In vivo recording of suprachiasmatic nucleus dynamics reveals a dominant role of arginine vasopressin neurons in circadian pacesetting.

The central circadian clock of the suprachiasmatic nucleus (SCN) is a network consisting of various types of neurons and glial cells. Individual cells have the autonomous molecular machinery of a cellular clock, but their intrinsic periods vary considerably. Here, we show that arginine vasopressin (AVP) neurons set the ensemble period of the SCN network in vivo to control the circadian behavior rhythm. Artificial lengthening of cellular periods by deleting casein kinase 1 delta (CK1δ) in the whole SCN lengthened the free-running period of behavior rhythm to an extent similar to CK1δ deletion specific to AVP neurons. However, in SCN slices, PER2::LUC reporter rhythms of these mice only partially and transiently recapitulated the period lengthening, showing a dissociation between the SCN shell and core with a period instability in the shell. In contrast, in vivo calcium rhythms of both AVP and vasoactive intestinal peptide (VIP) neurons in the SCN of freely moving mice demonstrated stably lengthened periods similar to the behavioral rhythm upon AVP neuron-specific CK1δ deletion, without changing the phase relationships between each other. Furthermore, optogenetic activation of AVP neurons acutely induced calcium increase in VIP neurons in vivo. These results indicate that AVP neurons regulate other SCN neurons, such as VIP neurons, in vivo and thus act as a primary determinant of the SCN ensemble period.

Limitation of developmental test to measure functional independence of children: Relationship between the Japanese version of WeeFIM II® and KSPD.

PURPOSE: The purpose of the study was to explore whether a developmental test provides enough information to estimate a child's functional independence. The strength of the relationship between developmental level and functional independence of different skills was investigated. METHODS: The participants were 397 children (age 0-7 years) who were referred to NCCHD for suspected developmental delay. The participants' developmental level was measured with the Kyoto Scale of Psychological Development (KSPD) and their functional independence was assessed through a Japanese version of the WeeFIM II®. To calculate the strengths of the relationship between developmental age (DA) in different domains of the KSPD and WeeFIM II item scores, partial correlation analyses were conducted, controlling for chronological age. RESULTS: Partial correlation coefficients between the score of each of the 18 WeeFIM II items and each of the three KSPD domain DAs (controlling chronological age) fell in the ranges of r = 0.169-0.581 (Posture-Motor; P-M), r = 0.377-0.627 (Cognitive-Adaptive; C-A), and r = 0.332-0.655 (Language-Social; L-S). When the participants were divided into three age groups, the correlations ranged from -0.095 to 0.552 for the youngest group (mean age = 14.21 months), from 0.283 to 0.653 for the middle group (mean age = 32.98 months), and from 0.345-0.692 for the oldest group (mean age = 57.48 months), depending on the combinations of the WeeFIM II items/developmental domains of the KSPD. The results indicated that for most of the daily living skills, its functional independence was only partially explained by the scores of a developmental test, once chronological age was controlled. CONCLUSION: This study showed the limitation of a developmental test as a tool to measure the functional independence of children and the necessity of using an independent tool, such as WeeFIM II, to evaluate the level of required support for each daily living skill.

Immediate effect of different ankle-foot orthosis functions with the same dorsiflexed setting of initial ankle joint angle on walking ability in individuals with chronic stroke: a randomized crossover trial.

[Purpose] To investigate how different ankle-foot orthosis functions with the same dorsiflexed setting of initial ankle joint angle affect the walking ability in individuals with chronic stroke. [Participants and Methods] In this randomized crossover study, participants underwent a 10-m walking test and walked on a WalkWay MW-1000 three times under these conditions: (1) without ankle-foot orthosis; (2) with ankle-foot orthosis with an adjustable posterior strut at 5° of fixed dorsiflexion; and (3) with ankle-foot orthosis with an adjustable posterior strut at 5-20° of restricted dorsiflexion. The primary outcome was walking speed on the 10-m walking test. The secondary outcomes were walking speed and spatiotemporal factors measured by the WalkWay MW-1000. [Results] Fifteen individuals (mean [standard deviation] age, 60.9 [8.6] years; male, 12) were enrolled. Walking speeds of the ankle-foot orthosis with fixed and restricted dorsiflexion groups were significantly higher than those without the orthosis; however, no outcomes differed significantly between ankle-foot orthosis with fixed versus restricted dorsiflexion groups. [Conclusion] In individuals with chronic stroke, ankle-foot orthosis function may be less important than the dorsiflexed setting of initial ankle joint angle in the ankle-foot orthosis.

