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This work presents the synthesis of six new phase-transfer organocatalysts in which the squaramide unit is directly linked to the nitrogen atom of an aza-crown ether. Four chiral skeletons, namely hydroquinine, quinine, cinchonine (cinchonas), and α-d-glucopyranoside were responsible for the asymmetric construction of an all-carbon quaternary stereogenic center in α-alkylation and Michael addition reactions of malonic esters. We investigated the effects of these different chiral units and that of crown ethers with different sizes on catalytic activity and enantioselectivity. During extensive parameter investigations, both conventional and emerging green solvents were screened, providing valuable α,α-disubstituted malonic ester derivatives with excellent yields (up to 98%).
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This work presents the immobilization of cinchona squaramide organocatalysts on poly(glycidyl methacrylate) solid supports. Preparation of the well-defined monodisperse polymer microspheres was facilitated by comprehensive parameter optimization. By exploiting the reactive epoxy groups of the polymer support, three amino-functionalized cinchona derivatives were immobilized on this carrier. To explore the effect of the amino linker, these structurally varied precatalysts were synthesized by modifying the cinchona skeleton at different positions. The catalytic activities of the immobilized organocatalysts were tested in the Michael addition of pentane-2,4-dione and trans-ß-nitrostyrene with excellent yields (up to 98 %) and enantioselectivities (up to 96 %â ee). Finally, the catalysts were easily recovered five times by centrifugation without loss of activity.
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Having good digital skills is essential today, yet little is known about the cognitive factors that influence the development of these skills. Given the importance of executive functions (EFs) in adapting to environmental changes and acquiring skills, EFs might contribute to acquiring digital skills too. EFs might also influence people's approach toward ICTs and affect digital skills through emotional variables. Therefore, here, we tested whether cognitive control and flexibility are connected to computer and smartphone skills through emotional factors (learning confidence, stress, and attitude). A total of 269 participants (56 males, M = 30 years) filled out our survey which included questionnaires on demographic variables (age, education, and socioeconomic status), ICT motivation, digital skills, EFs, and technology-related emotional factors. EFs were also investigated through two performance-based measures. We used generalized linear models and structural equation modeling to test the associations between these variables. The results showed that smartphone skills were positively associated with self-reported cognitive flexibility through ICT learning confidence and technology-induced stress. Self-reported cognitive control and age were connected to smartphone skills directly. Self-reported cognitive flexibility was also associated with computer skills through ICT learning confidence. In addition, performance-based cognitive control and the level of education were directly linked to computer skills. These results may provide guidance to support digital skills and create digital skill training.
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Función Ejecutiva , Aprendizaje , Humanos , Masculino , Femenino , Adulto , Función Ejecutiva/fisiología , Aprendizaje/fisiología , Teléfono Inteligente , Adulto Joven , Encuestas y Cuestionarios , Persona de Mediana Edad , Cognición/fisiologíaRESUMEN
In this study, we describe the synthesis of cinchona (thio)squaramide and a novel cinchona thiourea organocatalyst. These catalysts were employed in pharmaceutically relevant catalytic asymmetric reactions, such as Michael, Friedel-Crafts, and A3 coupling reactions, in combination with Ag(I), Cu(II), and Ni(II) salts. We identified several organocatalyst-metal salt combinations that led to a significant increase in both yield and enantioselectivity. To gain insight into the active catalyst species, we prepared organocatalyst-metal complexes and characterized them using HRMS, NMR spectroscopy, and quantum chemical calculations (B3LYP-D4/def2-TZVP), which allowed us to establish a structure-activity relationship.
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A hepatitis C virus (HCV) screening and treatment program was conducted in Hungarian prisons on a voluntary basis. After HCV-RNA testing and genotyping for anti-HCV positives, treatments with direct-acting antiviral agents were commenced by hepatologists who visited the institutions monthly. Patients were supervised by the prisons' medical staff. Data were retrospectively collected from the Hungarian Hepatitis Treatment Registry, from the Health Registry of Prisons, and from participating hepatologists. Eighty-four percent of Hungarian prisons participated, meaning a total of 5779 individuals (28% of the inmate population) underwent screening. HCV-RNA positivity was confirmed in 317/5779 cases (5.49%); 261/317 (82.3%) started treatment. Ninety-nine percent of them admitted previous intravenous drug use. So far, 220 patients received full treatment and 41 patients are still on treatment. Based on the available end of treatment (EOT) + 24 weeks timepoint data, per protocol sustained virologic response rate was 96.8%. In conclusion, the Hungarian prison screening and treatment program, with the active participation of hepatologists and the prisons' medical staff, is a well-functioning model. Through the Hungarian experience, we emphasize that the "test-and-treat" principle is feasible and effective at micro-eliminating HCV in prisons, where infection rate, as well as history of intravenous drug usage, are high.
