Targeting the dermis for melasma maintenance treatment.

Melasma relapse is almost common after discontinuation of conventional treatment. Recent studies suggesting that photoaging dermis is the main pathomechanism of melasma, emphasize the dermal targeting therapy. We investigated maintenance effect of microneedling radiofrequency (RF) for melasma treatment. Subjects with melasma were administered oral tranexamic acid and triple combination cream for 2 months and a randomly assigned half face was treated with RF. After discontinuation of conventional therapy, the half face RF continued monthly over 6 months. Modified melasma area severity index (mMASI) score and L* value by a chromameter were collected monthly. Fifteen subjects were enrolled and eleven completed the 8-month study. At 2nd month of conventional therapy, all subjects showed improvement with a 64% reduction in mMASI score. With continuous RF treatment, the improvement was well maintained; whereas in untreated side, the Δ L* gradually decreased, returning to the baseline after the conventional therapy ended. The continuous microneedling RF therapy is beneficial in maintaining the conventional therapy of melasma suggesting the protective effect of dermal targeting therapy in melasma development.(Clinical Trial registration number: NCT05710068, date of first registration: 02/02/2023).

Ultraviolet-C light at 222 nm has a high disinfecting spectrum in environments contaminated by infectious pathogens, including SARS-CoV-2.

Ultraviolet light (UV) acts as a powerful disinfectant and can prevent contamination of personal hygiene from various contaminated environments. The 222-nm wavelength of UV-C has a highly effective sterilization activity and is safer than 275-nm UV-C. We investigated the irradiation efficacy of 222-nm UV-C against contaminating bacteria and viruses in liquid and fabric environments. We conducted colony-forming unit assays to determine the number of viable cells and a 50% tissue culture infectious dose assay to evaluate the virus titration. A minimum dose of 27 mJ/cm2 of 222-nm UV-C was required for >95% germicidal activity for gram-negative and -positive bacteria. A 25.1 mJ/cm2 dose could ensure >95% virucidal activity against low-pathogenic avian influenza virus and severe acute respiratory syndrome coronavirus (SARS-CoV-2). In addition, this energy dose of 222-nm UV-C effectively inactivated SARS-CoV-2 variants, Delta and Omicron. These results provide valuable information on the disinfection efficiency of 222-nm UV-C in bacterial and virus-contaminated environments and can also develop into a powerful tool for individual hygiene.

Preliminary Evaluation of a Conversational Agent to Support Self-management of Individuals Living With Posttraumatic Stress Disorder: Interview Study With Clinical Experts.

BACKGROUND: Posttraumatic stress disorder (PTSD) is a serious public health concern. However, individuals with PTSD often do not have access to adequate treatment. A conversational agent (CA) can help to bridge the treatment gap by providing interactive and timely interventions at scale. Toward this goal, we have developed PTSDialogue-a CA to support the self-management of individuals living with PTSD. PTSDialogue is designed to be highly interactive (eg, brief questions, ability to specify preferences, and quick turn-taking) and supports social presence to promote user engagement and sustain adherence. It includes a range of support features, including psychoeducation, assessment tools, and several symptom management tools. OBJECTIVE: This paper focuses on the preliminary evaluation of PTSDialogue from clinical experts. Given that PTSDialogue focuses on a vulnerable population, it is critical to establish its usability and acceptance with clinical experts before deployment. Expert feedback is also important to ensure user safety and effective risk management in CAs aiming to support individuals living with PTSD. METHODS: We conducted remote, one-on-one, semistructured interviews with clinical experts (N=10) to gather insight into the use of CAs. All participants have completed their doctoral degrees and have prior experience in PTSD care. The web-based PTSDialogue prototype was then shared with the participant so that they could interact with different functionalities and features. We encouraged them to "think aloud" as they interacted with the prototype. Participants also shared their screens throughout the interaction session. A semistructured interview script was also used to gather insights and feedback from the participants. The sample size is consistent with that of prior works. We analyzed interview data using a qualitative interpretivist approach resulting in a bottom-up thematic analysis. RESULTS: Our data establish the feasibility and acceptance of PTSDialogue, a supportive tool for individuals with PTSD. Most participants agreed that PTSDialogue could be useful for supporting self-management of individuals with PTSD. We have also assessed how features, functionalities, and interactions in PTSDialogue can support different self-management needs and strategies for this population. These data were then used to identify design requirements and guidelines for a CA aiming to support individuals with PTSD. Experts specifically noted the importance of empathetic and tailored CA interactions for effective PTSD self-management. They also suggested steps to ensure safe and engaging interactions with PTSDialogue. CONCLUSIONS: Based on interviews with experts, we have provided design recommendations for future CAs aiming to support vulnerable populations. The study suggests that well-designed CAs have the potential to reshape effective intervention delivery and help address the treatment gap in mental health.

