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The aim of this study was to investigate the clinical efficacy of a combination of nirmatrelvir and ritonavir (NMV-r) for treating COVID-19 in patients with diabetes mellitus (DM). This retrospective cohort study used the TriNetX research network to identify adult diabetic patients with COVID-19 between January 1, 2020, and December 31, 2022. Propensity score matching was used to match patients who received NMV-r (NMV-r group) with those who did not receive NMV-r (control group). The primary outcome was all-cause hospitalization or death during the 30-day follow-up period. Two cohorts comprising 13 822 patients with balanced baseline characteristics were created using propensity score matching. During the follow-up period, the NMV-r group had a lower risk of all-cause hospitalization or death than the control group (1.4% [n = 193] vs. 3.1% [n = 434]; hazard ratio [HR], 0.497; 95% confidence interval [CI], 0.420-0.589). Compared with the control group, the NMV-r group also had a lower risk of all-cause hospitalization (HR, 0.606; 95% CI, 0.508-0.723) and all-cause mortality (HR, 0.076; 95% CI, 0.033-0.175). This lower risk was consistently observed in almost all subgroup analyses, which examined sex (male: 0.520 [0.401-0.675]; female: 0.586 [0.465-0.739]), age (age 18-64 years: 0.767 [0.601-0.980]; ≥65 years: 0.394 [0.308-0.505]), level of HbA1c (<7.5%: 0.490 [0.401-0.599]; ≥7.5%: 0.655 [0.441-0.972]), unvaccinated (0.466 [0.362-0.599]), type 1 DM (0.453 [0.286-0.718]) and type 2 DM (0.430 [0.361-0.511]). NMV-r can help reduce the risk of all-cause hospitalization or death in nonhospitalized patients with DM and COVID-19.
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COVID-19 , Diabetes Mellitus , Adulto , Humanos , Feminino , Masculino , Adolescente , Adulto Jovem , Pessoa de Meia-Idade , Estudos Retrospectivos , Ritonavir/uso terapêutico , Tratamento Farmacológico da COVID-19 , Resultado do Tratamento , Diabetes Mellitus/tratamento farmacológicoRESUMO
Binding immunoglobulin protein (BiP, also known as GRP78), a chaperone and master regulator of the unfolded protein response (UPR) pathway, plays an essential role in several flavivirus infections, but its functional role in regulating dengue virus replication in the mosquito remains largely unknown. We here demonstrated the interaction between a dengue virus serotype 2 (DENV2) and BiP in Aedes aegypti and report the discovery of a novel functional role of BiP in mosquito vitellogenesis. Silencing Ae. aegypti BiP (AaBiP) expression resulted in the significant inhibition of DENV2 viral genome replication, viral protein production, and infectious viral particle biogenesis. Co-immunoprecipitation assays showed that the DENV2 non-structural protein 1 (NS1) interacts with the AaBiP protein, and silencing AaBiP expression led to enhanced DENV2 NS1 aggregation, indicating that AaBiP plays a role in viral protein stability. A kinetic study focusing on pulse treatment of MG132, a proteasome inhibitor, in AaBiP-silenced mosquitoes showed that DENV2 NS1 was drastically elevated, which further suggests that AaBiP-mediated viral protein degradation is mediated by proteasomal machinery. Silencing of AaBiP also resulted in a reduction in mosquito fertility and fecundity. Depletion of AaBiP inhibited mosquito vitellogenesis due to the reduction of vitellogenin mRNA and elevated aggregation of vitellogenin protein post blood meal, further suppressing ovary development and fecundity. Overall, our results suggest that AaBiP is a dual-function protein with roles in both the regulation of dengue virus replication and mosquito reproduction. Our findings will be useful in the establishment of more efficient strategies for vector-borne disease control.
