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1.
Crit Care Med ; 50(2): 235-244, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-34524155

RESUMO

OBJECTIVES: We investigated awakening time and characteristics of awakening compared nonawakening and factors contributing to poor neurologic outcomes in out-of-hospital cardiac arrest survivors in no withdrawal of life-sustaining therapy settings. DESIGN: Retrospective analysis of the Korean Hypothermia Network Pro registry. SETTING: Multicenter ICU. PATIENTS: Adult (≥ 18 yr) comatose out-of-hospital cardiac arrest survivors who underwent targeted temperature management at 33-36°C between October 2015 and December 2018. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We measured the time from the end of rewarming to awakening, defined as a total Glasgow Coma Scale score greater than or equal to 9 or Glasgow Coma Scale motor score equals to 6. The primary outcome was awakening time. The secondary outcome was 6-month neurologic outcomes (poor outcome: Cerebral Performance Category 3-5). Among 1,145 out-of-hospital cardiac arrest survivors, 477 patients (41.7%) regained consciousness 30 hours (6-71 hr) later, and 116 patients (24.3%) awakened late (72 hr after the end of rewarming). Young age, witnessed arrest, shockable rhythm, cardiac etiology, shorter time to return of spontaneous circulation, lower serum lactate level, absence of seizures, and multisedative requirement were associated with awakening. Of the 477 who woke up, 74 (15.5%) had poor neurologic outcomes. Older age, liver cirrhosis, nonshockable rhythm, noncardiac etiology, a higher Sequential Organ Failure Assessment score, and higher serum lactate levels were associated with poor neurologic outcomes. Late awakeners were more common in the poor than in the good neurologic outcome group (38/74 [51.4%] vs 78/403 [19.4%]; p < 0.001). The awakening time (odds ratio, 1.005; 95% CIs, 1.003-1.008) and late awakening (odds ratio, 3.194; 95% CIs, 1.776-5.746) were independently associated with poor neurologic outcomes. CONCLUSIONS: Late awakening after out-of-hospital cardiac arrest was common in no withdrawal of life-sustaining therapy settings and the probability of awakening decreased over time.


Assuntos
Hipotermia Induzida/normas , Parada Cardíaca Extra-Hospitalar/complicações , Fatores de Tempo , Suspensão de Tratamento/estatística & dados numéricos , Idoso , Estudos de Coortes , Feminino , Humanos , Hipotermia Induzida/métodos , Hipotermia Induzida/estatística & dados numéricos , Unidades de Terapia Intensiva/organização & administração , Unidades de Terapia Intensiva/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Parada Cardíaca Extra-Hospitalar/epidemiologia , Parada Cardíaca Extra-Hospitalar/mortalidade , República da Coreia/epidemiologia , Estudos Retrospectivos , Estatísticas não Paramétricas , Sobreviventes/estatística & dados numéricos
2.
Langmuir ; 38(26): 8003-8011, 2022 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-35737666

RESUMO

Despite innovative advances in stent technology, restenosis remains a crucial issue for the clinical implantation of stents. Reactive oxygen species (ROS) are known to potentially accelerate re-endothelialization and lower the risk of restenosis by selectively controlling endothelial cells and smooth muscle cells. Recently, several studies have been conducted to develop biodegradable polymeric stents. As biodegradable polymers are not electrically conductive, double metallic layers are required to constitute a galvanic couple for ROS generation. Here, we report a new biodegradable hybrid material composed of a biodegradable polymer substrate and double anodic/cathodic metallic layers for enhancing re-endothelialization and suppressing restenosis. Pure Zn and Mg films (3 µm thick) were deposited onto poly-l-lactic acid (PLLA) substrates by DC magnetron sputtering, and a long-term immersion test using biodegradable hybrid materials was performed in phosphate-buffered solution (PBS) for 2 weeks. The concentrations of superoxide anions and hydrogen peroxide generated by the corrosion of biodegradable metallic films were monitored every 1 or 2 days. Both superoxide anions and hydrogen peroxide were seamlessly generated even after the complete consumption of the anodic Mg layer. It was confirmed that the superoxide anions and hydrogen peroxide were formed not only by the galvanic corrosion between the anode and cathode layers but also by the corrosion of a single Mg or Zn layer. The corrosion products of the Mg and Zn films in PBS were phosphate, oxide, or chloride of the biodegradable metals. Thus, it is concluded that ROS generation by the corrosion of PLLA-based hybrid materials can be sustained until the exhaustion of the cathode metal layer.


