Merkel cell carcinoma (MCC) is an aggressive neuroendocrine carcinoma with a high rate of metastasis. MCC is rarely suspected during clinical examination, thus requiring biopsy to establish a pathologic diagnosis. In addition, MCC sometimes occurs in double primary cancers. Although there have been reviews on double primary cancers, only a few cases involving MCC have been described. Herein, we report a case of a 54-year-old female patient who presented to our clinic with a diagnosis of earlobe MCC following an excisional biopsy performed by another clinic. Further evaluation, including chest imaging, revealed a mass in the lung. The patient underwent a wide excision of the right earlobe, and video-assisted thoracic surgery on the lung. Pathology confirmed MCC in the right earlobe and adenocarcinoma in the lung. The patient underwent postoperative adjuvant chemotherapy followed by radiotherapy. Up to this point, 3 years after the surgery, there has been no evidence of recurrence.

In response to the Mpox domestic epidemic, South Korea initiated a nationwide vaccination program in May 2023, administering a 0.1 mL intradermal dose of JYNNEOS (Modified Vaccinia Ankara vaccine, Bavarian Nordic) to a high-risk group. To investigate the adverse reactions after intradermal JYNNEOS vaccination, an anonymous online survey was conducted at the National Medical Center from May 22 to July 31, 2023. Overall, 142 individuals responded. Over 80% of the respondents reported local reactions of predominantly mild severity. The predominant local reactions were pruritus, redness, and swelling; their incidence rates after the first dose were 66.2%, 48.1%, and 49.4%, respectively; the corresponding rates after the second dose were 69.2%, 60.6%, and 53.8%. Fewer respondents reported systemic symptoms. The most common systemic symptom was fatigue, the incidence rates of which after the first and second doses were 37.7% and 24.6%, respectively. Overall, the intradermally administered JYNNEOS vaccine appeared well tolerated.

Purpose: There is a lack of a report about the trajectories of allergen sensitization, although it is important to understand the change of allergen sensitization to manage allergic disease. This study aimed to analyze the change and trajectories of allergen sensitization in children with respiratory and allergic diseases. Methods: From 2006 to 2020, children with respiratory and allergic diseases or screened for allergic sensitization were evaluated. We visualized the alterations and the trajectories of allergen sensitization using stacked area graphs, box plots, and Sankey diagrams. Results: A total of 2,804 subjects were included, and allergic rhino-conjunctivitis was diagnosed in 1,931 children (68.9%). The mean age for the first test was 4.1 years, and that for the second test was 6.5 years. Children sensitized to class 1 food allergen before age 5 showed sensitizations more for other allergens and at a younger age after age 5 than children who were not. The atopic tendency continued once it had been obtained before the early school age in the persistence or the new development of sensitization. Conclusion Allergen sensitization has changed over time and has shown different patterns according to age. Its trajectory has taken a wide variety of courses in children with respiratory and allergic diseases until the early school age. These changes reflect the allergic diseases and socio-environmental characteristics of children and adolescents.

The programmed cell death ligand 1 (PD-L1) and its receptor programmed cell death 1 (PD-1) deliver inhibitory signals to regulate immunological tolerance during immune-mediated diseases. However, the role of PD-1 signaling and its blockade effect on human dental pulp stem cells (hDPSCs) differentiation into the osteo-/odontogenic lineage remain unknown. We show here that PD-L1 expression, but not PD-1, is downregulated during osteo-/odontogenic differentiation of hDPSCs. Importantly, PD-L1/PD-1 signaling has been shown to negatively regulate the osteo-/odontogenic differentiation of hDPSCs. Mechanistically, depletion of either PD-L1 or PD-1 expression increased ERK and AKT phosphorylation levels through the upregulation of Ras enzyme activity, which plays a pivotal role during hDPSCs osteo-/odontogenic differentiation. Treatment with nivolumab (a human anti-PD-1 monoclonal antibody), which targets PD-1 to prevent PD-L1 binding, successfully enhanced osteo-/odontogenic differentiation of hDPSCs through enhanced Ras activity-mediated phosphorylation of ERK and AKT. Our findings underscore that downregulation of PD-L1 expression accompanies during osteo-/odontogenic differentiation, and hDPSCs-intrinsic PD-1 signaling inhibits osteo-/odontogenic differentiation. These findings provide a significant basis that PD-1 blockade could be effective immunotherapeutic strategies in hDPSCs-mediated dental pulp regeneration.
B7-H1 Antigen/metabolism* ; Dental Pulp/metabolism* ; Humans ; Programmed Cell Death 1 Receptor/metabolism* ; Regeneration ; Stem Cells

