Revisiting roles of mast cells and neural cells in keloid: exploring their connection to disease activity.

Background: Mast cells (MCs) and neural cells (NCs) are important in a keloid microenvironment. They might contribute to fibrosis and pain sensation within the keloid. However, their involvement in pathological excessive scarring has not been adequately explored. Objectives: To elucidate roles of MCs and NCs in keloid pathogenesis and their correlation with disease activity. Methods: Keloid samples from chest and back regions were analyzed. Single-cell RNA sequencing (scRNA-seq) was conducted for six active keloids (AK) samples, four inactive keloids (IK) samples, and three mature scar (MS) samples from patients with keloids. Results: The scRNA-seq analysis demonstrated notable enrichment of MCs, lymphocytes, and macrophages in AKs, which exhibited continuous growth at the excision site when compared to IK and MS samples (P = 0.042). Expression levels of marker genes associated with activated and degranulated MCs, including FCER1G, BTK, and GATA2, were specifically elevated in keloid lesions. Notably, MCs within AK lesions exhibited elevated expression of genes such as NTRK1, S1PR1, and S1PR2 associated with neuropeptide receptors. Neural progenitor cell and non-myelinating Schwann cell (nmSC) genes were highly expressed in keloids, whereas myelinating Schwann cell (mSC) genes were specific to MS samples. Conclusions: scRNA-seq analyses of AK, IK, and MS samples unveiled substantial microenvironmental heterogeneity. Such heterogeneity might be linked to disease activity. These findings suggest the potential contribution of MCs and NCs to keloid pathogenesis. Histopathological and molecular features observed in AK and IK samples provide valuable insights into the mechanisms underlying pain and pruritus in keloid lesions.

Trends in obesity, leisure-time physical activity, and sedentary behavior in Korean adults: Korea national health and nutritional examinations survey from 2014 to 2021.

OBJECTIVES: This study aimed to investigate trends in obesity by dividing it based on body mass index (BMI) and waist circumference indicators, sedentary behavior, and leisure-time physical activity (LTPA) in Korean adults from 2014 to 2021. This study also aimed to determine the adherence rate of people with obesity to physical activity. METHODS: Data from the Korea National Health and Nutritional Examination Survey (KNHANES) from 2014 to 2021 were used. A total of 42,676 participants 19 years or older were included in the final analysis. Sociodemographic characteristics, anthropometric measurements, and physical activity levels were recorded. Physical activity levels were assessed using the Global Physical Activity Questionnaire, a self-reported questionnaire. Multivariable logistic regression analysis adjusted for covariates was used to investigate the prevalence of obesity and sitting time or adherence to meeting the physical activity guidelines for each survey year. RESULTS: This study included 42,676 adults. The weighted prevalence of obesity in all ages significantly increased from 30.8% (29.1%-32.5%) in 2014 to 34.5% (32.9%-36.2%) in 2017 and 37.3% (35.5%-39.1%) in 2021 (p for trend < 0.004). The weighted adherence rate to LTPA ranged from 25.5% (95% confidence interval [CI], 23.7%-27.2%) in 2014 to 20.5% (95% CI, 18.7%-22.2%) in 2021(p for trend < 0.001). The weighted prevalence of sitting time for 8 h/day or more significantly increased from 46.7% (44.4%-49.0%) in 2014 to 56.2% (54.4%-58.0%) in 2017 and 63% (60.7%-65.3%) in 2021 (p for trend < 0.001). According to this study, the LTPA level among women with obesity was significantly low. CONCLUSION: From 2014 to 2021, obesity and sedentary behavior significantly increased and adherence to LTPA decreased among Korean adults. Given these concerning trends, comprehensive interventions are needed at the national level to encourage healthy lifestyle behaviors.

Senolytic treatment reduces oxidative protein stress in an aging male murine model of post-traumatic osteoarthritis.

