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Abstract Background Colorectal cancer (CRC) screening decision aids can inform patients about CRC screening benefits, costs, and procedures. Patients who receive the decision aid report wanting to share the information with their families and friends. We evaluated a CRC screening decision aid on Hispanic patients’ communication to their alters and whether patient-alter communication leads to alters’ CRC screening intention. Methods We conducted a one-arm pre/post study of Hispanic patients and their alters; patients (n = 42) and their alters (n = 19) were recruited from a clinic site in Yakima County, Washington State. Patients viewed a CRC screening decision aid at the clinic site. Survey data from patients and alters were collected via telephone including patients’ communication with their alters about CRC screening after viewing the decision aid and alters’ intention to be screened for CRC after talking to the patient. Results Most participants reported sharing CRC information with their alters after viewing the decision aid, and most alters confirmed they had received CRC information from participants (68%). The decision aid was associated with participants' own intention to undergo CRC screening and with alters' intention to be screened for CRC using a fecal occult blood test (p = 0.014) and sigmoidoscopy (p = 0.011). Conclusions Patient decision aids have the potential to increase CRC screening behavior beyond the decision aid recipients to their social network. Trial registration Trials Registration Number: NCT04444232 “Retrospectively registered.”

Aortic dissection in pregnant patients results in an inpatient mortality rate of 8.6%. Owing to the pronounced mortality rate and speed at which aortic dissections progress, efficient early detection methods are crucial. Here, we highlight the importance of early chest computed tomography (CT) for differentiating aortic dissection from pulmonary embolism in pregnant patients with dyspnea. We present the unique case of a 38-year-old pregnant woman with elevated D-dimer and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, initially suspected of having a pulmonary embolism. Initial transthoracic echocardiography did not indicate aortic dissection. Surprisingly, after an emergency cesarean section, a chest CT scan revealed a DeBakey type I aortic dissection, indicating a diagnostic error. Our findings emphasize the need for early chest CT in pregnant patients with dyspnea and elevated D-dimer and NT-proBNP levels. This case report highlights the critical importance of considering both aortic dissection and pulmonary embolism in the differential diagnosis of such cases, which will inform future clinical practice.

Objective This study aimed to investigate the similarities and differences in risk factors for suicide among adult and adolescent women in South Korea and identify subtypes of suicidal ideation or suicide attempt in each group. Methods Multifaceted data were collected and analyzed by linking survey and social media data. Interpretable machine learning models were constructed to predict suicide risk and major risk factors were extracted by investigating their feature importance. Additionally, subtypes of suicidal adult and adolescent women were identified and explained using risk factors. Results The risk factors for adult women were primarily related to mental disorders, while those for adolescent women were primarily related to interpersonal experiences and needs. Two subtypes of suicidal adult women were one with high psychiatric symptoms and mental disorders of them and/or their families and the other with excessive social media use and high online victimization. Two subtypes of suicidal adolescent women were one with high psychiatric symptoms, high ACEs, and high social connectedness, and the other with frequent social media use, high online sexual victimization, and high social assurance. Conclusions These findings enable a stratified and targeted understanding of suicide in women and help develop customized suicide prevention plans in South Korea.

The present study aimed to understand how Chinese international students perceived and experience healthcare utilization in Korea and to broaden Andersen’s framework in the age of globalization, allowing easier maintenance of transnational relationships with one’s native country. We analyzed the in-depth personal interviews with 31 Chinese international students. The grounded theory was employed to analyze the interview data. Among factors suggested by Andersen, predisposing (perceptions about the Korean healthcare system) and enabling (financial barriers, language barriers, and lack of social support) factors contributed to healthcare utilization among Chinese international students in Korea. Self-medication via broad medical transnational ties with the home country (bringing medications from home) impeded their healthcare utilization. We highlighted the roles of their campus health center to promote optimal healthcare utilization for Chinese international students. It is important to educate international students about the risks or negative effects of self-medication.

BackgroundBirths at advanced maternal ages (≥ 35 years) are increasing. This has been associated with a higher incidence of placenta previa, which increases bleeding risk. Hybrid operating rooms, designed to accommodate interventions and cesarean sections, are becoming more prominent because of their dual capabilities and benefits. However, they have been associated with increased postoperative hypothermia in pediatric settings; moreover, this has not been studied in pregnant women with placenta previa.MethodsThis retrospective cohort study included pregnant women diagnosed with placenta previa who underwent elective cesarean section under general anesthesia between May 2019 and 2023. The patients were categorized according to the operating room type. The primary outcome was to determine whether the hybrid operating room is a risk factor for immediate postoperative hypothermia, defined as a tympanic membrane temperature below 36.0°C. The secondary outcomes were the effects of immediate postoperative hypothermia on the durations of postanesthetic care unit and postoperative hospital stays and incidence of complications.ResultsImmediate postoperative hypothermia (tympanic membrane temperature < 36.0°C) was more prevalent in the hybrid than in the standard operating room group (20% vs. 36.6%, p = 0.033), with a relative risk of 2.86 (95% confidence interval 1.24-6.64, p < 0.001). Patients undergoing surgery in the hybrid operating room who experienced immediate postoperative hypothermia stayed longer in the postanesthetic care unit (26 min vs. 40 min, p < 0.001) and in the hospital after surgery (4 days; range 3-5 vs. 4 days; range 4-11, p = 0.021). However, the complication rates of both groups were not significantly different (11.3% vs 7.3%, p = 0.743).ConclusionHybrid operating rooms may increase the risk of postoperative hypothermia. Postoperative hypothermia is associated with prolonged postanesthetic care unit and hospital stays. Preventing hypothermia in patients in hybrid operating rooms is of utmost importance.