Assuntos
Células Endoteliais , Peróxido de Hidrogênio , Materiais Biocompatíveis , Corrosão , Teste de Materiais , Metais , Fosfatos , Polímeros , Espécies Reativas de Oxigênio , Stents , Superóxidos
3.
Int J Mol Sci ; 22(9)2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33946465

RESUMO

Cortisol is an endogenous glucocorticoid (GC) and primary stress hormone that regulates a wide range of stress responses in humans. The adverse effects of cortisol on the skin have been extensively documented but the underlying mechanism of cortisol-induced signaling is still unclear. In the present study, we investigate the effect of cortisol on collagen type I expression and the effect of AP collagen peptides, collagen tripeptide-rich hydrolysates containing 3% glycine-proline- hydroxyproline (Gly-Pro-Hyp, GPH) from the fish skin, on the cortisol-mediated inhibition of collagen type I and the cortisol-induced signaling that regulates collagen type I production in human dermal fibroblasts (HDFs). We determine that cortisol downregulates the expression of collagen type I. AP collagen peptides or GC receptor (GR) inhibitors recover the cortisol-mediated inhibition of collagen type I and GR activation. AP collagen peptides or GR inhibitors also prevent the cortisol-dependent inhibition of transforming growth factor (TGF)-ß signaling. AP collagen peptides or GR inhibitors are effective in the prevention of collagen type I inhibition mediated by cortisol in senescent HDFs and reconstituted human skin models. Taken together, GR signaling might be responsible for the cortisol-mediated inhibition of TGF-ß. AP collagen peptides act as GR-mediated signaling blockers, preventing the cortisol-dependent inhibition of collagen type I. Therefore, AP collagen peptides have the potential to improve skin health.


Assuntos
Anti-Inflamatórios/farmacologia , Colágeno Tipo I/metabolismo , Fibroblastos/efeitos dos fármacos , Hidrocortisona/farmacologia , Oligopeptídeos/farmacologia , Animais , Linhagem Celular , Derme/citologia , Derme/efeitos dos fármacos , Derme/metabolismo , Fibroblastos/citologia , Fibroblastos/metabolismo , Peixes , Humanos , Transdução de Sinais/efeitos dos fármacos , Fator de Crescimento Transformador beta/metabolismo
4.
Pediatr Emerg Care ; 36(11): e659-e664, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31688704

RESUMO

The Pediatric Emergency Care Applied Research Network rule helps emergency physicians identify very low-risk children with minor head injury who can forgo head computed tomography. This rule contributes to reduction in lifetime risk of radiation-induced cancers while minimizing missing clinically important traumatic brain injury. However, in intermediate-risk children, decisions on whether to perform computed tomography remain at the emergency physicians' discretion. To reduce this gray zone, this review summarizes evidence for risk stratification of intermediate-risk children with minor head injury.


Assuntos
Traumatismos Craniocerebrais/diagnóstico por imagem , Tomada de Decisões , Serviço Hospitalar de Emergência , Medição de Risco , Tomografia Computadorizada por Raios X , Criança , Humanos , Doses de Radiação
5.
BMC Pediatr ; 19(1): 335, 2019 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-31521164

RESUMO

BACKGROUND: We aimed to study the prevalence of enterovirus (EV) meningitis without the presence of cerebrospinal fluid (CSF) pleocytosis and identify patient factors and clinical features associated with it. METHODS: This was a retrospective analysis of patients aged < 18 years old who were diagnosed with EV meningitis by CSF reverse-transcriptase polymerase chain reaction (RT-PCR) testing between January 2015 and December 2016. Clinical variables were compared with regard to the presence of CSF pleocytosis. RESULTS: A total of 305 patients were enrolled in study; 169 (55.4%) had no pleocytosis. Patients without pleocytosis were younger (median age 2 months vs. 67.0 months, p < 0.01) and had lower white blood cell (WBC) count (median, 8600/mm3 vs. 10,300/mm3, p < 0.01). Also absolute neutrophil (ANC) count were lower than pleocytosis group (median, 4674/mm3 vs. 7600/mm3, p < 0.01). Comparing three age groups, CSF apleocytosis was present in 106 of 128 patients (82.8%) aged ≤3 months, 7 of 13 patients (53.8%) aged 3 months-3 years and 56 of 164 patients (34.1%) aged > 3 years. Younger age groups had higher prevalence of CSF apleocytosis (p < 0.01). In patients aged ≤3 months, 94.5% underwent lumbar puncture within 24 h of symptom onset. The frequency of not having pleocytosis was higher than the frequency of having pleocytosis during peak EV infection prevalent months (summer and fall) (p < 0.01). CONCLUSION: This study shows that EV meningitis in young infants, with early lumbar puncture, or occurring during peak EV meningitis prevalent seasons cannot be solely excluded by pleocytosis. Also, a confirmation test for EV meningitis should be performed using RT-PCR.


