Phase I clinical trial in healthy adults of a nasal vaccine candidate containing recombinant hepatitis B surface and core antigens

SummaryBackgroundThe nasal vaccine candidate (NASVAC), comprising hepatitis B virus (HBV) surface (HBsAg) and core antigens (HBcAg), has been shown to be highly immunogenic in animal models.MethodsA phase I double-blinded, placebo-controlled randomized clinical trial was carried out in 19 healthy male adults with no serologic markers of immunity/infection to HBV. This study was aimed at exploring the safety and immunogenic profile of nasal co-administration of both HBV recombinant antigens. The trial was performed according to Good Clinical Practice guidelines. Participants ranged in age from 18 to 45 years and were randomly allocated to receive a mixture of 50μg HBsAg and 50μg HBcAg or 0.9% physiologic saline solution, as a placebo, via nasal spray in a five-dose schedule at 0, 7, 15, 30, and 60 days. A total volume of 0.5ml was administered in two dosages of 125μl per nostril. Adverse events were actively recorded 1h, 6h, 12h, 24h, 48h, 72h, 7 days and 30 days after each dose. Anti-HBs and anti-HBc titers were evaluated using corresponding ELISA kits at days 30 and 90.ResultsThe vaccine candidate was safe and well tolerated. Adverse reactions included sneezing (34.1%), rhinorrhea (12.2%), nasal stuffiness (9.8%), palate itching (9.8%), headache (9.8%), and general malaise (7.3%). These reactions were all self-limiting and mild in intensity. No severe or unexpected events were recorded during the trial. The vaccine elicited anti-HBc seroconversion in 100% of subjects as early as day 30 of the immunization schedule, while a seroprotective anti-HBs titer (≥10IU/l) was at a maximum at day 90 (75%). All subjects in the placebo group remained seronegative during the trial.ConclusionThe HBsAg–HBcAg vaccine candidate was safe, well tolerated and immunogenic in this phase I study in healthy adults. To our knowledge, this is the first demonstration of safety and immunogenicity for a nasal vaccine candidate comprising HBV antigens

Impact of biological agents on postsurgical complications in inflammatory bowel disease: A multicentre study of Geteccu

Background: The impact of biologics on the risk of postoperative complications (PC) in inflammatory bowel disease (IBD) is still an ongoing debate. This lack of evidence is more relevant for ustekinumab and vedolizumab. Aims: To evaluate the impact of biologics on the risk of PC. Methods: A retrospective study was performed in 37 centres. Patients treated with biologics within 12 weeks before surgery were considered “exposed”. The impact of the exposure on the risk of 30-day PC and the risk of infections was assessed by logistic regression and propensity score-matched analysis. Results: A total of 1535 surgeries were performed on 1370 patients. Of them, 711 surgeries were conducted in the exposed cohort (584 anti-TNF, 58 vedolizumab and 69 ustekinumab). In the multivariate analysis, male gender (OR: 1.5; 95% CI: 1.2–2.0), urgent surgery (OR: 1.6; 95% CI: 1.2–2.2), laparotomy approach (OR: 1.5; 95% CI: 1.1–1.9) and severe anaemia (OR: 1.8; 95% CI: 1.3–2.6) had higher risk of PC, while academic hospitals had significantly lower risk. Exposure to biologics (either anti-TNF, vedolizumab or ustekinumab) did not increase the risk of PC (OR: 1.2; 95% CI: 0.97–1.58), although it could be a risk factor for postoperative infections (OR 1.5; 95% CI: 1.03–2.27). Conclusions: Preoperative administration of biologics does not seem to be a risk factor for overall PC, although it may be so for postoperative infections

CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

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

ABX203, инновационная терапевтическая вакцина для больных хроническим гепатитом В