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Aedes , Vírus da Dengue , Dengue , Feminino , Animais , Aedes/metabolismo , Vírus da Dengue/fisiologia , Chaperona BiP do Retículo Endoplasmático , Vitelogeninas/metabolismo , Vitelogênese , Mosquitos Vetores/genética , Replicação Viral , Proteínas Virais/metabolismoRESUMO
BACKGROUND AND OBJECTIVES: Preoxygenation is crucial for providing sufficient oxygen reservoir to a patient before intubation and enables the extension of the period between breathing termination and critical desaturation (safe apnoea time). Conventionally, face mask ventilation is used for preoxygenation. Non-invasive ventilation is a new preoxygenation method. The study objective was to compare the outcomes of non-invasive ventilation and face mask ventilation for preoxygenation. METHOD: PubMed, Embase, Cochrane Library, and the ClinicalTrials.gov registry were searched for eligible studies published from database inception to September 2021. Individual effect sizes were standardized, and a meta-analysis was conducted using random effects models to calculate the pooled effect size. Inclusion criteria were randomised controlled trials of comparing the outcomes of non-invasive ventilation or face mask ventilation for preoxygenation in patients scheduled for surgeries. The primary outcome was safe apnea time, and the secondary outcomes were post-operative complications, number of patients who achieved the expired O2 fraction (FeO2) after 3 min of preoxygenation, minimal SpO2 during tracheal intubation, partial pressure of oxygen in the arterial blood (PaO2) and partial pressure of carbon dioxide (PaCO2) after preoxygenation, and PaO2 and PaCO2 after tracheal intubation. RESULTS: 13 trials were eligible for inclusion in this study. Significant differences were observed in safe apnoea time, number of patients who achieved FeO2 90% after preoxygenation for 3 min, and PaO2 and PaCO2 after preoxygenation and tracheal intubation. Only in the non-obese subgroup, no significant difference was observed in safe apnoea time (mean difference: 125.38, 95% confidence interval: - 12.26 to 263.03). CONCLUSION: Non-invasive ventilation appeared to be more effective than conventional methods for preoxygenation. We recommend non-invasive ventilation based on our results.
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Ventilação não Invasiva , Anestesia Geral/métodos , Apneia , Dióxido de Carbono , Humanos , Intubação Intratraqueal/métodos , Ventilação não Invasiva/métodos , Oxigênio , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
To present the natural course of keratoconus (KC) and compare pediatric and adult patients. Design A retrospective cohort study. Setting Hospital-based. Patient Population In total, 152 patients (288 eyes) diagnosed with KC at Chang Gung Memorial Hospital, Taiwan, were included. Previously managed patients and those with missing optical data were excluded. Observation Procedures Patients were divided into pediatric (≤ 18 years) and adult (> 18 years) groups. Demographics, clinical data, and optical variables were collected, including corrected distance visual acuity (CDVA), refractive error, and keratometric readings (K). Main Outcome Measure Optical variables at the final follow-up before aggressive treatment. Results In total, 20 pediatric (37 eyes) and 132 adults (251 eyes) patients were eligible for this study. The mean follow-up time was 2.98 years. Male predominance was observed in both groups. Both groups had similar clinical characteristics and optical variables at the initial diagnosis. Pediatric patients progressed significantly more rapidly in refractive errors, including spheres and cylinders, spherical equivalence, steep K, and flat K during the follow-up. However, significant change between the two study groups was only seen in sphere refractive error spherical equivalence. Conclusion Pediatric patients had more rapidly progressive KC than adult patients, so early detection and frequent follow-up for prompt interventions are necessary for these patients.
