Postnatal social support experiences in primiparous women in Korea: a phenomenological study.

PURPOSE: Social support is essential for postpartum well-being, but little is known about the postpnatal social support preferred by primiparous women. This study aimed to comprehensively understand and describe the meaning of postnatal social support experience in primiparous women. METHODS: The participants were seven primiparous women who were within 1 year after childbirth, recruited through purposive and snowball sampling from an online parenting community. The data were collected through in-depth interviews from November 14 to 28, 2022. Participants were interviewed face-to-face or via phone or online platform, according to their choice. Colaizzi's phenomenological qualitative research method was applied to analyze the meaning of the participants' experience. RESULTS: Five theme clusters and fourteen themes were identified from the data. The five theme clusters are as follows: (1) Shortcomings of the childbirth and postpartum care system I learned through my experience; (2) Government policies focusing on childbirth and child-rearing rather than postpartum recovery; (3) Driving force of postpartum recovery: Shared childbirth process; (4) Childcare on my own; and (5) Conflicted between being a stay-at-home mom and a working mom under inadequate maternity protection policies. CONCLUSION: Despite postpartum support from the government that was perceived as inadequate, first-time mothers regained confidence and motivation for parenting with the help of family, peers, and social networks. First-time mothers need support from professionals and reliable online communities for postpartum recovery and parenting.

Disruption of the creb3l1 gene causes defects in caudal fin regeneration and patterning in zebrafish Danio rerio.

BACKGROUND: The gene cAMP-Responsive Element Binding protein 3-like-1 (CREB3L1) has been implicated in bone development in mice, with CREB3L1 knock-out mice exhibiting fragile bones, and in humans, with CREB3L1 mutations linked to osteogenesis imperfecta. However, the mechanism through which Creb3l1 regulates bone development is not fully understood. RESULTS: To probe the role of Creb3l1 in organismal physiology, we used CRISPR-Cas9 genome editing to generate a Danio rerio (zebrafish) model of Creb3l1 deficiency. In contrast to mammalian phenotypes, the Creb3l1 deficient fish do not display abnormalities in osteogenesis, except for a decrease in the bifurcation pattern of caudal fin. Both, skeletal morphology and overall bone density appear normal in the mutant fish. However, the regeneration of caudal fin postamputation is significantly affected, with decreased overall regenerate and mineralized bone area. Moreover, the mutant fish exhibit a severe patterning defect during regeneration, with a significant decrease in bifurcation complexity of the fin rays and distalization of the bifurcation sites. Analysis of genes implicated in bone development showed aberrant patterning of shha and ptch2 in Creb3l1 deficient fish, linking Creb3l1 with Sonic Hedgehog signaling during fin regeneration. CONCLUSIONS: Our results uncover a novel role for Creb3l1 in regulating tissue growth and patterning during regeneration.

Lack of nuclear localization of the Creb3l1 transcription factor causes defects in caudal fin bifurcation in zebrafish Danio rerio.

The formation of normal bone and bone healing require the cAMP-responsive element binding protein 3-like-1 (Creb3l1) transmembrane transcription factor, as deletion of the murine CREB3L1 results in osteopenic animals with limited capacity to repair bone after fracture. Creb3l1 undergoes regulated intra-membrane proteolysis (RIP) to release the N-terminal transcription activating (TA) fragment that enters the nucleus and regulates the expression of target genes. To expand our understanding of Creb3l1 role in skeletal development and skeletal patterning, we aimed to generate animals expressing only the TA fragment of Creb3l1 lacking the transmembrane domain and thereby not regulated through RIP. However, the CRISPR/Cas9-mediated genome editing in zebrafish D. rerio caused a frame-shift mutation that added 56 random amino acids at the C-terminus of the TA fragment (TA+), making it unable to enter the nucleus. Thus, TA+ doesn't regulate transcription, and the creb3l1TA+/TA+ fish animals are creb3l1 transcriptional nulls. We document that the creb3l1TA+/TA+ fish exhibit defects in the patterning of caudal fin lepidotrichia, with significantly distalized points of proximal bifurcation and decreased secondary bifurcations. Moreover, using the caudal fin amputation model, we show that creb3l1TA+/TA+ fish have decreased capacity for regeneration, and that their regenerates replicate the distalization and bifurcation defects observed in intact fins of creb3l1TA+/TA+ animals. These defects correlate with altered expression of the shha and ptch2 components of the Sonic Hedgehog signaling pathway in creb3l1TA+/TA+ regenerates. Together, our results uncover a previously unknown intersection between Creb3l1 and the Sonic Hedgehog pathway, and document a novel role of Creb3l1 in tissue patterning.

