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1.  Hypothalamic QRFP: Regulation of Food Intake and Fat Selection 
QRFP, a member of the RFamide-related peptide family, is a strongly conserved hypothalamic neuropeptide that has been characterized in various species. Prepro-QRFP mRNA expression is localized to select regions of the hypothalamus, which are involved in the regulation of feeding behavior. The localization of the peptide precursor has led to the assessment of QRFP on feeding behaviors and the orexigenic effects of QRFP have been detected in mice, rats, and birds. QRFP acts in a macronutrient specific manner in satiated rats to increase the intake of a high fat diet, but not the intake of a low fat diet, and increases the intake of chow in food-restricted rats. Studies suggest that QRFP’s effects on food intake are mediated by the adiposity signal, leptin, and hypothalamic neuropeptides. Additionally, QRFP regulates the expression and release of hypothalamic Neuropeptide Y and proopiomelanocortin/α-Melanocyte-Stimulating Hormone. QRFP binds to receptors throughout the brain, including regions associated with food intake and reward. Taken together, these data suggest that QRFP is a mediator of motivated behaviors, particularly the drive to ingest high fat food. The present review discusses the role of QRFP in the regulation of feeding behavior, with emphasis on the intake of dietary fat.
PMCID: PMC4239704  PMID: 23979792
high fat diet; neuropeptide Y; agouti-related peptide; arcuate nucleus; ventromedial hypothalamus
2.  DNA-based species detection capabilities using laser transmission spectroscopy 
Early detection of invasive species is critical for effective biocontrol to mitigate potential ecological and economic damage. Laser transmission spectroscopy (LTS) is a powerful solution offering real-time, DNA-based species detection in the field. LTS can measure the size, shape and number of nanoparticles in a solution and was used here to detect size shifts resulting from hybridization of the polymerase chain reaction product to nanoparticles functionalized with species-specific oligonucleotide probes or with the species-specific oligonucleotide probes alone. We carried out a series of DNA detection experiments using the invasive freshwater quagga mussel (Dreissena bugensis) to evaluate the capability of the LTS platform for invasive species detection. Specifically, we tested LTS sensitivity to (i) DNA concentrations of a single target species, (ii) the presence of a target species within a mixed sample of other closely related species, (iii) species-specific functionalized nanoparticles versus species-specific oligonucleotide probes alone, and (iv) amplified DNA fragments versus unamplified genomic DNA. We demonstrate that LTS is a highly sensitive technique for rapid target species detection, with detection limits in the picomolar range, capable of successful identification in multispecies samples containing target and non-target species DNA. These results indicate that the LTS DNA detection platform will be useful for field application of target species. Additionally, we find that LTS detection is effective with species-specific oligonucleotide tags alone or when they are attached to polystyrene nanobeads and with both amplified and unamplified DNA, indicating that the technique may also have versatility for broader applications.
PMCID: PMC3565792  PMID: 23015524
DNA detection; Dreissena; polymerase chain reaction; laser transmission spectroscopy; ballast; invasive species
3.  Adherence to a Mediterranean diet and Alzheimer's disease risk in an Australian population 
Translational Psychiatry  2012;2(10):e164-.
The Mediterranean diet (MeDi), due to its correlation with a low morbidity and mortality for many chronic diseases, has been widely recognised as a healthy eating model. We aimed to investigate, in a cross-sectional study, the association between adherence to a MeDi and risk for Alzheimer's disease (AD) and mild cognitive impairment (MCI) in a large, elderly, Australian cohort. Subjects in the Australian Imaging, Biomarkers and Lifestyle Study of Ageing cohort (723 healthy controls (HC), 98 MCI and 149 AD participants) completed the Cancer Council of Victoria Food Frequency Questionnaire. Adherence to the MeDi (0- to 9-point scale with higher scores indicating higher adherence) was the main predictor of AD and MCI status in multinominal logistic regression models that were adjusted for cohort age, sex, country of birth, education, apolipoprotein E genotype, total caloric intake, current smoking status, body mass index, history of diabetes, hypertension, angina, heart attack and stroke. There was a significant difference in adherence to the MeDi between HC and AD subjects (P<0.001), and in adherence between HC and MCI subjects (P<0.05). MeDi is associated with change in Mini-Mental State Examination score over an 18-month time period (P<0.05) in HCs. We conclude that in this Australian cohort, AD and MCI participants had a lower adherence to the MeDi than HC participants.
