Metodologia para avaliação do status de uma Empresa de Alta Tecnologia

The economic and social development of Cuba requires the formation of companies that base their economy on the use of science and technological innovation. Based on this need, the bases were established for the emergence of a new form of management: High technology Companies. In this context, the emergence of High Technology Companies in Cuba means that the business sector requires tools that allow the Socialist State Company to evaluate the requirements established to achieve said condition. In relation to the above, this research has as a general objective: To develop a methodology based on the requirements of High Technology Companies to contribute to the categorization of the Cuban Socialist State Company towards that condition. As results of the application in the Lázaro Peña Cigar Company, the following is obtained: the evaluation of the EAT requirements and the contribution to the improvement of the behavior of the indicators of each evaluated requirement.El desarrollo económico y social de Cuba requiere de la formación de empresas que basen su economía en el uso de la ciencia y la innovación tecnológica, a partir de esta necesidad fueron establecidas las bases para el surgimiento de una nueva forma de gestión: Las Empresas de Alta Tecnología. En este contexto, el surgimiento de las Empresas de Alta Tecnología en Cuba conlleva a que el sector empresarial requiera de herramientas que le permitan a la Empresa Estatal Socialista evaluar los requisitos establecidos para alcanzar dicha condición. En relación a lo anterior esta investigación tiene como objetivo general: Desarrollar una metodología fundamentada en los requisitos de las Empresas de Alta Tecnología para contribuir a la categorización de la Empresa Estatal Socialista Cubana hacia esa condición. Como resultados de la aplicación en la Empresa de Cigarros Lázaro Peña se obtiene: la evaluación de los requisitos de EAT y la contribución a la mejora del comportamiento de los indicadores de cada requisito evaluado.Alta tecnologia. Neste contexto, o surgimento de Empresas de Alta Tecnologia em Cuba faz com que o setor empresarial necessite de ferramentas que permitam à Empresa Estatal Socialista avaliar os requisitos estabelecidos para atingir tal condição. Em relação ao exposto, esta pesquisa tem como objetivo geral: Desenvolver uma metodologia baseada nas exigências das Empresas de Alta Tecnologia para contribuir à categorização da Empresa Estatal Socialista Cubana nessa condição. Como resultados da aplicação na Lázaro Peña Cigar Company obtém-se: a avaliação dos requisitos do EAT e a contribuição para a melhoria do comportamento dos indicadores de cada requisito avaliado

Metodología para la evaluación de la condición de Empresa de Alta Tecnología

The economic and social development of Cuba requires the formation of companies that base their economy on the use of science and technological innovation. Based on this need, the bases were established for the emergence of a new form of management: High technology Companies. In this context, the emergence of High Technology Companies in Cuba means that the business sector requires tools that allow the Socialist State Company to evaluate the requirements established to achieve said condition. In relation to the above, this research has as a general objective: To develop a methodology based on the requirements of High Technology Companies to contribute to the categorization of the Cuban Socialist State Company towards that condition. As results of the application in the Lázaro Peña Cigar Company, the following is obtained: the evaluation of the EAT requirements and the contribution to the improvement of the behavior of the indicators of each evaluated requirement.Alta tecnologia. Neste contexto, o surgimento de Empresas de Alta Tecnologia em Cuba faz com que o setor empresarial necessite de ferramentas que permitam à Empresa Estatal Socialista avaliar os requisitos estabelecidos para atingir tal condição. Em relação ao exposto, esta pesquisa tem como objetivo geral: Desenvolver uma metodologia baseada nas exigências das Empresas de Alta Tecnologia para contribuir à categorização da Empresa Estatal Socialista Cubana nessa condição. Como resultados da aplicação na Lázaro Peña Cigar Company obtém-se: a avaliação dos requisitos do EAT e a contribuição para a melhoria do comportamento dos indicadores de cada requisito avaliado.El desarrollo económico y social de Cuba requiere de la formación de empresas que basen su economía en el uso de la ciencia y la innovación tecnológica, a partir de esta necesidad fueron establecidas las bases para el surgimiento de una nueva forma de gestión: Las Empresas de Alta Tecnología. En este contexto, el surgimiento de las Empresas de Alta Tecnología en Cuba conlleva a que el sector empresarial requiera de herramientas que le permitan a la Empresa Estatal Socialista evaluar los requisitos establecidos para alcanzar dicha condición. En relación a lo anterior esta investigación tiene como objetivo general: Desarrollar una metodología fundamentada en los requisitos de las Empresas de Alta Tecnología para contribuir a la categorización de la Empresa Estatal Socialista Cubana hacia esa condición. Como resultados de la aplicación en la Empresa de Cigarros Lázaro Peña se obtiene: la evaluación de los requisitos de EAT y la contribución a la mejora del comportamiento de los indicadores de cada requisito evaluado

