Metal-Bound Methisazone; Novel Drugs Targeting Prophylaxis and Treatment of SARS-CoV-2, a Molecular Docking Study.

SARS-CoV-2 currently lacks effective first-line drug treatment. We present promising data from in silico docking studies of new Methisazone compounds (modified with calcium, Ca; iron, Fe; magnesium, Mg; manganese, Mn; or zinc, Zn) designed to bind more strongly to key proteins involved in replication of SARS-CoV-2. In this in silico molecular docking study, we investigated the inhibiting role of Methisazone and the modified drugs against SARS-CoV-2 proteins: ribonucleic acid (RNA)-dependent RNA polymerase (RdRp), spike protein, papain-like protease (PlPr), and main protease (MPro). We found that the highest binding interactions were found with the spike protein (6VYB), with the highest overall binding being observed with Mn-bound Methisazone at -8.3 kcal/mol, followed by Zn and Ca at -8.0 kcal/mol, and Fe and Mg at -7.9 kcal/mol. We also found that the metal-modified Methisazone had higher affinity for PlPr and MPro. In addition, we identified multiple binding pockets that could be singly or multiply occupied on all proteins tested. The best binding energy was with Mn-Methisazone versus spike protein, and the largest cumulative increases in binding energies were found with PlPr. We suggest that further studies are warranted to identify whether these compounds may be effective for treatment and/or prophylaxis.

The Diagnostic Accuracy of Noninvasive Methods to Measure the Intracranial Pressure: A Systematic Review and Meta-analysis.

BACKGROUND: Although invasive monitoring is the standard method for intracranial pressure (ICP) measurement, it is not without potential for serious complications. Noninvasive methods have been proposed as alternatives to invasive ICP monitoring. The study aimed to investigate the diagnostic accuracy of the currently available noninvasive methods for intracranial hypertension (ICH) monitoring. METHODS: We searched 5 databases for articles evaluating the diagnostic accuracy of noninvasive methods in diagnosing ICH in PubMed, Institute of Science Index, Scopus, Cochrane Central Register of Controlled Trials (CENTRAL), and Embase. The quantitative analysis was conducted if there were at least 2 studies evaluating a specific method. The accuracy measures included the sensitivity, specificity, likelihood ratios, and diagnostic odds ratio. RESULTS: We included 134 articles. Ultrasonographic optic nerve sheath diameter (US ONSD) had high diagnostic accuracy (estimated sensitivity of 90%; 95% confidence interval [CI], 87-92, estimated specificity of 88%; 95% CI, 84-91) while the magnetic resonance imaging (MRI) ONSD had estimated sensitivity of 77%; 95% CI, 64-87 and estimated specificity of 89%; 95% CI, 84-93, and computed tomography (CT) ONSD had estimated sensitivity of 93%; 95% CI, 90-96 and estimated specificity of 79%; 95% CI, 56-92. All MRI signs had a very high estimated specificity ranging from 90% to 99% but a low estimated sensitivity except for sinus stenosis which had high estimated sensitivity as well as specificity (90%; 95% CI, 75-96 and 96%; 95% CI, 91-99, respectively). Among the physical examination signs, pupillary dilation had a high estimated specificity (86%; 95% CI, 76-93). Other diagnostic tests to be considered included pulsatility index, papilledema, transcranial Doppler, compression or absence of basal cisterns, and ≥10 mm midline shift. Setting the cutoff value of ICH to ≥20 mm Hg instead of values <20 mm Hg was associated with higher sensitivity. Moreover, if the delay between invasive and noninvasive methods was within 1 hour, the MRI ONSD and papilledema had a significantly higher diagnostic accuracy compared to the >1 hour subgroup. CONCLUSIONS: Our study showed several promising tools for diagnosing ICH. Moreover, we demonstrated that using multiple, readily available, noninvasive methods is better than depending on a single sign such as physical examination or CT alone.

Participation of the hospitals in the Republic of Ireland in international research over more than a decade: a bibliometric analysis.

BACKGROUND: This study provides an accurate awareness of the present situation of health research in Irish hospitals both public and private. We aimed to analyze factors that may influence it and provide recommendations for active steps to improve the current situation of Irish health research based on our findings. METHODS: We performed a bibliometric analysis to assess qualitatively and quantitatively the publications from Ireland over a period between 2007 and 2018. We also investigated the associated variables with the quality of research. Furthermore, we conducted a Joinpoint analysis to see the trends in Irish research over these years. RESULTS: From 12,828 included peer-reviewed articles, the average citation count per article was 19.98. Furthermore, we showed that a higher impact factor (IF) and institutions number, present per article, were significantly associated with more citations. Also, the publication count and the mean IF showed an increase over the years according to the Joinpoint analysis. Moreover, the oncology research had the highest output, followed by pediatrics, then neurology while the specialties with least publications were ear, nose, and throat (ENT), urology, plastic surgery, and dentistry. Additionally, cardiovascular, obstetrics and gynecology, oncology, pediatrics, pulmonology, dermatology, ophthalmology, dentistry, and radiology research showed an increased publication count trend in recent years. While anesthesiology, ENT, general surgery, gastroenterology and hepatology, infection and tropical medicine, nephrology, neurology, orthopedics, plastic surgery, and urology showed a decrease in the publications trend. CONCLUSIONS: Our findings may serve as a useful approach to benchmark scientific output from hospitals and guide the future allocation of research spending.