Kinase Inhibitors as Potential Therapeutic Agents in the Treatment of COVID-19.

Corona virus is quickly spreading around the world. The goal of viral management is to disrupt the virus's life cycle, minimize lung damage, and alleviate severe symptoms. Numerous strategies have been used, including repurposing existing antivirals or drugs used in previous viral outbreaks. One such strategy is to repurpose FDA-approved kinase inhibitors that are potential chemotherapeutic agents and have demonstrated antiviral activity against a variety of viruses, including MERS, SARS-CoV-1, and others, by inhibiting the viral life cycle and the inflammatory response associated with COVID-19. The purpose of this article is to identify licensed kinase inhibitors that have the ability to reduce the virus's life cycle, from entrance through viral propagation from cell to cell. Several of these inhibitors, including imatinib, ruxolitinib, silmitasertib, and tofacitinib (alone and in conjunction with hydroxychloroquine), are now undergoing clinical studies to determine their efficacy as a possible treatment drug. The FDA approved baricitinib (a Janus kinase inhibitor) in combination with remdesivir for the treatment of COVID-19 patients receiving hospital care in November 2020. While in vitro trials with gilteritinib, fedratinib, and osimertinib are encouraging, further research is necessary before these inhibitors may be used to treat COVID-19 patients.

How Do Pelvic Parameters Correlate With Postoperative Outcomes When the Parameters Are Not Measured Preoperatively in Patients Undergoing Instrumented Lumbar Fusion?

OBJECTIVE: A normal age-adjusted sagittal alignment is an important factor in achieving long-term functional results after lumbar spinal fusion. We aim to determine if the changes in spino-pelvic alignment (SPA) correlate with post-operative functional outcomes in patients who underwent instrumented lumbar spine surgery when the parameters were not measured before. METHOD: A retrospective review of medical records from 2012 to 2016, and radiographs of the patients who underwent instrumented fusion of the lumbar spine. The X-rays of the available preoperative lumbar spine were reviewed for SPA and compared with the last follow-up postoperative images. The patients were contacted by telephone to complete the EuroQoL 5 Dimensions 5-level questionnaire and visual analog scale for evaluation of their functional outcomes during 2017. Correlation studies were performed using Pearson's coefficient. RESULTS: Forty-six patients were included with a mean age of 53 years and a follow-up of 47 months. There was a significant improvement in the functional outcomes and pain in the whole group. All the patients showed improvement in their SPA, and those who underwent more than two levels of fusion showed a significant improvement (P<0.05). Lumbar lordosis and sacral slope had a significant correlation with postoperative clinical improvement (R=0.8). CONCLUSION: The study showed that single or double fusion has significant improvement in pain and functional outcome with a significant change in SPA.

Aroma Profiles Analysis of Two Populations of Salvia palaestina Benth. Collected from Mediterranean and Irano-Turanian Zones in Jordan.

The volatile principles emitted from different aerial organs of two S. palaestina Benth. populations (Mediterranean (Med) and Irano-Turanian (IrT)) growing wild in Jordan were extracted by Solid Phase Micro-Extraction (SPME) and analysed by GC/MS technique. Sesquiterpene hydrocarbons dominated stems (59.38%, 49.67%) and leaves (93.28%, 32.39%) emissions from Med and IrT zones, respectively while monoterpene hydrocarbons had the major contribution to the aroma of pre-flowering buds (78.62%, 74.96%), opened flowers (76.12%, 59.99%) and petals (69.57%, 54.28%) and were mostly represented by sabinene (in Med zone) and ociemene isomers (Z & E) in IrT zone. Multivariate analysis classified the two populations into two different clusters based on their origin and indicated the occurrence of two ecotypes of this species. Different organs from the same collection site showed emission profiles of similar chemical composition.

FT-IR Spectroscopy for the Detection of Diethylene Glycol (DEG) Contaminant in Glycerin-Based Pharmaceutical Products and Food Supplements.

