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1.
BMC Surg ; 24(1): 140, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38720305

RESUMO

BACKGROUND: We investigated the real-world efficacy of adjuvant therapy for stage I lung adenocarcinoma patients with pathological high-risk factors. METHODS: Study participants were enrolled from November 1, 2016 and December 31, 2020. Clinical bias was balanced by propensity score matching. Disease-free survival (DFS) outcomes were compared by Kaplan-Meier analysis. The Cox proportional hazards regression was used to identify survival-associated factors. p ≤ 0.05 was the threshold for statistical significance. RESULTS: A total of 454 patients, among whom 134 (29.5%) underwent adjuvant therapy, were enrolled in this study. One hundred and eighteen of the patients who underwent adjuvant therapy were well matched with non-treatment patients. Prognostic outcomes of the treatment group were significantly better than those of the non-treatment group, as revealed by Kaplan-Meier analysis after PSM. Differences in prevention of recurrence or metastasis between the targeted therapy and chemotherapy groups were insignificant. Adjuvant therapy was found to be positive prognostic factors, tumor size and solid growth patterns were negative. CONCLUSIONS: Adjuvant therapy significantly improved the DFS for stage I lung adenocarcinoma patients with high-risk factors. Larger prospective clinical trials should be performed to verify our findings.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Estadiamento de Neoplasias , Pontuação de Propensão , Humanos , Feminino , Masculino , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/mortalidade , Pessoa de Meia-Idade , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/cirurgia , Adenocarcinoma de Pulmão/terapia , Adenocarcinoma de Pulmão/mortalidade , Quimioterapia Adjuvante , Fatores de Risco , Idoso , Estudos Retrospectivos , Resultado do Tratamento , Pneumonectomia/métodos , Intervalo Livre de Doença , Prognóstico , Estimativa de Kaplan-Meier
2.
World J Surg Oncol ; 22(1): 26, 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38263144

RESUMO

OBJECTIVE: To explore the risk factors for disease progression after initial treatment of type B thymomas using a predictive nomogram model. METHODS: A single-center retrospective study of patients with type B thymoma was performed. The Cox proportional hazard model was used for univariate and multivariate analyses. Variables with statistical and clinical significance in the multivariate Cox regression were integrated into a nomogram to establish a predictive model for disease progression. RESULTS: A total of 353 cases with type B thymoma were retrieved between January 2012 and December 2021. The median follow-up was 58 months (range: 1-128 months). The 10-year progression-free survival (PFS) was 91.8%. The final nomogram model included R0 resection status and Masaoka stage, with a concordance index of 0.880. Non-R0 resection and advanced Masaoka stage were negative prognostic factors for disease progression (p < 0.001). No benefits of postoperative radiotherapy (PORT) were observed in patients with advanced stage and non-R0 resection (p = 0.114 and 0.284, respectively). CONCLUSION: The best treatment strategy for type B thymoma is the detection and achievement of R0 resection as early as possible. Long-term follow-up is necessary, especially for patients with advanced Masaoka stage and who have not achieved R0 resection. No prognostic benefits were observed for PORT.


Assuntos
Timoma , Neoplasias do Timo , Humanos , Nomogramas , Estudos Retrospectivos , Prognóstico , Progressão da Doença
3.
Microbiome ; 11(1): 117, 2023 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-37226179

RESUMO

BACKGROUND: The advent of culture-independent, next-generation DNA sequencing has led to the discovery of distinct lung bacterial communities. Studies of lung microbiome taxonomy often reveal only subtle differences between health and disease, but host recognition and response may distinguish the members of similar bacterial communities in different populations. Magnetic-activated cell sorting has been applied to the gut microbiome to identify the numbers and types of bacteria eliciting a humoral response. We adapted this technique to examine the populations of immunoglobulin-bound bacteria in the lung. METHODS: Sixty-four individuals underwent bronchoalveolar lavage (BAL). We separated immunoglobulin G-bound bacteria using magnetic-activated cell sorting and sequenced the 16S rRNA gene on the Illumina MiSeq platform. We compared microbial sequencing data in IgG-bound bacterial communities compared to raw BAL then examined the differences in individuals with and without HIV as a representative disease state. RESULTS: Immunoglobulin G-bound bacteria were identified in all individuals. The community structure differed when compared to raw BAL, and there was a greater abundance of Pseudomonas and fewer oral bacteria in IgG-bound BAL. Examination of IgG-bound communities in individuals with HIV demonstrated the differences in Ig-bound bacteria by HIV status that were not seen in a comparison of raw BAL, and greater numbers of immunoglobulin-bound bacteria were associated with higher pulmonary cytokine levels. CONCLUSIONS: We report a novel application of magnetic-activated cell sorting to identify immunoglobulin G-bound bacteria in the lung. This technique identified distinct bacterial communities which differed in composition from raw bronchoalveolar lavage, revealing the differences not detected by traditional analyses. Cytokine response was also associated with differential immunoglobulin binding of lung bacteria, suggesting the functional importance of these communities. Video Abstract.


