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2.  Integrated genomic approaches identify major pathways and upstream regulators in late onset Alzheimer’s disease 
Scientific Reports  2015;5:12393.
Previous studies have evaluated gene expression in Alzheimer’s disease (AD) brains to identify mechanistic processes, but have been limited by the size of the datasets studied. Here we have implemented a novel meta-analysis approach to identify differentially expressed genes (DEGs) in published datasets comprising 450 late onset AD (LOAD) brains and 212 controls. We found 3124 DEGs, many of which were highly correlated with Braak stage and cerebral atrophy. Pathway Analysis revealed the most perturbed pathways to be (a) nitric oxide and reactive oxygen species in macrophages (NOROS), (b) NFkB and (c) mitochondrial dysfunction. NOROS was also up-regulated, and mitochondrial dysfunction down-regulated, in healthy ageing subjects. Upstream regulator analysis predicted the TLR4 ligands, STAT3 and NFKBIA, for activated pathways and RICTOR for mitochondrial genes. Protein-protein interaction network analysis emphasised the role of NFKB; identified a key interaction of CLU with complement; and linked TYROBP, TREM2 and DOK3 to modulation of LPS signalling through TLR4 and to phosphatidylinositol metabolism. We suggest that NEUROD6, ZCCHC17, PPEF1 and MANBAL are potentially implicated in LOAD, with predicted links to calcium signalling and protein mannosylation. Our study demonstrates a highly injurious combination of TLR4-mediated NFKB signalling, NOROS inflammatory pathway activation, and mitochondrial dysfunction in LOAD.
PMCID: PMC4511863  PMID: 26202100
3.  CrEdit: CRISPR mediated multi-loci gene integration in Saccharomyces cerevisiae 
One of the bottlenecks in production of biochemicals and pharmaceuticals in Saccharomyces cerevisiae is stable and homogeneous expression of pathway genes. Integration of genes into the genome of the production organism is often a preferred option when compared to expression from episomal vectors. Existing approaches for achieving stable simultaneous genome integrations of multiple DNA fragments often result in relatively low integration efficiencies and furthermore rely on the use of selection markers.
Here, we have developed a novel method, CrEdit (CRISPR/Cas9 mediated genome Editing), which utilizes targeted double strand breaks caused by CRISPR/Cas9 to significantly increase the efficiency of homologous integration in order to edit and manipulate genomic DNA. Using CrEdit, the efficiency and locus specificity of targeted genome integrations reach close to 100% for single gene integration using short homology arms down to 60 base pairs both with and without selection. This enables direct and cost efficient inclusion of homology arms in PCR primers. As a proof of concept, a non-native β-carotene pathway was reconstructed in S. cerevisiae by simultaneous integration of three pathway genes into individual intergenic genomic sites. Using longer homology arms, we demonstrate highly efficient and locus-specific genome integration even without selection with up to 84% correct clones for simultaneous integration of three gene expression cassettes.
The CrEdit approach enables fast and cost effective genome integration for engineering of S. cerevisiae. Since the choice of the targeting sites is flexible, CrEdit is a powerful tool for diverse genome engineering applications.
Electronic supplementary material
The online version of this article (doi:10.1186/s12934-015-0288-3) contains supplementary material, which is available to authorized users.
PMCID: PMC4492099  PMID: 26148499
Metabolic engineering; CRISPR/Cas9; Genome editing; Saccharomyces cerevisiae; Carotenoid production; Genome integrations
4.  Characterizing Social Interaction in Tobacco-Oriented Social Networks: An Empirical Analysis 
Scientific Reports  2015;5:10060.
