The association of cold weather and all-cause and cause-specific mortality in the island of Ireland between 1984 and 2007

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.This article has been made available through the Brunel Open Access Publishing Fund.Background This study aimed to assess the relationship between cold temperature and daily mortality in the Republic of Ireland (ROI) and Northern Ireland (NI), and to explore any differences in the population responses between the two jurisdictions. Methods A time-stratified case-crossover approach was used to examine this relationship in two adult national populations, between 1984 and 2007. Daily mortality risk was examined in association with exposure to daily maximum temperatures on the same day and up to 6 weeks preceding death, during the winter (December-February) and cold period (October-March), using distributed lag models. Model stratification by age and gender assessed for modification of the cold weather-mortality relationship. Results In the ROI, the impact of cold weather in winter persisted up to 35 days, with a cumulative mortality increase for all-causes of 6.4% (95%CI=4.8%-7.9%) in relation to every 1oC drop in daily maximum temperature, similar increases for cardiovascular disease (CVD) and stroke, and twice as much for respiratory causes. In NI, these associations were less pronounced for CVD causes, and overall extended up to 28 days. Effects of cold weather on mortality increased with age in both jurisdictions, and some suggestive gender differences were observed. Conclusions The study findings indicated strong cold weather-mortality associations in the island of Ireland; these effects were less persistent, and for CVD mortality, smaller in NI than in the ROI. Together with suggestive differences in associations by age and gender between the two Irish jurisdictions, the findings suggest potential contribution of underlying societal differences, and require further exploration. The evidence provided here will hope to contribute to the current efforts to modify fuel policy and reduce winter mortality in Ireland

Hydrodynamic simulations of the KT Eridani nova super-remnant

A nova super-remnant (NSR) is an immense structure associated with a nova that forms when frequent and recurrent nova eruptions sweep up surrounding interstellar material (ISM) into a high density and distant shell. The prototypical NSR, measuring over 100 pc across, was discovered in 2014 around the annually erupting nova M31N 2008-12a. Hydrodynamical simulations demonstrated that the creation of a dynamic NSR by repeated eruptions transporting large quantities of ISM is not only feasible but that these structures should exist around all novae, whether the white dwarf (WD) is increasing or decreasing in mass. But it is only the recurrent nova (RNe) with the highest WD masses and accretion rates that should host observable NSRs. KT Eridani is, potentially, the eleventh RNe recorded in the Galaxy and is also surrounded by a recently unveiled H{\alpha} shell tens of parsecs across, consistent with a NSR. Through modelling the nova ejecta from KT Eri, we demonstrate that such an observable NSR could form in approximately 50,000 years, which fits with the proper motion history of the nova. We compute the expected H{\alpha} emission from the KT Eri NSR and predict that the structure might be accessible to wide-field X-ray facilities

TGF-beta 1 induces human alveolar epithelial to mesenchymal cell transition (EMT)

Background: Fibroblastic foci are characteristic features in lung parenchyma of patients with idiopathic pulmonary fibrosis (IPF). They comprise aggregates of mesenchymal cells which underlie sites of unresolved epithelial injury and are associated with progression of fibrosis. However, the cellular origins of these mesenchymal phenotypes remain unclear. We examined whether the potent fibrogenic cytokine TGF-β1 could induce epithelial mesenchymal transition (EMT) in the human alveolar epithelial cell line, A549, and investigated the signaling pathway of TGF-β1-mediated EMT. Methods: A549 cells were examined for evidence of EMT after treatment with TGF-β1. EMT was assessed by: morphology under phase-contrast microscopy; Western analysis of cell lysates for expression of mesenchymal phenotypic markers including fibronectin EDA (Fn-EDA), and expression of epithelial phenotypic markers including E-cadherin (E-cad). Markers of fibrogenesis, including collagens and connective tissue growth factor (CTGF) were also evaluated by measuring mRNA level using RT-PCR, and protein by immunofluorescence or Western blotting. Signaling pathways for EMT were characterized by Western analysis of cell lysates using monoclonal antibodies to detect phosphorylated Erk1/2 and Smad2 after TGF-β1 treatment in the presence or absence of MEK inhibitors. The role of Smad2 in TGF-β1-mediated EMT was investigated using siRNA. Results: The data showed that TGF-β1, but not TNF-α or IL-1β, induced A549 cells with an alveolar epithelial type II cell phenotype to undergo EMT in a time-and concentration-dependent manner. The process of EMT was accompanied by morphological alteration and expression of the fibroblast phenotypic markers Fn-EDA and vimentin, concomitant with a downregulation of the epithelial phenotype marker E-cad. Furthermore, cells that had undergone EMT showed enhanced expression of markers of fibrogenesis including collagens type I and III and CTGF. MMP-2 expression was also evidenced. TGF-β1-induced EMT occurred through phosphorylation of Smad2 and was inhibited by Smad2 gene silencing; MEK inhibitors failed to attenuate either EMT-associated Smad2 phosphorylation or the observed phenotypic changes. Conclusion: Our study shows that TGF-β1 induces A549 alveolar epithelial cells to undergo EMT via Smad2 activation. Our data support the concept of EMT in lung epithelial cells, and suggest the need for further studies to investigate the phenomenon

