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1.  A Low Selenium Level Is Associated with Lung and Laryngeal Cancers 
PLoS ONE  2013;8(3):e59051.
Purpose
It has been suggested that selenium deficiency is a risk factor for several cancer types. We conducted a case-control study in Szczecin, a region of northwestern Poland, on 95 cases of lung cancer, 113 cases of laryngeal cancer and corresponding healthy controls.
Methods
We measured the serum level of selenium and established genotypes for four variants in four selenoprotein genes (GPX1, GPX4, TXNRD2 and SEP15). Selenium levels in the cases were measured after diagnosis but before treatment. We calculated the odds of being diagnosed with lung or laryngeal cancer, conditional on selenium level and genotype.
Results
Among lung cancer cases, the mean selenium level was 63.2 µg/l, compared to a mean level of 74.6 µg/l for their matched controls (p<0.0001). Among laryngeal cancer cases, the mean selenium level was 64.8 µg/l, compared to a mean level of 77.1 µg/l for their matched controls (p<0.0001). Compared to a serum selenium value below 60 µg/l, a selenium level above 80 µg/l was associated with an odds ratio of 0.10 (95% CI 0.03 to 0.34; p = 0.0002) for lung cancer and 0.23 (95% CI 0. 09 to 0.56; p = 0.001) for laryngeal cancer. In analysis of four selenoprotein genes we found a modest evidence of association of genetic variant in GPX1 with the risk of lung and laryngeal cancers.
Conclusion
A selenium level below 60 µg/l is associated with a high risk of both lung and laryngeal cancer.
doi:10.1371/journal.pone.0059051
PMCID: PMC3596323
2.  Associations between Posttraumatic Stress Disorder Symptom Clusters and Cigarette Smoking 
Understanding the relationship between Posttraumatic stress disorder (PTSD) and cigarette smoking has been difficult due to PTSD’s symptomatic heterogeneity. This study examined common and unique lifetime cross-sectional relationships between PTSD symptom clusters (Re-experiencing [intrusive thoughts and nightmares about the trauma], Avoidance [avoidance of trauma-associated memories or stimuli], Emotional Numbing [loss of interest, interpersonal detachment, restricted positive affect], and Hyperarousal [irritability, difficulty concentrating, hypervigilance, insomnia]) and three indicators of smoking behavior: (1) smoking status; (2) cigarettes per day; and (3) nicotine dependence. Participants were adult respondents in the National Epidemiologic Survey of Alcohol and Related Conditions with a trauma history (N=23,635). All four symptom clusters associated with each smoking outcome in single-predictor models (ps<.0001). In multivariate models including all of the symptom clusters as simultaneous predictors, Emotional Numbing was the only cluster to retain a significant association with lifetime smoking over and above the other clusters, demographics, and Axis-I comorbidity (OR=1.30, p<.01). While Avoidance uniquely associated with smoking status and nicotine dependence in multivariate models, these relations fellow below significance after adjusting for demographics and comorbidity. No clusters uniquely associated with cigarettes per day. Hyperarousal uniquely related with nicotine dependence over and above the other clusters, demographics, and Axis-I comorbidity (OR=1.51, p<.001). These results suggest that: (a) common variance across PTSD symptom clusters contribute to PTSD’s linkage with smoking in the American population; and (b) certain PTSD symptom clusters may uniquely associate with particular indicators of smoking behavior. These findings may clarify the underpinnings of PTSD-smoking comorbidity and inform smoking interventions for trauma-exposed individuals.
doi:10.1037/a0024328
PMCID: PMC3307596  PMID: 21688875
Posttraumatic Stress Disorder; Smoking; Comorbidity; Nicotine Dependence; Posttraumatic Stress Disorder Symptom Clusters
3.  Can we update the Summary Hospital Mortality Index (SHMI) to make a useful measure of the quality of hospital care? An observational study 
BMJ Open  2013;3(1):e002018.
Objective
To advance methods for the estimation of hospital performance based upon mortality ratios.
Design
Observational study estimating trust performance in a year derived according to comparative standards from a 3-year period, accounting for patient-level case-mix and overdispersion (unexplained variability).
Participants
23 363 630 admissions to the English National Health Service (NHS) by NHS Trust.
