46 research outputs found
Epidemiological trends of HIV/HCV coinfection in Spain, 2015-2019
Objectives: We assessed the prevalence of anti-hepatitis C virus (HCV) antibodies and active HCV infection (HCV-RNA-positive) in people living with HIV (PLWH) in Spain in 2019 and compared the results with those of four similar studies performed during 2015-2018. Methods: The study was performed in 41 centres. Sample size was estimated for an accuracy of 1%. Patients were selected by random sampling with proportional allocation. Results: The reference population comprised 41 973 PLWH, and the sample size was 1325. HCV serostatus was known in 1316 PLWH (99.3%), of whom 376 (28.6%) were HCV antibody (Ab)-positive (78.7% were prior injection drug users); 29 were HCV-RNA-positive (2.2%). Of the 29 HCV-RNA-positive PLWH, infection was chronic in 24, it was acute/recent in one, and it was of unknown duration in four. Cirrhosis was present in 71 (5.4%) PLWH overall, three (10.3%) HCV-RNA-positive patients and 68 (23.4%) of those who cleared HCV after anti-HCV therapy (p = 0.04). The prevalence of anti-HCV antibodies decreased steadily from 37.7% in 2015 to 28.6% in 2019 (p < 0.001); the prevalence of active HCV infection decreased from 22.1% in 2015 to 2.2% in 2019 (p < 0.001). Uptake of anti-HCV treatment increased from 53.9% in 2015 to 95.0% in 2019 (p < 0.001). Conclusions: In Spain, the prevalence of active HCV infection among PLWH at the end of 2019 was 2.2%, i.e. 90.0% lower than in 2015. Increased exposure to DAAs was probably the main reason for this sharp reduction. Despite the high coverage of treatment with direct-acting antiviral agents, HCV-related cirrhosis remains significant in this population.This work was supported in part by the Spanish AIDS Research Network (RD16/0025/0017, RD16/0025/0018), which is included in the Spanish I+D+I Plan and is co-funded by the ISCIII-Subdirección General de Evaluación and European Funding for Regional Development (FEDER). The sponsors had no role in the study design, the collection, analysis and interpretation of data, the writing of the report, or the decision to submit the article for publication.S
Human Immunodeficiency Virus/Hepatits C Virus Coinfection in Spain: Elimination Is Feasible, but the Burden of Residual Cirrhosis Will Be Significant
Background: We assessed the prevalence of antibodies against hepatitis C virus (HCV-Abs) and active HCV infection in patients infected with human immunodeficiency virus (HIV) in Spain in 2016 and compared the results with those of similar studies performed in 2002, 2009, and 2015. Methods: The study was performed in 43 centers during October-November 2016. The sample was estimated for an accuracy of 2% and selected by proportional allocation and simple random sampling. During 2016, criteria for therapy based on direct-acting antiviral agents (DAA) were at least significant liver fibrosis, severe extrahepatic manifestations of HCV, and high risk of HCV transmissibility. Results: The reference population and the sample size were 38904 and 1588 patients, respectively. The prevalence of HCV-Abs in 2002, 2009, 2015, and 2016 was 60.8%, 50.2%, 37.7%, and 34.6%, respectively (P trend <.001, from 2002 to 2015). The prevalence of active HCV in 2002, 2009, 2015, and 2016 was 54.0%, 34.0%, 22.1%, and 11.7%, respectively (P trend <.001). The anti-HCV treatment uptake in 2002, 2009, 2015, and 2016 was 23.0%, 48.0%, 59.3%, and 74.7%, respectively (P trend <.001). In 2016, HCV-related cirrhosis was present in 7.6% of all HIV-infected individuals, 15.0% of patients with