RESUMO
Hepatitis C virus (HCV) encodes mechanisms to evade the multilayered antiviral actions of the host immune system. Great progress has been made in elucidating the strategies HCV employs to down-regulate interferon (IFN) production, impede IFN signaling transduction, and impair IFN-stimulated gene (ISG) expression. However, there is a limited understanding of the mechanisms governing how viral proteins counteract the antiviral functions of downstream IFN effectors due to the lack of an efficient approach to identify such interactions systematically. To study the mechanisms by which HCV antagonizes the IFN responses, we have developed a high-throughput profiling platform that enables mapping of HCV sequences critical for anti-IFN function at high resolution. Genome-wide profiling performed with a 15-nt insertion mutant library of HCV showed that mutations in the p7 region conferred high levels of IFN sensitivity, which could be alleviated by the expression of WT p7 protein. This finding suggests that p7 protein of HCV has an immune evasion function. By screening a liver-specific ISG library, we identified that IFI6-16 significantly inhibits the replication of p7 mutant viruses without affecting WT virus replication. In contrast, knockout of IFI6-16 reversed the IFN hypersensitivity of p7 mutant virus. In addition, p7 was found to be coimmunoprecipitated with IFI6-16 and to counteract the function of IFI6-16 by depolarizing the mitochondria potential. Our data suggest that p7 is a critical immune evasion protein that suppresses the antiviral IFN function by counteracting the function of IFI6-16.
Assuntos
Hepacivirus/patogenicidade , Hepatite C/imunologia , Interações Hospedeiro-Patógeno/imunologia , Evasão da Resposta Imune , Interferons/imunologia , Proteínas Mitocondriais/imunologia , Proteínas Virais/imunologia , Sistemas CRISPR-Cas , Linhagem Celular , Perfilação da Expressão Gênica , Técnicas de Inativação de Genes , Biblioteca Gênica , Genoma Viral , Hepacivirus/genética , Hepatite C/virologia , Humanos , Imunidade Inata , Interferons/genética , Interferons/metabolismo , Fígado/imunologia , Fígado/metabolismo , Potencial da Membrana Mitocondrial/imunologia , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Mutagênese Insercional , Transdução de Sinais , Proteínas Virais/genética , Replicação ViralRESUMO
We present an LC-MS/MS pipeline to identify taxon-specific tryptic peptide markers for the identification of Salmonella at the genus, species, subspecies, and serovar levels of specificity. Salmonella enterica subsp. enterica serovars Typhimurium and its four closest relatives, Saintpaul, Heidelberg, Paratyphi B, and Muenchen, were evaluated. A decision-tree approach was used to identify peptides common to the five Salmonella proteomes for evaluation as genus-, species-, and subspecies-specific markers. Peptides identified for two or fewer Salmonella strains were evaluated as potential serovar markers. Currently, there are approximately 140â¯000 assembled bacterial genomes publicly available, more than 8500 of which are for Salmonella. Consequently, the specificity of each candidate peptide marker was confirmed across all publicly available protein sequences in the NCBI nonredundant (nr) database. The performance of a subset of candidate taxon-specific peptide markers was evaluated in a targeted mass-spectrometry method. The presented workflow offers a marked improvement in specificity over existing MALDI-TOF-based bacterial identification platforms for the identification of closely related Salmonella serovars.
