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Corona virus disease 2019 (COVID-19) pandemic, sparked by the emergence of a novel coronavirus in early 2020, has prompted a surge in published articles. This study aims to systematically analyse the characteristics and trends of impactful research in the field. The 100 most-cited publications associated with COVID-19 were identified by two independent reviewers using the 'Web of Science' database across all available journals up to the year 2023. Data collected include country, citation count, subject, level of evidence (using Oxford Centre for Evidence-Based Medicine System 2011), impact factor, funding, and study design. We identified 394 038 publications, and the 100 most-cited publications were ranked. These were cited by a total of 283 034 articles (median citation = 767), median impact factor of 66.9 and 72 articles with fundings. China (n = 44), USA (n = 19), and UK (n = 13) were the three highest contributors (n = 220 505). Most articles were level 5 evidence (n = 48), followed by level 3 (n = 28), 4 (n = 14), 2 (n = 7), and 1 (n = 3). The main subjects were mechanism of action and structures of SARS-CoV-2 virus (n = 18) and impact of COVID-19 on public health (n = 18). Publications in 2022 and 2023 predominantly focused on the impact of COVID-19. Majority of the highly cited studies were of low-to-moderate quality, with only 10 consisting of randomized controlled trials or systematic reviews with or without meta-analysis. These findings reflect a growing interest in understanding the impact of COVID-19 pandemic on public and mental health. This analysis found the potential for future double-blinded randomized controlled trials to validate existing findings.
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Bibliometria , COVID-19 , SARS-CoV-2 , COVID-19/epidemiologia , Humanos , Fator de Impacto de Revistas , PandemiasRESUMO
Thick electrode with high-areal-capacity is a practical and promising strategy to increase the energy density of batteries, but development toward thick electrode is limited by the electrochemical performance, mechanical properties, and manufacturing approaches. In this work, we overcome these limitations and report an ultrathick electrode structure, called fiber-aligned thick or FAT electrode, which offers a novel electrode design and a scalable manufacturing strategy for high-areal-capacity battery electrodes. The FAT electrode uses aligned carbon fibers to construct a through-thickness fiber-aligned electrode structure with features of high electrode material loading, low tortuosity, high electrical and thermal conductivity, and good compression property. The low tortuosity of FAT electrode enables fast electrolyte infusion and rapid electron/ion transport, exhibiting a higher capacity retention and lower charge transfer resistance than conventional slurry-casted thick electrode design.
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This study applied RNA-seq technology to discover reproduction-related genes and pathways in female topmouth culter brain (including pituitary) and ovarian tissues. In functional analysis, 2479 and 2605 unigenes in the brain and ovary tissue were assigned to the "reproductive process" subcategory in addition to the 2660 and 2845 unigenes assigned to the "reproduction" subcategory. Twenty-three complete cDNA sequences were identified through the different gene expression (DGE) approach from five reproduction-related pathways (MAPK signaling pathway, neuroactive ligand-receptor interaction pathway, gonadotropin-releasing hormone signaling pathway, oocyte meiosis pathway, and steroid biosynthesis pathway). The expression levels of 16 candidate genes using qPCR in this study were in accordance with the results of transcriptome analysis. In addition, the expression levels of the FSH, 3ß-HSD, PGR, and NPYR genes in malformed gynogenetic ovaries were considerably low, which was consistent with the progress of oocytogenesis in the ovaries of topmouth culter. The high expression of these four genes in the ovaries of normal topmouth culter suggested they might involve in the preparation for the shift of oogenesis to ovulation. Hence, our work identified a set of annotated gene products that are candidate factors affecting reproduction in the topmouth culter H-P-G axis. These results could be essential for further research in functional genomics and genetic editing for topmouth culter reproduction.
