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1.
Artigo em Inglês | MEDLINE | ID: mdl-38743481

RESUMO

A Gram-stain-negative, yellow-pigmented, strictly aerobic, non-flagellated, motile by gliding, rod-shaped bacterium, designated strain YSD2104T, was isolated from a coastal sediment sample collected from the southeastern part of the Yellow Sea. Phylogenetic analysis based on the 16S rRNA gene sequences revealed that strain YSD2104T was closely related to three type strains, Lutimonas vermicola IMCC1616T (97.4 %), Lutimonas saemankumensis SMK-142T (96.9 %), and Lutimonas halocynthiae RSS3-C1T (96.8 %). Strain YSD2104T has a single circular chromosome of 3.54 Mbp with a DNA G+C content of 38.3 mol%. The average nucleotide identity and digital DNA-DNA hybridization values between strain YSD2104T and the three type strains (L. vermicola IMCC1616 T, L. saemankumensis SMK-142T, and L. halocynthiae RSS3-C1T) were 74.0, 86.2 and 73.6 %, and 17.9, 30.3 and 17.8 %, respectively. Growth was observed at 20-30 °C (optimum, 30 °C), at pH 6.5-8.5 (optimum, pH 7.0), and with NaCl concentrations of 1.5-3.5 % (optimum, 2.5 %). The major carotenoid was zeaxanthin, and flexirubin-type pigment was not produced. The major respiratory quinone was menaquinone-6. The major fatty acids (>10 %) were iso-C15 : 0, iso-C15 : 1 G, iso-C17 : 0 3-OH, summed feature 3 (C16 : 1 ω6c and/or C16 : 1 ω7c), and summed feature 9 (iso-C17 : 1 ω9c and/or 10-methyl C16 : 0). The major polar lipids were phosphatidylethanolamine, one unidentified aminophospholipid, two unidentified aminolipids, and eight unidentified lipids. Conclusively, based on this polyphasic approach, we classified strain YSD2104T (=KCTC 102008T=JCM 36287T) as representing a novel species of the genus Lutimonas and proposed the name Lutimonas zeaxanthinifaciens sp. nov.


Assuntos
Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano , Ácidos Graxos , Sedimentos Geológicos , Hibridização de Ácido Nucleico , Filogenia , RNA Ribossômico 16S , Água do Mar , Análise de Sequência de DNA , Vitamina K 2 , Zeaxantinas , Sedimentos Geológicos/microbiologia , RNA Ribossômico 16S/genética , DNA Bacteriano/genética , Vitamina K 2/análogos & derivados , Vitamina K 2/análise , Água do Mar/microbiologia , China
2.
Front Med (Lausanne) ; 11: 1335826, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38716413

RESUMO

Background: Limited data are available on the relationship of disseminated intravascular coagulation (DIC) with mortality in patients receiving extracorporeal membrane oxygenation (ECMO). Thus, we investigated the association of DIC score and antithrombin (AT) III with clinical outcomes in patients undergoing ECMO. Methods: We analyzed 703 patients who underwent ECMO between January 2014 and May 2022 at Samsung Medical Center. The DIC score was calculated using laboratory findings within 24 h of the ECMO initiation, and ≥ 5 was defined as overt DIC. In addition, the AT III level was measured to identify the correlation with the DIC score. Results: Among the study patients, 169 (24.0%) were diagnosed with overt DIC (DIC group) during early maintenance therapy. In-hospital mortality was significantly higher in the DIC group than in the non-DIC group (55.0% vs. 36.5%, p < 0.001). Bleeding events were significantly higher in the group of patients with a DIC score of 7 or 8 than in the other group (20.8% vs. 8.4%, p = 0.038). DIC score negatively correlated with AT III level (r = -0.417, p < 0.001). The predictive performance of AT III for overt DIC had statistical significance with a c-static of 0.81 (95% confidence interval (CI), 0.77-0.84, p < 0.001). Conclusion: Overt DIC was associated with higher in-hospital mortality and a tendency to bleed in ECMO patients. Furthermore, AT III plasma levels can easily predict overt DIC in patients undergoing ECMO. These findings suggest that monitoring AT III plasma levels may be important in the management of ECMO.