Assuntos
Proteínas de Bactérias/análise , Peptídeos/análise , Proteoma/análise , Salmonella/classificação , Sorotipagem/métodos , Sequência de Aminoácidos , Biomarcadores/análise , Cromatografia Líquida , Bases de Dados de Ácidos Nucleicos , Árvores de Decisões , Genoma Bacteriano , Proteômica/métodos , Salmonella/genética , Sorogrupo , Espectrometria de Massas em TandemRESUMO
OBJECTIVE: To investigate the clinical features, diagnosis and treatment of glucose transporter 1 deficiency syndrome (GLUT1-DS), as well as the diagnostic value of movement disorders. METHODS: The clinical data of four children with GLUT1-DS were collected, and their clinical features, treatment, and follow-up results were analyzed. RESULTS: There were two boys and two girls, with an age of onset of 2-15 months. Clinical manifestations included movement disorders, seizures, and developmental retardation. Seizures were the cause of the first consultation in all cases. The four children all had persistent ataxia, dystonia, and dysarthria; two had persistent tremor, two had paroxysmal limb paralysis, and two had eye movement disorders. Paroxysmal symptoms tended to occur in fatigue state. All four children had reductions in the level of cerebrospinal fluid glucose and its ratio to blood glucose, as well as SLC2A1 gene mutations. The four children were given a ketogenic diet, at a ketogenic ratio of 2:1 to 3:1, and achieved complete remission of paroxysmal symptoms within 5 weeks. CONCLUSIONS: GLUT1-DS should be considered for epileptic children with mental retardation and motor developmental delay complicated by various types of movement disorders. The ketogenic diet is effective at a ketogenic ratio of 2:1 to 3:1 for the treatment of GLUT1-DS.
Assuntos
Erros Inatos do Metabolismo dos Carboidratos/diagnóstico , Erros Inatos do Metabolismo dos Carboidratos/terapia , Proteínas de Transporte de Monossacarídeos/deficiência , Transtornos dos Movimentos/diagnóstico , Transtornos dos Movimentos/terapia , Erros Inatos do Metabolismo dos Carboidratos/genética , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Proteínas de Transporte de Monossacarídeos/genética , Transtornos dos Movimentos/genéticaRESUMO
We reported an integrated platform to explore serum protein variant pattern in cancer and its utility as a new class of biomarker panel for diagnosis. On the model study of serum amyloid A (SAA), we employed nanoprobe-based affinity mass spectrometry for enrichment, identification and quantitation of SAA variants from serum of 105 gastric cancer patients in comparison with 54 gastritis patients, 54 controls, and 120 patients from other cancer. The result revealed surprisingly heterogeneous and most comprehensive SAA bar code to date, which comprises 24 SAA variants including SAA1- and SAA2-encoded products, polymorphic isoforms, N-terminal-truncated forms, and three novel SAA oxidized isotypes, in which the variant-specific peptide sequence were also confirmed by LC-MS/MS. A diagnostic model was developed for dimension reduction and computational classification of the 24 SAA-variant bar code, providing good discrimination (AUC = 0.85 ± 3.2E-3) for differentiating gastric cancer group from gastritis and normal groups (sensitivity, 0.76; specificity, 0.81) and was validated with external validation cohort (sensitivity, 0.71; specificity, 0.74). Our platform not only shed light on the occurrence and modification extent of under-represented serum protein variants in cancer, but also suggested a new concept of diagnostic platform by serum protein variant profile.
Assuntos
Mucosa Gástrica/metabolismo , Gastrite/diagnóstico , Proteína Amiloide A Sérica/metabolismo , Neoplasias Gástricas/diagnóstico , Cromatografia Líquida , Diagnóstico Diferencial , Gastrite/metabolismo , Humanos , Isoformas de Proteínas , Neoplasias Gástricas/metabolismo , Espectrometria de Massas em TandemRESUMO
Widely used chemical genetic screens have greatly facilitated the identification of many antiviral agents. However, the regions of interaction and inhibitory mechanisms of many therapeutic candidates have yet to be elucidated. Previous chemical screens identified Daclatasvir (BMS-790052) as a potent nonstructural protein 5A (NS5A) inhibitor for Hepatitis C virus (HCV) infection with an unclear inhibitory mechanism. Here we have developed a quantitative high-resolution genetic (qHRG) approach to systematically map the drug-protein interactions between Daclatasvir and NS5A and profile genetic barriers to Daclatasvir resistance. We implemented saturation mutagenesis in combination with next-generation sequencing technology to systematically quantify the effect of every possible amino acid substitution in the drug-targeted region (domain IA of NS5A) on replication fitness and sensitivity to Daclatasvir. This enabled determination of the residues governing drug-protein interactions. The relative fitness and drug sensitivity profiles also provide a comprehensive reference of the genetic barriers for all possible single amino acid changes during viral evolution, which we utilized to predict clinical outcomes using mathematical models. We envision that this high-resolution profiling methodology will be useful for next-generation drug development to select drugs with higher fitness costs to resistance, and also for informing the rational use of drugs based on viral variant spectra from patients.
