Barriers and facilitating factors to healthcare accessibility among Nepalese migrants during COVID-19 crisis in Japan: an exploratory sequential mixed methods study.

BACKGROUND: The COVID-19 pandemic has highlighted the need for global unity and timely access to healthcare for all including multilingual and intercultural societies. This study aimed to identify barriers to healthcare access due to the COVID-19 crisis among Nepalese migrants in Japan and explore ways to counter these barriers, both in routine and crisis situations. METHODS: This study used an exploratory sequential mixed-methods study design. The researchers conducted 11 focus group discussions including 89 participants and an online survey involving 937 respondents. The integration of focus group discussions and logistic regression analysis from the survey was reported via a 'joint display'. RESULTS: Twenty-six themes on barriers to and six on facilitators of healthcare accessibility were identified by the focus group discussions among which 17 barriers like lack of knowledge of health insurance, language barriers, lack of hotline services, unawareness of available services, fear of discrimination etc. had significant association in our logistic regression analysis after adjusting for all confounders. Similarly, the only facilitator that had a significant impact, according to the multivariable logistic regression analysis, was receiving health information from Nepali healthcare professionals (OR = 1.36, 95% CI = (1.01 - 1.82), p-value < 0.05). CONCLUSION: The study suggests the need for a crisis information hub which could be coordinated by the Nepal embassy or concerned authorities, flexible policies for active deployment of Nepalese health workers and volunteers, accessible hotlines in the Nepali language, and incorporation of Nepali telehealth services in Japan.

Perioperative risk factors for new-onset postoperative atrial fibrillation after coronary artery bypass grafting: a systematic review.

BACKGROUND: Postoperative atrial fibrillation (POAF) is the most common cardiac dysrhythmia to occur after coronary artery bypass grafting (CABG). However, the risk factors for new-onset POAF after CABG during the perioperative period have yet to be clearly defined. Accordingly, the aim of our systematic review was to evaluate the perioperative predictors of new-onset POAF after isolated CABG. METHOD: Our review methods adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. We searched seven electronic databases (PubMed, Embase, CINAHL, PsycArticles, Cochrane, Web of Science, and SCOPUS) to identify all relevant English articles published up to January 2020. Identified studies were screened independently by two researchers for selection, according to predefined criteria. The Newcastle-Ottawa Scale was used to evaluate the quality of studies retained. RESULTS: After screening, nine studies were retained for analysis, including 4798 patients, of whom 1555 (32.4%) experienced new-onset POAF after CABG. The incidence rate of new-onset POAF ranged between 17.3% and 47.4%. The following risk factors were identified: old age (p < 0.001), a high preoperative serum creatinine level (p = 0.001), a low preoperative hemoglobin level (p = 0.007), a low left ventricle ejection fraction in Asian patients (p = 0.001), essential hypertension (p < 0.001), chronic obstructive pulmonary disease (p = 0.010), renal failure (p = 0.009), cardiopulmonary bypass use (p = 0.002), perfusion time (p = 0.017), postoperative use of inotropes (p < 0.001), postoperative renal failure (p = 0.001), and re-operation (p = 0.005). All studies included in the analysis were of good quality. CONCLUSIONS: The risk factors identified in our review could be used to improve monitoring of at-risk patients for early detection and treatment of new-onset POAF after CABG, reducing the risk of other complications and negative clinical outcomes.

Erratum to "Effects of Ammonium Chloride on Ozone-induced Airway Inflammation: the Role of Slc26a4 in the Lungs of Mice".

This corrects the article on p. e272 in vol. 35, PMID: 32808511.

Plastid Genomes of the Early Vascular Plant Genus Selaginella Have Unusual Direct Repeat Structures and Drastically Reduced Gene Numbers.