Identification and determination of diethylene glycol (DEG) in glycerin-based products was successfully achieved using FT-IR spectroscopy. Studied samples included 0.5% to 20% by mass DEGspiked into cough syrup, two paracetamol syrup formulations, and two food supplements. The characteristic DEGwavenumbers at 881 cm-1 and 1083 cm-1 were used for its quantitative determination in the studied samples. A very good accuracy in determining the DEG fraction was achieved with a mean error% of ±2.02% to ±7.69% upon using the corrected absorbance at 881 cm-1. The corrected absorbance at 1083 cm-1 band was used in the case of paracetamol formulations and resulted in a mean error% ranging from ±2.50% to ±10.28%. The values of limit of detection of the current method ranged from 0.051% to 0.068% DEG for all studied samples.

Aroma Profile of Two Populations of Salvia verbenaca Collected from Two Bio-Geographical Zones from Jordan.

The aroma emitted from the different organs of two Salvia verbenaca L. populations from Jordan were extracted by Solid Phase Micro-Extraction (SPME) and then analyzed by GC/MS. The emission profile of the stem, leaf and sepal samples from the Mediterranean zone (Al-Salt) was dominated by monoterpene hydrocarbons (68.0 %, 33.7 %, and 42.2 %, respectively). The emission profile of flowering parts including pre-flowering buds, fully expanded flowers and petals was dominated by oxygenated monoterpenes (58.6 %, 59.3 % and 87.1 %, respectively). The major constituent detected in these organs was trans-sabinene hydrate acetate (range 14.5 %-87.0 %). On the other hand, samples collected from Irano-Turanian zone showed different emission patterns. While the stems, leaves and petal emissions were dominated by sesquiterpene hydrocarbons (54.9 %, 76.8 % and 52.6 %, respectively), monoterpene hydrocarbons dominated the emission profiles of the pre-flowering buds (75.1 %) and fully expanded flowers (73.6 %). Petals emissions were characterized by high concentrations of oxygenated monoterpenes (58.8 %). Notably, trans-sabinene hydrate dominated most organs emissions except for leaves (range 20.0 %-58.8 %). Principle Component Analysis (PCA) and Cluster Analysis (CA) revealed two different clusters related to the two different geographical zones. The current investigation revealed two ecotypes of S. verbenaca that could result in two different chemotypes. Trans-sabinene hydrate acetate and trans-sabinene hydrate are suggested compounds for identifying these two chemotypes.

Prevalence of musculoskeletal normal variations of the lower limbs in pediatric orthopedic clinic.

OBJECTIVES: To determine the rate of pediatric orthopedic clinic visits attributable to normal musculoskeletal (MSK) variations in children less than 12 years of age; to characterize the etiology and to characterize the etiology and management plan in this group in an attempt to identify areas that could be improved in pediatric orthopedic clinical practice. METHODS: The study was a retrospective evaluation of 2,321 consecutive patients who visited a private pediatric orthopedic specialty clinic in Jeddah, Saudi Arabia between 2011-2016. All consultations were recorded in accordance with the standard protocol  via data record form. RESULTS: We identified 764 (32.9%) patients with normal variation of the lower limbs, age birth to 12 years old. No significant association between gender and normal variation was noticed. The following types of normal variation were registered: 189 (24.7 %) genu varus or valgus, 257 (33.6%) in-toe gait, and 318 (41.6%) flexible flat foot. Seven hundred and thirty-seven (96.5%) cases were normal variations, while only 27 cases (3.5%) were deemed pathological and required further treatment. CONCLUSION: Normal variations represent the most common complaint in pediatric orthopedic private practice. Inappropriate referrals, useless follow-up visits, and excessive investigations were a common practice, overloading the health care system. None of the previous efforts made any notable improvement.

Simultaneous determination of piroxicam and norfloxacin in biological fluids by high-performance liquid chromatography with fluorescence detection at zero-order emission mode.

