Current developments in LC-MS for pharmaceutical analysis

The current developments in liquid chromatography-mass spectrometry (LC-MS) and its applications to the analysis of pharmaceuticals are reviewed. Various mass spectrometric techniques, including electrospray and nanospray ionization, atmospheric pressure chemical ionization and photoionization and their interface with liquid chromatographic techniques are described. These include high performance liquid chromatography, capillary electrophoresis and capillary electrochromatography and the advantages and disadvantages of each technique are discussed. The applications of LC-MS to the studies of in vitro and in vivo drug metabolism, identification and characterization of impurities in pharmaceuticals, analysis of chiral impurities in drug substances and high-throughput LC-MS-MS systems for applications in the “accelerated drug discovery” process are described

An Integrated Korean Biodiversity and Genetic Information Retrieval System

Background: On-line biodiversity information databases are growing quickly and being integrated into general bioinformatics systems due to the advances of fast gene sequencing technologies and the Internet. These can reduce the cost and effort of performing biodiversity surveys and genetic searches, which allows scientists to spend more time researching and less time collecting and maintaining data. This will cause an increased rate of knowledge build-up and improve conservations. The biodiversity databases in Korea have been scattered among several institutes and local natural history museums with incompatible data types. Therefore, a comprehensive database and a nation wide web portal for biodiversity information is necessary in order to integrate diverse information resources, including molecular and genomic databases. Results: The Korean Natural History Research Information System (NARIS) was built and serviced as the central biodiversity information system to collect and integrate the biodiversity data of various institutes and natural history museums in Korea. This database aims to be an integrated resource that contains additional biological information, such as genome sequences and molecular level diversity. Currently, twelve institutes and museums in Korea are integrated by the DiGIR (Distributed Generic Information Retrieval) protocol, with Darwin Core2.0 format as its metadata standard for data exchange. Data quality control and statistical analysis functions have been implemented. In particular, integrating molecular and genetic information from the National Center for Biotechnology Information (NCBI) databases with NARIS was recently accomplished. NARIS can also be extended to accommodate other institutes abroad, and the whole system can be exported to establish local biodiversity management servers. Conclusion: A Korean data portal, NARIS, has been developed to efficiently manage and utilize biodiversity data, which includes genetic resources. NARIS aims to be integral in maximizing biofrom resource utilization for conservation, management, research, education, industrial applications, and integration with other bioinformation data resources. It can be found at http://www.naris.go.krclose1

Rapid short-pulses of focused ultrasound and microbubbles deliver a range of agent sizes to the brain

Focused ultrasound and microbubbles can non-invasively and locally deliver therapeutics and imaging agents across the blood–brain barrier. Uniform treatment and minimal adverse bioeffects are critical to achieve reliable doses and enable safe routine use of this technique. Towards these aims, we have previously designed a rapid short-pulse ultrasound sequence and used it to deliver a 3 kDa model agent to mouse brains. We observed a homogeneous distribution in delivery and blood–brain barrier closing within 10 min. However, many therapeutics and imaging agents are larger than 3 kDa, such as antibody fragments and antisense oligonucleotides. Here, we evaluate the feasibility of using rapid short-pulses to deliver higher-molecular-weight model agents. 3, 10 and 70 kDa dextrans were successfully delivered to mouse brains, with decreasing doses and more heterogeneous distributions with increasing agent size. Minimal extravasation of endogenous albumin (66.5 kDa) was observed, while immunoglobulin (~ 150 kDa) and PEGylated liposomes (97.9 nm) were not detected. This study indicates that rapid short-pulses are versatile and, at an acoustic pressure of 0.35 MPa, can deliver therapeutics and imaging agents of sizes up to a hydrodynamic diameter between 8 nm (70 kDa dextran) and 11 nm (immunoglobulin). Increasing the acoustic pressure can extend the use of rapid short-pulses to deliver agents beyond this threshold, with little compromise on safety. This study demonstrates the potential for deliveries of higher-molecular-weight therapeutics and imaging agents using rapid short-pulses

Post-operative rehabilitation using a digital healthcare system in patients who had undergone rotator cuff repair: protocol for a single-center randomized controlled trial