The early vascular plants in the genus Selaginella, which is the sole genus of the Selaginellaceae family, have an important place in evolutionary history, along with ferns, as such plants are valuable resources for deciphering plant evolution. In this study, we sequenced and assembled the plastid genome (plastome) sequences of two Selaginella tamariscina individuals, as well as Selaginella stauntoniana and Selaginella involvens. Unlike the inverted repeat (IR) structures typically found in plant plastomes, Selaginella species had direct repeat (DR) structures, which were confirmed by Oxford Nanopore long-read sequence assembly. Comparative analyses of 19 lycophytes, including two Huperzia and one Isoetes species, revealed unique phylogenetic relationships between Selaginella species and related lycophytes, reflected by structural rearrangements involving two rounds of large inversions that resulted in dynamic changes between IR and DR blocks in the plastome sequence. Furthermore, we present other uncommon characteristics, including a small genome size, drastic reductions in gene and intron numbers, a high GC content, and extensive RNA editing. Although the 16 Selaginella species examined may not fully represent the genus, our findings suggest that Selaginella plastomes have undergone unique evolutionary events yielding genomic features unparalleled in other lycophytes, ferns, or seed plants.

Effects of Ammonium Chloride on Ozone-induced Airway Inflammation: the Role of Slc26a4 in the Lungs of Mice.

BACKGROUND: Exposure to ozone (O3) induces neutrophilic inflammation and goblet cell hyperplasia in humans and experimental animals. Because the solute carrier family 26-member 4 (Slc26a4; pendrin) gene induces mucin production and intraluminal acidification in the airways, it was hypothesized to be a key molecule in O3-induced airway injury. Thus, we evaluated the role of Slc26a4 and the protective effects of ammonium chloride (NH4Cl) in O3-induced airway injury in mice. METHODS: Six-week-old female BALB/c mice were exposed to filtered air or O3 for 21 days (2 ppm for 3 hr/day). NH4Cl (0, 0.1, 1, and 10 mM) was administered intratracheally into the airways. Airway resistance was measured using a flexiVent system, and bronchoalveolar lavage fluid (BALF) cells were differentially counted. Slc26a4 and Muc5ac proteins and mRNA were measured via western blotting, real-time polymerase chain reaction, and immunostaining. Tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-17, IL-1ß, and caspase-1 were analyzed via western blotting. RESULTS: The levels Slc26a4 protein and mRNA significantly increased in lung tissues from Day 7 to Day 21 of O3 exposure, with concomitant increases in lung resistance, numbers of goblet cells in lung tissues, and inflammatory cells and thiocyanate (SCN-) levels in BALF in a time-dependent manner. Treatment with NH4Cl significantly reduced these changes to levels similar to those of sham-treated mice, with a concomitant reduction of Slc26a4 proteins in lung lysates and SCN- levels in BALF. Slc26a4 protein was co-expressed with muc5ac protein in the bronchial epithelium, as indicated by immunofluorescence staining. NH4Cl treatment also significantly attenuated the O3-induced increases in IFN-γ, TNF-α, IL-17, IL-1ß, and p20-activated caspase-1. CONCLUSION: Slc26a4 may be involved in O3-induced inflammatory and epithelial changes in the airways via activation of the inflammasome and the induction of IL-17 and IFN-γ. NH4Cl shows a potential as a therapeutic agent for controlling O3-induced airway inflammation and epithelial damage by modulating Slc26a4 expression.

Upregulation of interleukin-33 and thymic stromal lymphopoietin levels in the lungs of idiopathic pulmonary fibrosis.

BACKGROUND: Innate T helper type 2 (Th2) immune responses mediated by interleukin (IL)-33, thymic stromal lymphopoietin (TSLP), and IL-25 have been shown to play an important role in pulmonary fibrosis of animal models; however, their clinical implications remain poorly understood. METHODS: TSLP, IL-25, and IL-33 concentrations were measured in bronchoalveolar lavage fluids obtained from normal controls (NCs; n = 40) and from patients with idiopathic pulmonary fibrosis (IPF; n = 100), non-specific interstitial pneumonia (NSIP; n = 22), hypersensitivity pneumonitis (HP; n = 20), and sarcoidosis (n = 19). RESULTS: The TSLP and IL-33 levels were significantly higher in patients with IPF relative to the NCs (p = 0.01 and p = 0.0001, respectively), NSIP (p = 4.95E - 7 and p = 0.0002, respectively), HP (p = 0.00003 and p = 0.000005, respectively), and sarcoidosis groups (p = 0.003 and p = 0.0001, respectively). However, the IL-25 levels were not significantly different between NC and IPF group (p = 0.432). Receiver operating characteristic curves of the TSLP and IL-33 levels revealed clear differences between the IPF and NC groups (AUC = 0.655 and 0.706, respectively), as well as between the IPF and the other lung disease groups (AUC = 0.786 and 0.781, respectively). Cut-off values of 3.52 pg/µg TSLP and 3.77 pg/µg IL-33 were shown to differentiate between the IPF and NC groups with 99.2 and 94.3% accuracy. Cut-off values of 4.66 pg/µg TSLP and 2.52 pg/µg IL-33 possessed 99.4 and 93.2% accuracy for differentiating among the IPF and other interstitial lung disease groups. CONCLUSIONS: Innate immune responses may be associated with the development of IPF. Furthermore, the IL-33 and TSLP levels in BAL fluids may be useful for differentiating IPF from other chronic interstitial lung diseases.

