PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-12 (12)
 

Clipboard (0)
None

Select a Filter Below

Journals
more »
Year of Publication
Document Types
1.  Timing and Intensity of Light Correlate with Body Weight in Adults 
PLoS ONE  2014;9(4):e92251.
Light exposure can influence sleep and circadian timing, both of which have been shown to influence weight regulation. The goal of this study was to evaluate the relationship between ambient light, sleep and body mass index. Participants included 54 individuals (26 males, mean age 30.6, SD = 11.7 years). Light levels, sleep midpoint and duration were measured with wrist actigraphy (Actiwatch-L) for 7 days. BMI was derived from self-reported height and weight. Caloric intake was determined from 7 days of food logs. For each participant, light and activity data were output in 2 minute epochs, smoothed using a 5 point (10 minute) moving average and then aggregated over 24 hours. The mean light timing above 500 lux (MLiT500) was defined as the average clock time of all aggregated data points above 500 lux. MLiT500 was positively correlated with BMI (r = 0.51, p<0.001), and midpoint of sleep (r = 0.47, p<0.01). In a multivariable linear regression model including MLiT500 and midpoint of sleep, MLiT500 was a significant predictor of BMI (B = 1.26 SE = 0.34, β = 0.53 p = 0.001, r2Δ = 0.22). Adjusting for covariates, MLiT500 remained an independent predictor of BMI (B = 1.28 SE = 0.36, β = 0.54, p = 0.002, r2Δ = 0.20). The full model accounted for 34.7% of the variance in BMI (p = 0.01). Exposure to moderate levels of light at biologically appropriate times can influence weight, independent of sleep timing and duration.
doi:10.1371/journal.pone.0092251
PMCID: PMC3973603  PMID: 24694994
2.  Systematic evaluation of Axis-I DSM diagnoses in Delayed Sleep Phase Disorder and Evening-Type Circadian Preference 
Sleep medicine  2012;13(9):1171-1177.
Background
Alterations in circadian rhythms can have profound effects on mental health. High co-morbidity for psychiatric disorders has been observed in patients with circadian rhythm disorders, such as delayed sleep phase disorder (DSPD) and in those with an evening-type circadian preference. The aim of this study was to systematically determine the prevalence and type of DSM IV AXIS-I disorders in those with DSPD compared to evening-type controls.
Methods
Forty-eight DSPD and 25 evening-type participants took part in this study. Sleep and wake parameters were assessed with actigraphy, diary and questionnaires (Pittsburgh Sleep Quality Index (PSQI) and Functional Outcomes of Sleep Questionnaire (FOSQ)). Evening-type preference was defined by the Horne-Ostberg questionnaire. DSPD was determined by interview according to International Classification of Sleep Disorders criteria. Current and past diagnosis of psychiatric disorders were assessed with a Structured Clinical Interview for DSM-IV disorders.
Results
DSPD was associated with a later wake time, longer sleep time, higher PSQI score, lower Horne-Ostberg and FOSQ scores compared to evening-types. There were no significant differences in the prevalence or type of AXIS-I disorders between those with DSPD or evening type preference. Over 70% of participants met criteria for at least one past AXIS-I disorder. Approximately 40% of both the DSPD and evening-types met criteria for a past diagnosis of mood, anxiety (most frequently phobia) or substance use disorders. Evening types were more likely to have a past diagnosis of more that one AXIS-I disorder.
Conclusions
These results highlight the important link between circadian rhythms and mental disorders. Specifically, an evening circadian chronotype regardless of DSPD status is associated with a risk for anxiety, depressive or substance use disorders.
doi:10.1016/j.sleep.2012.06.024
PMCID: PMC3474860  PMID: 22910327
circadian; sleep; depression; delayed sleep phase disorder
4.  Racial Differences in Risks for First Cardiovascular Events and Non-Cardiovascular Death: the Atherosclerosis Risk in Communities Study (ARIC), the Cardiovascular Health Study (CHS), and the Multi-Ethnic Study of Atherosclerosis (MESA) 
Circulation  2012;126(1):50-59.
Background
No studies have compared first CVD events and non-CVD death between races in a competing risks framework, which examines risks for numerous events simultaneously.
