RESUMO
A photonic crystal microcavity with the liquid crystal resonant layer tunable by heating has been implemented. The multiple vanishing resonant lines corresponding to optical bound states in the continuum are observed. The abrupt change in the resonant linewidth near the vanishing point can be used for temperature sensing.
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The microcavity in the form of a liquid crystal defect layer embedded in a one-dimensional photonic crystal is considered. The microcavity mode has a tunable radiation decay rate in the vicinity of a bound state in the continuum. It is demonstrated that coupling between the microcavity mode and a Tamm plasmon polariton results in hybrid Tamm-microcavity modes with a tunable Q factor. The measured spectral features of hybrid modes are explained in the framework of the temporal coupled mode theory.
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Medical care refers to a risky type of activity, since as a result of its provision, harm to the patient's health may be caused and prerequisites for the onset of legal (civil, disciplinary, administrative and criminal) liability may arise. The legal liability of a pathologist in the event of an incorrect diagnosis by the attending physician on the basis of an incorrect conclusion of the pathologist may occur due to violations due to low qualifications, frivolity, negligence, failure to comply with the rules, procedures for providing medical care, job descriptions, official duties. If the incorrect conclusion of the pathologist was of an objective nature (for example, in the case of an incorrect interpretation of a diagnostically difficult case), it should go beyond the scope of punishable shortcomings in the activities of the pathologist. The financial responsibility of a pathologist may occur when its burden is placed on a medical organization for harm caused to the life or health of a patient, due to the establishment, among other things, of the legality of the actions (inaction) of a medical worker with whom the medical organization is in an employment relationship. A medical organization, in case of satisfaction of the patient's claims by the court, as a rule, in a regression procedure, may involve the relevant medical worker who caused the harm in the issue of compensation, compensate for their financial and reputational losses. The most important thing in such cases is to resolve the issue of establishing the grounds for bringing a medical worker to responsibility.
Assuntos
Imperícia , Patologistas , Humanos , Responsabilidade LegalRESUMO
A photonic crystal microcavity with a tunable quality factor (Q factor) has been implemented on the basis of a bound state in the continuum using the advanced liquid crystal cell technology platform. It has been shown that the Q factor of the microcavity changes from 100 to 360 in the voltage range of 0.6 V.
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The polarized optical states in the transmission spectrum of a twisted-nematic Fabry-Pérot cavity with the distinctly broken Mauguin's waveguide regime have been theoretically and experimentally investigated. Specific features of the electric field-induced transformation of the polarization and spectral characteristics of eigenmodes of the neighboring series at the overlap resonant frequencies have been examined. It is demonstrated that the linear polarizations of eigenmodes at the cavity boundaries remain nearly orthogonal and their frequency trajectories reproduce the avoided crossing phenomenon. The experimental data are confirmed analytically and by the numerical simulation of light transmission through the investigated anisotropic multilayer with the use of a Berreman matrix method. The results obtained can be generalized to any materials with the helix response.
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The paper considers the legal and organizational issues of the activity of pathology services in improving medical care. It shows the main (diagnostic and medico-organizational) areas of pathology work to improve the quality of medical care.
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Atenção à Saúde/organização & administração , Regulamentação Governamental , Patologia/organização & administração , Indicadores de Qualidade em Assistência à Saúde , Atenção à Saúde/legislação & jurisprudência , Atenção à Saúde/normas , Objetivos Organizacionais , Patologia/legislação & jurisprudência , Patologia/normas , Federação RussaRESUMO
The light transmission spectrum has been calculated for a "cholesteric liquid crystal-phase plate-metal" structure. It is shown that the system can have an isolated waveguide surface mode with characteristics efficiently controllable by external fields acting on the cholesteric. The degree of localization of surface modes and the transmission coefficients have been found to differ considerably for the light of different polarizations.
