Monoclonal B-cell lymphocytosis (MBL), CD4+/CD8weak T-cell large granular lymphocytic leukemia (T-LGL leukemia) and monoclonal gammopathy of unknown significance (MGUS): molecular and flow cytometry characterization of three concomitant hematological disorders

The diagnosis of T-cell large granular lymphocytic leukemia in association with other B-cell disorders is uncommon but not unknown. However, the concomitant presence of three hematological diseases is extraordinarily rare. We report an 88-year-old male patient with three simultaneous clonal disorders, that is, CD4+/CD8^weak T-cell large granular lymphocytic leukemia, monoclonal gammopathy of unknown significance and monoclonal B-cell lymphocytosis. The patient has only minimal complaints and has no anemia, neutropenia or thrombocytopenia. Lymphadenopathy and hepatosplenomegaly were not present. The three disorders were characterized by flow cytometry analysis, and the clonality of the T-cell large granular lymphocytic leukemia was confirmed by polymerase chain reaction. Interestingly, the patient has different B-cell clones, given that plasma cells of monoclonal gammopathy of unknown significance exhibited a kappa light-chain restriction population and, on the other hand, B-lymphocytes of monoclonal B-cell lymphocytosis exhibited a lambda light-chain restriction population. This finding does not support the antigen-driven hypothesis for the development of multi-compartment diseases, but suggests that T-cell large granular lymphocytic expansion might represent a direct antitumor immunological response to both B-cell and plasma-cell aberrant populations, as part of the immune surveillance against malignant neoplasms.     

Individual Trial Analysis for 7T fMRI Data by a Data-Driven Multi Scale Approach

An important interest in event-related single trial fMRI is the possibility of studying cognitive processes that vary in time (e.g. learning or adaptation). Region-specific modelling and the inter-trial variability of the evoked response play an important role. We showed how the use of the iterated multigrid priors (iMGP) method, a previously introduced data-driven multi scale Bayesian iterative approach, may be extended for a trial-by-trial analysis on ultra-high magnetic field data. We used both artificial (present real physiological noise) and real (unilateral finger tapping experiment) data at 7T and compared to other methods. Since the iMGP does not need to spatially smooth the data, avoiding a loss of sensitivity, we take advantage of the high SNR available at 7T. For artificial data, we showed receiver operating characteristic curves parametrized by the activity threshold and by the addition of extra thermal noise and compared with correlation technique results.The method showed be very robust in terms of specificity for very noisy data and capable of capturing the temporal variability imposed artificially across regions. For real data, we examined the inter-trial spatial relationships for four subjects and the time-to-peak of the evoked response estimated by the iMGP across trials, regions and subjects. To stress the reliability of the iMGP in single trial studies, an illustrative comparison with the variational Bayes approach (implemented in the very popular Statistical Parametric Mapping software) was done for a single subject. Despite the extravascular signals are still present at 7T and the confounds of physiological noise and hemodynamic variability affecting single trial approaches, we showed that with the iMGP method it is possible to detect individual HR robustly.     

A dose-response curve for biodosimetry from a 6 MV electron linear accelerator

Biological dosimetry (biodosimetry) is based on the investigation ofradiation-induced biological effects (biomarkers), mainly dicentric chromosomes, inorder to correlate them with radiation dose. To interpret the dicentric score interms of absorbed dose, a calibration curve is needed. Each curve should beconstructed with respect to basic physical parameters, such as the type of ionizingradiation characterized by low or high linear energy transfer (LET) and dose rate.This study was designed to obtain dose calibration curves by scoring of dicentricchromosomes in peripheral blood lymphocytes irradiated in vitro witha 6 MV electron linear accelerator (Mevatron M, Siemens, USA). Two software programs,CABAS (Chromosomal Aberration Calculation Software) and Dose Estimate, were used togenerate the curve. The two software programs are discussed; the results obtainedwere compared with each other and with other published low LET radiation curves. Bothsoftware programs resulted in identical linear and quadratic terms for the curvepresented here, which was in good agreement with published curves for similarradiation quality and dose rates.     

