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Background: Sleep‐disordered breathing (SDB) is highly prevalent in individuals with Down syndrome (DS), who cease growing earlier than individuals without DS. These characteristics may be associated with increased obesity and subsequent SDB signs, such as snoring and apnoea or excessive daytime sleepiness (EDS). Thus, we assessed the influence of growth on the association between obesity and SDB signs or EDS; we used questionnaires sent to young individuals with DS and their caregivers, in a cross‐sectional study. Methods: We sent out 2000 questionnaires to individuals with DS and their caregivers. The surveys included questions about SDB signs (witnessed snoring or apnoea), subjective sleeping time including witnessed midnight arousal, the Epworth sleepiness scale and witnessed napping as well as sex, age, body weight and body height. Results: Of the 1222 questionnaires we received, 660 were from young individuals and were included in the analysis. SDB signs were highly prevalent (77.1%), and frequency of SDB signs increased with growth (P‐trend: P = 0.02) in individuals with DS. Multivariate analyses showed that EDS (Epworth sleepiness scale > 10 points) was associated with body mass index Z‐score (Z‐BMI) in the 6–9 years age group (odds ratio [OR] 95% confidence interval [95% CI]: 1.69 [1.09–2.62], P = 0.02). Conversely, SDB signs were associated with Z‐BMI in the 13–15 (OR [95% CI]: 1.99 [1.06–3.72], P = 0.03) and 16–18 years age groups (OR [95% CI]: 3.04 [1.22–7.59], P = 0.02). For the 19–21 years age group, SDB signs were associated with only male sex (OR [95% CI]: 7.28 [1.22–43.38], P = 0.03). Conclusions: This study showed that the association between Z‐BMI and SDB or EDS was age dependent. In early school‐age children with DS, high Z‐BMI could not accurately predict the presence of SDB, but it was associated with EDS. In the pubescent period (i.e. 13–18 years), high Z‐BMI was associated with SDB signs but not with EDS. Overall, obesity affected SDB signs and EDS differently based on age in young individuals with DS. [ABSTRACT FROM AUTHOR]

Although sex differences in clinical backgrounds of patients with obstructive sleep apnea (OSA) are well known, studies of sex differences about the influencing factors on adherence to continuous positive airway pressure (CPAP) are very sparse. Our aim was to investigate the effects of CPAP use affecting therapeutic adherence in sex differences. We retrospectively assessed demographic data, clinical characteristics, OSA-related symptoms, and effects and adherence of CPAP use in 348 patients (264 males, median age 58 years) who continued CPAP for at least 1 year. Poor adherence was defined as CPAP dropout within 1 year after starting CPAP or the average cumulative CPAP use less than four hours/night. We also studied the predictors or influencing factors of CPAP adherence by multivariate logistic regression analyses. Age was higher and the severity of OSA was lower in female patients. Although the adherence level itself was not significantly different between both sexes, influencing factors were different. OSA severity, such as apnea–hypopnea index and sleepiness, and many effects from CPAP use (respiratory difficulty, difficult adaptation to CPAP use, improved awakening, reduced nocturia, and easy adaptation to CPAP) influenced adherence only in men. Common factors of poor adherence in both sexes were lower age, insomnia by CPAP use, and improved daytime sleepiness. No other specific factors predicted poor adherence in women. We found that there were sex differences in influencing factors on CPAP adherence not only in clinical characteristics of OSA, but also in effectiveness and side effects of CPAP use. [ABSTRACT FROM AUTHOR]

Abtsract: Sleep-disordered breathing (SDB) is often accompanied with the chronic heart failure (CHF). Hypoxemia due to pulmonary congestion from CHF and concurrent SDB might synergistically impair endothelial function and worsen the prognosis. However, the main factors affecting deterioration of endothelial function are unknown and whether the influence of hypoxemia differs in SDB patients with and without CHF remains unclear. Fifty-three patients (CHF group, n = 23; non-CHF group, n = 30) underwent polysomnography to evaluate their SDB and flow-mediated vasodilation (FMD) measurements to assess arterial endothelial function. We examined the relationships between FMD and SDB-related parameters, including our original index of accumulated hypoxemia by SDB throughout one-night sleep: the time desaturation summation index (TDS), calculated as follows: (100% − averaged arterial oxygen saturation during sleep) × total sleep time. The mean age in the CHF and non-CHF groups was 59.0 ± 13.5 and 57.7 ± 11.4 years, respectively. Although the FMD in the 2 groups were not significantly different, well-known adverse factors for FMD such as serum lipid profiles, blood pressure levels, and conventional indices of SDB were worse in the non-CHF group. Only the TDS was not significantly different between 2 groups and associated with FMD as shown by the univariate analysis (CHF: p < 0.05, non-CHF: p < 0.01) and multivariate analysis (CHF: p < 0.05, non-CHF: p < 0.01). Accumulated hypoxemia (TDS) rather than the frequency of hypoxemia might more influence on the endothelial function irrespective of the cardiac state. Removal of accumulation of nocturnal hypoxemia might be a target for treatment equally in the patients with and without CHF. [ABSTRACT FROM AUTHOR]

Background. Thermal therapy has been used as adjuvant therapy in patients with cardiovascular disease. However, little is known about responses to thermal stress in older adults. We examined the effects of thermal stress in younger and older healthy Japanese individuals. Methods: The study included 12 young (mean age, 22 years) and 12 older (mean age, 68 years) healthy adults and was performed under strict temperature and humidity control to minimize confounding. Participants lay supine throughout three consecutive 30-minute phases: Phase I (heating at 70°C in a dome-shaped sauna), Phase II (insulation in the sauna), and Phase III (cool down). Physiological parameters and subjective thermal sensations were compared within and between two age groups. Results: Mean skin temperature increased significantly in both age groups (Phase I) and after the first 10 minutes was higher among older adults (by 6.8°C vs 6.0°C among younger; p < .01). Mean rectal temperature increased by 0.6°C in both groups (Phase II). Mean heart rate increased significantly in both age groups (Phase II) and was higher among younger adults (by 21.4 vs 11.3 beats/min among older adults; p < .05). Both systolic (by 15.1 mmHg) and diastolic (by 10.5 mmHg) blood pressure dropped significantly among older adults (Phase I), returning to baseline in Phase III; no changes were noted among those younger. There was no between-group difference in fluid loss or thermal sensations. Conclusions: Compared with younger adults, older adults are more likely to drop blood pressure in response to thermal stress but had similar fluid loss and subjective responses. [ABSTRACT FROM AUTHOR]

Introduction Obstructive sleep apnea (OSA) is common sleep disorder characterized by repetitive episodes of airway closure which usually occurs in the retropalatal region of the oropharynx. It has been known that upper airway mucosa in OSA patients is described as edematous, but not fully clarified. Objectives This study aimed to investigate and establish magnetic resonance imaging (MRI) parameter to estimate tissue water content at retropalatal level and its relationship with sleep parameters in OSA patients. Methods Forty-eight subjects with OSA underwent overnight polysomnography and cervical MRI with 1.5-tesla [mean (SD) age 55 (14) years and apnea-hypopnea index (AHI) 45.2 (26.1) events/hour, 79.2% male]. On the axial T2-weighted images from epipharynx to oropharynx, the signal intensities of masseter muscle and peripharyngeal mucosa [T2 mucous-to-masseter intensity ratio (T2MMIR)], was used as water content estimation in the retropalatal region. Partial correlation analysis was performed to examine the correlation between T2MMIR and polysomnography parameters. Results We found that there were strong and positive correlations between the T2MMIR and AHI ( r = 0.545, P < 0.05), supine AHI ( r = 0.553, P < 0.05) and REM AHI ( r = 0.640, P < 0.01) by partial correlation analysis. Besides, in patients with less efficient sleep who had more stage 1 sleep, significantly higher T2MMIR was noted ( r = 0.357, P < 0.05). Conclusions This study confirmed that peripharyngeal T2MMIR can be a simple parameter representing peripharyngeal tissue water contents related to severe OSA. [ABSTRACT FROM AUTHOR]