Effects of Acute Beetroot Juice Supplementation and Exercise on Cardiovascular Function in Healthy Men in Preliminary Study: A Randomized, Double-Blinded, Placebo-Controlled, and Crossover Trial.

Nitrate-rich beetroot juice (NRBRJ) can potentially enhance exercise performance and improve cardiovascular function, leading to an increased use of NRBRJ over the years. However, the combined effects of NRBRJ supplementation and exercise on cardiovascular function remain unclear. Therefore, this study compared cardiovascular function responses to submaximal exercise with either placebo (PLA) or NRBRJ supplementation in healthy men. Twelve healthy men (aged 25.2 ± 2.3 years) completed the 30-min submaximal cycle ergometer exercise trials corresponding to 70% maximal heart rate (HRmax) with either PLA or NRBRJ supplementation in a random order. The mean exercise load, heart rate (HR), stroke volume (SV), cardiac output (CO), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and total peripheral resistance (TPR) were measured during exercise. The brachial-ankle pulse wave velocity (baPWV) and flow-mediated dilation (FMD) were measured before and after exercise. NRBRJ supplementation was more effective than PLA in increasing the mean exercise load and decreasing DBP and MAP during submaximal exercise. Furthermore, baPWV decreased in the NRBRJ trial and was considerably lower after exercise in the NRBRJ-supplemented group than in the PLA-supplemented group. FMD significantly increased in the PLA and NRBRJ trials; however, NRBRJ supplementation demonstrated a significantly higher FMD before and after exercise than PLA supplementation. In conclusion, acute NRBRJ supplementation and exercise were more effective than PLA supplementation and exercise in improving aerobic exercise capacity and cardiovascular function in healthy men.

The lipid flippase ATP8A1 regulates the recruitment of ARF effectors to the trans-Golgi Network.

Formation of transport vesicles requires the coordinate activity of the coating machinery that selects cargo into the nascent vesicle and the membrane bending machinery that imparts curvature to the forming bud. Vesicle coating at the trans-Golgi Network (TGN) involves AP1, GGA2 and clathrin, which are recruited to membranes by activated ARF GTPases. The ARF activation at the TGN is mediated by the BIG1 and BIG2 guanine nucleotide exchange factors (GEFs). Membrane deformation at the TGN has been shown to be mediated by lipid flippases, including ATP8A1, that moves phospholipids from the inner to the outer leaflet of the TGN membrane. We probed a possible coupling between the coating and deformation machineries by testing for an interaction between BIG1, BIG2 and ATP8A1, and by assessing whether such an interaction may influence coating efficiency. Herein, we document that BIG1 and BIG2 co-localize with ATP8A1 in both, static and highly mobile TGN elements, and that BIG1 and BIG2 bind ATP8A1. We show that the interaction involves the catalytic Sec7 domain of the GEFs and the cytosolic C-terminal tail of ATP8A1. Moreover, we report that the expression of ATP8A1, but not ATP8A1 lacking the GEF-binding cytosolic tail, increases the generation of activated ARFs at the TGN and increases the selective recruitment of AP1, GGA2 and clathrin to TGN membranes. This occurs without increasing BIG1 or BIG2 levels at the TGN, suggesting that the binding of the ATP8A1 flippase tail to the Sec7 domain of BIG1/BIG2 increases their catalytic activity. Our results support a model in which a flippase component of the deformation machinery impacts the activity of the GEF component of the coating machinery.