Senolytic drugs are designed to selectively clear senescent cells (SnCs) that accumulate with injury or aging. In a mouse model of osteoarthritis (OA), senolysis yields a pro-regenerative response, but the therapeutic benefit is reduced in aged mice. Increased oxidative stress is a hallmark of advanced age. Therefore, here we investigate whether senolytic treatment differentially affects joint oxidative load in young and aged animals. We find that senolysis by a p53/MDM2 interaction inhibitor, UBX0101, reduces protein oxidative modification in the aged arthritic knee joint. Mass spectrometry coupled with protein interaction network analysis and biophysical stability prediction of extracted joint proteins revealed divergent responses to senolysis between young and aged animals, broadly suggesting that knee regeneration and cellular stress programs are contrarily poised to respond as a function of age. These opposing responses include differing signatures of protein-by-protein oxidative modification and abundance change, disparate quantitative trends in modified protein network centrality, and contrasting patterns of oxidation-induced folding free energy perturbation between young and old. We develop a composite sensitivity score to identify specific key proteins in the proteomes of aged osteoarthritic joints, thereby nominating prospective therapeutic targets to complement senolytics.

Helminth egg derivatives as proregenerative immunotherapies.

The immune system is increasingly recognized as an important regulator of tissue repair. We developed a regenerative immunotherapy from the helminth Schistosoma mansoni soluble egg antigen (SEA) to stimulate production of interleukin (IL)-4 and other type 2-associated cytokines without negative infection-related sequelae. The regenerative SEA (rSEA) applied to a murine muscle injury induced accumulation of IL-4-expressing T helper cells, eosinophils, and regulatory T cells and decreased expression of IL-17A in gamma delta (γδ) T cells, resulting in improved repair and decreased fibrosis. Encapsulation and controlled release of rSEA in a hydrogel further enhanced type 2 immunity and larger volumes of tissue repair. The broad regenerative capacity of rSEA was validated in articular joint and corneal injury models. These results introduce a regenerative immunotherapy approach using natural helminth derivatives.

Suicide Screening Questionnaire-Self-Rating (SSQ-SR): Development, reliability, and validity in a clinical sample of Korean adults.

The goal of the present study was to evaluate the psychometric properties of the Suicide Screening Questionnaire-Self-Rating (SSQ-SR). A 25-item SSQ-SR is a newly developed suicide screening tool that measures suicide risk factors, including a history of suicidal thoughts and behaviors (STBs), life stress, and mental health problems. To investigate the reliability and validity of the SSQ-SR, we conducted a longitudinal case-control study with adults with and without STBs in the past six months. A total of 176 participants were recruited through 12 hospital-based Crisis Response Centers across South Korea. At the baseline, we administered the SSQ-SR, the Beck Scale for Suicide Ideation (BSSI), and the Patient Health Questionnaire-9 (PHQ-9). In a 6-months follow-up, we investigated whether the participants engaged in suicidal ideation, plan, or attempt since the baseline assessment. As a result, the SSQ-SR demonstrated a strong internal consistency (Cronbach's alpha coefficient = 0.96). In addition, the total score of SSQ-SR had concurrent validity compared to the total scores of the BSSI and the PHQ-9. In comparing the suicidal groups with the control group, the ROC analysis indicated the optimal cut point at 31 with a sensitivity rate of 0.97 and a specificity rate of 0.98. Through explanatory factor analysis, two factors were identified: Mental Health and Environmental Factors and Active Suicidal Thoughts and Behaviors. The SSQ-SR total and sub-factor scores were prospectively associated with subsequent suicidal ideation, plan, and attempt. These findings support that the SSQ-SR is a promising tool in prospectively screening those who are at risk of suicidal thoughts, plans, and nonfatal attempts.

Development and validation study of the suicide screening questionnaire-observer rating (SSQ-OR).

Background: Observer rating scales are necessary to evaluate the risk of suicide because individuals at risk for suicide are often unwilling to seek help on their own. Reliability and validity were evaluated for the newly developed Suicide Screening Questionnaire-Observer Rating (SSQ-OR). Methods: Preliminary items were assessed by 251 experts online and 25 questions were selected. 328 individuals at high-risk and 661 controls from 12 Crisis Response Centers and 5 university counseling centers were recruited to complete SSQ-OR, Beck Scale for Suicide Ideation (BSSI) and Patient Health Questionnaire-9 (PHQ-9). In a 6 months follow-up, we reached out to 176 participants to ask whether they had experienced a suicidal thought, plan, or attempt since the baseline assessment. Cronbach's α, Mann-Whitney U test, Spearman's correlation, factor analyses, Receiver operating characteristic (ROC) analysis and logistic regression analysis were used to verify the SSQ-OR. Results: Structural validity was supported by a two-factor solution using exploratory and confirmatory factor analyses. Excellent model fit indices for the two-factor structure using exploratory factor analysis were confirmed (RMSEA = 0.033, TLI = 0.980, CFI = 0.983). The SSQ-OR demonstrated strong internal consistency. The concurrent validity based on the correlations with other self-reported indicators of suicidal potential-BSSI and PHQ-9- revealed substantial relationships. The high-risk group was effectively characterized by a cut-off point of 4, with a sensitivity of 0.73 and a specificity of 0.79. The SSQ-OR scores were significant predictors of suicidal thoughts and behaviors within 6 months. Conclusions: The SSQ-OR exhibits sound psychometric properties, and could be used as a complement to a self-report or clinical-administered scale to screen suicide risk comprehensively.