Assuntos
Infecções por HIV , Microbiota , Humanos , RNA Ribossômico 16S/genética , Microbiota/genética , Imunoglobulina G , Citocinas , Dimercaprol , Fenômenos Magnéticos
4.
Thorac Cancer ; 14(15): 1339-1347, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37037477

RESUMO

BACKGROUND: This study aimed to examine the treatment and prognosis of patients with type B2 + B3 thymoma and compare it with those patients with type B2 and B3 thymoma. METHODS: We conducted a retrospective analysis of the results of 39 patients with type B2 + B3 thymoma, 133 patients with type B2 thymoma, and 64 patients with type B3 thymoma. The Kaplan-Meier technique was used to generate survival curves. For multivariate analysis, the Cox proportional hazard model was applied. RESULTS: With a median follow-up of 60 months (range: 1-128 months), the percentage of patients with tumor, node, metastasis (TNM) stage III and IV disease gradually increased from 19.5% to 25.6% to 35.9% among those with histological subtypes B2, B2 + B3, and B3, respectively, p = 0.045. Twenty-three patients experienced recurrence or metastasis. The total 10-year progression-free survival (PFS) rates were 86.0% overall (85.0% in type B2, 87.2% in type B2 + B3, and 87.5% in type B3). Age, R0 resection, and Masaoka-Koga stage were found to have a significant on PFS in all patients. There was no statistically significant difference in PFS between different histotypes of thymoma, p = 0.650. PFS was predicted by R0 resection in all histotypes and by the Masaoka-Koga stage in the type B2 subgroup. CONCLUSION: Combining the two staging methods to guide the diagnosis and treatment of patients with B2 + B3 thymoma is recommended. R0 resection is recommended to reduce recurrence. Patients with B2 + B3 thymoma have a prognosis similar to those with a B2 thymoma or a B3 thymoma alone.


Assuntos
Timoma , Neoplasias do Timo , Humanos , Timoma/cirurgia , Timoma/diagnóstico , Estudos Retrospectivos , Neoplasias do Timo/cirurgia , Neoplasias do Timo/diagnóstico , Prognóstico , Intervalo Livre de Progressão , Estadiamento de Neoplasias , Resultado do Tratamento
5.
J Org Chem ; 88(1): 189-197, 2023 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-36548942

RESUMO

The diverse structures of DNA serve as potent chiral scaffolds for DNA-based asymmetric catalysis, yet in most cases tens to hundreds of nucleotides in DNA hybrid catalysts hinder the deep insight into their structure-activity relationship. Owing to the structural simplicity and design flexibility of nucleotides, nucleotide-based catalysts have been emerging as a promising way to obtain fine structural information and understand the catalytic mechanisms. Herein, we found that a cyclic dinucleotide of cyclic di-AMP (c-di-AMP) and 1,10-phenanthroline copper(II) nitrate (Cu(phen)(NO3)2) are assembled to a c-di-AMP-based catalyst (c-di-AMP/Cu(phen)(NO3)2), which could fast achieve enantioselective fluorination in water with 90-99% yields and up to 90% enantiomeric excess (ee). The host-guest interaction between c-di-AMP and Cu(phen)(NO3)2 has been proposed mainly in a supramolecular interaction mode as evidenced by spectroscopic techniques of ultraviolet-visible, fluorescence, circular dichroism, and nuclear magnetic resonance. Cu(phen)(NO3)2 tightly binds to c-di-AMP with a binding constant of 1.7 ± 0.3 × 105 M-1, and the assembly of c-di-AMP/Cu(phen)(NO3)2 shows a modest rate enhancement to carbon-fluorine bond formations as supported by kinetic studies.