Assuntos
Farmacorresistência Viral , Perfilação da Expressão Gênica , Aptidão Genética , Hepacivirus/fisiologia , Hepatite C , Imidazóis/farmacologia , Replicação Viral , Carbamatos , Linhagem Celular , Farmacorresistência Viral/efeitos dos fármacos , Farmacorresistência Viral/genética , Hepatite C/tratamento farmacológico , Hepatite C/genética , Hepatite C/metabolismo , Hepatite C/patologia , Humanos , Pirrolidinas , Valina/análogos & derivados , Proteínas não Estruturais Virais/genética , Proteínas não Estruturais Virais/metabolismo , Replicação Viral/efeitos dos fármacos , Replicação Viral/genéticaRESUMO
The reaction of cadmium-binding human metallothionein-2A (Cd7MT) and N-ethylmaleimide (NEM) is investigated by electrospray ionization-ion mobility-mass spectrometry (ESI IM-MS). MS provides a direct measure of the distribution of the kinetic intermediates as the reaction proceeds and provides new insights into the relative kinetic stability of the individual metal-thiolate bonds in Cd7MT. The rate constants for the various metal-retaining intermediates (Cd(i), intermediate with i Cd²âº ions attached) differ by >3 orders of magnitude: Cd4< Cd3< Cd2< Cd1â¼ Cd6 < Cd7 < Cd5. The reaction is viewed as a two-component cooperative process, rapid loss of three Cd²âº ions followed by slow loss of the remaining four Cd²âº ions, and Cd4NEM10MT was observed as the least reactive intermediate during the entire displacement process. "MS-CID-IM-MS", a top-down approach that provides two-dimensional dispersion (size to charge by IM; mass to charge by MS) of the CID fragment ions, was used for direct analysis of the kinetic intermediate [Cd4NEM10MT]5⺠ion. The results provide direct evidence that the four Cd²âº ions located in the α-domain are retained, indicative of the greater kinetic stability for the α-domain. Further, the mapping of the alkylation sites in the [Cd4NEM10MT]5⺠ion reveals that not only the nine cysteines in the ß-domain but Cys33 in the α-domain is selectively labeled. The kinetic lability of the Cd-Cys33 bond is unexpected. The structural and functional implications of these findings are discussed.
Assuntos
Cádmio/química , Etilmaleimida/química , Metalotioneína/química , Espectrometria de Massas por Ionização por Electrospray , Etilmaleimida/metabolismo , Humanos , Cinética , Metalotioneína/metabolismo , Estrutura Secundária de Proteína , Estrutura Terciária de ProteínaRESUMO
Electrospray ionization ion mobility mass spectrometry (ESI IM-MS) and molecular dynamics (MD) simulations reveal new insights into metal-induced conformational changes and the mechanism for metalation of human metallothionein-2A (MT), an intrinsically disordered protein. ESI of solutions containing apoMT yields multiple charge states of apoMT; following addition of Cd(2+) to the solution, ESI yields a range of CdiMT (i = 1-7) product ions (see Chen et al. Anal. Chem. 2013, 85, 7826-33). Ion mobility arrival-time distributions (ATDs) for the CdiMT (i = 0-7) ions reveal a diverse population of ion conformations. The ion mobility data clearly show that the conformational diversity for apoMT and partially metalated ions converges toward ordered, compact conformations as the number of bound Cd(2+) ions increase. MD simulations provide additional information on conformation candidates of CdiMT (i = 0-7) that supports the convergence of distinct conformational populations upon metal binding. Integrating the IM-MS and MD data provides a global view that shows stepwise conformational transition of an ensemble as a function of metal ion bound. ApoMT is comprised of a wide range of conformational states that populate between globular-like compact and coil-rich extended conformations. During the initial stepwise metal addition (number of metal ions bound i = 1-3), the metal ions bind to different sites to yield distinct conformations, whereas for i > 4, the conformational changes appear to be domain-specific, attributed to different degrees of disorder of the ß domain; the ß domain becomes more ordered as additional metal ions are added, promoting convergences to the dumbbell-shaped conformation.
