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1.
J Phys Condens Matter ; 34(22)2022 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-35139497

RESUMO

A new approach is introduced to obtain information about the adiabatic potential energy surface of the Jahn-Teller (JT) complexes subject to theT⊗e+t2problem in doped crystals. It employs simulation of the contribution of the JT sub-system to ultrasonic attenuation with account of three mechanisms of relaxation and subsequent comparison with the experimental data on temperature dependence of the attenuation obtained with the use of doped crystal and nominally pure one. The approach has been applied to the CaF2crystal doped with chromium. The experiment has been carried out at the frequencies of (13-158) × 106Hz at low temperatures (4-170 K). Peak for all the ultrasonic normal modes propagating along the [110] axis has been observed at about 8 K. It has been considered as the JT effect manifestation by the sub-system of Cr2+F8-complexes. Symmetry properties of the global minima and saddle points have been identified, the JT stabilization energies and coordinates of the extrema points in the five-dimensional space of symmetrized displacements have been evaluated. Besides, a broad shoulder has been found at 15-40 K and attributed to contribution of the Cr3+F8-sub-system.

2.
J Endocrinol Invest ; 44(4): 851-863, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32776198

RESUMO

CONTEXT: In preclinical studies, high androgen levels during pregnancy are associated with low birth weight and rapid postnatal weight gain in the offspring. However, human data linking prenatal androgens with birth weight and early life weight gain in the offspring are scarce. DESIGN: We evaluated 516 mother-child pairs enrolled in the New England birth cohorts of the Collaborative Perinatal Project (1959-1966). We assayed androgen bioactivity in maternal sera during third-trimester using a receptor-mediated luciferase expression bioassay. Age and sex-specific BMI Z-scores (BMIz), defined using established standards, were assessed at birth, 4 months, 1 year, 4 years, and 7 years. We used linear mixed models to evaluate the relation of maternal androgens with childhood BMIz overall and by sex. We examined the association of maternal androgens with fetal growth restriction. The association of weight trajectories with maternal androgens was examined using multinomial logistic regression. RESULTS: Higher maternal androgen levels associated with lower BMIz at birth (ß = - 0.39, 95% CI: - 0.73, - 0.06); this relation was sex-dependent, such that maternal androgens significantly associated with BMIz at birth in girls alone (ß = - 0.72, 95% CI: - 1.40, - 0.04). The relation of maternal androgens with fetal growth restriction revealed dose threshold effects that differed by sex. There was no significant association between maternal androgens and weight trajectory overall. However, we found a significant sex interaction (p = 0.01); higher maternal androgen levels associated with accelerated catch-up growth in boys (aOR = 2.14, 95% CI: 1.14, 4.03). CONCLUSION: Our findings provide evidence that maternal androgens may have differential effects on the programming of intrauterine growth and postnatal weight gain depending on fetal sex.


Assuntos
Androgênios/sangue , Trajetória do Peso do Corpo , Terceiro Trimestre da Gravidez/sangue , Cuidado Pré-Natal , Adulto , Androgênios/análise , Peso ao Nascer , Índice de Massa Corporal , Criança , Desenvolvimento Infantil/fisiologia , Pré-Escolar , Estudos de Coortes , Correlação de Dados , Feminino , Humanos , Recém-Nascido , New England/epidemiologia , Gravidez , Cuidado Pré-Natal/métodos , Cuidado Pré-Natal/estatística & dados numéricos , Fatores Sexuais , Aumento de Peso/fisiologia
3.
Electrophoresis ; 40(11): 1558-1564, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30828828

