RNAi-mediated COPS3 gene silencing inhibits metastasis of osteogenic sarcoma cells

Metastatic disease is the primary cause of mortality among patients with osteogenic sarcoma (OGS). In this study, we aimed to identify the relationship of COPS3 gene expression to metastasis. Immunohistochemical staining for COPS3 was performed on 65 OGS samples (37 without and 28 with metastatic disease); 18.9% (7/37) of specimens from patients with no metastasis and 57.1% (16/28) of specimens from patients with metastasis showed intense staining of COPS3. Comparison of COPS3 expression between a poorly metastatic osteosarcoma cell line (SAOS-2) and highly metastatic osteosarcoma cell line (HOS) showed stronger expression of COPS3 in HOS cells. Inhibiting COPS3 function by siRNA resulted in reduced proliferation and migration of HOS cells. Inhibition of COPS3 gene downregulated expression of the MAPK signaling pathway, which has an important role in metastasis of OGS. Our results suggested that overexpression of the COPS3 gene might have important roles in metastasis of osteosarcoma cells

Viscoelastic haemostatic assay augmented protocols for major trauma haemorrhage (ITACTIC): a randomized, controlled trial

Purpose: Contemporary trauma resuscitation prioritizes control of bleeding and uses major haemorrhage protocols (MHPs) to prevent and treat coagulopathy. We aimed to determine whether augmenting MHPs with Viscoelastic Haemostatic Assays (VHA) would improve outcomes compared to Conventional Coagulation Tests (CCTs). Methods: This was a multi-centre, randomized controlled trial comparing outcomes in trauma patients who received empiric MHPs, augmented by either VHA or CCT-guided interventions. Primary outcome was the proportion of subjects who, at 24 h after injury, were alive and free of massive transfusion (10 or more red cell transfusions). Secondary outcomes included 28-day mortality. Pre-specified subgroups included patients with severe traumatic brain injury (TBI). Results: Of 396 patients in the intention to treat analysis, 201 were allocated to VHA and 195 to CCT-guided therapy. At 24 h, there was no difference in the proportion of patients who were alive and free of massive transfusion (VHA: 67%, CCT: 64%, OR 1.15, 95% CI 0.76–1.73). 28-day mortality was not different overall (VHA: 25%, CCT: 28%, OR 0.84, 95% CI 0.54–1.31), nor were there differences in other secondary outcomes or serious adverse events. In pre-specified subgroups, there were no differences in primary outcomes. In the pre-specified subgroup of 74 patients with TBI, 64% were alive and free of massive transfusion at 24 h compared to 46% in the CCT arm (OR 2.12, 95% CI 0.84–5.34). Conclusion: There was no difference in overall outcomes between VHA- and CCT-augmented-major haemorrhage protocols

Direct hospital costs of chest pain patients attending the emergency department: a retrospective study

BACKGROUND: Chest pain is one of the most common complaints in the Emergency Department (ED), but the cost of ED chest pain patients is unclear. The aim of this study was to describe the direct hospital costs for unselected chest pain patients attending the emergency department (ED). METHODS: 1,000 consecutive ED visits of patients with chest pain were retrospectively included. Costs directly following the ED visit were retrieved from the hospital economy system. RESULTS: The mean cost per patient visit was 26.8 thousand Swedish kronar (kSEK) (median 7.2 kSEK), with admission time accounting for 73% of all costs. Mean cost for patients discharged from the ED was 1.4 kSEK (median 1.3 kSEK), and for patients without ACS admitted 1 day or less 7.6 kSEK (median 6.9 kSEK). The practice in the present study to admit 67% of the patients, of whom only 31% proved to have ACS, was estimated to give a cost per additional life-year saved by hospital admission, compared to theoretical strategy of discharging all patients home, of about 350 kSEK (39 kEUR or 42 kUSD). CONCLUSION: Costs for chest pain patients are large and primarily due to admission time. The present admission practice seems to be cost-effective, but the substantial overadmission indicates that better ED diagnostics and triage could decrease costs considerably

WAP four-disulfide core domain protein 2 promotes metastasis of human ovarian cancer by regulation of metastasis-associated genes.

