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1.
Stroke ; 55(5): 1438-1448, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38648281

RESUMO

ARISE (Aneurysm/AVM/cSDH Roundtable Discussion With Industry and Stroke Experts) organized a one-and-a-half day meeting and workshop and brought together representatives from academia, industry, and government to discuss the most promising approaches to improve outcomes for patients with chronic subdural hematoma (cSDH). The emerging role of middle meningeal artery embolization in clinical practice and the design of current and potential future trials were the primary focuses of discussion. Existing evidence for imaging, indications, agents, and techniques was reviewed, and areas of priority for study and key questions surrounding the development of new and existing treatments for cSDH were identified. Multiple randomized, controlled trials have met their primary efficacy end points, providing high-level evidence that middle meningeal artery embolization is a potent adjunctive therapy to the standard (surgical and nonsurgical) management of neurologically stable cSDH patients in terms of reducing rates of disease recurrence. Pooled data analyses following the formal conclusion and publication of these trials will form a robust foundation upon which guidelines can be strengthened for cSDH treatment modalities and optimal patient selection, as well as delineate future lines of investigation.


Assuntos
Hematoma Subdural Crônico , Humanos , Consenso , Embolização Terapêutica/métodos , Hematoma Subdural Crônico/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto
2.
Anal Chem ; 96(21): 8772-8781, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38743842

RESUMO

The metabolic signature identification of colorectal cancer is critical for its early diagnosis and therapeutic approaches that will significantly block cancer progression and improve patient survival. Here, we combined an untargeted metabolic analysis strategy based on internal extractive electrospray ionization mass spectrometry and the machine learning approach to analyze metabolites in 173 pairs of cancer samples and matched normal tissue samples to build robust metabolic signature models for diagnostic purposes. Screening and independent validation of metabolic signatures from colorectal cancers via machine learning methods (Logistic Regression_L1 for feature selection and eXtreme Gradient Boosting for classification) was performed to generate a panel of seven signatures with good diagnostic performance (the accuracy of 87.74%, sensitivity of 85.82%, and specificity of 89.66%). Moreover, seven signatures were evaluated according to their ability to distinguish between cancer and normal tissues, with the metabolic molecule PC (30:0) showing good diagnostic performance. In addition, genes associated with PC (30:0) were identified by multiomics analysis (combining metabolic data with transcriptomic data analysis) and our results showed that PC (30:0) could promote the proliferation of colorectal cancer cell SW480, revealing the correlation between genetic changes and metabolic dysregulation in cancer. Overall, our results reveal potential determinants affecting metabolite dysregulation, paving the way for a mechanistic understanding of altered tissue metabolites in colorectal cancer and design interventions for manipulating the levels of circulating metabolites.


Assuntos
Neoplasias Colorretais , Aprendizado de Máquina , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/diagnóstico , Humanos , Metabolômica , Linhagem Celular Tumoral , Espectrometria de Massas por Ionização por Electrospray , Metaboloma , Proliferação de Células , Multiômica
3.
Mass Spectrom Rev ; 2023 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-37565588

RESUMO

The molecular composition of exhaled human breath can reflect various physiological and pathological conditions. Considerable progress has been achieved over the past decade in real-time analysis of exhaled human breath using direct mass spectrometry methods, including selected ion flow tube mass spectrometry, proton transfer reaction mass spectrometry, extractive electrospray ionization mass spectrometry, secondary electrospray ionization mass spectrometry, acetone-assisted negative photoionization mass spectrometry, atmospheric pressure photoionization mass spectrometry, and low-pressure photoionization mass spectrometry. Here, recent developments in direct mass spectrometry analysis of exhaled human breath are reviewed with regard to analytical performance (chemical sensitivity, selectivity, quantitative capabilities) and applications of the developed methods in disease diagnosis, targeted molecular detection, and real-time metabolic monitoring.