Assuntos
Halogenação , Água , Estereoisomerismo , Cinética , Cobre/química , Nucleotídeos , DNA/química
6.
Front Hum Neurosci ; 16: 949655, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35967006

RESUMO

Recently, researchers have expanded the investigation into attentional biases toward positive stimuli; however, few studies have examined attentional biases toward positive auditory information. In three experiments, the present study employed an emotional spatial cueing task using emotional sounds as cues and auditory stimuli (Experiment 1) or visual stimuli (Experiment 2 and Experiment 3) as targets to explore whether auditory or visual spatial attention could be modulated by positive auditory cues. Experiment 3 also examined the temporal dynamics of cross-modal auditory bias toward positive natural sounds using event-related potentials (ERPs). The behavioral results of the three experiments consistently demonstrated that response times to targets were faster after positive auditory cues than they were after neutral auditory cues in the valid condition, indicating that healthy participants showed a selective auditory attentional bias (Experiment 1) and cross-modal attentional bias (Experiment 2 and Experiment 3) toward positive natural sounds. The results of Experiment 3 showed that N1 amplitudes were more negative after positive sounds than they were after neutral sounds, which further provided electrophysiological evidence that positive auditory information enhances attention at early stages in healthy adults. The results of the experiments performed in the present study suggest that humans exhibit an attentional bias toward positive natural sounds.

7.
Clin Transl Med ; 12(1): e711, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-35083881

RESUMO

Treatments for pulmonary fibrosis (PF) are ineffective because its molecular pathogenesis and therapeutic targets are unclear. Here, we show that the expression of low-density lipoprotein receptor (LDLR) was significantly decreased in alveolar type II (ATII) and fibroblast cells, whereas it was increased in endothelial cells from systemic sclerosis-related PF (SSc-PF) patients and idiopathic PF (IPF) patients compared with healthy controls. However, the plasma levels of low-density lipoprotein (LDL) increased in SSc-PF and IPF patients. The disrupted LDL-LDLR metabolism was also observed in four mouse PF models. Upon bleomycin (BLM) treatment, Ldlr-deficient (Ldlr-/-) mice exhibited remarkably higher LDL levels, abundant apoptosis, increased fibroblast-like endothelial and ATII cells and significantly earlier and more severe fibrotic response compared to wild-type mice. In vitro experiments revealed that apoptosis and TGF-ß1 production were induced by LDL, while fibroblast-like cell accumulation and ET-1 expression were induced by LDLR knockdown. Treatment of fibroblasts with LDL or culture medium derived from LDL-pretreated endothelial or epithelial cells led to obvious fibrotic responses in vitro. Similar results were observed after LDLR knockdown operation. These results suggest that disturbed LDL-LDLR metabolism contributes in various ways to the malfunction of endothelial and epithelial cells, and fibroblasts during pulmonary fibrogenesis. In addition, pharmacological restoration of LDLR levels by using a combination of atorvastatin and alirocumab inhibited BLM-induced LDL elevation, apoptosis, fibroblast-like cell accumulation and mitigated PF in mice. Therefore, LDL-LDLR may serve as an important mediator in PF, and LDLR enhancing strategies may have beneficial effects on PF.


Assuntos
Lipoproteínas LDL/genética , Fibrose Pulmonar/etiologia , Receptores de LDL/metabolismo , Animais , Modelos Animais de Doenças , Lipoproteínas LDL/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL/genética , Camundongos Endogâmicos C57BL/metabolismo , Fibrose Pulmonar/genética
8.
Proc Biol Sci ; 288(1948): 20203045, 2021 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-33849320

