Objective: To quantitatively analyze and compare the forces and moments generated by thermoformed polyethylene terephthalate glycol (PETG) and direct-printed TC-85 clear aligners (CAs), with various margin designs, during premolar rotation. Methods: In total, 132 CAs were fabricated and divided into four groups (n = 33 per group). Group C consisted of thermoformed PETG aligners with a 2 mm gingival margin. Group E comprised direct-printed TC-85 aligners with equi-gingival margin, whereas Group G utilized direct-printed TC-85 aligners with 2 mm gingival margins.Finally, Group T featured direct-printed TC-85 aligners with an additional 1 mm thickness at the mesial embrasure. The forces and moments were measured using a 6-axis force/moment transducer at 2°, 3°, and 4° of rotation. All measurements were conducted at 37°C to simulate intraoral conditions. Forces were measured in the buccolingual, anteroposterior, and vertical directions, while moments were measured in the mesiodistal, buccolingual, and rotational planes. Results: The PETG aligners (Group C) showed significantly increased buccal and posterior force across the rotation angles (P < 0.05), whereas the intrusive force remained consistent. In contrast, the TC-85 aligners maintained consistent forces across all rotation angles.Direct-printed aligners demonstrated significantly lower intrusive forces than PETG aligners (P < 0.001). Group T exhibited reduced unwanted forces while maintaining effective rotational moments. Furthermore, all direct-printed aligners showed more predictable force delivery patterns than thermoformed aligners. Conclusions Direct-printed TC-85 aligners demonstrated superior force consistency and reduced unwanted side effects compared with traditional PETG aligners. Although marginal design modifications did not significantly improve rotational efficiency, they effectively reduced unwanted intrusive forces.

Background: The defense and veterans pain rating scale (DVPRS) is a pain assessment tool combining a numerical rating scale (NRS) with descriptive words, colors, and facial expressions. This study aimed to validate the Korean version of the DVPRS (K-DVPRS) for postoperative pain assessment. Methods: This study included patients who underwent elective laparoscopic or robotic abdominal surgery. The original DVPRS was translated into Korean using a forward-backward method. Pain intensities at rest and during coughing were assessed at 24 and 48 hours postoperatively using the NRS and K-DVPRS, respectively. The EuroQol 5-Dimension 5-Level (EQ-5D-5L) questionnaire was also used. The validity, reliability, and responsiveness of the K-DVPRS were evaluated. Results: Of the 174 patients screened, 150 were enrolled, and 148 completed the study. The K-DVPRS had strong convergent validity with the NRS at 24 and 48 hours postoperatively (ρ: 0.75 to 0.78, all P < 0.001). Construct validity was confirmed by significant differences in pain scores based on surgical extent and duration. The internal consistency was acceptable (Cronbach’s alpha: 0.77 and 0.85 at 24 and 48 hours, respectively), and test-retest reliability at 24 hours was excellent (intraclass correlation coefficient: 0.90 at rest and 0.95 during coughing).Responsiveness, measured by Cliff’s effect size, was high from preoperative to 24 hours postoperatively and moderate from 24 to 48 hours. At 48 hours, the K-DVPRS had stronger correlations with the EQ-5D-5L index and EQVAS than with the NRS. Conclusions The K-DVPRS is a valid, reliable, and responsive tool for assessing postoperative pain in Korean patients.

Microglial activation during aging is associated with neuroinflammation and cognitive impairment. Galectin-3 plays a crucial role in microglial activation and phagocytosis. However, the role of galectin-3 in the aged brain is not completely understood. In the present study, we investigated aging-related mechanisms and microglial galectin-3 expression in the mouse hippocampus using female 6-, 12-, and 24-month-old C57BL/6 mice. Western blot analysis revealed neurodegeneration, blood-brain barrier leakage, and increased levels of neuroinflammation-related proteins in 24-month-old mice compared to 6- and 12-month-old mice. Immunohistochemistry revealed an increase in activated microglia in the hippocampus of 24-month-old mice compared to 6- and 12-month-old mice. Furthermore, we found more galectin-3 and triggering receptor expressed on myeloid cells-2-positive microglia in 24-month-old mice compared to 6- and 12-month-old mice. Using primary mouse microglial cells, galectin -3 was also increased by lipopolysaccharide treatment. These findings suggest that galectin-3 may play an important role in microglial activation and neuroinflammation during brain aging.