This study evaluated the prevalence of obstructive sleep apnea-related symptoms and assessed the relationship with obesity or unusual sleep postures in Down syndrome patients in Japan. We obtained the demographic characteristics, sleep postures, and obstructive sleep apnea-related symptoms experienced by 90 people as reported by their caregivers. Although 71% reported snoring and 59% arousals, obstructive sleep apnea-related symptoms were not significantly different between obese and non-obese participants. The youngest age group had the fewest obstructive sleep apnea-related symptoms, especially symptoms of snoring. The odds for arousal, nocturia, and apnea tended to be higher in the unusual sleep-postures group. Unusual sleep postures were most frequent in the group 6-15 years of age. People with Down syndrome might sleep in unusual postures to avoid upper airway obstruction caused by other anatomical factors. For nurses and other health professionals working in mainstream service, it is important to screen all persons with Down syndrome for symptoms suggestive of obstructive sleep apnea, particularly those six years of age and older, and to refer them for further evaluation for sleep disorders. [ABSTRACT FROM AUTHOR]

People with Down syndrome ( DS) are prone to develop sleep-disordered breathing ( SDB), especially obstructive sleep apnea ( OSA) and they are reported to sleep in unusual sleep postures. The purpose of this study was to determine the relationship between sleep postures and SDB parameters, including the objective nocturnal oxygen desaturation in people with DS in Japan. Overnight pulse oximetry was measured in 32 people with DS (male 44%, mean age 18 ± 10 years) and a questionnaire was completed to obtain information on sleep postures and OSA-related symptoms. Subjects were divided by their dominant sleep postures into three groups: usual postures (supine and lateral), prone, and unusual postures (leaning forward and sitting). Subjects who slept mainly in unusual postures were younger (9.6 ± 5.0 years) than those who slept in prone (18.6 ± 12.4 years) and in usual postures (21.1 ± 8.9 years) ( P < 0.05). Snoring was the most reported symptom (81.3%) and was the only symptom positively correlated with 4% oxygen desaturation index ( ODI) (r = 0.386, P < 0.05). There was no significant association between 4% ODI and sleep postures among the three groups. DS children with prone and unusual sleep postures had significantly better 4% ODI and minimum SpO2 level compared with those of usual postures ( P < 0.05). Our results indicated that prone and unusual sleep postures in DS children might be compensation to alleviate against SDB. These postures could be related to alleviation of SDB resulting from the immaturity of people with DS. [ABSTRACT FROM AUTHOR]

Introduction Recently, direct-acting oral anticoagulants (DOACs) have been introduced, with increasing use in patients with non-valvular atrial fibrillation (NVAF). However, warfarin continues to be widely used and the benefits and risks of warfarin in NVAF patients warrant closer inspection. Materials and Methods Thromboembolism, major hemorrhage, and total and cardiovascular mortalities were analyzed in 7,406 NVAF patients in the J-RHYTHM Registry from January to July 2009, prior to DOAC introduction. Propensity score matching analysis was performed to reduce the differences in clinical characteristics between non-anticoagulant (n = 1002) and warfarin (n = 6404) cohorts to reassess warfarin outcomes over 2 years. Results The incidence of thromboembolism was significantly greater in the non-anticoagulant cohort (3.0%) than in the warfarin cohort (1.5%, P < 0.001) with less frequent major hemorrhage in the non-anticoagulant cohort (0.8%) than in the warfarin cohort (2.1%, P = 0.009). Using propensity score matching, new subsets (n = 896 each) were obtained, with matching of the clinical characteristics between warfarin and non-anticoagulant subsets. The warfarin subset had lower risk factors compared with the total warfarin cohort. The incidence of thromboembolism was higher in the non-anticoagulant subset (2.9%) than in the warfarin subset (0.7%, P < 0.001). However, major hemorrhage was not significantly different between the two subsets. Conclusions Although warfarin was associated with a significantly higher incidence of hemorrhage in the unmatched cohorts, propensity score matching revealed that warfarin reduced thromboembolism without a significant increase in hemorrhage in the matched subsets with lower risks. Propensity score matching reduced selection bias and provided rational comparisons although it had indwelling limitations. [ABSTRACT FROM AUTHOR]

Background: Up to 80% of patients with rectal cancer undergo sphincter-saving surgery, and almost 90% of them experience subsequent physical changes. The number of studies on gender differences in response to this surgery has increased, and the connection between gender and symptoms and patient outcomes has generated increasing interest. Nevertheless, little is known about the gender differences in quality of life and cancer-related symptoms. We examined gender differences and quality of life changes over a 1-year period among patients with lower rectal cancer who were treated with sphincter-saving surgery. Methods: Patients (men = 42; women = 33) completed a self-administered questionnaire on their quality of life and related factors before surgery and 1, 6, and 12 months afterwards. The questionnaire was developed by the European Organization for Research and Treatment of Cancer (EORTC QLQ-C30/CR-38). Results: Scores on physical, role, and social functioning and global health status/quality of life decreased 1 month after surgery, improved after 6 months, and returned to baseline within 12 months, with the exception of social functioning in men. Factors related to quality of life changed after surgery and differed between men and women. Women's global health status/quality of life was affected by fatigue, weight loss, defecation problems, and future perspective, while that of men was affected by fatigue, weight loss, future perspective, and role functioning, which was affected by pain, defecation problems, and financial difficulties. Conclusions: Gender differences should be considered when predicting the quality of life of cancer patients undergoing surgery. Identifying gender differences will help health care providers anticipate the unique needs of patients undergoing surgery for rectal cancer. [ABSTRACT FROM AUTHOR]

Serial changes of electrocardiograms (ECG) could be used to assess their clinical features in atrial septal defects (ASD) after transcatheter closure together with other clinical parameters. We retrospectively studied 100 ASD patients who underwent transcatheter closure. Complications of persistent atrial fibrillation occurred in five ASD patients, and they were excluded. We divided the other 95 patients according to PQ intervals before closure (normal: < 200 ms, n = 51; prolonged: ≥ 200 ms, n = 44) to evaluate their clinical characteristics and parameters such as echocardiography, chest X-rays, and brain natriuretic protein (BNP) levels. Individuals in the prolonged PQ group were significantly older, had higher incidences of paroxysmal atrial fibrillation (PAF) and heart failure (HF) treated with more β-blockers and diuretics, and with a higher tendency of NYHA functional classification and BNP levels than the normal PQ group. The prolonged PQ group also had a significantly higher incidence of complete right bundle branch block, wider QRS intervals, and larger cardiothoracic ratios in chest X-rays accompanied by larger right atrial-areas and larger left atrial dimensions in echocardiograms. Furthermore, the prolonged PQ intervals with less PQ interval shortening after transcatheter closure revealed that the patients were the oldest at the time of closures and showed less structural normalization of the right heart and left atrium after ASD closure. PAF and HF also occurred more frequently in this subgroup. These results suggested that the ASD patients with prolonged PQ intervals with less PQ shortening were accompanied by more advanced clinical conditions. Together with other clinical parameters, detailed analyses of ECG and their changes after closure could elucidate the clinical characteristics and status of ASD patients with transcatheter closure and were useful for predicting structural normalization after transcatheter closure. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate differences in fat-free mass and thicknesses of various muscles among judo athletes of different performance levels. The subjects were 69 male judo athletes of 3 different performance levels. Group A was composed of athletes who participated in the Olympic Games or Asian Games (n = 13). Groups B(n = 21) and C (n = 35) were composed of judo athletes at a university who did or did not participate in intercollegiate competitions (including qualifying matches), respectively. Muscle and fat thicknesses were measured by B-mode ultrasound at 9 sites. Fat percentage was calculated from fat thicknesses using a previously reported equation. Fat-free mass was calculated from fat percentage and body weight. Muscles thicknesses were normalized to the height of the individual. Group A had significantly larger fat-free mass than Group C (p < 0.05). The normalized thicknesses of the elbow extensor and flexor muscles were significantly larger in Group A than in Group C. The normalized thickness of the elbow flexor muscle was significantly larger in Group A than in Group B. The results of this study showed that judo athletes with low performance levels such as those in Group C had lower fat-free mass, and the degree of development of the brachialis muscles differed according to performance level. [ABSTRACT FROM AUTHOR]

