Plos One
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Cardiac failure is a major cause of mortality in patients with Duchenne muscular dystrophy (DMD). Antisense-mediated exon skipping has the ability to correct out-of-frame mutations in DMD to produce truncated but functional dystrophin. Traditional antisense approaches have however been limited by their poor uptake into cardiac muscle. ⋯ Pip6a-PMO treatment resulted in significant restoration of dystrophin in mdx and Cmah-/-mdx mice (37.5% and 51.6%, respectively), which was sufficient to significantly improve cardiac function, ameliorating both right and left ventricular dysfunction. Cmah-/-mdx mice showed an abnormal response to dobutamine stress test and this was completely ameliorated by PIP6a-PMO treatment. These encouraging data suggest that total restoration of dystrophin may not be required to significantly improve cardiac outcome in DMD patients and that it may be realistic to expect functional improvements with modest levels of dystrophin restoration which may be very achievable in future clinical trials.
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We investigated (1) the relationship between Type D personality, stress intensity appraisal of a self-selected stressor, coping, and perceived coping effectiveness and (2) the relationship between Type D personality and performance. In study one, 482 athletes completed the Type D personality questionnaire (DS14), stress thermometer and MCOPE in relation to a recently experienced sport stressor. Type D was associated with increased levels of perceived stress and selection of coping strategies (more emotion and avoidance coping) as well as perceptions of their effectiveness. ⋯ Type D was associated with poorer performance (reduced distance; more errors), decreases in pre-performance self-confidence and more use of maladaptive resignation/withdrawal coping. Findings suggest that Type D is associated with maladaptive coping and reduced performance. Type D individuals would benefit from interventions related to mood modification or enhancing interpersonal functioning.
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Hyperbilirubinemia (jaundice) is caused by raised levels of unconjugated bilirubin in the blood. When severe, susceptible brain regions including the cerebellum and auditory brainstem are damaged causing neurological sequelae such as ataxia, hearing loss and kernicterus. The mechanism(s) by which bilirubin exerts its toxic effect have not been completely understood to date. ⋯ Because of the rapid and reversible onset of toxicity in this novel model it represents a system to screen therapeutic compounds. We have demonstrated this by targeting inflammation genetically and with anti-inflammatory small molecules that offered protection against bilirubin toxicity. This also suggests that anti-inflammatory drugs could be of therapeutic use in hyperbilirubinemia.
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To assess the image quality of 3 different ultralow-dose CT protocols on pulmonary nodule depiction in a ventilated ex vivo-system. ⋯ The results of this experiment, conducted in a realistic setting show the feasibility of ultralow-dose CT for the detection of pulmonary nodules.
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Unrecognized endobronchial intubation frequently occurs after emergency intubation. However, no study has evaluated the effect of one-lung ventilation on end-tidal carbon dioxide (ETCO2) during cardiopulmonary resuscitation (CPR). We compared the hemodynamic parameters, blood gases, and ETCO2 during one-lung ventilation with those during conventional two-lung ventilation in a pig model of CPR, to determine the effect of the former on ETCO2. ⋯ However, the levels of these blood gases did not differ between the left-lung and two-lung ventilations. In a pig model of CPR, ETCO2 was significantly lower during right-lung ventilation than during two-lung ventilation. However, interestingly, ETCO2 during left-lung ventilation was comparable to that during two-lung ventilation.