Squamous cell carcinoma of the breast: a case report

<p>Abstract</p> <p>Background</p> <p>Squamous cells are normally not found inside the breast, so a primary squamous cell carcinoma of the breast is an exceptional phenomenon. There is a possible explanation for these findings.</p> <p>Case presentation</p> <p>A 72-year-old woman presented with a breast abnormality suspected for breast carcinoma. After the operation the pathological examination revealed a primary squamous cell carcinoma of the breast.</p> <p>Conclusion</p> <p>The presentation of squamous cell carcinoma could be similar to that of an adenocarcinoma. However, a squamous cell carcinoma of the breast could also develop from a complicated breast cyst or abscess. Therefore, pathological examination of these apparent benign abnormalities is mandatory.</p

Exploring the context of sedentary behaviour in older adults (what, where, why, when and with whom)

BACKGROUND: Older adults are the most sedentary segment of the population. Little information is available about the context of sedentary behaviour to inform guidelines and intervention. There is a dearth of information about when, where to intervene and which specific behaviours intervention should target. The aim of this exploratory study was to obtain objective information about what older adults do when sedentary, where and when they are sedentary and in what social context. METHODS: The study was a cross-sectional data collection. Older adults (Mean age = 73.25, SD ± 5.48, median = 72, IQR = 11) volunteers wore activPAL monitors and a Vicon Revue timelapse camera between 1 and 7 days. Periods of sedentary behaviour were identified using the activPAL and the context extracted from the pictures taken during these periods. Analysis of context was conducted using the Sedentary Behaviour International Taxonomy classification system. RESULTS: In total, 52 days from 36 participants were available for analysis. Participants spent 70.1 % of sedentary time at home, 56.9 % of sedentary time on their own and 46.8 % occurred in the afternoon. Seated social activities were infrequent (6.9 % of sedentary bouts) but prolonged (18 % of sedentary time). Participants appeared to frequently have vacant sitting time (41 % of non-screen sedentary time) and screen sitting was prevalent (36 % of total sedentary time). CONCLUSIONS: This study provides valuable information to inform future interventions to reduce sedentary behaviour. Interventions should consider targeting the home environment and focus on the afternoon sitting time, though this needs confirmation in a larger study. Tackling social isolation may also be a target to reduce sedentary time

