HES1 potentiates high salt stress response as an enhancer of NFAT5-DNA binding.

High salt conditions and subsequent hyperosmolarity are injurious cellular stresses that can activate immune signaling. Nuclear factor of activated T-cells 5 (NFAT5) is an essential transcription factor that induces osmoprotective genes such as aldose reductase (AR) and betaine-GABA transporter 1 (BGT1). High salt stress-mediated NFAT5 activation is also reported to accelerate the inflammatory response and autoimmune diseases. However, the systemic regulation of NFAT5 remains unclear. Here, we performed a genome-wide siRNA screen to comprehensively identify the regulators of NFAT5. We monitored NFAT5 nuclear translocation and identified one of the Notch signaling effectors, Hairy and enhancer of split-1 (HES1), as a positive regulator of NFAT5. HES1 was induced by high salinity via ERK signaling and facilitated NFAT5 recruitment to its target promoter region, resulting in the proper induction of osmoprotective genes and cytoprotection under high salt stress. These findings suggest that, though HES1 is well known as a transcriptional repressor, it positively regulates NFAT5-dependent transcription in the context of a high salinity/hyperosmotic response.

Protocol for a multicentre, prospective observational cohort study in Japan: association among hospital-acquired disability, regular exercise and long-term care dependency in older patients after cardiac surgery.

INTRODUCTION: Cardiac surgery for older patients, postoperative functional decline and the need for long-term care have received increasing attention as essential outcomes in recent years. Therefore, prevention of functional decline and long-term care dependency after cardiac surgery are important; however, our current understanding of postoperative functional trajectory and effects of postoperative regular exercise on long-term functional decline and long-term care dependency is limited. Therefore, we will conduct a multicentre, prospective cohort study to (1) examine the effect of hospital-acquired disability on long-term functional decline and long-term care dependency and (2) investigate the favourable effect of postoperative regular exercise on long-term functional decline and long-term care dependency in older patients after cardiac surgery. METHODS AND ANALYSIS: We designed a prospective, multicentre cohort study to enrol older patients aged≥65 years undergoing elective coronary artery bypass graft or valve surgery. We will conduct medical record reviews to collect data on patient demographics, comorbidities, operative details, progression of in-hospital postoperative cardiac rehabilitation and functional trajectory from a few days before cardiac surgery to the day before hospital discharge. They will be followed up for 2 years to obtain information on their health status including functional status, regular exercise and clinical events by mail. Primary endpoints of this study are long-term functional decline and long-term care dependency after cardiac surgery. Secondary endpoints are readmission due to cardiac events or all-cause mortality. ETHICS AND DISSEMINATION: The study protocol was approved by the Ethics Committee of the Department of Physical Therapy, Faculty of Health Science, Juntendo University, and of each collaborating hospital. We obtained written informed consent from all study participants after the description of the study procedures. Publication of the study results is anticipated in 2025.

Clinical characteristics of functional recovery after coronary artery bypass graft surgery in Japanese octogenarians.

[Purpose] This study aimed to elucidate characteristics of postoperative physical functional recovery in octogenarians undergoing coronary artery bypass graft surgery. [Subjects and Methods] This was a multi-center, retrospective study. Nine hundred and twenty-seven elective isolated coronary artery bypass graft surgeries were evaluated (746 males and 181 females, mean age: 68.6 years, range: 31-86 years). Participants were stratified according to age < 80 years (n = 840; mean age, 67.1; range, 31-79) or > 80 years (n = 87; mean age, 82.2; range, 80-86). Patient characteristics and postoperative physical functional recovery outcomes were compared between groups. [Results] There was no significant difference between groups when considering the postoperative day at which patients could sit on the edge of the bed, stand at bedside, or walk around the bed. The postoperative day at which patients could walk 100 m independently was later in octogenarians, when compared with non-octogenarians (6.1 ± 3.2 days vs. 4.9 ± 3.9 days). In octogenarians, the percentage of patients who could walk 100 m independently within 8 days after surgery was 79.5%. [Conclusion] A postoperative target time in octogenarians for independent walking, following coronary artery bypass grafting, can be set at approximately 6 days.

[Determinants of prolonged mechanical ventilation after cardiac surgery].

PURPOSE: This study aimed to examine factors that delay weaning from ventilation after cardiac surgery. METHODS: A retrospective examination was made on 1,033 patients who had undergone cardiac surgery through a midsternal incision between January 2009 and July 2011. The items examined were duration of postoperative ventilation, patient's background, and other surgical information. If patients were weaned within 24 hours from intensive care unit (ICU) admission, they were included in the timely weaning group. If patients required 24 hours or more to be weaned, they were included in the delayed weaning group. RESULTS: There was a relationship between prolonged ventilation and the following factors: emergency surgery, history of arrhythmia, history of motor system disorder, preoperative estimated glomerular filtration rate (eGFR), preoperative New York Heart Association (NYHA) classification, preoperative left ventricular ejection fraction (LVEF), operative method, operative time, blood loss, intraoperative fluid management, and number of days from surgery until achievement of independent gait. The independent factors delaying extubation were emergency surgery, preoperative NYHA classification, preoperative LVEF, operative method, operative time, blood loss, and intraoperative fluid management(p<0.05). CONCLUSION: Surgical invasiveness and preoperative heart failure were involved in the prolonged ventilation after cardiac surgery.

Factors determining achievement of early postoperative cardiac rehabilitation goal in patients with or without preoperative kidney dysfunction undergoing isolated cardiac surgery.

BACKGROUND: The aim of this multicenter study was to evaluate the relationship between preoperative kidney function, postoperative acute kidney injury (AKI), and postoperative fluid balance (POFB) with the progress of early postoperative cardiac rehabilitation (CR) in patients undergoing isolated cardiac surgery. METHODS: Four hundred twenty three consecutive patients (137 females, 286 males, aged 66±13 years) who underwent various elective cardiac surgeries in the participating institutes were selected and divided into 5 groups depending on chronic kidney disease (CKD) stage. We evaluated the effects of CKD stage on the progress of early postoperative CR, and analyzed the factors determining the achievement of Japanese Circulation Society (JCS) early postoperative CR guidelines goal. RESULTS: Initiation of sitting (F=7.59, p<0.01) and standing (F=4.83, p<0.01), walking (F=4.40, p<0.01), and 100-m unassisted walk (F=13.09, p<0.01) were related with severity of preoperative CKD stage. The proportion of patients who could not achieve JCS early postoperative CR guideline goal was 15.0% in patients with CKD and 12.9% in patients without CKD. Multivariable analyses identified Risk, Injury, Failure, Loss, and End-stage Kidney (RIFLE) classification (of postoperative AKI) and blood urea nitrogen as factors determining achievement of early postoperative CR goal in patients with CKD; and POFB/preoperative body weight (PBW), RIFLE classification as determinants in patients without CKD. Using the receiver-operating characteristics curve analysis to predict achievement of the early postoperative CR goal, POFB/PBW 4.9% was identified as the cut-off value for achievement of the JCS early postoperative CR guideline goal. CONCLUSION: Preoperative CKD stage correlated significantly with the progress of early postoperative CR after cardiac surgery. Independent determinants of achieving JCS early postoperative CR guideline goal were postoperative AKI in patients with or without CKD, and POFB/PBW only in patients without CKD.