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.

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.].

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.

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.

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).

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.

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.

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.

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.

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.

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.

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.

Factors Associated with In-Hospital Mortality after Continuous Renal Replacement Therapy for Critically Ill Patients: A Systematic Review and Meta-Analysis.

Continuous renal replacement therapy (CRRT) is a broadly-accepted treatment for critically ill patients with acute kidney injury to optimize fluid and electrolyte management. Despite intensive dialysis care, there is a high mortality rate among these patients. There is uncertainty regarding the factors associated with in-hospital mortality among patients requiring CRRT. This review evaluates how various risk factors influence the in-hospital mortality of critically ill patients who require CRRT. Five databases were surveyed to gather relevant publications up to 30 June 2020. We identified 752 works, of which we retrieved 38 in full text. Finally, six cohort studies that evaluated 1190 patients were eligible. The in-hospital mortality rate in these studies ranged from 38.6 to 62.4%. Our meta-analysis results showed that older age, lower body mass index, higher APACHE II and SOFA scores, lower systolic and diastolic blood pressure, decreased serum creatinine level, and increased serum sodium level were significantly associated with increased in-hospital mortality in critically ill patients who received CRRT. These results suggest that there are multiple modifiable factors that influence the risk of in-hospital mortality in critically ill patients undergoing CRRT. Further, healthcare professionals should take more care when CRRT is performed on older adults.

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.

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.

Zearalenone-Induced Interaction between PXR and Sp1 Increases Binding of Sp1 to a Promoter Site of the eNOS, Decreasing Its Transcription and NO Production in BAECs.

Zearalenone (ZEN) is a non-steroidal mycotoxin that has various toxicological impacts on mammalian health. Here, we found that ZEN significantly affected the production of nitric oxide (NO) and the expression of endothelial NO synthase (eNOS) of bovine aortic endothelial cells (BAECs). A promoter analysis using 5'-serially deleted human eNOS promoter revealed that the proximal region (-135 to +22) was responsible for ZEN-mediated reduction of the human eNOS promoter activity. This effect was reversed by mutation of two specificity protein 1 (Sp1) binding elements in the human eNOS promoter. A chromatin immunoprecipitation assay revealed that ZEN increased Sp1 binding to the bovine eNOS promoter region (-113 to -12), which is homologous to -135 to +22 of the human eNOS promoter region. We also found that ZEN promoted the binding of the pregnane X receptor (PXR) to Sp1 of the bovine eNOS, consequently decreasing eNOS expression. This reduction of eNOS could have contributed to the decreased acetylcholine-induced vessel relaxation upon ZEN treatment in our ex vivo study using mouse aortas. In conclusion, our data demonstrate that ZEN decreases eNOS expression by enhancing the binding of PXR-Sp1 to the eNOS promoter, thereby decreasing NO production and potentially causing vessel dysfunction.

Activation of ATM/Akt/CREB/eNOS Signaling Axis by Aphidicolin Increases NO Production and Vessel Relaxation in Endothelial Cells and Rat Aortas.

Although DNA damage responses (DDRs) are reported to be involved in nitric oxide (NO) production in response to genotoxic stresses, the precise mechanism of DDR-mediated NO production has not been fully understood. Using a genotoxic agent aphidicolin, we investigated how DDRs regulate NO production in bovine aortic endothelial cells. Prolonged (over 24 h) treatment with aphidicolin increased NO production and endothelial NO synthase (eNOS) protein expression, which was accompanied by increased eNOS dimer/monomer ratio, tetrahydrobiopterin levels, and eNOS mRNA expression. A promoter assay using 5'-serially deleted eNOS promoters revealed that Tax-responsive element site, located at -962 to -873 of the eNOS promoter, was responsible for aphidicolin-stimulated eNOS gene expression. Aphidicolin increased CREB activity and ectopic expression of dominantnegative inhibitor of CREB, A-CREB, repressed the stimulatory effects of aphidicolin on eNOS gene expression and its promoter activity. Co-treatment with LY294002 decreased the aphidicolin-stimulated increase in p-CREB-Ser133 level, eNOS expression, and NO production. Furthermore, ectopic expression of dominant-negative Akt construct attenuated aphidicolin-stimulated NO production. Aphidicolin increased p-ATM-Ser1981 and the knockdown of ATM using siRNA attenuated all stimulatory effects of aphidicolin on p-Akt-Ser473, p-CREB-Ser133, eNOS expression, and NO production. Additionally, these stimulatory effects of aphidicolin were similarly observed in human umbilical vein endothelial cells. Lastly, aphidicolin increased acetylcholine-induced vessel relaxation in rat aortas, which was accompanied by increased p-ATM-Ser1981, p-Akt-Ser473, p-CREB-Ser133, and eNOS expression. In conclusion, our results demonstrate that in response to aphidicolin, activation of ATM/Akt/CREB/eNOS signaling cascade mediates increase of NO production and vessel relaxation in endothelial cells and rat aortas.

DNAJB9 Inhibits p53-Dependent Oncogene-Induced Senescence and Induces Cell Transformation.

DNAJB9 is known to be a member of the molecular chaperone gene family, whose cellular function has not yet been fully characterized. Here, we investigated the cellular function of DNAJB9 under strong mitogenic signals. We found that DNAJB9 inhibits p53-dependent oncogene-induced senescence (OIS) and induces neoplastic transformation under oncogenic RAS activation in mouse primary fibroblasts. In addition, we observed that DNAJB9 interacts physically with p53 under oncogenic RAS activation and that the p53-interacting region of DNAJB9 is critical for the inhibition of p53-dependent OIS and induction of neoplastic transformation by DNAJB9. These results suggest that DNAJB9 induces cell transformation under strong mitogenic signals, which is attributable to the inhibition of p53-dependent OIS by physical interactions with p53. This study might contribute to our understanding of the cellular function of DNAJB9 and the molecular basis of cell transformation.

Effectiveness of Mobile Phone-Based Interventions for Improving Health Outcomes in Patients with Chronic Heart Failure: A Systematic Review and Meta-Analysis.

Mobile phone-based interventions are increasingly used to prevent adverse health outcomes in heart failure patients. However, the effects of mobile phone-based interventions on the health outcomes of heart failure patients remain unclear. Our review aims to synthesize the randomized controlled trials (RCT) of mobile phone-based interventions for heart failure patients and identify the intervention features that are most effective. Electronic searches of RCTs published from January 2000 to July 2019 were conducted. Primary outcomes included all-cause mortality, readmission, emergency department visits, length of hospital stays, and quality of life. Secondary outcomes were self-care behaviors, including medication adherence and other clinical outcomes. A total of eight studies with varying methodological quality met the inclusion criteria and were analyzed. Voice call intervention was more frequently used compared with telemonitoring and short message services. Our meta-analysis showed that voice call interventions had significant effects on the length of hospital stays. However, no significant effects on all-cause mortality, readmission, emergency department visits, or quality of life were found. Compared to other mobile phone-based interventions, voice calls were more effective in reducing the length of hospital stay. Future studies are needed to identify which features of mobile phone-based intervention most effectively improve health outcomes.