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CarboxypeptidaseA4 (CPA4) is a zinc-containing exopeptidases, and its aberrant expression has been implicated in cancer development and progression. However, few studies have investigated the association between CPA4 over-expression and clinical significance in gastric cancer (GC). In this study, we employed immunohistochemistry to evaluate the expression of CPA4 in gastric cancer tissues, and found that elevated CPA4 expression was detected in 64% (n=100) of primary GCs, but was weak or no staining in the normal mucosa. Clinical relevance analysis showed that positive staining for CPA4 was significantly associated with Tumor size, Stage, Lymph node metastasis, Depth of invasion and Distant metastasis. As tumor markers p53 and Ki67 are closely associated with tumor progression, we further analyzed the correlations between CPA4 levels and these two factors. We found that abnormal expression of CPA4 was positively associated with Ki67 (P=0.002) and reversely correlated with p53 (P=0.035) in GC. In Kaplan-Meier survival analysis, high levels of CPA4 were significantly associated with unfavorable survival in GC patients (P<0.001). Multivariate Cox regression model showed that high expression of CPA4 was an independent prognostic factor for GC patients. In conclusion, our results suggested that CPA4 was highly expressed in gastric cancer tissues. Overexpression of CPA4 can be used as an independent poor prognostic factor in gastric cancer.

Continued use of trastuzumab in PTEN-deficient HER2+ breast cancer induces the epithelial-to-mesenchymal transition (EMT), transforms HER2+ to triple negative breast cancer, and expands breast cancer stem cells (BCSCs). Using cancer cell lines with two distinct states, epithelial and mesenchymal, we identified novel targets during EMT in PTEN-deficient trastuzumab-resistant breast cancer. Differential gene expression and distinct responses to a small molecule in BT474 (HER2+ trastuzumab-sensitive) and the PTEN-deficient trastuzumab-resistant derivative (BT474-PTEN-LTT) provided the selection tools to identify targets during EMT. siRNA knockdown and small molecule inhibition confirmed MEOX1 as one of the critical molecular targets to regulate both BCSCs and mesenchymal-like cell proliferation. MEOX1 was associated with poor survival, lymph node metastasis, and stage of breast cancer patients. These findings suggest that MEOX1 is a clinically relevant novel target in BCSCs and mesenchymal-like cancer cells in PTEN-deficient trastuzumab resistant breast cancer and may serve as target for future drug development., Competing Interests: The authors declare no potential conflicts of interest related to this work.

Background: Postoperative impairment of the cerebral function can appear immediately after general anesthesia and may be predictive for a postoperative delirium. We compared three tools assessing patients on recovery room admission in order to detect early signs of postoperative brain dysfunction: the Postanesthetic Recovery Score (PARS), the Richmond Agitation-Sedation Scale (RASS) and the Nursing Delirium Screening Scale (Nu-DESC)., Methods: Inclusion criteria of this secondary analysis of the randomized SuDoCo trial were: age ≥60 years, schedule for elective non-cardiac surgery with an anticipated duration of ≥60 minutes, general anesthesia, ability to communicate in German language. A total of 996 patients were analyzed. Investigated scores were assessed 10 minutes after recovery room admission and analyzed in terms of association with postoperative delirium, mortality and length of stay in the recovery room. Multivariate analysis: linear or logistic regression., Results: Abnormal scores in patients: RASS (values ≤-2 and ≥1) 36.8%, Nu-DESC (≥2 points) 54.2%, PARS (≤7 points) 20.3%. Abnormal RASS values were associated with postoperative delirium (RASS values ≥1: odds ratio (OR) 3.1, 95% CI: 1.7-5.6, P<0.001; RASS values ≤-2: OR=2.1, 95% CI: 1.3-3.3, P=0.001). Abnormal Nu-DESC values were also associated with postoperative delirium (OR=2.4, 95% CI: 1.5-3.9, P<0.001). Abnormal PARS values were associated with a longer recovery room stay (in minutes, OR=16.6, 95% CI: 1.7-31.4, P=0.029)., Conclusions: The RASS and Nu-DESC were independent predictors for a delirium within seven postoperative days. Very early assessment of the cerebral function may help to advance detection, prevention and treatment of postoperative delirium in elderly patients.