Transcription factor Sp1 prevents TRF2(ΔBΔM)-induced premature senescence in human diploid fibroblasts.

Telomere uncapping is thought to be the fundamental cause of replicative cellular senescence, but the cellular machineries mediating this process have not been fully understood. In the present study, we present the role of Sp1 transcription factor in the state of telomere uncapping using the TRF2(ΔBΔM)-induced senescence model in human diploid fibroblasts. We observed that the expression of Sp1 is down-regulated in the TRF2(ΔBΔM)-induced senescence, which was mediated by ATM and p38 MAPK. In addition, overexpression of Sp1 prevented the TRF2(ΔBΔM)-induced senescence. Among transcriptional targets of Sp1, expression levels of nuclear transport genes such as karyopherin α, Nup107, and Nup50 were down-regulated in the TRF2(ΔBΔM)-induced senescence, which was prevented by Sp1 overexpression. Moreover, inhibition of the nuclear transport by wheat germ agglutinin (an import inhibitor) and leptomycin B (an export inhibitor) induced premature senescence. These results suggest that Sp1 is an anti-senescence transcription factor in the telomere uncapping-induced senescence and that down-regulation of Sp1 leads to the senescence via down-regulation of the nuclear transport.

Genome-wide SNP identification and QTL mapping for black rot resistance in cabbage.

BACKGROUND: Black rot is a destructive bacterial disease causing large yield and quality losses in Brassica oleracea. To detect quantitative trait loci (QTL) for black rot resistance, we performed whole-genome resequencing of two cabbage parental lines and genome-wide SNP identification using the recently published B. oleracea genome sequences as reference. RESULTS: Approximately 11.5 Gb of sequencing data was produced from each parental line. Reference genome-guided mapping and SNP calling revealed 674,521 SNPs between the two cabbage lines, with an average of one SNP per 662.5 bp. Among 167 dCAPS markers derived from candidate SNPs, 117 (70.1%) were validated as bona fide SNPs showing polymorphism between the parental lines. We then improved the resolution of a previous genetic map by adding 103 markers including 87 SNP-based dCAPS markers. The new map composed of 368 markers and covers 1467.3 cM with an average interval of 3.88 cM between adjacent markers. We evaluated black rot resistance in the mapping population in three independent inoculation tests using F2:3 progenies and identified one major QTL and three minor QTLs. CONCLUSION: We report successful utilization of whole-genome resequencing for large-scale SNP identification and development of molecular markers for genetic map construction. In addition, we identified novel QTLs for black rot resistance. The high-density genetic map will promote QTL analysis for other important agricultural traits and marker-assisted breeding of B. oleracea.

B56δ subunit of protein phosphatase 2A decreases phosphorylation of endothelial nitric oxide synthase at serine 116: Mechanism underlying aphidicolin-stimulated NO production.

DNA damage is significant in endothelial cells (EC), particularly in anticancer chemotherapy. Here, we explored whether and how aphidicolin, a DNA-damaging chemical with a promising anticancer activity, alters NO production in bovine aortic endothelial cells (BAEC). In addition to increasing eNOS-Ser1179 phosphorylation, aphidicolin decreased eNOS-Ser116 phosphorylation with a concomitant increase in NO production in a time-dependent manner. The amino acid sequence around the eNOS-Ser116 residue was identified as the substrate site of the regulatory subunit B56δ of protein phosphatase 2A (PP2A). As expected, okadaic acid, a specific PP2A inhibitor, reversed aphidicolin-induced eNOS-Ser116 dephosphorylation in a dose-dependent manner. Aphidicolin also increased B56δ-Ser566 phosphorylation, although expression of neither the catalytic subunit Cα (PP2A Cα) nor B56δ was altered. Ectopic expression of dominant negative (dn)-B56δ reversed all of the observed effects of aphidicolin with respect to phosphorylation of eNOS-Ser116 and B56δ-Ser566. Lastly, aphidicolin-stimulated NO production was also partially attenuated by ectopic expression of dn-B56δ. Taken together, our results are the first to demonstrate that aphidicolin decreases phosphorylation of eNOS-Ser116, at least in part by activating PP2A B56δ, resulting in NO release in BAEC.