Main outcome measures
Number of SDs (QUality and Outcomes Research Unit Measure, QUORUM banding) and comparative odds of hospital mortality difference from mean performance by trust compared for 2010/2011, 2008/2009 and 2009/2010, accounting for patient-level case-mix.
Results
The model was highly predictive of mortality (C statistic=0.93), and well calibrated by risk stratum. There was substantial overdispersion. No trusts were more than 3 SDs above the mean, and only one trust was more than 2 SDs above the mean for 2010/2011.
Conclusions
QUORUM is highly predictive of patient mortality in hospital or up to 30 days after admission. However, like the Summary Hospital Mortality Indicator (SHMI), QUORUM is subjected to considerable remaining legitimate but unexplained variation. It is unlikely that measures like QUORUM and SHMI will be useful beyond identifying a very small number of trusts as potential outliers.
doi:10.1136/bmjopen-2012-002018
PMCID: PMC3563139  PMID: 23370014
Public Health; Education & Training (See Medical Education & Training); Epidemiology
4.  Electrocorticography Links Human Temporoparietal Junction to Visual Perception 
Nature neuroscience  2012;15(7):957-959.
Electrical stimulation of visual cortex can produce a visual percept (phosphene). We electrically stimulated visual cortex in human patients implanted with subdural electrodes while recording from other brain sites. Across experimental manipulations, we found that phosphene perception occurred only if stimulation evoked high-frequency gamma oscillations in the temporoparietal junction (TPJ), a brain region associated with visual extinction and neglect. Electrical stimulation of TPJ modified detectability of low-contrast visual stimuli.
doi:10.1038/nn.3131
PMCID: PMC3386474  PMID: 22660480
7.  Protein Tyrosine Phosphatase µ (PTP µ or PTPRM), a Negative Regulator of Proliferation and Invasion of Breast Cancer Cells, Is Associated with Disease Prognosis 
PLoS ONE  2012;7(11):e50183.
Background
PTPRM has been shown to exhibit homophilic binding and confer cell-cell adhesion in cells including epithelial and cancer cells. The present study investigated the expression of PTPRM in breast cancer and the biological impact of PTPRM on breast cancer cells.
Design
Expression of PTPRM protein and gene transcript was examined in a cohort of breast cancer patients. Knockdown of PTPRM in breast cancer cells was performed using a specific anti-PTPRM transgene. The impact of PTPRM knockdown on breast cancer was evaluated using in vitro cell models.
Results
A significant decrease of PTPRM transcripts was seen in poorly differentiated and moderately differentiated tumours compared with well differentiated tumours. Patients with lower expression of PTPRM had shorter survival compared with those which had a higher level of PTPRM expression. Knockdown of PTPRM increased proliferation, adhesion, invasion and migration of breast cancer cells. Furthermore, knockdown of PTPRM in MDA-MB-231 cells resulted in increased cell migration and invasion via regulation of the tyrosine phosphorylation of ERK and JNK.
Conclusions
Decreased expression of PTPRM in breast cancer is correlated with poor prognosis and inversely correlated with disease free survival. PTPRM coordinated cell migration and invasion through the regulation of tyrosine phosphorylation of ERK and JNK.
doi:10.1371/journal.pone.0050183
PMCID: PMC3502354  PMID: 23185569
8.  Affective decision-making deficits, linked to a dysfunctional ventromedial prefrontal cortex, revealed in 10th grade Chinese adolescent binge drinkers 
Neuropsychologia  2007;46(2):714-726.
The primary aim of this study was to test the hypothesis that adolescent binge drinkers, but not lighter drinkers, would show signs of impairment on tasks of affective decision-making as measured by the Iowa Gambling Test (IGT), when compared to adolescents who never drank.
We tested 207 10th grade adolescents in Chengdu City, China, using two versions of the IGT, the original and a variant, in which the reward/punishment contingencies were reversed. This enables one to distinguish among different possibilities of impaired decision-making, such as insensitivity to long-term consequences, or hypersensitivity to reward. Furthermore, we tested working memory capacity using the Self-ordered Pointing Test (SOPT). Paper and pencil questionnaires were used to assess drinking behaviors and school academic performance.
