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Background and Objectives: Chronic hepatitis C (CHC) can be cured with direct-acting antiviral (DAA) therapy. In Korea, sofosbuvir (SOF) and ledipasvir (LDV)/SOF were launched in 2016. Patients who achieve a sustained virologic response (SVR) following DAA treatment are predicted to have a favorable prognosis. Nevertheless, little is known regarding the prognosis of Korean CHC patients who receive SOF-based treatment and achieve SVR. Therefore, the purpose of this study was to look into the long-term outcomes for these patients. Materials and Methods: This was a prospective, multicenter observational study. CHC patients were enrolled who, following SOF or LDV/SOF treatment, had achieved SVR. The last day for follow-up was December 2023. The primary endpoint was HCC occurrence, which was checked at least once per year. Results: A total of 516 patients were included in this analysis, with a median follow-up duration of 39.0 months. Among them, 231 were male patients (44.8%), with a median age of 62.0 years. Genotypes were 1 (90, 17.4%), 2 (423, 82.0%), and 3 (3, 0.6%). The combination of SOF plus ribavirin was the most common treatment (394, 76.4%). In total, 160 patients were cirrhotic (31.0%), and the mean Child-Pugh score was 5.1. Within a maximum of 7 years, 21 patients (4.1%) developed HCC. Patients with HCC were older (69 vs. 61 years, p = 0.013) and had a higher cirrhosis incidence (81.0 vs. 28.9%, p < 0.001), higher AFP (6.0 vs. 3.3, p = 0.003) and higher APRI (0.8 vs. 0.5, p = 0.005). Age over 65 (p = 0.016) and cirrhosis (p = 0.005) were found to be significant risk factors for HCC by Cox regression analysis. Conclusions: Patients who achieved SVR with SOF-based treatment had a relatively favorable prognosis. However, the risk of HCC was not eliminated, especially in older and cirrhotic patients. Therefore, routine follow-up, surveillance, and early treatment are required.
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Antivirais , Hepatite C Crônica , Sofosbuvir , Resposta Viral Sustentada , Humanos , Masculino , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/complicações , Sofosbuvir/uso terapêutico , Feminino , Pessoa de Meia-Idade , Estudos Prospectivos , Antivirais/uso terapêutico , República da Coreia/epidemiologia , Idoso , Prognóstico , Adulto , Neoplasias Hepáticas/epidemiologia , Carcinoma Hepatocelular/epidemiologiaRESUMO
In South Korea, because of manpower and budgetary limitations, antimicrobial stewardship programs have relied on preauthorization. This study analyzed the impact of a prospective audit and feedback (PAF) program targeting inpatients undergoing intermittent hemodialysis or continuous renal replacement therapy, which was implemented at two community-based university hospitals. During three years of PAF, 27,906 antimicrobial prescriptions were reviewed, with 622 (2.2%) interventions. The mean incidence density per 1000 patient days of multidrug-resistant organisms, except for carbapenem-resistant Acinetobacter baumannii, decreased in the study population, whereas it increased among inpatients. Multivariable Poisson regression analysis revealed that after PAF, the incidences of vancomycin-resistant Enterococcus and mortality decreased (incidence risk ratio, 95% confidence interval: 0.53, 0.31-0.93 and 0.70, 0.55-0.90, respectively). Notably, after PAF, incorrect antimicrobial dosing rates significantly decreased (tau -0.244; p = 0.02). However, the incidences of other multidrug-resistant organisms, Clostridioides difficile, length of stay, and readmission did not significantly change. This study shows that in patients undergoing intermittent hemodialysis or continuous renal replacement, targeted PAF can significantly reduce multidrug-resistant organism rates and all-cause hospital mortality, despite limited resources. Furthermore, it can improve antimicrobial dosage accuracy.