Assuntos
Cyprinidae/genética , Ovário/metabolismo , Reprodução/genética , Animais , Encéfalo/metabolismo , Cyprinidae/anormalidades , Feminino , Proteínas de Peixes/genética , Sistema Hipotálamo-Hipofisário , Ovário/anormalidades , Polimorfismo de Nucleotídeo Único , TranscriptomaRESUMO
OBJECTIVE: To explore the effects of Hongjing-1 Recipe (HJ-1) on erectile function and the expression of the gap junction protein Connexin43 (Cx43) in the penile tissue in male rats with bilateral cavernous nerve injury (BCNI). METHODS: Fifty male SD rats were randomly divided into five groups of an equal number: sham operation, BCNI model control, and low-, medium- and high-dose HJ-1. The BCNI model was made in the latter four groups by clamping the bilateral cavernous nerves with hemostatic forceps. Three days after modeling, the rats in the sham operation and BCNI model control groups were treated intragastrically with pure water and those in the low-, medium- and high-dose HJ-1 groups with HJ-1 at 2.835, 5.67 and 11.34 g/kg/d, respectively, all for 28 successive days. Then, the animals were subjected to intracavernous pressure (ICP) measurement for evaluation of their erectile function and immunofluorescence staining and Western blot for determination of the Cx43 level in the penile tissue. RESULTS: The BCNI model controls, compared with the rats in the sham operation group, showed a dramatically decreased ratio of maximum ICP to mean arterial pressure (mICP/MAP) (0.40 ± 0.04 vs 0.83 ± 0.10, P < 0.01) and that of total ICP to MAP (tICP/MAP) (21.89 ± 2.16 vs 50.27 ± 4.45, P < 0.01), as well as a down-regulated expression of Cx43 in the penile tissue (P < 0.01). In comparison with the rats in the BCNI model control group, those in the medium- and high-dose HJ-1 groups exhibited significantly increased ratios of mICP/MAP (0.54 ± 0.05, P < 0.05; 0.61 ± 0.06, P < 0.01) and tICP/MAP (31.20 ± 3.85, P < 0.01; 37.82 ± 4.17, P < 0.01) and up-regulated expression of Cx43 (P<0.05 and P<0.01). CONCLUSIONS: Hongjing-1 Recipe can effectively improve ED in rats with bilateral cavernous nerve injury, which may be attributed to its effect of maintaining the expression level of the gap junction protein Cx43 in the penile tissue.
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Conexina 43 , Medicamentos de Ervas Chinesas/uso terapêutico , Pênis/metabolismo , Traumatismos dos Nervos Periféricos/tratamento farmacológico , Animais , Conexina 43/metabolismo , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
AIM: To study the prophylactic effect of recombinant Lactococcus lactis (rLl) harbouring Ara h 2.02 peanut allergen, in sensitized and challenged mice. METHODS AND RESULTS: Ara h 2.02 cDNA was cloned into pNZ8048 for heterologous expression in L. lactis. The purified recombinant allergen showed IgE binding comparable with native Ara h 2. Balb/c mice were fed with either recombinant (rLl), nonrecombinant L. lactis (Ll) or NaHCO3 (Sham) prior to sensitization and challenged with rAra h 2.02, whereas the baseline group was only fed with Ll. Allergen-specific immunoglobulin and splenocyte cytokines responses were determined for each mouse. Mice fed with either Ll or rLl showed significant alleviation of IgE and IgG1 compared to the Sham group. Despite no significant decrease in Th2 (IL-4, IL-13, IL-6) or increase in Th1 (IFN-γ) cytokines, both groups showed lower IL-10 level, while the IL-4 : IFN-γ ratio was significantly lower for rLl compared to Ll group. CONCLUSIONS: Oral administration of rLl harbouring Ara h 2.02 demonstrated alleviation of Th2-associated responses in allergen-challenged mice and a possible added allergen-specific prophylactic effect. SIGNIFICANCE AND IMPACT OF THE STUDY: Ara h 2.02 coupled with the intrinsic properties of probiotic L. lactis as a delivery vehicle can be explored for the development of a commercially scalable vaccine.