3.
Eur J Pharmacol ; 969: 176466, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38431243

RESUMO

The chronic use of the novel synthetic cathinone mexedrone, like other psychoactive drugs, can be considered addictive, with a high potential for abuse and the ability to cause psychological dependence in certain users. However, little is known about the neurobehavioral effects of mexedrone in association with its potential for abuse. We investigated the abuse potential for mexedrone abuse through multiple behavioral tests. In addition, serotonin transporter (SERT) levels were measured in the synaptosome of the dorsal striatum, and serotonin (5-HT) levels were measured in the dorsal striatum of acute mexedreone (50 mg/kg)-treated mice. To clarify the neuropharmacological mechanisms underlying the locomotor response of mexedrone, the 5-HT2A receptor antagonist M100907 (0.5 or 1.0 mg/kg) was administered prior to the acute injection of mexedrone in the locomotor activity experiment in mice. Mexedrone (10-50 mg/kg) produced a significant place preference in mice and mexedrone (0.1-0.5 mg/kg/infusion) maintained self-administration behavior in rats in a dose-dependent manner. In the drug discrimination experiment, mexedrone (5.6-32 mg/kg) was fully substituted for the discriminative stimulus effects of cocaine in rats. Mexedrone increased locomotor activity, and these effects were reversed by pretreatment with M100907. Acute mexedrone significantly increased c-Fos expression in the dorsal striatum and decreased SERT levels in the synaptosome of the dorsal striatum of mice, resulting in an elevation of 5-HT levels. Taken together, our results provide the possibility that mexedrone has abuse potential, which might be mediated, at least in part, by the activation of the serotonergic system in the dorsal striatum.


Assuntos
Cocaína , Fluorbenzenos , Metanfetamina/análogos & derivados , Piperidinas , Catinona Sintética , Ratos , Camundongos , Masculino , Animais , Ratos Sprague-Dawley , Serotonina/metabolismo , Cocaína/farmacologia , Relação Dose-Resposta a Droga
4.
J Korean Med Sci ; 39(8): e75, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38442718

RESUMO

BACKGROUND: Limited data are available on the mortality rates of patients receiving extracorporeal membrane oxygenation (ECMO) support for coronavirus disease 2019 (COVID-19). We aimed to analyze the relationship between COVID-19 and clinical outcomes for patients receiving ECMO. METHODS: We retrospectively investigated patients with COVID-19 pneumonia requiring ECMO in 19 hospitals across Korea from January 1, 2020 to August 31, 2021. The primary outcome was the 90-day mortality after ECMO initiation. We performed multivariate analysis using a logistic regression model to estimate the odds ratio (OR) of 90-day mortality. Survival differences were analyzed using the Kaplan-Meier (KM) method. RESULTS: Of 127 patients with COVID-19 pneumonia who received ECMO, 70 patients (55.1%) died within 90 days of ECMO initiation. The median age was 64 years, and 63% of patients were male. The incidence of ECMO was increased with age but was decreased after 70 years of age. However, the survival rate was decreased linearly with age. In multivariate analysis, age (OR, 1.048; 95% confidence interval [CI], 1.010-1.089; P = 0.014) and receipt of continuous renal replacement therapy (CRRT) (OR, 3.069; 95% CI, 1.312-7.180; P = 0.010) were significantly associated with an increased risk of 90-day mortality. KM curves showed significant differences in survival between groups according to age (65 years) (log-rank P = 0.021) and receipt of CRRT (log-rank P = 0.004). CONCLUSION: Older age and receipt of CRRT were associated with higher mortality rates among patients with COVID-19 who received ECMO.