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Ceratocone , Erros de Refração , Adulto , Criança , Substância Própria , Topografia da Córnea/métodos , Reagentes de Ligações Cruzadas , Feminino , Seguimentos , Humanos , Ceratocone/diagnóstico , Ceratocone/tratamento farmacológico , Ceratocone/epidemiologia , Masculino , Fármacos Fotossensibilizantes/uso terapêutico , Refração Ocular , Erros de Refração/tratamento farmacológico , Estudos RetrospectivosRESUMO
PURPOSE: To evaluate the 2-year efficacy and safety of micropulse transscleral cyclophotocoagulation (MP-TSCPC) in Taiwanese patients with glaucoma. METHODS: We included the patients who received standardized MP-TSCPC with follow-up examinations on a regular basis for 24 months. Treatment success was defined as the attainment of a postoperative intraocular pressure (IOP) between 6 and 21 mmHg or a ≥ 20% reduction in IOP from baseline without an increase in glaucoma medications. RESULTS: A total of 60 eyes from 56 patients who underwent MP-TSCPC for refractory glaucoma were included. The median age at MP-TSCPC intervention was 58.9 ± 12.4 years. The percentage of treatment success was 88.3% at 3 months, 83.3% at 6 months, 78.3% at 12 months, and 75.0% at 24 months. The mean baseline IOP prior to MP-TSCPC was 34 ± 11.9 mmHg (range 14-56 mmHg). The mean postoperative IOP decreased to 20.9 ± 10.0 mmHg, 18.0 ± 7.8 mmHg, 17.5 ± 6.4 mmHg, and 18.2 ± 7.1 mmHg after 3 months, 6 months, 12 months, and 24 months, respectively, in successful cases. The mean number of glaucoma medications at baseline was 3.8 ± 0.2, and the mean numbers of glaucoma medications at postoperative months 3, 6, 12, and 24 were 2.6 ± 0.7, 2.8 ± 0.6, 2.5 ± 1.4 and 2.6 ± 1.4, respectively, in successful cases. Younger age and prior CW-TSCPC significantly contributed to surgical failure in the multivariate model. Complications after MP-TSCPC included mild anterior chamber inflammation, conjunctival hemorrhage, hypotony, and mydriasis, and all subsided after treatment. None of the eyes developed vitreous hemorrhage, cystoid macular edema, or phthisis bulbi in the late postoperative period. CONCLUSIONS: This study demonstrated that younger age and prior CW-TSCPC were risk factors for MP-TSCPC failure within 2 years. MP-TSCPC might be safe and effective for refractory glaucoma patients with maximal antiglaucoma medications.
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Fotocoagulação a Laser , Lasers Semicondutores , Corpo Ciliar/cirurgia , Humanos , Pressão Intraocular , Lasers Semicondutores/uso terapêutico , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento , Acuidade VisualRESUMO
PURPOSE: The aim of this study was to determine the sociodemographic and risk factors for keratoconus (KC) patients with a nationwide Asian database. DESIGN: Population-based matched case-control study. METHODS: We performed a secondary data analysis of the Taiwan National Health Insurance Research Database (NHIRD). Cases were patients with newly diagnosed KC in 1998-2015. Controls were patients without KC and matched 4:1 with the KC cases by age, sex, and index date. Comorbidities diagnosed before KC included diabetes mellitus (DM), asthma, allergic rhinitis, mitral valve prolapse, collagen vascular disease, aortic aneurysm, Down syndrome, sleep apnea, depression, hyperlipidemia, astigmatism, and myopia. Conditional logistic regression with forward selection were used to obtain risk factors for KC. RESULTS: A total of 5,055 patients with KC were matched with 20,220 controls. The average age at KC first diagnosis was 29.76 years. Individuals who lived in suburban and rural area had lower odds ratio of KC (adjusted odds ratio [OR] 0.86, 95% confidence interval [CI] 0.80-0.94; and 0.73, 95% CI 0.67-0.79; respectively) when comparing with those who lived in urban area. Multivariate analysis revealed that Down syndrome, astigmatism, myopia, allergic rhinitis, and asthma were positively associated with KC with adjusted odds ratios (adjusted OR 8.69, 95% CI 3.74-20.19; 6.23, 95% CI 5.35-7.24; 2.99, 95% CI 2.70-3.32; 1.22, 95% CI 1.14-1.32; and 1.18, 95% CI 1.07-1.30, respectively). On the other hand, hyperlipidemia, depression, and DM (uncomplicated and complicated) were negatively associated with KC (adjusted OR 0.67, 95% CI 0.59-0.77; 0.58, 95% CI 0.48-0.71; 0.77, 95% CI 0.64-0.93; and 0.61, 95% CI 0.44-0.86, respectively). CONCLUSIONS: Our study found that patients with hyperlipidemia, depression, or DM were less likely to have KC, and patients with asthma, allergic rhinitis, astigmatism, myopia, or Down syndrome had higher odds ratio of KC.
