Medicine, Dentistry & Health Sciences Collected Works - Research Publications
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ItemGenome analysis and CRISPR typing of Salmonella enterica serovar Virchow(BMC, 2014-05-21)BACKGROUND: Salmonella enterica subsp. enterica serovar Virchow has been recognized as a significant health burden in Asia, Australia and Europe. In addition to its global distribution, S. Virchow is clinically significant due to the frequency at which it causes invasive infections and its association with outbreaks arising from food-borne transmission. Here, we examine the genome of an invasive isolate of S. Virchow SVQ1 (phage type 8) from an outbreak in southeast Queensland, Australia. In addition to identifying new potential genotyping targets that could be used for discriminating between S. Virchow strains in outbreak scenarios, we also aimed to carry out a comprehensive comparative analysis of the S. Virchow genomes. RESULTS: Genome comparisons between S. Virchow SVQ1 and S. Virchow SL491, a previously published strain, identified a high degree of genomic similarity between the two strains with fewer than 200 single nucleotide differences. Clustered Regularly Interspaced Palindromic Repeats (CRISPR) regions were identified as a highly variable region that could be used to discriminate between S. Virchow isolates. We amplified and sequenced the CRISPR regions of fifteen S. Virchow isolates collected from seven different outbreaks across Australia. We observed three allelic types of the CRISPR region from these isolates based on the presence/absence of the spacers and were able to discriminate S. Virchow phage type 8 isolates originating from different outbreaks. A comparison with 27 published Salmonella genomes found that the S. Virchow SVQ1 genome encodes 11 previously described Salmonella Pathogenicity Islands (SPI), as well as additional genomic islands including a remnant integrative conjugative element that is distinct from SPI-7. In addition, the S. Virchow genome possesses a novel prophage that encodes the Type III secretion system effector protein SopE, a key Salmonella virulence factor. The prophage shares very little similarity to the SopE prophages found in other Salmonella serovars suggesting an independent acquisition of sopE. CONCLUSIONS: The availability of this genome will serve as a genome template and facilitate further studies on understanding the virulence and global distribution of the S. Virchow serovar, as well as the development of genotyping methods for outbreak investigations.
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ItemRing Chromosome 4 in a Child with Multiple Congenital Abnormalities: A Case Report and Review of the Literature.(Hindawi Limited, 2016)A female child born preterm with intrauterine growth retardation and presenting with facial dysmorphism with clefts, microcephaly, limb deformities, and congenital abnormalities involving cardiovascular and urinary systems is described. Chromosomal analysis showed a de novo 46,XX,r(4)(p15.3q35) karyotype. The clinical features of the patient were compared with the phenotypic characteristics of 17 previously reported cases with ring chromosome 4 and those with Wolf-Hirschhorn syndrome (4p-). Clinical features observed in this case are consistent with the consensus phenotype in ring chromosome 4. Patent ductus arteriosus and bilateral talipes equinovarus observed in this baby widen the phenotypic spectrum associated with ring chromosome 4.
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ItemRetropupillary iris claw intraocular lens implantation in aphakia for dislocated intraocular lens (vol 9, pg 261, 2016)(DOVE MEDICAL PRESS LTD, 2016)[This corrects the article on p. 261 in vol. 9, PMID: 27621670.].
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ItemRetropupillary iris claw intraocular lens implantation in aphakia for dislocated intraocular lens(DOVE MEDICAL PRESS LTD, 2016)BACKGROUND: Nowadays, dislocated intraocular lenses (IOLs) and inadequate capsular support are becoming a challenge for every ophthalmic surgeon. Explantation of dislocated IOL and iris claw IOL (ICIOL) are the techniques that have been used in our ophthalmic department. The aim of this study is to report our technique for retropupillar ICIOL. METHODS: This study is a retrospective case series. A total of 105 eyes with dislocated IOL from the patients at the Department of Ophthalmology in Santa Maria Hospital, a tertiary reference hospital in Lisbon, Portugal, from January 2012 until January 2016, had been analyzed. Of these 105 eyes, 66 eyes had dislocated one-piece IOL and 39 eyes had dislocated three-piece IOL. The latter underwent iris suture of the same IOL and were excluded from this study. The remaining 66 eyes with dislocated one-piece IOL underwent pars plana vitrectomy, that is, explantation of dislocated IOL through corneal incision and an implantation of retropupillary ICIOL. Operative data and postoperative outcomes included best corrected visual acuity, IOL position, intraocular pressure, pigment dispersion, clinical signs of endothelial cell loss, and anterior chamber depth. RESULTS: The mean follow-up was 23 months (range: 6-48 months). The mean preoperative best corrected visual acuity was 1.260±0.771 logMAR, and postoperative best corrected visual acuity was 0.352±0.400 logMAR units. Mean vision gain was 0.909 logMar units. The patients had the following complications: 1) retinal detachment was found in one patient, 2) corneal edema was found in three patients, 3) high intraocular pressure was observed in twelve patients, 4) subluxation of the IOL was observed in one patient, and 5) macular edema was found in three eyes. CONCLUSION: The results demonstrate that retropupillary ICIOL is an easy and effective method for the correction of aphakia in patients not receiving capsule support. The safety of this procedure must be interpreted in the context of a surgery usually indicated in complicated cases.
