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1.  Exploring How the Tobacco Industry Presents and Promotes Itself in Social Media 
Background
The commercial potential of social media is utilized by tobacco manufacturers and vendors for tobacco promotion online. However, the prevalence and promotional strategies of pro-tobacco content in social media are still not widely understood.
Objective
The goal of this study was to reveal what is presented by the tobacco industry, and how it promotes itself, on social media sites.
Methods
The top 70 popular cigarette brands are divided into two groups according to their retail prices: group H (brands with high retail prices) and group L (brands with low retail prices). Three comprehensive searches were conducted on Facebook, Wikipedia, and YouTube respectively using the top 70 popular cigarette brands as keywords. We identified tobacco-related content including history and culture, product features, health warnings, home page of cigarette brands, and Web-based tobacco shops. Furthermore, we examined the promotional strategies utilized in social media.
Results
According to the data collected from March 3, 2014 to March 10, 2014, 43 of the 70 representative cigarette brands had created 238 Facebook fan pages, 46 cigarette brands were identified in Wikipedia, and there were over 120,000 pro-tobacco videos on YouTube, associated with 61 cigarette brands. The main content presented on the three social media websites differs significantly. Wikipedia focuses on history and culture (67%, 32/48; P<.001). Facebook mainly covers history and culture (37%, 16/43; P<.001) and major products (35%, 15/43), while YouTube focuses on the features of major tobacco products (79%, 48/61; P=.04) and information about Web-based shops (49%, 30/61; P=.004). Concerning the content presented by groups H and L, there is no significant difference between the two groups. With regard to the promotional strategies used, sales promotions exist extensively in social media. Sales promotion is more prevalent on YouTube than on the other two sites (64%, 39/61 vs 35%, 15/43; P=.004). Generally, the sale promotions of higher-cost brands in social media are more prevalent than those of lower-cost brands (55%, 16/29 vs 7%, 1/14; P<.001 for Facebook; 78%, 28/36 vs 44%, 11/25; P=.005 for YouTube).
Conclusions
The prevalence of cigarette brands in social media allows more pro-tobacco information to be accessed by online users. This dilemma indicates that corresponding regulations should be established to prevent tobacco promotion in social media.
doi:10.2196/jmir.3665
PMCID: PMC4319084  PMID: 25608524
cigarette brands; promotional strategy; social media; tobacco control; tobacco promotion
2.  Religiosity and the Transition to Nonmarital Parity 
Nonmarital parity is associated with several negative outcomes, including health problems, educational problems, and poverty. Understanding the risk and protective factors associated with nonmarital parenthood can inform policy and interventions, reducing both the incidences and associated consequences. The current study focuses on how intrinsic and extrinsic religiosity (the degree to which individuals or groups employ religious ideology in forming values and making decisions) are related to the timing of nonmarital parity using discrete time hazard modeling of a nationally representative sample of adolescent females (N=7,367) from the National Longitudinal Study of Adolescent Health. The majority of the sample (86 %) claimed a religious affiliation and almost a third (32 %) had a nonmarital birth during the study. Even though the majority of the sample is White (67 %), Black and Hispanic females were more likely to experience a nonmarital birth. Results indicate that intrinsic and extrinsic religiosity and religious affiliation assert protective effects for some populations while religious affiliation increases risk in the full model. Recommendations for policy, intervention, and future research are offered.
doi:10.1007/s13178-014-0153-x
PMCID: PMC4186654  PMID: 25298755
Nonmarital fertility; Religiosity; Reproductive and sexual health; Add Health; Health inequalities
3.  Neurological Outcome Scale for Traumatic Brain Injury: III. Criterion-Related Validity and Sensitivity to Change in the NABIS Hypothermia-II Clinical Trial 
Journal of Neurotrauma  2013;30(17):1506-1511.
