Alzheimer’s disease (AD) is characterized by progressive cognitive deterioration and significant depression. However, the mechanisms linking depression to AD pathology remain unclear. Here, we investigated whether Notch2 signaling mediates depressionlike behaviors in presenilin-2 (PS2) N141I mutant mice, an early-onset AD model. PS2 wild-type (WT) and mutant (MT) mice aged 12-15 months were subjected to unpredictable chronic mild stress (UCMS) for 4 weeks, followed by sucrose preference, tail-hanging, and forced swimming tests. Behavioral assessments showed that UCMS exacerbated anhedonia and immobility only in PS2 MT mice. Molecular analysis revealed concomitant increases in plasma corticosterone, hippocampal γ-secretase activity, and Notch2 expression, and elevated total and phosphorylated glucocorticoid receptor levels in PS2 MT-UCMS mice. Gene expression profiling of human hippocampal datasets confirmed upregulation of NOTCH2 in Alzheimer’s disease and depression.Pharmacological inhibition of γ-secretase and Notch signaling with DAPT normalizes depressive behavior, reduces corticosterone release, attenuates GR phosphorylation, and inhibits Notch2 signaling in PS2 MT mice. These findings identify Notch2 as a pivotal mediator linking chronic stress to molecular changes associated with depression and AD, and suggest that targeting Notch2 signaling may provide therapeutic benefits for comorbid mood and neurodegenerative disorders.

Purpose: This study aimed to investigate the differences in sleep disturbance changes between patients receiving two hormone therapies (“tamoxifen plus ovarian function suppression group [T+OFS group]” versus “tamoxifen group [T group]”) and the chronological changes in sleep disturbances in each group. Methods: Premenopausal women with unilateral breast cancer who underwent surgery and were scheduled to receive hormone therapy (HT) with tamoxifen alone or with tamoxifen plus gonadotropin-releasing hormone (GnRH) agonist for ovarian function suppression were included. The enrolled patients wore an actigraphy watch for two weeks and completed questionnaires (insomnia, sleep quality, physical activity [PA], and quality of life [QOL]) at five time points: immediately before HT and 2, 5, 8, and 11 months after HT. Results: Among the 39 enrolled patients (21 and 18 patients in the T+OFS group and T group, respectively), 25 (17 and 8 patients in the T+OFS group and T group, respectively) were finally analyzed. There were no differences between the two groups in time-dependent changes in insomnia, sleep quality, total sleep time, rapid eye movement sleep rate, QOL, and PA;however, the severity of hot flashes was significantly higher in the T+OFS group than in the T group. Although the interaction between group and time was not significant, insomnia and sleep quality significantly worsened at 2–5 months of HT when changes over time were analyzed within the T+OFS group. In both the groups, PA and QOL were maintained without significant changes. Conclusion Unlike tamoxifen alone, tamoxifen plus GnRH agonist initially worsened insomnia and sleep quality, but gradually improved with long-term follow-up. Patients who initially experience insomnia during tamoxifen plus GnRH agonist administration can be reassured based on the results of this study, and active supportive care may be used during this period.

We aimed to develop evidence-based recommendations for treating axial spondylarthritis (axSpA) in Korea. The development committee was constructed, key clinical questions were determined, and the evidence was searched through online databases including MEDLINE, Embase, Cochrane, KoreaMed, and KMbase. Systematic literature reviews were conducted, quality of evidence was determined, and draft recommendations were formulated according to the Grading of Recommendations Assessment, Development, and Evaluations methodology. Recommendations that reached 80% consensus among a voting panel were finalized. Three principles and 21 recommendations were determined. Recommendations 1 and 2 pertain to treatment strategies, regular disease status assessment, and rheumatologist-steered multidisciplinary management. Recommendations 3 and 4 strongly recommend patient education, exercise, and smoking cessation. Recommendations 5~12 address pharmacological treatment of active disease using nonsteroidal anti-inflammatory drugs, glucocorticoids, sulfasalazine, biologics, and Janus kinase inhibitors.Recommendations 13~16 address treatment in stable disease. We suggest against spa and acupuncture as therapies (Recommendation 17). Recommendations 18 and 19 pertain to total hip arthroplasty and spinal surgery. Monitoring of comorbidities and drug toxicities are recommended (Recommendations 20 and 21). Recommendations for axSpA treatment in a Korean context were developed based on comprehensive clinical questions and evidence. These are intended to guide best practice in the treatment of axSpA.