Assuntos
Albuminas 2S de Plantas/imunologia , Antígenos de Plantas/imunologia , Lactococcus lactis/genética , Lactococcus lactis/imunologia , Hipersensibilidade a Amendoim/prevenção & controle , Albuminas 2S de Plantas/genética , Administração Oral , Animais , Antígenos de Plantas/genética , Citocinas/imunologia , Feminino , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Hipersensibilidade a Amendoim/imunologia , Probióticos/administração & dosagemRESUMO
Objective: To explore the efficacy and safety of the covered airway stent loaded with (125)I seeds for the treatment of tracheal adenoid cystic carcinoma (TACC). Methods: We retrospectively reviewed the clinical data from 8 patients with TACC who had received placement of the covered stent loaded with (125)I seeds between December 2014 and July 2017 in the endoscopic center of the Second Affiliated Hospital of Xiamen Medical College. We compared the difference in the dyspnea index, the diameter of the airway lumen, and the lesion surrounding the airway wall before and after treatment. The complications were also recorded during follow-up. Results: Eight patients underwent successful placement of a total of 11 radioactive stents (2 straight-type stents, 2 L-shape stents, and 7 Y-shape stents, all loaded a total of 243 radioactive particles). Displacement of stents took place within 2 weeks in 2 patients, who were managed with re-stenting and fixation. No further displacement occurred during follow-up. The median time to stent removal was 2.9(interquartile range: 2.3,3.0) months. After stent placement, the dyspnea index was significantly decreased compared with pre-treatment level (mean: 0.1 vs. 3.4, t=8.881, P<0.001). Bronchoscopic re-assessment showed that the residual tumor within the airway was detected in only one patient and that the tumor completely disappeared in the remaining 7 patients. Treatment with stents loaded with radioactive particles yielded smooth and pale airway mucosa with formation of partial scar formation. Chest computed tomography re-assessment demonstrated significantly larger luminal diameter than that before treatment (mean: 13.1 mm vs. 3.3 mm, t=-7.839, P<0.001). The airway wall thickness was notably reduced after treatment (mean: 4.3 mm vs. 14.4 mm, t=7.620, P<0.001). The lesions surrounding the airway wall completely disappeared in 7 patients and decreased for more than 50% in a single patient. The median duration of follow-up was 28.0(interquartile range: 24.8,31.5) months. Recurrence of tumor was documented in a single case within 2 years. Six patients did not experience recurrence within the 2-year follow-up period. No death or severe complications were recorded during follow-up. Conclusion: The (125)I radioactive stent is effective for dilating the stenotic airway and ameliorating the symptoms, and thus might be an effective and safe method for the treatment of TACC. Further studies that explore the efficacy of stents loaded with (125)I particles are needed.
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Carcinoma Adenoide Cístico/patologia , Carcinoma Adenoide Cístico/cirurgia , Radioisótopos do Iodo , Stents , Neoplasias da Traqueia/patologia , Neoplasias da Traqueia/cirurgia , Estenose Traqueal/terapia , Obstrução das Vias Respiratórias/etiologia , Carcinoma Adenoide Cístico/complicações , Humanos , Recidiva Local de Neoplasia , Estudos Retrospectivos , Neoplasias da Traqueia/complicações , Resultado do TratamentoRESUMO
A lectin gene from the Tiger Milk Mushroom Lignosus rhinocerus TM02® was successfully cloned and expressed via vector pET28a in Escherichia coli BL21(DE3). The recombinant lectin, Rhinocelectin, with a predicted molecular mass of 22.8 kDa, was overexpressed in water-soluble form without signal peptide and purified via native affinity chromatography Ni-NTA agarose. Blast protein analysis indicated the lectin to be homologous to jacalin-related plant lectin. In its native form, Rhinocelectin exists as a homo-tetramer predicted with four chains of identical proteins consisting of 11 beta-sheet structures with only one alpha-helix structure. The antiproliferative activity of the Rhinocelectin against human cancer cell lines was concentration dependent and selective. The IC50 values against triple negative breast cancer cell lines MDA-MB-231 and breast cancer MCF-7 are 36.52 ± 13.55 µg mL-1 and 53.11 ± 22.30 µg mL-1 , respectively. Rhinocelectin is only mildly cytotoxic against the corresponding human nontumorigenic breast cell line 184B5 with IC50 value at 142.19 ± 36.34 µg mL-1 . The IC50 against human lung cancer cell line A549 cells is 46.14 ± 7.42 µg mL-1 while against nontumorigenic lung cell line NL20 is 41.33 ± 7.43 µg mL-1 . The standard anticancer drug, Doxorubicin exhibited IC50 values mostly below 1 µg mL-1 for the cell lines tested. Flow cytometry analysis showed the treated breast cancer cells were arrested at G0/G1 phase and apoptosis induced. Rhinocelectin agglutinated rat and rabbit erythrocytes at a minimal concentration of 3.125 µg mL-1 and 6.250 µg mL-1 , respectively.
