Who benefits from guided internet-based interventions? A systematic review of predictors and moderators of treatment outcome.

To our knowledge, no systematic review has been conducted on predictors or moderators of treatment outcome across diagnoses in guided internet-based interventions (IBIs) for adults. To identify who benefits from this specific format and therein inform future research on improving patient-treatment fit, we aimed to aggregate results of relevant studies. 2100 articles, identified by searching the databases PsycInfo, Ovid Medline, and Pubmed and through snowballing, were screened in April/May 2021 and October 2022. Risk of bias and intra- and interrater reliability were assessed. Variables were grouped by predictor category, then synthesized using vote counting based on direction of effect. N = 60 articles were included in the review. Grouping resulted in 88 predictors/moderators, of which adherence, baseline symptoms, education, age, and gender were most frequently assessed. Better adherence, treatment credibility, and working alliance emerged as conclusive predictors/moderators for better outcome, whereas higher baseline scores predicted more reliable change but higher post-treatment symptoms. Results of all other predictors/moderators were inconclusive or lacked data. 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.

Novel pyrrolidine melanin-concentrating hormone receptor 1 antagonists with reduced hERG inhibition.

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.

Identification of piperazine-bisamide GHSR antagonists for the treatment of obesity.

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.

Chlamydomonas DIP13 and human NA14: a new class of proteins associated with microtubule structures is involved in cell division.

We have cloned and characterized a single copy C. reinhardtii gene containing an open reading frame of 333 nucleotides encoding a 12.7 kDa protein. The novel protein, DIP13, exhibits 60% identity with two mammalian proteins, human NA14 and an unnamed mouse protein. Homologous sequences are also present in several protozoan, trematode and fish genomes, but no homologs have been found in the completed genomes of yeast, Drosophila, C. elegans and A. thaliana. By using a specific antibody we have localized DIP13 to microtubule structures, namely basal bodies, flagellar axonemes and cytoplasmic microtubules. Anti-DIP13 antibody also specifically recognized human NA14 by immunofluorescence and stained basal bodies and flagella of human sperm cells as well as the centrosome of HeLa cells. Expression of the DIP13 open reading frame in antisense orientation in Chlamydomonas resulted in multinucleate, multiflagellate cells, which suggests a role for this protein in ensuring proper cell division. Thus, DIP13/NA14 could represent the founding members of a new class of highly conserved proteins that are associated with microtubule structures.