Design, synthesis, and biological evaluation of dinaciclib and CAN508 hybrids as CDK inhibitors.

The scaffolds of two known CDK inhibitors (CAN508 and dinaciclib) were the starting point for synthesizing two series of pyarazolo[1,5-a]pyrimidines to obtain potent inhibitors with proper selectivity. The study presented four promising compounds; 10d, 10e, 16a, and 16c based on cytotoxic studies. Compound 16a revealed superior activity in the preliminary anticancer screening with GI % = 79.02-99.13 against 15 cancer cell lines at 10 µM from NCI full panel 60 cancer cell lines and was then selected for further investigation. Furthermore, the four compounds revealed good safety profile toward the normal cell lines WI-38. These four compounds were subjected to CDK inhibitory activity against four different isoforms. All of them showed potent inhibition against CDK5/P25 and CDK9/CYCLINT. Compound 10d revealed the best activity against CDK5/P25 (IC50 = 0.063 µM) with proper selectivity index against CDK1 and CDK2. Compound 16c exhibited the highest inhibitory activity against CDK9/CYCLINT (IC50 = 0.074 µM) with good selectivity index against other isoforms. Finally, docking simulations were performed for compounds 10e and 16c accompanied by molecular dynamic simulations to understand their behavior in the active site of the two CDKs with respect to both CAN508 and dinaciclib.

Prevalence of dietary supplement use and knowledge, attitudes, practice (KAP) and associated factors in student population: A cross-sectional study.

Dietary supplements (DSs) intake has been increasing worldwide despite no consensus evidence for the efficacy and safety of disease prevention, control, or treatment in nutrient-replete populations. This study aimed to determine the prevalence of DSs use, knowledge, attitude, and practice (KAP) and associated factors among university students in Jordan. A national cross-sectional study was carried over across universities in Jordan. Participants completed a valid and reliable online questionnaire (Cronbach's alpha = 0.802 and correlation coefficients between 0.72 and 0.26). Univariate analyses were used to determine the relationship between variables. Multivariable regression was carried out to identify significant factors contributing DSs usage. A total of 448 university students completed the study (73.7% females). More than half of the students used DSs (60.9%), with single-nutrient ingredient supplements being the most commonly used type. The primary motivators were maintaining health and most students reported no side effects associated with consumption. The results revealed poor knowledge, a negative attitude towards DSs usage among all participants, even non-users, and high-risk practices among the DSs users. Normal weight and overweight individuals were more likely to use DSs (OR:2.88, 95%CI:1.61-5.16, OR:1.95, 95%CI:1.01-3.79, respectively). Low and medium-family income categories were more likely to use DSs than those in the high-income category (OR: 0.04, 95%CI: 0.02-0.07, OR: 0.06, 95CI:0.03-0.11, respectively). Undergraduate students were more likely to use DSs than postgraduate students (OR:5.56, 95%CI:3.19-9.69). In this study, a high prevalence of DSs use was highlighted. The results suggest that nutrition education is required to improve awareness of DSs and to promote safe practices.

Solvent Bar Microextraction Combined with HPLC-DAD for Simultaneous Determination of Diuretics in Human Urine and Plasma Samples.

BACKGROUND: A simple and powerful microextraction procedure, the solvent bar microextraction (SBME), was used for the simultaneous determination of two diuretics, furosemide and spironolactone in human urine and plasma samples, using high-performance liquid chromatography coupled with diode array detection (HPLC-DAD). METHODS: The appropriate amount (2 µL) of 1-octanol as an organic solvent confined within 2.5 cm of a porous hollow fiber micro-tube, sealed at both ends was used for this procedure. The conditions for the SBME were optimized in water and the analytical performance was examined in spiked human urine and plasma samples. RESULTS: The optimized method exhibited good linearity (R2> 0.997) over the studied range of higher than 33 to 104µg L-1 for furosemide and spironolactone in urine and plasma samples, illustrating a satisfactory precision level with RSD values between 2.1% and 9.1%. DISCUSSION: The values of the limits of detection were found to be in the range of 6.39 to 9.67µg L-1, and extraction recovery ˃ 58.8% for both diuretics in urine and plasma samples. The applicability and effectiveness of the proposed method for the determination of furosemide and spironolactone in patient urine samples were tested. CONCLUSION: In comparison with reference methods, the attained results demonstrated that SBME combined with HPLC-DAD was proved to be simple, inexpensive, and promising analytical technology for the simultaneous determination of furosemide and spironolactone in urine and plasma samples.

