Publications by authors named "Ruth Lee"

31 Publications

Identification of the Functional Binding Site for the Convulsant Tetramethylenedisulfotetramine in the Pore of the GABA Receptor.

Mol Pharmacol 2021 01 27;99(1):78-91. Epub 2020 Oct 27.

Departments of Pharmacology (B.P., R.D.L, H.W.) and Entomology and Nematology, and Comprehensive Cancer Center (B.B., B.D.H.), University of California, Davis, California

Tetramethylenedisulfotetramine (TETS) is a so-called "caged" convulsant that is responsible for thousands of accidental and malicious poisonings. Similar to the widely used GABA receptor type A (GABA) antagonist picrotoxinin, TETS has been proposed to bind to the noncompetitive antagonist (NCA) site in the pore of the receptor channel. However, the TETS binding site has never been experimentally mapped, and we here set out to gain atomistic level insights into how TETS inhibits the human GABA receptor. Using the Rosetta molecular modeling suite, we generated three homology models of the receptor in the open, desensitized, and closed/resting state. Three different ligand-docking algorithms (RosettaLigand, Glide, and Swissdock) identified two possible TETS binding sites in the channel pore. Using a combination of site-directed mutagenesis, electrophysiology, and modeling to probe both sites, we demonstrate that TETS binds at the T6' ring in the closed/resting-state model, in which it shows perfect space complementarity and forms hydrogen bonds or makes hydrophobic interactions with all five pore-lining threonine residues of the pentameric receptor. Mutating T6' in either the or subunit reduces the IC of TETS by ∼700-fold in whole-cell patch-clamp experiments. TETS is thus interacting at the NCA site in the pore of the GABA receptor at a location that is overlapping but not identical to the picrotoxinin binding site. SIGNIFICANCE STATEMENT: Our study identifies the binding site of the highly toxic convulsant tetramethylenedisulfotetramine (TETS), which is classified as a threat agent by the World Health Organization. Using a combination of homology protein modeling, ligand docking, site-directed mutagenesis, and electrophysiology, we show that TETS is binding in the pore of the αβγ GABA receptor type A receptor at the so-called T6' ring, wherein five threonine residues line the permeation pathway of the pentameric receptor channel.
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http://dx.doi.org/10.1124/molpharm.120.000090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746976PMC
January 2021

Molecular Analysis of the Bloodmeals of spp. Mosquitoes at Natural Habitats in Singapore to Investigate the Potential Risk of Japanese Encephalitis Virus and West Nile Virus Transmission.

Vector Borne Zoonotic Dis 2020 09 16;20(9):703-714. Epub 2020 Jun 16.

Environmental Health Institute, National Environment Agency, Singapore, Singapore.

Japanese encephalitis virus (JEV) and West Nile virus (WNV) are arboviruses primarily transmitted by spp. mosquitoes. Birds are the primary hosts for JEV and WNV. Recent WNV outbreaks in Europe and United States and their association with migratory birds highlight the importance of understanding the feeding host preference of potential vectors for outbreak preparedness, especially in nonendemic settings. Singapore is nonendemic to JEV and WNV, but is a stopover site for migratory birds of the East Asian-Australasian Flyway. Therefore, we elucidated the feeding host range of spp. mosquitoes captured in four natural (bird) habitats in Singapore from January 2011 to December 2012. We characterized feeding host DNA in field-caught mosquitoes using a PCR sequencing-based assay targeting the mitochondrial gene regions. Of 22,648 mosquitoes captured, 21,287 belonged to the subgroup. The host DNA analysis showed that mosquitoes from the subgroup are opportunistic biters, feeding on a range of birds and mammals. subgroup, and , was primarily ornithophagic, although they fed opportunistically on mammals, including humans. and , in contrast, fed mainly on mammals. The presence of ornitho- and anthropophilic mosquito vectors and susceptible avian and mammalian hosts poses a risk spill-over transmission of JEV and WNV among humans, should these viruses be introduced through migratory birds and establish persistent transmission in resident birds and animal hosts in Singapore.
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http://dx.doi.org/10.1089/vbz.2019.2576DOI Listing
September 2020

Pain in the Past and Pleasure in the Future: The Development of Past-Future Preferences for Hedonic Goods.

Cogn Sci 2020 09;44(9):e12887

School of Psychology, Queen's University Belfast.

It seems self-evident that people prefer painful experiences to be in the past and pleasurable experiences to lie in the future. Indeed, it has been claimed that, for hedonic goods, this preference is absolute (Sullivan, 2018). Yet very little is known about the extent to which people demonstrate explicit preferences regarding the temporal location of hedonic experiences, about the developmental trajectory of such preferences, and about whether such preferences are impervious to differences in the quantity of envisaged past and future pain or pleasure. We find consistent evidence that, all else being equal, adults and children aged 7 and over prefer pleasure to lie in the future and pain in the past and believe that other people will, too. They also predict that other people will be happier when pleasure is in the future rather than the past but sadder when pain is in the future rather than the past. Younger children have the same temporal preferences as adults for their own painful experiences, but they prefer their pleasure to lie in the past and do not predict that others' levels of happiness or sadness vary dependent on whether experiences lie in the past or the future. However, from the age of 7, temporal preferences were typically abandoned at the earliest opportunity when the quantity of past pain or pleasure was greater than the quantity located in the future. Past-future preferences for hedonic goods emerge early developmentally but are surprisingly flexible.
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http://dx.doi.org/10.1111/cogs.12887DOI Listing
September 2020

Detection of Japanese Encephalitis Virus in Mosquitoes in Singapore.