Novel technology at hand to measure skin hydration by Biodisplay smartphone touch screen panel.

Skin hydration is generally evaluated using devices that measure capacitance or conductance. A new technology (Biodisplay) was developed to provide accurate measurements of skin hydration at the contact site. This study aimed to test the reliability of the Biodisplay by comparing its performance results with those of similar devices currently used to objectively assess skin hydration. For each of the 30 participants, skin hydration was measured at each of the defined points on the forearm three times using the Biodisplay and a Hydration probe (HP), an objective measurement device of skin hydration. We also evaluated skin hydration of the arm using both tools after applying moisturizers to evaluate interferences from skin care products. The reliability and reproducibility of each device were analyzed by intraclass correlation coefficients (ICC), and the correlation of the two devices was evaluated by Pearson's correlation coefficients (PCC). The Biodisplay demonstrated moderate-to-excellent reliability (ICC: (0.741-0.980)), but lower reliability than the HP (ICC: (0.953-0.980)). The skin hydration measurements made by the two devices were demonstrated to be significantly correlated, showing moderate correlations (PCC: 0.601). The Biodisplay can provide reasonably reliable and accurate measurements for skin hydration with the strong points of portability and accessibility.

Duration of Oral Antibiotics Administration for Cetuximab-Induced Acneiform Eruption.

BACKGROUND: Acneiform eruption is the most common cutaneous adverse event associated with cetuximab. As it can affect quality of life and adversely affect chemotherapy schedule, additional medical care is required. OBJECTIVES: To investigate the adherence to and the duration of antibiotic administration to treat cetuximab-induced acneiform eruption. METHODS: Medical data of patients who were referred to the Department of Dermatology were reviewed from January 2013 to June 2018. Dermatologists assessed the severity of acneiform eruption and prescribed tetracycline-class antibiotics according to the severity every 2 or 4 weeks. We investigated the duration and amount of oral antibiotic administration and analyzed the factors that may affect the control of acneiform eruption statistically. RESULTS: A total of 207 of 267 patients referred to the Department of Dermatology showed acneiform eruption; 124 patients were treated with minocycline, 34 patients with doxycycline, 27 patients with both, and 22 patients with topical agents. The mean duration of oral antibiotic medication was 82.7 days. A statistical analysis of the factors that prolonged the use of antibiotics for more than 90 days showed that male and younger age were risk factors. Shorter time interval from starting cetuximab to starting antibiotics was associated with longer duration of antibiotic use, statistically. CONCLUSIONS: Cetuximab-induced acneiform eruption can be well controlled with tetracycline-class antibiotics in about 3 months. It can last longer in male and younger patients. The sooner and the more severe it appears, the longer it can last.

Evolutionary processes of melanomas from giant congenital melanocytic nevi.

Melanoma can develop in a congenital melanocytic nevus (CMN). In fact, a large CMN is associated with a high risk of developing melanoma. Although melanomas arising from CMNs are thought to have a pathogenesis distinct from conventional melanomas, no studies have been conducted on the evolution or tumor heterogeneity of CMN melanomas. We applied multi-region whole-exome sequencing to investigate the clonal nature of driver events and evolutionary processes in CMNs and melanomas arising from CMNs. In two patients, we observed an independent subclonal evolution in cancerized fields of CMNs and chromosome 8q amplification in both melanomas arising from CMNs. The amplification of MYC, located in chromosome 8q, was correlated with the percentage of tumor cells expressing high levels of MYC protein detected in melanoma cells by immunohistochemistry. Our analysis suggests that each CMN cell may evolve sporadically and that amplification of MYC might be a key event for melanoma development in CMNs.

Biomaterials for Stem Cell Therapy for Cardiac Disease.