Assuntos
Infecções por Enterovirus/líquido cefalorraquidiano , Leucocitose/líquido cefalorraquidiano , Meningite Viral/líquido cefalorraquidiano , Fatores Etários , Criança , Pré-Escolar , Infecções por Enterovirus/complicações , Infecções por Enterovirus/diagnóstico , Feminino , Cefaleia/etiologia , Humanos , Lactente , Contagem de Leucócitos , Leucocitose/complicações , Leucocitose/epidemiologia , Masculino , Meningite Viral/complicações , Meningite Viral/diagnóstico , Neutrófilos , Prevalência , República da Coreia/epidemiologia , Estudos Retrospectivos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Estações do Ano , Punção Espinal , Vômito/etiologia
6.
Crit Care ; 22(1): 323, 2018 11 22.
Artigo em Inglês | MEDLINE | ID: mdl-30466477

RESUMO

BACKGROUND: We evaluated whether Alberta Stroke Program Early Computed Tomography Score (ASPECTS) with some modifications could be used to predict neurological outcomes in patients after extracorporeal cardiopulmonary resuscitation (ECPR). METHODS: This was a retrospective, multicenter, observational study of adult unconscious patients who were evaluated by brain computed tomography (CT) within 48 hours after ECPR between May 2010 and December 2016. ASPECTS, bilateral ASPECTS (ASPECTS-b), and modified ASPECTS (mASPECTS) were assessed by ROC curves to predict neurological outcomes. The primary outcome was neurological status upon hospital discharge assessed with the Cerebral Performance Categories (CPC) scale. RESULTS: Among 58 unconscious patients, survival to discharge was identified in 25 (43.1%) patients. Of these 25 survivors, 19 (32.8%) had good neurological outcomes (CPC score of 1 or 2). Interrater reliability of CT scores was excellent. Intraclass correlation coefficients of ASPECTS, ASPECTS-b, and mASPECTS were 0.918 (95% CI, 0.865-0.950), 0.918 (95% CI, 0.866-0.951), and 0.915 (95% CI, 0.860-0.949), respectively. The predictive performance of mASPECTS for poor neurological outcome was better than that of ASPECTS or ASPECTS-b (C-statistic for mASPECTS vs. ASPECTS, 0.922 vs. 0.812, p = 0.004; mASPECTS vs. ASPECTS-b, 0.922 vs. 0.818, p = 0.003). A cutoff of 25 for poor neurological outcome had a sensitivity of 84.6% (95% CI, 69.5-94.1%) and a specificity of 89.5% (95% CI, 66.9-98.7%) in mASPECTS. CONCLUSIONS: mASPECTS might be useful for predicting neurological outcomes in patients after ECPR.


Assuntos
Reanimação Cardiopulmonar/normas , Oxigenação por Membrana Extracorpórea/métodos , Prognóstico , Acidente Vascular Cerebral/terapia , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Alberta , Reanimação Cardiopulmonar/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Projetos de Pesquisa , Ressuscitação/métodos , Ressuscitação/normas , Estudos Retrospectivos , Resultado do Tratamento
7.
J Emerg Med ; 55(2): 226-234, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29885734

RESUMO

BACKGROUND: An automatic simultaneous sternothoracic cardiopulmonary resuscitation (SST-CPR) device is an apparatus that performs CPR by providing simultaneous cyclic compressions of the thorax with a thoracic strap and compression of the sternum with a piston. OBJECTIVE: This study was conducted to compare the hemodynamic effects of CPR with an automatic SST-CPR device to those with standard CPR (STD-CPR) in cardiac arrest patients. METHODS: A randomized trial was performed on victims of out-of-hospital cardiac arrest resistant to initial 20 min of CPR after emergency department (ED) arrival. Patients were instrumented with femoral arterial and internal jugular venous lines before enrollment. Informed consent was waived per protocol. Patients were randomized to SST-CPR or STD-CPR based on the day of the month. The primary outcome was a comparison of the mean estimated coronary perfusion pressure (CPP) between SST-CPR and STD-CPR. The secondary outcome was a comparison of compression arterial systolic pressure, compression arterial diastolic pressure, right atrial systolic pressure, right atrial diastolic pressure, return of spontaneous circulation rate, survival to hospital admission, survival at 30 days, favorable neurologic outcomes at 30 days, and adverse events between two groups. RESULTS: Of 62 patients with non-traumatic, adult, out-of-hospital cardiac arrest who presented to the ED, 24 received CPR with an automatic SST-CPR device (SST-CPR group), and 38 received standard CPR (STD-CPR group). Acquisition and analysis of hemodynamic data were completed in 11 (46%) patients in the SST-CPR group and 14 (37%) patients in the STD-CPR group. Compression arterial systolic pressure, right atrial systolic/diastolic pressures, and end-tidal carbon dioxide tension were not different between the two groups. Median compression arterial diastolic pressure (femoral arterial pressure during relaxation) was 20 mm Hg (mean 22 mm Hg; 95% confidence interval [CI] 5 to 38 mm Hg) and 0 mm Hg (mean -2 mm Hg; 95% CI -21 to 18 mm Hg) in the SST-CPR group and the STD-CPR group (p = 0.002), respectively. Median estimated CPP was 10 mm Hg (mean 16 mmHg; 95% CI 1 to 31 mm Hg) and 2 mm Hg (mean 4 mm Hg; 95% CI -4 to 12 mm Hg) in the SST-CPR group and the STD-CPR group (p = 0.017), respectively. CONCLUSIONS: CPR with an automatic SST-CPR device results in higher estimated CPP compared to standard CPR in patients with non-traumatic, out-of-hospital cardiac arrest.


