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1.
Br J Dermatol ; 186(2): 257-265, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34227101

RESUMO

BACKGROUND: There is a lack of population-based information on the disease burden and management of alopecia areata (AA). OBJECTIVES: To describe the epidemiology of AA, focusing on incidence, demographics and patterns of healthcare utilization. METHODS: Population-based cohort study of 4·16 million adults and children, using UK electronic primary care records from the Oxford-Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) network database, 2009-2018. The incidence and point prevalence of AA were estimated. Variation in AA incidence by age, sex, deprivation, geographical distribution and ethnicity was examined. Patterns of healthcare utilization were evaluated in people with incident AA. RESULTS: The AA incidence rate was 0·26 per 1000 person-years. AA point prevalence in 2018 was 0·58% in adults. AA onset peaked at age 25-29 years for both sexes, although the peak was broader in females. People of nonwhite ethnicity were more likely to present with AA, especially those of Asian ethnicity [incidence rate ratio (IRR) 3·32 (95% confidence interval 3·11-3·55)]. Higher AA incidence was associated with social deprivation [IRR most vs. least deprived quintile 1·47 (1·37-1·59)] and urban living [IRR 1·23 (1·14-1·32)]. People of higher social deprivation were less likely to be referred for specialist dermatology review. CONCLUSIONS: By providing the first large-scale estimates of the incidence and point prevalence of AA, our study helps to understand the burden of AA on the population. Understanding the variation in AA onset between different population groups may give insight into the pathogenesis of AA and its management.


Assuntos
Alopecia em Áreas , Adulto , Alopecia em Áreas/epidemiologia , Criança , Estudos de Coortes , Feminino , Humanos , Incidência , Masculino , Atenção Primária à Saúde , Reino Unido/epidemiologia
2.
Osteoporos Int ; 31(1): 193-201, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31642977

RESUMO

Following 150 mg of oral ibandronate, Taiwanese females have greater serum and urine levels of this drug and bone resorption marker suppression than Caucasian women. These inter-ethnic differences seems to be partly explained by a 2.48-fold higher bioavailability of ibandronate in Taiwanese postmenopausal women. INTRODUCTION: Interethnic differences in the pharmacokinetics of oral ibandronate for osteoporosis are unknown. We compared the disposition of oral ibandronate between Caucasian and Taiwanese postmenopausal women. METHODS: Ibandronate 150 mg was administered to 35 Caucasian and 16 Taiwanese postmenopausal women in two separate phase 1 studies. Interethnic comparisons were performed to assess pharmacokinetic properties, including the area under the concentration-time curve (AUC), peak concentration (Cmax), elimination half-life, urinary drug recovery (Ae%), renal clearance (CLr), apparent total clearance (CL/F), and apparent volume of distribution (Vd/F). RESULTS: The mean AUC, Cmax, and Ae% were 2.41-, 1.69-, and 2.95-fold greater in the Taiwanese than in the Caucasian subjects, and the average CL/F and Vd/F were 2.48- and 2.46-fold smaller. There were no significant differences in mean CLr and half-life between both groups. As bisphosphonates are not biotransformed but are mainly excreted in the urine, the total body clearance is close to the CLr. These results suggested a larger bioavailability in the Taiwanese group which resulted in the differences in the CL/F and Vd/F. Multiple linear regression analysis demonstrated ethnicity influences of the pharmacokinetic properties after adjusting for the other variables. CONCLUSIONS: Bioavailability was largely responsible for the interethnic pharmacokinetic differences following oral administration of 150 mg ibandronate and seemed greater in the Taiwanese compared with the Caucasian subjects. Further dose-ranging studies are warranted to determine the optimal dosages of oral ibandronate in patients of Asian or Taiwanese ethnicity.