Aim: Nurses' skills and confidence in providing oral care to patients play important roles in healthcare. Studies have proved that peer‐to‐peer learning and assessment can help improve nurses' skills and confidence. However, no study has investigated it using an objective assessment checklist. This study investigated an oral hygiene practice training program for nursing students. It focused on their oral healthcare skills, confidence, and perspectives regarding implementing an objective structured clinical examination (OSCE). Methods: A pre‐ and post‐survey of 97 nursing students from a nursing school in Japan was conducted as a peer‐to‐peer oral health education training program that included an assessment and performance checklist. Results: Confidence in performing and assessing oral care significantly improved after attending the program. Furthermore, the changes were significantly greater in the developed program than in the training program without the checklist. The mean total assessment scores (0–25) of the first, second, third, and fourth participants in the four‐student groups were 22.1, 23.4, 23.9, and 24.1, respectively. The mean scores of the second, third, and fourth participant groups were significantly higher than that of the first participant group (p <.01). Fifty‐two positive and 58 negative comments were received regarding the implementation of the program with professional assessments and the checklist. The most common positive comment mentioned that the evaluation by professionals improved oral care learning and skills. Conclusions: This study developed a program to improve nursing students' confidence and oral care delivery skill building in an OSCE‐style delivery. [ABSTRACT FROM AUTHOR]

Background: Precise mapping of the Purkinje fiber network is essential in catheter ablation of Purkinje‐related ventricular arrhythmias (PrVAs). We sought to evaluate the mapping ability of a multi‐spline duodecapolar catheter (PentaRay) for PrVAs. Methods: Mappings of Purkinje fibers by PentaRay catheters were compared with those by conventional mapping catheters in consecutive patients undergoing catheter ablation of PrVAs from 2015 to 2022. Results: Sixteen PrVAs (7 premature ventricular contractions or non‐reentrant fascicular tachycardias [PVCs/NRFTs] and 9 fascicular ventricular tachycardias [FVTs]) were retrospectively studied. In PVCs/NRFTs, earliest preceding Purkinje potentials (PPs) could be recorded by the PentaRay catheters but not by the mapping and ablation catheters in 5 cases. At the earliest PP sites, the precedence from the QRS onset was greater, and the amplitude of the preceding potentials was higher in the PentaRay catheter compared with those in the mapping and ablation catheter (−62.0 ± 42.8 vs. −29.4 ± 34.2 ms, P = 0.02; 0.45 ± 0.43 vs. 0.09 ± 0.08 mV, P = 0.02). In FVTs, late diastolic potentials (P1) were recorded by the PentaRay catheters but not by the mapping and ablation catheters or the linear duodecapolar catheter in 2 cases. The amplitude of P1 was higher in the PentaRay catheter compared with that in the linear duodecapolar catheter and the mapping and ablation catheters (0.72 ± 0.49 vs. 0.17 ± 0.18 vs. 0.27 ± 0.21 mV, P = 0.0006, P = 0.002). The localized critical PPs, defined as the earliest preceding potentials in PVCs/NRFTs and P1 in FVTs, could be recorded in all the patients by the PentaRay catheter. The mapping ability of critical PPs of PrVAs was better with the PentaRay catheter than with the conventional mapping catheters (16/16 vs. 9/16, P = 0.004 by McNemar exact test). Conclusions: The PentaRay catheter has clinical advantages in mapping of the Purkinje fiber network to reveal critical PPs as ablation targets of PrVAs. [ABSTRACT FROM AUTHOR]

Azacitidine (AZA) and venetoclax (VEN) were initiated as salvage chemotherapy [[3]]. The 5-day AZA (75 mg/m SP 2 sp ) and daily 200 mg/day of VEN (21-day administration with 28-day interval) were feasibly continued (only the ninth cycle of AZA and VEN was delayed because of persistent neutropenia). The patient was successfully treated with AZA and VEN for relapsed and refractory (R/R) AML, even if the patient received hemodialysis for end-stage CKD. [Extracted from the article]

Introduction: Obstructive sleep apnea (OSA) is a common sleep disorder characterized by repetitive episodes of airway closure which usually occur in the retro-palatal region of the oropharynx. It has been known that upper airway mucosa in OSA patients is described as edematous. Recurrent injuries owing to vibration of the upper airway tissues or repetitive negative pressure may contribute to this phenomenon. On the other hand, fluid redistribution from the lower to the upper body during nocturnal recumbency could shift the fluid into neck and tissue around airway. The combination of these might contribute the occurrence or worsening of OSA by compressing the airway. Therefore, this study aims to investigate and establish simple magnetic resonance imaging (MRI) parameters, namely T2 mucous-to- masseter intensity ratio (T2MMIR), to assess the degree of tissue water content at the retro-palatal level and its relationship with sleep parameters in OSA patients. Materials and methods: Twenty-seven subjects with OSA underwent polysomnography and cervical MRI with 1.5-tesla during wakefulness (age 55.0±16.5 y, 77.8% male, with apnea-hypopnea index (AHI) 54.1±27.6 and a body mass index (BMI) 29.4± 5.5) were included. On the axial T2-weighted images from the epipharynx to the oropharynx, the signal intensities for masseter muscle and peripharyngeal mucosa were measured. T2 mucous-to-masseter intensity ratio was calculated, and was used as an estimate of water content in the retro-palatal region. Pearson correlation analysis was performed to examine the correlation between peripharyngeal T2MMIR and polysomnography parameters. Results: T2 mucous-to-masseter intensity ratio had moderate, positive correlation with supine AHI (r =0.388, P <0.05), AHI (r =0.408, P <0.05), arousal index (r =0.411, P <0.05), and stage 1 sleep (r =0.419, P <0.05). Strong, positive correlation in the T2MMIR and REM AHI was also noted (r =0.645, P <0.001). Meanwhile, mean oxygen saturation had moderate, negative correlation with T2MMIR (r =−0.401, P <0.05). Conclusion: This is the first report to establish peripharyngeal T2MMIR as one simple parameter representing peripharyngeal mucosal water contents due to inflammatory edema and/or fluid redistribution during recumbency, related to severity of OSA. This finding suggested its potential usefulness in reevaluation of change of peripharyngeal mucosa after OSA treatment to confirm its success. [Copyright &y& Elsevier]

Sleep quality is often impaired in patients with chronic heart failure (HF), which may worsen their quality of life and even prognosis. Leg thermal therapy (LTT), topical leg warming, has been shown to improve endothelial function, oxidative stress, and cardiac function in patients with HF. However, its short-term influence to sleep quality has not been evaluated in HF patients. Eighteen of 23 patients with stable HF received LTT (15 min of warming at 45 °C and 30 min of insulation) at bedtime for 3 consecutive nights and 5 patients served as control. Subjective sleep quality was evaluated by St. Mary's Hospital Sleep Questionnaire, Oguri-Shirakawa-Azumi Sleep Inventory, and Epworth sleepiness scale, and also objectively evaluated by polysomnography. LTT significantly improved subjective sleep quality indicated by depth of sleep ( p < 0.01), sleep duration ( p < 0.05), number of awaking ( p < 0.01), nap duration ( p < 0.01), sleep quality ( p < 0.05), and sleep satisfaction ( p < 0.05). It was also objectively affirmed by a slight but significant decrease of sleep stage N1 ( p < 0.01), and increase in sleep stage N2 ( p < 0.05). No significant changes occurred in the controls. Hence, the short-term LTT could improve subjective and objective sleep quality in patients with HF. LTT can be a complimentary therapy to improve sleep quality in these patients. [ABSTRACT FROM AUTHOR]