Background : Operative repair of a rotator cuff tear requires up to 12 weeks of post-operative (post-op) home-based rehabilitation. Maintaining patients’ compliance in the post-op rehabilitation program is a pivotal component for generating successful outcomes. By developing a post-op rehabilitation-oriented digital healthcare system and applying it in patients who had undergone rotator cuff repair, we aim to increase the efficacy of the rehabilitation program and raise patients’ compliance levels. Here, we present a protocol developed for comparing the efficacy of rehabilitation using a newly developed augmented reality (AR)-based digital healthcare system with that of conventional rehabilitation for post-op rehabilitation of rotator cuff repair. Methods : This study will recruit a total of 115 patients who had undergone rotator cuff repair within 3 days after surgery. Patients will be randomly allocated to rehabilitation using an AR-based digital healthcare system (digital group) or conventional rehabilitation (conventional group). Patients in both groups will perform brochure-based exercises from the immediate post-op period to post-op 6 weeks. From post-op 6 weeks to 12 weeks, patients in the digital group will use the AR-based system for post-op exercises, whereas patients in the conventional group will continue brochure-based rehabilitation exercises. The primary outcome will be scores on the Simple Shoulder Test at post-op 12 weeks. Secondary outcomes include numeric rating scale scores for pain, measures of range of motion and muscle strength of the affected shoulder, grip strength of the affected arm, scores on the Disabilities of the Arm, Shoulder and Hand test, the Shoulder Pain and Disability Index, and the EuroQoL-5D-5L quality-of-life measure. Analyses will be conducted using an intention-to-treat approach. Discussion : This study will examine the effectiveness of an AR-based digital healthcare system for post-op rehabilitation in the patients after rotator cuff repair. The study will add evidence for the application of digital healthcare systems in post-op rehabilitation. Trial registration : ClinicalTrials.gov NCT04511377. Registered on 10 August 2020.This research is supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number : HI19C0781). The funding source has no role in the design of this study and its execution, analyses, interpretation of the data, or decision to submit results

Camera for QUasars in EArly uNiverse (CQUEAN)

We describe the overall characteristics and the performance of an optical CCD camera system, Camera for QUasars in EArly uNiverse (CQUEAN), which is being used at the 2.1 m Otto Struve Telescope of the McDonald Observatory since 2010 August. CQUEAN was developed for follow-up imaging observations of red sources such as high redshift quasar candidates (z >= 5), Gamma Ray Bursts, brown dwarfs, and young stellar objects. For efficient observations of the red objects, CQUEAN has a science camera with a deep depletion CCD chip which boasts a higher quantum efficiency at 0.7 - 1.1 um than conventional CCD chips. The camera was developed in a short time scale (~ one year), and has been working reliably. By employing an auto-guiding system and a focal reducer to enhance the field of view on the classical Cassegrain focus, we achieve a stable guiding in 20 minute exposures, an imaging quality with FWHM >= 0.6" over the whole field (4.8' * 4.8'), and a limiting magnitude of z = 23.4 AB mag at 5-sigma with one hour total integration time.Comment: Accepted for publication in PASP. 26 pages including 5 tables and 24 figure

BioBarcode: a general DNA barcoding database and server platform for Asian biodiversity resources

<p>Abstract</p> <p>Background</p> <p>DNA barcoding provides a rapid, accurate, and standardized method for species-level identification using short DNA sequences. Such a standardized identification method is useful for mapping all the species on Earth, particularly when DNA sequencing technology is cheaply available. There are many nations in Asia with many biodiversity resources that need to be mapped and registered in databases.</p> <p>Results</p> <p>We have built a general DNA barcode data processing system, BioBarcode, with open source software - which is a general purpose database and server. It uses mySQL RDBMS 5.0, BLAST2, and Apache httpd server. An exemplary database of BioBarcode has around 11,300 specimen entries (including GenBank data) and registers the biological species to map their genetic relationships. The BioBarcode database contains a chromatogram viewer which improves the performance in DNA sequence analyses.</p> <p>Conclusion</p> <p>Asia has a very high degree of biodiversity and the BioBarcode database server system aims to provide an efficient bioinformatics protocol that can be freely used by Asian researchers and research organizations interested in DNA barcoding. The BioBarcode promotes the rapid acquisition of biological species DNA sequence data that meet global standards by providing specialized services, and provides useful tools that will make barcoding cheaper and faster in the biodiversity community such as standardization, depository, management, and analysis of DNA barcode data. The system can be downloaded upon request, and an exemplary server has been constructed with which to build an Asian biodiversity system <url>http://www.asianbarcode.org</url>.</p