Social media is becoming a new battlefield for tobacco “wars”. Evaluating the current situation is very crucial for the advocacy of tobacco control in the age of social media. To reveal the impact of tobacco-related user-generated content, this paper characterizes user interaction and social influence utilizing social network analysis and information theoretic approaches. Our empirical studies demonstrate that the exploding pro-tobacco content has long-lasting effects with more active users and broader influence, and reveal the shortage of social media resources in global tobacco control. It is found that the user interaction in the pro-tobacco group is more active, and user-generated content for tobacco promotion is more successful in obtaining user attention. Furthermore, we construct three tobacco-related social networks and investigate the topological patterns of these tobacco-related social networks. We find that the size of the pro-tobacco network overwhelms the others, which suggests a huge number of users are exposed to the pro-tobacco content. These results indicate that the gap between tobacco promotion and tobacco control is widening and tobacco control may be losing ground to tobacco promotion in social media.
PMCID: PMC4473607  PMID: 26091553
5.  Mental Health Problems in Adolescence and the Interpretation of Unambiguous Threat 
PLoS ONE  2015;10(6):e0127167.
Aberrant threat perception has been linked to paranoia, anxiety and other mental health problems, and is widely considered to be a core, transdiagnostic feature of psychopathology. However, to date there has been only limited investigation of whether mental health problems are associated with a biased interpretation of stimuli that have explicit (as opposed to ambiguous) connotations of threat. In the present study, 41 adolescents diagnosed with a mental illness and 45 demographically matched controls were asked to provide danger ratings of stimuli normatively rated as being either low or high in potential threat. All participants were also asked to complete background measures of cognitive function, mental health and wellbeing. The results indicated that the two groups did not differ in their capacity to discriminate between low and high threat stimuli, nor did they differ in the absolute level of threat that they attributed to these stimuli. However, for the control group, the overall level of threat perceived in facial stimuli was correlated with two important indices of mental health (depression and anxiety). No associations emerged in the clinical group. These data are discussed in relation to their potential implications for the role of aberrant threat perception in transdiagnostic models of mental health.
PMCID: PMC4454485  PMID: 26039081
6.  Effects of Ambient Coarse, Fine, and Ultrafine Particles and Their Biological Constituents on Systemic Biomarkers: A Controlled Human Exposure Study 
Environmental Health Perspectives  2015;123(6):534-540.
Ambient coarse, fine, and ultrafine particles have been associated with mortality and morbidity. Few studies have compared how various particle size fractions affect systemic biomarkers.
We examined changes of blood and urinary biomarkers following exposures to three particle sizes.
Fifty healthy nonsmoking volunteers, mean age of 28 years, were exposed to coarse (2.5–10 μm; mean, 213 μg/m3) and fine (0.15–2.5 μm; mean, 238 μg/m3) concentrated ambient particles (CAPs), and filtered ambient and/or medical air. Twenty-five participants were exposed to ultrafine CAP (< 0.3 μm; mean, 136 μg/m3) and filtered medical air. Exposures lasted 130 min, separated by ≥ 2 weeks. Blood/urine samples were collected preexposure and 1 hr and 21 hr postexposure to determine blood interleukin-6 and C-reactive protein (inflammation), endothelin-1 and vascular endothelial growth factor (VEGF; vascular mediators), and malondialdehyde (lipid peroxidation); as well as urinary VEGF, 8-hydroxy-deoxy-guanosine (DNA oxidation), and malondialdehyde. Mixed-model regressions assessed pre- and postexposure differences.
One hour postexposure, for every 100-μg/m3 increase, coarse CAP was associated with increased blood VEGF (2.41 pg/mL; 95% CI: 0.41, 4.40) in models adjusted for O3, fine CAP with increased urinary malondialdehyde in single- (0.31 nmol/mg creatinine; 95% CI: 0.02, 0.60) and two-pollutant models, and ultrafine CAP with increased urinary 8-hydroxydeoxyguanosine in single- (0.69 ng/mg creatinine; 95% CI: 0.09, 1.29) and two-pollutant models, lasting < 21 hr. Endotoxin was significantly associated with biomarker changes similar to those found with CAPs.
Ambient particles with various sizes/constituents may influence systemic biomarkers differently. Endotoxin in ambient particles may contribute to vascular mediator changes and oxidative stress.
