[Evaluation of Diffusional Kurtosis Inference Using Synthetic q-space Learning and Bias Correction].

PURPOSE: In synthetic q-space learning (synQSL), which uses deep learning to infer the diffusional kurtosis (K), a bias that depends on the noise level added to the synthetic training data occurs. The purpose of this study was to evaluate K inference using synQSL and bias correction. METHODS: Using the synthetic test data and the real image data, K was inferred by synQSL, and bias correction was performed. Then, those results were compared with K inferred by fitting by the least-squares fitting (LSF) method. At this time, the noise level of the training data was set to 3 types, the noise level of the synthesis test data was set to 5 types, and the number of excitation (NEX) of the real image data was set to 4 types. Robustness of inference was evaluated by the outlier rate, which is the ratio of K outliers to the whole brain. We also evaluated the root mean square error (RMSE) of the inferred K. RESULTS: The outlier rate inferred by synQSL without correction was significantly lower in the test data of each noise level than that by the LSF method and was further reduced by correction. In addition, the RMSE of NEX 1 with NEX 4 as the correct answer based on the real image data had the smallest correction result of K by synQSL. CONCLUSION: Inferring K using synQSL and bias correction is a robust and small error method compared to that using the LSF method.

Anterior capsule coverage and rotational stability of an acrylic toric intraocular lens.

PURPOSE: To investigate factors related to the rotational stability of an acrylic toric intraocular lens (IOL). SETTING: Four ophthalmic surgical sites in Japan. DESIGN: Prospective case series. METHODS: The study included 120 eyes of 120 patients undergoing phacoemulsification and implantation of a toric IOL (AcrySof IQ, Alcon Laboratories, Inc.). At 1 hour postoperatively, the area of continuous curvilinear capsulorhexis (CCC) was measured, and the state of anterior capsule coverage on the IOL optic (total on or partial on) was recorded. The toric IOL axis orientation was assessed at the end of surgery and at 1 hour, 1 week, 1 month, and 6 months postoperatively. Multiple regression analysis was performed to explore any clinical factors relevant to IOL rotation from the end of surgery to 6 months postoperatively. The explanatory variables included age, anterior chamber depth preoperatively, axial length, type of corneal astigmatism (with-the-rule, against-the-rule, or oblique astigmatism), area of CCC, state of anterior capsule overlap on IOL optic (total coverage vs partial coverage), and surgical sites (surgeons). RESULTS: The multiple regression analysis in 110 eyes of 110 patients indicated that anterior capsule overlap on the IOL optic was the only variable associated with IOL rotation at 6 months postoperatively (P = .0482). The mean absolute rotation at 6 months was 1.96 ± 1.81 degrees in the total on group and 3.79 ± 3.12 degrees in the partial on group (P = .0004). CONCLUSIONS: Rotational stability of a single-piece, acrylic toric IOL was better in eyes with total anterior capsule coverage than that in those with partial anterior capsule coverage on the IOL optic.

Clarifying the structure of serious head and spine injury in youth Rugby Union players.

This study aimed to clarify the cause of rugby head and spinal cord injuries through a network centrality analysis of 14-year (2004-2018) longitudinal data in Japan. The study hypothesis is that understanding the causal relationship among the occurrence of serious injuries, the quality of player experience and play situation as a network structure could be possible to obtain practical knowledge on injury prevention. In this study, bipartite graphs are used to make it easier to understand the situation of players and injuries. This would also help to elucidate more characteristic subgroup. A network bipartite graph and subgroup (cluster) analyses were performed to clarify the injured players' experience and the cause of injury. We used the algorithm of R program, IGRAPH, clustering edge betweenness. For subgroup extraction, the modularity Q value was used to determine which step to cut. The Japanese rugby population was 93,873 (2014-2018 average), and 27% were high school students. The data showed that careful attention would be particularly needed for groups of inexperienced Japanese high school players. Our study suggests that we should consider introducing rules that prohibit "head-on collisions" in youth rugby.

QRFP-Deficient Mice Are Hypophagic, Lean, Hypoactive and Exhibit Increased Anxiety-Like Behavior.

How the hypothalamus transmits hunger information to other brain regions to govern whole brain function to orchestrate feeding behavior has remained largely unknown. Our present study suggests the importance of a recently found lateral hypothalamic neuropeptide, QRFP, in this signaling. Qrfp-/- mice were hypophagic and lean, and exhibited increased anxiety-like behavior, and were hypoactive in novel circumstances as compared with wild type littermates. They also showed decreased wakefulness time in the early hours of the dark period. Histological studies suggested that QRFP neurons receive rich innervations from neurons in the arcuate nucleus which is a primary region for sensing the body's metabolic state by detecting levels of leptin, ghrelin and glucose. These observations suggest that QRFP is an important mediator that acts as a downstream mediator of the arcuate nucleus and regulates feeding behavior, mood, wakefulness and activity.

