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1.
Phys Rev Lett ; 131(20): 201802, 2023 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-38039466

RESUMO

We search for energetic electron recoil signals induced by boosted dark matter (BDM) from the galactic center using the COSINE-100 array of NaI(Tl) crystal detectors at the Yangyang Underground Laboratory. The signal would be an excess of events with energies above 4 MeV over the well-understood background. Because no excess of events are observed in a 97.7 kg·yr exposure, we set limits on BDM interactions under a variety of hypotheses. Notably, we explored the dark photon parameter space, leading to competitive limits compared to direct dark photon search experiments, particularly for dark photon masses below 4 MeV and considering the invisible decay mode. Furthermore, by comparing our results with a previous BDM search conducted by the Super-Kamionkande experiment, we found that the COSINE-100 detector has advantages in searching for low-mass dark matter. This analysis demonstrates the potential of the COSINE-100 detector to search for MeV electron recoil signals produced by the dark sector particle interactions.

2.
Hong Kong Med J ; 28(6): 475-481, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35815480

RESUMO

INTRODUCTION: Kidney cancer, primarily renal cell carcinoma (RCC), ranks among the top 10 most common malignancies in the male population of Hong Kong. In 2019, members of two medical societies in Hong Kong formed an expert panel to establish a set of consensus statements for the management of metastatic RCC. On 22 June 2021, the same panel met to review recent evidence and reassess their positions regarding the management of advanced and metastatic RCC, with the aim of providing recommendations for physicians in Hong Kong. PARTICIPANTS: The panel included 12 experts (6 clinical oncologists and 6 urologists) who had extensive experience managing patients with RCC in Hong Kong. EVIDENCE: The panel reviewed randomised controlled trials, observational studies, systematic reviews/meta-analyses, and international clinical guidelines to address key clinical questions that were identified before the meeting. CONSENSUS PROCESS: In total, 15 key clinical questions were identified before the meeting, covering the surgical and systemic treatment of advanced or metastatic clear cell, sarcomatoid, and non-clear cell RCCs. At the meeting, the panellists voted on these questions, then discussed relevant evidence and practical considerations. CONCLUSIONS: The treatment landscape for advanced and metastatic RCC continues to evolve. More immune checkpoint inhibitor (ICI)-based combination regimens will be indicated for the treatment of metastatic clear cell RCC. There is increasing evidence concerning the benefit of adjuvant ICI treatment for resected advanced RCC. This article summarises recent evidence and expert insights regarding a series of key clinical questions about the management of advanced and metastatic RCC.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Masculino , Carcinoma de Células Renais/terapia , Neoplasias Renais/terapia , Hong Kong/epidemiologia , Consenso , Sociedades Médicas
3.
Br J Anaesth ; 121(3): 559-566, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30115253

RESUMO

BACKGROUND: The modified Marsh and Schnider pharmacokinetic models for propofol consistently produce negatively and positively biased predictions in underweight patients, respectively. We aimed to develop a new pharmacokinetic model of propofol in underweight patients. METHODS: Twenty underweight (BMI<18.5 kg m-2) patients aged 20-68 yr were given an i.v. bolus of propofol (2 mg kg-1) for induction of anaesthesia. Anaesthesia was maintained with a zero-order infusion (8 mg kg-1 h-1) of propofol and target-controlled infusion of remifentanil. Arterial blood was sampled at preset intervals. A population pharmacokinetic analysis was performed using non-linear mixed effects modelling. The time to peak effect (tpeak, maximally reduced bispectral index) was measured in 28 additional underweight patients receiving propofol 2 mg kg-1. RESULTS: In total, 455 plasma concentration measurements from the 20 patients were used to characterise the pharmacokinetics of propofol. A three-compartment mammillary model well described the propofol concentration time course. BMI and lean body mass (LBM) calculated using the Janmahasatian formula were significant covariates for the rapid peripheral volume of distribution and for the clearance of the final pharmacokinetic model of propofol, respectively. The parameter estimates were as follows: V1(L)=2.02, V2(L)=12.9(BMI/18.5), V3(L)=139, Cl (L⋅min-1)=1.66(LBM/40), Q1 (L⋅min-1)=1.44, Q2 (L⋅min-1)=0.87+0.0189×(LBM-40). The median tpeak of propofol was 1.32 min (n=48). CONCLUSIONS: A three-compartment mammillary model can be used to administer propofol via target effect-site concentration-controlled infusion of propofol in underweight patients. CLINICAL TRIAL REGISTRATION: KCT0001760.


