Discovery of Pyrano[2,3-c]pyrazole Derivatives as Novel Potential Human Coronavirus Inhibitors: Design, Synthesis, In Silico, In Vitro, and ADME Studies.

The SARS-CoV-2 pandemic at the end of 2019 had major worldwide health and economic consequences. Until effective vaccination approaches were created, the healthcare sectors endured a shortage of operative treatments that might prevent the infection's spread. As a result, academia and the pharmaceutical industry prioritized the development of SARS-CoV2 antiviral medication. Pyranopyrazoles have been shown to play a prominent function in pharmaceutical chemistry and drug sighting because of their significant bioactive properties. We provide herein a novel sequence of pyranopyrazoles and their annulated systems whose antiviral efficacy and cytotoxicity were explored versus human coronavirus 229E (HCoV-229E) Vero-E6 cell lines as a model for the Coronaviridae family. Fifteen synthetic congeners pointed out miscellaneous antiviral efficacies against HCoV-229E with variable inhibition degrees. Compound 18 showed a high selectivity index (SI = 12.6) that established spectacular inhibitory capacity against human coronavirus 229E. Compounds 6, 7, and 14 exposed moderate efficacies. Compounds 6, 7, 14, and 18 exhibited substantial antiviral action through the replication phase with reduction percentages extending from 53.6%, 60.7%, and 55% to 82.2%, correspondingly. Likewise, when assessed to the positive control tipranavir (88.6%), the inhibitory efficiency of compounds 6, 7, 14, and 18 versus the SARS-CoV2 Mpro provided high percentages of 80.4%, 73.1%, 81.4% and up to 84.5%, respectively. In silico studies were performed to investigate further the biological activity and the target compounds' physical and chemical features, including molecular dynamic (MD) simulations, protein-ligand docking, ADME studies, and density functional theory (DFT) calculations. These inquiries demonstrated that this series of metabolically stable pyranopyrazoles and their annulated systems are effective human coronavirus inhibitors that inhibit the viral Mpro protein and may have emerged as a novel COVID-19 curative option.

Usefulness of right ventricular strain assessment in submassive pulmonary thromboembolism undergoing ultrasound-facilitated thrombolysis.

Massive and submassive pulmonary thromboembolism carry significant morbidity and mortality. We present an elderly female who was diagnosed with a submassive pulmonary embolism by computed tomographic angiography and treated with ultrasound-facilitated thrombolysis (UFT). This case demonstrates the usefulness of right ventricular longitudinal strain measurements by two-dimensional speckle tracking echocardiography in the evaluation of right ventricular function before and after UFT. Evaluation of right ventricle longitudinal strain by speckle tracking echocardiography may supplement other parameters in the assessment of right ventricular function in these patients.

Incremental value of right parasternal transthoracic echocardiographic examination over the left parasternal approach in assessing ascending aorta size: Additional benefit of three-dimensional echocardiography.

BACKGROUND: The ascending aorta (AA) has not been well studied using two-dimensional right parasternal transthoracic echocardiographic examination (2DRPE). AIM: The aim of the present study was to assess the incremental value of 2DRPE over two-dimensional left parasternal transthoracic echocardiographic examination (2DLPE) in evaluating the size of AA in adult patients (pts) and, secondly, to determine whether live/real time three-dimensional (3D) RPE provided any additional benefit over 2DRPE. MATERIALS AND METHODS: The AA was successfully imaged by 2DLPE, 2DRPE, and 3D RPE in 87 of 141 (61.7%) pts which comprised of two groups of consecutive pts separated by an interval of 2 weeks. RESULTS: The maximum length of AA visualized by 2DRPE (4.98 ± 0.89) was larger than 2DLPE in 76/87(87%) pts (P < 0.001). Both the maximum systolic AA inner luminal width and leading edge-to-leading edge width by 2DRPE were greater than 2DLPE (P < 0.001). Similar to other noninvasive imaging modalities where mid-AA width is taken at level of right pulmonary artery, mid-AA width could also be taken at this level by 2DRPE in 79/87(91%) pts since this landmark was visualized during 2DRPE. However, this vessel could be visualized in only 2/87 (2%) pts with 2DLPE. 3DRPE conferred additional benefit over 2DRPE. The maximal AA length by 3DRPE was larger than 2DRPE in 60/87(69%) pts, and the maximal inner lumen and leading edge to leading edge widths were larger in 54/87(62%) and 66/87(76%) pts, respectively. CONCLUSION: Our preliminary study demonstrates significant incremental value of 2DRPE over 2DLPE in the assessment of AA. 3DRPE confers an additional advantage over 2DRPE.

Clinical and immunological pattern and outcome of Egyptian systemic lupus erythematosus patients: a single center experience.