VDAC: old protein with new roles in diabetes.

A decrease in capillary density due to an increase in endothelial cell apoptosis in the heart is implicated in cardiac ischemia in diabetes. The voltage-dependent anion channel (VDAC) plays a crucial role in the regulation of mitochondrial metabolic function and mitochondria-mediated apoptosis. This study is designed to examine the role of VDAC in coronary endothelial dysfunction in diabetes. Endothelial cells (ECs) were more apoptotic in diabetic left ventricle of diabetic mice and mouse coronary ECs (MCECs) isolated from diabetic mice exhibited significantly higher mitochondrial Ca(2+) concentration and VDAC protein levels than control MCECs. The expression of VDAC-short hairpin RNA (shRNA) not only decreased the resting mitochondrial Ca(2+) concentration but also attenuated mitochondrial Ca(2+) uptake in diabetic MCECs. Furthermore, the downregulation of VDAC in diabetic MCECs significantly decreased mitochondrial superoxide anion (O(2)(-)) production and the activity of the mitochondrial permeability transition pore (mPTP) opening (an indirect indicator of cell apoptosis) toward control levels. These data suggest that the increased VDAC level in diabetic MCECs is responsible for increased mitochondrial Ca(2+) concentration, mitochondrial O(2)(-) production, and mPTP opening activity. Normalizing VDAC protein level may help to decrease endothelial cell apoptosis, increase capillary density in the heart, and subsequently decrease the incidence of cardiac ischemia in diabetes.

Pharmacogenetic modulation of orexin neurons alters sleep/wakefulness states in mice.

Hypothalamic neurons expressing neuropeptide orexins are critically involved in the control of sleep and wakefulness. Although the activity of orexin neurons is thought to be influenced by various neuronal input as well as humoral factors, the direct consequences of changes in the activity of these neurons in an intact animal are largely unknown. We therefore examined the effects of orexin neuron-specific pharmacogenetic modulation in vivo by a new method called the Designer Receptors Exclusively Activated by Designer Drugs approach (DREADD). Using this system, we successfully activated and suppressed orexin neurons as measured by Fos staining. EEG and EMG recordings suggested that excitation of orexin neurons significantly increased the amount of time spent in wakefulness and decreased both non-rapid eye movement (NREM) and rapid eye movement (REM) sleep times. Inhibition of orexin neurons decreased wakefulness time and increased NREM sleep time. These findings clearly show that changes in the activity of orexin neurons can alter the behavioral state of animals and also validate this novel approach for manipulating neuronal activity in awake, freely-moving animals.

Coordinated intracellular translocation of phosphoinositide-specific phospholipase C-delta with the cell cycle.

The delta family phosphoinositide (PI)-specific phospholipase C (PLC) are most fundamental forms of eukaryotic PI-PLCs. Despite the presence of lipid targeting domains such as the PH domain and C2 domain, the isoforms are also found in the cytoplasm and nucleus as well as at the plasma membrane. The isoforms have sequences or regions that can serve as a nuclear localization signal (NLS) and a nuclear export signal (NES). Their intracellular localization differs from one isoform to another, presumably due to the difference in the transport equilibrium balanced by the strength of the two signals of each isoform. Even for a particular isoform, its intracellular localization seems to vary during the cell cycle. As an example, PLCdelta(1), which is generally found at the plasma membrane and in the cytoplasm of quiescent cells, localizes to discrete nuclear structures in the G(1)/S boundary of the cell cycle. This may be at least partly due to an increase in intracellular Ca(2+), since Ca(2+) facilitates the formation of a nuclear transport complex comprised of PLCdelta(1) and importin beta1, a carrier molecule for the nuclear import. PLCdelta(1) as well as PLCdelta(4) may play a pivotal role in controlling the initiation of DNA synthesis in S phase. Spatio-temporal changes in the levels of PtdIns(4,5)P(2) seem to be another major determinant for the localization and regulation of the delta isoforms. High nuclear PtdIns(4,5)P(2) levels are associated with the G(1)/S phases. After entering M phase, PtdIns(4,5)P(2) synthesis at sites of cell division occurs and PLCs seem to localize to the cleavage furrow during cytokinesis. Coordinated translocation of PLCs with the cell cycle or with stress responses may result in changes in intra-nuclear environments and local membrane architectures that modulate proliferation and differentiation. In this review, recent findings regarding the molecular machineries and mechanisms of the nucleocytoplasmic shuttling as well as roles in the cell cycle progression of the delta isoforms of PLC will be discussed.