Pseudoknot-targeting Cas13b combats SARS-CoV-2 infection by suppressing viral replication.

CRISPR-Cas13-mediated viral genome targeting is a novel strategy for defending against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. Here, we generated mRNA-encoded Cas13b targeting the open reading frame 1b (ORF1b) region to effectively degrade the RNA-dependent RNA polymerase gene. Of the 12 designed CRISPR RNAs (crRNAs), those targeting the pseudoknot site upstream of ORF1b were found to be the most effective in suppressing SARS-CoV-2 propagation. Pseudoknot-targeting Cas13b reduced expression of the spike protein and attenuated viral replication by 99%. It also inhibited the replication of multiple SARS-CoV-2 variants, exhibiting broad potency. We validated the therapeutic efficacy of this system in SARS-CoV-2-infected hACE2 transgenic mice, demonstrating that crRNA treatment significantly reduced viral titers. Our findings suggest that the pseudoknot region is a strategic site for targeted genomic degradation of SARS-CoV-2. Hence, pseudoknot-targeting Cas13b could be a breakthrough therapy for overcoming infections by SARS-CoV-2 or other RNA viruses.

Single-center real-world treatment outcomes of ablative fractional laser-assisted photodynamic therapy for actinic keratosis.

BACKGROUND: Among various treatment modalities of actinic keratosis (AK), ablative fractional laser-assisted photodynamic therapy (fractional PDT) has shown higher efficacy despite shorter incubation time. However, there are lack of real-world studies on the therapeutic response of ablative PDT for AK and the factors that can predict the therapeutic response. PURPOSE: The aim of this study was to analyze the association between clinical characteristics and treatment outcomes of fractional PDT. METHODS: One hundred fifty-six patients who were histologically diagnosed with AK and treated with fractional PDT were retrospectively reviewed. The Kruskal-Wallis test was used to compare treatment session differences according to grades. RESULTS: In multivariate analysis, the grade 2 category tended to be more clinically nonresponders than the grade 1 (OR, 5.17; 95% CI, 1.011-26.439; p = .048) and the group treated four or more times with ablative fractional laser-assisted PDT were more likely to show no response compared with the single treatment session group (OR, 8.78; 95% CI, 1.355-56.874; p = .023). Treatment sessions were significantly lower in grade 1 (1.72 ± 0.63, mean ± SD) when compared to grades 2 and 3, respectively (2.17 ± 0.76; 2.60 ± 1.60, mean ± SD). Recurrence was highest in grade 2, and most of them occurred after 1 year. CONCLUSION: On average, two treatment sessions are sufficient for AK lesions, but the thicker the lesion, the more treatment sessions may be required. Although there are relatively smaller number of grade 3 patients were included, recurrence was more frequent in higher grade of AK category, which needs special attention to thicker lesions.

Production of lactobionic acid at high salt concentrations by Acinetobacter halotolerans isolated from seaside soil.

A lactobionic acid (LBA)-producing bacterium isolated from seaside soils was identified as Acinetobacter halotolerans and designated as strain KRICT-1. We determined whether KRICT-1 can produce LBA at high salt concentrations. The KRICT-1 strain grew on a nutrient broth (NB) agar plate with up to 7.0% NaCl, indicating high NaCl tolerance, and 30 °C was the optimum growth temperature for LBA production. We produced LBA using the KRICT-1 strain in NB medium containing various concentrations of NaCl. While Pseudomonas taetrolens, an efficient LBA-producing bacterium, could produce LBA with up to 5.5% NaCl, the KRICT-1 strain could produce LBA at up to 7.0% NaCl and produced more LBA than P. taetrolens with over 5.5% NaCl. We produced LBA using NB medium containing 7.0% NaCl by batch fermentation of the KRICT-1 strain in a 5 L fermenter. The LBA production titer and productivity of the KRICT-1 strain were 32.1 g/L and 0.22 g/L/h, respectively, which were approximately 1.35- and 1.38-fold higher than those (23.7 g/L and 0.16 g/L/h) obtained from flask culture. Additionally, quinoprotein glucose dehydrogenase is an LBA-producing enzyme in A. halotolerans. We demonstrated that the A. halotolerans KRICT-1 strain is appropriate for LBA production at high salt concentrations.