Am J Trop Med Hyg 2020 09;103(3):1234-1240

Environmental Health Institute, National Environment Agency, Singapore.

Mosquito-borne flaviviruses are emerging pathogens of an increasing global public health concern because of their rapid increase in geographical range and the impact of climate change. Japanese encephalitis virus (JEV) and West Nile virus (WNV) are of concern because of the risk of reemergence and introduction by migratory birds. In Singapore, human WNV infection has never been reported and human JEV infection is rare. Four sentinel vector surveillance sites were established in Singapore to understand the potential risk posed by these viruses. Surveillance was carried out from August 2011 to December 2012 at Pulau Ubin, from March 2011 to March 2013 at an Avian Sanctuary (AS), from December 2010 from October 2012 at Murai Farmway, and from December 2010 to December 2013 at a nature reserve. The present study revealed active JEV transmission in Singapore through the detection of JEV genotype II in collected from an Avian Sanctuary. flavivirus (CxFV), similar to the Quang Binh virus isolated from in Vietnam and CxFV-LSFlaviV-A20-09 virus isolated in China, was also detected in spp. ( subgroup) No WNV was detected. This study demonstrates the important role that surveillance plays in public health and strongly suggests the circulation of JEV among wildlife in Singapore, despite the absence of reported human cases. A One Health approach involving surveillance, the collaboration between public health and wildlife managers, and control of mosquito populations remains the key measures in risk mitigation of JEV transmission in the enzootic cycle between birds and mosquitoes.
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http://dx.doi.org/10.4269/ajtmh.19-0377DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7470584PMC
September 2020

Mosquitoes (Diptera: Culicidae) of Singapore: Updated Checklist and New Records.

J Med Entomol 2019 01;56(1):103-119

Department of Entomology, Walter Reed Biosystematics Unit, Smithsonian Institution, Museum Support Center (MRC534), Suitland, MD.

Prior to 1965, Singapore was part of the Malaya (now Malaysia) and was usually not mentioned when mosquito records were reported for Malaya. Consequently, many species that occurred in Singapore were not listed in the world mosquito catalog, and the available checklist for Singapore since 1986 is incomplete, with some imprecise species information. In updating this checklist, we examined and verified mosquito specimens collected from Singapore in various depositories, including a thorough review of past taxonomic literature. Here, we report a checklist of 182 mosquito species, 33 new distribution records, and a consolidated status list of vectors for Singapore. As Singapore is a travel hub and hosts one of the busiest container ports in the world, there is a risk of introducing mosquito species and their associated pathogens of human disease to the country. Hence, the distribution records are important to increase our knowledge on mosquito ecology as well as to understand the risk of newly introduced vectors and their associated pathogens.
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http://dx.doi.org/10.1093/jme/tjy154DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6324193PMC
January 2019

Hypertension Prevalence, Health Service Utilization, and Participant Satisfaction: Findings From a Pilot Randomized Controlled Trial in Aged Chinese Canadians.

Inquiry 2017 01;54:46958017724942

2 University of Toronto, Toronto, Ontario, Canada.

Responding to high prevalence of hypertension and patients' preference of integrating traditional Chinese medicine for blood pressure control, the Dietary Approach to Stop Hypertension With Sodium Reduction for Chinese Canadian (DASHNa-CC) intervention was newly designed as a culturally sensitive dietary educational intervention to facilitate middle-aged and senior Chinese Canadians' blood pressure control in community. The aim of this study was to report the hypertension prevalence rate according to the data from blood pressure screening events, to describe the characteristics of health service utilization among aged Chinese Canadians, and to report the evaluation of participant satisfaction to the DASHNa-CC intervention. This study was designed as a pilot randomized controlled trial with a sample size of 60. Among 618 Chinese Canadians participated in blood pressure screening events, 54.5% (n = 337) having various levels of hypertension. Across 2 months, 38 (63.3%) participants made a total of 47 visits to see their family physicians; 20 (33.3%) participants consulted their family members 224 times for lifestyle modifications and hypertension self-management. Various forms of Chinese media were frequently used as sources of health care information, and English media were rarely accessed. Participants highly satisfied with the contents, delivery approaches, and integration of traditional Chinese medicine in the intervention. Results indicated that middle-aged and senior Chinese Canadians have high hypertension prevalence and specific characteristics of health service utilization. It is important to implement interventions, which are culturally tailored, language appropriate, using proper technology and incorporating traditional Chinese medicine, in Chinese Canadian community for hypertension control.
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http://dx.doi.org/10.1177/0046958017724942DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5798669PMC
January 2017

Osteoporotic Fractures in Postmenopausal Women.

J Am Geriatr Soc 2017 03 26;65(3):e76. Epub 2016 Dec 26.

Kaiser Permanente Geriatrics Medicine Fellowship, Fontana, California.

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http://dx.doi.org/10.1111/jgs.14693DOI Listing
March 2017

Draft Genome Sequences of Two Pseudoalteromonas porphyrae Strains Isolated from Seagrass Sediment.

Genome Announc 2016 Mar 17;4(2). Epub 2016 Mar 17.

University of California Davis Genome Center, Davis, California, USA.

