Search

Introduction Muscle strength is known to play an important role in the health of older adults. The health burden of cigarette smoking among older adults remains significant. We investigated the association between smoking cessation and dynapenia among older lifetime smokers in Korea. Methods This study is a secondary dataset analysis of cross-sectional data from the Korea National Health and Nutrition Examination Survey (KNHANES) 2016– 2019. We included 1450 participants aged 65–79 years, excluding those who had never smoked. Dynapenia was defined as grip strength

Metastatic lateral pelvic lymph nodes (LPNs) in rectal cancer significantly impact the prognosis and treatment strategies. Western practices emphasize neoadjuvant chemoradiotherapy (CRT), whereas Eastern approaches often rely on LPN dissection (LPND). This review examines the evolving role of LPND in the context of modern treatments, including total neoadjuvant therapy (TNT), and the impact of CRT on the management of clinically suspicious LPNs. We comprehensively reviewed the key literature comparing the outcomes of LPND versus preoperative CRT for rectal cancer, focusing on recent advancements and ongoing debates. Key studies, including the JCOG0212 trial and recent multicenter trials, were analyzed to assess the efficacy of LPND, particularly in conjunction with preoperative CRT or TNT. Current evidence indicates that LPND can reduce local recurrence rates compared to total mesorectal excision alone in patients not receiving radiation therapy. However, the benefit of LPND in the context of neoadjuvant CRT is influenced by the size and pretreatment characteristics of LPNs. While CRT can effectively control smaller metastatic LPNs, larger or clinically suspicious LPNs may require LPND for optimal outcomes. Advances in surgical techniques, such as robotic-assisted LPND, offer potential benefits but also present challenges and complications. The role of TNT in controlling metastatic LPNs and improving patient outcomes is emerging but remains underexplored. The decision to perform LPND should be individualized based on patient-specific factors, including LPN size, response to neoadjuvant treatment, and surgeon expertise. Future research should focus on optimizing treatment protocols and further evaluating the role of TNT in managing metastatic LPNs.

BackgroundBreast implants, including textured variants, have been widely used in aesthetic and reconstructive mammoplasty. However, the textured type, which is one of the shell texture types of breast implants, has been identified as a possible etiologic factor for lymphoma, specifically breast implant–associated anaplastic large cell lymphoma (BIA-ALCL). Identifying the shell texture type of the implant is critical to diagnosing BIA-ALCL. However, distinguishing the shell texture type can be difficult due to the loss of human memory and medical history. An alternative approach is to use ultrasonography, but this method also has limitations in quantitative assessment. ObjectiveThis study aims to determine the feasibility of using a deep learning model to classify the shell texture type of breast implants and make robust predictions from ultrasonography images from heterogeneous sources. MethodsA total of 19,502 breast implant images were retrospectively collected from heterogeneous sources, including images captured from both Canon and GE devices, images of ruptured implants, and images without implants, as well as publicly available images. The Canon images were trained using ResNet-50. The model’s performance on the Canon dataset was evaluated using stratified 5-fold cross-validation. Additionally, external validation was conducted using the GE and publicly available datasets. The area under the receiver operating characteristic curve (AUROC) and the area under the precision-recall curve (PRAUC) were calculated based on the contribution of the pixels with Gradient-weighted Class Activation Mapping (Grad-CAM). To identify the significant pixels for classification, we masked the pixels that contributed less than 10%, up to a maximum of 100%. To assess the model’s robustness to uncertainty, Shannon entropy was calculated for 4 image groups: Canon, GE, ruptured implants, and without implants. ResultsThe deep learning model achieved an average AUROC of 0.98 and a PRAUC of 0.88 in the Canon dataset. The model achieved an AUROC of 0.985 and a PRAUC of 0.748 for images captured with GE devices. Additionally, the model predicted an AUROC of 0.909 and a PRAUC of 0.958 for the publicly available dataset. This model maintained the PRAUC values for quantitative validation when masking up to 90% of the least-contributing pixels and the remnant pixels in breast shell layers. Furthermore, the prediction uncertainty increased in the following order: Canon (0.066), GE (0072), ruptured implants (0.371), and no implants (0.777). ConclusionsWe have demonstrated the feasibility of using deep learning to predict the shell texture type of breast implants. This approach quantifies the shell texture types of breast implants, supporting the first step in the diagnosis of BIA-ALCL.

To protect skin from harmful ultraviolet (UV) radiation, there has been a resurgence in the use of natural dyes with metal mordants to reduce contamination by advanced chemicals. This study achieved natural dyeing in violet and yellow colors from Gromwell red roots and Cape jasmine seeds for UV-protective materials. The dyed fabrics were subjected to zinc oxide (ZnO) and polyphenol treatments, as well as copper post-mordanting. The SEM, TEM, and XRD tests showed that the ZnO nanoparticles, with hexagonal crystal structures, stuck to the fiber surfaces, and twisted strands resulted in the K/S reduction. First, this study found that the untreated cotton in violet, despite the highest K/S, faded the most intensely when exposed to UV. The color variation of untreated polyester was narrow, with little change in L, a*, and K/S. The color change of yellow-dyed samples treated with ZnO/polyphenol was not considerable in yellowness (b*: 28.838), while the violet fabrics displayed a significant decrease in K/S and an increase in b*. The combination of ZnO and polyphenol treatment improved UV absorption at 350 to 250 nm. Among the Cu-mordanted fabrics after ZnO/phenols treatment, the violet cotton turned reddish from blueish (negative to positive b*), with a hue change of 316° to 59° and the highest ΔE (25.90 ± 4.34) after UV exposure. In this study, the combination of ZnO/polyphenol with Cu-mordants allowed the Cape jasmine-dyed polyester to achieve a minimum ΔE as well as to keep its chroma and hue after UV exposure.

Purpose The Korean Society of Coloproctology has been conducting Colorectal Cancer Awareness Campaign, also known as the Gold Ribbon Campaign, every September since 2007. The 2022 campaign was held through a metaverse platform targeting the younger age group under the slogan of raising awareness of early-onset colorectal cancer (CRC). This study aimed to analyze the impact of the 2022 campaign on a metaverse platform. Methods Anonymized survey data were collected from participants in the metaverse campaign from September 1 to 15, 2022. The satisfaction score of the participants was evaluated by sex, age group, and previous campaign participation status. Results During the campaign, 2,770 people visited the metaverse. Among them, 455 people participated in the survey (response rate, 16.4%). Approximately 95% of the participants reported being satisfied with the information provided by the campaign, understood the necessity of undergoing screening for and prevention of early-onset CRC, and were familiar with the structure of the metaverse. The satisfaction score for campaign information tended to decrease as the participants’ age increased. When the participants’ overall level of satisfaction with the metaverse platform was assessed, teenagers scored particularly lower than the other age groups. The satisfaction scores for CRC information provided in the metaverse, as well as the scores for recognizing the seriousness and necessity of screening for early-onset CRC, indicated a high positive tendency (P