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Herein, we report a case of uncomplicated falciparum malaria with late parasitological failure in a 45-year-old businessman returning from Ghana. The patient visited the emergency department with high fever, headache, and dizziness. He traveled without antimalarial chemoprophylaxis. Laboratory tests led to the diagnosis of uncomplicated falciparum malaria with an initial density of 37,669 parasites per µL of blood (p/µL). The patient was treated with intravenous artesunate followed by atovaquone/proguanil. He was discharged with improved condition and decreased parasite density of 887 p/µL. However, at follow-up, parasite density increased to 7,630 p/µL despite the absence of any symptoms. Suspecting treatment failure, the patient was administered intravenous artesunate and doxycycline for seven days and then artemether/lumefantrine for three days. Blood smear was negative for asexual parasitemia after re-treatment but positive for gametocytemia until day 101 from the initial diagnosis. Overall, this case highlights the risk of late parasitological failure in patients with imported uncomplicated falciparum malaria.
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Antimaláricos , Atovaquona , Malária Falciparum , Plasmodium falciparum , Proguanil , Humanos , Malária Falciparum/tratamento farmacológico , Malária Falciparum/diagnóstico , Gana , Antimaláricos/uso terapêutico , Pessoa de Meia-Idade , Masculino , Plasmodium falciparum/isolamento & purificação , Proguanil/uso terapêutico , Atovaquona/uso terapêutico , Viagem , Artemisininas/uso terapêutico , Artesunato/uso terapêutico , Parasitemia/tratamento farmacológico , Parasitemia/diagnóstico , Doxiciclina/uso terapêutico , Combinação de Medicamentos , Falha de Tratamento , Combinação Arteméter e Lumefantrina/uso terapêuticoRESUMO
BACKGROUND: The ability to regulate one's emotional state is an important predictor of several behaviors such as reframing a challenging situation to reduce anger or anxiety, concealing visible signs of sadness or fear, or focusing on reasons to feel happy or calm. This capacity is referred to as emotion regulation. Deficits in this ability can adversely affect one's adaptive coping, thus are associated with a variety of other psychopathological symptoms, including but not limited to depression, borderline personality disorder, substance use disorders, eating disorders, and somatoform disorders. METHODS: The present study examined emotion regulation in relation to the virtue-based psychosocial adaptation model (V-PAM). 595 participants were clustered based on their Difficulties in Emotion Regulation Scale (DERS) score, producing two clusters (i.e., high functioning vs. low functioning). Then, emotion regulation group membership was discriminated by using five V-PAM virtue constructs, including courage, integrity, practical wisdom, committed action, and emotional transcendence. RESULTS: Results show that five virtues contribute to differentiating group membership. Practical wisdom was the strongest contributor, followed by integrity, emotional transcendence, committed action, and courage. Predictive discriminant analysis was conducted and 71% of cases were correctly classified. A discussion of the relationship between emotion regulation and virtues was elaborated. CONCLUSION: The concept of virtue holds significant importance in the comprehension of an individual's capacity to regulate their emotions, meriting future study.
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Regulação Emocional , Humanos , Virtudes , Emoções/fisiologia , Ira , AnsiedadeRESUMO
BACKGROUND/AIMS: The model for end-stage liver disease (MELD) serves as an indicator for short-term mortality among patients diagnosed with liver cirrhosis (LC) and is used to prioritize patients for liver transplantation. In 2021, the updated version of MELD, MELD-3.0, was introduced to improve the accuracy of the mortality prediction of MELD. Therefore, this study aimed to compare the efficacy of MELD 3.0 and MELD-Na in predicting mortality among Korean patients with LC. METHODS: A retrospective review was conducted using the medical records of patients diagnosed with LC who were admitted to Konkuk University Hospital From 2011 to 2021. The study calculated the predictive values of MELD-Na and MELD-3.0 for 3- and 6-months mortality using the area under the receiver operating curve (AUROC) and compared the results using the DeLong test. RESULTS: Of the 3,034 patients enrolled in the study, 339 (11.2%) died within 3 months and 421 (14.4%) died within 6 months. The AUROCs values for predicting 3 months mortality were 0.846 for MELD-Na and 0.851 for MELD-3.0. The corresponding AUROC values for predicting 6 months mortality were 0.843 for MELD-Na and 0.848 for MELD-3.0. MELD-3.0 exhibited better discrimination ability than MELD-Na for both 3 (p = 0.03) and 6 months mortality (p = 0.01). CONCLUSION: Our study found a significant difference between the performance of MELD-3.0 and MELD-Na in Korean patients with LC.