Here, we present the draft genome sequences of Pseudoalteromonas porphyrae UCD-SED9 and UCD-SED14 (phylum Proteobacteria). These strains were isolated from sediment surrounding the roots of the seagrass, Zostera marina, collected near the UC, Davis Bodega Marine Laboratory (Bodega Bay, California). The assemblies contain 4,847,456 bp and 4,817,752 bp, respectively.
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http://dx.doi.org/10.1128/genomeA.00092-16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4796117PMC
March 2016

Draft Genome Sequences of Two Vibrio splendidus Strains, Isolated from Seagrass Sediment.

Genome Announc 2016 Feb 18;4(1). Epub 2016 Feb 18.

University of California Davis Genome Center, Davis, California, USA.

Here, we present the draft genome sequences of Vibrio splendidus UCD-SED7 and UCD-SED10 (phylum Proteobacteria). These strains were isolated from sediment surrounding Zostera marina roots near the UC Davis Bodega Marine Laboratory (Bodega, Bay, California). These assemblies contain 5,334,236 bp and 5,904,824 bp, respectively.
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http://dx.doi.org/10.1128/genomeA.01769-15DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4759083PMC
February 2016

Draft Genome Sequence of Bacillus vietnamensis Strain UCD-SED5 (Phylum Firmicutes).

Genome Announc 2015 Nov 19;3(6). Epub 2015 Nov 19.

University of California Davis Genome Center, Davis, California, USA.

Here, we present the draft genome sequence of Bacillus vietnamensis UCD-SED5 (phylum Firmicutes). This strain was isolated from sediment surrounding Zostera marina roots near the UC Davis Bodega Marine Laboratory (Bodega Bay, California) and represents the second genome of this species. The assembly consists of 4,325,707 bp, in 108 contigs.
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http://dx.doi.org/10.1128/genomeA.01376-15DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4653803PMC
November 2015

Draft Genome Sequence of Pseudoalteromonas tetraodonis Strain UCD-SED8 (Phylum Gammaproteobacteria).

Genome Announc 2015 Nov 5;3(6). Epub 2015 Nov 5.

Davis Genome Center, University of California, Davis, California, USA.

Here, we present the draft genome sequence of Pseudoalteromonas tetraodonis UCD-SED8, a marine bacterium normally associated with the production of tetrodotoxin in pufferfish. This strain was isolated from sediment samples surrounding Zostera marina roots collected from Bodega Marine, California. The assembly consists of 4,017,727 bp contained in 35 contigs.
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http://dx.doi.org/10.1128/genomeA.01276-15DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4645199PMC
November 2015

How patients fare after anaesthesia for elective surgery: a survey of postoperative nausea and vomiting, pain and confusion.

Singapore Med J 2015 Jan;56(1):40-6

Department of Anaesthesia, National University Hospital, 5 Lower Kent Ridge Road, Singapore 119074.

Introduction: Postoperative nausea and vomiting (PONV), and postoperative pain are common during the early postoperative period. In addition to these problems, elderly patients risk developing postoperative confusion. This study aimed to identify the risk factors associated with these problems, and the extent of these problems, in a Singapore inpatient surgical population.

Methods: Over a period of six weeks, we surveyed 707 elective surgical inpatients aged ≥ 18 years who received general anaesthesia and/or regional anaesthesia.

Results: The incidence of PONV was 31.8% (95% confidence interval [CI] 34.8-41.9). The incidence increased with increasing Apfel score (p < 0.001) and were higher in female patients (odds ratio [OR] 1.74, 95% CI 1.28-2.36), non-smokers (OR 1.72, 95% CI 1.04-2.88), patients with a history of PONV and/or motion sickness (OR 3.45, 95% CI 2.38-5.24), patients who received opioids (OR 1.39, 95% CI 1.03-1.88), and patients who received general anaesthesia (OR 1.76, 95% CI 1.11-2.79). Moderate to severe pain at rest and with movement were reported in 19.9% and 52.5% of patients, respectively. Among the patients who were predicted to experience mild pain, 29.5% reported moderate pain and 8.1% reported severe pain. The prevalence of postoperative confusion was 3.9% in the geriatric population.

Conclusion: Higher Apfel scores were associated with a higher risk of PONV and multimodal treatment for postoperative pain management was found to be insufficient. The incidence of postoperative confusion was low in this study.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4325575PMC
http://dx.doi.org/10.11622/smedj.2015008DOI Listing
January 2015

Distancing, self-esteem, and subjective well-being in head and neck cancer.

Psychooncology 2015 Nov 28;24(11):1506-13. Epub 2015 Jan 28.

Princess Margaret Cancer Center and University of Toronto, Canada.

Background: Distancing (i.e. construing oneself as dissimilar to a negatively-stereotyped group) preserves self-esteem and may benefit other domains of subjective well-being. Head and neck cancer (HNC) is stigmatized because major risk factors include avoidable lifestyle variables (smoking, alcohol consumption, and human papilloma virus). Because the benefits of coping efforts, such as distancing, are most evident when people are under stress, we hypothesize that the psychosocial benefits of distancing will be most pronounced when cancer and its treatment interfere substantially with participation in valued activities and interests (i.e. high illness intrusiveness).

Objective: To test whether distancing preserves self-esteem and other domains of subjective well-being (SWB) in HNC, especially when illness intrusiveness is high.

Methods: Five hundred and twenty-two HNC outpatients completed a semantic-differential measure of perceived similarity to the 'cancer patient' and measures of illness intrusiveness, self-esteem, depressive symptoms, and psychological well-being in structured interviews. Evaluations of the 'cancer patient' reflected cancer stereotypes.

