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Objective: To our knowledge, no systematic review or meta-analysis has been conducted on all predictors or moderators of treatment outcome across diagnoses in guided internet-based interventions (IBIs) for adults. We aimed to aggregate the results of relevant studies and identify research gaps. Methods: After duplicate removal, 1615 articles, identified by searching the databases PsycInfo, Ovid Medline, and Pubmed and through snowballing, were screened following detailed in- and exclusion criteria in April and May 2021. Risk of bias (QUIPS) and intra- and interrater reliability for screening and risk of bias were assessed. Variables were grouped and categorized, then synthesized using vote counting based on direction of effect. Results: N=50 articles were included in the review. Seventy-seven predictors or moderators were generated, of which adherence, baseline symptoms, education, age, and gender were most frequently assessed. Adherence, treatment credibility, working alliance, and baseline scores emerged as conclusive predictors/moderators. Results for other variables were mainly inconsistent or inconclusive. Conclusion: Our review highlights that it is currently difficult to predict, across diagnoses, who will benefit from guided IBIs. Further rigorous research is needed to identify predictors and moderators based on a sufficient number of studies. PROSPERO registration: CRD42021242305.

We discovered novel pyrrolidine MCHR1 antagonist 1 possessing moderate potency. Profiling of pyrrolidine 1 demonstrated that it was an inhibitor of the hERG channel. Investigation of the structure-activity relationship of this class of pyrrolidines allowed us to optimize the MCHR1 potency and decrease the hERG inhibition. Increasing the acidity of the amide proton by converting the benzamide in lead 1 to an anilide provided single digit nanomolar MCHR1 antagonists while replacing the dimethoxyphenyl ring of 1 with alkyl groups possessing increased polarity dramatically reduced the hERG inhibition.

Piperazine-bisamide analogs were discovered as partial agonists of human growth hormone secretagogue receptor (GHSR) in a high throughput screen. The partial agonists were optimized for potency and converted into antagonists through structure–activity relationship (SAR) studies. The efforts also led to the identification of potent antagonist with favorable PK profile suitable as a tool compound for in vivo studies.

Eukaryotic flagella and cilia are highly dynamic organelles. In green algae like Chlamydomonas reinhardtii, flagella absorption and resynthesis is a normal process during the vegetative cell cycle. Rapid regeneration also occurs after stress-induced shedding of flagella. Ca2+ ions, protein synthesis, and a kinase activity are the main factors known to affect resynthesis. Recently, we have detected that certain small G proteins (Ypt/Rab) and a GTPase regulator (GDP dissociation inhibitor), known as regulatory elements of intracellular vesicle transport, are present in flagellar membranes of green algae, raising the possibility that the organelle's synthesis and/or integrity depends on functional membrane traffic. In this study, we examined the effect of brefeldin A (BFA), an inhibitor of intracellular membrane flow and Golgi function in animal and plant cells, on flagella regeneration in the colonial green alga Gonium pectorale. We show that low BFA concentrations (1 microgram/ml) inhibit flagella out-growth, while higher amounts cause dose-dependent deflagellation and cell death. Our findings provide experimental evidence for a direct connection between intracellular transport and eukaryotic flagella synthesis.