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Doença Hepática Terminal , Humanos , Doença Hepática Terminal/diagnóstico , Prognóstico , Sódio , Valor Preditivo dos Testes , Índice de Gravidade de Doença , Cirrose Hepática/diagnóstico , Estudos Retrospectivos , República da Coreia/epidemiologia , Curva ROCRESUMO
BACKGROUND: Psychological status affects dietary intake, and recognizing genetic information can lead to behavior changes by influencing psychological factors such as anxiety or depression. OBJECTIVES: In this study, we examined the effects of disclosing genetic information on anxiety or depression levels and the association between these psychological factors and dietary intake. METHODS: A total of 100 healthy adults were randomly assigned to an intervention group (n = 65) informed about their genetic test results regarding body mass index and lipid profiles (triglyceride and cholesterol concentrations) and a not-informed control group (CON, n = 35). Based on polygenic risk scores, participants in the intervention group were subclassified into an intervention-low risk (ILR, n = 32) and an intervention-high risk (IHR, n = 33) group. Nutrient and food intakes were assessed via a 3-day dietary record at baseline and at 3 and 6 months. Depression and anxiety levels were measured using PHQ-9 and GAD-7 questionnaires, and the relative levels of blood metabolites were measure using GC-MS/MS analysis. RESULTS: Noticeable changes in dietary intake as well as psychological factors were observed in male subjects, with those perceiving their genetic risks as low (ILR) showing a significant increase in protein intake at 3 months compared to baseline (ILR: 3.9 ± 1.4, p<0.05). Meat intake also increased significantly in males in the ILR group at 3 months, but not in the IHR and CON groups (ILR: 49.4 ± 30.8, IHR: -52.2 ± 25.4, CON: -5.3 ± 30.3 g/d). ILR group showed a significant decrease in anxiety levels at 3 months, and their anxiety scores showed a negative association with meat intake (standardized ß = -0.321, p<0.05). The meat intake at 3 months was associated with the relative levels of arginine and ornithine (standardized ß = 0.452, p<0.05 and standardized ß = 0.474, p<0.05, respectively). CONCLUSIONS: Taken together, anxiety levels were decreased in male subjects who perceived their genetic risk to be low, and the decrease in anxiety levels was associated with an increase in meat intake. This suggests that recognizing genetic information may affect psychological factors and dietary intake.
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Depressão , Espectrometria de Massas em Tandem , Adulto , Masculino , Humanos , Triglicerídeos , Índice de Massa Corporal , Depressão/genética , Ansiedade/genética , Fatores de Risco , Lipoproteínas , CarneRESUMO
Aim and Objectives: Direct-acting antiviral (DAA) therapy can cure chronic hepatitis C (CHC), and daclatasvir (DCV)/asunaprevir (ASV) was the first interferon-free DAA therapy introduced in Korea. Patients who achieve sustained virologic response (SVR) after DAA treatment are expected to have good prognoses. Therefore, in this study, we aimed to investigate the prognosis of these patients. Materials and Methods: This multicenter prospective observational study included patients with CHC who achieved SVR after DCV/ASV treatment. The primary endpoint was hepatocellular carcinoma (HCC) occurrence, which was reviewed annually. Results: We included 302 patients (median follow-up duration: 38 [16.5-60.0] months; median age: 58 [49-67] years) in the study. Cirrhosis was observed in 103 patients (34.1%), and the median Child-Pugh score was 5.0. HCC occurred in 16 patients (5.3%) within six years post-SVR; these patients were older and had higher cirrhosis prevalence, alpha-fetoprotein levels, and fibrosis-4 index scores than did those without HCC development. Cox proportional hazards analysis revealed that age > 71 years (p = 0.005) and cirrhosis (p = 0.035) were significant risk factors for HCC occurrence. Conclusions: Although the prognoses of patients who achieved SVR with DCV/ASV therapy were generally good, the risk for HCC was present, especially in older patients and in those with cirrhosis. Hence, early treatment at younger ages and regular follow-up surveillance after achieving SVR are warranted.
