Circadian Rhythmicity as a Predictor of Quality of Life in Allogeneic Hematopoietic Cell Transplant Patients

Context

Quality of life (QoL) is increasingly recognized as an important outcome of cancer treatment. Previous studies have examined clinical predictors of QoL, but with the increasing prevalence of wearable sensors that monitor sleep and activity patterns, further investigation into whether these behaviors are predictive of post-treatment QoL is now feasible. Among patients receiving aggressive cancer treatment such as hematopoietic cell transplantation (HCT), analysis of circadian rhythms (24-hour patterns of sleep and activity) via wearable sensors is limited.

Reliability and validity of the Japanese version of the Biological Rhythms Interview of assessment in neuropsychiatry-self report for delayed sleep-wake phase disorder

ObjectiveThe Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN) might be applicable for assessing delayed sleep-wake phase disorder (DSWPD). We aimed to investigate the reliability and validity of the Japanese version of the BRIAN self-report (J-BRIAN-SR) in DSWPD patients and determine a cutoff score to identify the presence of the disorder.MethodsWe enrolled 60 newly diagnosed DSWPD outpatients and 64 age-matched healthy controls. We used Cronbach's alpha for internal reliability to evaluate J-BRIAN-SR. We confirmed the reliability of the A test and re-test using Pearson's correlation coefficient in the controls. We used confirmatory factor analysis to evaluate the factor structure of J-BRIAN-SR and referenced the Morningness-Eveningness Questionnaire (MEQ) to check concurrent validity. We analyzed the receiver operating characteristic curve (ROC) to determine the J-BRIAN-SR cutoff point for the presence of DSWPD.ResultsThe 18-component scores of the J-BRIAN-SR had an overall reliability coefficient (Cronbach's alpha) of 0.82. We confirmed a high test-retest reliability using an intraclass correlation coefficient (r = 0.84). The correlation between J-BRIAN-SR and MEQ was 0.38 (p = 0.003). The J-BRIAN-SR that we extracted by exploratory factor analysis consisted of three factors. A score of 40 points provided a sensitivity of 80.0% and a specificity of 75.6% for the positivity of DSWPD.ConclusionsThe results of the present study revealed that J-BRIAN-SR is a valid and reliable instrument for screening and evaluating the severity of DSWPD. Our findings will be useful to physicians and patients in Japan and those in clinical settings.     

Continuous measurement of intra‐oral pH and temperature: development,validation of an appliance and a pilot study

To describe a novel approach for continuous measurement of intra‐oral pH and temperature in individuals carrying out normal daily activities over 24 h. We designed, validated and constructed a custom‐made appliance fitted with a pH probe and a thermocouple. Six subjects wore the appliance over a 24‐h period for two non‐consecutive days, while the intra‐oral pH and temperature were measured continuously and recorded. Intra‐oral pH and temperature were very similar across different recording days, the difference being not statistically significant (P ≥ 0·14). There was a noticeable difference in the pattern of variation of pH between day and night. During the day, the mean pH was 7·3 (±0·4) and dropped markedly only after consumption of acidic food and drinks. The intra‐oral pH decreased slowly during sleep with an average pH of 6·6 (±0·4) being recorded. The difference between day and night was statistically significant (P = 0·002). The mean intra‐oral temperature was 33·9 °C (±0·9) during daytime and 35·9 °C (±0·5) during sleep (P = 0·013) with minor fluctuations occurring over 24 h. The continuous and simultaneous intra‐oral pH and temperature measurement system described in this report is reliable, easy to construct, able to measure variables over a sustained period and may serve as a future diagnostic tool in a number of applications.     

Prevalence of shift work disorder among hospital personnel: A cross‐sectional study using objective working hour data

