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Background: Islet transplantation holds promise for treating selected type 1 diabetes mellitus patients, yet the scarcity of human donor organs impedes widespread adoption. Porcine islets, deemed a viable alternative, recently demonstrated successful longterm survival without zoonotic risks in a clinically relevant pig-to-non-human primate islet transplantation model. This success prompted the development of a clinical trial protocol for porcine islet xenotransplantation in humans. Methods: A single-center, open-label clinical trial initiated by the sponsor will assess the safety and efficacy of porcine islet transplantation for diabetes patients at Gachon Hospital. The protocol received approval from the Gachon Hospital Institutional Review Board (IRB) and the Korean Ministry of Food and Drug Safety (MFDS) under the Investigational New Drug (IND) process. Two diabetic patients, experiencing inadequate glycemic control despite intensive insulin treatment and frequent hypoglycemic unawareness, will be enrolled. Participants and their family members will engage in deliberation before xenotransplantation during the screening period. Each patient will receive islets isolated from designated pathogen-free pigs. Immunosuppressants and systemic infection prophylaxis will follow the program schedule. The primary endpoint is to confirm the safety of porcine islets in patients, and the secondary endpoint is to assess whether porcine islets can reduce insulin dose and the frequency of hypoglycemic unawareness. Conclusion: A clinical trial protocol adhering to global consensus guidelines for porcine islet xenotransplantation is presented, facilitating streamlined implementation of comparable human trials worldwide.
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BACKGRUOUND: It is well known that a large number of patients with diabetes also have dyslipidemia, which significantly increases the risk of cardiovascular disease (CVD). This study aimed to evaluate the efficacy and safety of combination drugs consisting of metformin and atorvastatin, widely used as therapeutic agents for diabetes and dyslipidemia. METHODS: This randomized, double-blind, placebo-controlled, parallel-group and phase III multicenter study included adults with glycosylated hemoglobin (HbA1c) levels >7.0% and <10.0%, low-density lipoprotein cholesterol (LDL-C) >100 and <250 mg/dL. One hundred eighty-five eligible subjects were randomized to the combination group (metformin+atorvastatin), metformin group (metformin+atorvastatin placebo), and atorvastatin group (atorvastatin+metformin placebo). The primary efficacy endpoints were the percent changes in HbA1c and LDL-C levels from baseline at the end of the treatment. RESULTS: After 16 weeks of treatment compared to baseline, HbA1c showed a significant difference of 0.94% compared to the atorvastatin group in the combination group (0.35% vs. -0.58%, respectively; P<0.0001), whereas the proportion of patients with increased HbA1c was also 62% and 15%, respectively, showing a significant difference (P<0.001). The combination group also showed a significant decrease in LDL-C levels compared to the metformin group (-55.20% vs. -7.69%, P<0.001) without previously unknown adverse drug events. CONCLUSION: The addition of atorvastatin to metformin improved HbA1c and LDL-C levels to a significant extent compared to metformin or atorvastatin alone in diabetes and dyslipidemia patients. This study also suggested metformin's preventive effect on the glucose-elevating potential of atorvastatin in patients with type 2 diabetes mellitus and dyslipidemia, insufficiently controlled with exercise and diet. Metformin and atorvastatin combination might be an effective treatment in reducing the CVD risk in patients with both diabetes and dyslipidemia because of its lowering effect on LDL-C and glucose.