Assuntos
COVID-19 , Oxigenação por Membrana Extracorpórea , Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Feminino , COVID-19/terapia , Estudos Retrospectivos , Morte , Fatores de Risco
5.
Aging Cell ; 23(4): e14077, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38303548

RESUMO

Idiopathic Parkinson's disease (PD) is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta, which is associated with neuroinflammation and reactive gliosis. The underlying cause of PD and the concurrent neuroinflammation are not well understood. In this study, we utilize human and murine neuronal lines, stem cell-derived dopaminergic neurons, and mice to demonstrate that three previously identified genetic risk factors for PD, namely SATB1, MIR22HG, and GBA, are components of a single gene regulatory pathway. Our findings indicate that dysregulation of this pathway leads to the upregulation of glucocerebrosides (GluCer), which triggers a cellular senescence-like phenotype in dopaminergic neurons. Specifically, we discovered that downregulation of the transcriptional repressor SATB1 results in the derepression of the microRNA miR-22-3p, leading to decreased GBA expression and subsequent accumulation of GluCer. Furthermore, our results demonstrate that an increase in GluCer alone is sufficient to impair lysosomal and mitochondrial function, thereby inducing cellular senescence. Dysregulation of the SATB1-MIR22-GBA pathway, observed in both PD patients and normal aging, leads to lysosomal and mitochondrial dysfunction due to the GluCer accumulation, ultimately resulting in a cellular senescence-like phenotype in dopaminergic neurons. Therefore, our study highlights a novel pathway involving three genetic risk factors for PD and provides a potential mechanism for the senescence-induced neuroinflammation and reactive gliosis observed in both PD and normal aging.


Assuntos
Proteínas de Ligação à Região de Interação com a Matriz , MicroRNAs , Doença de Parkinson , Humanos , Camundongos , Animais , Neurônios Dopaminérgicos/metabolismo , Proteínas de Ligação à Região de Interação com a Matriz/genética , Proteínas de Ligação à Região de Interação com a Matriz/metabolismo , Glucosilceramidas/metabolismo , Gliose , Doenças Neuroinflamatórias , Doença de Parkinson/genética , Doença de Parkinson/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Senescência Celular/genética , Fatores de Transcrição/metabolismo , Fenótipo
6.
J Microbiol Biotechnol ; 34(4): 978-984, 2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38379308

RESUMO

Genome-scale metabolic model (GEM) can be used to simulate cellular metabolic phenotypes under various environmental or genetic conditions. This study utilized the GEM to observe the internal metabolic fluxes of recombinant Escherichia coli producing gamma-aminobutyric acid (GABA). Recombinant E. coli was cultivated in a fermenter under three conditions: pH 7, pH 5, and additional succinic acids. External fluxes were calculated from cultivation results, and internal fluxes were calculated through flux optimization. Based on the internal flux analysis, glycolysis and pentose phosphate pathways were repressed under cultivation at pH 5, even though glutamate dehydrogenase increased GABA production. Notably, this repression was halted by adding succinic acid. Furthermore, proper sucA repression is a promising target for developing strains more capable of producing GABA.


Assuntos
Escherichia coli , Ácido gama-Aminobutírico , Escherichia coli/genética , Escherichia coli/metabolismo , Ácido gama-Aminobutírico/metabolismo , Ácido gama-Aminobutírico/biossíntese , Concentração de Íons de Hidrogênio , Fermentação , Glicólise , Ácido Succínico/metabolismo , Via de Pentose Fosfato , Análise do Fluxo Metabólico , Modelos Biológicos , Reatores Biológicos/microbiologia , Glutamato Desidrogenase/metabolismo , Glutamato Desidrogenase/genética , Engenharia Metabólica/métodos
7.
Cell Stem Cell ; 31(2): 196-211.e6, 2024 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-38237586

