56 research outputs found

    In situ test: cotton sheets against mosquito bites in India

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    [EN] Historically, fabrics were considered as a source of warmth and protection against weather conditions. Nowadays, fabrics can be converted into smart textiles and through this process new properties are conferred to them. For that purpose, microcapsules can play an important role in that they can be used within many application areas including medicine or pharmaceuticals. Malaria, dengue fever and other diseases are typically spread through mosquito bites. This is a concern of many authorities in affected countries and significant research is being conducted today in order to reduce incidence. The aim of the study reported here is not only to demonstrate the effectiveness of microcapsules on cotton fabrics as a prevention to mosquito bites but also to test this in situ. Different fabrics were prepared and tested in two Indian regions. Laboratory tests were performed according to a standard designed by the Swiss Tropical laboratory. Results demonstrated that the fabrics repellence to mosquitos could be considered as very good and that the repellent effect of the microcapsules was maintained for more than 10 laundry cycles. Furthermore, our experiments conducted in situ confirmed the effectiveness of the technology.The authors would like to express their gratitude to the "Fundacion Vicente Ferrer" and to the project CDTI IDI/20090482. Authors would also acknowledge Electron Microscopy Service of the UPV for their professional support on the SEM images analysis.Bonet-Aracil, M.; Bou-Belda, E.; Gisbert Paya, J.; Ibañez Garcia, F. (2019). In situ test: cotton sheets against mosquito bites in India. Cellulose. 26(7):4655-4663. https://doi.org/10.1007/s10570-019-02395-zS46554663267Anuar AA, Yusof N (2016) Methods of imparting mosquito repellent agents and the assessing mosquito repellency on textile. Fash Text 3(1):12Berger J, Reist M, Mayer JM, Felt O, Peppas NA, Gurny R (2004) Structure and interactions in covalently and ionically crosslinked chitosan hydrogels for biomedical applications. Eur J Pharm Biopharm 57:19–34Bonet Aracil M, Monllor P, Capablanca L, Gisbert J, Díaz P, Montava I (2015) A comparison between padding and bath exhaustion to apply microcapsules onto cotton. Cellulose 22:2117–2127. https://doi.org/10.1007/s10570-015-0600-8Bonet-Aracil M, Capablanca L, Monllor P, Díaz P, Montava I (2012) Studying bath exhaustion as a method to apply microcapsules on fabrics. J Text Inst 103(6):629–635Carter R, Mendis KN (2002) Evolutionary and historical aspects of the burden of malaria. Clin Microbiol Rev 15(4):564–594Carvalho IT, Estevinho BN, Santos L (2016) Application of microencapsulated essential oils in cosmetic and personal healthcare products—a review. Int J Cosmet Sci 38(2):109–119Dewettinck K, Huyghebaert A (1999) Fluidized bed coating in food technology. Trends Food Sci Technol 10:163–168Downham A (2000) Collins Paul. Colouring our foods in the last and next millennium. Int J Food Sci Technol 35:5–22Goldman L, Ausiello D (2009) Cecil tratado de medicina interna (No. 616). ElsevierGouin S (2004) Microencapsulation: industrial appraisal of existing technologies and trends. Trend Food Sci Technol 15:330–347Gupta RK, Rutledge LC, Reifenrath WG, Gutierrez GA, Korte JD (1989) Effects of weathering on fabrics treated with permethrin for protection against mosquitoes. J Am Mosq Control Assoc 5(2):176–179Hatefi A, Amsden B (2002) Biodegradabe injectable in situ forming drug delivery systems. J Control Release 80:9–28Heinzelmann K, Franke K (1999) Using freezing and drying techniques of emulsions for the microencapsulation of fish oil to improve oxidation stability. Colloid Surf B 12:223–229Hirech K, Payan S, Carnelle G, Brujes L, Legrand J (2003) Microencapsulation of an insecticide by interfacial polymerization. Powder Technol 130:324–330Kamsuk K, Choochote W, Chaithong U, Jitpakdi A, Tippawangkosol P, Riyong D, Pitasawat B (2007) Effectiveness of Zanthoxylum piperitum-derived essential oil as an alternative repellent under laboratory and field applications. Parasitol Res 100:339–345Liu J, Fung D, Jiang J, Zhu Y (2014) Ultrafine particle emissions from essential-oil-based mosquito repellent products. Indoor Air 24:327–335Magnin D, Lefebvre J, Chornet E, Dumitriu S (2004) Physicochemical and structural characterization of a polyionic matrix of interest in biotechnology, in the pharmaceutical and biomedical fields. Carbohydr Polym 55:437–453Majeti N, Ravi Kumar V (2000) Nano and microspheres as controlled drug delivery devices. J Pharm Pharm Sci 3(2):234–258Maji TK, Baruah I, Dube S, Hussain MR (2007) Microencapsulation of Zanthoxylum limonella oil (ZLO) in glutaraldehyde crosslinked gelatin for mosquito repellent application. Bioresour Technol 98:840–844Monllor P, Cases FJ, Bonet M (2007) Characterization of the behaviour of flavour microcapsules in cotton fabrics. Eur Polym J 43:2481–2490Moretti M, Sanna-Passino G, Demontis S, Bazzoni E (2004) Essential oil formulations useful as a new tool for insect pest control. AAPS Pharm Sci Technol 3(2):62–64Muzzarelli C, Stanic V, Gobbi L, Tosi G, Muzzarelli RAA (2004) Spray-drying of solutions containing chitosan together with polyuronans and characterisation of the microspheres. Carbohydr Polym 57:73–82Nelson G (1991) Microencapsulates in textile coloration and finishing. Rev Prog Color 21:72–85Senjković R, Jalŝenjak I (1981) Surface topography of microcapsules and the drug release. J Pharm Pharmacol 33(1):665–666Solomon B, Sahle FF, Gebre-Mariam T, Asres K, Neubert RHH (2012) Microencapsulation of citronella oil for mosquito-repellent application: formulation and in vitro permeation studies. Eur J Pharm Biopharm 80:61–66Thavara U, Tawatsin A, Chompoosri J (2002). Phytochemicals as repellents against mosquitoes in Thailand. In: International conference on biopesticide, Malaysia, pp 233–242Wen-Tao Q, Wei-ting Y, Xie Y, Xiaojun M (2005) Optimization of Saccaromyces cerevisiae culture in alginate-chitosan-alginate microcapsule. Biochem Eng J 25:151–157WHO, “World Malaria Report 2015,” Geneva, 27 SwitzerlandWibowo S, Velazquez G, Savant V, Torres JA (2005) Surimi wash water treatment for protein recovery: effect of chitosanalginate complex concentration and treatment time on protein adsorption. Biores Technol 96:665–67

