Additive-Driven Nanoscale Architecture of Solid Electrolyte Interphase Revealed by Cryogenic Transmission Electron Microscopy.

In Li metal batteries (LMBs), which boast the highest theoretical capacity, the chemical structure of the solid electrolyte interphase (SEI) serves as the key component that governs the growth of reactive Li. Various types of additives have been developed for electrolyte optimization, representing one of the most effective strategies to enhance the SEI properties for stable Li plating. However, as advanced electrolyte systems become more chemically complicated, the use of additives is empirically optimized. Indeed, their role in SEI formation and the resulting cycle life of LMBs are not well-understood. In this study, we employed cryogenic transmission electron microscopy combined with Raman spectroscopy, theoretical studies including molecular dynamics (MD) simulations and density functional theory (DFT) calculations, and electrochemical measurements to explore the nanoscale architecture of SEI modified by the most representative additives, lithium nitrate (LiNO3) and vinylene carbonate (VC), applied in a localized high-concentration electrolyte. We found that LiNO3 and VC play distinct roles in forming the SEI, governing the solvation structure, and influencing the kinetics of electrochemical reduction. Their collaboration leads to the desired SEI, ensuring prolonged cycle performance for LMBs. Moreover, we propose mechanisms for different Li growth and cycling behaviors that are determined by the physicochemical properties of SEI, such as uniformity, elasticity, and ionic conductivity. Our findings provide critical insights into the appropriate use of additives, particularly regarding their chemical compatibility.

Development and Validation of the Mental Health Scale for Maltreated Children.

OBJECTIVE: This study aimed to develop and validate a comprehensive self-report questionnaire to assess emotional and behavioral problems and psychological trauma in maltreated children. METHODS: The Mental Health Scale for Maltreated Children (MHS-MC) was constructed to encompass five major symptoms (depression, anxiety, inattention/hyperactivity/impulsivity, aggression/defiance, and psychological trauma) prevalent in maltreated children. Critical items and ego-resilience subscale were also devised to increase clinical utility. After informed consent, 205 children (maltreated children, n=157, 76.6%) were recruited nationwide, and they answered a package of self-report measures, including the MHS-MC. Reliability, construct validity, concurrent validity, and criterion-related validity were examined to explore the psychometric properties. RESULTS: The reliability was good to excellent. Confirmatory factor analysis yielded a five-factorial solution for the symptom subscales supporting construct validity. In logistic regression, the total scores of the MHS-MC predicted membership in the maltreated group. Criterion-related validity was generally satisfactory in that all subscales of the MHS-MC showed significant correlations with relevant measures in the expected direction. CONCLUSION: This is the first attempt to develop a comprehensive psychological scale based on nationwide data collected from maltreated Korean children. We hope that the continued standardization of this scale will contribute to evidence-based clinical and policy decisionmaking for maltreated children.

Lowering Barriers to Health Risk Assessments in Promoting Personalized Health Management.

This study investigates the feasibility of accurately predicting adverse health events without relying on costly data acquisition methods, such as laboratory tests, in the era of shifting healthcare paradigms towards community-based health promotion and personalized preventive healthcare through individual health risk assessments (HRAs). We assessed the incremental predictive value of four categories of predictor variables-demographic, lifestyle and family history, personal health device, and laboratory data-organized by data acquisition costs in the prediction of the risks of mortality and five chronic diseases. Machine learning methodologies were employed to develop risk prediction models, assess their predictive performance, and determine feature importance. Using data from the National Sample Cohort of the Korean National Health Insurance Service (NHIS), which includes eligibility, medical check-up, healthcare utilization, and mortality data from 2002 to 2019, our study involved 425,148 NHIS members who underwent medical check-ups between 2009 and 2012. Models using demographic, lifestyle, family history, and personal health device data, with or without laboratory data, showed comparable performance. A feature importance analysis in models excluding laboratory data highlighted modifiable lifestyle factors, which are a superior set of variables for developing health guidelines. Our findings support the practicality of precise HRAs using demographic, lifestyle, family history, and personal health device data. This approach addresses HRA barriers, particularly for healthy individuals, by eliminating the need for costly and inconvenient laboratory data collection, advancing accessible preventive health management strategies.

