The efficacy and safety of low- versus high-fluence fractional picosecond Nd:YAG 1064-nm laser in the treatment of acne scars: A randomized split-face comparison study.

BACKGROUND: Differences in clinical efficacy based on the fluence of fractional picosecond laser treatment for acne scars are unknown. OBJECTIVE: To compare the efficacy and safety of low-fluence versus high-fluence fractional picosecond Nd:YAG 1064-nm laser treatment in acne scar patients. METHODS: In this 12-week, investigator-blinded, randomized, split-face study, 25 patients with moderate-to-severe acne scars received three sessions of high-fluence laser treatment (1.0 J/cm2 ) on one side of their face and low-fluence (0.3 J/cm2 ) on the other side every 4 weeks. Patients were assessed using acne scar counts, the scar global assessment (SGA), and the ECCA scar grading scale every 4 weeks. The histological analysis compared the acne scars obtained before and 4 weeks after treatment. RESULTS: At their last visit, 88.00% and 92.00% of the subjects achieved >30% reduction in scar counts on the low- and high-fluence sides, respectively, without a significant difference between the two sides. On both sides, the scar counts, SGA, and ECCA score significantly improved 4 weeks after the last treatment. Although the high-fluence side showed a greater reduction in scar counts (-66.73%) than the low-fluence side (-62.13%), the two sides had no significant difference in the grading scores. The high-fluence side showed significantly more severe pain and higher side-effect scores immediately and 4 weeks after treatment. Histological analysis revealed a significantly increased collagen, elastin, and vimentin expression after treatment on the low-fluence side. CONCLUSIONS: The low-fluence setting demonstrated comparable efficacy and superior safety in treating acne scars compared with the high-fluence setting.

Knowledge and the behavioral patterns of photoprotection among Koreans with skin disease.

BACKGROUND: Photoprotection is crucial in preventing the development and progression of various skin diseases. However, patients with skin disease have limited awareness of photoprotection. We evaluated the knowledge and behavioral patterns of photoprotection among Koreans with skin diseases. METHODS: A cross-sectional study was conducted in 11 general hospitals across South Korea. The study population consisted of patients aged 19 years or older who visited dermatologic clinics for their skin diseases. A self-administered questionnaire was used to collect patient demographics, knowledge of photoprotection, and photoprotective habits. RESULTS: In this study, 1173 patients with skin cancer, hyperpigmentary disorders, hypopigmentary disorders, or other skin diseases participated. Females scored significantly higher in knowledge of photoprotection compared to males (mean score 8.4 vs. 7.8; p < .001), and younger patients (<50 years) scored higher than older patients (mean score 8.7 vs. 7.5; p < .001). Males also reported longer sun exposure times and lower usage of photoprotective measures (both p < .001). Patients with skin cancer had the lowest mean knowledge score (7.1 ± 2.6) and were less likely to use photoprotective measures compared to other groups (p < .001). In contrast, patients with hyperpigmentation actively avoided sun exposure compared with other groups (p < 0.001). CONCLUSIONS: Knowledge of photoprotection among Korean patients with skin diseases varied depending on the gender, age, and type of skin disease. Their photoprotective behaviors were inadequate, especially among males and those with skin cancer. These findings emphasize the importance of educating and tailoring photoprotection strategies for patients with skin diseases.

Efficacy and safety of HIP1601 (dual delayed-release esomeprazole) 40 mg in erosive esophagitis compared to HGP1705 (delayed-release esomeprazole) 40 mg: a multicenter, randomized, double-blind, non-inferiority study.

