Background: Psoriasis is a multifactorial, chronic immunological disease, in which a specific allele HLA-Cw6 is associated with various clinical manifestations. However, information regarding this genetic factor in Korean patients with psoriasis remains limited. Objective: We aimed to explore the differences in clinical patterns and treatment responsiveness, depending on the expression of HLA-Cw6, in Korean patients with psoriasis. Methods: We divided patients into two groups, namely HLA-Cw6-positive and HLACw6-negative, based on the HLA-Cw6 allelic analysis using the single specific primerpolymerase chain reaction method. All clinical information regarding these patients was collected in a retrospective manner. Next, we evaluated the levels of serum Th17-related cytokines in 34 patients diagnosed with psoriasis using a multiplex immunoassay. Finally, we performed immunohistochemical staining of interleukin (IL)-22 and IL-31, as these cytokines showed the maximum differential expression between the HLA-Cw6 positive and negative groups. Results: HLA-Cw6 positive and negative groups comprised of 13 and 21 patients, respectively. HLA-Cw6-positive group had more chance of having metabolic comorbidities (76.9% for HLA-Cw6-positive group; 28.6% for HLA-Cw6-negative group; p=0.002). Also, HLA-Cw6-positive group showed significantly higher treatment response (38.5% in positive group showed Psoriasis Area and Severity Index 90% improvement compared to 4.8% in the negative group; p=0.012). However, all Th17-related cytokines were not significantly different across the two groups. Furthermore, IL-22 and IL-31 immunohistochemical staining did not correlate with the serum cytokines levels. Conclusion HLA-Cw6 types can be associated with disease severity, comorbidities, and treatment responsiveness in Korean patients with psoriasis.

The primary somatosensory (S1) cortex plays a key role in distinguishing different sensory stimuli. Vibrotactile touch information is conveyed from the periphery to the S1 cortex through three major classes of mechanoreceptors: slowly adapting type 1 (SA1), rapidly adapting (RA), and Pacinian (PC) afferents. It has been a long-standing question whether specific populations in the S1 cortex preserve the peripheral segregation by the afferent submodalities. Here, we investigated whether S1 neurons exhibit specific responses to two distinct vibrotactile stimuli, which excite different types of mechanoreceptors (e.g., SA1 and PC afferents). Using in vivo two-photon microscopy and genetically encoded calcium indicator, GCaMP6s, we recorded calcium activities of S1 L2/3 neurons. At the same time, static (<1 Hz) and dynamic (150 Hz) vibrotactile stimuli, which are known to excite SA1 and PC, respectively, were pseudorandomly applied to the right hind paw in lightly anesthetized mice. We found that most active S1 neurons responded to both static and dynamic stimuli, but more than half of them showed preferred responses to either type of stimulus. Only a small fraction of the active neurons exhibited specific responses to either static or dynamic stimuli. However, the S1 population activity patterns by the two stimuli were markedly distinguished. These results indicate that the vibrotactile inputs driven by excitation of distinct submodalities are converged on the single cells of the S1 cortex, but are well discriminated by population activity patterns composed of neurons that have a weighted preference for each type of stimulus.

Microglia, the resident macrophages in the central nervous system, can rapidly respond to pathological insults. Toll-like receptor 2 (TLR2) is a pattern recognition receptor that plays a fundamental role in pathogen recognition and activation of innate immunity. Although many previous studies have suggested that TLR2 contributes to microglial activation and subsequent pathogenesis following brain tissue injury, it is still unclear whether TLR2 has a role in microglia dynamics in the resting state or in immediate-early reaction to the injury in vivo. By using in vivo two-photon microscopy imaging and Cx3cr1(GFP/+) mouse line, we first monitored the motility of microglial processes (i.e. the rate of extension and retraction) in the somatosensory cortex of living TLR2-KO and WT mice; Microglial processes in TLR2-KO mice show the similar motility to that of WT mice. We further found that microglia rapidly extend their processes to the site of local tissue injury induced by a two-photon laser ablation and that such microglial response to the brain injury was similar between WT and TLR2-KO mice. These results indicate that there are no differences in the behavior of microglial processes between TLR2-KO mice and WT mice when microglia is in the resting state or encounters local injury. Thus, TLR2 might not be essential for immediate-early microglial response to brain tissue injury in vivo.
Animals ; Brain ; Brain Injuries ; Central Nervous System ; Immunity, Innate ; Laser Therapy ; Macrophages ; Mice ; Microglia ; Microscopy ; Somatosensory Cortex ; Toll-Like Receptor 2* ; Toll-Like Receptors*