    Adaptability in aerospace production using Cyberphysical Systems

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    Una característica en la industria automatizada son los cambios de ingeniería y problemas de producción respecto a los mantenimientos correctivos y preventivos de los robots. Esto aunado a los problemas de faltantes de material y retrasos en el arribo de componentes; repercutiendo en pérdidas de tiempo de producción, que da como resultado planes de producción muy cambiantes, perdida de dinero y un estresante modo de operación en todos los departamentos. Este artículo describe cómo los sistemas ciberfisicos, son una herramienta importante para una industria con ritmo acelerado; nuestro caso de estudio es la industria aeroespacial debido a su gran crecimiento en México. Actualmente a pesar de que se encuentran automatizadas las plantas aeroespaciales, el software que se utiliza en el proceso es independiente uno de otro, los componentes de software necesitan grados de libertad en forma de parámetros, para que puedan reaccionar a los nuevos requisitos que la industria aeroespacial requiere sin poner en riesgo la calidad.A characteristic in the automated industry are the engineering changes and production problems with respect to the corrective and preventive maintenance of the robots. This coupled with the problems of missing material and delays in the arrival of components; resulting in lost production time, which results in very changing production plans, loss of money and a stressful mode of operation in all departments. This article describes how cyberphysical systems are an important tool for an industry with an accelerated rhythm; Our case study is the aerospace industry due to its great growth in Mexico. Currently, although aerospace plants are automated, the software used in the process is independent of each other, the software components need degrees of freedom in the form of parameters, so that they can react to the new requirements that the industry aerospace requires without compromising quality