Liu L, Urch B, Poon R, Szyszkowicz M, Speck M, Gold DR, Wheeler AJ, Scott JA, Brook JR, Thorne PS, Silverman FS. 2015. Effects of ambient coarse, fine, and ultrafine particles and their biological constituents on systemic biomarkers: a controlled human exposure study. Environ Health Perspect 123:534–540;
PMCID: PMC4455587  PMID: 25616223
7.  Multi-Service Highly Sensitive Rectifier for Enhanced RF Energy Scavenging 
Scientific Reports  2015;5:9655.
Due to the growing implications of energy costs and carbon footprints, the need to adopt inexpensive, green energy harvesting strategies are of paramount importance for the long-term conservation of the environment and the global economy. To address this, the feasibility of harvesting low power density ambient RF energy simultaneously from multiple sources is examined. A high efficiency multi-resonant rectifier is proposed, which operates at two frequency bands (478–496 and 852–869 MHz) and exhibits favorable impedance matching over a broad input power range (−40 to −10 dBm). Simulation and experimental results of input reflection coefficient and rectified output power are in excellent agreement, demonstrating the usefulness of this innovative low-power rectification technique. Measurement results indicate an effective efficiency of 54.3%, and an output DC voltage of 772.8 mV is achieved for a multi-tone input power of −10 dBm. Furthermore, the measured output DC power from harvesting RF energy from multiple services concurrently exhibits a 3.14 and 7.24 fold increase over single frequency rectification at 490 and 860 MHz respectively. Therefore, the proposed multi-service highly sensitive rectifier is a promising technique for providing a sustainable energy source for low power applications in urban environments.
PMCID: PMC4423474  PMID: 25951137
8.  Factors Influencing the Likelihood of Instrumental Delivery Success 
Obstetrics and gynecology  2014;123(4):796-803.
To evaluate risk factors for unsuccessful instrumental delivery when variability between individual accoucheurs is taken into account.
We conducted a retrospective cohort study of attempted instrumental deliveries over a 5-year period (2008–2012 inclusive) in a tertiary U.K. center. To account for inter-accoucheur variability, we matched unsuccessful deliveries (cases) with successful deliveries (controls) by the same operators. Multivariate logistic regression was used to compare successful and unsuccessful instrumental deliveries.
Three thousand seven hundred ninety-eight Instrumental deliveries of vertex-presenting, single, term infants were attempted, of which 246 were unsuccessful (6.5%). Increased birth weight (OR=1.11 p<0.001), second-stage duration (OR=1.01 p<0.001), rotational delivery (OR=1.52 p<0.05) and use of ventouse versus forceps (OR=1.33 p<0.05) were associated with unsuccessful outcome. When interaccoucheur variability was controlled for, instrument selection and decision to rotate were no longer associated with instrumental delivery success. More senior accoucheurs had higher rates of unsuccessful deliveries (12% v. 5%, p<0.05), but undertook more complicated cases. Cesarean delivery in the second stage without prior attempt at instrumental delivery was associated with higher birth weight (OR=1.07 p<0.001), increased maternal age (OR=1.03 p<0.01), and epidural analgesia (OR=1.46 p<0.001).
Results suggest that birth weight and head position are the most important factors in successful instrumental delivery, whereas the influence of instrument selection and rotational delivery appear to be operator-dependent. Risk factors for lack of instrumental delivery success are distinct from risk factors for requiring instrumental delivery, and these should not be conflated in clinical practice.
PMCID: PMC4009507  PMID: 24785607
9.  A coherent approach for analysis of the Illumina HumanMethylation450 BeadChip improves data quality and performance in epigenome-wide association studies 
Genome Biology  2015;16(1):37.
DNA methylation plays a fundamental role in the regulation of the genome, but the optimal strategy for analysis of genome-wide DNA methylation data remains to be determined. We developed a comprehensive analysis pipeline for epigenome-wide association studies (EWAS) using the Illumina Infinium HumanMethylation450 BeadChip, based on 2,687 individuals, with 36 samples measured in duplicate. We propose new approaches to quality control, data normalisation and batch correction through control-probe adjustment and establish a null hypothesis for EWAS using permutation testing. Our analysis pipeline outperforms existing approaches, enabling accurate identification of methylation quantitative trait loci for hypothesis driven follow-up experiments.