A new highly sensitive high-performance liquid chromatographic method with fluorescence detection (HPLC-FLD) in zero-order emission mode was developed for the first time for the simultaneous determination of piroxicam (PRX) and norfloxacin (NRF) in biological fluids. The fluorescence detector wavelengths were set at 278 nm for excitation and zero-order mode for emission. The zero-order emission mode produced greater sensitivity for the measurement of both drugs than a fixed emission wavelength (446 nm). The new developed method was validated according to International Conference of Harmonization (ICH) guidelines. Linearity was found to be over concentration ranges 0.001-20 µg/ml and 0.00003-0.035 µg/ml for PRX and NRF, respectively. The limits of detection were 4.87 × 10-4 and 1.32 × 10-5 µg/ml for PRX and NRF, and the limits of quantitation were 1.47 × 10-3 and 4.01 × 10-5 µg/ml, respectively. The current fluorescence method was found to be more sensitive than most commonly used analytical methods and was successfully applied for simultaneous determination of PRX and NRF in biological fluids (serum and urine) with recoveries ranging from 91.67% to 100.36% for PRX and from 96.00% to 101.43% for NRF.

An efficient resource utilization scheme within PMIPv6 protocol for urban vehicular networks.

Recently, the mobility management of urban vehicular networks has become great challenges for researchers due to its unique mobility requirements imposed by mobile users when accessing different services in a random fashion. To provide a ubiquitous Internet and seamless connectivity, the Internet Engineering Task Force (IETF) has proposed a Proxy Mobile IPv6 (PMIPv6) protocol. This is meant to address the signaling of the mobility transparent to the Mobile Node (MN) and also guarantee session continuity while the MN is in motion. However, performing a handoff by tens of thousands of MNs may harm the performance of the system significantly due to the high signaling overhead and the insufficient utilization of so-called Binding Cash Entry (BCE) at the Local Mobility Anchor (LMA). To address these issues, we propose an efficient scheme within the PMIPv6 protocol, named AE-PMIPv6 scheme, to effectively utilize the BCE at the LMA. This is primarily achieved by merging the BCEs of the MNs, thus, reducing the signaling overhead. Better utilization of the BCEs has been attained by employing virtual addresses and addressing pool mechanisms for the purpose of binding information of the MNs that are moving together towards the same network at a specific time, during their handoff process. Results obtained from our simulation demonstrates the superiority of AE-PMIPv6 scheme over E-PMIPv6 scheme. The AE-PMIPv6 succeeds in minimizing the signaling overhead, reduces the handover time and at the same time efficiently utilize the buffer resources.

Microbiological analysis, antimicrobial activity, and heavy-metals content of Jordanian Ma'in hot-springs water.

Ma'in hot springs are known as sites of balneotherapy. However, little is known about their microbiology and chemistry. In this study, we aim at evaluating the antimicrobial activity of Ma'in hot-springs water (MHSW), studying its microbiology, and determining its physicochemical properties including the heavy metals content. Therefore, water samples were collected from Ma'in hot springs and tested for antimicrobial activity using agar diffusion method. Water was then cultivated on nutrient agar to isolate and identify the dominant bacteria by chemical and molecular methods. The identified strains were tested by cross streak method to evaluate their antimicrobial activity against different clinical and standard strains. Finally, water samples were chemically analyzed and the heavy-metals content was assessed. Results revealed that MHSW was not active against any of the clinical isolates. Nevertheless, MHSW was found to be active against five standard bacterial strains, namely, Staphylococcus epidermidis ATCC 12228 (inhibition zone: 20mm), Staphylococcus aureus ATCC 29213 (inhibition zone: 19mm), Micrococcus luteus ATCC 9341 (inhibition zone: 15.3mm), and Bacillus cereus ATCC 11778 (inhibition zone: 12.3mm). After cultivation of MHSW, five bacterial isolates were obtained and identified based on 16S rRNA gene analysis as new strains of Anoxybacillus flavithermus (identity percentage ranges between 96-99%). Physicochemical analysis revealed that the in situ temperature was 59°C, pH was 7.8, salinity was 1.6ppt, and dissolved oxygen was 3.8mgl-1. In respect to heavy-metals content in MHSW, the following metals were present in the order: Cr (0.571ppm)>Mn(0.169ppm)>Fe (0.124ppm)>Zn (0.095)>Cu(0.070ppm)>Ni(0.058ppm)>Cd (0.023ppm)>Pb (0ppm). Cd, Cr, Ni and Mn were found to be higher than permissible levels set by international organizations and countries. This study highlights new chemical and microbiological data about Ma'in hot springs.