Prevalence and risk factors for in-hospital mortality of adult patients on veno-arterial extracorporeal membrane oxygenation for cardiogenic shock and cardiac arrest: A systematic review and meta-analysis.

OBJECTIVES: To synthesize quantitative research findings on the prevalence and risk factors for in-hospital mortality of patients on veno-arterial extracorporeal membrane oxygenation (VA-ECMO). METHODS: A comprehensive search was conducted for the period from May 2008 to December 2023 by searching the five electronic databases of PubMed, CINAHL, Web of Science, EMBASE, and Cochrane library. The quality of included studies was assessed using the Newcastle-Ottawa scale. The meta-analysis estimated the pooled odds ratio or standard mean difference and 95% confidence intervals. RESULTS: A total of twenty-five studies with 10,409 patients were included in the analysis. The overall in-hospital mortality of patients on VA-ECMO was 56.7 %. In the subgroup analysis, in-hospital mortality of VA-ECMO for cardiogenic shock and cardiac arrest was 49.2 % and 75.2 %, respectively. The number of significant factors associated with an increased risk of in-hospital mortality in the pre-ECMO period (age, body weight, creatinine, chronic kidney disease, pH, and lactic acid) was greater than that in the intra- and post-ECMO periods. Renal replacement, bleeding, and lower limb ischemia were the most significant risk factors for in-hospital mortality in patients receiving VA-ECMO. CONCLUSION: Early detection of the identified risk factors can contribute to reducing in-hospital mortality in patients on VA-ECMO. Intensive care unit nurses should provide timely and appropriate care before, during, and after VA-ECMO. IMPLICATIONS FOR CLINICAL PRACTICE: Intensive care unit nurses should be knowledgeable about factors associated with the in-hospital mortality of patients on VA-ECMO to improve outcomes. The present findings may contribute to developing guidelines for reducing in-hospital mortality among patients considering ECMO.

Induction of ICAM1 in Brain Vessels is Implicated in an Early AD Pathogenesis by Modulating Neprilysin.

Intercellular adhesion molecule 1 (ICAM1) is a vessel adhesion protein induced during brain vascular inflammation, which could be closely linked with the development of Alzheimer's disease (AD). This study investigated the effect of ICAM1 on amyloid-degrading enzymes (ADEs) in endothelial cells and their potential involvement in inflammation and AD progression. TNF-α treatment increased ICAM1 in human brain microvascular endothelial cells (HBMVECs) but decreased the neprilysin (NEP) protein level. Knock-down of ICAM1 using siRNA enhanced NEP, which increased the degradation of amyloid-ß. In the brains of 4-month-old AD transgenic mice (APPswe/PSEN1dE9), there were significantly higher levels of ICAM1 expression and amyloid deposits but lower levels of NEP and insulin-degrading enzymes (IDE), demonstrating an inverse correlation of ICAM1 with NEP and IDE expression. Further studies demonstrated significantly increased GFAP protein levels in the brain, specifically localized near blood vessels, of both TNF-α-injected and 4-month-old AD transgenic mice. Taken together, the induction of ICAM1 in endothelial cells suppresses NEP expression, accelerating the accumulation of amyloid-ß in blood vessels. It also enhances leukocyte adhesion to blood vessels stimulating the migration of leukocytes into the brain, subsequently triggering brain inflammation.

Associated Factors and Health Outcomes of Health Literacy and Physical Frailty Among Older Adults: A Systematic Review.