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Antivirales/administración & dosificación , Hepacivirus/aislamiento & purificación , Hepatitis C/tratamiento farmacológico , Adolescente , Adulto , Femenino , Hepacivirus/efectos de los fármacos , Hepacivirus/genética , Hepacivirus/inmunología , Hepatitis C/sangre , Hepatitis C/diagnóstico , Hepatitis C/virología , Humanos , Hungría , Masculino , Tamizaje Masivo , Persona de Mediana Edad , Prisiones/estadística & datos numéricos , Estudios Retrospectivos , Respuesta Virológica Sostenida , Adulto JovenRESUMEN
Introduction: Despite advancements in diagnostic capabilities and the availability of effective antimicrobial agents, community-acquired infections of the central nervous system (CNS) are still associated with high mortality rates. Aim: To assess the epidemiological and clinical characteristics of community-acquired CNS infections treated in the West Pannonian region between 2010 and 2016. Method: Clinical data of 176 patients were retrospectively analysed in two age cohorts: 15 to 65 and more than 65 years of age. Results: Neuroinfections were found to be bacterial in 81, viral in 91, parasitic in 1 and mixed in 3 cases during the observation period. The most frequent bacterial pathogens isolated were Streptococcus pneumoniae (20%) and Borrelia burgdorferi (16%). The most frequent viral pathogens isolated were tick-borne encephalitis virus (37%), herpes simplex virus (10%) and enterovirus (7%). Aetiology was unknown in 40 percent of all cases. The average incidence rate was 9.8/100 000 person/year with a mortality rate of 12%. In the cohort of patients aged >65 years, significantly higher frequencies of immunocompromising factors, lower Glasgow Coma Scale values at admission and confusion were observed (p-values: 0.008, 0.017, and 0.050, respectively). Prognosis was negatively influenced by low Glasgow Coma Scale values at admission (OR = 1.6 CI95%: 1.3-1.9; p<0.001), old age (OR = 6.5 CI95%: 2.5-17.1; p<0.001) and immunodeficiency (OR = 3.1 CI95%: 1.2-8.1; p = 0.019). Conclusions: S. pneumoniae remains the most frequently observed causative bacterial pathogen associated with community-acquired CNS infections. Incidence of tick-borne encephalitis in our county is higher than the national average (2.3 versus 0.35/100 000 person/year). Orv Hetil. 2019; 160(40): 1574-1583.
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Infecciones Bacterianas del Sistema Nervioso Central/microbiología , Infecciones del Sistema Nervioso Central/epidemiología , Enfermedades Virales del Sistema Nervioso Central/virología , Infecciones Comunitarias Adquiridas , Adolescente , Adulto , Distribución por Edad , Anciano , Anciano de 80 o más Años , Borrelia burgdorferi/aislamiento & purificación , Infecciones Bacterianas del Sistema Nervioso Central/diagnóstico , Infecciones del Sistema Nervioso Central/diagnóstico , Estudios de Cohortes , Infecciones Comunitarias Adquiridas/microbiología , Infecciones Comunitarias Adquiridas/virología , Encefalitis , Encefalitis Transmitida por Garrapatas/epidemiología , Enterovirus/aislamiento & purificación , Infecciones por Enterovirus/epidemiología , Femenino , Humanos , Hungría/epidemiología , Incidencia , Enfermedad de Lyme/epidemiología , Masculino , Persona de Mediana Edad , Infecciones Neumocócicas/epidemiología , Estudios Retrospectivos , Simplexvirus/aislamiento & purificación , Streptococcus pneumoniae , Adulto JovenRESUMEN
Numerous cinchona organocatalysts with different substituents at their quinuclidine unit have been described and tested, but the effect of those saturation has not been examined before. This work presents the synthesis of four widely used cinchona-based organocatalyst classes (hydroxy, amino, squaramide, and thiourea) with different saturation on the quinuclidine unit (ethyl, vinyl, ethynyl) started from quinine, the most easily available cinchona derivative. Big differences were found in basicity of the quinuclidine unit by measuring the pKa values of twelve catalysts in six solvents. The effect of differences was examined by testing the catalysts in Michael addition reaction of pentane-2,4-dione to trans-ß-nitrostyrene. The 1.6-1.7 pKa deviation in basicity of the quinuclidine unit did not result in significant differences in yields and enantiomeric excesses. Quantum chemical calculations confirmed that the ethyl, ethynyl, and vinyl substituents affect the acid-base properties of the cinchona-thiourea catalysts only slightly, and the most active neutral thione forms are the most stable tautomers in all cases. Due to the fact that cinchonas with differently saturated quinuclidine substituents have similar catalytic activity in asymmetric Michael addition application of quinine-based catalysts is recommended. Its vinyl group allows further modifications, for instance, recycling the catalyst by immobilization.