Visualizing Patterns of Medication Switching Among Major Depressive Patients with Various Stability and Difficulty to Treatments.

INTRODUCTION: Efforts have been made in assessing efficacy and tolerability to various antidepressants, but understanding personalized chances of stability to medication switching sequence is still inconclusive. This study aimed to identify naturalistic switching patterns of medication in stratifying MDD patients. METHODS: MDD patients were stratified based on treatment difficulty evaluated with the "Treatment Resistance to Antidepressants Evaluation Scale for Unipolar Depression" (TRADES). The duration of the time of diagnoses until the final switch to another class of antidepressants was used as prediction of unstable to drug therapy. ROC analysis was used to determine the cutoff values. A continuous temporal events function from the visual analytic tool was employed to perform patterns of switching between distinct pharmacological class such as selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs). RESULTS: TRADES scores of 4.5 and not-switching times of 12.5 months were used as cutoff values to divide patients into four subgroups: stable/easy-to-treat (SE), unstable/easy-to-treat (UE), stable/difficult-to-treat (SD) and unstable/difficult-to-treat (UD). A total of 80% and 76.9% of patients initially treated with the SSRIs paroxetine or fluoxetine, respectively, were predicted to be stable to drug therapy. Approximately 70%, 44.8% and 41.4% of patients initially treated with the SNRIs fluvoxamine, sertraline and venlafaxine, respectively, were predicted to be UD, and 60% of patients using duloxetine were predicted to be stable to drug therapy. Analysis of the switching phenomenon showed that SSRIs were the first prescribed medications and mostly taken by the stable subgroups, and SNRIs were the preferentially chosen switching alternative. Medication switching patterns in unstable MDD patients are discussed. CONCLUSION: Paroxetine, fluoxetine and duloxetine users were mostly stable among MDD patients in Taiwan with various stability and difficulty to treatments. Although responsiveness to specific medication sequence is likely required for clinical application, the results provide a baseline for such studies.

Phosphoproteomics and Bioinformatics Analyses Reveal Key Roles of GSK-3 and AKAP4 in Mouse Sperm Capacitation.

Protein phosphorylation can induce signal transduction to change sperm motility patterns during sperm capacitation. However, changes in the phosphorylation of sperm proteins in mice are still incompletely understood. Here, capacitation-related phosphorylation in mouse sperms were firstly investigated by label-free quantitative (LFQ) phosphoproteomics coupled with bioinformatics analysis using ingenuity pathway analysis (IPA) methods such as canonical pathway, upstream regulator, and network analysis. Among 1632 phosphopeptides identified at serine, threonine, and tyrosine residues, 1050 novel phosphosites, corresponding to 402 proteins, were reported. Gene heatmaps for IPA canonical pathways showed a novel role for GSK-3 in GP6 signaling pathways associated with capacitation for 60 min. At the same time, the reduction of the abundant isoform-specific GSK-3α expression was shown by western blot (WB) while the LFQ pY of this isoform slightly decreased and then increased. The combined results from WB and LFQ methods explain the less inhibitory phosphorylation of GSK-3α during capacitation and also support the predicted increases in its activity. In addition, pAKAP4 increased at the Y156 site but decreased at the Y811 site in a capacitated state, even though IPA network analysis and WB analysis for overall pAKAP revealed upregulated trends. The potential roles of GSK-3 and AKAP4 in fertility are discussed.

Constructing a bilingual website with validated database for Herb and Western medicine interactions using Ginseng, Ginkgo and Dong Quai as examples.

BACKGROUND: Concerns have been raised regarding the efficacy and safety resulting from the potential interactions of herbs with Western medications due to the use of both herbs and Western medicine by the general public. Information obtained from the web must be critically evaluated prior to its use in making decisions. DESCRIPTION: This study aimed to construct an herb-drug interaction (HDI) website (https://drug-herb-interaction.netlify.com) with a critically reviewed database. Node.js was used to store the database by running JavaScript. Vue.js is a front-end framework used for web interface development. A total of 135 sets of information related to the interactions of ginseng, ginkgo and dong quai with Western medicine from the literature identified in Medline were collected, followed by critical reviews to prepare nineteen items of information for each HDI monograph. A total of 80 sets of validated HDIs met all criteria and were further assessed at the individual reliability level (likely, possible, and unevaluable) and labeled with the "interaction" item. This query system of the website can be operated in both the Chinese and English languages to obtain all monographs on HDIs in the database, including bilingual interaction data. The database of HDI monographs can be updated by simply uploading a new version of the information Excel file. The designed "smart search" module, in addition to the "single search", is convenient for requesting multiple searches. Among the "likely" interactions (n = 26), 50% show negative HDIs. Ten of these can increase the effect of the Western drug, and the others (n = 3) imply that the HDI can be beneficial. CONCLUSIONS: The current study provides a website platform and 80 sets of validated bilingual HDIs involving ginseng, ginkgo and dong quai in an online database. A search of HDI monographs related to these three herbs can be performed with this bilingual, easy-to-use query website, which is feasible for professionals and the general public. The identified reliability level for each HDI may assist readers' decisions regarding whether taking Western medications concomitant with one of three herbal medicinal foods is safe or whether caution is required due to potentially serious outcomes.