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1.  Knowledge of prescribed medication information among patients with limited English proficiency in Sri Lanka 
BMC Research Notes  2012;5:658.
Background
Patients’ knowledge on prescribed medications play a key role in the long term management of cardiac diseases and in determining their outcome. The present study evaluates the knowledge about prescribed medication among cardiac patients and aim to identify factors influencing knowledge.
Methods
A descriptive-cross-sectional study was conducted among 200 adult patients attending clinics at the Cardiology Unit of the National Hospital of Sri Lanka. Knowledge assessment focused on four different sections; drug name, dose, frequency and indication. The total score of 60 was calculated by giving each component the following weighted scores; drug name = 20, indication = 20, drug dose = 10 and frequency = 10. A binary logistic regression analysis to evaluate factors associated with ‘good knowledge’ (total score ≥ 40) was performed.
Results
Among 200 participants 56.5% (n = 113) were males. Mean age was 59.7 ± 8.2 years and a majority (n = 170, 85.0%) were older than 50 years of age. Sinhala was the primary language of 91.5% (n = 183) of participants, while English was the primary language in only two of the study participants (1.0%). Eighty four percent of the participants were educated up to secondary education or above, while 2.5% (n = 5) had no formal education. The overall knowledge (total score-60) on prescribed medications among the study population was ‘poor’ (score ≤ 20) in 46%, ‘adequate’ (score 21–40) in 36.5% and ‘good’ (score ≥ 40) in 17.5%. The results of the binary logistic regression analysis indicates that Secondary (OR-1.53) and Tertiary levels (OR-2.79) of education, self-reported perception of illness as being Moderate (OR-1.23) or Severe (OR-1.70) and being educated by a doctor (as reported by patients) (OR-1.69) significantly increased the odds of having a ‘Good Knowledge of Drugs’. Majority of the patients were unable to read and understand the information written in English. The doctor’s contributed towards educating on drug information only in 33.0% of the patients.
Conclusion
In a resource-poor setting in patients with Limited English Proficiency, lower level of education and misperception of illness severity resulted in reduced knowledge on prescribed medications. Furthermore, being educated by a doctor significantly improved knowledge. However the doctors’ contribution at present to deliver quality health information to their patients was at an unsatisfactory level.
doi:10.1186/1756-0500-5-658
PMCID: PMC3532203  PMID: 23191984
Limited English proficiency; Health literacy; Sri Lanka; Cardiac disease
2.  Molecular Epidemiology of Influenza A(H1N1)pdm09 Virus among Humans and Swine, Sri Lanka 
Emerging Infectious Diseases  2014;20(12):2080-2084.
After multiple discrete introductions of influenza A(H1N1)pdm09 virus into Sri Lanka, the virus was transmitted among humans, then swine. The spread of virus between geographically distant swine farms is consistent with virus dispersal associated with a vehicle used for swine transportation, although this remains unproven.
doi:10.3201/eid2012.140842
PMCID: PMC4257816  PMID: 25417652
Influenza; viruses; A(H1N1); pandemic; pdm09; 2009; biosecurity; evolution; interspecies transmission; human; swine; fomite; Sri Lanka
3.  Protective-antigen (PA) based anthrax vaccines confer protection against inhalation anthrax by precluding the establishment of a systemic infection 
Human Vaccines & Immunotherapeutics  2013;9(9):1841-1848.
An intense effort has been launched to develop improved anthrax vaccines that confer rapid, long lasting protection preferably with an extended stability profile amenable for stockpiling. Protective antigen (PA)-based vaccines are most favored as immune responses directed against PA are singularly protective, although the actual protective mechanism remains to be unraveled. Herein we show that contrary to the prevailing view, an efficacious PA-based vaccine confers protection against inhalation anthrax by preventing the establishment of a toxin-releasing systemic infection. Equally importantly, antibodies measured by the in vitro lethal toxin neutralization activity assay (TNA) that is considered as a reliable correlate of protection, especially for PA protein-based vaccines adjuvanted with aluminum salts appear to be not absolutely essential for this protective immune response.
doi:10.4161/hv.25337
PMCID: PMC3906346  PMID: 23787486
anthrax; vaccines; protective antigen; vaccinia; IL-15; bioluminescence
4.  Socio-Economic and Nutritional Determinants of Low Birth Weight in India 
Background:
Low birth weight (LBW) is an important risk factor for childhood morbidity and mortality, consequently an important public health concern.
Aim:
This study aims to identify significant socio-economic and nutritional determinants associated with LBW in India.
Materials and Methods:
Data from 2005 to 2006 National Family Health Survey-3 (NFHS-3) of India was analyzed. A total of 20,946 women (15-49 years) who gave birth at least once 5 years preceding the NFHS-3 were included in this study. Infant's LBW (<2500 grams) as outcome variable was examined in association with all independent predictors as infant's sex, maternal household wealth status, caste, age, education, body mass index (BMI), stature, anemia level, parity, inter-pregnancy interval, antenatal care received, and living place.