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Atorvastatina , LDL-Colesterol , Diabetes Mellitus Tipo 2 , Quimioterapia Combinada , Dislipidemias , Hemoglobinas Glicadas , Hipoglicemiantes , Metformina , Humanos , Atorvastatina/uso terapêutico , Atorvastatina/administração & dosagem , Metformina/uso terapêutico , Metformina/administração & dosagem , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/sangue , Masculino , Feminino , Método Duplo-Cego , Pessoa de Meia-Idade , Dislipidemias/tratamento farmacológico , Dislipidemias/sangue , Hemoglobinas Glicadas/análise , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/administração & dosagem , Idoso , LDL-Colesterol/sangue , Resultado do Tratamento , AdultoRESUMO
PURPOSE: We evaluated the correlation between quantitative background activities on electroencephalography (EEG) and serum neuron specific enolase (NSE) in patients with hypoxic-ischemic encephalopathy as well as a diagnostic value of prognostication. METHODS: This retrospective cohort study enrolled patients with return of spontaneous circulation after cardiac arrest from March 2010 to March 2020. The inclusion criteria were (1) older than the age of 16 years and (2) patients who had both EEG and NSE. The median time for EEG and NSE were 3 days (interquartile range 2-5 days) and 3 days (interquartile range 2-4 days), respectively. The quantification of background activity was conducted with the suppression ratio (SR). We used a machine learning (eXtreme Gradient Boosting algorithm) to evaluate whether the SR could improve the accuracy of prognostication. RESULTS: We enrolled 151 patients. The receiver operating characteristic analysis revealed a cut-off value of serum NSE and the SR for poor outcome, serum NSE (>31.9 µg/L, area under curve [AUC] = 0.88), and the SR (>21.5%, AUC = 0.75 in the right hemisphere, >34.4%, AUC = 0.76 in the left hemisphere). There was a significant positive correlation between the severity of SR and the level of NSE (ρ = 0.57, p < 0.0001 for the right hemisphere, ρ = 0.58, p < 0.0001 for the left hemisphere). The SR showed an excellent diagnostic value for predicting poor outcome (93% specificity, 60% sensitivity in the right hemisphere and 93% specificity, 58% sensitivity in the left hemisphere). With machine learning analysis, there was an increment in distinguishing the neurological outcome by adding SR on clinical factors. CONCLUSIONS: The SR showed a positive correlation with the level of serum NSE. The diagnostic value of the SR for predicting poor outcome was excellent, suggesting that it can be a possible biomarker for neuroprognostication in patients with hypoxic-ischemic encephalopathy.
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Pyrethroid insecticides are used in agriculture to treat parasites in livestock. This study developed a simultaneous residue analysis method to measure seventeen pyrethroid insecticides in foods of animal origin, including beef, pork, chicken, milk, and eggs. The method, which comprises instrumental analysis using gas chromatography-tandem mass spectrometry and a modified QuEChERS (quick, easy, cheap, effective, rugged, and safe) method for pretreatment, was optimized to verify the applicability of the method. A mixture of acetonitrile, ethyl acetate, and original salt (MgSO4 4 g, NaCl 1 g) was used as the extraction solvent and salt. MgSO4 (150 mg) primary secondary amine (25 mg) and graphitized carbon black (25 mg) were selected for dispersive solid phase extraction (d-SPE). The method limit of quantitation was 0.01 mg/L, and the linearity of the matrix-matched calibration curves was reasonable (R2 > 0.99). Recovery tests were performed at three concentrations (LOQ, 10 LOQ, and 50 LOQ). Good recoveries (75.2109.8%) and reproducibility (coefficient of variation <10%) were obtained. The matrix effects were in the range of −35.8 to 56.0%. The established method was fully validated and can be used as an official analytical method for quantifying pyrethroid insecticides in animal commodities.
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OBJECTIVE: The aim of this study was to evaluate the feasibility of machine learning based on diffusion tensor imaging (DTI) measures to distinguish patients with focal epilepsy versus healthy controls and antiseizure medication (ASM) responsiveness. METHODS: This was a retrospective study performed at a tertiary hospital. We enrolled 456 patients with focal epilepsy, who underwent DTI and were taking ASMs. We enrolled 100 healthy subjects as a control. We obtained the conventional DTI measures and structural connectomic profiles from the DTI. RESULTS: The support vector machine (SVM) classifier based on the conventional DTI measures revealed an accuracy of 76.5% and an area under curve (AUC) of 0.604 (95% Confidence interval (CI), 0.506-0.695). Another SVM classifier combined with structural connectomic profiles demonstrated an accuracy of 82.8% and an AUC of 0.701 (95% CI, 0.606-0.784). Of the 456 patients with epilepsy, 242 patients were ASM good responders, whereas 214 patients were ASM poor responders. In the classification of the ASM responders, an SVM classifier based on the conventional DTI measures revealed an accuracy of 54.9% and an AUC of 0.551 (95% CI, 0.443-0.655). Another SVM classifier combined with structural connectomic profiles demonstrated an accuracy of 59.3% and an AUC of 0.594 (95% CI, 0.485-0.695). CONCLUSION: DTI using a machine learning is useful for differentiating patients with focal epilepsy from healthy controls, but it cannot classify ASM responsiveness. Combining structural connectomic profiles results in a better classification performance than the use of conventional DTI measures alone for identifying focal epilepsy and ASM responsiveness.