Betaine, a compound found in plants and sea foods, is known to be beneficial against non-alcoholic fatty liver disease (NAFLD), but its hepatoprotective and anti-steatogenic mechanisms have been not fully understood. In the present study, we investigated the mechanisms underlying betaine-mediated alleviation of NAFLD induced by a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) in mice, with special focus on the contribution of betaine-stimulated autophagy to NAFLD prevention. Male ICR mice were fed a CDAHFD with or without betaine (0.2–1% in drinking water) for 1 week. Betaine ameliorated the CDAHFD-induced fatty liver by restoring sulfur amino acid (SAA)-related metabolites, such as S-adenosylmethionine and homocysteine, and the phosphorylation of AMPK and ACC. In addition, it reduced the CDAHFD-induced ER stress (BiP, ATF6, and CHOP) and apoptosis (Bax, cleaved caspase-3, and cleaved PARP); however, it induced autophagy (LC3II/I and p62) which was downregulated by CDAHFD. To determine the role of autophagy in the improvement of NAFLD, chloroquine (CQ), an autophagy inhibitor, was injected into the mice fed a CDAHFD and betaine (0.5 % in drinking water). CQ did not affect SAA metabolism but reduced the beneficial effects of betaine as shown by the increases of hepatic lipids, ER stress, and apoptosis. Notably, the betaine-induced improvements in lipid metabolism determined by protein levels of p-AMPK, p-ACC, PPARα, and ACS1, were reversed by CQ. Thus, the results of this study suggest that the activation of autophagy is an important upstream mechanism for the inhibition of steatosis, ER stress, and apoptosis by betaine in NAFLD.

Abstract Background Rural Latino children have higher rates of obesity compared to non-Latino Whites. Schools are in a unique position to address rural childhood obesity through policies. While evidence exists on factors that promote or impede school-based physical activity (PA) and nutrition policies, only a fraction has been in rural communities. This study seeks to understand 1) the knowledge and perceptions of school nutrition and PA policies and 2) barriers and facilitators to their implementation among rural school stakeholders from Washington State. Methods We conducted 20 semi-structured, in-depth interviews with school stakeholders (e.g., principals and school nutrition directors) from four K–12 school districts in the Lower Yakima Valley of Eastern Washington State. Thematic analysis was conducted using inductive, constant comparison approach to identify themes around knowledge and perceptions of policies and barriers and facilitators of policy implementation. Results Three main themes were identified: perceptions and knowledge of school PA and nutrition policies, barriers to policy implementation, and facilitators of policy implementation. The majority of stakeholders were supportive of school-based policies promoting PA and a healthy diet, even when lacking a specific understanding of these policies. Four subthemes were identified as barriers to policy implementation: viewing PA as a low priority, misuse of recess time, funding constraints, and lack of strong leadership. Facilitators of implementation included strong leadership at the district level, creating healthy norms through school-community linkages and pooling community resources to improve nutrition and PA among children. Conclusions Schools provide a unique setting to promote healthy diet and PA behaviors among children and their families. Study findings show that while knowledge of specific nutrition and PA policies may vary, support for such policies were high among rural stakeholders. Study findings can inform policy development and support strategies for policy implementation in rural settings. Future studies may want to examine whether implementation of strategies addressing the barriers and enhancing facilitators lead to success in rural school settings.

Abstract In this study, we reveal the distinctive communication network structures and contents of online breast cancer community posts in accordance with different cancer stages. Using data collected from community.breastcancer.org, a major online breast cancer community (28,139 original posts and 663,748 replies), we traced the communication network structures and contents of replies associated with its severity. By combining network and quantitative content analyses, we deciphered the functions and utilities of health-related online communication. We found an inverse relationship between offline epidemiological prevalence and online communication activation. Despite the relatively small percentage of breast cancer patients, it was found that the more severe the condition of breast cancer, the more active online communication was. We further found that as pathological severity advances, communication networks move from informational exchange to emotional support. The capture of online social networks based on the cancer stage can help unpack the distinctive communication patterns found across different cancer severities. Our results provide insights into a possible online communication intervention design tailored to symptom severity.

BackgroundTechnology can assist in providing effective infectious disease management, but it can also become a source of social injustice and inequality. To control the rapidly increasing SARS-CoV-2 infections and promote effective vaccine administration, both South Korea and Japan have been using several technology-based systems and mobile apps. However, their different approaches to technology use have yielded contrasting social implications. ObjectiveThrough comparative studies of the use of digital technologies for pandemic management and its social implications in Japan and South Korea, this study aimed to discuss whether the active and optimal use of technology for pandemic management can occur without subverting or compromising important social values, such as privacy and equality. MethodsThis study compared the social implications of Japan’s and South Korea’s contrasting approaches to technology implementation for COVID-19 pandemic management in early 2022. ResultsDigital technologies have been actively and comprehensively used in South Korea, enabling effective COVID-19 management, but have raised serious concerns about privacy and social equality. In Japan, technologies have been more carefully implemented, thereby not causing similar social concerns, but their effectiveness in supporting COVID-19 regulations has been criticized. ConclusionsPotential social implications such as equality concerns, the balance between public interest and individual rights, and legal implications must be carefully assessed in conjunction with effective and optimal infectious disease control to achieve sustainable use of digital health technologies for infectious disease management in the future.

Bone differentiation is crucial for skeletal development and maintenance. Its dysfunction can cause various pathological conditions such as rickets, osteoporosis, osteogenesis imperfecta, or Paget’s disease. Although traditional two-dimensional cell culture systems have contributed significantly to our understanding of bone biology, they fail to replicate the intricate biotic environment of bone tissue. Three-dimensional (3D) spheroid cell cultures have gained widespread popularity for addressing bone defects. This review highlights the advantages of employing 3D culture systems to investigate bone differentiation. It highlights their capacity to mimic the complex in vivo environment and crucial cellular interactions pivotal to bone homeostasis. The exploration of 3D culture models in bone research offers enhanced physiological relevance, improved predictive capabilities, and reduced reliance on animal models, which have contributed to the advancement of safer and more effective strategies for drug development. Studies have highlighted the transformative potential of 3D culture systems for expanding our understanding of bone biology and developing targeted therapeutic interventions for bone-related disorders. This review explores how 3D culture systems have demonstrated promise in unraveling the intricate mechanisms governing bone homeostasis and responses to pharmacological agents.