The prevalence of shift work disorder (SWD) has been studied using self‐reported data and the International Classification of Sleep Disorders, Second Edition (ICSD‐2) criteria. We examined the prevalence in relation to ICSD‐2 and ICSD‐3 criteria, work schedules and the number of non‐day shifts (work outside 06:00–18:00 hours) using objective working‐hours data. Secondly, we explored a minimum cut‐off for the occurrence of SWD symptoms. Hospital shift workers without (n = 1,813) and with night shifts (n = 2,917) and permanent night workers (n = 84) answered a survey (response rate 69%) on SWD and fatigue on days off. The prevalence of SWD was calculated for groups with ≥1, ≥3, ≥5 and ≥7 monthly non‐day shifts utilizing the working hours registry. ICSD‐3‐based SWD prevalence was 2.5%–3.7% (shift workers without nights), 2.6%–9.5% (shift workers with nights) and 6.0% (permanent night workers), depending on the cut‐off of non‐day shifts (≥7–1/month, respectively). The ICSD‐2‐based prevalence was higher: 7.1%–9.2%, 5.6%–33.5% and 16.7%, respectively. The prevalence was significantly higher among shift workers with than those without nights (p‐values <.001) when using the cut‐offs of ≥1–3 non‐day shifts. Shift workers with nights who had ≥3 days with ICSD‐3‐based SWD symptoms/month more commonly had fatigue on days off (49.3%) than those below the cut‐off (35.8%, p < .05). The ICSD‐3 criteria provided lower estimates for SWD prevalence than ISCD‐2 criteria, similarly to exclusion of employees with the fewest non‐day shifts. The results suggest that a plausible cut‐off for days with ICSD‐3‐based SWD symptoms is ≥3/month, resulting in 3%–6% prevalence of SWD.     

Assessing the role of nocturnal core body temperature dysregulation as a biomarker of neurodegeneration

The vast majority of patients with idiopathic rapid eye movement sleep behaviour disorder will develop a neurodegenerative α‐synuclein‐related condition, such as Parkinson’s disease or dementia with Lewy bodies. The pathology underlying dream enactment overlaps anatomically with the brainstem regions that regulate circadian core body temperature. Previously, nocturnal core body temperature regulation has been shown to be impaired in Parkinson’s disease. However, no study to date has investigated nocturnal core body temperature changes in patients with idiopathic rapid eye movement sleep behaviour disorder, which may prove to be an early objective biomarker for α‐synucleinopathies. Ten healthy controls, 15 patients with idiopathic rapid eye movement sleep behaviour disorder, 31 patients with Parkinson’s disease and six patients with dementia with Lewy bodies underwent clinical assessment and nocturnal polysomnography with core body temperature monitoring. A validated cosinor method was utilised for core body temperature analysis. No differences in mesor, nadir or time of nadir were observed between groups. However, when compared with healthy controls, the amplitude of the nocturnal core body temperature (mesor minus nadir) was significantly reduced in patients with idiopathic rapid eye movement sleep behaviour disorder, Parkinson’s disease with concurrent rapid eye movement sleep behaviour disorder and dementia with Lewy bodies (p < 0.001, p = 0.043 and p = 0.017, respectively). Importantly, this relationship was not seen in those patients with Parkinson’s disease without rapid eye movement sleep behaviour disorder. In addition, there was a significant negative correlation between amplitude of the core body temperature and self‐reported rapid eye movement sleep behaviour disorder symptoms. Changes in thermoregulatory circadian rhythm may be specifically associated with the pathology underlying rapid eye movement sleep behaviour disorder rather than simply that of α‐synucleinopathy. These findings implicate thermoregulatory dysfunction as a potential early biomarker for development of rapid eye movement sleep behaviour disorder‐associated neurodegeneration, and suggest that subpopulations with differing pathological underpinnings might exist in Parkinson’s disease.     

Melatonin modulates dysregulated circadian clocks in mice with diethylnitrosamine‐induced hepatocellular carcinoma