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Carcinoma Hepatocelular , Hepatite C Crônica , Neoplasias Hepáticas , Humanos , Idoso , Pessoa de Meia-Idade , Antivirais/uso terapêutico , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Prognóstico , Cirrose Hepática/etiologia , GenótipoRESUMO
Quinalphos is a long-term, wide-spectrum organophosphate insecticide with residual problems in the natural environment. Cunninghamella elegans (C. elegans) is a member of Mucoromycotina. Since the degradation products of its exogenous compounds are similar to those of mammals, it is often used to simulate the metabolism pathways of mammals. In this study, the detailed metabolic pathways of quinalphos were investigated with C. elegans. Quinalphos was degraded by 92% in 7 days, while ten metabolites were produced. The metabolites were analyzed and identified by GC-MS. To determine the responsible enzymes in quinalphos metabolism, piperonyl butoxide (PB) and methimazole included in the culture flasks, and the kinetic responses of quinalphos and its metabolites by C. elegans were measured. Results indirectly demonstrated that cytochrome P450 monooxygenases were involved in the metabolism of quinalphos, but that methimazole inhibited the metabolism less efficiently. Comprehensive metabolic pathways can be deduced from the detailed analysis of metabolite profiles in control and inhibitor assays.
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Cunninghamella , Metimazol , Metimazol/metabolismo , Cunninghamella/metabolismo , Redes e Vias MetabólicasRESUMO
OBJECTIVES: Issues regarding antibiotic use in end-of-life patients with advanced cancer present a challenging ethical dilemma in academic referral centres. This study aimed to investigate the role of palliative care consultation on antibiotic prescription patterns among hospitalized patients with advanced cancer during their last days of life. METHODS: This retrospective cohort study included adult patients with metastatic solid cancer admitted to a tertiary referral hospital for at least 4 days and subsequently died and who were given antibiotics 4 days before death between January 2018 and December 2021. Patients were divided into palliative care consultation (PC) and non-consultation (non-PC) groups. The outcomes were the proportion of patients who received antibiotic combination treatment, antibiotic escalation and antibiotic de-escalation within 3 days of death. Propensity score analysis with the inverse probability of the treatment weighting method was used to compare the outcomes. RESULTS: Among the 1177 patients enrolled, 476 (40.4%) received palliative care consultation and 701 (59.6%) did not. The PC group received considerably less antibiotic combination treatment (49.0% versus 61.1%, adjusted OR: 0.69, 95% CI: 0.53-0.90, Pâ=â0.006) and antibiotic escalation (15.8% versus 34.8%, adjusted OR: 0.41, 95% CI: 0.30-0.57, Pâ<â0.001) than the non-PC group. Additionally, the PC group reported significantly higher antibiotic de-escalation (30.7% versus 17.4%, adjusted OR: 1.74, 95% CI: 1.28-2.36, Pâ<â0.001). CONCLUSION: Receiving palliative care consultation may minimize aggressive antibiotic prescription patterns in the last days of patients with advanced cancer in an academic referral centre setting.