Assuntos
Reanimação Cardiopulmonar/instrumentação , Reanimação Cardiopulmonar/métodos , Desenho de Equipamento/normas , Hemodinâmica/fisiologia , Parada Cardíaca Extra-Hospitalar/terapia , Idoso , Idoso de 80 Anos ou mais , Débito Cardíaco/fisiologia , Desenho de Equipamento/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esterno/lesões
8.
Circ J ; 81(11): 1628-1635, 2017 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-28592725

RESUMO

BACKGROUND: The Alberta Stroke Program Early CT Score (ASPECTS) is used to assess early ischemic stroke damage. This study compared bilateral ASPECTS (ASPECTS-b) with the gray:white matter ratio (GWR) and quantitative regional abnormality (QRA) to evaluate the prognostic utility of early computed tomography (CT) findings in post-cardiac arrest patients.Methods and Results:Out-of-hospital cardiac arrest patients with return of spontaneous circulation (ROSC) who underwent brain CT (<6 h after onset) and therapeutic hypothermia were recruited from a university hospital over a 2-year period. General demographics, ROSC characteristics, ASPECTS-b (total score=20 points), GWR, and QRA were assessed. Multivariate logistic regression analysis was used to predict neurologic outcome using cerebral performance category (CPC) at 1 month. The study population was divided into good (n=20; CPC 1-2) and poor (n=47; CPC 3-5) outcome groups. The good (vs. poor) outcome group was younger (mean [±SD] age 46.7±11.8 vs. 60.3±17.2 years; P=0.002) and had more initial shockable rhythms (40.0% vs. 8.5%; P=0.002). In addition, the good outcome group had a higher mean ASPECTS-b score (15.3±2.7 vs. 9.0±4.9; P<0.001), despite no differences in QRA and mean GWR. Age and ASPECTS-b were independent predictors of outcome after adjusting for potential confounders. CONCLUSIONS: These findings suggest that an initial CT score (ASPECTS-b) could help estimate early neurologic outcomes in post-cardiac arrest patients treated with therapeutic hypothermia.


Assuntos
Hipotermia Induzida/métodos , Parada Cardíaca Extra-Hospitalar/terapia , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neuroimagem/métodos , Parada Cardíaca Extra-Hospitalar/diagnóstico por imagem , Prognóstico
9.
J Lipid Res ; 57(4): 563-73, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26658689

RESUMO

Lipin-1 is an Mg(2+)-dependent phosphatidate phosphatase that facilitates the dephosphorylation of phosphatidic acid to generate diacylglycerol. Little is known about the expression and function of lipin-1 in normal human epidermal keratinocytes (NHEKs). Here, we demonstrate that lipin-1 is present in basal and spinous layers of the normal human epidermis, and lipin-1 expression is gradually downregulated during NHEK differentiation. Interestingly, lipin-1 knockdown (KD) inhibited keratinocyte differentiation and caused G1 arrest by upregulating p21 expression. Cell cycle arrest by p21 is required for commitment of keratinocytes to differentiation, but must be downregulated for the progress of keratinocyte differentiation. Therefore, reduced keratinocyte differentiation results from sustained upregulation of p21 by lipin-1 KD. Lipin-1 KD also decreased the phosphorylation/activation of protein kinase C (PKC)α, whereas lipin-1 overexpression increased PKCα phosphorylation. Treatment with PKCα inhibitors, like lipin-1 KD, stimulated p21 expression, while lipin-1 overexpression reduced p21 expression, implicating PKCα in lipin-1-induced regulation of p21 expression. Taken together, these results suggest that lipin-1-mediated downregulation of p21 is critical for the progress of keratinocyte differentiation after the initial commitment of keratinocytes to differentiation induced by p21, and that PKCα is involved in p21 expression regulation by lipin-1.