Loss of HNRNPU in Skeletal Muscle Increases Intramuscular Infiltration of Ly6C Positive Cells, leading to Muscle Atrophy through Activation of NF-κB Signaling.

Heterogeneous nuclear ribonucleoprotein U (hnRNPU) is known to play multiple biological roles by regulating transcriptional expression, RNA splicing, RNA stability, and chromatin structure in a tissue-dependent manner. The role of hnRNPU in skeletal muscle development and maintenance has not been previously evaluated. In this study, skeletal muscle specific hnRNPU knock out mice is utilized and evaluated skeletal muscle mass and immune cell infiltration through development. By 4 weeks, muscle-specific hnRNPU knockout mice revealed Ly6C+ monocyte infiltration into skeletal muscle, which preceded muscle atrophy. Canonical NF-kB signaling is activated in a myofiber-autonomous manner with hnRNPU repression. Inducible hnRNPU skeletal muscle knockout mice further demonstrated that deletion of hnRNPU in adulthood is sufficient to cause muscle atrophy, suggesting that hnRNPU's role in muscle maintenance is not during development alone. Treatment with salirasib, to inhibit proliferation of immune cells, prevents muscle atrophy in muscle-specific hnRNPU knock out mice, indicating that immune cell infiltration plays causal role in muscle atrophy of hnRNPU knock out mice. Overall, the findings suggest that loss of hnRNPU triggers muscle inflammation and activates NF-κB signaling in a cell-autonomous manner, culminating in muscle atrophy.

Microwave-transparent metallic metamaterials for autonomous driving safety.

Maintaining the surface transparency of protective covers using transparent heaters in extreme weather is imperative for enhancing safety in autonomous driving. However, achieving both high transmittance and low sheet resistance, two key performance indicators for transparent heaters, is inherently challenging. Here, inspired by metamaterial design, we report microwave-transparent, low-sheet-resistance heaters for automotive radars. Ultrathin (approximately one ten-thousandth of the wavelength), electrically connected metamaterials on a millimetre-thick dielectric cover provide near-unity transmission at specific frequencies within the W band (75-110 GHz), despite their metal filling ratio exceeding 70 %. These metamaterials yield the desired phase delay to adjust Fabry-Perot resonance at each target frequency. Fabricated microwave-transparent heaters exhibit exceptionally low sheet resistance (0.41 ohm/sq), thereby heating the dielectric cover above 180 °C at a nominal bias of 3 V. Defrosting tests demonstrate their thermal capability to swiftly remove thin ice layers in sub-zero temperatures.

Identifying facilitators of and barriers to the adoption of dynamic consent in digital health ecosystems: a scoping review.

BACKGROUND: Conventional consent practices face ethical challenges in continuously evolving digital health environments due to their static, one-time nature. Dynamic consent offers a promising solution, providing adaptability and flexibility to address these ethical concerns. However, due to the immaturity of the concept and accompanying technology, dynamic consent has not yet been widely used in practice. This study aims to identify the facilitators of and barriers to adopting dynamic consent in real-world scenarios. METHODS: This scoping review, conducted in December 2022, adhered to the PRISMA Extension for Scoping Reviews guidelines, focusing on dynamic consent within the health domain. A comprehensive search across Web of Science, PubMed, and Scopus yielded 22 selected articles based on predefined inclusion and exclusion criteria. RESULTS: The facilitators for the adoption of dynamic consent in digital health ecosystems were the provision of multiple consent modalities, personalized alternatives, continuous communication, and the dissemination of up-to-date information. Nevertheless, several barriers, such as consent fatigue, the digital divide, complexities in system implementation, and privacy and security concerns, needed to be addressed. This study also investigated current technological advancements and suggested considerations for further research aimed at resolving the remaining challenges surrounding dynamic consent. CONCLUSIONS: Dynamic consent emerges as an ethically advantageous method for digital health ecosystems, driven by its adaptability and support for continuous, two-way communication between data subjects and consumers. Ethical implementation in real-world settings requires the development of a robust technical framework capable of accommodating the diverse needs of stakeholders, thereby ensuring ethical integrity and data privacy in the evolving digital health landscape.

