Fundamental progress in investigating drug resistance with electronic multidrug compliance monitoring (e-MCM)

Current definitions of drug resistance are shaped by the pharmacotherapeutic fields they occurred in. They usually mention various contributing factors and refer either to the clinical or the biomarker level. Particular attention has been attracted by antiplatelet resistance, a phenomenon with clinical, cellular and pharmacogenetical contributors. However, the impact of every single factor to antiplatelet resistance in outpatients under prescribed antiplatelet therapy has not been comprehensively evaluated so far, neither has the temporal pattern of drug intake been studied as a possible contributor

Identifying mutations in Tunisian families with retinal dystrophy.

Retinal dystrophies (RD) are a rare genetic disorder with high genetic heterogeneity. This study aimed at identifying disease-causing variants in fifteen consanguineous Tunisian families. Full ophthalmic examination was performed. Index patients were subjected to IROme analysis or whole exome sequencing followed by homozygosity mapping. All detected variations were confirmed by direct Sanger sequencing. Mutation analysis in our patients revealed two compound heterozygous mutations p.(R91W);(V172D) in RPE65, and five novel homozygous mutations: p.R765C in CNGB1, p.H337R in PDE6B, splice site variant c.1129-2A > G and c.678_681delGAAG in FAM161A and c.1133 + 3_1133 + 6delAAGT in CERKL. The latter mutation impacts pre-mRNA splicing of CERKL. The other changes detected were six previously reported mutations in CNGB3 (p.R203*), ABCA4 (p.W782*), NR2E3 (p.R311Q), RPE65 (p.H182Y), PROM1 (c.1354dupT) and EYS (c.5928-2A > G). Segregation analysis in each family showed that all affected individuals were homozygotes and unaffected individuals were either heterozygote carriers or homozygous wild type allele. These results confirm the involvement of a large number of genes in RD in the Tunisian population

The RNA Helicase DDX6 Controls Cellular Plasticity by Modulating P-Body Homeostasis

Post-transcriptional mechanisms have the potential to influence complex changes in gene expression, yet their role in cell fate transitions remains largely unexplored. Here, we show that suppression of the RNA helicase DDX6 endows human and mouse primed embryonic stem cells (ESCs) with a differentiation-resistant, “hyper-pluripotent” state, which readily reprograms to a naive state resembling the preimplantation embryo. We further demonstrate that DDX6 plays a key role in adult progenitors where it controls the balance between self-renewal and differentiation in a context-dependent manner. Mechanistically, DDX6 mediates the translational suppression of target mRNAs in P-bodies. Upon loss of DDX6 activity, P-bodies dissolve and release mRNAs encoding fate-instructive transcription and chromatin factors that re-enter the ribosome pool. Increased translation of these targets impacts cell fate by rewiring the enhancer, heterochromatin, and DNA methylation landscapes of undifferentiated cell types. Collectively, our data establish a link between P-body homeostasis, chromatin organization, and stem cell potency

Mental healthcare goes online:Practitioners' experiences of providing mental healthcare during the COVID-19 pandemic

The outbreak of the COVID-19 pandemic has necessitated sudden and radical changes in mental health care delivery, as strict social distancing and lockdown measures were imposed in the early phases of the pandemic. Almost overnight, practitioners were forced to transfer their face-to-face care practice to online means. To understand the implications of this drastic change for mental health care, and to improve the online care offerings, an online qualitative survey was held among mental health care professionals in Netherlands (n = 51). Our findings indicate that technological and usability problems pose a significant challenge, as do difficulties to establish rapport with clients. Moreover, not all mental health issues and treatment forms are equally amenable to online interaction. In contrast, in many instances, practitioners were positive about the effectiveness of treatment, and reported flexibility, a lower threshold for contact, and lack of travel time as advantages. Their most prominent needs concern better technological, organizational, and logistical support. It is critical that these needs are acted upon by institutions and governments. In addition, current results inform future research on the improvement of e-mental health technologies