Mitigation effect of hesperidin on X-ray radiation-induced intestinal barrier dysfunction in Caco-2 cell monolayers.

The tight junctions (TJs) and barrier function of the intestinal epithelium are highly sensitive to radiation. However, polyphenols can be used to reverse the effects of radiation. Here, we investigated the effects of hesperidin (hesperetin-7-rhamnoglucoside) on X-ray-induced intestinal barrier dysfunction in human epithelial Caco-2 monolayers. To examine whether hesperidin mitigated the effects of X-ray exposure (2 Gy), cell survival was evaluated and intestinal barrier function was assessed by measuring the transepithelial flux, apparent permeability coefficient (Papp), and barrier integrity. Hesperidin improved the survival of Caco-2 cell monolayers and attenuated X-ray exposure-induced intestinal barrier dysfunction. For fluorescein transport experiments, transepithelial flux and Papp of fluorescein in control group were significantly elevated by X-ray, but were restored to near control by 10 µM hesperidin pretreatment. Further, X-ray exposure decreased the barrier integrity and TJ interruption by reducing TJ-related proteins occludin and claudin-4, whereas cell monolayers pretreated with hesperidin before X-ray exposure were reinstated to control level. It was concluded that hesperidin treatment before X-ray exposure alleviated X-ray-induced intestinal barrier dysfunction through regulation of TJ-related proteins. These results indicate that hesperidin prevents and mitigates X-ray-induced intestinal barrier dysfunction.

Understanding the Interplay of Religion, Social Relationships, and Depressive Symptoms in Later Life: An Analysis of Dynamics in Individual and Dyadic Contexts.

This study examined how religious participation at the individual level and the dyadic religious similarity at the couple level influenced depressive symptoms via social relationships among older Korean couples aged 65 and above. The sample included 1,191 couples from the seventh assessment of the Korean Longitudinal Study of Ageing. The findings indicated that older adults who participated in religious activities more frequently showed lower levels of depressive symptoms through increased social interactions and marital satisfaction. Additionally, older couples with similar religious backgrounds showed higher levels of marital satisfaction than those without similar religious backgrounds, subsequently leading to lower levels of depressive symptoms. Overall, the associations between religion and depressive symptoms were similar for both genders. The findings provided insights into potential mechanisms leading to later-life depressive symptoms at both the individual and couple levels in terms of religion and social relationships and informed practical implications for older couples' marital relationships.

Tractable Quinolone Hydrazides Exhibiting Sub-Micromolar and Broad Spectrum Antitrypanosomal Activities.

Nagana and Human African Trypanosomiasis (HAT), caused by (sub)species of Trypanosoma, are diseases that impede human and animal health, and economic growth in Africa. The few drugs available have drawbacks including suboptimal efficacy, adverse effects, drug resistance, and difficult routes of administration. New drugs are needed. A series of 20 novel quinolone compounds with affordable synthetic routes was made and evaluated in vitro against Trypanosoma brucei and HEK293 cells. Of the 20 compounds, 12 had sub-micromolar potencies against the parasite (EC50 values=0.051-0.57 µM), and most were non-toxic to HEK293 cells (CC50 values>5 µM). Two of the most potent compounds presented sub-micromolar activities against other trypanosome (sub)species (T. cruzi and T. b. rhodesiense). Although aqueous solubility is poor, both compounds possess good logD values (2-3), and either robust or poor microsomal stability profiles. These varying attributes will be addressed in future reports.

A study on longitudinal relationship between ultrafine dust and the prevalence of depression.