RESUMO

Human acetyl-coenzyme A carboxylase 2 catalyzes the carboxylation of acetyl coenzyme A to form malonyl coenzyme A, along with the conversion of magnesium-adenosine triphosphate complex to magnesium-adenosine diphosphate complex. A simple off-column capillary electrophoresis assay for human acetyl-coenzyme A carboxylase 2 was developed based on the separation of magnesium-adenosine triphosphate complex, magnesium-adenosine diphosphate complex, acetyl coenzyme A and malonyl coenzyme A with detection by ultraviolet absorption at 256 nm. When Mg2+ was absent from the separation buffer, the zones due to magnesium-adenosine triphosphate complex and magnesium-adenosine diphosphate complex both split and migrated as two separate peaks. With Mg2+ added to the separation buffer, magnesium-adenosine triphosphate complex and magnesium-adenosine diphosphate complex produced single peaks, and the reproducibility of peak shape and area improved for human acetyl-coenzyme A carboxylase 2 assay components. The final separation buffer used was 30.0 mM HEPES, 3.0 mM MgCl2 , 2.5 mM KHCO3 , and 2.5 mM potassium citrate at pH 7.50. The same buffer was used for the enzyme-catalyzed reaction (off-column). Inhibition of human acetyl-coenzyme A carboxylase 2 by CP-640186, a known inhibitor, was detected using the capillary electrophoresis assay.


Assuntos
Acetil-CoA Carboxilase/análise , Eletroforese Capilar/métodos , Soluções Tampão , Desenho de Equipamento , Humanos , Magnésio/química , Morfolinas/farmacologia , Piperidinas/farmacologia
4.
Epidemiol Psychiatr Sci ; 29: e18, 2019 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-30712520

RESUMO

AIMS: To examine the impact of multiple psychiatric disorders over the lifetime on risk of mortality in the general population. METHODS: Data came from a random community-based sample of 1397 adults in Atlantic Canada, recruited in 1992. Major depression, dysthymia, panic disorder, generalised anxiety disorder and alcohol use disorders were assessed using the Diagnostic Interview Schedule (DIS). Vital status of participants through 2011 was determined using probabilistic linkages to the Canadian Mortality Database. Cox proportional hazard models with age at study entry as the time scale were used to investigate the relationship between DIS diagnoses and mortality, adjusted for participant education, smoking and obesity at baseline. RESULTS: Results suggested that mood and anxiety disorders rarely presented in isolation - the majority of participants experienced multiple psychiatric disorders over the lifetime. Elevated risk of death was found among men with both major depression and dysthymia (HR 2.56; 95% CI 1.12-5.89), depression and alcohol use disorders (HR 2.45; 95% CI 1.18-5.10) and among men and women who experienced both panic disorder and alcohol use disorders (HR 3.80; 95% CI 1.19-12.16). CONCLUSION: The experience of multiple mental disorders over the lifetime is extremely common, and associated with increased risk of mortality, most notably among men. Clinicians should be aware of the importance of considering contemporaneous symptoms of multiple psychiatric conditions.


Assuntos
Transtornos Mentais/epidemiologia , Adulto , Canadá/epidemiologia , Estudos de Coortes , Feminino , Humanos , Masculino , Transtornos Mentais/mortalidade
5.
Obes Rev ; 19(9): 1248-1255, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30035359

RESUMO

INTRODUCTION: Uncontrolled family factors may bias the estimation of the association between maternal smoking during pregnancy and offspring body mass index (BMI). The objective was to assess if there is an association between maternal smoking during pregnancy and offspring BMI z-score independent of factors in the siblings' shared environment and if such association is linear. METHODS: We performed an individual patient data meta-analysis using five studies providing sibling data (45,299 children from 14,231 families). In a multi-level model, separating within-family and between-family effects and with random intercept for families, we analysed the dose-response association between maternal number of cigarettes per day during pregnancy and offspring's BMI z-score using B-splines to allow for non-linear associations. RESULTS: A linear within-family effect for number of cigarettes smoked in the range from 1 to 30 cigarettes per day on the offspring's BMI z-score was observed. Each additional cigarette per day between sibling pregnancies resulted in an increase in BMI z-score of 0.007 (95% CI [0.006, 0.009]). A between family-effect emerged only with doses ≥25 cigarettes per day. CONCLUSIONS: The number of cigarettes mothers smoke per day during pregnancy is positively associated with offspring BMI z-score even among siblings, suggesting that the association is not entirely explained by confounding by family factors.