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Imagem de Tensor de Difusão/métodos , Epilepsias Parciais/diagnóstico por imagem , Interpretação de Imagem Assistida por Computador/métodos , Máquina de Vetores de Suporte , Adulto , Anticonvulsivantes/uso terapêutico , Conectoma/métodos , Epilepsias Parciais/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
BACKGROUND: Notch signaling pathway plays an important role in regulating pancreatic endocrine and exocrine cell fate during pancreas development. Notch signaling is also expressed in adult pancreas. There are few studies on the effect of Notch on adult pancreas. Here, we investigated the role of Notch in islet mass and glucose homeostasis in adult pancreas using Notch1 antisense transgenic (NAS). METHODS: Western blot analysis was performed for the liver of 8-week-old male NAS mice. We also conducted an intraperitoneal glucose tolerance test (IPGTT) and intraperitoneal insulin tolerance test in 8-week-old male NAS mice and male C57BL/6 mice (control). Morphologic observation of pancreatic islet and ß-cell was conducted in two groups. Insulin secretion capacity in islets was measured by glucose-stimulated insulin secretion (GSIS) and perifusion. RESULTS: NAS mice showed higher glucose levels and lower insulin secretion in IPGTT than the control mice. There was no significant difference in insulin resistance. Total islet and ß-cell masses were decreased in NAS mice. The number of large islets (≥250 µm) decreased while that of small islets (<250 µm) increased. Reduced insulin secretion was observed in GSIS and perifusion. Neurogenin3, neurogenic differentiation, and MAF bZIP transcription factor A levels increased in NAS mice. CONCLUSION: Our study provides that Notch1 inhibition decreased insulin secretion and decreased islet and ß-cell masses. It is thought that Notch1 inhibition suppresses islet proliferation and induces differentiation of small islets. In conclusion, Notch signaling pathway may play an important role in ß-cell mass determination and diabetes.
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Diabetes Mellitus , Ilhotas Pancreáticas , Animais , Diferenciação Celular , Insulina , Masculino , Camundongos , Camundongos Endogâmicos C57BLRESUMO
Islet transplantation has emerged as a promising treatment for type 1 diabetes mellitus. Liraglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, protects beta cells after islet transplantation by improving glycemic control through several mechanisms. In this study, we compared the effects of local pretreatment and systemic treatment with liraglutide on islet transplantation in a diabetic mouse model. Streptozotocin (STZ)-induced diabetic C57BL/6 mice were transplanted with syngeneic islets under the kidney capsule. Isolated islets were either locally treated with liraglutide before transplantation or mice were treated systemically by intraperitoneal injection after islet transplantation. Local pretreatment of islets with liraglutide was more effective in increasing body weight, decreasing hemoglobin A1c levels, and lowering blood glucose levels in STZ-diabetic mice transplanted with islets. Local pretreatment was also more effective in increasing insulin secretion and islet survival in STZ-diabetic mice. Histological analysis of the transplantation site revealed fewer apoptotic cells following local pretreatment compared with systemic injection of liraglutide. These findings indicate that liraglutide administered once locally before transplantation might have superior effects on islet preservation than systemic administration.