Assuntos
Cristais Líquidos/química , Modelos Químicos , Refratometria/métodos , Prata/química , Ressonância de Plasmônio de Superfície/métodos , Simulação por Computador , Luz , Espalhamento de RadiaçãoRESUMO
We evaluated overall and relapse-free survival in patients with metastatic renal cell carcinoma (MRCC) with poor prognosis. The study involved 92 patients (median age 54.1 years, male 63%, female 29%), retrospectively; 48.9% had poor prognosis. They received oral sunitinib 59 mg/day in 6 cycles (4 weeks on, 2 weeks off). Median overall survival was 17.6 months, relapse-free--10.8 months. Risk of progression in the poor and good prognosis groups was identical (HR=09). Overall response was 29% in poor prognosis and 40%--in good one (p = 0.07). Drug tolerability was acceptable in both groups. Sunitinib was effective in both groups of MRCC patients.
Assuntos
Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Indóis/uso terapêutico , Neoplasias Renais/tratamento farmacológico , Pirróis/uso terapêutico , Idoso , Inibidores da Angiogênese/uso terapêutico , Carcinoma de Células Renais/secundário , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Sunitinibe , Análise de Sobrevida , Resultado do TratamentoRESUMO
An open comparative randomized study of paroxetine (selective inhibitor of serotonin re-uptake) and tricyclic antidepressant amitriptiline has been conducted. These drugs were used for the treatment of 43 patients with recurrent depression (RD) with frequent relapses (ICD-10 F33.0-F33.2) during 12 months. There were 2 groups matched for demographic and clinical data, one included 21 patients treated by paroxetine and the other 22 patients switched to amitriptiline. Basing on clinical records and scores on a number of scales, i.e. HAM-D, CGI, quality of life, high efficacy of the drugs was confirmed, being estimated as 90,5% responders in the paroxetine group and 69,2% in the amitriptiline one, with the marked advantage of the former medication. The better tolerability, possibility of single intake and absence of severe side-effects argue for preferable use of paroxetine during long-term therapy in RD patients with frequent relapses.
Assuntos
Amitriptilina/uso terapêutico , Antidepressivos de Segunda Geração/uso terapêutico , Antidepressivos Tricíclicos/uso terapêutico , Depressão/tratamento farmacológico , Paroxetina/uso terapêutico , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Adolescente , Adulto , Idoso , Amitriptilina/administração & dosagem , Amitriptilina/efeitos adversos , Antidepressivos de Segunda Geração/administração & dosagem , Antidepressivos de Segunda Geração/efeitos adversos , Antidepressivos Tricíclicos/administração & dosagem , Antidepressivos Tricíclicos/efeitos adversos , Interpretação Estatística de Dados , Depressão/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Paroxetina/administração & dosagem , Paroxetina/efeitos adversos , Qualidade de Vida , Recidiva , Inibidores Seletivos de Recaptação de Serotonina/administração & dosagem , Inibidores Seletivos de Recaptação de Serotonina/efeitos adversos , Fatores de Tempo , Resultado do TratamentoRESUMO
The anti-HIV activity of new membranotropic compounds, i.e. of the polycarboxylate matrix and of its derivatives modified by adamantane and norbonene, was studied in respect of HIV-1 strains, whose tropicity to coreceptors CCR5 and CXCR4 was different, as well as in respect of HIV-1 variants resistant to azidothymidine (AZT) in a continuous culture of human lymphoid cells (MT-4) and in mononuclear cells of peripheral blood from healthy donors. Testing of complex compounds in a culture of infected MT-4 human lymphoid cells showed an effective inhibition of viral reproduction of LAV.04 (CXCR4-tropic variant) and of HIV11(EVK) as well as AZT-resistant variants. The studied pharmacophores-modified compounds displayed, in infection of the primary culture of human mononuclear cells of the HIV-1 R5 and X4 strains, a notable antiviral activity with their HIV efficiency significantly exceeding the one of the original matrix.
