The middle east respiratory syndrome coronavirus respiratory infection: an emerging infection from the arabian peninsula

This article is made available for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.Middle East Respiratory Syndrome coronavirus (MERS-CoV) was initially isolated from a patient who was admitted to a private hospital in the Western part of the Kingdom of Saudi Arabia in 2012. Subsequently, MERS-CoV resulted in many sporadic cases, multiple intrafamilial transmission, and major outbreaks in healthcare settings. Of all the cases reported within the Kingdom of Saudi Arabia, 38% of the cases were primary, 45% were healthcare-associated infection, and 14% were household infections. The clinical spectrum of the MERS-CoV infection ranges from asymptomatic infections, mild or moderately symptomatic cases, and severe disease requiring intensive care unit admissions and may result in death. Within healthcare settings, transmissions of MERS-CoV are facilitated by overcrowding, poor infection control measures, unrecognized infections, and superspreader phenomenon. Currently, there is no approved therapy for MERS-CoV and there are no vaccines

Super-spreading Events and Contribution to Transmission of MERS, SARS, and COVID-19

There is no clear definition for the term ‘super-spreader’ or ‘super-spreading event’. The World Health Organization refers to a super-spreader as a patient (or an event) that may transmit infection to a larger number of individuals than is usual by one individual (or event). In the severe acute respiratory syndrome (SARS) situation, a super-spreading event was defined as the transmission of SARS to at ≥8 contacts, and other authors defined this as individuals infecting an unusually large number of secondary cases [ 1 , 2 ]. A super-spreading event could merely be defined as an event in which one patient infects far more people than an average patient does, which is estimated by the basic reproduction number (R0)

Hematologic, hepatic, and renal function changes in hospitalized patients with Middle East respiratory syndrome coronavirus

Background There are no longitudinal data on the changes in hematologic, hepatic, and renal function findings in patients with Middle East respiratory syndrome coronavirus (MERS‐CoV) infection. Methods This is a retrospective cohort study of 16 MERS‐CoV patients, to describe the hematological, hepatic, and renal findings of patients with MERS‐CoV. Results During the 21 days of observation, there was no significant change in the hepatic panel or creatinine tests. There was a significant increase in the mean ± SD of the white blood cell count from 8.3 ± 4.6 to 14.53 ± 7 (P value = 0.001) and an increase in mean ± SD of the absolute neutrophil count from 6.33 ± 4.2 to 12 ± 5.5 (P value = 0.015). Leukocytosis was observed in 31% (5/16) of the patients on day 1 and in 80% (4/5) on day 21. Transient leukopenia developed in 6% (1/16) of the patients on day 1 and in 13% (1/8) on day 8. None of the patients had neutropenia. Lymphopenia was a prominent feature with a rate of 44% (7/16) of the patients on day 1 and 60% (3/5) on day 21. Lymphocytosis was not a feature of MERS‐CoV infection. Thrombocytopenia developed in 31% (5/16) of the patients on day 1 and 40% (2/5) on day 21. Thrombocytosis was not a prominent feature and was observed in 6% (1/16) of the patients on day 1 and 17% (1/6) on day 9. Conclusions Patients with MERS‐CoV infection showed variable hematologic parameters over time. Lymphocytosis and neutropenia were not features of MERS‐CoV infection

COMPARATIVE BIOAVAILABILITY (BIOEQUIVALENCE) STUDY FOR FIXED DOSE COMBINATION TABLET CONTAINING AMLODIPINE, VALSARTAN, AND HYDROCHLOROTHIAZIDE USING A NEWLY DEVELOPED HPLC-MS/MS METHOD

