343 resultados para 321011 Medical Genetics


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Background Prescribing is a complex task, requiring specific knowledge and skills, and the execution of effective, context-specific clinical reasoning. Systematic reviews indicate medical prescribing errors have a median rate of 7% [IQR 2%-14%] of medication orders [1-3]. For podiatrists pursuing prescribing rights, a clear need exists to ensure practitioners develop a well-defined set of prescribing skills, which will contribute to competent, safe and appropriate practice. Aim To investigate the methods employed to teach and assess the principles of effective prescribing in the undergraduate podiatry program and compare and contrast these findings with four other non-medical professions who undertake prescribing after training at Queensland University of Technology. Method The NPS National Prescribing Competency Standards were employed as the prescribing standard. A curriculum mapping exercise was undertaken to determine whether the prescribing principles articulated in the competency standards were addressed by each profession. Results A range of methods are currently utilised to teach prescribing across disciplines. Application of prescribing competencies to the context of each profession appears to influence the teaching methods used. Most competencies were taught using a multimodal format, including interactive lectures, self-directed learning, tutorial sessions and clinical placement. In particular clinical training was identified as the most consistent form of educating safe prescribers across all five disciplines. Assessment of prescribing competency utilised multiple techniques including written and oral examinations and research tasks, case studies, objective structured clinical examination exercises and the assessment of clinical practice. Effective and reliable assessment of prescribing undertaken by students in diverse settings remains challenging e.g. that occurring in the clinical practice environment. Conclusion Recommendations were made to refine curricula and to promote efficient cross-discipline teaching by staff from the disciplines of podiatry, pharmacy, nurse practitioner, optometry and paramedic science. Students now experience a sophisticated level of multidisciplinary learning in the clinical setting which integrates the expertise and skills of experience prescribers combined with innovative information technology platforms (CCTV and live patient assessments). Further work is required to establish a practical, effective approach to the assessment of prescribing competence especially between the university and clinical settings.

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The opportunities and challenges faced by litigants who strategically plead intentional torts are borne out by two recent medical cases. Both arose out of dental treatment. Dean v Phung established some key principles which were clarified in White v Johnston. Before considering those two cases it is worth examining the environment in which such intentional torts claims now exist. Following the Ipp Review of the Law of Negligence, non-uniform legislative changes to the law of negligence were introduced across Australia which have imposed limitations on liability and quantum of damages in cases where a person has been injured through the fault of another. While it seems that, given the limitation of the scope of the review and recommendations to negligently caused damage, the Ipp Review reforms were meant to be limited to injury resulting from negligent acts rather than intentional torts, the extent to which the civil liability legislation applies to intentional torts differs across Australia.

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Observational studies have shown that medical and dental students have poor psychological health worldwide; however, few interventional studies have been used to test approaches to help students. This thesis used a randomised control trial study design to evaluate the effect of a self-development coaching program on psychological health and the academic performance among medical and dental students in Saudi Arabia. The outcomes indicated that these medical and dental students in Saudi Arabia experienced high levels of depression, anxiety and stress, and that the self-development coaching program was a promising intervention to improve students' psychological health.

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The identification of molecular networks at the system level in mammals is accelerated by next-generation mammalian genetics without crossing, which requires both the efficient production of whole-body biallelic knockout (KO) mice in a single generation and high-performance phenotype analyses. Here, we show that the triple targeting of a single gene using the CRISPR/Cas9 system achieves almost perfect KO efficiency (96%–100%). In addition, we developed a respiration-based fully automated noninvasive sleep phenotyping system, the Snappy Sleep Stager (SSS), for high-performance (95.3% accuracy) sleep/wake staging. Using the triple-target CRISPR and SSS in tandem, we reliably obtained sleep/wake phenotypes, even in double-KO mice. By using this system to comprehensively analyze all of the N-methyl-D-aspartate (NMDA) receptor family members, we found Nr3a as a short-sleeper gene, which is verified by an independent set of triple-target CRISPR. These results demonstrate the application of mammalian reverse genetics without crossing to organism-level systems biology in sleep research.

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The international traveller needs to plan ahead to ensure medicines are available and used as directed for optimal therapeutic outcome. The planning needs to take account of legal and customs requirements for travelling with medicines for personal use. The standard advice by travel health providers is that travellers should check with the country of destination for requirements when travelling into the country with medicines for personal use. This is akin to introducing a barrier to care for this category of travellers. Innovative method of care for this group of traveller is needed.