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Proliferação de Células/efeitos dos fármacos , Lectinas/genética , Neoplasias/tratamento farmacológico , Polyporaceae/genética , Células A549 , Antineoplásicos/química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Clonagem Molecular , Regulação Fúngica da Expressão Gênica/efeitos dos fármacos , Humanos , Lectinas/química , Lectinas/farmacologia , Células MCF-7 , Neoplasias/patologia , Polyporaceae/químicaRESUMO
AIMS: To investigate the biofilm inhibitory activity of betacyanins from red pitahaya (Hylocereus polyrhizus) and red spinach (Amaranthus dubius) against Staphylococcus aureus and Pseudomonas aeruginosa biofilms. METHODS AND RESULTS: The pulp of red pitahaya and the leaves of red spinach were extracted using methanol followed by subfractionation to obtain betacyanin fraction. The anti-biofilm activity was examined using broth microdilution assay on polystyrene surfaces and expressed as minimum biofilm inhibitory concentration (MBIC). The betacyanin fraction from red spinach showed better anti-biofilm activity (MBIC: 0·313-1·25 mg ml-1 ) against five Staph. aureus strains while the betacyanin fraction from red pitahaya showed better anti-biofilm activity (MBIC: 0·313-0·625 mg ml-1 ) against four P. aeruginosa strains. Both betacyanin fraction significantly reduced hydrophobicity of Staph. aureus and P. aeruginosa strains. Numbers of Staph. aureus and P. aeruginosa attached to polystyrene were also reduced without affecting their cell viability. CONCLUSION: Betacyanins can act as anti-biofilm agents against the initial step of biofilm formation, particularly on a hydrophobic surface like polystyrene. SIGNIFICANCE AND IMPACT OF THE STUDY: This study is the first to investigate the use of betacyanin as a biofilm inhibitory agent. Betacyanin could potentially be used to reduce the risk of biofilm-associated infections.
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Amaranthus/química , Antibacterianos/farmacologia , Betacianinas/farmacologia , Biofilmes/efeitos dos fármacos , Cactaceae/química , Extratos Vegetais/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Antibacterianos/isolamento & purificação , Betacianinas/isolamento & purificação , Testes de Sensibilidade Microbiana , Extratos Vegetais/isolamento & purificação , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/fisiologia , Staphylococcus aureus/fisiologiaRESUMO
OBJECTIVE:: To determine the factors that influence the decision to transfer children in septic shock from level II to level I pediatric intensive care unit (PICU) care. DESIGN:: Interviews with level II PICU physicians in Michigan and Northwest Ohio. A hypothetical scenario of a 14-year-old boy in septic shock was presented. BASELINE:: 40 mL/kg fluid resuscitation, central venous and peripheral arterial access, and high-dose vasopressor infusions were provided. ESCALATION POINT:: After 2 hours. When the patient is in catecholamine-resistant shock and oliguric, invasive mechanical ventilation is initiated. MEASUREMENTS AND MAIN RESULTS:: All 19 eligible physicians participated. At baseline, respondents would assess measures of perfusion and hemodynamics: blood pressure (BP; 15 [79%]), lactate (12 [63%]), and central venous oxygen saturation (ScvO2; 10 [53%]). Poor clinical response was signified by low BP (11 [58%]), elevated lactate (9 [47%]), low urine output (8 [42%]), and low ScvO2 (6 [32%]). At the escalation point, 13 of 18 respondents felt there was <50% probability of clinical turnaround without escalating treatment, though only 3 (16%) would call to discuss transfer. Seven (37%) respondents would give more fluid, whereas 8 (42%) would use central venous pressure to guide fluid resuscitation. Ultimately, 15 (79%) respondents would transfer for extracorporeal membrane oxygenation (ECMO) or renal replacement therapy if there was no response to escalated care. Four (21%) respondents would not transfer the patient: 1 felt appropriate care could be provided in the level II PICU, 2 felt transfer was unconventional, and 1 was unaware ECMO could be provided in refractory septic shock. CONCLUSIONS:: Level II to level I PICU transfer of children with septic shock is triggered by perceived nonresponse to locally available therapies. Few referring physicians do not transfer children in refractory septic shock. This study provides new insight into decision-making that influences the interhospital transfer of children with septic shock.
