Plos One
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The molecular pathways involved in the transition from uterine quiescence to overt labour are mapped and form the currently established pharmacological targets for both the induction and inhibition of human labour. However, both spontaneous premature labour and functional dystocia occur and are difficult to treat adequately. The identification of upstream regulators involved in the onset and orchestration of labour pathways is essential to develop additional therapies that will contribute to the regulation of the timing of birth. ⋯ Gene expression profiling of mice uterus from E6.5 to E17.5 results in 7 unique gene expression clusters from early to late pregnancy that define the landscape of molecular events in ongoing pregnancy. In the current dataset progesterone is predicted as an activated upstream regulator and maintainer of myometrial quiescence and is active till E10.5. Progesterone is predicted as an inhibited upstream regulator at E12.5. We identify 22 upstream regulators in the E10.5 to E12.5 time window where the switch to progesterone withdrawal occurs. They are putative relevant upstream activators of labour.
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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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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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Malaria is one of the transfusion transmissible infections in malaria endemic countries such as Ghana. Healthy blood donors may harbour Plasmodium parasites without showing signs of malaria. Blood from such donors constitutes a risk to transfusion recipients and the recipients of this blood may go on to develop transfusion transmitted malaria (TTM). ⋯ Out of 100 health workers surveyed, 26% (26/100) had never heard of transfusion transmitted malaria. In an emergency situation, 41% health workers were willing to transfuse malaria positive blood but only 2%, 4% and 8% were willing to transfuse blood that was positive for HIV, Hepatitis B and Syphilis respectively. Regular training workshops may help improve the knowledge of health workers as a quarter of workers had not heard about transfusion transmitted malaria and 6.8% did not know that malaria was transmissible by transfusion.
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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.