Early Osteogenic-Induced Adipose-Derived Stem Cells and Canine Bone Regeneration Potential Analyzed Using Biodegradable Scaffolds.

The complex process of bone regeneration is influenced by factors such as inflammatory responses, tissue interactions, and progenitor cells. Currently, multiple traumas can interfere with fracture healing, causing the prolonging or failure of healing. In these cases, bone grafting is the most effective treatment. However, there are several drawbacks, such as morbidity at the donor site and availability of suitable materials. Advantages have been provided in this field by a variety of stem cell types. Adipose-derived stem cells (ASCs) show promise. In the radiological examination of this study, it was confirmed that the C/S group showed faster regeneration than the other groups, and Micro-CT also showed that the degree of bone formation in the defect area was highest in the C/S group. Compared to the control group, the change in cortical bone area in the defect area decreased in the sham group (0.874), while it slightly increased in the C/S group (1.027). An increase in relative vascularity indicates a decrease in overall bone density, but a weak depression filled with fibrous tissue was observed outside the compact bone. It was confirmed that newly formed cortical bone showed a slight difference in bone density compared to surrounding normal bone tissue due to increased distribution of cortical bone. In this study, we investigated the effect of bone regeneration by ADMSCs measured by radiation and pathological effects. These data can ultimately be applied to humans with important clinical applications in various bone diseases, regenerative, and early stages of formative differentiation.

Vitamin C and glutathione supplementation: a review of their additive effects on exercise performance.

PURPOSE: This review aimed to investigate the effects of vitamin C and glutathione supplementation on exercise performance. METHODS: We conducted a literature search across the PubMed, Google Scholar, and Web of Science databases using the keywords vitamin C, glutathione, antioxidants, exercise, and oxidative stress. RESULTS: The effects of vitamin C supplementation on exercise performance and oxidative stress levels are inconsistent. Glutathione, with its diverse forms of supplementation and methods, presents mixed outcomes. Vitamin C and glutathione have deeply interconnected antioxidant functions and are mutually essential to each other. Research investigating the combined intake of these two substances, which are intricately linked biochemically, and their effects on exercise performance remain largely unexplored. CONCLUSION: Studies on the effects of vitamin C and glutathione intake on exercise have been conducted using diverse approaches; however, the results have not been consistent. Although an additive effect is anticipated with the combined intake of vitamin C and glutathione, research on this topic is currently insufficient, and further studies are required.

Effect of exercise intervention using mobile healthcare on blood lipid level and health-related physical fitness in obese women: a randomized controlled trial.

PURPOSE: This study aimed to evaluate the effects of 12 weeks of non-face-to-face exercise intervention using mobile health (mHealth) on blood lipid levels and health-related physical fitness in obese women. METHODS: Thirty obese women (aged: 39.40 ± 11.07 years, percent body fat: 37.05 ± 5.15%) were enrolled, and all completed the study. Non-face-to-face exercises were performed for 12 weeks using a mHealth and smart tracker (Charge 4, Fitbit, USA). Participants were randomly assigned to an experimental (EXP) or control (CON) group. The 12-week exercise program using mHealth included resistance (twice a week for 60 min), aerobics (five times a week for 50 min), and flexibility (five times a week for 10 min). RESULTS: The results showed that high-density lipoprotein cholesterol (Post - Pre: 9.07 mg·dL-1, p < 0.001) and ratio of low-density to high-density lipoprotein cholesterol (Post - Pre: -0.71 mg·dL-1, p < 0.05) significantly changed during the intervention period in EXP. There were significant increases in sit-ups (Post - Pre: 7.73 numbers, p < 0.001), grip strength (Post - Pre: 2.92 kg, p < 0.001), and sit and reach (Post - Pre: 2.51 cm, p < 0.01) in EXP. CONCLUSION: Non-face-to-face exercise using mHealth for 12 weeks improved blood lipid levels and health-related physical fitness; therefore, it can help improve compliance through self-monitoring and lifestyle changes by increasing physical activity.

