Background: Acral melanoma is the most common subtype of melanoma among Koreans, and regional or distant metastasis is an indicator of poor prognosis. Yes-associated protein (YAP), a key effector of the Hippo pathway, is known to induce tumor progression and metastasis in various cancers. Objective: We aimed to analyze the clinical and histopathological characteristics of acral melanoma among Koreans and to evaluate their association with YAP expression. Methods: This retrospective review included 27 patients with acral melanoma. Clinical features including age, sex, lesion site, and stage were obtained from the medical records and images. Biopsy slides of patients with acral melanoma were reviewed, and immunohistochemical staining for YAP was performed. Results: The rate of YAP expression was significantly higher in patients having acral melanoma with regional or distant lymph node (LN) metastasis than in those without metastasis (n=4/5, 80.0% vs. n=2/22, 9.1%; p=0.004). Histopathologically, the rate of YAP expression was higher in patients having acral melanoma with lymphovascular invasion than in those without lymphovascular invasion (n=4/8, 50.0% vs. n=2/19, 10.5%; p=0.044). Among the 27 lesions, 14 (51.9%) were on stress-bearing sites such as the forefoot and heel. However, the rate of YAP expression did not differ significantly between weight-bearing and non-weight-bearing locations (p=0.834). Conclusion YAP expression is significantly associated with metastasis, especially LN metastasis, in patients with acral melanoma. Therefore, YAP expression may be used as a prognostic factor for LN metastasis and a target for novel treatments in patients with melanoma.

Background: We investigated whether fasting glucose (FG) variability could predict the risk of dementia. Methods: This cohort study analyzed data from Koreans with diabetes after at least three health examinations by the Korean National Health Insurance Corporation between 2005 and 2010, which included at least one examination between 2009 and 2010. A total of 769,554 individuals were included, excluding those aged <40 years and those with dementia. FG variability was measured using the variability independent of the mean (FG-VIM). The incidence of dementia was defined by the International Classification of Diseases 10th Revision codes and prescription of anti-dementia medication and was subdivided into Alzheimer’s disease (AD) and vascular dementia (VD). Results: During the 6.9-year follow-up, 54,837, 41,032, and 6,892 cases of all-cause dementia, AD, and VD, respectively, were identified. Cox proportional regression analyses showed that as the FG-VIM quartile increased, the risk of dementia serially increased after adjustment for metabolic factors, income status, and diabetes-related characteristics, including the mean FG. Participants in FG-VIM quartile 4 showed a 18%, 19%, and 17% higher risk for all-cause dementia, AD, and VD, respectively, than those in quartile 1; this particularly included non-obese patients with a longer duration of diabetes, high FG levels, dyslipidemia, and those taking glucose-lowering medications. Conversely, the baseline FG status and dementia showed a U-shaped association. Conclusion Increased FG variability over 5 years can predict the risk of dementia in individuals with diabetes in Korea. This finding was more pronounced in patients with less favorable metabolic profiles.

Background: Alopecia areata (AA) is an autoimmune disease characterized by chronic inflammation, the pathogenesis of which is unknown. Stress is believed to play a role; however, evidence remains insufficient. A recent study showed that substance P (SP) damaged hair follicles by causing neurogenic inflammation, activating perifollicular mast cells, and inducing keratinocyte apoptosis. Objective: We aimed at studying the role of SP in AA pathogenesis. We investigated the SP levels in the lesional scalp tissues and serum. We also studied the effect of SP on the inflammatory response and hair growth in the outer root sheath (ORS) cells. Methods: We compared the serum levels of SP in 58 AA patients and 28 healthy subjects.Then, we checked the expression of SP and SP receptor, neurokinin-1 receptor (NK-1R) in the scalps of AA patients and healthy controls using immunohistochemical staining.Finally, we analyzed the mRNA expression of inflammatory cytokines and hair growthrelated factors in ORS cells. Results: SP and NK-1R expression were markedly higher in the hair follicles and interfollicular epidermis of the scalp lesions of AA patients. However, there was no statistically significant difference in serum SP levels between controls and patients, regardless of the type of alopecia. SP significantly increased the mRNA expression of inflammatory cytokines and decreased hair growth-related growth factors in ORS cells, but the results were not dramatic. Conclusion SP triggered a localized micro-inflammation in lesional hair follicles, provoked an inf lammatory response, and inhibited hair growth, thereby confirming the pathogenic role of SP in AA.