Assuntos
Índice de Massa Corporal , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Fumar , Feminino , Humanos , Gravidez
6.
Transl Psychiatry ; 7(5): e1139, 2017 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-28556831

RESUMO

Prior studies provide limited and contradictory evidence regarding sex differences in the incidence of depression during adolescence, a critical period for development of the disorder. Data from six consecutive years (2009-2014) of a national survey of US adolescents aged 12-17 (N=101 685) are used to characterize sex differences in the incidence of depression by age and to compare recent first-onset and persistent depression with respect to impairment, suicide attempts, conduct problems and academic functioning. Projecting from age-specific incidence proportions, the cumulative incidence of depression between the ages of 12 and 17 is 13.6% among male and 36.1% among female subjects. The sex difference in incidence is significant at the age of 12 years (5.2% in female versus 2.0% in male subjects, P<0.0001), and it is significantly larger at ages of 13 through 17 years than at the age of 12 years (P-values<0.05). Depression-related impairment is lower in recent first-onset than in persistent depression among female but not among male subjects. The prevalence of conduct problems and poor academic functioning is higher in both recent first-onset and persistent depression relative to those with no depression for both male and female subjects. The incidence of depression during adolescence is higher than that suggested by prior studies based on retrospective recall. Contrary to prior studies, evidence suggests that the sex difference in depression originates during childhood and grows in magnitude during adolescence. High levels of impairment, suicide attempts, conduct problems and poor academic functioning argue against a 'wait and see' approach to clinical treatment of recent first-onset depression.


Assuntos
Idade de Início , Depressão/epidemiologia , Caracteres Sexuais , Adolescente , Criança , Feminino , Humanos , Incidência , Masculino , Prevalência , Estudos Retrospectivos , Tentativa de Suicídio/estatística & dados numéricos
7.
Mol Psychiatry ; 22(4): 544-551, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27431294

RESUMO

The 2013 US Veterans Administration/Department of Defense Clinical Practice Guidelines (VA/DoD CPG) require comprehensive suicide risk assessments for VA/DoD patients with mental disorders but provide minimal guidance on how to carry out these assessments. Given that clinician-based assessments are not known to be strong predictors of suicide, we investigated whether a precision medicine model using administrative data after outpatient mental health specialty visits could be developed to predict suicides among outpatients. We focused on male nondeployed Regular US Army soldiers because they account for the vast majority of such suicides. Four machine learning classifiers (naive Bayes, random forests, support vector regression and elastic net penalized regression) were explored. Of the Army suicides in 2004-2009, 41.5% occurred among 12.0% of soldiers seen as outpatient by mental health specialists, with risk especially high within 26 weeks of visits. An elastic net classifier with 10-14 predictors optimized sensitivity (45.6% of suicide deaths occurring after the 15% of visits with highest predicted risk). Good model stability was found for a model using 2004-2007 data to predict 2008-2009 suicides, although stability decreased in a model using 2008-2009 data to predict 2010-2012 suicides. The 5% of visits with highest risk included only 0.1% of soldiers (1047.1 suicides/100 000 person-years in the 5 weeks after the visit). This is a high enough concentration of risk to have implications for targeting preventive interventions. An even better model might be developed in the future by including the enriched information on clinician-evaluated suicide risk mandated by the VA/DoD CPG to be recorded.