active HCV, and 31.5% of patients who cleared HCV after anti-HCV therapy. Conclusions: Our findings suggest that with universal access to DAA-based therapy and continued efforts in prevention and screening, it will be possible to eliminate active HCV among HIV-infected individuals in Spain in the short term. However, the burden of HCV-related cirrhosis will continue to be significant among HIV-infected individuals.This work was funded by grant Ref. no. GLD14-00279 from the GILEAD Fellowship Programme (Spain) and by the Spanish AIDS Research Network (RD16/0025/0017, RD16/0025/0018) that is included in the Spanish I+D+I Plan and is co-financed by ISCIII-Subdirección General de Evaluacion and European Funding for Regional Development (FEDER).S
Epidemiological trends of HIV/HCV coinfection in Spain, 2015-2019
Altres ajuts: Spanish AIDS Research Network; European Funding for Regional Development (FEDER).Objectives: We assessed the prevalence of anti-hepatitis C virus (HCV) antibodies and active HCV infection (HCV-RNA-positive) in people living with HIV (PLWH) in Spain in 2019 and compared the results with those of four similar studies performed during 2015-2018. Methods: The study was performed in 41 centres. Sample size was estimated for an accuracy of 1%. Patients were selected by random sampling with proportional allocation. Results: The reference population comprised 41 973 PLWH, and the sample size was 1325. HCV serostatus was known in 1316 PLWH (99.3%), of whom 376 (28.6%) were HCV antibody (Ab)-positive (78.7% were prior injection drug users); 29 were HCV-RNA-positive (2.2%). Of the 29 HCV-RNA-positive PLWH, infection was chronic in 24, it was acute/recent in one, and it was of unknown duration in four. Cirrhosis was present in 71 (5.4%) PLWH overall, three (10.3%) HCV-RNA-positive patients and 68 (23.4%) of those who cleared HCV after anti-HCV therapy (p = 0.04). The prevalence of anti-HCV antibodies decreased steadily from 37.7% in 2015 to 28.6% in 2019 (p < 0.001); the prevalence of active HCV infection decreased from 22.1% in 2015 to 2.2% in 2019 (p < 0.001). Uptake of anti-HCV treatment increased from 53.9% in 2015 to 95.0% in 2019 (p < 0.001). Conclusions: In Spain, the prevalence of active HCV infection among PLWH at the end of 2019 was 2.2%, i.e. 90.0% lower than in 2015. Increased exposure to DAAs was probably the main reason for this sharp reduction. Despite the high coverage of treatment with direct-acting antiviral agents, HCV-related cirrhosis remains significant in this population
Monitoring of chicken meat freshness by means of a colorimetric sensor array
A new optoelectronic nose to monitor chicken meat ageing has been developed. It is based on 16
pigments prepared by the incorporation of different dyes (pH indicators, Lewis acids, hydrogenbonding derivatives, selective probes and natural dyes) into inorganic materials (UVM-7, silica and
alumina). The colour changes of the sensor array were characteristic of chicken ageing in a modi¿ed
packaging atmosphere (30% CO2¿70% N2). The chromogenic array data were processed with
qualitative (PCA) and quantitative (PLS) tools. The PCA statistical analysis showed a high degree of
dispersion, with nine dimensions required to explain 95% of variance. Despite this high dimensionality,
a tridimensional representation of the three principal components was able to differentiate ageing with
2-day intervals. Moreover, the PLS statistical analysis allows the creation of a model to correlate the
chromogenic data with chicken meat ageing. The model offers a PLS prediction model for ageing with