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Tomada de Decisão Clínica , Unidades de Terapia Intensiva Pediátrica/organização & administração , Transferência de Pacientes , Choque Séptico/terapia , Adolescente , Cateterismo Venoso Central , Terapia Combinada , Oxigenação por Membrana Extracorpórea , Hidratação/métodos , Humanos , Masculino , Pesquisa Qualitativa , Terapia de Substituição Renal , Vasoconstritores/uso terapêuticoRESUMO
The present work characterizes the spatiotemporal variations of air pollution at four sites in Xi'an city. The investigations lasted for 1 year: January 1 through December 31, 2015. The concentrations of CO, NO2, O3, PM and SO2 were systematically monitored. The gray correlation analysis was used to correlate PM2.5 and gaseous pollutants. The formation mechanisms of sulfate and nitrate aerosols were discussed. Results clearly revealed severe air pollution by PM2.5, PM10 and NO2 at all four sites. Significant monthly variations were observed for PM2.5, PM10, SO2 and CO with the maximum values in December/January and minimum values in June/July. The O3 level showed an opposite trend. Spatially, high variations were observed for PM and some gaseous pollutants at individual sites. Gray correlation analysis revealed the significance of various major influencing factors on seasonal PM2.5 values at each site. In general, PM10, SO2 and NO2 affect the PM2.5 more than other pollutants. For a more efficient control of air pollution, a systematic spatial characterization of the seasonal variability of individual influencing factors is necessary.
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Poluentes Atmosféricos/análise , Gases/química , Material Particulado/análise , Poluição do Ar/análise , Cidades , Monitoramento Ambiental , Humanos , Óxidos de Nitrogênio/análise , Estações do AnoRESUMO
Delayed diagnosis is common in patients with pulmonary arterial hypertension (PAH). Right-sided heart catheterization, the gold standard for diagnosis, is invasive and cannot be applied for routine screening. Some biomarkers have been looked into; however, due to the lack of a clear pathological mechanism linking the marker to PAH, the search for an ideal one is still ongoing. Elastin is a significant structural constituent of blood vessels. Its synthesis involves cross-linking of monomers by 2 amino acids, desmosine and isodesmosine (D&I). Being extremely stable, elastin undergoes little metabolic turnover in healthy individuals resulting in very low levels of D&I amino acids in the human plasma, urine, or sputum. We hypothesized that in PAH patients, the elastin turnover is high; which in turn should result in elevated levels of D&I in plasma and urine. Using mass spectrometry, plasma and urine levels of D&I were measured in 20 consecutive patients with PAH confirmed by cardiac catheterization. The levels were compared with 13 healthy controls. The mean level of total plasma D&I in patients with PAH was 0.47 ng/mL and in controls was 0.19 ng/mL (P = 0.001). The mean levels of total D&I in the urine of PAH patients was 20.55 mg/g creatinine and in controls was 12.78 mg/g creatinine (P = 0.005). The mean level of free D&I in the urine of PAH patients was 10.34 mg/g creatinine and in controls was 2.52 mg/g creatinine (P < 0.001). This is the first study highlighting that the serum and urine D&I has a potential to be a novel screening biomarker for patients with PAH. It paves the way for larger studies to analyze its role in assessing for disease severity and response to treatment.
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Desmosina/análise , Elastina/metabolismo , Hipertensão Pulmonar Primária Familiar/sangue , Hipertensão Pulmonar Primária Familiar/urina , Isodesmosina/análise , Adulto , Idoso , Biomarcadores/análise , Cromatografia Líquida , Diagnóstico Tardio/prevenção & controle , Hipertensão Pulmonar Primária Familiar/diagnóstico , Feminino , Humanos , Masculino , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Projetos Piloto , Escarro/química , Espectrometria de Massas em TandemRESUMO
The use of biomacromolecular therapeutics has revolutionized disease treatment, but frequent injections are required owing to their short half-life in vivo. Thus there is a need for a drug delivery system that acts as a reservoir and releases the drug remotely "on demand". Here we demonstrate a simple light-triggered local drug delivery system through photo-thermal interactions of polymer-coated gold nanoparticles (AuNPs) inside an agarose hydrogel as therapeutic depot. Localized temperature increase induced by the visible light exposure caused reversible softening of the hydrogel matrix to release the pre-loaded therapeutics. The release profile can be adjusted by AuNPs and agarose concentrations, light intensity and exposure time. Importantly, the biological activity of the released bevacizumab was highly retained. In this study we demonstrate the potential application of this facile AuNPs/hydrogel system for ocular therapeutics delivery through its versatility to release multiple biologics, compatibility to ocular cells and spatiotemporal control using visible light.