Abstract
The Neurological Outcome Scale for Traumatic Brain Injury (NOS-TBI) is a measure assessing neurological functioning in patients with TBI. We hypothesized that the NOS-TBI would exhibit adequate concurrent and predictive validity and demonstrate more sensitivity to change, compared with other well-established outcome measures. We analyzed data from the National Acute Brain Injury Study: Hypothermia-II clinical trial. Participants were 16–45 years of age with severe TBI assessed at 1, 3, 6, and 12 months postinjury. For analysis of criterion-related validity (concurrent and predictive), Spearman's rank-order correlations were calculated between the NOS-TBI and the Glasgow Outcome Scale (GOS), GOS-Extended (GOS-E), Disability Rating Scale (DRS), and Neurobehavioral Rating Scale-Revised (NRS-R). Concurrent validity was demonstrated through significant correlations between the NOS-TBI and GOS, GOS-E, DRS, and NRS-R measured contemporaneously at 3, 6, and 12 months postinjury (all p<0.0013). For prediction analyses, the multiplicity-adjusted p value using the false discovery rate was <0.015. The 1-month NOS-TBI score was a significant predictor of outcome in the GOS, GOS-E, and DRS at 3 and 6 months postinjury (all p<0.015). The 3-month NOS-TBI significantly predicted GOS, GOS-E, DRS, and NRS-R outcomes at 6 and 12 months postinjury (all p<0.0015). Sensitivity to change was analyzed using Wilcoxon's signed rank-sum test of subsamples demonstrating no change in the GOS or GOS-E between 3 and 6 months. The NOS-TBI demonstrated higher sensitivity to change, compared with the GOS (p<0.038) and GOS-E (p<0.016). In summary, the NOS-TBI demonstrated adequate concurrent and predictive validity as well as sensitivity to change, compared with gold-standard outcome measures. The NOS-TBI may enhance prediction of outcome in clinical practice and measurement of outcome in TBI research.
doi:10.1089/neu.2013.2925
PMCID: PMC3751279  PMID: 23617608
assessment tools; neuropsychology; outcome measures; recovery; traumatic brain injury
4.  Western Cold and Flu (WeCoF) aerosol study – preliminary results 
BMC Research Notes  2014;7(1):563.
Background
Influenza virus is responsible for annual deaths due to seasonal epidemics and is the cause of major pandemics which have claimed millions of human lives over the last century. Knowledge about respiratory virus transmission is advancing. Spread is likely through the air, but much work remains to be done to characterize the aerosols produced by infected individuals, including viral particle survival and infectivity. Although coughs have been characterized, little work has been done to examine coughs from infected individuals. The WeCoF project aims at providing evidence to support prevention measures to mitigate person-to-person influenza transmission in critical locations, such as hospitals, and during pandemics.
Findings
A novel experimental cough chamber facility – the FLUGIE – has been developed to study the far-field aerodynamics and aerosol transport of droplets produced by the coughs from humans naturally-infected with influenza. The flow field of each cough is measured using Particle Image Velocimetry (PIV). A preliminary study involving 12 healthy individuals has been carried out in order to quantify the strengths of their coughs at a distance of 1 m from the mouth. The spatially averaged maximum velocity was determined and the average value was 0.41 m/s across 27 coughs of good data quality. The peak value of velocity was also extracted and compared with the average velocity.
Conclusions
Preliminary results show that there is significant air motion associated with a cough (on the order of 0.5 m/s) as far away as 1 m from the mouth of the healthy person who coughs. The results from this pilot study provide the framework for a more extensive participant recruitment campaign that will encompass a statistically-significant cohort.
doi:10.1186/1756-0500-7-563
PMCID: PMC4150972  PMID: 25148847
Cough; Cold; Influenza; Particle Image Velocimetry; Airflow sampling; Bioaerosol
5.  The South Asian Genome 
PLoS ONE  2014;9(8):e102645.
The genetic sequence variation of people from the Indian subcontinent who comprise one-quarter of the world's population, is not well described. We carried out whole genome sequencing of 168 South Asians, along with whole-exome sequencing of 147 South Asians to provide deeper characterisation of coding regions. We identify 12,962,155 autosomal sequence variants, including 2,946,861 new SNPs and 312,738 novel indels. This catalogue of SNPs and indels amongst South Asians provides the first comprehensive map of genetic variation in this major human population, and reveals evidence for selective pressures on genes involved in skin biology, metabolism, infection and immunity. Our results will accelerate the search for the genetic variants underlying susceptibility to disorders such as type-2 diabetes and cardiovascular disease which are highly prevalent amongst South Asians.
doi:10.1371/journal.pone.0102645
PMCID: PMC4130493  PMID: 25115870
6.  Validity of the diagnostic criteria for chronic cerebrospinal venous insufficiency and association with multiple sclerosis 
Background:
The chronic cerebrospinal venous insufficiency theory proposes that altered cerebral venous hemodynamics play a role in the pathophysiology of multiple sclerosis. We aimed to explore the validity of this hypothesis by assessing the diagnostic criteria for chronic cerebrospinal venous insufficiency in persons with and without multiple sclerosis.