Assuntos
Anestesia Geral/métodos , Anestésicos Intravenosos/sangue , Propofol/sangue , Magreza/sangue , Adulto , Idoso , Anestésicos Intravenosos/administração & dosagem , Índice de Massa Corporal , Peso Corporal/fisiologia , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Propofol/administração & dosagem , Estudos Prospectivos , Magreza/fisiopatologia , Adulto Jovem
4.
J Clin Pharm Ther ; 43(3): 366-376, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29468708

RESUMO

WHAT IS KNOWN AND OBJECTIVE: Drug therapies are critical for preventing secondary complications in acute coronary syndrome (ACS). The purpose of this study was to develop and apply a pharmaceutical care service (PCS) algorithm for ACS and confirm that it is applicable through a prospective clinical trial. METHODS: The ACS-PCS algorithm was developed according to extant evidence-based treatment and pharmaceutical care guidelines. Quality assurance was conducted through two methods: literature comparison and expert panel evaluation. The literature comparison was used to compare the content of the algorithm with the referenced guidelines. Expert evaluations were conducted by nine experts for 75 questionnaire items. A trial was conducted to confirm its effectiveness. Seventy-nine patients were assigned to either the pharmacist-included multidisciplinary team care (MTC) group or the usual care (UC) group. The endpoints of the trial were the prescription rate of two important drugs, readmission, emergency room (ER) visit and mortality. RESULTS AND DISCUSSION: The main frame of the algorithm was structured with three tasks: medication reconciliation, medication optimization and transition of care. The contents and context of the algorithm were compliant with class I recommendations and the main service items from the evidence-based guidelines. Opinions from the expert panel were mostly positive. There were significant differences in beta-blocker prescription rates in the overall period (P = .013) and ER visits (four cases, 9.76%, P = .016) in the MTC group compared to the UC group, respectively. WHAT IS NEW AND CONCLUSION: We developed a PCS algorithm for ACS based on the contents of evidence-based drug therapy and the core concept of pharmacist services.


Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Equipe de Assistência ao Paciente/organização & administração , Assistência Farmacêutica/organização & administração , Farmacêuticos/organização & administração , Síndrome Coronariana Aguda/mortalidade , Antagonistas Adrenérgicos beta/administração & dosagem , Adulto , Idoso , Algoritmos , Serviço Hospitalar de Emergência/estatística & dados numéricos , Prática Clínica Baseada em Evidências/organização & administração , Feminino , Humanos , Masculino , Reconciliação de Medicamentos , Pessoa de Meia-Idade , Readmissão do Paciente/estatística & dados numéricos , Guias de Prática Clínica como Assunto , Estudos Prospectivos
5.
Hong Kong Med J ; 24(3): 218-225, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29807949

RESUMO

INTRODUCTION: Salvage radiotherapy (SRT) provides effective biochemical control for patients with prostate cancer who have prostate specific antigen (PSA) failure after radical prostatectomy. However, the effect of SRT on long-term clinical outcomes remains unknown. Therefore, we report the natural history of patients treated with SRT. METHODS: We identified 84 Chinese patients with prostate cancer treated with SRT to the prostatic fossa alone during 2006-2017 at Tuen Mun Hospital, Hong Kong. Survival was calculated using Kaplan-Meier method. Log-rank test and Cox regression were used to determine significance of clinical parameters with outcomes. RESULTS: Median SRT dose given was 70 Gy (range, 64-76 Gy). Median pre-SRT PSA level was 0.4 ng/mL (0.2-7.4 ng/mL). After SRT, 47 (56%) patients had undetectable (<0.1 ng/mL) PSA levels. After median follow-up of 48 months (2 months to 10 years), 25 (30%) patients had further biochemical progression. Subsequently, 12 patients received androgen deprivation therapy and nine (11%) developed distant metastasis. The 5-year biochemical progression-free survival, androgen deprivation therapy-free survival and metastasis-free survival were 62.7%, 83.5% and 86.7%, respectively. Early PSA failure after radical prostatectomy (hazard ratio 7.4), negative surgical margin (hazard ratio 2.7), positive extracapsular extension (hazard ratio 4.6), and detectable PSA levels after SRT (hazard ratio 17.3) were associated with lower biochemical progression-free survival after SRT. CONCLUSIONS: High-dose SRT with intensity-modulated radiotherapy/volumetric modulated arc radiotherapy is an effective local treatment that can prevent distant metastasis and avoid the need for androgen deprivation therapy in Chinese patients who have PSA failure after radical prostatectomy.


