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Abstract Understanding how marine organisms adapt to local environments is crucial for predicting how populations will respond to global climate change. The genomic basis, environmental factors and evolutionary processes involved in local adaptation are however not well understood. Here we use Atlantic herring, an abundant, migratory and widely distributed marine fish with substantial genomic resources, as a model organism to evaluate local adaptation. We examined genomic variation and its correlation with environmental variables across a broad environmental gradient, for 15 spawning aggregations in Atlantic Canada and the United States. We then compared our results with available genomic data of northeast Atlantic populations. We confirmed that population structure lies in a fraction of the genome including likely adaptive genetic variants of functional importance. We discovered 10 highly differentiated genomic regions distributed across four chromosomes. Nine regions show strong association with seasonal reproduction. One region, corresponding to a known inversion on chromosome 12, underlies a latitudinal pattern discriminating populations north and south of a biogeographic transition zone on the Scotian Shelf. Genome–environment associations indicate that winter seawater temperature best correlates with the latitudinal pattern of this inversion. The variation at two so‐called ‘islands of divergence’ related to seasonal reproduction appear to be private to the northwest Atlantic. Populations in the northwest and northeast Atlantic share variation at four of these divergent regions, simultaneously displaying significant diversity in haplotype composition at another four regions, which includes an undescribed structural variant approximately 7.7 Mb long on chromosome 8. Our results suggest that the timing and geographic location of spawning and early development may be under diverse selective pressures related to allelic fitness across environments. Our study highlights the role of genomic architecture, ancestral haplotypes and selection in maintaining adaptive divergence in species with large population sizes and presumably high gene flow.

Background: GP trainees may not have experienced a systematic and comprehensive education in safe prescribing. Therefore, a self-assessment prescribing review was developed. Aim: To determine whether the assessment was feasible, had face validity, and did not disadvantage particular groups of participants. Design & setting: An online survey that evaluates the opinions of GPs in training of a prescribing assessment in the UK. All full-time UK trainees who started their final year of GP training in August 2019 undertook the prescribing assessment along with their trainers, after which they completed an online anonymous feedback questionnaire. Method: The questionnaire completed by trainees sought their opinions of the assessment, and collected ethnicity and disability data. The trainer questionnaire was similar but did not include any demographic information. Results: The questionnaire was completed by 1741 trainees and 1576 trainers. There was no evidence that ethnic group and disability were related to aspects of the review. Most of the trainees (76.4%, n = 1330) and trainers (82.0%, n = 1293) agreed or strongly agreed that the prescribing review was helpful for assessing and learning about the trainee’s prescribing. However, most participants (63.2%, n = 1092) took >4 hours to review their prescriptions. A majority of trainees (90.2%, n = 1571) reported that completing the assessment had resulted in a change in their prescribing practice. Conclusion: The majority of trainers and trainees reported that the prescribing assessment was helpful. The study was not able to assess whether there had been an actual change in practice that resulted in an error reduction.

Alternative pre-mRNA splicing (AS) is a biological process that results in proteomic diversity. However, implications of AS alterations in cancer remain poorly understood. Herein, we performed a comprehensive AS analysis in cancer driver gene transcripts across fifteen cancer types and found global alterations in inclusion rates of the PBAF SWI/SNF chromatin remodeling complex subunit Polybromo 1 (PBRM1) exon 27 (E27) in most types of cancer tissues compared with those in normal tissues. Further analysis confirmed that PBRM1 E27 is excluded by the direct binding of RBFOX2 to intronic UGCAUG elements. In addition, the E27-included PBRM1 isoform upregulated PD-L1 expression via enhanced PBAF complex recruitment to the PD-L1 promoter. PBRM1 wild-type patients with clear cell renal cell carcinoma were resistant to PD-1 blockade therapy when they expressed low RBFOX2 mRNA levels. Overall, our study suggests targeting of RBFOX2-mediated AS of PBRM1 as a potential therapeutic strategy for immune checkpoint blockade., Competing Interests: Disclosure and competing interests statement The authors declare no competing interests., (© 2024. The Author(s).)

Purpose: Laparoscopic colon surgery is now commonly used for colorectal cancer (CRC) resection. The objective of this study was to compare the oncologic outcomes between open conversion and laparoscopic surgery, and to identify risk factors for open conversion., Methods: We retrospectively reviewed the medical records of patients who underwent curative resection for stage 0-III CRC at five Hallym University-affiliated hospitals between January 2011 and June 2021. The patients were divided into the conversion and laparoscopic groups according to whether laparoscopic surgery was completed., Results: Out of 2231 patients, laparoscopic surgery was completed in 2131 patients and 100 (4.5 %) converted to open surgery. The operation time (P = 0.028) and postoperative hospital stay (P = 0.036) were longer in the conversion group than in the laparoscopic group. Overall (P = 0.022) and severe (Clavien-Dindo classification grade ≥3) (P = 0.048) complications were more frequent in the conversion group than in the laparoscopic group. The 5-year recurrence-free survival (RFS) rate was worse in the conversion group than in the laparoscopic group (P = 0.002). In the multivariable analysis, open conversion was not a prognostic factor for RFS (P = 0.082). Abdominal surgery history (P = 0.021), obstruction (P < 0.001), and T4 stage (P < 0.001) were independently associated with open conversion., Conclusion: The conversion group had worse perioperative and oncologic outcomes. History of abdominal surgery, obstruction, and T4 stage were associated with open conversion. However, conversion itself was not associated with RFS., Competing Interests: Declarations of competing interest None., (Copyright © 2024. Published by Elsevier Ltd.)

A food exchange list is a tool developed to help diabetic patients control their energy intake and plan balanced meals. Korean food exchange lists were first developed in 1988, revised in 1995, and updated again in 2010. With rapidly changing dietary habits and increasing demand for diverse food cultures, the Korean Diabetes Association in cooperation with 4 related organizations established a Task Force Team (TFT) to revise food exchange lists in March 2022. Starting with a workshop, TFT held 11 official revision meetings, culminating in a public hearing in May 2023. The final revised version of Korean food exchange lists was published in December 2023. Key outcomes of the revision are summarized as follows: 1. Based on the National Standard Food Composition Table 10.0 database, the existing classification system and nutrient standards for each food group remain unchanged this time. 2. Based on a survey conducted among diabetes educators, the number of items on the food exchange lists has increased from 339 in 2010 to 435 this time. 3. Considering patients' usual eating habits, meal planning examples were developed distributing food group exchange units by energy level based on 3 types of proportions of carbohydrate energy (40%-45%, 50%-55%, 60%-65%). 4. Due to limitations in real-time updates for rapidly changing information, detailed guidance on how to access and interpret the data is provided. These revisions will help people with diabetes manage their blood sugar levels and facilitate the implementation of healthy meal planning in various other conditions, including obesity., Competing Interests: Conflict of Interest: The authors declare that they have no competing interests., (Copyright © 2024. The Korean Society of Clinical Nutrition.)

