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Baeyer-Villiger monooxygenases (BVMOs) are remarkable biocatalysts for the Baeyer-Villiger oxidation of ketones to generate esters or lactones. The regioselectivity of BVMOs is essential for determining the ratio of the two regioisomeric products ("normal" and "abnormal") when catalyzing asymmetric ketone substrates. Starting from a known normal-preferring BVMO sequence from Pseudomonas putida KT2440 (PpBVMO), a novel BVMO from Gordonia sihwensis (GsBVMO) with higher normal regioselectivity (up to 97/3) was identified. Furthermore, protein engineering increased the specificity constant (kcat /KM ) 8.9-fold to 484â s-1 mM-1 for 10-ketostearic acid derived from oleic acid. Consequently, by using the variant GsBVMOC308L as an efficient biocatalyst, 10-ketostearic acid was efficiently transformed into 9-(nonanoyloxy)nonanoic acid, with a space-time yield of 60.5â g L-1 d-1 . This study showed that the mutant with higher regioselectivity and catalytic efficiency could be applied to prepare medium-chain ω-hydroxy fatty acids through biotransformation of long-chain aliphatic keto acids derived from renewable plant oils.
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Oxigenasas de Función Mixta/metabolismo , Ingeniería de Proteínas , Actinobacteria/enzimología , Biocatálisis , Oxigenasas de Función Mixta/genética , Mutagénesis Sitio-Dirigida , Ácido Oléico/química , Ácido Oléico/metabolismo , Oxidación-Reducción , Pseudomonas putida/enzimología , Ácidos Esteáricos/química , Ácidos Esteáricos/metabolismo , Estereoisomerismo , Especificidad por SustratoRESUMEN
Artificial resuscitation has potential to reverse a premature death or to prolong the dying process. The resuscitation decision is one of life and death making it imperative that healthcare providers understand patients' beliefs. Making the decision to resuscitate has been associated with patients' spiritual/religious beliefs. Clinicians' assumptions based upon a patients' religion or spiritual beliefs may bias the resuscitation decision. The purpose of this study was to determine associations between hospitalized patients' spiritual/religious beliefs and their resuscitation decisions. A single-site, correlational study was conducted with a convenience sample of hospitalized patients in Honolulu, HI. Patients were enrolled November 2015 to January 2016. Spiritual/religious beliefs were assessed using two validated metrics. Two questions were used to determine the resuscitation decision (chest compressions and intubation). The sample of 84 patients represented no ethnic majority among Caucasian, Asian, and Native Hawaiian/Pacific Islander. Seventy-nine percent of the participants identified theistic spiritual beliefs. No associations were found between resuscitation decisions with either spiritual/religious beliefs or demographic characteristics of this study sample. Interestingly, 20% of the participants answered yes to only one of the resuscitation decision questions. Thus, providers' assumptions should not be made about an association between spiritual/religious beliefs and resuscitation decisions. It is imperative that patients are aware of the necessity for both medical interventions of chest compressions and intubation. Further research should address the complexity of the resuscitation decision, including patients understanding of medical interventions and anticipated prognosis, and other influencing factors.