The aim of this study was to compare the degree of conversion and polymerization shrinkage of low and high viscosity bulk-fill giomer-based and resin-based composites. Two bulk-fill giomer (Beautifil Bulk Restorative (BBR), Beautifil Bulk Flowable (BBF)), two bulk-fill (Tetric N-Ceram Bulk-fill (TBF), SureFil SDR flow (SDR)) and two conventional resin composites (Tetric N-Ceram (TN), Tetric N-flow (TF)) were selected for this study. The degree of conversion was measured by using Fourier transform infrared spectroscopy. Polymerization shrinkage was measured with the linometer. For all depth, BBR had the lowest degree of conversion and SDR had the highest. At 4 mm, the degree of conversion of low and high viscosity bulk-fill giomer resin composites was lower than that of bulk-fill resin composites (p < 0.05). At the depth between 2 mm and 4 mm, there were significant difference with TBF, TN and TF (p < 0.05), while no significant difference in the degree of conversion was measured for BBR, BBF and SDR. Polymerization shrinkage of six resin composites decreased in the following order: TF > SDR > BBF > TBF > TN and BBR (p < 0.05). Polymerization shrinkage of bulk-fill giomer resin composites was lower than that of bulk-fill resin composites (p < 0.05). From this study, it is found that the bulk-fill giomer resin composites and TBF were not sufficiently cured in 4 mm depth. The degree of conversion of low and high viscosity bulk-fill giomer resin composites was significantly lower than bulk-fill resin composites in both 2 mm and 4 mm depths. Therefore, such features of bulk-fill giomer resin composites should be carefully considered in clinical application.
Polymerization ; Polymers ; Spectroscopy, Fourier Transform Infrared ; Viscosity

Objective: This study aimed to investigate the feasibility of ultrafast magnetic resonance imaging (MRI) and radiomic features derived from breast MRI for predicting the upstaging of ductal carcinoma in situ (DCIS) diagnosed using percutaneous needle biopsy. Materials and Methods: Between August 2018 and June 2020, 95 patients with 98 DCIS lesions who underwent preoperative breast MRI, including an ultrafast sequence, and subsequent surgery were included. Four ultrafast MRI parameters were analyzed:time-to-enhancement, maximum slope (MS), area under the curve for 60 s after enhancement, and time-to-peak enhancement.One hundred and seven radiomic features were extracted for the whole tumor on the first post-contrast T1WI and T2WI using PyRadiomics. Clinicopathological characteristics, ultrafast MRI findings, and radiomic features were compared between the pure DCIS and DCIS with invasion groups. Prediction models, incorporating clinicopathological, ultrafast MRI, and radiomic features, were developed. Receiver operating characteristic curve analysis and area under the curve (AUC) were used to evaluate model performance in distinguishing between the two groups using leave-one-out cross-validation. Results: Thirty-six of the 98 lesions (36.7%) were confirmed to have invasive components after surgery. Compared to the pure DCIS group, the DCIS with invasion group had a higher nuclear grade (P < 0.001), larger mean lesion size (P = 0.038), larger mean MS (P = 0.002), and different radiomic-related characteristics, including a more extensive tumor volume; higher maximum gray-level intensity; coarser, more complex, and heterogeneous texture; and a greater concentration of high graylevel intensity. No significant differences in AUCs were found between the model incorporating nuclear grade and lesion size (0.687) and the models integrating additional ultrafast MRI and radiomic features (0.680–0.732). Conclusion High nuclear grade, larger lesion size, larger MS, and multiple radiomic features were associated with DCIS upstaging.However, the addition of MS and radiomic features to the prediction model did not significantly improve the prediction performance.

Background: Psoriasis is a chronic relapsing inflammatory disease, with several cytokines related to its pathophysiology and clinical manifestations, such as disease activity, severity, and clinical subtype. However, there is limited information regarding Korean psoriasis patients.
Objective
We investigated the association between serum inflammatory cytokines and clinical characteristics of psoriasis, including treatment modalities. Methods: We evaluated the serum Th17-related cytokine levels of 70 patients diagnosed with psoriasis using a multiplex immunoassay. All clinical information of patients was collected by reviewing electronic medical records and photo documentation in a retrospective manner. Results: The serum IL-23 level was significantly higher in the young age group (＜40 years), and the IL-6, TNFβ, and IL-28A levels were significantly higher in the early onset group (＜40 years). In addition, patients with moderate-to-severe psoriasis (PASI≥10 and body surface area ≥10%) exhibited significantly lower serum IL-28A levels. We observed high serum TNF-α and CCL20 levels in patients with metabolic comorbidities and those with psoriatic arthritis, respectively, and biologics use and systemic treatment modality were also significantly associated with the serum levels of some cytokines. Conclusion Disease severity, comorbidities, presence of psoriatic arthritis, and treatment responsiveness might affect the inflammatory cytokine levels in psoriasis patients. Therefore, the serum cytokine levels can be used to predict the severity or treatment responsiveness of psoriasis patients.

