Involvement of the HLXB9 homeobox gene in Currarino syndrome [2]

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Tumour-derived alkaline phosphatase regulates tumour growth, epithelial plasticity and disease-free survival in metastatic prostate cancer

BACKGROUND: Recent evidence suggests that bone-related parameters are the main prognostic factors for overall survival in advanced prostate cancer (PCa), with elevated circulating levels of alkaline phosphatase (ALP) thought to reflect the dysregulated bone formation accompanying distant metastases. We have identified that PCa cells express ALPL, the gene that encodes for tissue nonspecific ALP, and hypothesised that tumour-derived ALPL may contribute to disease progression. METHODS: Functional effects of ALPL inhibition were investigated in metastatic PCa cell lines. ALPL gene expression was analysed from published PCa data sets, and correlated with disease-free survival and metastasis. RESULTS: ALPL expression was increased in PCa cells from metastatic sites. A reduction in tumour-derived ALPL expression or ALP activity increased cell death, mesenchymal-to-epithelial transition and reduced migration. Alkaline phosphatase activity was decreased by the EMT repressor Snail. In men with PCa, tumour-derived ALPL correlated with EMT markers, and high ALPL expression was associated with a significant reduction in disease-free survival. CONCLUSIONS: Our studies reveal the function of tumour-derived ALPL in regulating cell death and epithelial plasticity, and demonstrate a strong association between ALPL expression in PCa cells and metastasis or disease-free survival, thus identifying tumour-derived ALPL as a major contributor to the pathogenesis of PCa progression.British Journal of Cancer advance online publication, 22 December 2016; doi:10.1038/bjc.2016.402 www.bjcancer.com

Antitubercular therapy decreases nitric oxide production in HIV/TB coinfected patients

BACKGROUND: Nitric oxide (NO) production is increased among patients with human immunodeficiency virus (HIV) infection and also among those with tuberculosis (TB). In this study we sought to determine if there was increased NO production among patients with HIV/TB coinfection and the effect of four weeks chemotherapy on this level. METHODS: 19 patients with HIV/TB coinfection were studied. They were treated with standard four drug antitubercular therapy and sampled at baseline and four weeks. 20 patients with HIV infection, but no opportunistic infections, were disease controls and 20 individuals were healthy controls. Nitrite and citrulline, surrogate markers for NO, were measured spectrophotometrically. RESULTS: The mean age of HIV/TB patients was 28.4 ± 6.8 years and CD4 count was 116 ± 36.6/mm. Mean nitrite level among HIV/TB coinfected was 207.6 ± 48.8 nmol/ml. This was significantly higher than 99.7 ± 26.5 nmol/ml, the value for HIV infected without opportunistic infections and 46.4 ± 16.2 nmol/ml, the value for healthy controls (p value < 0.01). The level of HIV/TB coinfected NO in patients declined to 144.5 ± 34.4 nmol/ml at four weeks of therapy (p value < 0.05). Mean citrulline among HIV/TB coinfected was 1446.8 ± 468.8 nmol/ml. This was significantly higher than 880.8 ± 434.8 nmol/ml, the value for HIV infected without opportunistic infections and 486.6 ± 212.5 nmol/ml, the value for healthy controls (p value < 0.01). Levels of citrolline in HIV/TB infected declined to 1116.2 ± 388.6 nmol/ml at four weeks of therapy (p value < 0.05). CONCLUSIONS: NO production is elevated among patients with HIV infection, especially so among HIV/TB coinfected patients, but declines significantly following 4 weeks of antitubercular therapy

Measuring educational needs among patients with rheumatoid arthritis using the Dutch version of the Educational Needs Assessment Tool (DENAT)

The Educational Needs Assessment Tool (ENAT) was developed in the United Kingdom (UK) to systematically assess the educational needs of patients with arthritis. The aim of the present study was to describe the educational needs of Dutch patients with rheumatoid arthritis (RA) by using the Dutch version of the ENAT (DENAT). The original UK version of the ENAT, comprising 39 items grouped into seven domains, was translated into Dutch according to international guidelines for cross-cultural translation and adaptation. The DENAT was then sent to a random sample of 319 RA patients registered at the outpatient clinic of a university hospital. For each domain (score range 1–5, equalling low–high educational needs), a median score with the inter-quartile range was computed. The Kruskal–Wallis test was used to determine possible associations between educational needs and age, disease duration, gender and educational background. The response rate was 165 out of 319 (52%). The median educational needs scores were 2.5 for “managing pain”, 3.0 for “movement”, 2.0 for “feelings”, 4.0 for “arthritis process”, 4.0 for “treatments from health professionals”, 3.5 for “self-help measures” and 2.5 for “support systems”. Lower age and shorter disease duration were associated with more educational needs in the domain “support systems”. In addition, younger patients had more educational needs regarding managing pain and feelings than older patients. There were no associations between gender or educational background and educational needs. The DENAT has demonstrated its ability to identify individual educational needs of Dutch patients with RA. The lower age and shorter disease duration were associated with more educational needs. The practical applicability of the DENAT needs further research