Anti-melanoma differentiation-associated gene-5 (MDA-5) antibody is an autoantibody found in patients with dermatomyositis. These antibody-positive patients are clinically characterized by complications of rapidly progressive interstitial pneumonia resistant to treatment and with poor prognosis. We describe herein a patient with MDA-5 antibody-positive interstitial lung disease, which progressed rapidly to death after a period of slow progress. Recently, attention has been paid to the similarities in clinical courses and CT images between MDA-5 antibody-positive interstitial lung disease and coronavirus disease 2019 (COVID-19)-associated pneumonia. Patients with MDA-5 antibody do not always have diffuse and evenly distributed bilateral opacities at the time of first presentation. This patient had significant laterality of such opacities. It should be considered that MDA-5 antibody-positive patients with such laterality in opacities might progress rapidly. Chest physicians, dermatologists, and dermatologists need to be aware of the characteristics of the disease for optimal treatment choices.

Using digital technology to adapt to their host country is an integral part of social inclusion for migrant and refugee populations. However, researchers have not empirically examined how digital technology use may affect subjective well-being among migrant populations. This study aimed to examine the association between increased digital technology use, technological self-efficacy, and subjective well-being. Using the 2020 Digital Divide Survey in Korea, our sample consists of 6520 native South Koreans and 699 North Korean migrants aged 18 years and older. We examined the three-way interaction of technological self-efficacy and being North Korean migrants in the relationship between the increase in the use of five types of digital technology, technological self-efficacy, and subjective well-being, using hierarchical linear regressions. North Korean migrants were statistically lower than South Korean natives in all types of increased digital technology use. Moderation analysis showed that technological self-efficacy positively moderated the relationship between increased digital technology use and subjective well-being. A three-way interaction showed that this relationship was stronger in North Korean migrants for three types of utilization, networking, information sharing, and life services. A psychosocial approach needs to be taken to digital technology education for North Korean migrants, in light of the potential benefits of technological self-efficacy.

COVID-19 has worsened adolescents' mental and physical health. Several studies have reported that the effect may be greater in girls; however, relevant socio-ecological factors have not been examined. This study aimed to examine the factors associated with physical and mental health status among adolescents and the moderating role of gender on the relationship between physical and mental health status and perceived household financial decline. We analyzed the cross-sectional 2020 Korea Youth Risk Behavior Web-based Survey (KYRBS) collected between August and November 2020 in South Korea. It included 54,809 adolescents (28,269 males and 26,540 females), on average aged 15.1. We conducted ordinary least squares (OLS) regressions to examine the factors associated with physical and mental health outcomes. Gender differences were observed in associated factors. Then, we tested the moderating effect of gender by including an interaction term between gender and perceived household financial decline due to the COVID-19 pandemic. Perceived household financial decline due to COVID-19 negatively affected both groups. Perceiving moderate and severe financial decline due to COVID-19 is negatively associated with self-rated health among female adolescents than male counterparts. Female adolescents were also more vulnerable to mental health outcomes (i.e., distress, anxiety, and loneliness) when they perceived severe or moderate household financial decline due to COVID-19 compared to their male peers. Our findings suggest that female adolescents are more vulnerable to household financial shocks due to COVID-19, especially in households that have experienced a severe decline. We suggest the need for gender-sensitive policy interventions for adolescent mental health.

Abstract Introduction: The Institute of Translational Health Sciences (Clinical and Translational Science Awards Program hub) developed a program coined Community Voices to invite communities to submit project ideas and be matched with academic researchers. We describe formative research to understand community and academic researcher perspectives on how the program could facilitate collaborations addressing community priorities. Methods: We conducted four focus groups with 31 community-based organization (CBO) representatives and 11 semi-structured interviews with academic researchers in the Washington, Wyoming, Alaska, Montana, and Idaho regions. Questions included the appeal of Community Voices to engage community and academic partners, potential program usefulness, and Community Voices’ potential role in building community–academic partnerships. We used an inductive, constant comparison approach to code transcripts and thematic analysis to generate themes. Results: Most CBO representatives were female (87.1%) and Hispanic/Latino (61.3%). Most academic researchers had a PhD (63.6%) and worked at a university (81.8%). The themes were: (1) community–academic partnerships built on trust will offer mutual benefit, (2) community-initiated project ideas should prioritize community needs, (3) matchmaking will accelerate connections but should not replace time to foster partnership, (4) Community Voices should go beyond matchmaking and provide ongoing support/training, and (5) fostering effective communication is key to partnership success. Conclusions: Community Voices is a novel, bidirectional community engagement program model that advances current practices of prioritizing researchers’ project ideas. This community-driven program may shift the future direction of community engagement practices where prioritizing community’s ideas becomes the norm of community–academic partnerships in clinical and translational science.

Abstract Background Research on the relationship between medical tourism—traveling abroad for healthcare and cervical cancer screening is lacking. This study examines (1) the association between medical tourism and cervical cancer screening among immigrant women and (2) whether the association varies across years in the U.S. Methods We analyzed the New Immigrant Survey data of immigrant women aged 21–65 (n = 999). The outcome was having had a Pap smear since becoming a permanent resident, and the main predictor was medical tourism. Logistic regressions were conducted. Results Immigrant women who engaged in medical tourism had higher cervical cancer screening rates compared to those who did not engage in medical tourism (84.09% vs. 71.68%). This relationship was statistically significant only among women who have recently immigrated, after controlling for covariates. Conclusions Immigrant women who engaged in medical tourism had 2.18 higher odds of receiving a Pap smear than immigrant women who did not, after controlling for other covariates. Health educators should be aware of the practice of medical tourism and consider providing education on adherence to cancer screening guidelines and follow up abnormal results to ensure that immigrant women receive continuous cancer care.