Results: A statistically significant interaction supported the central hypothesis: When people held negative stereotypes, those who construed themselves as similar to the 'cancer patient' reported lower self-esteem than those who construed themselves as dissimilar. Distancing did not benefit other SWB variables. Some results were counter-intuitive: e.g. Emotional distress increased with increasing illness intrusiveness when people did not hold negative cancer stereotypes, but when they held highly negative stereotypes, distress decreased with increasing illness intrusiveness.

Conclusions: Overall, distancing preserved self-esteem in people with HNC and was associated with benefits in other SWB domains.
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http://dx.doi.org/10.1002/pon.3760DOI Listing
November 2015

DNA barcoding: complementing morphological identification of mosquito species in Singapore.

Parasit Vectors 2014 Dec 12;7:569. Epub 2014 Dec 12.

Environmental Health Institute, National Environment Agency, 11 Biopolis Way, Helios Block, #06-05/08, Singapore, 138667, Singapore.

Background: Taxonomy that utilizes morphological characteristics has been the gold standard method to identify mosquito species. However, morphological identification is challenging when the expertise is limited and external characters are damaged because of improper specimen handling. Therefore, we explored the applicability of mitochondrial cytochrome C oxidase subunit 1 (COI) gene-based DNA barcoding as an alternative tool to identify mosquito species. In the present study, we compared the morphological identification of mosquito specimens with their differentiation based on COI barcode, in order to establish a more reliable identification system for mosquito species found in Singapore.

Methods: We analysed 128 adult mosquito specimens, belonging to 45 species of 13 genera. Phylogenetic trees were constructed for Aedes, Anopheles, Culex and other genera of mosquitoes and the distinctive clustering of different species was compared with their taxonomic identity.

Results: The COI-based DNA barcoding achieved a 100% success rate in identifying the mosquito species. We also report COI barcode sequences of 16 mosquito species which were not available previously in sequence databases.

Conclusions: Our study utilised for the first time DNA barcoding to identify mosquito species in Singapore. COI-based DNA barcoding is a useful tool to complement taxonomy-based identification of mosquito species.
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http://dx.doi.org/10.1186/s13071-014-0569-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4282734PMC
December 2014

Draft Genome Sequence of the Endosymbiont "Candidatus Ruthia magnifica" UCD-CM (Phylum Proteobacteria).

Genome Announc 2014 Jul 17;2(4). Epub 2014 Jul 17.

Here, we present the draft genome of the endosymbiont "Candidatus Ruthia magnifica" UCD-CM, a member of the phylum Proteobacteria, found from the gills of a deep-sea giant clam, Calyptogena magnifica. The assembly consists of 1,160,249 bp contained in 18 contigs.
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http://dx.doi.org/10.1128/genomeA.00717-14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4102874PMC
July 2014

The association of cytokines with disease activity and damage scores in systemic lupus erythematosus patients.

Rheumatology (Oxford) 2014 Sep 4;53(9):1586-94. Epub 2014 Apr 4.

Department of Rheumatology, Beaumont Hospital, Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Department of Rheumatology, St James Hospital and Department of Rheumatology, Mater Misericordiae University Hospital, Dublin, Ireland.

Objective: The aim of this study was to explore the role of cytokines in the pathogenesis of SLE in a genetically homogeneous Caucasian SLE patient population.

Methods: Serum levels of the following cytokines were determined by ELISA in SLE patients (diagnosed as per ACR diagnostic criteria): IL-1β, IL-10, IL-12p70 and TNF-α. Demographic data, disease activity as per the SLEDAI and damage scores (SLICC) at the 5-year follow-up were calculated.

Results: Enhanced production of TNF-α, IL-1 and IL-10 were observed in SLE patients compared with controls. A strong positive correlation was seen between levels of IL-12p70 and IL-10. In addition, IL-10, TNF-α and IL-1 demonstrated a significant relationship with disease activity. Interestingly, elevated levels of IL-10 were observed in SLE patients with CNS involvement while patients with elevated levels of TNF-α were more likely to have renal involvement and sustain damage over the follow-up period. Additionally, the ratio of all cytokines assayed to IL-12p70 levels were significantly higher in SLE patients when compared with controls, with an association seen between damage accrual and the IL-1β/IL-12p70 ratio (r = 0.431, P = 0.003), IL-10/IL-12p70 ratio (r = 0.351, P = 0.018) and TNF-α/IL-12p70 ratio (r = 0.33, P = 0.028). When the respective ratios were analysed for organ-specific disease, significant differences were observed for the IL-1β/IL-12p70 ratio (0.79 vs 0.47, P = 0.036), IL-10/IL-12p70 ratio (4.29 vs 1.87, P = 0.018) and TNF-α/IL-12p70 ratio (7.49 vs 5.21, P = 0.018) with respect to renal involvement.

Conclusion: Increased levels of a number of immunomodulatory cytokines relative to IL-12p70 in this Caucasian SLE patient population are seen in patients with renal involvement and are associated with increased accrual of damage at the 5-year follow-up.
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http://dx.doi.org/10.1093/rheumatology/ket428DOI Listing
September 2014

Estrogen receptor α regulates tripartite motif-containing protein 21 expression, contributing to dysregulated cytokine production in systemic lupus erythematosus.