Results:
Almost 20% of the infants were born with LBW. Mother's low education level, BMI <18.5, short stature (height <145 centimeters) and lack of antenatal visits (<4 visits) were significant predictors of LBW. Male gender has a protective effect against LBW.
Conclusion:
Maternal education, nutritional status and antenatal care received are key determinants that need to be addressed to reduce prevalence of LBW in India. Continue implementation of multifaceted health promotion interventions are needed to address these factors effectively.
doi:10.4103/1947-2714.136902
PMCID: PMC4114006  PMID: 25077077
Child's birth weight; Infant; India; Low birth weight; Pregnancy
5.  Tofacitinib, a janus kinase inhibitor demonstrates efficacy in an IL-15 transgenic mouse model that recapitulates pathologic manifestations of celiac disease 
Journal of clinical immunology  2012;33(3):586-594.
Celiac disease (CD) is an immune-mediated, inflammatory disorder of the small intestines with a defined genetic etiological component associated with the expression of HLA-DQ2 and/or HLA-DQ8 haplotypes. The dietary consumption of gluten-rich cereals triggers a gluten-specific immune response in genetically susceptible individuals leading to a spectrum of clinical manifestations ranging from an inapparent subclinical disease, to overt enteropathy that can in some individuals progress to enteropathy-associated T cell lymphoma (EATL). The tissue-destructive pathologic process of CD is driven by activated NK-like intraepithelial CD8+ lymphocytes and the proinflammatory cytokine IL-15 has emerged to be pivotal in orchestrating this perpetual tissue destruction and inflammation. Moreover, transgenic mice that over-express human IL-15 from an enterocyte-specific promoter (T3b-hIL-15 Tg) recapitulate many of the disease-defining T and B cell-mediated pathologic features of CD, further supporting the evolving consensus that IL-15 represents a valuable target in devising therapeutic interventions against the form of the disease that is especially refractory to gluten-free diet. In the present study, we evaluated the potential efficacy of tofacitinib, a pan-JAK inhibitor that abrogates IL-15 signaling, as a therapeutic modality against CD using T3b-hIL-15 Tg mice. We demonstrate that tofacitinib therapy leads to a lasting reversal of pathologic manifestations in the treated mice, thereby highlighting the potential value of tofacitininb as a therapeutic modality against refractory CD for which no effective therapy exists currently. Additionally, the visceral adiposity observed in the tofacitinib-treated mice underscores the importance of continued evaluation of the drug's impact on the lipid metabolism.
doi:10.1007/s10875-012-9849-y
PMCID: PMC3594487  PMID: 23269601
6.  The role of Interleukin-15 in inflammation and immune responses to infection: implications for its therapeutic use 
Interleukin-15 (IL-15) is a pleiotropic cytokine with a broad range of biological functions in many diverse cell types. It plays a major role in the development of inflammatory and protective immune responses to microbial invaders and parasites by modulating immune cells of both the innate and adaptive immune systems. This review provides an overview of the mechanisms by which IL-15 modulates the host response to infectious agents and its utility as a cytokine adjuvant in vaccines against infectious pathogens.
doi:10.1016/j.micinf.2011.10.006
PMCID: PMC3270128  PMID: 22064066
IL-15; infectious diseases; vaccines; inflammation; molecular adjuvants
7.  Swine Influenza in Sri Lanka 
Emerging Infectious Diseases  2013;19(3):481-484.
To study influenza viruses in pigs in Sri Lanka,we examined samples from pigs at slaughterhouses. Influenza (H3N2) and A(H1N1)pdm09 viruses were prevalent during 2004–2005 and 2009–2012, respectively. Genetic and epidemiologic analyses of human and swine influenza viruses indicated 2 events of A(H1N1)pdm09 virus spillover from humans to pigs.
doi:10.3201/eid1903.120945
PMCID: PMC3647653  PMID: 23621918
swine influenza; Sri Lanka; epidemiology; viruses; spillover; ecology; A(H1N1)pdm09; influenza
8.  A rapid multi-disciplinary biodiversity assessment of the Kamdebooberge (Sneeuberg, Eastern Cape, South Africa): implications for conservation 
SpringerPlus  2012;1(1):56.
Botanical work since 2008 on the Sleeping Giant section of the Kamdebooberge (Sneeuberg mountain complex, Eastern Cape, South Africa) has indicated that these mountains may be of significant conservation value. Accordingly, a precursory, rapid multi-disciplinary biodiversity assessment was undertaken in January 2011, focusing on plants, tetrapod vertebrates and leafhoppers. The botanical results confirm the Kamdebooberge as being of high botanical conservation value, hosting three strict endemics, healthy populations of five other Sneeuberg endemics, and fynbos communities comprising species not found elsewhere in the Sneeuberg. The Kamdebooberge are important for herpetofauna (excluding serpentoids) and mammals, hosting several range-restricted and regional endemics. The expedition uncovered three new leafhopper species, together with several species previously only known from the Cape Floristic Region. Further detailed faunal work may provide further interesting results from these mountains, which show a high conservation value unique to the southern Escarpment.