Objective The present study aims to examine the threshold of coronavirus disease 2019 (COVID-19) vaccine hesitancy over time and public discourse around COVID-19 vaccination hesitancy. Methods We collected 3,952 questions and 66,820 answers regarding COVID-19 vaccination posted on the social question-and-answer website Quora between June 2020 and June 2021 and employed Word2Vec and Sentiment Analysis to analyze the data. To examine changes in the perceptions and hesitancy about the COVID-19 vaccine, we segmented the data into 25 bi-weekly sections. Results As positive sentiment about vaccination increased, the number of new vaccinations in the United States also increased until it reached a ceiling point. The vaccine hesitancy phase was identified by the decrease in positive sentiment from its highest peak. Words that occurred only when the positive answer rate peaked (e.g., safe, plan, best, able, help) helped explain factors associated with positive perceptions toward vaccines, and the words that occurred only when the negative answer rate peaked (e.g., early, variant, scientists, mutations, effectiveness) suggested factors associated with vaccine hesitancy. We also identified a period of vaccine resistance, where people who decided not to be vaccinated were unlikely to be vaccinated without further enforcement or incentive. Conclusions Findings suggest that vaccine hesitancy occurred because concerns about vaccine safety were high due to a perceived lack of scientific evidence and public trust in healthcare authorities has been seriously undermined. Considering that vaccine-related conspiracy theories and fake news prevailed in the absence of reliable information sources, restoring public trust in healthcare leaders will be critical for future vaccination efforts.

Abstract Targeted sequencing for somatic mutations across the hotspots of 50 cancer-related genes was performed using biopsy specimens to investigate whether clinicopathological factors and genomic alterations correlated with prognosis in locally advanced cervical cancer. Seventy patients diagnosed with International Federation of Obstetrics and Gynecology (FIGO) stage III to IVA cervical cancer underwent radiotherapy or concurrent chemoradiotherapy at the National Cancer Center Hospital between January 2008 and December 2017. Mutations were detected in 47 of 70 [67% of cases; frequency of genetic alterations was as follows: PIK3CA (51%), FBXW7 (10%), PTEN (7.1%), and TP53 (5.7%)]. The Cancer Genome Atlas (TCGA) datasets showed a similar distribution of somatic mutations, but PIK3CA mutation frequency was significantly higher in our cohort than in TCGA datasets (P = 0.028). Patients with TP53 mutation were significantly related to poor progression-free survival (PFS) (hazard ratio [HR] = 3.53, P = 0.042). Patients with tumor diameters > 70 mm were associated with poor prognosis (HR = 2.96, P = 0.0048). Patients with non-HPV16/18 genotypes had worse prognosis than those with HPV16/18 genotypes (HR = 2.15, P = 0.030). Hence, patients with locally advanced cervical cancer, TP53 mutation, large tumor diameter, and non-HPV16/18 genotype were independently correlated with poor PFS, despite concurrent chemoradiotherapy.

Ovarian clear cell carcinoma (OCCC), one of the histopathological types of ovarian cancer, has a poor prognosis when it recurs; however, it is difficult to precisely predict the risk of recurrence. Here, we analyzed pathological images of OCCC to elucidate the relationship between pathological findings and recurrence, and using machine learning, we established a classifier to predict the recurrence and several other prognosis indicators of this disease. In total, 110 patients with OCCC treated with primary surgery at a single institution were enrolled in this study. We used the deep-learning neural networks to process the whole slide images of OCCC obtained by digitally scanning the original hematoxylin and eosin-stained glass slides. The images were preprocessed and used as input to the machine learning pipeline. We fine-tuned its parameters to predict the recurrence, progression-free survival, and the overall survival days of all patients. We predicted the recurrence of OCCC with an overall accuracy of 93%, area under the receiver operating characteristic curve of 0.98, and sensitivity/specificity above 0.92 using Resnet 34. Furthermore, we predicted progression-free survival/overall survival of the patients with ~90% accuracy. In conclusion, our study demonstrates the feasibility of using a machine learning system to predict different features of OCCC samples using histopathological images as input. This novel application provides accurate prognosis information and aids in the development of personalized treatment strategies.

Background: With the rising prevalence of obesity, anesthesiologists are expected to increasingly encounter patients with obesity, which poses challenges for anesthetic management. The use of remimazolam, an intravenous anesthetic agent approved in 2020, may be beneficial in these patients. However, its use in patients with super-super obesity remains underexplored. Case Description: A 55-year-old woman with a body mass index (BMI) of 60.6 kg/m2 and moderate obstructive sleep apnea (OSA) underwent laparoscopic sleeve gastrectomy under general anesthesia. The transnasal humidified rapid-insufflation ventilatory exchange (THRIVE) technique was used along with the administration of remimazolam at a rate of 6 mg/kg/h based on the total body weight. The patient was sedated within 125 s without any signs of hemodynamic instability, and the surgery was completed successfully. Conclusions: This case study demonstrates the potential effectiveness of remimazolam infusion for inducing general anesthesia in patients with super-super obesity. The infusion rate, derived from the total body weight, yielded an outcome comparable with that observed in individuals without obesity. Further studies with larger cohorts are required to confirm these findings.

Abstract Background Human Papillomavirus (HPV) vaccine uptake is low among East African adolescents in the US. Adolescents’ preferences influence HPV vaccine decisions, yet few interventions exist that address East African adolescents’ beliefs about HPV vaccines. We describe a multi-step process on how to create a theory-based comic book by integrating empirical findings, theory and focus group data from East African parents in the US. Methods Our multi-methods process included conducting focus groups with Somali, Ethiopian, and Eritrean mothers (n = 30) to understand mothers and adolescents socio-cultural beliefs and information needs about the HPV vaccine, creating comic book messages integrating the focus group findings, and assessing the acceptability of the finalized comic book among Somali, Ethiopian, and Eritrean adolescents (n = 134). Results We identified categories around socio-cultural beliefs (such ethnic representation and concerns about pork gelatin in vaccines), HPV vaccine information needs, and diffusion of information. We then mapped the categories to theoretical constructs and operationalized them into the comic book. Finally, we describe the overall acceptability of the comic book and specifics on comic book structure, appeal of characters, and message relevance. Conclusions A rigorous multi-step process that integrates theory and focus group data can help create culturally appropriate health messages that can educate and appeal to the community.