Arthritis Rheumatol 2014 Jan;66(1):163-72

Royal College of Surgeons in Ireland, Dublin, Ireland.

Objective: To examine the role of 17β-estradiol in the regulation of the autoantigen tripartite motif-containing protein 21 (TRIM-21) in patients with systemic lupus erythematosus (SLE).

Methods: Monocytes isolated from healthy control subjects and patients with SLE were stimulated with 17β-estradiol and/or the estrogen receptor α (ERα) antagonist methyl-piperidino-pyrazole dihydrochloride. TRIM-21, ERα, and CREMα expression was determined by real-time polymerase chain reaction (PCR) analysis. MatInspector software was used to identify putative binding sites within the TRIM-21 promoter. ERα binding to the TRIM-21 gene promoter region in monocytes was analyzed by chromatin immunoprecipitation (ChIP) assay. TRIM-21 and interferon regulatory factor 3 protein levels were analyzed by Western blotting.

Results: Real-time PCR analysis demonstrated a role of estrogen in the regulation of TRIM-21 expression in monocytes, which correlated positively with ERα gene expression in patients with SLE. Investigations into the human TRIM-21 promoter revealed the presence of an estrogen response element, with ChIP assays confirming ERα binding to this site. Studies into estrogen-induced TRIM-21 expression revealed a hyperresponsiveness of SLE patients to 17β-estradiol, which led to the enhanced levels of TRIM-21 observed in these individuals.

Conclusion: Our results demonstrate a role of estrogen in the regulation of TRIM-21 expression through an ERα-dependent mechanism, a pathway that we observed to be overactive in SLE patients. Treatment of monocytes with an ERα antagonist abrogated estrogen-induced TRIM-21 expression and, as a consequence, decreased the expression of interleukin-23. These findings identify TRIM-21 as a novel ERα-regulated gene and provide novel insights into the link between estrogen and the molecular pathogenesis of SLE.
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http://dx.doi.org/10.1002/art.38187DOI Listing
January 2014

Mosquito fauna of Ubin Island, Singapore.

J Am Mosq Control Assoc 2012 Sep;28(3):248-54

Environmental Health Institute, National Environment Agency, 11 Biopolis Way, #06-05/08, Helios Block, Singapore 138667.

We report the mosquito species and their distribution records for Ubin Island, Singapore, based on our field collections in February 2010, routine adult and larval surveys from 1993 to 2009 by Singapore operational officers, and accessioned specimens deposited in the Environmental Health Institute, Singapore, and the US National Museum of Natural History, Washington, DC. A total of 25 species and 6 unidentified species belonging to 9 genera (Aedes, Anopheles, Armigeres, Coquillettidia, Culex, Lutzia, Mansonia, Uranotaenia, and Verrallina) were identified and recorded from Ubin Island, based on specimens collected from 1993 to 2010.
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http://dx.doi.org/10.2987/12-6239R.1DOI Listing
September 2012

Elevated B lymphocyte stimulator levels are associated with increased damage in an Irish systemic lupus erythematosus cohort.

Rheumatology (Oxford) 2013 Jul 11;52(7):1279-84. Epub 2013 Mar 11.

Department of Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, 123 St Stephens Green, Dublin, Ireland.

Objective: The overall aim of this study is to identify clinical and serological features that are associated with B lymphocyte stimulator (BLyS) elevation in a homogeneous Caucasian SLE population and thereby identify patients who are most likely to benefit from BLyS blockade.

Methods: Patients with SLE (as per ACR criteria) were recruited. Clinical history, disease activity measures and laboratory measures of disease were recorded. BLyS levels were determined by ELISA.

Results: BLyS elevation was defined as being higher than the 95th percentile of BLyS levels measured in controls. Patients were divided into two groups: those with elevated BLyS levels (group 1, n = 23) and those with normal BLyS levels (group 2, n = 22). Elevated BLyS levels were significantly associated with patients of younger age and shorter disease duration. In keeping with previous reports, patients with elevated BLyS levels had more active disease (SLEDAI 5.1 vs 0.86, P < 0.001); however, our analysis also demonstrates that BLyS elevation was significantly associated with increased organ damage at 5-year follow-up [Systemic Lupus International Collaborating Clinics/ACR Damage Index (SLICC/ACR DI) 0.53 vs 0.13, P = 0.012]. Furthermore, the presence of Sm autoantibody significantly predicted elevated BLyS levels in a Caucasian population. BLyS levels were significantly higher in those with musculoskeletal involvement, malar rash, renal disease and evidence of immunological activity.

Conclusion: BLyS blockade may be most beneficial if introduced early in the course of disease in young Caucasian patients presenting with renal, musculoskeletal and skin disease in an effort to reduce long-term damage.
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http://dx.doi.org/10.1093/rheumatology/ket120DOI Listing
July 2013

Negative cancer stereotypes and disease-specific self-concept in head and neck cancer.

Psychooncology 2013 May 13;22(5):1055-63. Epub 2012 Jun 13.

Faculty of Medicine, University of Toronto, Toronto, ON, Canada.

Background: Life-threatening diseases, such as head and neck cancer (HNCa), can stimulate the emergence of a new disease-specific self-concept. We hypothesized that (i) negative cancer-stereotypes invoke distancing, which inhibits the adoption of a disease-specific self-concept and (ii) patient characteristics, disease and treatment factors, and cancer-related stressors moderate the phenomenon.

