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The polygenic nature of schizophrenia (SCZ) implicates many variants in disease development. Rare variants of high penetrance have been shown to contribute to the disease prevalence. Whole-exome sequencing of a large three-generation family with SCZ and bipolar disorder identified a single segregating novel, rare, non-synonymous variant in the gene CASKIN1. The variant D1204N is absent from all databases, and CASKIN1 has a gnomAD missense score Z = 1.79 and pLI = 1, indicating its strong intolerance to variation. We find that introducing variants in the proline-rich region where the D1204N resides results in significant cellular changes in iPSC-derived neurons, consistent with CASKIN1’s known functions. We observe significant transcriptomic changes in 368 genes (padj < 0.05) involved in neuronal differentiation and nervous system development. We also observed nominally significant changes in the frequency of action potentials during differentiation, where the speed at which the edited and unedited cells reach the same level of activity differs. Our results suggest that CASKIN1 is an excellent gene candidate for psychosis development with high penetrance in this family.

Delirium is a critical issue in the intensive care unit (ICU), and the correct diagnosis and treatment of this disorder by the ICU team are doubtful on many occasions due to a lack of information. This research is intended to test the awareness and control of ICU delirium by the ICU nurses. A nonexperimental, quantitative, descriptive, cross-sectional study was conducted using a previously adopted and translated to Arabic and validated questionnaire. The sample include nurses who work in ICUs of 10 Palestinian hospitals (private and public) located in the West Bank and Jerusalem participated in this study; each gave consent to be part of this study. Approval was received from the Palestinian Ministry of Health and the Ethical Committee at Birzeit University. Version 19 of the Social Sciences Statistical Package (SPSS) software was used to analyze the data. The results showed that ICU nurses hold moderate to low levels of knowledge and lack of adequate clinical experience to handle delirium. Delirium is a common complication in the ICU that increases morbidity and mortality and increases the length of ICU stay, therefore the cost of health care rise and the quality of life is decreased. In clinical practice, there are no assessment guidelines and protocols for patients with delirium.

Scarless genome editing is an important tool for the accurate recapitulation of genetic variation in human disease models. Various CRISPR/Cas9-based scarless editing methods have been reported. However, some of these methods have low editing efficiency (1-5%) and require manual selection of hundreds of clones to reach the desired number. Other protocols use large selection cassettes with laborious vector assembly and specialized reagents and equipment, or have poorly understood off-target effects. To address these limitations, we developed a simple, highly efficient scarless editing strategy to edit DNA sequences in induced pluripotent stem cells, which we call CRISPR Del/Rei. This novel editing strategy consists of a two-step deletion-reinsertion strategy that produces isogenic clones in ~8 weeks using accessible, user-friendly reagents. The editing efficiency ranges from ~15-100% for Step 1 and ~5-20% for Step 2 after selection, which greatly reduces the amount of required manual clone isolation. Screening the transfected bulk cells and the individual clones is rapid and simple, consisting of PCR and gel electrophoresis. Despite the two editing steps, off-target effects are rare. Additionally, the experiment is well-controlled because the same protocol generates isogenic clones carrying all variant alleles. In this way, CRISPR Del/Rei serves as a valuable addition to the evolving CRISPR/Cas9 gene-editing toolset.

PURPOSE OF REVIEW: We review the ways in which stem cells are used in psychiatric disease research, including the related advances in gene-editing and directed cell differentiation. RECENT FINDINGS: The recent development of induced pluripotent stem cell (iPSC) technologies has created new possibilities for the study psychiatric disease. iPSCs can be derived from patients or controls and differentiated to an array of neuronal and non-neuronal cell types. Their genomes can be edited as desired, and they can be assessed for a variety of phenotypes. This makes them especially interesting for studying genetic variation, which is particularly useful today now that our knowledge on the genetics of psychiatric disease is quickly expanding. SUMMARY: The recent advances in cell engineering have led to powerful new methods for studying psychiatric illness including schizophrenia, bipolar disorder, and autism. There is a wide array of possible applications as illustrated by the many examples from the literature, most of which are cited here.

Schizophrenia is a devastating mental illness with a strong genetic component that is the subject of extensive research. Despite the high heritability, it is well recognized that non-genetic factors such as certain infections, cannabis use, psychosocial stress, childhood adversity, urban environment, and immigrant status also play a role. Whenever genetic and non-genetic factors co-exist, interaction between the two is likely. This means that certain exposures would only be of consequence given a specific genetic makeup. Here, we provide a brief review of studies reporting evidence of such interactions, exploring genes and variants that moderate the effect of the environment to increase risk of developing psychosis. Discovering these interactions is crucial to our understanding of the pathogenesis of complex disorders. It can help in identifying individuals at high risk, in developing individualized treatments and prevention plans, and can influence clinical management.

Aim The aim was to decipher Europe‐wide spatio‐temporal patterns of forest growth dynamics and their associations with carbon isotope fractionation processes inferred from tree rings as modulated by climate warming. Location Europe and North Africa (30‒70° N, 10° W‒35° E). Time period 1901‒2003. Major taxa studied Temperate and Euro‐Siberian trees. Methods We characterize changes in the relationship between tree growth and carbon isotope fractionation over the 20th century using a European network consisting of 20 site chronologies. Using indexed tree‐ring widths (TRWi), we assess shifts in the temporal coherence of radial growth across sites (synchrony) for five forest ecosystems (Atlantic, boreal, cold continental, Mediterranean and temperate). We also examine whether TRWi shows variable coupling with leaf‐level gas exchange, inferred from indexed carbon isotope discrimination of tree‐ring cellulose (Δ13Ci). Results We find spatial autocorrelation for TRWi and Δ13Ci extending over a maximum of 1,000 km among forest stands. However, growth synchrony is not uniform across Europe, but increases along a latitudinal gradient concurrent with decreasing temperature and evapotranspiration. Latitudinal relationships between TRWi and Δ13Ci (changing from negative to positive southwards) point to drought impairing carbon uptake via stomatal regulation for water saving occurring at forests below 60° N in continental Europe. An increase in forest growth synchrony over the 20th century together with increasingly positive relationships between TRWi and Δ13Ci indicate intensifying impacts of drought on tree performance. These effects are noticeable in drought‐prone biomes (Mediterranean, temperate and cold continental). Main conclusions At the turn of this century, convergence in growth synchrony across European forest ecosystems is coupled with coordinated warming‐induced effects of drought on leaf physiology and tree growth spreading northwards. Such a tendency towards exacerbated moisture‐sensitive growth and physiology could override positive effects of enhanced leaf intercellular CO2 concentrations, possibly resulting in Europe‐wide declines of forest carbon gain in the coming decades. Spanish Government, Grant/Award Number: AGL2015‐68274 ‐C3 ‐3‐R; Sixth Framework Programme, Grant/AwardNumber: EVK2‐2001 ‐00237; Seventh Framework Programme, Grant/AwardNumber: COST ‐STSM ‐ECOST ‐STSM ‐FP1304‐140915‐066395 and ERANET‐Mundus program (Grant agreement 20112573)