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Despite their importance in determining the dosing regimen of drugs in the clinic, only a few studies have investigated methods for predicting blood-to-plasma concentration ratios (Rb). This study established an Rb prediction model incorporating typical human pharmacokinetics (PK) parameters. Experimental Rb values were compiled for 289 compounds, offering reliable predictions by expanding the applicability domain. Notably, it is the largest list of Rb values reported so far. Subsequently, human PK parameters calculated from plasma drug concentrations, including the volume of distribution (Vd), clearance, mean residence time, and plasma protein binding rate, as well as 2702 kinds of molecular descriptors, were used to construct quantitative structure-PK relationship models for Rb. Among the evaluated PK parameters, logVd correlated best with Rb (correlation coefficient of 0.47). Thus, in addition to molecular descriptors selected by XGBoost, logVd was employed to construct the prediction models. Among the analyzed algorithms, artificial neural networks gave the best results. Following optimization using six molecular descriptors and logVd, the model exhibited a correlation coefficient of 0.64 and a root-mean-square error of 0.205, which were superior to those previously reported for other Rb prediction methods. Since Vd values and chemical structures are known for most medications, the Rb prediction model described herein is expected to be valuable in clinical settings.Coastal lagoons are among the most vulnerable ecosystems as they are often exposed to different anthropogenic activities. The Polychaetes, which are dominant components in macrobenthic community, are particularly exposed to contamination. The current study was designed to assess and compare the sensitivity of different polychaetes species towards urban pollution. To do this, three polychaete species Perinereis cultrifera, Diopatra neapolitana, and Marphysa sanguinea, were collected from the Tunis South Lagoon during summer 2013. A set of biomarkers indicative of genotoxicity (DNA damage), biotransformation, and oxidative stress (glutathione S-transferase, GST) as well as immune response (cyclooxygenase activity (COX), lysozyme activity, and nitric oxide level (NOx)), was used. The results revealed that D. neapolitana and P. cultrifera exhibited higher genetic alteration and GST activity and more prominent immune response when compared with M. sanguinea. These findings denote of the higher sensitivity of D. neapolitana and P. cultrifera to urban pollution and suggest their possible use in environmental biomonitoring programs.Suspicion of myelodysplastic syndromes (MDS) is the most common reason for bone marrow aspirate in elderly patients. This study aimed to prospectively validate the accuracy for flow cytometric analysis of peripheral blood neutrophil myeloperoxidase expression in ruling out MDS. We enrolled 62 consecutive patients who were referred for suspected MDS, based on medical history and peripheral blood cytopenia. selleck kinase inhibitor The accuracy of intra-individual robust coefficient of variation (RCV) for peripheral blood neutrophil myeloperoxidase expression was assessed with a prespecified 30% threshold. Cytomorphological evaluation of bone marrow aspirate performed by experienced hematopathologists confirmed MDS in 23 patients (prevalence, 37%), unconfirmed MDS in 32 patients (52%, including 3 patients with idiopathic cytopenia of undetermined significance (ICUS)), and was uninterpretable in 7 patients (11%). The median intra-individual RCV values for neutrophil myeloperoxidase expression in peripheral blood were 37.4% (range, 30.7-54.1), 29.2% (range, 28.1-32.1), and 29.1% (range, 24.7-37.8) for patients with confirmed suspicion of MDS, ICUS, and unconfirmed suspicion of MDS, respectively (P less then 0.001). The area under the ROC curve was 0.92 (95% confidence interval, 0.86-0.99). An intra-individual RCV value lower than 30% ruled out MDS for 35% (i.e., 19/55) patients referred for suspected disease, with 100% sensitivity (95% CI, 85-100%) and 100% negative predictive value (95% CI, 82-100%) estimates. This study shows that flow cytometric analysis of peripheral blood neutrophil myeloperoxidase expression might obviate the need for bone marrow aspirate for 35% of patients with suspected MDS. Trial registration ClinicalTrials.gov identifier NCT03363399 (first posted on December 6, 2017).We aimed to assess the frequency and coexistence of vertebral artery hypoplasia (VAH) and high jugular bulb (HJB) in subjects who underwent cranial magnetic resonance imaging (MRI) for diverse indications. This was a retrospective study in which 2184 consecutive patients who underwent cranial MRI were screened. Age, sex, and reasons for ordering cranial MRI were obtained from hospital database. Nineteen patients were excluded from the study. We defined VAH as a vertebral artery whose diameter was smaller than 2 mm with an asymmetry ratio of ≤ 11.7. HJB was defined as the jugular bulb lying higher than the inferior portion of the internal acoustic meatus. Pearson's χ2 test was used to study the association between VAH and HJB. A total of 2165 subjects were included in the final analysis. Median age was 34 years (min-max 1-98 years). Females constituted 51.4%. The most common complaint for which brain MRI was ordered was headache (68.5%), followed by vertigo (13%). VAH was present in 890 subjects (40.9%). The majority of the patients had unilateral VAH, mainly on the right side (72.9%). HJB was present in 1067 subjects (48.9%) and 24.9% of the temporal bones. HJB was three times more common on the right side than on the left (71.6%). Five-hundred and seventy-three (26.5%) had VAH and HJB concurrently. When a patient had either VAH or HJV, the likelihood of patient having the other condition was significant (p  less then  0.001). Binary logistic regression analysis showed that presence of VAH increased the probability of occurrence of HJB threefold and vice versa (p  less then  0.001, CI 2.502-3.574). This was the first report of significantly common co-occurrence of VAH and HJB.

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