Methods: Head and neck cancer outpatients (N = 522) completed a semantic-differential measure of disease-specific self-concept (perceived similarity to the 'cancer patient') and other self-report measures in structured interviews. Negative cancer-stereotypes were represented by the number of semantic-differential dimensions (0-3) along which respondents evaluated the stereotypic 'cancer patient' negatively (i.e., negative valence). We tested the two-way interactions between negative valence and hypothesized moderator variables.

Results: We observed significant negative valence × moderator interactions for the following: (i) patient characteristics (education, employment, social networks); (ii) disease and treatment factors (cancer-symptom burden); and (iii) cancer-related stressors (uncertainty, lack of information, and existential threats). Negative cancer stereotypes were consistently associated with distancing of self from the stereotypic 'cancer patient,' but the effect varied across moderator variables. All significant moderators (except employment and social networks) were associated with increasing perceived similarity to the 'cancer patient' when respondents maintained negative stereotypes; perceived similarity decreased when people were employed or had extensive social networks. Moderator effects were less pronounced when respondents did not endorse negative cancer stereotypes.

Discussion: When they hold negative stereotypes, people with HNCa distance themselves from a 'cancer patient' identity to preserve self-esteem or social status, but exposure to cancer-related stressors and adaptive demands may attenuate these effects.
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http://dx.doi.org/10.1002/pon.3109DOI Listing
May 2013

The burden of stress in head and neck cancer.

Psychooncology 2013 Mar 5;22(3):668-76. Epub 2012 Mar 5.

Ontario Cancer Institute, Toronto, Canada.

Background: Head and neck cancer (HNCa) introduces numerous stressors. We developed the Cancer-Related Stressors Checklist (CRSC), which documents exposure to seven categories of common stressors and emotional distress. We surveyed HNCa survivors and examined associations among exposure to cancer-related stressors, illness intrusiveness (i.e., cancer-induced interference with lifestyles, activities, and interests), and distress. We also investigated whether reported exposure rates differ between self-administered and interviewer-administered measures.

Methods: Respondents included HNCa survivors, stratified by sex, who participated in one of two clinical studies (N1  = 162; N2  = 408) examining the psychosocial impact of illness intrusiveness. All completed the CRSC, the Center for Epidemiologic Studies Depression Scale, and the Illness Intrusiveness Ratings Scale. Study 1 respondents self-administered the instruments; an interviewer administered them in Study 2. We gathered clinical data by self-report and from medical records.

Results: High inter-rater reliability corroborated the 8-subscale structure of the CRSC (Krippendorff alpha = .92). Cancer-related stressor exposures differed significantly across categories (interpersonal stressors were most common). Controlling for empirically identified covariates and distress, exposure to each cancer-related stressor correlated significantly and uniquely with illness intrusiveness. All stressor categories correlated significantly with distress, but coefficients were low to moderate, substantiating incremental validity. Respondents reported fewer exposures when materials were self-administered as compared with interviewer-administered, but reported distress levels did not differ by mode of administration.

Conclusions: Cancer-related stressors are common and burdensome in HNCa and, therefore, merit clinical attention. Identifying specific stressors will allow more targeted and effective interventions to alleviate and prevent distress.
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http://dx.doi.org/10.1002/pon.3050DOI Listing
March 2013

Perceptions of professionalism among nursing faculty and nursing students.

West J Nurs Res 2013 Feb 16;35(2):248-71. Epub 2011 May 16.

School of Nursing, McMaster University, 1200 Main St. West, Hamilton, Ontario, Canada.

Although there is no consensus about the definition of professionalism, some generally recognized descriptors include knowledge, specialization, intellectual and individual responsibility, and well-developed group consciousness. In this study, Q-methodology was used to identify common viewpoints about professionalism held by nursing faculty and students, and four viewpoints emerged as humanists, portrayers, facilitators, and regulators. The humanists reflected the view that professional values include respect for human dignity, personal integrity, protection of patient privacy, and protection of patients from harm. The portrayers believed that professionalism is evidenced by one's image, attire, and expression. For facilitators, professionalism not only involves standards and policies but also includes personal beliefs and values. The regulators believed that professionalism is fostered by a workplace in which suitable beliefs and standards are communicated, accepted, and implemented by its staff. The differences indicate that there may be numerous contextual variables that affect individuals' perceptions of professionalism.
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http://dx.doi.org/10.1177/0193945911408623DOI Listing
February 2013

Obstructive sleep apnea in chronic obstructive pulmonary disease patients.

Curr Opin Pulm Med 2011 Mar;17(2):79-83

Pulmonary and Sleep Disorders Unit, St. Vincent's University Hospital, Dublin, Ireland.

Purpose Of Review: Chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) represent two of the most prevalent chronic respiratory disorders and cardiovascular diseases are major co-morbidities in both. Co-existence of both disorders (overlap syndrome) occurs in 1% of adults and overlap patients have worse nocturnal hypoxemia and hypercapnia than COPD and OSA patients alone. The present review discusses recent data concerning the pathophysiological and clinical significance of the overlap syndrome.

Recent Findings: The severity of obstructive ventilatory impairment and hyperinflation, especially the inspiratory capacity to total lung capacity (TLC) ratio, correlates with the severity of sleep-related breathing disturbances. Early treatment with continuous positive airway pressure (CPAP) improves survival, reduces hospitalization and pulmonary hypertension, and also reduces hypoxemia. Evidence of systemic inflammation and oxidative stress in COPD and sleep apnea provides insight into potential interactions between both disorders that may predispose to cardiovascular disease. Long-term outcome studies of overlap patients currently underway should provide further evidence of the clinical significance of the overlap syndrome.

