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Objectives:Previous studies using objective parameters have shown that irregular sleep is associated with the disease incidence, progression, or mortality. This study aimed to determine the association between subjective sleep duration and sleep regularity, with mortality in a large population., Methods:Participants were from the Japan Multi-Institutional Collaborative Cohort study. We obtained information from each participant on sleep duration, sleep regularity, and demographics and overall lifestyle using self-administered questionnaires. We defined sleep regularity according to participants' subjective assessment of sleep/wake time regularity. Participants (n = 81,382, mean age: 58.1 ± 9.1years, males: 44.2%) were classified into 6 groups according to sleep duration and sleep regularity. Hazard ratios (HR) for time-to-event of death were calculated using the Cox proportional hazards model., Results:The mean follow-up period was 9.1 years and the mean sleep duration was 6.6 h/day. Irregular sleep significantly increased the risk of all-cause mortality in all models compared with regular sleep (HR 1.30, 95% confidence interval; CI, 1.18-1.44), regardless of sleep duration. Multivariable analysis of the 6 groups by sleep pattern (sleep regularity and duration) showed irregular sleep and sleep durations of, Conclusions:Our study shows an association between sleep irregularity and all-cause mortality in a large Japanese population. Our findings provide further confirmation of the need to consider not only sleep duration, but also the regularity aspect of sleep schedules.

The glutamate α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs) is an important molecule in neurotransmission. We have recently developed the first positron emission tomography (PET) tracer [11C]K-2 to visualize and quantify AMPARs in the living human brain. After injection, [11C]K-2 is hydrolyzed at the terminal amide (and is thus metabolized to a major metabolite, [11C]K-2OH) within 10 min, representing the PET image in rodents and humans. Here, we found that K-2OH did not penetrate the cell membrane but slowly passed through the blood brain barrier (BBB) with paracellular transport. Furthermore, major efflux transporters in the BBB did not carry K-2OH. Logan graphical analysis exhibited reversible binding kinetics of this radiotracer in healthy individuals; these results demonstrated that the PET image of this tracer represents cell surface AMPARs with passive penetration of [11C]K-2OH through the BBB, resulting in reversible binding kinetics. Thus, PET images with this tracer depict the physiologically crucial fraction of AMPARs.

Superconducting quantum interference devices (SQUIDs) are magnetometers with ultra-high sensitivity that have garnered attention owing to their potential application in flux qubits for quantum computing. The Josephson junction is an important component that determines the characteristics of a SQUID. Based on the superconductivity of heavily boron-doped diamond (111) homoepitaxial layers with a high critical temperature (Tc > 10 K), we propose two types of Josephson junction structures with discontinuous (111) boundaries. These structures allow the SQUID to operate above liquid helium temperature (4.2 K) with high reproducibility. We analyzed local misorientation and strain (i.e., compressive, tensile, and shear strain) at the boundary via electron backscatter diffraction. The Josephson junction characteristics were attributed to the weak link with discontinuous boundaries of diamond (111) sectors.

Summary Introduction Bone defect reconstruction in orbital wall fractures with absorbable alloplastic such as the unsintered hydroxyapatite and poly L-lactide composite (u-HA/PLLA) system is gaining popularity. The u-HA/PLLA material has osteoconductive and osteosynthetic properties. However, quantitative, long-term outcome data after the use of u-HA/PLLA for orbital wall fractures are lacking. Patients and Methods We retrospectively analyzed 115 patients who underwent surgical repair of orbital wall fractures with a u-HA/PLLA sheet from 2011 to 2016. A chart review was performed, and the time-dependent changes at fracture sites were assessed by imaging. The immediate postoperative and the latest follow-up bony orbital volumes of the affected side were compared. Results Seventy patients were eligible for this study (mean age, 44.6 ± 22.1 years; 48 men and 22 women; mean follow-up period, 29.7 ± 12.8 months). Except for one case of hematoma, there were no postoperative wound complications. Of the 70 patients, 10 had postoperative diplopia and 2 had enophthalmos; these conditions were presumably caused by the extension and severity of the fracture. Satisfactory reduction in the entire orbital wall, without pathological changes, was demonstrated. There were no significant differences in the mean bony orbital volumes of the affected side immediately after surgery (24.774 ± 3.092 cm3) and at the latest follow-up (24.749 ± 3.205 cm3) (p = 0.756). Conclusion The u-HA/PLLA sheet is useful for orbital wall fracture reconstruction because of its desirable handling characteristics, initial mechanical strength, long-term maintenance of structural stability, radiopacity, and few associated complications. Future randomized controlled trials need to be performed to compare u-HA/PLLA with other conventional materials.