Hepatitis C Virus Nonstructural Protein 5A Interacts with Immunomodulatory Kinase IKKε to Negatively Regulate Innate Antiviral Immunity.

Hepatitis C virus (HCV) infection can lead to chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. HCV employs diverse strategies to evade host antiviral innate immune responses to mediate a persistent infection. In the present study, we show that nonstructural protein 5A (NS5A) interacts with an NF-κB inhibitor immunomodulatory kinase, IKKε, and subsequently downregulats beta interferon (IFN-ß) promoter activity. We further demonstrate that NS5A inhibits DDX3-mediated IKKε and interferon regulatory factor 3 (IRF3) phosphorylation. We also note that hyperphosphorylation of NS5A mediats protein interplay between NS5A and IKKε, thereby contributing to NS5A-mediated modulation of IFN-ß signaling. Lastly, NS5A inhibits IKKε-dependent p65 phosphorylation and NF-κB activation. Based on these findings, we propose NS5A as a novel regulator of IFN signaling events, specifically by inhibiting IKKε downstream signaling cascades through its interaction with IKKε. Taken together, these data suggest an additional mechanistic means by which HCV modulates host antiviral innate immune responses to promote persistent viral infection.

Evaluation of Antiviral Effect against SARS-CoV-2 Propagation by Crude Polysaccharides from Seaweed and Abalone Viscera In Vitro.

Crude polysaccharides, extracted from two seaweed species (Hizikia fusiforme and Sargassum horneri) and Haliotis discus hannai (abalone) viscera, were evaluated for their inhibitory effect against SARS-CoV-2 propagation. Plaque titration revealed that these crude polysaccharides efficiently inhibited SARS-CoV-2 propagation with IC50 values ranging from 0.35 to 4.37 µg/mL. The crude polysaccharide of H. fusiforme showed the strongest antiviral effect, with IC50 of 0.35 µg/mL, followed by S. horneri and abalone viscera with IC50 of 0.56 and 4.37 µg/mL, respectively. In addition, immunofluorescence assay, western blot, and quantitative RT-PCR analysis verified that these polysaccharides could inhibit SARS-CoV-2 replication. In Vero E6 cells, treatment with these crude polysaccharides before or after viral infection strongly inhibited the expression level of SARS-CoV-2 spikes, nucleocapsid proteins, and RNA copies of RNA-dependent RNA-polymerase and nucleocapsid. These results show that these crude marine polysaccharides effectively inhibit SARS-CoV-2 propagation by interference with viral entry.

Efficient Production of Lactobionic Acid Using Escherichia coli Capable of Synthesizing Pyrroloquinoline Quinone.

Lactobionic acid (LBA) is an emerging chemical that has been widely utilized in food, cosmetic, and pharmaceutical industries. We sought to produce LBA using Escherichia coli. LBA can be produced from lactose in E. coli, which is innately unable to produce LBA, by coexpressing a heterologous quinoprotein glucose dehydrogenase (GDH) and a pyrroloquinoline quinone (PQQ) synthesis gene cluster. Using a recombinant E. coli strain, we successfully produced LBA without additional supplementation of PQQ, and changing the type of heterologous GDH improved the LBA production titer and productivity. To further enhance LBA production, culture conditions, such as growth temperature and isopropyl-ß-d-1-thiogalactopyranoside concentration, were optimized. Using optimized culture conditions, batch fermentation of the recombinant E. coli strain was performed using a 5 L bioreactor. After fermentation, this strain produced an LBA titer of 209.3 g/L, a yield of 100%, and a productivity of 1.45 g/L/h. To our best knowledge, this is the first study to produce LBA using heterologous GDH in an E. coli strain without any additional cofactors. Our results provide a simple method to produce LBA from lactose in a naturally non-LBA-producing bacterium and lay the groundwork for highly efficient LBA production in E. coli, which is one of the most versatile metabolite-producing bacterial hosts.

Objective stress monitoring based on wearable sensors in everyday settings.

