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BACKGROUND: The phenomenon of antibiotic resistance shows no sign of stopping, despite global policies to combat it that have been in place for several years. The risk of forms of pathogenic microorganisms that are increasingly resistant to common antibiotics has led health authorities around the world to pay greater attention to the phenomenon. The worrying situation, has led to further recommendations from the World Health Organization (WHO) and national recommendations in Italy through the new National Plan against Antibiotic Resistance 2022-2025 (PNCAR 2022-2025). AIM: This manuscript aims to raise the awareness of all health professionals to follow what is suggested by regulatory agencies and scientific societies. METHOD: We conducted a retrospective study of antibiotic pharmacoutilization in Italy, in the Campania region at the Azienda Sanitaria Locale (ASL) Napoli 3 Sud, on consumption in the first half of 2022 in a population of more than 1 million people. RESULT: The results indicate that consumption, based on defined daily doses (DDDs), is above the national average. Probably the COVID-19 pandemic has influenced this growth in prescriptions. CONCLUSIONS: Our study suggests an informed and appropriate use of antibiotics, so as to embark on a virtuous path in the fight against antibiotic resistance.
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COVID-19 , SARS-CoV-2 , Humanos , COVID-19/epidemiologia , Estudos Retrospectivos , Pandemias , Antibacterianos/uso terapêutico , Itália/epidemiologia , Prescrições de MedicamentosRESUMO
We discuss the Sherrington-Kirkpatrick mean-field version of a spin glass within the distributional zeta function method (DZFM). In the DZFM, since the dominant contribution to the average free energy is written as a series of moments of the partition function of the model, the spin-glass multivalley structure is obtained. Also, an exact expression for the saddle points corresponding to each valley and a global critical temperature showing the existence of many stables or at least metastable equilibrium states is presented. Near the critical point, we obtain analytical expressions of the order parameters that are in agreement with phenomenological results. We evaluate the linear and nonlinear susceptibility and we find the expected singular behavior at the spin-glass critical temperature. Furthermore, we obtain a positive definite expression for the entropy and we show that ground-state entropy tends to zero as the temperature goes to zero. We show that our solution is stable for each term in the expansion. Finally, we analyze the behavior of the overlap distribution, where we find a general expression for each moment of the partition function.
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The pandemic caused by the new SARS-CoV2 coronavirus has led to an effort to find treatments that are effective against this disease that the World Health Organization calls COVID-19. In severe cases of COVID-19, there is an increase in cytokines, among which IL-6 seems to play an important role. A search has been performed for studies using IL-6 blocking drugs (tocilizumab, siltuximab, and sarilumab) in PubMed, Web of Science, and Scopus. Also, a search of ongoing trials registered at clinicaltrials.gov was performed. We found very little published clinical experience with these drugs, consisting mainly of case reports or case series with few patients. The results of clinical trials are necessary to clarify the role of these drugs in patients with COVID-19.
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Anticorpos Monoclonais Humanizados/farmacologia , Anticorpos Monoclonais/farmacologia , Antivirais/farmacologia , Betacoronavirus/efeitos dos fármacos , Interleucina-6/antagonistas & inibidores , Betacoronavirus/imunologia , COVID-19 , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Humanos , Interleucina-6/imunologia , Pandemias/prevenção & controle , Pneumonia Viral/diagnóstico , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/imunologia , SARS-CoV-2RESUMO
Additive manufacturing techniques such as Selective Laser Melting (SLM) can produce complex shapes with relatively thin sections and fine detail. However, common materials for the process, such as Ti-6Al-4V, have microstructure and properties that are sensitive to the pickup of interstitial impurities, such as oxygen, which the material will be exposed to during the process. This problem would be especially severe for parts with thin sections, where surface effects can be more significant, and where poor properties may coincide with locally-elevated stress. Here we explore the effects of oxygen level in thin sections with the use of lattice materials (materials which can be considered to consist exclusively of near-surface material). Oxygen levels are artificially raised using repeated melting passes to result in more pickup, leading to significantly reduced ductility and hence reduced strength measured in compression. A ductile to brittle transition in strut failure mechanism is found with increasing number of melting passes, with significant modification in chemistry and crystallographic structure, despite the presence of a similar fine plate-like microstructure throughout.