The Impact of Isolation on Elderly Patients with Mild to Moderate COVID-19.

Objectives: Patients with mild to moderate COVID-19 who require hospitalization are prone to physical inactivity. This study examined the impact of mild to moderate COVID-19 on the activities of daily living (ADLs) of patients who received rehabilitation therapy. Methods: Between February 1, 2020, and January 31, 2021, of 216 patients with mild to moderate COVID-19, 36 were selected for rehabilitation therapy. Of these, 28 received direct rehabilitation therapy, whereas 7 were discharged before rehabilitation therapy could start and 1 carried out indirect rehabilitation. The Barthel Index (BI) scores at the beginning and the end of therapy were compared in 18 patients (10 patients who did not undergo a final BI evaluation were excluded). Results: In total, 27 of the 28 patients receiving direct rehabilitation therapy were more than 65 years of age or had underlying diseases. The BI score decreased in 6 patients and was maintained or improved in 12 patients. However, the 6 patients with decreased BI scores after rehabilitation therapy had significantly higher BI values at the start of therapy (P=0.014). Conclusions: It was considered that the isolated environment of these COVID-19 patients likely resulted in a decrease in activity levels, leading to a decrease in ADLs. Older adults with mild to moderate COVID-19 need to reduce their isolation as much as possible to ensure adequate activity levels.

Secretin receptor-deficient mice exhibit robust food anticipatory activity.

In mammals, the suprachiasmatic nucleus (SCN) is a principal circadian pacemaker that optimizes the timing of behavioral rhythms and physiological events. Normally, circadian behavioral rhythms are entrained by the environmental light-dark (LD) cycle via the SCN. However, daily rhythms of other synchronizing signals, such as food availability, also emerge. When food availability is restricted to a single recurring daytime meal in nocturnal rodents, they exhibit increased activity during the hours immediately preceding feeding time; this is called food anticipatory activity (FAA). Many reports suggest that FAA is mediated by the food-entrainable oscillator (FEO) with circadian properties, but not the SCN. However, the neural locus and timekeeping mechanisms of the FEO, including its relationship with gastrointestinal hormone signaling, remain unclear. Herein, to examine whether secretin receptor signaling is necessary for the FEO, the effect of daily food restriction was studied in secretin receptor-deficient (Sctr-/-) mice. Adult wild-type (WT) and Sctr-/- mice were housed in separate cages containing a running wheel, with ad libitum food access and in a LD cycle (12 hours:12 hours) for at least 2 weeks. After acclimation to the condition, food access times were gradually restricted and 4-hour restricted feeding lasted over 10 days. Subsequently, mice had ad libitum food access for 2 days and then fasted for 2 days. Thereafter, robust FAAs were observed in both WT and Sctr-/- mice during restricted feeding and subsequent fasting. These results indicate that secretin receptor signaling is not essential for the timekeeping mechanism of FEO.

Roles of Early Mobilization Program in Preventing Muscle Weakness and Decreasing Psychiatric Disorders in Patients with Coronavirus Disease 2019 Pneumonia: A Retrospective Observational Cohort Study.

Although many coronavirus 2019 patients have experienced persistent symptoms and a long-term decline in quality of life after discharge, the details of these persistent symptoms and the effect of early rehabilitation are still unclear. We conducted a single-center, retrospective observational study to investigate the prevalence of persistent symptoms three months after discharge from the intensive care unit by checking the medical records. All patients received an early mobilization program. Four out of 13 patients (31%) had postintensive care syndrome. No patients had muscle weakness, and 11 patients (85%) returned to their previous work. However, psychiatric disorder, such as anxiety (23%) and posttraumatic stress disorder (15%), were observed. Eleven patients claimed persistent symptoms, including fatigue and numbness in the extremities. Our results suggest that the implementation of an early rehabilitation program plays some role in preventing muscle weakness and that decreasing psychiatric disorders should be a next target of patient care in the intensive care unit.