BACKGROUND: WAP four-disulfide core domain protein 2 (WFDC2) shows a tumor-restricted upregulated pattern of expression in ovarian cancer. METHODS: In this study, we evaluated the role of WFCD2 in tumor mobility, invasion and metastasis of ovarian cancer in clinical tissue and in ovarian cancer cells, both in vitro and in vivo. RESULTS: Our results revealed WFCD2 was overexpressed in ovarian tissues, and the expression level of WFCD2 was associated with metastasis and lymph node metastasis. Higher expression of WFCD2 was also observed in aggressive HO8910-PM cells than in HO8910 cells, and WFCD2 knockdown halted cell migration, invasion, tumorigenicity and metastasis in ovarian cancer cells, both in vitro and in vivo. Knockdown of WFDC2 induced the down-regulation of ICAM-1, CD44, and MMP2. CONCLUSION: In summary, our work demonstrates that WFCD2 promotes metastasis in ovarian cancer. These findings suggest that WFCD2 plays a critical role in promoting metastasis and may constitute a potential therapeutic target of ovarian cancer

Factors affecting exhaled nitric oxide measurements: the effect of sex

<p>Abstract</p> <p>Background</p> <p>Exhaled nitric oxide (F_ENO) measurements are used as a surrogate marker for eosinophilic airway inflammation. However, many constitutional and environmental factors affect F_ENO, making it difficult to devise reference values. Our aim was to evaluate the relative importance of factors affecting F_ENO in a well characterised adult population.</p> <p>Methods</p> <p>Data were obtained from 895 members of the Dunedin Multidisciplinary Health and Development Study at age 32. The effects of sex, height, weight, lung function indices, smoking, atopy, asthma and rhinitis on F_ENO were explored by unadjusted and adjusted linear regression analyses.</p> <p>Results</p> <p>The effect of sex on F_ENO was both statistically and clinically significant, with F_ENO levels approximately 25% less in females. Overall, current smoking reduced F_ENO up to 50%, but this effect occurred predominantly in those who smoked on the day of the F_ENO measurement. Atopy increased F_ENO by 60%. The sex-related differences in F_ENO remained significant (p < 0.001) after controlling for all other significant factors affecting F_ENO.</p> <p>Conclusion</p> <p>Even after adjustment, F_ENO values are significantly different in males and females. The derivation of reference values and the interpretation of F_ENO in the clinical setting should be stratified by sex. Other common factors such as current smoking and atopy also require to be taken into account.</p

Attitudes toward and Uptake of H1N1 Vaccine among Health Care Workers during the 2009 H1N1 Pandemic

BACKGROUND: Though recommended by many and mandated by some, influenza vaccination rates among health care workers, even in pandemics, remain below optimal levels. The objective of this study was to assess vaccination uptake, attitudes, and distinguishing characteristics (including doctor-nurse differences) of health care workers who did and did not receive the pandemic H1N1 influenza vaccine in late 2009. METHODOLOGY/PRINCIPAL FINDINGS: In early 2010 we mailed a self-administered survey to 800 physicians and 800 nurses currently licensed and practicing in Minnesota. 1,073 individuals responded (cooperation rate: 69%). 85% and 62% of Minnesota physicians and nurses, respectively, reported being vaccinated. Accurately estimating the risk of vaccine side effects (OR 2.0; 95% CI 1.5-2.7), agreeing with a professional obligation to be vaccinated (OR 10.1; 95% CI 7.1-14.2), an ethical obligation to follow public health authorities' recommendations (OR 9.9; 95% CI 6.6-14.9), and laws mandating pandemic vaccination (OR 3.1; 95% CI 2.3-4.1) were all independently associated with receiving the H1N1 influenza vaccine. CONCLUSIONS/SIGNIFICANCE: While a majority of health care workers in one midwestern state reported receiving the pandemic H1N1 vaccine, physicians and nurses differed significantly in vaccination uptake. Several key attitudes and perceptions may influence health care workers' decisions regarding vaccination. These data inform how states might optimally enlist health care workers' support in achieving vaccination goals during a pandemic