RESUMO

The decline in species richness at higher latitudes is among the most fundamental patterns in ecology. Whether changes in species composition across space (beta-diversity) contribute to this gradient of overall species richness (gamma-diversity) remains hotly debated. Previous studies that failed to resolve the issue suffered from a well-known tendency for small samples in areas with high gamma-diversity to have inflated measures of beta-diversity. Here, we provide a novel analytical test, using beta-diversity metrics that correct the gamma-diversity and sampling biases, to compare beta-diversity and species packing across a latitudinal gradient in tree species richness of 21 large forest plots along a large environmental gradient in East Asia. We demonstrate that after accounting for topography and correcting the gamma-diversity bias, tropical forests still have higher beta-diversity than temperate analogues. This suggests that beta-diversity contributes to the latitudinal species richness gradient as a component of gamma-diversity. Moreover, both niche specialization and niche marginality (a measure of niche spacing along an environmental gradient) also increase towards the equator, after controlling for the effect of topographical heterogeneity. This supports the joint importance of tighter species packing and larger niche space in tropical forests while also demonstrating the importance of local processes in controlling beta-diversity.


Assuntos
Biodiversidade , Árvores , Ecologia , Ásia Oriental
9.
PLoS One ; 16(3): e0248853, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33755703

RESUMO

Hyperglycemia during sepsis is associated with increased organ dysfunction and higher mortality. The role of the host immune response in development of hyperglycemia during sepsis remains unclear. We performed a retrospective analysis of critically ill adult septic patients requiring mechanical ventilation (n = 153) to study the relationship between hyperglycemia and ten markers of the host injury and immune response measured on the first day of ICU admission (baseline). We determined associations between each biomarker and: (1) glucose, insulin, and c-peptide levels at the time of biomarker collection by Pearson correlation; (2) average glucose and glycemic variability in the first two days of ICU admission by linear regression; and (3) occurrence of hyperglycemia (blood glucose>180mg/dL) by logistic regression. Results were adjusted for age, pre-existing diabetes mellitus, severity of illness, and total insulin and glucocorticoid dose. Baseline plasma levels of ST2 and procalcitonin were positively correlated with average blood glucose and glycemic variability in the first two days of ICU admission in unadjusted and adjusted analyses. Additionally, higher baseline ST2, IL-1ra, procalcitonin, and pentraxin-3 levels were associated with increased risk of hyperglycemia. Our results suggest associations between the host immune response and hyperglycemia in critically ill septic patients particularly implicating the interleukin-1 axis (IL-1ra), the interleukin-33 axis (ST2), and the host response to bacterial infections (procalcitonin, pentraxin-3).


Assuntos
Interações Hospedeiro-Patógeno/imunologia , Hiperglicemia/imunologia , Imunidade , Respiração Artificial , Sepse/imunologia , Doença Aguda , Idoso , Biomarcadores/metabolismo , Glicemia/metabolismo , Feminino , Hospitalização , Humanos , Hiperglicemia/sangue , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Sepse/sangue
10.
Sci Rep ; 11(1): 5096, 2021 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-33658530

RESUMO

Current codes for fire protection of buildings are mainly based on the movement of adults and neglect the movement characteristic of pre-school children. Having a profound comprehension of the difference between children and adults passing bottlenecks is of great help to improve the safety levels of preschool children. This paper presents an experimental study on the bottleneck flow of pre-school children in a room. The movement characteristics of children's and adults' bottleneck flow are investigated with two macroscopic properties: density and speed profiles as well as microscopic characteristic time: motion activation time, relaxation time, exit travel time and time gap. Arch-like density distributions are observed both for highly motivated children and adults, while the distance between the peak density region and the exit location is shorter for children and longer for adults. Children's movement is less flexible manifested as longer motion activation time and longer relaxation time compared to that of adults. The findings from this study could enhance the understanding of crowd dynamics among the children population and provide supports for the scientific building design for children's facilities.


Assuntos
Aglomeração/psicologia , Incêndios , Motivação/fisiologia , Segurança , Velocidade de Caminhada/fisiologia , Adolescente , Adulto , Pré-Escolar , Feminino , Humanos , Masculino , Movimento (Física) , Relaxamento , Estudantes , Fatores de Tempo , Adulto Jovem
11.
J Hazard Mater ; 412: 125176, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-33517055