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Planificación Anticipada de Atención/clasificación , Órdenes de Resucitación/psicología , Espiritualidad , Adulto , Anciano , Análisis de Varianza , Correlación de Datos , Femenino , Hawaii , Humanos , Masculino , Persona de Mediana Edad , Encuestas y CuestionariosRESUMEN
The temporal trend of hospitalizations, cost, and outcomes associated with preeclampsia with severe features have been inadequately studied. The publicly available Healthcare Cost and Utilization Project (HCUP) National Inpatient Sample (NIS) database was accessed to examine the temporal trend of total number of discharges, age, death, and mean charges per admission associated with preeclampsia with severe features. Eleven-year temporal trends (2004 to 2014) of these measures were compared using linear regression and run charts using the statistical process control rule. From 2004 to 2014, the total number of discharges related to preeclampsia with severe features increased both for Hawai'i and the U.S. (United States) (Hawai'i: 104 to 231; U.S.: 35,082 to 55,235; both P<.0001). The corresponding rates of discharges per 100,000 population also both increased (Hawai'i: 8.2 to 16.3; U.S.: 12.0 to 17.3; both P<.0001). Comparing the temporal trends between Hawai'i and the U.S., Hawai'i had a significantly higher average annual increase in the rate of incidence than the national level (an annual increase rate of 9.2% in Hawai'i vs 4.2% nationally; P=.0004). The cost of hospitalization for preeclampsia with severe features also showed an increased trend for both Hawai'i and the U.S. (Hawai'i: 33.1% increase, P=.0005; U.S.: 41.1% increase, P<.0001). In the U.S., in-hospital mortality rates associated with this condition decreased from 0.09% in 2004 to 0.02% in 2014 (P=.03). In conclusion, the number of discharges related to preeclampsia with severe features increased over an 11-year period in Hawai'i and the U.S., and the rate of increase was higher in Hawai'i than the U.S. Maternal mortality rates from this condition also declined over the study period.
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Costos de Hospital/estadística & datos numéricos , Hospitalización/estadística & datos numéricos , Preeclampsia/mortalidad , Bases de Datos Factuales , Femenino , Hawaii/epidemiología , Humanos , Preeclampsia/economía , Embarazo , Índice de Severidad de la Enfermedad , Estados UnidosRESUMEN
BACKGROUND: In bowel obstruction and biliary pancreatitis, patients receive more expedient surgical care when admitted to surgical compared with medical services. This has not been studied in acute cholecystitis. METHODS: Retrospective analysis of clinical and cost data from July 2013 to September 2015 for patients with cholecystitis who underwent laparoscopic cholecystectomy in a tertiary care inpatient hospital. One hundred ninety lower-risk (Charlson-Deyo) patients were included. We assessed admitting service, length of stay (LOS), time from admission to surgery, time from surgery to discharge, number of imaging studies, and total cost. RESULTS: Patients admitted to surgical (n = 106) versus medical (n = 84) service had shorter mean LOS (1.4 days vs. 2.6 days), shorter time from admission to surgery (0.4 days vs. 0.8 days), and shorter time from surgery to discharge (0.8 days vs. 1.1 days). Surgical service patients had fewer CT (38% vs. 56%) and magnetic resonance imaging (MRI) (5% vs. 16%) studies. Cholangiography (30% vs. 25%) and endoscopic retrograde cholangiopancreatography (ERCP) (3 vs. 8%) rates were similar. Surgical service patients had 39% lower median total costs (US $7787 vs. US $12572). CONCLUSION: Nonsurgical admissions of patients with cholecystitis are common, even among lower-risk patients. Routine admission to the surgical service should decrease LOS, resource utilization and costs. LEVEL OF EVIDENCE: Therapeutic/care management, level IV.