The Arf-GEF GBF1 undergoes multi-domain structural shifts to activate Arf at the Golgi.

Golgi homeostasis require the activation of Arf GTPases by the guanine-nucleotide exchange factor requires GBF1, whose recruitment to the Golgi represents a rate limiting step in the process. GBF1 contains a conserved, catalytic, Sec7 domain (Sec7d) and five additional (DCB, HUS, HDS1-3) domains. Herein, we identify the HDS3 domain as essential for GBF1 membrane association in mammalian cells and document the critical role of HDS3 during the development of Drosophila melanogaster. We show that upon binding to Golgi membranes, GBF1 undergoes conformational changes in regions bracketing the catalytic Sec7d. We illuminate GBF1 interdomain arrangements by negative staining electron microscopy of full-length human GBF1 to show that GBF1 forms an anti-parallel dimer held together by the paired central DCB-HUS core, with two sets of HDS1-3 arms extending outward in opposite directions. The catalytic Sec7d protrudes from the central core as a largely independent domain, but is closely opposed to a previously unassigned α-helix from the HDS1 domain. Based on our data, we propose models of GBF1 engagement on the membrane to provide a paradigm for understanding GBF1-mediated Arf activation required for cellular and organismal function.

Site-specific phosphorylations of the Arf activator GBF1 differentially regulate GBF1 function in Golgi homeostasis and secretion versus cytokinesis.

Diverse cellular processes, including membrane traffic, lipid homeostasis, cytokinesis, mitochondrial positioning, and cell motility are critically dependent on the Sec7 domain guanine nucleotide exchange factor GBF1. Yet, how the participation of GBF1 in a particular cellular function is regulated is unknown. Here, we show that the phosphorylation of specific highly conserved serine and tyrosine residues within the N-terminal domain of GBF1 differentially regulates its function in maintaining Golgi homeostasis and facilitating secretion versus its role in cytokinesis. Specifically, GBF1 mutants containing single amino acid substitutions that mimic a stably phosphorylated S233, S371, Y377, and Y515 or the S233A mutant that can't be phosphorylated are fully able to maintain Golgi architecture and support cargo traffic through the secretory pathway when assessed in multiple functional assays. However, the same mutants cause multi-nucleation when expressed in cells, and appear to inhibit the progression through mitosis and the resolution of cytokinetic bridges. Thus, GBF1 participates in distinct interactive networks when mediating Golgi homeostasis and secretion versus facilitating cytokinesis, and GBF1 integration into such networks is differentially regulated by the phosphorylation of specific GBF1 residues.

Enhancing Supplemental Effects of Acute Natural Antioxidant Derived from Yeast Fermentation and Vitamin C on Sports Performance in Triathlon Athletes: A Randomized, Double-Blinded, Placebo-Controlled, Crossover Trial.

This study investigated the acute effects of natural antioxidants, derived from yeast fermentation containing glutathione and dietary vitamin C supplementation, on metabolic function, skeletal muscle oxygenation, cardiac function, and antioxidant function during submaximal exercise in middle-aged triathlon athletes. Twelve participants (aged 49.42 ± 5.9 years) completed 90 min submaximal cycling trials corresponding to 70% maximal oxygen uptake with either vitamin C and glutathione (VitC+Glu), vitamin C (VitC), glutathione (Glu) supplementation, or placebo. Metabolic function (minute ventilation, oxygen uptake, carbon dioxide output [VCO2], respiratory exchange ratio [RER], oxygen pulse [O2pulse], carbohydrate oxidation, fat oxidation, and energy expenditure), skeletal muscle oxygenation (oxidized hemoglobin and myoglobin in skeletal muscle tissue, total hemoglobin and myoglobin in skeletal muscle tissue [tHb]), cardiac function (heart rate [HR], stroke volume [SV], cardiac output, end-diastolic volume, end-systolic volume, and ejection fraction), and antioxidant function parameters (blood lactate, superoxide dismutase, catalase, glutathione peroxidases, glutathione [GSH], diacron reactive oxygen metabolite [dROM], and biological antioxidant potential [BAP]) were measured during submaximal exercise and recovery. VCO2, RER, HR, blood lactate after exercise, and dROM were significantly lower, and O2pulse, tHb, and BAP were significantly higher for VitC+Glu than for the other trials (p < 0.05). In conclusion, combined vitamin C and glutathione supplementation was more effective in improving metabolic function, skeletal oxygenation, cardiac function, and antioxidant function during prolonged submaximal exercise in middle-aged triathletes.