Assuntos
Metalotioneína/química , Cádmio/química , Cádmio/metabolismo , Metalotioneína/metabolismo , Modelos Moleculares , Simulação de Dinâmica Molecular , Conformação Proteica , Estrutura Terciária de Proteína , Espectrometria de Massas por Ionização por Electrospray/métodosRESUMO
The University of California-Davis_Primary (UCD_P) chemical transport model was developed and applied to compute the primary airborne particulate matter (PM) trace chemical concentrations from â¼ 900 sources in California through a simulation of atmospheric emissions, transport, dry deposition and wet deposition for a 7-year period (2000-2006) with results saved at daily time resolution. A comprehensive comparison between monthly average model results and available measurements yielded Pearson correlation coefficients (R) ≥ 0.8 at ≥ 5 sites (out of a total of eight) for elemental carbon (EC) and nine trace elements: potassium, chromium, zinc, iron, titanium, arsenic, calcium, manganese, and strontium in the PM2.5 size fraction. Longer averaging time increased the overall R for PM2.5 EC from 0.89 (1 day) to 0.94 (1 month), and increased the number of species with strong correlations at individual sites. Predicted PM0.1 mass and PM0.1 EC exhibited excellent agreement with measurements (R = 0.92 and 0.94, respectively). The additional temporal and spatial information in the UCD_P model predictions produced population exposure estimates for PM2.5 and PM0.1 that differed from traditional exposure estimates based on information at monitoring locations in California Metropolitan Statistical Areas, with a maximum divergence of 58% at Bakersfield. The UCD_P model has the potential to improve exposure estimates in epidemiology studies of PM trace chemical components and health.
Assuntos
Poluentes Atmosféricos/química , Monitoramento Ambiental/métodos , Material Particulado/química , Poluentes Atmosféricos/análise , California/epidemiologia , Estudos Epidemiológicos , Saúde , Humanos , Tamanho da Partícula , Material Particulado/análiseRESUMO
BACKGROUND: Acute disseminated encephalomyelitis (ADEM) is an autoimmune disease that typically follows a monophasic course and may affect any age group. The precise population-based incidence of ADEM is still unknown in most countries. In China, there is no ADEM surveillance system. The exact incidence of ADEM is difficult to estimate, and other epidemiological characteristics of ADEM are unknown. The purpose of this study is to investigate the epidemiological characteristics of ADEM in Nanchang, China. METHODS: A retrospective investigation was conducted with ADEM patients admitted to second-level and third-level hospitals in Nanchang from 2008 to 2010, aiming to analyse the epidemiologic characteristics of ADEM in the population in Nanchang. ADEM patients, defined as patients who were diagnosed according to the consensus definition of ADEM provided by the International Pediatric MS Study Group, were enrolled in the study. The data were extracted from the ADEM patients' medical records. RESULTS: Forty-seven ADEM patients were investigated. The average annual incidence was 0.31/100,000; the incidence among males (0.31/100,000) was nearly equal to that among females (0.31/100,000). The median age of onset was 25.97 years old, and the peak incidence was observed in the 5- to 9-year-old age group (0.75/100,000), followed by the over-60 age group (0.55/100,000). ADEM occurs throughout the year, but it occurs most frequently in March (n = 7) and least frequently in April and July (both n = 2). The patient numbers are roughly even in the other months. In the 2 months before the onset of ADEM, 15 patients presented with a preceding infection, but none of the patients received a vaccination. An increased number of vaccination was not accompanied by a corresponding increased number of cases of ADEM. CONCLUSIONS: The average annual incidence of ADEM was 0.31/100,000 in Nanchang. The incidence among males was nearly equal to that among females. The peak age of onset was 5-9 years old. The peak season of onset was not apparent. There was no evidence of an association between increased number of vaccines administered and number of cases of ADEM in Nanchang, China.