Assuntos
Conservadores da Densidade Óssea , Ácido Ibandrônico , Osteoporose Pós-Menopausa , Pós-Menopausa , Administração Oral , Idoso , Povo Asiático , Disponibilidade Biológica , Conservadores da Densidade Óssea/farmacocinética , Difosfonatos/uso terapêutico , Feminino , Humanos , Ácido Ibandrônico/farmacocinética , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/tratamento farmacológico , Fatores Raciais , População Branca
3.
Phys Rev Lett ; 122(7): 077602, 2019 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-30848616

RESUMO

The effect of electron-electron interactions on Dirac fermions, and the possibility of an intervening spin-liquid phase between the semimetal and antiferromagnetic (AF) regimes, has been a focus of intense quantum simulation effort over the last five years. We use determinant quantum Monte Carlo simulations to study the Holstein model on a honeycomb lattice and explore the role of electron- phonon interactions on Dirac fermions. We show that they give rise to charge-density-wave (CDW) order and present evidence that this occurs only above a finite critical interaction strength. We evaluate the temperature for the transition into the CDW which, unlike the AF transition, can occur at finite values owing to the discrete nature of the broken symmetry.

4.
Phys Rev Lett ; 122(6): 066401, 2019 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-30822065

RESUMO

Using the satellite structure of the Lγ_{1} line in nonresonant x-ray emission spectra, we probe the high-pressure evolution of the bare 4f signature of the early light lanthanides at ambient temperature. For Ce and Pr the satellite peak experiences a sudden reduction concurrent with their respective volume collapse (VC) transitions. These new experimental results are supported by calculations using state-of-the-art extended atomic structure codes for Ce and Pr, and also for Nd, which does not exhibit a VC. Our work suggests that changes to the 4f occupation are more consistently associated with evolution of the satellite than is the reduction of the 4f moment. Indeed, we show that in the case of Ce, mixing of a higher atomic angular momentum state, driven by the increased hybridization, acts to obscure the expected satellite reduction. These measurements emphasize the importance of a unified study of a full set of microscopic observables to obtain the most discerning test of the underlying, fundamental f-electron phenomena at high pressures.

5.
Pharm Res ; 36(12): 180, 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31728737

RESUMO

PURPOSE: To examine the potential of stratum corneum (SC) sampling via tape-stripping in humans to assess bioequivalence of topical acyclovir drug products, and to explore the potential value of alternative metrics of local skin bioavailability calculable from SC sampling experiments. METHODS: Three acyclovir creams were considered in two separate studies in which drug amounts in the SC after uptake and clearance periods were measured and used to assess bioequivalence. In each study, a "reference" formulation (evaluated twice) was compared to the "test" in 10 subjects. Each application site was replicated to achieve greater statistical power with fewer volunteers. RESULTS: SC sampling revealed similarities and differences between products consistent with results from other surrogate bioequivalence measures, including dermal open-flow microperfusion experiments. Further analysis of the tape-stripping data permitted acyclovir flux into the viable skin to be deduced and drug concentration in that 'compartment' to be estimated. CONCLUSIONS: Acyclovir quantities determined in the SC, following a single-time point uptake and clearance protocol, can be judiciously used both to objectively compare product performance in vivo and to assess delivery of the active into skin tissue below the barrier, thereby permitting local concentrations at or near to the site of action to be determined.


Assuntos
Aciclovir/farmacocinética , Antivirais/farmacocinética , Creme para a Pele/farmacocinética , Aciclovir/administração & dosagem , Administração Tópica , Adulto , Antivirais/administração & dosagem , Disponibilidade Biológica , Transporte Biológico , Liberação Controlada de Fármacos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Permeabilidade , Pele/metabolismo , Absorção Cutânea , Creme para a Pele/administração & dosagem , Equivalência Terapêutica
6.
Hong Kong Med J ; 25(5): 363-371, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31619575

RESUMO

OBJECTIVES: There is no guideline in Hong Kong regarding respiratory syncytial virus (RSV) immunoprophylaxis for children with heart disease because of a lack of local data on RSV infection. Therefore, this study evaluated the epidemiology and impact of RSV infection on children with heart disease in Hong Kong, with the goal of providing recommendations regarding RSV immunoprophylaxis. METHODS: This multicentre retrospective case-control study on paediatric RSV infection was conducted in four local regional hospitals from 2013 to 2015. The patients' demographic and clinical data were retrieved and analysed. RESULTS: There were 3538 RSV hospitalisations during the study period, and the mortality rate was 0.14%. Some RSV seasonality was present in Hong Kong, primarily in spring and summer. Respiratory syncytial virus infection was positively correlated with relative humidity and negatively correlated with wind speed and atmospheric pressure. Patients with heart disease had a more severe outcome than those without, including longer median hospital stay (4 vs 2 days, P<0.001), higher complication rate (28.6% vs 9.8%, P<0.001), and higher rates of intensive care (11.6% vs 1.4%, P<0.001) and mechanical ventilation (3.6% vs 0.4%, P=0.003). Complications in non-cardiac patients included myocarditis and Kawasaki disease. Predictors of severe RSV infection in patients with heart disease were heart failure, pulmonary hypertension, and severe airway abnormalities associated with congenital heart disease. CONCLUSIONS: Respiratory syncytial virus infection occurs mainly in spring and summer in Hong Kong, and is related to meteorological conditions. Respiratory syncytial virus infection poses a heavy disease burden on children with heart disease. A local guideline on RSV immunoprophylaxis for these children is therefore needed.