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Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Liraglutida/uso terapêutico , Animais , Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/metabolismo , Hemoglobinas Glicadas/metabolismo , Sobrevivência de Enxerto/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BLRESUMO
OBJECTIVES: This study evaluated the structural and functional connectivity of patients with genetic generalized epilepsy (GGE) compared to healthy subjects. We also investigated whether there are differences in structural and functional connectivity among different GGE syndromes. METHODS: We enrolled 100 patients with a clinical diagnosis of GGE. The patients were classified into different syndrome groups(12 cases of childhood absence epilepsy, 13 cases of juvenile absence epilepsy, 56 cases of juvenile myoclonic epilepsy, and 19 cases of epilepsy with GTC alone). We applied graph theoretical analysis to structural brain volumes and EEG to evaluate structural and functional connectivity in the GGE patients. RESULTS: The global network measures showed significant differences in the structural and functional connectivity between the patients with GGE and the healthy controls, and the local network measures revealed hub reorganization in the GGE patients. The global efficiency, local efficiency, and clustering coefficients of the structural connectivity were significantly decreased, whereas the characteristic path length and small-worldness index were increased in the GGE patients. The global efficiency and local efficiency were increased and the small-worldness index decreased in the functional connectivity. The patients with juvenile myoclonic epilepsy had the most extensive changes in structural and functional connectivity compared to the healthy subjects. SIGNIFICANCE: This study's main finding is that structural and functional connectivity in patients with GGE is significantly different from that in healthy controls. We find that the different GGE syndromes show distinct structural and functional connectivity, which can lead further understanding of the pathogenesis of GGE syndromes.
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Epilepsia Tipo Ausência , Epilepsia Generalizada , Epilepsia Mioclônica Juvenil , Criança , Epilepsia Generalizada/genética , Humanos , Epilepsia Mioclônica Juvenil/genética , SíndromeRESUMO
Growth hormone (GH) deficiency is caused by congenital or acquired causes and occurs in childhood or adulthood. GH replacement therapy brings benefits to body composition, exercise capacity, skeletal health, cardiovascular outcomes, and quality of life. Before initiating GH replacement, GH deficiency should be confirmed through proper stimulation tests, and in cases with proven genetic causes or structural lesions, repeated GH stimulation testing is not necessary. The dosing regimen of GH replacement therapy should be individualized, with the goal of minimizing side effects and maximizing clinical improvements. The Korean Endocrine Society and the Korean Society of Pediatric Endocrinology have developed a position statement on the diagnosis and treatment of GH deficiency. This position statement is based on a systematic review of evidence and expert opinions.
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Transtornos do Crescimento/diagnóstico , Transtornos do Crescimento/tratamento farmacológico , Terapia de Reposição Hormonal , Hormônio do Crescimento Humano/administração & dosagem , Hormônio do Crescimento Humano/deficiência , Guias de Prática Clínica como Assunto/normas , Criança , Humanos , Prognóstico , Sociedades CientíficasRESUMO
INTRODUCTION: Seizures as acute stroke mimics are a diagnostic challenge. OBJECTIVE: The aim of the study was to characterize the perfusion patterns on perfusion computed tomography (PCT) in patients with seizures masquerading as acute stroke. METHODS: We conducted a study on patients with acute seizures as stroke mimics. The inclusion criteria for this study were patients (1) initially presenting with stroke-like symptoms but finally diagnosed to have seizures and (2) with PCT performed within 72 h of seizures. The PCT of seizure patients (n = 27) was compared with that of revascularized stroke patients (n = 20) as the control group. RESULTS: Among the 27 patients with seizures as stroke mimics, 70.4% (n = 19) showed characteristic PCT findings compared with the revascularized stroke patients, which were as follows: (1) multi-territorial cortical hyperperfusion {(73.7% [14/19] vs. 0% [0/20], p = 0.002), sensitivity of 73.7%, negative predictive value (NPV) of 80%}, (2) involvement of the ipsilateral thalamus {(57.9% [11/19] vs. 0% [0/20], p = 0.007), sensitivity of 57.9%, NPV of 71.4%}, and (3) reduced perfusion time {(84.2% [16/19] vs. 0% [0/20], p = 0.001), sensitivity of 84.2%, NPV of 87%}. These 3 findings had 100% specificity and positive predictive value in predicting patients with acute seizures in comparison with reperfused stroke patients. Older age was strongly associated with abnormal perfusion changes (p = 0.038), with a mean age of 66.8 ± 14.5 years versus 49.2 ± 27.4 years (in seizure patients with normal perfusion scan). CONCLUSIONS: PCT is a reliable tool to differentiate acute seizures from acute stroke in the emergency setting.