BACKGROUND: Recently, the fine dust problem caused by rapid industrialization and science and technological development has emerged as a severe social issue worldwide. This also increases the interest in its effect on human life. In particular, there is a growing concern about the harm of fine dust in Korea. METHODS: This study is based on the PM 2.5 data from 2017 to 2021 provided by Air Korea to estimate changes in ultrafine dust. In addition, the data from the Community Health Survey provided by the Korea Centers for Disease Control and Prevention (KCDC) from 2017 to 2021 were used to examine the effect between the change in ultra-fine dust and the prevalence of depression. A total of 229 local governments were included in the analysis. The Latent Growth Modeling was carried out to estimate the change in ultra-fine dust and the prevalence of depressions and verify the relationship between ultra-fine dust and the prevalence of depression. RESULTS: The analysis result revealed that the ultra-fine dust concentration continued to decrease from 2017 to 2021. However, the depression prevalence increased from an average of 2.60% in 2017 to an average of 3.12% in 2021, suggesting the need for adequate and sufficient welfare policies for depression treatment. As a result of estimating the initial value and change rate of ultra-fine dust and depression prevalence, the higher the initial value of ultra-fine dust, the greater the decrease in ultra-fine dust. In terms of depression, the lower the initial value of the prevalence of depression, the larger the increase in depression prevalence. CONCLUSIONS: This study is significant in that it revealed the strong association of the longitudinal relationship between ultra-fine dust and depression, one of the biggest issues in Korea, by utilizing large-scale longitudinal data.

Serum KL-6 levels predict the occurrence and severity of treatment-related interstitial lung disease in lung cancer.

In this study, we aimed to investigate the feasibility of serum Krebs von den Lungen-6 (KL-6) as a potential biomarker for treatment-related ILD (TR-ILD) in lung cancer. We recruited patients with lung cancer in whom KL-6 was measured to differentiate between pneumonia and ILD (category 1), diagnose and assess the severity of suspicious ILD (category 2), or evaluate baseline levels before cancer treatment (category 3). Among 1,297 patients who underwent KL-6 testing, 422 had lung cancer, and TR-ILD was detected in 195 patients. In categories 1-2, median KL-6 level was higher in drug-induced ILD or acute exacerbation of underlying ILD than in no ILD or radiation-induced pneumonitis, and it was correlated with the severity of TR-ILD. High KL-6 level (cut-off: > 436U/mL) was an independent risk factor for severe TR-ILD, and low KL-6 level with high procalcitonin level (> 0.5 ng/mL) could exclude severe TR-ILD. Patients with severe TR-ILD had worse overall survival than those without, whereas high baseline KL-6 level was associated with worse survival, especially in patients without severe TR-ILD. Therefore, serum KL-6 may be a surrogate marker for predicting the occurrence and assessing the severity of TR-ILD at the time of suspected ILD and before lung cancer treatment.

Assessment of Oxidative Stress-Induced Oral Epithelial Toxicity.

Reactive oxygen species (ROS) are highly reactive molecules generated in living organisms and an excessive production of ROS culminates in oxidative stress and cellular damage. Notably, oxidative stress plays a critical role in the pathogenesis of a number of oral mucosal diseases, including oral mucositis, which remains one of cancer treatments' most common side effects. We have shown previously that oral keratinocytes are remarkably sensitive to oxidative stress, and this may hinder the development and reproducibility of epithelial cell-based models of oral disease. Here, we examined the oxidative stress signatures that parallel oral toxicity by reproducing the initial events taking place during cancer treatment-induced oral mucositis. We used three oral epithelial cell lines (an immortalized normal human oral keratinocyte cell line, OKF6, and malignant oral keratinocytes, H357 and H400), as well as a mouse model of mucositis. The cells were subjected to increasing oxidative stress by incubation with hydrogen peroxide (H2O2) at concentrations of 100 µM up to 1200 µM, for up to 24 h, and ROS production and real-time kinetics of oxidative stress were investigated using fluorescent dye-based probes. Cell viability was assessed using a trypan blue exclusion assay, a fluorescence-based live-dead assay, and a fluorometric cytotoxicity assay (FCA), while morphological changes were analyzed by means of a phase-contrast inverted microscope. Static and dynamic real-time detection of the redox changes in keratinocytes showed a time-dependent increase of ROS production during oxidative stress-induced epithelial injury. The survival rates of oral epithelial cells were significantly affected after exposure to oxidative stress in a dose- and cell line-dependent manner. Values of TC50 of 800 µM, 800 µM, and 400 µM were reported for H400 cells (54.21 ± 9.04, p < 0.01), H357 cells (53.48 ± 4.01, p < 0.01), and OKF6 cells (48.64 ± 3.09, p < 0.01), respectively. Oxidative stress markers (MPO and MDA) were also significantly increased in oral tissues in our dual mouse model of chemotherapy-induced mucositis. In summary, we characterized and validated an oxidative stress model in human oral keratinocytes and identified optimal experimental conditions for the study of oxidative stress-induced oral epithelial toxicity.