Summary: Studies of overlap syndrome patients at a clinical, physiological and molecular level should provide insight into disease mechanisms and consequences of COPD and sleep apnea, in addition to identifying potential relationships with cardiovascular disease.
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http://dx.doi.org/10.1097/MCP.0b013e32834317bbDOI Listing
March 2011

Safety and quality assessment of 175 illegal sexual enhancement products seized in red-light districts in Singapore.

Drug Saf 2009 ;32(12):1141-6

Applied Sciences Group, Pharmaceutical Division, Health Sciences Authority, Singapore.

Background: In recent years, there has been increasing interest in the use of herbs and supplements as an alternative to drugs used for the treatment of erectile dysfunction, in order to enhance sexual performance. Over the years, adverse events associated with the consumption of natural health products for sexual enhancement and the treatment of erectile dysfunction have been reported.

Objective: The objective of this work was to assess the safety and quality of 175 sexual enhancement health products seized from makeshift stalls in red-light districts of Singapore.

Method: Seven raids were conducted by the Health Sciences Authority, Singapore, in two red-light districts in February and March 2008. 175 sexual enhancement health products seized from makeshift stalls were extracted with methanol and screened for Western drug adulterants using high performance liquid chromatography and gas chromatography-mass spectrometry. The labels and claims of the products were also evaluated.

Results: Of the 175 products evaluated, 134 (77%) were found to be adulterated with Western drugs or their analogues. Most of these 134 samples (123 [92%]) were found to be adulterated with sildenafil. The extent of adulteration of these illegal health products with Western drugs, including synthetic phosphodiesterase type 5 enzyme (PDE-5) inhibitors, and the risks of consuming such illegal sexual enhancement products are discussed in this study. Because of the scope of the raids, sildenafil was the most common adulterant found. In addition, some products were found to contain high contents of sildenafil (>100 mg) and high contents of the antidiabetic drug, glibenclamide (glyburide). The resultant severe hypoglycaemia has led to ten fatalities.

Conclusion: The presence of Western drug adulterants and their analogues in illegal sexual enhancement products seized from red-light districts in Singapore, and their often misleading labels and claims, put the health of consumers at risk. To safeguard public health, greater public awareness of the danger of consuming such illegal products and the lack of quality control of these illegal sexual enhancement health products is important.
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http://dx.doi.org/10.2165/11316690-000000000-00000DOI Listing
January 2010

An evaluation of the impact of apheresis platelets used in the setting of massively transfused trauma patients.

J Trauma 2009 Apr;66(4 Suppl):S77-84; discussion S84-5

Walter Reed Army Medical Center, Washington, DC 20307, USA.

Introduction: Trauma is a major cause of morbidity and mortality worldwide. Of patients arriving to trauma centers, patients requiring massive transfusion (MT, >or=10 units in 24 hours) are a small patient subset but are at the highest risk of mortality. Transfusion of appropriate ratios of blood products to such patients has recently been an area of interest to both the civilian and military medical community. Plasma is increasingly recognized as a critical component, though less is known about appropriate ratios of platelets. Combat casualties managed at the busiest combat hospital in Iraq provided an opportunity to examine this question.

Methods: In-patient records for 8,618 trauma casualties treated at the military hospital in Baghdad more than a 3-year interval between January 2004 and December 2006 were retrospectively reviewed and patients requiring MT (n = 694) were identified. Patients who required MT in the first 24 hours and did not receive fresh whole blood were divided into study groups defined by source of platelets: (1) patient receiving a low ratio of platelets (<1:16 apheresis platelets per stored red cell unit, aPLT:RBC) (n = 214), (2) patients receiving a medium ratio of platelets (1:16 to <1:8 aPLT:RBC) (n = 154), and (3) patients receiving a high ratio of platelets (>or=1:8 aPLT:RBC) (n = 96). The primary endpoint was survival at 24 hours and at 30 days.

Results: At 24 hours, patients receiving a high ratio of platelets had higher survival (95%) as compared with patients receiving a medium ratio (87%) and patients receiving the lowest ratio of platelets (64%) (log-rank p = 0.04 and p < 0.001, respectively). The survival benefit for the high and medium ratio groups remained at 30 days as compared with those receiving the lowest ratio of platelets (75% and 60% vs. 43%, p < 0.001 for both comparisons). On multivariate regression, plasma:RBC ratios and aPLT:RBC were both independently associated with improved survival at 24 hours and at 30 days.

Conclusion: Transfusion of a ratio of >or=1:8 aPLT:RBC is associated with improved survival at 24 hours and at 30 days in combat casualties requiring a MT within 24 hours of injury. Although prospective study is needed to confirm this finding, MT protocols outside of investigational research should consider incorporation of appropriate ratios of both plasma and platelets.
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http://dx.doi.org/10.1097/TA.0b013e31819d8936DOI Listing
April 2009

Assessment of two culturally competent diabetes education methods: individual versus individual plus group education in Canadian Portuguese adults with type 2 diabetes.

Ethn Health 2007 Apr;12(2):163-87

School of Nutrition, Ryerson University, Victoria St, Toronto, Ontario, Canada.