Purpose: This study evaluated the reliability, validity, and responsiveness of the Japanese version of the European Organization for Research and Treatment of Cancer (EORTC) QLQ-ELD14 and measured the health-related quality of life (HRQOL) of elderly Japanese patients with cancer aged ≥ 60 and ≥ 70 years. Methods: The study recruited elderly Japanese patients with cancer aged ≥ 60 (≥ 70) years (n = 1803 [n = 1236]). The EORTC QLQ-ELD14 was evaluated for reliability, validity, responsiveness, and correlations of changes in score between the EORTC QLQ-ELD14 and the EORTC QLQ-C30 before and after the commencement of the COVID-19 pandemic. Results: In both age groups, the proportion of missing items was low (< 3%). Cronbach's α was good at ≥ 0.70, except for two of the seven items. All the intraclass coefficient constants were good at ≥ 0.70. The concurrent validity was good but correlation with the EORTC QLQ-C30 was not strong, except for the hypothesis items. Regarding the assessment of responsiveness, only one item ("maintaining purpose") of the EORTC QLQ-ELD14 worsened (− 6.14 ± 29.20, standard response of mean > 0.2) after the commencement of the COVID-19 pandemic. The changes in score between the EORTC QLQ-ELD14 and the "global health status/QOL" and "summary score" of the EORTC QLQ-C30 had moderate-to-high negative correlations for all items, except two. Hypotheses to evaluate construct validity were accepted at 90%, while responsiveness was accepted at 80%. Conclusion: The Japanese version of the EORTC QLQ-ELD14 questionnaire appears to have acceptable reliability, validity, and responsiveness to evaluate HRQOL in elderly Japanese people with cancer. [ABSTRACT FROM AUTHOR]

Progressive multifocal leukoencephalopathy (PML) is a rare neurological disease caused by the reactivation of latent John Cunningham polyomavirus. Hematological disorders associated with immunomodulatory monoclonal antibodies and hematopoietic stem cell transplantation (HSCT) are risk factors for PML. Blinatumomab is a novel antileukemic immunomodulatory agent and more effective for relapsed and refractory acute lymphoblastic leukemia (ALL) than conventional chemotherapy. But, blinatumomab suppresses humoral immunity due to long-lasting B-cell depletion during and after the treatment. The development of PML involves cellular immunity and impairment of humoral immunity. Although few cases of blinatumomab-related PML have been reported, the use of blinatumomab after allogeneic HSCT may increase the risk of developing PML. The current case report presents a patient of Philadelphia chromosome-positive ALL wherein PML developed after cord blood stem cell transplantation and administrating blinatumomab. [ABSTRACT FROM AUTHOR]

Many previous clinical studies have suggested that atrial fibrillation (AF) is closely associated with hypertension. However, the benefits of antihypertensive therapy on AF are still inconsistent, and it is necessary to explore the factors augmenting AF in hypertensive rats. The aim of the present study was to investigate the correlation between arterial pressure or voltage stimulus and to the duration of electrically induced AF in normotensive or hypertensive rats. Methods. AF was reproducibly induced by transesophageal atrial burst pacing in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). We did the burst pacing at high (20 V) or low (5 V) voltage. Results. Duration of AF did not correlate with systolic blood pressure (SBP) and stimulus voltage in WKY. However, only in SHR, duration of AF with high stimulus voltage significantly correlated with SBP and was significantly longer in high than in low voltage stimulus. Discussion and Conclusion. Duration of AF is augmented by high voltage stimulus with higher blood pressure in SHR. [ABSTRACT FROM AUTHOR]

Many previous clinical studies have suggested that atrial fibrillation (AF) is closely associated with hypertension. However, the benefits of antihypertensive therapy on AF are still inconsistent, and it is necessary to explore the factors augmenting AF in hypertensive rats. The aim of the present study was to investigate the correlation between arterial pressure or voltage stimulus and to the duration of electrically induced AF in normotensive or hypertensive rats. Methods. AF was reproducibly induced by transesophageal atrial burst pacing in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). We did the burst pacing at high (20 V) or low (5 V) voltage. Results. Duration of AF did not correlate with systolic blood pressure (SBP) and stimulus voltage in WKY. However, only in SHR, duration of AF with high stimulus voltage significantly correlated with SBP and was significantly longer in high than in low voltage stimulus. Discussion and Conclusion. Duration of AF is augmented by high voltage stimulus with higher blood pressure in SHR. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To examine the manner in which cardiac function affects the magnitude and timing of aortic contrast enhancement during coronary CT angiography (CTA). Materials and methods: Twenty-nine patients (21 men, 8 women; mean age, 64.4±13.4 years; mean weight, 59.4±10.3kg) underwent measurement of cardiac output within 2 weeks of coronary CTA. The cardiac output of each patient was measured by the thermodilution technique and the cardiac index was calculated from the body surface area. During coronary CTA, attenuation of the descending aorta was measured at the workstation every 3s. The aortic peak time (APT) and aortic peak enhancement (APE) of each patient were calculated. Pearson''s correlation coefficient analysis was used to investigate the relationships between the cardiac output or cardiac index and APT or APE. Furthermore, the relationship between patient factors or parameters on test bolus injection and APT or APE was also evaluated. Results: The range of cardiac output, cardiac index, APT, and APE was 1.55–10.46L/min (mean: 4.77±2.13), 1.11–5.30L/(min-m2) (mean: 3.28±1.08), 25–51s (mean: 38.3±7.5), and 273.1–598.1HU (mean: 390.4±72.1), respectively. With an increase in the cardiac index, both APT (r =−0.698, p <0.0001) and APE (r =−0.573, p =0.0009) decreased. There were significant correlations between the patient body weight and APT and APE with the test bolus injection, and with APT and APE during coronary CTA. Conclusion: The APT and APE during coronary CTA are closely related to cardiac function. [Copyright &y& Elsevier]

Background: Pulmonary vein isolation (PVI) is an established ablation procedure for atrial fibrillation (AF), however, PVI alone is insufficient to suppress AF recurrence. Non-pulmonary vein (non-PV) trigger ablation is one of the promising strategies beyond PVI and has been shown to be effective in refractory/persistent AF cases. To make non-PV trigger ablation more standardized, it is essential to develop a simple method to localize the origin of non-PV triggers. Methods: We retrospectively analyzed 37 non-PV triggers in 751 ablation sessions for symptomatic AF from January 2017 to December 2020. Regarding non-PV triggers, intra-atrial activation interval from the earliest in right atrium (RA) to proximal coronary sinus (CS) (RA-CSp) and that from the earliest in RA to distal CS (RA-CSd) obtained by a basically-positioned duodecapolar RA-CS catheter were compared among 3 originating non-PV areas [RA, atrial septum (SEP) and left atrium (LA)]. Results: RA-CSp of RA non-PV trigger (56.4 ± 23.4 ms) was significantly longer than that of SEP non-PV (14.8 ± 25.6 ms, p = 0.019) and LA non-PV (-24.9 ± 27.9 ms, p = 0.0004). RA-CSd of RA non-PV (75.9 ± 32.1 ms) was significantly longer than that of SEP non-PV (34.2 ± 32.6 ms, p = 0.040) and LA non-PV (-13.3 ± 41.2 ms, p = 0.0008). RA-CSp and RA-CSd of SEP non-PV were significantly longer than those of LA non-PV (p = 0.022 and p = 0.016, respectively). Sensitivity and specificity of an algorithm to differentiate the area of non-PV trigger using RA-CSp (cut-off value: 50 ms) and RA-CSd (cut-off value: 0 ms) were 88% and 97% for RA non-PV, 81% and 73% for SEP non-PV, 65% and 95% for LA non-PV, respectively. Conclusions: The analysis of intra-atrial activation sequences was useful to differentiate non-PV trigger areas. A simple algorithm to localize the area of non-PV trigger would be helpful to identify non-PV trigger sites in AF ablation. [ABSTRACT FROM AUTHOR]

Introduction: Ectopic beats originating from the pulmonary vein (PV) trigger atrial fibrillation (AF). The purpose of this study was to clarify the electrophysiological determinant of AF initiation from the PVs. Methods: Pacing studies were performed with a single extra stimulus mimicking an ectopic beat in the left superior PVs (LSPVs) in 62 patients undergoing AF ablation. Inducibility of AF, effective refractory period (ERP), and conduction properties within the PVs were analyzed. Results: A single extra stimulus in LSPV induced AF in 20 patients (32% of all patients) at the mean coupling interval (CI) of 172 ms. A CI‐dependent anisotropic conduction at the AF onset was visualized in a three‐dimensional mapping. Onset of AF was site‐specific with reproducibility in each individual. Mean ERP in LSPV in the AF‐inducible group was shorter than that in the AF‐noninducible group (182 ± 55 vs. 254 ± 51 ms, p <.0001). LSPV ERP dispersion was greater in the AF‐inducible group than in the AF‐noninducible group (45 ± 28 vs. 27 ± 19 ms, p <.01). Circumferential intra‐PV conduction time (IPVCT) exhibited decremental properties in response to shortening of CI and the prolongation of IPVCT in the AF‐inducible site was greater than that in the AF‐noninducible site (p <.05) in each individual. Conclusions: Location and CI of an ectopic excitation ultimately determine the initiation of AF from the PVs. ERP dispersion and circumferential conduction delay may lead to anisotropic conduction and reentry within the PVs that initiate AF. [ABSTRACT FROM AUTHOR]