Electronic supplementary material
The online version of this article (doi:10.1186/2193-1801-1-56) contains supplementary material, which is available to authorized users.
doi:10.1186/2193-1801-1-56
PMCID: PMC3540356  PMID: 23316449
Endemics; Great escarpment; Kamdebooberge; Plants; Invertebrates; Sneeuberg centre of floristic endemism; Vertebrates
9.  Effects of Cinnamomum zeylanicum (Ceylon cinnamon) on blood glucose and lipids in a diabetic and healthy rat model 
Pharmacognosy Research  2012;4(2):73-79.
Objectives:
To evaluate short- and long-term effects of Cinnamomum zeylanicum on food consumption, body weight, glycemic control, and lipids in healthy and diabetes-induced rats.
Materials and Methods:
The study was conducted in two phases (Phase I and Phase II), using Sprague-Dawley rats in four groups. Phase I evaluated acute effects on fasting blood glucose (FBG) (Groups 1 and 2) and on post-oral glucose (Groups 3 and 4) blood glucose. Groups 1 and 3 received distilled-water and Groups 2 and 4 received cinnamon-extracts. Phase II evaluated effects on food consumption, body weight, blood glucose, and lipids over 1 month. Group A (n = 8, distilled-water) and Group B (n = 8, cinnamon-extracts) were healthy rats, while Group C (n = 5, distilled-water) and Group D (n = 5, cinnamon-extracts) were diabetes-induced rats. Serum lipid profile and HbA1c were measured on D-0 and D-30. FBG, 2-h post-prandial blood glucose, body weight, and food consumption were measured on every fifth day.
Results:
Phase I: There was no significant difference in serial blood glucose values in cinnamon-treated group from time 0 (P > 0.05). Following oral glucose, the cinnamon group demonstrated a faster decline in blood glucose compared to controls (P < 0.05). Phase II: Between D0 and D30, the difference in food consumption was shown only in diabetes-induced rats (P < 0.001). Similarly, the significant difference following cinnamon-extracts in FBG and 2-h post-prandial blood glucose from D0 to D30 was shown only in diabetes-induced rats. In cinnamon-extracts administered groups, total and LDL cholesterol levels were lower on D30 in both healthy and diabetes-induced animals (P < 0.001).
Conclusions:
C. zeylanicum lowered blood glucose, reduced food intake, and improved lipid parameters in diabetes-induced rats.
doi:10.4103/0974-8490.94719
PMCID: PMC3326760  PMID: 22518078
Blood glucose; Ceylon cinnamon; Cinnamomum zeylanicum; diabetes mellitus; lipids; Sprague-Dawley rats
10.  Smallpox vaccine with integrated IL-15 demonstrates enhanced in vivo viral clearance in immunodeficient mice and confers long term protection against a lethal monkeypox challenge in cynomolgus monkeys 
Vaccine  2010;28(43):7081-7091.
Despite the eradication of smallpox, there is heightened concern that it could be reintroduced as a result of intentional release of Variola major virus through an act of bioterrorism. The live vaccine that was pivotal in the eradication of smallpox though considered a gold standard for its efficacy still retains sufficient residual virulence that can cause life-threatening sequelae especially in immune deficient individuals. Therefore, a safer smallpox vaccine that can match the efficacy of first generation vaccines is urgently needed. We previously reported that the integration of human IL-15 cytokine into the genome of Wyeth strain of vaccinia (Wyeth/IL-15), the same strain as the licensed vaccine, generates a vaccine with superior immunogenicity and efficacy in a mouse model. We now demonstrate that Wyeth/IL-15 is non-lethal to athymic nude mice when administered intravenously at a dose of 107 plaque forming units and it undergoes enhanced in vivo clearance in these immune deficient mice. Furthermore, a majority of cynomolgus monkeys vaccinated with vaccinia viruses with integrated IL-15, when challenged 3 years later with a lethal dose of monkeypox virus displayed milder clinical manifestations with complete recovery supporting the utility of Wyeth/IL-15 for contemporary populations as a safer and efficacious smallpox vaccine.
doi:10.1016/j.vaccine.2010.08.008
PMCID: PMC2952667  PMID: 20728526
11.  Brain Targeted Transcranial Administration of Diazepam and Shortening of Sleep Latency in Healthy Human Volunteers 
Application of medicated oils on scalp had been practiced for centuries in the Ayurvedic system of medicine in diseases associated with the central nervous system. It is possible that the effectiveness of the therapy may be a result of targeted delivery of active compounds to the brain transcranially. Evidence also comes from two previous studies with positive results on brain targeted transcranial delivery of methadone base and diazepam on rat models. Possibility of transcranial drug delivery was investigated in healthy human volunteers using electroencephalography techniques by assessing the ability of transcranially administered diazepam in bringing about β activity in the electroencephalographic wave patterns and shortening of the sleep latency period. Non polar drug molecules dissolved in a non-aqueous sesame oil based vehicle is a significant feature in the transcranial dosage design. The study was under taken in two phases. In the Phase-I study scalp application of a single dose of 2 mg/3 ml of the oil was employed and in the Phase-II study repeat application of three doses 24 h apart were employed. Sleep latency changes were monitored with Multiple Sleep Latency Tests with 5 naps employing the standard electroencephalography, electroocculography and electromyography electrodes. Sleep onset was identified with the first epoch of any sleep stage non rapid eye movement 1, 2, 3, 4 or rapid eye movement using electroencephalography, electroocculography and electromyography criteria. In both phases of the study there was significant reduction in the sleep latencies. It was much more pronounced in the Phase-II study. None of the subjects however displayed beta activity in the electroencephalography. Sleep latency reduction following scalp application in both the phases are suggestive of transcranial migration of diazepam molecules to the receptor sites of the nerve tissue of the brain eliciting its pharmacological effect of sedation. Transcranial brain targeted dosage design is therefore feasible.