The current review aimed to systematically describe and synthesize health outcomes and factors associated with health literacy and physical frailty among older adults. Seven electronic databases were searched for observational studies published in English, from database inception to March 31, 2021. The study protocol was registered with PROSPERO. Two reviewers independently performed study selection, data extraction, and quality assessment using the Newcastle-Ottawa Scale. Among the 479 studies identified, nine (6,337 participants) met eligibility criteria. Common factors associated with health literacy and physical frailty were lower educational level, multiple comorbidities, and cognitive dysfunction. Health literacy was mainly associated with self-reported outcomes, whereas physical frailty was related to clinical outcomes. Prospective studies are required to identify the impact of limited health literacy, combined with frailty, on long-term health outcomes in older adults. Health literacy interventions should consider the older adult population with multiple comorbidities. [Research in Gerontological Nursing, 15(1), 39-52.].

Zearalenone Induces Endothelial Cell Apoptosis through Activation of a Cytosolic Ca2+/ERK1/2/p53/Caspase 3 Signaling Pathway.

Zearalenone (ZEN) is a mycotoxin that has been reported to damage various types of cells/tissues, yet its effects on endothelial cells (ECs) have never been investigated. Therefore, this study investigates the potential effects of ZEN using bovine aortic ECs (BAECs). In this study, we found that ZEN induced apoptosis of BAECs through increased cleavage of caspase 3 and poly ADP-ribose polymerase (PARP). ZEN also increased phosphorylation of ERK1/2 and p53, and treatment with the ERK1/2 or p53 inhibitor reversed ZEN-induced EC apoptosis. Transfection of BAECs with small interfering RNA against ERK1/2 or p53 revealed ERK1/2 as an upstream target of p53 in ZEN-stimulated apoptosis. ZEN increased the production of reactive oxygen species (ROS), yet treatment with the antioxidant did not prevent EC apoptosis. Similarly, blocking of estrogen receptors by specific inhibitors also did not prevent ZEN-induced apoptosis. Finally, chelation of cytosolic calcium (Ca2+) using BAPTA-AM or inhibition of endoplasmic reticulum (ER) Ca2+ channel using 2-APB reversed ZEN-induced EC apoptosis, but not by inhibiting ER stress using 4-PBA. Together, our findings demonstrate that ZEN induces EC apoptosis through an ERK1/2/p53/caspase 3 signaling pathway activated by Ca2+ release from the ER, and this pathway is independent of ROS production and estrogen receptor activation.

Prevalence and Associated Factors of Frailty and Mortality in Patients with End-Stage Renal Disease Undergoing Hemodialysis: A Systematic Review and Meta-Analysis.

Hemodialysis is the most common type of treatment for end-stage renal disease (ESRD). Frailty is associated with poor outcomes such as higher mortality. ESRD patients have a higher prevalence of frailty. This systematic review and meta-analysis aimed to identify the prevalence and associated factors of frailty and examine whether it is a predictor of mortality among ESRD patients undergoing hemodialysis. Five electronic databases including PubMed, Embase, CINAHL, Web of Science, and Cochrane Library were searched for relevant studies up to 30 November 2020. A total of 752 articles were found, and seven studies with 2604 participants in total were included in the final analysis. The pooled prevalence of frailty in patients with ESRD undergoing hemodialysis was 46% (95% Confidence interval (CI) 34.2-58.3%). Advanced age, female sex, and the presence of diabetes mellitus increased the risk of frailty in ESRD patients undergoing hemodialysis. Our main finding showed that patients with frailty had a greater risk of all-cause mortality compared with those without (hazard ratio (HR): 2.02, 95% CI: 1.65-2.48). To improve ESRD patient outcomes, healthcare professionals need to assess the frailty of older ESRD patients, particularly by considering gender and comorbidities. Comprehensive frailty screening tools for ESRD patients on hemodialysis need to be developed.

Nanostructured Fe2O3/TiO2 composite particles with enhanced NIR reflectance for application to LiDAR detectable cool pigments.

Nanostructured Fe2O3/TiO2 composite pigments with improved NIR reflectance were prepared by a homogeneous precipitation method using urea and NH4OH. The optical and morphological properties of the resulting pigment were investigated by varying the weight ratio of Fe2O3 to TiO2 and the calcination temperature. The resulting composite pigment has a nanostructure in which Fe2O3 nanoparticles of 20-30 nm size are well coated on the surface of TiO2 (∼100 nm) and the reflectance is greatly improved in the wavelength range of 620-1350 nm. The ratio of Fe2O3 to TiO2 and the calcination temperature were optimized to provide both high NIR reflectance and red color, which were 0.1 and 700 °C. As a result, compared with pure Fe2O3 (E g = 2.06 eV, a* = 22.6), the optimized Fe2O3/TiO2 composite pigment (E g = 2.09 eV, a* = 24.8) showed similar color properties and improved NIR reflectance by about 23.8%. In addition, the Fe2O3/TiO2 composite pigment showed about 62.7% larger reflectance at 905 nm than Fe2O3. According to a temperature rise test under IR illumination, the Fe2O3/TiO2 composite pigment was confirmed to have improved heat shielding properties. Therefore, the nanostructured Fe2O3/TiO2 powder could be potentially applied as a LiDAR detectable cool red pigment for autonomous vehicles.