values of 0.9937, 0.0389 and 0.994 for the slope, the intercept and the regression coef¿cient,
respectively, and is in agreement with the perfect ¿t between the predicted and measured values
observed. The results suggest the feasibility of this system to help develop optoelectronic noses that
monitor food freshness.Salinas Soler, Y.; Ros-Lis, JV.; Vivancos, J.; Martínez Mañez, R.; Marcos Martínez, MD.; Aucejo Romero, S.; Herranz, N.... (2012). Monitoring of chicken meat freshness by means of a colorimetric sensor array. Analyst. 137(16):3635-3643. doi:10.1039/C2AN35211GS3635364313716Anang, D. M., Rusul, G., Ling, F. H., & Bhat, R. (2010). Inhibitory effects of lactic acid and lauricidin on spoilage organisms of chicken breast during storage at chilled temperature. International Journal of Food Microbiology, 144(1), 152-159. doi:10.1016/j.ijfoodmicro.2010.09.014HINTON, A., & INGRAM, K. D. (2005). Microbicidal Activity of Tripotassium Phosphate and Fatty Acids toward Spoilage and Pathogenic Bacteria Associated with Poultry. Journal of Food Protection, 68(7), 1462-1466. doi:10.4315/0362-028x-68.7.1462Jeremiah, L. . (2001). Packaging alternatives to deliver fresh meats using short- or long-term distribution. Food Research International, 34(9), 749-772. doi:10.1016/s0963-9969(01)00096-5Ellis, D. I., & Goodacre, R. (2001). Rapid and quantitative detection of the microbial spoilage of muscle foods: current status and future trends. Trends in Food Science & Technology, 12(11), 414-424. doi:10.1016/s0924-2244(02)00019-5Vinci, G., & Antonelli, M. . (2002). Biogenic amines: quality index of freshness in red and white meat. Food Control, 13(8), 519-524. doi:10.1016/s0956-7135(02)00031-2Lovestead, T. M., & Bruno, T. J. (2010). Detection of poultry spoilage markers from headspace analysis with cryoadsorption on a short alumina PLOT column. Food Chemistry, 121(4), 1274-1282. doi:10.1016/j.foodchem.2010.01.044Bota, G. M., & Harrington, P. B. (2006). Direct detection of trimethylamine in meat food products using ion mobility spectrometry. Talanta, 68(3), 629-635. doi:10.1016/j.talanta.2005.05.001Grau, R., Sánchez, A. J., Girón, J., Iborra, E., Fuentes, A., & Barat, J. M. (2011). Nondestructive assessment of freshness in packaged sliced chicken breasts using SW-NIR spectroscopy. Food Research International, 44(1), 331-337. doi:10.1016/j.foodres.2010.10.011Sahar, A., Boubellouta, T., & Dufour, É. (2011). Synchronous front-face fluorescence spectroscopy as a promising tool for the rapid determination of spoilage bacteria on chicken breast fillet. Food Research International, 44(1), 471-480. doi:10.1016/j.foodres.2010.09.006Lin, M., Al-Holy, M., Mousavi-Hesary, M., Al-Qadiri, H., Cavinato, A. G., & Rasco, B. A. (2004). Rapid and quantitative detection of the microbial spoilage in chicken meat by diffuse reflectance spectroscopy (600-1100 nm). Letters in Applied Microbiology, 39(2), 148-155. doi:10.1111/j.1472-765x.2004.01546.xMartínez-Máñez, R., & Sancenón, F. (2003). Fluorogenic and Chromogenic Chemosensors and Reagents for Anions. Chemical Reviews, 103(11), 4419-4476. doi:10.1021/cr010421eAmendola, V., Fabbrizzi, L., & Mosca, L. (2010). Anion recognition by hydrogen bonding: urea-based receptors. Chemical Society Reviews, 39(10), 3889. doi:10.1039/b822552bQuang, D. T., & Kim, J. S. (2010). Fluoro- and Chromogenic Chemodosimeters for Heavy Metal Ion Detection in Solution and Biospecimens. Chemical Reviews, 110(10), 6280-6301. doi:10.1021/cr100154pAmendola, V., Bonizzoni, M., Esteban-Gómez, D., Fabbrizzi, L., Licchelli, M., Sancenón, F., & Taglietti, A. (2006). Some