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Ceratocone/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Asma/epidemiologia , Astigmatismo/epidemiologia , Estudos de Casos e Controles , Criança , Bases de Dados Factuais , Síndrome de Down/epidemiologia , Feminino , Humanos , Ceratocone/diagnóstico , Masculino , Pessoa de Meia-Idade , Miopia/epidemiologia , Razão de Chances , Estudos Retrospectivos , Rinite Alérgica/epidemiologia , Fatores de Risco , População Rural/estatística & dados numéricos , Fatores Socioeconômicos , Taiwan/epidemiologia , População Urbana/estatística & dados numéricos , Adulto JovemRESUMO
Molecular models have enabled understanding of biological structures and functions and allowed design of novel macro-molecules. Graphical user interfaces (GUIs) in molecular modeling are generally focused on atomic representations, but, especially for proteins, do not usually address designs of complex and large architectures, from nanometers to microns. Therefore, we have developed Elfin UI as a Blender add-on for the interactive design of large protein architectures with custom shapes. Elfin UI relies on compatible building blocks to design single- and multiple-chain protein structures. The software can be used: (1) as an interactive environment to explore building blocks combinations; and (2) as a computer aided design (CAD) tool to define target shapes that guide automated design. Elfin UI allows users to rapidly build new protein shapes, without the need to focus on amino acid sequence, and aims to make design of proteins and protein-based materials intuitive and accessible to researchers and members of the general public with limited expertise in protein engineering.
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BACKGROUND AND OBJECTIVE: To investigate clinical features and surgical outcomes of vitrectomy in posterior or combined persistent fetal vasculature (PFV) in an Asian pediatric population. PATIENTS AND METHODS: This study was a retrospective, noncomparative, interventional case series relating the surgical outcome of PFV. Eyes that underwent pars plicata vitrectomy and/or lensectomy for posterior or combined PFV between 2006 and 2015 were included. The main outcome measures were the anatomic and functional results as well as the complications after the vitrectomy with or without lensectomy. RESULTS: A total of 25 eyes of 18 patients younger than 8 years of age were included in the study. The mean age of the patients receiving first pars plicata vitrectomy and/or lensectomy was 15.2 months ± 21.7 months (range: 1 month to 83 months). Postoperatively, successful anatomic correction in the posterior segment was observed in 20 eyes (80%). In addition, 19 of the 25 eyes (76%) had visual acuity (VA) better than 20/4000, and the mean logMAR VA of these 19 eyes was 1.74 (range: 0.48 to 2.30). The mean change of axial length of the eyes receiving surgery was 0.7 mm ± 1.4 mm (range: -1.0 mm to 2.4 mm; P = .18). None of the patients ended up with phthisis or glaucoma. CONCLUSIONS: This study suggests that vitrectomy and/or lensectomy in patients with posterior or combined PFV with macular involvement may result in an acceptable anatomical outcome; however, the functional outcome remained poor despite surgical intervention in these patients. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:377-384.].
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Vítreo Primário Hiperplásico Persistente/cirurgia , Acuidade Visual/fisiologia , Vitrectomia/estatística & dados numéricos , Povo Asiático , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Vítreo Primário Hiperplásico Persistente/fisiopatologia , Complicações Pós-Operatórias , Estudos Retrospectivos , Vitrectomia/métodosRESUMO
The need for screening for retinopathy in patients with type 1 diabetes mellitus (T1DM) has been emphasised, but diagnostic delays were reported when screening was done at fixed intervals. To establish an individualised risk-prediction model to assist screening non-proliferative diabetic retinopathy (NPDR) in T1DM, we performed a retrospective cohort study enrolling participants in the Chang Gung Juvenile Diabetes Eye Study. There were 413 patients with 12 381 records analysed from 2005 to 2015. A time-dependent Cox proportional hazard analysis was used to evaluate the risks of NPDR development and a nomogram with risk-stratification indicators was established based on the results. During 97 months of follow-up, 43 of 413 patients (10.4%) developed NPDR. Male sex (HR: 0.4, 95% CI: 0.19-0.85), age 5-14 years at onset of T1DM (6.38, 2.41-16.87), duration of diabetes (1.57, 1.41-1.75), and hemoglobin A1c level (1.56, 1.35-1.80) were independently associated with NPDR. Using the nomogram offers a quick method in the clinical setting to interpret the risk of NPDR development. Based on its weighting, each of the independent factors is allocated a score, and the total points indicate the probabilities of NPDR occurring within 6 months, 1 year, and 3 years.