Assuntos
Cardiopatias Congênitas/virologia , Infecções por Vírus Respiratório Sincicial/mortalidade , Adolescente , Distribuição por Idade , Criança , Pré-Escolar , Feminino , Cardiopatias Congênitas/mortalidade , Hong Kong/epidemiologia , Humanos , Lactente , Recém-Nascido , Unidades de Terapia Intensiva Pediátrica , Tempo de Internação/estatística & dados numéricos , Modelos Lineares , Masculino , Respiração Artificial , Infecções por Vírus Respiratório Sincicial/terapia , Estudos Retrospectivos , Fatores de Risco , Estações do Ano
7.
Phys Rev Lett ; 120(18): 187003, 2018 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-29775370

RESUMO

The Holstein model describes the interaction between fermions and a collection of local (dispersionless) phonon modes. In the dilute limit, the phonon degrees of freedom dress the fermions, giving rise to polaron and bipolaron formation. At higher densities, the phonons mediate collective superconducting (SC) and charge-density wave (CDW) phases. Quantum Monte Carlo (QMC) simulations have considered both these limits but have not yet focused on the physics of more general phonon spectra. Here we report QMC studies of the role of phonon dispersion on SC and CDW order in such models. We quantify the effect of finite phonon bandwidth and curvature on the critical temperature T_{cdw} for CDW order and also uncover several novel features of diagonal long-range order in the phase diagram, including a competition between charge patterns at momenta q=(π,π) and q=(0,π) which lends insight into the relationship between Fermi surface nesting and the wave vector at which charge order occurs. We also demonstrate SC order at half filling in situations where a nonzero bandwidth sufficiently suppresses T_{cdw}.

8.
Psychol Med ; 48(9): 1560-1571, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29173244

RESUMO

BACKGROUND: The treatment gap between the number of people with mental disorders and the number treated represents a major public health challenge. We examine this gap by socio-economic status (SES; indicated by family income and respondent education) and service sector in a cross-national analysis of community epidemiological survey data. METHODS: Data come from 16 753 respondents with 12-month DSM-IV disorders from community surveys in 25 countries in the WHO World Mental Health Survey Initiative. DSM-IV anxiety, mood, or substance disorders and treatment of these disorders were assessed with the WHO Composite International Diagnostic Interview (CIDI). RESULTS: Only 13.7% of 12-month DSM-IV/CIDI cases in lower-middle-income countries, 22.0% in upper-middle-income countries, and 36.8% in high-income countries received treatment. Highest-SES respondents were somewhat more likely to receive treatment, but this was true mostly for specialty mental health treatment, where the association was positive with education (highest treatment among respondents with the highest education and a weak association of education with treatment among other respondents) but non-monotonic with income (somewhat lower treatment rates among middle-income respondents and equivalent among those with high and low incomes). CONCLUSIONS: The modest, but nonetheless stronger, an association of education than income with treatment raises questions about a financial barriers interpretation of the inverse association of SES with treatment, although future within-country analyses that consider contextual factors might document other important specifications. While beyond the scope of this report, such an expanded analysis could have important implications for designing interventions aimed at increasing mental disorder treatment among socio-economically disadvantaged people.