doi:10.4103/0250-474X.98985
PMCID: PMC3425060  PMID: 22923861
Brain targeted; electroencephalography; emissary veins; diazepam; sesame oil; sleep latency; transcranial
12.  A Multi-valent Vaccinia Virus-based Tuberculosis Vaccine Molecularly Adjuvanted with Interleukin-15 Induces Robust Immune Responses in Mice 
Vaccine  2009;27(15):2121-2127.
Tuberculosis caused by Mycobacterium tuberculosis is responsible for nearly two million deaths every year globally. A single licensed vaccine derived from Mycobacterium bovis, bacille Calmette-Guerin (BCG) administered perinatally as a prophylactic vaccine has been in use for over 80 years and confers substantial protection against childhood tuberculous meningitis and miliary tuberculosis. However, the BCG vaccine is virtually ineffective against the adult pulmonary form of tuberculosis that is pivotal in the transmission of tuberculosis that has infected almost 33% of the global population. Thus, an effective vaccine to both prevent tuberculosis and reduce its transmission is urgently needed. We have generated a multi-valent, vectored vaccine candidate utilizing the modified virus Ankara (MVA) strain of vaccinia virus to tandemly express five antigens, ESAT6, Ag85A, Ag85B, HSP65 and Mtb39A of Mycobacterium tuberculosis that have been reported to be protective individually in certain animal models together with an immunostimulatory cytokine interleukin 15 (MVA/IL-15/5Mtb). Although, immunological correlates of protection against tuberculosis in humans remain to be established, we demonstrate that our vaccine induced comparable CD4+ T cell and greater CD8+ T cell and antibody responses against Mycobacterium tuberculosis in vaccinated mice in a direct comparison with the BCG vaccine and conferred protection against an aerogenic challenge of M. tuberculosis, thus warranting its further preclinical development.
doi:10.1016/j.vaccine.2009.01.132
PMCID: PMC2667804  PMID: 19356615
Tuberculosis; vaccine; IL-15
13.  Vaccinia virus-based multivalent H5N1 avian influenza vaccines adjuvanted with IL-15 confer sterile cross-clade protection in mice1 
The potential for a global influenza pandemic remains significant with epidemiologic and ecologic indicators revealing the entrenchment of highly pathogenic avian influenza A H5N1 in both wild bird populations and domestic poultry flocks in Asia and in many African and European countries. Indisputably, the single most effective public health intervention in mitigating the devastation such a pandemic could unleash is the availability of a safe and effective vaccine that can be rapidly deployed for pre-exposure vaccination of millions of people. We have developed two vaccinia-based influenza vaccines that are molecularly adjuvanted with the immune-stimulatory cytokine IL-15. The pentavalent Wyeth/IL-15/5Flu vaccine expresses the hemagglutinin, neuraminidase, and nucleoprotein, derived from the H5N1 influenza virus A/Vietnam/1203/2004 and the matrix proteins M1 and M2 from H5N1 A/CK/Indonesia/PA/2003 virus on the backbone of a currently licensed smallpox vaccine. The bivalent MVA/IL-15/HA/NA vaccine expresses only the H5 hemagglutinin and N1 neuraminidase on the modified vaccinia virus Ankara (MVA) backbone. Both vaccines induced cross-neutralizing antibodies and robust cellular immune responses in vaccinated mice and conferred sterile cross-clade protection when challenged with H5N1 virus of a different clade. In addition to having the potential as a universal influenza vaccine, in the event of an impending pandemic, the Wyeth/IL-15/5Flu is also readily amenable for bulk production to cover the global population. For those individuals for whom the use of Wyeth vaccine is contraindicated, our MVA/IL-15/HA/NA offers a substitute or a prevaccine to be used in a mass vaccination campaign similar to the smallpox eradication campaigns of few decades ago.
doi:10.4049/jimmunol.0803467
PMCID: PMC2656349  PMID: 19234203
Viral; Cytokines; vaccination
14.  Training simulated patients: evaluation of a training approach using self-assessment and peer/tutor feedback to improve performance 
Background
Most medical schools use simulated patients (SPs) for teaching. In this context the authenticity of role play and quality of feedback provided by SPs is of paramount importance. The available literature on SP training mostly addresses instructor led training where the SPs are given direction on their roles. This study focuses on the use of peer and self evaluation as a tool to train SPs.