Assuntos
Recidiva Local de Neoplasia/radioterapia , Próstata/patologia , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/radioterapia , Terapia de Salvação , Idoso , Progressão da Doença , Hong Kong/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Antígeno Prostático Específico/sangue , Prostatectomia/efeitos adversos , Neoplasias da Próstata/cirurgia , Dosagem Radioterapêutica , Análise de Sobrevida , Resultado do Tratamento
6.
Prep Biochem Biotechnol ; 48(6): 522-527, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29932808

RESUMO

'Shielding' effect of a conjugated PEG molecule could cause a change in the electrostatic interaction characteristics of a PEGylate. We investigated how PEG chain length (or molecular weight) alters the electrostatic interaction potential of exenatide variants using their mono-PEGylates in a branched and linear form as model PEGylates. First, we performed the experiments to demonstrate the elution time changes of the mono-PEGylates conjugated with various MW PEGs (5, 10, 20, and 40 kD) using cation exchange chromatography (HiTrap® SP) at various pHs (2.5, 3.0, 3.5, and 4.0). Then, we calculated the net surface charge of each mono-PEGylate to propose the PEG molecule's shielding range in terms of the number of amino acids adjacent to the conjugation residue, assuming that a PEG molecule in solution sweeps out a spherical space and an exenatide molecule have a secondary structure. The net charge calculation result was well-correlated with the experimental elution time data, where 5, 10, 20, and 40 kD PEG hindered the electrostatic potential of 5, 8, 12, and 17 amino acid residues in maximum, respectively, on each side of the conjugation point.


Assuntos
Exenatida/química , Polietilenoglicóis/química , Aminoácidos/análise , Resinas de Troca de Cátion , Cromatografia por Troca Iônica/métodos , Hidrodinâmica , Concentração de Íons de Hidrogênio , Estrutura Molecular , Peso Molecular , Estrutura Secundária de Proteína , Cloreto de Sódio/química , Eletricidade Estática
7.
Osteoporos Int ; 28(1): 231-237, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27509834

RESUMO

The study aims to evaluate the rate of transition to osteoporosis in 360 RA patients and estimate the rescreening intervals of bone mineral density (BMD) testing. Osteoporosis was newly developed in 24.8 % during mean follow-up of 7.4 years. The estimated time of a BMD testing interval was dependent on the baseline T-score in RA patients. INTRODUCTION: Although BMD testing is routinely performed in RA patients, the interval between BMD tests has not been determined. METHODS: We retrospectively recruited 360 consecutive female patients with RA, who underwent repeated BMD testing, with a mean age of 53.7 ± 10.2 years and a mean follow-up duration of 7.4 ± 5.0 years. We stratified the study participants into five groups based on their baseline T-score range. The testing interval was defined as the estimated time for 10 % of patients in each subgroup to transition to osteoporosis. Competing-risk analyses were performed with sensitivity analysis by menopausal status and risk factors for transition to osteoporosis. RESULTS: At baseline, 15 % of screened patients had osteoporosis, and during follow-up, that proportion increased to 24.8 %. The estimated BMD testing interval for 10 % of patients to develop osteoporosis was 9.6 years for those with normal BMD, 7.6 years for those with mild osteopenia, 4.7 years for those with moderate osteopenia, and 2.1 years for those with severe osteopenia. No significant risk factor for transition to osteoporosis was identified in this cohort. CONCLUSIONS: Our data indicate that osteoporosis will develop in less than 10 % of female RA patients during rescreening intervals of approximately 9 years for those with normal bone density at baseline, 7 years for those with mild osteopenia, 4 years for those with moderate osteopenia, and 2 years for those with severe osteopenia at baseline. BMD interval in RA patients could be adjusted according to their baseline BMD T-scores.


Assuntos
Artrite Reumatoide/complicações , Densidade Óssea/fisiologia , Osteoporose/diagnóstico , Osteoporose/etiologia , Absorciometria de Fóton , Adulto , Idoso , Artrite Reumatoide/fisiopatologia , Doenças Ósseas Metabólicas/diagnóstico , Doenças Ósseas Metabólicas/etiologia , Doenças Ósseas Metabólicas/fisiopatologia , Progressão da Doença , Feminino , Seguimentos , Humanos , Programas de Rastreamento/organização & administração , Pessoa de Meia-Idade , Osteoporose/fisiopatologia , Estudos Retrospectivos , Medição de Risco/métodos
8.
Br J Anaesth ; 118(6): 883-891, 2017 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-28541533

