Impact of the COVID-19 pandemic on telogen effluvium: a nationwide multicentre interrupted time series study.

BACKGROUND: There is ongoing debate regarding the association between telogen effluvium (TE) and COVID-19, as well as COVID-19 vaccines. OBJECTIVES: To investigate the impact of the COVID-19 pandemic and vaccination on the development of TE among patients visiting dermatology clinics in South Korea. METHODS: Between 2017 and 2022, data regarding patients with TE and other types of hair loss were collected from 22 hospitals in South Korea. An interrupted time series analysis was conducted, dividing the time into periods before and after the COVID-19 pandemic, as well as before and after the COVID-19 vaccination. RESULTS: There was a significant slope change in the percentage of cases of TE during the postpandemic period (slope change 0.011, 95% confidence interval 0.005-0.017, P < 0.001), but no significant changes were observed after vaccination. The percentage of patients with other types of hair loss was not associated with COVID-19 or vaccination. The retrospective nature of the study may have limited the ability to establish causation. CONCLUSIONS: This multicentre study provides insights into the epidemiology of TE, showing a significant increase in cases of TE following the COVID-19 pandemic. However, there was no association between the occurrence of TE and COVID-19 vaccines.

Evaluation of ventricular pacing suppression algorithms in dual chamber pacemaker: Results of "LEADER" study.

Background: There is limited research on the intra-individual efficacy of ventricular pacing minimization algorithms developed by Biotronik-the Ventricular Pace Suppression algorithm (VpS) and the Intrinsic Rhythm Support plus algorithm (IRSplus) (BIOTRONIK SE & Co. KG, Berlin, Germany). We performed a randomized pilot trial that evaluated the efficacy of two algorithms in patients with symptomatic sinus node dysfunction (SND) who received a dual-chamber pacemaker. Methods: The trial was conducted in 11 tertiary hospitals in South Korea. The patients were randomized to either the VpS or IRSplus algorithm group after a 3-month period of fixed atrioventricular (AV) delay. The primary outcome was the ventricular pacing percentage (Vp%) at each follow-up visit. The secondary outcomes were the occurrence of heart failure (HF) and atrial fibrillation (AF) during the study period. Results: Data from 131 patients were analyzed. Initially, their average Vp% over 3 months with a fixed AV interval was 14.1 ± 19.4%. Patients were randomly assigned to VpS and IRSplus groups, with 66 and 65 in each. Algorithms reduced average Vp% to 4.0 ± 11.3% at 9 months and 6.7 ± 14.9% at 15 months. These algorithms were more effective for patients with paced AV delay (PAVD) ≤300 ms compared to those with PAVD >300 ms. Both algorithms were equally effective in reducing Vp%. Clinical AF or HF hospitalization was not observed during the study period. Conclusion: The VpS and IRSplus algorithms are effective and safe in minimizing unnecessary ventricular pacing in patients with SND.

Plasma apixaban concentrations and thrombin generation assay parameters in response to dose reduction for atrial fibrillation.

AIMS: To investigate plasma apixaban concentrations and thrombin generation assay (TGA) parameters across different apixaban doses in atrial fibrillation patients who had dose-reduction criteria for apixaban. METHODS: This observational study included 374 patients (mean age 75.6 ± 7.7 years, 54.8% female) with dose-reduction criteria for apixaban. The patients were divided into 3 groups: (i) on-label standard dose (5 mg twice daily, n = 166); (ii) on-label reduced dose (2.5 mg twice daily, n = 55); and (iii) off-label underdose (2.5 mg twice daily, n = 153). Apixaban concentrations determined via the anti-Xa assay and TGA parameters were compared at trough levels. RESULTS: The off-label underdose group exhibited significantly lower apixaban trough concentrations than the on-label reduced-dose and standard-dose groups (56.7 ± 42.9 vs. 83.7 ± 70.4 vs. 129.9 ± 101.8 ng/mL, all P < .001). Less than 70% of all patients fell within the expected range of apixaban concentrations. Proportions exceeding the upper limit of the expected range were significantly lower in the off-label underdose group (1.3%) than in the on-label reduced-dose (9.1%, P = .005) and standard-dose (12.7%, P < .001) groups. The TGA parameters showed the on-label standard-dose group displaying the lowest thrombogenic profiles. Lower creatinine clearance was the most significant predictor of higher apixaban concentrations. CONCLUSION: Off-label underdosed apixaban resulted in lower apixaban concentrations than both on-label standard and reduced-dose regimens. A considerable proportion of the patients exhibited apixaban concentrations outside the expected range, suggesting the potential benefits of plasma concentration monitoring. Further studies are needed to compare dosages directly, investigate the impact of plasma apixaban concentration monitoring and validate the current dose-reduction criteria.