Predictors of unplanned 30-day readmissions after coronary artery bypass graft: a systematic review and meta-analysis of cohort studies.

AIMS: Coronary artery bypass graft (CABG) is one of the most performed cardiac surgery globally. CABG is known to have a high rate of short-term readmissions. The 30-day unplanned readmission rate as a quality measure is associated with adverse health outcomes. This study aimed to identify and synthesize the perioperative risk factors for 30-day unplanned readmission after CABG. METHODS AND RESULTS: We systematically searched seven databases and reviewed studies to identify all eligible English articles published from 1 October 1999 to 30 September 2019. Random-effect models were employed to perform pooled analyses. Odds ratio and 95% confidence interval were used to estimate the risk factors for 30-day unplanned readmission. The 30-day hospital readmission rates after CABG ranged from 9.2% to 18.9% in 14 cohort studies. Among preoperative characteristics, older adults, female, weight loss, high serum creatinine, anticoagulant use or dialysis, and comorbidities were found to be statistically significant. Postoperative complications, prolonged length of hospital stay, and mechanical ventilation were revealed as the postoperative risk factors for 30-day unplanned readmission. However, intraoperative risk factors were not found to be significant in this review. CONCLUSION: Our findings emphasize the importance of a comprehensive assessment during the perioperative period of CABG. Healthcare professionals can perform a readmission risk stratification and develop strategies to reduce readmission rates after CABG using the risk factors identified in this review. Future studies with prospective cohort samples are needed to identify the personal or psychosocial factors influencing readmission after CABG, including perioperative risk factors.

Cyclooxygenase-2 induces neoplastic transformation by inhibiting p53-dependent oncogene-induced senescence.

Much in vivo evidence indicates that cyclooxygenase-2 (COX-2) is deeply involved in tumorigenesis. Although it has been proposed that COX-2-derived pro-inflammatory prostanoids mediate the tumorigenic activity of COX-2, the tumorigenic mechanisms of COX-2 are not yet fully understood. Here, we investigated the mechanism by which COX-2 causes transformation from normal cells to malignant cells by using normal murine or human cells. We found that COX-2 inhibits the pro-senescent function of p53 under oncogenic RAS activation, by which it prevents oncogene-induced senescence (OIS) and induces neoplastic transformation. We also found that COX-2 physically interacts with p53 in the nucleus under oncogenic RAS activation, and that this COX-2-p53 interaction rather than the catalytic activity is involved in the COX-2-mediated inhibition of the pro-senescent function of p53 and OIS, and induction of neoplastic transformation. These findings strongly suggest that the oncogenic property of COX-2 is closely related to its ability to inactivate p53 under strong mitogenic signals, and that aberrant activation of the COX-2/a mitogenic oncogene combination can be a potent driving force for tumorigenesis. This study might contribute to our understanding of the molecular basis for the tumorigenic activity of COX-2 and the development of novel anti-tumor drugs targeting COX-2-p53 interactions.

Far-infrared irradiation inhibits breast cancer cell proliferation independently of DNA damage through increased nuclear Ca2+/calmodulin binding modulated-activation of checkpoint kinase 2.