RESUMO

BACKGROUND: : In our preliminary study, the modified Marsh (M-Marsh) model caused an inadvertent underdosing of propofol in underweight patients. However, the predictive performance of the M-Marsh and Schnider models incorporated in commercially available target-controlled infusion (TCI) pumps was not evaluated in underweight patients. METHODS: : Thirty underweight patients undergoing elective surgery were randomly allocated to receive propofol via TCI using the M-Marsh or Schnider models. The target effect-site concentrations (Ces) of propofol were, in order, 2.5, 3, 4, 5, 6 and 2 µg ml -1 . Arterial blood samples were obtained at least 7 min after achieving each pseudo-steady-state. RESULTS: A total of 172 plasma samples were used to determine the predictive performance of both models. The pooled median (95% confidence interval) biases and inaccuracies at a target Ce ≤ 3 µg ml -1 were -22.6 (-28.8 to -12.6) and 31.9 (24.8-36.8) for the M-Marsh model and 9.0 (1.7-16.4) and 28.5 (21.7-32.8) for the Schnider model, respectively. These values at Ce ≥ 4 µg ml -1 were -9.6 (-16.0 to -6.0) and 24.7 (21.1-27.9) for the M-Marsh model and 19.8 (12.9-25.7) and 36.2 (31.4-39.7) for the Schnider model, respectively. CONCLUSIONS: The pooled biases and inaccuracies of both models were clinically acceptable. However, the M-Marsh and Schnider models consistently produced negatively and positively biased predictions, respectively, in underweight patients. In particular, the M-Marsh model showed greater inaccuracy at target Ce ≤ 3 µg ml -1 and the Schnider model showed greater inaccuracy at target Ce ≥ 4 µg ml -1 . Therefore, it is necessary to develop a new pharmacokinetic model for propofol in underweight patients. CLINICAL TRIAL REGISTRATION: KCT0001502.


Assuntos
Anestesia Geral/métodos , Anestesia Intravenosa/métodos , Anestésicos Intravenosos/administração & dosagem , Propofol/administração & dosagem , Magreza/complicações , Adulto , Anestésicos Intravenosos/sangue , Simulação por Computador , Procedimentos Cirúrgicos Eletivos , Feminino , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Valor Preditivo dos Testes , Propofol/sangue , Estudos Prospectivos , Reprodutibilidade dos Testes , Magreza/fisiopatologia
9.
Ann Oncol ; 27(4): 608-18, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26712901

RESUMO

BACKGROUND: Guidelines recommend primary prophylaxis (PP) with granulocyte-colony-stimulating factors (G-CSF) for patients above a febrile neutropenia (FN) risk threshold of 20%. Practitioners often use FN rates of regimens based on data from randomized, controlled trials (RCTs), which are often comprised of highly selected patients. Patients in the community setting may be at higher risk of FN. MATERIALS AND METHODS: A systematic literature search was conducted for full-length articles reporting FN rates for breast cancer-related chemotherapies between January 1996 and February 2014. A regimen was included if there was at least one RCT and one observational study. Meta-regression was used to model the odds of FN. RESULTS: 130 studies involving 29 regimens and 50 069 patients were identified. Sixty-five observational study (n = 7812) and 110 RCT (n = 42 257) cohorts were included. The unadjusted FN rate was 11.7% in observational and 7.9% in RCT cohorts. The univariable odds ratio (OR) for FN in the observational study compared with RCT cohorts was 1.58 [95% confidence interval (CI) 1.09-2.28; P = 0.017]. The FN rates remained significantly higher in the observational study compared with RCT cohorts (OR = 1.74; 95% CI 1.15-2.62; P = 0.012) after adjusting for age, chemotherapy intent, and regimen; this meant that a 13% (95% CI 8.7% to 17.9%) FN rate in RCT would translate into 20% FN rate in observational study. CONCLUSIONS: FN rates in the observational studies are significantly higher than suggested by RCTs. Guidelines should clarify how FN rates from RCTs should be applied in clinical practice. Large population-based studies are needed to confirm FN rates in the real world.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Neutropenia Febril/epidemiologia , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Neoplasias da Mama/patologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Neutropenia Febril/induzido quimicamente , Neutropenia Febril/patologia , Feminino , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
10.
J Mol Recognit ; 29(9): 446-51, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27060481

RESUMO

A fluorescent reporter, 8-anilino-1-naphthalene sulfonic acid (ANS), can serve as a reference molecule for conformational transition of a protein because its aromatic carbons have strong affinity with hydrophobic cores of partially unfolded molten globules. Using a typical calcium-binding protein, bovine α-lactalbumin (BLA), as a model protein, we compared the ANS binding thermodynamics to the decalcified (10 mM EDTA treated) apo-BLA at two representative temperatures: 20 and 40 °C. This is because the authentic molten globule is known to form more heavily at an elevated temperature such as 40 °C. Isothermal titration calorimetry experiments revealed that the BLA-ANS interactions at both temperatures were entropy-driven, and the dissociation constants were similar on the order of 10(-4) M, but there was a dramatic changeover in the binding thermodynamics from endothermic at 20 °C to exothermic at 40 °C. We believe that the higher subpopulation of authentic molten globules at 40 °C than 20 °C would be responsible for the results, which also indicate that weak binding is sufficient to alter the ANS binding mechanisms. We expect that the thermodynamic properties obtained from this study would serve as a useful reference for investigating the binding of other hydrophobic ligands such as oleic acid to apo-BLA, because oleic acid is known to have tumor-selective cytotoxicity when complexed with partially unfolded α-lactalbumin. Copyright © 2016 John Wiley & Sons, Ltd.