Results indicated that relative to never-drinkers, adolescent binge drinkers, but not other (ever, past 30-day) drinkers, showed significantly lower net scores on the original version of the IGT especially in the latter trials. Furthermore, the profiles of behavioral performance from the original and variant versions of the IGT were consistent with a decision-making impairment attributed to hypersensitivity to reward. In addition, working memory and school academic performance revealed no differences between drinkers (at all levels) and never-drinkers. Logistic regression analysis showed that after controlling for demographic variables, working memory, and school academic performance, the IGT significantly predicted binge-drinking.
These findings suggest that a “myopia” for future consequences linked to hypersensitivity to reward is a key characteristic of adolescents with binge-drinking behavior, and that underlying neural mechanisms for this “myopia” for future consequences may serve as a predisposing factor that renders some adolescents more susceptible to future addictive behaviors.
doi:10.1016/j.neuropsychologia.2007.09.012
PMCID: PMC3498846  PMID: 17996909
Executive function; Affective control; Reward; Working memory; Adolescent drinking; Iowa Gambling Test
9.  Boosting a Teen Substance Use Prevention Program with Motivational Interviewing 
Substance use & misuse  2012;47(4):418-428.
A brief motivational interviewing (MI) intervention may be a viable adjunct to school-based substance abuse prevention programs. This article describes the development and implementation of a brief MI intervention with 573 adolescents (mean age 16.8; 40.3% female, 68% Latino) enrolled in eight continuation high schools in Southern California. Study participants were assigned to the MI condition in a randomized controlled trial of Project Toward No Drug Abuse. Data are provided on dosage, topics discussed, and quality of MI determined with the Motivational Interviewing Skill Code (MISC). Results suggest that the protocol was feasible and implemented with adequate fidelity. The study’s limitations are noted.
doi:10.3109/10826084.2011.641057
PMCID: PMC3496395  PMID: 22216936
adolescent; motivational interviewing; substance use; prevention; intervention; telephone; school-based; booster
10.  Gene therapy using the human telomerase catalytic subunit gene promoter enables targeting of the therapeutic effects of vesicular stomatitis virus matrix protein against human lung adenocarcinoma 
The catalytic subunit of telomerase, human telomerase reverse transcriptase (hTERT), is highly active in immortalized cells and more than 90% of human cancer cells, but is quiescent in the majority of normal somatic cells. Thus, the hTERT promoter has been extensively used in targeted cancer gene therapy. Vesicular stomatitis virus (VSV) matrix protein (MP) induces the apoptosis of tumor cells in the absence of other viral components. In our previous studies, we successfully constructed the pVAX-M plasmid from the pVAX plasmid, which expressed wild-type VSV MP (VSV MP is under the control of the CMV promoter) and demonstrated that pVAX-M efficiently suppresses the growth of malignant tumors via the induction of apoptosis in vitro and in vivo. The present study was designed to construct the plasmid phTERTM (VSV MP is under the control of the hTERT promoter) and investigate whether it had a targeted antitumor effect in nude mice bearing human lung adenocarcinoma. In vitro, A549 human lung adenocarcinoma cells were treated with NS, Lip-null, etoposide, Lip-pVAX-M or Lip-phTERT-M, and examined for cell viability through MTT assays or for apoptosis by flow cytometry and TUNEL assays. In vivo, A549 human lung carcinoma models in nude mice were established. Mice were treated with 10 4-weekly intravenous administrations of NS, Lip-null, etoposide (2 mg/kg), Lip-pVAX-M or Lip-phTERT-M. Subsequently, Lip-phTERT-M was found to be the most efficient inhibitor of tumor growth and inducer of tumor cell apoptosis when compared with the other groups in vivo and in vitro (P<0.05). Notably, immunohistochemical staining showed that Lip-phTERT-M significantly limited the overexpression of VSV MP to the tumor tissues and reduced VSV MP expression in other organs in comparison with Lip-pVAX-M (P<0.05). Therefore, it can be concluded that phTERT-M demonstrates a targeted antitumor effect on A549 human lung adenocarcinoma cells. These observations suggest that phTERT-M gene therapy may be a novel and potent strategy for targeting human lung adenocarcinoma.
doi:10.3892/etm.2012.679
PMCID: PMC3493746  PMID: 23226739
vesicular stomatitis virus matrix protein; phTERT-M; pVAX-M; apoptosis; targeted antitumor effect
11.  Histological and immunohistochemical features of the spleen in persistent polyclonal B-cell lymphocytosis closely mimic splenic B-cell lymphoma 
Diagnostic Pathology  2012;7:107.