PMCID: PMC3565821  PMID: 23032941
AIBL; Alzheimer's disease; Australia; Mediterranean diet; MCI
4.  Dynamics of maternal and paternal effects on embryo and seed development in wild radish (Raphanus sativus) 
Annals of Botany  2010;106(2):309-319.
Background and Aims
Variability in embryo development can influence the rate of seed maturation and seed size, which may have an impact on offspring fitness. While it is expected that embryo development will be under maternal control, more controversial hypotheses suggest that the pollen donor and the embryo itself may influence development. These latter possibilities are, however, poorly studied. Characteristics of 10-d-old embryos and seeds of wild radish (Raphanus sativus) were examined to address: (a) the effects of maternal plant and pollen donor on development; (b) the effects of earlier reproductive events (pollen tube growth and fertilization) on embryos and seeds, and the influence of embryo size on mature seed mass; (c) the effect of water stress on embryos and seeds; (d) the effect of stress on correlations of embryo and seed characteristics with earlier and later reproductive events and stages; and (e) changes in maternal and paternal effects on embryo and seed characteristics during development.
Eight maternal plants (two each from four families) and four pollen donors were crossed and developing gynoecia were collected at 10 d post-pollination. Half of the maternal plants experienced water stress. Characteristics of embryos and seeds were summarized and also compared with earlier and later developmental stages.
Key Results
In addition to the expected effects of the maternal plants, all embryo characters differed among pollen donors. Paternal effects varied over time, suggesting that there are windows of opportunity for pollen donors to influence embryo development. Water-stress treatment altered embryo characteristics; embryos were smaller and less developed. In addition, correlations of embryo characteristics with earlier and later stages changed dramatically with water stress.
The expected maternal effects on embryo development were observed, but there was also evidence for an early paternal role. The relative effects of these controls may change over time. Thus, there may be times in development when selection on the maternal, paternal or embryo contributions to development are more and less likely.
PMCID: PMC2908165  PMID: 20519237
Raphanus sativus; embryo development; maternal effects; paternal effects; seed development; seed size; water stress; wild radish
5.  Continuous positive airway pressure reduces daytime sleepiness in mild to moderate obstructive sleep apnoea: a meta‐analysis 
Thorax  2006;61(5):430-434.
Obstructive sleep apnoea syndrome (OSAS) affects an estimated 2–4% of the middle aged population. Meta‐analyses of randomised controlled trials have shown that the severe presentation of the syndrome (apnoea hypopnoea index (AHI) >30/hour) is effectively treated with continuous positive airway pressure (CPAP). Until recently there have been insufficient data to determine whether CPAP improves sleepiness in the larger subgroup with mild to moderate OSAS (AHI 5–30/hour).
A systematic search of Medline and a hand search identified seven randomised controlled trials where CPAP was compared with either a placebo or with conservative management in the treatment of mild to moderate OSAS (AHI 5–30/hour). All trials used the Epworth Sleepiness Scale (ESS), four used the Multiple Sleep Latency Test (MSLT), and three used the Maintenance of Wakefulness Test (MWT) to measure sleepiness.
Meta‐analyses indicated that CPAP significantly reduced subjective daytime sleepiness (ESS) by 1.2 points (95% CI 0.5 to 1.9, p = 0.001), improved objective daytime wakefulness (MWT) by 2.1 minutes (95% CI 0.5 to 3.7, p = 0.011), but did not affect objective daytime sleepiness (MSLT, mean benefit −0.2 minutes, 95% CI −1.0 to 0.6, p = 0.6). The two significant effects were small (effect size <0.30).
CPAP elicits small improvements in subjective sleepiness and objective wakefulness in people with mild to moderate OSAS. However, the effects on sleepiness are of limited clinical significance.
PMCID: PMC2111183  PMID: 16467072
continuous positive airway pressure; obstructive sleep apnoea; meta‐analysis
6.  Clinical importance of the Step 3 choice in asthma 
Thorax  2006;61(2):180-181.
PMCID: PMC2104568  PMID: 16443711
asthma; long acting beta agonists; inhaled corticosteroids; inflammation
PMCID: PMC1765644  PMID: 14645459
10.  Botulinum toxin and spasticity 
PMCID: PMC1737055  PMID: 10896682
11.  Botulinum Toxin in the Treatment of Cerebral Palsy. 
PMCID: PMC1736963  PMID: 10811713
12.  Botulinum toxin (Dysport®) treatment of hip adductor spasticity in multiple sclerosis: a prospective, randomised, double blind, placebo controlled, dose ranging study 
OBJECTIVE—To define a safe and effective dose of Dysport for treating hip adductor spasticity.