Prolapsed Uterine Smooth Muscle Tumor of Uncertain Malignant Potential: A Case Report and Review of Radiologic Findings.

INTRODUCTION: Uterine smooth muscle tumor of uncertain malignant potential (STUMP) is a rare tumor that arises in the myometrium of the uterus. It is regarded as an intermediate malignant tumor according to the recent World Health Organization classification. Few studies have reported the radiologic findings of STUMP, and the differentiation of STUMP from leiomyoma remains controversial. CASE DESCRIPTION: A 42-year-old nulliparous female presented at our institution with massive vaginal bleeding. Radiological studies, including ultrasonography, computed tomography (CT), and magnetic resonance imaging, revealed an oval-shaped mass with well-defined margins in the uterus protruding into the vagina. The patient underwent a total abdominal hysterectomy, and the final pathology was confirmed as STUMP. CONCLUSION: Distinguishing STUMP from leiomyomas based solely on radiological findings can be challenging. However, if the uterine mass appears as a single mass lacking acoustic shadowing on ultrasound and demonstrates diffusion restriction with high T2 signal intensity on magnetic resonance imaging, consideration of STUMP may be necessary for proper patient management, given the poor prognosis associated with this tumor.

Huge Primary Clear Cell Hepatocellular Carcinoma: a Case Report and Review of Radiologic Findings.

INTRODUCTION: Clear cell hepatocellular carcinoma (HCC) is a rare subtype of HCC. Histologically, clear cell HCC is characterized by the cytoplasmic accumulation of glycogen with a clear cell appearance, constituting > 80% of tumor cells. Radiologically, clear cell HCC demonstrates early enhancement and washout similar to conventional HCC. Occasionally, enhancing capsule and intratumoral fat are accompanied by clear cell HCC. CASE DESCRIPTION: A 57-year-old male presented to our hospital with right upper quadrant abdominal pain. Ultrasonography, computed tomography, and magnetic resonance imaging revealed a large mass with a well-defined margin in the right hemiliver. The patient underwent a right hemihepatectomy, and the final histopathology revealed clear cell-type HCC. CONCLUSION: Distinguishing clear cell types from other types of HCC solely based on radiological findings is challenging. If hepatic tumors exhibit encapsulated margins, enhancing rims, intratumoral fat, and arterial phase hyperenhancement/washout pattern despite their large size, consideration of clear cell subtypes in the differential diagnosis list will aid patient management, implying better prognosis than not-otherwise-specified HCC.

Effects of Visual Communication Design Accessibility (VCDA) Guidelines for Low Vision on Public and Open Government Health Data.

Since 2019, the Korean government's investments in making data more accessible to the public have grown by 337%. However, open government data, which should be accessible to everyone, are not entirely accessible to people with low vision, who represent an information-vulnerable class. Emergencies, such as the COVID-19 pandemic, decrease face-to-face encounters and inevitably increase untact encounters. Thus, the information gap experienced by low-vision people, who are underprivileged in terms of information, will be further widened, and they may consequently face various disadvantages. This study proposed visual communication design accessibility (VCDA) guidelines for people with low vision. Introduced screens enhanced by accessibility guidelines were presented to 16 people with low vision and 16 people with normal vision and the speed of visual information recognition was analyzed. No statistically significant difference (p > 0.05) was found due to the small sample size; however, this study's results approached significance with improved visual recognition speed for people with low vision after adopting VCDA. As a result of the intervention, the visual information recognition speed of both normal and low-vision people improved. Thus, our results can help improve information recognition speed among people with normal and low vision.