A prediction model of risk factors for complications among SARS-CoV2 positive patients: Cases from Jordan.

BACKGROUND: The number of COVID-19 infected patients has been soaring in the Middle East countries. The disease poses a significant threat, decisions about prioritizing care should be made in accordance with the proven risk factors for complications. OBJECTIVE: The present study provides the first bespoke prediction model in the Middle East to identify COVID-19 patients, who are at higher risk for complications. METHOD: A case-control study design was adopted to compare the characteristics of successfully recovered patients with those who had complications. Complications were defined as admission to the intensive care unit, mechanical ventilation, sepsis or septic shock, pneumonia or respiratory failure, and death. The prediction model was created through multivariable logistic regression. Overall statistical significance tests for the model were carried out. RESULTS: All COVID-19 infected hospitalized patients (n = 133) in Amman - Jordan were included in the study. Successfully recovered were 125 patients. The median age (IRQ) was 26 (10-40). Almost 30% were >40 years. Patients with complications were eight patients, age 63 (51.5-71.5). The prediction model identified the following variables as risk factors: diabetes (OR = 59.7; 95% CI: 3.5-1011.5, p = 0.005), fever (OR = 24.8; 95% CI: 1.4-447.3, p = 0.029), SHORTNESS OF BREATH (OR = 15.9; 95% CI: 1.3-189.7, p = 0.029), body mass index (OR = 0.74; 95% CI: 0.61-0.88, p = 0.001), abnormal Neutrophils (OR = 16.8; 95% CI: 1.0-292.0, p = 0.053). Prediction model was statistically significant, χ2(5) = 86.1, p < 0.0005. CONCLUSIONS: Unlike reports from China, the most influential variables that led to disease progression in Jordanian patients were diabetes, fever, shortness of breath, body mass index, and abnormal neutrophils. Similar to reports from the USA, smoking was not a leading factor for complications. Comorbidities and patient health status, rather than age, were the primary risk factors for complications. Treatment with Hydroxychloroquine showed no protective effect.

Clinical and laboratory characteristics of SARS-CoV2-infected paediatric patients in Jordan: serial RT-PCR testing until discharge.

BACKGROUND: Data on COVID-19 in children are limited. This study aimed to identify the clinical characteristics, laboratory results and longitudinal RT-PCR- testing pattern in children infected with theSARS-CoV2 virus and admitted to a hospital in Jordan. METHODS: The study is a retrospective chart review of patients admitted between 16 March and 23 April 2020. All infected children in Jordan were hospitalised. Serial RT-PCR testing was undertaken 7 days after the first test and then on alternate days until discharge. The association between patient symptoms and laboratory results and whether there was a statistically significant median difference in the number of days until negative RT-PCR results between patients was studied. RESULTS: Sixty-one patients with positive SARS-CoV2 swabs were admitted, 34 (55.7%) of whom were symptomatic. The most common symptom was nasal congestion (21/61, 34.3%), followed by generalised malaise and headache (12/6, 19.7%). A rash was detected in 5/61 (8.2%) of them. Fifty-five patients (90.1%) underwent investigations: 4 (7.4%) of them had lymphopenia, 4 (7.4%) had eosinopenia, 8 (14.5%) had eosinophilia, and platelets were elevated in 5 (9.1%) children. CRP was measured in 33/61 (54.1%) patients and all were normal. ESR levels were available for 11/61 (18%) patients and were elevated in 5 (45.5%). There was a statistically significant association between laboratory results and symptom expression (p = 0.011). The longest time until the first negative RT-PCR result was 39 days. CONCLUSION: All children admitted who tested positive for SARS-CoV2 had mild symptoms and five had cutaneous manifestations. RT-PCR may remain positive for over one month.