BACKGROUND/OBJECTIVES: The effectiveness of natural compounds in improving athletic ability has attracted attention in both sports and research. Gynostemma pentaphyllum (Thunb.) leaves are used to make traditional herbal medicines in Asia. The active components of G.pentaphyllum, dammarane saponins, or gypenosides, possess a range of biological activities. On the other hand, the anti-fatigue effects from G. pentaphyllum extract (GPE) and its effective compound, gypenoside L (GL), remain to be determined.MATERIALS/METHODS: This study examined the effects of GPE on fatigue and exercise performance in ICR mice. GPE was administered orally to mice for 6 weeks, with or without treadmill training. The biochemical analysis in serum, glycogen content, mRNA, and protein expressions of the liver and muscle were analyzed. RESULTS: The ExGPE (exercise with 300 mg/kg body weight/day of GPE) mice decreased the fat mass percentage significantly compared to the ExC mice, while the ExGPE showed the greatest lean mass percentage compared to the ExC group. The administration of GPE improved the exercise endurance and capacity in treadmill-trained mice, increased glucose and triglycerides, and decreased the serum creatine kinase and lactate levels after intensive exercise. The muscle glycogen levels were higher in the ExGPE group than the ExC group. GPE increased the level of mitochondrial biogenesis by enhancing the phosphorylation of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) protein and the mRNA expression of nuclear respiratory factor 1, mitochondrial DNA, peroxisome proliferatoractivated receptor-δ, superoxide dismutase 2, and by decreasing the lactate dehydrogenase B level in the soleus muscle (SOL). GPE also improved PGC-1α activation in the SOL significantly through AMPK/p38 phosphorylation. CONCLUSIONS These results showed that GPE supplementation enhances exercise performance and has anti-fatigue activity. In addition, the underlying molecular mechanism was elucidated. Therefore, GPE is a promising candidate for developing functional foods and enhancing the exercise capacity and anti-fatigue activity.

BACKGROUND/OBJECTIVES: Peroxisome proliferator-activated receptor-gamma co-activator-1α (PGC-1α) has a central role in regulating muscle differentiation and mitochondrial metabolism. PGC-1α stimulates muscle growth and muscle fiber remodeling, concomitantly regulating lactate and lipid metabolism and promoting oxidative metabolism.Gynostemma pentaphyllum (Thumb.) has been widely employed as a traditional herbal medicine and possesses antioxidant, anti-obesity, anti-inflammatory, hypolipemic, hypoglycemic, and anticancer properties. We investigated whether G. pentaphyllum extract (GPE) and its active compound, gypenoside L (GL), affect muscle differentiation and mitochondrial metabolism via activation of the PGC-1α pathway in murine C2C12 myoblast cells.MATERIALS/METHODS: C2C12 cells were treated with GPE and GL, and quantitative reverse transcription polymerase chain reaction and western blot were used to analyze the mRNA and protein expression levels. Myh1 was determined using immunocytochemistry.Mitochondrial reactive oxygen species generation was measured using the 2′7′-dichlorofluorescein diacetate assay. RESULTS: GPE and GL promoted the differentiation of myoblasts into myotubes and elevated mRNA and protein expression levels of Myh1 (type IIx). GPE and GL also significantly increased the mRNA expression levels of the PGC-1α gene (Ppargc1a), lactate metabolismregulatory genes (Esrra and Mct1), adipocyte-browning gene fibronectin type III domaincontaining 5 gene (Fndc5), glycogen synthase gene (Gys), and lipid metabolism gene carnitine palmitoyltransferase 1b gene (Cpt1b). Moreover, GPE and GL induced the phosphorylation of AMP-activated protein kinase, p38, sirtuin1, and deacetylated PGC-1α. We also observed that treatment with GPE and GL significantly stimulated the expression of genes associated with the anti-oxidative stress response, such as Ucp2, Ucp3, Nrf2, and Sod2<>/i>. CONCLUSIONS The results indicated that GPE and GL enhance exercise performance by promoting myotube differentiation and mitochondrial metabolism through the upregulation of PGC-1α in C2C12 skeletal muscle.

Background: Gaucher disease (GD) is an autosomal recessive disorder characterized by excessive accumulation of glucosylceramide in multiple organs. This study was performed to determine the detection rate of GD in a selected patient population with unexplained splenomegaly in Korea. Methods: This was a multicenter, observational study conducted at 18 sites in Korea between December 2016 and February 2020. Adult patients with unexplained splenomegaly were enrolled and tested for β-glucosidase enzyme activity on dried blood spots (DBS) and in peripheral blood leukocytes. Mutation analysis was performed if the test was positive or indeterminate for the enzyme assay. The primary endpoint was the percentage of patients with GD in patients with unexplained splenomegaly. Results: A total of 352 patients were enrolled in this study (male patients, 199; mean age, 48.42 yr). Amongst them, 14.77% of patients had concomitant hepatomegaly. The most common sign related to GD was splenomegaly (100%), followed by thrombocytopenia (44.32%) and, anemia (40.91%). The β-glucosidase activity assay on DBS and peripheral leukocytes showed abnormal results in sixteen and six patients, respectively. Eight patients were tested for the mutation, seven of whom were negative and one patient showed a positive mutation analysis result. One female patient who presented with splenomegaly and thrombocytopenia was diagnosed with type 1 GD. The detection rate of GD was 0.2841% (exact 95% CI, 0.0072‒). Conclusion The detection rate of GD in probable high-risk patients in Korea was lower than expected.However, the role of hemato-oncologists is still important in the diagnosis of GD.