Background. Carboxypeptidase A4 (CPA4) belongs to a member of the metallocarboxypeptidase family, and its expression in lung cancer samples and clinical significance are still not investigated until now. In this study, we aimed to evaluate the level of CPA4 in non-small-cell lung cancer (NSCLC) samples and correlate its level with clinical outcome. Methods. CPA4 gene expression in lung cancer tissues were analyzed by using the Oncomine database (www.oncomine.org). The expression of CPA4, Survivin and VEGF in lung cancer and adjacent normal tissues were evaluated by IHC using the corresponding primary antibodies on two different commercial tissue arrays (Shanghai Biochip Co., Ltd., Shanghai, China). Their levels in serum were determined by using commercial human enzyme-linked immunosorbent assay kits. We also examined their relations to clinicopathologic parameters, and explored the diagnostic and prognostic value in NSCLC. Results. We identified an elevation of CPA4 in mRNA level and gene amplification in lung cancer tissues in comparison to normal lung tissues. High CPA4 expression was observed in 120/165 (72.7%) NSCLC samples, and significantly correlated with Tumor size, Depth of invasion, Lymph Node Metastasis, Stage, VEGF level and Survivin level. High CPA4 expression is associated with poor prognosis of NSCLC patients. Multivariable Cox regression analysis demonstrated that CPA4 expression was an independent prognostic factor. Furthermore, serum CPA4 level was also significantly higher in NSCLC patients than in healthy controls. Logistic regression analysis revealed that serum CPA4 and CYFRA21-1 level were the significant parameters for detecting NSCLC. Receiver operating characteristic curves (ROC) in NSCLC patients versus normal people yielded the optimal cut-off value was 2.70 ng/ml for CPA4 and 19 ng/ml for CYFRA21-1, respectively. The area under ROC curve (AUC) was 0.830 for the combination of the two tumor markers. Conclusion. Our results demonstrated that overexpression of CPA4 in NSCLC is associated with an unfavorable prognosis, and serum CPA4 level combining with serum CYFRA21-1 level could be used to aid early detection of NSCLC.

There is growing evidence that projected climate change has the potential to significantly affect public health. In the UK, much of this impact is likely to arise by amplifying existing risks related to heat exposure, flooding, and chemical and biological contamination in buildings. Identifying the health effects of climate change on the indoor environment, and risks and opportunities related to climate change adaptation and mitigation, can help protect public health. We explored a range of health risks in the domestic indoor environment related to climate change, as well as the potential health benefits and unintended harmful effects of climate change mitigation and adaptation policies in the UK housing sector. We reviewed relevant scientific literature, focusing on housing-related health effects in the UK likely to arise through either direct or indirect mechanisms of climate change or mitigation and adaptation measures in the built environment. We considered the following categories of effect: (i) indoor temperatures, (ii) indoor air quality, (iii) indoor allergens and infections, and (iv) flood damage and water contamination. Climate change may exacerbate health risks and inequalities across these categories and in a variety of ways, if adequate adaptation measures are not taken. Certain changes to the indoor environment can affect indoor air quality or promote the growth and propagation of pathogenic organisms. Measures aimed at reducing greenhouse gas emissions have the potential for ancillary public health benefits including reductions in health burdens related heat and cold, indoor exposure to air pollution derived from outdoor sources, and mould growth. However, increasing airtightness of dwellings in pursuit of energy efficiency could also have negative effects by increasing concentrations of pollutants (such as PM2.5, CO and radon) derived from indoor or ground sources, and biological contamination. These effects can largely be ameliorated by mechanical ventilation with heat recovery (MVHR) and air filtration, where such solution is feasible and when the system is properly installed, operated and maintained. Groups at high risk of these adverse health effects include the elderly (especially those living on their own), individuals with pre-existing illnesses, people living in overcrowded accommodation, and the socioeconomically deprived. A better understanding of how current and emerging building infrastructure design, construction, and materials may affect health in the context of climate change and mitigation and adaptation measures is needed in the UK and other high income countries. Long-term, energy efficient building design interventions, ensuring adequate ventilation, need to be promoted., (Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.)