Methods
SPs at the medical school participated in a staff development and training programme which included a) self-assessment of their performance while observing video-tapes of their role play using a structured guide and b) peer group assessment of their performance under tutor guidance. The pre and post training performance in relation to authenticity of role play and quality of feedback was blindly assessed by students and tutors using a validated instrument and the scores were compared. A focus group discussion and a questionnaire assessed acceptability of the training programme by the SPs.
Results
The post-training performance assessment scores were significantly higher (p < 0.05) than the pre-training scores. The degree of improvement in the quality of feedback provided to students was more when compared to the improvement of role play. The acceptability of the training by the SPs was very satisfactory scoring an average of 7.6 out of 10. The majority of the SPs requested the new method of training to be included in their current training programme as a regular feature.
Conclusion
Use of structured self-reflective and peer-interactive, practice based methods of SP training is recommended to improve SP performance. More studies on these methods of training may further refine SP training and lead to improvement of SP performance which in turn may positively impact medical education.
doi:10.1186/1472-6920-9-37
PMCID: PMC2711071  PMID: 19563621
15.  The prevalence of macrovascular disease and lipid abnormalities amongst diabetic patients in Sri Lanka. 
Postgraduate Medical Journal  1993;69(813):557-561.
The prevalence of macrovascular disease and hyperlipidaemia was examined in 500 patients with non-insulin-dependent diabetes mellitus attending a diabetic clinic in a Sri Lankan teaching hospital and 250 controls matched for age and gender. Macrovascular disease was assessed using a modified World Health Organisation questionnaire and modified Minnesota coding of electrocardiogram recordings. Twenty-one per cent of diabetic patients and 14.3% of controls had hypercholesterolaemia (P < 0.05). Macrovascular disease was present in 13.4% of diabetic patients and 8.2% of controls. Significant differences were seen in the prevalence of hypertension (15.6% vs 4.8%, P < 0.05), obesity (16.2% vs 9.7%, P < 0.05), peripheral vascular disease (5.6% vs 2%, P < 0.05) and electrocardiographic abnormalities (12% vs 6%, P < 0.05) in diabetic patients when compared to controls. Hyperlipidaemia and macrovascular disease is common in non-insulin-dependent diabetic patients in Sri Lanka and accounts for significant morbidity.
PMCID: PMC2399866  PMID: 8415344
16.  Mechanosignaling in Bone Health, Trauma and Inflammation 
Antioxidants & Redox Signaling  2014;20(6):970-985.
Abstract
Significance: Mechanosignaling is vital for maintaining the structural integrity of bone under physiologic conditions. These signals activate and suppress multiple signaling cascades regulating bone formation and resorption. Understanding these pathways is of prime importance to exploit their therapeutic potential in disorders associated with bone loss due to disuse, trauma, or disruption of homeostatic mechanisms. Recent Advances: In the case of cells of the bone, an impressive amount of data has been generated that provides evidence of a complex mechanism by which mechanical signals can maintain or disrupt cellular homeostasis by driving transcriptional regulation of growth factors, matrix proteins and inflammatory mediators in health and inflammation. Mechanical signals act on cells in a magnitude dependent manner to induce bone deposition or resorption. During health, physiological levels of these signals are essential for maintaining bone strength and architecture, whereas during inflammation, similar signals can curb inflammation by suppressing the nuclear factor kappa B (NF-κB) signaling cascade, while upregulating matrix synthesis via mothers against decapentaplegic homolog and/or Wnt signaling cascades. Contrarily, excessive mechanical forces can induce inflammation via activation of the NF-κB signaling cascade. Critical Issues: Given the osteogenic potential of mechanical signals, it is imperative to exploit their therapeutic efficacy for the treatment of bone disorders. Here we review select signaling pathways and mediators stimulated by mechanical signals to modulate the strength and integrity of the bone. Future Directions: Understanding the mechanisms of mechanotransduction and its effects on bone lay the groundwork for development of nonpharmacologic mechanostimulatory approaches for osteodegenerative diseases and optimal bone health. Antioxid. Redox Signal. 20, 970–985.
