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This study analyzed RWA using the SINBAR EMG montage in early- and advanced-stage of PD and showed higher RWA in mentalis and flexor digitorum superficialis muscles and SINBAR EMG index in advanced-PD patients compared to patients in the early stage. Also, PSG-confirmed RBD was more common in advanced versus early-stage patients. Our findings suggest that RWA worsens or is more intense or more frequent with disease progression.<br /><br />This study analyzed RWA using the SINBAR EMG montage in early- and advanced-stage of PD and showed higher RWA in mentalis and flexor digitorum superficialis muscles and SINBAR EMG index in advanced-PD patients compared to patients in the early stage. Also, PSG-confirmed RBD was more common in advanced versus early-stage patients. Our findings suggest that RWA worsens or is more intense or more frequent with disease progression.<br /><br /> We examined the mediating role of friends smoking in the association between depressive symptoms and daily/weekly cigarette smoking from adolescence into adulthood.<br /><br /> Data were drawn from the Nicotine Dependence In Teens study (NDIT, Canada) and the Avon Longitudinal Study of Parents and Children (ALSPAC, UK) studies. Three age groups were investigated in NDIT age 13-14 (n=1189), 15-16 (n=1107), and 17-18 (n=1075), and one in ALSPAC (n=4482, age 18-21). Multivariable mediation models decomposed the total effect (TE) of depressive symptoms on smoking into a natural direct effect (NDE) and natural indirect effect (NIE) through friends smoking.<br /><br /> The ORs for the TE were relatively constant over time with estimates ranging from 1.12 to 1.35. Friends smoking mediated the association between depressive symptoms and smoking in the two youngest samples (OR (95%CI) 1.09 (1.01,1.17) in 13-14-year-olds; 1.10 (1.03,1.18) in 15-16-year-olds). In the two older samples, NDE of depressive symptoms was close to the TE, suggestive that mediation was absent or too small to detect.<br /><br /> Friends smoking mediates the association between depressive symptoms and daily/weekly cigarette smoking in young adolescents.<br /><br /> If young adolescents use cigarettes to self-medicate depressive symptoms, then interventions targeting smoking that ignore depressive symptoms may be ineffective. Our results also underscore the importance of the influence of friends in younger adolescents, suggestive that preventive intervention should target the social environment including social relationships.<br /><br />If young adolescents use cigarettes to self-medicate depressive symptoms, then interventions targeting smoking that ignore depressive symptoms may be ineffective. Our results also underscore the importance of the influence of friends in younger adolescents, suggestive that preventive intervention should target the social environment including social relationships.Sleep disruption, and especially REM sleep disruption, is associated with fear inhibition impairment in animals and humans. The REM sleep-fear inhibition relationship raises concern for individuals with PTSD, whose sleep disturbance is commonly treated with hypnotics which disrupt and/or decrease REM sleep, such as benzodiazepines or 'Z-drugs'. Here, we examined the effects of the Z-drug zolpidem, a GABAA receptor positive allosteric modulator, as well as suvorexant, an orexin receptor antagonist (hypnotics which decrease and increase REM sleep, respectively) in the context of circadian disruption in murine models of fear inhibition-related processes (i.e., fear extinction and safety learning). Adult male C57Bl/6J mice completed fear and safety conditioning before undergoing shifts in the light-dark (LD) cycle or maintaining a consistent LD schedule. Fear extinction and recall of conditioned safety were thereafter tested daily. Immediately prior to onset of the light phase between testing sessions, mice were treated with zolpidem, suvorexant, or vehicle (methylcellulose). EEG/EMG analysis showed temporal distribution of REM sleep was misaligned during LD cycle-shifts, while REM sleep duration was preserved. Suvorexant increased REM sleep and improved fear extinction rate, relative to zolpidem, which decreased REM sleep. Survival analysis demonstrated LD shifted mice treated with suvorexant were faster to achieve complete extinction than vehicle and zolpidem-treated mice in the LD shifted condition. By contrast, retention of conditioned safety memory was not influenced by either treatment. This study thus provides preclinical evidence for the potential clinical utility of hypnotics which increase REM sleep for fear extinction after PTSD-relevant sleep disturbance.Inhibition kinetics assays were conducted with 16 commercial organophosphate (OP) pesticides or their metabolites on acetylcholinesterase (AChE) in erythrocyte "ghost" preparations from 18 individual humans (both sexes; adults, juveniles and cord blood samples; mixed races/ethnicities) and pooled samples from adult rats (both sexes). A well established spectrophotometric assay using acetylthiocholine as substrate and a chromogen was employed. The kinetic parameters bimolecular rate constant (ki), dissociation constant (KI) and phosphorylation constant (kp) were calculated for each compound. As expected, a wide range of potencies were displayed among the tested compounds. Statistical analysis of the resultant data indicated no differences in sex, age or race/ethnicity among the human samples that are unexpected based on chance (4.2% statistically significant out of 48 parameters calculated) and no differences between the sexes in rats. The bimolecular rate constants for 10 of the compounds were not statistically different between rats and humans. [https://www.selleckchem.com/products/msc-4381.html MSC-4381 research buy] The data indicate that, consistent with the high level of conservation of AChE among species and the fact that AChE at different locations within a species arises from the same gene, the inhibition kinetic parameters calculated from rat erythrocyte ghost preparations should be useful in estimating potencies of OP compounds on target AChE in humans. Additionally the data indicate that differences in sensitivities among individual humans were not apparent. Impact Statement These data are expected to be useful in consideration of the intraspecies and interspecies uncertainty factors in OP pesticide risk assessment.