Assuntos
Naftalenossulfonato de Anilina/metabolismo , Temperatura Alta , Lactalbumina/metabolismo , Termodinâmica , Calorimetria , Concentração de Íons de Hidrogênio , Ácido Oleico/metabolismo , Ligação Proteica , Dobramento de Proteína
11.
Clin Radiol ; 71(12): 1240-1247, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27289324

RESUMO

AIM: To describe characteristic magnetic resonance imaging (MRI) abnormalities in hyperglycaemia-induced seizures, and evaluate the diagnostic value of contrast-enhanced fluid-attenuated inversion recovery (FLAIR) imaging. Possible underlying mechanisms of this condition are also discussed. MATERIALS AND METHODS: Eleven patients with hyperglycaemia-induced seizures and MRI abnormalities were retrospectively studied. Clinical manifestations, laboratory findings, MRI findings, and clinical outcomes were analysed. RESULTS: All patients, except one, presented with focal seizures, simple or complex partial seizures, or negative motor seizures. All patients had long-standing uncontrolled diabetes mellitus. The MRI abnormalities observed acutely were focal subcortical hypointensities on T2-weighted imaging and FLAIR imaging in all patients with overlying cortical gyral T2 hyperintensities in five. Focal overlying cortical or leptomeningeal enhancement on contrast-enhanced T1-weighted imaging or contrast-enhanced FLAIR imaging was observed in all patients. Contrast-enhanced FLAIR imaging was superior to contrast-enhanced T1-weighted imaging for detecting characteristic cortical or leptomeningeal enhancement. Diffusion-weighted imaging showed mildly restricted diffusion in four of five patients with cortical gyral T2 hyperintensity. In nine patients, the lesions were localised in the parietal or parieto-occipital lobes. The other two patients showed localised precentral gyral lesions. After treatment, the neurological symptoms, including the seizures, improved in all patients. On clinical recovery, the subcortical T2 hypointensity, gyral or leptomeningeal enhancement, and overlying cortical T2 hyperintensities resolved. CONCLUSION: Recognition of these radiological abnormalities in patients with hyperglycaemia-induced seizures is important in restricting unwarranted investigations and initiating early therapy. These patients generally have a good prognosis.


Assuntos
Encéfalo/diagnóstico por imagem , Meios de Contraste , Hiperglicemia/complicações , Aumento da Imagem/métodos , Imageamento por Ressonância Magnética/métodos , Convulsões/etiologia , Idoso , Encéfalo/patologia , Feminino , Humanos , Hiperglicemia/patologia , Masculino , Pessoa de Meia-Idade , Compostos Organometálicos , Reprodutibilidade dos Testes , Estudos Retrospectivos , Convulsões/patologia
12.
Toxicol Appl Pharmacol ; 284(2): 254-61, 2015 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-25576766

RESUMO

Sodium meta-arsenite (SA) is an orally available arsenic compound. We investigated the effects of SA on the development of autoimmune type 1 diabetes. Female non-obese diabetic (NOD) mice were orally intubated with SA (5mg/kg/day) from 8weeks of age for 8weeks. The cumulative incidence of diabetes was monitored until 30weeks of age, islet histology was examined, and lymphocytes including T cells, B cells, CD4+ IFN-γ+ cells, CD8+ IFN-γ+ cells, CD4+ IL-4+ cells, and regulatory T cells were analyzed. We also investigated the diabetogenic ability of splenocytes using an adoptive transfer model and the effect of SA on the proliferation, activation, and expression of glucose transporter 1 (Glut1) in splenocytes treated with SA in vitro and splenocytes isolated from SA-treated mice. SA treatment decreased the incidence of diabetes and delayed disease onset. SA treatment reduced the infiltration of immunocytes in islets, and splenocytes from SA-treated mice showed a reduced ability to transfer diabetes. The number of total splenocytes and T cells and both the number and the proportion of CD4+ IFN-γ+ and CD8+ IFN-γ+ T cells in the spleen were significantly reduced in SA-treated NOD mice compared with controls. The number, but not the proportion, of regulatory T cells was decreased in SA-treated NOD mice. Treatment with SA either in vitro or in vivo inhibited proliferation of splenocytes. In addition, the expression of Glut1 and phosphorylated ERK1/2 was decreased by SA treatment. These results suggest that SA reduces proliferation and activation of T cells, thus preventing autoimmune diabetes in NOD mice.