Monitoring people's stress levels has become an essential part of behavioural studies for physical and mental illnesses conducted within the biopsychosocial framework. There have been several stress assessment studies in laboratory-based controlled settings. However, the results of these studies do not always translate effectively to an everyday context. The current state of wearable sensor technology allows us to develop systems measuring the physiological signals reflecting stress 24/7 while capturing the context. In this paper, we present a stress monitoring system that provides objective daily stress measurements in everyday settings based on three physiological signals: electrocardiogram (ECG), photoplethysmogram (PPG), and galvanic skin response (GSR) using Shimmer3 ECG, Shimmer3 GSR+, and Empatica E4 wearable sensors. We perform controlled stress assessment experiments on 17 participants in which we successfully detect stress with a 94.55% accuracy for 10-fold cross-validation and an 85.71% accuracy for subject-wise cross-validation. In everyday settings, the system assesses stress with an 81.82% accuracy. We also examine whether motion artefacts affect stress assessment and filter the low-confidence readings to minimise false alarms.

Comparison of Various Frequency Matching Schemes for Geometric Correction of Geostationary Ocean Color Imager.

Current precise geometric correction of Geostationary Ocean Color Imager (GOCI) image slots is performed by shoreline matching. However, it is troublesome to handle slots with few or no shorelines, or slots covered by clouds. Geometric correction by frequency matching has been proposed to handle these slots. In this paper, we further extend previous research on frequency matching by comparing the performance of three frequency domain matching methods: phase correlation, gradient correlation, and orientation correlation. We compared the performance of each matching technique in terms of match success rate and geometric accuracy. We concluded that the three frequency domain matching method with peak search range limits was comparable to geometric correction performance with shoreline matching. The proposed method handles translation only, and assumes that rotation has been corrected. We need to do further work on how to handle rotation by frequency matching.

Computer aided diagnosis sensor integrated outdoor shirts for real time heart disease monitoring.

The typical method of monitoring arrhythmia is to use a body patch type sensor with a wet electrode. It has several problems caused by wet electrodes for long-term monitoring. Thus, a monitoring sensor integrated into clothes with a dry electrode is proposed. In this study, we develop a smart outdoor shirt equipped with a dry electrode electrocardiogram (ECG) sensor for a cardiac arrhythmia computer aided diagnosis system. The sensor can be inserted in a console close to the chest, charged, used to communicate wirelessly, and connected with a smartphone application. The ECG signals measured by the smart shirt indicated that 97.5 ± 1% of the signals could be measured in an immobile state and at least 85.2 ± 2% of the signals could be measured during movement. We propose a computer aided diagnosis system for detecting cardiac arrhythmia. It was determined through experiments that the system can detect arrhythmia with an accuracy of 98.2 ± 2%. This study suggests that smart shirt which can diagnose arrhythmia will provide information that can quickly recognize arrhythmia in daily life or exercise.

Telephone follow-up care for disabled patients discharged after receiving dental treatment under outpatient general anesthesia.

BACKGROUND: Patients were subjected to post-discharge follow-up (by telephone) in order to investigate the potential complications of outpatient general anesthesia or deep sedation that could develop in disabled dental patients discharged from the hospital. The ultimate aim of this study was to establish an appropriate response measure for such complications. METHODS: The caregivers of 79 disabled patients who underwent dental procedures under general anesthesia at our outpatient clinic were interviewed over telephone. Necessary care instructions were provided during the phone calls when required. The patient satisfaction level regarding the telephonic follow-up care was surveyed by additional telephone calls. RESULTS: Most of the patients did not suffer any serious complications; however, some reported fever and bleeding. The data obtained in this study can be utilized towards the development of caregiver education pertaining to the ambulatory general anesthesia of dental patients with disabilities. CONCLUSIONS: Additionally, we hope that the findings of this study will help minimize the effects of complications experienced by disabled dental patients undergoing ambulatory general anesthesia, as well as increase the overall patient satisfaction level.

Emergency response team activation in the outpatient clinic of a single dental teaching hospital in Korea: a retrospective study of 10 years' records.