BACKGROUND: Proton-pump inhibitors (PPIs) are the most effective drugs for treating acid-related disorders. However, once-daily dosing with conventional PPIs fail to fully control acid secretion over 24 h. This study aimed to compare the efficacy and safety of HIP1601 (dual delayed-release esomeprazole) and HGP1705 (delayed-release esomeprazole) in patients with erosive esophagitis (EE). METHODS: We enrolled 213 patients with EE randomized in a 1:1 ratio to receive 40 mg HIP1601 (n = 107) or HGP1705 (n = 106) once daily for 4 or 8 weeks. The primary endpoint was the EE healing rate, confirmed by endoscopy up to week 8. GERD-related symptoms and treatment-emergent adverse events were compared between both groups. RESULTS: By week 8, the estimated healing rates of EE were 97.8% and 96.8% in the HIP1601 and HGP1705 groups, respectively, with a 95% confidence interval of -4.7 to 7.2. After 4 or 8 weeks of treatment, the EE healing rate at week 4, complete resolution rate of symptoms, time to sustained resolution of symptoms, and number of rescue medications used were similar in both groups. The proportion of heartburn- and acid regurgitation-free nights by week 4 were higher in the HIP1601 group compared to the HGP1705 group, but the difference did not reach clinical significance (87.7% vs. 85.8%, P = 0.514, 87.5% vs. 85.8%, P = 0.774). The number of adverse events did not differ significantly between the two groups. CONCLUSIONS: The efficacy and safety of HIP1601 40 mg were comparable to those of HGP1705 40 mg for the treatment of EE and symptomatic improvement of GERD. TRIAL REGISTRATION: NCT04080726 ( https://classic. CLINICALTRIALS: gov/ct2/show/NCT04080726 ), registration date: 25/10/2018.

Dasatinib Attenuates Fibrosis in Keloids by Decreasing Senescent Cell Burden.

Keloids are skin tumours caused by aberrant growth of dermal fibroblasts. Cellular senescence contributes to aging and various pathological conditions, including cancer, atherosclerosis, and fibrotic diseases. However, the effects of cellular senescence and senolytic drugs on keloids remain largely unknown. This study investigated senescent fibroblasts in keloids and assessed the effects of dasatinib on these cells. Tissues acquired from keloid removal surgery were analysed for senescence-associated ß-galactosidase-positive cells, p16 expression, and the effects of dasatinib treatment on keloids. Keloid tissue was xenotransplanted into mice, and the effect of intralesional dasatinib injection on keloid growth was observed. The results showed that the numbers of ß-galactosidase-positive and p16-expressing cells were higher in the keloids compared with in the controls. Dasatinib induced selective clearance of senescent cells and decreased procollagen expression in cultured keloid fibroblasts. In this xenotransplant keloid mouse model, intralesional injection of dasatinib reduced gross keloid tissue weight and the expression of both procollagen and p16. In addition, dasatinib-treated keloid fibroblasts conditioned medium reduced procollagen and p16 expression in cultured keloid fibroblasts. In conclusion, these results suggest that an increased number of senescent fibroblasts may play an important role in the pathogenesis of keloids. Therefore, dasatinib could be an alternative treatment for patients with keloids.

A case of mitomycin C toxicity after XEN gel stent implantation with the XEN air technique in a glaucoma patient.

BACKGROUND: To discuss the first case of mitomycin C (MMC) toxicity after XEN® gel stent implantation in a glaucoma patient, conducted using the XEN "air" technique with an ophthalmic viscosurgical device (OVD). CASE PRESENTATION: A 44-year-old Asian male presented with increased intraocular pressure (IOP; 52 mmHg) accompanied by keratic precipitates and an edematous cornea. He was diagnosed with uveitic glaucoma in the left eye, and the IOP was controlled with a topical anti-glaucoma agent. However, glaucoma progression was revealed by Humphrey visual field (HVF) and optical coherence tomography (OCT) examinations. The patient underwent uneventful XEN gel stent implantation using the XEN air technique and an MMC (0.02%, 0.1 mL) injection, with subconjunctival air and OVD injection provided prior to XEN implantation in the left eye. The patient exhibited a decreased IOP (11 mmHg), elevated bleb, and extensive subconjunctival hemorrhage on postoperative day 1. On postoperative day 18, diffuse conjunctival injection and a large avascular bleb was noticed around the XEN gel stent. The patient complained of severe eye pain and discomfort, suggestive of MMC toxicity, and the IOP was 12 mmHg. The patient was treated with a topical steroid and antibiotics tapered over a 6-month period. Finally, the toxicity was successfully controlled, with the IOP stabilizing at around 15 mmHg. CONCLUSIONS: Although significantly greater lowering of the IOP can be expected with the use of subconjunctival OVD injection and MMC during XEN gel stent implantation, a cautious approach and a longer monitoring period are required.

Pigmented contact dermatitis and hair dyes: A retrospective case-control multicentre study in Korea.