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Neoplasias , Cuidados Paliativos , Adulto , Humanos , Cuidados Paliativos/métodos , Estudos Retrospectivos , Neoplasias/tratamento farmacológico , Encaminhamento e Consulta , Centros de Atenção TerciáriaRESUMO
Background and Objectives: The Child-Pugh (CP) score and Model for End-Stage Liver Disease (MELD) are classical systems for predicting mortality in patients with liver cirrhosis (LC). The MELD-GFR assessment in liver disease-sodium (MELD-GRAIL-Na) was designed to better reflect renal function and, therefore, provide better mortality predictions. This study aimed to compare the prediction accuracy of MELD-GRAIL-Na compared to CP and MELD in predicting short-term (1- and 3-month) mortality in Korean patients. Materials and Methods: Medical records of patients with LC admitted to the Konkuk University Hospital from 2015 to 2020 were retrospectively reviewed. Predictive values of the CP, MELD, and MELD-GRAIL-Na for 1-month and 3-month mortality were calculated using the area under the receiver operating curve (AUROC) and were compared using DeLong's test. Results: In total, 1249 patients were enrolled; 102 died within 1 month, and 146 within 3 months. AUROCs of CP, MELD, and MELD-GRAIL-Na were 0.831, 0.847, and 0.857 for 1-month mortality and 0.837, 0.827, and 0.835 for 3-month mortality, respectively, indicating no statistical significance. For patients with CP classes B and C, AUROCs of CP, MELD, and MELD-GRAIL-Na were 0.782, 0.809, and 0.825 for 1-month mortality and 0.775, 0.769, and 0.786 for 3-month mortality, respectively. There was a significant difference between CP and MELD-GRAIL-Na in predicting 1-month mortality (p = 0.0428) and between MELD and MELD-GRAIL-Na in predicting 1-month (p = 0.0493) and 3-month mortality (p = 0.0225). Conclusions: Compared to CP and MELD, MELD-GRAIL-Na was found to be a better and more useful system for evaluating short-term (1- and 3-month) mortality in Korean patients with cirrhosis, especially those with advanced cirrhosis (CP class B and C).
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Doença Hepática Terminal , Cirrose Hepática , Humanos , Doença Hepática Terminal/mortalidade , Cirrose Hepática/mortalidade , Valor Preditivo dos Testes , Prognóstico , República da Coreia/epidemiologia , Estudos Retrospectivos , Curva ROC , Índice de Gravidade de Doença , Sódio , População do Leste AsiáticoRESUMO
BACKGROUND: Posttraumatic anger is a commonly reported emotion among people who have experienced traumatic events. The current study aimed to demonstrate the reliability and validity of the South Korean version of the DAR-5 (DAR-5-K). The DAR-5 is a single scale with 5 items which measures posttraumatic anger. The DAR-5 is composed of five items that measure anger frequency, intensity, duration, aggression, and its interference with social relations. METHODS: Data were collected from 814 South Korean adults who had experienced traumatic events and participated in the study and analyzed via the combination of exploratory factor analysis (n = 405) and confirmatory factor analysis (n = 409). RESULTS: Results supported the one-factor structure, as reported in previous validation studies. The scale demonstrated robust internal reliability and concurrent validity with measures of posttraumatic stress disorder (PTSD) symptoms, depression, anxiety, and self-esteem. The DAR-5 cut-off score of 12 that was established in the original validation study successfully differentiated high from low scorers with regard to PTSD symptoms, depression, anxiety, and self-esteem. CONCLUSION: The results confirm that the DAR-5-K is a brief and psychometrically robust measure of anger that can be used to examine South Korean adults who have experienced traumatic events.
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Transtornos de Estresse Pós-Traumáticos , Humanos , Adulto , Reprodutibilidade dos Testes , Inquéritos e Questionários , Psicometria , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Transtornos de Estresse Pós-Traumáticos/psicologia , Ira , República da CoreiaRESUMO
As one of the effort to cope with the energy crisis and carbon neutrality, utilization of low-grade energy generated indoors (e.g., light) is imperative because this saves building and house energy, which accounts for ≈40% of total energy consumption. Although photovoltaic devices could contribute to energy savings, it is also necessary to harvest heat from indoor lights to generate electricity because the light absorbed by materials is mostly transformed into heat. For daily life uses, materials should not only have high absorptance and low emittance but also be easily processed into various forms. To this end, this work synthesizes black aqueous suspensions containing winding and bent linear gold nanostructures with diameters of 3-5 nm and length-to-diameter ratios of ≈4-10. Their optical and photo-thermal characteristics are understood through experimental and theoretical investigations. Black gold nanostructures are conveniently processed into metal-dielectric films on metal, glass, and flexible substrates. The film on copper has an absorptance of 0.97 and an emittance of 0.08. Under simulated sunlight and indoor LED light illumination, the film has equivalent photo-thermal and photo-thermoelectric performances to a top-tier sunlight-collecting film. This work attempts to modify the film structure to generate more usable electricity from low-energy indoor light.