Atherosclerosis is a major contributor to cardiovascular disease, characterized by inflammation and lipid accumulation in arterial walls, leading to plaque formation. Elevated low-density lipoprotein cholesterol is a primary risk factor for atherosclerosis. All-trans retinoic acid (ATRA), a metabolite of vitamin A, has demonstrated anti-inflammatory effects and potential in regulating vascular injury. 9-cisretinoic acid (9cRA) is an active metabolite of vitamin A and activates the retinoid X receptor. This study investigates whether potassium retinoate (PA9RA), a synthetic combination of ATRA and 9cRA, offers superior efficacy in treating atherosclerosis compared to established treatments such as clopidogrel and atorvastatin. Male ApoE -/- mice were fed a Western-type diet and treated with PA9RA, clopidogrel, or atorvastatin for 10 weeks. The body weight, organ weight, serum biochemistry, and histopathology, including atherosclerotic lesion area and liver steatosis were assessed. PA9RA treatment led to a significant reduction in body weight and inguinal fat, with the 45 mg/kg/day dose showing marked efficacy in decreasing atherosclerotic lesion size and ameliorating liver steatosis. Histopathological evaluation revealed decreased foam cell formation and improved liver histology in PA9RA-treated groups compared to controls. Notable side effects included epidermal hyperplasia and gastric hyperplasia at high doses of PA9RA. PA9RA exhibits superior efficacy over clopidogrel and atorvastatin in ameliorating atherosclerosis and fatty liver in ApoE –/–mice. This study highlights PA9RA's potential as a promising therapeutic agent for atherosclerosis. Further research is needed to elucidate its mechanisms of action and assess long-term safety and efficacy.

Colorectal cancer ranks third in global incidence and is the second leading cause of cancer-related mortality. Doxorubicin, an anthracycline chemotherapeutic drug, is integral to current cancer treatment protocols. However, toxicity and resistance to doxorubicin poses a significant challenge to effective therapy. Panobinostat has emerged as a critical agent in colorectal cancer treatment due to its potential to overcome doxorubicin resistance and enhance the efficacy of existing therapeutic protocols. This study aimed to evaluate the capability of panobinostat to surmount doxorubicin toxicity and resistance in colorectal cancer. Specifically, we assessed the efficacy of panobinostat in enhancing the therapeutic response to doxorubicin in colorectal cancer cells and explored the potential synergistic effects of their combined treatment. Our results demonstrate that the combination treatment significantly reduces cell viability and colony-forming ability in colorectal cancer cells compared to individual treatments. The combination induces significant apoptosis, as evidenced by increased levels of cleaved PARP and cleaved caspase-9, while also resulting in a greater reduction in p-Akt/p-GSK-3β/mTOR expression, along with substantial decreases in c-Myc and SREBP-1 levels, compared to monotherapies. Consistent with the in vitro experimental results, the combination treatment significantly inhibited tumor formation in colorectal cancer xenograft nude mice compared to the groups treated with either agent alone. In conclusion, our research suggests that the panobinostat effectively enhances the effect of doxorubicin and combination of two drugs significantly reduced colorectal cancer tumor growth by targeting the Akt/ GSK-3β/mTOR signaling pathway, indicating a synergistic therapeutic potential of these two drugs in colorectal cancer treatment.

The 5-hydroxytryptamine type3 (5-HT3 ) receptor, a ligand-gated ion channel, plays a critical role in synaptic transmission. It has been implicated in various neuropsychiatric disorders. This study aimed to elucidate the mechanism by which quetiapine, an atypical antipsychotic, could inhibit 5-HT3 receptor-mediated currents in NCB20 neuroblastoma cells. Whole-cell patch-clamp recordings were used to study effects of quetiapine on receptor ion channel kinetics and its competitive antagonism. Co-application of quetiapine shifted 5-HT concentration-response curve rightward, significantly increasing the EC50 without altering the maximal response (Emax ), suggesting a competitive inhibition. Quetiapine's IC50 varied with 5-HT concentration and treatment condition. The IC50 value of quetiapine was 0.58 μM with 3μM 5-HT and 25.23 μM with 10 μM 5-HT, indicating an inverse relationship between quetiapine efficacy and agonist concentration. Pretreatment of quetiapine significantly enhanced its inhibitory potency, reducing its IC50 from 25.23 μM to 0.20 μM.Interaction kinetics experiments revealed an IC50 of 5.17 μM for an open state of the 5-HT3 receptor, suggesting weaker affinity during receptor activation. Quetiapine also accelerated receptor deactivation and desensitization, suggesting that it could stabilize the receptor in non-conducting states. Additionally, quetiapine significantly prolonged recovery from desensitization without affecting recovery from deactivation, demonstrating its selective impact on receptor kinetics. Inhibition of the 5-HT3 receptor by quetiapine was voltage-independent, and quetiapine exhibited no usedependency, further supporting its role as a competitive antagonist. These findings provide insights into inhibitory mechanism of quetiapine on 5-HT3 receptor and suggest its potential therapeutic implications for modulating serotonergic pathways in neuropsychiatric disorders.