X-ray radiation-induced intestinal barrier dysfunction in human epithelial Caco-2 cell monolayers.

Radiation therapy and unwanted radiological or nuclear exposure, such as nuclear plant accidents, terrorist attacks, and military conflicts, pose serious health issues to humans. Dysfunction of the intestinal epithelial barrier and the leakage of luminal antigens and bacteria across the barrier have been linked to various human diseases. Intestinal permeability is regulated by intercellular structures, termed tight junctions (TJs), which are disrupted after radiation exposure. In this study, we investigated radiation-induced alterations in TJ-related proteins in an intestinal epithelial cell model. Caco-2 cells were irradiated with 2, 5, and 10 Gy and harvested 1 and 24 h after X-ray exposure. The trypan blue assay revealed that cell viability was reduced in a dose-dependent manner 24 h after X-ray exposure compared to that of non-irradiated cells. However, the WST-8 assay revealed that cell proliferation was significantly reduced only 24 h after radiation exposure to 10 Gy compared to that of non-irradiated cells. In addition, a decreased growth rate and increased doubling time were observed in cells irradiated with X-rays. Intestinal permeability was significantly increased, and transepithelial electrical resistance values were remarkably reduced in Caco-2 cell monolayers irradiated with X-rays compared to non-irradiated cells. X-ray irradiation significantly decreased the mRNA and protein levels of ZO-1, occludin, claudin-3, and claudin-4, with ZO-1 and claudin-3 protein levels decreasing in a dose-dependent manner. Overall, the present study reveals that exposure to X-ray induces dysfunction of the human epithelial intestinal barrier and integrity via the downregulation of TJ-related genes, which may be a key factor contributing to intestinal barrier damage and increased intestinal permeability.

Factors influencing nursing students' knowledge, attitudes, and infection management behavior for emerging respiratory infectious diseases: A cross-sectional study.

Understanding the factors influencing infection management behavior related to Emerging Respiratory Infectious Diseases (ERIDs) among nursing students is important because nursing students play a vital role in preventing the spread of ERIDs. This study aimed to determine factors influencing infection management behavior related to ERIDs among nursing students in Korea. In this cross-sectional survey study, data were collected from May 3 to June 30, 2022, using a questionnaire. Data collected from 481 nursing students were analyzed using descriptive statistics, an independent t-test, a one-way analysis of variance, Pearson correlation coefficients, and hierarchical multiple regression using the SPSS program. The key factors influencing respondents' ERID-related infection management behavior were attitude (ß = 0.554, p<0.001) and knowledge (ß = 0.282, p<0.001). The explanatory power of this model was 40.2%, and the regression model was found to be statistically significant (F = 27.935, p<0.001). To improve nursing students' ERID-related infection management behavior, their knowledge of and attitudes toward ERIDs should be enhanced by repeatedly providing them with accurate professional information about ERIDs. Therefore, intensive efforts should be taken to develop a systematic educational program that can help nursing students better perform infection management.

Improving the knowledge of and compliance with infection control for emerging respiratory infectious diseases among nursing students using importance-performance analysis: A descriptive survey study.