Background: Interleukin (IL)-17 and IL-23 inhibitors have helped achieve clear skin in many patients with psoriasis. However, real-world data to compare short- and long-term efficacy of these biologics in Korean patients are lacking. Objective: To compare short- and long-term efficacy of IL-17A and IL-23 inhibitors in patients with moderateto-severe psoriasis. Methods: We retrospectively evaluated efficacy of IL-17A and IL-23 inhibitors among patients treated at Ajou University Hospital from 2017 to 2022. The specific agents studied were as follows: secukinumab, 32 patients; ixekizumab, four patients; guselkumab, 13 patients; and risankizumab, 31 patients. Patients who were followed up for less than a year or changed biologics were excluded. Results: The rates of psoriasis area and severity index (PASI) 90 achievement of secukinumab were 62.5%, 86.7%, 89.3%, 80.8%, and 70.8% at weeks 16, 40, 88, 112, and 136, respectively. For ixekizumab, the PASI90 achievement rates were 75%, 100%, 75%, and 100% at weeks 16, 40, 64, and 88, respectively. The PASI90 achievement rates of guselkumab were 53.8%, 76.9%, 72.7%, and 77.8% at weeks 20, 44, 68, and 92, respectively. For risankizumab, PASI90 achievement rates were 69.7%, 90.0%, 93.7%, and 100% at weeks 28, 52, 76, and 100, respectively. Before 52 weeks, PASI90 achievement was significantly lower with guselkumab than with secukinumab (hazardratio=0.22). After 52 weeks, PASI90 achievement was significantly higher with risankizumab than with secukinumab (hazard ratio=2.00). Conclusion PASI90 was achieved faster with IL-17A inhibitors than with IL-23 inhibitors. However, IL-23 inhibitors afforded the maintenance of a higher PASI score after 52 weeks.

Cancer chemotherapy often triggers peripheral neuropathy in patients, leading to neuropathic pain in the extremities. While previous research has explored various nerve stimulation to alleviate chemotherapy-induced peripheral neuropathy (CIPN), evidence on the effectiveness of noninvasive auricular vagus nerve stimulation (aVNS) remains uncertain. This study aimed to investigate the efficacy of non-invasive aVNS in relieving CIPN pain. To induce CIPN in experimental animals, oxaliplatin was intraperitoneally administered to rats (6 mg/kg). Mechanical and cold allodynia, the representative symptoms of neuropathic pain, were evaluated using the von Frey test and acetone test, respectively. The CIPN animals were randomly assigned to groups and treated with aVNS (5 V, square wave) at different frequencies (2, 20, or 100 Hz) for 20 minutes. Results revealed that 20 Hz aVNS exhibited the most pronounced analgesic effect, while 2 or 100 Hz aVNS exhibited weak effects. Immunohistochemistry analysis demonstrated increased c-Fos expression in the locus coeruleus (LC) in the brain of CIPN rats treated with aVNS compared to sham treatment. To elucidate the analgesic mechanisms involving the adrenergic descending pathway, α 1 -, α 2 -, or β-adrenergic receptor antagonists were administered to the spinal cord before 20 Hz aVNS. Only the β-adrenergic receptor antagonist, propranolol, blocked the analgesic effect of aVNS.These findings suggest that 20 Hz aVNS may effectively alleviate CIPN pain through β-adrenergic receptor activation.

Background: Nickel is a leading cause of allergic contact dermatitis. Patients with nickel allergy may suffer from persistent dermatitis not only through contact with nickel-plated items but also through ingestion of nickel-containing food. Objective: This study aimed to evaluate the current nickel content in Korean food products and provide more up-to-date Korean nickel-restricted diets that would increase patient compliance. Methods: The most frequently consumed food items were selected with replicates. Food samples were prepared according to the practices of normal consumers. The solid specimens were finely ground, and the liquid specimens were homogenized using a sterilized mixer. Tea bags were brewed in 100 mL of distilled water at 100 °C for 5 minutes. Solid (0.5 g) and liquid (2 g) specimens were subjected to microwave-assisted nitric acid digestion using inductively coupled plasma-mass spectrometry. Results: In total, 147 samples were collected from different food categories, including plant-based products, animal-based products, packaged foods, and drinks. Cocoa powder had the highest concentration of nickel (1.56 mg/kg), which is consistent with the results of previous studies. Soy products such as fermented soybean paste (Doenjang) (1.16 mg/kg), fermented soybean with red chili paste (Ssamjang) (0.67 mg/kg), and tofu (0.37 mg/kg) had elevated concentration of nickel. Moreover, nut-derived products such as chocolate (1.10 mg/kg), ground coffee (0.86 mg/kg), almond (0.84 mg/kg), and peanuts (0.64 mg/kg) contained elevated nickel concentration. Conclusion The nickel content in food constantly changes depending on the food processing procedures and place of origin. Therefore, revising the nickel-restricted diet is necessary to enhance patients’ understanding of it and help reduce dietary nickel intake.