Novel links between ciliopathies and FGF-related craniofacial syndromes

K Liu1*, JT Tabler1, HL Szabo-Rogers1, A Mesbahi1, C Healy1, W Barrell1, B Wlodarczyk2, Author Affiliations 1 King's College London, UK 2 University of Texas Southwestern, USA 3 University of Texas at Austin, USAOral Presentation : Recent studies suggest that planar cell polarity (PCP) genes coordinate cell polarity, ciliogenesis and signalling during mammalian development. FUZ is a PCP gene implicated in human congenital anomalies, including neural tube defects and orofacial clefting. Our analysis of fuzzy mutant mice reveals ciliogenesis defects in craniofacial tissues as well as a suite of phenotypes reminiscent of FGF-related craniofacial disorders. Mutants have coronal synostosis, shortened facial extensions, low-set ears and a high-arched palate. To our surprise, we found that the facial defects are due to increased neural crest migration into the first branchial arch (BA1), resulting in maxillary hyperplasia. Furthermore, the neural crest cells migrate in a disorganized fashion, deeper than normal and with fewer cell-cell contacts. This ectopic migration correlates with a dramatic increase in FGF signaling, first in the mid-hindbrain boundary, and then in the BA1 epithelia. The increased tissue causes a medial positional shift in the palatal primordia that manifests as a high-arched palate with pseudo-cleft. Genetic loss of fgf8 rescues the maxillary hyperplasia. Taken together, our data suggest a novel interplay between ciliogenesis, FGF signalling and migration of neural crest which may underlie congenital craniofacial dysmorphologies.Molecular [email protected]

Human Platelet-Rich Plasma- and Extracellular Matrix-Derived Peptides Promote Impaired Cutaneous Wound Healing In Vivo

Previous work in our laboratory has described several pro-angiogenic short peptides derived from endothelial extracellular matrices degraded by bacterial collagenase. Here we tested whether these peptides could stimulate wound healing in vivo. Our experiments demonstrated that a peptide created as combination of fragments of tenascin X and fibrillin 1 (comb1) applied into cranial dermal wounds created in mice treated with cyclophosphamide to impair wound healing, can improve the rate of wound closure. Furthermore, we identify and characterize a novel peptide (UN3) created and modified from two naturally-occurring peptides, which are present in human platelet-rich plasma. In vitro testing of UN3 demonstrates that it causes a 50% increase in endothelial proliferation, 250% increase in angiogenic response and a tripling of epithelial cell migration in response to injury. Results of in vivo experiments where comb1 and UN3 peptides were added together to cranial wounds in cyclophosphamide-treated mice leads to improvement of wound vascularization as shown by an increase of the number of blood vessels present in the wound beds. Application of the peptides markedly promotes cellular responses to injury and essentially restores wound healing dynamics to those of normal, acute wounds in the absence of cyclophosphamide impairment. Our current work is aimed at understanding the mechanisms underlying the stimulatory effects of these peptides as well as identification of the cellular receptors mediating these effects.National Institutes of Health (U.S.) (Grant EY15125)National Institutes of Health (U.S.) (Grant EY19533)Wound Care Partners, LL

Prognostic Value of Body Mass Index on Short-Term and Long-Term Outcome after Resection of Esophageal Cancer

Introduction: Cachexia and obesity have been suggested to be risk factors for postoperative complications. However, high body mass index (BMI) might result in a higher R0-resection rate because of the presence of more fatty tissue surrounding the tumor. The purpose of this study was to investigate whether BMI is of prognostic value with regard to short-term and long-term outcome in patients who undergo esophagectomy for cancer. Methods: In 556 patients who underwent esophagectomy (1991-2007), clinical and pathological outcome were compared between different BMI classes (underweight, normal weight, overweight, obesity). Results: Overall morbidity, mortality, and reoperation rate did not differ in underweight and obese patients. However, severe complications seemed to occur more often in obese patients (p = 0.06), and the risk for anastomotic leakage increased with higher BMI (12.5% in underweight patients compared with 27.6% in obese patients, p = 0.04). Histopathological assessment showed comparable pTNM stages, although an advanced pT stage was seen more often in patients with low/normal BMI (p = 0.02). A linear association between BMI and R0-resection rate was detected (p = 0.02): 60% in underweight patients compared with 81% in obese patients. However, unlike pT-stage (p < 0.001), BMI was not an independent predictor for R0 resection (p = 0.12). There was no significant difference in overall or disease-free 5-year survival between the BMI classes (p = 0.25 and p = 0.6, respectively). Conclusions: BMI is not of prognostic value with regard to short-term and long-term outcome in patients who undergo esophagectomy for cancer and is not an independent predictor for radical R0 resection. Patients oncologically eligible for esophagectomy should not be denied surgery on the basis of their BMI class