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Autoimmune hepatitis (AIH) is an immune-mediated inflammatory liver disease with an uncertain cause. The diagnosis of AIH is based on the characteristic clinical and laboratory findings (elevated liver enzyme and hypergammaglobulinemia), the presence of characteristic autoantibodies, and compatible histological abnormalities. AIH lacks a signature diagnostic marker, and the diagnosis requires the exclusion of other diseases (viral hepatitis, alcoholic liver disease, non-alcoholic steatohepatitis, drug-induced liver injury, Wilson's disease, and hereditary hemochromatosis). Therefore, collaboration between the clinical physician, laboratory medicine experts, and pathologists is important for a diagnosis. In December 2022, the Korean Association for the Study of the Liver (KASL) clinical practice guidelines were established. This review article summarizes the diagnosis part of these guidelines.
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Doença Hepática Induzida por Substâncias e Drogas , Hepatite Autoimune , Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatite Autoimune/diagnóstico , Hepatite Autoimune/patologia , AutoanticorposRESUMO
BACKGROUND: Exposure of agricultural workers in rice paddies to the insecticide chlorantraniliprole and its subsequent potential health risks were investigated during two scenarios (mixing/loading and hand-held spraying). The exposure factors, such as the outer dosimeter, inner dosimeter, gauze, and nitrile gloves, were calculated using whole-body dosimetry to measure dermal exposure. The inhalation exposure was determined using a fiberglass filter which is set with an Institute of Occupational Medicine (IOM) sampler. A recovery test was performed to evaluate the accuracy of the analytical method. RESULTS: The exposure amounts of various matrices were calculated from extraction volume and concentration of the target compound. The dermal exposure to chlorantraniliprole was 0.6 mg [0.001% of the total active ingredient (a.i.)] for mixing and loading, and 28.6 mg (0.066% of the total a.i.) for application. The inhalation exposure to chlorantraniliprole was 7.2 µg (1.3%, 1.2 × 10-5 % of the total applied a.i.) for mixing and loading, and 1.9 µg (0.006%, 4.4 × 10-6 % of the total applied a.i.) for application. The most exposed part of the body was the hand (90.4%) during mixing and loading, whereas the primary sites during application were the thighs (32.8%) and shins (22.6%). For mixing and loading, the amount of actual dermal exposure was 5.5 µg day-1 and that of actual inhalation exposure was 21.9 µg day-1 . By contrast, in the application, the amounts of actual dermal and actual inhalation exposures were 34 178.7 and 5.9 µg day-1 , respectively. CONCLUSIONS: The risk assessment results demonstrated that the risk of chlorantraniliprole exposure in rice paddies was low during application than during mixing and loading. © 2022 Society of Chemical Industry.
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Inseticidas , Exposição Ocupacional , Oryza , Humanos , Inseticidas/análise , Exposição Ocupacional/análise , Fazendeiros , Medição de Risco , Exposição por Inalação/análiseRESUMO
OBJECTIVES: A substantial number of hospitalized patients with terminal cancer at the end-of-life phase receive antibiotics, even with imminent death. We evaluated the impact of palliative care consultation on antibiotic use in hospitalized patients with terminal cancer during the end-of-life phase. METHODS: We identified adult patients with metastatic solid cancer who died at a tertiary medical centre in Seoul, Republic of Korea, following at least 4â days of hospitalization (January 2018-December 2020). Patients were divided into palliative and non-palliative care consultation groups. Propensity score-weighted, multivariable logistic regression analysis was used to compare the proportion of patients receiving antibiotics within 3â days before death between the two groups. RESULTS: Among 1143 patients analysed, 940 (82.2%) received antibiotics within 3â days before death. The proportion of patients receiving antibiotics was significantly lower (propensity score-weighted Pâ<â0.001) in the palliative care consultation group (344/468; 73.5%) than in the non-palliative care consultation group (596/675; 88.3%). The decrease in the proportion of patients receiving antibiotics in the palliative care consultation group was significant for a carbapenem (42.4% versus 22.4%; Pâ<â0.001), a glycopeptide (23.3% versus 11.1%; Pâ<â0.001) and a quinolone (30.5% versus 19.4%; Pâ=â0.012). In the multivariable logistic regression analysis, receiving palliative care consultation (adjusted OR 0.46, 95% CI 0.33-0.65; Pâ<â0.001) was independently associated with reduced antibiotic use during the end-of-life phase. CONCLUSIONS: Palliative care consultation may reduce aggressive antibiotic use in hospitalized patients with terminal cancer during the end-of-life phase.