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Adamantano/química , Anidridos/química , Fármacos Anti-HIV/farmacologia , HIV-1/efeitos dos fármacos , Norbornanos/química , Fármacos Anti-HIV/química , Linhagem Celular , Farmacorresistência Viral , HumanosAssuntos
Antineoplásicos/administração & dosagem , Interleucina-2/administração & dosagem , Neoplasias Renais/tratamento farmacológico , Síndromes Paraneoplásicas/tratamento farmacológico , Vasculite/tratamento farmacológico , Humanos , Infusões Intravenosas , Neoplasias Renais/complicações , Masculino , Pessoa de Meia-Idade , Síndromes Paraneoplásicas/etiologia , Vasculite/etiologiaRESUMO
Clinical and laboratory data on the treatment of 19 children with chronic toxoplasmosis were used for estimation of the efficacy of drug combination, such as spiramycin + lidase and lincomycin + lidase vs. the traditional therapy (co-trimoxazole, metronidazole). The combination designed by us, i.e. spiramycin + lidase, lincomycin + lidase used in consecutive courses proved to be more efficient.
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Coccidiostáticos/uso terapêutico , Hialuronoglucosaminidase/uso terapêutico , Lincomicina/uso terapêutico , Espiramicina/uso terapêutico , Toxoplasmose/tratamento farmacológico , Administração Oral , Criança , Doença Crônica , Coccidiostáticos/administração & dosagem , Quimioterapia Combinada , Humanos , Hialuronoglucosaminidase/administração & dosagem , Injeções Intramusculares , Lincomicina/administração & dosagem , Espiramicina/administração & dosagemRESUMO
The purpose was to develop an effective drug of local intravaginal membranetropic microbicide based on polycarboxylate and matrix modified by norbonene and/or peptide (simulator of CCR5 coreceptor). The drug was added to the composition of polyacrykic acid-polyvinylpyrrolidone (interpolymer complexes) in order to prevent the interplay of its non-specific groups with proteins. The antiviral effect and absence of toxicity of the finished microbicide form were demonstrated on the human lymphoid MT-4 culture.
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Fármacos Anti-HIV/administração & dosagem , Portadores de Fármacos/farmacologia , HIV-1/efeitos dos fármacos , Resinas Acrílicas/farmacologia , Resinas Acrílicas/toxicidade , Animais , Linhagem Celular , Portadores de Fármacos/toxicidade , Sistemas de Liberação de Medicamentos , Lipossomos , Linfócitos/efeitos dos fármacos , Linfócitos/virologia , Camundongos , Camundongos Endogâmicos BALB C , Povidona/farmacologia , Povidona/toxicidadeRESUMO
Analysis of molecular mechanisms of HIV-infection and targets for therapeutic intervention allowed to offer strategy for design of new effective anti-HIV/AIDS agents on the basis of two key principles: 1) intervention to infectious process beginning from the earliest stages of the virus penetration into cells; 2) blockade of not only one but several molecular targets of the HIV life cycle. The paper presents the results of the in vitro investigation of the anti-HIV activity (against several HIV-1 strains, including AZT-resistant ones) of new generation complex substances synthesized with application of the molecular substrategy for bifunctional inhibitors on the basis of a combination of nonspecific antiviral active polymeric anions with selective virus sensitive membranotropic pharmacophores of the adamantane and norbornene lines. The HIV-1 inhibiting potential of polymeric carboxylic acids (PKA) of various nature: synthetic polymeric analogues of succinic acid and carboxymethylated dextran was evaluated. It was shown that the antiviral action of PKA is located at the initial stages of HIV-1 penetration into cells and is markedly defined by balance of electrostatic activity and conformational mobility of the macromolecules. This corresponds to the evidence of the negatively charged macromolecules ability to bind the positively charged V3 loop within the viral protein gp120, preventing the HIV-1 adsorption on the surface of permissive cells. Chemical conjugation of the PKA with derivatives of the adamantane (amantadine and rimantadine analogues) or norbornene (related to deitiforin and natural bicyclic therpenoids) via spacer groups provides synergistic elevation of the anti-HIV-1 activity, first of all for the flexible chain PKA. The obtained result experimentally confirmed the theoretically predicted expansion of the anti-HIV-1 action of the bifunctional kind antivirals due to cooperation of the electrostatic potential of PKA with the virus specific hydrophobic activity needed to block postadsorption events of the HIV-1 life cycle, including both the virus penetration into cells and the virus posterity release from the infected cells. Additional cooperation of PKA with some special vectors targeted towards "Raft" domains of cellular membranes, epicentres for natural location of initial and completed stages of the HIV-1 replication cycle was also shown promising. The structure-function optimized samples exhibit high indexes of anti-HIV-1 selectivity up to IS50 = 10000.