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Sistemas de Liberação de Medicamentos , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Luz , Fotoquimioterapia , Proteínas/química , Ouro/química , Humanos , Nanopartículas Metálicas/química , Tamanho da Partícula , Polímeros/química , Propriedades de SuperfícieRESUMO
Understanding the mechanisms involved in cellular immune responses against control of human immunodeficiency virus (HIV) infection is key to development of effective immunotherapeutic strategies against viral proliferation. Clear insights into the regulation of cytotoxic CD8+ T cells is crucial to development of effective immunotherapeutic strategies due to their unique ability to eliminate virus-infected cells during the course of infection. Here, we reviewed the roles of transcription factors, co-inhibitory molecules and regulatory cytokines following HIV infection and their potential significance in regulating the cytotoxic potentials of CD8+ T cells.
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Citotoxicidade Imunológica/imunologia , Infecções por HIV/imunologia , HIV-1/imunologia , Linfócitos T Citotóxicos/imunologia , Citocinas/imunologia , Granzimas/metabolismo , Infecções por HIV/virologia , Humanos , Perforina/metabolismo , Fatores de Transcrição/imunologiaRESUMO
OBJECTIVE: To determine the effect of therapeutic plasma exchange on hemodynamics, organ failure, and survival in children with multiple organ dysfunction syndrome due to sepsis requiring extracorporeal life support. DESIGN: A retrospective analysis. SETTING: A PICU in an academic children's hospital. PATIENTS: Fourteen consecutive children with sepsis and multiple organ dysfunction syndrome who received therapeutic plasma exchange while on extracorporeal life support from 2005 to 2013. INTERVENTIONS: Median of three cycles of therapeutic plasma exchange with median of 1.0 times the estimated plasma volume per exchange. MEASUREMENTS AND MAIN RESULTS: Organ Failure Index and Vasoactive-Inotropic Score were measured before and after therapeutic plasma exchange use. PICU survival in our cohort was 71.4%. Organ Failure Index decreased in patients following therapeutic plasma exchange (mean ± SD: pre, 4.1 ± 0.7 vs post, 2.9 ± 0.9; p = 0.0004). Patients showed improved Vasoactive-Inotropic Score following therapeutic plasma exchange (median [25th-75th]: pre, 24.5 [13.0-69.8] vs post, 5.0 [1.5-7.0]; p = 0.0002). Among all patients, the change in Organ Failure Index was greater for early therapeutic plasma exchange use than late use (early, -1.7 ± 1.2 vs late, -0.9 ± 0.6; p = 0.14), similar to the change in Vasoactive-Inotropic Score (early, -67.5 [28.0-171.2] vs late, -12.0 [7.2-18.5]; p = 0.02). Among survivors, the change in Organ Failure Index was greater among early therapeutic plasma exchange use than late use (early, -2.3 ± 1.0 vs late, -0.8 ± 0.8; p = 0.03), as was the change in Vasoactive-Inotropic Score (early, -42.0 [16.0-76.3] vs late, -12.0 [5.3-29.0]; p = 0.17). The mean duration of extracorporeal life support after therapeutic plasma exchange according to timing of therapeutic plasma exchange was not statistically different among all patients or among survivors. CONCLUSIONS: The use of therapeutic plasma exchange in children on extracorporeal life support with sepsis-induced multiple organ dysfunction syndrome is associated with organ failure recovery and improved hemodynamic status. Initiating therapeutic plasma exchange early in the hospital course was associated with greater improvement in organ dysfunction and decreased requirement for vasoactive and/or inotropic agents.
