin expression in normal and neoplastic human pancreas Aims:  Tricellulin is a member of the family of tight junction proteins, which are found concentrated mainly at tricellular contacts. Altered expression of several tight junction components has been observed during carcinogenesis. In the present study, we have analysed the expression of tricellulin in normal human pancreas, and in primary exocrine and endocrine pancreatic tumours. Methods and results:  A total of 96 cases were studied: 20 normal pancreas, 58 pancreatic ductal adenocarcinomas, 15 pancreatic endocrine neoplasms, and three acinar cell carcinomas. Immunohistochemistry (analysed by digital morphometry), immunofluorescence, western blot analysis and reverse transcription polymerase chain reaction were performed. Tricellulin was localized apically in normal ducts and acini as intensive, spotty immunopositivity at tricellular contacts, whereas weaker signals were observed at the junction between two cells. Islets of Langerhans were negative. Well-differentiated ductal adenocarcinomas significantly overexpressed tricellulin as compared with poorly differentiated adenocarcinomas. Acinar cell carcinomas expressed tricellulin in tumour cells. All endocrine tumours were tricellulin-negative. Conclusions:  This is the first report to describe the tricellulin expression profile in normal and neoplastic human pancreas. Both normal and neoplastic pancreatic exocrine tissues expressed tricellulin, whereas no expression was seen in normal or neoplastic endocrine cells. Tricellulin expression in pancreatic ductal adenocarcinomas showed a significant negative correlation with the degree of differentiation.

OBJECTIVE Central corneal thickness (CCT) affects intraocular pressure (IOP) readings; however, CCT influence on topical medication efficacy is unknown. We evaluated the IOP-lowering effect of topical prostaglandin analogues (PGAs) in relation to CCT. DESIGN Post hoc analysis of a randomized prospective trial. METHOD Subjects randomized to a PGA were followed for 24 weeks and were analyzed for relationship between CCT and IOP lowering. PARTICIPANTS Patients with either newly diagnosed ocular hypertension or open-angle glaucoma. RESULTS 75 subjects were enrolled. The mean age was 62.7 ± 10.5 years; 48 were Caucasian. The mean CCT was 562.4 ± 41.4 μ. At repeated measures, ANCOVA analysis showed a significant effect of both baseline IOP (p < 0.0001) and CCT (p = 0.003) on IOP. At week 12, a regression analysis of the effect of CCT on baseline IOP showed that for every 10 μ increase in CCT there was 0.3 mm Hg less IOP decrease from baseline. CONCLUSIONS We found a statistically significantly association between a lower mean IOP and a thinner cornea when baseline IOP is controlled for. The magnitude of the relationship is small but may be clinically significant in patients with either very thin or very thick corneas.

Objectives. The magnocellular neurons in the hypothalamic paraventricular (PVN) and supraoptic nuclei (SON) either contain vasopressin or oxytocin. Even though both hormones are released after systemic administration of nicotine, the mechanism through which the two populations of neurons are activated is not known. This study was carried out in the rat to investigate the effect of increasing doses of nicotine on subsets of magnocellular neurons containing either oxytocin or vasopressin.Methods. The activated neurons were identified by means of Fos immunohistochemistry and the induction of Fos in magnocellular subdivisions was investigated by means of dual-immunohistochemistry.Results. While oxytocinergic neurons were sensitive to systemic administration of 0.5 mg/kg of nicotine, vasopressinergic neurons were not affected at doses up to 1 mg/kg. The vast majority (85%) of oxytocinergic neurons in the PVN was affected by nicotine, whilst only about half of the vasopressinergic neurons were stimulated, and only at maximal doses. Notably, the sensitivity of oxytocinergic neurons to nicotine was found to be different in the PVN and SON, because only about 55% of the SON oxytocinergic neurons co-stored Fos even after the highest dose of nicotine.Conclusion. These data show that magnocellular neurons are differentially regulated by nicotine and that their sensitivity is dependent on both their peptidergic phenotype and their location within the hypothalamus. Keywords: acetylcholine, vasopressin, oxytocin, Fos, stress, cell counting.