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STUDY OBJECTIVES: Patients with sleep-disordered breathing have cyclic variation of heart rate (CVHR) in response to respiratory events. However, limited data are available regarding the utility of CVHR as a screening tool for sleep-disordered breathing in patients with mixed heart failure (HF) and those without HF. METHODS: We enrolled consecutive patients with and without HF who underwent full polysomnographies with simultaneous Holter electrocardiogram monitoring. We determined the temporal position of the individual dips comprising the CVHR score using time-domain methods. RESULTS: The data of 101 patients, including 70 with and 31 without HF, were analyzed. The CVHR score was significantly correlated with the apnea-hypopnea index (r = .667, P < .001) and limits of agreement between the apnea-hypopnea index and CVHR score were −21.8 to 35.2. The receiver operating characteristic analysis demonstrated that the CVHR score (best cut-off of 23.5 events/h) identified severe sleep-disordered breathing with a sensitivity of 83.3%, specificity of 79.5%, and the area under the curve of 0.856. In addition, there was no interaction between the presence or absence of HF and the apnea-hypopnea index–CVHR score relationship (P = .323). CONCLUSIONS: The CVHR score, determined by Holter electrocardiogram monitoring, is a useful tool for evaluating sleep-disordered breathing even in patients with mixed HF and patients without HF. CITATION: Yatsu S, Kasai T, Naito R, et al. Utility of cyclic variation of heart rate score as a screening tool for sleep-disordered breathing in patients with heart failure. J Clin Sleep Med. 2021;17(11):2187–2196.

(1) Background: When measuring anaerobic work threshold (AT), the conventional V-slope method includes the subjectivity of the examiner, which cannot be eliminated completely. Therefore, we implemented an engineering method using strucchange to objectively search for the inflection point of AT. (2) Methods: Seventeen subjects (15 men and 2 women) were included in the study. The subjects rode an ergometer and performed a ramp load test for 18 min and 30 s. (3) Results: In VE (Ventilation), 11 out of 12 subjects had the same results with 95% confidence intervals for the AT by the strucchange and respiratory metabolic apparatus. In VCO2 (Carbon dioxide emissions), 9 out of 12 subjects had the same results with 95% confidence intervals for the AT with the strucchange and respiratory metabolic apparatus. In VE, 3 out of 12 subjects showed the same results for respiratory metabolic analysis and the AT by the V-slope method. In VCO2, 3 out of 12 subjects showed the same results for the respiratory metabolic analysis and AT by the V-slope method in VCO2. (4) Conclusions: Strucchange was more objective and significant in identifying the AT than the V-slope method.

Cyclin-dependent kinase (CDK) 4 and CDK6 inhibitors are effective therapeutic options for hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer. Although CDK4/6 inhibitors mainly target the cyclin D-CDK4/6-retinoblastoma tumor suppressor protein (RB) axis, little is known about the clinical impact of inhibiting phosphorylation of other CDK4/6 target proteins. Here, we focused on other CDK4/6 targets, SMAD proteins. We showed that a CDK4/6 inhibitor palbociclib and activin-SMAD2 signaling cooperatively inhibited cell cycle progression of a luminal-type breast cancer cell line T47D. Palbociclib enhanced SMAD2 binding to the genome by inhibiting CDK4/6-mediated linker phosphorylation of the SMAD2 protein. We also showed that cyclin G2 plays essential roles in SMAD2-dependent cytostatic response. Moreover, comparison of the SMAD2 ChIP-seq data of T47D cells with those of Hs578T (triple-negative breast cancer cells) indicated that palbociclib augmented different SMAD2-mediated functions based on cell type, and enhanced SMAD2 binding to the target regions on the genome without affecting its binding pattern. In summary, palbociclib enhances the cytostatic effects of the activin-SMAD2 signaling pathway, whereas it possibly strengthens the tumor-promoting aspect in aggressive breast cancer.