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Resumen Introducción: El personal de enfermería se enfrenta cotidianamente a diferentes eventos asociados al estrés, factores psicosociales y otros mecanismos que afectan su salud mental. Objetivo: Evaluar la correlación entre la demanda psicológica, el control laboral, el apoyo social, el estrés psicológico, y las dimensiones del Síndrome de Burnout (ilusión por el trabajo, desgaste psíquico, indolencia y culpa), en un modelo de trayectorias en enfermeras mexicanas. Metodología: Estudio transversal, observacional, analítico, conducido en 357 profesionales de enfermería de Morelos, México, seleccionados por conveniencia. Los datos fueron colectados empleando tres cuestionarios, la Escala de Estrés Percibido, el Cuestionario del Contenido del Trabajo y el Cuestionario para la Evaluación del Síndrome de Quemarse por el Trabajo. Los programas SPSS 19 y LISREL 8.3 fueron empleados para el procesamiento y modelaje de los datos. Resultados: En el modelo de trayectorias, se especificó como variable mediadora de los factores psicosociales y de las dimensiones del Síndrome de Quemarse por el Trabajo (SQT), al estrés psicológico. Los índices de ajuste fueron aceptables. Se encontraron altos niveles de apoyo social, control laboral e ilusión por el trabajo; grados moderados de demanda psicológica y estrés psicológico; y bajos niveles de desgaste psíquico, indolencia y culpa. Conclusión: Implicaciones para la disciplina, se propone implementar estrategias de intervención efectivas para mantener en el personal de enfermería bajos niveles de demandas psicológicas, altos niveles de control laboral, altos niveles de apoyo social, y niveles moderados de estrés, para prevenir, el SQT.
Abstract Introduction: Nurses frequently face different events associated with stress, psychosocial factors, and other issues which have impacts on their mental health. Objective: To assess the correlation between psychological demand, work control, social support, psychological stress, and burnout dimensions (illusion for the activity, psychic wear, indolence, guilt), within a model of trajectories among Mexican nurses. Methodology: This is a transversal, observational, and analytical study conducted on a convenience sample of 357 nursing professionals from the state of Morelos, Mexico. Data were gathered using three questionnaires, the Perceived Stress Scale, the Job Content Questionnaire, y el Maslach Burnout Inventory. SPSS 19 and LISREL 8.3 were used to process and model the data. Results: Psychological Stress was specified as the mediating variable of the psychosocial factors and dimensions of burnout within the model of trajectories. Adjustment indexes were acceptable. High levels of social support, work control, and illusion for the activity were found. Moderate degrees of psychological demand and psychological stress were found. Low levels of psychic wear, indolence, and guilt were found. Conclusion: It is recommended to implement effective intervention strategies to maintain nursing personnel within low levels of psychological demand, high levels of work control, high levels of social support, and moderate levels of stress, all these in order to prevent the Syndrome of Burnout.
Resumo Introdução: O pessoal de enfermagem se enfrenta cotidianamente a diferentes eventos associados ao estresse, fatores psicossociais e outros mecanismos que afetam sua saúde mental. Objetivo: Avaliar a correlação entre a demanda psicológica, o controle laboral, o apoio social, o estresse psicológico, e as dimensões e da Síndrome de Burnout (ilusão pelo trabalho, desgaste psíquico, indolência e culpa), em um modelo de trajetórias em enfermeiras mexicanas. Metodologia: Estudo transversal, observacional, analítico, conduzido em 357 profissionais de enfermagem de Morelos, México, selecionados por conveniência. Os dados foram coletados empregando três questionários, a Escala de Estresse Percebido, o Questionário do Conteúdo do Trabalho e o Questionário para a Avaliação da Síndrome de Burnout no Trabalho. Os programas SPSS 19 e LISREL 8.3 foram empregados para o processamento e modelagem dos dados. Resultados: No modelo de trajetórias, especificou-se como variável mediadora dos fatores psicossociais e das dimensões da Síndrome de Burnout no Trabalho (SQT), ao estresse psicológico. Os índices de ajuste foram aceitáveis. Encontraram-se altos níveis de apoio social, controle laboral e ilusão pelo trabalho; graus moderados de demanda psicológica e estresse psicológico; e baixos níveis de desgaste psíquico, indolência e culpa. Conclusão: Implicações para a disciplina, propõe-se implementar estratégias de intervenção efetivas para manter no pessoal de enfermagem baixos níveis de demandas psicológicas, altos níveis de controle laboral, altos níveis de apoio social, e níveis moderados de estresse, para prevenir, o SQT.