Assuntos
Arsenitos/farmacologia , Doenças Autoimunes/prevenção & controle , Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 1/prevenção & controle , Compostos de Sódio/farmacologia , Animais , Doenças Autoimunes/metabolismo , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/metabolismo , Proliferação de Células/efeitos dos fármacos , Diabetes Mellitus Tipo 1/metabolismo , Feminino , Transportador de Glucose Tipo 1/metabolismo , Interferon gama/metabolismo , Interleucina-4/metabolismo , Ilhotas Pancreáticas/efeitos dos fármacos , Ilhotas Pancreáticas/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos NOD , Fosforilação/efeitos dos fármacos , Baço/efeitos dos fármacos , Baço/metabolismo
13.
Public Health ; 129(5): 424-35, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25753281

RESUMO

OBJECTIVES: This study examined the influence of home and school environments, and individual health-risk behaviours on body weight outcomes in Korean adolescents. STUDY DESIGN: This was a cross-sectional observational study. METHODS: Quantile regression models to explore heterogeneity in the association of specific factors with body mass index (BMI) over the entire conditional BMI distribution was used. A nationally representative web-based survey for youths was used. RESULTS: Paternal education level of college or more education was associated with lower BMI for girls, whereas college or more education of mothers was associated with higher BMI for boys; for both, the magnitude of association became larger at the upper quantiles of the conditional BMI distribution. Girls with good family economic status were more likely to have higher BMIs than those with average family economic status, particularly at the upper quantile of the conditional BMI distribution. Attending a co-ed school was associated with lower BMI for both genders with a larger association at the upper quantiles. Substantial screen time for TV watching, video games, or internet surfing was associated with a higher BMI with a larger association at the upper quantiles for both girls and boys. Dental prevention was negatively associated with BMI, whereas suicide consideration was positively associated with BMIs of both genders with a larger association at a higher quantile. CONCLUSIONS: These findings suggest that interventions aimed at behavioural changes and positive parental roles are needed to effectively address high adolescent BMI.


Assuntos
Índice de Massa Corporal , Obesidade Infantil/epidemiologia , Assunção de Riscos , Meio Social , Adolescente , Estudos Transversais , Feminino , Humanos , Internet/estatística & dados numéricos , Masculino , Higiene Bucal/psicologia , Pais , Análise de Regressão , República da Coreia/epidemiologia , Fatores de Risco , Instituições Acadêmicas/estatística & dados numéricos , Distribuição por Sexo , Fatores Socioeconômicos , Ideação Suicida , Televisão/estatística & dados numéricos , Jogos de Vídeo/psicologia
14.
Int J Obes (Lond) ; 38(8): 1035-43, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24173405

RESUMO

OBJECTIVE: Adipogenesis can be spatially and temporally regulated by extracellular matrix (ECM). We hypothesized that the regulation of hyaluronic acid (HA), a component of the ECM, can affect adipogenesis in fat cells. The effects of HA on adipogenesis were investigated in vitro in 3T3-L1 cells and in vivo in high-fat diet-feeding C57BL/6J mice. METHODS: We investigated the effects of HA by degradation of pre-existing or synthesized HA and artificial inhibition of HA synthesis in adipogenesis. RESULTS: In vitro adipogenesis in 3T3-L1 cells was inhibited by treating them with exogenous hyaluronidase (HYAL) and with 4-methylumbelliferone, which inhibited the synthesis of HA in a concentration-dependent manner. In vivo, abdominal fat accumulation in high-fat diet-feeding C57BL/6J mice was suppressed by exogenous HYAL 10(4) IU injections, which was associated with reduction of lipid accumulation in liver and increase of insulin sensitivity. CONCLUSION: Changes in the ECM such as accumulation of high molecular weight of HA by HAS and degradation of HA by endogenous HYAL were essential for adipogenesis both in vitro and in vivo.


Assuntos
Células 3T3-L1/metabolismo , Gordura Abdominal/metabolismo , Adipogenia , Dieta Hiperlipídica , Matriz Extracelular/metabolismo , Ácido Hialurônico/metabolismo , Animais , Diferenciação Celular , Regulação para Baixo , Regulação da Expressão Gênica , Resistência à Insulina , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Obesidade/fisiopatologia , Obesidade/prevenção & controle
15.
Gene Ther ; 20(8): 785-96, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23388701