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Antibacterianos , Neoplasias , Adulto , Humanos , Pontuação de Propensão , Antibacterianos/uso terapêutico , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Encaminhamento e Consulta , Morte , Estudos RetrospectivosRESUMO
The ability of Mycobacterium tuberculosis (Mtb) to persist in its host may enable an evolutionary advantage for drug resistant variants to emerge. A potential strategy to prevent persistence and gain drug efficacy is to directly target the activity of enzymes that are crucial for persistence. We present a method for expedited discovery and structure-based design of lead compounds by targeting the hypoxia-associated enzyme L-alanine dehydrogenase (AlaDH). Biochemical and structural analyses of AlaDH confirmed binding of nucleoside derivatives and showed a site adjacent to the nucleoside binding pocket that can confer specificity to putative inhibitors. Using a combination of dye-ligand affinity chromatography, enzyme kinetics and protein crystallographic studies, we show the development and validation of drug prototypes. Crystal structures of AlaDH-inhibitor complexes with variations at the N6 position of the adenyl-moiety of the inhibitor provide insight into the molecular basis for the specificity of these compounds. We describe a drug-designing pipeline that aims to block Mtb to proliferate upon re-oxygenation by specifically blocking NAD accessibility to AlaDH. The collective approach to drug discovery was further evaluated through in silico analyses providing additional insight into an efficient drug development strategy that can be further assessed with the incorporation of in vivo studies.
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Alanina Desidrogenase , Mycobacterium tuberculosis , Alanina Desidrogenase/metabolismo , Mycobacterium tuberculosis/metabolismo , Nucleosídeos , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química , Descoberta de DrogasRESUMO
Simultaneous multiresidual pesticide analysis of saliva samples was performed using scaled-down QuEChERS extraction with LC-MS/MS and GC-MS/MS. The optimum extraction procedure using acidified acetonitrile was applicable to 336 pesticides (287 for LC-MS/MS and 49 for GC-MS/MS). To determine pesticide multiresidues in saliva, 100 µL of the sample was extracted with 200 µL of 0.1% formic acid in acetonitrile, and the initial extract was partitioned with 40 mg of MgSO4 and 10 mg of NaCl. The organic supernatants (120 µL) were then mixed with acetonitrile (30 µL) for matrix-matching (4:1, v/v), and the final extract solution was injected into the LC-MS/MS (4 µL) and GC-MS/MS (2 µL) systems. The established analytical method showed a good LOQs between 5 and 25 ng/mL with reliable accuracy/precision values and recovery results (50-140%) for the target pesticides. Under the two different storage conditions, most of the analytes did not undergo chemical changes in the saliva samples, whereas some pesticides were more stable in freeze-thaw processes than those left at room temperature. Biomonitoring of farmers (ten mixers and ten sprayers) was successfully applied using the validated method, and two carbamates (fenobucarb and propamocarb) were determined at trace concentrations (12.5-675.0 ng/mL from 11 positively detected samples).