Assuntos
Diferenciação Celular , Regulação Enzimológica da Expressão Gênica , Queratinócitos/citologia , Fosfatidato Fosfatase/genética , Fosfatidato Fosfatase/metabolismo , Ciclo Celular , Inibidor de Quinase Dependente de Ciclina p21/genética , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Diglicerídeos/metabolismo , Regulação para Baixo , Ativação Enzimática , Células Epidérmicas , Técnicas de Silenciamento de Genes , Humanos , Recém-Nascido , Fosfatidato Fosfatase/deficiência , Proteína Quinase C-alfa/metabolismo , Proteína Supressora de Tumor p53/metabolismo
10.
J Biol Chem ; 288(9): 6427-37, 2013 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-23335564

RESUMO

Yeast App1p is a phosphatidate phosphatase (PAP) that associates with endocytic proteins at cortical actin patches. App1p, which catalyzes the conversion of phosphatidate (PA) to diacylglycerol, is unique among Mg(2+)-dependent PAP enzymes in that its reaction is not involved with de novo lipid synthesis. Instead, App1p PAP is thought to play a role in endocytosis because its substrate and product facilitate membrane fission/fusion events and regulate enzymes that govern vesicular movement. App1p PAP was purified from yeast and characterized with respect to its enzymological, kinetic, and regulatory properties. Maximum PAP activity was dependent on Triton X-100 (20 mm), PA (2 mm), Mg(2+) (0.5 mm), and 2-mercaptoethanol (10 mm) at pH 7.5 and 30 °C. Analysis of surface dilution kinetics with Triton X-100/PA-mixed micelles yielded constants for surface binding (Ks(A) = 11 mm), interfacial PA binding (Km(B) = 4.2 mol %), and catalytic efficiency (Vmax = 557 µmol/min/mg). The activation energy, turnover number, and equilibrium constant were 16.5 kcal/mol, 406 s(-1), and 16.2, respectively. PAP activity was stimulated by anionic lipids (cardiolipin, phosphatidylglycerol, phosphatidylserine, and CDP-diacylglycerol) and inhibited by zwitterionic (phosphatidylcholine and phosphatidylethanolamine) and cationic (sphinganine) lipids, nucleotides (ATP and CTP), N-ethylmaleimide, propranolol, phenylglyoxal, and divalent cations (Ca(2+), Mn(2+), and Zn(2+)). App1p also utilized diacylglycerol pyrophosphate and lyso-PA as substrates with specificity constants 4- and 7-fold lower, respectively, when compared with PA.


Assuntos
Proteínas dos Microfilamentos/química , Proteínas dos Microfilamentos/isolamento & purificação , Fosfatidato Fosfatase/química , Fosfatidato Fosfatase/isolamento & purificação , Proteínas de Saccharomyces cerevisiae/química , Proteínas de Saccharomyces cerevisiae/isolamento & purificação , Saccharomyces cerevisiae/enzimologia , Diglicerídeos/química , Diglicerídeos/metabolismo , Cinética , Lipídeos/biossíntese , Lipídeos/química , Micelas , Proteínas dos Microfilamentos/metabolismo , Octoxinol/química , Fosfatidato Fosfatase/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Especificidade por Substrato/fisiologia
11.
Adv Healthc Mater ; : e2401700, 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39036863

RESUMO

Catheter-associated urinary tract infection (CAUTI) is the most common healthcare-associated infection; however, current therapeutic strategies remain insufficient for standard clinical application. A novel urinary catheter featuring a dual-layer nanoengineering approach using zinc (Zn) and silver nanoparticles (AgNPs) is successfully fabricated. This design targets microbial resistance, minimizes cytotoxicity, and maintains long-term efficacy. The inner AgNPs layer provides immediate antibacterial effects against the UTI pathogens, while the outer porous Zn layer controls zero-order Ag release and generates reactive oxygen species, thus enhancing long-term bactericidal performance. Enhanced antibacterial properties of Zn/AgNPs-coated catheters are observed, resulting in 99.9% of E. coli and 99.7% of S. aureus reduction, respectively. The Zn/AgNPs-coated catheter significantly suppresses biofilm with sludge formation compared to AgNP-coated and uncoated catheters (all, p < 0.05). The Zn/AgNP-coated catheter in a rabbit model demonstrated a durable, effective barrier against bacterial colonization, maintaining antimicrobial properties during the catheter indwelling period with significantly reduced inflammation and epithelial disruption compared with AgNP and uncoated groups. This innovation has the potential to revolutionize the design of antimicrobial medical devices, particularly for applications requiring long-term implantation. Although further preclinical studies are required to verify its efficacy and safety, this strategy seems to be a promising approach to preventing CAUTI-related complications.