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A methodology has been demonstrated to consolidate Ti-6Al-4V powder without taking it to the liquid state by novel combination of the electron beam melting additive manufacture and hot isostatic pressing processes. This results in improved static mechanical properties (both strength and yield) in comparison to standard EBM processed material. In addition, the ability to generate microstructurally graded components has been demonstrated by generating a component with a significant change in both microstructure and mechanical properties. This is revealed by the use of electron backscattered diffraction and micro hardness testing to produce maps showing a clear distinction between materials consolidated in different ways. The variation in microstructure and mechanical properties is attributed to the different thermal history experienced by the material at different locations. In particular, it is found that the rapid cooling experienced during EBM leads to a typical fine α lath structure, whereas a more equiaxed α grains generated by diffusion is found in HIP consolidated powder.
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Hydrogen embrittlement is a complex phenomenon, involving several length- and timescales, that affects a large class of metals. It can significantly reduce the ductility and load-bearing capacity and cause cracking and catastrophic brittle failures at stresses below the yield stress of susceptible materials. Despite a large research effort in attempting to understand the mechanisms of failure and in developing potential mitigating solutions, hydrogen embrittlement mechanisms are still not completely understood. There are controversial opinions in the literature regarding the underlying mechanisms and related experimental evidence supporting each of these theories. The aim of this paper is to provide a detailed review up to the current state of the art on the effect of hydrogen on the degradation of metals, with a particular focus on steels. Here, we describe the effect of hydrogen in steels from the atomistic to the continuum scale by reporting theoretical evidence supported by quantum calculation and modern experimental characterisation methods, macroscopic effects that influence the mechanical properties of steels and established damaging mechanisms for the embrittlement of steels. Furthermore, we give an insight into current approaches and new mitigation strategies used to design new steels resistant to hydrogen embrittlement.
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INTRODUCTION: Muscle-invasive bladder malignancies represent 20-30% of all bladder cancers. These patients require imaging tests to determine the regional and distant staging. OBJECTIVE: To describe the role of various imaging tests in the diagnosis, staging and follow-up of muscle-invasive bladder cancer. To assess recent developments in radiology aimed at improving the sensitivity and specificity of local staging and treatment response. ACQUISITION OF EVIDENCE: We conducted an updated literature review. SYNTHESIS OF THE EVIDENCE: Computed tomography and magnetic resonance imaging (MRI) are the tests of choice for performing proper staging prior to surgery. Computed tomography urography is currently the most widely used technique, although it has limitations in local staging. Ultrasonography still has a limited role. Recent developments in MRI have improved its capacity for local staging. MRI has been suggested as the test of choice for the follow-up, with promising results in assessing treatment response. Positron emission tomography could improve the detection of adenopathies and extrapelvic metastatic disease. CONCLUSIONS: Imaging tests are essential for the diagnosis, staging and follow-up of muscle-invasive bladder cancer. Recent technical developments represent important improvements in local staging and have opened the possibility of assessing treatment response.
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Carcinoma/diagnóstico por imagem , Neoplasias da Bexiga Urinária/diagnóstico por imagem , Carcinoma/patologia , Seguimentos , Humanos , Imageamento por Ressonância Magnética , Músculo Liso , Invasividade Neoplásica , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X , Neoplasias da Bexiga Urinária/patologiaRESUMO
Metallic powder bed additive manufacturing is capable of producing complex, functional parts by repeatedly depositing thin layers of powder particles atop of each other whilst selectively melting the corresponding part cross-section into each layer. A weakness with this approach arises when melting overhanging features, which have no prior melted material directly beneath them. This is due to the lower thermal conductivity of the powder relative to solid material, which as a result leads to an accumulation of heat and thus distortion. The Electron Beam Melting (EBM) process alleviates this to some extent as the powder must first be sintered (by the beam itself) before it is melted, which results in the added benefit of increasing the thermal conductivity. This study thus sought to investigate to what extent the thermal conductivity of local regions in a titanium Ti-6Al-4V powder bed could be varied by imparting more energy from the beam. Thermal diffusivity and density measurements were taken of the resulting sintered samples, which ranged from being loosely to very well consolidated. It was found that the calculated thermal conductivity at two temperatures, 40 and 730 °C, was more than doubled over the range of input energies explored.
