187 research outputs found
A Study of the Genetics and Physical Properties of Dentine Defects
Dentinogenesis Imperfecta (DI) and Dentine Dysplasia (DD) are rare inherited condition affecting the dentine. Previous studies have reported the histological presentation of teeth with dentine defects but the differences between clinical appearances and physical properties, and how do they link to the underlying gene defects, is limited. In addition, the differences between primary and permanent teeth are poorly understood. Aim and Objective: The aim of this study was to investigate if there is an association between the underlying gene defect (genotype) and the physical properties and appearance (phenotype) of teeth with dentine defects. The objectives were to assess the colour, radiographic feature and dentine hardness of the teeth with dentine defects, to discover any other unidentified genes that might involve in causing inherited dentine diseases, and to relate them to the phenotype recorded clinically. Materials and Method: The discolouration and radiographic features of teeth from 16 patients (6 DI type I, 5DI type II, 4 OI and 1 DD type I respectively) were recorded. 20 control primary teeth and five DI teeth (four DI type I, one DI type II) were sectioned transversely using a diamond wheel saw. The dentine hardness measurement was done using Wallace Hardness Machine and recorded as Vickers Hardness Number (VHN). Dentine microstructure was examined using scanning electron microscope (SEM). Saliva samples were obtained from 14 patients for genomic analysis. Results: All DI type II and DI type I patients had marked discolouration of their teeth. DD and OI patients had normal teeth colour. The mean value of dentine hardness of control teeth was VHN=57.11±62. The VHN for DI teeth were significantly low compared to control teeth. The mean value for DI teeth was 30.61±8.24 VHN. Histologically, both DI type I and DI type II teeth showed reduced number of dentine tubules. DI type II had irregular dentine surface, while DI type I dentine showed a tear-like appearance on an empty dentine surface. Genetic analysis did not show any known mutations on COL1A1 and no novel genetic mutations has been observed. Conclusion: Collagen plays a role in maintenance of healthy dentine. Therefore, defects on COL1A1 and COL1A2 lead to abnormality of collagen thus the occurrence of OI and DI type I. Mutation in DSPP caused disruption in dentine mineralisation which also present as dentine defects in DI type II. Both DSPP and COL1A1/COL1A2 caused dentine abnormalities which present as teeth discolouration, abnormal appearance and reduced dentine hardness
Knowledge of Hypertension and Compliance with Therapy Among Hypertensive Patients in the Bamenda Health District of Cameroon: A Cross-sectional Study
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Does intensive management improve remission rates in patients with intermediate rheumatoid arthritis? (the TITRATE trial): study protocol for a randomised controlled trial.
BACKGROUND: Uncontrolled active rheumatoid arthritis can lead to increasing disability and reduced quality of life over time. 'Treating to target' has been shown to be effective in active established disease and also in early disease. However, there is a lack of nationally agreed treatment protocols for patients with established rheumatoid arthritis who have intermediate disease activity. This trial is designed to investigate whether intensive management of disease leads to a greater number of remissions at 12 months. Levels of disability and quality of life, and acceptability and cost-effectiveness of the intervention will also be examined. METHODS: The trial is a 12-month, pragmatic, randomised, open-label, two-arm, parallel-group, multicentre trial undertaken at specialist rheumatology centres across England. Three hundred and ninety-eight patients with established rheumatoid arthritis will be recruited. They will currently have intermediate disease activity (disease activity score for 28 joints assessed using an erythrocyte sedimentation rate of 3.2 to 5.1 with at least three active joints) and will be taking at least one disease-modifying anti-rheumatic drug. Participants will be randomly selected to receive intensive management or standard care. Intensive management will involve monthly clinical reviews with a specialist health practitioner, where drug treatment will be optimised and an individualised treatment support programme delivered based on several principles of motivational interviewing to address identified problem areas, such as pain, fatigue