RESUMO

Adding steel slag to the acidic contaminated mine soil can immobilize heavy metal ions, but immobilization persistence of the metal ions needs to be determined. In this study, dynamic column simulation experiments were set up to compare the immobilization persistence of Cu, Cr, Pb and Zn ions in original soil and with the addition of slag, lime or fly ash to the soil during a simulated 36-month of acid rain leaching. After adding slag and lime, the pH, organic matter content and cation exchange capacity of soil were significantly increased. Compared with the original soil, additions of slag and lime to the soil were able to persistently immobilize the metal ions, whereas fly ash additions had little effect. During simulation, the metal ion concentrations in the slag group leaching solution were essentially consistent with Standard IV for groundwater. The metal ions were immobilized to form instable hydroxides and stable fractions following adding slag to soil. The hydroxide could rerelease metal ions by acid rain leaching, part of which were re-immobilized into stable fractions by entering slag lattice and complexing with soil organic matter. Therefore, adding slag to soil can persistently immobilize metal ions for heavy metal-contaminated acidic mine soil.

12.
Thorax ; 76(3): 239-247, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33268457

RESUMO

BACKGROUND: Lung microbiota profiles in patients with early idiopathic pulmonary fibrosis (IPF) have been associated with disease progression; however, the topographic heterogeneity of lung microbiota and their roles in advanced IPF are unknown. METHODS: We performed a retrospective, case-control study of explanted lung tissue obtained at the time of lung transplantation or rapid autopsy from patients with IPF and other chronic lung diseases (connective tissue disease-associated interstitial lung disease (CTD-ILD), cystic fibrosis (CF), COPD and donor lungs unsuitable for transplant from Center for Organ Recovery and Education (CORE)). We sampled subpleural tissue and airway-based specimens (bronchial washings and airway tissue) and quantified bacterial load and profiled communities by amplification and sequencing of the 16S rRNA gene. FINDINGS: Explants from 62 patients with IPF, 15 patients with CTD-ILD, 20 patients with CF, 20 patients with COPD and 20 CORE patients were included. Airway-based samples had higher bacterial load compared with distal parenchymal tissue. IPF basilar tissue had much lower bacterial load compared with CF and CORE lungs (p<0.001). No microbial community differences were found between parenchymal tissue samples from different IPF lobes. Dirichlet multinomial models revealed an IPF cluster (29%) with distinct composition, high bacterial load and low alpha diversity, exhibiting higher odds for acute exacerbation or death. INTERPRETATION: IPF explants had low biomass in the distal parenchyma of all three lobes with higher bacterial load in the airways. The discovery of a distinct subgroup of patients with IPF with higher bacterial load and worse clinical outcomes supports investigation of personalised medicine approaches for microbiome-targeted interventions.


Assuntos
Fibrose Pulmonar Idiopática/microbiologia , Transplante de Pulmão , Pulmão/microbiologia , Microbiota/fisiologia , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Líquido da Lavagem Broncoalveolar/microbiologia , Estudos de Casos e Controles , Progressão da Doença , Humanos , Fibrose Pulmonar Idiopática/diagnóstico , Fibrose Pulmonar Idiopática/cirurgia , Pulmão/diagnóstico por imagem , Pulmão/cirurgia , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
13.
Am J Respir Crit Care Med ; 202(12): 1666-1677, 2020 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-32717152

RESUMO

Rationale: Host inflammatory responses have been strongly associated with adverse outcomes in critically ill patients, but the biologic underpinnings of such heterogeneous responses have not been defined.Objectives: We examined whether respiratory tract microbiome profiles are associated with host inflammation and clinical outcomes of acute respiratory failure.Methods: We collected oral swabs, endotracheal aspirates (ETAs), and plasma samples from mechanically ventilated patients. We performed 16S ribosomal RNA gene sequencing to characterize upper and lower respiratory tract microbiota and classified patients into host-response subphenotypes on the basis of clinical variables and plasma biomarkers of innate immunity and inflammation. We derived diversity metrics and composition clusters with Dirichlet multinomial models and examined our data for associations with subphenotypes and clinical outcomes.Measurements and Main Results: Oral and ETA microbial communities from 301 mechanically ventilated subjects had substantial heterogeneity in α and ß diversity. Dirichlet multinomial models revealed a cluster with low α diversity and enrichment for pathogens (e.g., high Staphylococcus or Pseudomonadaceae relative abundance) in 35% of ETA samples, associated with a hyperinflammatory subphenotype, worse 30-day survival, and longer time to liberation from mechanical ventilation (adjusted P < 0.05), compared with patients with higher α diversity and relative abundance of typical oral microbiota. Patients with evidence of dysbiosis (low α diversity and low relative abundance of "protective" oral-origin commensal bacteria) in both oral and ETA samples (17%, combined dysbiosis) had significantly worse 30-day survival and longer time to liberation from mechanical ventilation than patients without dysbiosis (55%; adjusted P < 0.05).Conclusions: Respiratory tract dysbiosis may represent an important, modifiable contributor to patient-level heterogeneity in systemic inflammatory responses and clinical outcomes.