The G protein-coupled receptor GPRC6A regulates various physiological processes in response to its interaction with multiple ligands, such as extracellular basic amino acids, divalent cations, testosterone, and the uncarboxylated form of osteocalcin (GluOC). Global ablation of GPRC6A increases the susceptibility of mice to diet-induced obesity and related metabolic disorders. However, given that GPRC6A is expressed in many tissues and responds to a variety of hormonal and nutritional signals, the cellular and molecular mechanisms underlying the development of metabolic disorders in conventional knockout mice have remained unclear. On the basis of our previous observation that long-term oral administration of GluOC markedly reduced adipocyte size and improved glucose tolerance in WT mice, we examined whether GPRC6A signaling in adipose tissue might be responsible for prevention of metabolic disorders. We thus generated adipocyte-specific GPRC6A knockout mice, and we found that these animals manifested increased adipose tissue weight, adipocyte hypertrophy, and adipose tissue inflammation when fed a high-fat and high-sucrose diet compared with control mice. These effects were associated with reduced lipolytic activity because of downregulation of lipolytic enzymes such as adipose triglyceride lipase and hormone-sensitive lipase in adipose tissue of the conditional knockout mice. Given that, among GPR6CA ligands tested, GluOC and ornithine increased the expression of adipose triglyceride lipase in cultured 3T3-L1 adipocytes in a manner dependent on GPRC6A, our results suggest that the constitutive activation of GPRC6A signaling in adipocytes by GluOC or ornithine plays a key role in adipose lipid handling and the prevention of obesity and related metabolic disorders. [ABSTRACT FROM AUTHOR]

Bone invasion is a critical factor in determining the prognosis of oral squamous cell carcinoma (OSCC) patients. Transforming growth factor β (TGF-β) is abundantly expressed in the bone matrix and is involved in the acquisition of aggressiveness by tumors. TGF-β is also important to cytoskeletal changes during tumor progression. In this study, we examined the relationship between TGF-β signaling and cytoskeletal changes during bone invasion by OSCC. Immunohistochemical staining of OSCC samples from five patients showed the expression of p130Cas (Crk-associated substrate) in the cytoplasm and phosphorylated Smad3 expression in the nucleus in OSCC cells. TGF-β1 induced the phosphorylation of Smad3 and p130Cas, as well as epithelial–mesenchymal transition (EMT) accompanied by the downregulation of the expression of E-cadherin, a marker of epithelial cells, and the upregulation of the expression of N-cadherin, or Snail, a marker of mesenchymal cells, in human HSC-2 cells and mouse squamous cell carcinome VII (SCCVII) cells. SB431542, a specific inhibitor of Smad2/3 signaling, abrogated the TGF-β1-induced phosphorylation of p130Cas and morphological changes. Silencing p130Cas using an short hairpin RNA (shRNA) or small interfering RNA in SCCVII cells suppressed TGF-β1-induced cell migration, invasion, EMT and matrix metalloproteinase-9 (MMP-9) production. Compared with control SCCVII cells, SCCVII cells with silenced p130Cas strongly suppressed zygomatic and mandibular destruction in vivo by reducing the number of osteoclasts, cell proliferation and MMP-9 production. Taken together, these results showed that the expression of TGF-β/p130Cas might be a new target for the treatment of OSCC bone invasion. [ABSTRACT FROM AUTHOR]

The purposes of this study were: (1) to confirm the prevalence of sleep-disordered breathing (SDB) in Japanese children using nocturnal pulse oximetry (NPOx) as a screening tool and (2) to examine what kind of parameters are suitable for the evaluation of SDB in children. We conducted a study of 99 children between 4 and 15-year-old and obtained their demographic characteristics and the presence of SDB-related symptoms by questionnaire from their parents. In our study, 36% had been Down syndrome (DS), 25% had cardiovascular disease and 34% had dental/oral abnormality. As SDB-related symptoms, snoring (35%), awake disturbance (48%), arousal (41%) and nocturia (19%) were reported. We analyzed each parameter based on the previous reported data of children and temporary defined normal range as follows; 3%ODI < 2.04, 4%ODI < 0.78, SpO2 nadir > 89% and McGill oximetry score = 1. In non-DS group, each parameter showed abnormal value especially in younger group (abnormality; 61–94%), but the abnormality was decreased during the growth (abnormality; 11–63%). Interestingly, in DS group the value of each parameter was kept on abnormal during the growth (abnormality; 55–100%). We investigated the correlation between McGill oximetry score and ODI or SpO2 nadir. There was a significant positive correlation between McGill oximetry score and 3% or 4% ODI. Moreover, there was a significant negative correlation between McGill oximetry score and SpO2 nadir. Based on NPOx screening, prevalence of SDB was high; however, it was decreased during the growth in non-DS group. Each parameter might be useful for SDB screening in children. [ABSTRACT FROM AUTHOR]

Highlights • We examined rectal cancer patients' health-related quality of life (HR-QOL) by age. • No pre-operative HR-QOL differences in were found in patients. • Patients aged <60 had lower role functioning at 1 month post-operation. • Patients aged ≥60 had worse global health status/QOL and cognitive functioning 1 month post-operation. • Age influenced the specific factors affecting HR-QOL. Abstract Purpose To examine age-related factors influencing health-related quality of life (HR-QOL) among patients with lower rectal cancer during the 12-month period after sphincter-saving surgery (SSS). Material and methods In this 1-year longitudinal study, 137 patients (120 patients completed, and 82 aged ≥60 years) answered the European Organization for Research and Treatment of Cancer questionnaire (EORTC-C30/CR38) assessing their HR-QOL and related factors during the 12 months after SSS. Results No significant differences in HR-QOL were found before surgery. Only among those aged ≥60 years, global health status/QOL and cognitive functioning showed a significant decrease one month after surgery. At one month after SSS, the role functioning of groups <60 years old (which is negatively related to defecation problems, insomnia, and financial difficulties) was lower compared to those aged ≥60 years; and role functioning was significantly related to global health status/QOL. Six months after SSS, the global health status/QOL had recovered. In both groups, global health status/QOL was related to role and social functioning. Among participants aged <60 years, global health status/QOL was significantly related to emotional functioning, which is related to future perspective. Among participants aged ≥60 years only, global health status/QOL was significantly related to cognitive functioning; pain, financial difficulties, and defecation problems negatively influenced HR-QOL. Symptoms specific after SSS: defecation problems (in both group), micturition problems (only ≥60 years), and sexual problems (only<60 years) influenced HR-QOL. Conclusion Health care providers should assess the influence of age-related factors during the early post-operative period after SSS to improve HR-QOL. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: The severity of obstructive sleep apnea (OSA) is assessed by the apnea–hypopnea index (AHI) determined from polysomnography (PSG). However, PSG requires a specialized facility with well‐trained specialists and takes overnight. Therefore, simple tools, which could distinguish severe OSA, have been needed before performing PSG. Objectives: We propose the new index using cine‐MRI as a screening test to differentiate severe OSA patients, who would need PSG and proper treatment. Methods: Thirty‐six patients with suspected OSA (mean age 54.6 y, mean AHI 52.6 events/h, 33 males) underwent airway cine‐MRI at the fourth cervical vertebra level during 30 s of free breathing and PSG. The minimum airway ellipticity (AE) in 30 s duration was measured, and was defined as the severity of OSA. Patients were divided into severe OSA, not‐severe OSA, and normal groups, according to PSG results. The comparison of AE between any two of the three groups was performed by Wilcoxon rank‐sum test. Receiver operating characteristic (ROC) curve analysis was performed to determine the optimal cut‐off of AE for identifying severe OSA patients. Results: The minimum AE for severe OSA was significantly lower than that for not‐severe OSA and normal (severe, 0.17 ± 0.16; not severe, 0.31 ± 0.17; normal, 0.38 ± 0.19, P < .05). ROC analysis revealed that the optimal cutoff of the minimum AE 0.21 identified severe OSA patients, with an area under the curve of 0.75, 68% sensitivity, and 83% specificity. Conclusion: AE is a feasible quantitative index, and a promising screening test for detecting severe OSA patients. [ABSTRACT FROM AUTHOR]