Objective: The aim of the study was to evaluate the bioequivalence between a newly developed generic tablet containing fixed-dose combination of amlodipine besylate, valsartan and hydrochlorothiazide (10/160/25 mg), and the reference brand product Exforge HCT® tablet; using a newly developed HPLC-MS/MS method for simultaneous determination of these drugs in human plasma.Methods: The brand (reference) and the test (generic) products were administered to thirty-nine healthy subjects. A fasting, laboratory blind, single-dose, two-treatment, two-period, two-sequence, randomized crossover design was conducted with 14 d washout period between dosing. Serial blood samples were withdrawn from each subject immediately before dosing (zero time), and then at 0.33, 0.66, 1.0, 1.33, 1.66, 2.0, 2.5, 3.0, 3.5, 4.0, 5.0, 6.0, 6.5, 7.0, 7.5, 8.0, 8.5, 9.0, 9.5, 10, 11, 12, 14, 16, 24, 48 and eventually at 72 h post dosing. Plasma samples were analyzed for simultaneous determination of amlodipine, valsartan and hydrochlorothiazide by a newly developed HPLC coupled with MS/MS detector. The linearity of the method was established for plasma concentration ranges of 0.2-12 ng/ml, 50-8000 ng/ml, and 2-250 ng/ml for amlodipine, valsartan, and hydrochlorothiazide, respectively.Results: Plasma concentration-time data of each individual were analyzed by non-compartmental method to measure the pharmacokinetics parameters; Cmax, Tmax, AUC0-t, AUC0-¥, lZ, T1/2. For amlodipine truncated AUC72hr was calculated. The 90% confidence interval for the pharmacokinetic parameters used for bioequivalence evaluation (Cmax and AUC) for amlodipine, valsartan, and hydrochlorothiazide were well within FDA acceptable ranges of 80-125%.Conclusion: It is concluded that the newly devolved generic product is bioequivalent with the brand product Exforge HCT® tablet. Thus, both products are clinically interchangeable.Keywords: Amlodipine, Valsartan, Hydrochlorothiazide, Pharmacokinetics, Bioequivalence, HPLC-MS/M

Low rate of non-compliance to antituberculous therapy under the banner of directly observed treatment short course (DOTS) strategy and well organized retrieval system: a call for implementation of this strategy at all DOTS centers in Saudi Arabia

Introduction: The objective of this study was to show the effectiveness of revised retrieval system on non-compliance. Methods: We retrospectively evaluated the effectiveness of a revised retrieval system on non-compliance during continuous phase of antituberculous treatment (Jan-2005 to Dec-2010) compared to baseline non-compliance (Jan-2002 to Dec-2004). Results: In the baseline period, 141 of 501 (28%) patients did not attend their first appointment. Of these 141 patients, 63 (45%) patients could be brought back to treatment while 78 patients (16%) dropped out and could not be retrieved. During the 2nd phase after launching a revised retrieval system, 98 of 835 (13%) patients did not attend their first appointment. Using the retrieval system, 79 (81%)  atients were brought back for regular follow up, and 19 patients could not be retrieved, a dropout rate of 2.27%. By virtue of revised retrieval system, there was a significant drop in non-compliance by 15% and a decline in net dropout rate by 14%. The number of those brought back to treatment by revised retrieval system almost doubled (81%) compared to 44% retrieval in initial period. Conclusion: The revised retrieval system had a significant impact on the reduction of dropout rate and significant improvement in the retrieval of those patients

Synthesis And Characterization of Novel Functionalized Tetradentate Ligand Type H3NS3 And Its Metal Complexes With Re(V), Ni(II), Cu(II), Cd(II) & Hg(II)

This work represents the preparation of the tetradentate ligand H3NS3 (H3L) andits metal complexes with rhenium(V), nickle(II), copper(II), cadmium(II) andmercurry(II) metal ions. The ligand and its complexes were characterized when neededby Infrared, Ultraviolet–visible, HPLC, Mass, 1H nuclear magnetic resonance, andatomic absorption spectroscopic techniques, elemental analysis, and electricalconductivity. The proposed structure for (H3NS3) with Re(V) is square pyramidal, withNi(II) is distorted square planar, and with the rest of metal ions is distorted tetrahedra

Spread, circulation, and evolution of the Middle East respiratory syndrome coronavirus

The Middle East respiratory syndrome coronavirus (MERS-CoV) was first documented in the Kingdom of Saudi Arabia (KSA) in 2012 and, to date, has been identified in 180 cases with 43% mortality. In this study, we have determined the MERS-CoV evolutionary rate, documented genetic variants of the virus and their distribution throughout the Arabian peninsula, and identified the genome positions under positive selection, important features for monitoring adaptation of MERS-CoV to human transmission and for identifying the source of infections. Respiratory samples from confirmed KSA MERS cases from May to September 2013 were subjected to whole-genome deep sequencing, and 32 complete or partial sequences (20 were ≥99% complete, 7 were 50 to 94% complete, and 5 were 27 to 50% complete) were obtained, bringing the total available MERS-CoV genomic sequences to 65. An evolutionary rate of 1.12 × 10−3 substitutions per site per year (95% credible interval [95% CI], 8.76 × 10−4; 1.37 × 10−3) was estimated, bringing the time to most recent common ancestor to March 2012 (95% CI, December 2011; June 2012). Only one MERS-CoV codon, spike 1020, located in a domain required for cell entry, is under strong positive selection. Four KSA MERS-CoV phylogenetic clades were found, with 3 clades apparently no longer contributing to current cases. The size of the population infected with MERS-CoV showed a gradual increase to June 2013, followed by a decline, possibly due to increased surveillance and infection control measures combined with a basic reproduction number (R0) for the virus that is less than 1