Myocardial Infarction (MI) in cardiac disease is the result of heart muscle losses due to a wide range of factors. Cardiac muscle failure is a crucial condition that provokes life-threatening outcomes. Heretofore, regeneration therapies in MI have used stem-cell-based therapy instantly after a myocardial injury to prevent the disease process and tissue malfunction. Despite the therapeutic utility of stem-cell-based regenerative therapy, barriers to successful treatment have been addressed. In this chapter, we illustrate a variety of emerging biomaterial strategies for enhancing the function of therapeutic stem cells, such as cell surface modification to synthetically endowing stem cells with new characteristics and hydrogels with its biological and mechanical properties. These investments offer a potential accompaniment to traditional stem-cell-based therapies for enhancing the efficacy of stem cell therapy to design properly activating cardiac tissues.

The effects of topical nitric oxide on healing of partial thickness porcine burns.

BACKGROUND: Nitric oxide is a wound mediator that promotes wound healing. We hypothesized that topical application of nitric oxide would speed reepithelialization, enhance angiogenesis, and reduce scar thickness in a partial thickness porcine burn model. METHODS: While under general anesthesia, 20 partial thickness burns were created on the backs of four female Yorkshire swine using a 2.5cm×2.5cm×7.5cm, 150-g aluminum bar, preheated to 80°C and applied for 20s. The necrotic epidermis was removed and the burns were randomized to low, medium, and high concentrations of a novel nitric-oxide (NO) releasing drug or its ointment vehicle applied 3 times weekly for 28 days. Full thickness punch biopsies were performed at 8, 11, 14 and 28 days after injury to determine percentage wound reepithelialization and scar thickness using H&E staining and blood vessel density using CD31 staining. RESULTS: At day 11, the percentages (SD) wound reepithelialization were: control, 26.3 (34.6); low NO, 23.9 (36.9); medium NO, 43.3 (42.9); and high NO, 59.9 (43.6); ANOVA, P=0.02. The number of CD31 stained blood vessels at days 8 and 11 were greater in wounds treated with high dose NO vs. controls (48.1 vs. 22.9 [P<0.001] and 44.0 vs. 33.5 [P=0.05] per 1mm2 respectively). Scar thicknesses (SD) in mm at day 28 by treatment allocation were: control, 4.8 (1.2); low NO, 4.7 (1.2); medium NO, 4.3 (1.2); and high NO, 4.1 (1.0); P=0.22. CONCLUSIONS: Treatment of partial thickness porcine burns with high concentrations of topical NO resulted in earlier reepithelization and increased angiogenesis but not reduced scar thickness compared with its control vehicle in a partial thickness porcine burn model.

Unexplained persistent dyspnea in a young woman with eosinophilic angiocentric fibrosis.

Eosinophilic angiocentric fibrosis (EAF) is a rare inflammatory disease that primarily involves the nose and sinuses. Involvement of the eye orbit and larynx has also been described. However, it is very rare for this disease to involve the lower respiratory tract and cause dyspnea. We describe a rare case of EAF involving the lower respiratory tract with airway narrowing. A 29-year-old female with a 7-year history of nasal obstruction presented with unexplained persistent dyspnea. EAF was diagnosed via endoscopic biopsy of an irregular mucosal lesion in the posterior wall of the right maxillary sinus. Chest computed tomography and bronchoscopy showed a diffuse inflammatory narrowing of the airway in the tracheobronchial trees. EAF can affect lower respiratory tracts with airway narrowing that can be characterized by dyspnea. We must consider narrowing of the lower respiratory tracts in patients with EAF complaining of unexplained persistent dyspnea.

Ultrafast biexciton spectroscopy in semiconductor quantum dots: evidence for early emergence of multiple-exciton generation.

Understanding multiple-exciton generation (MEG) in quantum dots (QDs) requires in-depth measurements of transient exciton dynamics. Because MEG typically faces competing ultrafast energy-loss intra-band relaxation, it is of central importance to investigate the emerging time-scale of the MEG kinetics. Here, we present ultrafast spectroscopic measurements of the MEG in PbS QDs via probing the ground-state biexciton transients. Specifically, we directly compare the biexciton spectra with the single-exciton ones before and after the intra-band relaxation. Early emergence of MEG is evidenced by observing transient Stark shift and quasi-instantaneous linewidth broadening, both of which take place before the intra-band relaxation. Photon-density-dependent study shows that the broadened biexciton linewidth strongly depends on the MEG-induced extra-exciton generation. Long after the intra-band relaxation, the biexciton broadening is small and the single-exciton state filling is dominant.