HNF4A Haploinsufficiency in MODY1 Abrogates Liver and Pancreas Differentiation from Patient-Derived Induced Pluripotent Stem Cells.

Maturity-onset diabetes of the young 1 (MODY1) is a monogenic diabetes condition caused by heterozygous HNF4A mutations. We investigate how HNF4A haploinsufficiency from a MODY1/HNF4A mutation influences the development of foregut-derived liver and pancreatic cells through differentiation of human induced pluripotent stem cells from a MODY1 family down the foregut lineage. In MODY1-derived hepatopancreatic progenitors, which expressed reduced HNF4A levels and mislocalized HNF4A, foregut genes were downregulated, whereas hindgut-specifying HOX genes were upregulated. MODY1-derived hepatocyte-like cells were found to exhibit altered morphology. Hepatic and β cell gene signatures were also perturbed in MODY1-derived hepatocyte-like and β-like cells, respectively. As mutant HNF4A (p.Ile271fs) did not undergo complete nonsense-mediated decay or exert dominant negativity, HNF4A-mediated loss of function is likely due to impaired transcriptional activation of target genes. Our results suggest that in MODY1, liver and pancreas development is perturbed early on, contributing to altered hepatic proteins and β cell defects in patients

HNF4A haploinsufficiency in MODY1 abrogates liver and pancreas differentiation from patient-derived induced pluripotent stem cells

Maturity-onset diabetes of the young 1 (MODY1) is a monogenic diabetes condition caused by heterozygous HNF4A mutations. We investigate how HNF4A haploinsufficiency from a MODY1/HNF4A mutation influences the development of foregut-derived liver and pancreatic cells through differentiation of human induced pluripotent stem cells from a MODY1 family down the foregut lineage. In MODY1-derived hepatopancreatic progenitors, which expressed reduced HNF4A levels and mislocalized HNF4A, foregut genes were downregulated, whereas hindgut-specifying HOX genes were upregulated. MODY1-derived hepatocyte-like cells were found to exhibit altered morphology. Hepatic and β cell gene signatures were also perturbed in MODY1-derived hepatocyte-like and β-like cells, respectively. As mutant HNF4A (p.Ile271fs) did not undergo complete nonsense-mediated decay or exert dominant negativity, HNF4A-mediated loss of function is likely due to impaired transcriptional activation of target genes. Our results suggest that in MODY1, liver and pancreas development is perturbed early on, contributing to altered hepatic proteins and β cell defects in patients.publishedVersio

A Case of Post-Streptococcal Glomerulonephritis with Diffuse Alveolar Hemorrhage

Acute post-streptococcal glomerulonephritis (PSGN) is characterized by an abrupt onset of edema, hypertension, and hematuria. Life-threatening diffuse alveolar hemorrhage (DAH) is rarely associated with acute PSGN. There have been only two reported cases worldwide, and no case has been reported previously in Korea. Here, we present a patient who clinically presented with pulmonary-renal syndrome; the renal histology revealed post-infectious glomerulonephritis of immune complex origin. A 59-yr-old woman was admitted with oliguria and hemoptysis two weeks after pharyngitis. Renal insufficiency rapidly progressed, and respiratory distress developed. Chest radiography showed acute progressive bilateral pulmonary infiltrates. The clinical presentation suggested DAH with PSGN. Three days after treatment with high-dose steroids, the respiratory distress and pulmonary infiltrates resolved. Electron microscopy of a renal biopsy specimen sample revealed diffuse proliferative glomerulonephritis with characteristic subendothelial deposits of immune complex ("hump"). The renal function of the patient was restored, and the serum creatinine level was normalized after treatment