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Neuroimagem/métodos , Imagem de Perfusão/métodos , Convulsões/diagnóstico por imagem , Acidente Vascular Cerebral/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Encéfalo/diagnóstico por imagem , Diagnóstico Diferencial , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Masculino , Pessoa de Meia-IdadeRESUMO
AIM: MLR-1023, called Tolimidone when evaluated unsuccessfully by Pfizer for gastric ulcer disease, has been repurposed as a novel oral insulin sensitizer with its effects mediated by selective activation of Lyn kinase. We aimed to evaluate the optimal dose, efficacy and safety of MLR-1023 in patients with type 2 diabetes. METHODS: Type 2 diabetes patients (18-75â¯years) on diet/exercise therapy were randomized and double-blinded to receive MLR-1023 (100-mg or 200-mg, once-daily [qd] or twice-daily [bid]) or matching placebo for 28â¯days. The primary endpoint was postprandial glucose (PPG) area under the curve (AUC0-3h) in a mixed meal tolerance test (MMTT) at day 29. Secondary endpoints included changes in fasting plasma glucose (FPG), insulin, HbA1c, lipids and body weight and adverse events. ANCOVA model was used for efficacy analysis. RESULTS: The placebo-corrected least-squares mean differences (ΔLSM) in MMTT PPG AUC0-3â¯h (mmol/L) were -5.96 and -5.6 (both pâ¯=â¯0.03) in the MLR-1023 100-mg qd and 100-mg bid groups, respectively. The placebo-corrected ΔLSM in FPG (mmol/L) was -2.34 (pâ¯=â¯0.003) in the MLR-1023 100-mg qd group. Triglycerides improved with MLR-1023 (ΔLSM, -0.56â¯mmol/L, pâ¯=â¯0.07 and -0.59â¯mmol/L, pâ¯=â¯0.05) in the 200mgqd and 200â¯mg bid groups, respectively. Reductions in fasting insulin, HbA1c and body weight were not statistically significant. Most common adverse events with MLR-1023 treatment were headache (4.2%) and somnolence (2.5%). CONCLUSIONS: MLR-1023 100-mg once-daily for 4â¯weeks was the most effective dose with significant reduction in PPG AUC following a MMTT. MLR-1023 was safe and well-tolerated in patients with type 2 diabetes. Clinical Trials Registration Number: NCT02317796.
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Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Pirimidinonas/uso terapêutico , Adolescente , Adulto , Idoso , Diabetes Mellitus Tipo 2/fisiopatologia , Método Duplo-Cego , Feminino , Humanos , Hipoglicemiantes/farmacologia , Resistência à Insulina , Masculino , Pessoa de Meia-Idade , PPAR gama , Pirimidinonas/farmacologia , Resultado do Tratamento , Adulto Jovem , Quinases da Família srcRESUMO
Microcephaly is a prevalent phenotype in patients with neurodevelopmental problems, often with genetic causes. We comprehensively investigated the clinical phenotypes and genetic background of microcephaly in 40 Korean patients. We analyzed their clinical phenotypes and radiologic images and conducted whole exome sequencing (WES) and analysis of copy number variation (CNV). Infantile hypotonia and developmental delay were present in all patients. Thirty-four patients (85%) showed primary microcephaly. The diagnostic yield from the WES and CNV analyses was 47.5%. With WES, we detected pathogenic or likely pathogenic variants that were previously associated with microcephaly in 12 patients (30%); nine of these were de novo variants with autosomal dominant inheritance. Two unrelated patients had mutations in the KMT2A gene. In 10 other patients, we found mutations in the GNB1, GNAO1, TCF4, ASXL1, SMC1A, VPS13B, ACTG1, EP300, and KMT2D genes. Seven patients (17.5%) were diagnosed with pathogenic CNVs. Korean patients with microcephaly show a genetic spectrum that is different from that of patients with microcephaly of other ethnicities. WES along with CNV analysis represents an effective approach for diagnosis of the underlying causes of microcephaly.