    Early detection of intentional harm in the human amygdala

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    A decisive element of moral cognition is the detection of harm and its assessment as intentional or unintentional. Moral cognition engages brain networks supporting mentalizing, intentionality, empathic concern and evaluation. These networks rely on the amygdala as a critical hub, likely through frontotemporal connections indexing stimulus salience. We assessed inferences about perceived harm using a paradigm validated through functional magnetic resonance imaging, eye-tracking and electroencephalogram recordings. During the task, we measured local field potentials in three patients with depth electrodes (n = 115) placed in the amygdala and in several frontal, temporal, and parietal locations. Direct electrophysiological recordings demonstrate that intentional harm induces early activity in the amygdala (5 200 ms), which-in turn-predicts intention attribution. The amygdala was the only site that systematically discriminated between critical conditions and predicted their classification of events as intentional. Moreover, connectivity analysis showed that intentional harm induced stronger frontotemporal information sharing at early stages. Results support the 'many roads' view of the amygdala and highlight its role in the rapid encoding of intention and salience-critical components of mentalizing and moral evaluation.Fil: Hesse Rizzi, Eugenia Fátima. Universidad de Buenos Aires; Argentina. Universidad Diego Portales; Chile. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva. Fundación Favaloro. Instituto de Neurociencia Cognitiva; ArgentinaFil: Mikulan, Ezequiel Pablo. Universidad Diego Portales; Chile. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva. Fundación Favaloro. Instituto de Neurociencia Cognitiva; ArgentinaFil: Decety, Jean. University of Chicago; Estados UnidosFil: Sigman, Mariano. Universidad de Buenos Aires; Argentina. Universidad Torcuato Di Tella; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Del Carmen Garcia, María. Hospital Italiano. Instituto Universitario - Escuela de Medicina; ArgentinaFil: Silva, Walter. Hospital Italiano. Instituto Universitario - Escuela de Medicina; ArgentinaFil: Ciraolo, Carlos. Hospital Italiano. Instituto Universitario - Escuela de Medicina; ArgentinaFil: Vaucheret, Esteban. Hospital Italiano. Instituto Universitario - Escuela de Medicina; ArgentinaFil: Baglivo, Fabricio. Universidad Favaloro; Argentina. Universidad de Buenos Aires; Argentina. Universidad Diego Portales; Chile. Instituto de Neurología Cognitiva; ArgentinaFil: Huepe, David. Universidad Diego Portales; ChileFil: Lopez, Vladimir. Pontificia Universidad Católica de Chile; ChileFil: Manes, Facundo Francisco. Universidad Diego Portales; Chile. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva. Fundación Favaloro. Instituto de Neurociencia Cognitiva; ArgentinaFil: Bekinschtein, Tristán Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. University of Cambridge; Reino UnidoFil: Ibañez, Agustin Mariano. Universidad Diego Portales; Chile. Universidad Autonoma del Caribe; Colombia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva. Fundación Favaloro. Instituto de Neurociencia Cognitiva; Argentin

    In-Host HEV Quasispecies Evolution Shows the Limits of Mutagenic Antiviral Treatments