Methods and Results
We used competing Cox models to estimate hazards for first CVD events and non-CVD death within and between races in three multi-center, NHLBI-sponsored cohorts. Of 14569 ARIC study participants aged 45–64y with mean follow up of 10.5y, 11.6% had CVD and 5.0% had non-CVD death as first events; among 4237 CHS study participants aged 65–84y and followed for 8.5y, these figures were 43.2% and 15.7%, respectively. Middle-aged blacks were significantly more likely than whites to experience any CVD as a first event; this disparity disappeared by older adulthood and after adjustment for CVD risk factors. The pattern of results was similar for MESA participants. Traditional Cox and competing risks models yielded different results for CHD risk. Black men appeared somewhat more likely than white men to experience CHD using a standard Cox model (HR 1.06; 95% CI 0.90, 1.26) whereas they appeared less likely than white men to have a first CHD event using a competing risks model (HR 0.77; 95% CI 0.60, 1.00).
Conclusions
CVD affects blacks at an earlier age than whites; this may be partially attributable to elevated CVD risk factor levels among blacks. Racial disparities in first CVD incidence disappear by older adulthood. Competing risks analyses may yield somewhat different results than traditional Cox models and provide a complementary approach to examining risks for first CVD events.
doi:10.1161/CIRCULATIONAHA.111.057232
PMCID: PMC3437934  PMID: 22693351
cardiovascular diseases; epidemiology; prevention; risk factors; survival
5.  Proton therapy for hepatocellular carcinoma 
Proton radiotherapy has seen an increasing role in the treatment of hepatocellular carcinoma (HCC). Historically, external beam radiotherapy has played a very limited role in HCC due to a high incidence of toxicity to surrounding normal structures. The ability to deliver a high dose of radiation to the tumor is a key factor in improving outcomes in HCC. Advances in photon radiotherapy have improved dose conformity and allowed dose escalation to the tumor. However, despite these advances there is still a large volume of normal liver that receives a considerable radiation dose during treatment. Proton beams do not have an exit dose along the beam path once they enter the body. The inherent physical attributes of proton radiotherapy offer a way to maximize tumor control via dose escalation while avoiding excessive radiation to the remaining liver, thus increasing biological effectiveness. In this review we discuss the physical attributes and rationale for proton radiotherapy in HCC. We also review recent literature regarding clinical outcomes of using proton radiotherapy for the treatment of HCC.
doi:10.3978/j.issn.1000-9604.2012.10.09
PMCID: PMC3551328  PMID: 23359779
Proton radiotherapy; hepatocellular carcinoma (HCC)
6.  Quantitative prediction of cellular metabolism with constraint-based models: the COBRA Toolbox v2.0 
Nature Protocols  2011;6(9):1290-1307.
Over the past decade, a growing community of researchers has emerged around the use of COnstraint-Based Reconstruction and Analysis (COBRA) methods to simulate, analyze and predict a variety of metabolic phenotypes using genome-scale models. The COBRA Toolbox, a MATLAB package for implementing COBRA methods, was presented earlier. Here we present a significant update of this in silico ToolBox. Version 2.0 of the COBRA Toolbox expands the scope of computations by including in silico analysis methods developed since its original release. New functions include: (1) network gap filling, (2) 13C analysis, (3) metabolic engineering, (4) omics-guided analysis, and (5) visualization. As with the first version, the COBRA Toolbox reads and writes Systems Biology Markup Language formatted models. In version 2.0, we improved performance, usability, and the level of documentation. A suite of test scripts can now be used to learn the core functionality of the Toolbox and validate results. This Toolbox lowers the barrier of entry to use powerful COBRA methods.
doi:10.1038/nprot.2011.308
PMCID: PMC3319681  PMID: 21886097
Systems Biology; Computational Biology; MATLAB; Flux Balance Analysis; Fluxomics; Visualization; Gap Filling; Metabolic Engineering
7.  Association of the 4 g/5 g polymorphism of plasminogen activator inhibitor-1 gene with sudden sensorineural hearing loss. A case control study 
Background
The 5 G/5 G genotype of PAI-1 polymorphism is linked to decreased plasminogen activator inhibitor-1 (PAI-1) levels and it has been suggested that lower PAI-1 levels may provide protective effects on inflammation, local microcirculatory disturbance, and fibrotic changes, which are likely associated with development of sudden sensorineural hearing loss (SSNHL).