Assuntos
Previsões/métodos , Prevenção do Suicídio , Suicídio/psicologia , Adulto , Teorema de Bayes , Simulação por Computador , Humanos , Masculino , Transtornos Mentais/psicologia , Saúde Mental , Militares , Pacientes Ambulatoriais , Resiliência Psicológica , Medição de Risco , Fatores de Risco , Suicídio/estatística & dados numéricos , Tentativa de Suicídio/psicologia , Estados Unidos
8.
Transl Psychiatry ; 6(5): e822, 2016 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-27244231

RESUMO

Maternal immune functioning during pregnancy contributes to sex-dependent deficits in neurodevelopment and to behaviors associated with affective traits in preclinical studies, and has been indirectly associated with offspring depression in epidemiologic studies. We therefore investigated the association between immune activity during pregnancy and the risk of depression among male and female offspring. We conducted a case-control study of depression (n=484 cases and n=774 controls) using data from the New England Family Study, a pregnancy cohort enrolled between 1959 and 1966 that assessed psychiatric outcomes in adult offspring (mean age=39.7 years). We assayed concentrations of three pro-inflammatory cytokines, interleukin (IL)-1ß, IL-6 and tumor necrosis factor (TNF)-α, and the anti-inflammatory cytokine, IL-10, in maternal serum collected at the end of the second and beginning of the third trimesters. High maternal TNF-α was associated with reduced odds of depression among both male and female offspring (odds ratio (OR)=0.68; confidence interval (CI)=0.48, 0.98). However, when considering the TNF-α to IL-10 ratio, a measure of the ratio of pro- to anti-inflammatory loading, maternal immune effects on offspring depression differed significantly by sex (χ(2)=13.9, degrees of freedom=4, P=0.008). Among females, higher maternal TNF-α:IL-10 was associated with reduced odds of depression (OR=0.51; CI=0.32, 0.81), whereas, among males, high maternal TNF-α:IL-10 was associated with elevated odds of depression (OR=1.86; CI=1.02, 3.39). Thus, the balance between TNF-α and IL-10 in maternal prenatal serum was associated with depression in a sex-dependent manner. These findings are consistent with the role of TNF-α in the maturation of the sexually dimorphic fetal brain circuitry that regulates stress and affective responses, and support a prenatal stress-immune model of depression pathogenesis.


Assuntos
Filhos Adultos/psicologia , Transtorno Depressivo Maior/imunologia , Transtorno Depressivo Maior/psicologia , Mediadores da Inflamação/sangue , Transtornos do Neurodesenvolvimento/imunologia , Complicações na Gravidez/imunologia , Efeitos Tardios da Exposição Pré-Natal/imunologia , Adolescente , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Recém-Nascido , Interleucina-10/sangue , Masculino , Gravidez , Fatores de Risco , Fatores Sexuais
9.
Public Health ; 132: 86-91, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26795678

RESUMO

OBJECTIVES: Food insecurity is associated with elevated risk of mental illness. This risk may be further compounded by stressful life events and by social isolation. This study investigated whether the risk of mental illness is higher among individuals experiencing food insecurity along with greater stress and social isolation. STUDY DESIGN: Cross-sectional self-report survey data from the 2009-10 Canadian Community Health Survey (N = 100,401). METHODS: We estimated prevalence differences of the risk of self-reported mental illness associated with food insecurity alone and in combination with stressful life events and social isolation. Sensitivity analyses were conducted on a sub-sample who completed a structured diagnostic interview. RESULTS: Overall, the prevalence of mental illness was 18.4% [95% CI 16.7-20.1] higher for women and 13.5% higher [95% CI 11.9, 15.2] for men in severely food insecure households compared to those reporting food security. The increased risk of mental illness associated with food insecurity was more pronounced among females and those reporting higher stress and social isolation. CONCLUSIONS: Individuals reporting food insecurity are at increased risk of mental illness. This increased risk is further exacerbated in high stress and socially isolated environments. Policies, clinical and public health interventions must address broader constellations of risks that exist when food insecurity is present.