Assuntos
Encefalomielite Aguda Disseminada/epidemiologia , Adolescente , Adulto , Fatores Etários , Idade de Início , Criança , Pré-Escolar , China/epidemiologia , Encefalomielite Aguda Disseminada/etiologia , Feminino , Humanos , Incidência , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Estações do Ano , Fatores Sexuais , Adulto JovemRESUMO
OBJECTIVE: The main goal of the present research is to explore the potential link of body mass index (BMI) with different survival metrics in breast cancer patients. Our aim is to offer the latest and most thorough meta-analysis, assessing the strength and reliability of the connection that BMI has with prognostic indicators in this disease. PATIENTS AND METHODS: As of January 2024, we conducted a systematic literature search across PubMed, Embase, Web of Science, and the Cochrane Library databases. Our search aimed to identify studies examining BMI as an exposure factor, with breast cancer patients constituting the study population, and utilizing adjusted hazard ratio (HR) as the data type of interest. RESULTS: The evidence synthesis incorporated a total of 61 eligible articles involving 201,006 patients. Being underweight posed a risk factor for overall survival (OS) in breast cancer patients compared to normal weight (HR 1.15, 95% CI 0.98-1.35; P = 0.08). Overweight or obesity, in comparison to normal weight, was a risk factor for OS (HR 1.18, 95% CI 1.14-1.23; P < 0.00001), disease-free survival (DFS) (HR 1.11, 95% CI 1.08-1.13; P < 0.00001), relapse-free survival (RFS) (HR 1.14, 95% CI 1.06-1.22; P = 0.03), and breast cancer-specific survival (BCSS) (HR 1.18, 95% CI 1.11-1.26; P < 0.00001), but not for progression-free survival (PFS) (HR 0.91, 95% CI 0.76-1.10; P = 0.33). Notably, in subgroup analyses, overweight patients achieved prolonged PFS (HR 0.80, 95% CI 0.64-0.99; P = 0.04), and compared to the obese population, the overweight cohort exhibited a significant difference in OS (HR 1.11, 95% CI 1.05-1.16; P < 0.00001) and DFS (HR 1.06, 95% CI 1.03-1.10; P = 0.0004), with a considerably stronger association. Furthermore, compared to HER- patients, HER + patients exhibited a greater predictive value for OS (HR 1.23, 95% CI 1.10-1.37; P = 0.0004), RFS (HR 1.30, 95% CI 1.03-1.64; P < 0.00001), and DFS (HR 1.10, 95% CI 1.03-1.17; P = 0.003). CONCLUSIONS: The results of our meta-analysis reveal a notable association between BMI and various survival measures in breast cancer prognosis. These findings provide a solid basis for predicting breast cancer outcomes and implementing more effective therapeutic approaches.
RESUMO
PURPOSE: PAFAH1B1, also known as LIS1, is associated with type I lissencephaly in humans, which is a severe developmental brain disorder believed to result from abnormal neuronal migration. Our objective was to characterize the genotypes and phenotypes of PAFAH1B1-related epilepsy. METHODS: We conducted a comprehensive analysis of the medical histories, magnetic resonance imaging findings, and video-electroencephalogram recordings of 11 patients with PAFAH1B1 variants at the Neurology Department of Beijing Children's Hospital from June 2017 to November 2022. RESULTS: The age of onset of epilepsy ranged from 2 months to 4 years, with a median onset age of 5 months. Among these 11 patients (comprising 6 boys and 5 girls), all were diagnosed with lissencephaly type 1. Predominantly, generalized tonic-clonic and spasm seizures characterized PAFAH1B1-related epilepsy. Additionally, 10 out of the 11 patients exhibited severe developmental disorders. All patients exhibited de novo variants, with three individuals displaying 17p13.3 deletions linked to haploinsufficiency of PAFAH1B1. Four variants were previously unreported. Notably, three patients with 17p13.3 deletions displayed developmental delay and drug resistant epilepsy, whereas the single patient with mild developmental delay, Intelligence Quotient (IQ) 57 and well-controlled seizures had a splicing-site variant. CONCLUSION: The severity of the phenotype in patients with PAFAH1B1 variants ranged from drug-responsive seizures to severe epileptic encephalopathy. These observations underscore the clinical heterogeneity of PAFAH1B1-related disorders, with most patients exhibiting developmental disorders. Moreover, the severity of epilepsy appears to be linked to genetic variations.