Objective: To examine the impact of two culturally competent diabetes education methods, individual counselling and individual counselling in conjunction with group education, on nutrition adherence and glycemic control in Portuguese Canadian adults with type 2 diabetes over a three-month period.

Design: The Diabetes Education Centre is located in the urban multicultural city of Toronto, Ontario, Canada. We used a three-month randomized controlled trial design. Eligible Portuguese-speaking adults with type 2 diabetes were randomly assigned to receive either diabetes education counselling only (control group) or counselling in conjunction with group education (intervention group). Of the 61 patients who completed the study, 36 were in the counselling only and 25 in the counselling with group education intervention. We used a per-protocol analysis to examine the efficacy of the two educational approaches on nutrition adherence and glycemic control; paired t-tests to compare results within groups and analysis of covariance (ACOVA) to compare outcomes between groups adjusting for baseline measures. The Theory of Planned Behaviour was used to describe the behavioural mechanisms that influenced nutrition adherence.

Results: Attitudes, subjective norms, perceived behaviour control, and intentions towards nutrition adherence, self-reported nutrition adherence and glycemic control significantly improved in both groups, over the three-month study period. Yet, those receiving individual counselling with group education showed greater improvement in all measures with the exception of glycemic control, where no significant difference was found between the two groups at three months.

Conclusions: Our study findings provide preliminary evidence that culturally competent group education in conjunction with individual counselling may be more efficacious in shaping eating behaviours than individual counselling alone for Canadian Portuguese adults with type 2 diabetes. However, larger longitudinal studies are needed to determine the most efficacious education method to sustain long-term nutrition adherence and glycemic control.
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http://dx.doi.org/10.1080/13557850601002148DOI Listing
April 2007

Transfer of accountability: transforming shift handover to enhance patient safety.

Healthc Q 2006 ;9 Spec No:75-9

Henderson and Chedoke Hospitals, Hamilton Health Sciences, ON, Canada.

Communication of information between healthcare providers is a fundamental component of patient care. The information shared between providers who are changing shifts, referred to as "handover," helps plan patient care, identifies safety concerns and facilitates continuity of information. Absent or inaccurate information can have deleterious effects on patient care. According to the Joint Commission on Accreditation of Healthcare Organizations (JCAHO 2003), almost 70% of all sentinel events are caused by breakdown in communication. Issues and concerns regarding the effectiveness of handover at shift change were raised by nurses throughout Hamilton Health Sciences (HHS), leading to the approval of a hospital-wide project to implement evidenced-based Transfer of Accountability (TOA) Guidelines and a bedside patient safety checklist. This article describes the development of the guidelines, the results of the pilot study and the ongoing implementation of the project. The observed impact on patient safety within HHS is presented.
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http://dx.doi.org/10.12927/hcq.2006.18464DOI Listing
December 2006

Gender, ethnocultural, and psychosocial barriers to diabetes self-management in Italian women and men with type 2 diabetes.

Behav Med 2006 ;31(4):153-60

University Health Network, Toronto General Hospital, ON, Canada.

Although several ethnic groups experience a greater burden of diabetes, this has not been examined in first-generation Italians, who compose one of the largest ethnocultural groups in Canada. In this cross-sectional study, the authors examined the relationship among gender and ethnocultural factors, family support, depressive symptomatology, and illness perceptions on diabetes self-management (DSM) in 50 Italian women and men with type 2 diabetes. The authors first conducted a focus group to explore cultural barriers. They then assessed gender, ethnocultural, and psychosocial barriers quantitatively by an interviewer-administered questionnaire. Compared with Italian men, Italian women reported significantly greater depressive symptomatology and perceived disease seriousness. Greater depressive symptomatology was significantly associated with perceived family sabotage and DSM barriers. In univariate analyses, shorter duration of diabetes and greater perceived treatment effectiveness significantly predicted better DSM. In conclusion, certain illness perceptions and culturally relevant gender-specific barriers should be addressed by health care providers to maximize DSM in this population. Index Terms: diabetes, diet, gender, self-management
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http://dx.doi.org/10.3200/BMED.31.4.153-160DOI Listing
June 2006

International nursing recruitment experience.

J Nurs Adm 2005 Nov;35(11):478-81

Ambulatory Surgery Unit, Johns Hopkins Bayview Medical Center, Baltimore, MD 21224, USA.

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http://dx.doi.org/10.1097/00005110-200511000-00003DOI Listing
November 2005

Effectiveness of a burn prevention campaign for older adults.

J Burn Care Rehabil 2004 Sep-Oct;25(5):445-51

University of Toronto, Toronto, Ontario, Canada.

Older adults are involved in one fifth of burn injury admissions in the Province of Ontario Canada. Most burn injuries in this population occur at home while cooking, bathing, or smoking. The purpose of this study was to evaluate the effectiveness of an educational campaign to improve burn prevention knowledge in older adults of a major metropolitan city. Changes in participants' burn prevention knowledge were determined using standardized precampaign and postcampaign (4-6 weeks) surveys. Of 209 older adult participants, 126 (60.3%) completed the precampaign and postcampaign surveys. There was a significant increase (P <.05) in burn prevention knowledge postintervention. Age, education level, and living conditions did not influence the change in burn prevention knowledge. This burn prevention campaign for older adults was effective in improving burn prevention knowledge, but it remains unclear as to whether this will ultimately result in a change in burn prevention behavior.
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http://dx.doi.org/10.1097/01.bcr.0000138293.18189.25DOI Listing
January 2005