Persistent polyclonal B-cell lymphocytosis (PPBL) is rare and intriguing hematological disorder predominantly reported in young to middle- aged smoking women. It is characterized by persistent moderate polyclonal B-cell lymphocytosis with circulating hallmark binucleated lymphocytes and elevated polyclonal serum IgM. Most patients have benign clinical course on long-term follow-up. Some pathologic features of PPBL may resemble malignant lymphoma, including morphology as well as frequent cytogenetic and molecular abnormalities. Significant symptomatic splenomegaly requiring splenectomy is very unusual for this disorder; therefore there is a lack of descriptions of the morphologic features of the spleen in the literature. We present here one of the first detailed descriptions of the morphologic and immunohistochemical features of the spleen from a young female with PPBL who developed massive splenomegaly during 6-year follow up. Splenectomy was performed for symptomatic relief and suspicion of malignant process. The morphological and immunohistochemical features of the spleen closely mimicked involvement by B-cell lymphoma, however there was no monotypic surface light chain restriction seen by flow cytometry and no clonal rearrangement of IgH gene was detected by molecular analysis. Evaluating a splenectomy sample in cases like this may present a diagnostic challenge to pathologists. Therefore, correlation with B cell clonality studies (by flow cytometry and molecular analysis), clinical findings and peripheral blood morphology searching for characteristic binucleated lymphocytes is essential to avoid misdiagnosing this benign process as B-cell lymphoma. We also present here a literature review on pathogenesis of PPBL.
Virtual slides
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/5329558967545656
doi:10.1186/1746-1596-7-107
PMCID: PMC3488513  PMID: 22901769
Persistent polyclonal B cell lymphocytosis; Splenomegaly; Lymphoma; Binucleated lymphocytes
12.  Diabetes and Breast Cancer Among Women With BRCA1 and BRCA2 Mutations 
Cancer  2010;117(9):1812-1818.
BACKGROUND
Hyperinsulinemia and the metabolic syndrome are both risk factors for breast cancer. It is not clear if diabetes is associated with the risk of breast cancer in women with a BRCA1 or BRCA2 mutation.
METHODS
The authors reviewed the medical histories of 6052 women with a BRCA1 or BRCA2 mutation, half of whom had been diagnosed with breast cancer. They estimated the odds ratio for breast cancer, given a self-report of diabetes. They then estimated the hazard ratio for a new diagnosis of diabetes associated with a history of breast cancer.
RESULTS
There was no excess of diabetes in the period before the diagnosis of breast cancer, compared with controls with no diagnosis of breast cancer. The risk of diabetes was doubled among BRCA carriers in the 15-year period after the diagnosis of breast cancer (relative risk, 2.0; 95% confidence interval [CI], 1.4–2.8; P = .0001), compared with carriers without cancer. The risk was particularly high for women with a body mass index (BMI) >25.0 kg/m2 (odds ratio, 5.8; 95% CI, 4.0–8.6; P = .0001).
CONCLUSIONS
After a diagnosis of breast cancer, women with a BRCA1 or BRCA2 mutation face a 2-fold increase in the risk of diabetes, which is exacerbated by a high BMI.
doi:10.1002/cncr.25595
PMCID: PMC3413077  PMID: 21509758
BRCA1; BRCA2; breast cancer; diabetes
13.  Endogenous epinephrine protects against obesity induced insulin resistance 
Epinephrine (E) is a hormone released from the adrenal medulla in response to low blood sugar and other stresses. E and related β2-adrenergic agonists are used to treat asthma, but a side effect is high blood sugar. C57BL/6 mice prone to overfeeding induced type II diabetes had the PNMT gene knocked out to prevent E synthesis. These E deficient mice were very similar to control animals on a 14% fat diet. On a 40.6% fat diet they gained 20 to 33% more weight than control animals and increased their blood glucose response to a glucose tolerance test because they became resistant to insulin.
Although the short term effect of β2-agonists such as E is to raise blood glucose, some long acting β2-agonists improve muscle glucose uptake. Endogenous E protects against overfeeding induced diabetes. Since adrenal E release can be impaired with aging and diabetes, endogenous E may help prevent adult onset diabetes.
doi:10.1016/j.autneu.2011.01.009
PMCID: PMC3111898  PMID: 21354376
Phenylethanolamine N-methyltransferase; PNMT; mouse; glucose; diabetes mellitus
14.  Preparation and optimization of matrix metalloproteinase-1-loaded poly(lactide-co-glycolide-co-caprolactone) nanoparticles with rotatable central composite design and response surface methodology 
Nanoscale Research Letters  2012;7(1):359.