guidelines for the design of anion receptors. Coordination Chemistry Reviews, 250(11-12), 1451-1470. doi:10.1016/j.ccr.2006.01.006Chen, X., Zhou, Y., Peng, X., & Yoon, J. (2010). Fluorescent and colorimetric probes for detection of thiols. Chemical Society Reviews, 39(6), 2120. doi:10.1039/b925092aMohr, G. J. (2006). New chromogenic and fluorogenic reagents and sensors for neutral and ionic analytes based on covalent bond formation–a review of recent developments. Analytical and Bioanalytical Chemistry, 386(5), 1201-1214. doi:10.1007/s00216-006-0647-3Kerry, J. P., O’Grady, M. N., & Hogan, S. A. (2006). Past, current and potential utilisation of active and intelligent packaging systems for meat and muscle-based products: A review. Meat Science, 74(1), 113-130. doi:10.1016/j.meatsci.2006.04.024Rakow, N. A., & Suslick, K. S. (2000). A colorimetric sensor array for odour visualization. Nature, 406(6797), 710-713. doi:10.1038/35021028Lim, S. H., Kemling, J. W., Feng, L., & Suslick, K. S. (2009). A colorimetric sensor array of porous pigments. The Analyst, 134(12), 2453. doi:10.1039/b916571aPalacios, M. A., Nishiyabu, R., Marquez, M., & Anzenbacher, P. (2007). Supramolecular Chemistry Approach to the Design of a High-Resolution Sensor Array for Multianion Detection in Water. Journal of the American Chemical Society, 129(24), 7538-7544. doi:10.1021/ja0704784Wu, Y., Na, N., Zhang, S., Wang, X., Liu, D., & Zhang, X. (2009). Discrimination and Identification of Flavors with Catalytic Nanomaterial-Based Optical Chemosensor Array. Analytical Chemistry, 81(3), 961-966. doi:10.1021/ac801733kJanzen, M. C., Ponder, J. B., Bailey, D. P., Ingison, C. K., & Suslick, K. S. (2006). Colorimetric Sensor Arrays for Volatile Organic Compounds. Analytical Chemistry, 78(11), 3591-3600. doi:10.1021/ac052111sSuslick, B. A., Feng, L., & Suslick, K. S. (2010). Discrimination of Complex Mixtures by a Colorimetric Sensor Array: Coffee Aromas. Analytical Chemistry, 82(5), 2067-2073. doi:10.1021/ac902823wHuang, X., Xin, J., & Zhao, J. (2011). A novel technique for rapid evaluation of fish freshness using colorimetric sensor array. Journal of Food Engineering, 105(4), 632-637. doi:10.1016/j.jfoodeng.2011.03.034Anzenbacher, Jr., P., Lubal, P., Buček, P., Palacios, M. A., & Kozelkova, M. E. (2010). A practical approach to optical cross-reactive sensor arrays. Chemical Society Reviews, 39(10), 3954. doi:10.1039/b926220mRos-Lis, J. V., García, B., Jiménez, D., Martínez-Máñez, R., Sancenón, F., Soto, J., … Valldecabres, M. C. (2004). Squaraines as Fluoro−Chromogenic Probes for Thiol-Containing Compounds and Their Application to the Detection of Biorelevant Thiols. Journal of the American Chemical Society, 126(13), 4064-4065. doi:10.1021/ja031987iRos-Lis, J. V., Martínez-Máñez, R., Rurack, K., Sancenón, F., Soto, J., & Spieles, M. (2004). Highly Selective Chromogenic Signaling of Hg2+in Aqueous Media at Nanomolar Levels Employing a Squaraine-Based Reporter. Inorganic Chemistry, 43(17), 5183-5185. doi:10.1021/ic049422qRos-Lis, J. V., Marcos, M. D., Mártinez-Máñez, R., Rurack, K., & Soto, J. (2005). A Regenerative Chemodosimeter Based on Metal-Induced Dye Formation for the Highly Selective and Sensitive Optical Determination of Hg2+ Ions. Angewandte Chemie International Edition, 44(28), 4405-4407. doi:10.1002/anie.200500583Ros-Lis, J. V., Martínez-Máñez, R., & Soto, J. (2005). Colorimetric Signaling of Large Aromatic Hydrocarbons via the Enhancement of Aggregation Processes. Organic Letters, 7(12), 