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Colecistectomía Laparoscópica , Colecistitis Aguda , Costos de la Atención en Salud/estadística & datos numéricos , Hospitalización/economía , Servicio de Cirugía en Hospital/economía , Adulto , Colecistectomía Laparoscópica/métodos , Colecistectomía Laparoscópica/estadística & datos numéricos , Colecistitis Aguda/diagnóstico , Colecistitis Aguda/economía , Colecistitis Aguda/cirugía , Ahorro de Costo/métodos , Diagnóstico por Imagen/economía , Diagnóstico por Imagen/métodos , Diagnóstico por Imagen/estadística & datos numéricos , Pruebas Diagnósticas de Rutina/economía , Pruebas Diagnósticas de Rutina/métodos , Femenino , Hawaii , Humanos , Tiempo de Internación/economía , Tiempo de Internación/estadística & datos numéricos , Masculino , Periodo Posoperatorio , Tiempo de Tratamiento/estadística & datos numéricosRESUMEN
BACKGROUND: Chronic liver disease and cirrhosis is the 12th leading cause of death in the United States. Patients with decompensated-cirrhosis, especially with hepatic encephalopathy/coma (HC), have a higher rate of early readmission and contribute to higher healthcare cost. AIM: To evaluate the national inpatient trends of discharges, mortalities and financial impacts associated with four common conditions of cirrhosis. METHODS: The publicly available Healthcare Cost and Utilization Project National Inpatient Sample database was utilized to examine the temporal trends of total number of discharges, mortalities and inpatient costs related to hospitalization with a primary diagnosis of HC, transjugular intrahepatic portosystemic shunt (TIPS), esophageal varices with bleeding (EV) and spontaneous bacterial peritonitis (SBP) from 2005 to 2014. The ten-year temporal trends were assessed using simple linear regressions and multiple regression analysis. Two-sided P < 0.05 was considered statistically significant. RESULTS: From 2005 to 2014, the total number of discharges with cirrhosis-associated complications trended up for HC, SBP and EV (HC by 70% increase, P < 0.0001; SBP by 819% increase, P = 0.0002; EV by 9% increase, P = 0.016), but not for TIPS (P = 0.90). HC related to viral hepatitis showed faster increase by 357% (P < 0.0001) in comparison to HC not related to viral hepatitis by 33 % (P = 0.0006). Overall, in-hospital mortality rates for each condition decreased from 2005 to 2014 (HC by 29% reduction, P = 0.0024; SBP by 26% reduction, P = 0.0038; TIPS by 32% reduction, P = 0.021) except for EV (P = 0.34). After adjustment for inflation, aggregate cost of hospitalization for EV, HC, and SBP significantly increased by 20%, 86%, and 980%, respectively, from 2005 to 2014 (all P < 0.02), while TIPS had trend toward decreasing cost by 3% (P = 0.95). CONCLUSION: The number of hospitalizations and costs for some of the cirrhosis-associated conditions increased. However, the inpatient mortality rates for most of these conditions decreased.
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Understanding the impacts of the built environment on physical activity (PA) is essential to promoting children's PA. The purpose of this study was to investigate the effects of schoolyard renovations and a PA recess curriculum alone and in combination on children's PA. This was a 2 (learning landscape [LL] vs. non-LL) × 2 (curriculum intervention vs. no curriculum intervention) factorial design with random assignment to the curriculum intervention, and six elementary schools per condition. PA outcomes were assessed preprogram, mid-program, immediate postprogram, and one year postprogram. No meaningful intervention effects were found. Lack of an effect may be due to the brief dose of recess, the curriculum not being integrated within the schoolyard, the LL implementation occurring prior to the study, or the already high levels of PA. Potential avenues to promote PA include making recess longer, integrating recess into the school curricula, and developing recess PA curricula integrating schoolyards.
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Entorno Construido , Curriculum , Ejercicio Físico , Promoción de la Salud , Juego e Implementos de Juego , Instituciones Académicas , Acelerometría , Índice de Masa Corporal , Niño , Estudios Transversales , Femenino , Promoción de la Salud/métodos , Humanos , Masculino , Autoinforme , Factores de Tiempo , Resultado del TratamientoRESUMEN
Retention index under the programmed temperature gas chromatography (PTGC) conditions (IT) is widely accepted despite of its unsatisfactory reproducibility. Effects of heating rate (rT), stationary liquid film thickness (df), inlet pressure (pi), initial temperature (To) and polarity of stationary phase (sp) on IT reproducibility were studied in the present work. We found that excellent reproducibility and regularity of IT values are obtainable at conditions of relatively low To and relatively high rT and pi, as well as use of quality thick-film column under an operation in a single-retention behavior region (i.e., cubic equation model region). Most solutes were eluted in the dual-retention behavior region under the commonly used conditions described in the literature (i.e., relatively high To and relatively low rT for thin-film columns). The IT reproducibility under the optimum condition was approximately 37 times better than that under the commonly used conditions. The present work further validated the concept about dual- and single-retention behaviors of solutes in PTGC and proposed a principle to improve IT reproducibility.