BACKGROUND: Pigmented contact dermatitis (PCD), a rare variant of non-eczematous contact dermatitis, is clinically characterized by sudden-onset brown or grey pigmentation on the face and neck. It is hypothesized to be caused by repeated contact with low levels of allergens. OBJECTIVES: This study evaluated the risk of using hair dyes in patients with PCD in Korea. METHODS: A total of 1033 PCD patients and 1366 controls from 31 university hospitals were retrospectively recruited. We collected and analysed the data from the patient group, diagnosed through typical clinical findings of PCD and the control group, which comprised age/sex-matched patients who visited the participating hospitals with pre-existing skin diseases other than current allergic disease or PCD. RESULTS: Melasma and photosensitivity were significantly more common in the control group, and a history of contact dermatitis was more common in the PCD group. There were significantly more Fitzpatrick skin type V participants in the PCD group than in the control group. There was no significant difference in sunscreen use between the groups. Using dermatologic medical history, Fitzpatrick skin type and sunscreen use as covariates, we showed that hair dye use carried a higher PCD risk (odds ratio [OR] before adjustment: 2.06, confidence interval [CI]: 1.60-2.65; OR after adjustment: 2.74, CI: 1.88-4.00). Moreover, henna users had a higher risk of PCD (OR before adjustment: 5.51, CI: 4.07-7.47; OR after adjustment: 7.02, CI: 4.59-10.74), indicating a significant increase in the risk of PCD with henna dye use. Contact dermatitis history was more prevalent in henna users than in those using other hair dyes in the PCD group (17.23% vs. 11.55%). CONCLUSION: Hair dye use is a risk factor for PCD. The risk significantly increased when henna hair dye was used by those with a history of contact dermatitis.

Can we predict postinflammatory hyperpigmentation after laser treatment based on dermoscopic findings of solar lentigo?

Solar lentigo (SL) commonly occurs as hyperpigmented macules in areas exposed to ultraviolet radiation. It typically shows an increased number of melanocytes in the basal cell layer of the skin, with or without elongated rete ridges. This retrospective study aimed to evaluate the characteristic dermoscopic patterns, reflecting different histopathological features, which might be valuable in predicting the possibility of postinflammatory hyperpigmentation (PIH) occurring after laser treatment. In total, 88 Korean patients diagnosed with biopsy-proven SL (a total of 90 lesions were diagnosed) between January, 2016 and December, 2021 were included. Histopathological patterns were classified into six categories. Dermoscopic features were classified into six categories. Pseudonetwork pattern and rete ridge elongation showed a statistically significant negative correlation. This means that a flatter epidermis is likely to manifest as a pseudonetwork pattern. The erythema pattern showed a significant positive correlation with interface changes and inflammatory infiltration. Bluish-gray granules (peppering), a characteristic dermoscopic finding, showed significant positive correlations with interface changes, inflammatory infiltration, and dermal melanophages. Clinicians considering laser treatment for patients with SL should perform dermoscopic tests before treatment. The pseudonetwork relates to flattened epidermis and fewer Langerhans cells; thus, a lower remission of PIH after laser treatment might be expected. If bluish-gray granules or erythema are observed, inflammatory conditions are likely to be involved. In such cases, regression of the inflammatory response through drug therapy, such as topical corticosteroids, should be a priority option before laser treatment.

Intravitreal Administration of Retinal Organoids-Derived Exosomes Alleviates Photoreceptor Degeneration in Royal College of Surgeons Rats by Targeting the Mitogen-Activated Protein Kinase Pathway.

Increasing evidence suggests that exosomes are involved in retinal cell degeneration, including their insufficient release; hence, they have become important indicators of retinopathies. The exosomal microRNA (miRNA), in particular, play important roles in regulating ocular and retinal cell functions, including photoreceptor maturation, maintenance, and visual function. Here, we generated retinal organoids (ROs) from human induced pluripotent stem cells that differentiated in a conditioned medium for 60 days, after which exosomes were extracted from ROs (Exo-ROs). Subsequently, we intravitreally injected the Exo-RO solution into the eyes of the Royal College of Surgeons (RCS) rats. Intravitreal Exo-RO administration reduced photoreceptor apoptosis, prevented outer nuclear layer thinning, and preserved visual function in RCS rats. RNA sequencing and miRNA profiling showed that exosomal miRNAs are mainly involved in the mitogen-activated protein kinase (MAPK) signaling pathway. In addition, the expression of MAPK-related genes and proteins was significantly decreased in the Exo-RO-treated group. These results suggest that Exo-ROs may be a potentially novel strategy for delaying retinal degeneration by targeting the MAPK signaling pathway.

