Polyphosphate degradation by Nudt3-Zn²⁺ mediates oxidative stress response

Polyphosphate (polyP) is a polymer of hundreds of phosphate residues present in all organisms. In mammals, polyP is involved in crucial physiological processes, including coagulation, inflammation, and stress response. However, after decades of research, the metabolic enzymes are still unknown. Here, we purify and identify Nudt3, a NUDIX family member, as the enzyme responsible for polyP phosphatase activity in mammalian cells. We show that Nudt3 shifts its substrate specificity depending on the cation; specifically, Nudt3 is active on polyP when Zn2+ is present. Nudt3 has in vivo polyP phosphatase activity in human cells, and importantly, we show that cells with altered polyP levels by modifying Nudt3 protein amount present reduced viability upon oxidative stress and increased DNA damage, suggesting that polyP and Nudt3 play a role in oxidative stress protection. Finally, we show that Nudt3 is involved in the early stages of embryo development in zebrafish

Unsuspected and extensive transmission of a drug-susceptible Mycobacterium tuberculosis strain

<p>Abstract</p> <p>Background</p> <p>A large and unsuspected tuberculosis outbreak involving 18.7% of the total of the tuberculosis cases studied, was detected in a population-based molecular epidemiological study performed in Zaragoza (Spain) from 2001 to 2004.</p> <p>Methods</p> <p>The <it>Mycobacterium tuberculosis </it>drug-susceptible strain, named <it>MTZ </it>strain, was genetically characterized by IS<it>6110</it>-RFLP, Spoligotyping and by MIRU-VNTR typing and the genetic patterns obtained were compared with those included in international databases. The characteristics of the affected patients, in an attempt to understand why the <it>MTZ </it>strain was so highly transmitted among the population were also analyzed.</p> <p>Results</p> <p>The genetic profile of the <it>MTZ </it>strain was rare and not widely distributed in our area or elsewhere. The patients affected did not show any notable risk factor for TB.</p> <p>Conclusion</p> <p>The <it>M. tuberculosis </it>strain <it>MTZ</it>, might have particular transmissibility or virulence properties, and we believe that greater focus should be placed on stopping its widespread dissemination.</p

Usefulness of bone turnover markers as predictors of mortality risk, disease progression and skeletal-related events appearance in patients with prostate cancer with bone metastases following treatment with zoledronic acid: TUGAMO study

Owing to the limited validity of clinical data on the treatment of prostate cancer (PCa) and bone metastases, biochemical markers are a promising tool for predicting survival, disease progression and skeletal-related events (SREs) in these patients. The aim of this study was to evaluate the predictive capacity of biochemical markers of bone turnover for mortality risk, disease progression and SREs in patients with PCa and bone metastases undergoing treatment with zoledronic acid (ZA). Methods: This was an observational, prospective and multicenter study in which ninety-eight patients were included. Patients were treated with ZA (4mg every 4 weeks for 18 months). Data were collected at baseline and 3, 6, 9, 12, 15 and 18 months after the beginning of treatment. Serum levels of bone alkaline phosphtase (BALP), aminoterminal propeptide of procollagen type I (P1NP) and beta-isomer of carboxiterminal telopeptide of collagen I (b-CTX) were analysed at all points in the study. Data on disease progression, SREs development and survival were recorded. Results: Cox regression models with clinical data and bone markers showed that the levels of the three markers studied were predictive of survival time, with b-CTX being especially powerful, in which a lack of normalisation in visit 1 (3 months after the beginning of treatment) showed a 6.3-times more risk for death than in normalised patients. Levels of these markers were also predictive for SREs, although in this case BALP and P1NP proved to be better predictors. We did not find any relationship between bone markers and disease progression. Conclusion: In patients with PCa and bone metastases treated with ZA, b-CTX and P1NP can be considered suitable predictors for mortality risk, while BALP and P1NP are appropriate for SREs. The levels of these biomarkers 3 months after the beginning of treatment are especially importantThis study was supported by Novartis Oncology Spai

Evaluando el progreso de la eficiencia con tecnología en una cadena de hoteles española

This paper analyzes the changes in the total factor productivity index of a Spanish hotel chain in the period from 2007 to 2010 with the purpose of identifying efficiency patterns for the chain in a period of financial crisis. The data envelopment analysis (DEA) Malmquist productivity index was used to estimate productivity change in 38 hotels of the AC chain. Results reveal AC hotels’ efficiency trends and, therefore, their competitiveness in the recession period; they also show the changes experienced in these hotels’ total productivity and its components: technological and efficiency changes. Positive efficiency changes were due to positive technical efficiency rather than technological efficiency. The recession period certainly influenced the performance of AC Hotels, which focused on organizational changes rather than investing in technology.Este artigo analisa as mudanças no fator total de produtividade de uma cadeia de hotéis na Espanha, no período de 2007-2010, com o propósito de identificar os padrões da cadeia em um período de crise financeira. O índice data envelopment analysis (DEA) Malmquist de produtividade foi usado para estimar a mudança da produtividade nos 38 hotéis da AC Cadeia de Hotéis. Os resultados revelaram as tendências de eficiência e competitividade da AC Hotéis em um período de recessão, bem como as mudanças vivenciadas na produtividade total e, consequentemente, em seus componentes de eficiência e tecnológicos. O período de recessão influenciou, sem dúvida, o comportamento da AC Hotéis, que buscou mais mudanças organizacionais do que tecnológicas.Este artículo analiza los cambios del índice de productividad del factor total de una cadena de hoteles españoles en el periodo de 2007 hasta 2010, con el propósito de identificar patrones de eficiencia para la cadena en un periodo de crisis financiera. El índice de productividad data envelopment analysis (DEA) Malmquist fue utilizado para estimar el cambio de productividad en 38 hoteles de la cadena AC. Los resultados revelan las tendencias de la eficiencia de los hoteles AC y, por lo tanto, su competitividad en el periodo de recisión; ellos también demuestran los cambios experimentados en la productividad total de eses hoteles y sus componentes: cambios de eficiencia y tecnológicos. Cambios de eficiencia positivos se debieron más bien a eficiencias técnicas positivas que a eficiencias tecnológicas. El periodo de recesión ciertamente ha influenciado los Hoteles AC, que enfocaron más en los cambios organizacionales que en invirtiendo en tecnología