Gelatin methacryloyl (GelMA) hydrogels are used for stem cell encapsulation in bone tissue engineering due to their fast and stable photo-crosslinking. However, cell viability and ability to induce osteogenesis are reduced by reactive oxygen species (ROS) produced during the crosslinking reaction. In this study, we developed biomimetic nanoparticles (TMNs) by combining tannic acid (TA) and simulated body fluid (SBF) minerals, and used them to synthesize GelMA-based composite hydrogels for addressing those limitations. The optimal concentrations of TA and SBF were investigated to create nanoparticles that can effectively scavenge ROS and induce osteogenesis. The incorporation of TMNs into composite hydrogels (G-TMN) significantly enhanced the survival and proliferation of encapsulated human adipose-derived stem cells (hADSCs) by providing resistance to oxidative conditions. In addition, the ions that were released, such as Ca 2+ and PO 4 3- , stimulated stem cell differentiation into bone cells. The hADSCs encapsulated in G-TMN had 2.0 ± 0.8-fold greater viability and 1.3 ± 1.8 times greater calcium deposition than those encapsulated in the hydrogel without nanoparticles. Furthermore, the in vivo transplantation of G-TMN into a subcutaneous mouse model demonstrated the rapid degradation of the gel-network while retaining the osteoinductive particles and cells in the transplanted area. The increased cellular activity observed in our multifunctional composite hydrogel can serve as a foundation for novel and effective therapies for bone deformities., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Exposure to adverse experiences during early life is associated with an increased risk of psychopathology during adolescence. In a previous study, we demonstrated that neonatal maternal separation (NMS) combined with social isolation led to impulsive and depressive-like behaviors in male adolescents. Additionally, it significantly reduced the expression of excitatory amino acid carrier 1 (EAAC1) in the hippocampus. Building upon this work, we investigated the effects of N-acetylcysteine (NAC), a precursor to glutathione, in early-life stress (ELS) model rats and in EAAC1 -/- mice. EAAC1 plays a dual role in transporting both glutamate and cysteine into neurons. Our findings revealed that female adolescents subjected to in the ELS model also exhibited behavioral defects similar to those of males. NAC injection rescued depressive-like behaviors in both male and female NMS models, but it improved impulsive behavior only in males. Furthermore, we observed increased reactive oxidative stress (ROS) and neuroinflammation in the ventral hippocampus (vHPC) and prefrontal cortex of NMS model rats, which were mitigated by NAC treatment. Notably, NAC reversed the reduced expression of EAAC1 in the vHPC of NMS model rats. In EAAC1 -/- mice, severe impulsive and depressive-like behaviors were evident, and the NAC intervention improved only depressive-like behaviors. Collectively, our results suggest that ELS contributes to depression and impulsive behaviors during adolescence. Moreover, the cysteine uptake function of EAAC1 in neurons may be specifically related to depression rather than impulsive behavior., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

We present a case of a 13-year-old patient with a distinct tumor with both granular cell and perineurial elements, located on the lower lip. The patient presented with a long-standing lip mass that was clinically felt to most likely represent a mucocele. Following surgical excision, histopathological examination revealed a well-circumscribed tumor composed of granular cells with positive S100 protein staining and spindled cells positive for EMA and GLUT-1, confirming mixed neuroectodermal and perineurial origin. This is the first case documenting a perineurial-granular cell hybrid tumor in a patient under 18 years old, and the first to be reported in the head and neck. This case expands our understanding of hybrid PNSTs, emphasizing the importance of considering diverse clinical presentations, especially in the context of rare pediatric occurrences in atypical locations., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

This pilot study explored whether a socially assistive robot (SAR) would have positive effects on Korean American immigrant older adults' health behaviors and emotional well-being and whether the older adults would be receptive to the SAR. A total of 30 participants (age 65+) in a large metropolitan area participated in the study, and each participant was provided a SAR named Hyodol for 4 months and interacted with it in ways that they saw appropriate. We used one-group pre- and post-test design to assess changes between baseline and follow-up in medication adherence, depressive symptoms, loneliness, and disability. Additionally, we employed in-depth qualitative interviews to explore participants' perceptions about the SAR. At post-test, participants showed improved medication adherence, reduced depressive symptoms, and a slightly and statistically nonsignificant decrease in loneliness scores. Qualitative data suggested high adoptability of this particular SAR among the participants., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Previous studies have reported that amputation invokes body-wide responses in regenerative organisms, but most have not examined the implications of these changes beyond the region of tissue regrowth. Specifically, long-range epidermal responses to amputation are largely uncharacterized, with research on amputation-induced epidermal responses in regenerative organisms traditionally being restricted to the wound site. Here, we investigate the effect of amputation on long-range epidermal permeability in two evolutionarily distant, regenerative organisms: axolotls and planarians. We find that amputation triggers a long-range increase in epidermal permeability in axolotls, accompanied by a long-range epidermal downregulation in MAPK signaling. Additionally, we provide functional evidence that pharmacologically inhibiting MAPK signaling in regenerating planarians increases long-range epidermal permeability. These findings advance our knowledge of body-wide changes due to amputation in regenerative organisms and warrant further study on whether epidermal permeability dysregulation in the context of amputation may lead to pathology in both regenerative and non-regenerative organisms., Competing Interests: CONFLICT OF INTEREST J.L.W. is a co-founder of Matice Biosciences. Other authors declare no conflicts of interest.

Introduction: Nocardia farcinica is an opportunistic bacterium that causes bovine mastitis and pulmonary, cutaneous, and central nervous system infections in humans. Bovine abortion caused by N. farcinica has been sporadically reported. The purpose of this study was to analyze the pathological findings of bovine abortions caused by N. farcinica in the Republic of Korea and determine the antimicrobial resistance and genotypical characteristics of N. farcinica isolates., Case Presentation: Three cases of bovine abortions were submitted to the Animal and Plant Quarantine Agency for differential diagnosis. Grossly, one fetus showed severe lung consolidation following palpation of the entire lobes. Histologically, necrotizing granulomatous interstitial pneumonia was observed in all fetuses; a fetus with a gross lesion demonstrated necrotizing lymphadenitis in the mesenteric lymph nodes and necrotizing dermatitis in the ear. N. farcinica isolates were isolated from the abomasal contents and lungs of all fetuses. Finally, two cases were diagnosed as abortions due to N. farcinica , and one was diagnosed as an N. farcinica abortion coinfected with bovine viral diarrhea virus. According to the multilocus sequence analysis, all isolates were identified as N. farcinica and were determined to be genetically related to isolates from humans. Two N. farcinica isolates were resistant to trimethoprim-sulfamethoxazole, which is recommended as the first treatment for human nocardial infections., Conclusion: This is the first pathological report of bovine abortion caused by N. farcinica in the Republic of Korea. Further studies are needed to phenotypically and genotypically characterize N. farcinica isolates with various sources and continuously monitor antimicrobial resistance patterns., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kim, Yun, Bae, Lee, Moon, Lee, Jeoung, Ku and Kim.)