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Técnicas de Apoio para a Decisão , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/metabolismo , Adolescente , Idade de Início , Povo Asiático , Glicemia/análise , Criança , Pré-Escolar , Estudos de Coortes , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/metabolismo , Retinopatia Diabética/fisiopatologia , Progressão da Doença , Feminino , Hemoglobinas Glicadas/análise , Humanos , Masculino , Programas de Rastreamento , Nomogramas , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de RiscoRESUMO
Computational protein design methods have enabled the design of novel protein structures, but they are often still limited to small proteins and symmetric systems. To expand the size of designable proteins while controlling the overall structure, we developed Elfin, a genetic algorithm for the design of novel proteins with custom shapes using structural building blocks derived from experimentally verified repeat proteins. By combining building blocks with compatible interfaces, it is possible to rapidly build non-symmetric large structures (>1000 amino acids) that match three-dimensional geometric descriptions provided by the user. A run time of about 20min on a laptop computer for a 3000 amino acid structure makes Elfin accessible to users with limited computational resources. Protein structures with controlled geometry will allow the systematic study of the effect of spatial arrangement of enzymes and signaling molecules, and provide new scaffolds for functional nanomaterials.
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Algoritmos , Engenharia de Proteínas/métodos , Proteínas/química , Desenho Assistido por Computador , Bases de Dados de Proteínas , Modelos Moleculares , Conformação Proteica , Sequências Repetitivas de Aminoácidos , Espalhamento a Baixo Ângulo , Difração de Raios XRESUMO
PURPOSE: Mild traumatic brain injury (mTBI) is a major public health concern. The apolipoprotein E (APOE) gene contains three polymorphisms, and the APOE4 polymorphism may affect several physiological states, such as the recovery from mTBI as well as sleep. This study aims to investigate the association between APOE4 with the recovery of sleep disturbance after mTBI. METHODS: From May 2012 to Aug 2015, 189 mTBI patients completed baseline (1st week post-mTBI) and follow-up (6th week post-mTBI) sleep assessments that involved using the Pittsburgh Sleep Quality Index (PSQI). APOE genotypes were determined by sequencing the products of polymerase chain reaction from genomic DNA. Statistical analyses were performed using the Wilcox signed-rank or chi-square test. RESULTS: Thirty-five (18.5%) participants were APOE4 carriers. At baseline, the demographic data and the severity of sleep disturbance were similar in both groups. APOE4 carriers demonstrated significant improvement in the overall PSQI score (8.34±3.9 at baseline and 7.43±3.99 at follow-up, p = 0.05) and scores of several PSQI subscales, including sleep disturbance, sleep latency, daytime dysfunction caused by sleepiness, and overall sleep quality, which was similar to APOE4 noncarriers. CONCLUSION: APOE4 is not associated with the recovery of sleep disturbance after mTBI.
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Apolipoproteína E4 , Concussão Encefálica , Transtornos do Sono-Vigília , Alelos , Apolipoproteína E4/genética , Concussão Encefálica/complicações , Concussão Encefálica/genética , Humanos , Polimorfismo Genético , Transtornos do Sono-Vigília/genéticaRESUMO
In recent years, interventional cardiologists have discussed over a new clinical issue called longitudinal stent compression (LSC), a failure mode not previously observed in coronary stents. This phenomenon occurs when the physician attempts to cross a deployed stent with a second device, causing the stent to dramatically shorten when two devices are accidentally entangled. While this phenomenon has been observed with a number of stent platforms, it seems more common with the Element stent. In this paper, a computational LSC model using finite element analysis was developed. A systematic investigation was conducted in attempts to quantify individual contribution of the stent design pattern, connector number, design parameter, and connector location on LSC. Computational simulations were performed on two representative coronary stents resembling Element and Endeavor for comparison. Simulation results show that the connector number plays the most significant role in LSC. The LSC could be easily tripled or quadrupled for the same stent design simply by increasing the connector number from two to three. The design pattern and design parameter play a secondary role in LSC, with the LSC improved by up to 30 and 65 %, respectively. It was also found that the LSC could be doubled for the Element stent simply by rearranging its connector location. This small design tweak could help improve the current Element LSC significantly, while still maintaining the majority of its excellent deliverability. These findings could provide great insights into this new clinical issue and help optimize future stent design to reduce the associated risk involved in LSC.