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Hemodinâmica , Sistemas de Manutenção da Vida/estatística & dados numéricos , Insuficiência de Múltiplos Órgãos/terapia , Troca Plasmática/estatística & dados numéricos , Sepse/complicações , Adolescente , Criança , Pré-Escolar , Terapia Combinada/métodos , Feminino , Humanos , Lactente , Tempo de Internação/estatística & dados numéricos , Masculino , Insuficiência de Múltiplos Órgãos/etiologia , Insuficiência de Múltiplos Órgãos/fisiopatologia , Estudos Retrospectivos , Índice de Gravidade de Doença , Taxa de Sobrevida , Resultado do TratamentoRESUMO
Diabetes has become one of the major diseases affecting human health. Diabetic cataracts (DCs) are considered a common complication in diabetic patients. The present study investigated differences in lens proteomic profiles between DCs and age-related cataracts (ACs) to determine the mechanism underlying the formation of DCs. Intrasurgical samples were collected from eight DC patients and 12 AC patients, and lens proteins were extracted by lysis and separated using two-dimensional gel electrophoresis (2-DE). The electrophoretic bands were analysed using PD-Quest software 8.0.1. Differentially expressed proteins were identified by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and peptide mass fingerprinting combined with protein database searching. In the 2-DE maps, the DC and AC lens proteins migrated in the region of pH 5-9 with a relative molecular weight (RMW) of 14-97 kDa, whereas the RMW of more abundant crystallin was 20-31 kDa. Approximately three protein spots with differential intensity were detected. Two crystallin proteins (αB and ßB1) were identified using MALDI-TOF-MS. Proteomic analysis of the crystalline humour is feasible, and the proteins can be well separated; moreover, differentially expressed lens proteins can be analysed using 2-DE and mass spectrometry to compare DC and AC. The present results indicate that the αB and ßB1 crystallins may accelerate the development of DCs. These techniques offer new avenues for mechanistic evaluation and future prevention or therapy of DCs.
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Envelhecimento/genética , Catarata/genética , Complicações do Diabetes/genética , Diabetes Mellitus Tipo 1/complicações , Proteínas do Olho/biossíntese , Regulação da Expressão Gênica , Adulto , Envelhecimento/metabolismo , Envelhecimento/patologia , Catarata/etiologia , Catarata/metabolismo , Complicações do Diabetes/etiologia , Complicações do Diabetes/metabolismo , Eletroforese em Gel Bidimensional , Proteínas do Olho/genética , Perfilação da Expressão Gênica , Humanos , Cristalino/química , Espectrometria de Massas , Pessoa de Meia-Idade , Proteoma , Cadeia B de alfa-Cristalina/biossíntese , Cadeia B de alfa-Cristalina/genética , Cadeia B de beta-Cristalina/biossíntese , Cadeia B de beta-Cristalina/genéticaRESUMO
Desmosine-CH2, an analog of the elastic tissue degradation biomarker desmosine, can be regarded as a potential internal standard for precise quantification of desmosines by LC-MS/MS. In this study, the chemical synthesis of desmosine-CH2 was completed in 22% overall yield in five steps. The LC-MS/MS analysis of desmosine-CH2 was also achieved.
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Desmosina/análise , Elastina/química , Biomarcadores/análise , Cromatografia Líquida , Desmosina/síntese química , Conformação Molecular , Espectrometria de Massas em TandemRESUMO
Recently, a different class of collagen-like molecules has been identified in numerous bacteria. Initial studies have shown that these collagens are readily produced in Escherichia coli and they have been isolated and purified by various small-scale chromatography approaches. These collagens are non-cytotoxic, are non-immunogenic, and can be produced in much higher yields than mammalian collagens, making them potential new collagens for biomedical materials. One of the major drawbacks with large-scale fermentation of collagens has been appropriate scalable down-stream processing technologies. Like other collagens, the triple helical domains of bacterial collagens are particularly resistant to proteolysis. The present study describes the development and optimization of a simple, scalable procedure using a combination of acid precipitation of the E. coli host proteins, followed by proteolysis of residual host proteins to produce purified collagens in large scale without the use of chromatographic methods.