Methods:
We compared the proportion of venous outflow abnormalities between patients with multiple sclerosis and healthy controls using extracranial Doppler ultrasonography and gadolinium-enhanced magnetic resonance venography. Interpreting radiologists were blinded to the clinical status of participants.
Results:
We enrolled 120 patients with multiple sclerosis and 60 healthy controls. High proportions of both patients (67/115 [58%]) and controls (38/60 [63%]) met 1 or more of the proposed ultrasound criteria for diagnosis of chronic cerebrospinal venous insufficiency (p = 0.6). A minority of patients (23/115 [20%]) and controls (6/60 [10%]) fulfilled 2 or more of the proposed criteria (p = 0.1). There were no differences between patients and controls in the prevalence of each individual ultrasound criterion. Similarly, there were no differences in intracranial or extracranial venous patency between groups, as measured by magnetic resonance venography.
Interpretation:
We detected no differences in the proportion of venous outflow abnormalities between patients with multiple sclerosis and healthy controls. Moreover, our study revealed significant methodologic concerns regarding the proposed diagnostic criteria for chronic cerebrospinal venous insufficiency that challenge their validity.
doi:10.1503/cmaj.131431
PMCID: PMC4119167  PMID: 24890104
7.  Auditory Verbal Hallucinations in Persons With and Without a Need for Care 
Schizophrenia Bulletin  2014;40(Suppl 4):S255-S264.
Auditory verbal hallucinations (AVH) are complex experiences that occur in the context of various clinical disorders. AVH also occur in individuals from the general population who have no identifiable psychiatric or neurological diagnoses. This article reviews research on AVH in nonclinical individuals and provides a cross-disciplinary view of the clinical relevance of these experiences in defining the risk of mental illness and need for care. Prevalence rates of AVH vary according to measurement tool and indicate a continuum of experience in the general population. Cross-sectional comparisons of individuals with AVH with and without need for care reveal similarities in phenomenology and some underlying mechanisms but also highlight key differences in emotional valence of AVH, appraisals, and behavioral response. Longitudinal studies suggest that AVH are an antecedent of clinical disorders when combined with negative emotional states, specific cognitive difficulties and poor coping, plus family history of psychosis, and environmental exposures such as childhood adversity. However, their predictive value for specific psychiatric disorders is not entirely clear. The theoretical and clinical implications of the reviewed findings are discussed, together with directions for future research.
doi:10.1093/schbul/sbu005
PMCID: PMC4141313  PMID: 24936085
nonclinical; need for care; psychosis; prevalence
8.  Exposure to Beta-(1,3)-D-Glucan in House Dust at Age 7–10 Is Associated with Airway Hyperresponsiveness and Atopic Asthma by Age 11–14 
PLoS ONE  2014;9(6):e98878.
Background
Mould exposure has been linked to childhood asthma and bronchial hyper-responsiveness. Few studies have assessed beta-(1,3)-d-glucan (beta-glucan), a significant fungal cell wall constituent, in relation to asthma in adolescence.
Objective
To determine whether house dust-derived beta-glucan exposure at age 7–10 is associated with the development and persistence of atopic and non-atopic asthma, and bronchial hyper-responsiveness (BHR) by age 11–14.
Methods
Dust samples were collected from the 1995 Study of Asthma, Genes, and Environment (SAGE) birth cohort. This cohort was derived from Manitoba provincial healthcare administrative records of children high and low risk for asthma. Samples were collected from the homes of 422 children at age 7–10 and analyzed using beta-glucan and endotoxin-specific Limulus Amoebocyte Lysate assays. Asthma, atopy, and BHR status of each child were also assessed at ages 7–10 and 11–14.
Results
At age 7–10, beta-glucan dust levels in the home were associated with persistent atopic asthma at age 11–14 (OR 1.79 for each unit increase in levels, 95% CI 1.14–2.81), independent of endotoxin exposure, and Alternaria or Cladosporium sensitization. The likelihood of BHR almost doubled with unit increases in dust beta-glucan in asthmatic children. In children without asthma, exposure to high beta-glucan levels at age 7–10 also elevated risk for BHR in adolescence (OR 1.74, 95% CI 1.05–2.89). New-onset atopic asthma was twice more likely following high beta-glucan exposure in children without asthma but the association did not reach statistical significance. No associations were evident with concurrent asthma phenotype at age 7–10 or non-atopic asthma at age 11–14.