Methods
The association of the 4 G/5 G PAI-1 polymorphism with the development and clinical outcome of SSNHL is evaluated via a case control study. 103 patients with SSNHL and 113 age and sex-matched controls were enrolled at University of Ferrara, Italy and hearing loss outcome was measured at least 3 months after the onset of hearing loss. DNA was isolated from peripheral blood using the QIAamp kit and the 4 G/5 G polymorphism in the −675 promoter region was genotyped with an allele-specific PCR. Genotype distribution was tested in patients and compared to controls by chi-square and odd-ratio analysis. The codominant and recessive models were used for the multiple logistic regression analyses of the PAI-1 gene allele.
Results
In this population, 5 G/5 G genotype had a two-time lower frequency in SSNHL patients compared to healthy controls (15.5% vs 30.1%) and was associated with decreased odds compared to 4 G/5 G genotype (OR 0.37, 95% CI 0.19-0.75, p = 0.005). In addition, the patients with 5 G/5 G genotype showed a trend of more than 2 times higher ratio of hearing recovery (> 20 dB) after systemic corticosteroid treatment compared to 4 G/5 G genotype (OR 2.3, 95% CI 0.32 - 16.83, p = 0.39), suggesting a better clinical outcome.
Conclusions
The 5 G/5 G genotype of PAI-1 may be associated with a reduced risk of SSNHL in the Italian population.
doi:10.1186/1472-6815-12-5
PMCID: PMC3431267  PMID: 22672326
Sudden hearing loss; Plasminogen activator inhibitor-1; 4 G/5 G polymorphism
9.  Factors Associated with Presence and Extent of Coronary Calcium in Individuals Predicted to be at Low Risk Based on Framingham Risk Score (From The Multi-Ethnic Study of Atherosclerosis) 
The American journal of cardiology  2011;107(6):879-885.
Even among asymptomatic people at low risk (<10%) by Framingham Risk Score (FRS), high coronary artery calcium (CAC) scores signify higher predicted risk of coronary heart disease (CHD) events. We sought to determine non-invasive factors (without radiation exposure) significantly associated with CAC in low-risk, asymptomatic persons. In a cross-sectional analysis, we studied 3046 participants from MESA at low 10-year predicted risk (FRS <10%) for CHD events. Multivariable logistic regression was used to assess the association of novel markers with presence of any CAC (CAC >0) and advanced CAC (CAC ≥ 300). CAC >0 and CAC ≥ 300 were present in 30% and 3.5% of participants, respectively. Factor VIIIc, fibrinogen and sICAM were each associated with CAC presence (P ≤ 0.02); and C-reactive protein, D-dimer and carotid intima-media thickness (CIMT) with advanced CAC (P ≤ 0.03). The base model combining traditional risk factors had excellent discrimination for advanced CAC (C-statistic, 0.808). Addition of the 2 best-fit models combining biomarkers plus/minus CIMT improved the c-statistics to 0.822 and 0.820, respectively. All 3 models calibrated well, but were similar in estimating individual risk probabilities for advanced CAC (prevalence = 9.97%, 10.63% and 10.10% in the highest quartiles of predicted probabilities versus 0.26%, 0.26% and 0.26% in the lowest quartiles, respectively). In conclusion, in low risk individuals, traditional risk factors alone predicted advanced CAC with high discrimination and calibration. Biomarker combinations +/− CIMT were also significantly associated with advanced CAC, but improvement in prediction and estimation of clinical risk were modest compared to traditional risk factors alone.
doi:10.1016/j.amjcard.2010.10.072
PMCID: PMC3182475  PMID: 21376929
coronary calcium; biomarkers; novel markers; low-risk; risk factors
10.  Efficacy of High-dose Chemotherapy and Autologous Stem Cell Transplantation in Patients with Relapsed Medulloblastoma: A Report on The Korean Society for Pediatric Neuro-Oncology (KSPNO)-S-053 Study 
Journal of Korean Medical Science  2010;25(8):1160-1166.