Assuntos
Abastecimento de Alimentos/estatística & dados numéricos , Transtornos Mentais/epidemiologia , Adolescente , Adulto , Idoso , Canadá/epidemiologia , Estudos Transversais , Feminino , Inquéritos Epidemiológicos , Humanos , Acontecimentos que Mudam a Vida , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Isolamento Social/psicologia , Estresse Psicológico/psicologia , Adulto Jovem
10.
Anal Bioanal Chem ; 407(28): 8605-15, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26342315

RESUMO

Immunoassays exploit the highly selective interaction between antibodies and antigens to provide a vital method for biomolecule detection at low concentrations. Developers and practitioners of immunoassays have long known that non-specific binding often restricts immunoassay limits of quantification (LOQs). Aside from non-specific binding, most efforts by analytical chemists to reduce the LOQ for these techniques have focused on improving the signal amplification methods and minimizing the limitations of the detection system. However, with detection technology now capable of sensing single-fluorescence molecules, this approach is unlikely to lead to dramatic improvements in the future. Here, fundamental interactions based on the law of mass action are analytically connected to signal generation, replacing the four- and five-parameter fittings commercially used to approximate sigmoidal immunoassay curves and allowing quantitative consideration of non-specific binding and statistical limitations in order to understand the ultimate detection capabilities of immunoassays. The restrictions imposed on limits of quantification by instrumental noise, non-specific binding, and counting statistics are discussed based on equilibrium relations for a sandwich immunoassay. Understanding the maximal capabilities of immunoassays for each of these regimes can greatly assist in the development and evaluation of immunoassay platforms. While many studies suggest that single molecule detection is possible through immunoassay techniques, here, it is demonstrated that the fundamental limit of quantification (precision of 10 % or better) for an immunoassay is approximately 131 molecules and this limit is based on fundamental and unavoidable statistical limitations.


Assuntos
Anticorpos/química , Antígenos/química , Imunoensaio/estatística & dados numéricos , Limite de Detecção , Humanos , Análise Multivariada , Ligação Proteica , Razão Sinal-Ruído
11.
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
12.
Psychol Med ; 45(4): 717-26, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25359554

RESUMO

BACKGROUND: The Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS) has found that the proportional elevation in the US Army enlisted soldier suicide rate during deployment (compared with the never-deployed or previously deployed) is significantly higher among women than men, raising the possibility of gender differences in the adverse psychological effects of deployment. METHOD: Person-month survival models based on a consolidated administrative database for active duty enlisted Regular Army soldiers in 2004-2009 (n = 975,057) were used to characterize the gender × deployment interaction predicting suicide. Four explanatory hypotheses were explored involving the proportion of females in each soldier's occupation, the proportion of same-gender soldiers in each soldier's unit, whether the soldier reported sexual assault victimization in the previous 12 months, and the soldier's pre-deployment history of treated mental/behavioral disorders. RESULTS: The suicide rate of currently deployed women (14.0/100,000 person-years) was 3.1-3.5 times the rates of other (i.e. never-deployed/previously deployed) women. The suicide rate of currently deployed men (22.6/100,000 person-years) was 0.9-1.2 times the rates of other men. The adjusted (for time trends, sociodemographics, and Army career variables) female:male odds ratio comparing the suicide rates of currently deployed v. other women v. men was 2.8 (95% confidence interval 1.1-6.8), became 2.4 after excluding soldiers with Direct Combat Arms occupations, and remained elevated (in the range 1.9-2.8) after adjusting for the hypothesized explanatory variables. CONCLUSIONS: These results are valuable in excluding otherwise plausible hypotheses for the elevated suicide rate of deployed women and point to the importance of expanding future research on the psychological challenges of deployment for women.


