Hematocrit Self-Testing in Patients with Polycythemia Vera and Other Hematological Conditions: Assessing the Accuracy of the StatStrip Xpress® 2 LAC/Hb/Hct Device and User Opinion about the Device in Real-World Clinical Practice.

Maintaining hematocrit (Hct) levels below 45% can reduce morbidity and mortality in patients with polycythemia vera (PV). A device that patients can use to self-monitor Hct levels could enable timely interventions if Hct levels increase above 45%, and could improve quality of life (QoL). This study evaluated the accuracy of the StatStrip Xpress® 2 LAC/Hb/Hct meter (Hb/Hct meter) when used by healthcare professionals (HCPs) or patients in clinical practice. Blood samples from 68 visits for 60 patients with PV or other hematological conditions were collected and analyzed by HCPs using a laboratory hematological analyzer, and by patients (self-test) and HCPs (professional test) using the Hb/Hct meter at two Swiss centers. Accuracy was assessed as the mean difference in readings between two users/methods (mdiff, 90% confidence interval; Spearman correlation [r]). The Hct values were similar between the professional test and analyzer (n = 66 comparisons, mdiff = 0.1% [-0.5 to 0.8]; r = 0.95, p < 0.001), the self-test and professional test (n = 62 comparisons, mdiff = -0.2% [-1.1 to 0.7]; r = 0.93, p < 0.001), and the self-test and analyzer (n = 63 comparisons, mdiff = 0.0% [-0.8 to 0.7]; r = 0.94, p < 0.001). The hemoglobin values across users/methods were also similar. Reporting their opinion on the Hb/Hct meter at visit 1, 100% of the patients found it easy to use, and 97% were willing to use it at home. Of the patients with PV, approximately 71% and 56%, respectively, stated that they would feel safer using a self-testing device, and that it would improve their QoL. These findings demonstrate the potential of the Hb/Hct meter for HCP and patient use in real-world settings

Xist regulation and function eXplored

X chromosome inactivation (XCI) is a process in mammals that ensures equal transcript levels between males and females by genetic inactivation of one of the two X chromosomes in females. Central to XCI is the long non-coding RNA Xist, which is highly and specifically expressed from the inactive X chromosome. Xist covers the X chromosome in cis and triggers genetic silencing, but its working mechanism remains elusive. Here, we review current knowledge about Xist regulation, structure, function and conservation and speculate on possible mechanisms by which its action is restricted in cis. We also discuss dosage compensation mechanisms other than XCI and how knowledge from invertebrate species may help to provide a better understanding of the mechanisms of mammalian XCI

Mutagenic capacity of endogenous G4 DNA underlies genome instability in FANCJ-defective C. elegans

SummaryTo safeguard genetic integrity, cells have evolved an accurate but not failsafe mechanism of DNA replication. Not all DNA sequences tolerate DNA replication equally well [1]. Also, genomic regions that impose structural barriers to the DNA replication fork are a potential source of genetic instability [2, 3]. Here, we demonstrate that G4 DNA—a sequence motif that folds into quadruplex structures in vitro [4, 5]—is highly mutagenic in vivo and is removed from genomes that lack dog-1, the C. elegans ortholog of mammalian FANCJ [6, 7], which is mutated in Fanconi anemia patients [8–11]. We show that sequences that match the G4 DNA signature G3-5N1-3G3-5N1-3G3-5N1-3G3-5 are deleted in germ and somatic tissues of dog-1 animals. Unbiased aCGH analyses of dog-1 genomes that were allowed to accumulate mutations in >100 replication cycles indicate that deletions are found exclusively at G4 DNA; deletion frequencies can reach 4% per site per animal generation. We found that deletion sizes fall short of Okazaki fragment lengths [12], and no significant microhomology was observed at deletion junctions. The existence of 376,000 potentially mutagenic G4 DNA sites in the human genome could have major implications for the etiology of hereditary FancJ and nonhereditary cancers

Isolation of deletion alleles by G4 DNA-induced mutagenesis.

Metazoan genomes contain thousands of sequence tracts that match the guanine-quadruplex (G4) DNA signature G(3)N(x)G(3)N(x)G(3)N(x)G(3), a motif that is intrinsically mutagenic, probably because it can form secondary structures during DNA replication. Here we show how and to what extent this feature can be used to generate deletion alleles of many Caenorhabditis elegans genes.