Assuntos
Países Desenvolvidos/estatística & dados numéricos , Países em Desenvolvimento/estatística & dados numéricos , Disparidades em Assistência à Saúde/estatística & dados numéricos , Transtornos Mentais/terapia , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Fatores Socioeconômicos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Inquéritos Epidemiológicos , Humanos , Internacionalidade , Modelos Logísticos , Masculino , Saúde Mental , Pessoa de Meia-Idade , Análise Multivariada , Psicoterapia , Adulto Jovem
9.
Psychol Med ; 47(13): 2275-2287, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28374665

RESUMO

BACKGROUND: The U.S. Army uses universal preventives interventions for several negative outcomes (e.g. suicide, violence, sexual assault) with especially high risks in the early years of service. More intensive interventions exist, but would be cost-effective only if targeted at high-risk soldiers. We report results of efforts to develop models for such targeting from self-report surveys administered at the beginning of Army service. METHODS: 21 832 new soldiers completed a self-administered questionnaire (SAQ) in 2011-2012 and consented to link administrative data to SAQ responses. Penalized regression models were developed for 12 administratively-recorded outcomes occurring by December 2013: suicide attempt, mental hospitalization, positive drug test, traumatic brain injury (TBI), other severe injury, several types of violence perpetration and victimization, demotion, and attrition. RESULTS: The best-performing models were for TBI (AUC = 0.80), major physical violence perpetration (AUC = 0.78), sexual assault perpetration (AUC = 0.78), and suicide attempt (AUC = 0.74). Although predicted risk scores were significantly correlated across outcomes, prediction was not improved by including risk scores for other outcomes in models. Of particular note: 40.5% of suicide attempts occurred among the 10% of new soldiers with highest predicted risk, 57.2% of male sexual assault perpetrations among the 15% with highest predicted risk, and 35.5% of female sexual assault victimizations among the 10% with highest predicted risk. CONCLUSIONS: Data collected at the beginning of service in self-report surveys could be used to develop risk models that define small proportions of new soldiers accounting for high proportions of negative outcomes over the first few years of service.


Assuntos
Vítimas de Crime/estatística & dados numéricos , Inquéritos Epidemiológicos/estatística & dados numéricos , Transtornos Mentais/epidemiologia , Militares/estatística & dados numéricos , Modelos Estatísticos , Abuso Físico/estatística & dados numéricos , Medição de Risco/métodos , Autorrelato , Delitos Sexuais/estatística & dados numéricos , Tentativa de Suicídio/estatística & dados numéricos , Adolescente , Adulto , Feminino , Seguimentos , Humanos , Masculino , Prognóstico , Estados Unidos/epidemiologia , Adulto Jovem
10.
J Electrocardiol ; 50(6): 758-761, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28751012

RESUMO

OBJECTIVES: To evaluate performance of J-to-T-peak (JTP) measurements of 12-lead ECGs, in a five-arm study using drugs with various levels of electrolyte channel block. METHODS: The novel evaluation method distinguishes between different aspects of measurement. "Random noise" is the variability among repeated measurements made without changing the conditions. "Context noise" is the variability of changes in context of the measurement, e.g. T-wave morphology, autonomic nervous system state. RESULTS: The average random noise of our RR-corrected JTPc measurements in standard deviations was 3.0 ms and not dependent on the drug. The average context noise was 4.0 ms for ranolazine, verapamil, and placebo, and 8.8 ms for dofetilide and quinidine. Measurement consistency is corroborated by linear fit confidence intervals of baseline- and placebo-corrected JTPc versus drug concentration. CONCLUSIONS: Systematic differences were found in JTPc drug response between the Mortara method and published data. Residual signal component in the context noise may influence future study design.


Assuntos
Algoritmos , Biomarcadores/análise , Eletrocardiografia/métodos , Sistema de Condução Cardíaco/efeitos dos fármacos , Canais Iônicos/efeitos dos fármacos , Bloqueadores dos Canais de Potássio/farmacologia , Bloqueadores dos Canais de Sódio/farmacologia , Humanos , Fenetilaminas/farmacologia , Quinidina/farmacologia , Ranolazina/farmacologia , Sulfonamidas/farmacologia , Verapamil/farmacologia
11.
J Electrocardiol ; 50(6): 769-775, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29021091