Conclusion
These findings implicate home beta-glucan exposure at school-age as a risk factor for persistent atopic asthma and new-onset BHR. The higher prevalence of BHR in urban adolescents may be propagated by this home exposure.
doi:10.1371/journal.pone.0098878
PMCID: PMC4048218  PMID: 24905346
9.  Guidelines for Improving Entry Into and Retention in Care and Antiretroviral Adherence for Persons With HIV: Evidence-Based Recommendations From an International Association of Physicians in AIDS Care Panel 
Annals of internal medicine  2012;156(11):817-294.
Description
After HIV diagnosis, timely entry into HIV medical care and retention in that care are essential to the provision of effective antiretroviral therapy (ART). ART adherence is among the key determinants of successful HIV treatment outcome and is essential to minimize the emergence of drug resistance. The International Association of Physicians in AIDS Care convened a panel to develop evidence-based recommendations to optimize entry into and retention in care and ART adherence for people with HIV.
Methods
A systematic literature search was conducted to produce an evidence base restricted to randomized, controlled trials and observational studies with comparators that had at least 1 measured biological or behavioral end point. A total of 325 studies met the criteria. Two reviewers independently extracted and coded data from each study using a standardized data extraction form. Panel members drafted recommendations based on the body of evidence for each method or intervention and then graded the overall quality of the body of evidence and the strength for each recommendation.
Recommendations
Recommendations are provided for monitoring of entry into and retention in care, interventions to improve entry and retention, and monitoring of and interventions to improve ART adherence. Recommendations cover ART strategies, adherence tools, education and counseling, and health system and service delivery interventions. In addition, they cover specific issues pertaining to pregnant women, incarcerated individuals, homeless and marginally housed individuals, and children and adolescents, as well as substance use and mental health disorders. Recommendations for future research in all areas are also provided.
doi:10.7326/0003-4819-156-11-201206050-00419
PMCID: PMC4044043  PMID: 22393036
10.  Macular optical coherence tomography findings following blunt ocular trauma 
This case report describes the optical coherence tomography (OCT) results of Berlin’s edema in a male subject following blunt ocular trauma from a soccer ball. A 27-year-old male presented with blurred vision in his left eye following blunt trauma. On admission, he underwent a complete eye examination and an OCT of the macula. Fundoscopy revealed commotio retinae, observed as an abnormal cream-colored discoloration of the fovea. The OCT showed outer photoreceptor segment disruption, retinal pigment epithelium inter-digitation, and intra-retinal edema of the outer nuclear layer. Following initial management, a repeat OCT after 3 months showed near complete resolution. OCT can be a useful adjunct for monitoring the progress of Berlin’s edema secondary to blunt ocular trauma because Berlin’s edema may present similarly clinically to other ocular trauma, but can affect different layers of the retina depending on the type of injury to the eye.
doi:10.2147/OPTH.S64082
PMCID: PMC4038424  PMID: 24899795
Berlin’s edema; commotio retinae; optical coherence tomography; OCT; ocular trauma
11.  Child maltreatment and adolescent mental health problems in a large birth cohort 
Child abuse & neglect  2013;37(5):292-302.
Objective
To examine whether notified child maltreatment is associated with adverse psychological outcomes in adolescence, and whether differing patterns of psychological outcome are seen depending on the type of maltreatment.
Methods
The participants were 7223 mother and child pairs enrolled in a population-based birth cohort study in Brisbane, Australia. Exposure to suspected child maltreatment was measured by linkage with state child protection agency data. The primary outcomes were the internalizing and externalizing scales of the Youth Self Report (YSR) at approximately 14 years of age.