Mucosal Progranulin expression is induced by H. pylori, but independent of Secretory Leukocyte Protease Inhibitor (SLPI) expression

<p>Abstract</p> <p>Background</p> <p>Mucosal levels of Secretory Leukocyte Protease Inhibitor (SLPI) are specifically reduced in relation to <it>H. pylori</it>-induced gastritis. Progranulin is an epithelial growth factor that is proteolytically degraded into fragments by elastase (the main target of SLPI). Considering the role of SLPI for regulating the activity of elastase, we studied whether the <it>H. pylori</it>-induced reduction of SLPI and the resulting increase of elastase-derived activity would reduce the Progranulin protein levels both <it>ex vivo </it>and <it>in vitro</it>.</p> <p>Methods</p> <p>The expression of Progranulin was studied in biopsies of <it>H. pylori</it>-positive, -negative and -eradicated subjects as well as in the gastric tumor cell line AGS by ELISA, immunohistochemistry and real-time RT-PCR.</p> <p>Results</p> <p><it>H. pylori</it>-infected subjects had about 2-fold increased antral Progranulin expression compared to <it>H. pylori</it>-negative and -eradicated subjects (P < 0.05). Overall, no correlations between mucosal Progranulin and SLPI levels were identified. Immunohistochemical analysis confirmed the upregulation of Progranulin in relation to <it>H. pylori </it>infection; both epithelial and infiltrating immune cells contributed to the higher Progranulin expression levels. The <it>H. pylori</it>-induced upregulation of Progranulin was verified in AGS cells infected by <it>H. pylori</it>. The down-regulation of endogenous SLPI expression in AGS cells by siRNA methodology did not affect the Progranulin expression independent of the infection by <it>H. pylori</it>.</p> <p>Conclusions</p> <p>Taken together, Progranulin was identified as novel molecule that is upregulated in context to <it>H. pylori </it>infection. In contrast to other diseases, SLPI seems not to have a regulatory role for Progranulin in <it>H. pylori</it>-mediated gastritis.</p

Deficiency of the Mitochondrial Electron Transport Chain in Muscle Does Not Cause Insulin Resistance

It has been proposed that muscle insulin resistance in type 2 diabetes is due to a selective decrease in the components of the mitochondrial electron transport chain and results from accumulation of toxic products of incomplete fat oxidation. The purpose of the present study was to test this hypothesis.Rats were made severely iron deficient, by means of an iron-deficient diet. Iron deficiency results in decreases of the iron containing mitochondrial respiratory chain proteins without affecting the enzymes of the fatty acid oxidation pathway. Insulin resistance was induced by feeding iron-deficient and control rats a high fat diet. Skeletal muscle insulin resistance was evaluated by measuring glucose transport activity in soleus muscle strips. Mitochondrial proteins were measured by Western blot. Iron deficiency resulted in a decrease in expression of iron containing proteins of the mitochondrial respiratory chain in muscle. Citrate synthase, a non-iron containing citrate cycle enzyme, and long chain acyl-CoA dehydrogenase (LCAD), used as a marker for the fatty acid oxidation pathway, were unaffected by the iron deficiency. Oleate oxidation by muscle homogenates was increased by high fat feeding and decreased by iron deficiency despite high fat feeding. The high fat diet caused severe insulin resistance of muscle glucose transport. Iron deficiency completely protected against the high fat diet-induced muscle insulin resistance.The results of the study argue against the hypothesis that a deficiency of the electron transport chain (ETC), and imbalance between the ETC and β-oxidation pathways, causes muscle insulin resistance