Portal Vein Inflow From Enlarged Coronary Vein in Liver Transplantation: Surgical Approach and Technical Tips: A Case Report.

Portal vein thrombosis is common in patients with end-stage liver disease, with an incidence as high as 26% in liver transplant candidates. It is known to be associated with a high risk of morbidity and mortality posttransplantation, and its management can be challenging. The management options range from a simple thrombendvenectomy to multivisceral transplantation in cases with diffuse portomesenteric thrombosis. We report a case of liver transplantation in which we performed a rare reconstruction of the portal vein. Briefly, the patient had diffuse portomesenteric thrombosis, calcified aneurysmosis, and a large collateral coronary vein, to which we directly anastomosed the donor portal vein in an end-to-side fashion. This report describes a unique surgical approach for similar cases of severe portal vein thrombosis in liver transplant candidates.

Randomized controlled withdrawal study of upper airway stimulation on OSA: short- and long-term effect.

OBJECTIVE: To assess the efficacy and durability of upper airway stimulation via the hypoglossal nerve on obstructive sleep apnea (OSA) severity including objective and subjective clinical outcome measures. STUDY DESIGN: A randomized controlled therapy withdrawal study. SETTING: Industry-supported multicenter academic and clinical setting. SUBJECTS: A consecutive cohort of 46 responders at 12 months from a prospective phase III trial of 126 implanted participants. METHODS: Participants were randomized to either therapy maintenance ("ON") group or therapy withdrawal ("OFF") group for a minimum of 1 week. Short-term withdrawal effect as well as durability at 18 months of primary (apnea hypopnea index and oxygen desaturation index) and secondary outcomes (arousal index, oxygen desaturation metrics, Epworth Sleepiness Scale, Functional Outcomes of Sleep Questionnaire, snoring, and blood pressure) were assessed. RESULTS: Both therapy withdrawal group and maintenance group demonstrated significant improvements in outcomes at 12 months compared to study baseline. In the randomized assessment, therapy withdrawal group returned to baseline, and therapy maintenance group demonstrated no change. At 18 months with therapy on in both groups, all objective respiratory and subjective outcome measures showed sustained improvement similar to those observed at 12 months. CONCLUSION: Withdrawal of therapeutic upper airway stimulation results in worsening of both objective and subjective measures of sleep and breathing, which when resumed results in sustained effect at 18 months. Reduction of obstructive sleep apnea severity and improvement of quality of life were attributed directly to the effects of the electrical stimulation of the hypoglossal nerve.

An official American Thoracic Society statement: continuous positive airway pressure adherence tracking systems. The optimal monitoring strategies and outcome measures in adults.

BACKGROUND: Continuous positive airway pressure (CPAP) is considered the treatment of choice for obstructive sleep apnea (OSA), and studies have shown that there is a correlation between patient adherence and treatment outcomes. Newer CPAP machines can track adherence, hours of use, mask leak, and residual apnea-hypopnea index (AHI). Such data provide a strong platform to examine OSA outcomes in a chronic disease management model. However, there are no standards for capturing CPAP adherence data, scoring flow signals, or measuring mask leak, or for how clinicians should use these data. METHODS: American Thoracic Society (ATS) committee members were invited, based on their expertise in OSA and CPAP monitoring. Their conclusions were based on both empirical evidence identified by a comprehensive literature review and clinical experience. RESULTS: CPAP usage can be reliably determined from CPAP tracking systems, but the residual events (apnea/hypopnea) and leak data are not as easy to interpret as CPAP usage and the definitions of these parameters differ among CPAP manufacturers. Nonetheless, ends of the spectrum (very high or low values for residual events or mask leak) appear to be clinically meaningful. CONCLUSIONS: Providers need to understand how to interpret CPAP adherence tracking data. CPAP tracking systems are able to reliably track CPAP adherence. Nomenclature on the CPAP adherence tracking reports needs to be standardized between manufacturers and AHIFlow should be used to describe residual events. Studies should be performed examining the usefulness of the CPAP tracking systems and how these systems affect OSA outcomes.