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012

Successful treatment of Candida parapsilosis mural endocarditis with combined caspofungin and voriconazole

BACKGROUND: Fungal mural endocarditis is a rare entity in which the antemortem diagnosis is seldom made. Seven cases of mural endocarditis caused by Candida spp. have been collected from literature and six of these patients died after treatment with amphotericin B. CASE PRESENTATION: We report a case of mural endocarditis diagnosed by transesophageal echocardiogram and positive blood cultures to Candida parapsilosis. Because blood cultures continued to yield C. parapsilosis despite caspofungin monotherapy, treatment with voriconazole was added. CONCLUSION: This is the first description of successful treatment of C. parapsilosis mural endocarditis with caspofungin and voriconazole

p53 overexpression is associated with cytoreduction and response to chemotherapy in ovarian cancer

The aim of this study was to assess the association of p53 status with primary cytoreduction, response to chemotherapy and outcome in stage III–IV primary ovarian cancer patients. Immunohistochemical analysis of p53 was performed on formalin-fixed, paraffin-embedded specimens from 168 primary ovarian carcinomas by using the DO-7 monoclonal antibody. p53 nuclear positivity was found in 84 out of 162 (52%) malignant tumours. A higher percentage of p53 nuclear positivity was observed in patients with advanced stage of disease than in stage I–II (57% vs 23% respectively; P = 0.0022) and in poorly differentiated versus well/moderately differentiated tumours (59% vs 32% respectively; P = 0.0038). The multivariate analysis aimed to investigate the association of FIGO stage, grade and p53 status with primary cytoreduction in 136 stage III–IV patients showed that stage IV disease may influence the possibility to perform primary cytoreduction in ovarian cancer patients. p53-positivity also maintained a trend to be associated with poor chance of cytoreduction. In patients who underwent pathologic assessment of response, cases who did not respond to chemotherapy were much more frequently p53-positive than p53-negative (86% vs 14% respectively; P = 0.012). Moreover, patients with stage III disease and < 2-cm residual tumour were more likely to respond to treatment. In multivariate analysis, FIGO stage and p53 expression were independently correlated with pathologic response to chemotherapy. Time to progression and survival rates were shown not to be different in p53-positive versus p53-negative patients. © 1999 Cancer Research Campaig

Cross-cultural validation of the Educational Needs Assessment Tool in RA in 7 European countries

<p>Abstract</p> <p>Background</p> <p>The Educational Needs Assessment Tool (the ENAT) is a 39-item patient questionnaire originally developed in the UK to assess educational needs of patients with rheumatoid arthritis (RA). The objective of this study was to assess the cross-cultural validity of the ENAT in 7 European countries.</p> <p>Methods</p> <p>The ENAT was translated into Dutch, Finnish, Norwegian, Portuguese, Spanish and Swedish versions by using Beaton's cross-cultural adaptation process, and was completed by a convenience sample of patients with RA in each country. The generated country-specific data were assessed for construct validity and were then pooled and assessed for cross-cultural invariance using Rasch analysis.</p> <p>Results</p> <p>Individual country-specific analysis showed adequate fit to the Rasch model after adjustment for local dependency within domains. When data from the different countries were pooled, the 39 items deviated significantly from Rasch model's expectations (X²= 977.055, DF = 351, p = 0.000, PSI = 0.976). Again, most items within domains were found to be locally dependent, significantly affecting the fit. Consequently each domain was treated as a unit (i.e. testlet) and the ENAT was re-analysed as a seven-testlet scale resulting into a good fit to the Rasch model (X²= 71.909; DF = 63; p = 0.207, PSI = 0.951). A test of strict unidimensionality confirmed that all domains contributed to measuring a single construct. Cross-cultural non-invariance was discounted by splitting domains for DIF maintaining an excellent fit to the Rasch model. This allowed calibration of the ENAT into an interval scale.</p> <p>Conclusion</p> <p>The ENAT is a simple tool, which is a valid measure of educational needs of people with RA. Adjustment for cross-cultural non-invariance is available if data from the 7 European countries are to be pooled or compared.</p