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Cromatografía de Gases/métodos , Modelos Teóricos , Presión , Reproducibilidad de los Resultados , TemperaturaRESUMEN
Monocytes play a vital role in HIV-associated neurocognitive disorder (HAND), postulated to transport HIV into the brain and secrete pro-inflammatory cytokines. We analyzed cytokines released by cultured peripheral blood mononuclear cells enriched with the CD14 marker isolated from HIV-infected individuals with HAND and normal cognition (NC) in combination antiretroviral therapy naive and after 1 year on treatment. Interleukin-8 and monocyte chemoattractant protein-1 levels were higher in HAND compared with NC at baseline (P = 0.002 and P < 0.0001). These cytokines remained higher in HAND patients 1 year after combination antiretroviral therapy and were significant when NC patients who were initially HAND were excluded (P = 0.012 and P = 0.002). Both correlated with baseline CD14 peripheral blood mononuclear cell HIV DNA levels supporting the role of HIV DNA reservoir size and monocyte cytokines in HAND persistence.
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Complejo SIDA Demencia/metabolismo , Infecciones por VIH/metabolismo , Leucocitos Mononucleares/metabolismo , Receptores de Lipopolisacáridos/metabolismo , Complejo SIDA Demencia/fisiopatología , Citocinas , Perfilación de la Expresión Génica , Infecciones por VIH/fisiopatología , Humanos , Monocitos , Carga ViralRESUMEN
OBJECTIVE: Native Hawaiians and Pacific Islanders (NHPI) bear an unequal burden of hypertension and cardiovascular disease. Hula, the traditional dance of Hawaii, has shown to be a culturally meaningful form of moderate-vigorous physical activity for NHPI. A pilot study was done in Honolulu, Hawaii, to test a 12-week hula-based intervention, coupled with self-care education, on blood pressure management in NHPI with hypertension in 2013. METHOD: NHPI with a systolic blood pressure (SBP) ≥140 mmHg were randomized to the intervention (n = 27) or a wait-list control (n = 28). Blood pressure, physical functioning, and eight aspects of health-related quality of life (HRQL) were assessed. RESULTS: The intervention resulted in a reduction in SBP compared to control (-18.3 vs. -7.6 mmHg, respectively, p ≤ 0.05) from baseline to 3-month post-intervention. Improvements in HRQL measures of bodily pain and social functioning were significantly associated with SBP improvements in both groups. CONCLUSION: Using hula as the physical activity component of a hypertension intervention can serve as a culturally congruent strategy to blood pressure management in NHPI with hypertension. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01995812.
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Características Culturales , Baile , Promoción de la Salud/métodos , Hipertensión/etnología , Nativos de Hawái y Otras Islas del Pacífico/estadística & datos numéricos , Adulto , Anciano , Femenino , Hawaii , Disparidades en el Estado de Salud , Humanos , Hipertensión/prevención & control , Masculino , Persona de Mediana Edad , Proyectos Piloto , Evaluación de Programas y Proyectos de SaludRESUMEN
The current theory of programmed temperature gas chromatography considers that solutes are focused by the stationary phase at the column head completely and does not explicitly recognize the different effects of initial temperature (To ) and heating rate (rT ) on the retention time or temperature of a homologue series. In the present study, n-alkanes, 1-alkenes, 1-alkyl alcohols, alkyl benzenes, and fatty acid methyl esters standards were used as model chemicals and were separated on two nonpolar columns, one moderately polar column and one polar column. Effects of To and rT on the retention of nonstationary phase focusing solutes can be explicitly described with isothermal and cubic equation models, respectively. When the solutes were in the stationary phase focusing status, the single-retention behavior of solutes was observed. It is simple, dependent upon rT only and can be well described by the cubic equation model that was visualized through four sequential slope analyses. These observed dual- and single-retention behaviors of solutes were validated by various experimental data, physical properties, and computational simulation.