Assuntos
Militares/estatística & dados numéricos , Suicídio/estatística & dados numéricos , Adulto , Feminino , Humanos , Masculino , Risco , Fatores Sexuais , Estados Unidos/epidemiologia , United States Department of Defense/estatística & dados numéricos
13.
Mol Psychiatry ; 20(3): 329-36, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24751965

RESUMO

In treated cohorts, individuals with bipolar disorder are more likely to report childhood adversities and recent stressors than individuals without bipolar disorder; similarly, in registry-based studies, childhood adversities are more common among individuals who later become hospitalized for bipolar disorder. Because these types of studies rely on treatment-seeking samples or hospital diagnoses, they leave unresolved the question of whether or not social experiences are involved in the etiology of bipolar disorder. We investigated the role of childhood adversities and adulthood stressors in liability for bipolar disorder using data from the National Epidemiologic Survey on Alcohol and Related Conditions (n=33 375). We analyzed risk for initial-onset and recurrent DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) manic episodes during the study's 3-year follow-up period. Childhood physical abuse and sexual maltreatment were associated with significantly higher risks of both first-onset mania (odds ratio (OR) for abuse: 2.23; 95% confidence interval (CI)=1.71, 2.91; OR for maltreatment: 2.10; CI=1.55, 2.83) and recurrent mania (OR for abuse: 1.55; CI=1.00, 2.40; OR for maltreatment: 1.60; CI=1.00, 2.55). In addition, past-year stressors in the domains of interpersonal instability and financial hardship were associated with a significantly higher risk of incident and recurrent mania. Exposure to childhood adversity potentiated the effects of recent stressors on adult mania. Our findings demonstrate a role of social experiences in the initial onset of bipolar disorder, as well as in its prospective course, and are consistent with etiologic models of bipolar disorder that implicate deficits in developmentally established stress-response pathways.


Assuntos
Transtorno Bipolar/epidemiologia , Transtorno Bipolar/etiologia , Maus-Tratos Infantis , Meio Social , Adolescente , Adulto , Transtorno Bipolar/psicologia , Criança , Maus-Tratos Infantis/estatística & dados numéricos , Estudos de Coortes , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Recidiva , Adulto Jovem
14.
Psychol Med ; 44(12): 2579-92, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25055175

RESUMO

BACKGROUND: The US Army suicide rate has increased sharply in recent years. Identifying significant predictors of Army suicides in Army and Department of Defense (DoD) administrative records might help focus prevention efforts and guide intervention content. Previous studies of administrative data, although documenting significant predictors, were based on limited samples and models. A career history perspective is used here to develop more textured models. METHOD: The analysis was carried out as part of the Historical Administrative Data Study (HADS) of the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS). De-identified data were combined across numerous Army and DoD administrative data systems for all Regular Army soldiers on active duty in 2004-2009. Multivariate associations of sociodemographics and Army career variables with suicide were examined in subgroups defined by time in service, rank and deployment history. RESULTS: Several novel results were found that could have intervention implications. The most notable of these were significantly elevated suicide rates (69.6-80.0 suicides per 100 000 person-years compared with 18.5 suicides per 100 000 person-years in the total Army) among enlisted soldiers deployed either during their first year of service or with less than expected (based on time in service) junior enlisted rank; a substantially greater rise in suicide among women than men during deployment; and a protective effect of marriage against suicide only during deployment. CONCLUSIONS: A career history approach produces several actionable insights missed in less textured analyses of administrative data predictors. Expansion of analyses to a richer set of predictors might help refine understanding of intervention implications.


Assuntos
Militares/estatística & dados numéricos , Mortalidade , Suicídio/estatística & dados numéricos , Adolescente , Adulto , Fatores Etários , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade/tendências , Fatores de Risco , Suicídio/tendências , Estados Unidos/epidemiologia , Adulto Jovem
15.
Anal Biochem ; 447: 1-5, 2014 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-24444856