Ultrafast zero balance of the oscillator-strength sum rule in graphene.

Oscillator-strength sum rule in light-induced transitions is one general form of quantum-mechanical identities. Although this sum rule is well established in equilibrium photo-physics, an experimental corroboration for the validation of the sum rule in a nonequilibrium regime has been a long-standing unexplored question. The simple band structure of graphene is an ideal system for investigating this question due to the linear Dirac-like energy dispersion. Here, we employed both ultrafast terahertz and optical spectroscopy to directly monitor the transient oscillator-strength balancing between quasi-free low-energy oscillators and high-energy Fermi-edge ones. Upon photo-excitation of hot Dirac fermions, we observed that the ultrafast depletion of high-energy oscillators precisely complements the increased terahertz absorption oscillators. Our results may provide an experimental priori to understand, for example, the intrinsic free-carrier dynamics to the high-energy photo-excitation, responsible for optoelectronic operation such as graphene-based phototransistor or solar-energy harvesting devices.

Multiple pass ultrasound tightening of skin laxity of the lower face and neck.

BACKGROUND: Skin laxity is a common complaint of patients who request skin rejuvenation. Radiofrequency and infrared light are widely used for nonablative treatment of skin laxity. Intense focused ultrasound (IFUS) has been investigated as a tool for the treatment of solid benign and malignant tumors for many decades but is only now beginning to emerge as a potential noninvasive alternative to conventional nonablative therapy. OBJECTIVES: To evaluate the efficacy of IFUS for the treatment of face and neck laxity. METHODS: Twelve female volunteers were enrolled in the study, and 10 were ultimately evaluated. The device under investigation was an IFUS. Areas treated included the face and neck. For treatment, the 4-MHz, 4.5-mm probe was used first, followed by the 7-MHz, 3.0-mm probe. Two blinded, experienced clinicians evaluated paired pretreatment and post-treatment (day 90) photographs. Patient self-assessments were also obtained. RESULTS: On the first primary outcome measure, two blinded clinicians felt that 8 of 10 subjects (80%) showed clinical improvement 90 days after treatment. Nine of 10 subjects (90%) reported subjective improvement. CONCLUSIONS: IFUS has many advantages for skin tightening.

Imaging of viral thymidine kinase gene expression by replicating oncolytic adenovirus and prediction of therapeutic efficacy.

PURPOSE: We have used a genetically attenuated adenoviral vector which expresses HSVtk to assess the possible additive role of suicidal gene therapy for enhanced oncolytic effect of the virus. Expression of TK was measured using a radiotracer-based molecular counting and imaging system. MATERIALS AND METHODS: Replication-competent recombinant adenoviral vector (Ad-DeltaE1B19/55) was used in this study, whereas replication-incompetent adenovirus (Ad-DeltaE1A) was generated as a control. Both Ad-DeltaE1B19/55-TK and Ad-DeltaE1A-TK comprise the HSVtk gene inserted into the E3 region of the viruses. YCC-2 cells were infected with the viruses and incubated with 2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl-5-iodouracil (I-131 FIAU) to measure amount of radioactivity. The cytotoxicity of the viruses was determined, and gamma ray imaging of HSVtk gene was performed. MTT assay was also performed after GCV treatment. RESULTS: On gamma counter-analyses, counts/ minute (cpm)/microg of protein showed MOIs dependency with DeltaE1B19/55-TK infection. On MTT assay, Ad-DeltaE1B19/55-TK led to more efficient cell killing than Ad-DeltaE1A-TK. On plate imaging by gamma camera, both Ad-DeltaE1B19/55-TK and Ad-DeltaE1A-TK infected cells showed increased I-131 FIAU uptake in a MOI dependent pattern, and with GCV treatment, cell viability of DeltaE1B19/55-TK infection was remarkably reduced compared to that of Ad-DeltaE1A-TK infection. CONCLUSION: Replicating Ad-DeltaE1B19/55-TK showed more efficient TK expression even in the presence of higher-cancer cell killing effects compared to non-replicating Ad-DeltaE1A-TK. Therefore, GCV treatment still possessed an additive role to oncolytic effect of Ad-DeltaE1B19/55-TK. The expression of TK by oncolytic viruses could rapidly be screened using a radiotracer-based counting and imaging technique.