Matrix metalloproteases are key regulatory molecules in the breakdown of extracellular matrix and in inflammatory processes. Matrix metalloproteinase-1 (MMP-1) can significantly enhance muscle regeneration by promoting the formation of myofibers and degenerating the fibrous tissue. Herein, we prepared novel MMP-1-loaded poly(lactide-co-glycolide-co-caprolactone) (PLGA-PCL) nanoparticles (NPs) capable of sustained release of MMP-1. We established quadratic equations as mathematical models and employed rotatable central composite design and response surface methodology to optimize the preparation procedure of the NPs. Then, characterization of the optimized NPs with respect to particle size distribution, particle morphology, drug encapsulation efficiency, MMP-1 activity assay and in vitro release of MMP-1 from NPs was carried out. The results of mathematical modeling show that the optimal conditions for the preparation of MMP-1-loaded NPs were as follows: 7 min for the duration time of homogenization, 4.5 krpm for the agitation speed of homogenization and 0.4 for the volume ratio of organic solvent phase to external aqueous phase. The entrapment efficiency and the average particle size of the NPs were 38.75 ± 4.74% and 322.7 ± 18.1 nm, respectively. Further scanning electron microscopy image shows that the NPs have a smooth and spherical surface, with mean particle size around 300 nm. The MMP-1 activity assay and in vitro drug release profile of NPs indicated that the bioactivity of the enzyme can be reserved where the encapsulation allows prolonged release of MMP-1 over 60 days. Taken together, we reported here novel PLGA-PCL NPs for sustained release of MMP-1, which may provide an ideal MMP-1 delivery approach for tissue reconstruction therapy.
doi:10.1186/1556-276X-7-359
PMCID: PMC3457853  PMID: 22747956
Matrix metalloproteinase-1; PLGA-PCL; Nanoparticles; Rotatable central composite design; Response surface methodology
15.  Associations Between Depressive Symptom Dimensions and Smoking Dependence Motives 
Depressive symptoms are heterogeneous and can be parsed into four subdimensions (i.e., positive affect [PA], negative affect [NA], somatic features [SF], and interpersonal problems [IP]) that may have unique associations with the motivation to smoke. This study explored associations between depressive symptom dimensions and 13 theoretically distinct domains of smoking dependence motivation in current cigarette smokers (N = 212; 53% female, mean [M] age = 24 years). Results demonstrated substantial variability in the pattern of motivational correlates across depressive dimensions. Low PA exhibited the narrowest motivational profile, associating with only the tendency to prioritize smoking over other reinforcers. NA demonstrated a broader profile, associating with smoking for affect regulation and cognitive enhancement as well as prioritizing smoking. SF associated with prioritizing smoking and smoking because of cue exposure, craving, and weight control. IP demonstrated the broadest profile, associating with 7 of 13 motivational domains. These findings may assist the tailoring cessation interventions for smokers with depressive symptoms.
doi:10.1177/0163278710383562
PMCID: PMC3377364  PMID: 21059689
depressive symptoms; smoking dependence motivation; positive affect; negative affect; somatic features; interpersonal problems
17.  Unusual Presentation of Multiple Fibroadenomas in Bilateral Breasts and Axillary Accessory Breast 
We report an extremely rare case with a total of 50 fibroadenomas simultaneously presented in bilateral breasts and left axillary accessory breast, up to 8 cm in size, in a 20 year-old Chinese woman. The histopathologic and immunophenotypic features of the fibroadenomas are described and possible underlying pathogenesis is discussed. To our knowledge, this is the first case with such a large number of bilateral multiple breast fibroadenomas in a young female reported in the literature.