Disruption of circadian rhythms, which are regulated by the circadian clock machinery, plays an important role in different long‐term diseases including hepatocellular carcinoma (HCC ). Melatonin has been reported to alleviate promotion and progression of HCC , but the potential contribution of circadian clock modulation is unknown. We investigated the effects of melatonin in mice which received diethylnitrosamine (DEN ) (35 mg/kg body weight ip) once a week for 8 weeks. Melatonin was given at 5 or 10 mg kg^?1d^?1 ip beginning 4 weeks after the onset of DEN administration and ending at the sacrifice time (10, 20, 30, or 40 weeks). Liver expression of Bmal1, Clock, Npas2, Rorα, and Sirt1 increased, whereas Cry1, Per1, Per2, Per3, CK 1ε, Rev‐erbα, and Rev‐erbβ decreased following DEN administration. Melatonin treatment prevented changes in the expression of clock genes, and this effect was accompanied by an upregulation of the MT 1 receptor and reduced levels of the hypoxia‐inducible factors Hif‐1α and Hif‐2α. An increased expression of p21, p53, and PARP 1/2, a higher Bax/Bcl‐2 ratio, and a lower expression of Cyclin D1, CDK 6, HSP 70, HSP 90, and GRP 78 proteins were also observed in melatonin‐treated mice. Melatonin significantly potentiated the suppression of proliferation and cell cycle arrest induced by the synthetic REV ‐ERB agonist SR 9009 in human Hep3B cells, and BMAL 1 knocking down attenuated the pro‐apoptotic and antiproliferative effect of melatonin. Results support a contribution of changes in the circadian clock components to the beneficial effects of melatonin in HCC and highlight the usefulness of strategies modulating the circadian machinery in hepatocarcinogenesis.     

Mood disorders and biological rhythms in young adults: A large population-based study

BackgroundIt is known that sleep disturbance has been considered a trait-marker of mood disorders. However, the role of disruptions in biological rhythms, such as eating, activity, and social patterns, needs to be better understood.AimTo assess the differences in biological rhythms in subjects with bipolar disorder, major depressive disorder, and healthy controls. We also tested the association between disruptions of biological rhythms and circadian preferences.MethodsA cross-sectional, population-based study with a representative sample of 1023 young adults. Bipolar disorder and depression were diagnosed using The Mini International Neuropsychiatric Interview – PLUS and DSM Structured Clinical Interview. Self-reported biological rhythms and circadian preference were assessed using the Biological Rhythm Interview of Assessment in Neuropsychiatry (BRIAN).ResultsBipolar disorders and depression subjects presented higher rates of disruption in biological rhythms when compared to healthy controls even after adjusting for sex, socioeconomic status, alcohol, tobacco, illicit drug use, anxiety disorder and psychotropic medication use. Euthymic subjects showed higher biological rhythm disruption when compared to controls. Higher disruption in biological rhythms was observed in subjects with evening preferences.ConclusionHigher disruption in biological rhythms occurs in individuals with depression and bipolar disorder even on periods of euthymia.     

Chronobiologically Explored Effects of Telmisartan

Effects of Micardis (Telmisartan), alone or with low-dose aspirin, on blood pressure and other cardiovascular endpoints are examined in 20 patients with MESOR-hypertension in a crossover, double-blind, randomized study consisting of three stages, each lasting 7 days: I-placebo, II-Micardis, and III-Micardis with low-dose aspirin. Treatment was administered each day at a different circadian stage, upon awakening, and 3, 6, 9, 12, 15 and 18 hr after awakening. During each stage, the following variables were measured at 3-hr intervals during waking: systolic and diastolic blood pressure, heart rate, ejection fraction, intrarenal resistive index, acceleration time, and serum creatinine. Each data series was analyzed by single cosinor. Results were summarized by population-mean least squares spectra. At matched treatment times, the MESOR and circadian amplitude of each variable were compared among the three treatments by paired t-tests. A prominent circadian rhythm characterizes all variables. Micardis was associated not only with a lowering of blood pressure, but also with a reduction of the circadian blood pressure amplitude. The ejection fraction was increased, and the resistive index and acceleration time were decreased, the effect being more pronounced when low-dose aspirin was added to Micardis. Any circadian-stage dependent effect of Micardis, with or without low-dose aspirin, will require monitoring over spans longer than a single day for a given treatment administration time.     

Circadian rhythm in atopic dermatitis—Pathophysiology and implications for chronotherapy

Circadian rhythm is a biological clock that controls a wide range of physiological functions throughout the body, including various skin functions. A 24‐h diurnal cycle, governed by an endogenous clock in the brain, largely controls cutaneous diurnal rhythm, which external factors, including temperature, humidity, diet, and stress, also modulate locally. Circadian rhythm influences cutaneous blood flow and properties of skin barrier function, such as transepidermal water loss and capacitance, and has important implications in atopic dermatitis (AD). This review explores how aberrations in circadian rhythm may play a role in the pathogenesis of AD and proposes implementation of chronotherapy to improve treatment outcomes in patients with AD.