Background Elbow injuries are common in young baseball players and evaluating the characteristics of young baseball players in a large-scale population is necessary. However, few studies have compared playing position, length of baseball experience, physical findings, and elbow pain in young baseball players. This retrospective multi-regional cohort study sought to document the physical findings at the elbow in Japanese elementary school baseball players and to examine the relationship between playing position, length of baseball experience, physical findings at the elbow, and elbow pain. Methods In 2014, 720 fifth-grade baseball players from four regions in Japan were invited to participate in a questionnaire survey and undergo physical examination to obtain data on position played, length of baseball experience, presence of elbow pain, and physical findings at the elbow, including range of motion, tenderness, and valgus stress test results. Potential risk factors associated with elbow pain and correlations between physical findings and playing position, length of baseball experience, and elbow pain were investigated. Results The 720 subjects had a mean age of 10.4 years and 29.4% reported having experienced elbow pain for ≥1 week. Risk factors for elbow pain included playing pitcher and catcher, playing pitcher and fielder, and length of baseball experience. The most frequent finding was limitation of flexion (21.1%) followed by tenderness of the medial epicondyle (18.3%) and a positive valgus stress test (14.3%). These three findings were also significantly associated with elbow pain. Elbow extension was limited in 14.9% of subjects but there was no correlation with length of baseball experience or elbow pain. Conclusions Our data show that elementary school baseball players who experienced elbow pain are likely to have valgus stress overload. Elbow pain might be prevented by not playing pitcher and catcher.

The tricarboxylic acid (TCA) cycle (or citric acid cycle) is responsible for the complete oxidation of acetyl-CoA and formation of intermediates required for ATP production and other anabolic pathways, such as amino acid synthesis. Here, we uncovered an additional mechanism that may help explain the essential role of the TCA cycle in the early embryogenesis of Caenorhabditis elegans. We found that knockdown of citrate synthase (cts-1), the initial and rate-limiting enzyme of the TCA cycle, results in early embryonic arrest, but that this phenotype is not because of ATP and amino acid depletions. As a possible alternative mechanism explaining this developmental deficiency, we observed that cts-1 RNAi embryos had elevated levels of intracellular acetyl-CoA, the starting metabolite of the TCA cycle. Of note, we further discovered that these embryos exhibit hyperacetylation of mitochondrial proteins. We found that supplementation with acetylase-inhibiting polyamines, including spermidine and putrescine, counteracted the protein hyperacetylation and developmental arrest in the cts-1 RNAi embryos. Contrary to the hypothesis that spermidine acts as an acetyl sink for elevated acetyl-CoA, the levels of three forms of acetylspermidine, N(1)-acetylspermidine, N(8)-acetylspermidine, and N(1),N(8)-diacetylspermidine, were not significantly increased in embryos treated with exogenous spermidine. Instead, we demonstrated that the mitochondrial deacetylase sirtuin 4 (encoded by the sir-2.2 gene) is required for spermidine's suppression of protein hyperacetylation and developmental arrest in the cts-1 RNAi embryos. Taken together, these results suggest the possibility that during early embryogenesis, acetyl-CoA consumption by the TCA cycle in C. elegans prevents protein hyperacetylation and thereby protects mitochondrial function.

Applying a radian phase shift other than 2π is a key issue for superconducting circuits, such as flux qubits. The magnetic flux is useful when generating a phase shift. However, a quantized magnetic flux accompanying a trapped vortex in a superconductor does not have a phase shifter function. The magnetic flux generated by an external field generates noise. In this study, we propose a phase bias system that does not require an external field during operation. We confirm the phase shift of a direct current superconducting interference device (SQUID) placed on an ultrathin superconducting Nb bilayer with a through-hole by cooling it to a temperature below the superconducting transition temperature with an external field. Although the cause of the phase shift in our system is unclear, we believe that it may be caused by a fractional quantum in the bilayer. When the SQUID is replaced by a qubit, the phase shift can be applied to a phase bias.