Assuntos
Disbiose/etiologia , Disbiose/mortalidade , Microbiota/genética , Respiração Artificial/efeitos adversos , Respiração Artificial/mortalidade , Síndrome do Desconforto Respiratório/etiologia , Síndrome do Desconforto Respiratório/mortalidade , Sistema Respiratório/microbiologia , Adulto , Idoso , Estado Terminal/terapia , Feminino , Variação Genética , Humanos , Inflamação/etiologia , Inflamação/microbiologia , Masculino
14.
J Crit Care ; 56: 222-228, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32028223

RESUMO

PURPOSE: To assess the longitudinal evolution of radiographic edema using chest X-rays (CXR) in patients with Acute Respiratory Distress Syndrome (ARDS) and to examine its association with prognostic biomarkers, ARDS subphenotypes and outcomes. MATERIALS AND METHODS: We quantified radiographic edema on CXRs from patients with ARDS or cardiogenic pulmonary edema (controls) using the Radiographic Assessment of Lung Edema (RALE) score on day of intubation and up to 10 days after. We measured baseline plasma biomarkers and recorded clinical variables. RESULTS: The RALE score had good inter-rater agreement (r = 0.83, p < 0.0001) applied on 488 CXRs from 129 patients, with higher RALE scores in patients with ARDS (n = 108) compared to controls (n = 21, p = 0.01). Baseline RALE scores were positively correlated with levels of the receptor for end-glycation end products (RAGE) in ARDS patients (p < 0.05). Baseline RALE scores were not predictive of 30- or 90-day survival. Persistently elevated RALE scores were associated with prolonged need for mechanical ventilation (p = 0.002). CONCLUSIONS: The RALE score is easily implementable with high inter-rater reliability. Longitudinal RALE scoring appears to be a reproducible approach to track the evolution of radiographic edema in patients with ARDS and can potentially predict prolonged need for mechanical ventilation.


Assuntos
Pulmão/fisiopatologia , Edema Pulmonar/complicações , Respiração Artificial , Síndrome do Desconforto Respiratório/complicações , Adulto , Idoso , Biomarcadores , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Fenótipo , Prognóstico , Estudos Prospectivos , Edema Pulmonar/diagnóstico por imagem , Edema Pulmonar/terapia , Radiografia Torácica , Reprodutibilidade dos Testes , Síndrome do Desconforto Respiratório/terapia , Índice de Gravidade de Doença , Resultado do Tratamento
15.
Am J Respir Crit Care Med ; 201(4): 445-457, 2020 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-31682463

RESUMO

Rationale: Mechanisms of HIV-associated chronic obstructive pulmonary disease (COPD) are poorly understood. The oral microbiome shapes the lung microbiome, and gut dysbiosis can affect lung diseases; however, relationships of the oral and gut microbiome to COPD in HIV have not been explored.Objectives: To examine alterations in the oral and gut microbiome associated with pulmonary disease in persons with HIV (PWH).Methods: Seventy-five PWH and 93 HIV-uninfected men from the MACS (Multicenter AIDS Cohort Study) performed pulmonary function testing. Sequencing of bacterial 16S ribosomal RNA in saliva and stool was performed. We used nonmetric multidimensional scaling, permutational multivariate ANOVA, and linear discriminant analysis to analyze communities by HIV and lung function.Measurements and Main Results: Oral microbiome composition differed by HIV and smoking status. Alterations of oral microbial communities were observed in PWH with abnormal lung function with increases in relative abundance of Veillonella, Streptococcus, and Lactobacillus. There were no significant associations between the oral microbiome and lung function in HIV-uninfected individuals. No associations with HIV status or lung function were seen with the gut microbiome.Conclusions: Alterations of oral microbiota in PWH were related to impaired pulmonary function and to systemic inflammation. These results suggest that the oral microbiome may serve as a biomarker of lung function in HIV and that its disruption may contribute to COPD pathogenesis.