METHODS—Patients with definite or probable multiple sclerosis, and disabling spasticity affecting the hip adductor muscles of both legs, were randomised to one of four treatment groups. Dysport (500, 1000, or 1500 Units), or placebo was administered by intramuscular injection to these muscles. Patients were assessed at entry, and 2, 4 (primary analysis time-point), 8, and 12 weeks post-treatment.
RESULTS—A total of 74 patients were recruited. Treatment groups were generally well matched at entry. The primary efficacy variables—passive hip abduction and distance between the knees—improved for all groups. The improvement in distance between the knees for the 1500 Unit group was significantly greater than placebo (p=0.02). Spasm frequency was reduced in all groups, but muscle tone was reduced in the Dysport groups only. Pain was reduced in all groups, but improvements in hygiene scores were evident only in the 1000Unit and 1500 Unit groups. Duration of benefit was significantly longer than placebo for all Dysport groups (p<0.05). Adverse events were reported by 32/58 (55%) Dysport patients, and by 10/16 (63%) placebo patients. Compared with the two lower dose groups, twice as many adverse events were reported by the 1500 Unit group (2.7/patient). The incidence of muscle weakness was higher for the 1500 Unit group (36%) than for placebo (6%). The response to treatment was considered positive by two thirds of the patients in the 500 Unit group, and by about half the patients in the other groups.
CONCLUSION—Dysport reduced the degree of hip adductor spasticity associated with multiple sclerosis, and this benefit was evident despite the concomitant use of oral antispasticity medication and analgesics. Although evidence for a dose response effect was not statistically significant, there was a clear trend towards greater efficacy and duration of effect with higher doses of Dysport. Dysport treatment was well tolerated, with no major side effects seen at doses up to 1500 Units. The optimal dose for hip adductor spasticity seems to be 500-1000 Units, divided between both legs.

PMCID: PMC1736956  PMID: 10811692
14.  Integration of radiographic images with an electronic medical record. 
Radiographic images are important and expensive diagnostic tests. However, the provider caring for the patient often does not review the images directly due to time constraints. Institutions can use picture archiving and communications systems to make images more available to the provider, but this may not be the best solution. We integrated radiographic image review into the Regenstrief Medical Record System in order to address this problem. To achieve adequate performance, we store JPEG compressed images directly in the RMRS. Currently, physicians review about 5% of all radiographic studies using the RMRS image review function.
PMCID: PMC2243643  PMID: 11825241
15.  Representing and querying conceptual graphs with relational database management systems is possible. 
This is an experimental study on the feasibility of maintaining medical concept dictionaries in production grade relational database management systems (RDBMS.) In the past, RDBMS did not support transitive relational structures and had therefore been unsuitable for managing knowledge bases. The revised SQL-99 standard, however, may change this. In this paper we show that modern RDBMS that support recursive queries are capable of querying transitive relationships in a generic data model. We show a simple but efficient indexed representation of transitive closure. We could confirm that even challenging combined transitive relationships can be queried in SQL.
PMCID: PMC2243450  PMID: 11825256
16.  Evaluating scientific impact. 
Environmental Health Perspectives  2000;108(9):A392-A393.
PMCID: PMC2556936  PMID: 11017900
17.  Effective audit trails--a taxonomy for determination of information requirements. 
Current methods of detecting confidentiality breaches in electronic medical record systems are inadequate, partially due to the lack of necessary information at the point of audit trail analysis. In order to determine the information requirements for effective audit trail analysis, we have formulated a taxonomy of confidentiality breaches. By considering scenarios in which an inappropriate access might occur, we have identified "indicators" of confidentiality breaches, which may be thought of as evidence suggesting the possibility that a confidentiality breach has occurred. The collection of facts needed to describe the indicators provides insight into the types of information needed to improve confidentiality breach detection. Much of the information needed is unlikely to be available in the patient record. Research is needed exploring means of collecting and utilizing information from sources other than the patient record for use in improving patient information security.
PMCID: PMC2232638  PMID: 10566442
18.  Using external data sources to improve audit trail analysis. 
Audit trail analysis is the primary means of detection of inappropriate use of the medical record. While audit logs contain large amounts of information, the information required to determine useful user-patient relationships is often not present. Adequate information isn't present because most audit trail analysis systems rely on the limited information available within the medical record system. We report a feature of the STAR (System for Text Archive and Retrieval) audit analysis system where information available in the medical record is augmented with external information sources such as: database sources, Light-weight Directory Access Protocol (LDAP) server sources, and World Wide Web (WWW) database sources. We discuss several issues that arise when combining the information from each of these disparate information sources. Furthermore, we explain how the enhanced person specific information obtained can be used to determine user-patient relationships that might signify a motive for inappropriately accessing a patient's medical record.