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Mycobacterium smegmatis strain MC² 155 is an attractive model organism for the study of M. tuberculosis and other mycobacterial pathogens, as it can grow well using cholesterol as a carbon resource. However, its global transcriptomic response remains largely unrevealed. In this study, M. smegmatis MC² 155 cultivated in androstenedione, cholesterol and glycerol supplemented media were collected separately for a RNA-Sequencing study. The results showed that 6004, 6681 and 6348 genes were expressed in androstenedione, cholesterol and glycerol supplemented media, and 5891 genes were expressed in all three conditions, with 237 specially expressed in cholesterol added medium. A total of 1852 and 454 genes were significantly up-regulated by cholesterol compared with the other two supplements. Only occasional changes were observed in basic carbon and nitrogen metabolism, while almost all of the genes involved in cholesterol catabolism and mammalian cell entry (MCE) were up-regulated by cholesterol, but not by androstenedione. Eleven and 16 gene clusters were induced by cholesterol when compared with glycerol or androstenedione, respectively. This study provides a comprehensive analysis of the cholesterol responsive transcriptome of M. smegmatis. Our results indicated that cholesterol induced many more genes and increased the expression of the majority of genes involved in cholesterol degradation and MCE in M. smegmatis, while androstenedione did not have the same effect.
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Androstenodiona/metabolismo , Colesterol/metabolismo , Genoma Bacteriano , Glicerol/metabolismo , Mycobacterium smegmatis/metabolismo , Transcriptoma , Regulación Bacteriana de la Expresión Génica , Mycobacterium smegmatis/genética , Mycobacterium smegmatis/crecimiento & desarrolloRESUMEN
BACKGROUND: Inflammation may contribute to cardiovascular disease (CVD) among antiretrovirally suppressed HIV-infected individuals. We assessed relationships of monocyte, CD8 T-cell activation and plasma biomarkers to changes in carotid artery intima-media thickness (CIMT). METHODS: Longitudinal study of HIV-infected subjects ≥40 years and on stable antiretroviral therapy (ART) ≥3 months. Peripheral blood mononuclear cells were immunophenotyped by multiparameteric flow cytometry to quantify classical (CD14(++)CD16(-)), intermediate (CD14(++)CD16(+)), non-classical (CD14(low/+)CD16(++)) and transitional (CD14(+)CD16(-)) monocyte subsets and activated (CD38(+)HLA-DR(+)) CD8(+) T-cells at baseline. Plasma biomarkers were assessed by multiplex Luminex assay. High-resolution B-mode ultrasounds of right carotid arteries were obtained. Changes in CIMT over two years at the right common carotid artery (CIMTCCA) and right bifurcation (CIMTBIF) were outcome variables. RESULTS: We studied 50 subjects: 84% male, median age 49 (Q1, Q3; 46, 56) years, median CD4 count 461 (317, 578) cells/mm(3), and with HIV RNA ≤ 50 copies/mL in 84%. Change in CIMTBIF correlated with log values of baseline absolute count of non-classical monocytes (r = 0.37, p = 0.020), and with MCP-1 (r = 0.42, p = 0.0024) and TNF-α (r = 0.30, p = 0.036) levels. In multivariable linear regression, only non-classical monocytes and MCP-1 predicted the change in CIMTBIF, independent of Framingham Risk Score and baseline CIMTBIF. No correlation was noted between CD8 T-cell activation and CIMTBIF change. Monocyte subsets, CD8 T-cell activation, and biomarker concentrations were not correlated with changes in CIMTCCA. CONCLUSIONS: Our findings highlight the role of non-classical monocytes and MCP-1 in the progression of CIMTBIF in HIV-infected individuals on stable ART independent of traditional cardio-metabolic risk factors.