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Biotecnologia/métodos , Colágeno/metabolismo , Proteínas Recombinantes/metabolismo , Biotecnologia/economia , Colágeno/genética , Proteínas Recombinantes/genéticaRESUMO
BACKGROUND: Recent international guidance recommends the use of catheter-directed thrombolysis (CDT) in selected patients with symptomatic iliofemoral deep vein thrombosis (DVT). The aim of this study was to estimate the potential increase in workload as a result of this recommendation. METHODS: Using the radiology database, a review was performed of all DVTs diagnosed between August 2010 and February 2012 at a large tertiary referral hospital. The National Institute for Health and Clinical Excellence and American College of Chest Physicians guidance was applied retrospectively to this cohort, using case-note review by two independent clinicians to determine which patients would have been suitable for CDT. RESULTS: Some 563 patients had DVT confirmed radiologically over the 18-month interval. Fifty-three of the 128 patients with iliofemoral DVT would have been eligible for intervention with CDT, equivalent to 4·4 patients per 100 000 per year. Only eight (15 per cent) of the 53 were actually referred to vascular services for treatment. All eight patients had successful CDT, which involved a stay in critical care for monitoring (median 2 (range 1-3) sessions). CONCLUSION: Vascular units should be prepared for a major increase in the requirement for CDT for iliofemoral DVT. This increase will affect inpatient beds, the interventional radiology suite, critical care and interhospital referrals.
Assuntos
Cateterismo Periférico/métodos , Veia Femoral , Veia Ilíaca , Terapia Trombolítica/métodos , Trombose Venosa/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Assistência Ambulatorial/estatística & dados numéricos , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Extremidade Inferior/irrigação sanguínea , Masculino , Pessoa de Meia-Idade , Retratamento/estatística & dados numéricos , Estudos Retrospectivos , Trombectomia/métodos , Trombectomia/estatística & dados numéricos , Trombose Venosa/etiologia , Carga de Trabalho , Adulto JovemRESUMO
Chemical synthesis of the deuterium isotope desmosine-d4 has been achieved. This isotopic compound possesses all four deuterium atoms at the alkanyl carbons of the alkyl amino acid substitution in the desmosine molecule and is stable toward acid hydrolysis; this is required in the measurement of two crosslinking molecules, desmosine and isodesmosine, as biomarkers of elastic tissue degradation. The degradation of elastin occurs in several widely prevalent diseases. The synthesized desmosine-d4 is used as the internal standard to develop an accurate and sensitive isotope-dilution liquid chromatography-tandem mass spectrometry analysis, which can serve as a generalized method for an accurate analysis of desmosine and isodesmosine as biomarkers in many types of biological tissues involving elastin degradation.
Assuntos
Cromatografia Líquida/normas , Deutério/química , Elastina/metabolismo , Espectrometria de Massas em Tandem/normas , Biomarcadores/sangue , Biomarcadores/metabolismo , Lavagem Broncoalveolar , Desmosina/sangue , Desmosina/metabolismo , Humanos , Isodesmosina/sangue , Isodesmosina/metabolismo , Proteólise , Doença Pulmonar Obstrutiva Crônica/sangue , Padrões de ReferênciaRESUMO
OBJECTIVES: To compare the mid-term outcome and secondary intervention rate following elective open and endovascular aortic aneurysm repair (EVAR) in patients aged 65 years and younger. METHODS: A retrospective analysis of patients aged 65 years and younger who had elective abdominal aortic aneurysm repair (AAA) between 1994 and 2012. RESULTS: One hundred and sixty-five patients under the age of 65 years (mean age: 61 years ± 4; 8 women) had elective abdominal aneurysm repair (97 EVAR and 68 open). The overall 30-day mortality rate was 3.7% (2.1% EVAR and 5.9% open). Forty per cent of patients had died at a median follow up of 77 months (interquartile range, 36-140). Most deaths were not related to aneurysm. There was no difference in the long-term mortality between the EVAR and open groups (hazard ratio [HR] = 1.22; 95% confidence interval [CI] 0.75-1.98, p = .43), but there was a trend of better outcomes with the use of commercially made endografts over open repair (HR = 2.9; 95% CI 0.9-10.0, p = .08) and custom-made endografts (HR = 3.1, 95% CI 0.9-10.3; p = .07). Eleven per cent of patients who had EVAR required a further procedure compared with 13% who had open repair. All but one of the re-interventions in the EVAR group was performed on patients who had custom-made endografts. CONCLUSIONS: Young patients with AAA have significant comorbidities and do not necessarily have long lifespans. In the less fit younger patients with AAA, the results with EVAR are comparable with fit patients who had open AAA repair. The management of fitter young patients with AAA remains controversial, but improving results with EVAR over time may increase the role of EVAR in this group.