256 research outputs found

    Stable Expression of Antibiotic-Resistant Gene ble from Streptoalloteichus hindustanus in the Mitochondria of Chlamydomonas reinhardtii

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    The mitochondrial expression of exogenous antibiotic resistance genes has not been demonstrated successfully to date, which has limited the development of antibiotic resistance genes as selectable markers for mitochondrial site-directed transformation in Chlamydomonas reinhardtii. In this work, the plasmid pBSLPNCB was constructed by inserting the gene ble of Streptoalloteichus hindustanus (Sh ble), encoding a small (14-kilodalton) protective protein into the site between TERMINVREP-Left repeats and the cob gene in a fragment of mitochondrial DNA (mtDNA) of C. reinhardtii. The fusion DNA-construct, which contained TERMINVREP-Left, Sh ble, cob, and partial nd4 sequence, were introduced into the mitochondria of the respiratory deficient dum-1 mutant CC-2654 of C. reinhardtii by biolistic particle delivery system. A large number of transformants were obtained after eight weeks in the dark. Subsequent subculture of the transformants on the selection TAP media containing 3 ìg/mL Zeomycin for 12 months resulted in genetically modified transgenic algae MT-Bs. Sequencing and Southern analyses on the mitochondrial genome of the different MT-B lines revealed that Sh ble gene had been integrated into the mitochondrial genome of C. reinhardtii. Both Western blot, using the anti-BLE monoclonal antibody, and Zeomycin tolerance analysis confirmed the presence of BLE protein in the transgenic algal cells. It indicates that the Sh ble gene can be stably expressed in the mitochondria of C. reinhardtii

    An intervention program to reduce the number of hospitalizations of elderly patients in a primary care clinic

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    <p>Abstract</p> <p>Background</p> <p>The elderly population consumes a large share of medical resources in the western world. A significant portion of the expense is related to hospitalizations.</p> <p>Objectives</p> <p>To evaluate an intervention program designed to reduce the number of hospitalization of elderly patients by a more optimal allocation of resources in primary care.</p> <p>Methods</p> <p>A multidimensional intervention program was conducted that included the re-engineering of existing work processes with a focus on the management of patient problems, improving communication with outside agencies, and the establishment of a system to monitor quality of healthcare parameters. Data on the number of hospitalizations and their cost were compared before and after implementation of the intervention program.</p> <p>Results</p> <p>As a result of the intervention the mean expenditure per elderly patient was reduced by 22.5%. The adjusted number of hospitalizations/1,000 declined from 15.1 to 10.7 (29.3%). The number of adjusted hospitalization days dropped from 132 to 82 (37.9%) and the mean hospitalization stay declined from 8.2 to 6.7 days (17.9%). The adjusted hospitalization cost (/1,000patients)droppedfrom/1,000 patients) dropped from 32,574 to $18,624 (42.8%). The overall clinic expense, for all age groups, dropped by 9.9%.</p> <p>Conclusion</p> <p>Implementation of the intervention program in a single primary care clinic led to a reduction in hospitalizations for the elderly patient population and to a more optimal allocation of healthcare resources.</p

    Test-retest variability of high resolution positron emission tomography (PET) imaging of cortical serotonin (5HT2A) receptors in older, healthy adults

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    <p>Abstract</p> <p>Background</p> <p>Position emission tomography (PET) imaging using [<sup>18</sup>F]-setoperone to quantify cortical 5-HT<sub>2A </sub>receptors has the potential to inform pharmacological treatments for geriatric depression and dementia. Prior reports indicate a significant normal aging effect on serotonin 5HT<sub>2A </sub>receptor (5HT<sub>2A</sub>R) binding potential. The purpose of this study was to assess the test-retest variability of [<sup>18</sup>F]-setoperone PET with a high resolution scanner (HRRT) for measuring 5HT<sub>2A</sub>R availability in subjects greater than 60 years old. Methods: Six healthy subjects (age range = 65–78 years) completed two [<sup>18</sup>F]-setoperone PET scans on two separate occasions 5–16 weeks apart.</p> <p>Results</p> <p>The average difference in the binding potential (BP<sub>ND</sub>) as measured on the two occasions in the frontal and temporal cortical regions ranged between 2 and 12%, with the lowest intraclass correlation coefficient in anterior cingulate regions.</p> <p>Conclusion</p> <p>We conclude that the test-retest variability of [<sup>18</sup>F]-setoperone PET in elderly subjects is comparable to that of [<sup>18</sup>F]-setoperone and other 5HT<sub>2A</sub>R radiotracers in younger subject samples.</p