RESUMO

COVID-19 patients commonly present with signs of central nervous system and/or peripheral nervous system dysfunction. Here, we show that midbrain dopamine (DA) neurons derived from human pluripotent stem cells (hPSCs) are selectively susceptible and permissive to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. SARS-CoV-2 infection of DA neurons triggers an inflammatory and cellular senescence response. High-throughput screening in hPSC-derived DA neurons identified several FDA-approved drugs that can rescue the cellular senescence phenotype by preventing SARS-CoV-2 infection. We also identified the inflammatory and cellular senescence signature and low levels of SARS-CoV-2 transcripts in human substantia nigra tissue of COVID-19 patients. Furthermore, we observed reduced numbers of neuromelanin+ and tyrosine-hydroxylase (TH)+ DA neurons and fibers in a cohort of severe COVID-19 patients. Our findings demonstrate that hPSC-derived DA neurons are susceptible to SARS-CoV-2, identify candidate neuroprotective drugs for COVID-19 patients, and suggest the need for careful, long-term monitoring of neurological problems in COVID-19 patients.


Assuntos
COVID-19 , Células-Tronco Pluripotentes , Humanos , SARS-CoV-2 , Neurônios Dopaminérgicos , Sistema Nervoso Central
8.
Sci Rep ; 14(1): 597, 2024 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-38182719

RESUMO

The spread of carbapenem-resistant Enterobacterales (CRE) poses a public health threat worldwide. We aimed to compare the mortality rates between the carbapenemase-producing (CP) and non-CP CRE bacteremia. We conducted a retrospective cohort study in patients with CRE bacteremia after propensity score (PS) matching. We performed a Kaplan-Meier curve analysis to identify the cumulative hazard for 30-day mortality. There were 318 patients with CRE between January 1, 2018, and December 31, 2022. There were 252 patients with CP-CRE and 66 with non-CP-RE, respectively. Before PS matching, the 30-day mortality rates were 40.9% in the non-CP-CRE group and 53.2% in the CP-CRE group (p = 0.097). In patients in the intensive care unit (ICU), the mortality rates were 49.0% in the non-CP-CRE group and 57.1% in the CP-CRE group (p = 0.340). After PS matching, the hazard ratio (HR) for mortality in the CP-CRE group was 1.49 (95% confidence interval [CI] 0.74-3.03), p = 0.266). In ICU patients, the HR of CP-CRE was 1.11 (95% CI 0.36-3.39, p = 0.860). The Kaplan-Meier curve for 30-day mortality showed no difference in cumulative hazard. After PS matching, there was no difference in 30-day mortality between patients with CP-CRE and non-CP-CRE bacteremia.


Assuntos
Bacteriemia , Humanos , Pontuação de Propensão , Estudos Retrospectivos , Bacteriemia/tratamento farmacológico , Carbapenêmicos/farmacologia , Carbapenêmicos/uso terapêutico
9.
bioRxiv ; 2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38293122

RESUMO

Prime editing (PE) allows for precise genome editing in human pluripotent stem cells (hPSCs), such as introducing single nucleotide modifications, small deletions, or insertions at a specific genomic locus, a strategy that shows great promise for creating "Disease in a dish" models. To improve the effectiveness of prime editing in hPSCs, we systematically compared and combined the "inhibition of mismatch repair pathway and p53" on top of the "PEmax" to generate an all-in-one "PE-Plus" prime editor. We show that PE-Plus conducts the most efficient editing among the current PE tools in hPSCs. We further established an inducible prime editing platform in hPSCs by incorporating the all-in-one PE vector into a safe-harbor locus and demonstrated temporal control of precise editing in both hPSCs and differentiated cells. By evaluating disease-associated mutations, we show that this platform allows efficient creation of both monoallelic and biallelic disease-relevant mutations in hPSCs. In addition, this platform enables the efficient introduction of single or multiple edits in one step, demonstrating potential for multiplex editing. Therefore, our method presents an efficient and controllable multiplex prime editing tool in hPSCs and their differentiated progeny.

