Z-1,4-cis-ACHC-OH

The title compound, C(26)H(20), lies about an inversion centre. The naphthalene unit and the hexa-triene chain are each approximately planar (maximum deviations of 0.0143 and 0.0042 Å, respectively), and are inclined to one another at a dihedral angle of 49.20 (4)°. The dihedral angle between the two naphthalene ring systems of neighboring mol-ecules is 85.71 (4)°.

Importance: Questions of whether and how cortical thickness (CTh) alterations differ over the course of schizophrenia (SCZ) have yet to be resolved. Objective: To characterize CTh alterations across illness stages in SCZ. Data sources: PubMed, Embase, Web of Science, and Science Direct were screened for CTh studies published before June 15, 2021. Study selection: Original studies comparing whole-brain CTh alterations from healthy controls in individuals at clinical high-risk (CHR), first episode of psychosis (FEP), and long-term illness stages of SCZ were included. Data extraction and synthesis: This preregistered systematic review and meta-analysis followed PRISMA reporting guidelines. Separate and pooled meta-analyses were performed using seed-based d mapping. Meta-regression analyses were conducted. Main outcomes and measures: Cortical thickness differences from healthy control individuals across illness stages. Results: Ten studies comprising 859 individuals with CHR (mean [SD] age, 21.02 [2.66] years; male, 573 [66.7%]), 12 studies including 671 individuals with FEP (mean [SD] age, 22.87 [3.99] years; male, 439 [65.4%]), and 10 studies comprising 579 individuals with long-term SCZ (mean [SD] age, 41.58 [6.95] years; male, 396 [68.4%]) were included. Compared with healthy control individuals, individuals with CHR showed cortical thinning in bilateral medial prefrontal cortex (z = -1.01; P < .001). Individuals with FEP showed cortical thinning in right lateral superior temporal cortex (z = -1.34; P < .001), right anterior cingulate cortex (z = -1.44; P < .001), and right insula (z = -1.14; P = .002). Individuals with long-term SCZ demonstrated CTh reductions in right insula (z = -3.25; P < .001), right inferior frontal cortex (z = -2.19; P < .001), and left (z = -2.37; P < .001) and right (z = -1.94; P = .002) temporal pole. There were no significant CTh differences between CHR and FEP. Individuals with long-term SCZ showed greater cortical thinning in right insula (z = -2.58; P < .001), right inferior frontal cortex (z = -2.32; P < .001), left lateral temporal cortex (z = -1.91; P = .002), and right temporal pole (z = -1.82; P = .002) than individuals with FEP. Combining all studies on SCZ, accelerated age-related CTh reductions were found in bilateral lateral middle temporal cortex and right pars orbitalis in inferior frontal cortex. Conclusions and relevance: The absence of significant differences between FEP and CHR noted in this systematic review and meta-analysis suggests that the onset of psychosis was not associated with robust CTh reduction. The greater cortical thinning in long-term SCZ compared with FEP with accelerated age-related reduction in CTh suggests progressive neuroanatomic alterations following illness onset. Caution in interpretation is needed because heterogeneity in samples and antipsychotic treatment may confound these results.

(Z)-1-Chloro-2,3,3,3-tetrafluoropropene (HCFO-1224yd(Z)) is a colorless gas used as a single substance or in a mixture with other substances for refrigeration. The 4-h rat inhalation LC50 values from two studies were reported to be >20,180 ppm and >213,100 ppm. HCFO-1224yd(Z) is not expected to undergo significant metabolism. The no-observed-effect level of HCFO-1224yd(Z) for cardiac sensitization (in dogs) was 75,000 ppm. In a 5-day repeat inhalation study in rats, the only observation noted was repetitive movement of the mouth/jaws in some animals in the 50,000-ppm exposure group for 1-2 days during the first 3 exposure days. The toxicological significance of this observation was unknown; therefore, the study no-observed-adverse-effect level (NOAEL) was established at 50,000 ppm. In a good laboratory practice (GLP)-compliant, 4-week inhalation study in rats, there were no test substance-related adverse effects noted at any exposure concentration. The study NOAEL was established at 40,000 ppm. In a GLP-compliant inhalation developmental toxicity study, female rats were exposed for 6 h/day from gestation day 6 through 19. There were no test substance-related adverse effects on either the maternal or fetal rats at any exposure concentration. The NOAEL for developmental effects was established at 20,000 ppm. There are no chronic toxicity or carcinogenicity studies available. HCFO-1224yd(Z) gave mixed results in in vitro genotoxicity assays but was negative in an in vivo micronucleus assay. The NOAEL of 40,000 ppm for HCFO-1224yd(Z) from the 4-week, GLP-compliant inhalation study in rats was used at the point of departure (POD) for workplace environmental exposure level (WEEL) value development. This POD was adjusted to account for interindividual variability, duration of exposure, and database limitations. The resulting 8-h time-weighted average WEEL value of 1000 ppm is expected to provide a significant margin of safety against any potential adverse health effects in workers exposed to HCFO-1224yd(Z).