Clinical features and natural course of pediatric longitudinal melanonychia: A retrospective cohort study in Korea.

BACKGROUND: Large studies on the clinical features and natural course of pediatric longitudinal melanonychia (LM) are lacking. OBJECTIVE: To investigate the clinical features and natural course of pediatric LM. METHODS: Retrospective cohort analysis of pediatric patients (age ≤ 18 years) with LM. RESULTS: We examined 703 LM lesions in 381 children. Single, narrow, and homogeneously pigmented fingernail lesions were most frequently observed. Our results suggested that within 3, 4.5, and 9.5 years after onset, approximately 3%, 5%, and 10% of LM lesions, respectively, will completely regress and that single, left-sided, and homogeneously pigmented lesions are more likely to disappear completely. The age of onset, sex, finger/toe position, Hutchinson's sign, and nail dystrophy were not associated with complete regression. During follow-up, most cases demonstrated no change in color or width between the first and last visit, and early darkening/widening before stabilization or lightening/narrowing was common. The lightning of pigmentation was associated with complete regression, whereas change in width was not. LIMITATIONS: Retrospective study at a tertiary center. CONCLUSION: Our results suggest that clinicians ought to follow pediatric patients with LM without intervention for several years even if lesions grow darker or wider. Single, left-sided, and homogeneously colored lesions are more likely to regress.

The long-term risk of lymphoma and skin cancer did not increase after topical calcineurin inhibitor use and phototherapy in a cohort of 25,694 patients with vitiligo.

BACKGROUND: Topical calcineurin inhibitors have been used to treat vitiligo, either alone or in combination with phototherapy; however, the long-term safety of these agents remains controversial. OBJECTIVE: To investigate the risk of lymphoma and skin cancer in vitiligo patients who received topical calcineurin inhibitors or phototherapy. METHODS: A multicenter retrospective cohort study of 25,694 vitiligo patients who received topical calcineurin inhibitors or phototherapy for 6 weeks or more between 2001 and 2019 was performed. Cumulative doses of topical calcineurin inhibitors and total phototherapy sessions were determined. Outcomes were the development of lymphoma or skin cancer after enrollment, confirmed through chart review and pathology reports. RESULTS: During 95,203 person-years, 13 cases of lymphoma, 22 of actinic keratosis, 15 of nonmelanoma skin cancer, and 5 of melanoma were observed. The risk of lymphoma and skin cancer was not significantly increased by topical calcineurin inhibitor dose or phototherapy sessions. The interaction between the topical calcineurin inhibitors and phototherapy was not associated with an increased risk of skin cancer. LIMITATIONS: Retrospective study, individual follow-up duration less than 4 years, and no adjustment for comorbidities and medication history. Not generalizable to other races. CONCLUSION: The long-term risk of skin cancer or lymphoma was not associated with the use of topical calcineurin inhibitors, phototherapy, and both treatments in combination in patients with vitiligo.

Actin remodeling confers BRAF inhibitor resistance to melanoma cells through YAP/TAZ activation.

The activation of transcriptional coactivators YAP and its paralog TAZ has been shown to promote resistance to anti-cancer therapies. YAP/TAZ activity is tightly coupled to actin cytoskeleton architecture. However, the influence of actin remodeling on cancer drug resistance remains largely unexplored. Here, we report a pivotal role of actin remodeling in YAP/TAZ-dependent BRAF inhibitor resistance in BRAF V600E mutant melanoma cells. Melanoma cells resistant to the BRAF inhibitor PLX4032 exhibit an increase in actin stress fiber formation, which appears to promote the nuclear accumulation of YAP/TAZ. Knockdown of YAP/TAZ reduces the viability of resistant melanoma cells, whereas overexpression of constitutively active YAP induces resistance. Moreover, inhibition of actin polymerization and actomyosin tension in melanoma cells suppresses both YAP/TAZ activation and PLX4032 resistance. Our siRNA library screening identifies actin dynamics regulator TESK1 as a novel vulnerable point of the YAP/TAZ-dependent resistance pathway. These results suggest that inhibition of actin remodeling is a potential strategy to suppress resistance in BRAF inhibitor therapies.