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Desenho de Equipamento , Pressão , Stents , Cardiologia , Simulação por Computador , Análise de Elementos Finitos , Humanos , Estresse MecânicoRESUMO
OBJECTIVES: The detailed course of mental disorders at the acute and subacute stages of mild traumatic brain injury (mTBI), especially with regard to recovery from sleep disturbances, has not been well characterised. The aim of this study was to determine the course of depression, anxiety and sleep disturbance, following an mTBI. SETTING: We recruited patients with mTBI from three university hospitals in Taipei and healthy participants as control group for this study. PARTICIPANTS: 100 patients with mTBI (35 men) who were older than 20 years, with a Glasgow Coma Scale score of 13-15 and loss of consciousness for <30 min, completed the baseline and 6-week follow-up assessments. 137 controls (47 men) without TBI were recruited in the study. None of the participants had a history of cerebrovascular disease, mental retardation, previous TBI, epilepsy or severe systemic medical illness. PRIMARY OUTCOME MEASURES: The Beck Anxiety Inventory (BAI), the Beck Depression Inventory II (BDI), the Epworth Sleepiness Scale (ESS) and the Pittsburgh Sleep Quality Index (PSQI) were assessed for the patients with mTBI at baseline and 6 weeks after mTBI and for the controls. RESULTS: The ESS scores were not significantly different between the mTBI at baseline or at 6 weeks after mTBI and controls. Although the BAI, BDI and PSQI scores of the mTBI group were significantly different than those of the control group at baseline, all had improved significantly 6 weeks later. However, only the PSQI score improved to a level that was not significantly different from that of the control group. CONCLUSIONS: Daytime sleepiness is not affected by mTBI. However, mTBI causes depression and anxiety and diminished sleep quality. Although all these conditions improve significantly within 6 weeks post-mTBI, only sleep quality improves to a pre-mTBI level. Thus, recovery from mTBI-induced sleep disturbance occurs more rapidly than that of mTBI-induced depression and anxiety.
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Ansiedade/etiologia , Lesões Encefálicas/complicações , Depressão/etiologia , Transtornos do Sono-Vigília/etiologia , Adulto , Feminino , Seguimentos , Humanos , Masculino , Estudos Prospectivos , Fatores de TempoRESUMO
Longitudinal stent compression (LSC) is a new failure mode not previously observed in coronary stents. This phenomenon occurs when the physician tries to cross the deployed stent with other devices. While this phenomenon has been observed with a number of stent designs, it seems more common with the Element stent. A computational LSC model using finite element analysis was developed. Computational simulations were performed on two representative coronary stents in the current market resembling Element and Endeavor in attempts to quantify individual contribution of the stent design pattern and connector number on LSC. Simulation results show that the connector number plays the most significant role in the development of the LSC issue. The LSC could be easily tripled for the Element stent simply by increasing the connector number from two to three. The stent design pattern plays a secondary role in LSC. The LSC could be improved by up to 30% when the design pattern changes from the offset peak-to-peak design (Element) to the peak-to-peak design (Endeavor). Conclusions obtained from this paper may help clinical stent selection and future stent design optimization to reduce the risk associated with longitudinal stent compression.
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Cardiologia/instrumentação , Vasos Coronários/patologia , Falha de Prótese , Stents , Simulação por Computador , Desenho de Equipamento , Análise de Falha de Equipamento , Análise de Elementos Finitos , Humanos , Desenho de Prótese , Estresse MecânicoRESUMO
Infections due to Prototheca spp. are ubiquitous in nature, occurring in both immunocompetent and immunocompromised patients. The study cohort consisted of 14 cases of Prototheca algaemia reported over the past 5 decades and 2 recent cases from study hospitals. Prototheca wickerhamii was the most common species. The overall mortality rate was 62.5%. Prototheca algaemia, a healthcare-associated infection, was observed in immunocompromised patients and was associated with a poor prognosis.