Seroprotection against Vaccine-Preventable Diseases amongst Health Care Workers in a Community Hospital, Qatar

Background: Health care workers (HCW) are at high risk of contracting various infectious diseases and play a dual role in the transmission of infections in health care facilities. Objective: To determine the seroprotection against hepatitis B, measles, rubella, and varicella among HCWs in a community hospital in Qatar. Methods: This is a cross-sectional survey conducted in a 75-bed community hospital in Dukhan, Qatar. From August 2012 to December 2015, 705 HCWs were tested for the presence of IgG antibodies for measles, rubella, and varicella, and also for hepatitis B surface antigen (HBsAg). They were also asked about previous history of hepatitis B vaccination. Results: 595 (84.4%) HCWs received a full hepatitis B vaccination schedule; 110 (15.6%) received a single dose. The full schedule was reported with higher frequency by nurses (90.2%) compared to physicians (74.1%) or technicians (79.7%). Those aged ≥30 years (90.4%) and <20 years of work experience had received a full vaccination schedule more frequently than younger and less experienced HCWs. Female HCWs (87.8%) received full schedule more frequently than males (78.8%). 73.4% of the staff had seroprotection against heaptitis B, with the lowest anti-HBsAg titers observed in physicians (58.8%) compared with other categories; males (64.9%) were less protected than females. The seropositivity was 85.6%(95% CI 82.4% to 88.4%) for measles, 94.7% (95% CI 92.2% to 97.3%) for rubella, and 92.2% (95% CI 89.7% to 94.7%) for varicella. Conclusion: HCWs, particularly physicians, are not enough protected against hepatitis B. The seroprotection against measles, rubella, and varicella

Adenovirus Dodecahedron Allows Large Multimeric Protein Transduction in Human Cells

Adenovirus dodecahedron is a virus-like particle composed of only two viral proteins of human adenovirus serotype 3 that are responsible for virus attachment and internalization. We show here that this dodecameric particle, devoid of genetic information, efficiently penetrates human cells and can deliver large multimeric proteins such as immunoglobulins

THU0199 ABX464, A NOVEL DRUG IN THE FIELD OF INFLAMMATION, INCREASES MIR-124 AND MODULATES MACROPHAGES AND T-CELL FUNCTIONS.