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Recently in Mexico the number of cosmetic surgeries has increased. These procedures are often carried out by unqualified people using obsolete and contraindicated products such as injectable oil, which cause uncorrectable disfigurement or more serious complications, even death, after reaching the systemic circulation. We report the case of a fat embolism syndrome (FES) caused by injections of vitamin E (tocopherol) in order to increase the volume of the buttocks. This case of a FES caused by injections of vitamin E was confirmed by gas chromatography coupled to mass spectrometry.
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Nádegas , Embolia Gordurosa/induzido quimicamente , Vitamina E/intoxicação , Adulto , Cosméticos , Evolução Fatal , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Injeções , México , Síndrome , Vitaminas/intoxicação , Adulto JovemRESUMO
In this study, we report on a group of complementary human osteoblast in vitro test methods for the preclinical evaluation of 3D porous titanium surfaces. The surfaces were prepared by additive manufacturing (electron beam melting [EBM]) and plasma spraying, allowing the creation of complex lattice surface geometries. Physical properties of the surfaces were characterized by SEM and profilometry and 3D in vitro cell culture using human osteoblasts. Primary human osteoblast cells were found to elicit greater differences between titanium sample surfaces than an MG63 osteoblast-like cell line, particularly in terms of cell survival. Surface morphology was associated with higher osteoblast metabolic activity and mineralization on rougher titanium plasma spray coated surfaces than smoother surfaces. Differences in osteoblast survival and metabolic activity on titanium lattice structures were also found, despite analogous surface morphology at the cellular level. 3D confocal microscopy identified osteoblast organization within complex titanium surface geometries, adhesion, spreading, and alignment to the biomaterial strut geometries. Mineralized nodule formation throughout the lattice structures was also observed, and indicative of early markers of bone in-growth on such materials. Testing methods such as those presented are not traditionally considered by medical device manufacturers, but we suggest have value as an increasingly vital tool in efficiently translating pre-clinical studies, especially in balance with current regulatory practice, commercial demands, the 3Rs, and the relative merits of in vitro and in vivo studies. Biotechnol. Bioeng. 2016;113: 1586-1599. © 2015 The Authors. Biotechnology and Bioengineering Published by Wiley Periodicals, Inc.
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Materiais Biocompatíveis , Prótese Articular , Osteoblastos , Titânio , Materiais Biocompatíveis/química , Materiais Biocompatíveis/toxicidade , Linhagem Celular Tumoral , Humanos , Ortopedia , Osteoblastos/citologia , Osteoblastos/efeitos dos fármacos , Propriedades de Superfície , Titânio/toxicidadeRESUMO
Myiasis is the invasion of Diptera larvae in live vertebrates tissues. It has been registered in tropical areas, but not in urban animals of North America. Moreover, there is no information about lesions description, laboratory tests, and treatment applied to canines. We report a myiasis located in the dorsum of an overweight male canine. Insect larvae were identified as Lucilia eximia, an opportunistic species that scarcely infest live vertebrates, and with no records in North America animals before. Abnormalities of complete blood count like leukocytosis by neutrophilia and serum biochemical changes like elevations in alanine aminotransferase, aspartate aminotransferase, creatine kinase, globulins and amylase were detected. Because Lucilia is characterized by lower host-specificity and infestation outbreaks occur worldwide, it is imperative to continue increasing the understanding of Lucilia myiasis, its clinical presentation, risk factors, therapy and correct entomological classification. Otherwise, more cases could occur in animals and humans.
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Paralisia Cerebral/complicações , Paralisia Cerebral/epidemiologia , Constipação Intestinal/epidemiologia , Constipação Intestinal/etiologia , Proctite/complicações , Proctite/epidemiologia , Infecções Estreptocócicas/complicações , Infecções Estreptocócicas/epidemiologia , Streptococcus pyogenes , Adolescente , Causalidade , Criança , Estudos de Coortes , Constipação Intestinal/diagnóstico , Estudos Transversais , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Proctite/diagnóstico , Infecções Estreptocócicas/diagnóstico , SuíçaRESUMO
In vitro, Imatinib inhibits the proliferation and stimulates the osteogenic and adipogenic differentiation of mesenchymal stromal cells (MSC). However, it is unknown whether Imatinib affects the biology of MSC in vivo. We asked whether MSC from long-term Imatinib-treated CML patients were affected by the in vivo treatment. MSC from untreated and Imatinib-treated patients displayed normal functional properties (i.e. proliferation, immunophenotype, differentiation and hematopoietic supportive capacity) - but a decreased frequency. In vitro, Imatinib lost its effect when discontinued; which suggest that it has a reversible effect on MSC. Therefore it might lose its effect on MSC after discontinuation in vivo.
