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lts with prolonged treatment. This data is valuable for clinicians involved in the care of this growing demographic of patients. Further investigation on the safety and efficacy of teriparatide in higher doses for the long-term treatment of osteoporosis in postmenopausal women should be conducted through high-quality clinical trials.

High quality evidence supports the utilization of teriparatide 20 μg/day dose to significantly improve lumbar spine BMD and decrease incidence of vertebral fractures and pain severity relative to all comparators. 40 μg/day dose of teriparatide demonstrated significantly better results with prolonged treatment. This data is valuable for clinicians involved in the care of this growing demographic of patients. Further investigation on the safety and efficacy of teriparatide in higher doses for the long-term treatment of osteoporosis in postmenopausal women should be conducted through high-quality clinical trials.

The objectives of this study were to 1) evaluate patient radiation exposure in CT and 2) establish CT Diagnostic Reference Levels (DRL)s based on clinical indication (CI) in Qatar.

Patient data for 13 CIs were collected using specially designed collection forms from the dose management software (DMS) of Hamad Medical Corporation (HMC), the main Qatar healthcare provider. The methodology described in the International Commission on Radiological Protection (ICRP) Report 135 was followed to establish national clinical DRLs in terms of Volumetric Computed Tomography Dose Index (CTDIvol) and total Dose Length Product (DLPt). Effective dose (Ef) was estimated by DMS using DLPt and appropriate conversion factors and was analyzed for comparison purposes.

Data were retrospectively collected for 896 adult patients undergoing CT examinations in 4 hospitals and 7 CT scanners. CT for Diffuse infiltrative lung disease imparted the lowest radiation in terms of CTDIvol (5 mGy), DLPt (181 mGy.cm) and Ef (3.6 mSv). Total body CT for severe trauma imparted the highest DLPt (3137 mGy.cm) and Ef (38.6 mSv) of all CIs with a CTDIvol of 15 mGy. Rounded Third quartile CTDIvol and DLPt values were defined as the Qatar CT clinical DRLs. Comparison was limited due to sparse international literature. When this was possible data were lower or comparable with other studies.

This is the first study reporting national clinical DRLs in Asia and second one internationally after UK. For accurate comparison between studies, systemized CI nomenclature must be followed by researchers.

This is the first study reporting national clinical DRLs in Asia and second one internationally after UK. For accurate comparison between studies, systemized CI nomenclature must be followed by researchers.[This corrects the article DOI 10.1016/j.omtm.2019.09.008.].Affinity-based purification of adeno-associated virus (AAV) vectors has replaced density-based methods for vectors used in clinical settings. This method utilizes camelid single-domain antibodies recognizing AAV capsids. These include AVB Sepharose (AVB) and POROS CaptureSelect affinity ligand for AAV8 (CSAL8) and AAV9 (CSAL9). In this study, we utilized cryo-electron microscopy and 3D image reconstruction to map the binding sites of these affinity ligands on the capsids of several AAV serotypes, including AAV1, AAV2, AAV5, AAV8, and AAV9, representing the range of sequence and structure diversity among AAVs. The AAV-ligand complex structures showed that AVB and CSAL9 bound to the 5-fold capsid region, although in different orientations, and CSAL8 bound to the side of the 3-fold protrusion. The AAV contact residues required for ligand binding, and thus AAV purification, and the ability of the ligands to neutralize infection were analyzed. The data show that only a few residues within the epitopes served to block affinity ligand binding. Neutralization was observed for AAV1 and AAV5 with AVB, for AAV1 with CSAL8, and for AAV9 with CSAL9, associated with regions that overlap with epitopes for neutralizing monoclonal antibodies against these capsids. This information is critical and could be generally applicable in the development of novel AAV vectors amenable to affinity column purification.Limitations to successful gene therapy with adeno-associated virus (AAV) can comprise pre-existing neutralizing antibodies to the vector capsid that can block cellular entry, or inefficient transduction of target cells that can lead to sub-optimal expression of the therapeutic transgene. Recombinant serotype 3 AAV (AAV3) is an emerging candidate for liver-directed gene therapy. In this study, we integrated rational design by using a combinatorial library derived from AAV3B capsids with directed evolution by in vitro selection for liver-targeted AAV variants. The AAV3B-DE5 variant described herein was undetectable in the original viral library but gained a selective advantage upon in vitro passaging in human hepatocarcinoma spheroid cultures. AAV3B-DE5 contains 24 capsid amino acid substitutions compared with AAV3B, distributed among all five variable regions, with strong selective pressure on VR-IV, VR-V, and VR-VII. In vivo, AAV3B-DE5 demonstrated improved human hepatocyte tropism in a liver chimeric mouse model. Importantly, this variant exhibited reduced seroreactivity to human intravenous immunoglobulin (i.v. Ig), as well as individual serum samples from 100 healthy human donors. Therefore, molecular evolution using a combinatorial library platform generated a viral capsid with high hepatocyte tropism and enhanced evasion of pre-existing AAV neutralizing antibodies.Recombinant adeno-associated virus (rAAV) is one of the main vectors used in gene therapy. An accurate genome titer is not only critical for clinical dosing, but also a prerequisite for many analytical assays for AAV product characterization. AAV genome titer is traditionally determined by qPCR; however, assay precision is not optimal despite extensive efforts. More recently, droplet digital PCR (ddPCR) emerged as a powerful alternative that offers excellent accuracy and precision. see more However, currently ddPCR is not as widely available as qPCR and operates at a lower throughput and a higher cost. In this paper, we introduce an improved qPCR method with two major optimizations (1) using an AAV reference material as qPCR standard instead of plasmid DNA and (2) implementing a "digestion-free" method by adding 5% Tween 20 to standard and sample preparations. The new method has been extensively tested with AAV of different serotypes, purification status, and transgenes encapsidated and was found to be highly accurate, precise, and robust.