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Infecções Oportunistas/etiologia , Infecções Oportunistas/imunologia , Prototheca/isolamento & purificação , Sepse/etiologia , Sepse/imunologia , Adulto , Idoso , Criança , Estudos de Coortes , Feminino , Humanos , Hospedeiro Imunocomprometido , Masculino , Pessoa de Meia-Idade , Infecções Oportunistas/diagnóstico , Sepse/diagnósticoRESUMO
Urinary 3-hydroxy-benzo[a]pyrene (3-OHBaP) is considered as an exposure marker for assessing carcinogenic risks as it is a metabolite of benzo[a]pyrene (BaP). A controlled human study was conducted to examine the kinetics of urinary 3-OHBaP after consuming charcoal-barbecued meat. Two feeding experiments were performed, with meat doses of 15 and 30 g/kg (experiments 1 and 2, respectively). All voided urine over 7 days was collected and analyzed. The background urinary 3-OHBaP concentration was 0.002-0.085 ng/g creatinine, with large inter-individual (80-100%) and intra-individual of (90-100%) variations. The background amount of 3-OHBaP excreted by the current subjects was 40-50 pg/day. The amounts of urinary 3-OHBaP excreted within 12 h post-exposure increased significantly (P < 0.05) from background only in experiment 1. The proportion of the administered BaP dose that was excreted as urinary 3-OHBaP within 12 h post-exposure was 0.006 and 0.0012% in experiments 1 and 2, respectively. The excretion ratio declined as the dose increased. Urinary 3-OHBaP can be used to assess dietary exposure to BaP, but it may be not suitable for low-dose scenarios because of the low urinary excretion proportion and high variability of the background.
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Benzo(a)pireno/metabolismo , Benzopirenos/análise , Carcinógenos/análise , Culinária/métodos , Carne , Adulto , Benzo(a)pireno/administração & dosagem , Carcinógenos/metabolismo , Carvão Vegetal , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Adulto JovemRESUMO
We report the direct electrochemical and electrocatalytic properties of myoglobin (MB) on a multi-walled carbon nanotube/ciprofloxacin (MWCNT/CF) film-modified electrode. A highly homogeneous MWCNT thin-film was prepared on an electrode surface using ciprofloxacin (CF) as a dispersing agent. MB was then electrochemically deposited onto the MWCNT/CF-modified electrode. The MB/MWCNT/CF film was characterized by scanning electron microscopy and UV-visible spectroscopy (UV-vis). UV-vis spectra confirmed that MB retained its original state on the MWCNT/CF film. Direct electrochemical properties of MB on the MWCNT/CF film were investigated by cyclic voltammetry. The formal potential and electron transfer rate constant were evaluated in pH 7.2 buffer solution as -0.327V and 300s(-1), respectively. In addition, the MB/MWCNT/CF-modified electrode showed excellent electrocatalytic properties for the reduction of hydrogen peroxide (H(2)O(2)). The MB/MWCNT/CF-modified electrode was used for the detection of H(2)O(2) at concentrations from 1×10(-6)M to 7×10(-4)M in pH 7.2 buffer solution. Overall, the MB/MWCNT/CF-modified electrode was very stable and has potential for development as a H(2)O(2) sensor.
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Ciprofloxacina/farmacologia , Eletroquímica/métodos , Mioglobina/química , Nanotecnologia/métodos , Nanotubos de Carbono/química , Animais , Anti-Infecciosos/farmacologia , Técnicas Biossensoriais , Catálise , Cavalos , Peróxido de Hidrogênio/química , Concentração de Íons de Hidrogênio , Cinética , Modelos Químicos , Miocárdio/metabolismo , Espectrofotometria Ultravioleta/métodosRESUMO
Although urinary 1-hydroxypyrene (1-OHP) is the most relevant parameter for assessing exposure to polycyclic aromatic hydrocarbons, the inability to further elucidate the intra- and inter-individual variability, specificity and kinetics makes it difficult to enhance its value as an exposure predictor. Therefore, this human control study examined the excretion kinetics of urinary 1-OHP after consuming barbecued meat. Two feeding experiments were conducted, with doses of 15 and 30 g of barbecued meat per kg of body weight for experiments 1 and 2, respectively. All voided urine was collected for 7 days and analyzed for 1-OHP. In both experiments, the amounts of urinary 1-OHP excreted was significantly increased (P < 0.05) at 12 h post exposure but not at 12-24 h post exposure. Mean percentages of administered pyrene doses excreted as urinary 1-OHP at 0-12 h and 12-24 h post exposure were 3.80 and 0.61% in experiment 1 and 1.66 and 0.38% in experiment 2. Excretion ratio was inversely related to dose. A pattern of diurnal fluctuation (P < 0.05) in 1-OHP excretions was also identified. That is, 1-OHP excretions were smaller in the first half of the day (~0:00-12:00) than in the last half of the day (~12:00-24:00). This study demonstrated that, even at large dietary doses, most of the total urinary excretion of 1-OHP occurs within 12 h. Thus, subjects of occupational or environmental studies need only recall their diets for the current or previous day to diminish the influence from dietary pyrene.