2337-2339. doi:10.1021/ol050564dCliment, E., Marcos, M. D., Martínez-Máñez, R., Sancenón, F., Soto, J., Rurack, K., & Amorós, P. (2009). The Determination of Methylmercury in Real Samples Using Organically Capped Mesoporous Inorganic Materials Capable of Signal Amplification. Angewandte Chemie International Edition, 48(45), 8519-8522. doi:10.1002/anie.200904243Ábalos, T., Jiménez, D., Martínez-Máñez, R., Ros-Lis, J. V., Royo, S., Sancenón, F., … Parra, M. (2009). Hg2+ and Cu2+ selective detection using a dual channel receptor based on thiopyrylium scaffoldings. Tetrahedron Letters, 50(27), 3885-3888. doi:10.1016/j.tetlet.2009.04.060Climent, E., Giménez, C., Marcos, M. D., Martínez-Máñez, R., Sancenón, F., & Soto, J. (2011). Selective and sensitive chromo-fluorogenic sensing of anionic surfactants in water using functionalised silica nanoparticles. Chemical Communications, 47(24), 6873. doi:10.1039/c1cc11393cRoyo, S., Costero, A. M., Parra, M., Gil, S., Martínez-Máñez, R., & Sancenón, F. (2011). Chromogenic, Specific Detection of the Nerve-Agent Mimic DCNP (a Tabun Mimic). Chemistry - A European Journal, 17(25), 6931-6934. doi:10.1002/chem.201100602García-Acosta, B., Comes, M., Bricks, J. L., Kudinova, M. A., Kurdyukov, V. V., Tolmachev, A. I., … Amorós, P. (2006). Sensory hybrid host materials for the selective chromo-fluorogenic detection of biogenic amines. Chem. Commun., (21), 2239-2241. doi:10.1039/b602497aSancenón, F., Descalzo, A. B., Martínez-Máñez, R., Miranda, M. A., & Soto, J. (2001). A Colorimetric ATP Sensor Based on 1,3,5-Triarylpent-2-en-1,5-diones. Angewandte Chemie International Edition, 40(14), 2640-2643. doi:10.1002/1521-3773(20010716)40:143.0.co;2-aEsteban, J., Ros-Lis, J. V., Martínez-Máñez, R., Marcos, M. D., Moragues, M., Soto, J., & Sancenón, F. (2010). Sensitive and Selective Chromogenic Sensing of Carbon Monoxide by Using Binuclear Rhodium Complexes. Angewandte Chemie International Edition, 49(29), 4934-4937. doi:10.1002/anie.201001344Moragues, M. E., Esteban, J., Ros-Lis, J. V., Martínez-Máñez, R., Marcos, M. D., Martínez, M., … Sancenón, F. (2011). Sensitive and Selective Chromogenic Sensing of Carbon Monoxide via Reversible Axial CO Coordination in Binuclear Rhodium Complexes. Journal of the American Chemical Society, 133(39), 15762-15772. doi:10.1021/ja206251rRos-Lis, J. V., Martínez-Máñez, R., Sancenón, F., Soto, J., Rurack, K., & Weißhoff, H. (2007). Signalling Mechanisms in Anion-Responsive Push-Pull Chromophores: The Hydrogen-Bonding, Deprotonation and Anion-Exchange Chemistry of Functionalized Azo Dyes. European Journal of Organic Chemistry, 2007(15), 2449-2458. doi:10.1002/ejoc.200601111El Haskouri, J., Zárate, D. O. de, Guillem, C., Latorre, J., Caldés, M., Beltrán, A., … Amorós, P. (2002). Silica-based powders and monoliths with bimodal pore systemsElectronic supplementary information (ESI) available: UV–Vis spectrum of sample 3. See http://www.rsc.org/suppdata/cc/b1/b110883b/. Chemical Communications, (4), 330-331. doi:10.1039/b110883bDe Jong, S. (1993). SIMPLS: An alternative approach to partial least squares regression. Chemometrics and Intelligent Laboratory Systems, 18(3), 251-263. doi:10.1016/0169-7439(93)85002-xSmolander, M., Hurme, E., Latva-Kala, K., Luoma, T., Alakomi, H.