Assuntos
1-Alquil-2-acetilglicerofosfocolina Esterase , Epilepsia , Proteínas Associadas aos Microtúbulos , Humanos , Masculino , Feminino , 1-Alquil-2-acetilglicerofosfocolina Esterase/genética , Pré-Escolar , Lactente , Epilepsia/genética , Epilepsia/fisiopatologia , Eletroencefalografia , Fenótipo , Imageamento por Ressonância Magnética , Deficiências do Desenvolvimento/genética , CriançaRESUMO
BACKGROUND: The comprehensive impact of prolonged home-based resistance training on individuals grappling with chronic kidney disease (CKD) have yet to be fully elucidated. This study aimed to explore the outcomes of varying exercise durations on physical performance, nutritional status, and kidney function within this specific population, encompassing patients undergoing dialysis and those affected by severe sarcopenia. METHODS: This was a 1-year observational double cohort study following a 52-week longitudinal design, we enrolled 101 adult CKD outpatients. These participants were divided into two groups: the continuous group, comprising individuals who consistently exercised for over 6 months, and the interrupted group, which included those who did not sustain regular exercise for the same duration. The exercise regimen involved resistance exercises conducted at least 3 to 5 days per week, involving activities like lifting dumbbells and executing weighted wall squats. Physical activity assessments and biochemical blood tests were conducted at weeks 0, 4, 16, 28, 40, and 52 for all participants. RESULTS: The continuous exercise group exhibited better handgrip strength and sit-to-stand movement compared to the interrupted group. Their estimated glomerular filtration rate stayed steady while the interrupted group was declined. Additionally, those who exercised consistently had better metabolism: higher carbon dioxide levels, increased albumin, better nutritional scores, and lower levels of blood urea nitrogen, creatinine, fasting blood glucose, and body weight. Subsequent adjustments for potential confounding factors continued to show improved physical performance and kidney function over time. CONCLUSION: Our findings indicate the advantageous impact of extended resistance exercise training on overall health of CKD patients, even those on dialysis or with severe sarcopenia. Dedication to this exercise routine could improve kidney function, metabolism, and physical abilities in these patients.
Assuntos
Insuficiência Renal Crônica , Treinamento Resistido , Humanos , Insuficiência Renal Crônica/terapia , Insuficiência Renal Crônica/fisiopatologia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Estudos de Coortes , Taxa de Filtração Glomerular , Estudos Longitudinais , Sarcopenia/fisiopatologia , Força da Mão , Estado Nutricional , AdultoRESUMO
The solvent dependence of self-assembly/disassembly kinetics and conformer preferences of the gramicidin A (GA) dimer is investigated using a combination of techniques, viz., electrospray ionization-ion mobility-mass spectrometry (IM-MS), collision-induced dissociation (CID), and hydrogen/deuterium exchange (HDX)-MS. IM-MS measurements reveal that there are possibly three distinct GA dimeric species, detected as sodium ion adduct ions [2GA + 2Na](2+), and these are assigned as the parallel ß-helix, antiparallel ß-helix, and head-to-head dimer. The monomerization kinetics and equilibrium abundances of the dimer ions depend upon solvent polarity. The antiparallel ß-helix was the thermodynamically preferred species in less polar solvents. HDX measurements and collision-induced dissociation (CID) of the intermediate complex confirm the well-protected dimer geometry with strong intermolecular hydrogen bonds. This combined IM-HDX-CID methodology provides a comprehensive view of GA self-assembly/disassembly in low dielectric solutions, showing its potential utility in solving solution-phase protein self-assembly/disassembly kinetics and providing structural information of the multimers at the same time.