Purpose: This study aimed to conduct a comparison between 2D thin section intermediate-weighted Dixon turbo spin echo (TSE), 3D intermediate-weighted SPACE (sampling perfection with application-optimized contrasts using flip angle evolutions) TSE, and 2D fat-suppressed T2-weighted TSE in terms of their image quality and diagnostic performance for ankle ligament evaluation. Materials and Methods: Thirty-eight ankle MRI studies were retrospectively analyzed. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of the multiplanar reformation images of the sequences were obtained. For each sequence, the subjective image quality and the diagnostic performance for ankle ligament tear were analyzed. Results: The Dixon demonstrated the highest CNR both between ligament and fluid and between ligament and bone marrow. The 3D SPACE showed the highest SNR of the ligament. Regarding subjective image quality, it was significantly higher in the T2-weighted image than it was in the SPACE (p < 0.05), while there was no significant difference between the Dixon and the SPACE. The Dixon showed the highest sensitivity for anterior talofibular ligament (ATFL) tear (80.0%; 95% confidence interval [CI], 64.4–92.3) and deep deltoid ligament (DL) tear (86.4%; 95% CI, 65.1–97.1), and it showed the highest specificity for ATFL tear (70.2%; 95% CI, 59.3–79.7). The interobserver agreement was moderate to good (intraclass correlation coefficient [ICC], 0.50–0.93) in most cases except for the SNR of deep DL (ICC of 0.35–0.62). Conclusion For ankle ligament evaluation, the 2D thin section Dixon provides adequate image quality with high SNR and CNR and the highest sensitivity for detecting tears.

Purpose: The purpose of this study is to investigate the stress response and sleep state of the new patients who visit the hospital for prosthodontic treatment due to tooth loss to make reference to further treatment direction. Materials and methods: Examinations, consultations, and surveys were conducted on 236 patients (94 males, 142 females, and 24-86 years old), who newly registered at the department of prosthodontics at Pusan national university hospital, for 2 years from 2018. The number of remaining teeth, edentulous arch, possibility of mastication, and future prosthetic treatment directions were recorded. The visual analogue scale (VAS), stress response inventory (SRI) and Insomnia severity index (ISI) were used as tools to measure patient’s subjective discomfort, stress response, and sleep status. Results: Among the entire prosthodontic patient group, the average value of ‘fatigue’ was significantly higher among the 7 items of SRI, and the value of ‘aggression’ was significantly lower (P<.001). There are a significant difference between the edentulous and full dentition in the oral discomfort value measured by VAS (P=.004). In cases where less than 20 teeth remain, mastication is impossible, and patients who are planning treatment with removable prostheses, VAS value and ‘depression’ and ‘fatigue’ values in SRI were higher than those in the reverse case (P<.05).The patients showed severe level in VAS value have high value of ‘tension’, ‘somatization’, ‘depression’, ‘fatigue’and ‘frustration’in SRI than non-serious patients (P<.05). Clinical insomnia occurred in 11.4% of all patients, and women had significantly lower sleep quality than men (P=.044). Patients with insomnia showed significantly higher scores on the VAS value and all 7 SRI items than those of normal sleepers (P<.05). Conclusion The new prosthetics had high ‘fatigue’ value among the 7 items of SRI. The oral condition, number of residual teeth and mastication function and clinical insomnia affected oral discomfort and the stress response.

Purpose: The purpose of this study is to investigate the stress response and sleep state of the new patients who visit the hospital for prosthodontic treatment due to tooth loss to make reference to further treatment direction. Materials and methods: Examinations, consultations, and surveys were conducted on 236 patients (94 males, 142 females, and 24-86 years old), who newly registered at the department of prosthodontics at Pusan national university hospital, for 2 years from 2018. The number of remaining teeth, edentulous arch, possibility of mastication, and future prosthetic treatment directions were recorded. The visual analogue scale (VAS), stress response inventory (SRI) and Insomnia severity index (ISI) were used as tools to measure patient’s subjective discomfort, stress response, and sleep status. Results: Among the entire prosthodontic patient group, the average value of ‘fatigue’ was significantly higher among the 7 items of SRI, and the value of ‘aggression’ was significantly lower (P<.001). There are a significant difference between the edentulous and full dentition in the oral discomfort value measured by VAS (P=.004). In cases where less than 20 teeth remain, mastication is impossible, and patients who are planning treatment with removable prostheses, VAS value and ‘depression’ and ‘fatigue’ values in SRI were higher than those in the reverse case (P<.05).The patients showed severe level in VAS value have high value of ‘tension’, ‘somatization’, ‘depression’, ‘fatigue’and ‘frustration’in SRI than non-serious patients (P<.05). Clinical insomnia occurred in 11.4% of all patients, and women had significantly lower sleep quality than men (P=.044). Patients with insomnia showed significantly higher scores on the VAS value and all 7 SRI items than those of normal sleepers (P<.05). Conclusion The new prosthetics had high ‘fatigue’ value among the 7 items of SRI. The oral condition, number of residual teeth and mastication function and clinical insomnia affected oral discomfort and the stress response.