doi:10.4137/BCBCR.S9512
PMCID: PMC3337783  PMID: 22553423
multiple fibroadenoma; bilateral breasts; axillary accessory breast
18.  Anhedonia Associated With Stimulant Use and Dependence in a Population-Based Sample of American Adults 
Prior research suggests an association between anhedonia—diminished interest or pleasure in rewarding activities—and stimulant use in selected samples. However, it is unclear whether this association generalizes to the overall population and is consistent across stimulant drug types (amphetamine vs. cocaine) and outcome characteristics (any lifetime use vs. dependence). Questions also remain as to whether the anhedonia–stimulant relationship is unique from covariance with depressed mood, psychiatric disorders, and nonstimulant substance use. The current study addressed these questions by examining anhedonia–stimulant relationships in a cross-sectional population-based sample of 43,093 American adults. Results indicated that lifetime anhedonia and depressed mood each were positively associated with lifetime stimulant use and lifetime dependence among those who reported stimulant use. Anhedonia–stimulant relationships were consistent across amphetamine- and cocaine-related outcomes and distinct from covariance with depressed mood, which exhibited no association over and above the effect of anhedonia. After adjusting for demographic, psychiatric, and nonstimulant substance use characteristics, anhedonia–stimulant associations remained significant, although effect sizes were partially attenuated. Lifetime anhedonia was also more prevalent among respondents who initiated use but did not eventually progress to dependence in comparison with individuals who never once used a stimulant drug. Anhedonia appears to be uniquely associated with lifetime use of cocaine and amphetamines and lifetime progression from use to dependence in the American population. Albeit cross-sectional in nature, these findings add further support to the generalizability and specificity of the anhedonia–stimulant relationship. Future research utilizing longitudinal and experimental designs are warranted to clarify the underpinnings of this association.
doi:10.1037/a0021964
PMCID: PMC3307593  PMID: 21186931
anhedonia; stimulant dependence; amphetamine; cocaine; depressed mood
19.  Breastfeeding and the risk of breast cancer in BRCA1 and BRCA2 mutation carriers 
Introduction
Breastfeeding has been inversely related to breast cancer risk in the general population. Clarifying the role of breastfeeding among women with a BRCA1 or BRCA2 mutation may be helpful for risk assessment and for recommendations regarding prevention. We present an updated analysis of breastfeeding and risk of breast cancer using a large matched sample of BRCA mutation carriers.
Methods
We conducted a case-control study of 1,665 pairs of women with a deleterious mutation in either BRCA1 (n = 1,243 pairs) or BRCA2 (n = 422 pairs). Breast cancer cases and unaffected controls were matched on year of birth, mutation status, country of residence and parity. Information about reproductive factors, including breastfeeding for each live birth, was collected from a routinely administered questionnaire. Conditional logistic regression was used to estimate the association between ever having breastfed, as well as total duration of breastfeeding, and the risk of breast cancer.
Results
Among BRCA1 mutation carriers, breastfeeding for at least one year was associated with a 32% reduction in risk (OR = 0.68; 95% CI 0.52 to 0.91; P = 0.008); breastfeeding for two or more years conferred a greater reduction in risk (OR = 0.51; 95% CI 0.35 to 0.74). Among BRCA2 mutation carriers, there was no significant association between breastfeeding for at least one year and breast cancer risk (OR = 0.83; 95% CI 0.53 to 1.31; P = 0.43).
Conclusions
These data extend our previous findings that breastfeeding protects against BRCA1-, but not BRCA2-associated breast cancer. BRCA mutation carriers should be advised of the benefit of breastfeeding in terms of reducing breast cancer risk.
doi:10.1186/bcr3138
PMCID: PMC3446376  PMID: 22405187
20.  Concurrent and Predictive Relationships Between Compulsive Internet Use and Substance Use: Findings from Vocational High School Students in China and the USA 
Purpose: Compulsive Internet Use (CIU) has increasingly become an area of research among process addictions. Largely based on data from cross-sectional studies, a positive association between CIU and substance use has previously been reported. This study presents gender and country-specific longitudinal findings on the relationships between CIU and substance use. Methods: Data were drawn from youth attending non-conventional high schools, recruited into two similarly implemented trials conducted in China and the USA. The Chinese sample included 1,761 students (49% male); the US sample included 1,182 students (57% male) with over half (65%) of the US youth being of Hispanic ethnicity. Path analyses were applied to detect the concurrent and predictive relationships between baseline and one-year follow-up measures of CIU level, 30-day cigarette smoking, and 30-day binge drinking. Results: (1) CIU was not positively related with substance use at baseline. (2) There was a positive predictive relationship between baseline CIU and change in substance use among female, but not male students. (3) Relationships between concurrent changes in CIU and substance use were also found among female, but not male students. (4) Baseline substance use did not predict an increase in CIU from baseline to 1-year follow-up. Conclusions: While CIU was found to be related to substance use, the relationship was not consistently positive. More longitudinal studies with better measures for Internet Addiction are needed to ascertain the detailed relationship between Internet addiction and substance use.