Adiponectin-Based Peptide (ADP355) Inhibits Transforming Growth Factor-ß1-Induced Fibrosis in Keloids.

Keloids, benign cutaneous overgrowths of dermal fibroblasts, are caused by pathologic scarring of wounds during healing. Current surgical and therapeutic modalities are unsatisfactory. Although adiponectin has shown an antifibrotic effect, its large size and insolubility limit its potential use in keloid treatment. We investigated the effect of a smaller and more stable adiponectin-based peptide (ADP355) on transforming growth factor ß1 (TGF-ß1)-induced fibrosis in a primary culture of keloid fibroblasts prepared from clinically obtained keloid samples. Xenograft of keloid tissues on athymic nude mice was used to investigate the effect of intralesional injection of ADP355. ADP355 significantly attenuated the TGF-ß1-induced expression of procollagen type 1 in keloid fibroblasts (p < 0.05). Moreover, it inhibited the TGF-ß1-induced phosphorylation of SMAD3 and ERK, while amplifying the phosphorylation of AMP-activated protein kinase (p < 0.05). Knockdown of adiponectin receptor 1 reversed the attenuation of procollagen expression in ADP355-treated TGF-ß1-induced fibrosis (p < 0.05). ADP355 also significantly reduced the gross weight and procollagen expression of keloid tissues in xenograft mice compared to control animals. These results demonstrate the therapeutic potential of the adiponectin peptide ADP355 for keloids.

Export of membrane proteins from the Golgi complex to the primary cilium requires the kinesin motor, KIFC1.

Microtubule-based motors contribute to the efficiency and selectivity of Golgi exit and post-Golgi transport of membrane proteins that are targeted to distinct compartments. Cytoplasmic dynein moves post-Golgi vesicles that carry rhodopsin toward the base of the connecting cilium in photoreceptor cells; however, the identity of the motors that are involved in the vesicular trafficking of ciliary membrane proteins in nonphotoreceptor cells remains unclear. Here, we demonstrate that the minus end-directed kinesin KIFC1 (kinesin family member C1) is required for both ciliary membrane protein transport and serum starvation-induced ciliogenesis in retinal pigmented epithelial 1 cells. Although KIFC1 is known as a mitotic motor that is sequestered in the nucleus during interphase, KIFC1 immunoreactivity appeared in the Golgi region after serum starvation. Knockdown of KIFC1 inhibited the export of ciliary receptors from the Golgi complex. KIFC1 overexpression affected the Golgi localization of GMAP210 (Golgi microtubule-associated protein 210) and IFT20 (intraflagellar transport 20), which are involved in membrane protein transport to cilia. Moreover, KIFC1 physically interacted with ASAP1 (ADP-ribosylation factor GTPase-activating protein with SH3 domain, ankyrin repeat and PH domain 1), which regulates the budding of rhodopsin transport carriers from the Golgi complex, and KIFC1 depletion caused Golgi accumulation of ASAP1. A decrease in the centrosomal levels of IFT20 and TTBK2 (τ-tubulin kinase 2) was associated with ciliogenesis defects in KIFC1-depleted cells. Our results suggest that KIFC1 plays roles in the Golgi exit of ciliary receptors and in the recruitment of ciliogenesis regulators.-Lee, S.-H., Joo, K., Jung, E. J., Hong, H., Seo, J., Kim, J. Export of membrane proteins from the Golgi complex to the primary cilium requires the kinesin motor, KIFC1.

Nationwide antibiotic resistance mapping of Helicobacter pylori in Korea: A prospective multicenter study.