-L., & Ahvenainen, R. (2002). Myoglobin-based indicators for the evaluation of freshness of unmarinated broiler cuts. Innovative Food Science & Emerging Technologies, 3(3), 279-288. doi:10.1016/s1466-8564(02)00043-7Dainty, R. H. (1996). Chemical/biochemical detection of spoilage. International Journal of Food Microbiology, 33(1), 19-33. doi:10.1016/0168-1605(96)01137-3De Fernando, G. D. G., Nychas, G. J. E., Peck, M. W., & Ordóñez, J. A. (1995). Growth/survival of psychrotrophic pathogens on meat packaged under modified atmospheres. International Journal of Food Microbiology, 28(2), 221-231. doi:10.1016/0168-1605(95)00058-5Descalzo, A. B., Dolores Marcos, M., Monte, C., Martínez-Máñez, R., & Rurack, K. (2007). Mesoporous silica materials with covalently anchored phenoxazinone dyes as fluorescent hybrid materials for vapour sensing. Journal of Materials Chemistry, 17(44), 4716. doi:10.1039/b707473eDescalzo, A. B., Rurack, K., Weisshoff, H., Martínez-Máñez, R., Marcos, M. D., Amorós, P., … Soto, J. (2005). Rational Design of a Chromo- and Fluorogenic Hybrid Chemosensor Material for the Detection of Long-Chain Carboxylates. Journal of the American Chemical Society, 127(1), 184-200. doi:10.1021/ja045683nComes, M., Aznar, E., Moragues, M., Marcos, M. D., Martínez-Máñez, R., Sancenón, F., … Amorós, P. (2009). Mesoporous Hybrid Materials Containing Nanoscopic «Binding Pockets» for Colorimetric Anion Signaling in Water by using Displacement Assays. Chemistry - A European Journal, 15(36), 9024-9033. doi:10.1002/chem.200900890Nychas, G.-J. E., & Tassou, C. C. (1997). Spoilage Processes and Proteolysis in Chicken as Detected by HPLC. Journal of the Science of Food and Agriculture, 74(2), 199-208. doi:10.1002/(sici)1097-0010(199706)74:23.0.co;2-4Jiménez, S. M., Salsi, M. S., Tiburzi, M. C., Rafaghelli, R. C., Tessi, M. A., & Coutaz, V. R. (1997). Spoilage microflora in fresh chicken breast stored at 4 °C : influence of packaging methods. Journal of Applied Microbiology, 83(5), 613-618. doi:10.1046/j.1365-2672.1997.00276.xDe Fernando, G. D. G., Nychas, G. J. E., Peck, M. W., & Ordóñez, J. A. (1995). Growth/survival of psychrotrophic pathogens on meat packaged under modified atmospheres. International Journal of Food Microbiology, 28(2), 221-231. doi:10.1016/0168-1605(95)00058-5BALAMATSIA, C., PATSIAS, A., KONTOMINAS, M., & SAVVAIDIS, I. (2007). Possible role of volatile amines as quality-indicating metabolites in modified atmosphere-packaged chicken fillets: Correlation with microbiological and sensory attributes. Food Chemistry, 104(4), 1622-1628. doi:10.1016/j.foodchem.2007.03.013Balamatsia, C. C., Paleologos, E. K., Kontominas, M. G., & Savvaidis, I. N. (2006). Correlation between microbial flora, sensory changes and biogenic amines formation in fresh chicken meat stored aerobically or under modified atmosphere packaging at 4 °C: possible role of biogenic amines as spoilage indicators. Antonie van Leeuwenhoek, 89(1), 9-17. doi:10.1007/s10482-005-9003-4Smolander, M., Hurme, E., Latva-Kala, K., Luoma, T., Alakomi, H.-L., & Ahvenainen, R. (2002). Myoglobin-based indicators for the evaluation of freshness of unmarinated broiler cuts. Innovative Food Science & Emerging Technologies, 3(3), 279-288. doi:10.1016/s1466-8564(02)00043-7Dainty, R. H. (1996). Chemical/biochemical detection of spoilage. International Journal of Food Microbiology, 33(1), 19-33. doi:10.1016/0168-1605(96)01137-3Berrueta, L. A., Alonso-Salces, R. M., & Héberger, K. (2007). Supervised pattern recognition in food analysis. Journal of Chromatography A, 1158(1-2), 196-214. doi:10.1016/j.chroma.2007.05.02
Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study
Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation
Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes
Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues
Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries
Abstract
Background
Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres.