RESUMO

Interest in the effects of drugs on the heart rate-corrected JTpeak (JTpc) interval from the body-surface ECG has spawned an increasing number of scientific investigations in the field of regulatory sciences, and more specifically in the context of the Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative. We conducted a novel initiative to evaluate the role of automatic JTpc measurement technologies by comparing their ability to distinguish multi- from single-channel blocking drugs. A set of 5232 ECGs was shared by the FDA (through the Telemetric and Holter ECG Warehouse) with 3 ECG device companies (AMPS, Mortara, and Philips). We evaluated the differences in drug-concentration effects on these measurements between the commercial and the FDA technologies. We provide a description of the drug-induced placebo-corrected changes from baseline for dofetilide, quinidine, ranolazine, and verapamil, and discuss the various differences across all technologies. The results revealed only small differences between measurement technologies evaluated in this study. It also confirms that, in this dataset, the JTpc interval distinguishes between multi- and single-channel (hERG) blocking drugs when evaluating the effects of dofetilide, quinidine, ranolazine, and verapamil. However, in the case of quinidine and dofetilide, we noticed a poor consistency across technologies because of the lack of standard definitions for the location of the peak of the T-wave (T-apex) when the T-wave morphology is abnormal.


Assuntos
Algoritmos , Biomarcadores/análise , Eletrocardiografia Ambulatorial/métodos , Sistema de Condução Cardíaco/efeitos dos fármacos , Canais Iônicos/efeitos dos fármacos , Síndrome do QT Longo/induzido quimicamente , Bloqueadores dos Canais de Potássio/farmacologia , Bloqueadores dos Canais de Sódio/farmacologia , Torsades de Pointes/induzido quimicamente , Adolescente , Adulto , Voluntários Saudáveis , Humanos , Fenetilaminas/farmacologia , Quinidina/farmacologia , Ranolazina/farmacologia , Sulfonamidas/farmacologia , Verapamil/farmacologia
12.
J Acoust Soc Am ; 142(5): 2979, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-29195447

RESUMO

It is shown that elastodynamic reciprocity provides a simpler approach for deriving the far-field displacements due to buried (sub-surface) sources in a half-space, compared with integral transform techniques. The auxiliary fields employed in this approach are the fields associated with the reflection of plane waves of the three possible polarisations, and the required far field can be expressed in terms of these well-known auxiliary fields. The crucial step in this approach is to evaluate a surface integral involving cross-work terms between an outgoing spherical wavefront and the auxiliary fields consisting of incident and reflected plane waves. This integral can be evaluated by the stationary phase approximation for the two-dimensional case, or by a generalisation of this approximation for the three-dimensional case. Although this evaluation involves several distinct contributions, the final result is shown to be very simple, and it can be interpreted as a generalisation of a known result for the one-dimensional case, whereby the net contribution arises only from counter-propagating waves of the same mode. The results derived for a buried force are extended to the case of buried cracks by exploiting the body force equivalents for displacement discontinuities across a surface.

13.
Mol Psychiatry ; 20(11): 1286-93, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26100538

RESUMO

Huntington's disease (HD), a progressive neurodegenerative disease, is caused by an expanded CAG triplet repeat producing a mutant huntingtin protein (mHTT) with a polyglutamine-repeat expansion. Onset of symptoms in mutant huntingtin gene-carrying individuals remains unpredictable. We report that synthetic polyglutamine oligomers and cerebrospinal fluid (CSF) from BACHD transgenic rats and from human HD subjects can seed mutant huntingtin aggregation in a cell model and its cell lysate. Our studies demonstrate that seeding requires the mutant huntingtin template and may reflect an underlying prion-like protein propagation mechanism. Light and cryo-electron microscopy show that synthetic seeds nucleate and enhance mutant huntingtin aggregation. This seeding assay distinguishes HD subjects from healthy and non-HD dementia controls without overlap (blinded samples). Ultimately, this seeding property in HD patient CSF may form the basis of a molecular biomarker assay to monitor HD and evaluate therapies that target mHTT.


Assuntos
Doença de Huntington/líquido cefalorraquidiano , Doença de Huntington/genética , Mutação , Proteínas do Tecido Nervoso/genética , Peptídeos/líquido cefalorraquidiano , Agregação Patológica de Proteínas/líquido cefalorraquidiano , Animais , Células Cultivadas , Feminino , Humanos , Proteína Huntingtina , Masculino , Microscopia Eletrônica , Agregação Patológica de Proteínas/patologia , Ratos , Ratos Transgênicos , Transfecção
15.
Hong Kong Med J ; 22(6): 576-81, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27779096