We examined the effects of adjuvant chemotherapy on the health-related quality of life (HRQOL) of lower rectal cancer patients receiving sphincter-saving surgery (SSS). In all, 109 patients completed a questionnaire before surgery and 1, 6, and 12 months afterwards. In the chemotherapy group, physical and social functioning scores were significantly lower 12 months after surgery compared with the nonchemotherapy group. These effects of adjuvant chemotherapy suggest that a different clinical approach might more effectively improve physical and social functioning in lower-rectal cancer patients undergoing chemotherapy. Healthcare providers should be alert for adverse events in patients with lower-rectal cancer and promptly address such conditions. [ABSTRACT FROM PUBLISHER]

This longitudinal descriptive study examined whether rectal cancer patients report changes in health-related quality of life ( HRQOL) over a 6-month period after different types of sphincter-saving surgery ( SSS): intersphincteric resection ( ISR), ultra-low anterior resection ( ULAR) and low anterior resection ( LAR). It also compares HRQOL among the three groups of patients. Seventy-three patients from two hospitals in Japan completed questionnaires on HRQOL and defecation symptoms immediately before surgery and 1 and 6 months afterwards. Results showed that ISR patients had significantly worse HRQOL scores than ULAR and LAR patients and more defecation symptoms that persisted during the 6 months post- SSS. Thus, patients undergoing ISR require psychological and social support, including skills in competent self-management, during the early post-operative period. Furthermore, defecation problems substantially influence HRQOL. The first month post- SSS is particularly challenging. The assumption that HRQOL is better after SSS compared to living with a permanent stoma might not be valid. [ABSTRACT FROM AUTHOR]

Background People with Down syndrome (DS) often have sleep-disordered breathing (SDB). Unusual sleep postures, such as leaning forward and sitting, are observed in people with DS. This study aimed to clarify the prevalence of unusual sleep postures and their relationships with SDB-related symptoms (SDB-RSs), such as snoring, witnessed apnoea, nocturnal awakening and excessive daytime sleepiness. Methods A questionnaire, including demographic characteristics and the presence of unusual sleep postures, as well as SDB-RSs, was completed by 1149 parents of people with DS from Japan. Results Unusual sleep postures were recorded in 483 (42.0%) people with DS. These participants were significantly younger and had a history of low muscle tone more frequently than people without unusual sleep postures. In all ages, the leaning forward posture was more frequent than sitting. People with DS with unusual sleep postures suffered from SDB-RSs. Those who slept in the sitting posture had more frequent SDB-RSs than did those who slept with the leaning forward posture. Snoring, witnessed apnoea and nocturnal awakening were observed in 73.6, 27.2 and 58.2% of participants, respectively. Snoring increased with aging. Witnessed apnoea was more common in males and in those with hypothyroidism than in females and in those without hypothyroidism. Conclusions Our study shows that there is a close relationship between unusual sleep postures and SDB-RSs. We recommend that all people with DS with unusual sleep postures should be checked for the presence of SDB. [ABSTRACT FROM AUTHOR]

Purpose:Hyperthermia (HT), an adjuvant therapy for variable cancers, may cause physiological changes in the patients, which may lead to cardiovascular problems. Among various HT treatments, the physiological effects of deep regional HT are still unclear. We examined the physiological alterations throughout deep regional HT to improve the HT safety. Materials and methods:Thirty-one patients (age: 61 ± 12 years) with cancer received HT in the thoracic or upper abdominal regions using an 8-MHz radiofrequency-capacitive-device for 50 min. Rectal temperature (Trec), systolic and diastolic blood pressures (SBP and DBP), pulse rate (PR), respiratory rate (RR), percutaneous oxygen saturation (SpO2) and sweating volume were evaluated throughout HT. Results:At 50 min after starting HT,Trec, PR and RR were significantly increased compared with the baseline values (Trec: 38.2 ± 1.4 vs. 36.3 ± 0.8 °C,p < 0.001, PR: 104 ± 15 vs. 85 ± 16 bpm,p < 0.05, RR: 23 ± 3 vs. 21 ± 3/min,p < 0.05). Although the average SBP and DBP were both stable during HT in a recumbent position, these values dropped significantly in a standing position (SBP: 113 ± 16 vs. 127 ± 18 mmHg,p < 0.001, DBP: 70 ± 12 vs. 75 ± 13 mmHg,p < 0.01). The total amount of sweating was 356 ± 173 g/m2on average. Conclusions:Deep regional HT increased the deep body temperature and resulted in an increase of sweating with peripheral vasodilatation. Consequently, a significant reduction in BP would be induced on standing after HT. Careful attention is needed for patients receiving HT, especially when standing after HT. [ABSTRACT FROM AUTHOR]

Background: falls by inpatients often result in serious injuries and deterioration in a patient's physical abilities and quality of life, especially among older individuals. Although various factors have been found to be associated with falls, the combined effects of behavioural and ambient factors are not fully evaluated. Objective: we investigated the influence of both behavioural and ambient factors on inpatient falls, focusing on seasonal and diurnal variations. Design: retrospective study. Methods: we surveyed the incident reports related to falls from April 2010 to March 2014 and examined the relationship between the incidents and seasonal and diurnal variations in behavioural and ambient factors, including the sunrise time, the night-time length and temperature. Results: we identified 464 fallers from 3,037 incident reports. The average fall-rate of the study population was 1.4 ± 0.5/1,000 occupied bed-days. The seasonal and diurnal variations in falls were compared. The number of falls around dawn in October--February was higher than that in April--September. Toileting was the behaviour most frequently related to the falls (56.9%, n = 264), and 57.1% of the falls occurred at night. A multivariate analysis showed that the night-time length was significantly related to an increase in night-time falls (P =0.047). Conclusion: these results suggested that the inpatient falls increased in the early morning from November to March and tended to be related to toileting activities. Considering these results, additional attention and support during the higher risk hours and seasons, especially in relation to toileting activities, might help to reduce the incidence of falls. Clinical trial name, URL and registration number: N/A (Because of retrospective nature). [ABSTRACT FROM AUTHOR]

Background Concomitant use of vitamin K antagonist (VKA) and aspirin (ASA) is becoming increasingly prevalent among atrial fibrillation (AF) patients. We quantified the net clinical benefit of adding ASA to a VKA using nationwide prospective AF registry data. Methods We studied 6074 patients (VKA monotherapy: 83% and VKA + ASA: 17%) between January 2009 and July 2009, and followed them for a mean follow-up period of 2 years. The risk of strokes and bleeding was calculated by the CHA 2 DS 2 -VASc and HAS-BLED scores. The net clinical benefit was defined as the annual rate of ischemic strokes and systemic emboli prevented by VKAs minus intracranial hemorrhages attributable to the VKA + ASA, multiplied by an impact weight of 1.5. Results Patients on a VKA + ASA were older with more medical comorbidities than those on VKA alone. Using VKA monotherapy as a reference, higher major bleeding rates and all-cause death were evident in those on VKA + ASA. The net clinical benefit of VKA + ASA for the overall cohort was − 0.1%/year (95% confidence interval, − 0.74% to 0.46%). There was a trend toward a negative net clinical benefit from VKA + ASA in patients with a CHA 2 DS 2 -VASc ≥ 2 and HAS-BLED ≤ 2 (− 1.17%/year). The VKA + ASA yielded a positive net clinical benefit in patients with a CHA 2 DS 2 -VASc ≥ 2 and HAS-BLED ≥ 3 (1.16%/year). The result patterns were relatively constant using impact weight of 1.0 and 2.0. Conclusions Our estimates of the net clinical benefit can provide a useful anchoring point for adding ASA to VKA in patients with AF. [ABSTRACT FROM AUTHOR]