BACKGROUND: To prepare for possible emergency situations during dental treatment, it is helpful to know how often and what kinds of emergencies may arise. This study set out to evaluate the incidences, causes, treatments, and outcomes of emergency situations in the outpatient clinic of a dental teaching hospital in Korea. METHODS: We retrospectively reviewed the records of patients who had experienced an emergency situation and emergency response team activated in a selected outpatient clinic between November 2004 and November 2013. Specific information about the emergency cases was collected, including the patient characteristics and the frequency, types, treatments, and outcomes of the emergency situations. RESULTS: We identified 35 instances of emergency situations in 2,890,424 patients (incidence = 0.012 per 10,000 outpatients). The number of cases was as follows: 10 (28.6%) in the Department of Periodontics, 10 (28.6%) in the Department of Oral and Maxillofacial Surgery, 6 (17.1%) in the Department of Oral and Maxillofacial Radiology, 4 (11.4%) in the Department of Prosthodontics, 2 (5.7%) in the Department of Conservative Dentistry, 2 (5.7%) in the Department of Pediatric Dentistry, and 1 (2.9%) in the Department of Orthodontics. Three (8.6%) of the emergency situations arose before treatment, 22 (62.9%) during treatment, 7 (20.0%) after treatment, and 2 (5.7%) in a patient's guardian. CONCLUSIONS: In accordance with the growing elderly population and more aggressive dental procedures, the number of emergency situations may increase in the future. We recommend that clinicians keep in mind airway management and the active control of emergency situations.

Clinical considerations in the use of forced-air warming blankets during orthognathic surgery to avoid postanesthetic shivering.

BACKGROUND: During head and neck surgery including orthognathic surgery, mild intraoperative hypothermia occurs frequently. Hypothermia is associated with postanesthetic shivering, which may increase the risk of other postoperative complications. To improve intraoperative thermoregulation, devices such as forced-air warming blankets can be applied. This study aimed to evaluate the effect of supplemental forced-air warming blankets in preventing postanesthetic shivering. METHODS: This retrospective study included 113 patients who underwent orthognathic surgery between March and September 2015. According to the active warming method utilized during surgery, patients were divided into two groups: Group W (n = 55), circulating-water mattress; and Group F (n = 58), circulating-water mattress and forced-air warming blanket. Surgical notes and anesthesia and recovery room records were evaluated. RESULTS: Initial axillary temperatures did not significantly differ between groups (Group W = 35.9 ± 0.7℃, Group F = 35.8 ± 0.6℃). However, at the end of surgery, the temperatures in Group W were significantly lower than those in Group F (35.2 ± 0.5℃ and 36.2 ± 0.5℃, respectively, P = 0.04). The average body temperatures in Groups W and F were, respectively, 35.9 ± 0.5℃ and 36.2 ± 0.5℃ (P = 0.0001). In Group W, 24 patients (43.6%) experienced postanesthetic shivering, while in Group F, only 12 (20.7%) patients required treatment for postanesthetic shivering (P = 0.009, odds ratio = 0.333, 95% confidence interval: 0.147-0.772). CONCLUSIONS: Additional use of forced-air warming blankets in orthognathic surgery was superior in maintaining normothermia and reduced the incidence of postanesthetic shivering.

Suppression of E-cadherin mediates gallotannin induced apoptosis in Hep G2 hepatocelluar carcinoma cells.

Though gallotannin was known to have anti-oxidant and antitumor activity, the underlying antitumor mechanism of gallotannin still remains unclear. Thus, in the present study, antitumor mechanism of gallotannin was elucidated in hepatocellular carcinoma cells. Gallotannin significantly exerted cytotoxicity against Hep G2 and Chang hepatocellular carcinoma cells with the accumulation of the sub-G1 population and increase of terminal deoxynucleotidyltransferasedUTP nick end labeling (TUNEL) positive cells as an apoptotic feature. Also, gallotannin attenuated the expression of pro-caspase9, pro-caspase3, Bcl2 and integrin ß1 and cleaved poly(ADP)-ribose polymerase (PARP) in Hep G2 and Chang cancer cells. Furthermore, gallotannin suppressed cell repair motility by wound healing assay and also inhibited cell adhesion in Hep G2 cells. Of note, gallotannin attenuated the expression of epithelial cadherin (E-cadherin) to form cell-cell adhesion from the early stage, and also beta-catenin at late phase in Hep G2 cells. Consistently, Immunofluorescence assay showed that E-cadherin or ß-catenin expression was suppressed in a time dependent manner by gallotannin. Furthermore, silencing of E-cadherin by siRNA transfection method enhanced PAPR cleavage, caspase 3 activation and sub G1 population and attenuated the cell adhesion induced by gallotannin in Hep G2 cells. Overall, our findings demonstrate that the disruption of cell adhesion junction by suppression of E-cadherin mediates gallotannin enhanced apoptosis in Hep G2 liver cancer cells.