RESUMO

INTRODUCTION: Rainlily, the first one-stop crisis centre in Hong Kong, was set up in 2000 to protect female victims of sexual violence. This study aimed to analyse the characteristics of sexual assault cases and victims who presented to two hospitals in Hong Kong. The data are invaluable for health care professionals and policymakers to improve service provision to these victims. METHODS: This retrospective analysis of hospital records was conducted in two acute hospitals under the Hospital Authority in Hong Kong. Sexual assault victims who attended the two hospitals between May 2010 and April 2013 were included. Characteristics of the cases and the victims, the use of alcohol and drugs, involvement of violence, and the outcome of the victims were studied. RESULTS: During the study period, 154 sexual assault victims attended either one of the two hospitals. Their age ranged from 13 to 64 years. The time from assault to presentation ranged from 1 hour to more than 5 months. Approximately 50% of the assailants were strangers. Approximately 50% of victims presented with symptoms; the most common were pelvic and genitourinary symptoms. Those with symptoms (except pregnancy) presented earlier than those without. The use of alcohol and drugs was involved in 36.4% and 11.7% of cases, respectively. Approximately 10% of the screened victims were positive for Chlamydia trachomatis. There were 11 pregnancies with gestational age ranged from 6 weeks to 5 months at presentation. Less than half of the victims completed follow-up care. CONCLUSIONS: Involvement of alcohol and drugs is not uncommon in sexual assault cases. Efforts should be made to promote public education, enhance coordination between medical and social services, and improve the accessibility and availability of clinical care. Earlier management and better compliance with follow-up can minimise the health consequences and impact on victims.


Assuntos
Anticoncepção Pós-Coito/estatística & dados numéricos , Vítimas de Crime/estatística & dados numéricos , Delitos Sexuais/estatística & dados numéricos , Infecções Sexualmente Transmissíveis/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Demografia , Feminino , Hong Kong , Hospitais , Humanos , Pessoa de Meia-Idade , Gravidez , Estudos Retrospectivos , Infecções Sexualmente Transmissíveis/classificação , Adulto Jovem
16.
Clin Endocrinol (Oxf) ; 82(4): 604-10, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25079145

RESUMO

OBJECTIVE: Thyroid peroxidase antibodies (TPOAb) and thyroglobulin antibodies (TGAb) are frequently measured to investigate thyroid dysfunction in pregnancy. Despite the recognized fall of these autoantibodies in pregnancy, there is limited guidance on the timing of such testing. We assessed optimal test timing of TPOAb/TGAb for the detection of Hashimoto's thyroiditis and post-partum thyroid dysfunction (PPTD). DESIGN: Prospective longitudinal study with recruitment in Trimester 1. PATIENTS: Healthy women ≤13 weeks' gestation from Mercy Hospital for Women, a tertiary obstetric hospital in Melbourne. MEASUREMENTS: Serum TPOAb, TGAb, TSH and fT4 were measured at Trimester 1 (T1), Trimester 2(T2), Trimester 3(T3) and postpartum (PP) in each participant. Post-partum thyroid dysfunction (PPTD) was defined if TSH deviated from the assay's nonpregnant reference interval. Longitudinal random-effect logistic regression was used to investigate the association between time and positive/negative thyroid autoantibody status. RESULTS: Samples from 140 women at T1 (12·0: 10·3-13·0) (median: IQR weeks' gestation); 95 at T2 (24·3: 23·0-25·9), 79 at T3 (35·9: 34·8-36·7) and 83 at PP (12·4: 10·8-14·6 weeks post-partum) were attained. At T1, 13 (9%) and 15 (11%) women had positive TPOAb and TGAb, respectively. The odds of having a positive TPOAb were 96% lower at T2 [OR = 0·04 (95% CI: 0·02-0·8; P = 0·03)] and 97% lower at T3 [OR = 0·03 (95% CI: 0·001-0·6; P = 0·02)] than at T1. Similarly, the odds of having a positive TGAb were 99·4% lower [OR = 0·006 (95% CI: 0-0·3; P = 0·01)] at T2, and 99·5% lower [OR = 0·005 (95% CI: 0-0·4; P = 0·02)] at T3 than at T1. The ROC analysis diagnostic ORs for a positive TPOAb and/or TGAb to predict PPTD were 7·8 (95% CI: 2·2-27·6), 1·2 (95% CI: 0-8·9), 2·0 (95% CI: 0-16·8), and 12·2 (95% CI: 3·3-44·9) at T1, T2, T3 and post-partum, respectively. CONCLUSIONS: A significant proportion of pregnant women lose their thyroid autoantibody positivity after T1. The gestation-dependent loss of TPOAb/TGAb positivity and reduction in diagnostic accuracy for predicting PPTD limits the value of testing at T2 and T3.