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Enfermedades de las Arterias Carótidas/diagnóstico , Enfermedades de las Arterias Carótidas/etiología , Grosor Intima-Media Carotídeo , Infecciones por VIH/complicaciones , Infecciones por VIH/inmunología , Monocitos/inmunología , Terapia Antirretroviral Altamente Activa , Biomarcadores , Recuento de Linfocito CD4 , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Femenino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/metabolismo , Humanos , Inmunofenotipificación , Leucocitos Mononucleares/inmunología , Leucocitos Mononucleares/metabolismo , Activación de Linfocitos/inmunología , Masculino , Persona de Mediana Edad , Monocitos/metabolismo , Fenotipo , PronósticoRESUMEN
BACKGROUND: Persistent inflammation and immune activation has been hypothesized to contribute to increased prevalence of subclinical atherosclerosis and cardiovascular disease (CVD) risk in patients with chronic HIV infection. In this study, we examined the correlation of peripheral monocyte subsets and soluble biomarkers of inflammation to coronary artery calcium (CAC) progression, as measured by cardiac computed tomography scan. METHODS: We conducted a longitudinal analysis utilizing baseline data of 78 participants with HIV infection on stable antiretroviral therapy (ART) in the Hawaii Aging with HIV-Cardiovascular study who had available baseline monocyte subset analysis as well as CAC measurement at baseline and at 2-year follow up. Monocyte phenotypes were assessed from cryopreserved blood by flow cytometry and plasma was assayed for soluble biomarkers using antibody-coated beads in a high sensitivity Milliplex Luminex platform. Change in CAC over 2 years was analyzed as the primary outcome variable. RESULTS: Of all monocyte subsets and biomarkers tested, higher non-classical monocyte percentage (ρ = 0.259, p = 0.022), interleukin (IL)-6 (ρ = 0.311, p = 0.012), and monocyte chemoattractant protein (MCP)-1 (ρ = 0.524, p = <0.001) were significantly correlated to higher 2-year CAC progression in unadjusted Spearman's correlation. Non-classical monocyte percentage (ρ = 0.247, p = 0.039), and MCP-1 (ρ = 0.487, p = <0.001), remained significantly correlated to 2-year CAC progression, while IL-6 was not (ρ = 0.209, p = 0.120) after adjustment for age, hypertension, diabetes mellitus, total/HDL cholesterol ratio, smoking history, and BMI. CONCLUSION: The percentage of non-classical monocytes and plasma MCP-1 levels were independently associated with CAC progression and may be related to the progression of atherosclerosis and increased CVD risk associated with chronic HIV infection on stable ART.
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Calcio/metabolismo , Enfermedades Cardiovasculares/complicaciones , Quimiocina CCL2/sangre , Vasos Coronarios/fisiopatología , Infecciones por VIH/sangre , Monocitos/citología , Adulto , Envejecimiento , Antirretrovirales/uso terapéutico , Biomarcadores/sangre , Calcinosis/fisiopatología , Enfermedades Cardiovasculares/tratamiento farmacológico , Comorbilidad , Vasos Coronarios/patología , Progresión de la Enfermedad , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , VIH-1 , Hawaii , Humanos , Inflamación , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Fenotipo , Tomografía Computarizada por Rayos XRESUMEN
This research evaluated the 2-year test-retest reliability of the Immediate Postconcussion Assessment and Cognitive Testing (ImPACT) neuropsychological battery, and clarified the need for biennial updated baseline testing of high school athletes. This study compared the baseline test scores of 212 non-concussed athletes that were obtained in Grade 9 and again 2 years later when they were in Grade 11. Regression-based methods indicated that 4 of the 5 ImPACT scores were stable over 2 years, as they fell within the 80% and 95% confidence intervals (CIs). The results suggested that updating baseline testing for high school athletes after 2 years is not necessary. Further research into the consistency of computerized neuropsychological tests over 2 years with high school athletes is recommended.