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The announcement in the 2009 federal budget to allow nurse practitioners and midwives access to the Pharmaceutical Benefits Scheme (PBS) and the Medicare Benefits Scheme,1and the subsequent announcement of a November 2010 start date,2has brought non-medical prescribing into the public arena. Non-medical prescribing is not a new concept in Australia as nurse practitioners, podiatrists and optometrists have been authorised to prescribe under various state legislations for some time. However, state legislation is not uniform in relation to authorisation or formulary. Midwives are currently seeking prescribing rights,3and other groups such as physiotherapists and pharmacists are likely to seek them in the future.

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Epidemiological studies have demonstrated associations between endometriosis and certain histotypes of ovarian cancer, including clear cell, low-grade serous and endometrioid carcinomas. We aimed to determine whether the observed associations might be due to shared genetic aetiology. To address this, we used two endometriosis datasets genotyped on common arrays with full-genome coverage (3194 cases and 7060 controls) and a large ovarian cancer dataset genotyped on the customized Illumina Infinium iSelect (iCOGS) arrays (10 065 cases and 21 663 controls). Previous work has suggested that a large number of genetic variants contribute to endometriosis and ovarian cancer (all histotypes combined) susceptibility. Here, using the iCOGS data, we confirmed polygenic architecture for most histotypes of ovarian cancer. This led us to evaluate if the polygenic effects are shared across diseases. We found evidence for shared genetic risks between endometriosis and all histotypes of ovarian cancer, except for the intestinal mucinous type. Clear cell carcinoma showed the strongest genetic correlation with endometriosis (0.51, 95% CI = 0.18–0.84). Endometrioid and low-grade serous carcinomas had similar correlation coefficients (0.48, 95% CI = 0.07–0.89 and 0.40, 95% CI = 0.05–0.75, respectively). High-grade serous carcinoma, which often arises from the fallopian tubes, showed a weaker genetic correlation with endometriosis (0.25, 95% CI = 0.11–0.39), despite the absence of a known epidemiological association. These results suggest that the epidemiological association between endometriosis and ovarian adenocarcinoma may be attributable to shared genetic susceptibility loci.

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STUDY QUESTION Is there a contribution of the minor allele at the KRAS single nucleotide polymorphism (SNP) rs61764370 in the let-7 microRNA-binding site to endometriosis risk? SUMMARY ANSWER We found no evidence for association between endometriosis risk and rs61764370 or any other SNPs in KRAS. WHAT IS KNOWN ALREADY The rs61764370 SNP in the 3' untranslated region of the KRAS gene is predicted to disrupt a complementary binding site (LCS6) for the let-7 microRNA, and was recently reported to be at a high frequency (31%) in 132 women of varying ancestry with endometriosis compared with frequencies in a database of population controls (up to 7.6% depending on ancestry), suggesting a strong effect of this KRAS SNP in the aetiology of endometriosis. STUDY DESIGN, SIZE AND DURATION This was a case-control study with a total of 11 206 subjects. The study was performed between February 2012 and July 2012. PARTICIPANTS/MATERIALS, SETTINGAND METHODS We first investigated a possible association between common markers in KRAS and endometriosis risk from our genome-wide association (GWA) data in 3194 surgically confirmed endometriosis cases and 7060 controls of European ancestry. Although rs61764370 was not genotyped on the GWA arrays, five SNPs typed in the study were highly correlated with this variant. The rs61764370 and two SNPs highly correlated with rs61764370 were then genotyped in 933 endometriosis cases and 952 controls using the Sequenom MassARRAY platform. MAIN RESULTS AND THE ROLE OF CHANCE There was no evidence for an association between rs61764370 and endometriosis risk P = 0.411 and odds ratio = 1.10 (95% confidence intervals: 0.88-1.36). We also found no evidence for an association between the highly correlated SNP rs17387019 and endometriosis. Their minor allele frequencies in cases and controls were of 0.087-0.091 similar to the population frequency reported previously for this variant in controls. Analyses of endometriosis cases with revised American Fertility Society stage III/IV disease also showed no evidence for an association between these SNPs and endometriosis risk. LIMITATIONS AND REASONS FOR CAUTION The GWA and genotyped data sets were not independent since individuals and cases from some families overlap. Controls in our GWA study were not screened for endometriosis. WIDER IMPLICATIONS OF THE FINDINGS The key SNP, rs61764370, was genotyped in a subset of samples. Our results do not support the suggestion that carrying the minor allele at rs61764370 contributes to a significant number of endometriosis cases and rs61764370 is, therefore, unlikely to be a useful marker of endometriosis risk. STUDY FUNDING/COMPETING INTEREST(S) The research was funded by grants from the Australian National Health and Medical Research Council and Wellcome Trust. None of the authors has competing interests for the study.