12.
J Biol Chem ; 287(48): 40186-96, 2012 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-23071111

RESUMO

BACKGROUND: Phosphatidate phosphatase (PAP) plays diverse roles in lipid metabolism and cell signaling. RESULTS: A novel yeast PAP is identified as the actin patch protein encoded by APP1. CONCLUSION: APP1 and other known genes (PAH1, DPP1, LPP1) are responsible for all detectable PAP activity in yeast. SIGNIFICANCE: Identification of App1p as a PAP enzyme will facilitate the understanding of its cellular function. Phosphatidate phosphatase (PAP) catalyzes the dephosphorylation of phosphatidate to yield diacylglycerol. In the yeast Saccharomyces cerevisiae, PAP is encoded by PAH1, DPP1, and LPP1. The presence of PAP activity in the pah1Δ dpp1Δ lpp1Δ triple mutant indicated another gene(s) encoding the enzyme. We purified PAP from the pah1Δ dpp1Δ lpp1Δ triple mutant by salt extraction of mitochondria followed by chromatography with DE52, Affi-Gel Blue, phenyl-Sepharose, MonoQ, and Superdex 200. Liquid chromatography/tandem mass spectrometry analysis of a PAP-enriched sample revealed multiple putative phosphatases. By analysis of PAP activity in mutants lacking each of the proteins, we found that APP1, a gene whose molecular function has been unknown, confers ~30% PAP activity of wild type cells. The overexpression of APP1 in the pah1Δ dpp1Δ lpp1Δ mutant exhibited a 10-fold increase in PAP activity. The PAP activity shown by App1p heterologously expressed in Escherichia coli confirmed that APP1 is the structural gene for the enzyme. Introduction of the app1Δ mutation into the pah1Δ dpp1Δ lpp1Δ triple mutant resulted in a complete loss of PAP activity, indicating that distinct PAP enzymes in S. cerevisiae are encoded by APP1, PAH1, DPP1, and LPP1. Lipid analysis of cells lacking the PAP genes, singly or in combination, showed that Pah1p is the only PAP involved in the synthesis of triacylglycerol as well as in the regulation of phospholipid synthesis. App1p, which shows interactions with endocytic proteins, may play a role in vesicular trafficking through its PAP activity.


Assuntos
Aminopeptidases/metabolismo , Proteínas de Arabidopsis/metabolismo , Proteínas de Membrana/metabolismo , Saccharomyces cerevisiae/enzimologia , Motivos de Aminoácidos , Aminopeptidases/química , Aminopeptidases/genética , Proteínas de Arabidopsis/química , Proteínas de Arabidopsis/genética , Metabolismo dos Lipídeos , Proteínas de Membrana/química , Proteínas de Membrana/genética , Saccharomyces cerevisiae/química , Saccharomyces cerevisiae/genética
13.
RSC Adv ; 13(4): 2283-2293, 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36741181

RESUMO

Organic radical materials have been mainly reported on the stabilization of radical species because of their high energy and reactivity, while design strategies for controlling radical species beyond stabilization have remained challenging. Here, we report the electronic push-pull control spanning the neutral to the radical state of a series of perylene-based donor-π-acceptors (D-π-A). By introducing electron-withdrawing and -donating R groups to the donor of D-π-A, the observed intramolecular interactions controllable at the HOMO level led to the exploration of radical species. D-π-A with redox-active sites was transformed to (D-π-A)˙+ and (D-π-A)˙- in response to an external electrical stimulus under stabilization by perylene, resulting in new absorption peaks. In particular, the increasing absorption peaks of (D-π-A)˙+ showed a spectral shift and intensity change according to the R group, unlike those of (D-π-A)˙-. These experimental results support that the DFT/TD-DFT data suggests the radical cationic SOMO level variability. As a result, we provide a strategy for controlling the systematic radical species using the electron push-pull effect.

14.
J Med Food ; 26(5): 299-306, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37074675

RESUMO

Collagen-derived dipeptides and tripeptides have various physiological activities. In this study, we compared the plasma kinetics of free Hyp, peptide-derived Hyp, Pro-Hyp, cyclo(Pro-Hyp), Hyp-Gly, Gly-Pro-Hyp, and Gly-Pro-Ala after ingestion of four different collagen samples: AP collagen peptide (APCP), general collagen peptide, collagen, and APCP and γ-aminobutyric acid (GABA) combination. Each peptide was measured by high-performance liquid chromatography and triple quadrupole mass spectrometer. We found that, among all the peptides that were analyzed, only Gly-Pro-Hyp was significantly increased after ingestion of APCP compared with that of general collagen peptides and collagen. In addition, ingestion of the APCP and GABA combination improved the absorption efficiency of Gly-Pro-Ala. Finally, we reveal that Gly-Pro-Hyp was effective for preventing H2O2-induced reduction in extracellular matrix (ECM)-related genes, COL1A, elastin, and fibronectin, in dermal fibroblasts. Taken together, APCP significantly enhances the absorption of Gly-Pro-Hyp, which might act as an ECM-associated signaling factor in dermal fibroblasts, and the APCP and GABA combination promotes Gly-Pro-Ala absorption. Clinical Trial Registration number: UMIN000047972.


