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Objective

The reprogramming of cardiac fibroblasts into induced cardiomyocyte-like cells improves ventricular function in myocardial infarction models. Only integrating persistent expression vectors have thus far been used to induce reprogramming, potentially limiting its clinical applicability. We therefore tested the reprogramming potential of nonintegrating, acute expression adenoviral (Ad) vectors.

Methods

Ad or lentivirus vectors encoding Gata4 (G), Mef2c (M), and Tbx5 (T) were validated in vitro. Sprague-Dawley rats then underwent coronary ligation and Ad-mediated administration of vascular endothelial growth factor to generate infarct prevascularization. Three weeks later, animals received Ad or lentivirus encoding G, M, or T (AdGMT or LentiGMT) or an equivalent dose of a null vector (n = 11, 10, and 10, respectively). Outcomes were analyzed by echocardiography, magnetic resonance imaging, and histology.

Results

Ad and lentivirus vectors provided equivalent G, M, and T expression in vitro. AdGMT and LentiGMT both likewise induced expression of the cardiomyocyte marker cardiac troponin T in approximately 6% of cardiac fibroblasts versus <1% cardiac troponin T expression in AdNull (adenoviral vector that does not encode a transgene)-treated cells. Infarcted myocardium that had been treated with AdGMT likewise demonstrated greater density of cells expressing the cardiomyocyte marker beta myosin heavy chain 7 compared with AdNull-treated animals. Echocardiography demonstrated that AdGMT and LentiGMT both increased ejection fraction compared with AdNull (AdGMT: 21% ± 3%, LentiGMT: 14% ± 5%, AdNull: ?0.4% ± 2%; P < .05).

Conclusions

Ad vectors are at least as effective as lentiviral vectors in inducing cardiac fibroblast transdifferentiation into induced cardiomyocyte-like cells and improving cardiac function in postinfarct rat hearts. Short-term expression Ad vectors may represent an important means to induce cardiac cellular reprogramming in humans.  相似文献   
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Methods. To undertake a clinical study of postcoital bleeding (PCB) in a district general hospital we retrospectively reviewed the records of 248 patients referred to the gynaecology department over a 5-year period. Results. 63% were in the 21–40-year age group and 80% were multiparous. Seventy per cent were referred to the gynaecology out patients' clinic and 28% to the colposcopy clinic. Associated symptoms included menstrual abnormalities (39%) and dyspareunia (13%). Twenty per cent had benign polyps, including endometrial polyps and 25% had cervical ectropion. Cervical intraepithelial neoplasia was detected in 6.8% of cases. There was no case of invasive cancer of the lower genital tract. Conclusions. This is the first report of associated endometrial polyps contributing to PCB. We conclude that CIN may not always be asymptomatic and the incidence of cervical or endometrial cancer is low in women with PCB.  相似文献   
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Editorial     
The present study was conducted to determine whether older adults can learn and retain information on asthma and play a role as community health workers to teach children about asthma. A total of 36 older adults and 28 students in grades K-6 participated. Pre-tests and post-tests were administered to participants. Improvement in older adult scores after training was significant (p =. 001), and improvement persisted through the conclusion of teaching sessions (p = 0.001). The increase in lower student scores was significant (p = 0.050). Results suggest that older adults can learn and retain asthma information and schoolchildren can learn asthma-related information taught by older adults.  相似文献   
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Background A high prevalence of Helicobacter pylori infection has been reported among people with intellectual disability, especially those residing in hospital and similar settings. Surveys of inpatients have found unusually high rates of gastrointestinal malignancy, to which H. pylori infection predisposes. Methods Helicobacter pylori antibody testing was arranged for all residents of five inpatient units for people with intellectual disability and challenging behaviour or psychiatric disorder. Eradication triple therapy was prescribed for those people with a positive result. 13C urea breath testing was attempted after eradication therapy. Results Thirty‐seven residents were identified. It was possible to obtain blood for H. pylori antibody testing for 36 people. Twenty‐two (59%) had a positive result. Dividing the people studied according to length of stay in hospital showed that 4 of the 18 people resident in hospital for <4 years (22%) had a positive antibody test, compared with 16 of the 19 people resident in hospital for ≥4 years (84%; χ2 = 14.6; P < 0.001). Treatment led to eradication of H. pylori infection in 11 of the 12 people who were able to cooperate with testing. Conclusions Clinicians should have a high index of suspicion for H. pylori infection among people with intellectual disability who have a history of institutional care or prolonged hospital admission, especially those who have spent more than 4 years in such settings. Testing for H. pylori antibodies is well tolerated. Eradication therapy offers many health benefits, including a reduction of the risk for stomach malignancies.  相似文献   
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Bruxism is a movement disorder characterized by grinding and clenching of teeth. Awake bruxism is found more in females as compared to males while sleep bruxism shows no such gender prevalence. Etiology of bruxism can be divided into three groups psychosocial factors, peripheral factors and pathophysiological factors. Treatment modalities involve occlusal correction, behavioural changes and pharmacological approach. A literature search was performed using National Library of Medicine's (NLM) Medical Subject Headings (MeSH) Database, Pubmed and Google search engines. The search term 'Bruxism' yielded 2,358 papers out of which 230 were review papers. Most of the papers selected were recently published during the period of 1996-2010 and very few of them were published before 1996.  相似文献   
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Graefe's Archive for Clinical and Experimental Ophthalmology - To evaluate the retinal vasculature and vasoreactivity of patients with hypertension (HTN) using spectral domain optical coherence...  相似文献   
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Pulmonary hypertension in the neonate requires treatment with oxygen and positive pressure ventilation, both known to induce lung injury. The direct response of pulmonary artery smooth muscle cells, the most abundant cells in the artery wall, to the stress of positive pressure and hyperoxia has not been previously studied. Pulmonary artery smooth muscle cells were cultured in temperature- and pressure-controlled air-tight chambers under conditions of positive pressure or hyperoxia for 24 h. Control cells were cultured in room air under atmospheric pressure. After the exposure period, culture medium was collected and samples were analyzed by ELISA, Human Cytokine 25-Plex Panel using a Luminex 200 analyzer and Western blot. Secretion of various inflammatory mediators, specifically IL-6, IL-8, IL-2R, MIP-1β, MCP-1, IP-10, IL-7, IL-1RA, and IFN-α, was higher in the positive pressure and hyperoxia groups compared with control. The level of cyclin D1 was decreased in the hyperoxia and positive pressure group compared with control. Levels of fibronectin and α-smooth muscle actin were not different among the groups. Pulmonary artery smooth muscle cells directly produce multiple inflammatory mediators in response to oxidative and biophysical stress in vitro, which may be part of a cascade that leads to the vascular and perivascular changes in pulmonary hypertension.  相似文献   
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