Exposure to storage mite (SM) and house dust mite (HDM) allergens is a risk factor for sensitization and asthma development; however, the related immune responses and their pathology have not been fully investigated. The HDMs Dermatophagoides farinae and Dermatophagoides pteronyssinus and SM Tyrophagus putrescentiae are potent allergens that induce asthma. Most SM-related studies have focused on the allergic reactions of individuals by measuring their immunoglobulin (Ig)E expression. Considering the limited research on this topic, the present study aims to investigate the differences in the immune responses induced by HDMs and SMs and histologically analyze lung tissues in a mouse asthma model to understand the differential effects of HDM and SM. The results revealed that all mite species induced airway inflammation. Mice challenged with T. putrescentiae had the highest airway resistance and total cell, eosinophil, and neutrophil counts in the bronchoalveolar lavage fluid (BALF). The SM-sensitized groups showed more severe lesions and mucus hypersecretions than the HDM-sensitized groups. Although the degree of HDM and SM exposure was the same, the damage to the respiratory lung tissue was more severe in SM-exposed mice, which resulted in excessive mucin secretion and increased fibrosis. Furthermore, these findings suggest that SM sensitization induces a more significant hypersensitivity response in mucosal immunity than HDM sensitization in asthma models.

Acute stress caused by short-term exposure to deleterious chemicals can induce the aggregation of RNA-binding proteins (RBPs) in the cytosol and the formation of stress granules (SGs). The cytoplasmic RBP, Ras GTPase-activating protein-binding protein 1 (G3BP1) is a critical organizer of SG, and its aggregation is considered a hallmark of cellular stress. However, assembly of SG is a highly dynamic process that involves RBPs; hence, existing methods based on fixation processes or overexpression of RBPs exhibit limited efficacy in detecting the assembly of SG under stress conditions. In this study, we established a G3BP1- Green fluorescent protein (GFP) reporter protein in a human neuroblastoma cell line to overcome these limitations. GFP was introduced into the G3BP1 genomic sequence via homologous recombination to generate a G3BP1-GFP fusion protein and further analyze the aggregation processes. We validated the assembly of SG under stress conditions using the G3BP1-GFP reporter system. Additionally, this system supported the evaluation of bisphenol A-induced SG response in the established human neuroblastoma cell line. In conclusion, the established G3BP1-GFP reporter system enables us to monitor the assembly of the SG complex in a human neuroblastoma cell line in real time and can serve as an efficient tool for assessing potential neurotoxicity associated with short-term exposure to chemicals., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The emergence of drug-resistant Mycobacterium tuberculosis (M.tb) has led to the development of novel anti-tuberculosis (anti-TB) drugs. Common methods for testing the efficacy of new drugs, including two-dimensional cell culture models or animal models, have several limitations. Therefore, an appropriate model representative of the human organism is required. Here, we developed an M.tb infection model using human lung organoids (hLOs) and demonstrated that M.tb H37Rv can infect lung epithelial cells and human macrophages (hMφs) in hLOs. This novel M.tb infection model can be cultured long-term and split several times while maintaining a similar number of M.tb H37Rv inside the hLOs. Anti-TB drugs reduced the intracellular survival of M.tb in hLOs. Notably, M.tb growth in hLOs was effectively suppressed at each passage by rifampicin and bedaquiline. Furthermore, a reduction in inflammatory cytokine production and intracellular survival of M.tb were observed upon knockdown of MFN2 and HERPUD1 (host-directed therapeutic targets for TB) in our M.tb H37Rv-infected hLO model. Thus, the incorporation of hMφs and M.tb into hLOs provides a powerful strategy for generating an M.tb infection model. This model can effectively reflect host-pathogen interactions and be utilized to test the efficacy of anti-TB drugs and host-directed therapies., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Kim et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This study presents a deep learning model to predict phlebitis in patients with peripheral intravenous catheter (PIVC) insertions. Leveraging electronic health record data from 27,532 admissions and 70,293 PIVC events at a hospital in Seoul, South Korea, the study involved analyzing patient demographics, PIVC-specific features, and drug-related information. The developed deep learning model was benchmarked against various machine learning models, demonstrating superior performance with an accuracy of 0.93 and an AUC of 0.89. This highlights its potential as an effective tool for early detection of phlebitis, promising enhanced patient outcomes and healthcare efficiency.

Objectives: This study aimed to determine the risk of ischemic heart disease (IHD) and stroke among male couriers in Korea by linking the data from the National Health Insurance (NHI) and National Employee Insurance (NEI) databases., Methods: As of 2015, the NHI and NEI databases were linked using individual IDs. A cohort of male couriers, aged between 20 and 64 years, ( N = 5,012) was constructed using the Korean Employment Insurance Occupational Classification (KECO-2007). For comparison, a cohort of male total wage workers ( N = 5,429,176) and a cohort of office workers ( N = 632,848) within the same age group were also constructed. The follow-up was conducted until 31 December 2020 to confirm the occurrence of IHD and stroke. The diagnoses were defined using the 10th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-10) codes. The criteria included medical services for more than 1 day of hospitalization or more than 2 outpatient visits. The age-standardized incidence ratio (SIR) was calculated to evaluate the risk of occurrence. The hazard ratio (HR) was calculated using the Cox model after adjusting for age, alcohol consumption, smoking, obesity, income level, and employment duration as confounding variables., Results: The SIR of IHD for couriers was 1.54 (95% CI 1.31-1.78), while for office workers, it was 1.08 (95% CI 1.06-1.10), compared to male total wage workers. The SIR for stroke was higher for couriers at 1.84 (95% CI 1.40-2.28) and lower for office workers at 0.86, compared to male total wage workers. Couriers had a higher SIR for stroke at 1.84 (95% CI 1.40-2.28) and lower for office workers at 0.86 (0.83-0.89). Compared to total wage workers, couriers had a significantly higher adjusted HR for IHD at 1.60 (95% CI 1.37-1.87) and a higher HR for stroke at 1.39 (95% CI 1.07-1.79). Compared to office workers, couriers had a significantly higher HR for IHD at 1.34 (95% CI 1.13-1.59) as well as for for stroke at 1.43 (95% CI 1.08-1.88)., Conclusion: The incidence of IHD and stroke was higher among male couriers compared to male office workers and total wage workers, highlighting the need for implementing public health interventions to prevent IHD and stroke among couriers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yoon, Min, Kim, Kim and Kim.)

Exposure to toxic molecules from food or oral medications induces toxicity in colon cells that cause various human diseases; however, in vitro monitoring systems for colon cell toxicity are not well established. Stress granules are nonmembranous foci that form in cells exposed to cellular stress. When cells sense toxic environments, they acutely and systemically promote stress granule formation, with Ras GTPase-activating protein-binding protein 1 (G3BP1) acting as a core component to protect their mRNA from abnormal degradation. Here, we knocked in green fluorescent protein (GFP)-coding sequences into the C-terminal region of the G3BP1 gene in a human colon cell line through CRISPR-Cas9-mediated homologous recombination and confirmed the formation of stress granules with the G3BP1-GFP protein in these cells under cellular stress exposure. We demonstrated the formation and dissociation of stress granules in G3BP1-GFP expressing colon cells through real-time monitoring using a fluorescence microscope. Furthermore, we validated the toxicity monitoring system in the established colon cell line by observing stress granule formation following exposure to dihydrocapsaicin, bisphenol A, and sorbitol. Taken together, we established a stress granule reporter system in a colon cell line, providing a novel assessment for the real-time monitoring of colon toxicity in response to various chemicals., Competing Interests: The authors report no declarations of interest., (© 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