Assuntos
Colágeno , Fibroblastos , Peróxido de Hidrogênio , Peptídeos , Absorção Fisiológica , Colágeno/administração & dosagem , Colágeno/química , Ingestão de Alimentos , Fibroblastos/metabolismo
15.
Sci Rep ; 13(1): 21206, 2023 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-38040729

RESUMO

A knowledgebase (KB) transition of a clinical decision support (CDS) system occurred at the study site. The transition was made from one commercial database to another, provided by a different vendor. The change was applied to all medications in the institute. The aim of this study was to analyze the effect of KB transition on medication-related orders and alert patterns in an emergency department (ED). Data of patients, medication-related orders and alerts, and physicians in the ED from January 2018 to December 2020 were analyzed in this study. A set of definitions was set to define orders, alerts, and alert overrides. Changes in order and alert patterns before and after the conversion, which took place in May 2019, were assessed. Overall, 101,450 patients visited the ED, and 1325 physicians made 829,474 prescription orders to patients during visit and at discharge. Alert rates (alert count divided by order count) for periods A and B were 12.6% and 14.1%, and override rates (alert override count divided by alert count) were 60.8% and 67.4%, respectively. Of the 296 drugs that were used more than 100 times during each period, 64.5% of the drugs had an increase in alert rate after the transition. Changes in alert rates were tested using chi-squared test and Fisher's exact test. We found that the CDS system knowledgebase transition was associated with a significant change in alert patterns at the medication level in the ED. Careful consideration is advised when such a transition is performed.


Assuntos
Sistemas de Apoio a Decisões Clínicas , Sistemas de Registro de Ordens Médicas , Humanos , Erros de Medicação , Registros , Serviço Hospitalar de Emergência
16.
JMIR Med Inform ; 10(10): e40511, 2022 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-36194461

RESUMO

BACKGROUND: Alert fatigue is unavoidable when many irrelevant alerts are generated in response to a small number of useful alerts. It is necessary to increase the effectiveness of the clinical decision support system (CDSS) by understanding physicians' responses. OBJECTIVE: This study aimed to understand the CDSS and physicians' behavior by evaluating the clinical appropriateness of alerts and the corresponding physicians' responses in a medication-related passive alert system. METHODS: Data on medication-related orders, alerts, and patients' electronic medical records were analyzed. The analyzed data were generated between August 2019 and June 2020 while the patient was in the emergency department. We evaluated the appropriateness of alerts and physicians' responses for a subset of 382 alert cases and classified them. RESULTS: Of the 382 alert cases, only 7.3% (n=28) of the alerts were clinically appropriate. Regarding the appropriateness of the physicians' responses about the alerts, 92.4% (n=353) were deemed appropriate. In the classification of alerts, only 3.4% (n=13) of alerts were successfully triggered, and 2.1% (n=8) were inappropriate in both alert clinical relevance and physician's response. In this study, the override rate was 92.9% (n=355). CONCLUSIONS: We evaluated the appropriateness of alerts and physicians' responses through a detailed medical record review of the medication-related passive alert system. An excessive number of unnecessary alerts are generated, because the algorithm operates as a rule base without reflecting the individual condition of the patient. It is important to maximize the value of the CDSS by comprehending physicians' responses.

17.
Australas Emerg Care ; 24(4): 302-307, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33419698

RESUMO

BACKGROUND: Smartwatches could be used as a cardiopulmonary resuscitation (CPR) guidance system through its vibration function. This study was conducted to determine whether vibration guidance by a smartwatch application influences CPR performance compared to metronome guided CPR in a simulated noisy setting. METHODS: This study was randomised controlled trial. A total of 130 university students were enrolled. The experiment was conducted using a cardiac arrest model with hands-only CPR. Participants were randomly divided into two groups 1:1 ratio and performed 2-min metronome guidance or vibration guidance compression at the rate of 110/min. Basic life support quality data were compared in simulated noisy environments. RESULTS: There were significant differences between the audio and vibration guidance groups in the mean compression rate (MCR). However, there were no significant differences in correct or mean compression depth, correct hand position, and correctly released compression. The vibration guidance group resulted in 109 MCR (Interquartile range [IQR] 108-110), whereas the metronome guidance group resulted in 115 MCR (IQR 112-117) (p < 0.001). CONCLUSION: In a simulated noisy environment, vibration guided CPR showed to be particularly advantageous in maintaining a desired MCR during hands-only CPR compared to metronome guided CPR.


