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  • Bjerring posted an update 7 months, 1 week ago

    Hierarchical clustering analysis of individual primary and secondary metabolites revealed a metabolite-dependent response toward AMF and eCO2. The synchronous application of AMF and eCO2 resulted in promoted accumulation of the majority of the detected sugars, organic acids, amino acids, unsaturated fatty acids, phenolic acids and flavonoids, as compared with the sole treatments. Moreover, AMF and eCO2 acted synergistically in improving the antioxidant capacity and anti-lipid peroxidation activity of oregano. Therefore, this study suggests that AMF treatment induces a global metabolic change in oregano, the effect that is strengthened under eCO2. BACKGROUND The aim of the present study was to assess the predictive value of post-filter ionized calcium (pfCa) levels for filter-clotting during continuous veno-venous hemodialysis (CVVHD) with regional citrate anticoagulation (RCA). METHODS Retrospective analysis of a database derived from 6 intensive care units (ICU) at a university hospital. During the 3-year period 1070 patients were treated with RCA-CVVHD with a citrate starting dose of 4 mmol/L blood and a target-range for pfCa of 0.25-0.35 mmol/L. RESULTS The pfCa concentrations at RCA-CVVHD initiation were within the target range in 69.7% of patients. Within 12 h the fraction of patients with pfCa above target-range decreased significantly from 13.1% to 7.8% (p  less then  .001). There was no significant difference in filter survival between patients with a pfCa initially below, within, or above the target-range (83.7%, 89.5% and 90.4%; p = .228) and no significant correlation between the last pfCa and the incidence of filter clotting (rho 0.018, p = .572 and -0.054, p = .104; respectively). CONCLUSIONS CVVHD with a citrate starting dose of 4 mmol/L blood resulted in a pfCa within target in the majority of patients. The observation that pfCa was not associated with the incidence of circuit clotting suggests that less frequent measurements of pfCA might be safe. Parkinson’s disease (PD) is characterized by progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc). Levodopa (L-Dopa), the current main treatment for PD, reduces PD symptoms by partially replacing dopamine, but it does not slow neurodegeneration. Recent studies have evidenced that neuroinflammatory processes contribute to the degeneration of dopaminergic neurons in the SNc under cytopathic conditions, while other lines of inquiry have implicated phosphorylation of collapsin response mediator protein 2 (CRMP2) as a causal factor in axonal retraction after neural injury. We recently reported on the therapeutic effect of lanthionine ketimine ester (LKE) which associates with CRMP2 following axonal injury in the spinal cord. In the present study, we report that LKE protects SNc dopaminergic neurons after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) challenge, a common model for PD, and reduces the number of activated microglia proximal to the damaged SNc. The results also show that MPTP-induced motor impairment was suppressed in LKE treatment. Furthermore, the results show that LKE inhibits the elevation of CRMP2 phosphorylation in dopaminergic neurons in the SNc after MPTP injection. These data suggest that modification of CRMP2 phosphorylation and suppression of microglial activation with LKE administration may represent a novel strategy for slowing progress of pathological processes in PD. OBJECTIVE HIV is associated with an increased risk of stroke, but there are sparse data on risk factors for stroke in people living with HIV in Sub-Saharan African. The goal of this study was to identify HIV-specific stroke characteristics and risk factors among adults in Botswana. METHODS We conducted a prospective cohort study in Gaborone, Botswana from June 2015 to June 2017 comparing risk factors and outcomes among adults with and without HIV admitted for acute stroke. In addition, we conducted a case-control study comparing patients with HIV and stroke to outpatients with HIV and no history of stroke. RESULTS A total of 52 patients with imaging-confirmed acute stroke were enrolled. Stroke patients with HIV were younger than those without HIV (median age 40 vs 54, p = .005). this website Hypertension was the most common risk factor identified in both HIV+ and HIV- groups, but was more common in patients without HIV (81% vs. 55%, p = .04). Patients with HIV were significantly more likely to have a small-vessel lacunar syndrome compared to patients without HIV (67% vs. 29%, p = .02). In the case-control analysis, patients with HIV and stroke were more likely to have hypertension than stroke-free controls (53% vs. 16%; OR 7.2, 95% CI 1.5-33.8, p = .01), and were more likely to drink alcohol (53% vs. 21%, OR 3.7, 95% CI 1.1-12.1, p = .03). CONCLUSIONS Individuals with HIV present with strokes at younger ages than individuals without HIV. Among those with HIV, hypertension and alcohol use are significant risk factors for stroke. The native extracellular matrix (ECM) contains a host of matricellular proteins and bioactive factors that regulate cell behavior, and many ECM components have been leveraged to guide cell fate. However, the large size and chemical characteristics of these constituents complicate their incorporation into biomaterials without interfering with material properties, motivating the need for alternative approaches to regulate cellular responses. Mesenchymal stromal cells (MSCs) can promote osseous regeneration in vivo directly or indirectly through multiple means including (1) secretion of proangiogenic and mitogenic factors to initiate formation of a vascular template and recruit host cells into the tissue site or (2) direct differentiation into osteoblasts. As MSC behavior is influenced by the properties of engineered hydrogels, we hypothesized that the biochemical and biophysical properties of alginate could be manipulated to promote the dual contributions of encapsulated MSCs toward bone formation. We functionalized alginate with QK peptide to enhance proangiogenic factor secretion and RGD to promote adhesion, while biomechanical-mediated osteogenic cues were controlled by modulating viscoelastic properties of the alginate substrate. A 11 ratio of QKRGD resulted in the highest levels of both proangiogenic factor secretion and mineralization in vitro. Viscoelastic alginate outperformed purely elastic gels in both categories, and this effect was enhanced by stiffness up to 20 kPa. Furthermore, viscoelastic constructs promoted vessel infiltration and bone regeneration in a rat calvarial defect over 12 weeks. These data suggest that modulating viscoelastic properties of biomaterials, in conjunction with dual peptide functionalization, can simultaneously enhance multiple aspects of MSC regenerative potential and improve neovascularization of engineered tissues.

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