Purpose Tubulinopathy represents a group of disorders caused by variants in tubulin genes, which present with a wide spectrum of brain malformations. This study was conducted to provide insight into the phenotypic and genetic spectra of tubulinopathy within the Korean pediatric population. Methods Among individuals who underwent genetic testing at a pediatric neurology clinic between June 2011 and December 2021, 15 patients with tubulin gene variants were retrospectively recruited. Clinical features, genetic information, and brain imaging findings were retrospectively reviewed. Results The genetic spectra of the patients included TUBA1A (n=5, 33.3%), TUBB4A (n=6, 40.0%), TUBB3 (n=2, 13.3%), TUBB (n=1, 6.7%), and TUBB2A (n=1, 6.7%) variants. Two novel mutations were identified: a c.497A>G; p.(Lys166Arg) variant in TUBA1A and a c.907G>C; p.(Ala303Pro) variant in TUBB. All 15 patients exhibited developmental delays, with a broad spectrum of severity. Other common manifestations included microcephaly (n=10; 66.7%) and seizures (n=9; 60%). A review of the neuroimaging data revealed a range of findings that were both genotype-specific and overlapping across genotypes. In cases of TUBA1A mutation (n=5), four patients (80%) presented with pachygyria and polymicrogyria, while three (60%) displayed cerebellar hypoplasia and dysplasia. All patients with TUBB4A variants (n=6) exhibited hypomyelination, and three (50%) had cerebellar dysplasia. Conclusion This study represents the first cohort analysis of tubulin gene mutations associated with tubulinopathy in a Korean pediatric population. It suggests that these mutations can produce a broad spectrum of neurodevelopmental and neuroimaging findings and should be considered within the differential diagnosis in relevant clinical scenarios.

Abstract Despite the proposal of numerous advanced materials for batteries, there remains a notable lack of comprehensive assessment protocols that facilitate direct comparisons between laboratory-scale research and industrial trials. Here, we introduce a standardized method coined as extremely lean electrolytic testing (ELET), designed as a uniform framework for evaluating the performance across different battery systems. This approach replicates the cycling behaviour of larger pouch cells within the more manageable format of coin cells under ELET conditions. Employing ELET, we develop quantitative models to create contour maps that standardize cell performance metrics. To demonstrate the ELET efficacy, we explore the mitigation of electrolyte decomposition in lithium-ion batteries through applying polydopamine coatings on silicon/carbon composite anodes, achieving a 150% decrease in electrolyte decomposition compared to uncoated ones. Additionally, we employ the ELET method to compare the performance of various post-secondary and commercial batteries, demonstrating its full utility in battery evaluation.

Abstract Photoporation techniques based on plasmonic nanoparticles such as gold nanoparticles have been extensively studied for the intracellular delivery of substances via cell membrane disruption. However, the clinical application of AuNP is challenging due to its absorption in the 500 nm region of the light spectrum. To overcome this challenge, upconversion nanoparticles were employed to stimulate AuNP at NIR wavelengths. posAuNP@UCNPs nanocomposites were produced by coating 30 nm UCNPs on 80 nm AuNPs using DOPA-PEI, which were then irradiated with 980 nm NIR light to facilitate their intracellular delivery. TEM and DLS confirmed that posAuNP and UCNP combine to form nanocomposites. Additionally, multiphysics simulation was used to analyze the distribution of the posAuNP electric field based on morphological differences that change as the UCNP ratio increases. Next, effective LED irradiation conditions were established by applying upconverting-photon quenching-mediated perforation influx to C28/I2 cells as suspensions or spheroids. posAuNP@UCNP nanocomposites were confirmed to be effective for the delivery of baricitinib as a treatment for osteoarthritis in a three-dimensional osteoarthritis model. Finally, chondrocyte differentiation was induced through intracellular delivery of baricitinib using posAuNP@UCNPs. The findings suggest that posAuNP@UCNPs have great potential as a tool for non-invasive drug delivery via UCPPin. Graphical Abstract

Abstract Skin electronics, facilitating a high-quality interface between external devices and human skin for recording physiological and/or electrophysiological signals as well as delivering external electrical and/or mechanical energy into the human body, has shown significant progress. However, achieving mechanically conformal contact and electrically low contact resistance at the device-skin interface remains challenging. Here, we propose a material strategy to potentially address such an issue by using phase separation of silver nanowires and silver nanoparticles (Ag NWs and Ag NPs) within a stretchable conductive nanocomposite (NC). This phase-separated NC ensures low contact resistance and high conductivity, which are key requirements in skin electronics, while maintaining excellent mechanical contact with the skin. To achieve phase separation, we hydrophobically treated the surfaces of Ag NWs and Ag NPs. Then, as the NC solidified, the solvent contained in the NC was slowly evaporated to sufficiently precipitate Ag NPs within the NC. As a result, the phase-separated NC exhibited high conductivity (~ 18,535 S cm−1), excellent stretchability (~ 80%), and low contact resistance on both the top and bottom NC surfaces (average ~ 0.132 Ω). The phase-separated NC has enabled implementation of high performance skin-mounted devices, including strain sensors, electrophysiological sensors, and a wearable heater.

2-Mercaptomethylbenzo[d]imidazole (2-MMBI) derivatives were designed and synthesized as tyrosinase (TYR) chelators using 2-mercaptomethylimidazole scaffolds. Seven of the ten 2-MMBI derivatives exhibited stronger inhibition of mushroom TYR activity than kojic acid. Their ability to chelate copper ions was demonstrated through experiments using the copper chelator pyrocatechol violet and assays measuring TYR activity in the presence or absence of exogenous CuSO4. The inhibition mechanisms of derivatives 1, 3, 8, and 9, which showed excellent TYR inhibitory activity, were elucidated through kinetic studies and supported by the docking simulation results. Derivatives 3, 7, 8, and 10 significantly inhibited cellular TYR activity and melanin production in B16F10 cells in a dose-dependent manner, with stronger potency than kojic acid. Furthermore, in situ, derivatives 7 and 10 showed stronger inhibitory effects on B16F10 cell TYR activity than kojic acid. Six derivatives, including 8, showed highly potent depigmentation in zebrafish larvae, outpacing kojic acid even at 200–670 times lower concentrations. Additionally, all derivatives could scavenge for reactive oxygen species without causing cytotoxicity in epidermal cells. These results suggested that 2-MMBI derivatives are promising anti-melanogenic agents.

Abstract Background Preoperative (chemo)radiotherapy has been widely used as an effective treatment for locally advanced rectal cancer (LARC), leading to a significant reduction in pelvic recurrence rates. Because early administration of intensive chemotherapy for LARC has more advantages than adjuvant chemotherapy, total neoadjuvant therapy (TNT) has been introduced and evaluated to determine whether it can improve tumor response or treatment outcomes. This study aims to investigate whether short-course radiotherapy (SCRT) followed by intensive chemotherapy improves oncologic outcomes compared with traditional preoperative long-course chemoradiotherapy (CRT). Methods A multicenter randomized phase II trial involving 364 patients with LARC (cT3–4, cN+, or presence of extramural vascular invasion) will be conducted. Patients will be randomly assigned to the experimental or control arm at a ratio of 1:1. Participants in the experimental arm will receive SCRT (25 Gy in 5 fractions, daily) followed by four cycles of FOLFOX (oxaliplatin, 5-fluorouracil, and folinic acid) as a neoadjuvant treatment, and those in the control arm will receive conventional radiotherapy (45–50.4 Gy in 25–28 fractions, 5 times a week) concurrently with capecitabine or 5-fluorouracil. As a mandatory surgical procedure, total mesorectal excision will be performed 2–5 weeks from the last cycle of chemotherapy in the experimental arm and 6–8 weeks after the last day of radiotherapy in the control arm. The primary endpoint is 3-year disease-free survival, and the secondary endpoints are tumor response, overall survival, toxicities, quality of life, and cost-effectiveness. Discussion This is the first Korean randomized controlled study comparing SCRT-based TNT with traditional preoperative LC-CRT for LARC. The involvement of experienced colorectal surgeons ensures high-quality surgical resection. SCRT followed by FOLFOX chemotherapy is expected to improve disease-free survival compared with CRT, with potential advantages in tumor response, quality of life, and cost-effectiveness. Trial registration This trial is registered at Clinical Research Information under the identifier Service KCT0004874 on April 02, 2020, and at Clinicaltrial.gov under the identifier NCT05673772 on January 06, 2023.