Concentrations of trace elements and KRAS mutations in pancreatic ductal adenocarcinoma

Trace elements are a possible risk factor for pancreatic ductal adenocarcinoma (PDAC). However, their role in the occurrence and persistence of KRAS mutations remains unstudied. There appear to be no studies analyzing biomarkers of trace elements and KRAS mutations in any human cancer. We aimed to determine whether patients with KRAS mutated and nonmutated tumors exhibit differences in concentrations of trace elements. Incident cases of PDAC were prospectively identified in five hospitals in Spain. KRAS mutational status was determined through polymerase chain reaction from tumor tissue. Concentrations of 12 trace elements were determined in toenail samples by inductively coupled plasma mass spectrometry. Concentrations of trace elements were compared in 78 PDAC cases and 416 hospital-based controls (case–control analyses), and between 17 KRAS wild-type tumors and 61 KRAS mutated tumors (case–case analyses). Higher levels of iron, arsenic, and vanadium were associated with a statistically nonsignificant increased risk of a KRAS wild-type PDAC (OR for higher tertile of arsenic = 3.37, 95% CI 0.98–11.57). Lower levels of nickel and manganese were associated with a statistically significant higher risk of a KRAS mutated PDAC (OR for manganese = 0.34, 95% CI 0.14–0.80). Higher levels of selenium appeared protective for both mutated and KRAS wild-type PDAC. Higher levels of cadmium and lead were clear risk factors for both KRAS mutated and wild-type cases. This is the first study analyzing biomarkers of trace elements and KRAS mutations in any human cancer. Concentrations of trace elements differed markedly between PDAC cases with and without mutations in codon 12 of the KRAS oncogene, thus suggesting a role for trace elements in pancreatic and perhaps other cancers with such mutations. Environ. Mol. Mutagen., 60:693–703, 2019. © 2019 Wiley Periodicals, Inc.     

Association between RAPH1 Gene Haplotypes and CHE2 Locus Phenotypes

The human butyrylcholinesterase (BChE) is a serum esterase that has been associated with body mass index (BMI) and obesity. Its activity is conditioned by alleles of BCHE gene and the CHE2 locus that codifies an unknown BChE‐binding protein (C₅ complex). The hypothesis that the CHE2 locus is the RAPH1 gene, which encodes lamellipodin (Lpd), was raised in a study that observed Lpd peptides released from denatured BChE tetramers. The aim of this study was to test this hypothesis by evaluating SNPs of RAPH1 gene (rs2246118:C > T, rs3814365:A > G and rs2465520:C > T) in 34 CHE2 C5+ and 92 CHE2 C5– individuals, corresponding to the presence and absence of C₅ complex. The results showed association of two haplotypes (CAC and TGC) with CHE2 C5+ phenotype. RAPH1 haplotypes was also associated with intense (TGC) and faint (CAC) CHE2 C5+ phenotypes. BChE activity was higher in intense CHE2 C5+ than faint CHE2 C5+ phenotype. Our results corroborate the hypothesis that the RAPH1 gene is the CHE2 locus and suggest that the variable expressivity of the CHE2 C5+ phenotypes is, at least in part, due to its genetic heterogeneity, which is leading to increased BChE activity only in individuals with intense CHE2 C5+ phenotype.     

Benefits of skin application of piceatannol—A minireview

The skin is the largest organ of the human body and has several functions such as barrier against external agents, the maintenance of temperature and homeostatic functions. Skin ageing is a natural process that can be influenced by environmental factors, intrinsic skin factors and lifestyle. UV light plays an important role in skin ageing and can cause spots, requiring the use of depigmenting agents. Nowadays, there is a great demand for ingredients that prevent skin ageing, with natural agents occupying a promising position. Among the natural agents, polyphenols, such as resveratrol and piceatannol, found in grapes, passion fruits and other fruits, have a huge relevance. Great benefits of piceatannol have been reported, so thus, this work focuses specifically on a review of the literature regarding the application of this polyphenol in skin care products. This polyphenol can be used in a wound-healing, or as anti-ageing, antioxidant, anti-acne and skin whitening, among other effects.