BACKGROUND: Due to a lack of prior training on emerging respiratory infectious diseases (ERIDs), systematic nursing guidelines, supplies, and manpower, nurses experienced extreme physical and psychological stress while providing care to patients with infectious diseases during the pandemic. OBJECTIVES: This study aimed to investigate the knowledge of and compliance with infection control for ERIDs among nursing students, as well as identify the priorities in infection control knowledge and compliance using importance-performance analysis (IPA), to prepare supporting data for developing infection control training programs for ERIDs. DESIGN: This descriptive survey used IPA to examine nursing students' knowledge of infection control priorities and ERID compliance. SETTING: The participants were recruited from a convenience sample of first- to fourth-year nursing majors from one region of South Korea. PARTICIPANTS: Data were collected from 481 nursing students through a questionnaire survey conducted between May 3 and June 30, 2022. METHODS: Data were examined using descriptive statistics, an independent t-test, a one-way analysis of variance, and IPA. RESULTS: The IPA results showed that among 12 items related to nursing students' knowledge of infection control for ERIDs, item #1 (definition of ERID) belonged to quadrant C (low priority), whereas all other items (items #2-12) belonged to quadrant A (concentrate here). Among 12 items related to compliance with infection control for ERIDs, items #2 (hand hygiene) and #3 (mask wearing) belonged to quadrant B (keep up the good work), whereas the remaining 10 items belonged to quadrant A (concentrate here). CONCLUSION: In order to improve nursing students' knowledge of and compliance with infection control for ERIDs, infection control training with more specific material should replace the present curriculum in South Korea.

Telehealth interventions to support self-care of stroke survivors: An integrative review.

Background: Self-care is essential for stroke survivors to recover from neurological disorders caused by stroke and to prevent recurrences. Self-care behaviors are activities that individuals undertake to prevent recurrence and complications, and have a positive effect on the quality of life of patients. Telehealth is an emerging technology through which self-care intervention can be provided from a distance. Review-based research is needed to determine the value and development of telehealth-based self-care interventions for stroke survivors. Objective: Based on the middle range theory of self-care of chronic illness, to provide an effective guide when developing telehealth self-care interventions for stroke survivors by comprehensively understanding telehealth interventions to support self-care of stroke survivors. Methods: An integrative review, this study was performed in accordance with Whittemore and Knafl's stages of an integrative review (problem identification, literature search, data evaluation, data analysis, and presentation of the results). The key search terms included combinations of concepts related to stroke survivors and self-care, and telehealth. The research year of searched publications was not limited, and five electronic databases (PubMed, Ovid-MEDLINE, Ovid-EMBASE, CINAHL and Cochrane Library) were searched. Results: Four attributes were identified that represented telehealth's functions that appeared to be associated with a self-care intervention for stroke survivors. These included introducing the concept of interaction, monitoring, education, and store and forward. These self-care interventions were found to influence the behaviors of stroke survivors' self-care maintenance (physical activity and treatment adherence), self-care monitoring (blood pressure, healthy behaviors, health diet, psychological well-being, glucose control, and depression), and self-care management (sense of control, healthcare resource utilization, social integration, and support). Conclusions: The results of this study can provide a guide for developing effective telehealth self-care intervention by identifying the attributes of telehealth self-care intervention for stroke survivors.

Economic analysis of the circular economy based on waste plastic pyrolysis oil: a case of the university campus.