10.
Ann Pharmacother ; 58(4): 383-390, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37401103

RESUMO

BACKGROUND: Only some studies have directly compared and analyzed the roles of activated partial thromboplastin time (aPTT) and activated clotting time (ACT) in coagulation monitoring during argatroban administration. OBJECTIVES: This study aims to assess the correlation of argatroban dose with ACT and aPTT values and to identify the optimal coagulation test for argatroban dose adjustment. METHODS: We evaluated 55 patients on extracorporeal membrane oxygenation (ECMO) who received argatroban for more than 72 hours. The correlation between argatroban dose and aPTT and ACT values was evaluated. To compare argatroban dose and bleeding events according to liver dysfunction, the patients were divided into 2 groups based on alanine aminotransferase and total bilirubin. RESULTS: Among the 55 patients, a total of 459 doses and coagulation tests were evaluated. The aPTT and ACT values showed a weak correlation with argatroban dose, with the Pearson correlation coefficients of 0.261 (P < 0.001) and 0.194 (P = 0.001), respectively. The agreement between the target 150 to 180 seconds for ACT and 55 to 75 seconds for aPTT was observed in 140 patients (46.1%). Twenty-four patients (43.6%) had liver dysfunction when they started argatroban. The median argatroban dose was lower in the liver dysfunction group than in the control group (0.094 mcg/kg/min vs 0.169 mcg/kg/min, P = 0.020). Difference was not observed between the 2 groups in the amount of red blood cell (0.47 vs 0.43 pack, P = 0.909) and platelet (0.60 vs 0.08 pack, P = 0.079) transfusion per day. CONCLUSION AND RELEVANCE: A weak correlation was observed between argatroban dose and the aPTT and ACT values. However, the agreement between aPTT and ACT was only 46.1% regarding the scope of target range. Further research is necessary to determine how to assess the optimal argatroban dose for patients administered argatroban while undergoing ECMO at the intensive care unit.


Assuntos
Arginina/análogos & derivados , Oxigenação por Membrana Extracorpórea , Hepatopatias , Sulfonamidas , Humanos , Tempo de Tromboplastina Parcial , Heparina/efeitos adversos , Anticoagulantes/efeitos adversos , Oxigenação por Membrana Extracorpórea/efeitos adversos , Ácidos Pipecólicos
11.
Eur J Med Chem ; 265: 116050, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38128233

RESUMO

Poor intracellular uptake of therapeutics in the tumor parenchyma is a key issue in cancer therapy. We describe a novel approach to enhance tumor targeting and achieve targeted delivery of camptothecin (CPT) based on a tumor-homing internalizing RGD peptide (iRGD). We synthesized an iRGD-camptothecin conjugate (iRGD-CPT) covalently coupled by a heterobifunctional linker and evaluated its in vitro and in vivo activity in human colon cancer cells. In vitro studies revealed that iRGD-CPT penetrated cells efficiently and reduced colon cancer cell viability to a significantly greater extent at micromolar concentrations than did the parent drug. Furthermore, iRGD-CPT showed high distribution toward tumor tissue, effectively suppressed tumor progression, and showed enhanced antitumor effects relative to the parent drug in a mouse model, demonstrating that iRGD-CPT is effective in vivo cancer treatment. These results suggest that intracellular delivery of CPT via the iRGD peptide is a promising drug delivery strategy that will facilitate the development of CPT derivatives and prodrugs with improved efficacy.