Far-infrared (FIR) irradiation is reported to inhibit cell proliferation in various types of cancer cells; the underlying mechanism, however, remains unclear. We explored the molecular mechanisms using MDA-MB-231 human breast cancer cells. FIR irradiation significantly inhibited cell proliferation and colony formation compared to hyperthermal stimulus, with no alteration in cell viability. No increase in DNA fragmentation or phosphorylation of DNA damage kinases including ataxia-telangiectasia mutated kinase, ataxia telangiectasia and Rad3-related kinase, and DNA-dependent protein kinase indicated no DNA damage. FIR irradiation increased the phosphorylation of checkpoint kinase 2 (Chk2) at Thr68 (p-Chk2-Thr68) but not that of checkpoint kinase 1 at Ser345. Increased nuclear p-Chk2-Thr68 and Ca2+/CaM accumulations were found in FIR-irradiated cells, as observed in confocal microscopic analyses and cell fractionation assays. In silico analysis predicted that Chk2 possesses a Ca2+/calmodulin (CaM) binding motif ahead of its kinase domain. Indeed, Chk2 physically interacted with CaM in the presence of Ca2+, with their binding markedly pronounced in FIR-irradiated cells. Pre-treatment with a Ca2+ chelator significantly reversed FIR irradiation-increased p-Chk2-Thr68 expression. In addition, a CaM antagonist or small interfering RNA-mediated knockdown of the CaM gene expression significantly attenuated FIR irradiation-increased p-Chk2-Thr68 expression. Finally, pre-treatment with a potent Chk2 inhibitor significantly reversed both FIR irradiation-stimulated p-Chk2-Thr68 expression and irradiation-repressed cell proliferation. In conclusion, our results demonstrate that FIR irradiation inhibited breast cancer cell proliferation, independently of DNA damage, by activating the Ca2+/CaM/Chk2 signaling pathway in the nucleus. These results demonstrate a novel Chk2 activation mechanism that functions irrespective of DNA damage.

Data resource profile: the Korea National Hospital Discharge In-depth Injury Survey.

The Korea National Hospital Discharge In-depth Injury Survey (KNHDIS), which was started in 2005, is a national probability survey of general hospitals in Korea with 100 or more beds conducted by the Korea Disease Control and Prevention Agency (KDCA). The KNHDIS captures approximately 9% of discharged cases from sampled hospitals using a 2-stage stratified cluster sampling scheme, among which 13% are injury related cases, defined as S00-T98 (injury, poisoning, and certain other consequences of external causes) using International Classification of Diseases, 10th revision codes. The KNHDIS collects information on characteristics of injury-related discharges in order to understand the scale of injuries, identify risk factors, and provide data supporting prevention policies and intervention strategies. The types of data captured include the hospitals' information, detailed clinical information, and injury-related codes such as the mechanism, activities undertaken when injured (sports, leisure activities, work, treatment, and education), external causes of the injury, and location of the occurrence of the injury based on the International Classification of External Causes of Injuries. Furthermore, the means of transportation, risk factors for suicide, and toxic substances are recoreded. Annual reports of the KNHDIS are publicly accessible to browse via the KDCA website (http://www.kdca.go.kr) and microdata are available free of charge upon request via email (kcdcinjury@korea.kr).

Effectiveness of Nurse-Led Heart Failure Self-Care Education on Health Outcomes of Heart Failure Patients: A Systematic Review and Meta-Analysis.

Poor self-care behaviors can lead to an increase in the risk of adverse health outcomes among patients with heart failure. Although a number of studies have investigated the effectiveness of nurse-led self-care education, the evidence regarding the effects of nurse-led intervention in heart failure remains uncertain. This study aimed to evaluate evidence on the effectiveness of nurse-led heart failure self-care education on health outcomes in patients with heart failure. To identify studies testing nurse-led education designed to improve self-care among heart failure patients, comprehensive search methods were used between January 2000 and October 2019 to systematically search six electronic databases: PubMed, CINAHL, Embase, Cochrane library, Web of Science, and SCOPUS. All the eligible study data elements were independently assessed and analyzed using random-effects meta-analysis methods. Of 612 studies, eight articles were eligible for this study. Nurse-led heart failure self-care education significantly reduced the risk of all-cause readmission (risk ratio (RR) = 0.75, 95% confidence interval (CI) = 0.66-0.85), heart failure specific readmission (RR = 0.60, 95% CI = 0.42-0.85), and all-cause mortality or readmission (RR = 0.71, 95% CI = 0.61-0.82). However, nurse-led heart failure self-care education was not associated with improvements in the quality of life and heart failure knowledge. Studies on the effectiveness of nurse-led heart failure self-care education mostly report only the positive effects on patients' health outcomes, whereas evidence of the effectiveness of the nurse-led approach is still limited. Therefore, high quality randomized controlled trials with detailed and explicit descriptions on the components of the interventions are needed.