Spontaneous hemorrhage of a parathyroid adenoma into the mediastinum.

OBJECTIVE: To describe the case of a previously healthy 56-year-old woman, who presented with acute, nontraumatic pain in the left side of the neck and mild dysphagia. METHODS: We report the results of the physical examination, imaging studies, and clinical laboratory studies. In addition, we describe the patient's hospital course after surgical intervention. RESULTS: A patient who sought medical attention because of acute, nontraumatic neck pain and dysphagia was subsequently found to have acute extracapsular hemorrhage of a parathyroid adenoma. Computed tomography and magnetic resonance imaging studies revealed a mass effect beginning in the neck and extending into the mediastinum. Surgical exploration of the neck and histopathologic evaluation confirmed the diagnosis of spontaneous rupture of a parathyroid adenoma with associated hemorrhage. CONCLUSION: Extracapsular hemorrhage of a parathyroid adenoma is rare and necessitates a high index of clinical suspicion for diagnosis. This diagnosis should be considered in a patient who presents with acute anemia, hypercalcemia, and a neck mass.

Investigations on the physical structure and the mechanism of drug release from an enteric matrix microspheres with a near-zero-order release kinetics using SEM and quantitative FTIR.

The objectives of this study were to evaluate the physical structure and the release mechanisms of theophylline microspheres made of Eudragit S 100 polymer as an enteric polymer, combined with a nonerodible polymer, Eudragit RL 100. In the preparation process, polymer combinations (1:1) were dissolved in an organic solvent mixture composed of acetone and methanol at a specific ratio containing a theoretical drug loading of approximately 15%. Two microsphere formulations (LS1 and LS2) were prepared at two different total polymer concentrations (10% in LS1 and 12.7% in LS2). Dissolution studies were carried out using US Pharmacopeia Dissolution Apparatus II in an acidic medium for 8 h and in an acidic medium (2 h) followed by a slightly basic-buffered medium for 10 h. Both LS1 and LS2 microsphere formulations produced particles that were spherical in shape and had very narrow size distributions with one size fraction comprising 70-80% of the yield. Scanning electron microscopy and quantitative Fourier transform infrared were used for microsphere physical structure evaluation. Except for the absence of drug crystals, photomicrographs of both LS microspheres after dissolution in pH 1.2 and 7.2 buffer solutions were similar to those before dissolution. Dissolution results indicated the ability of LS microspheres to minimize drug release during the acid stage. However, in the slightly basic medium that followed the acidic stage, the drug release was sustained and controlled in its kinetics and data fitted to Peppas equation indicated a case II transport suggesting that the drug release is mainly through swelling/erosion mechanism.

Application of multi-way data analysis on excitation-emission spectra for plant identification.

The ability to distinguish among diets fed to Damascus goats using excitation-emission luminescence spectra was investigated. These diets consisted of Medicago sativa L. (alfalfa), Trifolium spp. (clover), Pistacia lentiscus, Phyllirea latifolia and Pinus brutia. The three-dimensional luminescence response surface from phosphate buffered saline (PBS) extracts of each material was analyzed using muti-way analysis chemometric tools (MPCA) and parallel factor analysis (PARAFAC). Using three principal components, the spectra from each diet material were distinguished. Additionally, fecal samples from goats fed diets of either alfalfa or clover hays were investigated. The application of MPCA and PARAFAC to these samples using models derived from the pre-digested diet materials was strongly suggestive of the utility of similarly derive training samples for the elucidation of botanical diet composition for animals.