Highly Adaptive Kirigami-Metastructure Adhesive with Vertically Self-Aligning Octopus-like 3D Suction Cups for Efficient Wet Adhesion to Complexly Curved Surfaces.

An essential requirement for biomedical devices is the capability of conformal adaptability on diverse irregular 3D (three-dimensional) nonflat surfaces in the human body that may be covered with liquids such as mucus or sweat. However, the development of reversible adhesive interface materials for biodevices that function on complex biological surfaces is challenging due to the wet, slippery, smooth, and curved surface properties. Herein, we present an ultra-adaptive bioadhesive for irregular 3D oral cavities covered with saliva by integrating a kirigami-metastructure and vertically self-aligning suction cups. The flared suction cup, inspired by octopus tentacles, allows adhesion to moist surfaces. Additionally, the kirigami-based auxetic metastructure with a negative Poisson's ratio relieves the stress caused by tensile strain, thereby mitigating the stress caused by curved surfaces and enabling conformal contact with the surface. As a result, the adhesive strength of the proposed auxetic adhesive is twice that of adhesives with a flat backbone on highly curved porcine palates. For potential application, the proposed auxetic adhesive is mounted on a denture and performs successfully in human subject feasibility evaluations. An integrated design of these two structures may provide functionality and potential for biomedical applications.

High Risk of Non-Melanoma Skin Cancer in Actinic Keratosis Patients with Skin of Color: A Nationwide Register-Based Cohort Study.

INTRODUCTION: Actinic keratoses (AKs) are rough, scaly patches from UV exposure, increasing the risk of non-melanoma skin cancer (NMSC). This study examines AK incidence in Korea and its role as a risk factor for NMSC. METHODS: A retrospective nationwide register-based cohort study analyzed 2,917 AK patients and 14,585 controls from 2002 to 2019. Patients diagnosed with AK were followed until NMSC occurrence, death, emigration, or December 2019. RESULTS: AK incidence reached 44.8 per 100,000 person-years in 2019. The adjusted hazard ratio for NMSC in AK patients was 8.91 (95% confidence interval, 5.72-13.90). Higher NMSC risk was observed in female AK patients, those under 60 years, and those with lower income levels. The 16-year cumulative incidence of NMSC was 4.19% in AK patients versus 0.44% in controls. CONCLUSION: AK significantly increases the risk of NMSC in Koreans, highlighting the need for tailored surveillance and treatment strategies.

Bis(2-hy-droxy-2,3-di-hydro-1H-inden-1-aminium) tetra-chlorido-palladate(II) hemihydrate.

A new square-planar palladium complex salt hydrate, (C9H12NO)2[PdCl4]·0.5H2O, has been characterized. The asymmetric unit of the complex salt comprises two [PdCl4]2- dianions, four 2-hy-droxy-2,3-di-hydro-1H-inden-1-aminium cations, each derived from (1R,2S)-(+)-1-amino-indan-2-ol, and one water mol-ecule of crystallization. In the crystal, a two-dimensional layer parallel to (001) features a number of O-H⋯O, N-H⋯O, O-H⋯Cl and N-H⋯Cl hydrogen bonds.

Artificial Octopus-Limb-Like Adhesive Patches for Cupping-Driven Transdermal Delivery with Nanoscale Control of Stratum Corneum.

Drug delivery through complex skin is currently being studied using various innovative structural and material strategies due to the low delivery efficiency of the multilayered stratum corneum as a barrier function. Existing microneedle-based or electrical stimulation methods have made considerable advances, but they still have technical limitations to reduce skin discomfort and increase user convenience. This work introduces the design, operation mechanism, and performance of noninvasive transdermal patch with dual-layered suction chamber cluster (d-SCC) mimicking octopus-limb capable of wet adhesion with enhanced adhesion hysteresis and physical stimulation. The d-SCC facilitates cupping-driven drug delivery through the skin with only finger pressure. Our device enables nanoscale deformation control of stratum corneum of the engaged skin, allowing for efficient transport of diverse drugs through the stratum corneum without causing skin discomfort. Compared without the cupping effect of d-SCC, applying negative pressure to the porcine, human cadaver, and artificial skin for 30 min significantly improved the penetration depth of liquid-formulated subnanoscale medicines up to 44, 56, and 139%. After removing the cups, an additional acceleration in delivery to the skin was observed. The feasibility of d-SCC was demonstrated in an atopic dermatitis-induced model with thickened stratum corneum, contributing to the normalization of immune response.