Assuntos
Antineoplásicos , Neoplasias do Colo , Animais , Camundongos , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Neoplasias do Colo/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Camptotecina/farmacologia , Camptotecina/uso terapêutico
12.
Int J Mol Sci ; 24(23)2023 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-38069026

RESUMO

Colorectal cancer (CRC) is one of the most common and deadly cancers in the world. However, no effective treatment for the disease has yet been found. For this reason, several studies are being carried out on the treatment of CRC. Currently, there is limited understanding of the role of CPNE7 (copine-7) in CRC progression and metastasis. The results of this study show that CPNE7 exerts an oncogenic effect in CRC. First, CPNE7 was shown to be significantly up-regulated in CRC patient tissues and CRC cell lines compared to normal tissues according to IHC staining, qRT-PCR, and western blotting. Next, this study used both systems of siRNA and shRNA to suppress CPNE7 gene expression to check the CPNE7 mechanism in CRC. The suppressed CPNE7 significantly inhibited the growth of CRC cells in in vitro experiments, including migration, invasion, and semisolid agar colony-forming assay. Moreover, the modified expression of CPNE7 led to a decrease in the levels of genes associated with epithelial-mesenchymal transition (EMT). The epithelial genes E-cadherin (CDH1) and Collagen A1 were upregulated, and the levels of mesenchymal genes such as N-cadherin (CDH2), ZEB1, ZEB2, and SNAIL (SNAL1) were downregulated after CPNE7 inhibition. This study suggests that CPNE7 may serve as a potential diagnostic biomarker for CRC patients.


Assuntos
Neoplasias Colorretais , Transdução de Sinais , Humanos , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Neoplasias Colorretais/patologia , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , Metástase Neoplásica , RNA Interferente Pequeno/genética
13.
Front Cardiovasc Med ; 10: 1278374, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38045915

RESUMO

Background: We investigated the predictors of poor neurological outcomes in extracorporeal cardiopulmonary resuscitation (ECPR) patients using machine learning (ML) approaches. Methods: This study was a retrospective, single-center, observational study that included adult patients who underwent ECPR while hospitalized between January 2010 and December 2020. The primary outcome was neurologic status at hospital discharge as assessed by the Cerebral Performance Categories (CPC) score (scores range from 1 to 5). We trained and tested eight ML algorithms for a binary classification task involving the neurological outcomes of survivors after ECPR. Results: During the study period, 330 patients were finally enrolled in this analysis; 143 (43.3%) had favorable neurological outcomes (CPC score 1 and 2) but 187 (56.7%) did not. From the eight ML algorithms initially considered, we refined our analysis to focus on the three algorithms, eXtreme Gradient Boosting, random forest, and Stochastic Gradient Boosting, that exhibited the highest accuracy. eXtreme Gradient Boosting models exhibited the highest accuracy among all the machine learning algorithms (accuracy: 0.739, area under the curve: 0.837, Kappa: 0.450, sensitivity: 0.700, specificity: 0.740). Across all three ML models, mean blood pressure emerged as the most influential variable, followed by initial serum lactate, and arrest to extracorporeal membrane oxygenation (ECMO) pump-on-time as important predictors in machine learning models for poor neurological outcomes following successful ECPR. Conclusions: In conclusion, machine learning methods showcased outstanding predictive accuracy for poor neurological outcomes in patients who underwent ECPR.

14.
Small ; : e2306296, 2023 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-38072812

RESUMO

Mesoscopic-scale stacking reconfigurations are investigated when van der Waals (vdW) films are stacked. A method to visualize complicated stacking structures and mechanical distortions simultaneously in stacked atom-thick films using Raman spectroscopy is developed. In the rigid limit, it is found that the distortions originate from the transfer process, which can be understood through thin film mechanics with a large elastic property mismatch. In contrast, with atomic corrugations, the in-plane strain fields are more closely correlated with the stacking configuration, highlighting the impact of atomic reconstructions on the mesoscopic scale. It is discovered that the grain boundaries do not have a significant effect while the cracks are causing inhomogeneous strain in stacked polycrystalline films. This result contributes to understanding the local variation of emerging properties from moiré structures and advancing the reliability of stacked vdW material fabrication.