Abstract Bioresorbable bioelectronics, with their natural degradation properties, hold significant potential to eliminate the need for surgical removal. Despite notable achievements, two major challenges hinder their practical application in medical settings. First, they necessitate sustainable energy solutions with biodegradable components via biosafe powering mechanisms. More importantly, reliability in their function is undermined by unpredictable device lifetimes due to the complex polymer degradation kinetics. Here, we propose an on-demand bioresorbable neurostimulator to address these issues, thus allowing for clinical operations to be manipulated using biosafe ultrasound sources. Our ultrasound-mediated transient mechanism enables (1) electrical stimulation through transcutaneous ultrasound-driven triboelectricity and (2) rapid device elimination using high-intensity ultrasound without adverse health effects. Furthermore, we perform neurophysiological analyses to show that our neurostimulator provides therapeutic benefits for both compression peripheral nerve injury and hereditary peripheral neuropathy. We anticipate that the on-demand bioresorbable neurostimulator will prove useful in the development of medical implants to treat peripheral neuropathy.

AbstractAcanthogobius lactipes is a demersal, euryhaline fish belonging to the suborder Gobiodei. This study sequenced and described the complete mitochondrial genome of A. lactipes for the first time. The circular genome of A. lactipes is 16,592 bp in length and contains 13 protein-coding genes, 22 transfer RNA genes, two ribosomal RNA genes, and a control region. The overall A, C, G, and T contents were 27.78, 27.31, 17.52, and 27.39%, respectively. Based on the 13 protein-coding genes, the phylogenetic tree showed that A. lactipes formed a well-supported cluster with the genus Acanthogobius and rooted with other family Oxudercidae species.

Interfaces between implantable bioelectrodes and tissues provide critical insights into the biological and pathological conditions of targeted organs, aiding diagnosis and treatment. While conventional bioelectronics, made from rigid materials like metals and silicon, have been essential for recording signals and delivering electric stimulation, they face limitations due to the mechanical mismatch between rigid devices and soft tissues. Recently, focus has shifted toward soft conductive materials, such as conductive hydrogels and hydrogel nanocomposites, known for their tissue-like softness, biocompatibility, and potential for functionalization. This review introduces these materials and provides an overview of recent advances in soft hydrogel nanocomposites for implantable electronics. It covers material strategies for conductive hydrogels, including both intrinsically conductive hydrogels and hydrogel nanocomposites, and explores key functionalization techniques like biodegradation, bioadhesiveness, injectability, and self-healing. Practical applications of these materials in implantable electronics are also highlighted, showcasing their effectiveness in real-world scenarios. Finally, we discuss emerging technologies and future needs for chronically implantable bioelectronics, offering insights into the evolving landscape of this field.

Inspired by the potent tyrosinase inhibitory activity of phenolic compounds with a 2-phenylbenzo[d]thiazole scaffold, we explored phenolic compounds 1–15 with 2-phenylbenzo[d]oxazole, which is isosterically related to 2-phenylbenzo[d]thiazole, as novel tyrosinase inhibitors. Among these, compounds 3, 8, and 13, featuring a resorcinol structure, exhibited significantly stronger mushroom tyrosinase inhibition than kojic acid, with compound 3 showing a nanomolar IC50 value of 0.51 μM. These results suggest that resorcinol plays an important role in tyrosinase inhibition. Kinetic studies using Lineweaver–Burk plots demonstrated the inhibition mechanisms of compounds 3, 8, and 13, while docking simulation results indicated that the resorcinol structure contributed to tyrosinase binding through hydrophobic and hydrogen bonding interactions. Additionally, these compounds effectively inhibited tyrosinase activity and melanin production in B16F10 cells and inhibited B16F10 tyrosinase activity in situ in a concentration-dependent manner. As these compounds showed no cytotoxicity to epidermal cells, melanocytes, or keratinocytes, they are appropriate for skin applications. Compounds 8 and 13 demonstrated substantially higher depigmentation effects on zebrafish larvae than kojic acid, even at 800- and 400-times lower concentrations than kojic acid, respectively. These findings suggest that 2-phenylbenzo[d]oxazole is a promising candidate for tyrosinase inhibition.

Abstract Atopic dermatitis (AD) is an allergic, inflammatory skin disease caused by immune dysregulation. In this study, we investigated anti-atopic and anti-inflammatory activities of Sanguisorba hakusanensis ethanol extract (SHE) both in vivo using NC/Nga mice and in vitro using human HaCaT keratinocytes. Oral administration of SHE suppressed several atopic symptoms associated with house dust mites (induced with Dermatophagoides farinae extract) in NC/Nga mice and decreased serum levels of inflammatory mediators such as immunoglobulin E, histamine, and inflammatory chemokines. Additionally, SHE treatment reduced the infiltration of immune cells such as mast cells and macrophages in AD skin lesions. In vitro, interferon-γ- and tumor necrosis factor-α-stimulated HaCaT cells exhibited increased expression of T helper 1 and 2 chemokines; their expression was inhibited by SHE treatment. The anti-inflammatory effects of SHE treatment involved blocking of the mitogen-activated protein kinase and signal transducer and activator of transcription 1 signaling pathways. In conclusion, SHE exerts potent anti-atopic and anti-inflammatory effects and should be considered for the clinical treatment of AD.

Abstract The microbiota enhances exercise performance and regulates host physiology and energy metabolism by producing beneficial metabolites via bacterial fermentation. In this study, we discovered that germ-free (GF) mice had a reduced capacity for aerobic exercise as well as low oxygen consumption rates and glucose availability. Surprisingly, GF mice showed lower body weight gain and lower fat mass than specific pathogen-free (SPF) mice. Therefore, we hypothesized that these paradoxical phenotypes could be mediated by a compensatory increase in lipolysis in adipose tissues owing to impaired glucose utilization in skeletal muscle. Our data revealed that gut microbiota depletion impairs host aerobic exercise capacity via the deterioration of glucose storage and utilization. The improved browning ability of GF mice may have contributed to the lean phenotype and negatively affected energy generation. These adaptations limit obesity in GF mice but impede their immediate fuel supply during exercise, resulting in decreased exercise performance.