Abstract Somatic genetic alteration analysis was performed for post-hysterectomy high-risk early-stage uterine cervical cancer patients who underwent post-operative radiation therapy. Post-operative radiation therapy was performed for patients with pathological features of pelvic lymph node metastasis, parametrium invasion, or positive vaginal margin, which corresponded to the post-operative high-risk category. DNA was extracted from paraffin-embedded surgical specimens, and 50 somatic hotspot genetic alternations were detected using Ion AmpliSeq Cancer Hotspot Panel. The existence of actionable mutation was assessed based on OncoKB evidence level > 3A. Between January 2008 and November 2019, 89 patients who underwent abdominal radical hysterectomy followed by post-operative radiation therapy were identified. The follow-up period for living patients was 82.3 months (range 9.3–153.9), and the 5-year relapse-free survival and overall survival rates were 72.6% and 85.9%, respectively. The most frequently detected somatic mutation was PIK3CA (26 [29.2%] patients); however, no prognostic somatic genetic alterations were identified. Actionable mutations were detected in 30 (33.7%) patients. Actionable mutations were detected in approximately one-third of patients, suggesting that precision medicine can be offered to patients with post-operative high-risk uterine cervical cancer in the near future.

Abstract Background Inflammatory bowel disease (IBD), including both Crohn’s disease and ulcerative colitis, are chronic human diseases that are challenging to cure and are often unable to be resolved. The inbred mouse strain C57BL/6 N has been used in investigations of IBD as an experimental animal model. The purpose of the current study was to compare the inflammatory responsiveness of C57BL/6NKorl mice, a sub-strain recently established by the National Institute of Food and Drug Safety Evaluation (NIFDS), with those of C57BL/6 N mice from two different sources using a dextran sulfate sodium (DSS)-induced colitis model. Results Male mice (8 weeks old) were administered DSS (0, 1, 2, or 3%) in drinking water for 7 days. DSS significantly decreased body weight and colon length and increased the colon weight-to-length ratio. Moreover, severe colitis-related clinical signs including diarrhea and rectal bleeding were observed beginning on day 4 in mice administered DSS at a concentration of 3%. DSS led to edema, epithelial layer disruption, inflammatory cell infiltration, and cytokine induction (tumor necrosis factor-α, interleukin-6, and interleukin-1β) in the colon tissues. However, no significant differences in DSS-promoted abnormal symptoms or their severity were found between the three sub-strains. Conclusions These results indicate that C57BL/6NKorl mice responded to DSS-induced colitis similar to the generally used C57BL6/N mice, thus this newly developed mouse sub-strain provides a useful animal model of IBD.

Objective: Many women with breast cancer refuse adjuvant treatments. How they arrive at their respective decisions and whether they are passively or actively involved in making decisions is less known. We explored the different decision-making behaviors of women who received treatments (receivers) after being diagnosed with breast cancer and those who refused (decliners). Methods: Seven women (four receivers and three decliners) were recruited from the Breast Cancer Integrative Oncology Study. We conducted an inductive content analysis based on in-depth semi-structured interviews with open-ended questions. Results: Receivers reported that doctors and family members influenced their decision-making. Decliners perceived their doctors as supportive of their decisions and reported that the experience of adjuvant therapy of family and friends, the results of Oncotest, and concerns about side effects influenced their decision-making. Receivers expressed discomfort about their decisions, relied on books, whereas decliners used various sources to find information. Both receivers and decliners believed that they had made the decisions themselves. However, receivers were somewhat negative about doctors' advice. Receivers also reported that, sometimes, the decision-making process was lacking and reported discomfort with the treatment process. Conclusions: Women with breast cancer need support in understanding the care they are prescribed and getting essential care.

Most studies on COVID-19 preventive behaviors have focused on single-level factors such as national policy, community social capital, or individuals' sociodemographic characteristics. Through a social-ecological model, this study attempts to comprehensively examine the multilevel factors associated with COVID-19 preventive practices in South Korea. Accordingly, a web survey involving 1,500 participants was conducted in December 2020. An ordinary least squares (OLS) regression was used to examine the multilevel factors (individual, interpersonal, community, and policy levels) related to COVID-19 preventive measures, which are based on wearing a mask, washing hands, covering the mouth when coughing or sneezing, and social distancing. When factors at each level were investigated, higher scores of COVID-19 fear and correct knowledge at the individual level, COVID-19 information share at the interpersonal level, and better evaluation of the national government policies in regard to COVID-19 at the policy level were positively associated with COVID-19 preventive behaviors. Community-level factors-neighborhood perception and community participation-were negatively significantly related to COVID-19 preventive behaviors. Additionally, older age, being female, and having a graduate-level education were positively related to better preventive behaviors. The findings of the current study suggest that multilevel efforts are needed to promote preventive behaviors. Specifically, more effort to alleviate COVID-19-related fear and disseminate correct knowledge among Korean citizens is needed as the individual-level characteristics explained the preventive behaviors more than the factors at upper levels.

Liver metabolic disorders and oxidative stress are crucial factors in the development of nonalcoholic fatty liver disease (NAFLD); however, treatment strategies to combat NAFLD remain poorly established, presenting an important challenge that needs to be addressed. Herein, we aimed to examine the effect of isoquercitrin on lipid accumulation induced by exogenous free fatty acids (FFA) using HepG2 cells and elucidate the underlying molecular mechanism. The cells were exposed to 0.5 mM FFA to induce intracellular lipid accumulation, followed by co-treatment with isoquercitrin to confirm the potential inhibitory effect on FFA-induced lipid production. HepG2 cells exposed to FFA alone exhibited intracellular lipid accumulation, compromised endoplasmic reticulum (ER) stress, and enhanced expression of proteins and genes involved in lipid synthesis; however, co-treatment with isoquercitrin decreased the expression of these molecules in a dose-dependent manner. Furthermore, isoquercitrin could activate AMP-activated protein kinase (AMPK), a key regulatory protein of hepatic fatty acid oxidation, suppressing new lipid production by phosphorylating acetyl-CoA carboxylase (ACC) and inhibiting sterol regulatory element-binding transcription factor 1 (SREBP-1)/fatty acid synthase (FAS) signals. Overall, these findings suggest that isoquercitrin can be employed as a therapeutic agent to improve NAFLD via the regulation of lipid metabolism by targeting the AMPK/ACC and SREBP1/FAS pathways.