Assuntos
Exposição Ambiental/análise , Poluentes Ambientais/urina , Pirenos/metabolismo , Adulto , Atmosfera/química , Biomarcadores/urina , Feminino , Fluorenos/análise , Humanos , Masculino , Carne/análise , Hidrocarbonetos Policíclicos Aromáticos/análise , Hidrocarbonetos Policíclicos Aromáticos/urina , Pirenos/análise , Adulto JovemRESUMO
In this study, we show that acid yellow 9 (4-amino-1-1'-azobenzene-3,4'-disulfonicacid, AY) is a good stabilizing agent for multi-walled carbon nanotubes (MWCNTs). MWCNTs dispersed in AY solution was remained stable about three months and even remained stable after centrifugation at 10,000 rpm for 30 min. Using MWCNTs/AY dispersion, thin-films were prepared on indium tin oxide coated glass electrode and glassy carbon electrodes. Further, dried films of MWCNTs/AY were subjected to electropolymerization in 0.1M H(2)SO(4) solution. Adsorbed AY molecules on MWCNTs get polymerized and they yield a polymer-MWCNTs nanocomposite film on electrode surface which is found to be electrochemically active in wide pH range (1-11). Characterization studies were performed using cyclic voltammetry and SEM. These studies are supported that hybrid material PAY/MWCNTs was obtained. Moreover, newly synthesized PAY-MWCNTs composite film showed excellent electrocatalytic activity towards oxidation of dopamine (DA) and ascorbic acid (AA) with high sensitivity in physiological pH. Linear sweep voltammetry was employed to the determination of DA in the presence of AA in the range of 2x10(-7) to 1.4x10(-6) M. Amperometry was employed to determination of AA at 0.0 V in the range from 1x10(-6) to 5.6x10(-5) M, and DA, uric acid are not interfered on the steady-state current of AA. In addition, real samples such as dopamine injection and AA spiked into human urine were analyzed using PAY/MWCNTs composite modified electrode and satisfactory results were obtained.
Assuntos
Ácido Ascórbico/análise , Técnicas Biossensoriais/métodos , Dopamina/análise , Nanotubos de Carbono , Compostos Azo , Técnicas Biossensoriais/instrumentação , Humanos , Microscopia Eletrônica de Varredura , Nanotubos de Carbono/ultraestrutura , Oxirredução , PolímerosRESUMO
Urinary 8-hydroxydeoxyguanosine (8-OHdG) is considered a noninvasive marker for oxidative stress and also a marker of carcinogenic potential for compounds such as polycyclic aromatic hydrocarbons (PAHs). Although human studies have investigated urinary 8-OHdG concentrations in PAH-exposed workers and the general population, the background level and excretion kinetics of urinary 8-OHdG in humans remain unclear. Two feeding experiments (consumption of barbecued meat of 15 and 30 g/kg for Experiments 1 and 2, respectively) were conducted to examine the excretion characteristics of urinary 8-OHdG. All urine voided over 7 days was collected, but only first morning (approximately 8 A.M.) and last afternoon (approximately 5 P.M.) samples were analyzed for 8-OHdG. Mean background urinary 8-OHdG concentration was 4.76 microg/g creatinine. Statistically significant increases (P < 0.05) in urinary 8-OHdG concentration were observed on the afternoon of the 3rd and 2nd days after barbecued meat consumption for Experiments 1 and 2, respectively. A pattern of diurnal fluctuation (P < 0.05) in 8-OHdG excretion rate was evident, in that the excretion of 8-OHdG was faster during the night than during the day. Additionally, significant (P < 0.05) and strong (r > 0.6) correlations were found between urinary 8-OHdG measured 2-3 days after exposure to barbecued meat, and 1-hydroxypyrene (1-OHP) and 3-hydroxy-benzo[a]pyrene (3-OHBaP) concentrations measured within a half day after such exposure. The current results demonstrate a lag in excretion of urinary 8-OHdG relative to 1-OHP and 3-PHBaP after dietary PAH exposure. These relationships highlight the importance of sampling time when assessing PAH-related DNA lesions through urinary 8-OHdG.