4.
Cerebrovasc Dis ; 2024 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-38432203

RESUMO

INTRODUCTION: Atrial fibrillation or flutter (AF) is a well-known risk factor for ischemic stroke. While female sex has been associated with higher stroke risk among AF patients, overall sex-specific real-world burdens of AF-related strokes and hemorrhages are unknown. METHODS: The 2016-2020 National Inpatient Sample was queried for hospitalizations, morbidity, and mortality due to AF-related ischemic strokes and bleeds. Patient demographic information, vascular risk factors, comorbidities, and stroke characteristics were extracted using ICD-10 codes. Overall incidences were calculated using total population estimates provided by the United States Census Bureau, and relative risk was calculated by comparing annual incidences between men and women. RESULTS: 2,420,870 ischemic stroke hospitalizations were identified; 542,635 (22.4%) were associated with AF. Overall, women had similar risk of hospitalization due to AF-related ischemic strokes compared to men; however, women had a higher risk of morbidity and mortality (RR 1.13 and 1.17, respectively; both p<0.001). In contrast, women had lower incidences of hospitalization, morbidity, and mortality due to AF-related bleeds (RR 0.82, 0.94, and 0.74, respectively; all p<0.001). Among patients with AF-related ischemic strokes, women had lower rates of anticoagulation use, higher rates of large vessel occlusion, and higher stroke severity (all p<0.001). These trends persisted among patients 80 years or older (all p<0.001). CONCLUSION: Women in the United States have higher incidences of morbidity and mortality from AF-related ischemic strokes than men. Future studies should investigate strategies to reduce morbidity and mortality due to AF-related strokes in women.

5.
J Stroke Cerebrovasc Dis ; 33(5): 107608, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38286159

RESUMO

BACKGROUND: While endovascular thrombectomy (EVT) is beneficial for patients with acute large vessel occlusion ischemic strokes, a significant portion of patients still do poorly despite successful recanalization. Identifying patients at high risk for poor outcomes can be helpful for future clinical trial design and optimizing acute stroke triage. METHODS: Consecutive EVT patients were identified from 2016 to 2021 at a Comprehensive Stroke Center, and clinical information was recorded. Poor outcome was defined as a 90-day modified Rankin Scale (mRS) of 4 or greater despite achieving a modified thrombolysis in cerebral infarction (mTICI) score of 2b or greater. Multivariable regression analyses were used to identify risk factors for poor outcomes, and a scoring system was constructed. RESULTS: 483 patients with successful recanalization were identified. From a randomly selected training cohort (n = 357), the 10-point BAND score was constructed from independent risk factors for poor outcomes: baseline disability (1 point: baseline mRS ≥ 2), age (1 point: 60-69 years, 2 points: 70-79 years, 3 points: 80-84 years, 4 points: 85 years or older), NIHSS (2 points: 13-17, 3 points: 18-22, and 4 points: ≥ 23), and delay from last known normal (1 point: ≥ 6 h). The BAND score was significantly associated with rates of poor outcomes (p < 0.001), and it achieved an area under the receiver-operating characteristic curve (AUC) of 0.80 (95 %CI 0.76-0.85) in our training cohort and 0.78 (95 %CI 0.70-0.86) in our validation cohort (n = 126). Overall, the BAND score had a significantly higher AUC value than the widely validated THRIVE score and the THRIVE-EVT calculation (p = 0.001 and 0.029, respectively). Among patients with high BAND scores (7 or higher), 88.2 % had poor outcomes. CONCLUSION: The BAND score is a simple tool to predict poor outcomes despite successful recanalization. Future studies are needed to confirm the BAND score's external validity.


Assuntos
Isquemia Encefálica , Procedimentos Endovasculares , Acidente Vascular Cerebral , Idoso , Humanos , Pessoa de Meia-Idade , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/terapia , Isquemia Encefálica/complicações , Infarto Cerebral/etiologia , Procedimentos Endovasculares/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/terapia , Acidente Vascular Cerebral/etiologia , Trombectomia/efeitos adversos , Resultado do Tratamento , Idoso de 80 Anos ou mais
6.
Stroke ; 54(2): 518-526, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36541211