doi:10.3390/ijerph9030660
PMCID: PMC3367268  PMID: 22690154
compulsive internet use; internet addiction; youth; cigarette smoking; binge drinking; addiction syndrome; addiction specificity
21.  Differing Relations to Early Atherosclerosis between Vitamin C from Supplements vs. Food in the Los Angeles Atherosclerosis Study: A Prospective Cohort Study 
Objective:
To determine the relationship of vitamin c intake from supplements vs food on early atherosclerosis detected by carotid intima media thickness (IMT).
Background:
Oxidative stress and endothelial dysfunction play a critical role in the pathogenesis of atherosclerosis. Dietary vitamin C appears to have anti-oxidant properties and beneficial relations to endothelial function, yet vitamin C taken as a vitamin supplement does not appear to protect from cardiovascular events. The impact of vitamin c intake from supplements vs food on progression of atherosclerosis is unknown.
Methods:
We examined 3-year progression of carotid IMT in a randomly sampled cohort of 573 healthy women and men aged 40-60 years. Progression of carotid IMT was determined bilaterally with B-mode ultrasound at 3 examinations (1.5-year intervals). Intake of dietary vitamin C was measured by six, 24-hour recall interviews. Intake of vitamin C from vitamin supplements was measured by questionnaire in quartiles of supplement intake and no supplement. Vitamin C wasmeasured in plasma as ascorbic acid.
Results:
Carotid IMT progressed 10.0±16.5 μm/year (mean±SD) among all those with follow-up (n=500; 87%). For those who took vitamin C supplements, carotid IMT progression increased with dose (p-trend=0.0009). Among persons in the highest quartile (857-5000 mg/day) of vitamin C supplement intake compared to those not consuming any vitamin C supplements, carotid IMT progression increased three-fold (20.3±2.6 versus 7.6±1.8 μm/year (mean±SD); p<0.001). The adverse association of vitamin C supplement intake with carotid IMT was two-fold greater in the upper tertile of serum cholesterol compared to the lower two tertiles (p=0.01). In contrast to the adverse association of vitamin C supplements, vitamin C intake from food had a weak protective relationship on carotid IMT progression (reduced progression -5.0±1.9 μm/year; p=0.008).
Conclusions:
Vitamin C supplementation is associated with accelerated early atherosclerosis measured by carotid IMT compared to a protective association with vitamin C from food. Theadverse association of vitamin C supplementation may be greater in patients with higher serum cholesterol levels. The current results provide a potential mechanistic understanding for the observed differences between Vitamin C in supplements vs food in prior studies. Given these observations,vitamin C supplementation does not appear to be currently advisable for prevention or treatment of atherosclerosis.
doi:10.2174/1874192401206010113
PMCID: PMC3447163  PMID: 23002405
Ascorbic acid; vitamin C; atherosclerosis; cardiovascular disease.
22.  Evaluating Depressive Symptom Interactions on Adolescent Smoking Prevention Program Mediators: A Mediated Moderation Analysis 
Nicotine & Tobacco Research  2010;12(11):1099-1107.
Introduction:
Smoking prevention interventions have been shown to be effective in reducing smoking prevalence in the United States. Further work is needed to address smoking in China, where over one third of the world’s current smokers reside. China, with more than 60% of the male population being smokers, also presents a unique opportunity to test cognitive processes involved in depression, social influences, and smoking. Adolescents at-risk for developing depression may process social information differently from low-risk counterparts.
Methods:
The Wuhan Smoking Prevention Trial was a school-based longitudinal randomized controlled trial aimed at preventing initiation and escalation of adolescent smoking behaviors. Thousand three hundred and ninety-one male seventh-grade students were assessed with a 200-item paper-and-pencil baseline survey, and it was readministered 1 year later following program implementation.
