New Highly-Sensitive Ultra-Performance Liquid Chromatography - Mass Spectrometry Method for Quantification of Telmisartan in Human Plasma

Purpose: To develop and validate a simple, rapid, sensitive and specific ultraperformance liquid chromatography mass spectrometry method for the quantification of the angiotensin II receptor antagonist, telmisartan (TEL), in human plasma.Methods: After simple protein precipitation using acetonitrile and methanol, TEL and internal standard (IS) abiraterone were separated on Acquity UPLC BEHTM C18 column (50 x 2.1 mm, i.d. 1.7 μm, Waters, USA) using a mobile phase consisting of acetonitrile: 8 mM ammonium acetate containing 0.15 % formic acid (v/v) (70:30) pumped at a flow rate of 0.3 mL/min and detected by tandem mass spectrometry with positive ion mode. The ion transitions recorded in multiple reaction monitoring mode were m/z 515.27→276.13 for telmisartan and m/z 350.1 > 156.0 for internal standard, abiraterone.Results: The assay exhibited a linear dynamic range of 1 – 200 ng/mL for telmisartan in human plasma with good correlation coefficient (0.995) and limit of quantitation of 1 ng/mL. The relative standard deviation for the intra- and inter-assay precision was between 0.75-11.50Conclusion: The developed UPLC-MS/MS method is simple, rapid and highly sensitive, and should thus be suitable for pharmacokinetic and toxicokinetic studies in both animals and humans.Keywords: Telmisartan, Ultra-Performance liquid chromatography, Tandem mass spectrometry, Pharmacokinetics, Toxicokinetics, High throughput analysi

Identification of Putative Vero Cell Protein(s) that Bind Specifically to Recombinant Envelope Protein of Dengue Virus Type 2

Purpose: To identify protein targets in host (vero) cell since there is currently no therapy or a licensed tetravalent vaccine to combat all the four virus serotypes of dengue virus.Methods: The domain III of the dengue virus encoded envelope protein was expressed in pET28a expression vector and the purified recombinant protein was labeled with biotin without altering its immunogenicity. Vero cell proteins on nitrocellulose membrane reacted with recombinant envelope protein domain III to identify viral target proteins in vero cells.Results: The 45 KDa, 43 KDa and 30 KDa plasma membrane proteins were identified as viral envelope targets. Competitive binding assay showed these proteins competing with dengue virus binding. MTT assay indicate that viability of vero cells increases in cultures pretreated with 45 KDa, 43 KDa and 30 KDa proteins before dengue infection.Conclusion: These results indicate the possible role of these proteins in viral binding to vero cells. The study provides a preliminary insight that would aid in determining the target epitopes against protein E domain III of dengue virus and hence, formulation of a vaccine for preparing neutralizing antibodies.Keywords: Dengue virus envelope, Biotinylation, Ni-NTA purification, Target epitopes, Plaque assay, Competitive blocking assa

Charge-Transfer Reaction of Cediranib with 2,3-Dichloro- 3,5-dicyano-1,4-benzoquinone: Spectrophotometric Investigation and Use in Development of Microwell Assay for Cediranib

Purpose: To investigate the charge-transfer (CT) reaction between cediranib (CRB) and 2, 3 - dichloro-5, 6- dicyano -1, 4 - benzoquinone (DDQ) and employment of the reaction as a basis for the development of a novel 96 - microwell spectrophotometric assay for CRB.Method: The reaction of CRB and DDQ was investigated in different solvents of varying dielectric constant and polarity index The reaction resulted in the formation of a red-colored product. Spectrophotometric investigations confirmed that the reaction proceeded through to the formation of a (CT) complex.Results: The molar absorptivity of the CT complex was linearly correlated with the dielectric constant and polarity index of the solvent; the correlation coefficients were 0.801 and 0.858, respectively. The association constant of the complex was 0.5 × 103 L mol−1 in 2-propanol. The reaction conditions were optimized for the development of the microwell assay for CRB. The assay limits of detection and quantitation were 6.8 and 20.6 μg/well, respectively. The assay was validated as per the guidelines of the International Conference on Harmonization (ICH) and successfully applied to the analysis of CRB in its bulk and dosage forms with good accuracy and precision.Conclusion: The developed assay has high throughput and consumed minimum volume of organic solvent; thus, it reduces the exposure of the analysts to the toxic effects of organic solvents, and should significantly lower the analysis cost.Keywords: Cediranib, 2,3-dichloro-3,5-dicyano-1,4-benzoquinone, Charge-transfer reaction, Spectrophotometry, Microwell assay, High throughput analysis