RESUMO

BACKGROUND: Osteoarthritis and other musculoskeletal disorders are the leading causes of disability in the United States. While osteoarthritis is not a direct risk factor for stroke, osteoarthritis may impact patient selection for endovascular thrombectomy (EVT) due to prestroke disability. This study investigates associations of osteoarthritis with EVT utilization and outcomes. METHODS: This was a large-scale cross-sectional study of the 2016 to 2019 National Inpatient Sample database. Adult patients with anterior large vessel ischemic strokes were identified. Patient demographics, stroke risk factors, stroke etiology, presence of osteoarthritis, medical comorbidities, EVT, intravenous thrombolysis treatments, and discharge destinations were recorded. Primary outcome was the rate of EVT treatment. Secondary outcomes include rates of discharge to home and in-hospital mortality. Propensity score matching and multivariable logistic regression models were used to account for possible confounders. RESULTS: Two hundred fifty-two thousand five hundred five patients were identified, of whom 8.5% (21 500 patients) had osteoarthritis. After propensity score matching for 32 clinical variables, osteoarthritis patients were found to be 17.3% less likely to receive EVT than non-osteoarthritis patients (14.4% versus 17.3%, respectively; P<0.001). In multivariable logistic regression analysis, osteoarthritis was associated with 22.6% lower odds of receiving EVT (OR, 0.77 [95% CI, 0.70-0.86]; P<0.001), an effect size larger than any medical comorbidity captured in this study other than dementia and nonstroke neurological disease. Among those treated with EVT, multivariable logistic regression models showed that osteoarthritis was not associated with different odds of being discharged home (OR, 0.99 [95% CI, 0.81-1.21]; P=0.93); however, osteoarthritis was marginally associated with lower odds of in-hospital mortality (OR, 0.74 [95% CI, 0.54-1.01]; P=0.054). CONCLUSIONS: Large vessel ischemic stroke patients with osteoarthritis were significantly less likely to receive EVT therapy despite similar post-EVT outcomes. These results warrant further investigation and prompt a critical review of current patient selection practices for stroke EVT therapy, specifically for patients with baseline disability due to musculoskeletal conditions such as osteoarthritis.


Assuntos
Isquemia Encefálica , Procedimentos Endovasculares , AVC Isquêmico , Osteoartrite , Acidente Vascular Cerebral , Adulto , Humanos , AVC Isquêmico/etiologia , Isquemia Encefálica/terapia , Estudos Transversais , Resultado do Tratamento , Procedimentos Endovasculares/métodos , Acidente Vascular Cerebral/terapia , Trombectomia/métodos
7.
J Am Chem Soc ; 145(41): 22639-22648, 2023 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-37788450

RESUMO

Disulfide bonds are widely found in natural peptides and play a pivotal role in stabilizing their secondary structures, which are highly associated with their biological functions. Herein, we introduce a light-mediated strategy to effectively control the formation of disulfides. Our strategy is based on 2-nitroveratryl (oNv), a widely used photolabile motif, which serves both as a photocaging group and an oxidant (after photolysis). We demonstrated that irradiation of oNv-caged thiols with UV light could release free thiols that are rapidly oxidized by locally released byproduct nitrosoarene, leading to a "break-to-bond" fashion. This strategy is highlighted by the in situ restoration of the antimicrobial peptide tachyplesin I (TPI) from its external disulfide-caged analogue TPI-1. TPI-1 exhibits a distorted structure and a diminished function. However, upon irradiation, the ß-hairpin structure and membrane activity of TPI were largely restored via rapid intramolecular disulfide formation. Our study proposes a powerful method to regulate the conformation and function of peptides in a spatiotemporal manner, which has significant potential for the design of disulfide-centered light-responsive systems.