Abstract Background Unexpected and repeated miscarriages in a woman's life cycle can be a mental and physical burden and lead to post-traumatic stress disorder. However, women may also experience inner growth with such experiences. Methods This study was qualitative descriptive research examining the experiences of South Korean women who had recurrent miscarriages three or more times. Results The average age of the participants was 34.6 years, and the average number of recurrent miscarriages was 3.87. Additionally, five themes were identified as follows: (1) Confusing as if in muddy water, (2) Self-examination of past daily life, (3) Empathy and comfort in homogeneous groups, (4) Religious beliefs that include the lost fetus, and (5) Transforming for internal growth. Conclusion Based on the results of this study, intervention strategies need to be implemented to support the inner growth of women who have experienced recurrent miscarriages.

Abstract The development of artificial tactile receptor systems is important in the fields of prosthetic devices, interfaces for the metaverse, and sensors. A pressure sensor and memory device may be used in this system to replicate the tactile detecting capabilities of human skin. The implementation of systems that take into account mass production and miniaturization is still difficult. Here, a flexible artificial tactile receptor built using conventional semiconductor processes that combine a vertically stacked piezoelectric sensor with neuromorphic memory is presented. As a fundamental component for both sensors and memory, hafnium zirconium oxide (HZO) formed by using semiconductor deposition technique is introduced. Due to its exceptional piezoelectric performance, the morphotropic phase boundary of HZO is studied. The entire materials and processes are highly compatible with conventional semiconductor processes, including microwave annealing‐based low‐temperature crystallization. Even after 10,000 times of bending stress, the sensor and memory constructed on a flexible substrate exhibit consistent pressure detection characteristics over a wide range of 2–25 kPa. The feasibility of the approach is further demonstrated by a deep neural network simulation, which reached 90.8% braille recognition accuracy. Wearable electronics and medical devices are two examples of industrial domains that can use these flexible, exceptionally durable devices.

Piper attenuatum Buch-Ham, a perennial woody vine belonging to the Piperaceae family, is traditionally used in Southeast Asia for treating various ailments such as malaria, headache, and hepatitis. This study described the isolation and identification of three new compounds, piperamides I-III (1–3), which belong to the maleimide-type alkaloid skeletons, along with fifteen known compounds (4–18) from the methanol extract of the aerial parts of P. attnuatum. Their chemical structures were elucidated using spectroscopic methods (UV, IR, ESI-Q-TOF-MS, and 1D/2D NMR). All the isolates were evaluated for their ability to inhibit IL-6 activity in the human embryonic kidney-Blue™ IL-6 cell line and their cytotoxic activity against ovarian cancer cell lines (SKOV3/SKOV3-TR) and chemotherapy-resistant variants (cisplatin-resistant A2780/paclitaxel-resistant SKOV3). The compounds 3, 4, 11, 12, 17, and 18 exhibited IL-6 inhibition comparable to that of the positive control bazedoxifene. Notably, compound 12 displayed the most potent anticancer effect against all the tested cancer cell lines. These findings highlight the importance of researching the diverse activities of both known and newly discovered natural products to fully unlock their potential therapeutic benefits.

Based on the fact that substances with a β-phenyl-α,β-unsaturated carbonyl (PUSC) motif confer strong tyrosinase inhibitory activity, benzylidene-3-methyl-2-thioxothiazolidin-4-one (BMTTZD) analogs 1–8 were prepared as potential tyrosinase inhibitors. Four analogs (1–3 and 5) inhibited mushroom tyrosinase strongly. Especially, analog 3 showed an inhibitory effect that was 220 and 22 times more powerful than kojic acid in the presence of l-tyrosine and l-dopa, respectively. A kinetic study utilizing mushroom tyrosinase showed that analogs 1 and 3 competitively inhibited tyrosinase, whereas analogs 2 and 5 inhibited tyrosinase in a mixed manner. A docking simulation study indicated that analogs 2 and 5 could bind to both the tyrosinase active and allosteric sites with high binding affinities. In cell-based experiments using B16F10 cells, analogs 1, 3, and 5 effectively inhibited melanin production; their anti-melanogenic effects were attributed to their ability to inhibit intracellular tyrosinase activity. Moreover, analogs 1, 3, and 5 inhibited in situ B16F10 cellular tyrosinase activity. In three antioxidant experiments, analogs 2 and 3 exhibited strong antioxidant efficacy, similar to that of the positive controls. These results suggest that the BMTTZD analogs are promising tyrosinase inhibitors for the treatment of hyperpigmentation-related disorders.

Age-related macular degeneration (AMD) severely affects central vision due to progressive macular degeneration and its staggering prevalence is rising globally, especially in the elderly population above 55 years. Increased oxidative stress with aging is considered an important contributor to AMD pathogenesis despite multifaceted risk factors including genetic predisposition and environmental agents. Wet AMD can be managed with routine intra-vitreal injection of angiogenesis inhibitors, but no satisfactory medicine has been approved for the successful management of the dry form. The toxic carbonyls due to photo-oxidative degradation of accumulated bisretinoids within lysosomes initiate a series of events including protein adduct formation, impaired autophagy flux, complement activation, and chronic inflammation, which is implicated in dry AMD. Therapy based on antioxidants has been extensively studied for its promising effect in reducing the impact of oxidative stress. This paper reviews the dry AMD pathogenesis, delineates the effectiveness of dietary and nutrition supplements in clinical studies, and explores pre-clinical studies of antioxidant molecules, extracts, and formulations with their mechanistic insights.

Multimodal tactile sensors have played an important role in enhancing robot intelligence by providing reliable datasets originating from their high accuracy and durability characteristics. Herein, bimodal tactile sensors capable of simultaneously recognizing the size and stiffness of grasped objects, even deformable ones, are produced. The bimodal tactile sensors are fabricated using the identical process of controlling the air gap between a flexible substrate and the sensing layer, allowing the sensorized gripper to measure pressure and bending characteristics with high accuracy and durability. The pressure sensor yields an excellent durability performance with a negligible change of ΔI/I o

AimIron dysregulation in conjunction with other disease processes may exacerbate retinal degeneration. We employed models of iron overload and iron chelation to explore the interactions between iron-catalyzed oxidation and photoreactive bisretinoid lipofuscin.MethodsThe mice were injected intravitreally with ferric ammonium citrate (FAC) or were treated using the iron chelator deferiprone (DFP) from birth to 2 months of age. Short-wavelength fundus autofluorescence (SW-AF) and spectral-domain optical coherence tomography (SD-OCT) scans were acquired. The bisretinoid levels were quantified using ultra performance liquid chromatography (UPLC) and in vivo through quantitative fundus autofluorescence (qAF). In histologic sections, the photoreceptor cell viability was assessed by measuring the thickness of the outer nuclear layer (ONL).ResultsThe levels of bisretinoids, all-trans-retinal dimers, and A2PE were significantly increased in the FAC-injected eyes of C57BL/6J mice. Seven days after FAC injection, hyperautofluorescent foci were visible in fundus autofluorescence (488 nm) images, and in SD-OCT scans, aberrant hyperreflectivity was present in the outer retina and ONL thinning was observed. In FAC-injected Abca4–/– mice with pronounced RPE bisretinoid lipofuscin accumulation, the hyperautofluorescent puncta were more abundant than in the wild-type mice, and the extent of ONL thinning was greater. Conversely, the intravitreal injection of FAC in Mertk–/– mice led to a more modest increase in A2PE after 2 days. In contrast to the effect of iron accumulation, chelation with DFP resulted in significantly increased levels of A2E and A2-GPE and qAF due to the reduced iron-catalyzed oxidation of bisretinoids. In Mertk–/– mice, the A2E level was significantly lower and the ONL area was smaller than in DFP-treated mice. DFP chelation did not impair the visual cycle in BALB/cJ mice.ConclusionIron accumulation was associated with progressive impairment in photoreceptor cells that was associated with the increased formation of a bisretinoid species known to form in photoreceptor outer segments as a precursor to A2E. Additionally, disease features such as the development of hyperautofluorescence puncta in fundus AF images, hyperreflectivity in the outer retina of SD-OCT scans, and ONL thinning were more pronounced when iron was delivered to Abca4–/– mice with a greater propensity for bisretinoid formation. Higher bisretinoid levels and enhanced qAF are indicative of lesser bisretinoid loss due to oxidation.