Haloperidol is a typical antipsychotic drug effective in alleviating positive symptoms of schizophrenia by blocking dopamine receptor 2 (DR2). However, it is also known to produce neuropsychiatric effects by acting on various targets other than DR. In this study, we investigated effect of haloperidol on function of 5-hydroxytryptamine (5-HT) 3 receptor, a ligand-gated ion channel belonging to the serotonin receptor family using the whole-cell voltage clamp technique and NCB20 neuroblastoma cells. When co-applied with 5-HT, haloperidol inhibited 5-HT3 receptormediated currents in a concentration-dependent manner. A reduction in maximal effect (E max ) and an increase in EC 50 observed during co-application indicated that haloperidol could act as a non-competitive antagonist of 5-HT3 receptors. Haloperidol inhibited the activation of 5-HT3 receptor, while also accelerating their deactivation and desensitization. The inhibitory effect of haloperidol showed no significant difference between pre- and co-application. Haloperidol did not alter the reversal potential of 5-HT3 receptor currents. Furthermore, haloperidol did not affect recovery from deactivation or desensitization of 5-HT3 receptors. It did not show a use-dependent inhibition either. These findings suggest that haloperidol can exert its inhibitory effect on 5-HT3 receptors by allosterically preventing opening of ion channels. This mechanistic insight enhances our understanding of relationships between 5-HT3 receptors and pharmacological actions of antipsychotics.

Purpose: The purpose of this study is to compare scapular alignment, muscle strength around the scapula and neck according to the classification of forward head posture (FHP), round shoulder posture (RSP) and forward head with round shoulder posture (FHRSP). Methods: Scapular alignment, muscle strength around the scapula, and neck strength were measured according to the FHP and RSP alignment classification for male college students. Scapular alignment was confirmed by measuring acromial depression, scapular lateral displacement, and scapular acromion distance. Muscle strength was measured during isometric contraction of upper trapezius (UT), middle trapezius (MT), lower trapezius (LT), and neck muscles. Results: Acromial depression was significantly greater in the FHP (7.20±1.02 cm) than in the RSP group (5.60±1.26 cm) and FHRSP (5.26±1.75 cm) (p＜0.05). The strength of the UT was significantly greater in the FHRSP (1.12±0.12 N/BW) than in the FHP (0.87±0.19 N/BW), and the strength of the LT was significantly greater in the control group (0.20±0.04 N/BW) than in the FHP (0.15±0.03 N/BW) and RSP (0.15±0.04 N/BW) (p＜0.05). The LT:UT ratio was significantly greater in the control group (0.20±0.05) than in the FHRSP (0.15±0.02) (p＜0.05). Conclusion UT strength was higher in RSP subjects with scapular elevation accompanied by FHP than in those with FHP alone. And LT strength and the LT:UT ratio were higher in subjects withno abnormalities in postural alignment. We suggest that these results can serve as a reference for evaluation and intervention according to postural alignment in clinical practice.

Peyronie’s disease is an acquired condition characterized by penile deformities caused by fibrosis of the penile tunica albuginea, leading to symptoms such as penile pain, erectile dysfunction, and other associated issues. Despite extensive research, the pathophysiology of this condition remains poorly understood, and standardized diagnostic and treatment protocols are lacking. While clinical guidelines from several professional societies exist, they do not consistently account for factors such as patient ethnicity, geography, and socioeconomic status. Thus, the Korean Society for Sexual Medicine and Andrology (KSSMA) aimed to develop recommendations tailored to clinical practice in Korea. These recommendations summarize the latest evidence, including clinical practice guidelines from various international professional societies, and represent the consensus opinion of an expert group within the KSSMA. They encompass all aspects of Peyronie’s disease, including the definition, diagnosis, non-surgical interventions, and surgical treatment options.

Purpose: Finasteride and dutasteride are used to treat benign prostatic hyperplasia (BPH) and reduce the risk of developing prostate cancer. Finasteride blocks only the type 2 form of 5-alpha-reductase, whereas dutasteride blocks both type 1 and 2 forms of the enzyme. Previous studies suggest the possibility that dutasteride may be superior to finasteride in preventing prostate cancer. We directly compared the effects of finasteride and dutasteride on the risk of prostate cancer in patients with BPH using a pooled analysis of 15 real-world databases. Materials and Methods: We conducted a multicenter, cohort study of new-users of finasteride and dutasteride. We include patients who were prescribed 5 mg finasteride or dutasteride for the first time to treat BPH and had at least 180 days of prescription. We excluded patients with a history of prostate cancer or a prostate-specific antigen level ≥ 4 ng/mL before the study drug prescription. Cox regression analysis was performed to examine the hazard ratio (HR) for prostate cancer after propensity score (PS) matching. Results: A total of 8,284 patients of new-users of finasteride and 8,670 patients of new-users of dutasteride were included across the 15 databases. In the overall population, compared to dutasteride, finasteride was associated with a lower risk of prostate cancer in both on-treatment and intent-to-treat time-at-risk periods. After 1:1 PS matching, 4,897 patients using finasteride and 4,897 patients using dutasteride were enrolled in the present study. No significant differences were observed for risk of prostate cancer between finasteride and dutasteride both on-treatment (HR=0.66, 95% confidence interval [CI]: 0.44–1.00; p=0.051) and intent-to-treat time-at-risk periods (HR=0.87, 95% CI: 0.67–1.14; p=0.310). Conclusions Using real-world databases, the present study demonstrated that dutasteride was not associated with a lower risk of prostate cancer than finasteride in patients with BPH.