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ItemA Rare Manifestation of Uveitis-glaucoma-hyphema Syndrome.(Jaypee Brothers Medical Publishing, 2016)AIMS: To report a case of a patient who developed uveitis-glaucoma-hyphema (UGH) syndrome after an uneventful cataract surgery and to discuss risk factors, diagnostic challenges, management options, and clinical implications. BACKGROUND: Uveitis-glaucoma-hyphema syndrome is a rare but potentially serious cataract surgery complication. Clinical manifestations include increased intraocular pressure (IOP), anterior chamber inflammation, and recurrent hyphema or microhyphema. Uveitis-glaucoma-hyphema Plus syndrome also includes accompanying vitreous hemorrhage. Although classically associated with rigid anterior chamber intraocular lenses (lOLs), cases of malpositioning and subluxated posterior chamber lOLs have also been described as possible triggers. CASE DESCRIPTION: We report a case of a 70-year-old Caucasian man who developed UGH Plus syndrome after an uneventful cataract surgery with an lOL implanted in the capsular bag. During postoperative follow-up, persistent intraocular inflammation, increased IOP, hyphema, and vitreous hemorrhage were consistent with this diagnosis. Slit-lamp examination demonstrated progressive localized iris atrophy, compatible with chafing of the posterior iris by the IOL haptic as the trigger for UGH syndrome. A pars plana vitrectomy was performed and a retropupillary intraocular lens was implanted. No further complications occurred during follow-up. CONCLUSION AND CLINICAL SIGNIFICANCE: Given the increasing prevalence of single-piece lOLs implanted in the capsular bag, it is important to recognize UGH syndrome as a rare but potentially serious complication. How to cite this article: Sousa DC, Leal I, Faria MY, Pinto LA. A Rare Manifestation of Uveitis-glaucoma-hyphema Syndrome. J Curr Glaucoma Pract 2016;10(2):76-78.
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ItemThe dopamine D2/D3 receptor agonist quinpirole increases checking-like behaviour in an operant observing response task with uncertain reinforcement: A novel possible model of OCD(ELSEVIER, 2014-05-01)Excessive checking is a common, debilitating symptom of obsessive-compulsive disorder (OCD). In an established rodent model of OCD checking behaviour, quinpirole (dopamine D2/3-receptor agonist) increased checking in open-field tests, indicating dopaminergic modulation of checking-like behaviours. We designed a novel operant paradigm for rats (observing response task (ORT)) to further examine cognitive processes underpinning checking behaviour and clarify how and why checking develops. We investigated i) how quinpirole increases checking, ii) dependence of these effects on D2/3 receptor function (following treatment with D2/3 receptor antagonist sulpiride) and iii) effects of reward uncertainty. In the ORT, rats pressed an 'observing' lever for information about the location of an 'active' lever that provided food reinforcement. High- and low-checkers (defined from baseline observing) received quinpirole (0.5mg/kg, 10 treatments) or vehicle. Parametric task manipulations assessed observing/checking under increasing task demands relating to reinforcement uncertainty (variable response requirement and active-lever location switching). Treatment with sulpiride further probed the pharmacological basis of long-term behavioural changes. Quinpirole selectively increased checking, both functional observing lever presses (OLPs) and non-functional extra OLPs (EOLPs). The increase in OLPs and EOLPs was long-lasting, without further quinpirole administration. Quinpirole did not affect the immediate ability to use information from checking. Vehicle and quinpirole-treated rats (VEH and QNP respectively) were selectively sensitive to different forms of uncertainty. Sulpiride reduced non-functional EOLPs in QNP rats but had no effect on functional OLPs. These data have implications for treatment of compulsive checking in OCD, particularly for serotonin-reuptake-inhibitor treatment-refractory cases, where supplementation with dopamine receptor antagonists may be beneficial.