Results:
Friend prevalence estimates were significantly higher among 30-day smokers and among those at highest risk for depression symptoms. The program appeared to be successful in changing the perception of friend smoking prevalence only among adolescents with a comorbidity of high scores of depression symptoms and who have experimented previously with smoking. This Program × Comorbidity interaction on perceived friend smoking prevalence was significant in predicting 30-day smoking 1 year after program implementation.
Conclusions:
This study provides evidence that those adolescents with high levels of depressive symptoms may be more sensitive to social influences associated with smoking prevalence. Individual Disposition × Social Environmental Influences may be important when developing future effective prevention programming.
doi:10.1093/ntr/ntq156
PMCID: PMC2964921  PMID: 20861150
23.  ONE-YEAR FOLLOW-UP EVALUATION OF THE PROJECT TOWARDS NO DRUG ABUSE (TND) DISSEMINATION TRIAL 
Preventive medicine  2010;51(3-4):313-319.
Objective
The aims of this trial, conducted 2004–2008, were to examine (1) the effectiveness of Project Towards No Drug Abuse (TND) at one-year follow-up when implemented on a large scale; and (2) the relative effectiveness of two training approaches for program implementers.
Method
A total of 65 high schools from 14 school districts across the United States were randomized to one of three conditions: regular workshop training, comprehensive implementation support, or standard care control. Physical education and health teachers delivered the program to students (n=2,538). Program effectiveness was assessed with dichotomous measures of 30-day substance use at baseline and one-year follow-up.
Results
When the program conditions were considered in aggregate and compared to controls, the program showed a marginally significant effect in lowering marijuana use from baseline to one-year follow up. Significant program effects on hard drug use were achieved for baseline non-users only. There were no differences in the effects of the two program conditions.
Conclusion
Positive outcomes may be achieved by trained teachers when they implement Project TND in real-world high school environments; however, program effects are likely to be weaker than those achieved in efficacy trials. Training workshops may be adequate to build capacity for successful program implementation.
doi:10.1016/j.ypmed.2010.07.016
PMCID: PMC2939247  PMID: 20655946
24.  High Frequency PMN-PT 1–3 Composite Transducer for Ultrasonic Imaging Application 
Ferroelectrics  2010;408(1):120-128.
Development of PMN-PT single crystal/epoxy 1–3 composites for high-frequency ultrasonic transducers application is presented. The composite was fabricated by using a DRIE dry etching process with a 45% volume fraction of PMN-PT. A 35 MHz ultrasound flat transducer was fabricated with the composite, which was found to have an effective electromechanical coupling coefficient of 0.81, an insertion loss of 18 db, and a –6 dB bandwidth as high as 100%. Tungsten wire phantom image shows that the transducer had an axial resolution of 30 μm, which was in good agreement with the theoretical expectation. The initial results showed that the PMN-PT/epoxy 1–3 composite has many attractive properties over conventional piezoelectric materials for medical imaging applications.
doi:10.1080/00150193.2010.48554
PMCID: PMC3159894  PMID: 21869845
PMN-PT; 1–3 composite; Ultrasonic transducer
25.  School disrepair and substance use among regular and alternative high school students 
The Journal of school health  2010;80(8):387-393.
Background
The physical environment influences adolescent health behavior and personal development. This paper examines the relationship between level of school disrepair and substance use among students attending regular (RHS) and alternative (AHS) high schools.
Methods
Data were collected from students (N=7,058) participating in two randomized controlled trials of a school-based substance abuse prevention program implemented across the United States. Students provided substance use and demographic information on a self-reported survey. Data for the physical disrepair of schools were collected from individual rater observations of each school environment. We hypothesized that school disrepair would be positively associated with substance use controlling for individual characteristics and an SES proxy. Multilevel mixed modeling was used to test the hypothesized association and accounted for students nested within schools.
Results
Findings indicated that students attending AHS with greater school disrepair were more likely to report the use of marijuana and other illicit drugs (i.e., cocaine, heroin). Students attending RHS with greater school disrepair were less likely to report smoking cigarettes.
Conclusions
Differences in findings between RHS and AHS students are discussed, and implications for substance use prevention programming are offered. Students attending AHS with greater school disrepair may require more substance abuse prevention programming, particularly to prevent illicit substance use.
doi:10.1111/j.1746-1561.2010.00518.x
PMCID: PMC2904640  PMID: 20618621
Child and adolescent health; drugs; research; public health

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