Exercise and nutrition are primary interventions for preventing and managing sarcopenia. Although combining the two interventions would provide an additive effect, combined effects remain largely unexplored. Therefore, this study aimed to investigate whether the short-term AR and voluntary wheel running (VWR) treatments contribute to attenuating alterations in the anabolic resistance in middle-aged mice. Middle-aged (40-week-old) C57BL/6J mice were randomly assigned to five groups, receiving either AR with VWR or AR without VWR for 4 weeks. AR and VWR had a shared or separate mechanism of action: their combination had additive effects, leading to increased phosphorylation of the Akt, FOXO protein and inhibition of downstream MuRF-1 and Atrogin-1 mRNA expressions, inhibiting protein degradation. These results propose a potential benefit of AR supplementation and aerobic exercise as a strategy to delay the onset or attenuate the progression of age-associated loss of skeletal muscle mass and function.

Abstract To accurately probe the tactile information on soft skin, it is critical for the pressure sensing array to be free of noise and inter-taxel crosstalk, irrespective of the measurement condition. However, on dynamically moving and soft surfaces, which are common conditions for on-skin and robotic applications, obtaining precise measurement without compromising the sensing performance is a significant challenge due to mechanical coupling between the sensors and with the moving surface. In this work, multi-level architectural design of micro-pyramids and trapezoid-shaped mechanical barrier array was implemented to enable accurate spatiotemporal tactile sensing on soft surfaces under dynamic deformations. Trade-off relationship between limit of detection and bending insensitivity was discovered, which was overcome by employing micropores in barrier structures. Finally, in-situ pressure mapping on dynamically moving soft surfaces without signal distortion is demonstrated while human skin and/or soft robots are performing complicated tasks such as reading Braille and handling the artificial organs.

Abstract Background Resistance exercise training is known to improve metabolic disorders, such as obesity and type2 diabetes. In this study, we investigated whether the beneficial effects of resistance exercise training persisted even after the discontinuation of training with high-fat diet (HFD)-induced metabolic stress. We further evaluated whether the improvement in skeletal muscle strength and endurance by training were correlated with improved metabolism. Eight-week-old male C57BL/6N mice were divided into groups that remained sedentary or had access to daily resistance exercise via ladder climbing for 8 weeks. Trained and untrained mice were fed an HFD for 1 week after the exercise training intervention (n = 5–8 per group). Results Resistance exercise-trained mice had a lean phenotype and counteracted diet-induced obesity and glucose tolerance, even after exercise cessation. Grip strength was significantly inversely correlated with the body weight, fat mass, and glucose tolerance. However, hanging time was significantly inversely correlated with body weight only. Conclusions These results have strong implications for the preventive effect of resistance exercise-induced metabolic improvement by enhancing skeletal muscle strength rather than endurance.

In November 2020, an unusual increase in fungal endophthalmitis cases after cataract surgery was reported to the Korea Disease Control and Prevention Agency, South Korea. We initiated an outbreak investigation to identify the cause. We identified 156 cases nationwide, 62 confirmed and 94 probable. Most case-patients were exposed during surgery to ocular viscoelastic devices (OVDs) from the same manufacturer (company A). We isolated Fusarium spp. from 50 confirmed cases. Molecular identification of 39 fungal isolates from clinical samples and 13 isolates from OVDs confirmed F. oxysporum caused the infections. The risk ratio for fungal endophthalmitis from company A’s OVDs was 86.0 (95% CI 27.4–256.9), much higher than risk from other manufacturers’ products. We determined this fungal endophthalmitis outbreak was caused by a contaminated lot of OVDs and recommended discontinued use of this product. Early recognition of outbreaks and joint responses from related government agencies can reduce risk for fungal endophthalmitis.

Purpose Patients with self-limited epilepsy with centrotemporal spikes (SLECTS) rarely experience generalized tonic-clonic seizures (GTCS) after remission, and post-remission GTCS has not been thoroughly described in earlier studies. Herein, we describe the clinical and electrographic features of GTCS after a substantial period of seizure freedom in patients with SLECTS. Methods This study included six patients (three boys and three girls) diagnosed with SLECTS who later developed GTCS after or near remission. Medical records, including clinical data and serial electroencephalography (EEG) recordings, were retrospectively reviewed for all patients. Results Patients’ age at SLECTS onset ranged from 5.2 to 10.2 years (mean, 8.4 years), while seizure cessation was achieved between 8 and 12.2 years. During SLECTS, typical centrotemporal spikes were observed in all patients, and generalized spike-and-wave discharges were observed in three patients. The age at the first episode of subsequent GTCS ranged from 14.4 to 17.3 years (mean, 15.8 years), constituting an average interval of 5.6 years after the last episode of seizures (range, 4.1 to 8.1 years). EEG at subsequent episodes of GTCS revealed generalized discharges in two patients, focal discharges in two other patients, and normal discharges in the remaining two patients. Two patients had multiple episodes of GTCS. Conclusion Although rare, GTCS may occur near or after remission in patients with SLECTS, and clinicians should be aware of this. Subsequent GTCS may be a manifestation of idiopathic generalized epilepsy. However, large-scale studies are needed to determine the nature of such episodes of GTCS and their associated risk factors.

Abstract Background Although many efforts have been made to decrease the incidence of anastomotic leak (AL), it remains one of the most serious complications of rectal cancer surgery. Many previous studies have reported an association between the ligation level of the inferior mesenteric artery (IMA) (high or low) and the incidence of AL after rectal cancer surgery. However, we cannot draw a solid conclusion because of the low quality and heterogeneity of those studies. Therefore, this study aims to investigate the impact of the IMA ligation level on the occurrence of AL after minimally invasive anterior resection of rectal cancer. Methods/design Patients with primary rectal cancer without distant metastases will be included after screening. They will be randomly assigned (1:1) to receive high or low ligation of the IMA. The primary endpoint is AL incidence; secondary endpoints are quality of life; urinary, sexual, and defecatory functions; and 3-year disease-free survival. We hypothesized that the incidence rate of AL would be 15% and 5% in the high- and low-ligation groups, respectively. With a two-sided α of 0.05 and a power of 0.8, the sample size is calculated to be 314 patients (157 per group), considering a 10% dropout rate. Discussion Although many studies have compared the short- and long-term outcomes of high and low ligation of the IMA in rectal cancer surgery, it is still debatable. This trial aims to help draw a more solid conclusion regarding the association between the IMA ligation level and AL incidence after rectal cancer surgery. We also hope to contribute to standardizing the method of rectal cancer surgery in this trial. Trial registration Clinical Research Information Service KCT0003523. Registered on February 18, 2019