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    Deep sequencing; Mutagens; QuasispeciesSeqüenciació profunda; Mutàgens; QuasiespècieSecuenciación profunda; Mutágenos; CuasiespecieHere, we report the in-host hepatitis E virus (HEV) quasispecies evolution in a chronically infected patient who was treated with three different regimens of ribavirin (RBV) for nearly 6 years. Sequential plasma samples were collected at different time points and subjected to RNA extraction and deep sequencing using the MiSeq Illumina platforms. Specifically, we RT-PCR amplified a single amplicon from the core region located in the open-reading frame 2 (ORF2). At the nucleotide level (genotype), our analysis showed an increase in the number of rare haplotypes and a drastic reduction in the frequency of the master (most represented) sequence during the period when the virus was found to be insensitive to RBV treatment. Contrarily, at the amino acid level (phenotype), our study revealed conservation of the amino acids, which is represented by a high prevalence of the master sequence. Our findings suggest that using mutagenic antivirals concomitant with high viral loads can lead to the selection and proliferation of a rich set of synonymous haplotypes that express the same phenotype. This can also lead to the selection and proliferation of conservative substitutions that express fitness-enhanced phenotypes. These results have important clinical implications, as they suggest that using mutagenic agents as a monotherapy treatment regimen in the absence of sufficiently effective viral inhibitors can result in diversification and proliferation of a highly diverse quasispecies resistant to further treatment. Therefore, such approaches should be avoided whenever possible.This study was partially supported by Plan Estratègic de Recerca i Innovació en Salut (PERIS)—Direcció General de Recerca i Innovació en Salut (DGRIS), Catalan Health Ministry, Generalitat de Catalunya; Centro para el Desarrollo Tecnológico Industrial (CDTI) from the Spanish Ministry of Economy and Business, grant number IDI-20200297, Grant PID2021-126447OB-I00 funded by MCIN/AEI/10.13039/501100011033 and by ERDF A way of making Europe; Projects PI19/00301 and PI22/00258 funded by Instituto de Salud Carlos III (ISCIII) and cofounded by the European Union; and Gilead’s biomedical research project GLD21/00006. S.C.-C has received support from Spanish Ministry of Education, grant FPU21/04150. M.I.-L. received the support of a fellowship from the “la Caixa” Foundation (ID 100010434), whose code is “LCF/BQ/DR23/12000020”

    The frequency of defective genomes in Omicron differs from that of the Alpha, Beta and Delta variants

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    Evolution; Genetics; Molecular biologyEvolució; Genètica; Biologia molecularEvolución; Genética; Biología molecularThe SARS-CoV-2 Omicron variant emerged showing higher transmissibility and possibly higher resistance to current COVID-19 vaccines than other variants dominating the global pandemic. In March 2020 we performed a study in clinical samples, where we found that a portion of genomes in the SARS-CoV-2 viral population accumulated deletions immediately before the S1/S2 cleavage site (furin-like cleavage site, PRRAR/S) of the spike gene, generating a frameshift and appearance of a premature stop codon. The main aim of this study was to determine the frequency of defective deletions in prevalent variants from the first to sixth pandemic waves in our setting and discuss whether the differences observed might support epidemiological proposals. The complete SARS-CoV-2 spike gene was deeply studied by next-generation sequencing using the MiSeq platform. More than 90 million reads were obtained from respiratory swab specimens of 78 COVID-19 patients with mild infection caused by the predominant variants circulating in the Barcelona city area during the six pandemic waves: B.1.5, B.1.1, B.1.177, Alpha, Beta, Delta, and Omicron. The frequency of defective genomes found in variants dominating the first and second waves was similar to that seen in Omicron, but differed from the frequencies seen in the Alpha, Beta and Delta variants. The changing pattern of mutations seen in the various SARS-CoV-2 variants driving the pandemic waves over time can affect viral transmission and immune escape. Here we discuss the putative biological effects of defective deletions naturally occurring before the S1/S2 cleavage site during adaption of the virus to human infection.This study was partially supported by Pla Estratègic de Recerca i Innovació en Salut (PERIS) – Direcció General de Recerca i Innovació en Salut (DGRIS), Catalan Health Ministry, Generalitat de Catalunya; the Spanish Network for the Research in Infectious Diseases (REIPI RD16/0016/0003) from the European Regional Development Fund (ERDF); Centro para el Desarrollo Tecnológico Industrial (CDTI) from the Spanish Ministry of Economy and Business, grant number IDI-20200297; Grant PI19/00301 from Instituto de Salud Carlos III cofinanced by the European Regional Development Fund (ERDF), and Gilead’s biomedical research project GLD21/00006. We gratefully acknowledge the authors, originating and submitting laboratories of the sequences from GISAID’s EpiCov Database on which this research is based

    Viscous dynamics associated with hypoexcitation and structural disintegration in neurodegeneration via generative whole-brain modeling

