Terrelllowery2671

Alterations in excitability represent an early hallmark in Amyotrophic Lateral Sclerosis (ALS). Therefore, deciphering the factors that impact motor neuron (MN) excitability offers an opportunity to uncover further aetiopathogenic mechanisms, neuroprotective agents, therapeutic targets, and/or biomarkers in ALS. Here, we hypothesised that the lipokine lysophosphatidic acid (lpa) regulates MN excitability via the G-protein-coupled receptor lpa

. Then, modulating lpa

-mediated signalling might affect disease progression in the ALS SOD1-G93A mouse model.

The influence of lpa-lpa

signalling on the electrical properties, Ca

dynamic and survival of MNs was tested in vitro. Expression of lpa

in cultured MNs and in the spinal cord of SOD1-G93A mice was analysed. ALS mice were chronically treated with a small-interfering RNA against lpa

(siRNA

) or with the lpa

inhibitor AM095. Motor skills, MN loss, and lifespan were evaluated.

AM095 reduced MN excitability. Conversely, exogenous lpa increased Min ALS.

The preoperative predictors of quality of life (QOL) in patients who undergo lung resection for lung cancer are poorly known. Here, we investigated these predictors in such patients using two QOL measures.

In this single-institutional prospective cohort study, we administered the EQ-5D-5 levels (EQ-5D-5L) from January 2015, and the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire with 30 items from April 2015 to April 2018 preoperatively (Pre) and at one month postoperatively (M1), and one year postoperatively (Y1). General health status was measured by the EQ-5D visual analogue scale (VAS) and EORTC global health status/QOL (GHS) scores. Multivariable linear regression analyses were used to explore the preoperative predictors of QOL at Y1.

A total of 223 patients were included in the study. The EQ-5D VAS and EORTC GHS scores, at Pre, M1, and Y1, were 80 ± 15, 77 ± 15, and 84 ± 11; and 74 ± 19, 65 ± 20, and 78 ± 17, respectively. In the multivariable analyses, the albumin level, preoperative VAS score, and preoperative pain/discomfort and anxiety/depression were identified as predictors by the EQ-5D VAS score. SB202190 p38 MAPK inhibitor The preoperative EORTC GHS score, absence of diabetes mellitus, preoperative cognitive function score, and preoperative symptom score of pain were identified as predictors by the EORTC GHS score.

The EQ-5D VAS and EORTC GHS scores traced similar trajectories of QOL. In both QOL measures, preoperative pain was found as a common predictor. These predictors may help improve patient/survivor care in the future.

The EQ-5D VAS and EORTC GHS scores traced similar trajectories of QOL. In both QOL measures, preoperative pain was found as a common predictor. These predictors may help improve patient/survivor care in the future.

The ageing of baby boomers is expected to confront addiction care with new challenges. This cohort had greater exposure to psychoactive substances in youth than earlier cohorts. In this study, we aimed to investigate whether Berlin addiction care is confronted with a sustained change in its clientele initiated by the baby boomers.

Using data from Berlin outpatient addiction care facilities, we contrasted type of primary substance use disorder and number of comorbid substance use disorders in baby boomers with an earlier and a later cohort. To isolate cohort effects, two-level random intercept regression models were applied in the overlapping age groups of the baby boomer cohort with each of the other cohorts.

Compared with the earlier cohort, alcohol use disorder lost importance whereas illicit substance use disorder gained importance in the baby boomers. Baby boomers presented a higher number of comorbid substance use disorders than the earlier cohort. Comparing baby boomers with the later cohort, these relationships pointed in the opposite direction.

Outpatient addiction care faces a sustained change to more illicit and comorbid substance use disorders. With increasing life expectancy and the ageing of baby boomers marked by higher substance use than previous cohorts, older clients, who had been under-represented in outpatient addiction care, will gain relevance. Hence, addiction care has to adapt its offers to appropriately meet the changing needs of its clientele.

Outpatient addiction care faces a sustained change to more illicit and comorbid substance use disorders. With increasing life expectancy and the ageing of baby boomers marked by higher substance use than previous cohorts, older clients, who had been under-represented in outpatient addiction care, will gain relevance. Hence, addiction care has to adapt its offers to appropriately meet the changing needs of its clientele.Although two thirds of patients with a cocaine use disorder (CUD) are female, little is known about sex differences in the (neuro)pathology of CUD. The aim of this explorative study was to investigate sex-dependent differences in prefrontal cortex (PFC) functioning during a working memory (WM) functional magnetic resonance imaging (fMRI) task in regular cocaine users (CUs), as PFC deficits are implicated in the shift from recreational cocaine use to CUD. Neural activation was measured using fMRI during a standard WM task (n-back task) in 27 male and 28 female CUs and in 26 male and 28 female non-cocaine users (non-CUs). Although there were no main or interaction effects of sex and group on n-back task performance, WM-related (2-back > 0-back) PFC functioning was significantly moderated by sex and group female compared with male CUs displayed higher WM-related activation of the middle frontal gyrus (MFG), whereas female compared with male non-CUs displayed lower WM-related MFG activation. Additionally, WM-related activation of the inferior frontal gyrus, insula, and putamen was negatively associated with cocaine use severity in female but not male CUs. These data support the hypothesis of sex-dependent PFC differences in CUs and speculatively suggest that PFC deficits may be more strongly implicated in the development, continuation, and possibly treatment of CUD in females. Most importantly, the current data stress the importance of studying both males and females in psychiatry research as not doing so could greatly bias our knowledge of CUD and other psychiatric disorders.