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Adamantano/análogos & derivados , Adamantano/farmacologia , Fármacos Anti-HIV/farmacologia , Ácidos Carboxílicos/química , HIV-1/efeitos dos fármacos , Norbornanos/farmacologia , Adamantano/química , Adamantano/toxicidade , Ânions , Fármacos Anti-HIV/química , Fármacos Anti-HIV/toxicidade , Células Cultivadas , Farmacorresistência Viral , Humanos , Norbornanos/química , Norbornanos/toxicidade , Polímeros , Relação Estrutura-Atividade , Zidovudina/farmacologiaAssuntos
Fármacos Anti-HIV/farmacologia , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , Fármacos Anti-HIV/química , Fármacos Anti-HIV/uso terapêutico , Membrana Celular/efeitos dos fármacos , Membrana Celular/fisiologia , Proteína gp120 do Envelope de HIV/fisiologia , Infecções por HIV/tratamento farmacológico , HIV-1/fisiologia , Humanos , Receptores de HIV/efeitos dos fármacosRESUMO
The capacity of a previously described plasmid vector pAZ to deliver bioactive proteins to targets in vivo has been studied. This vector molecule has a strong constitutive promoter, is extremely stable in cells of vaccinal S. choleraesuis strain, and encodes the synthesis of marker protein beta-galactosidase which helps monitor the vector's fate in the host. The gene encoding hepatitis B virus core antigen (HBcAg) has been inserted into pAZ under its constitutive promoter. The resultant recombinant plasmid p19-24 has been used to transform Enterobacteriaceae (E. coli and S. choleraesuis) cells. Transformed cells produce immunologically active HBcAg. p19-24 was stable in S. choleraesuis cells during their culturing and during this strain persistence in mice. Triple oral immunization of rabbits in a dose of 1 x 10(9) S. choleraesuis cells TC177 induced the production of virus-specific antibodies. Successful transformation of cells of another vaccinal strain S. abortus ovis by this plasmid extends the potentialities of the vector. The results demonstrate good prospects of using pAZ vector for the construction of live oral vaccines.
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Antígenos do Núcleo do Vírus da Hepatite B/genética , Plasmídeos , Salmonella/genética , Sequência de Aminoácidos , Animais , Clonagem Molecular , Relação Dose-Resposta Imunológica , Camundongos , Dados de Sequência Molecular , Coelhos , Proteínas Recombinantes/genética , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/genética , Vacinas Sintéticas/imunologiaRESUMO
Evidence was obtained that the changed gravity, tension profiles of the magnetic fields inside the orbital station and other spaceflight factors (SFF) substantially influence the cell genome and synthesis of recombinant proteins. The authors proposed a technique of fixation of possible alterations in genes and expressed recombinant proteins in strains-producers of human alpha-interferon: HuIFN-alpha 2b, HuIFN-alpha 8a, HuIFN-alpha 10a, and HuIFN-alpha 14a. Spaceflight factors were simulated by way of gamma-irradiation at 10 Gy and 50 Gy by a cobalt unit, and centrifugation of samples at 10 g and 50 g. Cultivation of the strains-producers during the SFF simulation yielded HuIFN-alpha proteins with altered functional characteristics. Following exposure to simulated SFF, strains-producers expressed HuIFN-alpha that preserved a high titre of antiviral activity (AVA) but suppressed the antiproliferative activity (APA) inferring some structural/functional shifts in the HuIFN-alpha molecule due to, presumably, mutations in the active center responsible for APA. Determination of species specificity of the HuIFN-alpha recombinant proteins following exposure to SFF revealed dissociation of cross-AVA in homologous and heterologous cell cultures which can be also attributed to the structural/functional shifts in the HuIFN-alpha molecule. These changes can be localized in the receptor cluster of molecule or consequent to modification of the center defining HuIFN-alpha species specificity. The proposed simulation system allows fixation of shifts in the HuIFN-alpha structural/functional characteristics and investigations of the stability of eucaryotic genes in long-term space flights.