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    INTRODUCTION Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD) lack mechanistic biophysical modeling in diverse, underrepresented populations. Electroencephalography (EEG) is a high temporal resolution, cost-effective technique for studying dementia globally, but lacks mechanistic models and produces non-replicable results. METHODS We developed a generative whole-brain model that combines EEG source-level metaconnectivity, anatomical priors, and a perturbational approach. This model was applied to Global South participants (AD, bvFTD, and healthy controls). RESULTS Metaconnectivity outperformed pairwise connectivity and revealed more viscous dynamics in patients, with altered metaconnectivity patterns associated with multimodal disease presentation. The biophysical model showed that connectome disintegration and hypoexcitability triggered altered metaconnectivity dynamics and identified critical regions for brain stimulation. We replicated the main results in a second subset of participants for validation with unharmonized, heterogeneous recording settings. DISCUSSION The results provide a novel agenda for developing mechanistic model-inspired characterization and therapies in clinical, translational, and computational neuroscience settings

    Relationship between olive oil consumption and ankle-brachial pressure index in a population at high cardiovascular risk

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    The aim of this study was to ascertain the association between the consumption of different categories of edible olive oils (virgin olive oils and olive oil) and olive pomace oil and ankle-brachial pressure index (ABI) in participants in the PREDIMED-Plus study, a trial of lifestyle modification for weight and cardiovascular event reduction in individuals with overweight/obesity harboring the metabolic syndrome. Methods: We performed a cross-sectional analysis of the PREDIMED-Plus trial. Consumption of any category of olive oil and olive pomace oil was assessed through a validated food-frequency questionnaire. Multivariable linear regression models were fitted to assess associations between olive oil consumption and ABI. Additionally, ABI ≤1 was considered as the outcome in logistic models with different categories of olive oil and olive pomace oil as exposure. Results: Among 4330 participants, the highest quintile of total olive oil consumption (sum of all categories of olive oil and olive pomace oil) was associated with higher mean values of ABI (beta coefficient: 0.014, 95% confidence interval [CI]: 0.002, 0.027) (p for trend = 0.010). Logistic models comparing the consumption of different categories of olive oils, olive pomace oil and ABI ≤1 values revealed an inverse association between virgin olive oils consumption and the likelihood of a low ABI (odds ratio [OR] 0.73, 95% CI [0.56, 0.97]), while consumption of olive pomace oil was positively associated with a low ABI (OR 1.22 95% CI [1.00, 1.48]). Conclusions: In a Mediterranean population at high cardiovascular risk, total olive oil consumption was associated with a higher mean ABI. These results suggest that olive oil consumption may be beneficial for peripheral artery disease prevention, but longitudinal studies are needed

    Country-level gender inequality is associated with structural differences in the brains of women and men

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    男女間の不平等と脳の性差 --男女間の不平等は脳構造の性差と関連する--. 京都大学プレスリリース. 2023-05-10.Gender inequality across the world has been associated with a higher risk to mental health problems and lower academic achievement in women compared to men. We also know that the brain is shaped by nurturing and adverse socio-environmental experiences. Therefore, unequal exposure to harsher conditions for women compared to men in gender-unequal countries might be reflected in differences in their brain structure, and this could be the neural mechanism partly explaining women’s worse outcomes in gender-unequal countries. We examined this through a random-effects meta-analysis on cortical thickness and surface area differences between adult healthy men and women, including a meta-regression in which country-level gender inequality acted as an explanatory variable for the observed differences. A total of 139 samples from 29 different countries, totaling 7, 876 MRI scans, were included. Thickness of the right hemisphere, and particularly the right caudal anterior cingulate, right medial orbitofrontal, and left lateral occipital cortex, presented no differences or even thicker regional cortices in women compared to men in gender-equal countries, reversing to thinner cortices in countries with greater gender inequality. These results point to the potentially hazardous effect of gender inequality on women’s brains and provide initial evidence for neuroscience-informed policies for gender equality

    Multiple Myeloma Treatment in Real-world Clinical Practice : Results of a Prospective, Multinational, Noninterventional Study