The liver produces and stores various nutrients that are necessary for the body and serves as a chemical plant, metabolizing carbohydrates, fats, hormones, vitamins, and minerals. It is also a vital organ for detoxifying drugs and exogenous harmful substances. Culturing liver cells in vitro under three-dimensional (3D) conditions is considered a primary mechanism for liver tissue engineering. The 3D cell culture system is designed to allow cells to interact in an artificially created environment and has the advantage of mimicking the physiological characteristics of cells in vivo. This system facilitates contact between the cells and the extracellular matrix. Several technically different approaches have been proposed, including bioreactors, chips, and plate-based systems in fluid or static media composed of chemically diverse materials. Compared to conventional two-dimensional monolayer culture in vitro models, the ability to predict the function of the tissues, including the drug metabolism and chemical toxicity, has been enhanced by developing three-dimensional liver culture models. This review discussed the methodology of 3D cell cultures and summarized the advantages of an in vitro liver platform using 3D culture technology.

Although age-related characteristics of hepatic metabolism are reported, those in infants are not fully understood. In the present study, we performed untargeted metabolomic profiling of the livers of infant (3-week-old) and adult (9-week-old) male ICR mice using 1H-NMR spectroscopy and compared 35 abundant hepatic metabolite concentrations between the two groups. The liver/body weight ratio did not differ between the two groups; however, serum glucose, blood urea nitrogen, total cholesterol, and triglyceride concentrations were lower in infants than in adults. Hepatic carbohydrate metabolites (glucose, maltose, and mannose) were higher, whereas amino acids (glutamine, leucine, methionine, phenylalanine, tyrosine, and valine) were lower in infant mice than in adult mice. The concentrations of ascorbate, betaine, sarcosine, and ethanolamine were higher, whereas those of taurine, inosine, and O-phosphocholine were lower in infant mice than in adult mice. The differences in liver metabolites between the two groups could be due to differences in their developmental stages and dietary sources (breast milk for infants and laboratory chow for adults). The above results provide insights into the hepatic metabolism in infants; however, the exact implications of the findings require further investigation.

Objective: To develop and evaluate an online continuing education (CE) course designed to improve healthcare provider self-efficacy to make strong adolescent HPV vaccine recommendations to East African immigrant families. Methods: Focus groups with providers and East African immigrant mothers informed course development. Providers serving East African immigrant families were recruited to view the course and complete pre-/post-test and two-month follow-up surveys. Pre-/post differences were compared with paired t-tests. Results: 202 providers completed the course and pre-/post-test; 158 (78%) completed two-month follow-up. Confidence to make strong HPV vaccine recommendations to East African families increased from 68% pre-test to 98% post-test. Confidence to address common parental concerns also increased: safety, 54% pre-test, 92% post-test; fertility, 55% pre-test, 90% post-test; child too young, 68% pre-test, 92% post-test; and pork gelatin in vaccine manufacturing, 38% pre-test, 90% post-test. Two-month follow-up scores remained high (97% for overall confidence, 94%–97% for addressing parental concerns). All pre-/post-test and pre-test/two-month follow-up comparisons were statistically significant (p

Abstract Acetaminophen (APAP) is the most common antipyretic analgesic worldwide. However, APAP overdose causes severe liver injury, especially centrilobular necrosis, in humans and experimental animals. At therapeutic dosage, APAP is mainly metabolized by sulfation and glucuronidation, and partly by cytochrome P450–mediated oxidation. However, APAP overdose results in production of excess reactive metabolite, N-acetyl-p-benzoquinone imine (NAPQI), by cytochromes P450; NAPQI overwhelms the level of glutathione (GSH), which could otherwise detoxify it. NAPQI binds covalently to proteins, leading to cell death. A number of studies aimed at the prevention and treatment of APAP-induced toxicity are underway. Rats are more resistant than mice to APAP hepatotoxicity, and thus mouse models are mainly used. In the present study, we compared the toxic responses induced by APAP overdose in the liver of ICR mice obtained from three different sources and evaluated the usability of the Korl:ICR stock established by the National Institute of Food and Drug Safety Evaluation in Korea. Administration of APAP (300 mg/kg) by intraperitoneal injection into male ICR mice enhanced CYP2E1 protein expression and depleted hepatic GSH level 2 h after treatment accompanied with significantly increased level of hepatic malondialdehyde, a product of lipid peroxidation. Regardless of the source of the mice, hepatotoxicity, as evidenced by activity of serum alanine aminotransferase, increased from 8 h and peaked at 24 h after APAP treatment. In summary, hepatotoxicity was induced after the onset of oxidative stress by overdose of APAP, and the response was the same over time among mice of different origins.

