Plos One
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Baboons receiving xenogeneic livers from wild type and transgenic pigs survive less than 10 days. One of the major issues is the early development of profound thrombocytopenia that results in fatal hemorrhage. Histological examination of xenotransplanted livers has shown baboon platelet activation, phagocytosis and sequestration within the sinusoids. In order to study the mechanisms of platelet consumption in liver xenotransplantation, we have developed an in vitro system to examine the interaction between pig endothelial cells with baboon platelets and to thereby identify molecular mechanisms and therapies. ⋯ Although pig hepatocytes and aortic endothelial cells directly caused aggregation of baboon platelets, only pig liver endothelial cells efficiently phagocytosed baboon platelets. Blocking vWF and integrin adhesion pathways prevented both aggregation and phagocytosis.
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Prolonged mechanical ventilation (PMV) is increasingly common worldwide, consuming enormous healthcare resources. Factors that modify PMV outcome are still obscure. ⋯ Among patients that need PMV care during an admission, the presence of de novo AKI requiring dialysis significantly increased short and long term mortality, and demand for health care resources.
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A broad spectrum of diseases can manifest cerebellar ataxia. In this study, we investigated whether proton magnetic resonance spectroscopy (MRS) may help differentiate spinocerebellar ataxias (SCA) from multiple systemic atrophy- cerebellar type (MSA-C). ⋯ By using MRS, significantly lower NAA/Cr, Cho/Cr and NAA/Cho in the cerebellar hemispheres and vermis were found in patients with ataxia (SCAs and MSA-C). Rapid neuronal degeneration and impairment of membrane activities were observed more often in patients with MSA-C than those with SCA, even in early stages. MRS could also help distinguish between SCA2 and other subtypes of SCAs. MRS ratios may be of use as biomarkers in early stages of disease and should be further assessed in a longitudinal study.
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Use of multiple prescribers and pharmacies is a means by which some individuals misuse opioids. Community characteristics may be important determinants of the likelihood of this phenomenon independent of individual-level factors. This was a retrospective cohort study with individual-level data derived from California's statewide prescription drug monitoring program (PDMP) and county-level socioeconomic status (SES) data derived from the United States Census. ⋯ Males had a lower incidence rate of new prescriber use and new pharmacy use than females. The total number of licensed physicians and surgeons in a county was positively, linearly, and independently associated with the number of prescribers and pharmacies that individuals used for prescription opioids. In summary, younger age, female gender, and living in counties with more licensed physicians and surgeons were associated with use of more prescribers and/or more pharmacies for obtaining prescription opioids.
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Joint degeneration observed in the rat monoiodoacetate (MIA) model of osteoarthritis shares many histological features with the clinical condition. The accompanying pain phenotype has seen the model widely used to investigate the pathophysiology of osteoarthritis pain, and for preclinical screening of analgesic compounds. We have investigated the pathophysiological sequellae of MIA used at low (1 mg) or high (2 mg) dose. ⋯ Additionally, while pregabalin significantly reduced deep dorsal horn evoked neuronal responses in animals treated with 2 mg MIA, this effect was much reduced or absent in the 1 mg or sham treated groups. These data demonstrate that intra-articular 2 mg MIA not only produces joint degeneration, but also evokes significant axonal injury to DRG cells including those innervating targets outside of the knee joint such as hindpaw skin. This significant neuropathic component needs to be taken into account when interpreting studies using this model, particularly at doses greater than 1 mg MIA.