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INTRODUCTION: The amino acid substitution A62V in reverse transcriptase was identified as a mutation correlated with virologic failure in patients on first-line therapy including tenofovir (TDF) and tenofovir alafenamide (TAF). A62V is a typically polymorphic mutation in HIV-1 sub-subtype A6, which is the most widespread virus variant in Russia. MATERIALS AND METHODS: The European EuResist (EIDB) database was queried to form two equivalent groups of patients: group 1 â patients with A62V at baseline treated with TDF or TAF on the first-line therapy, group 2 â patients without A62V at baseline treated with TDF or TAF on the first-line therapy. Each group included 23 patients. RESULTS: There was no statistical difference between the two groups in virologic efficacy in 4, 12, and 24 weeks after the start of antiretroviral therapy (ART) and in the frequency of virologic failures. CONCLUSION: This study has some limitations, and the exact role of A62V in the efficacy of the first-line ART based on tenofovir deserves further investigation.
Assuntos
Fármacos Anti-HIV , Infecções por HIV , Transcriptase Reversa do HIV , HIV-1 , Mutação , Tenofovir , Humanos , Tenofovir/uso terapêutico , Tenofovir/análogos & derivados , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Infecções por HIV/genética , Transcriptase Reversa do HIV/genética , HIV-1/genética , HIV-1/efeitos dos fármacos , Masculino , Feminino , Adulto , Fármacos Anti-HIV/uso terapêutico , Pessoa de Meia-Idade , Farmacorresistência Viral/genética , Substituição de Aminoácidos , Alanina/uso terapêutico , Federação Russa/epidemiologia , Adenina/análogos & derivados , Adenina/uso terapêutico , Inibidores da Transcriptase Reversa/uso terapêutico , Carga Viral/efeitos dos fármacosRESUMO
Psychological constructs related to health outcomes and well-being, such as metacognitive beliefs, have been linked to executive functions in general, and cognitive flexibility more specifically. However, such effects have previously only been discussed on a theoretical level and behavioral flexibility has most often been measured through self-report, only approximating information processing capacities. Objectively measured executive functions may be a more potent predictor of health outcomes. We set out to test whether cognitive flexibility capacity was associated with sick leave in a medium sized company. We included 111 subjects of widely different occupations and assessed their executive functions using Delis-Kaplan Executive Function System test battery (D-KEFS). To assess cognitive flexibility capacity, we included Design Fluency (DF) and Verbal Fluency (VF) and computed these into an index of cognitive flexibility (DFVF). Detailed information on sick leave for the last 5 years was gathered from the company. Our results showed that there was a significant negative correlation between DFVF and sick leave [rs(109) = -0.23, p = 0.015] in the full group as well as in the group that had at least 1 day of sick leave [rs(72) = -0.25, p = 0.03]. The results withstood adjustment for sex, age, occupation, and several core executive functions as well as autistic and ADHD-traits. The results remained for separate analyses using DF or VF. Our main findings were conceptually replicated in a group of bipolar disorder patients. This study shows that objectively measured capacity of cognitive flexibility is associated with key health outcomes such as sick leave.
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BSTS epitaxial thin film topological insulators were grown using the MBE technique on two different types of substrates i.e., Si (111) and SiC/graphene with Bi0.7Sb1.6Te1.8Se0.9 and Bi0.9Sb1.5Te1.8Se1.1, respectively. The crystallographic properties of BSTS films were investigated via X-ray diffraction, which showed the strongest reflections from the (0 0 l) facets corresponding to the rhombohedral phase. Superior epitaxial growth, homogeneous thickness, smooth surfaces, and larger unit cell parameters were observed for the films grown on the Si substrate. Polarization dependent Raman spectroscopy showed a weak appearance of the Ag mode in cross--polarized geometry. In contrast, a strong Eg mode was observed in both parallel and cross-polarized geometries which correspond to the rhombohedral crystal symmetry of BSTS films. A redshift of Ag and Eg modes was observed in the Raman spectra of BSTS films grown on the Si substrate, compared to those on SiC/graphene, which was directly associated with the unit cell parameter and composition of the films. Raman spectra showed four fundamental modes with asymmetric line shape, and deconvolution of the peaks resulted in additional modes in both the BSTS thin films. The sum of relative ratios of linewidths of fundamental modes (Ag and Eg) of BSTS films grown on Si substrate was lower, indicating a more ordered structure with lower contribution of defects as compared to BSTS film grown on SiC/graphene substrate.
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High X-ray absorption combined with photothermal properties make bismuth nanoparticles (Bi NP) a promising agent for multimodal cancer theranostics. However, the synthesis of Bi NP by the "classical" chemical methods has numerous limitations, including potential toxicity of the produced nanomaterials. Here we studied in vitro toxicity of laser-synthesized Bi NP coated with Pluronic F-127 on mouse fibroblast cell line L929. The survival of L929 cells decreased linearly with increasing the concentration of Bi NP in a concentration range of 3-500 µg/ml; the LC50 value was 57 µg/ml. The unique combination of functional properties and moderate toxicity of the laser-synthesized Bi NP makes them a new promising platform for sensitization of multimodal cancer theranostics.
Assuntos
Nanopartículas Metálicas , Animais , Camundongos , Bismuto/toxicidade , Bismuto/química , Linhagem Celular Tumoral , Nanopartículas Metálicas/toxicidade , Nanopartículas Metálicas/química , Nanopartículas/toxicidade , Nanopartículas/química , Nanoestruturas , Neoplasias/metabolismo , Fototerapia/métodosRESUMO
Among numerous disinfection by-products (DBP) forming during aqueous chlorination nitrogen containing species are of special concern due to their toxicological properties. Nevertheless, corresponding reaction products of these natural and anthropogenic compounds are not sufficiently studied so far. An interesting reaction involves dealkylation of the substituted amine moiety. Here we present the results of the comparative study of one-electron oxidation and aqueous chlorination of several aliphatic and aromatic amines. The reaction products were reliably identified with gas chromatography - high resolution mass spectrometry (GC-HRMS), high pressure liquid chromatography - electrospray ionization high resolution mass spectrometry HPLC-ESI/HRMS), and electrochemistry - electrospray ionization high resolution mass spectrometry (EC-ESI/HRMS). Certain similarities dealing with the formation of the corresponding aldehydes and substitution of alkyl groups at the nitrogen atom for hydrogen were shown for the studied processes. The mechanism of the substituted amines' aqueous chlorination involving one-electron oxidation is proposed and confirmed by the array of the observed reaction products. Alternative reactions taking place in conditions of aqueous chlorination, i.e. aromatic electrophilic substitution, may successfully compete with dealkylation and produce major products.