INTRODUCTION: The eradication rates for Helicobacter pylori have decreased in Korea although the prevalence of this bacterium has also decreased. Antibiotic resistance is likely to be a crucial factor in H. pylori eradication success, and we therefore mapped these resistance patterns nationwide in Korea. MATERIALS AND METHODS: Five hundred and ninety adult subjects were prospectively enrolled from 2017 to 2018 from 15 centers across six geographic areas of Korea. A total of 580 biopsy tissues had been sampled from these patients during an upper endoscopy and were frozen at -80°C and delivered to a central laboratory. The agar dilution method was used to determine the minimum inhibitory concentration of amoxicillin, clarithromycin, metronidazole, tetracycline, ciprofloxacin, and levofloxacin for each H. pylori isolate. RESULTS: The culture success rate was 60.2% (349/580). Resistance rates against clarithromycin, metronidazole, amoxicillin, tetracycline, levofloxacin, and ciprofloxacin were 17.8%, 29.5%, 9.5%, 0%, 37.0%, and 37.0%, respectively. The geographic distribution of metronidazole and quinolone resistance was highly variable. Some subjects had multiple H. pylori strains in the antrum and body of the stomach and showed a heterogeneous resistance profile between these anatomic areas. The H. pylori multidrug resistance (MDR) rate was 25.2% (88/349) among amoxicillin, clarithromycin, metronidazole, tetracycline, and quinolone and 11.2% (39/349) among four of these major antibiotics except for quinolone. The Seoul and Chungcheong areas showed a relatively lower MDR rate. CONCLUSION: The antibiotic resistance of H. pylori differs by drug and geographic area in Korea. Detailed nationwide antibiotic resistance mapping is needed to develop an effective H. pylori eradication strategy.

Long-term outcomes of laser treatment for congenital melanocytic nevi.

BACKGROUND: Although various laser treatments have been tried for congenital melanocytic nevi (CMNs), only small retrospective studies with short-term follow-up had been done to assess outcomes. OBJECTIVE: We analyzed the long-term outcomes of laser treatment for CMN and compared these outcomes with those of a combination treatment including partial excision and lasers. METHODS: Patients with CMN treated with lasers were retrospectively reviewed, and patients with >3 years of follow-up were grouped as the long-term follow-up group. RESULTS: A total of 67 cases of CMN were reviewed. Among 20 patients (20/52, 38.5%) with near total clearance during laser-only treatment, 11 patients were in the long-term follow-up group, and 5 of 11 showed repigmentation. In total, 15 patients showed repigmentation regardless of clearance, and the mean period until repigmentation was 3.93 years from the initial treatment. Patients with partial excision and laser combination treatment showed higher Investigator's Global Assessment scores, fewer laser treatments, and shorter treatment periods compared with patients with laser-only treatment. LIMITATIONS: This is a retrospective study, and various laser devices were used. CONCLUSION: More than 4 years of follow-up is required to evaluate the efficacy of lasers in CMN, and partial excision and laser combination treatment might be an effective treatment option.

Comparison of treatment options for small to medium congenital melanocytic nevi: A retrospective review of 119 cases.

OBJECTIVES: For small to medium sized congenital melanocytic nevi (CMN), the treatment of choice is staged surgical excision. Ablative lasers or pigment-specific lasers have also been recommended for lesions difficult for surgical removal or to avoid surgery. In this study, we retrospectively analyzed the results of several treatment options for CMN to find out the optimal treatment method. METHODS: Patients with small to medium sized CMN were retrospectively reviewed. Treatment options were categorized into four groups: (i) Excision only; (ii) Excision followed by scar laser; (iii) Excision followed by pigment-specific laser; and (iv) Laser only. Treatment response was assessed by investigator's global assessment (IGA) score on a seven-point scale. RESULTS: A total of 119 cases were included. Lesions were most commonly located on the face (59/119, 49.6%), measured 2 ∼ 10 cm in size (72/119, 60.5%), and treated with excision only (50/119, 42.0%). Among treatment options, excision followed by scar laser showed the highest IGA score of 6.38. Options including surgical methods showed higher IGA scores compared to laser-only treatment (P < 0.01). Staged excisions and single excisions showed no difference in IGA scores. Patient satisfaction scores increased after scar laser treatment of the staged excision scar. CONCLUSIONS: For the treatment of small to medium sized CMN, treatment strategies including surgical methods are cosmetically superior to laser-only treatment. Also, the combination of surgical excision with scar laser has the potential for better clinical outcomes and patient satisfaction. Lasers Surg. Med. 51:62-67, 2019. © 2018 Wiley Periodicals, Inc.