Assuntos
Autoanticorpos/sangue , Complicações na Gravidez/imunologia , Tireoglobulina/química , Glândula Tireoide/imunologia , Adulto , Feminino , Doença de Hashimoto/imunologia , Humanos , Iodeto Peroxidase/química , Estudos Longitudinais , Período Pós-Parto , Gravidez , Estudos Prospectivos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Tireoglobulina/imunologia , Doenças da Glândula Tireoide/sangue , Doenças da Glândula Tireoide/complicações , Resultado do Tratamento
17.
Psychol Med ; 45(15): 3293-304, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26190760

RESUMO

BACKGROUND: Civilian suicide rates vary by occupation in ways related to occupational stress exposure. Comparable military research finds suicide rates elevated in combat arms occupations. However, no research has evaluated variation in this pattern by deployment history, the indicator of occupation stress widely considered responsible for the recent rise in the military suicide rate. METHOD: The joint associations of Army occupation and deployment history in predicting suicides were analysed in an administrative dataset for the 729 337 male enlisted Regular Army soldiers in the US Army between 2004 and 2009. RESULTS: There were 496 suicides over the study period (22.4/100 000 person-years). Only two occupational categories, both in combat arms, had significantly elevated suicide rates: infantrymen (37.2/100 000 person-years) and combat engineers (38.2/100 000 person-years). However, the suicide rates in these two categories were significantly lower when currently deployed (30.6/100 000 person-years) than never deployed or previously deployed (41.2-39.1/100 000 person-years), whereas the suicide rate of other soldiers was significantly higher when currently deployed and previously deployed (20.2-22.4/100 000 person-years) than never deployed (14.5/100 000 person-years), resulting in the adjusted suicide rate of infantrymen and combat engineers being most elevated when never deployed [odds ratio (OR) 2.9, 95% confidence interval (CI) 2.1-4.1], less so when previously deployed (OR 1.6, 95% CI 1.1-2.1), and not at all when currently deployed (OR 1.2, 95% CI 0.8-1.8). Adjustment for a differential 'healthy warrior effect' cannot explain this variation in the relative suicide rates of never-deployed infantrymen and combat engineers by deployment status. CONCLUSIONS: Efforts are needed to elucidate the causal mechanisms underlying this interaction to guide preventive interventions for soldiers at high suicide risk.


Assuntos
Militares/estatística & dados numéricos , Suicídio/estatística & dados numéricos , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Ocupações/estatística & dados numéricos , Resiliência Psicológica , Estados Unidos/epidemiologia , United States Department of Defense/estatística & dados numéricos , Adulto Jovem
18.
Oral Dis ; 21(3): 320-7, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25040852

RESUMO

OBJECTIVES: The aims of this study were to examine the expression of androgen receptors (AR) in oral squamous cell carcinoma (OSCC) cells and tumors and to determine the role of AR in regulating OSCC cell growth. MATERIALS AND METHODS: Four OSCC cell lines were used for analyzing AR expression and transcriptional activity. The effects of AR knockdown on the growth and tumorigenicity of OSCC cells were examined. A series of 11 benign, 22 premalignant, and 21 malignant lesions of the oral cavity were used for analyzing AR expression. RESULTS: OSCC cells expressed AR proteins with differential activities. Stimulation of AR by dihydrotestosterone in OSCC cells caused an increase in cyclin D1 expression and promoted cell growth, whereas treatment with bicalutamide led to decreased cyclin D1 expression and inhibited cell growth. Knockdown of AR expression in OSCC cells resulted in decreased proliferation, increased apoptosis, and inhibited tumorigenicity. Results from immunohistochemical studies showed that AR immunoreactivity was found in 27% (3/11) of benign lesions, while 68% (15/22) of premalignant and 67% (14/21) of malignant lesions showed positive AR staining. CONCLUSION: Our data suggest that OSCC cells express functional AR proteins which are critical for promoting cell growth and causing malignant disease.