Improvement in activities of daily living and exercise tolerance in a patient with severe COVID-19 and femoral nerve palsy after Kaifukuki rehabilitation: a case report.

Yashiro T, Wada Y, Sugiyama M, Tateno H, Kasai F, Kawate N. Improvement in activities of daily living and exercise tolerance in a patient with severe COVID-19 and femoral nerve palsy after Kaifukuki rehabilitation: a case report. Jpn J Compr Rehabil Sci 2021; 12: 53-57. Introduction: There have been many reports on rehabilitation techniques for patients with coronavirus disease 2019 (COVID-19). However, few have reported on the use of Kaifukuki rehabilitation for severe COVID-19 cases with complications of femoral nerve palsy after veno-venous extracorporeal membrane oxygenation (VV-ECMO) management. Case: A male in his 50s who underwent VV-ECMO management during the course of his treatment for COVID-19 developed femoral nerve palsy due to iliopsoas hematoma. From day 120 after admission, he underwent Kaifukuki rehabilitation focusing on exercise therapy, activities of daily living (ADL) training, and respiratory rehabilitation to improve ADL and exercise tolerance. His respiratory function, functional independence measure scores, and 6-min walk test results improved. The patient was discharged on day 196. His recovery progressed without any further deterioration. Discussion: Kaifukuki rehabilitation, focusing on respiratory rehabilitation, contributed to the improvement of ADL and exercise tolerance in a patient with severe COVID-19. In addition, attention should be paid to femoral nerve palsy after VV-ECMO.

Secretin receptor-deficient mice exhibit altered circadian rhythm in wheel-running activity.

In mammals, the timing of behavior and physiological activity is controlled by the suprachiasmatic nucleus (SCN) in the hypothalamus. Incidentally, secretin is a peptide hormone that promotes digestive activities and regulates water reabsorption. In recent studies, exogenous administration of secretin has been reported to induce secretion of oxytocin in the supraoptic nucleus of the hypothalamus and modulate social behavior. These results indicate that secretin is involved in the neural network that controls social behavior and plays important roles in the central nervous system. In the present study, we investigated the effects of secretin on circadian rhythms, by assessing circadian rhythms during wheel-running behavior in secretin receptor-deficient (Sctr-/-) mice. Male adult wild-type (WT) and Sctr-/- mice were housed in separate cages containing a wheel. Every minute of the wheel-running activity was monitored during the normal light-dark (LD) cycle (12:12 h) and in constant darkness (DD). Significant differences were observed in the free-running period between the WT and Sctr-/- mice. However, no significant differences were observed in the daily wheel-running revolutions between WT and Sctr-/- mice, in the LD and DD conditions. Moreover, the ratio of the daily activity phase to the rest phase (α/ρ) was significantly smaller in Sctr-/- than that in WT mice in the DD condition. Secretin receptors were expressed in the SCN cells. These findings suggest that secretin receptors are involved in the central circadian clock in the SCN and the circadian system in general.

Photic phase-response curves for cycling female mice.

The photic entrainment system is critical for the internal circadian clock to be synchronized by external time cues. In nocturnal rodents, exposure to light during the early subjective night causes a phase delay, whereas it causes a phase advance during the late subjective night. This is represented by a phase-response curve (PRC). The PRC of females has not been well studied due to their estrous cycles. Our aim in this study was to understand the characteristics of photic entrainment in female cycling rodents and identify differences in photic entrainment among the stages of the estrous cycle. To establish two types of PRC, immediate PRC (iPRC) and steady state PRC (ssPRC), in each stage of the estrous cycle, we recorded circadian rhythms of wheel running activity, applying a 15-min light pulse to cycling female mice in constant darkness. In the iPRC, which was evaluated on the next day of the light pulse, the amount of phase shift in the diestrus was larger than that in the metestrus stage at circadian time (CT) 2. Similarly, the amount of phase shift in metestrus was larger than that in proestrus at CT 10. In the ssPRC, which was evaluated after completion of a new steady state, no significant estrous variations in the amount of photic phase shifts were detected for any CTs. Although these results indicate that the intrinsic photic entrainment system is not influenced by the estrous cycle, it may affect photoreception and cause sudden behavioral changes.