and adherence. Standard care will follow standard local pathways and will be in line with current English guidelines from the National Institute for Health and Clinical Excellence. Patients will be assessed initially and at 6 and 12 months through self-completed questionnaires and clinical evaluation. DISCUSSION: The trial will establish whether the known benefits of intensive treatment strategies in active rheumatoid arthritis are also seen in patients with established rheumatoid arthritis who have moderately active disease. It will evaluate both the clinical and cost-effectiveness of intensive treatment. TRIAL REGISTRATION: Current Controlled Trials, ID: ISRCTN70160382 . Registered on 16 January 2014.MRC Funding: MC_UP_1302/3
NIHR Funding: RP-PG-0610-1006
Regular Khat (Catha edulis) chewing is associated with elevated diastolic blood pressure among adults in Butajira, Ethiopia: A comparative study
<p>Abstract</p> <p>Background</p> <p>Fresh leaves and buds of the Khat plant (<it>Catha edulis</it>) contain Cathinone, an amphetamine like alkaloid responsible for its pharmacological action. Chewing of Khat has been associated with a transient rise in blood pressure and heart rate in experimental studies. Few studies examined the effect of regular or frequent Khat chewing on blood pressure at the population level. This study was conducted to examine the association of regular Khat chewing with blood pressure among adults.</p> <p>Methods</p> <p>We compared systolic and diastolic blood pressure of adults 35-65 years of age who reported regular chewing of Khat during the preceding five years to those who never chewed Khat during the same period. Study participants were recruited from purposively selected urban and rural villages of Butajira District in Ethiopia. The comparative groups, chewers (334) and non-chewers (330), were identified from among the general population through a house-to-house visit using a screening questionnaire. They were frequency-matched for sex and age within a five-year range. Data were collected through structured interviews and physical measurements including blood pressure, weight and height.</p> <p>Results</p> <p>The prevalence of hypertension was significantly higher among Khat chewers (13.4%) than non-chewers (10.7%), odds ratio (OR) = 1.66 (95% confidence interval (CI) 1.05, 3.13). A considerably high proportion of chewers (29.9%) than non-chewers (20.6%) had sub-optimal diastolic blood pressure (> 80 mmHg). The mean (sd) diastolic blood pressure was significantly higher among Khat chewers [75.0 (11.6)] than non-chewers [72.9 (11.7)], P < 0.05. Similarly, Khat chewers had significantly higher mean (sd) heart rate [76.3 (11.5)] than non-chewers [73.9 (12.6)], P < 0.05. There was no significant difference in mean systolic blood pressure between the two groups.</p> <p>Conclusion</p> <p>Regular chewing of Khat is associated with elevated mean diastolic blood pressure, which is consistent with the peripheral vasoconstrictor effect of Cathinone. Regular Khat chewing may have sustained effects on the cardiovascular system that can contribute to elevated blood pressure at the population level.</p
Late gadolinium uptake demonstrated with magnetic resonance in patients where automated PERFIT analysis of myocardial SPECT suggests irreversible perfusion defect
<p>Abstract</p> <p>Background</p> <p>Myocardial perfusion single photon emission computed tomography (MPS) is frequently used as the reference method for the determination of myocardial infarct size. PERFIT<sup>® </sup>is a software utilizing a three-dimensional gender specific, averaged heart model for the automatic evaluation of myocardial perfusion. The purpose of this study was to compare the perfusion defect size on MPS, assessed with PERFIT, with the hyperenhanced volume assessed by late gadolinium enhancement magnetic resonance imaging (LGE) and to relate their effect on the wall motion score index (WMSI) assessed with cine magnetic resonance imaging (cine-MRI) and echocardiography (echo).</p> <p>Methods</p> <p>LGE was performed in 40 patients where clinical MPS showed an irreversible uptake reduction suggesting a myocardial scar. Infarct volume, extent and major coronary supply were compared between MPS and LGE as well as the relationship between infarct size from both methods and WMSI.</p> <p>Results</p> <p>MPS showed a slightly larger infarct volume than LGE (MPS 29.6 ± 23.2 ml, LGE 22.1 ± 16.9 ml, p = 0.01), while no significant difference was found in infarct extent (MPS 11.7 ± 9.4%, LGE 13.0 ± 9.6%). The correlation coefficients between methods in respect to infarct size and infarct extent were 0.71 and 0.63 respectively. WMSI determined with cine-MRI correlated moderately with infarct volume and infarct extent (cine-MRI vs MPS volume r = 0.71, extent r = 0.71, cine-MRI vs LGE volume r = 0.62, extent r = 0.60). Similar results were achieved when wall motion was determined with echo. Both MPS and LGE showed the same major coronary supply to the infarct area in a majority of patients, Kappa = 0.84.</p> <p>Conclusion</p> <p>MPS and LGE agree moderately in the determination of infarct size in both absolute and relative terms, although infarct volume is slightly larger with MPS. The correlation between WMSI and infarct size is moderate.</p