The skin, the organ with the largest surface area in the body, is the most susceptible to chemical exposure from the external environment. In this study, we aimed to establish an in vitro skin toxicity monitoring system that utilizes the mechanism of stress granule (SG) formation induced by various cellular stresses. In HaCaT cells, a keratinocyte cell line that comprises the human skin, a green fluorescent protein (GFP) was knocked in at the C-terminal genomic locus of Ras GTPase-activating protein-binding protein 1 (G3BP1), a representative component of SGs. The G3BP1-GFP knock-in HaCaT cells and wild-type (WT) HaCaT cells formed SGs containing G3BP1-GFP upon exposure to arsenite and household chemicals, such as bisphenol A (BPA) and benzalkonium chloride (BAC), in real-time. In addition, the exposure of G3BP1-GFP knock-in HaCaT cells to BPA and BAC promoted the phosphorylation of eukaryotic initiation factor 2 alpha and protein kinase R-like endoplasmic reticulum kinase, which are cell signaling factors involved in SG formation, similar to WT HaCaT cells. In conclusion, this novel G3BP1-GFP knock-in human skin cell system can monitor SG formation in real-time and be utilized to assess skin toxicity to various substances., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Bladder cancer (BCa) is the most common malignancy of the urinary system. It has a high recurrence rate and requires longterm follow-up. Significant advances in BCa research have been made in recent years; however, the initial diagnosis and follow-up of BCa relies on cystoscopy, which is an invasive and expensive procedure. Over the past decade, liquid biopsies (e.g., blood and urine) have proven to be highly efficient methods for the discovery of BCa biomarkers. This noninvasive sampling method is used to analyze unique tumor components released into body fluids and enables serial sampling and longitudinal monitoring of tumor progression. Several liquid biopsy biomarkers have been studied extensively and have shown promising results in the clinical applications of BCa, including early detection, microscopic residual disease detection, recurrence prediction, and treatment response. Therefore, this review aims to provide an update on various new liquid biopsy markers and the advantages and current limitations of liquid biopsy in the diagnosis of BCa.

Objectives: To evaluate if there is a difference in International Normalized Ratio (INR) readings taken within the 15 second time frame after lancing the finger vs 30-60 seconds of obtaining a blood drop utilizing a CoaguChek ® XS Plus point-of-care (POC) INR machine in patients on warfarin therapy. Methods: All adult patients on anticoagulation therapy with warfarin who were managed in a pharmacist-run anticoagulation clinic were considered for inclusion in the study. The mean difference of INR readings taken less than 15 seconds vs between 30-60 seconds after the blood drop was obtained from the finger was assessed. Results: A total of 62 pairs of INR results were included in the study. There was a mean difference in INR of .076 (95% CI 0.011-.140; P = .0217) when comparing INR readings taken less than 15 seconds and between 30-60 seconds after the blood drop was obtained from the finger. Conclusions: There was a significant difference in INR readings taken less than 15 seconds vs 30-60 seconds after obtaining the blood drop when utilizing a POC INR machine. INR readings taken 30-60 seconds after obtaining a blood drop with the CoaguChek ® XS Plus POC INR machine is not acceptable for use to monitor patients on warfarin., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The objective of standard guideline for utilization of human lung organoids is to provide the basic guidelines required for the manufacture, culture, and quality control of the lung organoids for use in non-clinical efficacy and inhalation toxicity assessments of the respiratory system. As a first step towards the utilization of human lung organoids, the current guideline provides basic, minimal standards that can promote development of alternative testing methods, and can be referenced not only for research, clinical, or commercial uses, but also by experts and researchers at regulatory institutions when assessing safety and efficacy.

Accurate simulation of different cell type interactions is crucial for physiological and precise in vitro drug testing. Human tissue-resident macrophages are critical for modulating disease conditions and drug-induced injuries in various tissues; however, their limited availability has hindered their use in in vitro modeling. Therefore, this study aimed to create macrophage-containing organoid co-culture models by directly incorporating human-induced pluripotent stem cell (hiPSC)-derived pre-macrophages into organoid and scaffold cell models. The fully differentiated cells in these organoids exhibited functional characteristics of tissue-resident macrophages with enriched pan-macrophage markers and the potential for M1/M2 subtype specialization upon cytokine stimulation. In a hepatic organoid model, the integrated macrophages replicated typical intrinsic properties, including cytokine release, polarization, and phagocytosis, and the co-culture model was more responsive to drug-induced liver injury than a macrophage-free model. Furthermore, alveolar organoid models containing these hiPSC-derived macrophages also showed increased drug and chemical sensitivity to pulmonary toxicants. Moreover, 3D adipocyte scaffold models incorporating macrophages effectively simulated in vivo insulin resistance observed in adipose tissue and showed improved insulin sensitivity on exposure to anti-diabetic drugs. Overall, the findings demonstrated that incorporating hiPSC-derived macrophages into organoid culture models resulted in more physiological and sensitive in vitro drug evaluation and screening systems., (Creative Commons Attribution license.)

Naturally occurring canine invasive urinary carcinoma (iUC) closely resembles human muscle invasive bladder cancer in terms of histopathology, metastases, response to therapy, and low survival rate. The heterogeneous nature of the disease has led to the association of large numbers of risk loci in humans, however most are of small effect. There exists a need for new and accurate animal models of invasive bladder cancer. In dogs, distinct breeds show markedly different rates of iUC, thus presenting an opportunity to identify additional risk factors and overcome the locus heterogeneity encountered in human mapping studies. In the association study presented here, inclusive of 100 Shetland sheepdogs and 58 dogs of other breeds, we identify a homozygous protein altering point mutation within the NIPAL1 gene which increases risk by eight-fold (OR = 8.42, CI = 3.12-22.71), accounting for nearly 30% of iUC risk in the Shetland sheepdog. Inclusion of six additional loci accounts for most of the disease risk in the breed and explains nearly 75% of the phenotypes in this study. When combined with sequence data from tumors, we show that variation in the MAPK signaling pathway is an overarching cause of iUC susceptibility in dogs., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: The importance of the peripheral intravenous catheter (PIVC) practices on patient safety is increasing. Small and medium-sized hospitals play a central role in the provision of healthcare services in South Korea, but lack a system for quality improvement, leaving patient safety at risk. This study aimed to identify the extent to which the PIVC practice knowledge of nurses, the nursing working environment, and the patient safety-culture perception affect PIVC practices and thereby provide basic data for improving the PIVC practices in small and medium-sized hospitals., Methods: This study had a cross-sectional descriptive design to identify the factors affecting PIVC nursing practices in small and medium-sized hospitals. Questionnaires returned by 149 nurses collected data on general characteristics, practical knowledge of PIVC nursing, nursing working environment, patient safety-culture perception, and PIVC practices. The questionnaire data were analysed using descriptive statistics, the independent t-test, one-way ANOVA, Scheffé's test, Pearson correlation, and hierarchical regression analysis., Results: The mean score of PIVC practices was 4.60 out of 5. Length of clinical experience, practical knowledge of PIVC nursing and patient safety-culture perception were significant factors affecting the PIVC nursing practices, with these variables explaining 26.2% of the variance therein., Conclusions: The PIVC practices of nurses in small and medium-sized hospitals can be improved by providing education and training based on the latest standard or guideline to facilitate the acquisition of knowledge and skills. And campaigns and programs to strengthen patient safety culture perception specific to small and medium-sized hospital should be implemented. to ensure the safety of PIVC practice., (© 2024. The Author(s).)