doi:10.1089/ars.2013.5467
PMCID: PMC3924811  PMID: 23815527
17.  Genome-wide association analyses identify three new susceptibility loci for primary angle closure glaucoma 
Vithana, Eranga N | Khor, Chiea-Chuen | Qiao, Chunyan | Nongpiur, Monisha E | George, Ronnie | Chen, Li-Jia | Do, Tan | Abu-Amero, Khaled | Huang, Chor Kai | Low, Sancy | Tajudin, Liza-Sharmini A | Perera, Shamira A | Cheng, Ching-Yu | Xu, Liang | Jia, Hongyan | Ho, Ching-Lin | Sim, Kar Seng | Wu, Ren-Yi | Tham, Clement C Y | Chew, Paul T K | Su, Daniel H | Oen, Francis T | Sarangapani, Sripriya | Soumittra, Nagaswamy | Osman, Essam A | Wong, Hon-Tym | Tang, Guangxian | Fan, Sujie | Meng, Hailin | Huong, Dao T L | Wang, Hua | Feng, Bo | Baskaran, Mani | Shantha, Balekudaru | Ramprasad, Vedam L | Kumaramanickavel, Govindasamy | Iyengar, Sudha K | How, Alicia C | Lee, Kelvin Y | Sivakumaran, Theru A | Yong, Victor H K | Ting, Serena M L | Li, Yang | Wang, Ya-Xing | Tay, Wan-Ting | Sim, Xueling | Lavanya, Raghavan | Cornes, Belinda K | Zheng, Ying-Feng | Wong, Tina T | Loon, Seng-Chee | Yong, Vernon K Y | Waseem, Naushin | Yaakub, Azhany | Chia, Kee-Seng | Allingham, R Rand | Hauser, Michael A | Lam, Dennis S C | Hibberd, Martin L | Bhattacharya, Shomi S | Zhang, Mingzhi | Teo, Yik Ying | Tan, Donald T | Jonas, Jost B | Tai, E-Shyong | Saw, Seang-Mei | Hon, Do Nhu | Al-Obeidan, Saleh A | Liu, Jianjun | Chau, Tran Nguyen Bich | Simmons, Cameron P | Bei, Jin-Xin | Zeng, Yi-Xin | Foster, Paul J | Vijaya, Lingam | Wong, Tien-Yin | Pang, Chi-Pui | Wang, Ningli | Aung, Tin
Nature genetics  2012;44(10):1142-1146.
Primary angle closure glaucoma (PACG) is a major cause of blindness worldwide. We conducted a genome-wide association study including 1,854 PACG cases and 9,608 controls across 5 sample collections in Asia. Replication experiments were conducted in 1,917 PACG cases and 8,943 controls collected from a further 6 sample collections. We report significant associations at three new loci: rs11024102 in PLEKHA7 (per-allele odds ratio (OR) = 1.22; P = 5.33 × 10−12), rs3753841 in COL11A1 (per-allele OR = 1.20; P = 9.22 × 10−10) and rs1015213 located between PCMTD1 and ST18 on chromosome 8q (per-allele OR = 1.50; P = 3.29 × 10−9). Our findings, accumulated across these independent worldwide collections, suggest possible mechanisms explaining the pathogenesis of PACG.
doi:10.1038/ng.2390
PMCID: PMC4333205  PMID: 22922875
18.  Cell Permeable Au@ZnMoS4 Core-Shell Nanoparticles: Towards a Novel Cellular Copper Detoxifying Drug for Wilson’s Disease 
A layer-by-layer self-assembly method leads to the formation of Au@ZnMoS4 core-shell nanoparticles (NPs). The PEGylated Au@ZnMoS4 NPs are highly water-dispersible, exhibit no cytotoxicity and can penetrate the cell membrane to selectively remove copper(I) ions from HepG2 cells in the presence of other endogenous and biologically essential metal ions including Mg(II), Ca(II), Mn(II) and Fe(II), demonstrating their potential as a novel intracellular copper detoxifying agent.
doi:10.1021/cm402147u
PMCID: PMC4331036
Core/Shell Nanoparticles; Drug Delivery; Functional Coatings; Gold Nanoparticles; Biomedical Applications; Layer-by-Layer Self-Assembly
19.  Lead toxicity among traffic wardens: a high risk group exposed to atmospheric lead, is it still a cause for concern? 
Background
Traffic policemen are identified to be at a higher risk of exposure to air pollution and its contaminants such as lead. A study done prior to the introduction of unleaded petroleum in Sri Lanka revealed a mean blood lead level of 53.07 μg/dL, which was well above the Center for Disease Control defined acceptable safe levels. This study aimed to determine whether unleading of fuel has made an impact on the blood lead levels of traffic police working in an urban area with high traffic density.
Method
A cross-sectional survey of 168 traffic police personnel working within Colombo city limits of Sri Lanka, a high traffic density area, was conducted. Blood lead levels of participants were measured using nitric acid, perchloric acid ashing method and atomic absorption spectrophotometry. An interviewer administered questionnaire was used for a targeted history and examination.
Results and discussion
Mean age of the sample population was 37 years. Thirty eight percent had detectable levels of lead in blood and 24.4% of the study sample had blood lead levels above Centre for disease control defined safe limits. Sample mean was 4.82 μg/dL (95% CI 3.58-6.04), and this is a 91% overall reduction when compared to data prior to unleading. Neither symptoms nor signs of classic lead toxicity showed significant correlation with toxic lead levels.
Conclusion
Lead poisoning though still present in the high risk traffic warden population shows a considerable reduction following unleading. The need to have a low threshold to suspect lead poisoning is highlighted by the non-specific nature of the symptoms and signs of lead poisoning and its lack of association even in those found to have elevated lead levels. Further studies are required to elucidate a cause for the prevalence of lead poisoning despite cessation of using lead as an additive in petroleum.
doi:10.1186/s12995-015-0046-9
PMCID: PMC4323022  PMID: 25670963
Lead toxicity; Sri Lanka; Unleading; Traffic police
20.  Identification of a novel lncRNA in gluteal adipose tissue and evidence for its positive effect on preadipocyte differentiation 
Obesity (Silver Spring, Md.)  2014;22(8):1781-1785.