The efficacy and toxicity of high-dose chemotherapy and autologous stem cell transplantation (HDCT/ASCT) were investigated for improving the outcomes of patients with relapsed medulloblastoma. A total of 15 patients with relapsed medulloblastoma were enrolled in the KSPNO-S-053 study from May 2005 to May 2007. All patients received approximately 4 cycles of salvage chemotherapy after relapse. Thirteen underwent HDCT/ASCT; CTE and CM regimen were employed for the first HDCT (HDCT1) and second HDCT (HDCT2), respectively, and 7 underwent HDCT2. One transplant related mortality (TRM) due to veno-occlusive disease (VOD) occurred during HDCT1 but HDCT2 was tolerable with no further TRM. The 3-yr overall survival probability and event-free survival rates ±95% confidence intervals (CI) were 33.3±12.2% and 26.7% ±11.4%, respectively. When analysis was confined to only patients who had a complete response (CR) or partial response (PR) prior to HDCT, the probability of 3-yr overall survival rates ±95% CI was 40.0±15.5%. No patients with stable disease (SD) or progressive disease (PD) survived. Survival rates from protocol KSPNO-S-053 are encouraging and show that tumor status prior to HDCT/ASCT is an important factor to consider for improving survival rates of patients with relapsed medulloblastoma.
doi:10.3346/jkms.2010.25.8.1160
PMCID: PMC2908784  PMID: 20676326
Recurrence; Medulloblastoma; Transplantation, Autologous; Tandem; Hematopoietic Stem Cell Transplantation
11.  An Association between Clotting Factor VII and Carotid Intima-Media Thickness: The CARDIA Study 
Purpose
To investigate associations of procoagulants (FVII, FVIII, von Willebrand factor [vWF]) with subclinical atherosclerosis, we examined participants in The Coronary Artery Risk Development in Young Adults (CARDIA) Study.
Methods
Clotting factor assays were performed in 1254 participants ages 23–37 (baseline) and repeated at ages 38–50 (follow-up). Carotid intima-media thickness (IMT) was measured at follow-up.
Results
Baseline levels of procoagulants (%): mean (SD) were: FVII: 76(18), FVIII: 102(38), and vWF: 108(47). At follow-up, all had increased by 40%–55%. After age adjustment, mean common carotid (CC) IMT increased from the lowest to the highest tertile of FVII in the total group (0.787 to 0.801, P=0.007), in whites (0.772 to 0.790, P=0.002), and in men (0.807 to 0.827, P=0.015). All associations were attenuated by multivariable adjustment. However, participants with FVII values in the highest tertile at one or both examinations, as compared with those in the lowest tertile, had greater CC-IMT after age and multivariable adjustment (0.806 versus 0.778, P<0.05). Baseline FVIII was associated with greater internal carotid (IC) IMT in the total group, in whites, and in women after age but not multivariable adjustment. No associations were seen for vWF.
Conclusions
FVII is associated with CC-IMT in young adults, but the strength of the association is modified by other cardiovascular disease risk factors, such as body mass index. FVIII is associated with IC IMT only in age-adjusted analyses, and no associations were observed for vWF.
doi:10.1161/STROKEAHA.110.580100
PMCID: PMC2894290  PMID: 20466994
Factor VII; Carotid Thickening; Atherosclerosis; Factor VIII
12.  5-Halogenated pyrimidine lesions within a CpG sequence context mimic 5-methylcytosine by enhancing the binding of the methyl-CpG-binding domain of methyl-CpG-binding protein 2 (MeCP2) 
Nucleic Acids Research  2005;33(9):3057-3064.
Perturbations in cytosine methylation signals are observed in the majority of human tumors; however, it is as yet unknown how methylation patterns become altered. Epigenetic changes can result in the activation of transforming genes as well as in the silencing of tumor suppressor genes. We report that methyl-CpG-binding proteins (MBPs), specific for methyl-CpG dinucleotides, bind with high affinity to halogenated pyrimidine lesions, previously shown to result from peroxidase-mediated inflammatory processes. Emerging data suggest that the initial binding of MBPs to methyl-CpG sequences may be a seeding event that recruits chromatin-modifying enzymes and DNA methyltransferase, initiating a cascade of events that result in gene silencing. MBD4, a protein with both methyl-binding and glycosylase activity demonstrated repair activity against a series of 5-substituted pyrimidines, with the greatest efficiency against 5-chlorouracil, but undetectable activity against 5-chlorocytosine. The data presented here suggest that halogenated pyrimidine damage products can potentially accumulate and mimic endogenous methylation signals.
doi:10.1093/nar/gki612
PMCID: PMC1140371  PMID: 15917437

Results 1-12 (12)