Despite the existence of effective prophylactic vaccines, chronic hepatitis B remains a major public health problem, with more than 350 million people infected   worldwide.  Chronic  infection   increases the  risk of serious  liver diseases  such  as cirrhosis and  hepatocellular carcinoma.  Available therapies for chronic  hepatitis  B  have  limited  efficacy and require  long-term   continuous  treatments;  that  is why the  development of therapeutic vaccines has been  investigated as  promising  approach.  In this sense, a novel  vaccine  formulation  called ABX203 (HeberNasvac), based  on  the  combination of the hepatitis B virus nucleocapsid and surface antigens, was developed. ABX203 has been studied in phase I, phase II and phase III clinical trial in treatment-naïve chronically infected  patients  in Bangladesh  and  in healthy  volunteers  in Cuba with promising  results. In the present work we reviewed the main preclinical and   clinical  results  of  ABX203 development. Altogether, the data demonstrates safety and immunogenicity of ABX203 vaccine and support  its use as a novel and competitive treatment alternative for chronic hepatitis B. The vaccine has been granted marketing authorization in Cuba.Несмотря на существование эффективной вакцинопрофилактики, хронический гепатит В, которым  во  всем  мире  инфицировано  более 350 млн человек, остается одной из основных проблем здравоохранения. Хроническая инфекция увеличивает  риск серьезной печеночной  патологии  – цирроза  и гепатоцеллюлярного рака. Существующие методы лечения хронического  гепатита В недостаточно  эффективны и требуют длительной непрерывной терапии. Вот почему в качестве перспективного подхода изучается возможность разработки терапевтических  вакцин. В этих целях был создан инновационный вакцинальный препарат ABX203 (Назвак),  в состав которого входят сердцевинный (HBcAg) и поверхностный (HBsAg) антигены вируса  гепатита В.  Терапевтическая двухкомпонентная вакцина ABX203, зарегистрированная на  Кубе,  изучалась  в  клинических исследованиях  I,  II  и III  фазы у ранее  не леченных хронически  инфицированных  пациентов в Бангладеш и у здоровых добровольцев на Кубе и показала многообещающие результаты. Эта статья представляет собой обзор основных результатов доклинических и клинических исследований  вакцины ABX203. На основании анализа  представленных  данных можно говорить о безопасности  и иммуногенности вакцины ABX203, что позволяет применять ее как инновационный и конкурентоспособный вариант лечения хронического гепатита В

Carbon monoxide and methanol oxidations on Pt/X@MoO3/C (X = Mo2C, MoO2, Mo0) electrodes at different temperatures

The present study is focused in the use of core–shell molybdenum substrates as supports for Pt electrocatalysts. These substrates are prepared by the carbothermal-reduction method and present a core–shell structure, with a reduced-Mo core (Mo2C, MoO2 and/or Mo0) and a MoO3 shell. Kinetic and mechanistic studies were performed through potentiodynamic and potentiostatic experiments for carbon monoxide and methanol oxidation reactions on Pt/X@MoO3/C (X = Mo2C, MoO2, Mo0) catalysts in an intermediate temperature range (20 < T < 70 °C). Results reveal the promoter effect and the great stability of Mo-carbide based substrates for both reactions in the temperature range studied. Carbon monoxide and methanol oxidation on Pt/X@MoO3/C are enhanced by a facile oxygenated species formation, better dispersion of the active phase and electronic effects. It is concluded that the best catalyst performance during the methanol oxidation reaction was obtained with the substrate that contains only Mo2C-phase in its core.The authors wish to thank Spanish Ministry of Economy and Competitiveness (SMEC) for the financial support to project CTQ2011-28913-C02-02. RGL acknowledges the SMEC for her contract in the Project ENE2010-21198-C04-01. GG acknowledges to the JAE program (CSIC) for financial support. Also the use of General Research Services at the University of La Laguna (SEGAI-ULL) is acknowledged.Peer Reviewe

Structural and morphological characterization of YBa2Cu3O7-x films deposited by screen printing from YBa2Cu3O6.962 superconductor in bulk

YBa _2 Cu _3 O _7-x films were deposited onto flexible copper substrates by screen printing technique. YBa _2 Cu _3 O _7-x films were prepared from a YBa _2 Cu _3 O _7-x superconductor powder with ethylene glycol. The mixtures were screen printed and then sintered in air at different temperatures: 373, 473, and 573 K. The structural characterization showed the presence of different phases; the proportion of phases in films depends on sintering temperature. Scanning electron microscope images showed that an annealing temperature increase leads to an increase in grain size due to a coalescence process, which promotes the growth of superconductor phases with higher oxygen content

Effect of the sulfur and fluorine concentration on physical properties of CdS films grown by chemical bath deposition

Undoped and F-doped CdS thin films were grown on glass slides by chemical bath deposition using thiourea, cadmium acetate and ammonium fluoride as sulfur, cadmium, and fluorine sources, respectively. Undoped CdS films were deposited varying the concentration of thiourea. Once the optimal thiourea concentration was determined, based on the crystalline quality of the samples, this concentration was maintained and ammonium fluoride was added at different concentrations in order to explore the effect of the F nominal concentration on properties of CdS films. Undoped and F-doped CdS films were characterized by X-ray diffraction, UV–Vis, room temperature photoluminescence, and four probe resistivity measurements. Results showed highly transparent F-doped CdS films with strong PL and low resistivity were obtained. Keywords: CdS films, F-doped CdS films, Chemical bath deposition, Optical properties, Room temperature photoluminescenc