Assuntos
Microbioma Gastrointestinal , Infecções por HIV/complicações , Infecções por HIV/microbiologia , Microbiota , Boca/microbiologia , Doença Pulmonar Obstrutiva Crônica/etiologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes de Função Respiratória
16.
Respir Res ; 20(1): 265, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31775777

RESUMO

BACKGROUND: Metagenomic sequencing of respiratory microbial communities for pathogen identification in pneumonia may help overcome the limitations of culture-based methods. We examined the feasibility and clinical validity of rapid-turnaround metagenomics with Nanopore™ sequencing of clinical respiratory specimens. METHODS: We conducted a case-control study of mechanically-ventilated patients with pneumonia (nine culture-positive and five culture-negative) and without pneumonia (eight controls). We collected endotracheal aspirates and applied a microbial DNA enrichment method prior to metagenomic sequencing with the Oxford Nanopore MinION device. For reference, we compared Nanopore results against clinical microbiologic cultures and bacterial 16S rRNA gene sequencing. RESULTS: Human DNA depletion enabled in depth sequencing of microbial communities. In culture-positive cases, Nanopore revealed communities with high abundance of the bacterial or fungal species isolated by cultures. In four cases with resistant clinical isolates, Nanopore detected antibiotic resistance genes corresponding to the phenotypic resistance in antibiograms. In culture-negative pneumonia, Nanopore revealed probable bacterial pathogens in 1/5 cases and Candida colonization in 3/5 cases. In controls, Nanopore showed high abundance of oral bacteria in 5/8 subjects, and identified colonizing respiratory pathogens in other subjects. Nanopore and 16S sequencing showed excellent concordance for the most abundant bacterial taxa. CONCLUSIONS: We demonstrated technical feasibility and proof-of-concept clinical validity of Nanopore metagenomics for severe pneumonia diagnosis, with striking concordance with positive microbiologic cultures, and clinically actionable information obtained from sequencing in culture-negative samples. Prospective studies with real-time metagenomics are warranted to examine the impact on antimicrobial decision-making and clinical outcomes.


Assuntos
DNA Bacteriano/genética , Microbiota/genética , Nanoporos , Pneumonia/genética , Pneumonia/terapia , Antibacterianos/administração & dosagem , Estudos de Casos e Controles , Estudos de Viabilidade , Feminino , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Masculino , Metagenômica/métodos , Pneumonia/diagnóstico , Valores de Referência , Respiração Artificial/métodos , Insuficiência Respiratória/diagnóstico , Insuficiência Respiratória/genética , Insuficiência Respiratória/terapia , Fatores de Risco , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Fatores de Virulência/genética
17.
Crit Care Med ; 47(12): 1724-1734, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31634231

RESUMO

OBJECTIVES: Classification of patients with acute respiratory distress syndrome into hyper- and hypoinflammatory subphenotypes using plasma biomarkers may facilitate more effective targeted therapy. We examined whether established subphenotypes are present not only in patients with acute respiratory distress syndrome but also in patients at risk for acute respiratory distress syndrome (ARFA) and then assessed the prognostic information of baseline subphenotyping on the evolution of host-response biomarkers and clinical outcomes. DESIGN: Prospective, observational cohort study. SETTING: Medical ICU at a tertiary academic medical center. PATIENTS: Mechanically ventilated patients with acute respiratory distress syndrome or ARFA. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We performed longitudinal measurements of 10 plasma biomarkers of host injury and inflammation. We applied unsupervised latent class analysis methods utilizing baseline clinical and biomarker variables and demonstrated that two-class models (hyper- vs hypoinflammatory subphenotypes) offered improved fit compared with one-class models in both patients with acute respiratory distress syndrome and ARFA. Baseline assignment to the hyperinflammatory subphenotype (39/104 [38%] acute respiratory distress syndrome and 30/108 [28%] ARFA patients) was associated with higher severity of illness by Sequential Organ Failure Assessment scores and incidence of acute kidney injury in patients with acute respiratory distress syndrome, as well as higher 30-day mortality and longer duration of mechanical ventilation in ARFA patients (p < 0.0001). Hyperinflammatory patients exhibited persistent elevation of biomarkers of innate immunity for up to 2 weeks postintubation. CONCLUSIONS: Our results suggest that two distinct subphenotypes are present not only in patients with established acute respiratory distress syndrome but also in patients at risk for its development. Hyperinflammatory classification at baseline is associated with higher severity of illness, worse clinical outcomes, and trajectories of persistently elevated biomarkers of host injury and inflammation during acute critical illness compared with hypoinflammatory patients. Our findings provide strong rationale for examining treatment effect modifications by subphenotypes in randomized clinical trials to inform precision therapeutic approaches in critical care.