Assuntos
Dissulfetos , Compostos de Sulfidrila , Dissulfetos/química , Estrutura Secundária de Proteína , Compostos de Sulfidrila/química
8.
Cerebrovasc Dis ; 2023 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-37931607

RESUMO

INTRODUCTION: Endovascular treatment (EVT) is a therapeutic option for cerebral venous thrombosis (CVT); however, its benefit over conservative medical management has not been proven. Whether current patient selection practices are appropriate for EVT is unclear. METHODS: This was a nationwide study of the 2016-2020 National Inpatient Sample database. Adult CVT patients and EVT treatments were identified. Patient demographics, medical comorbidities, CVT risk factors, and CVT manifestations were identified. Presence of radiographic signs of advanced and severe CVT (venous infarction, cerebral edema, and intracranial hemorrhage) were recorded. Primary and secondary outcomes were good discharge outcomes and in-hospital mortality, respectively. RESULTS: 17,130 CVT patients were identified, and 56.7% had good discharge outcomes while 4.6% died during hospitalization. 945 (5.5%) received EVT, and EVT patients were more likely to have cerebral infarction (35.4% vs. 21.8%, p<0.001), edema (35.4% vs. 20.1%, p<0.001), and hemorrhage (37.6% vs. 19.7%, p<0.001). After multivariable adjustments, EVT for patients without infarction, edema, or hemorrhage was moderately associated with higher odds of good outcomes (OR 1.86 [95%CI 0.98 - 3.53], p=0.059) and resulted in zero deaths. However, with increasing burden of radiographic signs of advanced CVT measured by the cumulative presence of infraction, edema, and hemorrhage, EVT was associated with decreasing odds of good outcomes and increasing odds of in-hospital mortality compared to medical management (interaction p=0.046 and 0.029, respectively). CONCLUSIONS: EVT may lead to higher rates of favorable hospitalization outcomes in patients who have not yet developed overt parenchymal manifestations of backpressure changes; presence of infarction, edema, and hemorrhage may diminish the short-term effectiveness of EVT.

9.
Molecules ; 28(17)2023 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-37687031

RESUMO

Obesity, diabetes, and cardiovascular diseases are the major chronic metabolic diseases that threaten human health. In order to combat these epidemics, there remains a desperate need for effective, safe, and easily available therapeutic strategies. Recently, the development of natural product research has provided new methods and options for these diseases. Numerous studies have demonstrated that microRNAs (miRNAs) are key regulators of metabolic diseases, and natural products can improve lipid and glucose metabolism disorders and cardiovascular diseases by regulating the expression of miRNAs. In this review, we present the recent advances involving the associations between miRNAs and natural products and the current evidence showing the positive effects of miRNAs for natural product treatment in metabolic diseases. We also encourage further research to address the relationship between miRNAs and natural products under physiological and pathological conditions, thus leading to stronger support for drug development from natural products in the future.


Assuntos
Produtos Biológicos , Doenças Cardiovasculares , Doenças Metabólicas , MicroRNAs , Humanos , Doenças Metabólicas/tratamento farmacológico , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Desenvolvimento de Medicamentos , MicroRNAs/genética
10.
J Am Chem Soc ; 144(51): 23614-23621, 2022 12 28.
Artigo em Inglês | MEDLINE | ID: mdl-36530144

RESUMO

We have developed a new concept for reversible peptide stapling that involves macrocyclization between two amino groups and decyclization promoted via dual 1,4-elimination. Depending on the trigger moiety, this strategy could be employed to selectively deliver peptides to either intracellular or extracellular targets. As a proof of concept, a peptide inhibitor targeting a lysine-specific demethylase 1 (LSD1) was temporarily cyclized to enhance its stability and ability to cross the cell membrane. Once inside the cells, the biologically active linear peptide was released under reducing environment. Moreover, we have developed reversibly stapled peptides using antimicrobial peptides (RStAMPs) whose bioactive helical conformation can be temporarily destabilized by stapling the peptide backbone. The resulting helix-distorted RStAMPs are nontoxic and highly resistant to protease hydrolysis, while at the infection site, RStAMPs can be rapidly activated by the overproduced H2O2 through the dual 1,4-elimination. The latter restored the helical structure of the native peptide and its antimicrobial activity. This work illustrates a highly valuable macrocyclization strategy for the peptide community and should greatly benefit the field of peptide delivery.