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Células Eucarióticas/fisiologia , Interferon-alfa/genética , Proteínas Recombinantes/genética , Voo Espacial , Movimento Celular/fisiologia , Escherichia coli/genética , Engenharia Genética , Humanos , Hipergravidade , Hipogravidade , Indutores de Interferon , Fatores de TempoRESUMO
To solve the problems of biological safety of the cosmonaut on long-duration space mission and prediction of changes in macroorganism as a whole and constituting protein molecules under these conditions, it is important to study the influence of spaceflight factors (SFF) on microorganisms-carriers of modeled structures, protein molecules and pro- and eukaryotic genes in particular. Within the framework of scientific cooperation NAUKA-NASA, the authors proposed a model system of prokaryotic producers of pro- and eukaryotic proteins--staphylococcus alpha-toxin (SAT)--as a key protein in pathogenesis of staphylococcal infections, and human leukocytic interferon (HuIFN-alpha) as one of the homeostasis regulating proteins with well-studied structural and functional properties. Recombinant strains of E. coli with either a single or duplicated HuIFN-alpha 2b gene or other genes of the HuIFN-alpha family: HuIFN-alpha 8a, HuIFN-alpha 10a and HuIFN-alpha 14a were selected as producers of SAT and HuIFN-alpha. This biotechnologic system allows imitation and assessment of the SFF mutagenic effect both at the levels of genome of strain-carrier and gene-insertion and expressed CAT and HuIFN-alpha molecules including transcription, translation, assembly and post-translatory modifications of the target-protein. The developed methodology allows determination of highly mutable and conservative regions in the primary structure of a hypothetical protein associated with its functional activity, prediction of specific amino acid substitutes in these regions, and comparison of test calculations with a pool of natural mutations in the family of proteins under study. The structural/functional analysis of proteins and HuIFN-alpha genes made it possible to isolate and systematize functionally significant areas in the structure of hypothetical protein HuUFN-alpha, on the basis of which the most probable amino acid substitutions were prognosticated. This will present a possibility to identify expectable mutation events in HuIFN-alpha proteins, which so far have not been found in natural genes of the human interferon. Comparison of results of SFF modeling and space experiments aboard the International Space Station with monitoring of HuIFN-alpha mutant forms will help estimation of the extent of influence of the spaceflight factors on evolution of protein molecules.
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Proteínas Hemolisinas/fisiologia , Interferon-alfa/fisiologia , Voo Espacial , Toxinas Bacterianas , Humanos , Biossíntese de ProteínasRESUMO
The causes of lethal outcomes (n = 60) and postoperative complications which occurred in 26.1% of 610 patients operated on for lung cancer were investigated with due consideration for the regularities of thermodynamics of nonequilibrium processes and theory of disasters. A total systems pathological inflammatory reaction, which augments the injury by many times and develops as a result of inadequate anesthesiological protection, underlies the development of the most unfavorable variant of response to surgery leading to life-threatening complications, such as pneumonia, thromboembolism, or ulcerative hemorrhages.
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Neoplasias Pulmonares/cirurgia , Complicações Pós-Operatórias/etiologia , Perda Sanguínea Cirúrgica , Humanos , Neoplasias Pulmonares/mortalidade , Pessoa de Meia-Idade , Pneumonectomia , Complicações Pós-Operatórias/mortalidade , Cuidados Pré-Operatórios , Respiração Artificial , Fatores de RiscoRESUMO
Molecular, biological, and immunological studies on the recently identified human herpesvirus-6 (HHV-6) suggest that the virus is involved in the etiology of at least several lymphoproliferative diseases. Furthermore, HHV-6 may be an important cofactor in the pathogenesis of several other diseases, including cervical carcinoma, oral carcinoma, multiple sclerosis, and HIV infection. Analyzing the data available in the literature shows it necessary to conduct systematic investigations and to emphasize the importance of the problem for national public health.