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BACKGROUND: Both obstructive sleep apnea (OSA) and obesity are associated with poor sleep quality. However, there have been no studies investigating sleep quality in OSA patients with obesity. The aims of this study were to (1) evaluate the sleep quality in OSA patients with obesity and (2) identify the parameters most related to sleep quality in OSA patients with obesity. METHODS: Of the patients with polysomnography (PSG), OSA patients with obesity (body mass index [BMI] ≥25) were enrolled and then divided into 2 groups based on the Pittsburg Sleep Questionnaire Index (PSQI): patients with good sleep quality (PSQI ≤5, good sleepers) and those with poor sleep quality (PSQI >5, poor sleepers). In addition, we enrolled OSA patients without obesity as a disease control group. RESULTS: Eighty-two OSA patients with obesity met the inclusion criteria (28 were good sleepers, whereas 54 were poor sleepers). We found that the BMI of the poor sleepers was significantly higher than that of the good sleepers, whereas the N-stage sleep ratio of good sleepers was higher than that of poor sleepers. Logistic -regression analysis also showed that a high BMI and low -N-stage sleep ratio were independently associated with poor sleep quality. In addition, BMI and N-stage sleep ratio were significantly correlated with PSQI. However, in 56 OSA patients (n = 56) without obesity, there were no differences of demographic/clinical characteristics and PSG parameters between the good (n = 18) and poor sleepers (n = 38). DISCUSSIONS: About two-thirds of OSA patients with obesity show poor sleep quality. The sleep quality of these patients was more affected by the severity of obesity, but not the severity of OSA. Thus, we recommend weight loss in OSA patients with obesity to improve sleep quality as well as the severity of OSA.
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Obesidade , Apneia Obstrutiva do Sono , Sono/fisiologia , Adulto , Índice de Massa Corporal , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Polissonografia , Estudos Retrospectivos , Apneia Obstrutiva do Sono/etiologia , Inquéritos e QuestionáriosRESUMO
The dissipation behaviors of acetamiprid and chlorantraniliprole in kimchi cabbages were studied under open-field conditions. A simple and rapid analytical method was developed using ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS). The multiple reaction monitoring (MRM) conditions of two pesticides were optimized to quantify and identify the pesticide residues. Sample preparation was performed by the QuEChERS (quick, easy, cheap, effective, rugged, and safe) method. Average recovery rates at the different spiked levels (0.05 and 0.25 mg/kg) were in the range of 103.6-113.9% (acetamiprid) and 80.8-91.2% (chlorantraniliprole), and the relative standard deviations were ≤4.3% for all. The dissipation kinetics were assessed using first-order equations after spraying acetamiprid and chlorantraniliprole individually on kimchi cabbages. The biological half-lives in field 1 and 2 were 5.2 and 6.3 days (acetamiprid) and 10.0 and 15.2 days (chlorantraniliprole), respectively. Based on the dissipation equations, the pre-harvest residue limits (PHRLs) corresponding to each day before harvest were suggested as the guidelines to meet the MRL on harvest day. It was also predicted that the terminal residues observed after multiple sprayings (three and seven days) would be below the MRL when harvested, in compliance with the established pre-harvest intervals.
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Brassica/química , Cromatografia Líquida de Alta Pressão , Neonicotinoides/análise , Resíduos de Praguicidas/análise , Espectrometria de Massas em Tandem , ortoaminobenzoatos/análise , Contaminação de Alimentos/análise , Limite de Detecção , Estrutura Molecular , Resíduos de Praguicidas/química , ortoaminobenzoatos/químicaRESUMO
Background and objective: The effects of age and related factors on insulin sensitivity have not been definitively evaluated in East Asian populations. We proposed a reference range for the glucose disposal rate (M-value) on hyperinsulinemic-euglycemic study and its association with other parameters. Methods: Healthy, non-diabetic young (n=10) and elderly (n=13) male subjects with normal body mass index were eligible for this study. Subjects who passed the oral glucose tolerance test (OGTT) underwent hyperinsulinemic-euglycemic clamp with high-dose (80 mU/m2·min) insulin infusion. Results: M-values were normalized to body weight (MBW) and fat-free mass (MFFM). Neither M-value was significantly different between age groups (P=0.458 and P=0.900, respectively). An inverse correlation was observed between MFFM and baseline insulin (r=-0.418; P=0.047), baseline C-peptide (r=-0.426; P=0.043) and OGTT 2-hour glucose (r=-0.452; P=0.030). Regarding correlations with other insulin sensitivity indices, M-values were positively associated with the Matsuda index but not with homeostasis model assessment of insulin resistance. Conclusion: Our results suggest that age is not a critical determinant of insulin sensitivity, while fasting insulin and C-peptide levels, OGTT 2-hour glucose level, and Matsuda index are predictable markers of insulin sensitivity in healthy Koreans.