Results
The YSR was completed by 5172 subjects (71.6%), with increased attrition of cases of notified maltreatment. After adjustment for potential confounders, notified maltreatment was significantly associated with both internalizing behavior and externalizing behavior at 14. When evaluated as non-exclusive categories of maltreatment, physical abuse, neglect, and emotional abuse were each significantly associated with both internalizing and externalizing behavior after adjustment. When evaluated using an expanded hierarchical scheme that included combinations of multi-type maltreatment, the following groups had significantly higher internalizing behavior after adjustment: emotional abuse (with or without neglect), and multi-type maltreatment including physical (but not sexual) abuse with neglect and/or emotional abuse. The following groups were associated with externalizing behavior after adjustment: emotional abuse (with or without neglect), and multi-type maltreatment including physical abuse (with neglect and/or emotional abuse), or sexual abuse (with neglect and/or emotional abuse, and/or physical abuse).
Conclusions
This study suggests that child neglect and emotional abuse have serious adverse effects on adolescent mental health and warrant the attention given to other forms of child maltreatment. Additionally, it confirms that young people who are notified for more than one type of maltreatment are at particular risk of adolescent mental health problems.
doi:10.1016/j.chiabu.2012.11.008
PMCID: PMC3918944  PMID: 23380430
12.  Adaptive Expression of MicroRNA-125a in Adipose Tissue in Response to Obesity in Mice and Men 
PLoS ONE  2014;9(3):e91375.
MicroRNAs are emerging as new mediators in the regulation of adipose tissue biology and the development of obesity. An important role of microRNA-125a has been suggested in the pathogenesis of insulin resistance (IR). Here, we characterized the function of microRNA-125a in adipose tissue in a context of experimentally-induced IR and obesity in mice and in obese patients. We showed time dependent overexpression of the microRNA in adipose tissue of BALB/c and C57BL/6J mice in response to high fat diet (HFD) feeding. MicroRNA-125a expression was downregulated in vitro in insulin resistant 3T3-L1 adipocytes and ex vivo in adipose tissue of obese patients. In vitro modulation of microRNA-125a expression in 3T3-L1 adipocytes did not affect glucose uptake. Gene set enrichment analysis (GSEA) identified significantly altered expression patterns of predicted microRNA-125a gene targets in transcriptomic datasets of adipose tissue from HFD-fed mice and obese patients. Among genes that contributed to global enrichment of altered expression of microRNA-125a targets, Thyrotroph embryonic factor (Tef), Mannan-binding lectin serine peptidase 1, Reticulon 2 and Ubiquitin-conjugating enzyme E2L3 were significantly differentially expressed in adipose tissue in these groups. We showed that Tef expression is reduced in adipose tissue of obese patients following gastric bypass surgery. Our findings indicate that microRNA-125a expression in adipose tissue adapts to IR and may play a role in the development of obesity in mice and obese subjects through uncoupled regulation of the expression of microRNA-125a and its targets.
doi:10.1371/journal.pone.0091375
PMCID: PMC3967993  PMID: 24675842
18.  Coronary heart disease in Indian Asians 
The Indian Asian population accounts for a fifth of all global deaths from coronary heart disease (CHD). CHD deaths on the Indian subcontinent have doubled since 1990, and are predicted to rise a further 50% by 2030. Reasons underlying the increased CHD mortality among Indian Asians remain unknown. Although conventional cardiovascular risk factors contribute to CHD in Indian Asians as in other populations, these do not account for their increased risk. Type-2 diabetes, insulin resistance and related metabolic disturbances are more prevalent amongst Indian Asians than Europeans, and have been proposed as major determinants of higher CHD risk among Indian Asians. However, this view is not supported by prospective data. Genome-wide association studies have not identified differences in allele frequencies or effect sizes in known loci to explain the increased CHD risk in Indian Asians. Limited knowledge of mechanisms underlying higher CHD risk amongst Indian Asians presents a major obstacle to reducing the burden of CHD in this population. Systems biology approaches such as genomics, epigenomics, metabolomics and transcriptomics, provide a non-biased approach for discovery of novel biomarkers and disease pathways underlying CHD. Incorporation of these ‘omic’ approaches in prospective Indian Asian cohorts such as the London Life Sciences Population Study (LOLIPOP) provide an exciting opportunity for the identification of new risk factors underlying CHD in this high risk population.
doi:10.5339/gcsp.2014.4
PMCID: PMC4104373  PMID: 25054115
Coronary heart disease; Indian Asian; LOLIPOP; genome; epigenome; metabolome; GWAS
19.  MRI texture heterogeneity in the optic nerve predicts visual recovery after acute optic neuritis☆ 
NeuroImage : Clinical  2014;4:302-307.