Uncarboxylated osteocalcin (GluOC), a bone-derived hormone, regulates energy metabolism by stimulating insulin secretion, pancreatic β-cell proliferation, and adiponectin expression in adipocytes. Previously, we showed that long-term intermittent or daily oral administration of GluOC reduced the fasting blood glucose level, improved glucose tolerance, and increased the fasting serum insulin concentration as well as pancreatic β-cell area in female mice fed a normal or high-fat, high-sucrose diet. We have now performed similar experiments with male mice and found that such GluOC administration induced glucose intolerance, insulin resistance, and adipocyte hypertrophy in those fed a high-fat, high-sucrose diet. In addition, GluOC increased the circulating concentration of testosterone and reduced that of adiponectin in such mice. These phenotypes were not observed in male mice fed a high-fat, high-sucrose diet after orchidectomy, but they were apparent in orchidectomized male mice or intact female mice that were fed such a diet and subjected to continuous testosterone supplementation. Our results thus reveal a sex difference in the effects of GluOC on glucose homeostasis. Given that oral administration of GluOC has been considered a potentially safe and convenient option for the treatment or prevention of metabolic disorders, this sex difference will need to be taken into account in further investigations. [ABSTRACT FROM AUTHOR]

Uncarboxylated osteocalcin (GluOC), a bone-derived hormone, regulates energy metabolism by stimulating insulin secretion and pancreatic β-cell proliferation. We previously showed that the effect of GluOC on insulin secretion is mediated largely by glucagon-like peptide-1 (GLP-1) secreted from the intestine in response to GluOC exposure. We have now examined the effect of oral administration of GluOC on glucose utilization as well as the fate of such administered GluOC in mice. Long-term intermittent or daily oral administration of GluOC reduced the fasting blood glucose level and improved glucose tolerance in mice without affecting insulin sensitivity. It also increased the fasting serum insulin concentration as well as the β-cell area in the pancreas. A small proportion of orally administered GluOC reached the small intestine and remained there for at least 24 h. GluOC also entered the general circulation, and the serum GLP-1 concentration was increased in association with the presence of GluOC in the intestine and systemic circulation. The putative GluOC receptor, GPRC6A was detected in intestinal cells, and was colocalized with GLP-1 in some of these cells. Our results suggest that orally administered GluOC improved glucose handling likely by acting from both the intestinal lumen and the general circulation, with this effect being mediated in part by stimulation of GLP-1 secretion. Oral administration of GluOC warrants further study as a safe and convenient option for the treatment or prevention of metabolic disorders. [ABSTRACT FROM AUTHOR]

Introduction: Down syndrome (DS) is known to be often (30–50%) comorbid with sleep disordered breathing (SDB) for their facial anatomical deformation, muscular hypotonia. Daytime sleepiness resulted from SDB may relate to impaired cognitive function even in general public. In DS, congenital heart diseases (CHD) are also highly complicated (30–60%). Such CHD and SDB may cause a vicious cycle and early intervention to SDB in DS would contribute to their better intellectual and physical development. We reported that some of the DS slept in unusual postures. Thus, we studied the mutual relation among them in DS. Materials and methods: We recruited 90 caregivers of the DS in Fukuoka. The questionnaires for the DS contained demographic descriptions including CHD, sleeping postures, Epworth sleepiness scale (ESS), and SDB symptoms (easiness of getting to sleep, snoring, arousal, witnessed apneic episodes, nocturnal urination, nap, hardness of awakening). We calculated individual Caup index (0–5yo), Rhorer index (6–13yo), and BMI (14-yo) for judging obesity. We analyzed the relation between SDB symptoms and these items using chi-square test. Results: Seventy of 90 DS (34 men, 18 10yo) responded to the survey. Thirty-seven DS (53%, 15 men, 15 9yo) had CHD. Symptoms of SDB were as follows: “easiness of getting to sleep” in 90%, “snore” in 75%, “nocturnal arousal” in 52%, “witnessed apneic episodes” in 40%, “night urination” in 19%, “nap” in 41%, “hard to awaken” in 15%. There was significantly higher proportion of obese DS in “hard to awaken” than in “easy to awaken” (78% vs. 33%, P <0.05), and tendency of higher proportion of unusual sleep postures in “easy to awaken” than “hard to awaken” (67% vs. 33%, P <0.1). Furthermore, higher ESS was in “nocturnal arousal” and “night urination” than in “no arousal” and “no night urination” (38% and 55% vs. 4% and 13%, P <0.01, respectively). Finally, there were tendencies of higher comorbidity of CHD in those with SDB symptoms. Conclusion: Preventing obesity seems to be useful to improve SDB also in DS. The complication of CHD in the DS with SDB suggested formation of the vicious cycle. The unusual sleeping postures in the DS seem to be self-defending behaviors to protect from SDB. In conclusion, we need not only to take general care of SDB like reducing weight but also to give attention to specific risk factors of SDB in DS. Acknowledgements: Our deepest appreciation goes to the members of the Fukuoka branch of Japan Down Syndrome Society. [Copyright &y& Elsevier]

Purpose: We investigated the clinical performance of evaluation of cardiac mechanical dyssynchrony with longitudinal strain analysis using four-chamber (4CH) cine magnetic resonance imaging (MRI). Materials and methods: We retrospectively enrolled 73 chronic heart failure patients (41 men, 32 women; mean age, 57 years, NYHA 2, 3, and 4) who underwent a cardiac MRI in the present study. The left ventricular dyssynchrony (LVD) and interventricular dyssynchrony (IVD) indices were calculated by longitudinal strain analysis using 4CH cine MRI. The LVD and IVD indices were compared by the Wilcoxon rank-sum test between the patients with indication for cardiac resynchronization therapy (CRT) (n =13) and without indication for CRT (n =60), with LGE (n =40) and without LGE (n =27), the CRT responders (n =8) and non-responders (n =6), respectively. Results: LVD in the patients with indication for CRT were significantly longer than those without indication for CRT (LVD: 92±65 vs. 28±40ms, P <.01). LVD and IVD were significantly longer in the patients with LGE than those without LGE (LVD: 54±58 vs. 21±30ms, P <.01 and IVD: 51±39 vs. 23±34ms, P <.01). LVD and IVD in the CRT responders were significantly longer than the CRT non-responders (LVD: 126±55 vs. 62±55ms, P <.01 and IVD: 96±39 vs. 52±40ms, P <.05). Conclusion: Longitudinal strain analysis with 4CH cine MRI could be useful for clinical examination in the evaluation of cardiac mechanical dyssynchrony. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the effects of 6-h exposure to low relative humidity ( RH) and low air pressure in a simulated air cabin environment on body fluid loss ( BFL) and blood viscosity. Fourteen young healthy male subjects were exposed to four conditions, which combined RH (10% RH or 60% RH) and air pressure ( NP: sea level or LP: equivalent to an altitude of 2000 m). Subjects remained seated on a chair in the chamber for 6 h. Their diet and water intake were restricted before and during the experiment. Insensible water loss ( IWL) in LP10% condition was significantly greater than in NP60% condition; thus, combined 10% RH and LP conditions promoted a greater amount of IWL. The BFL under the LP condition was significantly greater than that under the NP condition. Blood viscosity significantly increased under LP conditions. Increases in red blood cell counts ( RBCs) and BFL likely contributed to the increased blood viscosity. These findings suggest that hypobaric-induced hypoxia, similar to the conditions in the air cabin environment, may cause increased blood viscosity and that the combined low humidity and hypobaric hypoxia conditions increase IWL. [ABSTRACT FROM AUTHOR]

