The aim of the study was to determine changes of baroreflex sensitivity in humans between 11 and 20 years of age. Continuous 5 min blood pressure recordings using a Finapres were taken in 415 healthy subjects while in a sitting, resting position (breathing at a frequency of 0.33 Hz). Beat-by-beat values of interbeat intervals (IBI) or heart rate, and systolic and diastolic blood pressures were measured. Baroreflex sensitivity in ms/mmHg (BRS) and in mHz/mmHg (BRSf) was determined at an average frequency of 0.1 Hz by spectral analysis. BRS did not correlate with age, but BRSf significantly decreased with age (p < 0.001). BRS correlated with mean IBI (p < 0.001) in all subjects and also in the particular subgroups, but BRSf was IBI-independent. Results of multiregression equations were BRS = 1.37 - 0.56 x age (years) + 0.02 x IBI (ms) (p < 0.001 for BRS vs. age and for BRS vs. IBI); BRSf = 34.74 - 0.97 x age (years) - 0.001 x IBI (ms) (p < 0.001 only for BRS vs. age), where age was measured in years and IBI was measured in ms. The limits of BRS were estimated for the total group: 5th percentile, 3.9; 50th percentile, 9.1; and 95th percentile, 18.7 ms/mmHg; and limits for BRSf were 5th percentile, 8.5; 50th percentile, 16.4; and 95th percentile, 33.6 mHz/mmHg. We conclude that IBI-dependent BRS was unchanged in the particular age groups, but the standardization of BRS on IBI decreased with age. BRSf was IBI-independent and better reflected the development of the BRS.

Identification of changes of phospholipid (PL) composition occurring during colorectal cancer (CRC) development may help us to better understand their roles in CRC cells. Here, we used LC-MS/MS-based PL profiling of cell lines derived from normal colon mucosa, or isolated at distinct stages of CRC development, in order to study alterations of PL species potentially linked with cell transformation. We found that a detailed evaluation of phosphatidylinositol (PI) and phosphatidylserine (PS) classes allowed us to cluster the studied epithelial cell lines according to their origin: i) cells originally derived from normal colon tissue (NCM460, FHC); ii) cell lines derived from colon adenoma or less advanced differentiating adenocarcinoma cells (AA/C1, HT-29); or, iii) cells obtained by in vitro transformation of adenoma cells and advanced colon adenocarcinoma cells (HCT-116, AA/C1/SB10, SW480, SW620). Although we tentatively identified several PS and PI species contributing to cell line clustering, full PI and PS profiles appeared to be a key to the successful cell line discrimination. In parallel, we compared PL composition of primary epithelial (EpCAM-positive) cells, isolated from tumor and adjacent non-tumor tissues of colon cancer patients, with PL profiles of cell lines derived from normal colon mucosa (NCM460) and from colon adenocarcinoma (HCT-116, SW480) cells, respectively. In general, higher total levels of all PL classes were observed in tumor cells. The overall PL profiles of the cell lines, when compared with the respective patient-derived cells, exhibited similarities. Nevertheless, there were also some notable differences in levels of individual PL species. This indicated that epithelial cell lines, derived either from normal colon tissue or from CRC cells, could be employed asONE | https://doi.org/10.1371/journal.pone.0228010 January 30, 2020 1 / 21 OPEN ACCESS Citation: Hofmanová J, Slavík J, Ovesná P, Tylichová Z, Dušek L, Straková N, et al. (2020) Phospholipid profiling enables to discriminate tumor-and non-tumor-derived human colon epithelial cells: Phospholipidome similarities and differences in colon cancer cell lines and in patientderived cell samples. PLoS ONE 15(1): e0228010.

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Aim of the study:The aim was to determine the blood concentrations of hydroxychloroquine in Moroccan systemic lupus erythematosus patients and identify the factors associated with interindividual variation. Methods: A cross-sectional study enrolled patients with lupus erythematosus. We recorded demographic features of patients and main clinical and biological characteristics of the disease. We determined the blood concentrations of hydroxychloroquine for the entire patient enrolled in this study by liquid chromatographymass spectrometry. Patients were divided according to their blood hydroxychloroquine level into three groups: low blood concentration (<500 ng/mL), therapeutic range (500-2000 ng/mL) and high blood HCQ concentration (>2000). Results: Eighty subjects were included; 77 were female and the mean age was 36.9±12, 2 years. The median concentration of hydroxychloroquine was 830 ng/mL (range: 35-3,200 ng/mL); 13 patients (16%) had low blood levels, 59 (74%) were in therapeutic range while 8 (10%) had high blood concentrations. Low body mass index and the use of corticosteroids were associated with high hydroxychloroquine concentrations (p=0.03 and p=0.02 respectively). Conclusion: We report for the first time the blood concentration of hydroxychloroquine in Moroccan lupus patients and we found significant variability between patients for the same dose. Various factors affected this concentration and further studies are needed to expand the sample.

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The aim of this study was to evaluate the association of single nucleotide polymorphisms (SNPs) T-786C and G894T in the gene encoding eNOS with blood pressure variability (BPV) in man.Blood pressure was recorded beat-to-beat at rest three times in periods of one week (5 min, Finapres, breathing at 0.33 Hz) in 152 subjects (19-24 years). Systolic (SBPV 0.1r /SBPV 0.1a ) and diastolic (DBPV 0.1r /DBPV 0.1a ) blood pressure variabilities in relative (r.u.) and absolute (mmHg 2 /Hz) units were determined by the spectral method as spectral power at the frequency of 0.1 Hz.Genotypes of both polymorphisms were detected using polymerase chain reaction and restriction analysis using enzymes Msp I and Ban II. Significant differences were observed in BPV among genotypes of T-786C SNP (p<0.05; Kruskal-Wallis), and among haplotypes of both SNPs (p<0.05; Kruskal-Wallis) as well.In T-786C SNP, carriers of less frequent allele (CC homozygotes and TC heterozygotes) showed significantly greater SBPV 0.1r and SBPV 0.1a compared to TT homozygotes (Mann-Whitney; p<0.05).The G894T variant showed no significant differences, but, both SNPs were in linkage disequilibrium (D'=0.37; p<0.01). Carriers of haplotype CT/CT (CC homozygotes of -786C/T and TT homozygotes of G894T) displayed significantly greater SBPV 0.1r , SBPV 0.1a and DBPV 0.1a compared to carriers of other haplotype combinations (Kruskal-Wallis; p=0.015, p=0.048, and p=0.026, respectively). In conclusion, the haplotype formed by less frequent alleles of both eNOS variants was associated with increased systolic and diastolic BPV in this study.