Assuntos
Carcinoma de Células Escamosas/química , Neoplasias Bucais/química , Lesões Pré-Cancerosas/química , Receptores Androgênicos/genética , Receptores Androgênicos/metabolismo , Antagonistas de Androgênios/farmacologia , Androgênios/farmacologia , Anilidas/farmacologia , Animais , Apoptose , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Transformação Celular Neoplásica/genética , Ciclina D1/efeitos dos fármacos , Ciclina D1/metabolismo , Di-Hidrotestosterona/farmacologia , Técnicas de Silenciamento de Genes , Humanos , Camundongos , Neoplasias Bucais/patologia , Nitrilas/farmacologia , Receptores Androgênicos/análise , Compostos de Tosil/farmacologia
19.
Orthod Craniofac Res ; 18(4): 202-11, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26083593

RESUMO

OBJECTIVES: To investigate changes in masseter muscle function following intramuscular injection of different dose-dependent botulinum toxin type A (BTXA). SETTING AND SAMPLE POPULATION: Department of Orthodontics at Taipei Medical University. Fifty-two, 70-day-old male Wistar rats were randomly divided into four groups. Group I received 7.5 U of BTXA (0.3 ml), Group II received 5.0 U, and Group III received 2.5 U in the right masseter muscle, respectively. Group IV is the control and received no BTXA injection. MATERIALS AND METHODS: A wire electrode device was implanted to record muscle activity. One week after implantation, the rats were fed every 2 h and EMG signals were recorded during the first hour. All signals were recorded for 12 weeks. Thereafter, EMG data were analyzed for statistical calculation and weights of masseter muscles were measured. RESULTS: Masseter muscle activity decreased 99% during the first week after BTXA injection and gradually recovered from the 3rd week on in Groups I-III. By the 12th week, muscle activity recovered to 41% in Groups I and II and 56.26% in Group III. No significant changes of muscle activity were observed in Group IV. CONCLUSION: BTXA induced a reduction in masseter muscle activity and an increased toxin dose resulted in greater depression of muscle activity.


Assuntos
Toxinas Botulínicas Tipo A/administração & dosagem , Músculo Masseter/efeitos dos fármacos , Fármacos Neuromusculares/administração & dosagem , Conversão Análogo-Digital , Animais , Relação Dose-Resposta a Droga , Eletromiografia/efeitos dos fármacos , Masculino , Músculo Masseter/anatomia & histologia , Mastigação/fisiologia , Tamanho do Órgão/efeitos dos fármacos , Distribuição Aleatória , Ratos , Ratos Wistar , Fatores de Tempo
20.
Biomed Microdevices ; 16(3): 465-78, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24627216

RESUMO

The epithelial to mesenchymal transition (EMT) is known to involve several physiological and pathological phenomena. In this study, we utilized a microplate measurement system (MMS) approach based on the deflection of a flexible micro-cantilever to measure cell stiffness (in Pa) and adhesion force (in nN) of a single cell during EMT with nN resolution. Our results demonstrated that after transforming growth factor-ß1 (TGF-ß1) induced EMT (tEMT), NMuMG cells became stiffer due to thicker and more abundant F-actin and displayed stronger vinculin accumulation after long-term cell-substrate adhesion. The MMS could distinguish differences in compressive stiffness (219 ± 10 and 287 ± 14 Pa), tensile stiffness (114 ± 14 and 132 ± 12 Pa), and adhesion force (150 ± 42 and 192 ± 31 nN) between cells before and after tEMT. However, without proper development of the F-actin structure and adequate adherent time, the mechanical differences were diminished. After tEMT, the cells with increased stiffness and a cell-substrate adhesion force benefited by migrating more rapidly and had more invasiveness. Thus, this technology has the potential to benefit research focused on cancer diagnosis, drug development, and cell-substrate interactions.


Assuntos
Actinas/metabolismo , Diferenciação Celular/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Fenômenos Mecânicos , Microtecnologia/instrumentação , Fator de Crescimento Transformador beta1/farmacologia , Animais , Fenômenos Biomecânicos , Caderinas/metabolismo , Adesão Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Citocalasina D/farmacologia , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Camundongos , Vinculina/metabolismo
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