Beta 2 Adrenergic Receptor Selective Antagonist Enhances Mechanically Stimulated Bone Anabolism in Aged Mice.

The anabolic response of aged bone to skeletal loading is typically poor. Efforts to improve mechanotransduction in aged bone have met with limited success. This study investigated whether the bone response to direct skeletal loading is improved by reducing sympathetic suppression of osteoblastic bone formation via ß2AR. To test this possibility, we treated aged wild-type C57BL/6 mice with a selective ß2AR antagonist, butaxamine (Butax), before each of nine bouts of cantilever bending of the right tibia. Midshaft periosteal bone formation was assessed by dynamic histomorphometry of loaded and contralateral tibias. Butax treatment did not alter osteoblast activity of contralateral tibias. Loading alone induced a modest but significant osteogenic response. However, when loading was combined with Butax pretreatment, the anabolic response was significantly elevated compared with loading preceded by saline injection. Subsequent studies in osteoblastic cultures revealed complex negative interactions between adrenergic and mechanically induced intracellular signaling. Activation of ß2AR by treatment with the ß1, ß2-agonist isoproterenol (ISO) before fluid flow exposure diminished mechanically stimulated ERK1/2 phosphorylation in primary bone cell outgrowth cultures and AKT phosphorylation in MC3T3-E1 pre-osteoblast cultures. Expression of mechanosensitive Fos and Ptgs2 genes was enhanced with ISO treatment and reduced with flow in both MC3T3-E1 and primary cultures. Finally, co-treatment of MC3T3-E1 cells with Butax reversed these ISO effects, confirming a critical role for ß2AR in these responses. In combination, these results demonstrate that selective inhibition of ß2AR is sufficient to enhance the anabolic response of the aged skeleton to loading, potentially via direct effects upon osteoblasts. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Deconvoluting complex correlates of COVID19 severity with local ancestry inference and viral phylodynamics: Results of a multiomic pandemic tracking strategy

The SARS-CoV-2 pandemic has differentially impacted populations of varied race, ethnicity and socioeconomic status. Admixture mapping and local ancestry inference represent powerful tools to examine genetic risk within multi-ancestry genomes independent of these confounding social constructs. Here, we leverage a pandemic tracking strategy in which we sequence viral and host genomes and transcriptomes from 1,327 nasopharyngeal swab residuals and integrate them with digital phenotypes from electronic health records. We demonstrate over-representation of individuals possessing Oceanian and Indigenous American ancestry in SARS-CoV-2 positive populations. Genome-wide-association disaggregated by admixture mapping reveals regions of chromosomes 5 and 14 associated with COVID19 severity within African and Oceanic local ancestries, respectively, independent of overall ancestry fraction. Phylodynamic tracking of consensus viral genomes reveals no association with disease severity or inferred ancestry. We further present summary data from a multi-omic investigation of human-leukocyte-antigen (HLA) typing, nasopharyngeal microbiome and human transcriptomics that reveal metagenomic and HLA associations with severe COVID19 infection. This work demonstrates the power of multi-omic pandemic tracking and genomic analyses to reveal distinct epidemiologic, genetic and biological associations for those at the highest risk.

Coefficient Variations of Serum Levels of Phenytoin, Carbamazepine, and Valproic Acid in Compliant Epileptics

Compliance of epileptic patients is one of the most important factors for adequate therapy. Recently, it had been shown that the variability of three serial measurement of the serum levels of antiepileptic drug(AED) may be used as an indication of the degree of compliance. Coefficient variation(CV) of serum drug levels calculated by only one AED had been used to determine the compliance in epileptic patients who took multiple AEDs. We attempted to evaluate the CV of AEDs and then find the objective clue of compliance and the compatible therapeutic planing according to CV. Ninety seven epileptic patients of outpatients department of the Gyengsang National University Hospital were entered to this study. All patients were taking medication at least for 6 months without any changes of drug regimen. Patient's information was acquired by reviewing the chart and interview with questionnaire. With these informations, we determined the compliance of the patients. Antiepileptic serum levels were measured three times at intervals of at least two to four weeks apart, and their CV was calculated. We compared the CV between the compliant and non-compliant group in each AED(phenytoin, carbamazepine , valproic acid) and three drugs in the compliant group. The mean CVs of phenytoin, carbamazepine and valproic acid in the compliant group were 18.3+/-13.0, 15.2+/-10.2 and 23.8+/-8.9, respectively(mean+/-SD). The mean of CV in the compliant and the non-compliant group were 17.9+/-10.9 and 38.8+/-27.2, respectively. The CVs of the compliant group were significantly lower than those of the non-compliant group(p<0.05). However, CVs had no significant difference between three antiepileptic drugs. This study showed that CVs of AEDs were not different between each AEDs, even though they possess different pharmacokinetic properties. Therefore, the CV of one AED can be used in determining the compliance of the epileptics who are taking multiple AEDs.

Physical Aspect of The Gamma Knife and Its Clinical Application / 대한치료방사선과학회지

The first Leksell Gamma Knife unit(LGU-type B) for radiosurgery in Asia was installed in Asan Medical Center. Mechanical accuracy, output, dose profiles for each collimators were measure during acceptance test. Sixty eight patients (sixty nine cases) had undergone radiosurgery from May 1990 to September 1990. AVM cases were 24 cases (35%), acoustic tumor 10 (14%), pituitary adenoma 4 (6%), metastatic tumor 18 (26%), meningioma 6 (9%) and others 18 (26%). Dose of 25 Gy-100 Gy was delivered at one time according to disease, location and sizes.