Assuntos
Síndrome do Desconforto Respiratório/sangue , Síndrome do Desconforto Respiratório/complicações , Adulto , Idoso , Biomarcadores/sangue , Feminino , Humanos , Inflamação/sangue , Inflamação/complicações , Masculino , Pessoa de Meia-Idade , Fenótipo , Prognóstico , Estudos Prospectivos , Síndrome do Desconforto Respiratório/classificação , Síndrome do Desconforto Respiratório/genética , Medição de Risco
18.
Anxiety Stress Coping ; 32(3): 298-311, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30782012

RESUMO

BACKGROUND AND OBJECTIVES: Previous studies have not consistently concluded whether high-anxious persons exhibit attentional bias towards negative natural auditory stimuli. The present study explores whether auditory negative stimuli could induce attentional bias to negative sounds in real life and investigates the exact nature of these biases using an emotional spatial cueing task. DESIGN: Experimental study with a mixed factorial design. METHOD: We created two groups according to the state-trait anxiety scale, namely high and low trait anxiety. Participants (N = 68 undergraduate students) were required to respond to an auditory target after receiving a negative (aversive sounds from natural life) or neutral auditory stimuli. RESULTS: A 2 (Validity: valid/invalid) × 2 (Cue Valence: negative/neutral) × 2 (Anxiety Group: LA/HA) repeated-measures ANOVA on reaction times revealed that participants with high trait anxiety exhibited slower reaction times in invalid trials following negative cues than following neutral cues. Higher levels of trait anxiety were associated with more difficult attentional disengagement from negative auditory information. CONCLUSIONS: The results demonstrate that impaired attentional disengagement was one of the mechanisms by which high-anxious participants exhibited auditory attentional bias to natural negative information.


Assuntos
Estimulação Acústica/psicologia , Ansiedade/psicologia , Viés de Atenção , Ansiedade/etiologia , Atenção , Feminino , Humanos , Masculino , Personalidade , Escalas de Graduação Psiquiátrica , Tempo de Reação , Adulto Jovem
19.
Rev Sci Instrum ; 82(9): 093301, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21974579

RESUMO

An in-chamber, mini x-ray imaging instrument employs a pinhole and a logarithmic spiral crystal has been developed for obtaining K-shell line images of the imploding aluminum wire array on the "Yang" accelerator. The logarithmic spiral crystal acts as a monochromator and a non-dispersive mirror that reflects the pinhole image to a x-ray film detector with a very narrow photon energy bandwidth (<1 eV, mainly determined by the width of rocking curve of the crystal). Two imaging configurations with the use of Quartz (10 ̅10) crystal and Mica (002) crystal are designed, respectively, to image the Al Ly(α2) line (1727.7 eV) emission and Al He(α) intercombination line (1588.3 eV) emission. The primary experimental data corresponding to these two configurations are presented and discussed.

20.
Rev Sci Instrum ; 80(6): 063106, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19566195

RESUMO

An unfolding algorithm using parabolic B-splines to smoothly reconstruct the soft x-ray spectra from the measurements of a filtered x-ray diode array is proposed. This array has been fabricated for the study of the soft x ray emitted by Z-pinch plasma. Unfolding results show that for the simulated noise-free blackbody spectra with temperature ranging from 20 to 250 eV, both the spectra and the total power are accurately recovered. Typical experimental waveforms along with the unfolded spectra and total power of x rays are presented. Possible defects due to the adoption of parabolic B-splines instead of conventionally used histograms are discussed.

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