The role of Wnt/ß-catenin signaling in the restoration of induced pluripotent stem cell-derived retinal pigment epithelium after laser photocoagulation.

To investigate the role of Wnt/ß-catenin signaling pathway in the restoration of induced pluripotent stem cell-derived retinal pigment epithelium (hiPSC-RPE) after laser photocoagulation. After differentiation of RPE cells from hiPSCs, laser photocoagulation was performed. Activation of Wnt/ß-catenin signaling at days 1 and 5 after laser photocoagulation was evaluated by expression of ß-catenin. Cell proliferation and alteration in cell-to-cell contact at day 5 after laser photocoagulation with or without Dickkopf-1 (Dkk-1) treatment were studied using ethynyl-2'-deoxyuridine (EdU) assay and zonula occludens-1 (ZO-1) expression analysis, respectively. The mRNA levels of Wnt genes at day 5 after laser photocoagulation were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). Activation of Wnt/ß-catenin signaling at days 1 and 5 after laser photocoagulation was confirmed by ß-catenin accumulation in the cytoplasm and nucleus of hiPSC-RPE. Many EdU-positive cells also expressed ß-catenin, and the number of EdU-positive cells was decreased at day 5 after laser photocoagulation after Dkk-1 treatment, indicating that Wnt/ß-catenin signaling mediated hiPSC-RPE proliferation. ZO-1 expression was not decreased with Dkk-1 treatment at day 5 after laser photocoagulation, indicating that Wnt/ß-catenin signaling mediated hiPSC-RPE restoration. At day 5, after laser photocoagulation, mRNA levels of Wnt2b, Wnt3, Wnt5a, Wnt7a, and Wnt10b were increased. Wnt/ß-catenin signaling has a crucial role in restoration of hiPSC-RPE proliferation after laser photocoagulation. Manipulation of Wnt/ß-catenin signaling while elucidating the underlying mechanisms of RPE restoration might have a therapeutic potential in retinal degenerative diseases.

Molecular and functional characterization of inwardly rectifying K+ currents in murine proximal colon.

KEY POINTS: Interstitial cells of Cajal (ICC) from murine colonic muscles express genes encoding inwardly rectifying K+ channels. Transcripts of Kcnj2 (Kir2.1), Kcnj4 (Kir2.3), Kcnj14 (Kir2.4), Kcnj5 (Kir3.4), Kcnj8 (Kir 6.1) and Kcnj11 (Kir6.2) were found in colonic ICC. A conductance with properties consistent with Kir2 channels was observed in ICC but not in smooth muscle cells (SMC). Despite expression of gene transcripts, G-protein gated K+ channel (Kir3) and KATP (Kir6) currents were not resolved in ICC. KATP is a conductance prominent in SMC. Kir2 antagonist caused depolarization of freshly dispersed ICC and colonic smooth muscles, suggesting that this conductance is active under resting conditions in colonic muscles. The conclusion of the present study is that ICC express the Ba2+ -sensitive, inwardly rectifying K+ conductance in colonic muscles. This conductance is most probably a result of heterotetramers of Kir2 gene products, with this regulating resting potentials and the excitability of colonic muscles. ABSTRACT: Membrane potentials of gastrointestinal muscles are important because voltage-dependent Ca2+ channels in smooth muscle cells (SMC) provide the Ca2+ that triggers contraction. Regulation of membrane potential is complicated because SMC are electrically coupled to interstitial cells of Cajal (ICC) and PDGFRα+ cells. Activation of conductances in any of these cells affects the excitability of the syncytium. We explored the role of inward rectifier K+ conductances in colonic ICC that might contribute to regulation of membrane potential. ICC expressed Kcnj2 (Kir2.1), Kcnj4 (Kir2.3), Kcnj14 (Kir2.4), Kcnj5 (Kir3.4), Kcnj8 (Kir 6.1) and Kcnj11 (Kir6.2). Voltage clamp experiments showed activation of inward current when extracellular K+ ([K+ ]o ) was increased. The current was inwardly rectifying and inhibited by Ba2+ (10 µm) and ML-133 (10 µm). A similar current was not available in SMC. The current activated in ICC by elevated [K+ ]o was not affected by Tertiapin-Q. Gßγ, when dialysed into cells, failed to activate a unique, Tertiapin-Q-sensitive conductance. Freshly dispersed ICC showed no evidence of functional KATP . Pinacidil failed to activate current and the inward current activated by elevated [K+ ]o was insensitive to glibenclamide. Under current clamp, ML-133 caused the depolarization of isolated ICC and also that of cells impaled with microelectrodes in intact muscle strips. These findings show that ICC, when isolated freshly from colonic muscles, expressed a Ba2+ -sensitive, inwardly rectifying K+ conductance. This conductance is most probably a result of the expression of multiple Kir2 family paralogues, and the inwardly rectifying conductance contributes to the regulation of resting potentials and excitability of colonic muscles.