Abstract: Background: The mortality and morbidity rates of various cardiovascular diseases differ between Western countries and Japan. The age- and gender-specific prevalence rate of atrial fibrillation (AF) in the general population of Japan was determined using the data from periodic health examinations in 2003. Methods: Data of 630,138 subjects aged 40 years or more (47% were men and 34% were employees of companies and local governments) were collected from northern to southern Japan. The prevalence of diagnosed AF in each 10-year age group of both men and women was determined. Based on these prevalence rates and the Registry of Residents, the number of people having AF in Japan was estimated. Results: The prevalence rate of AF increased as both male and female subjects aged, and it was 4.4% for men but only 2.2% for women aged 80 years or more (p <0.0001). As a whole, the AF prevalence of men was three times that of women (1.35 versus 0.43%, p <0.0001). There may be approximately 716,000 people (95% confidence interval (CI), 711,000–720,000) with AF in Japan, an overall prevalence of 0.56%. The number of people having AF was projected to be 1.034 (95% CI, 1.029–1.039) million, an overall prevalence of 1.09%, in 2050. Conclusions: The prevalence of AF increased in Japan as the population aged, as in Western countries. The overall prevalence of AF in Japan is approximately two-thirds of that in the USA. The projected increase in the number of people having AF is modest in Japan in 2050. [Copyright &y& Elsevier]

Abstract: The DPPH radical-scavenging activity of 25 inorganic salts, two buffer systems, and crude water extract of aerial parts of Varthemia (Varthemia iphionoides) before and after resins purification were investigated. Eight of the 25 inorganic salts tested quenched the DPPH radical colour. Na2S2O3 and FeCl2 showed markedly high DPPH colour-quenching activity, with inhibition of 65.3% and 47.7% respectively, at a concentration of 10μg/ml. Four salts slightly increased the intensity of DPPH radical colour. The rest of tested salts, acetate buffer, and phosphate buffer at a concentration less than 0.1mM did not affect DPPH radical colour. The DPPH radical-scavenging activity of BHT and catechol was considerably affected by the concentration of phosphate buffer (pH 7.0), and by acetate buffer (pH 5.0) at concentrations more than 0.01mM in the case of BHT only. The DPPH radical-scavenging activity of a crude water extract of aerial parts of Varthemia iphionoides was much higher than that of an extract desalted by cation-exchange resin, indicating that iron ions apparently elevated the DPPH radical-scavenging activity of the extract. Therefore, desalting of plant extracts is important in order to obtain the true value of DPPH radical-scavenging activity. [Copyright &y& Elsevier]

Aim In Japan, the incidence of water bathing-related cardiopulmonary accidents among older people is high in winter. The purpose of the present study was to investigate alterations in physiological characteristics and subjective thermal sensations of older people when bathing in a cool environment. Methods We assessed the skin temperature, rectal temperature, blood pressure, pulse rate, body fluid loss (sweat and urine), and subjective thermal responses of 11 older healthy male and 10 young male volunteers throughout 42°C and 39°C bathing in a room at 20°C with 50% humidity. Results At 42°C bathing, the rectal temperature during bathing and in the post-bathing period were significantly lower in the older men than in the young men, and skin temperature during the post-bathing period decreased gradually in the older men. Systolic blood pressure and pulse rate immediately increased just after entering 42°C water and decreased during bathing in the older men. With the activities of dressing, systolic blood pressure increased followed by a decrease during the post-bathing period. Thus, double product (pulse rate × systolic blood pressure) increased during the bathing period. Although there was no significant difference in body fluid loss between the older and younger men in 42°C water, the older men produced significantly less sweat. The older men also reported feeling less warm after 42°C bathing, and feeling less cold during the post-bathing period after 39°C bathing. Conclusions These results suggest that hot water bathing during cold seasons might induce more serious physiological changes in older people. Geriatr Gerontol Int 2017; 17: 2164-2170. [ABSTRACT FROM AUTHOR]

Introduction: Individuals with Down syndrome (DS) are at increased risk of sleep disordered breathing (SDB). Anatomical characteristics of DS, such as mid-facial hypoplasia, small jaw and obesity, are also risk factors for SDB, and may differ with ethnicity. Untreated SDB can lead to adverse cardiac outcomes and impaired cognitive function, thus early diagnosis and treatment may be important in DS. To date, no systematic population survey or cultural comparison has been made in DS individuals. This study aims to compare prevalence of SDB among adults aged >16years with DS in two diverse cultures: Japan and Scotland. Materials and methods: Questionnaires including physical profile, traditional or pictorial Epworth Sleepiness Scale (ESS) and witnessed signs of SDB (e.g. apnoeic episodes and snoring) were sent to adults aged >16years with DS and their caregivers in Japan (J) and Scotland (S). 705 questionnaires were valid for analysis (J: 461; S: 244). Standard statistical analysis was undertaken. Results: Similar gender distributions (male/female J: 259/202 vs. S: 139/105) and ESS (J: 6± 5 vs. S: 7±5) were observed among Japanese and Scottish responders. Adults with DS in Scotland were older and had higher BMI than those in Japan (J: 24±8 vs. S: 32±11years; J: 24.0±4.1 vs. S: 29.6±7.4kg/m2). In Japan, 80% of responders snored and 30% had witnessed apnoeas. Similarly, in Scotland, 74% snored and 24% had witnessed apnoeas. In Japan, snorers had significantly higher BMI (OR 1.1, 95%Cl 1.0–1.2, p <0.01) and ESS (OR 1.2, 95%Cl 1.1–1.3, p <0.001), and tended to be younger (OR 1.0 95%Cl 0.9–1.0, p =0.06). Similar associations were found in Scotland, with snorers being younger (OR 1.0, 95%Cl 0.9–1.0, p <0.05) and having significantly higher ESS (OR 1.3, 95%Cl 1.0–1.4, p <0.01). In Japan, witnessed apnoeas were significantly associated with higher ESS (OR 1.2, 95%Cl 1.1–1.2, p <0.001). Conclusion: Prevalence of symptoms of SDB was high among adults with DS in both countries. The DS population in Scotland was significantly more obese. These results imply that the anatomical characteristics of DS might overshadow the racial and anatomical differences in terms of causing SDB, although further research is required. Appropriate evaluation and treatment should be offered if symptoms of SDB are observed, regardless of ethnicity, in adults with DS. Both studies are ongoing. Acknowledgements: We sincerely appreciate Donna Fairley, RN, for helpful effort. Hiroyuki Sawatari and Elizabeth A Hill were joint 1st author. Renata L Riha and Shin-ich Ando were Joint supervisors. [ABSTRACT FROM AUTHOR]

Introduction: An increasing number of patients with chronic heart failure (CHF) is suffering from insomnia, which is also impairing their quality of life (QOL) and might worsen heart failure. Previous studies reported that sleep depth and sleep onset were strongly affected by body temperatures before sleeping. We developed a leg thermal therapy (LTT) in which we used infra-red radiation to heat lower legs and could increase core body temperatures by 0.4 C without any harmful hemodynamic changes in patients with CHF. We also found that the LTT was effective in improving the hemodynamics, vascular endothelial function, and reducing oxidative stress in patients with CHF. In present study, we evaluated the effects of the LTT on sleep quality in CHF from both subjective and objective sides. Materials and methods: Fifteen inpatients with CHF (age: 53_}14 y.o., Male: 13, NYHA: II–III) underwent the LTT (45 C) for 15min followed by 30min insulation for 3 consecutive nights before sleep. For objective evaluation of the LTT on sleep fragmentations, we recorded type-2 polysomnography before the LTT and just after three days_f LTT. We assessed subjective sleep quality using the Oguri-Shirakawa-Azumi sleep inventory and St. Mary_fs Hospital sleep questionnaires every morning. We evaluated vascular endothelial function using flow-mediated vasodilation measurement in the early morning. Results: Three consecutive nights protocol of the LTT showed significant decrease of sleep stage I, and the sum of sleep stage I and II (p <0.05 and p <0.05, respectively). Furthermore, from the questionnaires, the LTT improved subjective sleep quality of difficulty in falling asleep, decreased frequency of dreams, and lengthened sleeping duration (p <0.1, p <0.05, and p <0.1; respectively). Conclusion: Three nights protocol of the LTT actually decreased light sleep and improved subjective sleep quality in patients with CHF. LTT had potential as a safety and complementary therapy that can improve sleep quality, QOL and prognosis in patients with CHF. Although the long term effects of LTT on sleep disturbance or prognosis on CHF remain to be investigated, current result suggests that the LTT could be used to improve QOL of CHF patients through improvement of their sleep quality. [Copyright &y& Elsevier]