Purpose
To test the feasibility of using multi-scale MRI texture analysis to assess optic nerve pathology and to investigate how visual recovery relates to the severity of acute tissue damage in the optic nerve in patients after optic neuritis (ON).
Materials and Methods
We recruited 25 patients with acute ON. Retinal nerve fiber layer (RNFL) thickness; MRI lesion length and enhancement; optic nerve area ratio; and multi-scale MRI texture analysis, a measure of structural integrity, were used to assess tissue damage at baseline, and at 6 and 12 months. The recovery in vision was defined as the functional outcome. Eight healthy subjects were imaged for control.
Results
We identified 25 lesions in the affected eyes (9 enhanced) and 5 in the clinically non-affected eyes (none enhanced). At baseline, we found that RNFL values were 20% thicker and lesion texture 14% more heterogeneous in the affected eyes than in the non-affected eyes, and lesion texture ratio of affected to non-affected eyes was greater in patients than in controls. In the affected eyes, visual acuity recovered significantly over 6 (18/23 patients) and 12 months (18/21 patients) when RNFL thickness and optic nerve area ratio decreased over time. Texture heterogeneity in the standard MRI of acute optic nerve lesions was the only measure that predicted functional recovery after ON.
Conclusions
Tissue heterogeneity may be a potential measure of functional outcome in ON patients and advanced analysis of the texture in standard MRI could provide insights into mechanisms of injury and recovery in patients with similar disorders.
Highlights
•We studied structure–function relationships in patients after acute optic neuritis.•Besides standard MRI and OCT, we used MRI texture analysis to assess tissue damage.•Vision recovered significantly at 6 and 12 months, but not tissue injury.•Only MRI texture heterogeneity in the optic nerve predicted visual recovery.•Novel texture analysis may help advance patient care in diagnostic MRI.
doi:10.1016/j.nicl.2014.01.003
PMCID: PMC4107369  PMID: 25061567
Acute tissue damage; MRI; Texture heterogeneity; Visual recovery; Prediction; Optic neuritis
20.  Intraventricular Hemorrhage and Multiple Intracranial Cysts Associated with Congenital Cytomegalovirus Infection 
Journal of Clinical Microbiology  2013;51(7):2466-2468.
Intraventricular hemorrhage with congenital cytomegalovirus (CMV) infection is rare and has been reported only in extremely premature infants or in association with thrombocytopenia. We report the first case of a full-term male infant with congenital CMV infection and intraventricular hemorrhage with a normal platelet count and coagulation profile. The infant also had a left subependymal cyst and bilateral occipital cysts without any other manifestations of CMV infection.
doi:10.1128/JCM.00842-13
PMCID: PMC3697656  PMID: 23678057
21.  Nutrigenomics of High Fat Diet Induced Obesity in Mice Suggests Relationships between Susceptibility to Fatty Liver Disease and the Proteasome 
PLoS ONE  2013;8(12):e82825.
Nutritional factors play important roles in the etiology of obesity, type 2 diabetes mellitus and their complications through genotype x environment interactions. We have characterised molecular adaptation to high fat diet (HFD) feeding in inbred mouse strains widely used in genetic and physiological studies. We carried out physiological tests, plasma lipid assays, obesity measures, liver histology, hepatic lipid measurements and liver genome-wide gene transcription profiling in C57BL/6J and BALB/c mice fed either a control or a high fat diet. The two strains showed marked susceptibility (C57BL/6J) and relative resistance (BALB/c) to HFD-induced insulin resistance and non alcoholic fatty liver disease (NAFLD). Global gene set enrichment analysis (GSEA) of transcriptome data identified consistent patterns of expression of key genes (Srebf1, Stard4, Pnpla2, Ccnd1) and molecular pathways in the two strains, which may underlie homeostatic adaptations to dietary fat. Differential regulation of pathways, including the proteasome, the ubiquitin mediated proteolysis and PPAR signalling in fat fed C57BL/6J and BALB/c suggests that altered expression of underlying diet-responsive genes may be involved in contrasting nutrigenomic predisposition and resistance to insulin resistance and NAFLD in these models. Collectively, these data, which further demonstrate the impact of gene x environment interactions on gene expression regulations, contribute to improved knowledge of natural and pathogenic adaptive genomic regulations and molecular mechanisms associated with genetically determined susceptibility and resistance to metabolic diseases.
doi:10.1371/journal.pone.0082825
PMCID: PMC3855786  PMID: 24324835
22.  Caspase 3 activity in isolated fetal rat lung fibroblasts and rat periodontal ligament fibroblasts: cigarette smoke induced alterations 
Tobacco Induced Diseases  2013;11(1):25.