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BACKGROUND: Baltic amber-bead necklaces or bracelets are commonly used for managing teething symptoms in infants. The effectiveness of these beads is claimed to be from succinic acid release (a compound with analgesic and anti-inflammatory properties), which is then absorbed through the skin. AIM: To investigate whether Baltic amber teething necklaces purchased in Australia contained succinic acid, and to quantify succinic acid release from the beads. METHODS: Infrared spectroscopy was used to confirm that the teething necklaces were made of Baltic amber. The amount of succinic acid contained within the beads was quantified, and succinic acid release from intact beads was measured in phosphate buffered saline (PBS) pH 5.5 or octanol to simulate aqueous or oily skin environments. RESULTS: Each necklace (33 beads in length) contained 19.17±4.89 mg of succinic acid (mean±se). Over a 6-month period, no succinic acid was detected in PBS, while 0.13±0.09 mg of succinic acid per necklace was released in octanol. Only one replicate of amber beads in octanol released succinic acid, and they had fragmented, with shards free-floating in the solvent. DISCUSSION: It is likely succinic acid was only detected because the beads were breaking down in octanol, which does not occur when worn around the neck of a child. Furthermore, the hydrophilic properties of succinic acid would not favour its absorption across hydrophobic layers of the skin and into the bloodstream. CONCLUSION: While the teething necklaces do contain small quantities of succinic acid, it is highly unlikely to be released from intact beads.

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Variation in personality traits is 30-60% attributed to genetic influences. Attempts to unravel these genetic influences at the molecular level have, so far, been inconclusive. We performed the first genome-wide association study of Cloninger's temperament scales in a sample of 5117 individuals, in order to identify common genetic variants underlying variation in personality. Participants' scores on Harm Avoidance, Novelty Seeking, Reward Dependence, and Persistence were tested for association with 1,252,387 genetic markers. We also performed gene-based association tests and biological pathway analyses. No genetic variants that significantly contribute to personality variation were identified, while our sample provides over 90% power to detect variants that explain only 1% of the trait variance. This indicates that individual common genetic variants of this size or greater do not contribute to personality trait variation, which has important implications regarding the genetic architecture of personality and the evolutionary mechanisms by which heritable variation is maintained.

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OBJECTIVES To investigate: - (1) whether shared genetic factors influence migraine and anxious depression; - (2) whether the genetic architecture of migraine depends on anxious depression; - (3) whether the association between migraine and anxious depression is causal. BACKGROUND Migraine and anxious depression frequently occur together, but little is known about the mechanisms causing this association. METHODS A twin study was conducted to model the genetic architecture of migraine and anxious depression and the covariance between them. Anxious depression was also added to the model as a moderator variable to examine whether anxious depression affects the genetic architecture of migraine. Causal models were explored with the co-twin control method. RESULTS Modest but significant phenotypic (rP=0.28), genetic (rG=0.30), and nonshared environmental (rE=0.26) correlations were found between the 2 traits. Interestingly, the heritability of migraine depended on the level of anxious depression: the higher the anxious depression score, the lower the relative contribution of genetic factors to the individual differences in migraine susceptibility. The observed risk patterns in discordant twins are most consistent with a bidirectional causal relationship. CONCLUSIONS These findings confirm the genetic association between migraine and anxious depression and are consistent with a syndromic association between the 2 traits. This highlights the importance of taking comorbidity into account in genetic studies of migraine, especially in the context of selection for large-scale genotyping efforts. Genetic studies may be most effective when migraine with and without comorbid anxious depression are treated as separate phenotypes.