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    Funding Information: The authors would like to thank all patients and their families and all the EMMOS investigators for their valuable contributions to the study. The authors would like to acknowledge Robert Olie for his significant contribution to the EMMOS study. Writing support during the development of our report was provided by Laura Mulcahy and Catherine Crookes of FireKite, an Ashfield company, a part of UDG Healthcare plc, which was funded by Millennium Pharmaceuticals, Inc, and Janssen Global Services, LLC. The EMMOS study was supported by research funding from Janssen Pharmaceutical NV and Millennium Pharmaceuticals, Inc. Funding Information: The authors would like to thank all patients and their families and all the EMMOS investigators for their valuable contributions to the study. The authors would like to acknowledge Robert Olie for his significant contribution to the EMMOS study. Writing support during the development of our report was provided by Laura Mulcahy and Catherine Crookes of FireKite, an Ashfield company, a part of UDG Healthcare plc, which was funded by Millennium Pharmaceuticals, Inc, and Janssen Global Services, LLC. The EMMOS study was supported by research funding from Janssen Pharmaceutical NV and Millennium Pharmaceuticals, Inc. Funding Information: M.M. has received personal fees from Janssen, Celgene, Amgen, Bristol-Myers Squibb, Sanofi, Novartis, and Takeda and grants from Janssen and Sanofi during the conduct of the study. E.T. has received grants from Janssen and personal fees from Janssen and Takeda during the conduct of the study, and grants from Amgen, Celgene/Genesis, personal fees from Amgen, Celgene/Genesis, Bristol-Myers Squibb, Novartis, and Glaxo-Smith Kline outside the submitted work. M.V.M. has received personal fees from Janssen, Celgene, Amgen, and Takeda outside the submitted work. M.C. reports honoraria from Janssen, outside the submitted work. M. B. reports grants from Janssen Cilag during the conduct of the study. M.D. has received honoraria for participation on advisory boards for Janssen, Celgene, Takeda, Amgen, and Novartis. H.S. has received honoraria from Janssen-Cilag, Celgene, Amgen, Bristol-Myers Squibb, Novartis, and Takeda outside the submitted work. V.P. reports personal fees from Janssen during the conduct of the study and grants, personal fees, and nonfinancial support from Amgen, grants and personal fees from Sanofi, and personal fees from Takeda outside the submitted work. W.W. has received personal fees and grants from Amgen, Celgene, Novartis, Roche, Takeda, Gilead, and Janssen and nonfinancial support from Roche outside the submitted work. J.S. reports grants and nonfinancial support from Janssen Pharmaceutical during the conduct of the study. V.L. reports funding from Janssen Global Services LLC during the conduct of the study and study support from Janssen-Cilag and Pharmion outside the submitted work. A.P. reports employment and shareholding of Janssen (Johnson & Johnson) during the conduct of the study. C.C. reports employment at Janssen-Cilag during the conduct of the study. C.F. reports employment at Janssen Research and Development during the conduct of the study. F.T.B. reports employment at Janssen-Cilag during the conduct of the study. The remaining authors have stated that they have no conflicts of interest. Publisher Copyright: © 2018 The AuthorsMultiple myeloma (MM) remains an incurable disease, with little information available on its management in real-world clinical practice. The results of the present prospective, noninterventional observational study revealed great diversity in the treatment regimens used to treat MM. Our results also provide data to inform health economic, pharmacoepidemiologic, and outcomes research, providing a framework for the design of protocols to improve the outcomes of patients with MM. Background: The present prospective, multinational, noninterventional study aimed to document and describe real-world treatment regimens and disease progression in multiple myeloma (MM) patients. Patients and Methods: Adult patients initiating any new MM therapy from October 2010 to October 2012 were eligible. A multistage patient/site recruitment model was applied to minimize the selection bias; enrollment was stratified by country, region, and practice type. The patient medical and disease features, treatment history, and remission status were recorded at baseline, and prospective data on treatment, efficacy, and safety were collected electronically every 3 months. Results: A total of 2358 patients were enrolled. Of these patients, 775 and 1583 did and did not undergo stem cell transplantation (SCT) at any time during treatment, respectively. Of the patients in the SCT and non-SCT groups, 49%, 21%, 14%, and 15% and 57%, 20%, 12% and 10% were enrolled at treatment line 1, 2, 3, and ≥ 4, respectively. In the SCT and non-SCT groups, 45% and 54% of the patients had received bortezomib-based therapy without thalidomide/lenalidomide, 12% and 18% had received thalidomide/lenalidomide-based therapy without bortezomib, and 30% and 4% had received bortezomib plus thalidomide/lenalidomide-based therapy as frontline treatment, respectively. The corresponding proportions of SCT and non-SCT patients in lines 2, 3, and ≥ 4 were 45% and 37%, 30% and 37%, and 12% and 3%, 33% and 27%, 35% and 32%, and 8% and 2%, and 27% and 27%, 27% and 23%, and 6% and 4%, respectively. In the SCT and non-SCT patients, the overall response rate was 86% to 97% and 64% to 85% in line 1, 74% to 78% and 59% to 68% in line 2, 55% to 83% and 48% to 60% in line 3, and 49% to 65% and 36% and 45% in line 4, respectively, for regimens that included bortezomib and/or thalidomide/lenalidomide. Conclusion: The results of our prospective study have revealed great diversity in the treatment regimens used to manage MM in real-life practice. This diversity was linked to factors such as novel agent accessibility and evolving treatment recommendations. Our results provide insight into associated clinical benefits.publishersversionPeer reviewe