We previously designed and synthesized a series of histamine analogues with an imidazolylcyclopropane scaffold and identified potent non-selective antagonists for histamine H3 and H4 receptor subtypes. In this study, to develop H4 selective ligands, we newly designed and synthesized cyclopropane-based derivatives having an indole, benzimidazole, or piperazine structure, which are components of representative H4 selective antagonists such as JNJ7777120 and JNJ10191584. Among the synthesized derivatives, imidazolylcyclopropanes 12 and 13 conjugated with a benzimidazole showed binding affinity to the H3 and H4 receptors comparable to that of a well-known non-selective H3/H4 antagonist, thioperamide. These results suggest that the binding modes of the cyclopropane-based H3/H4 ligands in the H4 receptor can be different from those of the indole/benzimidazole-piperazine derivatives.

An ultrathin superconducting bilayer creates a coreless fractional vortex when only the second layer has a hole. The quantization is broken by the hole, and the normal core disappears. The magnetic flux is no longer confined near the normal core. The divergence of the magnetic flux density is truncated around the center. We propose basic design of a practical device to realize a coreless fractional vortex.

An ultrathin superconducting bilayer can admit a monotonic magnetic field when one layer has a slit even in a Meissner state. The rotation of the superconducting quantum phase by a vector potential for the magnetic field is compensated by a phase shift accompanying an inter-layer phase difference mode which grows from the slit. This phase difference mode may grow to form a fractional vortex, and it may show a close relationship with experimentally observed fractional vortices.

Background Whole body vibration (WBV) has been widely used as a modality for physical activity. In fact, WBV has been used for physical rehabilitation, and to improve muscle performance; but there is little information about its effects on heart rate variability (HRV). Aim The aim of this study was to evaluate the effect of vibration on HRV of the elderly using the vibratory platform. Methods Eleven older adults (7 men, 4 women), aged between 60 and 75 years, were subjected to WBV. The study consisted of a single session of WBV with volunteers standing upright for 10 min on the oscillating platform, with frequency of vibration set at 20 Hz (displacement ± 6 mm; orbital vibration). Pre (baseline) and post-WBV electrocardiograph signals were acquired using a cardiac monitor; and data were statistically analyzed using paired Student's t-test or Wilcoxon test, as appropriate. Results The results demonstrated an increase in SDNN (standard deviation (SD) beat-to-beat, N–N intervals), rMSSD (square root of the mean squared difference of successive N–Ns) and pNN50 (proportion of N–N50 divided by total number of N–Ns) post WBV (p = 0.032, p = 0.024 e p = 0.044, respectively), compared to baseline. The present study thus demonstrated that time domain variables (i.e., SDNN, rMSSD, and pNN50) increase post WBV. Conclusions Older individuals are at high risk of developing cardiovascular diseases. As seen in the study, WBV improves HRV; and may help reduce risk of cardiac ailments. Moreover, WBV does not require extensive physical activity on the part of the participant. This makes WBV potentially beneficial to the elderly population. Further studies on WBV using different frequencies and training schedules may improve its applicability in clinics.

We report the experimental formation of a fractional vortex generated by using a thin superconducting bi-layer in the form of a niobium bi-layer, observed as a magnetic flux distribution image taken by a scanning superconducting quantum interference device (SQUID) microscope. Thus, we demonstrated that multi-component superconductivity can be realized by an s-wave conventional superconductor, because, in these superconductors, the magnetic flux is no longer quantized as it is destroyed by the existence of an inter-component phase soliton (i-soliton).

Spinal cord injury is a significant public health issue with high psychological and financial costs to both the family and the society. Effective treatment strategies are hence of immense value. Several reports have suggested application of amniotic membrane for treating injuries, and there is evidence that it may be used to treat spinal injuries. In this animal model study, we explore biochemical changes in amniotic membrane treated injured spinal cord with respect to untreated injured and uninjured spinal cord using Raman spectroscopy. Multivariate statistical analysis is able to classify control, untreated, and treated with 92%, 87%, and 80% efficiency, respectively; suggesting unique biochemical changes in each group. Such studies may lead to development of minimally invasive methodologies for spinal cord injury treatment monitoring.