Assuntos
Peróxido de Hidrogênio , Peptídeos , Peptídeos/farmacologia , Peptídeos/química , Conformação Molecular
11.
Anal Chem ; 94(10): 4175-4182, 2022 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-35235307

RESUMO

Sensitive analysis of metabolites in a single cell is of fundamental significance for the better understanding of biological variability, differential susceptibility in disease therapy, and cell-to-cell heterogeneity as well. Herein, polarity-specific profiling of metabolites in a single cell was implemented by probe electrophoresis mass spectrometry (PEMS), which combined electrophoresis sampling of metabolites from a single cell and nanoelectrospray ionization-mass spectrometry (nanoESI-MS) analysis of the sampled metabolites. Enhanced extraction of either negatively or positively charged metabolites from a single cell was achieved by applying a DC voltage offset of +2.0 and -2.0 V to the probe, respectively. The experimental data demonstrated that PEMS features high throughput (≥200 peaks) and high sensitivity (≥10-times signal enhancement for [Choline + H]+, [Glutamine + H]+, [Arginine + H]+, etc.) in comparison with direct nanoESI-MS analysis. The biological effects of CdSe quantum dots (QDs) and γ-radiation on Allium cepa cells were investigated by PEMS, which revealed that CdSe QDs lead to the increase of intracellular amines while γ-radiation causes the decrease of intracellular acids. Therefore, this work provides an alternative platform to probe novel insights of cells by sensitive analysis of polarity-specific metabolites in a single cell.


Assuntos
Pontos Quânticos , Espectrometria de Massas por Ionização por Electrospray , Eletroforese , Cebolas/química , Espectrometria de Massas por Ionização por Electrospray/métodos
12.
Anal Chem ; 94(34): 11821-11830, 2022 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-35976989

RESUMO

The application of rapid and accurate diagnostic methods can improve colorectal cancer (CRC) survival rates dramatically. Here, we used a non-targeted metabolic analysis strategy based on internal extractive electrospray ionization mass spectrometry (iEESI-MS) to detect metabolite ions associated with the progression of CRC from 172 tissues (45 stage I/II CRC, 41 stage III/IV CRC, and 86 well-matched normal tissues). A support vector machine (SVM) model based on 10 differential metabolite ions for differentiating early-stage CRC from normal tissues was built with a good prediction accuracy of 92.6%. The biomarker panel consisting of lysophosphatidylcholine (LPC) (18:0) has good diagnostic potential in differentiating early-stage CRC from advanced-stage CRC. We showed that the down-regulation of LPC (18:0) in tumor tissues is associated with CRC progression and related to the regulation of the epidermal growth factor receptor. Pathway analysis showed that metabolic pathways in CRC are related to glycerophospholipid metabolism and purine metabolism. In conclusion, we built an SVM model with good performance to distinguish between early-stage CRC and normal groups based on iEESI-MS and found that LPC (18:0) is associated with the progression of CRC.


Assuntos
Biomarcadores Tumorais , Neoplasias Colorretais , Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/patologia , Regulação para Baixo , Humanos , Metabolismo dos Lipídeos , Espectrometria de Massas por Ionização por Electrospray
13.
Nutr Cancer ; 74(10): 3479-3491, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35703897

RESUMO

Although some epidemiological studies have reported the associations between vitamin C and risk of esophageal cancer, these results are inconsistent. Therefore, we performed an updated meta-analysis to explore the associations between dietary vitamin C intake and risk of esophageal cancer. We used PubMed, Embase, and the Web of Science to screen all published articles, which yielded 18 papers eligible for data extraction (involving 4,126 cases and 36,902 controls), and then pooled the odds ratios (ORs) and corresponding 95% confidence intervals (CIs) using random-effects model. As we detected the associations in highest category and the lowest type of dietary vitamin C intake, we discovered that dietary vitamin C intake was negatively correlated to the risk of esophageal cancer. The analysis of subgroup showed a significant counter proportion between vitamin C and the risk of ESCC and EAC. Moreover, the dose-analysis indicated that if increasing dietary intake of vitamin C of 50 mg/day, esophageal cancer risk dropped down 10% (OR = 0.81, 95%CI: 0.75-0.87). In summary, our study provides a comprehensive and updated epidemiological evidence to elucidate the relationships between dietary vitamin C and reduction of esophageal cancer risk. Nevertheless, we still need larger case-control and cohort studies to confirm these connections.