Assuntos
Reanimação Cardiopulmonar , Parada Cardíaca , Adulto , Parada Cardíaca/terapia , Humanos , Manequins , Pressão , Vibração/uso terapêutico
18.
RSC Adv ; 11(55): 34945-34954, 2021 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-35494739

RESUMO

A series of meta-terphenyl linked donor-π-acceptor (D-π-A) dyads were prepared to understand the electronic effects of a meta-terphenyl linker according to the electron-accepting ability change. The energy band gaps of the dyads were controlled by tuning the accepting ability, which resulted in emission colors ranging from blue-green to red. In the Lippert-Mataga plots, intramolecular charge transfer (ICT) behavior was observed, which showed gradually increased ICT characteristics as the accepting ability was increased. On the other hand, in the absorption spectra, a red shift of the ICT transition was observed differently from the electron-accepting ability tendency. Thus, the experimental results show that the ICT is determined by steric hindrance rather than the acceptor ability in the ground state due to the lack of π-conjugation of the terphenyl linker by the electron node in the meta-position, whereas ICT in the excited state is controlled by electron-accepting ability.

19.
Front Biosci (Elite Ed) ; 13(2): 237-248, 2021 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-34937311

RESUMO

Balanced skin microbiota is crucial for maintaining healthy normal skin function; however, disruption of the balance in skin microbiota is linked with skin diseases such as atopic dermatitis, acne vulgaris, dandruff, and candidiasis. Lactoplantibacillus species with proved with health benefits are probiotics that improve the balance of microbiome in skin and gut. In the present study, we investigated the potential antimicrobial activity of Lactiplantibacillus plantarum APsulloc 331261 (APsulloc 331261) and Lactiplantibacillus plantarum APsulloc 331266 (APsulloc 331266) derived from green tea, in inhibiting five skin pathogenic strains (Staphylococcus aureus (S. aureus), Cutibacterium acnes (C. acnes), Candia albicans (C. albicans), Malassezia globosa (M. globose), and Malassezia restricta (M. restricta)) associated with skin infection. Viability of S. aureus, C. acnes, C. albicans, M. globosa, and M. restricta was inhibited by indirect co-culture with APsulloc 331261 or APsulloc 331266 at various ratios. Different concentrations of the cell-free conditioned media (CM) derived from APsulloc 331261 or APsulloc 331266 inhibited the vaibility of S. aureus, C. acnes, C. albicans, M. globosa, and M. restricta in a dose dependent manner. Moreover, susceptibility of S. aureus, C. acnes and C. albicans against APsulloc 331261 or APsulloc 331266 was confirmed following agar overlay methods. Results of the agar overlay confirmed that various concentrations of APsulloc 331261 and APsulloc 331266 exhibited low to high inhibitory activity on the growth of S. aureus (ZDI 20.3 ± 2.1-32.3 ± 2.1 mm, R value 5.7 ± 0.8-7.8 ± 1.3 mm), C. acnes (ZDI 15.0 ± 1.7-22.2 ± 1.7 mm, R value 3.2 ± 1.3-5.5 ± 1.3 mm) and C. albicans (ZDI 13.3 ± 4.0-27.0 ± 3.6 mm, R value 2.8 ± 1.9-5.5 ± 1.7 mm). Finally, standard PCR analysis identified the presence of the of plantaricin genes encoding antimicrobial peptides in APsulloc 331261 and APsulloc 331266. These results suggest that APsulloc 331261 and APsulloc 331266 has a potential effect in the improvement of the balance of skin microbiota by inhibiting skin pathogenic strains.


Assuntos
Anti-Infecciosos , Microbiota , Peptídeos Antimicrobianos , Pele , Staphylococcus aureus
20.
J Clin Med ; 10(15)2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34362167

RESUMO

Early and precise neurological prognostication without self-fulfilling prophecy is challenging in post-cardiac arrest syndrome (PCAS), particularly during the targeted temperature management (TTM) period. This study aimed to investigate the feasibility of vasomotor reactivity (VMR) using transcranial Doppler (TCD) to determine whether final outcomes of patients with comatose PCAS are predicted. This study included patients who had out-of-hospital cardiac arrest in a tertiary referral hospital over 4 years. The eligible criteria included age ≥18 years, successful return of spontaneous circulation, TTM application, and bedside TCD examination within 72 h. Baseline demographics and multimodal prognostic parameters, including imaging findings, electrophysiological studies, and TCD-VMR parameters, were assessed. The final outcome parameter was cerebral performance category scale (CPC) at 1 month. Potential determinants were compared between good (CPC 1-2) and poor (CPC 3-5) outcome groups. The good outcome group (n = 41) (vs. poor (n = 117)) showed a higher VMR value (54.4% ± 33.0% vs. 25.1% ± 35.8%, p < 0.001). The addition of VMR to conventional prognostic parameters significantly improved the prediction power of good outcomes. This study suggests that TCD-VMR is a useful tool at the bedside to evaluate outcomes of patients with comatose PCAS during the TTM.

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