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  • Hart posted an update 7 months, 1 week ago

    Since the discovery of penicillin by Alexander Fleming in 1928, the use of antibiotics has become the golden standard in the treatment of bacterial infections of all kinds […].As pharmacogenomic (PGx) use in healthcare increases, a better understanding of patient needs will be necessary to guide PGx result delivery. The Coriell Personalized Medicine Collaborative (CPMC) is a prospective study investigating the utility of personalized medicine. Participants received online genetic risk reports for 27 potentially actionable complex diseases and 7 drug-gene pairs and could request free, telephone-based genetic counseling (GC). To explore the needs of individuals receiving PGx results, we conducted a retrospective qualitative review of inquiries from CPMC participants who requested counseling from March 2009 to February 2017. Eighty out of 690 (12%) total GC inquiries were focused on the discussion of PGx results, and six salient themes emerged “general help”, “issues with drugs”, “relevant disease experience”, “what do I do now?”, “sharing results”, and “other drugs”. The number of reported medications with a corresponding PGx result and participant engagement were significantly associated with PGx GC requests (p less then 0.01 and p less then 0.02, respectively). Our work illustrates a range of questions raised by study participants receiving PGx test results, most of which were addressed by a genetic counselor with few requiring referrals to prescribing providers or pharmacists. These results further support a role for genetic counselors in the team-based approach to optimal PGx result delivery.Ageing is associated with disrupted redox signalling and increased circulating inflammatory cytokines. Skeletal muscle homeostasis depends on the balance between muscle hypertrophy, atrophy and regeneration, however during ageing this balance is disrupted. The molecular pathways underlying the age-related decline in muscle regenerative potential remain elusive. microRNAs are conserved robust gene expression regulators in all tissues including skeletal muscle. Here, we studied satellite cells from adult and old mice to demonstrate that inhibition of miR-21 in satellite cells from old mice improves myogenesis. We determined that increased levels of proinflammatory cytokines, TNFα and IL6, as well as H2O2, increased miR-21 expression in primary myoblasts, which in turn resulted in their decreased viability and myogenic potential. Inhibition of miR-21 function rescued the decreased size of myotubes following TNFα or IL6 treatment. Moreover, we demonstrated that miR-21 could inhibit myogenesis in vitro via regulating IL6R, PTEN and FOXO3 signalling. In summary, upregulation of miR-21 in satellite cells and muscle during ageing may occur in response to elevated levels of TNFα and IL6, within satellite cells or myofibrillar environment contributing to skeletal muscle ageing and potentially a disease-related decline in potential for muscle regeneration.Diabetic nephropathy (DN) is considered the main cause of kidney disease in which myofibroblasts lead to renal fibrosis. Macrophages were recently identified as the major source of myofibroblasts in a process known as macrophage-myofibroblast transition (MMT). Adenosine levels increase during DN and in vivo administration of MRS1754, an antagonist of the A2B adenosine receptor (A2BAR), attenuated glomerular fibrosis (glomerulosclerosis). We aimed to investigate the association between A2BAR and MMT in glomerulosclerosis during DN. click here Kidneys/glomeruli of non-diabetic, diabetic, and MRS1754-treated diabetic (DM+MRS1754) rats were processed for histopathologic, transcriptomic, flow cytometry, and cellular in vitro analyses. Macrophages were used for in vitro cell migration/transmigration assays and MMT studies. In vivo MRS1754 treatment attenuated the clinical and histopathological signs of glomerulosclerosis in DN rats. Transcriptomic analysis demonstrated a decrease in chemokine-chemoattractants/cell-adhesion genes of monocytes/macrophages in DM+MRS1754 glomeruli. The number of intraglomerular infiltrated macrophages and MMT cells increased in diabetic rats. This was reverted by MRS1754 treatment. In vitro cell migration/transmigration decreased in macrophages treated with MRS1754. Human macrophages cultured with adenosine and/or TGF-β induced MMT, a process which was reduced by MRS1754. We concluded that pharmacologic blockade of A2BAR attenuated some clinical signs of renal dysfunction and glomerulosclerosis, and decreased intraglomerular macrophage infiltration and MMT in DN rats.Composites of g-C3N4/TiO2 were one-step prepared using electron impact with dielectric barrier discharge (DBD) plasma as the electron source. Due to the low operation temperature, TiO2 by the plasma method shows higher specific surface area and smaller particle size than that prepared via conventional calcination. Most interestingly, electron impact produces more oxygen vacancy on TiO2, which facilitates the recombination and formation of heterostructure of g-C3N4/TiO2. The composites have higher light absorption capacity and lower charge recombination efficiency. g-C3N4/TiO2 by plasma can produce hydrogen at a rate of 219.9 μmol·g-1·h-1 and completely degrade Rhodamine B (20mg·L-1) in two hours. Its hydrogen production rates were 3 and 1.5 times higher than that by calcination and pure g-C3N4, respectively. Electron impact, ozone and oxygen radical also play key roles in plasma preparation. Plasma has unique advantages in metal oxides defect engineering and the preparation of heterostructured composites with prospective applications as photocatalysts for pollutant degradation and water splitting.Background and objectives In order to increase the accuracy of lytic lesion detection in multiple myeloma, a dedicated second-opinion interpretation of medical images performed by subspecialty musculoskeletal radiologists could increase accuracy. Therefore, the purpose of this study is to evaluate the added value (increased accuracy) of subspecialty second-opinion (SSO) consultations for Computed Tomography (CT) examinations in Multiple Myeloma (MM) patients undergoing stem cell transplantation on standard computed tomography with a focus on focal lesion detection. Materials and Methods Approval from the institutional review board was obtained. This retrospective study included 70 MM consecutive patients (mean age, 62 years ± 11.3 (standard deviation); range, 35-88 years) admitted in the last six years. Pre-transplant total-body CT (reported by general radiologists) was the only inclusion criteria. Each of these CT examinations had a second-opinion interpretation by two experienced subspecialty musculoskeletal (MSK) radiologists (13 years of experience and 6 years of experience, mean 9.

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