We aimed to develop evidence-based recommendations for treating axial spondylarthritis (axSpA) in Korea. The development committee was constructed, key clinical questions were determined, and the evidence was searched through online databases including MEDLINE, Embase, Cochrane, KoreaMed, and Kmbase. Systematic literature reviews were conducted, quality of evidence was determined, and draft recommendations were formulated according to the Grading of Recommendations Assessment, Development, and Evaluations methodology. Recommendations that reached 80% consensus among a voting panel were finalized. Three principles and 21 recommendations were determined. Recommendations 1 and 2 pertain to treatment strategies, regular disease status assessment, and rheumatologist-steered multidisciplinary management. Recommendations 3 and 4 strongly recommend patient education, exercise, and smoking cessation. Recommendations 5–12 address pharmacological treatment of active disease using nonsteroidal anti-inflammatory drugs, glucocorticoids, sulfasalazine, biologics, and Janus kinase inhibitors. Recommendations 13–16 address treatment in stable disease. We suggest against spa and acupuncture as therapies (Recommendation 17). Recommendations 18 and 19 pertain to total hip arthroplasty and spinal surgery. Monitoring of comorbidities and drug toxicities are recommended (Recommendations 20 and 21). Recommendations for axSpA treatment in a Korean context were developed based on comprehensive clinical questions and evidence. These are intended to guide best practice in the treatment of axSpA.

KRAS activating mutations, which are present in more than 90% of pancreatic cancers, drive tumor dependency on the RAS/ mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/AKT signaling pathways. Therefore, combined targeting of RAS/MAPK and PI3K/AKT signaling pathways may be required for optimal therapeutic effect in pancreatic cancer.However, the therapeutic efficacy of combined MAPK and PI3K/AKT signaling target inhibitors is unsatisfactory in pancreatic cancer treatment, because it is often accompanied by MAPK pathway reactivation by PI3K/AKT inhibitor. Therefore, we developed an inRas37 antibody, which directly targets the intra-cellularly activated GTP-bound form of oncogenic RAS mutation and investigated its synergistic effect in the presence of the PI3K inhibitor BEZ-235 in pancreatic cancer. In this study, inRas37 remarkably increased the drug response of BEZ-235 to pancreatic cancer cells by inhibiting MAPK reactivation. Moreover, the co-treatment synergistically inhibited cell proliferation, migration, and invasion and exhibited synergistic anticancer activity by inhibiting the MAPK and PI3K pathways. The combined administration of inRas37and BEZ-235 significantly inhibited tumor growth in mouse models. Our results demonstrated that inRas37 synergistically increased the antitumor activity of BEZ-235 by inhibiting MAPK reactivation, suggesting that inRas37 and BEZ-235 co-treatment could be a potential treatment approach for pancreatic cancer patients with KRAS mutations.

Low anterior resection syndrome (LARS) is a condition of anorectal dysfunction that occurs frequently following anal sphincter-preserving surgery for rectal cancer and can reduce the quality of life. In this review, we summarize the main symptoms and pathophysiology of this syndrome and discuss the treatment approaches. Early evaluation and initiation of appropriate treatment postoperatively are crucial. The most frequently used tool to evaluate the severity of LARS is the LARS score, and an anorectal manometer is used for objective evaluation. LARS is believed to be caused by multiple factors, and some of its causes include direct structural damage to the anal sphincter, damage to the innervation, loss of rectoanal inhibitory reflex, and decreased rectal volume and compliance. Diet modifications, medications, pelvic floor muscle training and biofeedback are the primary treatments, and rectal irrigation can be added as a secondary treatment. If LARS symptoms persist even after 1 to 2 years and significantly reduce the quality of life, antegrade irrigation, sacral nerve stimulation or definitive stoma may be considered. High-quality evidence-based studies on LARS treatment are lacking, and randomized controlled trials aimed at developing severity-based treatment algorithms are needed.

Purpose: This prospective, single-center, open-label, therapeutic confirmatory, randomized clinical trial aimed to assess the alleviation of anal pain by applying structured anal skin care including skin protectants in rectal cancer patients with low anterior resection syndrome (LARS) combined with anal pain. Methods: From December 2017 to May 2020, 42 patients with LARS (scores of ≥21) and anal pain (visual analogue scale [VAS] score of ≥3) were randomly assigned and observed for 4 weeks. The conventional treatment consisted of dietary management, sitz baths, prohibition of anal scrubbing, loperamide, and dioctahedral smectite. In the anal care group, cleanser, barrier cream, and barrier spray were applied to the anal skin after defecation following the conventional treatment. The primary outcome was analgesic effect on anal pain after 2 weeks of structured treatment (anal care group) or conventional (control group). The cutoff for analgesic effect was a decrease in the anal pain score (VAS score of ≥2 or ≥30% reduction). Results: As a primary outcome, the analgesic effect was significantly higher in the anal care group (P = 0.034). The incontinence-associated dermatitis skin condition score was significantly improved in the anal care group than control group after 4 weeks (P = 0.023). There were no significant differences in LARS scores and quality of life scores between 2 groups. Conclusion Structured anal skin care has a significant analgesic effect in reducing anal pain and improving anal skin conditions in patients with LARS after rectal cancer surgery.

When a patient represents pain in foot, physician can easily overlook compression neuropathy of peripheral nerve as it is uncommon. Among nerve entrapment syndrome encountered in the foot, selective compression in lateral branch of deep peroneal nerve (DPN) is rare. We report a case of a patient with pain and dysesthesia in dorsolateral foot which turned out as lateral branch of deep peroneal nerve entrapment syndrome caused by talonavicular joint effusion. We would like to share diagnostic work up flow and conservative treatment courses. This case manifests the importance of the deep peroneal nerve and its branches in clinical setting of pain and ankle instability.