This study demonstrates the crucial role of reduction kinetics in phase-controlled synthesis of noble-metal nanocrystals using Ru nanocrystals as a case study. We found that the reduction kinetics played a more important role than the templating effect from the preformed seed in dictating the crystal structure of the deposited overlayers despite their intertwined effects on successful epitaxial growth. By employing two different polyols, a series of Ru nanocrystals with tunable sizes of 3-7 nm and distinct patterns of crystal phase were synthesized by incorporating different types of Ru seeds. Notably, the use of ethylene glycol and triethylene glycol consistently resulted in the formation of Ru shell in natural hexagonal close-packed ( hcp ) and metastable face-centered cubic ( fcc ) phases, respectively, regardless of the size and phase of the seed. Quantitative measurements and theoretical calculations suggested that this trend was a manifestation of the different reduction kinetics associated with the precursor and the chosen polyol, which, in turn, affected the reduction pathway (solution versus surface) and packing sequence of the deposited Ru atoms. This work not only underscores the essential role of reduction kinetics in controlling the packing of atoms and thus the phase taken by Ru nanocrystals but also suggests a potential extension to other noble-metal systems.

The prevalence of obesity in children and adolescents has been gradually increasing in recent years and has become a major health problem. Childhood obesity can readily progress to adult obesity. It is associated with obesity-related comorbidities, such as type 2 diabetes mellitus, hypertension, obstructive sleep apnea, non-alcoholic fatty liver disease, and the risk factor for cardiovascular disease. It is important to make an accurate assessment of overweight and obesity in children and adolescents with consideration of growth and development. Childhood obesity can then be prevented and treated using an appropriate treatment goal and safe and effective treatment strategies. This article summarizes the clinical practice guidelines for obesity in children and adolescents that are included in the 8th edition of the Clinical Practice Guidelines for Obesity of the Korean Society for the Study of Obesity.

Urinary tract infections (UTIs) are among the most common bacterial infections worldwide and are particularly prevalent in women. Recurrent UTIs significantly diminish quality of life due to their symptoms and frequent relapses. Patients often experience immediate relapse following slightly strenuous activities or intense psychological stress. In this review, we explore why infections persist despite the advent of various treatments and suggest strategies to manage recurrent cystitis by targeting the mechanisms of adhesion and infection. Vitamin D levels and the expression of neutrophil gelatinase-associated lipocalin are linked to the recurrence of UTIs. During a UTI, bacteria employ adhesins to invade the urinary tract, adhere to urothelial cells, and then penetrate these cells, where they rapidly multiply to establish intracellular bacterial communities. Bacteria can also form quiescent intracellular reservoirs that escape immune responses and antibiotic treatments, leading to recurrence under certain conditions. The surface proteins of bacteria and D-mannose are crucial in the adhesion of bacteria to the urothelium. Understanding these processes provides valuable insights into potential therapeutic approaches that focus on preventing bacterial attachment and cluster formation. By disrupting the ability of bacteria to adhere to and form clusters on cells, we can better manage recurrent UTIs and improve patient outcomes.

Background: Hair loss occurs due to various biological and environmental causes, which can have psychosocial consequences. The Wnt/β-catenin signaling is well-known for its role in hair growth and regeneration, as it induces the proliferation and differentiation of hair cells. When the leucine-rich G protein-coupled receptor 5 (Lgr5) interacts with the R-spondins, the frizzled receptor (FZD), a Wnt receptor, becomes stabilized, resulting in an increased β-catenin activity., Aim: We investigated whether the octapeptide that binds to Lgr5 enhances proliferation and differentiation of human primary hair cells through the activation of Wnt/β-catenin signaling., Methods: The binding affinity of the octapeptide to Lgr5 was evaluated using surface plasmon resonance (SPR). We confirmed changes in proliferation and related factors like β-catenin activation and growth factors (GFs) expression in human hair follicle dermal papilla cells (HHFDPCs). Additionally, we observed the proliferation and the expression of differentiation markers in human hair follicle outer root sheath cells (HHFORSCs), human hair follicle germinal matrix cells (HHFGMCs), and human hair follicle stem cells (HHFSCs). We used three-dimensional HHFDPC spheroid culture treated with dihydrotestosterone (DHT) to create in vitro conditions that mimic androgenetic alopecia, and we studied the effects of octapeptide on Wnt expression and HHFSC differentiation., Results: The binding of the octapeptide to Lgr5 was confirmed using SPR analysis. In HHFDPCs, treatment with octapeptide resulted in a concentration-dependent increase in proliferation. We also observed increased nuclear translocation of β-catenin and increased expression of its downstream targets. HHFDPCs treated with octapeptide exhibited increased expression of growth factors and phosphorylation of Akt and ERK. In addition, we confirmed that octapeptide increased proliferation and induced differentiation in HHFORSCs, HHFGMCs, and HHFSCs. Under the HHFDPC spheroid culture conditions, we found that octapeptide restored the inhibition of Wnt-5a and Wnt-10b expressions by DHT. In HHFSCs treated with HHFDPC spheroid culture media, we observed that octapeptide recovered the inhibition of differentiation by DHT., Conclusion: We found that octapeptides activated the Wnt/β-catenin signaling and induced the proliferation and differentiation of human primary hair cells by acting as an exogenous ligand for Lgr5. In addition, octapeptides recovered inhibited hair regeneration characters by DHT in androgenetic alopecia-mimic in vitro model. These findings suggest that octapeptides may be a promising therapeutic option for treating hair loss., (© 2023 The Authors. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

The Korean Workers' Compensation-National Health Insurance Service (KoWorC-NHIS) cohort was established to investigate the longitudinal health outcomes of Korean workers who have been compensated for occupational injuries or diseases. This cohort study, which utilized data spanning from 2004 to 2015, merged workers' compensation insurance claim data with the National Health Insurance Database (NHID), encompassing 858,793 participants. The data included socio-demographic factors such as age, sex, income, address, insurance type, and disability grade. It also covered the types of occupational accidents, International Classification of Diseases, 10th revision codes for diseases or accidents, work tenure, industry, occupation code, and company size. Additional details such as the occupational hire date, date of claim, date of recognition, and affected body parts were recorded. The cohort predominantly consisted of male workers (80.0%), with the majority experiencing their first occupational accident in their 40s (27.6%) or 50s (25.3%). Notably, 93.1% of the cases were classified as occupational injuries. By integrating this data with that from the NHID, updates on health utilization, employment status, and income changes were made annually. The follow-up period for this study is set to conclude in 2045.