Recently, the concept of a circular economy for carbon neutrality is emerging. In particular, waste plastics are one of the key wastes, and efforts are being made to recycle them as energy rather than dispose of them. Accordingly, the technology of producing and utilizing pyrolysis oil from waste plastics attracts attention. As it is an early stage of technology development, however, there are not many demonstrations and papers that analyze the technology broadly. The goal of this study is to propose building a circular economy on a university campus through waste plastic pyrolysis oil technology. To show its feasibility, waste plastic pyrolysis oil technology is analyzed comprehensively from economic, environmental, and policy perspectives using the scenario analysis technique on the university campus level. A methodology of the scenario analysis technique enables predicting the uncertainties. Since plastic pyrolysis oil technologies and carbon neutrality are accompanied by many uncertainties, this technique is expected to be an appropriate methodology for this study. First, the amount of pyrolysis oil production from waste plastics from the campus is estimated. Then, the cost and carbon emissions from waste plastics are estimated if the pyrolysis oil technology is used instead of the traditional waste disposal process. As a result, the total economic profits of up to 425,484,022 won/year (354,570.01 $/year) are expected when a circular economy is built using waste plastic pyrolysis oil. In addition, it is also confirmed that greenhouse gas (GHG) emissions can be reduced by up to 840,891 kgCO2eq/year. The waste plastic pyrolysis oil satisfies Korea's gas pollutant standards and is consistent with the GHG reduction policy. It can be concluded that building a circular economy at the university campus level using waste plastic pyrolysis oil technology is suitable from economic, environmental, and policy perspectives.

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.

Case Report: A case of ultra-late recurrence of KIF13A-RET fusion non-small cell lung cancer response to selpercatinib.

Background: Cancer recurrence remains a significant problem, and most postoperative recurrences of non-small cell lung cancer (NSCLC) develop within 5 years after resection. We present a rare case of ultra-late recurrence of NSCLC accompanying choroidal metastasis with KIF13A-RET fusion 14 years after the definitive surgery. Case description: A 48-year-old female patient who had never-smoked presented with decreased visual acuity. She had been treated with right upper lobe lobectomy followed by adjuvant chemotherapy 14 years prior. Fundus photographs revealed bilateral choroidal metastatic lesions. Positron emission tomography-computed tomography (PET-CT) scans showed extensive bone metastases and focal hypermetabolism in the left uterine cervix. An excision biopsy of the uterus showed primary lung adenocarcinoma with immunohistochemistry of TTF-1+. Plasma next-generation sequencing (NGS) identified the presence of KIF13A-RET fusion. After 6 months of selpercatinib therapy, PET-CT revealed a partial response for bone and uterine metastasis and stable disease for choroidal lesions. Conclusion: In this case report, we are reporting a rare case of ultra-late recurrence of NSCLC in a patient with choroidal metastasis. Furthermore, the diagnosis of NSCLC with RET fusion was based on liquid-based NGS rather than tissue-based biopsy. The patient showed a good response to selpercatinib, which supports the efficacy of selpercatinib as a treatment for RET-fusion-positive NSCLC with choroidal metastasis.

Effective Timing of Introducing an Inpatient Smoking Cessation Program to Cancer Patients.

PURPOSE: We aimed to identify factors influencing smoking cessation success among cancer patients registered in an inpatient smoking cessation program at a single cancer center. MATERIALS AND METHODS: The electronic medical records of enrolled patients with solid cancer were retrospectively reviewed. We evaluated factors associated with 6-month smoking cessation. RESULTS: A total of 458 patients with cancer were included in this study. Their mean age was 62.9±10.3 years, and 56.3% of the participants had lung cancer. 193 (42.1%) had not yet begun their main treatment. The mean number of counseling sessions for the participants was 8.4±3.5, and 46 (10.0%) patients were prescribed smoking cessation medications. The 6-month smoking cessation success rate was 48.0%. Multivariate analysis showed that younger age (<65 years), cohabited status, early stage, and the number of counseling sessions were statistically significant factors affecting 6-month smoking cessation success (p<0.05). Initiation of a cessation program before cancer treatment was significantly associated with cessation success (odds ratio, 1.66; 95% confidence interval, 1.02-2.70; p=0.040). CONCLUSION: Smoking cessation intervention must be considered when establishing a treatment plan immediately after a cancer diagnosis among smokers.

Risk factors and clinical outcomes associated with acquired hypofibrinogenemia in patients administered hemocoagulase batroxobin for hemoptysis.