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Context: Identifying susceptibility genes for schizophrenia may be complicated by phenotypic heterogeneity, with some evidence suggesting that phenotypic heterogeneity reflects genetic heterogeneity. Objective: To evaluate the heritability and conduct genetic linkage analyses of empirically derived, clinically homogeneous schizophrenia subtypes. Design: Latent class and linkage analysis. Setting: Taiwanese field research centers. Participants: The latent class analysis included 1236 Han Chinese individuals with DSM-IV schizophrenia. These individuals were members of a large affected-sibling-pair sample of schizophrenia (606 ascertained families), original linkage analyses of which detected a maximum logarithm of odds (LOD) of 1.8 (z = 2.88) on chromosome 10q22.3. Main Outcome Measures: Multipoint exponential LOD scores by latent class assignment and parametric heterogeneity LOD scores. Results: Latent class analyses identified 4 classes, with 2 demonstrating familial aggregation. The first (LC2) described a group with severe negative symptoms, disorganization, and pronounced functional impairment, resembling “deficit schizophrenia.” The second (LC3) described a group with minimal functional impairment, mild or absent negative symptoms, and low disorganization. Using the negative/deficit subtype, we detected genome-wide significant linkage to 1q23-25 (LOD = 3.78, empiric genome-wide P = .01). This region was not detected using the DSM-IV schizophrenia diagnosis, but has been strongly implicated in schizophrenia pathogenesis by previous linkage and association studies.Variants in the 1q region may specifically increase risk for a negative/deficit schizophrenia subtype. Alternatively, these results may reflect increased familiality/heritability of the negative class, the presence of multiple 1q schizophrenia risk genes, or a pleiotropic 1q risk locus or loci, with stronger genotype-phenotype correlation with negative/deficit symptoms. Using the second familial latent class, we identified nominally significant linkage to the original 10q peak region. Conclusion: Genetic analyses of heritable, homogeneous phenotypes may improve the power of linkage and association studies of schizophrenia and thus have relevance to the design and analysis of genome-wide association studies.

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CONTEXT People meeting diagnostic criteria for anxiety or depressive disorders tend to score high on the personality scale of neuroticism. Studying this personality dimension can give insights into the etiology of these important psychiatric disorders. OBJECTIVES To undertake a comprehensive genome-wide linkage study of neuroticism using large study samples that have been measured multiple times and to compare the results between countries for replication and across time within countries for consistency. DESIGN Genome-wide linkage scan. SETTING Twin individuals and their family members from Australia and the Netherlands. PARTICIPANTS Nineteen thousand six hundred thirty-five sibling pairs completed self-report questionnaires for neuroticism up to 5 times over a period of up to 22 years. Five thousand sixty-nine sibling pairs were genotyped with microsatellite markers. METHODS Nonparametric linkage analyses were conducted in MERLIN-REGRESS for the mean neuroticism scores averaged across time. Additional analyses were conducted for the time-specific measures of neuroticism from each country to investigate consistency of linkage results. RESULTS Three chromosomal regions exceeded empirically derived thresholds for suggestive linkage using mean neuroticism scores: 10p 5 Kosambi cM (cM) (Dutch study sample), 14q 103 cM (Dutch study sample), and 18q 117 cM (combined Australian and Dutch study sample), but only 14q retained significance after correction for multiple testing. These regions all showed evidence for linkage in individual time-specific measures of neuroticism and 1 (18q) showed some evidence for replication between countries. Linkage intervals for these regions all overlap with regions identified in other studies of neuroticism or related traits and/or in studies of anxiety in mice. CONCLUSIONS Our results demonstrate the value of the availability of multiple measures over time and add to the optimism reported in recent reviews for replication of linkage regions for neuroticism. These regions are likely to harbor causal variants for neuroticism and its related psychiatric disorders and can inform prioritization of results from genome-wide association studies.

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Accurate determination of same-sex twin zygosity is important for medical, scientific and personal reasons. Determination may be based upon questionnaire data, blood group, enzyme isoforms and fetal membrane examination, but assignment of zygosity must ultimately be confirmed by genotypic data. Here methods are reviewed for calculating average probabilities of correctly concluding a twin pair is monozygotic, given they share the same genotypes across all loci for commonly utilized multiplex short tandem repeat (STR) kits.