Context
Peripheral lower body fat is associated with lower cardiometabolic risk. Physiological differences in gluteal compared to abdominal subcutaneous (sc) adipocyte functions are known but the molecular basis for depot differences in adipocyte function is poorly understood.
Objective
To identify novel gene regulatory pathways that underlie the heterogeneity of human fat distribution.
Design and methods
Abdominal and gluteal adipose tissue aspirates obtained from 35 subjects (age=30±1.6 years; BMI=27.3±1.3kg/m2) were analyzed using Illumina microarrays and confirmed by RT-PCR. The HOTAIR gene was stably transfected into primary cultured human abdominal sc preadipocytes using a lentivirus and effects on adipogenic differentiation were analyzed.
Results
We identified a long non-coding RNA, HOTAIR that was expressed in gluteal but not in Abd sc adipose tissue. This difference was retained throughout in vitro differentiation and was maximal at day 4. Ectopic expression of HOTAIR in abdominal preadipocytes produced an increase in differentiation as reflected by a higher percentage of differentiated cells, and increased expression of key adipogenic genes including PPARγ and LPL.
Conclusion
HOTAIR is expressed in gluteal adipose and may regulate key processes in adipocyte differentiation. The role of this lncRNA in determining the metabolic properties of gluteal compared to abdominal adipocytes merits further study.
doi:10.1002/oby.20793
PMCID: PMC4228784  PMID: 24862299
HOTAIR; Gluteal adipose tissue; adipogenic differentiation
21.  Evaluation of Commercially Available RNA Amplification Kits for RNA Sequencing Using Very Low Input Amounts of Total RNA 
This article includes supplemental data. Please visit http://www.fasebj.org to obtain this information.Multiple recent publications on RNA sequencing (RNA-seq) have demonstrated the power of next-generation sequencing technologies in whole-transcriptome analysis. Vendor-specific protocols used for RNA library construction often require at least 100 ng total RNA. However, under certain conditions, much less RNA is available for library construction. In these cases, effective transcriptome profiling requires amplification of subnanogram amounts of RNA. Several commercial RNA amplification kits are available for amplification prior to library construction for next-generation sequencing, but these kits have not been comprehensively field evaluated for accuracy and performance of RNA-seq for picogram amounts of RNA. To address this, 4 types of amplification kits were tested with 3 different concentrations, from 5 ng to 50 pg, of a commercially available RNA. Kits were tested at multiple sites to assess reproducibility and ease of use. The human total reference RNA used was spiked with a control pool of RNA molecules in order to further evaluate quantitative recovery of input material. Additional control data sets were generated from libraries constructed following polyA selection or ribosomal depletion using established kits and protocols. cDNA was collected from the different sites, and libraries were synthesized at a single site using established protocols. Sequencing runs were carried out on the Illumina platform. Numerous metrics were compared among the kits and dilutions used. Overall, no single kit appeared to meet all the challenges of small input material. However, it is encouraging that excellent data can be recovered with even the 50 pg input total RNA.
doi:10.7171/jbt.15-2601-001
PMCID: PMC4310221  PMID: 25649271
cDNA synthesis kits; polyA; ribodepletion
22.  Measurement of Cancer Health Literacy and Identification of Patients with Limited Cancer Health Literacy 
Journal of health communication  2014;19(0 2):205-224.
Health literacy is related to a broad range of health outcomes. This study was designed to develop a psychometrically sound instrument designed to measure cancer health literacy along a continuum (CHLT-30), to develop another instrument designed to determine whether a patient has limited cancer health literacy (CHLT-6), and to estimate the prevalence of limited cancer health literacy. The Cancer Health Literacy Study involving 1,306 Black and White cancer patients was conducted between April 2011 and April 2013 in the Virginia Commonwealth University Massey Cancer Center and surrounding oncology clinics. A continuous latent variable modeling framework was adopted to dimensionally represent cancer health literacy, whereas discrete latent variable modeling was used to estimate the prevalence rates of limited cancer health literacy. Self confidence about engaging in health decisions was used as the primary outcome in external validation of new instruments. Results from a comprehensive analysis strongly supported the construct validity and reliability of the CHLT-30 and CHLT-6. For both instruments, measurement invariance tests ruled out item/test bias to explain gender and race/ethnicity differences in test scores. The limited cancer health literacy rate was 18%, a subpopulation consisting of overrepresented Black, undereducated, and low-income cancer patients. Overall, the results supported the conclusion that the CHLT-30 accurately measures cancer health literacy along a continuum and that the CHLT-6 efficiently identifies patients with limited cancer health literacy with high accuracy.
doi:10.1080/10810730.2014.943377
PMCID: PMC4283207  PMID: 25315594
23.  Significant interactions between maternal PAH exposure and haplotypes in candidate genes on B[a]P-DNA adducts in a NYC cohort of non-smoking African-American and Dominican mothers and newborns 
Carcinogenesis  2013;35(1):69-75.