Background: Hemocoagulase batroxobin is used to prevent hemostasis or bleeding in surgical and trauma patients; however, the role of batroxobin in patients with hemoptysis is not well understood. We evaluated the risk factors and prognosis of acquired hypofibrinogenemia in hemoptysis patients treated systemically with batroxobin. Methods: We retrospectively reviewed the medical charts of hospitalized patients who were administered batroxobin for hemoptysis. Acquired hypofibrinogenemia was defined as a plasma fibrinogen level >150 mg/dL at baseline, decreasing to <150 mg/dL after batroxobin administration. Results: Overall, 183 patients were enrolled, of whom 75 had acquired hypofibrinogenemia after the administration of batroxobin. There was no statistical difference in the median age of the patients in the non-hypofibrinogenemia and hypofibrinogenemia groups (72.0 vs. 74.0 years, respectively). The patients in the hypofibrinogenemia group showed a higher rate of intensive care unit (ICU) admission (11.1% vs. 22.7%; P=0.041) and tended to have more massive hemoptysis than those in the non-hyperfibrinogenemia group (23.1% vs. 36.0%; P=0.068). The patients in the hypofibrinogenemia group further showed a higher requirement for transfusion (10.2% vs. 38.7%; P<0.000) than those in the non-hyperfibrinogenemia group. Low levels of baseline plasma fibrinogen and a prolonged and higher total dose of batroxobin were associated with the development of acquired hypofibrinogenemia. Acquired hypofibrinogenemia was associated with increased 30-day mortality [hazard ratio (HR), 4.164; 95% confidence interval (CI), 1.318-13.157]. Conclusions: The plasma fibrinogen levels in patients who were administered batroxobin for hemoptysis should be monitored, and batroxobin should be discontinued if hypofibrinogenemia occurs.

Structure-activity relationship of dibenzylideneacetone analogs against the neglected disease pathogen, Trypanosoma brucei.

Trypanosoma brucei is a protozoan parasite that causes Human African Trypanosomiasis (HAT), a neglected tropical disease (NTD) that is endemic in 36 countries in sub-Saharan Africa. Only a handful drugs are available for treatment, and these have limitations, including toxicity and drug resistance. Using the natural product, curcumin, as a starting point, several curcuminoids and related analogs were evaluated against bloodstream forms of T. b. brucei. A particular subset of dibenzylideneacetone (DBA) compounds exhibited potent in vitro antitrypanosomal activity with sub-micromolar EC50 values. A structure-activity relationship study including 26 DBA analogs was initiated, and several compounds exhibited EC50 values as low as 200 nM. Cytotoxicity counter screens in HEK293 cells identified several compounds having selectivity indices above 10. These data suggest that DBAs offer starting points for a new small molecule therapy of HAT.

Hesperidin enhances intestinal barrier function in Caco-2 cell monolayers via AMPK-mediated tight junction-related proteins.

The intestinal epithelium is a single-cell layer on the mucosal surface that absorbs food-derived nutrients and functions as a barrier that protects mucosal integrity. Hesperidin (hesperetin-7-rhamnoglucoside) is a flavanone glycoside composed of the flavanone hesperetin and the disaccharide rutinose, which has various physiological benefits, including antioxidative, anti-inflammatory, and antiallergic effects. Here, we used human intestinal Caco-2 cell monolayers to examine the effect of hesperidin on intestinal barrier function. Hesperidin-treated Caco-2 cell monolayers displayed enhanced intestinal barrier integrity, as indicated by an increase in transepithelial electrical resistance (TEER) and a decreased apparent permeability (Papp ) for fluorescein. Hesperidin elevated the mRNA and protein levels of occludin, MarvelD3, JAM-1, claudin-1, and claudin-4, which are encoded by tight junction (TJ)-related genes. Moreover, hesperidin significantly increased the phosphorylation of AMP-activated protein kinase (AMPK), indicating improved intestinal barrier function. Thus, our results suggest that hesperidin enhances intestinal barrier function by increasing the expression of TJ-related occludin, MarvelD3, JAM-1, and claudin-1 via AMPK activation in human intestinal Caco-2 cells.