Electronic supplementary material
The online version of this article (doi:10.1186/s13059-015-0600-x) contains supplementary material, which is available to authorized users.
PMCID: PMC4365767  PMID: 25853392
10.  Exploring How the Tobacco Industry Presents and Promotes Itself in Social Media 
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.
The goal of this study was to reveal what is presented by the tobacco industry, and how it promotes itself, on social media sites.
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.
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).
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.
PMCID: PMC4319084  PMID: 25608524
cigarette brands; promotional strategy; social media; tobacco control; tobacco promotion
11.  Dietary cholesterol directly induces acute inflammasome-dependent intestinal inflammation 
Nature Communications  2014;5:5864.
Prolonged ingestion of a cholesterol- or saturated fatty acid-enriched diet induces chronic, often systemic, auto-inflammatory responses resulting in significant health problems worldwide. In vivo information regarding the local and direct inflammatory effect of these dietary components in the intestine and, in particular, on the intestinal epithelium is lacking. Here we report that both mice and zebrafish exposed to high-fat (HFDs) or high-cholesterol (HCDs) diets develop acute innate inflammatory responses within hours, reflected in the localized interleukin-1β-dependent accumulation of myeloid cells in the intestine. Acute HCD-induced intestinal inflammation is dependent on cholesterol uptake via Niemann-Pick C1-like 1 and inflammasome activation involving apoptosis-associated Speck-like protein containing a caspase recruitment domain, which leads to Caspase-1 activity in intestinal epithelial cells. Extended exposure to HCD results in localized, inflammation-dependent, functional dysregulation as well as systemic pathologies. Our model suggests that dietary cholesterol initiates intestinal inflammation in epithelial cells.
Chronic consumption of a Western-type diet leads to systemic inflammation of undefined origin, which contributes to metabolic disease. Here Progatzky et al. identify an immediate early step in the process by showing that dietary cholesterol rapidly activates inflammasomes in the gut epithelium.
PMCID: PMC4284652  PMID: 25536194
12.  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.
PMCID: PMC4186654  PMID: 25298755
Nonmarital fertility; Religiosity; Reproductive and sexual health; Add Health; Health inequalities
13.  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.
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.
PMCID: PMC3751279  PMID: 23617608
assessment tools; neuropsychology; outcome measures; recovery; traumatic brain injury
14.  Western Cold and Flu (WeCoF) aerosol study – preliminary results 
BMC Research Notes  2014;7:563.
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.
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.
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.
PMCID: PMC4150972  PMID: 25148847
Cough; Cold; Influenza; Particle Image Velocimetry; Airflow sampling; Bioaerosol
15.  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.
PMCID: PMC4130493  PMID: 25115870
16.  Validity of the diagnostic criteria for chronic cerebrospinal venous insufficiency and association with multiple sclerosis 
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.
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.
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.
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.
PMCID: PMC4119167  PMID: 24890104
17.  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.
PMCID: PMC4141313  PMID: 24936085
nonclinical; need for care; psychosis; prevalence
18.  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.
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.
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.
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.
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.
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.
PMCID: PMC4048218  PMID: 24905346
19.  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.
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.
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 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.
PMCID: PMC4044043  PMID: 22393036
20.  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.
PMCID: PMC4038424  PMID: 24899795
Berlin’s edema; commotio retinae; optical coherence tomography; OCT; ocular trauma
21.  Child maltreatment and adolescent mental health problems in a large birth cohort 
Child abuse & neglect  2013;37(5):292-302.
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.
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.
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).
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.
PMCID: PMC3918944  PMID: 23380430
22.  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.
PMCID: PMC3967993  PMID: 24675842

Results 1-25 (116)