Objectives: The purpose of this study was to assess the effectiveness of human papillomavirus (HPV) vaccination administered to adolescent girls through Korea's National Immunization Program., Methods: This retrospective cohort study included patients who were 12-13 years old, whether vaccinated or unvaccinated, between July 2016 and December 2017. The incidence of genital warts (GWs) was monitored through 2021. Time-stratified hazard ratios (HRs) were estimated, adjusting for birth year, socioeconomic status, and the level of urbanization of the region, and were presented with 95% confidence intervals (CIs). Data were sourced from the Immunization Registry Integration System, linked with the National Health Information Database., Results: The study included 332,062 adolescent girls, with an average follow-up period of approximately 4.6 years. Except for the first year, the HRs for the vaccinated group were lower than those for the unvaccinated group. The HRs for specific cut-off years were as follows: year 2, 0.62 (95% CI, 0.31 to 1.13); year 3, 0.58 (95% CI, 0.35 to 0.96); and year 4 and beyond, 0.39 (95% CI, 0.28 to 0.52)., Conclusions: Our findings indicate that HPV vaccination was associated with a reduction in the risk of GWs among adolescent girls. Notably, this reduction became significant as the incidence of GWs increased with age.

Under various cellular stress conditions, including exposure to toxic chemicals, RNA-binding proteins (RBPs), including Ras GTPase-activating protein-binding protein 1 (G3BP1), aggregate and form stress granule complexes, which serve as hallmarks of cellular stress. The existing methods for analyzing stress granule assembly have limitations in the rapid detection of dynamic cellular stress and ignore the effects of constitutively overexpressed RBP on cellular stress and stress-related processes. Therefore, to overcome these limitations, we established a G3BP1-GFP reporter in a human lung epithelial cell line using CRISPR/Cas9-based knock-in as an alternative system for stress granule analysis. We showed that the G3BP1-GFP reporter system responds to stress conditions and forms a stress granule complex similar to that of native G3BP1. Furthermore, we validated the stress granule response of an established cell line under exposure to various household chemicals. Overall, this novel G3BP1-GFP reporter human lung cell system is capable of monitoring stress granule dynamics in real time and can be used for assessing the lung toxicity of various substances in vitro., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Vertically ordered Si needles are of particular interest for long-term intracellular recording owing to their capacity to infiltrate living cells with negligible damage and minimal toxicity. Such intracellular recordings could greatly benefit from simultaneous live cell imaging without disrupting their culture, contributing to an in-depth understanding of cellular function and activity. However, the use of standard live imaging techniques, such as inverted and confocal microscopy, is currently impeded by the opacity of Si wafers, typically employed for fabricating vertical Si needles. Here, we introduce a transparent intracellular sensing platform that combines vertical Si needles with a percolated network of Au-Ag nanowires on a transparent elastomeric substrate. This sensing platform meets all prerequisites for simultaneous intracellular recording and imaging, including electrochemical impedance, optical transparency, mechanical compliance, and cell viability. Proof-of-concept demonstrations of this sensing platform include monitoring electrical potentials in cardiomyocyte cells and in three-dimensionally engineered cardiovascular tissue, all while conducting live imaging with inverted and confocal microscopes. This sensing platform holds wide-ranging potential applications for intracellular research across various disciplines such as neuroscience, cardiology, muscle physiology, and drug screening.

Background: The objective of this study was to compare the long-term prognosis of patients with T1 and T2 colorectal cancer (CRC) according to lymph node metastasis (LNM) and to identify risk factors for LNM., Methods: We retrospectively reviewed patients who underwent curative resection for T1 or T2 CRC at five University-affiliated hospitals between January 2012 and December 2021. The patients were divided into several groups depending on the presence of LNM or the number of risk factors., Results: Of the total 765 patients, 87 (11.3%) patients had LNM. These patients had poorer recurrence-free survival (RFS) than patients without LNM (72.6% vs. 88.6%). The multivariable analysis showed that high-grade tumors ( p = 0.003), lymphovascular invasion ( p < 0.001), and rectal location ( p = 0.049) were independent predictors of LNM. When divided into groups according to the number of the three risk factors, the risk of LNM increased from 5.4% (ultralow-risk group; no risk factor) to 60.0% (high-risk group; all three risk factors) and the 5-year RFS rate decreased from 96.3% in the ultralow-risk group to 60% in the high-risk group ( p < 0.001)., Conclusion: Radical surgery should be considered for T1 and T2 CRC patients with these risk factors.

The aim of this study was to examine the inhibitory effect of blue light (BL) on the proliferation of metastatic cancer cells and synergistic properties with chemo-drugs. BL significantly inhibited the proliferation of B cell lymphoma (A20 and RAMOS) cells in a dose-dependent manner. Anti-proliferative effect of BL irradiation was identified to be associated with the inhibition of proliferating-cell nuclear antigen expression and cell cycle by decreasing S-phase cells. Consistent with its inhibitory effects, BL irradiation at 20 J/cm 2 daily for 10 days inhibited metastasis of cancer cells which were distributed and invaded to other organs including bone marrow, liver, kidney, etc., and induced paraplegia, thereby leading to an increased survival rate of tumor-bearing mice. Anti-proliferative activity of BL was expanded in solid tumor cells including pancreatic carcinoma (Mia PaCa-2, PANC-1), lung carcinoma A549 and colorectal carcinoma HCT116 cells. Additionally, combination with chemo-drugs such as 5-FU and gemcitabine resulted in an increase in the anti-proliferative activity after BL irradiation accompanied by regulating mRNA translational process via inhibition of p70S6K, 4EBP-1 and eIF4E phosphorylation during cellular proliferation. These results indicate the anti-metastatic and photo-biogoverning abilities of BL irradiation as a potent therapeutic potential for repressing the progression of tumor cells., (© 2023 American Society for Photobiology.)

Alternative pre-mRNA splicing is a critical mechanism that generates multiple mRNA from a single gene, thereby increasing the diversity of the proteome. Recent research has highlighted the significance of specific splicing isoforms in cellular processes, particularly in regulating cell numbers. In this review, we examine the current understanding of the role of alternative splicing in controlling cancer cell growth and discuss specific splicing factors and isoforms and their molecular mechanisms in cancer progression. These isoforms have been found to intricately control signaling pathways crucial for cell cycle progression, proliferation, and apoptosis. Furthermore, studies have elucidated the characteristics and functional importance of splicing factors that influence cell numbers. Abnormal expression of oncogenic splicing isoforms and splicing factors, as well as disruptions in splicing caused by genetic mutations, have been implicated in the development and progression of tumors. Collectively, these findings provide valuable insights into the complex interplay between alternative splicing and cell proliferation, thereby suggesting the potential of alternative splicing as a therapeutic target for cancer., (© 2023. BioMed Central Ltd., part of Springer Nature.)

This study detected two potential pathogens, Vibro parahaemolyticus , which causes acute hepatopancreatic necrosis disease (AHPND), and white spot syndrome virus (WSSV), in fishing bait in South Korea. However, their infectious nature was not confirmed, possibly due to the degradation caused by freezing/thawing or prolonged storage under frozen conditions. While infectivity was not confirmed in this study, there is still a significant risk of exposure to these aquatic products. Furthermore, fishing bait and feed should be handled with caution as they are directly exposed to water, increasing the risk of disease transmission. In Australia, cases of WSSV infection caused by imported shrimp intended for human consumption have occurred, highlighting the need for preventive measures. While freezing/thawing is a method for inactivating pathogens, there are still regulatory and realistic issues to be addressed.