    Dopamine D2 receptor occupancy and cognition in schizophrenia : analysis of the CATIE data

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    Introduction: Antipsychotic drugs exert antipsychotic effects by blocking dopamine D2 receptors in the treatment of schizophrenia. However, effects of D2 receptor blockade on neurocognitive function still remain to be elucidated. The objective of this analysis was to evaluate impacts of estimated dopamine D2 receptor occupancy with antipsychotic drugs on several domains of neurocognitive function in patients with schizophrenia in the Clinical Antipsychotic Trials in Intervention Effectiveness (CATIE) trial. Methods: The dataset from the CATIE trial was used in the present analysis. Data were extracted from 410 subjects who were treated with risperidone, olanzapine, or ziprasidone, received assessments for neurocognitive functions (verbal memory, vigilance, processing speed, reasoning, and working memory) and psychopathology, and provided plasma samples for the measurement of plasma antipsychotic concentrations. D2 receptor occupancy levels on the day of neurocognitive assessment were estimated from plasma antipsychotic concentrations, using population pharmacokinetic analysis and our recently developed model. A multivariate general linear model was used to examine effects of clinical and demographic characteristics, including estimated D2 occupancy levels, on neurocognitive functions. Results: D2 occupancy levels showed significant associations with the vigilance and the summary scores. Neurocognitive functions, including vigilance, were especially impaired in subjects who showed D2 receptor occupancy level of >77%. Discussion: These findings suggest a nonlinear relationship between prescribed antipsychotic doses and overall neurocognitive function and vigilance. This study shows that D2 occupancy above approximately 80% not only increases the risk for extrapyramidal side effects as consistently reported in the literature but also increases the risk for cognitive impairment.peer-reviewe

    Mental distress in the general population in Zambia: Impact of HIV and social factors

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    <p>Abstract</p> <p>Background</p> <p>Population level data on mental health from Africa are limited, but available data indicate mental problems to represent a substantial public health problem. The negative impact of HIV on mental health suggests that this could particularly be the case in high prevalence populations. We examined the prevalence of mental distress, distribution patterns and the ways HIV might influence mental health among men and women in a general population.</p> <p>Methods</p> <p>The relationship between HIV infection and mental distress was explored using a sample of 4466 participants in a population-based HIV survey conducted in selected rural and urban communities in Zambia in 2003. The Self-reporting questionnaire-10 (SRQ-10) was used to assess global mental distress. Weights were assigned to the SRQ-10 responses based on DSM IV criteria for depression and a cut off point set at 7/20 for probable cases of mental distress. A structural equation modeling (SEM) was established to assess the structural relationship between HIV infection and mental distress in the model, with maximum likelihood ratio as the method of estimation.</p> <p>Results</p> <p>The HIV prevalence was 13.6% vs. 18% in the rural and urban populations, respectively. The prevalence of mental distress was substantially higher among women than men and among groups with low educational attainment vs. high. The results of the SEM showed a close fit with the data. The final model revealed that self-rated health and self perceived HIV risk and worry of being HIV infected were important mediators between underlying factors, HIV infection and mental distress. The effect of HIV infection on mental distress was both direct and indirect, but was particularly strong through the indirect effects of health ratings and self perceived risk and worry of HIV infection.</p> <p>Conclusion</p> <p>These findings suggest a strong effect of HIV infection on mental distress. In this population where few knew their HIV status, this effect was mediated through self-perceptions of health status, found to capture changes in health perceptions related to HIV, and self-perceived risk and worry of actually being HIV infected.</p
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