Background
Cigarette smoking is the leading cause of preventable death and has been implicated in pathogenesis of pulmonary, oral and systemic diseases. Smoking during pregnancy is a risk factor for the developing fetus and may be a major cause of infant mortality. Moreover, the oral cavity, and all cells within are the first to be exposed to cigarette smoke and may be a possible source for the spread of toxins to other organs of the body. Fibroblasts in general are morphologically heterogeneous connective tissue cells with diverse functions. Apoptosis or programmed cell death is a crucial process during embryogenesis and for the maintenance of homeostasis throughout life. Deregulation of apoptosis has been implicated in abnormal lung development in the fetus and disease progression in adults. Caspases are proteases which belong to the family of cysteine aspartic acid proteases and are key components for downstream amplification of intracellular apoptotic signals. Of 14 known caspases, caspase-3 is the key executioner of apoptosis. In the present study we explored the hypothesis that cigarette smoke (CS) extract activates caspase-3 in two types of fibroblasts, both of which would be exposed directly to cigarette smoke, isolated fetal rat lung fibroblasts and adult rat periodontal ligament (PDL) fibroblasts.
Methods
Isolated fetal rat lung fibroblasts and adult PDLs were used. Cells were exposed to different concentrations of CS for 60 min. Caspase-3 activity and its inhibition by Z-VAD-fmk were measured by caspase-3 fluorometric assay. The effect of CSE on cellular viability was measured using the MTT formazan assay. Caspase-3 expression was detected by western blot analysis and cellular localization of caspase-3 was determined by immunofluorescence using fluorescence microscopy.
Results
It was observed in fetal rat lung fibroblast cells that CSE extract significantly (p<0.05) increased caspase-3 activity and decrease cell proliferation. However, no significant changes in activity or viability were observed in PDLs.
Conclusions
This indicates CS activates caspase-3 the key regulatory point in apoptosis in fetal rat lung fibroblast cells suggesting that smoking during pregnancy may alter the developmental program of fetal lung, jeopardizing the establishment of critical cellular mechanisms necessary to expedite pulmonary maturation at birth.of critical cellular mechanisms necessary to expedite pulmonary maturation at birth.
doi:10.1186/1617-9625-11-25
PMCID: PMC4029472  PMID: 24314135
Cigarette smoke extract; Fetal rat lung fibroblasts; Protease; Caspase-3; Lung development; Developmental toxicity; Periodontal ligament fibroblast; Periodontitis
23.  Genome-wide association study in people of South Asian ancestry identifies six novel susceptibility loci for type 2 diabetes 
Nature genetics  2011;43(10):984-989.
We carried out a genome wide association study of type-2 diabetes (T2D) amongst 20,119 people of South Asian ancestry (5,561 with T2D); we identified 20 independent SNPs associated with T2D at P<10−4 for testing amongst a further 38,568 South Asians (13,170 with T2D). In combined analysis, common genetic variants at six novel loci (GRB14, ST6GAL1, VPS26A, HMG20A, AP3S2 and HNF4A) were associated with T2D (P=4.1×10−8 to P=1.9×10−11); SNPs at GRB14 were also associated with insulin sensitivity, and at ST6GAL1 and HNF4A with pancreatic beta-cell function respectively. Our findings provide additional insight into mechanisms underlying T2D, and demonstrate the potential for new discovery from genetic association studies in South Asians who have increased susceptibility to T2D.