Introduction: The American Society of Health-Systems Pharmacists (ASHP) and American College of Clinical Pharmacy (ACCP) Residency Directories are two of the more traditional resources available to pharmacy students and residents looking for post-graduate programs. More recently, social media platforms have grown as an innovative means of resident recruitment and program marketing. Objective: The objective of this study was to evaluate the use of social media by both PGY1 and PGY2 candidates in their pursuit of post-graduate training through the disbursement of a survey. Methods: A survey consisting of 14 questions ranging from multiple-choice questions to free-text options was emailed out to the Office of Experiential Education from 141 ACCP-accredited pharmacy schools and 1341 ASHP-accredited PGY1 Pharmacy Residency Program Directors, requesting them to forward the email to their students or residents. Results: There were a total of 714 respondents to the survey. A majority of surveyors were in the process of completing a PGY1 residency training program (70.6%). The most common platform used to research pharmacy residency programs was the ASHP directory (97.3%). A majority of respondents did not use social media to research residency programs (66.7%). Out of the ones who did use social media, Instagram was the most common platform used and provided the greatest insight into the residency program. About 60% of respondents preferred Zoom as the virtual meeting platform during interviews. Conclusion: Although social media may not be the main source of information candidates are using, residency program accounts can provide residency programs with a free additional tool for recruitment.

Muscle tissue engineering has been the focus of extensive research due to its potential for numerous medical applications, including ex vivo actuator development and clinical treatments. In this study, we developed a method for harvesting muscle fiber in a floatable and translocatable manner utilizing thermally expandable hydrogels with a chemically patterned polydopamine (PD) layer generated by microcontact printing (μCP). The μCP of PD on the hydrogel facilitated the formation of stripe patterns with varying widths of printed/nonprinted area (50/50, 100/100, and 200/200 μm). The spatially controlled adhesion of C2C12 myoblasts on the PD patterns produced clearly distinguishable muscle fibers, and translocated muscle fibers exhibited preserved extracellular matrix and junction proteins. Furthermore, the development of anisotropic arrangements and mature myotubes within the fibers suggests the potential for functional control of engineered muscle tissues. Overall, the muscle fiber harvesting method developed herein is suitable for both translocation and floating and is a promising technique for muscle tissue engineering as it mimics the structure-function relationship of natural tissue.

Since the first African swine fever (ASF) outbreak occurred at a pig farm in South Korea in September 2019, as of 31 January 2023, 31 ASF cases have occurred at pig farms, while 2799 ASF virus (ASFV)-infected wild boars have been identified. The circulation of ASFV in wild boar populations poses a high risk of spillover to pig farms in the country. However, information on the changes in the pathogenicity of Korean ASFV strains from wild boars is not available. Investigating the pathogenicity of ASFV strains from pig farms is the only way to predict their alterations. In a previous study, no changes in the pathogenicity of ASFV strains circulating during 2019-2021 were identified through animal experiments. In this study, we chose two ASFV strains with potentially reduced pathogenicity among ten viruses obtained from pig premises from 2022 to January 2023 and estimated their pathogenicities and pathological characteristics. All the inoculated pigs died 8-10 days post-inoculation after showing pyrexia, depression, anorexia, and recumbency together with the common pathological lesions of enlarged hemorrhagic lymph nodes and splenomegaly with infarction. These results support that the pathogenicity among ASFV isolates in South Korea still remained unchanged during the study period.

Methyltransferase-like 3 (METTL3), a key component of the m6A methyltransferase complex, regulates the splicing, nuclear transport, stability, and translation of its target genes. However, the mechanism underlying the regulation of METTL3 expression by alternative splicing (AS) remains unknown. We analyzed the expression pattern of METTL3 after AS in human tissues and confirmed the expression of an isoform retaining introns 8 and 9 (METTL3-IR). We confirmed the different intracellular localizations of METTL3-IR and METTL3 proteins using immunofluorescence microscopy. Furthermore, the endogenous expression of METTL3-IR at the protein level was different from that at the mRNA level. We found that 3'-UTR generation by intron retention (IR) inhibited the export of METTL3-IR mRNA to the cytoplasm, which in turn suppressed protein expression. To the best of our knowledge, this is the first study to confirm the regulation of METTL3 gene expression by AS, providing evidence that the suppression of METTL3 protein expression by IR is an integral part of the mechanism by which 3'-UTR generation regulates protein expression via inhibition of RNA export to the cytoplasm. [BMB Reports 2023; 56(9): 514-519].

Melanocortin and neuropeptide-Y (NPY) are both involved in feeding and energy regulation, and they have opposite effects in the paraventricular nucleus of the hypothalamus (PVN). The present study examined an interaction between melanocortin in the nucleus of the solitary tract (NTS) and NPY in the PVN. Male Sprague-Dawley rats were implanted with cannulae in the injection sites of interest. In Experiment 1, subjects received either the melanocortin 3/4-receptor (MC3/4) antagonist SHU9119 (0, 10, 50 and 100 pmol/0.5 μl) or the MC3/4 agonist MTII (0, 10, 50, 100 and 200 pmol/0.5 μl) into the NTS. Food intake was measured at 1, 2, 4, 6 and 24-h post-injection. Administration of SHU9119 into the NTS significantly and dose-dependently increased food intake at 1, 2, 4, 6 and 6-24-h, and administration of MTII into the NTS significantly and dose-dependently decreased 24-h free feeding. In Experiment 2, subjects received the MC3/4 agonist MTII (0, 10, 50, 100 and 200 pmol/0.5 μl) into the NTS just prior to NPY (0 and 1μg/0.5 μl) in the PVN. PVN injection of NPY stimulated feeding, and administration of MTII (50, 100 and 200 pmol) into the NTS significantly and dose-dependently decreased NPY-induced feeding at 2, 4, 6 and 6-24-h. These data suggest that there could be a neuronal association between melanocortin in the NTS and NPY in the PVN, and that the melanocortin system in the NTS has an antagonistic effect on NPY-induced feeding in the PVN., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. None., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Chloromethylisothiazolinone (CMIT), a humidifier disinfectant, is known to be toxic to the respiratory system. While the toxic effect of CMIT on the lungs has been widely investigated, its effect on the skin is well unknown. In this study, we examined stress granule (SG) formation to investigate the cytotoxic effects of CMIT on human keratinocytes. We assessed the viability of the cells following CMIT exposure and performed immunofluorescence microscopy and immunoblot analyses to determine SG formation and downstream pathways. The IC 50 values in human keratinocyte HaCaT cells after CMIT exposure for 1 and 24 h were 11 and 8 μg/mL, respectively, showing no significant difference. As determined using immunofluorescence microscopy, SG formation was effectively induced after CMIT exposure. Moreover, the phosphorylation of eukaryotic initiation factor-2α (eIF2α), a translation initiation factor, and protein kinase R-like endoplasmic reticulum (ER) kinase, which plays a role in the ER stress-mediated eIF2α phosphorylation, was confirmed by CMIT exposure. These results suggest that exposure to CMIT can have detrimental effects on the skin, even briefly, by inducing SG formation through ER stress in keratinocytes., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

We report the use of four-layer graphene (4LG) as a highly reliable transparent conductive electrode (TCE) for polymer-dispersed liquid crystal (PDLC)-based smart window devices. The adhesion between 4LG and the substrate was successfully improved through a water-induced interface-cleaning (WIIC) process. We compared the performance of a device with a WIIC-processed 4LG electrode with that of devices with a conventional indium tin oxide (ITO) electrode and a 4LG electrode without a WIIC. With the application of the WIIC process, the PDLC smart window with a 4LG electrode exhibited reduced turn-on voltage and haze compared to 4LG without the WIIC process and characteristics comparable to those of the ITO electrode. The WIIC-processed 4LG electrode demonstrated enhanced electrical properties and better optical performance, leading to improved device efficiency and reliability. Furthermore, our study revealed that the WIIC process not only improved the adhesion between 4LG and the substrate but also enhanced the compatibility and interfacial interactions, resulting in the superior performance of the smart window device. These findings suggest that 4LG with WIIC holds great promise as a transparent conductive electrode for flexible smart windows, offering a cost-effective and efficient alternative to conventional ITO electrodes.