A comparative study of clinical presentation and risk factors for adverse outcome in patients hospitalised with acute respiratory disease due to MERS coronavirus or other causes

Middle East Respiratory syndrome (MERS) first emerged in Saudi Arabia in 2012 and remains a global health concern. The objective of this study was to compare the clinical features and risk factors for adverse outcome in patients with RT-PCR confirmed MERS and in those with acute respiratory disease who were MERS-CoV negative, presenting to the King Fahad Medical City (KFMC) in Riyadh between October 2012 and May 2014. The demographics, clinical and laboratory characteristics and clinical outcomes of patients with RT-PCR confirmed MERS-CoV infection was compared with those testing negative MERS-CoV PCR. Health care workers (HCW) with MERS were compared with MERS patients who were not health care workers. One hundred and fifty nine patients were eligible for inclusion. Forty eight tested positive for MERS CoV, 44 (92%) being hospital acquired infections and 23 were HCW. There were 111 MERS-CoV negative patients with acute respiratory illnesses included in this study as 'negative controls'. Patient with confirmed MERS-CoV infection were not clinically distinguishable from those with negative MERS-CoV RT-PCR results although diarrhoea was commoner in MERS patients. A high level of suspicion in initiating laboratory tests for MERS-CoV is therefore indicated. Variables associated with adverse outcome were older age and diabetes as a co-morbid illness. Interestingly, co-morbid illnesses other than diabetes were not significantly associated with poor outcome. Health care workers with MERS had a markedly better clinical outcome compared to non HCW MERS patients.published_or_final_versio

The Origin and Initial Rise of Pelagic Cephalopods in the Ordovician

BACKGROUND: During the Ordovician the global diversity increased dramatically at family, genus and species levels. Partially the diversification is explained by an increased nutrient, and phytoplankton availability in the open water. Cephalopods are among the top predators of today's open oceans. Their Ordovician occurrences, diversity evolution and abundance pattern potentially provides information on the evolution of the pelagic food chain. METHODOLOGY/PRINCIPAL FINDINGS: We reconstructed the cephalopod departure from originally exclusively neritic habitats into the pelagic zone by the compilation of occurrence data in offshore paleoenvironments from the Paleobiology Database, and from own data, by evidence of the functional morphology, and the taphonomy of selected cephalopod faunas. The occurrence data show, that cephalopod associations in offshore depositional settings and black shales are characterized by a specific composition, often dominated by orthocerids and lituitids. The siphuncle and conch form of these cephalopods indicate a dominant lifestyle as pelagic, vertical migrants. The frequency distribution of conch sizes and the pattern of epibionts indicate an autochthonous origin of the majority of orthocerid and lituitid shells. The consistent concentration of these cephalopods in deep subtidal sediments, starting from the middle Tremadocian indicates the occupation of the pelagic zone early in the Early Ordovician and a subsequent diversification which peaked during the Darriwilian. CONCLUSIONS/SIGNIFICANCE: The exploitation of the pelagic realm started synchronously in several independent invertebrate clades during the latest Cambrian to Middle Ordovician. The initial rise and diversification of pelagic cephalopods during the Early and Middle Ordovician indicates the establishment of a pelagic food chain sustainable enough for the development of a diverse fauna of large predators. The earliest pelagic cephalopods were slowly swimming vertical migrants. The appearance and early diversification of pelagic cephalopods is interpreted as a consequence of the increased food availability in the open water since the latest Cambrian