Abstract Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease worldwide. It is characterized by the accumulation of lipids without alcohol intake and often progresses to non-alcoholic steatohepatitis (NASH), liver fibrosis, and end-stage liver diseases such as cirrhosis or cancer. Although animal models have greatly contributed to the understanding of NAFLD, studies on the disease progression in humans are still limited. In this study, we used the recently reported high-fat L-methionine-defined and choline-deficient (HFMCD) diet to rapidly induce NASH and compared the responses to HFMCD in ICR mice from three different countries: Korea (supplied by the National Institute of Food and Drug Safety Evaluation), USA, and Japan during 6 weeks. Feeding HFMCD did not cause significant differences in weight gain in comparison with mice fed control diet. Relative weight of the liver increased gradually, while the relative weight of the kidneys remained unchanged. The parameters of liver injury (serum activities of alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase) increased rapidly from 1 week and remained elevated for as long as 6 weeks. Histopathological analysis showed that the accumulation of hepatic lipids induced by HFMCD was prominent at 1 week after diet supplementation and increased further at 6 weeks. Inflammatory markers were significantly increased in a time-dependent manner by HFMCD. The mRNA levels of TNF-α and IL-6 were elevated approximately 15-fold relative to control diet and that of IL-1β was increased more than 20-folds at 6 week after the onset of HFMCD intake. In addition, mRNA expression of fibrosis markers such as α-SMA, TGFβ1, and Col1a1 were also significantly increased at 6 week. In summary, the responses of Korl:ICR mice by intake of HFMCD diet were similar to those of ICR mice from other sources, which suggests that Korl:ICR mice is also a useful resource to study the pathogenesis of diet-induced NAFLD.

Abstract Animal models have been used to elucidate the pathophysiology of varying diseases and to provide insight into potential targets for therapeutic intervention. Although alternatives to animal testing have been proposed to help overcome potential drawbacks related to animal experiments and avoid ethical issues, their use remains vital for the testing of new drug candidates and to identify the most effective strategies for therapeutic intervention. Particularly, the study of metabolic diseases requires the use of animal models to monitor whole-body physiology. In line with this, the National Institute of Food and Drug Safety Evaluation (NIFDS) in Korea has established their own animal strains to help evaluate both efficacy and safety during new drug development. The objective of this study was to characterize the response of C57BL/6NKorl mice from the NIFDS compared with that of other mice originating from the USA and Japan in a chemical-induced diabetic condition. Multiple low-dose treatments with streptozotocin were used to generate a type-1 diabetic animal model which is closely linked to the known clinical pathology of this disease. There were no significantly different responses observed between the varying streptozotocin-induced type-1 diabetic models tested in this study. When comparing control and diabetic mice, increases in liver weight and disturbances in serum amino acids levels of diabetic mice were most remarkable. Although the relationship between type-1 diabetes and BCAA has not been elucidated in this study, the results, which reveal a characteristic increase in diabetic mice of all origins are considered worthy of further study.

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver dysfunction characterized by excess lipid accumulation; non-alcoholic steatohepatitis can transform into more severe conditions, such as cirrhosis and hepatocellular carcinoma. Although several pharmacologic approaches have been evaluated in clinical trials, there are no approved therapies for NAFLD. Previous studies have suggested that taurine supplementation alleviates fatty liver; however, the underlying mechanism remains obscure. In this study, we investigated the beneficial effects of taurine on fatty liver injury in vivo induced by tunicamycin, a chemical endoplasmic reticulum (ER) stressor. The mice were administered 2% taurine for 2 weeks prior to intraperitoneal tunicamycin injection; after 72 h of treatment, the mice were euthanized. Tunicamycin treatment significantly increased the levels of serum ALT and AST and hepatic triglycerides. Notably, these changes were alleviated by taurine supplementation. Taurine normalized the protein and/or mRNA levels involved in ER stress signaling (IRE1a, p-IRE1a, ATF6, XBP1, BiP, and CHOP) and lipid metabolism (CD36, MTTP, and ApoB), which were dysregulated by tunicamycin treatment. The stimulation of hepatic lipid export by taurine was evidenced by the recovery of blood VLDL levels. Furthermore, taurine supplementation prevented tunicamycin-induced lipid peroxidation and decreased glutathione (GSH) levels by correcting abnormal cysteine catabolism involved in the production of both taurine and GSH. Therefore, taurine supplementation can prevent tunicamycin-induced liver injury by counteracting oxidative and ER stress.

Overdose of acetaminophen (APAP) can cause severe liver injury. Although alcohol is considered a risk factor for APAP toxicity, the mechanism underlying the interaction between alcohol and APAP remains unclear. Binge alcohol (5 g/kg every 12 h, 3 doses) reduced the concentration of cysteine and glutathione (GSH) and decreased expression of cystathionine β-synthase (CβS), cystathionine γ-lyase (CγL), and glutamate cysteine ligase catalytic subunit (GCLC) in the livers of male C57BL/6 mice. Furthermore, the levels of GSH S-transferase (GST) and GSH peroxidase (GPx) were decreased. To evaluate the effect of binge drinking on APAP-induced liver injury, 300 mg APAP was administered following alcohol binges. APAP in the binge group significantly amplified the serum ALT more than two fold and enhanced the pro-apoptotic proteins with a severe centrilobular necrosis compared to APAP alone. APAP treatment after alcohol binges caused lower levels of hepatic cysteine and GSH than APAP alone over 24 h, indicating that alcohol binges reduced GSH regenerating potential. Exposure to APAP after binge treatment significantly increased oxidative stress (lipid peroxidation) and endoplasmic reticulum (ER) stress (Grp78 and ATF6) markers at 6 h after treatment. Notably, the IRE1α/ASK1/MKK4/JNK pathway was activated, whereas CHOP expression was reduced by APAP administration in mice with pre-exposed alcohol binges compared with APAP alone. Thus, pretreatment with binge alcohol decreases GSH-mediated antioxidant capacity and contributes to augmentation of liver injury caused by subsequent APAP administration through differential ER stress signaling pathway.

Abstract Doxorubicin is a widely used chemotherapeutic agents and is now part of standard therapeutic regimens for a variety of cancers (eg, hematopoietic malignancies and advanced solid tumors of the breast, ovary, thyroid, and bone). However, a potentially lethal and dose-dependent cardiotoxicity that appears within a short time after treatment limits the usage of doxorubicin in cancer patients. Although the mechanism of doxorubicin-induced cardiotoxicity is not completely understood, it is thought that free radical-induced oxidative stress and excessive production of reactive oxygen species are primary drivers of its toxicity. In this study, we compared the doxorubicin-induced cardiotoxicity of ICR mice obtained from three different sources and evaluated the utility of Korl:ICR stock established by the Korean FDA. Because doxorubicin-induced cardiotoxicity is thought to involve the excessive generation of ROS followed by oxidative stress, we determined the representative tissue index of oxidation, lipid peroxidation, and antioxidant, glutathione (GSH), as well as the parameters of heart injury. Doxorubicin treatment successfully induced cardiotoxicity as evidenced by histological examination and serum parameters (eg, levels of LDH and CK activities) in ICR mice. It was accompanied by increased lipid peroxidation and a decrease in both cysteine and GSH, further supporting previous reports that oxidative stress is a potential mechanism of doxorubicin-induced cardiotoxicity. Of interest, we did not observe a significant difference in doxorubicin-induced cardiotoxicity among mice of different origins. Collectively, our results suggest that Korl:ICR strain may be useful in the research of doxorubicin-induced cardiotoxicity.