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The Korean Endocrine Society (KES) published clinical practice guidelines for the treatment of acromegaly in 2011. Since then, the number of acromegaly cases, publications on studies addressing medical treatment of acromegaly, and demands for improvements in insurance coverage have been dramatically increasing. In 2017, the KES Committee of Health Insurance decided to publish a position statement regarding the use of somatostatin analogues in acromegaly. Accordingly, consensus opinions for the position statement were collected after intensive review of the relevant literature and discussions among experts affiliated with the KES, and the Korean Neuroendocrine Study Group. This position statement includes the characteristics, indications, dose, interval (including extended dose interval in case of lanreotide autogel), switching and preoperative use of somatostatin analogues in medical treatment of acromegaly. The recommended approach is based on the expert opinions in case of insufficient clinical evidence, and where discrepancies among the expert opinions were found, the experts voted to determine the recommended approach.
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Acromegalia/tratamento farmacológico , Neuroendocrinologia/organização & administração , Somatostatina/análogos & derivados , Acromegalia/complicações , Acromegalia/epidemiologia , Acromegalia/fisiopatologia , Acromegalia/cirurgia , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Antineoplásicos Hormonais/administração & dosagem , Antineoplásicos Hormonais/uso terapêutico , Atitude , Consenso , Tomada de Decisões , Prova Pericial/métodos , Humanos , Injeções Intramusculares , Seguro Saúde/normas , Octreotida/administração & dosagem , Octreotida/uso terapêutico , Peptídeos Cíclicos/administração & dosagem , Peptídeos Cíclicos/uso terapêutico , Guias de Prática Clínica como Assunto , Período Pré-Operatório , República da Coreia/epidemiologia , Somatostatina/administração & dosagem , Somatostatina/uso terapêuticoRESUMO
PURPOSE: As most of patients with Myasthenia Gravis have limitations in their physical functioning, many experience changes in psychological states and often have depression. The objective of the current study was to examine the roles of communication with medical professionals, patients' loneliness, and patients' depression, in relation to their effects on the patients' quality of life. METHODS: For 120 patients with MG of 18 years and older, demographic variables, along with communication with medical professionals, loneliness, depression, and quality of life were measured. RESULTS: As a result, people suffering from MG experienced lower quality of life when their career has changed due to the illness. At the same time, depression was a significant predictor of their quality of life, both in physical and mental domains. CONCLUSIONS: The implications for clinical settings and the suggestions for future research are discussed.
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Miastenia Gravis/psicologia , Adulto , Idoso , Depressão/etiologia , Feminino , Humanos , Solidão/psicologia , Masculino , Pessoa de Meia-Idade , Miastenia Gravis/complicações , Miastenia Gravis/fisiopatologia , Participação do Paciente/psicologia , Qualidade de Vida/psicologiaRESUMO
OBJECTIVE: Hybrid Fc-fused rhGH (GX-H9) is a long-acting recombinant human growth hormone (GH) under clinical development for both adults and children with GH deficiency (GHD). We compared the safety, pharmacokinetics and pharmacodynamics of weekly and every other week (EOW) dosages of GX-H9 with those of daily GH administration in adult GHD (AGHD) patients. DESIGN: This was a randomized, open-label, active-controlled and dose-escalation study conducted in 16 endocrinology centers in Europe and Korea. METHODS: Forty-five AGHD patients with or without prior GH treatment were enrolled. Patients with prior GH treatments were required to have received the last GH administration at least 1 month prior to randomization. Subjects were sequentially assigned to treatment groups. Fifteen subjects were enrolled to each treatment group and randomly assigned to receive either GX-H9 or Genotropin (4:1 ratio). GX-H9 dosage regimens for Groups 1, 2 and 3 were 0.1 mg/kg weekly, 0.3 mg/kg EOW and 0.2 mg/kg EOW, respectively. All Genotropin-assigned subjects received 6 µg/kg Genotropin, regardless of treatment group. Main outcome analyses included measurements of serum insulin-like growth factor 1 (IGF-I), safety, pharmacokinetics, pharmacodynamics and immunogenicity. RESULTS: Mean GX-H9 peak and total exposure increased with an increase in dose after a single-dose administration. The mean IGF-I response was sustained above baseline over the intended dose interval of 168 h for the weekly and 336 h for the EOW GX-H9 groups. Safety profiles and immunogenicity were not different across the treatment groups and with Genotropin. CONCLUSIONS: GX-H9 has the potential for up to twice-monthly administration.