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Atletas/psicología , Conmoción Encefálica/diagnóstico , Pruebas Neuropsicológicas/estadística & datos numéricos , Reproducibilidad de los Resultados , Adolescente , Femenino , Humanos , Masculino , Instituciones AcadémicasRESUMEN
First, simply expounded the purpose and meaning of detecting tungsten extracted from prefi lable syringes: And then, designed simulation experiment for extracting tungsten from prefi lable glass syringes. and established determination methods of tungsten content by ICP-MSL Finaly, evaluated the limit of content of tungsten ?extracting from simulation experiment.
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Jeringas , TungstenoRESUMEN
HIV DNA in monocytes has been linked to HIV-associated neurocognitive disorders (HAND), however, characterization of monocyte subsets associated with HAND remains unclear. We completed a prospective study of antiretroviral therapy-naïve, HIV-infected Thais, with varying degrees of cognitive impairment, compared to HIV-uninfected controls. Monocyte subsets' CCR2, CCR5 and CD163 expression were profiled and inflammatory markers in plasma and cerebrospinal fluid (CSF), measured. Lower numbers of CCR2(+)non-classical monocytes were associated with worse neuropsychological test performance (r=0.43, p=0.024). CCR2(+)non-classical monocyte count inversely correlated with CSF neopterin (r=-0.43, p=0.035) and plasma TNF-α levels (r=-0.40, p=0.041). These data benchmark CCR2(+)non-classical monocytes as an independent index of cognitive impairment.
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Complejo SIDA Demencia/inmunología , Trastornos del Conocimiento/inmunología , Monocitos/virología , Adulto , Pueblo Asiatico , ADN Viral/análisis , Femenino , Citometría de Flujo , Humanos , Masculino , Monocitos/inmunología , Receptores CCR2/inmunología , TailandiaRESUMEN
Attention deficit/hyperactivity disorder (ADHD) is one of the most common psychiatric disorders of childhood. Despite its prevalence, the critical factors involved in its development remain to be identified. It was recently suggested that epigenetic mechanisms probably contribute to the etiology of ADHD. The present study was designed to examine the associations of epigenetic markers with ADHD among Chinese Han children, aiming to establish the prediction model for this syndrome from the epigenetic perspective. We conducted a pair-matching case-control study, and the ADHD children were systematically evaluated via structured diagnostic interviews, including caregiver interviews, based on the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, revised criteria (DSM-IV-R). The expression levels of risk genes DAT1, DRD4, DRD5, as well as their promoter methylation, were determined respectively, followed by the expression profiles of histone-modifying genes p300, MYST4, HDAC1, MeCP2. The multivariate logistic regressions were performed to establish ADHD prediction models. All of the seven genes tested were identified as risk factors for ADHD. The methylation of one critical CpG site located upstream of DRD4 was shown to affect its transcription, suggesting a role in ADHD's development. Aberrant DNA methylation and histone acetylation were indicated in ADHD patients. In addition, a prediction model was established using the combination of p300, MYST4 and HDAC1, with the accuracy of 0.9338. This is, to our knowledge, the first study to clearly demonstrate the associations between epigenetic markers and ADHD, shedding light on the preliminary diagnosis and etiological studies of this widespread disorder.
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Trastorno por Déficit de Atención con Hiperactividad/epidemiología , Trastorno por Déficit de Atención con Hiperactividad/genética , Trastorno por Déficit de Atención con Hiperactividad/fisiopatología , Epigénesis Genética/fisiología , Trastorno por Déficit de Atención con Hiperactividad/inducido químicamente , Niño , China/epidemiología , China/etnología , Islas de CpG/genética , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/genética , Femenino , Histona Acetiltransferasas/genética , Histona Desacetilasas/genética , Humanos , Plomo/toxicidad , Modelos Logísticos , Masculino , Proteína 2 de Unión a Metil-CpG/genética , ARN Mensajero/metabolismo , Receptores Dopaminérgicos/genética , Factores de Riesgo , Factores Sexuales , Metiltransferasa de ADN de Sitio Específico (Adenina Especifica)/genética , Estadística como AsuntoRESUMEN
Statistical principles and methods are critical to the success of biomedical and translational research. However, it is difficult to track and evaluate the monetary value of a biostatistician to a medical school (SoM). Limited published data on this topic is available, especially comparing across SoMs. Using National Institutes of Health (NIH) awards and American Association of Medical Colleges (AAMC) faculty counts data (2010-2013), together with online information on biostatistics faculty from 119 institutions across the country, we demonstrated that the number of biostatistics faculty was significantly positively associated with the amount of NIH awards, both as a school total and on a per faculty basis, across various sizes of U.S. SoMs. Biostatisticians, as a profession, need to be proactive in communicating and advocating the value of their work and their unique contribution to the long-term success of a biomedical research enterprise.