Novel dichloro(bis{2-[1-(4-methylphenyl)-1H-1,2,3-triazol-4-yl-κN3]pyridine-κN})metal(II) coordination compounds of seven transition metals (Mn, Fe, Co, Ni, Cu, Zn and Cd)

© 2018 Elsevier Ltd. The synthesis, characterization, DFT and, in two cases, the structure of seven novel dichloro(bis{2-[1-(4-methylphenyl)-1H-1,2,3-triazol-4-yl-κN3]pyridine-κN})metal(II) coordination compounds ([M(L2)2Cl2]), containing transition metals of groups 7–12, are described. Both experimentally measured magnetic moment and DFT calculations showed that d5Mn(II) (with µeff= 5.62 B.M., S = 5/2), d6Fe(II) (with µeff= 5.26 B.M., S = 2), d7Co(II) (with µeff= 3.98 B.M., S = 3/2), d8Ni(II) (with µeff= 3.00 B.M., S = 1) and d9Cu(II) (with µeff= 1.70 B.M., S = ½) are all paramagnetic, while d10Zn(II) and Cd(II) are diamagnetic with S = 0. DFT calculations on the possible isomers of these coordination compounds, showed that the cis–cis–trans and the trans–trans–trans isomers, with the pyridyl groups trans to each other, are the lowest in energy. The trans–trans–trans isomers were experimentally characterized by X-ray crystallography for [Ni(L2)2Cl2] and [Zn(L2)2Cl2]·L2in this study. In the solid state the coordination compounds are connected by intermolecular hydrogen bonds, mainly involving the chloride atoms, to form 3D supramolecular structures. Computational chemistry calculations, using Natural Bonding Orbital calculations, identified these inter-molecular hydrogen bonds, C–H⋯Cl, by a donor–acceptor interaction from a filled lone pair NBO on Cl to an empty antibonding NBO on (C–H). The inter-molecular hydrogen bonds were also identified by QTAIM determined bonding paths between Cl and the respective hydrogen. The theoretically calculated computational chemistry results thus give an understanding on a molecular level why in the solid state where inter-molecular forces and packing play a role, the trans–trans–trans isomers are mostly obtained

Synthesis, characterization, experimental and theoretical structure of novel Dichloro(bis{2-[1-(4-methoxyphenyl)-1H-1,2,3-triazol-4-yl-κN3]pyridine-κN})metal(II) compounds, metal = Mn, Co and Ni

© 2018 Elsevier B.V. The syntheses, characterizations and structures of three novel dichloro(bis{2-[1-(4-methoxyphenyl)-1H-1,2,3-triazol-4-yl-κN 3 ]pyridine-κN})metal(II), [M(L) 2 Cl 2 ], complexes (metal = Mn, Co and Ni) are presented. In the solid state the molecules are arranged in infinite hydrogen-bonded 3D supramolecular structures, further stabilized by weak intermolecular π…π interactions. The DFT results for all the different spin states and isomers of dichloro(bis{2-[1-phenyl-1H-1,2,3-triazol-4-yl-κN 3 ]pyridine-κN})metal(II) complexes, [M(L 1 ) 2 Cl 2 ], support experimental measurements, namely that (i) d 5 [Mn(L 1 ) 2 Cl 2 ] is high spin with S = 5/2; (ii) d 7 [Co(L 1 ) 2 Cl 2 ] has a spin state of S = 3/2, (iii) d 8 [Ni(L 1 ) 2 Cl 2 ] has a spin state of S = 1; and (iv) for all [M(L 1 ) 2 Cl 2 ] and [M(L) 2 Cl 2 ] comple xes, with M = Mn, Co and Ni, the cis-cis-trans and the trans-trans-trans isomers, with the pyridyl groups trans to each other, have the lowest energy