Assuntos
Adenocarcinoma , Neoplasias Esofágicas , Ácido Ascórbico , Dieta , Neoplasias Esofágicas/epidemiologia , Neoplasias Esofágicas/etiologia , Neoplasias Esofágicas/prevenção & controle , Humanos , Estado Nutricional , Fatores de Risco , Vitaminas
14.
J Cell Physiol ; 236(5): 3641-3659, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33044023

RESUMO

Random-pattern skin flaps are widely applied to rebuild and restore soft-tissue damage in reconstructive surgery; however, ischemia and subsequent ischemia-reperfusion injury lead to flap necrosis and are major complications. Exenatide, a glucagon-like peptide-1 analog, exerts therapeutic benefits for diabetic wounds, cardiac injury, and nonalcoholic fatty liver disease. Furthermore, Exenatide is a known activator of autophagy, which is a complex process of subcellular degradation that may enhance the viability of random skin flaps. In this study, we explored whether exenatide can improve skin flap survival. Our results showed that exenatide augments autophagy, increases flap viability, enhances angiogenesis, reduces oxidative stress, and alleviates pyroptosis. Coadministration of exenatide with 3-methyladenine and chloroquine, potent inhibitors of autophagy, reversed the beneficial effects, suggesting that the therapeutic benefits of exenatide for skin flaps are due largely to autophagy activation. Mechanistically, we identified that exenatide enhanced activation and nuclear translocation of TFE3, which leads to autophagy activation. Furthermore, we found that exenatide activates the AMPK-SKP2-CARM1 and AMPK-mTOR signaling pathways, which likely lead to exenatide's effects on activating TFE3. Overall, our findings suggest that exenatide may be a potent therapy to prevent flap necrosis, and we also reveal novel mechanistic insight into exenatide's effect on flap survival.


Assuntos
Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Exenatida/farmacologia , Sobrevivência de Enxerto/efeitos dos fármacos , Transplante de Pele , Pele/irrigação sanguínea , Adenina/análogos & derivados , Adenina/farmacologia , Adenilato Quinase/metabolismo , Animais , Autofagia/efeitos dos fármacos , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Regulação para Baixo/efeitos dos fármacos , Edema/patologia , Masculino , Camundongos Endogâmicos C57BL , Neovascularização Fisiológica/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Transporte Proteico/efeitos dos fármacos , Proteína-Arginina N-Metiltransferases/metabolismo , Piroptose/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Regulação para Cima/efeitos dos fármacos
15.
Crit Care Med ; 49(10): e989-e1000, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34259439

RESUMO

OBJECTIVES: Paroxysmal sympathetic hyperactivity occurs in a subset of critically ill traumatic brain injury patients and has been associated with worse outcomes after traumatic brain injury. The goal of this study was to identify admission risk factors for the development of paroxysmal sympathetic hyperactivity in traumatic brain injury patients. DESIGN: Retrospective case-control study of age- and Glasgow Coma Scale-matched traumatic brain injury patients. SETTING: Neurotrauma ICU at the R. Adams Cowley Shock Trauma Center of the University of Maryland Medical System, January 2016 to July 2018. PATIENTS: Critically ill adult traumatic brain injury patients who underwent inpatient monitoring for at least 14 days were included. Cases were identified based on treatment for paroxysmal sympathetic hyperactivity with institutional first-line therapies and were confirmed by retrospective tabulation of established paroxysmal sympathetic hyperactivity diagnostic and severity criteria. Cases were matched 1:1 by age and Glasgow Coma Scale to nonparoxysmal sympathetic hyperactivity traumatic brain injury controls, yielding 77 patients in each group. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Admission characteristics independently predictive of paroxysmal sympathetic hyperactivity included male sex, higher admission systolic blood pressure, and initial CT evidence of diffuse axonal injury, intraventricular hemorrhage/subarachnoid hemorrhage, complete cisternal effacement, and absence of contusion. Paroxysmal sympathetic hyperactivity cases demonstrated significantly worse neurologic outcomes upon hospital discharge despite being matched for injury severity at admission. CONCLUSIONS: Several anatomical, epidemiologic, and physiologic risk factors for clinically relevant paroxysmal sympathetic hyperactivity can be identified on ICU admission. These features help characterize paroxysmal sympathetic hyperactivity as a clinical-pathophysiologic phenotype associated with worse outcomes after traumatic brain injury.