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Antineoplásicos/uso terapêutico , Benzamidas/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Células-Tronco Mesenquimais/fisiologia , Piperazinas/uso terapêutico , Pirimidinas/uso terapêutico , Diferenciação Celular , Proteínas de Fusão bcr-abl/metabolismo , Humanos , Mesilato de Imatinib , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Células-Tronco Mesenquimais/citologia , FenótipoRESUMO
BACKGROUND: Human-to-human transmission of Fusobacterium necrophorum has not been described before. CASE PRESENTATION: We present the case of a 15-year-old girl with Lemierre Syndrome and possible nosocomial transmission of F. necrophorum to her treating physician in hospital. CONCLUSION: Early diagnosis and treatment of anaerobic pharyngitis is critical to prevent Lemierre Syndrome. Respiratory precautions should be recommended to medical staff caring for patients with suspected Lemierre Syndrome to prevent nosocomial transmission.
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Infecção Hospitalar/transmissão , Infecções por Fusobacterium/transmissão , Fusobacterium necrophorum , Transmissão de Doença Infecciosa do Paciente para o Profissional , Internato e Residência , Síndrome de Lemierre/tratamento farmacológico , Síndrome de Lemierre/transmissão , Pediatria/educação , Tonsilite/diagnóstico , Adolescente , Combinação Amoxicilina e Clavulanato de Potássio/uso terapêutico , Antibacterianos/uso terapêutico , Infecção Hospitalar/diagnóstico , Infecção Hospitalar/tratamento farmacológico , Quimioterapia Combinada , Diagnóstico Precoce , Feminino , Infecções por Fusobacterium/diagnóstico , Infecções por Fusobacterium/tratamento farmacológico , Humanos , Processamento de Imagem Assistida por Computador , Veias Jugulares/patologia , Síndrome de Lemierre/diagnóstico , Pneumonia Bacteriana/diagnóstico , Pneumonia Bacteriana/tratamento farmacológico , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/tratamento farmacológico , Choque Séptico/diagnóstico , Choque Séptico/tratamento farmacológico , Tomografia Computadorizada por Raios X , Tonsilite/tratamento farmacológicoRESUMO
The satisfaction level of a patient that receives home care, is an indicator that is rarely ever evaluated. This is also due to the fact that it is objectively difficult to gather data concerning this issue and there are a countless number of variables that could influence an evaluation. The objective of this study is to quantify the satisfaction level of those that use the Home Care Services of the Trento District. A validated questionnaire with 30 questions was used to explore the organizational, relational and professional aspects, communication, information and patient education in addition to the satisfaction level of certain aspects that concerned the availability/delivery of medical supplies and aids. Together with this information, data was also gathered concerning the patient's formal and informal social network. 122 patients, that received care by the nursing services of the territory and that received home care at least twice a week, were enrolled in the survey. The responses that emerged from this sample of patients, concerning the satisfaction level, were very positive. Each aspect had a high satisfaction percentage that was always beyond 75%. This survey must be used within the trust's continuous quality improvement plan, by addressing the needs that have been expressed and not, by empowering human and organizational resources and by integrating the numerous health care operators that work within the territory to improve citizens' health.