RESUMO

Complete arginase I deficiency is the least severe urea cycle disorder, characterized by hyperargininemia and infrequent episodes of hyperammonemia. Patients suffer from neurological impairment with cortical and pyramidal tract deterioration, spasticity, loss of ambulation and seizures, and is associated with intellectual disability. In mice, onset is heralded by weight loss beginning around day 15; gait instability follows progressing to inability to stand and development of tail tremor with seizure-like activity and death. Here we report that hyperargininemic mice treated neonatally with an adeno-associated virus (AAV)-expressing arginase and followed long-term lack any presentation consistent with brain dysfunction. Behavioral and histopathological evaluation demonstrated that treated mice are indistinguishable from littermates, and that putative compounds associated with neurotoxicity are diminished. In addition, treatment results in near complete resolution of metabolic abnormalities early in life; however, there is the development of some derangement later with decline in transgene expression. Ammonium challenging revealed that treated mice are affected by exogenous loading much greater than littermates. These results demonstrate that AAV-based therapy for hyperargininemia is effective and prevents development of neurological abnormalities and cognitive dysfunction in a mouse model of hyperargininemia; however, nitrogen challenging reveals that these mice remain impaired in the handling of waste nitrogen.


Assuntos
Arginase/genética , Terapia Genética , Hiperargininemia/genética , Doenças do Sistema Nervoso/genética , Doenças Neurodegenerativas/genética , Animais , Arginase/metabolismo , Dependovirus , Modelos Animais de Doenças , Humanos , Hiperamonemia/genética , Hiperamonemia/patologia , Hiperamonemia/terapia , Hiperargininemia/patologia , Hiperargininemia/terapia , Camundongos , Camundongos Transgênicos , Doenças do Sistema Nervoso/patologia , Doenças do Sistema Nervoso/terapia , Doenças Neurodegenerativas/patologia , Doenças Neurodegenerativas/terapia
16.
Clin Radiol ; 68(12): e689-97, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23969153

RESUMO

Differentiation between solitary metastatic lesions and glioblastomas, two of the most common malignant brain neoplasms, is often a diagnostic challenge. The purpose of this review is to emphasize the potential roles of advanced magnetic resonance imaging (MRI) techniques, including diffusion-based techniques, such as diffusion-weighted imaging (DWI), exponential DWI, and diffusion tensor imaging, MR perfusion, and MR spectroscopy, as well as conventional MRI, in making a distinction between glioblastomas and solitary metastases in peritumoural regions. Integration of advanced MRI features with conventional MRI, may provide valuable information for differentiating glioblastoma from solitary metastatic lesions.


Assuntos
Neoplasias Encefálicas/diagnóstico , Glioblastoma/diagnóstico , Imageamento por Ressonância Magnética/métodos , Neuroimagem/métodos , Idoso , Encéfalo/patologia , Neoplasias Encefálicas/patologia , Diagnóstico Diferencial , Feminino , Glioblastoma/patologia , Humanos , Masculino , Pessoa de Meia-Idade
17.
Acta Anaesthesiol Scand ; 57(5): 613-22, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23496092

RESUMO

BACKGROUND: Laparoscopic surgery performed with a patient in the Trendelenburg position is known to have adverse effects on pulmonary gas exchange and respiratory mechanics. We supposed that prolonged inspiratory time can improve gas exchange at lower airway pressure. METHODS: One hundred patients undergoing gynaecologic laparoscopic surgery were randomly assigned to one of four groups: conventional inspiratory-to-expiratory (I : E) ratio (Group 1 : 2), I : E ratio of 1 : 1 (Group 1 : 1), 2 : 1 (Group 2 : 1), or 1 : 2 with external positive end-expiratory pressure (PEEP) of 5 cmH2 O (Group 1 : 2 PEEP). Tidal volume was set to 6 ml/kg, and I : E ratio was adjusted at the onset of pneumoperitoneum. Arterial blood gas analysis with measurements of partial pressure of arterial oxygen/fraction of inspired oxygen (PaO2 /FiO2 ), and physiologic dead space-to-tidal volume ratio (VD /VT ) was performed 15 min after anaesthetic induction (T1), and 30 (T2) and 60 min (T3) after onset of CO2 insufflation. RESULTS: PaO2 /FiO2 at T3 in Groups 1 : 1, 2 : 1, and 1 : 2 PEEP were higher than Group 1 : 2. The partial pressure of arterial carbon dioxide at T3 in Group 2 : 1 was lower than the other groups. The VD /VT at T2 and T3 were lower in Groups 1 : 1 and 2 : 1 than Groups 1 : 2 and 1 : 2 PEEP. Peak or plateau airway pressure was higher in Group 1 : 2 PEEP than the other groups. CONCLUSIONS: A prolonged inspiratory time demonstrated a beneficial effect on oxygenation. Furthermore, it showed better CO2 elimination without elevating the peak or plateau airway pressure compared with applying external PEEP. In terms of gas exchange and respiratory mechanics, a prolonged inspiratory time appears to be superior to applying external PEEP in patients undergoing laparoscopic surgery in the Trendelenburg position.