Most studies on the pathogenesis of inflammatory bowel disease (IBD) focus on gut function damage and gastrointestinal symptoms; however, psychiatric disorders, including depression and anxiety, have also been recognized as significant causes. Recently, we reported that Magnolia officinalis bark extract (MBE) alleviated enterocyte death in dextran sulfate sodium (DSS)-induced colitis mouse model that mimics IBD; however, the therapeutic effects of MBE on neurological symptoms and underlying mechanisms of IBD remain unclear. In this study, we aimed to elucidate the mechanisms by which microglia and astrocytes improve MBE-induced depression and anxiety. We found that MBE treatment improved DSS-induced weight loss, colon-length shortening, and cell death, with ameliorateon of depression/anxiety-like behavioral disorders. Systemic treatment with MBE significantly decreased DSS-induced proliferation of microglia and astrocytes in the hippocampal region, and attenuated the increase in pro-inflammatory cytokines, including IL-6 and COX-2. Interestingly, MBE alleviated DSS-induced alterations of the serotonergic system by improving serotonin levels, and expression of serotonin 4 receptor (5-HT4R) and cAMP response element-binding protein (CREB) phosphorylation in the hippocampus. Overall, our findings indicate that MBE exerts protective effects not only on gastrointestinal function but also on neuropsychiatric disorders caused by colitis, which may be developed to treat IBD.

Developing new plant varieties plays a crucial role in competitiveness in the agricultural and food industries and enhancing food security. Daehong (DH) is a new variety of Crataegus pinnatifida Bunge (CP); however, its physiological functions and potential as a nutraceutical ingredient remain unknown. Here, the efficacy of DH on inflammatory bowel disease (IBD) was investigated using dextran sulfate sodium (DSS)-induced colitis mice, and its relative pharmacological effects were analyzed against CP. DH improved colitis-induced weight loss, colon shortening, and inflammatory responses and reduced intestinal permeability. The reactive oxygen species (ROS)-mediated necroptotic signal that triggers enterocyte cell death in DSS-induced colitis was effectively controlled by DH, attributed to epicatechin. DSS-induced gut dysbiosis was recovered into a healthy gut microbiome environment by DH, increasing beneficial bacteria, like Akkermansia muciniphila, and changing harmful bacteria, including Bacteroides vulgatus and Peptostreptococcaceae. DH shows potential as a dietary or pharmaceutical ingredient to promote gut health and to prevent and treat IBD.

Abstract Realizing highly immersive tactile interactions requires a skin-integrated, untethered, high-definition tactile transducer devices that can record and generate tactile stimuli. However, the rigid and bulky form factor, and insufficient resolution of existing actuators are hindering the reproduction of sophisticated tactile sensations and immersive user experiences. Here, we demonstrate an ultra-flexible tactile interface with high spatial resolution of 1.8 mm for telehaptic communication on human skin. Dual mechanism sensors and sub-mm scale piezoceramic actuators are designed to record and generate the static and dynamic pressures in a wide frequency range (1 Hz to 1 kHz). Moreover, actuators are integrated on ultra-flexible substrate with chessboard pattern to minimize stress during mechanical deformations. Finally, remote transmissions of various tactile stimuli, such as shapes, textures, and vibration patterns were demonstrated by the telehaptic system with low latency (

Transtracheal jet ventilation can be used for resuscitation of partial airway obstruction. A prerequisite for jet ventilation is that at least a minimum airway opening for gas escape must be secured. Therefore, another option should be considered in cases of complete airway obstruction. The following methods or devices has been used under cricothyrotomy using an intravenous cannula: 1) Ambu (bag valve mask) bagging, 2) Ventrain®, 3) Rapid-O2 oxygen insufflation device (Rapid-O2), and 4) jet ventilation using a dual lumen catheter. During Ambu bagging, extraordinarily high insufflation pressure is required to force oxygen through the cannula. When using a 12-G cannula, long and slow positive-pressure ventilations (10–12 breaths/min) are required, which makes it extremely difficult to compress the bag. Therefore, a 10-G or larger is recommended. Ventrain® is an expiratory assist device capable of forcibly expelling insufflated oxygen through a transtracheal cannula. It is recommended to adjust the inspiratory and expiratory times while observing the chest wall movements. Rapid-O2 is a rescue oxygenation device with adequate ventilation of less importance; therefore, the resulting hypercarbia is inevitable. A 14-G cannula is used. Lastly, jet ventilation using a dual-lumen catheter with a 16-G inflow lumen and 10-G outflow lumen was used to obtain both oxygenation and ventilation. However, the addition of the outer diameters of 16-G and 10-G results in an outer diameter of 5.1 mm, which is too large to puncture the cricothyroid membrane. In conclusion, Ventrain® is considered the most ideal device for use among the devices developed to date.

Abstract Oxygen supplementation is crucial for awake tracheal intubation (ATI) using a flexible bronchoscope in patients with an anticipated difficult airway. However, the modality of optimal oxygen delivery remains unclear. This retrospective study compared high-flow nasal oxygen (HFNO) and conventional low-flow oxygen supply during ATI. We applied inverse probability of treatment weighting (IPTW) to account for biases due to clinical characteristic differences between the groups. The primary endpoint was the lowest oxygen saturation during ATI. The secondary endpoints were incidence of desaturation, multiple attempts, failure rate, and procedural duration. After IPTW adjustment, the lowest oxygen saturation in the HFNO group during ATI was significantly higher than that in the conventional oxygenation group (99.3 ± 0.2 vs. 97.5 ± 0.5, P

Stretchable metallic nanocomposites are viable material candidates for high‐performance soft biointerfacing electrodes. However, it is still challenging to fabricate a stretchable metallic nanocomposite that features outstanding charge transfer capability and low impedance as well as high conductivity and mechanical stability. Herein, a material strategy for a stretchable conductor that meets such requirements by integrating stretchable conductive nanocomposites with stretchable conductive nanomembranes (NMs) is presented. The silver nanowire (Ag NW) NM fabricated by the float assembly method is integrated with the Ag NW nanocomposite prepared by the drop‐casting method. The compactly assembled NWs in the NM maximize conductivity by reinforcing the percolation networks of the nanocomposite. Moreover, the NM lowers impedance by allowing efficient charge transfer to the target tissue through the exposed NWs. After their integration, a high conductivity of ≈35 700 S cm−1 is obtained, and the impedance is decreased by ≈88.9% (at 1000 Hz) in comparison with the original Ag NW‐based nanocomposite (i.e., without integration of the NM). The soft bioelectrode using the stretchable conductor successfully records electrograms from the rat heart, recognizes various arrhythmic events, and applies feedback pacing.