New prognostic scoring system for mortality in idiopathic pulmonary fibrosis by modifying the gender, age, and physiology model with desaturation during the six-minute walk test.

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing interstitial lung disease (ILD) with variable and heterogeneous clinical course. The GAP (gender, age, and physiology) model had been used to predict mortality in patients with IPF, but does not contain exercise capacity. Therefore, our aim in this study was to develop new prognostic scoring system in the Korea IPF Cohort (KICO) registry. Materials and methods: This is a retrospective study of Korean patients with IPF in KICO registry from June 2016 to August 2021. We developed new scoring system (the GAP6) based on the GAP model adding nadir saturation of percutaneous oxygen (SpO2) during six-minute walk test (6MWT) in the KICO registry and compared the efficacy of the GAP and the GAP6 model. Results: Among 2,412 patients in KICO registry, 966 patients were enrolled. The GAP6 model showed significant prognostic value for mortality between each stage [HR Stage II vs. Stage I = 2.89 (95% CI = 2.38-3.51), HR Stage III vs. Stage II = 2.68 (95% CI = 1.60-4.51)]. In comparison the model performance with area under curve (AUC) using receiver operating characteristic (ROC) curve analysis, the GAP6 model showed a significant improvement for predicting mortality than the GAP model (AUC the GAP vs. the GAP6, 0.646 vs. 0.671, p < 0.0019). Also, the C-index values slightly improved from 0.674 to 0.691 for mortality. Conclusion: The GAP6 model adding nadir SpO2 during 6WMT for an indicator of functional capacity improves prediction ability with C-index and AUC. Additional multinational study is needed to confirm these finding and validate the applicability and accuracy of this risk assessment system.

Synthesis of 1,4-Dialkoxynaphthalene-Based Imidazolium Salts and Their Cytotoxicity in Cancer Cell Lines.

In this study, we designed and synthesized novel 1,4-dialkoxynaphthalene-2-alkyl imidazolium salt (IMS) derivatives containing both 1,4-dialkoxynaphthalene and imidazole, which are well known as pharmacophores. The cytotoxicities of these newly synthesized IMS derivatives were investigated in order to explore the possibility of using them to develop anticancer drugs. It was found that some of the new IMS derivatives showed good cytotoxic activities. In addition, an initial, qualitative structure-activity relationship is presented on the basis of observations of activity changes corresponding to structural changes.

Limaprost and the Risk of Bleeding: A Self-Controlled Case Series Study.

OBJECTIVE: To investigate the association between the use of limaprost and the risk of bleeding. METHODS: A self-controlled case series analysis was conducted using the National Health Insurance Service-National Sample Cohort database in South Korea. We identified patients aged 18 years or older who had at least one prescription of limaprost and were diagnosed with at least one case of bleeding between 2003 and 2019. The incidence rate ratio (IRR) of bleeding was calculated by dividing the incidence rate in the exposed period to limaprost by that in the unexposed period and adjusted for age using conditional Poisson regression model. RESULTS: Among 72,860 patients with limaprost prescriptions and bleeding diagnoses, there were 184,732 events of bleeding. After adjusting for age, the IRR was 1.47 (95% confidence interval [CI], 1.43-1.50), wherein the IRR was the highest during the 0-7 days after limaprost initiation (IRR, 2.11; 95% CI, 2.03-2.18). Risk of bleeding was higher when limaprost was concomitantly used with antithrombotics or other drugs for spinal stenosis treatment, and when higher daily doses of limaprost were administered. CONCLUSION: Our findings suggest that the risk of bleeding increased by 1.5-fold in periods of limaprost exposure compared to unexposed periods, with particularly higher risks observed during the first week after limaprost initiation, with concomitant drugs related to bleeding, and with a higher daily dose. A careful risk-benefit assessment is warranted when initiating limaprost, especially when administered with other medications or in higher daily doses.