Assuntos
Lesões Encefálicas Traumáticas/complicações , Agitação Psicomotora/etiologia , Adulto , Lesões Encefálicas Traumáticas/enzimologia , Estudos de Casos e Controles , Feminino , Escala de Coma de Glasgow , Hospitalização/estatística & dados numéricos , Humanos , Modelos Logísticos , Masculino , Maryland/epidemiologia , Pessoa de Meia-Idade , Agitação Psicomotora/epidemiologia , Estudos Retrospectivos , Fatores de Risco
16.
Analyst ; 146(18): 5675-5681, 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34388232

RESUMO

The wide application of nano-particles (NPs) has raised a serious concern over their impact on plants. However, evaluation of the effects of NPs on plant metabolism by direct detection of chemicals inside solid tissues presents a challenge. In this study, we report on a direct ionization method in mass spectrometry, internal extractive electrospray ionization (iEESI), for the direct evaluation of phytotoxicity of three different NPs (including CdTe quantum dots (CdTe QDs), gold nano-particles (Au NPs), and silver nano-particles (Ag NPs)) both on surfaces and inside solid tissues from the mung bean seeds (Vigna radiata) that were cultured in aqueous solutions of three NPs at 50 µg mL-1. The results showed that NPs could stimulate the biological accumulation of trigonelline and the decomposition of polysaccharides/oligosaccharides to glucose and maltose within 21 h of culture. To the best of our knowledge, this is the first study to apply internal extractive electrospray ionization mass spectrometry (iEESI-MS) for the direct measurement of solid tissue samples to evaluate the phytotoxicity of NPs on mung bean sprouts. Our study lays a solid foundation for further examination of other NPs-induced damaging effects such as apoptosis/necrosis, helping us to understand the phytotoxicity of NPs on plants.


Assuntos
Compostos de Cádmio , Pontos Quânticos , Vigna , Pontos Quânticos/toxicidade , Espectrometria de Massas por Ionização por Electrospray , Telúrio
17.
Analyst ; 146(16): 5037-5044, 2021 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-34231556

RESUMO

The levels of acetone and other ketones in exhaled human breath can be associated with various metabolic conditions, e.g. ketosis, lung cancer, dietary fat loss and diabetes. In this study, ketones in breath samples were charged through the reaction with water radical cations to form [M + H2O]˙+ ions, which were detected by mass spectrometry. Our experimental data indicate that under the optimized experimental conditions, the limit of detection for acetone using our approach is 0.14 ng L-1 (∼0.06 ppb). The linear dynamic range of detection spans four orders of magnitude. The developed approach was applied to real-time semi-quantitative analysis of acetone in the exhaled breath of human volunteers, revealing significantly higher levels of acetone in the breath of smokers compared to non-smokers. The developed approach features the obviation of sample collection, easy operation, high speed of analysis (10 s per run), high sensitivity, and spectral interpretation, which indicates the potential of ambient corona discharge ionization mass spectrometry as a selective, sensitive and noninvasive technique for the determination of exhaled ketones in clinical diagnosis including lung cancer, diabetes, etc.