Background The present study evaluated the clinical implications of adjuvant chemotherapy according to the mismatch repair (MMR) status and clinicopathologic features of patients with intermediate- and high-risk stage II colon cancer (CC). Methods This study retrospectively reviewed 5,774 patients who were diagnosed with CC and underwent curative surgical resection at Kyungpook National University Chilgok Hospital. The patients were enrolled according to the following criteria: (1) pathologically diagnosed with primary CC; (2) stage II CC classified based on the 7th edition of the American Joint Committee on Cancer staging system; (3) intermediate- and high-risk features; and (4) available test results for MMR status. A total of 286 patients met these criteria and were included in the study. Results Among the 286 patients, 54 (18.9%) were identified as microsatellite instability-high (MSI-H) or deficient MMR (dMMR). Although all the patients identified as MSI-H/dMMR showed better survival outcomes, T4 tumors and adjuvant chemotherapy were identified as independent prognostic factors for survival. For the intermediate-risk patients identified as MSI-low (MSI-L)/microsatellite stable (MSS) or proficient MMR (pMMR), adjuvant chemotherapy exhibited a significantly better disease-free survival (DFS) but had no impact on overall survival (OS). Oxaliplatin-containing regimens showed no association with DFS or OS. Adjuvant chemotherapy was not associated with DFS in intermediate-risk patients identified as MSI-H/dMMR. Conclusion The current study found that the use of adjuvant chemotherapy was correlated with better DFS in MSI-L/MSS or pMMR intermediate-risk stage II CC patients.

Peri-implantitis is an inflammatory lesion leading to bone destruction resulting from bacterial infection and biofilm formation. Treatments of peri-implantitis aim at bacterial controls and decontamination to promote re-osseointegration. The present study aimed to assess the decontamination of biofilm and the osseointegration of titanium discs in a rabbit tibia model. Discs were immersed in culture medium inoculated with Staphylococcus aureus and incubated at 37 °C for 24 h and allocated to different treatments (n = five per group). The decontamination methods were an air-polishing system, 0.12% chlorhexidine rinse, and Er:Yag laser treatments. Each disc from the experimental groups was observed using scanning electron micrography. The rest of the discs were then implanted in four male New Zealand rabbits. Histological and radiographic evaluations were performed. For the quantification of bone density in radiographic data, the fractal dimension (FD) and mean grayscale value (GV) were measured. The Kruskal–Wallis test was used to compare bone density (p < 0.05). Statistically significant differences in FD were observed between the air-polishing treatment with chlorhexidine rinse and the air-polishing treatment with chlorhexidine rinse and Er:Yag laser treatment compared to the contaminated group (p < 0.05). Also, there were statistically significant differences in the results obtained for the group undergoing air-polishing treatment with chlorhexidine rinse and Er:Yag laser treatment compared to the contaminated group (p < 0.05). The decontamination method using air polishing treatment, chlorhexidine rinse, and Er:Yag treatment showed favorable osseointegration with good bone quality.

C1q nephropathy is a rare glomerulopathy that typically presents with nephrotic syndrome in children. Treatment with immunosuppressive agents renders patients vulnerable to infection and its complications. Gastroenteritis is common in children, and rotavirus is a leading cause. Extraintestinal manifestations of rotavirus have recently been reported; however, there is a paucity of cases exploring the involvement of a rotavirus on the respiratory system. Acute respiratory distress syndrome (ARDS) is a rapid onset respiratory failure characterized by noncardiogenic pulmonary edema and hypoxemia. Causes of ARDS include sepsis, pneumonia, pancreatitis, aspiration, and trauma. In this paper, we report a case of ARDS after rotavirus infection in a child with C1q nephropathy who had been treated with immunosuppressive agents.

Abstract We aimed to evaluate whether a short distal resection margin (

Nanotechnology has made biocompatible nanofibers grow in the healthcare industry. Herein, a cellulose acetate (CA) electrospun membrane was characterized by nanofibers of 438 (nm) in diameter between virus and bacteria, pore areas of 36.3%, and a pore size of 395 ± 263 (nm). This structure led to excellent air-water transfer through pore connectivity, contributing to sufficient wettability, air permeability, and water vapor transmission rate (WVTR). The air permeability of pristine CA membranes became predictable through multiple linear regression, based on the correlation to thickness, bulk density (Pearson’s coefficients: 0.754, −0.538). Nonetheless, the tensile strength of the pristine CA needed to be reinforced by spray coating with waterborne polyurethane (WPU) and graphene oxide (GO). The WPU/GO 6:1 (v/v) ratio was optimal due to the increase in ultimate tensile stress to 132.96% due to a synergy of GO’s covalent bonds with WPU’s hard segments and elongation at break to 113.40% from WPU polyols. The WPU/GO 6:1 coated CA membrane possessed still comparable air permeability (36.53 l/m 2 /s), and WVTR (5736 g/m 2 /day). Its rapid wetting transition from the Cassie-Baxter’s to Wenzel’s state was attributed to GO’s hydrophilic functional groups. These achievements in reinforcement of tensile strength and wettability would pave the way for filtration, and wound dressing.

Predicting individual radiotherapy (RT) response is valuable in managing head and neck squamous cell carcinoma (HNSCC). We assessed the feasibility of our novel 3D culture platform to measure radioresponse using patient-derived cells (PDCs) from HNSCC patients.Cells from the FaDu line and tumor samples from 39 HNSCC patients were cultivated serially in MatrigelTM on a 3D pillar/well array culture system. The 3D tumor models were exposed to 0 to 8 Gy of radiation dose, and the radioresponse index (RTauc, area under the dose-response curve) was measured quantitatively with Calcein AM staining of live tumor cells. Calcein AM fluorescence showed reduced density and the number of FaDu colonies as radiation increased, implying a dose-dependent effect on cell viability in the 3D pillar/well culture system. 3D tumor models using PDCs were established successfully from 39 HNSCC patient tumor samples, maintaining original genomic and pathological characteristics. These 3D tumor models were exposed to ionizing radiation on a 3D pillar/well array, with a mean period of 12 days from tumor harvest to the measurement of RTauc. The RTauc of all PDCs varied from 3.5 to 9.4, and the lower 40th percentile (Z-score = -0.26) was considered a good radioresponse group with a threshold RTauc of 4.6. The good radioresponse group showed fewer adverse features than others. As of the last follow-up, recurrence-free survival was better in the good radioresponse group (p = 0.037). 3D pillar/well array platforms using PDC could rapidly quantify radioresponse index in patients with HNSCC, showing potential as a novel prognosticator.

Ten 2-mercaptobenzimidazole (2-MBI) analogs were synthesized as potential tyrosinase inhibitors because mercapto-containing compounds can bind to copper ions at the active site of tyrosinase to inhibit enzyme activity. Nine 2-MBI analogs showed sub-micromolar IC50 values for mushroom tyrosinase monophenolase activity; analog 4 was 280-fold more potent than kojic acid, and in diphenolase activity, 6 was 970-fold more potent than kojic acid. The inhibition mode of the 2-MBI analogs was investigated using kinetic studies supported by docking simulations. Benzimidazoles without the 2-mercapto substituent of the 2-MBI analogs lost their tyrosinase inhibitory activity, implying that the 2-mercapto substituent plays an important role in tyrosinase inhibition. The 2-MBI analogs exerted potent antioxidant effects against 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS), 2,2-diphenyl-1-picrylhydrazyl (DPPH), and reactive oxygen species (ROS). The results obtained from apple slices and human embryonic kidney cells (HEK-293) suggest that most 2-MBI analogs are sufficiently safe candidates to delay the browning of apple slices effectively. Thus, these results support the potential use of 2-MBI analogs as anti-browning agents in foods such as mushrooms, vegetables, and fruits.