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Resíduos de Praguicidas , Praguicidas , Humanos , Praguicidas/análise , Cromatografia Líquida , Espectrometria de Massas em Tandem/métodos , Resíduos de Praguicidas/análise , Cromatografia Gasosa-Espectrometria de Massas/métodos , Monitoramento Biológico , Fazendeiros , Saliva/química , Cloreto de Sódio/análise , Acetonitrilas/análise , Carbamatos/análise , Extratos Vegetais/análiseRESUMO
The effects of the grain size of Pt bottom electrodes on the ferroelectricity of hafnium zirconium oxide (HZO) were studied in terms of the orthorhombic phase transformation. HZO thin films were deposited by chemical solution deposition on the Pt bottom electrodes with various grain sizes which had been deposited by direct current sputtering. All the samples were crystallized by rapid thermal annealing at 700 °C to allow a phase transformation. The crystallographic phases were determined by grazing incidence X-ray diffraction, which showed that the bottom electrode with smaller Pt grains resulted in a larger orthorhombic phase composition in the HZO film. As a result, capacitors with smaller Pt grains for the bottom electrode showed greater ferroelectric polarization. The smaller grains produced larger in-plane stress which led to more orthorhombic phase transformation and higher ferroelectric polarization.
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Recently developed fabrication methods for inorganic patterns (such as laser printing and optical lithography) can avoid some patterning processes conducted by conventional etching and lithography (such as substrate etching and modulation) and are thereby useful for applications in which the substrates and materials must not be damaged during patterning. Simultaneously, it is also necessary to develop facile and economical methods producing inorganic patterns on various substrates without requiring a special apparatus while attaining the above-mentioned advantages. The present study proposes a reaction-based method for fabricating inorganic patterns by immersing substrates coated with a colloidal nanosheet into an aqueous solution containing inorganic precursors. Silica and TiO2 patterns spontaneously developed during the conversion of each inorganic precursor. These patterns were successful on rigid and flexible substrates. We fabricated these patterns on a wafer-sized silicon and large flexible poly(ethylene terephthalate) film, suggesting the scalability. We fabricated a biomimetic pattern on both sides of a glass window, as a photovoltaic roof, for minimal optical losses to maximally present photovoltaic effects of a solar cell. The TiO2 pattern on glass window exhibits sustainable sunlight-driven-cleaning activity for contaminants. The method could provide a platform for economical high-performance inorganic patterns for energy, environmental, electronics, and other areas.
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Dermal & inhalation exposure was examined and according to these results, risk assessment of agricultural workers to thiamethoxam was performed during pesticide mixing/loading and hand-held sprayer application (11 replicates, each of about 1000 L of spray suspension) in vineyards. For the whole body dosimetry (WBD), clothing (Outer and inner), gauze, and nitrile gloves were analyzed to determine dermal exposure using whole-body dosimetry exposure protocol. The inhalation exposure was measured using a glass fiber filter with an IOM sampler. Analytical method validation of exposure matrices was evaluated including the field recovery and breakthrough test. The dermal exposure amount during mixing/loading was 0.163 mg (0.0004% of the total mixed/loaded active ingredient [a.i.]), whereas there was no inhalation exposure. The gloves (0.154 mg, 94.5%) were the most exposed body parts followed by the chest and stomach (0.009 mg, 5.5%). During application, the dermal and inhalation exposure amounts were 32.3 mg (0.07% of the total applied a.i.) and 10.8 µg (2.4 × 10-6% of the total applied a.i), respectively. The shin (35.1%) had the highest exposure to pesticides, followed by the chest & stomach (15.6%) and pelvis (12.6%). In case of mixing/loading, the amounts of actual dermal exposure (ADE) and actual inhalation exposure (AIE) were 0.0 and 0.0 µg/day, while those of ADE and AIE were 4707.6 and 15.8 µg/day for application. In risk assessment of the two different scenarios, the risk index was much lower than 1 (mixing/loading:0.000, application:0.014), indicating that vineyard workers are at low risk of thiamethoxam exposure. To determine the validity of the risk assessment using WBD method, the urinary metabolite was analyzed. Comparison of biomonitoring data and WBD exposure data show a reliable correlation (r = 0.885, p = 0.0003), suggesting that these are suitable methods to estimate exposure.