doi:10.1038/ng.921
PMCID: PMC3773920  PMID: 21874001
24.  Genetic loci influencing kidney function and chronic kidney disease in man 
Chambers, John C | Zhang, Weihua | Lord, Graham M | van der Harst, Pim | Lawlor, Debbie A | Sehmi, Joban S | Gale, Daniel P | Wass, Mark N | Ahmadi, Kourosh R | Bakker, Stephan JL | Beckmann, Jacqui | Bilo, Henk JG | Bochud, Murielle | Brown, Morris J | Caulfield, Mark J | Connell, John M C | Cook, Terence | Cotlarciuc, Ioana | Smith, George Davey | de Silva, Ranil | Deng, Guohong | Devuyst, Olivier | Dikkeschei, Lambert D. | Dimkovic, Nada | Dockrell, Mark | Dominiczak, Anna | Ebrahim, Shah | Eggermann, Thomas | Farrall, Martin | Ferrucci, Luigi | Floege, Jurgen | Forouhi, Nita G | Gansevoort, Ron T | Han, Xijin | Hedblad, Bo | van der Heide, Jaap J Homan | Hepkema, Bouke G | Hernandez-Fuentes, Maria | Hypponen, Elina | Johnson, Toby | de Jong, Paul E | Kleefstra, Nanne | Lagou, Vasiliki | Lapsley, Marta | Li, Yun | Loos, Ruth J F | Luan, Jian'an | Luttropp, Karin | Maréchal, Céline | Melander, Olle | Munroe, Patricia B | Nordfors, Louise | Parsa, Afshin | Penninx, Brenda W. | Perucha, Esperanza | Pouta, Anneli | Prokopenko, Inga | Roderick, Paul J | Ruokonen, Aimo | Samani, Nilesh | Sanna, Serena | Schalling, Martin | Schlessinger, David | Schlieper, Georg | Seelen, Marc AJ | Shuldiner, Alan R | Sjögren, Marketa | Smit, Johannes H. | Snieder, Harold | Soranzo, Nicole | Spector, Timothy D | Stenvinkel, Peter | Sternberg, Michael JE | Swaminathan, Ramasamyiyer | Tanaka, Toshiko | Ubink-Veltmaat, Lielith J. | Uda, Manuela | Vollenweider, Peter | Wallace, Chris | Waterworth, Dawn | Zerres, Klaus | Waeber, Gerard | Wareham, Nicholas J | Maxwell, Patrick H | McCarthy, Mark I | Jarvelin, Marjo-Riitta | Mooser, Vincent | Abecasis, Goncalo R | Lightstone, Liz | Scott, James | Navis, Gerjan | Elliott, Paul | Kooner., Jaspal S
Nature genetics  2010;42(5):373-375.
Chronic kidney disease (CKD), the result of permanent loss of kidney function, is a major global problem. We identify common genetic variants at chr2p12-p13, chr6q26, chr17q23 and chr19q13 associated with serum creatinine, a marker of kidney function (P=10−10 to 10−15). SNPs rs10206899 (near NAT8, chr2p12-p13) and rs4805834 (near SLC7A9, chr19q13) were also associated with CKD. Our findings provide new insight into metabolic, solute and drug-transport pathways underlying susceptibility to CKD.
doi:10.1038/ng.566
PMCID: PMC3748585  PMID: 20383145
25.  Service Use for Mental Health Problems in People with Delusional-Like Experiences: A Nationwide Population Based Survey 
PLoS ONE  2013;8(8):e71951.
Objective
Previous population-based studies have found that delusional-like experiences (DLEs) are prevalent in the community, and are associated with a wide range of mental health disorders. The aim of the study was to investigate mental health service use by people with DLEs.
Methods
Subjects were drawn from the Australian National Survey of Mental Health and Wellbeing 2007 of 8 841community residents aged between 16 and 85 years. The Composite International Diagnostic Interview (CIDI) was used to identify DLEs. Service utilization was assessed using a module that elicited information about hospital admissions, consultations with various health professionals, and prescription medication use. This study focussed on service use for mental health problems. We used logistic regression to examine the association, adjusting for potential confounding factors.
Results
Of 8 773 included participants, 8.4% (n = 776) positively endorsed one or more DLEs. With respect to consultations for mental health needs, individuals who endorsed DLEs were more likely to consult health professionals compared with those who did not endorse DLEs. Individuals with DLEs were also more likely to use prescription medicine. When we repeated the main analysis in a subgroup excluding any CIDI diagnosis of mental health disorders the results remained largely unchanged.
Conclusions
DLEs are common in the general population, and individuals with DLEs have an increased rate of accessing services for their mental health needs. Individuals endorsing both DLEs and increased help-seeking may identify a group of vulnerable people who have increased risk of developing psychotic illnesses later in life. This needs closer scrutiny in longitudinal prospective studies.
doi:10.1371/journal.pone.0071951
PMCID: PMC3749219  PMID: 23991012

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