Seroprevalence of Helicobacter pylori in Korea: A multicenter, nationwide study conducted in 2015 and 2016.

BACKGROUND: The Korean College of Helicobacter and Upper Gastrointestinal Research has studied Helicobacter pylori (H. pylori) prevalence since 1998 and found a dynamic change in its prevalence in Korea. The aim of this study was to determine the recent H. pylori prevalence rate and compare it with that of previous studies according to socioeconomic variables. METHODS: We planned to enroll 4920 asymptomatic Korean adults from 21 centers according to the population distribution of seven geographic areas (Seoul, Gyeonggi, Gangwon, Chungcheong, Kyungsang, Cholla, and Jeju). We centrally collected serum and tested H. pylori serum IgG using a chemiluminescent enzyme immunoassay. RESULTS: We analyzed 4917 samples (4917/4920 = 99.9%) from January 2015 to December 2016. After excluding equivocal serologic results, the H. pylori seropositivity rate was 51.0% (2414/4734). We verified a decrease in H. pylori seroprevalence compared with previous studies performed in 1998, 2005, and 2011 (P < .0001). The H. pylori seroprevalence rate differed by area: Cholla (59.5%), Chungcheong (59.2%), Kyungsang (55.1%), Jeju (54.4%), Gangwon (49.1%), Seoul (47.4%), and Gyeonggi (44.6%). The rate was higher in those older than 40 years (38.1% in those aged 30-39 years and 57.7% in those aged 40-49 years) and was lower in city residents than in noncity residents at all ages. CONCLUSIONS: Helicobacter pylori seroprevalence in Korea is decreasing and may vary according to population characteristics. This trend should be considered to inform H. pylori-related policies.

Predictors and clinical outcomes of follow-up loss in patients with inflammatory bowel disease.

BACKGROUND AND AIM: Nonadherence is a risk factor of disease worsening in inflammatory bowel disease (IBD). We analyzed the frequency, predictors, and clinical outcomes of patients with IBD who are lost to follow-up in outpatient clinics. METHODS: Medical records of 784 IBD patients visiting our IBD clinic between January 2010 and December 2015 were reviewed retrospectively. Overall, 285 newly diagnosed IBD patients who were followed up for at least 12 months were included in the analysis. RESULTS: For 285 IBD patients (161 ulcerative colitis and 124 Crohn's disease), the mean disease duration was 66.3 ± 34.0 months (7-137 months). Forty-two patients (14.7%; 27 ulcerative colitis and 15 Crohn's disease) were lost to follow-up. On multivariate regression analysis, travel time to clinic (odds ratio, 2.37; 95% confidence interval, 1.63-3.45; P = 0.01) and C-reactive protein levels at diagnosis (odds ratio, 0.63; 95% confidence interval, 0.43-0.68; P = 0.01) were significantly associated with follow-up loss. Among the 42 patients lost to follow-up, 36 (85.7%) revisited the clinic. The cause of revisit was disease flare-up in 22 patients (61.1%). Step-up treatment was needed in 15 patients (41.7%). Steroid was introduced in 14 patients (38.9%). Azathioprine and an antitumor necrosis factor agent were newly prescribed in three patients (8.3%) and one patient (2.8%), respectively. CONCLUSIONS: Follow-up loss rate for IBD patients in remission state was 14.7%, and the predictors were far from hospital and low C-reactive protein levels. Because most of follow-up loss patients experienced flare-up, clinicians need to try to encourage patients to keep their adherence.