Abstract Non-alcoholic fatty liver disease (NAFLD) is believed to be the most prevalent liver disease worldwide and a major cause of chronic liver injury. It is characterized by lipid accumulation in the absence of significant alcohol consumption and frequently progresses to steatohepatitis, liver fibrosis, and hepatocellular carcinoma. Although many studies have been conducted to better understand NAFLD since it was first recognized, there are still many gaps in knowledge of etiology, prognosis, prevention and treatment. Methionine-choline deficient (MCD) diet, a well-established experimental model of NAFLD in rodents, rapidly and efficiently produces the clinical pathologies including macrovesicular steatosis and leads to disease progression. In this study, we measured the response to MCD diet in C57BL/6N mice obtained from three different sources; Korea NIFDS, USA, and Japan. We evaluated changes in body weight, food consumption, and relative weights of tissues such as liver, kidney, gonadal white adipose tissue, inguinal white adipose tissue, and brown adipose tissue. These basic parameters of mice with an MCD diet were not significantly different among the sources of mice tested. After 3 weeks on an MCD diet, histopathological analyses showed that the MCD diet induced clear fat vacuoles involving most area of the acinus in the liver of all mice. It was accompanied by increased serum activities of alanine aminotransferase and aspartate aminotransferase, and decreased levels of serum triglyceride and cholesterol. In conclusion, the response of C57BL6N mice originating from different sources to the MCD diet showed no significant differences as measured by physiological, biochemical, and histopathological parameters.

A series of twenty-six compounds of furfuryl or benzyl tetrahydropyrazino[1,2-a]indole analogs were synthesized and evaluated for cytotoxic activity against the estrogen receptor (ER)-positive breast cancer cell line (MCF-7) and the epidermal growth factor receptor (EGFR) over-expressed triple-negative breast cancer cell line (MDA-MB-468). Among them, compounds 2b, 2f and 2i showed more potent activity and selectivity against MDA-MB-468 cells than gefitinib, as an EGFR- tyrosine kinase inhibitor. In addition, it was confirmed by means of isobologram analysis of combinational treatment with gefitinib that they have a synergistic effect, especially compounds 2b and 2f, which inhibit Akt T308 phosphorylation. Moreover, it was confirmed that 2-benzyl-1-oxo-1,2,3,4-tetrahydropyrazino[1,2-a]indole-3-carboxamide analogs (2b, 2f, and Ref 2) tend to selectively inhibit PI3Kβ, which is involved in the phosphorylation of Akt.

Purpose: The aim of this study was to estimate inter-rater reliability and validate magnetic resonance elastography (MRE) as a tool to measure liver elasticity.Materials and Methods: The study protocol was approved by the institutional review board at our institution. In all, 10 normal volunteers and 110 patients, who provided written informed consent, were enrolled. The pathological fibrosis score was applied as a standard reference of liver fibrosis in 21 patients. MRE was performed with a 1.5-T magnetic resonance imaging scanner with a cylindrical passive longitudinal shear wave driver placed over the right chest wall to deliver vibrations. A gradient-echo MRE sequence was used to acquire axial wave images, which were automatically converted to elastograms representing elasticity (in kilopascals, or kPa). The region of interest was placed in the right lobe of the liver on elastograms by two raters independently. To evaluate interrater reliability, the intraclass correlation coefficient was calculated. The elasticity measurements correlated with the pathological fibrosis score (F1-F4) in 21 patients.Results: The intraclass correlation coefficient was almost perfect (0.993) between the elasticities measured by the two raters. The mean elasticity value for patients with F4 was 5.7 kPa; F3, 4.4 kPa; F2, 3.1 kPa; F1, 2.2 kPa; and F0, 2.1 kPa.Conclusion: MRE is a reliable tool to measure liver elasticity. [ABSTRACT FROM AUTHOR]

Aim: To examine if it is possible to shorten the examination time of gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB)-enhanced MRI by omitting hepatocyte-phase images of 20-min delay time (Im-20) for detecting focal liver lesions.Materials and Methods: Four hundred ninety-five malignant focal liver lesions observed on Im-20 in 265 patients were included. The hepatocyte phase was obtained 10 min (Im-10) and 20 min (Im-20) after Gd-EOB injection. Liver enhancement was evaluated using a 4-point scale [excellent/good/poor/non-diagnostic; visual liver-spleen contrast (V-LSC)] and a quantitative liver-spleen contrast ratio (Q-LSC). Two radiologists evaluated lesion conspicuity for assessing the sensitivity of lesion detection. As Im-20 was used as the standard of reference for the lesions, Im-20 artificially had 100% sensitivity.Results: The results showed that although sensitivities and Q-LSC significantly increased from Im-10 to Im-20 (sensitivity/mean Q-LSC: Im-5, 81%/1.4 Im-10, 96%/1.7: Im-20, 100%/1.9), the sensitivity of Im-10 achieved 100% (the same as Im-20) in patients with good/excellent V-LSC or Q-LSC of more than 1.5. On Im-10, 202 patients (77%) were assigned as having good/excellent V-LSC (78%), and 161 (61%) were assigned as having Q-LSC of more than 1.5.Conclusion: We concluded that Im-20 can be omitted in at least 61% of the patients. [ABSTRACT FROM AUTHOR]