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Although reduced bone mineral density in survivors of childhood acute lymphoblastic leukemia (ALL) is well documented, the degree of demineralization and relation to age are not well described. This is a retrospective chart analysis of 58 patients consecutively treated for ALL without relapse, cranial irradiation, or transplantation. Bone mineral densities were measured by dual-energy x-ray absorptiometry and patients were divided by sex and age (≤5, 6 to 10, and >10 y) at diagnosis. Serial scans for 6 years after therapy were analyzed as Z-scores. Over 6 years after therapy, 93.1% of patients exhibited a decreased Z-score in at least 1 anatomic site. The difference in Z-score among the age cohorts was significant at both the lumbar spine and femoral neck. Patients older than 10 years at diagnosis had the lowest Z-scores: -2.78 and -2.87 for boys and -2.39 and -2.91 for girls at the lumbar spine and femoral neck, respectively. Children after ALL therapy exhibit a significant bone mineral deficit shortly after completion of therapy that persists for at least 6 years. The degree of bone demineralization can be followed up by a dual-energy x-ray absorptiometry scan and is most severe in patients older than 10 years at the initiation of therapy.
Asunto(s)
Densidad Ósea/efectos de los fármacos , Densidad Ósea/efectos de la radiación , Osteoporosis/epidemiología , Osteoporosis/etiología , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Absorciometría de Fotón , Antineoplásicos/efectos adversos , Huesos/efectos de los fármacos , Huesos/patología , Huesos/efectos de la radiación , Niño , Preescolar , Irradiación Craneana/efectos adversos , Femenino , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Lactante , Masculino , Estudios Retrospectivos , SobrevivientesRESUMEN
HIV-associated neurocognitive disorders (HAND) continues to be prevalent (30-50%) despite plasma HIV-RNA suppression with combination antiretroviral therapy (cART). There is no proven therapy for individuals on suppressive cART with HAND. We have shown that the degree of HIV reservoir burden (HIV DNA) in monocytes appear to be linked to cognitive outcomes. HIV infection of monocytes may therefore be critical in the pathogenesis of HAND. A single arm, open-labeled trial was conducted to examine the effect of maraviroc (MVC) intensification on monocyte inflammation and neuropsychological (NP) performance in 15 HIV subjects on stable 6-month cART with undetectable plasma HIV RNA (<48 copies/ml) and detectable monocyte HIV DNA (>10 copies/10(6) cells). MVC was added to their existing cART regimen for 24 weeks. Post-intensification change in monocytes was assessed using multiparametric flow cytometry, monocyte HIV DNA content by PCR, soluble CD163 (sCD163) by an ELISA, and NP performance over 24 weeks. In 12 evaluable subjects, MVC intensification resulted in a decreased proportion of circulating intermediate (median; 3.06% (1.93, 6.45) to 1.05% (0.77, 2.26)) and nonclassical (5.2% (3.8, 7.9) to 3.2% (1.8, 4.8)) CD16-expressing monocytes, a reduction in monocyte HIV DNA content to zero log10 copies/10(6) cells and in levels of sCD163 of 43% by 24 weeks. This was associated with significant improvement in NP performance among six subjects who entered the study with evidence of mild to moderate cognitive impairment. The results of this study suggest that antiretroviral therapy with potency against monocytes may have efficacy against HAND.