Combination Therapy with Monoamine Oxidase Inhibitors and Other Antidepressants or Stimulants: Strategies for the Management of Treatment‐Resistant Depression

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111275/1/phar1576.pd

Preliminary Validation Study of the Korean Version of the DSM-5 Level 2 Cross-Cutting Symptom Measure: Depression and Irritability for Parents of Children Aged 6-17 Years

Objectives: This study investigated the reliability and validity of the Korean version of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) Level 2 Cross-Cutting Symptom Measure-Patient-Reported Outcomes Measurement Information System (PROMIS)-Depression and the Irritability for parents of children aged 6-17 years. Methods: Participants were 190 children diagnosed with depressive disorder (n=14), anxiety disorder (n=21), attention-deficit/hyperactivity disorder (ADHD; n=111), ADHD with anxious depression (n=13), and tic disorder with somatic symptoms (n=31). Patients were 8-15 years of age. The participants' mothers completed the Korean versions of the DSM-5 Level 2 Cross-Cutting Symptom Measure-PROMIS Depression and Irritability (Affective Reactivity Index, ARI), and the Korean Child Behavior Checklist (K-CBCL). Using these data, we calculated the reliability coefficient and examined the concurrent and discriminant validity of the PROMIS Depression and the Irritability (ARI) scales for assessing depression and irritability in children. Results: The reliability coefficienT of the PROMIS Depression scale (Cronbach's alpha) was 0.93. The correlation coefficient with the KCBCL DSM emotional problem score was 0.71. The PROMIS Depression scale significantly discriminated children with depressive disorders from those with other conditions. The reliability coefficient of the Irritability (ARI) scale was 0.91, suggesting its high reliability. Conclusion: Our results suggest that the Korean version of the DSM-5 Level 2 Cross-Cutting Symptom Measure for Depression and Irritability Scales for parents of children aged 6-17 years is reliable and valid and may be an efficient alternative to the K-CBCL.N

Experimental determination of carbon content in hydrothermal carbonization (HTC) liquid

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TRAIL & EGFR affibody dual-display on a protein nanoparticle synergistically suppresses tumor growth

The TNF-related apoptosis-inducing ligand (TRAIL) is a promising anticancer drug candidate because it selectively binds to the proapoptotic death receptors, which are frequently overexpressed in a wide range of cancer cells, subsequently inducing strong apoptosis in these cells. However, the therapeutic benefit of TRAIL has not been clearly proven, mainly because of its poor pharmacokinetic characteristics and frequent resistance to its application caused by the activation of a survival signal via the EGF/epidermal growth factor receptor (EGFR) signaling pathway. Here, a lumazine synthase protein cage nanoparticle isolated from Aquifex aeolicus (AaLS) was used as a multiple ligand-displaying nanoplatform to display polyvalently both TRAIL and EGFR binding affibody molecules (EGFRAfb) via a SpyTag/SpyCatcher protein-ligation system, to form AaLS/TRAIL/EGFRAfb. The dual-ligand-displaying AaLS/TRAIL/EGFRAfb exhibited a dramatically enhanced cytotoxicity on TRAIL-resistant and EGFR-overexpressing A431 cancer cells in vitro, effectively disrupting the EGF-mediated EGFR survival signaling pathway by blocking EGF/EGFR binding as well as strongly activating both the extrinsic and intrinsic apoptotic pathways synergistically. The AaLS/TRAIL/EGFRAfb selectively targeted A431 cancer cells in vitro and actively reached the tumor sites in vivo. The A431 tumor-bearing mice treated with AaLS/TRAIL/EGFRAfb exhibited a significant suppression of the tumor growth without any significant side effects. Collectively, these findings showed that the AaLS/TRAIL/EGFRAfb could be used as an effective protein-based therapeutic for treating EGFR-positive cancers, which are difficult to manage using mono-therapeutic approaches