Background:ABX464 is a small oral molecule with a novel mode of action. It binds the Cap Binding Complex, involved in the biogenesis of RNAs and predominantly upregulates the expression of a microRNA miR-124 in PBMCs and T cells (1). miR-124 has been widely described for its anti-inflammatory properties, with many confirmed targets i.e. monocyte chemoattractant protein 1 (MCP-1, CXCL-1, SERPIN-E1, STAT-3, IL-6 receptor. It post-transcriptionally regulates the expression of MCP-1 in rheumatoid arthritis (RA) synoviocytes and decreases their proliferation (2). While miR-124 is decreased in synoviocytes of RA patients, its injection in joint improved arthritis in rats (3). miR-124 expression in macrophages leads to the induction and maintenance of anti-inflammatory M2 phenotype (4). Its effect in T cells remains controversial.Objectives:(i) To assess the effect of ABX464 on miR-124 expressionin vitroin macrophages andin vivoin patients; (ii) to assess the effect of ABX464 on arthritis in mice and (iii) to decipher the effect of ABX464 on human macrophages and T cells.Methods:miR-124 was measured in human monocyte-derived macrophages (huMDM) treated with ABX464 for 4 days and in patients with ulcerative colitis included in a phase IIa RCT in blood and rectal biopsies at day 56 by TaqMan qPCR. Collagen-induced arthritis (CIA) was induced using usual protocol and ABX464 was given by gavage 2 weeks at 40 mg/kg after the 2ndinjection of collagen and Freund adjuvant. HuMDM were exposed to 5 µM of ABX464 or DMSO (control) for 4 days, during a M1-polarization. Cytokines and chemokines were assessed in supernatants using both Proteome Profiler Array and Luminex. PBMCs were exposed to ABX464 (5 µM) for 6 days. Th1 (IFN-g+), Th17 (CCR6+IL-17+), Th2 (CRTH2+ IL-4+) and Tregs (CD25+CD125-/loFoxP3+) were assessed by flow cytometry. IL-6 receptor was assessed in CD4+ supernatant using ELISA.Results:ABX464 increased miR-124 in vitro by 3.41 folds in huMDM (p=0.001) compared to DMSO. The phase IIa RCT conducted in 32 patients with moderate to severe active ulcerative colitis showed a good safety profile and significant clinical efficacy. A strong increase of miR-124 was observed both in blood and rectal biopsies of patients treated with ABX464 (637 and 7.69 folds respectively, compared to placebo, p&lt;0.05). The use of ABX464 drastically decreased the incidence of arthritis from 52% (15/ 29 mice) to 10% (3/30 mice) in a CIA model. Macrophages treated with ABX464 produced significantly less MCP-1 (median decrease -67%, p=0.004), CXCL-1 (-18%, p=0.004) and SERPIN-E1 (-53%, p=0.004), as confirmed by the two technics (n=9). ABX464 significantly decreased Th17 (-56%, p=0.02), while increasing Th2 (+21%, p=0.01). IL-6 soluble receptor was significantly decreased in supernatant of PBMCs treated with ABX464 (-43%, p=0.04).Conclusion:We demonstrated that ABX464 increases miR-124 bothin vitroand in ulcerative colitis patients.In vitro, ABX464 decreased the expression of miR-124 target genes, that is MCP-1, CXCL-1, SERPIN-E1 in macrophages and decreases the number of Th17 as well as IL-6 soluble receptor in CD4+ T cells. A phase IIa RCT is currently ongoing in patients with rheumatoid arthritis and inadequate response to methotrexate and/or TNF-inhibitors (n=60). Results are expected during 2020 summer.References:[1]Vautrin A et al. Sci Rep. 2019;9:792[2]Nakamachi Y et al. Arthritis Rheum 2009; 60:1294-304[3]Nakamachi Y et al. Ann Rheum Dis 2016; 75:601-8[4]Veremeyko T et al. PLoS ONE 2013; 8:e81774Disclosure of Interests:Christina BEGON-PESCIA: None declared, Julie Mielle: None declared, Noélie Campose Employee of: ABIVAX, Karim Chebli Consultant of: ABIVAX, Laurent Manchon: None declared, Julien Santo Employee of: ABIVAX, Cécile Apolit Employee of: ABIVAX, Kévin Martin Grant/research support from: ABIVAX, Laure Lapasset Employee of: ABIVAX, Audrey Vautrin Employee of: ABIVAX, Didier Scherrer Employee of: ABIVAX, Aude Garcel Employee of: ABIVAX, Jamal Tazi Shareholder of: ABIVAX, Grant/research support from: ABIVAX, Consultant of: ABIVAX, Employee of: ABIVAX, Paid instructor for: ABIVAX, Speakers bureau: ABIVAX, Claire DAIEN Grant/research support from: from Pfizer, Abbvie, Roche-Chugaï, Novartis, Abivax, Sandoz, Consultant of: Abbvie, Abivax, BMS, MSD, Roche-Chugaï, Lilly, Novartis, Speakers bureau: Abbvie, Abivax, BMS, MSD, Roche-Chugaï, Lilly, Novartis</jats:sec

Long lasting control of viral rebound with a new drug ABX464 targeting Rev - mediated viral RNA biogenesis

BACKGROUND: Current therapies have succeeded in controlling AIDS pandemic. However, there is a continuing need for new drugs, in particular those acting through new and as yet unexplored mechanisms of action to achieve HIV infection cure. We took advantage of the unique feature of proviral genome to require both activation and inhibition of splicing of viral transcripts to develop molecules capable of achieving long lasting effect on viral replication in humanized mouse models through inhibition of Rev-mediated viral RNA biogenesis. RESULTS: Current HIV therapies reduce viral load during treatment but titers rebound after treatment is discontinued. We devised a new drug that has a long lasting effect after viral load reduction. We demonstrate here that ABX464 compromises HIV replication of clinical isolates of different subtypes without selecting for drug resistance in PBMCs or macrophages. ABX464 alone, also efficiently compromised viral proliferation in two humanized mouse models infected with HIV that require a combination of 3TC, Raltegravir and Tenofovir (HAART) to achieve viral inhibition in current protocols. Crucially, while viral load increased dramatically just one week after stopping HAART treatment, only slight rebound was observed following treatment cessation with ABX464 and the magnitude of the rebound was maintained below to that of HAART for two months after stopping the treatment. Using a system to visualize single HIV RNA molecules in living cells, we show that ABX464 inhibits viral replication by preventing Rev-mediated export of unspliced HIV-1 transcripts to the cytoplasm and by interacting with the Cap Binding Complex (CBC). Deep sequencing of viral RNA from treated cells established that retained viral RNA is massively spliced but importantly, normal cellular splicing is unaffected by the drug. Consistently ABX464 is non-toxic in humans and therefore represents a promising complement to current HIV therapies. CONCLUSIONS: ABX464 represents a novel class of anti-HIV molecules with unique properties. ABX464 has a long lasting effect in humanized mice and neutralizes the expression of HIV-1 proviral genome of infected immune cells including reservoirs and it is therefore a promising drug toward a functional cure of HIV