Methods
This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries.
Results
In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia.
Conclusion
This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries
Evaluation of the fracture risk assessment tool for determining bone disease and the impact of secondary causes of osteoporosis in people living with HIV
Background Among HIV-infected individuals, screening for bone disease is encouraged to assess reversible risk factors and plan therapeutic interventions. Objective We assessed the usefulness of Fracture Risk Assessment (FRAX) tool to identify candidates for dual X-ray absorptiometry (DXA) scan, or individuals with bone loss progression. We further explored how secondary causes of osteoporosis are reflected on FRAX. Methods Longitudinal study of 217 consecutive individuals (mean, 45.8 years, 24% females) included after DXA scan. FRAX was calculated without/with femoral neck bone mineral density (BMD), checking the box of “secondary osteoporosis” for all the individuals. Results Low BMD was observed in 133/217 (61%) individuals, of whom 98.5% had not been selected as candidates for DXA by current FRAX thresholds. Specifically, 23% of individuals aged <50 had low BMD but none was candidate for DXA. Adding BMD data, FRAX results increased by 50–100%, with 2/217 individuals (1%) above the thresholds. Classical and HIV-related secondary causes of osteoporosis (observed in 98% overall) correlated with low BMD, modifying significantly FRAX results (HCV coinfection, +124%; longer time of HIV infection, +93%; longer time on antiretroviral therapy, +147%; tenofovir exposure +36%). Individuals with lower BMD and higher FRAX results at inclusion had less bone decline in a follow-up DXA after a median of 3.5 years. Conclusions Currently recommended FRAX thresholds are not useful to select candidates for DXA scan, which could delay its performance in a population with a high prevalence of secondary factors for low BMD. Classical and HIV-related factors alter BMD and fracture risk estimation
Análisis y modificación de conducta
Resumen tomado de la revistaEl trabajo consiste en la presentación de los resultados obtenidos en un estudio epidemiológico sobre el juego de apuesta y el juego patológico realizado en el municipio de Punta Umbría (Huelva). Se muestran los datos recogidos sobre un grupo de 486 sujetos mayores de edad, utilizando el South Oaks gambling Screen (SOGS), donde podemos observar que el 91,65 por ciento no presentaría problemas de juego, el 4,9 por ciento sería jugador con problemas leves y el 3,5 por ciento podríamos clasificarlo como probable jugador patológico. Tras describir distintas características sociodemográficas, destacamos que el 11,8 por ciento de los jugadores patológicos sobrepasan los 18 puntos en el Inventario de Depresión de Beck (BDI), el 10,9 por ciento desearía suicidarse o lo haría si tuviera la oportunidad y el 29,4 por ciento de ellos podrían presentar problems de alcoholismo medido con el Cuestionario Breve de Alcoholismo (CBA).ValenciaES