Assuntos
Hormônio do Crescimento Humano/administração & dosagem , Hormônio do Crescimento Humano/deficiência , Proteínas Recombinantes de Fusão/administração & dosagem , Adulto , Feminino , Humanos , Imunoglobulina D , Fragmentos Fc das Imunoglobulinas , Imunoglobulina G , Fator de Crescimento Insulin-Like I/análise , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
In this study, we developed a multiresidue method for the analysis of 310 pesticides in representative agricultural produce (brown rice, orange, and spinach) using ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) combined with a modified QuEChERS procedure. The optimal mobile phase composition (Methanol containing 5â¯mM ammonium formate and 0.1% formic acid) produced high sensitivity and reliable results. Also, the relationship between injection volume and repeatability of peak area was investigated. Most of the target pesticides had a limit of quantitation under 10â¯ngâ¯g-1, and correlation coefficients (r2)â¯>â¯0.99 in matrix-matched standards within the range of 1-100â¯ngâ¯g-1. To validate the optimized method, recovery tests were performed with each of the crops at 10 and 50â¯ngâ¯g-1 spiking levels (nâ¯=â¯5). Satisfactory recoveries were achieved showing that 86.8-88.7% (at 10â¯ngâ¯g-1) and 91.9-96.1% (at 50â¯ngâ¯g-1) of the pesticides met the validation criteria (recoveries in the range of 70-120% and relative standard deviationâ¯≤â¯20%). Fifteen compounds were found to show a loss of recovery due to adsorption by primary and secondary amine or graphite carbon black. In the case of brown rice, 86.1% of pesticides showed an insignificant matrix effect (<±20%), while 35.2% and 41.6% of pesticides in orange and spinach were in that range, respectively. Sixteen apple samples from local markets were analyzed to evaluate the applicability of the optimized method. Nineteen pesticides were detected, of which the concentrations were lower than the maximum residue limit.
Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Citrus sinensis/metabolismo , Oryza/metabolismo , Resíduos de Praguicidas/análise , Spinacia oleracea/metabolismo , Espectrometria de Massas em Tandem/métodosRESUMO
In this research, the pyroelectric and piezoelectric properties of (1 - x)Na0.5K0.5NbO3-xBiScO3 ceramics were investigated and analyzed. (Na, K)NbO3 based (1 - x)Na0.5K0.5NbO3-xBiScO3 ceramics were prepared by a conventional mixed oxide method. As the substituent, BiScO3 material enhanced the sintering mechanism of NKN ceramic, which improved the density, pyroelectric and piezoelectric properties, without any structural distortion. In this study, the structural dependent improved piezoelectric properties of (1 - x)Na0.5K0.5NbO3-xBiScO3 ceramics were investigated with various sintering temperatures. Also, the pyroelectric properties of (1 - x)Na0.5K0.5NbO3-xBiScO3 ceramics were observed up to 200 °C for the devices applications. The crystalline structures of the (1-x)Na0.5K0.5NbO3-x BiScO3 ceramics were measured by X-ray diffraction (XRD). The microstructure was examined by field emission scanning electron microscopy (FE-SEM). In addition, piezo-electric charge coefficient d33 and pyroelectric coefficient will be discussed.