Background: Current evidence support that the gut microbiota plays a potential role in obesity. Bariatric surgery can reduce excess weight and decrease the risk of life-threatening weight-related health problems and may also influence gut microbiota. In this study, we aimed to investigate the changes in gut microbiota before and after bariatric surgery and evaluate the association of the gut microbial shift and altered body mass index (BMI) after bariatric surgery. Methods: Between January 2019 and July 2020, stools from 58 patients scheduled for bariatric surgery were collected. Six months after bariatric surgery, stools from 22 of these patients were re-collected, and the changes in gut microbiota before and after bariatric surgery were evaluated. In addition, the differences in gut microbiota between patients with severe obesity (BMI >35 kg/m2, n=42) and healthy volunteers with normal BMI (18.8 to 22.8 kg/m2, n=41) were investigated. Results: The gut microbiota of patients who underwent bariatric surgery showed increased α-diversity and differed β-diversity compared with those before surgery. Interestingly, Blautia was decreased and Bacteriodes was increased at the genus level after bariatric surgery. Further, the Blautia/Bacteroides ratio showed a positive correlation with BMI. To validate these results, we compared the gut microbiota from severely obese patients with high BMI with those from healthy volunteers and demonstrated that the Blautia/Bacteroides ratio correlated positively with BMI. Conclusion In the gut microbial analysis of patients who underwent bariatric surgery, we presented that the Blautia/Bacteroides ratio had changed after bariatric surgery and showed a positive correlation with BMI.

Background: Cataracts are the leading cause of impaired vision or blindness in dogs. There are many antioxidants that can prevent cataract progression, but whether they are clinically effective in dogs has not been established. Objectives: To analyze the delaying or preventing effect of oral antioxidants on canine senile cataracts through retrospective analysis. Methods: Medical records of dogs from January 1, 2015 to July 10, 2020 were reviewed. Dogs that were 8 yr of age or older with senile cataracts were included in this study. The dogs were divided into two treatment groups (dogs administered with Ocu-GLO supplement and dogs administered with Meni-One Eye R/C supplement) and a control group (dogs that were not administered any supplement). Dogs with incipient and immature cataracts were included in this study. Altogether, 112 dogs (156 eyes) with incipient cataracts and 60 dogs (77 eyes) with immature cataracts were included. The period of time that cataracts progressed from incipient to immature, and from immature to mature was recorded for each dog. Results: There was no significant delaying effect on the progression of incipient cataracts.However, both Ocu-GLO (hazard ratio = 0.265, p = 0.026) and Meni-One (hazard ratio = 0.246, p = 0.005) significantly delayed the progression of immature cataracts compared to the control group. Conclusions Although there was no significant delaying effect of oral antioxidants on incipient cataract progression, antioxidants could be used to delay the progression of senile immature cataract.

Background: Increased sebum secretion is considered the main causative factor in the pathogenesis of acne. There is an unmet pharmacological need for a novel drug that can control sebum production with a favorable adverse effect profile. Objective: To investigate the effect of azidothymidine on lipid synthesis in sebocytes and to identify the underlying mechanism of the inhibitory effect of azidothymidine on insulin-like growth factor (IGF)-1-induced lipid synthesis in sebocytes. Methods: Immortalized human sebocytes were used for the analysis. Thin-layer chromatography (TLC) and Oil Red O staining were performed to evaluate lipid synthesis in the sebocytes. The differentiation, lipid synthesis, mitochondrial biogenesis, and mitophagy in sebocytes were investigated. Results: TLC and Oil Red O staining revealed that azidothymidine reduced IGF-1 induced lipid synthesis in the immortalized human sebocytes. Azidothymidine also reduced IGF-1-induced expression of transcriptional factors and enzymes involved in sebocyte differentiation and lipid synthesis, respectively. Moreover, we found that IGF-1 upregulated the levels of peroxisome proliferator-activated receptor-gamma coactivator-1α, LC-3B, p62, and Parkin, major regulators of mitochondrial biogenesis and mitophagy in immortalized human sebocytes. In contrast, azidothymidine inhibited IGF-1 induced mitochondrial biogenesis and mitophagy in the sebocytes. Conclusion These results suggest that azidothymidine downregulates IGF-1-induced lipogenesis by dysregulating the quality of mitochondria through suppression of mitochondrial biogenesis and mitophagy in immortalized human sebocytes. Our study provides early evidence that azidothymidine may be an effective candidate for a new pharmacological agent for controlling lipogenesis in sebocytes.

Neurofibromatosis type 1 (NF1) is a relatively common inherited disorder characterized by the formation of neurofibromas, pigmentary abnormalities of the skin, Lisch nodules of the iris, and skeletal abnormalities. Multiple cutaneous neurofibromas are benign nerve sheath tumors and the main manifestation of NF1. Cardiac neurofibroma associated with NF1 is very rare, and few cases have been reported in the literature. Herein, we present the CT and MRI findings of a surgically confirmed left ventricular neurofibroma in a 32-year-old female with NF1.