15.
BMC Infect Dis ; 23(1): 887, 2023 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-38114902

RESUMO

BACKGROUND: Data regarding the clinical effects of bacteremia on severe community-acquired pneumonia (CAP) are limited. Thus, we investigated clinical characteristics and outcomes of severe CAP patients with bacteremia compared with those of subjects without bacteremia. In addition, we evaluated clinical factors associated with bacteremia at the time of sepsis awareness. METHODS: We enrolled sepsis patients diagnosed with CAP at emergency departments (EDs) from an ongoing nationwide multicenter observational registry, the Korean Sepsis Alliance, between September 2019 and December 2020. For evaluation of clinical factors associated with bacteremia, we divided eligible patients into bacteremia and non-bacteremia groups, and logistic regression analysis was performed using the clinical characteristics at the time of sepsis awareness. RESULT: During the study period, 1,510 (47.9%) sepsis patients were caused by CAP, and bacteremia was identified in 212 (14.0%) patients. Septic shock occurred more frequently in the bacteremia group than in the non-bacteremia group (27.4% vs. 14.8%; p < 0.001). In multivariable analysis, hematologic malignancies and septic shock were associated with an increased risk of bacteremia. However, chronic lung disease was associated with a decreased risk of bacteremia. Hospital mortality was significantly higher in the bacteremia group than in the non-bacteremia group (27.3% vs. 40.6%, p < 0.001). The most prevalent pathogen in blood culture was Klebsiella pneumoniae followed by Escherichia coli in gram-negative pathogens. CONCLUSION: The incidence of bacteremia in severe CAP was low at 14.0%, but the occurrence of bacteremia was associated with increased hospital mortality. In severe CAP, hematologic malignancies and septic shock were associated with an increased risk of bacteremia.


Assuntos
Bacteriemia , Infecções Comunitárias Adquiridas , Neoplasias Hematológicas , Pneumonia , Sepse , Choque Séptico , Humanos , Bacteriemia/epidemiologia , Infecções Comunitárias Adquiridas/epidemiologia , Escherichia coli , Neoplasias Hematológicas/complicações , Pneumonia/epidemiologia , Pneumonia/complicações , Estudos Retrospectivos , Fatores de Risco , Sepse/complicações , Estudos Multicêntricos como Assunto , Estudos Observacionais como Assunto
16.
bioRxiv ; 2023 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-38014048

RESUMO

Triggering receptor expressed on myeloid cells 2 (TREM2) plays a central role in microglial biology and the pathogenesis of Alzheimer's disease (AD). Besides DNAX-activating protein 12 (DAP12), a communal adaptor for TREM2 and many other receptors, other cellular interactors of TREM2 remain largely elusive. We employed a 'proximity labeling' approach using a biotin ligase, TurboID, for mapping protein-protein interactions in live mammalian cells. We discovered novel TREM2-proximal proteins with diverse functions, including those localized to the Mitochondria-ER contact sites (MERCs), a dynamic subcellular 'hub' implicated in a number of crucial cell physiology such as lipid metabolism. TREM2 deficiency alters the thickness (inter-organelle distance) of MERCs, a structural parameter of metabolic state, in microglia derived from human induced pluripotent stem cells. Our TurboID-based TREM2 interactome study suggest novel roles for TREM2 in the structural plasticity of the MERCs, raising the possibility that dysregulation of MERC-related TREM2 functions contribute to AD pathobiology.