Dietary α‐Linolenic Acid, Marine ω‐3 Fatty Acids, and Mortality in a Population With High Fish Consumption: Findings From the PREvención con DIeta MEDiterránea (PREDIMED) Study

Background: Epidemiological evidence suggests a cardioprotective role of α‐linolenic acid (ALA), a plant‐derived ω‐3 fatty acid. It is unclear whether ALA is beneficial in a background of high marine ω‐3 fatty acids (long‐chain n‐3 polyunsaturated fatty acids) intake. In persons at high cardiovascular risk from Spain, a country in which fish consumption is customarily high, we investigated whether meeting the International Society for the Study of Fatty Acids and Lipids recommendation for dietary ALA (0.7% of total energy) at baseline was related to all‐cause and cardiovascular disease mortality. We also examined the effect of meeting the society's recommendation for long‐chain n‐3 polyunsaturated fatty acids (≥500 mg/day). Methods and Results: We longitudinally evaluated 7202 participants in the PREvención con DIeta MEDiterránea (PREDIMED) trial. Multivariable‐adjusted Cox regression models were fitted to estimate hazard ratios. ALA intake correlated to walnut consumption (r=0.94). During a 5.9‐y follow‐up, 431 deaths occurred (104 cardiovascular disease, 55 coronary heart disease, 32 sudden cardiac death, 25 stroke). The hazard ratios for meeting ALA recommendation (n=1615, 22.4%) were 0.72 (95% CI 0.56–0.92) for all‐cause mortality and 0.95 (95% CI 0.58–1.57) for fatal cardiovascular disease. The hazard ratios for meeting the recommendation for long‐chain n‐3 polyunsaturated fatty acids (n=5452, 75.7%) were 0.84 (95% CI 0.67–1.05) for all‐cause mortality, 0.61 (95% CI 0.39–0.96) for fatal cardiovascular disease, 0.54 (95% CI 0.29–0.99) for fatal coronary heart disease, and 0.49 (95% CI 0.22–1.01) for sudden cardiac death. The highest reduction in all‐cause mortality occurred in participants meeting both recommendations (hazard ratio 0.63 [95% CI 0.45–0.87]). Conclusions: In participants without prior cardiovascular disease and high fish consumption, dietary ALA, supplied mainly by walnuts and olive oil, relates inversely to all‐cause mortality, whereas protection from cardiac mortality is limited to fish‐derived long‐chain n‐3 polyunsaturated fatty acids. Clinical Trial Registration URL: http://www.Controlled-trials.com/. Unique identifier: ISRCTN35739639

Nurses' perceptions of aids and obstacles to the provision of optimal end of life care in ICU

Contains fulltext : 172380.pdf (publisher's version ) (Open Access

The value of the continuous genotyping of multi-drug resistant tuberculosis over 20 years in Spain

Molecular epidemiology of circulating clinical isolates is crucial to improve prevention strategies. The Spanish Working Group on multidrug resistant tuberculosis (MDR-TB) is a network that monitors the MDR-TB isolates in Spain since 1998. The aim of this study was to present the study of the MDR-TB and extensively drug-resistant tuberculosis (XDR-TB) patterns in Spain using the different recommended genotyping methods over time by a national coordinated system. Based on the proposed genotyping methods in the European Union until 2018, the preservation of one method, MIRU-VNTR, applied to selected clustered strains permitted to maintain our study open for 20 years. The distribution of demographic, clinical and epidemiological characteristics of clustered and non-clustered cases of MDR/XDR tuberculosis with proportion differences as assessed by Pearson’s chi-squared or Fisher’s exact test was compared. The differences in the quantitative variables using the Student's-t test and the Mann–Whitney U test were evaluated. The results obtained showed a total of 48.4% of the cases grouped in 77 clusters. Younger age groups, having a known TB case contact (10.2% vs 4.7%) and XDR-TB (16.5% vs 1.8%) were significantly associated with clustering. The largest cluster corresponded to a Mycobacterium bovis strain mainly spread during the nineties. A total of 68.4% of the clusters detected were distributed among the different Spanish regions and six clusters involving 104 cases were grouped in 17 and 18 years. Comparison of the genotypes obtained with those European genotypes included in The European Surveillance System (TESSy) showed that 87 cases had become part of 20 European clusters. The continuity of MDR strain genotyping in time has offered a widespread picture of the situation that allows better management of this public health problem. It also shows the advantage of maintaining one genotyping method over time, which allowed the comparison between ancient, present and future samples