Assuntos
Laparoscopia , Troca Gasosa Pulmonar/fisiologia , Respiração Artificial/métodos , Mecânica Respiratória/fisiologia , Adulto , Dióxido de Carbono/sangue , Feminino , Humanos , Oxigênio/sangue , Respiração com Pressão Positiva , Estudos Prospectivos , Método Simples-Cego , Volume de Ventilação Pulmonar/fisiologia , Fatores de Tempo
18.
Appl Radiat Isot ; 193: 110654, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36646029

RESUMO

The CUP array of germanium (CAGe) is an array of fourteen high-purity germanium (HPGe) detectors. The detection efficiency of full-energy-peak emitted from the various samples assayed on the CAGe was calculated using the Monte Carlo simulation toolkit GEANT4. If the dead layer on the surface of the crystal is treated in the simulation as a continuous part of the active crystal, then the detection efficiency will be overestimated. Thus, the detection efficiency of the CAGe was adjusted using multi-nuclide source data and Monte Carlo simulations. The gamma spectra of the known activity source were obtained for each HPGe detector of the CAGe. The detection efficiency measured by the multi-source data was smaller than that of simulation data if the simulation treated the whole volume of germanium crystals as active for gamma detection. By optimizing the dead layers' thicknesses in the simulation, the detection efficiency calculated by the simulation could be matched to that of multi-source data.

19.
Poult Sci ; 91(10): 2502-6, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22991534

RESUMO

In total, 39 clinical cases of fowl adenoviruses (FAdV) infection in chickens (28 broiler, 7 native, and 4 layer chickens) between 2007 and 2010 in Korea were investigated. The FAdV types 4, 8b, and 11 comprised 18, 9, and 12 clinical cases, respectively. All FAdV type 4 cases showed clinical hydropericardium (HPS) lesions as well as inclusion body hepatitis (IBH), whereas all FAdV types 8b and 11 cases exhibited IBH lesions without HPS. All 3 types were detected in broiler (9-30 d old) and layer chickens (23-112 d old), whereas most native chickens (14-65 d old) were affected only by FAdV type 4. Infectious bursal disease virus and chicken infectious anemia virus were complications in 51.3% of FAdV cases, with mortalities of 55% to <0.1%. Chicken infectious anemia virus was detected in all native chicken cases. These results indicate that preventive measures against FAdV infection and immunosuppressive diseases on poultry farms should be implemented.


Assuntos
Infecções por Adenoviridae/veterinária , Galinhas , Surtos de Doenças/veterinária , Adenovirus A das Aves/genética , Doenças das Aves Domésticas/virologia , Infecções por Adenoviridae/epidemiologia , Infecções por Adenoviridae/virologia , Animais , Epidemiologia Molecular , Filogeografia , Doenças das Aves Domésticas/epidemiologia , República da Coreia/epidemiologia
20.
J Vet Pharmacol Ther ; 35(4): 329-41, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21790660

RESUMO

This study aimed at assessing the predictive performance of a target-controlled infusion (TCI) system, which incorporates canine PK-PD models for microemulsion and long-chain triglyceride emulsion (LCT) propofol and at investigating time independency of propofol effect on the observed electroencephalographic approximate entropy (ApEn) in TCI. Using a crossover design with a 7-day washout period, 28 healthy beagle dogs were randomized to receive TCI of both formulations in a stepwise or constant manner. Plasma propofol concentrations and ApEn were measured at preset intervals. Pooled biases, inaccuracies, divergences, and wobbles in pharmacokinetic and pharmacodynamic predictions were 2.1% (95% CI: -0.8 to 4.9), 18.1% (15.6-20.5), 1.9%/h, 7.3% (5.4-9.3), and -0.5% (-2.6 to 1.6), 8.7% (7.3-10.1), 2.5%/h, 6.0% (4.1-7.2) for microemulsion propofol, and -9.3% (-11.6 to -6.9), 20.1% (18.2-22.0), 5.1%/h, 7.6% (6.1-9.1) and 5.6% (4.1-7.1), 8.0% (6.9-9.3), 4.7%/h, 4.1% (3.1-5.1) for LCT propofol. Observed ApEn values over time were statistically not different across all time points in a TCI with constant manner. Canine PK-PD model of microemulsion propofol showed good predictive performances. Propofol effect (ApEn) was time independent as long as time is allowed for equilibration.


Assuntos
Anestésicos Intravenosos/farmacocinética , Cães/sangue , Emulsões/química , Propofol/farmacocinética , Triglicerídeos/química , Anestésicos Intravenosos/administração & dosagem , Anestésicos Intravenosos/química , Animais , Química Farmacêutica , Relação Dose-Resposta a Droga , Feminino , Bombas de Infusão/veterinária , Masculino , Propofol/administração & dosagem , Propofol/química , Reprodutibilidade dos Testes
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