A novel nerve block technique for nail surgery.

In pediatric patients, nail unit anesthesia is frequently required for procedures including matrixectomy or nail avulsion. However, nail unit anesthesia is very painful and requires a significant amount of time to take complete effect, causing a great deal of distress for most pediatric patients. By targeting the palmar and dorsal digital nerves in the distal part of the fingers, our method enables fast, simple, and less painful anesthesia.

Association between unpredictable work schedule and work-family conflict in Korea.

Background: As unpredictable work schedule (UWS) has increased worldwide, various studies have been conducted on the resulting health effects on workers. However, research on the effect of UWS on workers' well-being in Korea is still insufficient. This study aimed to investigate the relationship between UWS and work-family conflict (WFC) using 6th Korean Working Conditions Survey (KWCS). Methods: Both UWS and WFC were measured using self-reported questionnaires, using data from the 6th KWCS conducted between 2020 and 2021, including 31,859 participants. UWS was measured by questions regarding the frequency of changes in work schedules and limited advanced notice. WFC was measured by questions regarding work to family and family to work conflicts. Logistic regression analysis was conducted to investigate the association between UWS and WFC. Results: The prevalence of UWS was higher among men, those under 40 years old, service and sales workers and blue-collar workers, and those with higher salaries. Workplace size also influenced UWS prevalence, with smaller workplaces (less than 50 employees) showing a higher prevalence. The odds ratio (OR) for WFC was significantly higher in workers with UWS compared to workers without UWS after adjusting for gender, age, marital status, occupation, salary, education, weekly working hours, shift work, company size, and having a child under the age of 18 years, employment status (OR: 3.71; 95% confidence interval: 3.23-4.25). Conclusions: The analysis of nationwide data revealed that UWS interferes with workers' performance of family roles, which can lead to WFC. Our findings suggest that it is crucial to implement policies to address unfair work schedule management, promoting a healthier work-life balance and fostering a conducive environment for family responsibilities.

Identification of concealed cardiomyopathy using next-generation sequencing-based genetic testing in Korean patients initially diagnosed with idiopathic ventricular fibrillation.

AIMS: Idiopathic ventricular fibrillation (IVF) is a disease in which the cause of ventricular fibrillation cannot be identified despite comprehensive clinical evaluation. This study aimed to investigate the clinical yield and implications of genetic testing for IVF. METHODS AND RESULTS: This study was based on the multi-centre inherited arrhythmia syndrome registry in South Korea from 2014 to 2017. Next-generation sequencing-based genetic testing was performed that included 174 genes previously linked to cardiovascular disease. A total of 96 patients were clinically diagnosed with IVF. The mean age of the onset was 41.2 ± 12.7 years, and 79 patients were males (82.3%). Of these, 74 underwent genetic testing and four (5.4%) of the IVF probands had pathogenic or likely pathogenic variants (each having one of MYBPC3, MYH7, DSP, and TNNI3). All pathogenic or likely pathogenic variants were located in genes with definite evidence of a cardiomyopathy phenotype, either hypertrophic cardiomyopathy or arrhythmogenic right ventricular cardiomyopathy. CONCLUSION: Next-generation sequencing-based genetic testing identified pathogenic or likely pathogenic variants in 5.4% of patients initially diagnosed with IVF, suggesting that genetic testing with definite evidence genes of cardiomyopathy may enable molecular diagnosis in a minority of patients with IVF. Further clinical evaluation and follow-up of patients with IVF with positive genotypes are needed to unveil concealed phenotypes, such as the pre-clinical phase of cardiomyopathy.

The CRL3gigaxonin ubiquitin ligase-USP15 pathway governs the destruction of neurofilament proteins.

Giant axonal neuropathy (GAN) is caused by mutations in the GAN gene encoding for gigaxonin (GIG), which functions as an adaptor of the CUL3-RBX1-GIG (CRL3GIG) E3 ubiquitin ligase complex. The pathological hallmark of GAN is characterized by the accumulation of densely packed neurofilaments (NFs) in the axons. However, there are fundamental knowledge gaps in our understanding of the molecular mechanisms by which the ubiquitin-proteasome system controls the homeostasis of NF proteins. Recently, the deubiquitylating enzyme USP15 was reported to play a crucial role in regulating ubiquitylation and proteasomal degradation of CRL4CRBN substrate proteins. Here, we report that the CRL3GIG-USP15 pathway governs the destruction of NF proteins NEFL and INA. We identified a specific degron called NEFLL12 degron for CRL3GIG. Notably, mutations in the C-terminal Kelch domain of GIG, represented by L309R, R545C, and C570Y, disrupted the binding of GIG to NEFL and INA, leading to the accumulation of these NF proteins. This accounts for the loss-of-function mutations in GAN patients. In addition to regulating NFs, CRL3GIG also controls actin filaments by directly targeting actin-filament-binding regulatory proteins TPM1, TPM2, TAGLN, and CNN2 for proteasomal degradation. Thus, our findings broadly impact the field by providing fundamental mechanistic insights into regulating extremely long-lived NF proteins NEFL and INA by the CRL3GIG-USP15 pathway and offering previously unexplored therapeutic opportunities to treat GAN patients and other neurodegenerative diseases by explicitly targeting downstream substrates of CRL3GIG.