PMCID: PMC2232542  PMID: 10566469
20.  Large scale database scrubbing using object oriented software components. 
Now that case managers, quality improvement teams, and researchers use medical databases extensively, the ability to share and disseminate such databases while maintaining patient confidentiality is paramount. A process called scrubbing addresses this problem by removing personally identifying information while keeping the integrity of the medical information intact. Scrubbing entire databases, containing multiple tables, requires that the implicit relationships between data elements in different tables of the database be maintained. To address this issue we developed DBScrub, a Java program that interfaces with any JDBC compliant database and scrubs the database while maintaining the implicit relationships within it. DBScrub uses a small number of highly configurable object-oriented software components to carry out the scrubbing. We describe the structure of these software components and how they maintain the implicit relationships within the database.
PMCID: PMC2232311  PMID: 9929271
21.  A 3-(3-hydroxyphenyl)propionic acid catabolic pathway in Rhodococcus globerulus PWD1: cloning and characterization of the hpp operon. 
Journal of Bacteriology  1997;179(19):6145-6153.
Rhodococcus globerulus PWD1, a soil isolate from a polluted site in The Netherlands, is able to degrade a broad range of aromatic compounds. A novel gene cluster which appears to encode a pathway for the degradation of phenolic acids such as 3-(3-hydroxyphenyl)propionate (3HPP) has been cloned from the chromosome of this organism. Sequence analysis of a 7-kb region identified five open reading frames (ORFs). Analysis of mRNA showed that the genes were expressed during growth on 3HPP and 3-hydroxyphenylacetate (3HPA) but not during growth on m-cresol or succinate. The first ORF, hppA, which appears to be separately transcribed, had considerable amino acid identity with a number of hydroxylases. Transcriptional analysis indicates that the next four ORFs, hppCBKR, which are tightly clustered, constitute a single operon. These genes appear to encode a hydroxymuconic semialdehyde hydrolase (HppC), an extradiol dioxygenase (HppB), a membrane transport protein (HppK), and a member of the IclR family of regulatory proteins (HppR). The activities of HppB and HppC have been confirmed by enzyme assay of Escherichia coli hosts. The substrate specificity of HppB expressed from the cloned gene matches that of the meta-cleavage dioxygenase expressed from wild-type Rhodococcus grown on both 3HPP and 3HPA and is considerably more active against acid than against neutral catechols. The deduced amino acid sequences of the gene products have a recognizable homology with a broad range of enzymes and proteins involved in biodegradation and appear most similar to the mhp operon from E. coli K-12, which also encodes the degradation of 3HPP.
PMCID: PMC179521  PMID: 9324265
22.  Commentary 
PMCID: PMC1332536
24.  Design of access control methods for protecting the confidentiality of patient information in networked systems. 
Public awareness of the potential for violation of personal privacy in clinical information systems is increasing. Much of this increase can be attributed to the popularity and publicity of the World Wide Web. Nightly news reports of intruder break-ins and flaws in Internet software security have stimulated public interest in the security of clinical information systems available over the web. As part of the development of systems designed to provide clinical narratives to physicians over the Internet, we are exploring designs that provide additional protection and security to these systems. Specifically, we are developing and testing automated access control measures based on provider-patient relationships for controlling access to personally identifiable patient information.
PMCID: PMC2233354  PMID: 9357586
25.  Characterization and sequence analysis of a stable cryptic plasmid from Enterococcus faecium 226 and development of a stable cloning vector. 
A small cryptic plasmid, pMBB1, isolated from Enterococcus faecium 226 was characterized. The plasmid contained an extremely stable replicon which has limited homology to the lactococcal plasmid pCI305. Sequence analysis of the replicon detected one open reading frame of 822 bp capable of encoding a 32-kDa protein. No detectable single-stranded intermediates were found for the replicon, suggesting that pMBB1 may be included in the same family as pCI305, although pCI305 exhibits a more narrow host range. A small stably maintained vector able to replicate in a variety of lactic acid bacteria, containing a large multiple cloning region, was constructed by using the pMBB1 replicon.
PMCID: PMC167923  PMID: 8919818

Results 1-25 (54)