New models of health care delivery are inevitable. There is likely to be increasing emphasis on patient self-monitoring, health care delivery at patient homes, interdisciplinary treatment plans, a greater percentage of medical care delivered by non-physician health professionals, targeted health educational materials, and greater involvement and training of informal caregivers. The Information Technologies (IT) infrastructure of health systems will need to adapt. We have begun sorting out the implications of this future within a County public hospital system: defining the desirable features, relevant technologies, necessary modifications to the network, and additional data elements to be captured. We seek to build an infrastructure that will support new patient-focused technologies designed to more efficiently and effectively support older individuals. We hypothesize utility to further exploring the impact that new health care delivery models will have on health systems' IT infrastructures.

The U.K. government has committed to an 80% reduction in carbon emissions by 2050, with housing accounting for 27% of total current emissions. There are several drivers both to reduce emissions from homes and to reduce fuel poverty, promoting a range of building and behavioural measures in homes. The health benefits of warmer homes in winter have been described, but there has been less consideration of the potential negative impacts of some of these measures. We examine the changes in U.K. homes, and the possible consequences for health. The main concerns for health surround the potential for poor indoor air quality if ventilation is insufficient and the possible risks of overheating in heatwave conditions. This paper notes a limited evidence base and the need for further research on the health effects of energy-efficient homes, particularly with regard to ventilation.

Many air pollutants which are considered important in ambient (outdoor) air are also found, sometimes at higher levels, in indoor air. With demanding standards having been set for many of these pollutants, both in the workplace and ambient air, consideration of the problems posed by indoor pollution is gaining pace. Studies on exposure to pollutants found in the indoor domestic environment are increasing and are contributing to an already significant compilation of datasets. Improvement in monitoring techniques has helped this process. Documented reports of fatalities from carbon monoxide poisonings are still worrying. However, studies on health effects of non-fatal, long term, low dose, indoor exposure to carbon monoxide and other pollutants, are still inconclusive and too infrequently documented. Of particular concern are the levels of air pollutants found in the domestic indoor environment in developing countries, despite simple interventions such as vented stoves having shown their value. Exposure to biomass smoke is still a level that would be considered unacceptable on health grounds in developed countries. As in the occupational environment, steps need to be taken to control the risks from exposure to the harmful constituents of indoor air in the home. However, the difficulty regarding regulation of the domestic indoor environment is its inherent privacy. Monitoring levels of pollutants in the home and ensuring regulations are adhered to, would likely prove difficult, especially when individual behaviour patterns and activities have the greatest influence on pollutant levels in indoor air. To this end, the Department of Health is developing guidance on indoor air pollution to encourage the reduction of pollutant levels in indoor domestic air. The importance of the effects of domestic indoor air on health and its contribution to the health of the worker are increasingly appreciated. Occupational physicians, by training and interest, are well placed to extend their interests into the environmental field and to focus on this important area.

The effect of oxygen radicals on superior mesenteric artery (SMA) blood flow and splanchnic prostaglandin release was examined during early hemorrhage/reperfusion injury. Sprague-Dawley rats were hemorrhaged to 30 mm Hg for 5, 10, or 15 min without (SK5, SK10, and SK15) or with (SK10+R, and SK15+R) blood reperfusion. The SK15+R group were treated with or without superoxide dismutase (SOD 10 000 units/kg intravenously). In vivo SMA blood flow was measured continuously for 100 min by a transonic flow probe. The in vitro-perfused superior mesenteric artery and end organ intestine (SV+SI) were assayed for release of 6-keto-PGF1 alpha, thromboxane B2 (TXB2) and PGE2 by radioimmunoassay. Acute hemorrhage for 10 and 15 minutes increased SV+SI 6-keto-PGF1 alpha release 2-fold and 10-fold respectively compared to the sham (p < 0.01), which was abolished by blood reperfusion. SMA blood flow was decreased by 4% and 60% in the SK10+R and SK15+R groups respectively compared with the sham (p < 0.01). SOD treatment restored both SV+SI release of 6-keto-PGF1 alpha and SMA blood flow to control levels in the SK10+R and SK15+R groups. Oxygen-derived free radicals produced within 15 min of acute hemorrhage/reperfusion injury inhibited splanchnic PGI2 synthesis, which contributed to decreased splanchnic blood flow.