680 research outputs found

    Unconventional secretion of α-Crystallin B requires the Autophagic pathway and is controlled by phosphorylation of its serine 59 residue

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    α-Crystallin B (CRYAB or HspB5) is a chaperone member of the small heat-shock protein family that prevents aggregation of many cytosolic client proteins by means of its ATP-independent holdase activity. Surprisingly, several reports show that CRYAB exerts a protective role also extracellularly, and it has been recently demonstrated that CRYAB is secreted from human retinal pigment epithelial cells by an unconventional secretion pathway that involves multi-vesicular bodies. Here we show that autophagy is crucial for this unconventional secretion pathway and that phosphorylation at serine 59 residue regulates CRYAB secretion by inhibiting its recruitment to the autophagosomes. In addition, we found that autophagosomes containing CRYAB are not able to fuse with lysosomes. Therefore, CRYAB is capable to highjack and divert autophagosomes toward the exocytic pathway, inhibiting their canonical route leading to the lysosomal compartment. Potential implications of these findings in the context of disease-associated mutant proteins turn-over are discussed

    A one-year cost–utility analysis of resuscitative endovascular balloon occlusion of the aorta versus resuscitative thoracotomy with aortic cross-clamping for non-compressible torso haemorrhage

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    Introduction Major trauma is a leading cause of death and disability in young adults, especially from massive non- compressible torso haemorrhage. The standard technique to control distal haemorrhage and maximise central perfusion is resuscitative thoracotomy with aortic cross-clamping (RTACC). More recently, the minimally invasive technique of resuscitative endovascular balloon occlusion of the aorta (REBOA) has been developed to similarly limit distal haemor- rhage without the morbidity of thoracotomy; cost–utility studies on this intervention, however, are still lacking. The aim of this study was to perform a one-year cost–utility analysis of REBOA as an intervention for patients with major traumatic non-compressible abdominal haemorrhage, compared to RTACC within the U.K.’s National Health Service. Methods A retrospective analysis of the outcomes following REBOA and RTACC was conducted based on the published literature of survival and complication rates after intervention. Utility was obtained from studies that used the EQ- 5D index and from self-conducted surveys. Costs were calculated using 2016/2017 National Health Service tariff data and supplemented from further literature. A cost–utility analysis was then conducted. Results A total of 12 studies for REBOA and 20 studies for RTACC were included. The mean injury severity scores for RTACC and REBOA were 34 and 39, and mean probability of death was 9.7 and 54%, respectively. The incremental cost- effectiveness ratio of REBOA when compared to RTACC was £44,617.44 per quality-adjusted life year. The incremental cost-effectiveness ratio, by exceeding the National Institute for Health and Clinical Effectiveness’s willingness-to-pay threshold of £30,000/quality-adjusted life year, suggests that this intervention is not cost-effective in comparison to RTACC. However, REBOA yielded a 157% improvement in utility with a comparatively small cost increase of 31.5%. Conclusion Although REBOA has not been found to be cost-effective when compared to RTACC, ultimately, clinical experience and expertise should be the main factor in driving the decision over which intervention to prioritise in the emergency context

    Comparison of in vivo and in vitro digestibility in donkeys

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    We compared in vivo and in vitro dry matter (DM) and neutral detergent fiber (NDF) digestibility in donkeys using feces as microbial inoculum. Four donkeys were used in a 4 × 4 Latin square design with a 2 × 2 factorial arrangement of treatments. The animals were fed two types of hay, with or without flaked barley. For the in vivo procedure, total feces were collected for 6 days from each donkey; digestibility was calculated as the difference between ingested and excreted DM and NDF. For the in vitro procedure, donkey feces were buffered and used as microbial inoculum in an Ankom DaisyII Incubator; digestibility was estimated after 60 h of incubation. In vivo results showed that the addition of barley to hays did not change the digestibility values. In vivo estimates were higher than in vitro ones. The equations used to predict in vivo estimates from in vitro data were not reliable (R2 = 0.47 and 0.21; P = 0.003 and 0.078 for NDF and DM digestibility, respectively). Further studies need to evaluate different sample size and digestion times
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