17.
BMC Med ; 21(1): 394, 2023 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-37858177

RESUMO

BACKGROUND: Previous studies that assessed the risk of cardiovascular outcomes in survivors of coronavirus disease 2019 (COVID-19) were likely limited by lack of generalizability and selection of controls nonrepresentative of a counterfactual situation regarding COVID-19-related hospitalization. This study determined whether COVID-19 hospitalization was associated with incident cardiovascular outcomes compared to non-COVID-19 pneumonia hospitalization. METHODS: Nationwide population-based study conducted using the Korean National Health Insurance Service database. A cohort of 132,784 inpatients with COVID-19 (October 8, 2020-September 30, 2021) and a cohort of 31,173 inpatients with non-COVID-19 pneumonia (January 1-December 31, 2019) were included. The primary outcome was the major adverse cardiovascular event (MACE; a composite of myocardial infarction and stroke). Hazard ratios (HRs) with 95% confidence intervals (CIs) of all outcomes of interest were estimated between inverse probability of treatment-weighted patients with COVID-19 and non-COVID-19 pneumonia. RESULTS: After weighting, the COVID-19 and non-COVID-19 pneumonia groups included 125,810 (mean [SD] age, 47.2 [17.6] years; men, 49.3%) and 28,492 patients (mean [SD] age, 48.6 [18.4] years; men, 47.2%), respectively. COVID-19 hospitalization was not associated with an increased risk of the MACE (HR, 0.84; 95% CI 0.69-1.03). However, the MACE (HR, 7.30; 95% CI 3.29-16.21), dysrhythmia (HR, 1.88; 95% CI 1.04-3.42), acute myocarditis (HR, 11.33; 95% CI 2.97-43.20), myocardial infarction (HR, 6.78; 95% CI 3.03-15.15), congestive heart failure (HR, 1.95; 95% CI 1.37-2.77), and thrombotic disease (HR, 8.26; 95% CI 4.06-16.83) risks were significantly higher in patients with COVID-19 aged 18-39 years. The findings were consistent after adjustment for preexisting cardiovascular disease. COVID-19 hospitalization conferred a higher risk of acute myocarditis (HR, 6.47; 95% CI 2.53-16.52) or deep vein thrombosis (HR, 1.97; 95% CI 1.38-2.80), regardless of vaccination status. CONCLUSIONS: Hospitalized patients with COVID-19 were not at an increased risk of cardiovascular outcomes compared to patients with non-COVID-19 pneumonia. Further studies are needed to evaluate whether the increased risk of cardiovascular outcomes is confined to younger patients.


Assuntos
COVID-19 , Doenças Cardiovasculares , Infarto do Miocárdio , Miocardite , Pneumonia , Masculino , Humanos , Pessoa de Meia-Idade , Estudos de Coortes , Miocardite/complicações , Fatores de Risco , COVID-19/complicações , COVID-19/epidemiologia , Doenças Cardiovasculares/etiologia , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/complicações
18.
Materials (Basel) ; 16(18)2023 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-37763480

RESUMO

In this study, the characteristics in the lead-free piezoelectric ceramic 0.5Ba(Zr0.2Ti0.8)O3-0.5(Ba0.7Ca0.3)TiO3 (0.5BZT-0.5BCT) were investigated to assess its potential for Rosen-type piezoelectric transformers. This piezoelectric ceramic has a piezoelectric charge coefficient d33 of 430 pC/N, an electromechanical coupling factor kp of 49%, a dielectric constant εr of 2836, a remnant polarization Pr of 4.98 µC/cm2, and a coercive electric field Ec of 2.41 kV/cm. Sb2O3 was soft doped with 0.05, 0.1, 0.15, and 0.2 mol%, respectively, and exhibited excellent physical properties at 0.1 mol%. Based on this, a piezoelectric transformer was fabricated and measured, and it showed better output characteristics than pure 0.5BZT-0.5BCT. The amplification ratio (Vout/Vin) was optimized based on the device geometry and properties of the piezoelectric material. Moreover, the output characteristics of the Rosen-type piezoelectric transformer were simulated with the PSpice program. Output values of the fabricated and simulated piezoelectric transformers for the r vibrational frequency were compared and analyzed. Accordingly, the step-up amplification ratios Vout/Vin of the fabricated and simulated devices at the vibrational frequency were compared as well. This piezoelectric transformer could replace silicon steel transformers and be used for the creation of black light and for laptop chargers.

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