Gene expression of NMDA receptor subunits in the cerebellum of elderly patients with schizophrenia
To determine if NMDA receptor alterations are present in the cerebellum in schizophrenia, we measured NMDA receptor binding and gene expression of the NMDA receptor subunits in a post-mortem study of elderly patients with schizophrenia and non-affected subjects. Furthermore, we assessed influence of genetic variation in the candidate gene neuregulin-1 (NRG1) on the expression of the NMDA receptor in an exploratory study. Post-mortem samples from the cerebellar cortex of ten schizophrenic patients were compared with nine normal subjects. We investigated NMDA receptor binding by receptor autoradiography and gene expression of the NMDA receptor subunits NR1, NR2A, NR2B, NR2C and NR2D by in situ hybridization. For the genetic study, we genotyped the NRG1 polymorphism rs35753505 (SNP8NRG221533). Additionally, we treated rats with the antipsychotics haloperidol or clozapine and assessed cerebellar NMDA receptor binding and gene expression of subunits to examine the effects of antipsychotic treatment. Gene expression of the NR2D subunit was increased in the right cerebellum of schizophrenic patients compared to controls. Individuals carrying at least one C allele of rs35753505 (SNP8NRG221533) showed decreased expression of the NR2C subunit in the right cerebellum, compared to individuals homozygous for the T allele. Correlation with medication parameters and the animal model revealed no treatment effects. In conclusion, increased NR2D expression results in a hyperexcitable NMDA receptor suggesting an adaptive effect due to receptor hypofunction. The decreased NR2C expression in NRG1 risk variant may cause a deficit in NMDA receptor function. This supports the hypothesis of an abnormal glutamatergic neurotransmission in the right cerebellum in the pathophysiology of schizophrenia
Reliable measurement of E. coli single cell fluorescence distribution using a standard microscope set-up
Background: Quantifying gene expression at single cell level is fundamental for the complete characterization of synthetic gene circuits, due to the significant impact of noise and inter-cellular variability on the system's functionality. Commercial set-ups that allow the acquisition of fluorescent signal at single cell level (flow cytometers or quantitative microscopes) are expensive apparatuses that are hardly affordable by small laboratories. Methods: A protocol that makes a standard optical microscope able to acquire quantitative, single cell, fluorescent data from a bacterial population transformed with synthetic gene circuitry is presented. Single cell fluorescence values, acquired with a microscope set-up and processed with custom-made software, are compared with results that were obtained with a flow cytometer in a bacterial population transformed with the same gene circuitry. Results: The high correlation between data from the two experimental set-ups, with a correlation coefficient computed over the tested dynamic range > 0.99, proves that a standard optical microscope- when coupled with appropriate software for image processing- might be used for quantitative single-cell fluorescence measurements. The calibration of the set-up, together with its validation, is described. Conclusions: The experimental protocol described in this paper makes quantitative measurement of single cell fluorescence accessible to laboratories equipped with standard optical microscope set-ups. Our method allows for an affordable measurement/quantification of intercellular variability, whose better understanding of this phenomenon will improve our comprehension of cellular behaviors and the design of synthetic gene circuits. All the required software is freely available to the synthetic biology community (MUSIQ Microscope flUorescence SIngle cell Quantification)
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