Assuntos
Acetona , Água , Testes Respiratórios , Cátions , Expiração , Humanos
18.
Anal Chem ; 92(21): 14309-14313, 2020 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-33138379

RESUMO

Fractionation information on arsenic (As) in complex samples, particularly solid samples, is of immense interest. Herein, selective extraction of various As species adsorbed onto ferrihydrite as the model substrate was online-adapted to inductively coupled plasma-mass spectrometry (ICP-MS) for sensitive detection. The As-adsorbed ferrihydrite sample was loaded into a homemade online sequential elution device using two commercially available micropipette tips, and then, each fraction of As including nonspecifically adsorbed, specifically adsorbed, iron oxide bonded, and residual species was successively extracted for ICP-MS detection, with H2O, NH4NO3, NH4H2PO4, ammonium oxalate, and HF as the eluents, respectively. While no water-soluble As was detected, the fraction of As bonded to iron oxide was detected as the dominant species (>80%), and the specifically adsorbed As and residual As also accounted for a substantial amount (10%). The method had a detection limit of 0.008 µg/kg for As(III) and 0.013 µg/kg for As(V), with merits such as extremely low sample consumption, high throughput, and minimized experimental manipulation, presenting an alternative strategy for sensitive fractionation analysis of As adsorbed onto solid substrates (e.g., iron oxides, etc.).


Assuntos
Arsênio/análise , Arsênio/isolamento & purificação , Fracionamento Químico/métodos , Compostos Férricos/química , Espectrometria de Massas , Adsorção , Arsênio/química , Limite de Detecção , Propriedades de Superfície
19.
Anal Chem ; 92(5): 4137-4145, 2020 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-32027489

RESUMO

A total of 15 representative organophosphorus pesticides (OPPs), a class of water pollutants causing serious global concerns, have been sensitively quantified by internal extractive electrospray ionization mass spectrometry (iEESI-MS) after enrichment with Fe3O4-ZrO2 innovatively synthesized in our lab by a one step coprecipitation method. For the premium enrichment, the amounts of Fe3O4-ZrO2, pH value, adsorption time, type and volume of desorption solvent, and shaking time of desorption were systematically optimized. Under optimized conditions, the proposed method provided low limits of detection (LODs) of 0.14-16.39 ng L-1 with relative standard deviations (RSDs) of less than 8.7%. A wide linear response range of about 4 orders of magnitude was achieved with linear coefficients (R2) of 0.9921-0.9999 for all the analytes tested. The present method also provided good recoveries (85.4-105.9%) with acceptable precision (RSDs < 7.2%) in spiked environmental water samples. Furthermore, multiple analytes including dimethoate, omethoate, etc. were simultaneously detected in a single sample run, which was accomplished within 1 min, resulting in significantly improved analytical throughput for quantitative analysis of bulk amounts of samples. The experimental results demonstrated that Fe3O4-ZrO2-iEESI-MS provided advantages, including high sensitivity, high speed, and reasonable selectivity for the detection of OPPs, showing potential applications in environmental water sample analysis and environmental science.


Assuntos
Magnetismo , Nanocompostos/química , Praguicidas/análise , Espectrometria de Massas por Ionização por Electrospray/métodos , Poluentes Químicos da Água/análise , Zircônio/química , Óxido Ferroso-Férrico/química , Água Doce/análise , Concentração de Íons de Hidrogênio , Limite de Detecção , Compostos Organofosforados/análise , Compostos Organofosforados/isolamento & purificação , Praguicidas/isolamento & purificação , Extração em Fase Sólida , Poluentes Químicos da Água/isolamento & purificação
20.
Analyst ; 145(2): 313-320, 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31872201

RESUMO

Lung cancer is one of the most common malignancies and the leading cause of cancer-related death worldwide. Among the technologies suitable for the rapid and accurate molecular diagnosis of lung cancer, ambient mass spectrometry (AMS) has gained increasing interest as it allows the direct profiling of molecular information from various biological samples (e.g., tissue, serum, urine and sputum) in real-time and with minimal or no sample pretreatment. This minireview summarizes the applications of AMS in lung cancer studies (including tissue molecular identification, the discovery of potential biomarkers, and surgical margin assessment), and discusses the challenges and perspectives of AMS in the clinical precision molecular diagnosis of lung cancer.


Assuntos
Biomarcadores Tumorais/análise , Neoplasias Pulmonares/diagnóstico , Espectrometria de Massas/métodos , Humanos , Neoplasias Pulmonares/cirurgia
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