Complete mitochondrial genome of the crinoid Poliometra prolixa (Crinoidea: Comatulida: Antedonidae).

Poliometra prolixa Sladen, 1881, is a comatulid crinoid found in the Arctic deep sea. In this study, we report the complete mitochondrial genome sequence of P. prolixa (Comatulida: Antedonidae). The complete mitogenome of P. prolixa was 15,916 bp long and comprised 13 protein-coding genes (PCGs), 22 transfer RNA genes, and 2 ribosomal RNA genes. The base composition of the P. prolixa mitogenome was 24.0% A, 44.9% T, 19.0% G, and 12.1% C. Phylogenetic analysis using all PCGs of the complete mitogenome confirmed the inclusion of P. prolixa within the Comatulida.

Clinical and Genetic Features of Korean Inherited Arrhythmia Probands.

BACKGROUND AND OBJECTIVES: Inherited arrhythmia (IA) is a more common cause of sudden cardiac death in Asian population, but little is known about the genetic background of Asian IA probands. We aimed to investigate the clinical characteristics and analyze the genetic underpinnings of IA in a Korean cohort. METHODS: This study was conducted in a multicenter cohort of the Korean IA Registry from 2014 to 2017. Genetic testing was performed using a next-generation sequencing panel including 174 causative genes of cardiovascular disease. RESULTS: Among the 265 IA probands, idiopathic ventricular fibrillation (IVF) and Brugada Syndrome (BrS) was the most prevalent diseases (96 and 95 cases respectively), followed by long QT syndrome (LQTS, n=54). Two-hundred-sixteen probands underwent genetic testing, and 69 probands (31.9%) were detected with genetic variant, with yield of pathogenic or likely pathogenic variant as 6.4%. Left ventricular ejection fraction was significantly lower in genotype positive probands (54.7±11.3 vs. 59.3±9.2%, p=0.005). IVF probands showed highest yield of positive genotype (54.0%), followed by LQTS (23.8%), and BrS (19.5%). CONCLUSIONS: There were significant differences in clinical characteristics and genetic yields among BrS, LQTS, and IVF. Genetic testing did not provide better yield for BrS and LQTS. On the other hand, in IVF, genetic testing using multiple gene panel might enable the molecular diagnosis of concealed genotype, which may alter future clinical diagnosis and management strategies.

Tailored ablation index based on left atrial wall thickness assessed by computed tomography for pulmonary vein isolation in patients with atrial fibrillation.

INTRODUCTION: Although left atrial wall thickness (LAWT) is known to be varied, a fixed target Ablation Index (AI) based pulmonary vein isolation (PVI) has been suggested in catheter ablation for atrial fibrillation (AF). We aimed to evaluate the efficacy and safety of PVI applying tailored AI based on LAWT assessed by cardiac computed tomography (CT). METHODS: The thick segment was defined as the segment including ≥LAWT grade 3 (≥1.5 mm). The fixed AI strategy was defined as AI targets were 450 on the anterior/roof segments and 350 on the posterior/inferior/carina segments regardless of LAWT. The tailored AI strategy consisted of AI increasing the targets to 500 on the anterior/roof segments and to 400 on the posterior/inferior/carina segments when ablating the thick segment. After PVI, acute pulmonary vein (PV) reconnection, defined by the composite of residual potential and early reconnection, was evaluated. RESULTS: A total of 156 patients (paroxysmal AF 72%) were consecutively included (86 for the fixed AI group and 70 for the tailored AI group). The tailored AI group showed a significantly lower rate of segments with acute PV reconnection than the fixed AI group (8% vs. 5%, p = .007). The tailored AI group showed a trend for shorter ablation time for PVI. One-year AF/atrial tachycardia free survival rate was similar in two groups (87.2% in the fixed AI group and 90.0% in the tailored AI group, p = .606). CONCLUSION: Applying tailored AI based on the LAWT was a feasible and effective strategy to reduce acute PV reconnection after PVI.