Purpose: This study aimed to identify the prevalence of fatigue and its associated factors leading to the fatigue among Korean commercial airline pilots. Methods: An anonymous, web-based questionnaire collecting data on sleep related characteristics was completed by airline pilots. The final 1,029 samples of completed questionnaires were analyzed. The association of the risk factors with fatigue was determined using logistic regression analysis. Results: The prevalence of fatigue was 60% (Fatigue Severity Scale index≥3.2), disturbed sleep 28% (Pittsburgh Sleep Quality Index≥9), daytime sleepiness 17% (Epworth Sleepiness Scale≥10), and sleep apnea (Berlin Questionnaire≥2) 11%. The fully adjusted logistic regression showed that quality of life (odds ratio [OR]=0.16, confidence interval [CI]=0.11–0.24), daytime sleepiness (OR=1.26, CI=1.18–1.34), sleep quality (OR=1.44, CI=1.29–1.61), mental workload (OR=1.10, CI=1.05–1.14), vigorous physical activity (OR=0.82, CI=0.72–0.92), late starts (OR=1.25, CI=1.06– 1.46) and average weekly flying hours (OR=1.02, CI=1.00–1.03) were associated with higher levels of fatigue. Conclusion: Lower quality of life, disturbed sleep, more subjective sleepiness, shorter sleep duration, higher mental workload, less vigorous physical activity, frequent late starts, and longer flying hour were shown to be risk factors for fatigue in airline pilots. These findings should be taken into account in the development of sleep and fatigue countermeasures for airline pilots.

Abstract Sarcopenia along with nutritional status are associated with postoperative pulmonary complications in various surgical fields. Recently, the creatinine/cystatin C ratio and CONtrolling NUTritional status score were introduced as biochemical indicators for sarcopenia and malnutrition, respectively. We aimed to investigate the associations among these indicators and postoperative pulmonary complications in elderly patients undergoing off-pump coronary artery bypass surgery. We reviewed the medical records of 605 elderly patients (aged ≥ 65 years) who underwent off-pump coronary artery bypass surgery from January 2010 to December 2019. Postoperative pulmonary complications (pneumonia, prolonged ventilation [> 24 h], and reintubation during post-surgical hospitalisation) occurred in 80 patients. A 10-unit increase of creatinine/cystatin C ratio was associated with a reduced risk of postoperative pulmonary complications (odds ratio: 0.80, 95% confidence interval: 0.69–0.92, P = 0.001); the optimal cut-off values for predicting postoperative pulmonary complications was 89.5. Multivariable logistic regression analysis revealed that age, congestive heart failure, and creatinine/cystatin C ratio

Background Due to their powerful immune surveillance activity and ability to kill and clear cancer cells, natural killer (NK) cells are an emerging anticancer immunotherapeutic agent. Therefore, there is much interest in developing efficient technologies that further enhance the therapeutic antitumor efficacy of NK cells.Methods To produce chemically primed NK cells, we screened polymers with various electric charges and examined their ability to enhance the cytotoxicity of NK cells. The effect of primary amine and electric charges of 25 kDa branched polyethylenimine (25KbPEI) was investigated by fluorination of the chemical. The role of 25KbPEI in determining the major priming mechanism was investigated in terms of calcium influx into NK cells. In vivo therapeutic efficacy of chemically primed NK cells was evaluated against solid tumor mouse model of triple negative breast and ovarian cancers.Results Chem_NK that was produced by the priming activity of 25KbPEI showed potent antitumor activity to various cancer cells. Chem_NK showed an activated phenotype, which manifests as increased expression of activating/adhesion/chemokine receptors and perforin accumulation, leading to enhanced migration ability and antitumor activity. Chem_NK display potent therapeutic efficacy against in vivo mouse model of triple negative breast and ovarian cancers. Fluorination of the primary amine group reduces the activity of 25KbPEI to prime NK cells, indicating that the cationic charge on the chemical plays a critical role in NK cell activation. A major priming mechanism was 25KbPEI-mediated calcium influx into NK cells, which occurred mainly via the Ca2+-permeable non-selective cation channel transient receptor potential melastatin 2.Conclusions NK cells can be chemically primed with 25KbPEI to express potent antitumor activity as well as enhanced migration ability. Because PEI is a biocompatible and Food and Drug Administration-approved chemical for biomedical use, these results suggest a cost-effective and simple method of producing therapeutic NK cells.

To facilitate the movement of retinoids through the visual cycle and to limit nonspecific chemical reaction, multiple mechanisms are utilized to handle these molecules when not contained within the binding pocket of opsin. Vitamin A aldehyde is sequestered by reversible Schiff base formation with phosphatidylethanolamine (PE) and subsequently undergoes NADPH-dependent reduction. Otherwise inefficient handling of retinaldehyde can lead to the formation of fluorescent di-retinal compounds within the outer segments of photoreceptor cells. These bisretinoid fluorophores initiate photooxidative processes having adverse consequences for retina. Various carrier proteins confer water solubility and maintain the 11-cis-retinoid configuration. Mechanisms for sequestration of retinoid include the formation of a reversible Schiff base between retinaldehyde and taurine (A1-taurine, A1T), the most abundant amino acid in photoreceptor cells. Here we have undertaken to examine the effects of taurine depletion using the transport inhibitors guanidinoethyl sulfonate (GES) and β-alanine. Oral treatment of BALB/cJ mice with β-alanine reduced ocular A1T and the mice exhibited significantly lower scotopic and photopic a-wave amplitudes. As a secondary effect of retinal degeneration, A1T was not detected and taurine was significantly reduced in mice carrying a P23H opsin mutation. The thinning of ONL that is indicative of reduced photoreceptor cell viability in albino Abca4−/− mice was more pronounced in β-alanine treated mice. Treatment of agouti and albino Abca4−/− mice with β-alanine and GES was associated with reduced bisretinoid measured chromatographically. Consistent with a reduction in carbonyl scavenging activity by taurine, methylglyoxal-adducts were also increased in the presence of β-alanine. Taken together these findings support the postulate that A1T serves as a reservoir of vitamin A aldehyde, with diminished A1T explaining reduced photoreceptor light-sensitivity, accentuated ONL thinning in Abca4−/− mice and attenuated bisretinoid formation.

Abstract Predicting difficult laryngoscopy is an essential component of the airway management. We aimed to evaluate the use of anterior neck soft tissue measurements on computed tomography for predicting difficult laryngoscopy and to present a clear measurement protocol. In this retrospective study, 281 adult patients whose tracheas were intubated using a direct laryngoscope for thyroidectomy were enrolled. On computed tomography, the distances from the midpoint of the thyrohyoid membrane to the closest concave point of the vallecular (membrane-to-vallecula distance; dMV), and to the most distant point of the epiglottis (membrane-to-epiglottis distance; dME) were measured, respectively. The extended distances straight to the skin anterior from the dMV and dME were called the skin-to-vallecula distance (dSV) and skin-to-epiglottis distance (dSE), respectively. Difficult laryngoscopy was defined by a Cormack-Lehane grade of > 2. Difficult laryngoscopy occurred in 40 (14%) cases. Among four indices, the dMV showed the highest prediction ability for difficult laryngoscopy with an area under the receiver operating characteristic curve of 0.884 (95% confidence interval 0.841–0.919, P