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Serviços de Assistência Domiciliar/estatística & dados numéricos , Satisfação do Paciente/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Feminino , Pesquisas sobre Atenção à Saúde/métodos , Serviços de Assistência Domiciliar/normas , Humanos , Itália , Masculino , Serviços de Enfermagem/normas , Avaliação de Processos e Resultados em Cuidados de Saúde , Educação de Pacientes como Assunto/estatística & dados numéricos , Participação do Paciente/estatística & dados numéricos , Qualidade da Assistência à Saúde/normas , Estudos de Amostragem , Inquéritos e QuestionáriosRESUMO
A water-soluble [meso-tetra(4-nido-carboranylphenyl)porphyrin] (H(2)TCP) bearing 36 boron atoms was studied for its accumulation and its radio/photo-sensitization efficiency towards murine melanotic melanoma cells. The amount of H(2)TCP in the cells increased with the porphyrin dose in the incubation medium up to 100 microM with no significant dark toxicity. Fluorescence microscopy observations showed that the porphyrin was largely localized intracellularly. Based on these "in vitro" results our investigations were pursued using the B16F1 melanotic melanoma subcutaneously transplanted in C57BL6 mice as "in vivo" model. Phormacokinetic studies were performed by injection of H(2)TCP intratumorally (1 mg/kg) and intravenously (10 mg/kg). At 0.5h after i.t. administration or at 24 h after i.v. injection, the amounts of (10)B in the tumour were about 60 ppm and about 6 ppm, respectively. The distribution of H(2)TCP in the tumour after intravenous or intratumoural injection was also assessed by fluorescence microscopy analyses. Under these conditions, preliminary BNCT studies were carried out using a new thermal column called HYTOR (HYbrid Thermal spectrum sHifter TapirO Reactor) inserted in the fast nuclear reactor Tapiro at Enea Casaccia, Italy. The mice were exposed to HYTHOR radiation field for 20 min at a reactor power of 5 kW. In spite of different amounts of (10)B in the tumour at the irradiation time, a similar significant delay in tumour growth (5-6 days) was induced by neutron irradiation in intratoumorally and intravenously injected mice. The response of the melanotic melanoma to H(2)TCP-BNCT was compared with that obtained by irradiation after intraperitoneal injection of boron-phenylalanine.
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Compostos de Boro/uso terapêutico , Terapia por Captura de Nêutron de Boro/métodos , Melanoma Experimental/radioterapia , Porfirinas/uso terapêutico , Radiossensibilizantes/uso terapêutico , Animais , Sobrevivência Celular/efeitos da radiação , Técnicas In Vitro , Melanoma Experimental/patologia , Camundongos , Camundongos Endogâmicos C57BLRESUMO
A recently defined charge set, to be used in conjunction with the all-atom CHARMM27r force field, has been validated for a series of phosphatidylcholine lipids. The work of Sonne et al. successfully replicated experimental bulk membrane behaviour for dipalmitoylphosphatidylcholine (DPPC) under the isothermal-isobaric (NPT) ensemble. Previous studies using the defined CHARMM27r charge set have resulted in lateral membrane contraction when used in the tensionless NPT ensemble, forcing the lipids to adopt a more ordered conformation than predicted experimentally. The current study has extended the newly defined charge set to 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine (POPC) and 1-palmitoyl-2-docosahexaenoyl-sn-glycero-3-phosphatidylcholine (PDPC). Molecular dynamics simulations were run for each of the lipids (including DPPC) using both the CHARMM27r charge set and the newly defined modified charge set. In all three cases a significant improvement was seen in both bulk membrane properties and individual atomistic effects. Membrane width, area per lipid and the depth of water penetration were all seen to converge to experimental values. Deuterium order parameters generated with the new charge set showed increased disorder across the width of the bilayer and reflected both results from experiment and similar simulations run with united atom models. These newly validated models can now find use in mixed biological simulations under the tensionless ensemble without concern for lateral contraction.
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Fosfatidilcolinas/química , 1,2-Dipalmitoilfosfatidilcolina/química , Simulação por Computador , Membranas Artificiais , Modelos MolecularesRESUMO
BACKGROUND: Sequencing by hybridisation is an effective method for obtaining large amounts of DNA sequence information at low cost. The efficiency of SBH depends on the design of the probe library to provide the maximum information for minimum cost. Long probes provide a higher probability of non-repeated sequences but lead to an increase in the number of probes required whereas short probes may not provide unique sequence information due to repeated sequences. We have investigated the effect of probe length, use of reference sequences, and thermal filtering on the design of probe libraries for several highly variable target DNA sequences. RESULTS: We designed overlapping probe libraries for a range of highly variable drug target genes based on known sequence information and develop a formal terminology to describe probe library design. We find that for some targets these libraries can provide good coverage of a previously unseen target whereas for others the coverage is less than 30%. The optimal probe length varies from as short at 12 nt to as large as 19 nt and depends on the sequence, its variability, and the stringency of thermal filtering. It cannot be determined from inspection of an example gene sequence. CONCLUSIONS: Optimal probe length and the optimal number of reference sequences used to design a probe library are highly target specific for highly variable sequencing targets. The optimum design cannot be determined simply by inspection of input sequences or of alignments but only by detailed analysis of the each specific target. For highly variable sequences, shorter probes can in some cases provide better information than longer probes. Probe library design would benefit from a general purpose tool for analysing these issues. The formal terminology developed here and the analysis approaches it is used to describe will contribute to the development of such tools.