This is the author’s version of the work. It is posted here by permission of the AAAS for personal use, not for redistribution. The definitive version was published in Science Signaling on 12 Nov 2019:Vol. 12, Issue 607, DOI: 10.1126/scisignal.aay4430, UTokyo FOCUS Articles "Gene causing rare heart and lung disease identified : Genomewide screening, animal studies used in long-term research on pulmonary arterial hypertension" https://www.u-tokyo.ac.jp/focus/en/articles/z0508_00081.html

Since objective biomarkers for major depressive disorder (MDD) are not readily available, clinical psychiatrists diagnose patients with MDD subjectively based on clinical interviews and diagnostic criteria. It often raises various concerns, including false responses by patients, subjective factors, and inexperience of the attendants leading to incorrect diagnosis. Here, we developed a self-monitoring system for simple and objective screening of MDD using a photoplethysmography (PPG) sensor and a 24-GHz microwave radar, which was based on the analysis of heart rate variability (HRV) during paced respiration and mental task conditions. In our previous study, we assessed the reactivity of HRV measurements during a mental task (random number generation) condition in patients with MDD and healthy control subjects. The HRV indices are less reactive in patients with MDD compared to healthy subjects during the mental task, which enabled us to identify the patients at risk for depression. In this study, the reactivity of HRV was measured not only in the mental task but also during paced respiration (i.e., 5-s inhalation and 5-s exhalation) conditions, thereby assessing more detailed autonomic nervous system (ANS) activity via HRV indices. To investigate the effect of paced respiration on MDD screening, we compared the ANS activity via HRV indices in with/without paced respiration conditions in 28 drug-naïve patients with MDD and 27 healthy control subjects. The result showed that ANS significantly activated during the paced respiration condition (p;0.05). The sensitivity in detecting patients with MDD was 86% under paced respiration and mental task conditions, which was higher than the sensitivity (68%) under mental task condition alone.

The Implicit Positive and Negative Affect Test (IPANAT) is an instrument for the indirect assessment of positive and negative affect. A Japanese version of the IPANAT was developed and its reliability and validity were examined. In Study 1, factor analysis identified two independent factors that could be interpreted as implicit positive and negative affect, which corresponded to the original version. The Japanese IPANAT also had sufficient internal consistency and acceptable test-retest reliability. In Study 2, we demonstrated that the Japanese IPANAT was associated with explicit state affect (e.g., PANAS), extraversion, and neuroticism, which indicated its adequate construct validity. In Study 3, we examined the extent to which the Japanese IPANAT was sensitive to changes in affect by assessing a set of IPANAT items after the presentation of positive, negative, or neutral photographs. The results indicated that the Japanese IPANAT was sufficiently sensitive to changes in affect resulting from affective stimuli. Taken together, these studies suggest that the Japanese version of the IPANAT is a useful instrument for the indirect assessment of positive and negative affect.

This research investigated how to overcome temptations and protect high-order goals while pursuing a goal. We hypothesized that in order to promote self-regulation, individuals non-cousciously engage in asymmetric evaluative responses to goal-relevant and temptation-relevant stimuli. In an experiment, we manipulated either diet goal or academic goal. Then, we measured evaluations of either sugary drinks (e.g., Coke, Fanta) or healthy drinks (e.g., Healthya Green Tea, Black Oolong Tea). The results showed that participants who activated a diet goal had significantly more positive evaluations of healthy drinks than sugary drinks. In addition, this tendency was moderated by the means of dieting (i.e., only participants who cut down on sweets when going on a diet). The role of non-consious asymmetric evaluations for self-regulation is discussed.

GH secretion is mainly regulated at the hypothalamus by a dual interplay between growth hormone releasing hormone (GHRH) and somatostatin, which are modulated by various factors. We examined the regulatory mechanism of GH secretion in an apparently healthy young man without decreased IGF-1 concentration and nocturnal GH secretion, but who showed low responses to insulin tolerance (ITT) and to GHRP-2 tests. The patient also had no GH response to acute aerobic exercise. However, he had normal secretion of pituitary hormone based on hypothalamic releasing hormone tests combined with CRH, GRH as GHRH, LH-RH and TRH. In addition, he had a GH response without paradoxical secretion to TRH stimulation as well as an ACTH response to subcutaneous glucagon stimulation, and AVP secretion responded to 5% hypertonic saline infusion, though it was not adequately stimulated by ITT. MRI showed no structural abnormalities in the hypothalamus-pituitary gland. These findings indicate that this subject may have an undiscovered neurocircuit for regulating GH secretion, as well as other neurohormones, to maintain homeostasis, even though there were low responses of the hormones to ITT and GHRP-2 stimuli, probably via altered secretion of hypothalamic hormones.