RESUMO

An assay was developed for phosphofructokinase-1 (PFK-1) using capillary electrophoresis (CE). In the glycolytic pathway, this enzyme catalyzes the rate-limiting step from fructose-6-phosphate and magnesium-bound adenosine triphosphate (Mg-ATP) to fructose-1,6-bisphosphate and magnesium-bound adenosine diphosphate (Mg-ADP). This enzyme has recently become a research target because of the importance of glycolysis in cancer and obesity. The CE assay for PFK-1 is based on the separation and detection by ultraviolet (UV) absorbance at 260 nm of Mg-ATP and Mg-ADP. The separation was enhanced by the addition of Mg²âº to the separation buffer. Inhibition studies of PFK-1 by aurintricarboxylic acid and palmitoyl coenzyme A were also performed. An IC50 value was determined for aurintricarboxylic acid, and this value matched values in the literature obtained using coupled spectrophotometric assays. This assay for PFK-1 directly monitors the enzyme-catalyzed reaction, and the CE separation reduces the potential of spectral interference by inhibitors.


Assuntos
Eletroforese Capilar/métodos , Ensaios Enzimáticos/métodos , Fosfofrutoquinase-1/metabolismo , Difosfato de Adenosina/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Inibidores Enzimáticos/farmacologia , Fosfofrutoquinase-1/antagonistas & inibidores , Coelhos
16.
Anal Biochem ; 437(1): 32-8, 2013 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-23435309

RESUMO

A simple off-column capillary electrophoretic (CE) assay for measuring acetyl coenzyme A carboxylase holoenzyme (holo-ACC) activity and inhibition was developed. The two reactions catalyzed by the holo-ACC components, biotin carboxylase (BC) and carboxyltransferase (CT), were simultaneously monitored in this assay. Acetyl coenzyme A (CoA), malonyl-CoA, adenosine triphosphate (ATP), and adenosine diphosphate (ADP) were separated by capillary electrophoresis, and the depletion of ATP and acetyl-CoA as well as the production of ADP and malonyl-CoA were monitored. Inhibition of holo-ACC by the BC inhibitor, 2-amino-N,N-dibenzyloxazole-5-carboxamide, and the carboxyltransferase inhibitor, andrimid, was confirmed using this assay. A previously reported off-column CE assay for only the CT component of ACC was optimized, and an off-column CE assay for the BC component of ACC also was developed.


Assuntos
Acetil-CoA Carboxilase/metabolismo , Eletroforese Capilar/métodos , Ensaios Enzimáticos/métodos , Acetilcoenzima A/metabolismo , Acetil-CoA Carboxilase/antagonistas & inibidores , Trifosfato de Adenosina/metabolismo , Biocatálise , Carbono-Nitrogênio Ligases/metabolismo , Carboxil e Carbamoil Transferases/metabolismo , Inibidores Enzimáticos/farmacologia , Escherichia coli/enzimologia , Holoenzimas/metabolismo
17.
Psychol Med ; 43(2): 303-16, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22640506

RESUMO

BACKGROUND: Axis IV is for reporting 'psychosocial and environmental problems that may affect the diagnosis, treatment and prognosis of mental disorders'. No studies have examined the prognostic value of Axis IV in DSM-IV. METHOD: We analyzed data from 2497 participants in the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) with major depressive episode (MDE). We hypothesized that psychosocial stressors predict a poor prognosis of MDE. Secondarily, we hypothesized that psychosocial stressors predict a poor prognosis of anxiety and substance use disorders. Stressors were defined according to DSM-IV's taxonomy, and empirically using latent class analysis (LCA). RESULTS: Primary support group problems, occupational problems and childhood adversity increased the risks of depressive episodes and suicidal ideation by 20-30%. Associations of the empirically derived classes of stressors with depression were larger in magnitude. Economic stressors conferred a 1.5-fold increase in risk for a depressive episode [95% confidence interval (CI) 1.2-1.9]; financial and interpersonal instability conferred a 1.3-fold increased risk of recurrent depression (95% CI 1.1-1.6). These two classes of stressors also predicted the recurrence of anxiety and substance use disorders. Stressors were not related to suicidal ideation independent from depression severity. CONCLUSIONS: Psychosocial and environmental problems are associated with the prognosis of MDE and other Axis I disorders. Although DSM-IV's taxonomy of stressors stands to be improved, these results provide empirical support for the prognostic value of Axis IV. Future work is needed to determine the reliability of Axis IV assessments in clinical practice, and the usefulness of this information to improving the clinical course of mental disorders.