Summary
Our study, conducted within a New York City-based cohort, identified novel interactions between maternal PAH exposure and maternal and newborn genetic haplotypes in key B[a]P metabolism genes on B[a]P-DNA adducts in paired cord blood samples.
Polycyclic aromatic hydrocarbons (PAH) are a class of chemicals common in the environment. Certain PAH are carcinogenic, although the degree to which genetic variation influences susceptibility to carcinogenic PAH remains unclear. Also unknown is the influence of genetic variation on the procarcinogenic effect of in utero exposures to PAH. Benzo[a]pyrene (B[a]P) is a well-studied PAH that is classified as a probable human carcinogen. Within our New York City-based cohort, we explored interactions between maternal exposure to airborne PAH during pregnancy and maternal and newborn haplotypes (and in one case, a single-nucleotide polymorphism) in key B[a]P metabolism genes on B[a]P-DNA adducts in paired cord blood samples. The study subjects included non-smoking African-American (n = 132) and Dominican (n = 235) women with available data on maternal PAH exposure, paired cord adducts and genetic data who resided in the Washington Heights, Central Harlem and South Bronx neighborhoods of New York City. We selected seven maternal and newborn genes related to B[a]P metabolism, detoxification and repair for our analyses: CYP1A1, CYP1A2, CYP1B1, GSTM3, GSTT2, NQO1 and XRCC1. We found significant interactions between maternal PAH exposure and haplotype on cord B[a]P-DNA adducts in the following genes: maternal CYP1B1, XRCC1 and GSTM3, and newborn CYP1A2 and XRCC1 in African-Americans; and maternal XRCC1 and newborn NQO1 in Dominicans. These novel findings highlight differences in maternal and newborn genetic contributions to B[a]P-DNA adduct formation, as well as ethnic differences in gene–environment interactions, and have the potential to identify at-risk subpopulations who are susceptible to the carcinogenic potential of B[a]P.
doi:10.1093/carcin/bgt339
PMCID: PMC3871941  PMID: 24177223
24.  Polycyclic Aromatic Hydrocarbon Exposure, Obesity and Childhood Asthma in an Urban Cohort 
Environmental research  2013;128:35-41.
Background
Exposure to traffic-related air pollutants, including polycyclic aromatic hydrocarbons (PAHs) from traffic emissions and other combustion sources, and childhood obesity, have been implicated as risk factors for developing asthma. However, the interaction between these two on asthma among young urban children has not been studied previously.
Methods
Exposure to early childhood PAHs was measured by two week residential indoor monitoring at age 5–6 years in the Columbia Center for Children's Environmental Health birth cohort (n=311). Semivolatile [e.g., methylphenanthrenes] and nonvolatile [e.g., benzo(a)pyrene] PAHs were monitored. Obesity at age 5 was defined as a body mass index (BMI) greater than or equal to the 95th percentile of the year 2000 age- and sex- specific growth charts (Center for Disease Control). Current asthma and recent wheeze at ages 5 and 7 were determined by validated questionnaires. Data were analyzed using a modified Poisson regression in generalized estimating equations (GEE) to estimate relative risks (RR), after adjusting for potential covariates.
Results
Neither PAH concentrations or obesity had a main effect on asthma or recent wheeze. In models stratified by presence/absence of obesity, a significant positive association was observed between an interquartile range (IQR) increase in natural log-transformed 1-methylphenanthrene (RR [95% CI]: 2.62 [1.17–5.88] with IQRln=0.76), and 9-methylphenanthrene (2.92 [1.09–7.82] with IQRln=0.73) concentrations and asthma in obese children (n=63). No association in non-obese (n=248) children was observed at age 5 (Pinteraction < 0.03). Similar associations were observed for 3-methylphenanthrene, 9-methylphenanthrene, and 3,6-dimethylphenanthrene at age 7.
Conclusions
Obese young children may be more likely to develop asthma in association with greater exposure to PAHs, and methylphenanthrenes in particular, than non-obese children.
doi:10.1016/j.envres.2013.12.002
PMCID: PMC3912566  PMID: 24407477
Childhood obesity; methylphenanthrenes; polycyclic aromatic hydrocarbons; asthma; nonatopic children
25.  Hospital-Associated Transmission of Brucella melitensis outside the Laboratory1 
Emerging Infectious Diseases  2015;21(1):150-152.
Brucella melitensis was identified in an aspirate obtained from a patient’s hip joint during a procedure at a hospital in Canada. We conducted an investigation into possible exposures among hospital workers; 1 worker who assisted with the procedure tested positive for B. melitensis. Aerosol-generating procedures performed outside the laboratory may facilitate transmission of this bacterium.
doi:10.3201/eid2101.141247
PMCID: PMC4285263  PMID: 25531198
Brucella; Brucella melitensis; nosocomial infection; health care workers; laboratory-acquired infection; transmission; bacteria

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