Assuntos
Gramicidina/química , Solventes/química , Espectrometria de Massas por Ionização por Electrospray/métodos , Sequência de Aminoácidos , Dados de Sequência Molecular , Conformação ProteicaRESUMO
Metalation and demetalation of human metallothionein-2A (MT) with Cd(2+) is investigated by using chemical labeling and "bottom-up" and "top-down" proteomics approaches. Both metalation and demetalation of MT-2A by Cd(2+) are shown to be domain specific and occur as two distinct processes. Metalation involves sequential addition of Cd(2+) to the α-domain resulting in formation of an intermediate, Cd4MT. Chemical labeling with N-ethylmaleimide (NEM) and tandem mass spectrometry experiments clearly show that the four metal ions are located in the α-domain. In the presence of excess Cd(2+), the Cd4MT intermediate reacts to add Cd(2+) to the ß-domain to yield the fully metalated Cd7MT. Demetalation occurs in the reverse order, i.e., Cd(2+) is removed (by EDTA) first from the ß-domain followed by Cd(2+) removal from the α-domain. Metalation of human MT-2A is shown to be metal ion specific by comparing relative metal ion binding constants for Cd(2+) and Zn(2+).
Assuntos
Metalotioneína/metabolismo , Espectrometria de Massas por Ionização por Electrospray/métodos , Espectrometria de Massas em Tandem/métodos , Sequência de Aminoácidos , Sítios de Ligação/fisiologia , Humanos , Transporte de Íons/fisiologia , Marcação por Isótopo/métodos , Metalotioneína/análise , Dados de Sequência MolecularRESUMO
BACKGROUND & PROBLEMS: Detailed descriptions of nursing shift tasks are necessary to achieve comprehensive nursing care. The 22 cases of postoperative recovery ward error reported by our unit included chest tube obstructions, lost dentures and other nursing issues. To improve patient health and nurse shift quality, our unit established an ad hoc group to collect data helpful to overcoming problems attributable to nurse shift changes. We aimed to better nursing care by facilitating individualized patient care and avoiding accidents detrimental to patient safety. PURPOSE: This project was designed to raise the rate of 100% completion of nursing shift-change tasks to 91% of postoperative recovery room nurses. RESOLUTION: Newly revised operating standards regarding the recovery period after anesthesia established guidelines for a regular audit mechanism and in-service education programs for recovery room shift tasks. RESULT: Full completion of shift tasks in the postoperative recovery room improved from 73.5% to 98.6% of nurses. CONCLUSION: Comprehensive completion of postoperative nursing shift-change tasks increases communication between team members, provides continuous care for patients, and enhances overall nursing care quality.
Assuntos
Registros de Enfermagem , Recursos Humanos de Enfermagem Hospitalar/provisão & distribuição , Admissão e Escalonamento de Pessoal , Sala de Recuperação , Humanos , Período Pós-OperatórioRESUMO
Diabetic kidney disease is the leading cause of end-stage renal disease in developing and developed countries. The growing prevalence and clinical challenges of sarcopenic obesity have been associated with the frailty and disability of diabetic kidney disease. It has been reported that insulin resistance, chronic inflammation, enhanced oxidative stress and lipotoxicity contribute to the pathophysiology of muscle loss and visceral fat accumulation. Sarcopenic obesity, which is diagnosed with dual-energy X-ray absorptiometry, is associated with worse outcomes in kidney disease. Growing evidence indicates that adherence to healthy lifestyles, including low protein diet, proper carbohydrate control, vitamin D supplement, and regular physical training, has been shown to improve clinical prognosis. Based on the higher risk of sarcopenic-obesity-related renal function decline, it has led to the exploration and investigation of the pathophysiology, clinical aspects, and novel approach of these controversial issues in daily practice.