Ultra Performance Liquid Chromatography Tandem Mass Spectrometric Method Development and Validation for Determination of Neratinib in Human Plasma

This study was designed to develop and validate a UPLC-MS/MS method for quantification of neratinib in human plasmsa. Neratinib is an irreversible tyrosine kinase inhibitor against the pan-ErbB (ErbB-1, -2, -4) receptor. UPLC-MS/MS is an excellent analytical methodology for rapid biomedical analysis, decreasing the time for analysis and maintaining good efficiency. Crizotinib was used as internal standard (IS). Samples where extracted by plasma protein precipitation (PPT) procedure with acetonitrile and methanol and analysis was performed on a C18Acquity UPLCBEHTM column. The ion transitions where recorded in positive ion multiple reaction monitoring mode m/z 557.51®112.17 for neratinib and m/z 450.0®260.0 for IS. The mobile phase used was methanol:water: formic acid (70:30:0.1 %, v/v/v) with a flow rate of 0.3mL min–1. The linearity of the assay was found to be 4–500 ngmL–1 for neratinib in human plasma with lower limit of quatification of 4 ngmL–1. The intra- and inter-assay precision relative standard deviations did not exceed 10.99 and mean extraction recovery was found to be 69.12 ± 3.58.KEYWORDS Neratinib, UPLC, LC-MS/MS, pharmacokinetic study, human plasma

Hospital Bring-Your-Own-Device Security Challenges and Solutions: Systematic Review of Gray Literature

BACKGROUND: As familiarity with and convenience of using personal devices in hospitals help improve the productivity, efficiency, and workflow of hospital staff, the health care bring-your-own-device (BYOD) market is growing consistently. However, security concerns owing to the lack of control over the personal mobile devices of staff, which may contain sensitive data such as personal health information of patients, make it one of the biggest health care information technology (IT) challenges for hospital administrations. OBJECTIVE: Given that the hospital BYOD security has not been adequately addressed in peer-reviewed literature, the aim of this paper was to identify key security challenges associated with hospital BYOD usage as well as relevant solutions that can cater to the identified issues by reviewing gray literature. Therefore, this research will provide additional practical insights from current BYOD practices. METHODS: A comprehensive gray literature review was conducted, which followed the stepwise guidelines and quality assessment criteria set out by Garousi et al. The searched literature included tier 1 sources such as health care cybersecurity market reports, white papers, guidelines, policies, and frameworks as well as tier 2 sources such as credible and reputed health IT magazines, databases, and news articles. Moreover, a deductive thematic analysis was conducted to organize the findings based on Schlarman's People Policy Technology model, promoting a holistic understanding of hospitals' BYOD security issues and solutions. RESULTS: A total of 51 sources were found to match the designed eligibility criteria. From these studies, several sociotechnical issues were identified. The major challenges identified were the use of devices with insufficient security controls by hospital staff, lack of control or visibility for the management to maintain security requirements, lack of awareness among hospital staff, lack of direction or guidance for BYOD usage, poor user experience, maintenance of legal requirements, shortage of cybersecurity skills, and loss of devices. Although technologies such as mobile device management, unified endpoint management, containerization, and virtual private network allow better BYOD security management in hospitals, policies and people management measures such as strong security culture and staff awareness and training improve staff commitment in protecting hospital data. CONCLUSIONS: The findings suggest that to optimize BYOD security management in hospitals, all 3 dimensions of the security process (people, policy, and technology) need to be given equal emphasis. As the nature of cybersecurity attacks is becoming more complex, all dimensions should work in close alignment with each other. This means that with the modernization of BYOD technology, BYOD strategy, governance, education, and relevant policies and procedures also need to adapt accordingly