Objective The objective of this study was to describe the clinical and immunological pattern and disease outcome in Egyptian systemic lupus erythematosus patients. Patients and methods The medical records of 770 systemic lupus erythematosus patients who were followed from 2002-2015 at Kasr Alainy Hospital, Cairo University, were retrospectively reviewed. Results There were 707 (91.8%) females. The mean age at disease onset was 22.1 ± 8.6 and the disease duration was 6.1 ± 4.5 years. The main clinical manifestations were mucocutaneous (90.8% with oral ulcers affecting 52.5%), arthritis (80.3%), nephritis (67.8%), hematologic involvement (64.9%), serositis (55.2%) and neuropsychiatric manifestations (44.3%). The frequencies of antinuclear antibodies were 94.3%, anti-dsDNA 74.8%, anti-Smith 11%, anticardiolipin antibodies 29.5% and lupus anticoagulant 19.8%. Infections, predominantly bacterial, affected 337 (43.8%) patients. Thirty-three (4.3%) patients died. The main causes of death were sepsis and disease activity. The five- and 10-year survival rates for the total cohort were 97.4% and 96.3%, respectively, and were 96% and 92%, respectively for those with nephritis ( p = 0.008). Autoimmune hemolytic anemia, thrombocytopenia, elevated serum creatinine, a higher damage index, infections, a higher glucocorticoid dose and cyclophosphamide use ≥ six months were associated with an increased risk of mortality with odds ratios of 3.69, p < 0.01; 4.12, p < 0.001; 1.54, p < 0.001; 1.43, p < 0.001; 5.08, p < 0.001; 5.04, p < 0.001 and 2.25, p = 0.03, respectively. Conclusion Compared to other cohorts, a relatively lower mean age at systemic lupus erythematosus onset and higher frequencies of oral ulcers, serositis and nephritis were found.

Renal outcomes among Egyptian lupus nephritis patients: a retrospective analysis of 135 cases from a single centre.

OBJECTIVES: The objective of this paper is to describe renal outcomes in a group of Egyptian patients with lupus nephritis and to identify variable prognostic factors. PATIENTS AND METHODS: The records of 135 patients (129 females, six males) with biopsy-proven lupus nephritis seen between 1999 and 2011 at Kasr Al-Aini Hospital, Cairo University, were reviewed and included in a retrospective analysis. Biopsies were classified according to the WHO classification. Renal outcomes were defined according to the Renal Subcommittee of Renal Insufficiency of the American College of Rheumatology. RESULTS: The mean follow-up period was 55.64 ± 25.68 (range 4-156) months. Thirty-nine patients (29.9%) developed an adverse final outcome. This composite outcome, defined as persistent elevation of serum creatinine ≥ 1.2 mg/dl, chronic renal insufficiency, end-stage renal disease or death, was seen in 12 (8.9%), seven (5.2%), three (2.2%) and 17 (12.6%) patients, respectively. The overall patient survival was 93.5% and 87.5% at five and 10 years, respectively. Factors associated with an adverse outcome included male gender (p = 0.037), hypertension at nephritis onset (p = 0.001), serum creatinine ≥1.2 mg/dl (p < 0.001), urinary casts (p = 0.006), anticardiolipin antibodies (p = 0.03), class IV nephritis (p < 0.001), hyaline thrombosis (0.003), glomerular sclerosis (p = 0.002), tubular atrophy(p < 0.001), interstitial fibrosis (p < 0.001) and a higher chronicity index (p = 0.006). Time-dependent factors associated with an adverse outcome included failure to achieve remission within the first year, uncontrolled hypertension, persistently low C3 and development of flares (p = 0.003, < 0.001, = 0.004, = 0.003, respectively). CONCLUSION: The association of several adverse prognostic factors with the development of poor renal outcome has been confirmed in this study.

Effects of temperature on the fluoride release and recharging ability of glass ionomers.

This study investigated the effects of environmental temperature on the fluoride release and recharging ability of glass ionomers. Five disk specimens (15 mm in diameter and 1 mm thick) were made of each of the following materials: a conventional luting glass ionomer, two high viscosity restorative glass ionomers and a restorative resin-modified glass ionomer. The fluoride release of each material was measured at 4 degrees C, 37 degrees C and 55 degrees C. An additional three groups, which were made of the same materials, were stored in distilled and deionized water for 30 days and recharged in 250 ppm fluoride solution at 4 degrees C, 37 degrees C and 55 degrees C for five minutes. The fluoride re-release was measured daily from two days prior to two days after the recharging process. At all temperatures, the luting glass ionomers showed the greatest fluoride release and recharging ability, followed by the resin-modified glass ionomer, then the high viscosity glass ionomers. For each material, the fluoride release increased with increasing temperature and all glass ionomers showed greater recharging ability at higher temperatures. An increase in environmental temperature increased both the fluoride release and recharging of the glass ionomers. This may be important in developing regimes for improving the delivery of topical fluoride products.

Hypermobility among Egyptian children: prevalence and features.

OBJECTIVE: To determine the prevalence, clinical manifestations, and possible associated features of hypermobility among Egyptian children in a prospective study. METHODS: Nine hundred ninety-seven healthy children from 4 different educational areas for primary and presecondary schools were screened for the presence of hypermobility. A hypermobility score was used to denote the degree of laxity. Sites and possible clinical associations of hypermobility were determined. RESULTS: The presence of hypermobility was 16. 1% among Egyptian children. Hypermobility was more frequent among girls (18%). than boys (14.4%), although the difference was not statistically significant. Age was inversely correlated with the frequency of hypermobility (r = 4).967, p < 0.001) and degree of joint laxity (r = -0.789, p < 0.01). Hypermobility was most prevalent in fingers (96.9%) and least prevalent in knee joints (3.1%). Hypermobility was statistically more frequent in nondominant than dominant fingers (p < 0.002). Arthralgia, high palate, flat feet, Raynaud's phenomenon, and easy bruising were more common among the hypermobility group. CONCLUSION: Our results suggest that hypermobility is not uncommon among Egyptian children. Increased awareness of the condition is needed among pediatricians and other concerned physicians.