RESUMO
This study uses a coupled atmosphere-ocean model with different numerical settings to investigate the mean and eddy momentum transfer processes responsible for Typhoon Muifa's (2011) early rapid intensification (RI). Three experiments are conducted. Two use the coupled model with a horizontal resolution of either 1 km (HRL) or 3 km (LRL). The third (NoTCFB) is the same as LRL but excludes tropical cyclone (TC)-induced sea-surface temperature (SST) cooling. HRL reasonably reproduces Muifa's intensity during its rapid intensification and weakening periods. The azimuthal mean tangential and radial momentum budgets are analysed before the RI rates diverge between HRL and LRL. Results show that the dominant processes responsible for Muifa's intensification are different in HRL and LRL. For HRL, the net eddy effect intensifies the storm's circulation and contracts the eyewall during early RI, and it dominates the net mean-flow effect inside the radius of maximum wind (RMW), except near the surface and between 2 and 5 km close to the RMW. In contrast, the mean and eddy effects in LRL almost cancel inside the RMW, while the mean-flow effects dominate and intensify tangential winds outside. Without TC-induced SST cooling, Muifa in NoTCFB reaches a similar storm intensity as in HRL but its rapid weakening rate is substantially underestimated. The dominant mechanisms for tangential wind intensification in NoTCFB are similar to those in LRL, but their magnitudes are larger, implying a misrepresentation of the dominant momentum transfer processes in NoTCFB during RI. For the radial momentum budget analysis, the dominant processes are similar among the three experiments except for some differences in their locations and strengths.
RESUMO
BACKGROUND: Organ and tissue transplantation are now commonly preformed procedures. Improper organ bank handling procedures may increase infection risks. Execution accuracy in terms of tissue storage and distribution at our bone bank was 80%. We thus proposed an execution improvement project to enhance procedures in order to fulfill the intent of donors and ensure recipient safety. PURPOSE: This project was designed to raise nurse professionalism, and ensure patient safety through enhanced tissue storage and distribution procedures. RESOLUTION: Education programs developed for this project focus on teaching standard operating procedures for bone and ligament storage and distribution, bone bank facility maintenance, trouble shooting and solutions, and periodic inspection systems. RESULTS: Cognition of proper storage and distribution procedures rose from 81% to 100%; Execution accuracy also rose from 80% to 100%. CONCLUSIONS: The project successfully conveyed concepts essential to the correct execution of organ storage and distribution procedures and proper organ bank facility management. Achieving and maintaining procedural and management standards is crucial to continued organ donations and the recipient safety.
Assuntos
Bancos de Ossos , Coleta de Tecidos e Órgãos/métodos , Educação em Enfermagem , Humanos , Segurança do Paciente , Coleta de Tecidos e Órgãos/normas , Obtenção de Tecidos e ÓrgãosRESUMO
BACKGROUNDS: Inappropriate patient positioning during surgery causes respiratory pattern changes, inadequate gaseous exchange, tissue hypoperfusion and disruption of skin integrity. Inadvertent loosening of positioning devices on a patient in our ward during surgery caused surgical field contamination. We thus proposed a project to promote patient positioning accuracy in operating rooms to improve patient safety. PURPOSES: This project was intended to promote accurate patient positioning by operating room nurses, raise nursing professionalism, ensure patient safety, and avoid unnecessary patient injury. RESOLUTIONS: Under the project, we held educational training programs, developed patient positioning standard operating procedures (SOPs) and check lists, inspected all positioning assistance devices, purchased additional belt restraint straps, and conducted periodic monitoring. RESULTS: Patient positioning execution accuracy increased from 80% to 100%; cognition of patient positioning increased from 88% to 100%. CONCLUSIONS: The operating room committee adopted the proposed procedures and they are now SOPs in all operating rooms at our hospital. We suggest including the SOPs developed in this project in continuous education programs and urge making well-designed positioning assistance devices available to protect patient safety during surgery.