Assuntos
Transtorno Depressivo Maior/epidemiologia , Manual Diagnóstico e Estatístico de Transtornos Mentais , Acontecimentos que Mudam a Vida , Modelos Estatísticos , Meio Social , Estresse Psicológico/epidemiologia , Criança , Classificação , Transtorno Depressivo Maior/diagnóstico , Inquéritos Epidemiológicos , Humanos , Prognóstico , Reprodutibilidade dos Testes , Estresse Psicológico/classificação
18.
Anal Chim Acta ; 739: 99-103, 2012 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-22819055

RESUMO

A data treatment method is presented to detect fluorescence anisotropy (FA) peaks in capillary electrophoresis electropherograms. The data treatment method converts plots of fluorescence anisotropy vs. time that contain no peaks that are distinguishable from the noise of the anisotropy background into plots that show distinct fluorescence anisotropy peaks. The method was demonstrated using laser-induced fluorescence anisotropy data from individual Aß (1-42) aggregates separated using capillary electrophoresis. Applying this data treatment method enabled the detection of anisotropy peaks for individual Aß aggregate fluorescence peaks that were not observed prior to the data treatment method. The data treatment method is not specifically designed for Aß aggregate analysis or capillary electrophoresis, and it should be applicable to other applications and other separation methods with FA detection.


Assuntos
Peptídeos beta-Amiloides/análise , Eletroforese Capilar , Polarização de Fluorescência , Fragmentos de Peptídeos/análise , Processamento de Sinais Assistido por Computador , Algoritmos , Humanos , Lasers
19.
Analyst ; 137(14): 3227-9, 2012 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-22575916

RESUMO

Here we report a novel method for the manipulation and concentration of Aß amyloid fibrils, implicated in Alzheimer's disease, using DC insulating gradient dielectrophoresis (DC-iGDEP). Fibril enrichment was found to be ∼400%. Simulations suggest that capture of the full range of amyloid protein aggregates is possible with optimized device design.


Assuntos
Peptídeos beta-Amiloides/química , Peptídeos beta-Amiloides/isolamento & purificação , Condutividade Elétrica , Eletroforese/métodos , Multimerização Proteica , Impedância Elétrica , Estrutura Secundária de Proteína
20.
Electrophoresis ; 33(5): 827-33, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22437880

RESUMO

Significant changes in the formation and retention of magnetic bead plugs in a capillary during electrophoresis were studied, and it was demonstrated that these effects were due to the type of biological molecule immobilized on the surface of these beads. Three biological molecules, an antibody, an oligonucleotide, and alkaline phosphatase (AP), were attached to otherwise identical streptavidin-coated magnetic beads through biotin-avidin binding in order to isolate differences in bead immobilization in a magnetic field resulting from the type of biological molecule immobilized on the bead surface. AP was also attached to the magnetic beads using epoxy groups on the bead surfaces (instead of avidin-biotin binding) to study the impact of immobilization chemistry. The formation and retention of magnetic bead plugs were studied quantitatively using light scattering detection of magnetic particles eluting from the bead plugs and qualitatively using microscopy. Both the types of biomolecule immobilized on the magnetic bead surface and the chemistry used to link the biomolecule to the magnetic bead impacted the formation and retention of the bead plugs.


Assuntos
Reatores Biológicos , Eletroforese Capilar/instrumentação , Imãs , Microesferas , Fosfatase Alcalina , Anticorpos Imobilizados/química , Eletroforese Capilar/métodos , Enzimas Imobilizadas/química , Compostos de Epóxi , Oligonucleotídeos/química , Estreptavidina
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