The prevalence of obesity has consistently increased worldwide, and many obesity-related diseases are emerging as major health problems. Body mass index (BMI) is used to define obesity and is highly correlated with body fat mass. Moreover, obesity-related morbidities increase linearly with the increase in BMI. The Korean Society for the Study of Obesity defined overweight as a BMI ≥23 kg/m 2 and obesity as a BMI ≥25 kg/m 2 , based on a significant increase in obesity-related diseases. A waist circumference of ≥90 cm in men and ≥85 cm in women are defined as abdominal obesity, which is also correlated with obesity-related diseases. These diagnostic criteria are the same as in the previous version; however, the updated guidelines put greater emphasis on the use of morbidity as the basis for obesity and abdominal obesity diagnoses. These new guidelines will help to identify and manage high-risk groups for obesity-related comorbidities among Korean adults.

Peripheral venous catheterization (PVC) is the most commonly used invasive technique, and its importance to patient safety is increasing. And phlebitis is a common complication which can lead to increased costs and extended hospital stays. This study attempted to characterize the current status of phlebitis based on incident reports in the Korea Patient Safety Reporting & Learning System. This retrospective descriptive study analysed 259 phlebitis cases reported in that system from 1 July 2017 to 31 December 2019. The analysis results were summarized using numbers and percentages or means with standard deviations. Among the reported phlebitis cases, antibiotics and high-osmolarity fluids comprised 48.2% of the intravenous inflammatory drugs used. All reported cases presented blood-flow infections. Insufficient observation or management was the most common cause of phlebitis. It was found that interventions for phlebitis were inconsistent with those recommended in evidence-based guidelines. Recommendations for nurses to alleviate complications in PVC must be promoted and educated. It is necessary to provide feedback from the incident reports analysis.

Background: Drinking usually begins in adolescence and is a major public health concern. Few studies have identified multilevel factors considering the frequency and amount of drinking among adolescents. This study aimed to identify the multilevel factors associated with lifetime, current, and binge drinking among Korean adolescents based on the ecological model., Methods: This cross-sectional study used data from the 2018 Korea Youth Risk Behavior Survey (N = 60,040). Hierarchal multinomial logistic regression analyses were performed using complex sample data., Results: Overall, 15,030 (25.4%), 4,629 (8.0%), and 5,038 (8.9%) subjects were involved in lifetime, current, and binge drinking, respectively. The following multilevel factors revealed significant associations with lifetime, current, and binge drinking: boys, high school students, depression, suicidal ideation at individual level, family acceptance of alcohol use, poor household economic status at family level, poor academic achievement, not receiving education on alcohol use at school level, possible alcohol access, and harm caused by drinkers at social level (all ps < .01). The main risk factors were family acceptance of alcohol use (lifetime, current, and binge drinking vs. OR = 3.95, 6.88, and 5.46, respectively) and possible alcohol access (OR = 5.65, 19.78, and 93.62)., Discussion: This study revealed multilevel factors associated with lifetime, current, and binge drinking. School nurses and community leaders are necessary to develop customized drinking prevention programs considering drinking frequency and amount, and individual, family, school, and social factors. Especially, the implementation of a drinking prevention program that reduces family acceptance of alcohol use and access to alcohol could be an effective strategy., Competing Interests: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the article., (Copyright © 2023 International Nurses Society on Addictions.)

The goal of the 8th edition of the Clinical Practice Guidelines for Obesity is to help primary care physician provide safe, effective care to patients with obesity by offering evidence-based recommendations to improve the quality of treatment. The Committee for Clinical Practice Guidelines comprised individuals with multidisciplinary expertise in obesity management. A steering board of seven experts oversaw the entire project. Recommendations were developed as the answers to key questions formulated in patient/problem, intervention, comparison, outcomes (PICO) format. Guidelines underwent multi-level review and cross-checking and received endorsement from relevant scientific societies. This edition of the guidelines includes criteria for diagnosing obesity, abdominal obesity, and metabolic syndrome; evaluation of obesity and its complications; weight loss goals; and treatment options such as diet, exercise, behavioral therapy, pharmacotherapy, and bariatric and metabolic surgery for Korean people with obesity. Compared to the previous edition of the guidelines, the current edition includes five new topics to keep up with the constantly evolving field of obesity: diagnosis of obesity, obesity in women, obesity in patients with mental illness, weight maintenance after weight loss, and the use of information and communication technology-based interventions for obesity treatment. This edition of the guidelines features has improved organization, more clearly linking key questions in PICO format to recommendations and key references. We are confident that these new Clinical Practice Guidelines for Obesity will be a valuable resource for all healthcare professionals as they describe the most current and evidence-based treatment options for obesity in a well-organized format.

Cardiomyocytes derived from human pluripotent stem cells (hPSCs) can be used in various applications including disease modeling, drug safety screening, and novel cell-based cardiac therapies. Here, we report an optimized selection and maturation method to induce maturation of cardiomyocytes into a specific subtype after differentiation driven by the regulation of Wnt signaling. The medium used to optimize selection and maturation was in a glucose starvation conditions, supplemented with either a nutrition complex or ascorbic acid. Following optimized selection and maturation, more cardiac Troponin T (cTnT)-positive cardiomyocytes were detected using albumin and ascorbic acid than B27. In addition, ascorbic acid enriched maturation of ventricular cardiomyocytes. We compared cardiomyocyte-specific gene expression patterns under different selection and maturation conditions by next-generation sequencing (NGS) analysis. Our optimized conditions will enable simple and efficient maturation and specification of the desired cardiomyocyte subtype, facilitating both biomedical research and clinical applications., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Several studies have identified mutations in neuroprotective genes in a few cases of Parkinson's disease (PD); however, the role of alternative splicing changes in PD remains unelucidated. Based on the transcriptome analysis of substantia nigra (SN) tissues obtained from PD cases and age-matched healthy controls, we identified a novel alternative splicing variant of DJ-1 , lacking exon 6 ( DJ-1 ΔE6 ), frequently detected in the SN of patients with PD. We found that the exon 6 skipping of DJ-1 induces mitochondrial dysfunction and impaired antioxidant capability. According to an in silico modeling study, the exon 6 skipping of DJ-1 disrupts the structural state suitable for the oxidation of the cysteine 106 residue that is a prerequisite for activating its neuroprotective roles. Our results suggest that change in DJ-1 alternative splicing may contribute to PD progression and provide an insight for studying PD etiology and its potential therapeutic targets., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors.)