    Effect of aliskiren on post-discharge outcomes among diabetic and non-diabetic patients hospitalized for heart failure: insights from the ASTRONAUT trial

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    Aims The objective of the Aliskiren Trial on Acute Heart Failure Outcomes (ASTRONAUT) was to determine whether aliskiren, a direct renin inhibitor, would improve post-discharge outcomes in patients with hospitalization for heart failure (HHF) with reduced ejection fraction. Pre-specified subgroup analyses suggested potential heterogeneity in post-discharge outcomes with aliskiren in patients with and without baseline diabetes mellitus (DM). Methods and results ASTRONAUT included 953 patients without DM (aliskiren 489; placebo 464) and 662 patients with DM (aliskiren 319; placebo 343) (as reported by study investigators). Study endpoints included the first occurrence of cardiovascular death or HHF within 6 and 12 months, all-cause death within 6 and 12 months, and change from baseline in N-terminal pro-B-type natriuretic peptide (NT-proBNP) at 1, 6, and 12 months. Data regarding risk of hyperkalaemia, renal impairment, and hypotension, and changes in additional serum biomarkers were collected. The effect of aliskiren on cardiovascular death or HHF within 6 months (primary endpoint) did not significantly differ by baseline DM status (P = 0.08 for interaction), but reached statistical significance at 12 months (non-DM: HR: 0.80, 95% CI: 0.64-0.99; DM: HR: 1.16, 95% CI: 0.91-1.47; P = 0.03 for interaction). Risk of 12-month all-cause death with aliskiren significantly differed by the presence of baseline DM (non-DM: HR: 0.69, 95% CI: 0.50-0.94; DM: HR: 1.64, 95% CI: 1.15-2.33; P < 0.01 for interaction). Among non-diabetics, aliskiren significantly reduced NT-proBNP through 6 months and plasma troponin I and aldosterone through 12 months, as compared to placebo. Among diabetic patients, aliskiren reduced plasma troponin I and aldosterone relative to placebo through 1 month only. There was a trend towards differing risk of post-baseline potassium ≥6 mmol/L with aliskiren by underlying DM status (non-DM: HR: 1.17, 95% CI: 0.71-1.93; DM: HR: 2.39, 95% CI: 1.30-4.42; P = 0.07 for interaction). Conclusion This pre-specified subgroup analysis from the ASTRONAUT trial generates the hypothesis that the addition of aliskiren to standard HHF therapy in non-diabetic patients is generally well-tolerated and improves post-discharge outcomes and biomarker profiles. In contrast, diabetic patients receiving aliskiren appear to have worse post-discharge outcomes. Future prospective investigations are needed to confirm potential benefits of renin inhibition in a large cohort of HHF patients without D
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