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ItemInflammatory Myofibroblastic Tumor of the Urinary Bladder: A Case Report.(Elsevier BV, 2016-05)Inflammatory myofibroblastic tumor is a rare but benign clinical entity. Its ability to mimic malignancy poses a diagnostic challenge. Here, we report the first case in Australia, of inflammatory myofibroblastic tumor in the bladder in a 40-year-old male, removed via transurethral resection.
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ItemDirect Oral Anticoagulants in Dental Patients Including the Frail Elderly Population.(MDPI AG, 2016-03-19)Direct oral anticoagulants (DOACs) have led to a paradigm shift in the field of anticoagulation, providing safe and convenient anticoagulation without the need for regular blood testing. Currently, there are three major DOACs available-Factor Xa inhibitors (apixaban and rivaroxaban) and direct thrombin inhibitors (dabigatran)-that are available for use in atrial fibrillation and venous thromboembolism. While these agents have been shown to be as effective as warfarin, with a similar or better bleeding profile, there remains some concern of the use of these drugs in vulnerable populations, such as the frail elderly patients; particularly since reversal agents and drug monitoring are not routinely available. We aim to provide a review of the use of DOACs and the impact of DOACs on dental treatment in the elderly population.
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ItemNo Preview AvailableIdentification of Inhibitors of Triacylglyceride Accumulation in Muscle Cells: Comparing HTS Results from 1536-Well Plate-Based and High-Content Platforms(SAGE PUBLICATIONS INC, 2014-01)Excess caloric consumption leads to triacylglyceride (TAG) accumulation in tissues that do not typically store fat, such as skeletal muscle. This ectopic accumulation alters cells, contributing to the pathogenesis of metabolic syndrome, a major health problem worldwide. We developed a 1536-well assay to measure intracellular TAG accumulation in differentiating H9c2 myoblasts. For this assay, cells were incubated with oleic acid to stimulate TAG accumulation prior to adding compounds. We used Nile red as a fluorescent dye to quantify TAG content with a microplate reader. The cell nuclei were counterstained with DAPI nuclear stain to assess cell count and filter cytotoxic compounds. In parallel, we developed an image-based assay in H9c2 cells to measure lipid accumulation levels via high-content analysis, exploiting the dual-emission spectra characteristic of Nile red staining of neutral and phospholipids. Using both approaches, we successfully screened ~227,000 compounds from the National Institutes of Health library. The screening data from the plate reader and IC50 values correlated with that from the Opera QEHS cell imager. The 1536-well plate reader assay is a powerful high-throughout screening platform to identify potent inhibitors of TAG accumulation to better understand the molecular pathways involved in lipid metabolism that lead to lipotoxicity.
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ItemNo Preview AvailableCardioprotective inhibitors of reperfusion injury(National Center for Biotechnology Information (US), 2014-01-10)An understanding of the mechanisms and pathways that mediate cardiac myocyte death is critical for the development of pharmacological therapies to limit heart damage during myocardial infarction (“heart attack”). We have completed the first unbiased cell-based screen of the MLSMR library consisting of ~360,000 compounds to identify small molecule probes that protect cardiac myocytes against oxidative and metabolic stresses, both precipitants of cell death during myocardial infarction. Oxidative stress was modeled with hydrogen peroxide treatment, and metabolic stress by inhibition of glycolysis using 2-deoxyglucose (2-DG). Since cardiac myocytes in vivo are terminally differentiated cells that cannot be expanded to the numbers needed for these studies, two cardiac myocyte model cell lines were used: H9c2 cells, derived fetal rat heart; and HL-1 cells, derived from the hearts of mice with cardiac-specific expression of an SV40 T-antigen transgene. Based on the activities of compounds in each of these cell types in response to each of these death stimuli (4 assays), 10 scaffolds were prioritized for reorder of their powders and available analogs for “analog-by-catalog” (ABC) testing. Two scaffolds advanced through multiple rounds of analog synthesis and structure-activity studies to result in the first probe molecule ML330. ML330 protects both H9c2 and HL-1 cell lines (EC50 0.4–4.0 μM & Emax 42–99 %) from both oxidative and metabolic stress induced by hydrogen peroxide and 2-DG, respectively. A second probe ML331, was identified preferentially protects both cell lines (EC50 0.6–9.0 μM & Emax 39–74 %) from metabolic stress induced by 2-DG. Probe molecules ML330 and ML331 will be useful to map and understand the critical cell death pathways in cardiac myocytes and lead to the development of a pharmacological agent to limit heart damage during myocardial infarction in humans. The probe molecules may also find broad utility in studies to understand relationships that regulate connections between various cell death programs, such as apoptosis and necrosis. Moreover, these findings may also extend to other ischemic syndromes such as stroke.