The effect of lemborexant on insomnia in patients with psychiatric disorders: Detailed evaluation using the Athens Insomnia Scale.

Aim: Chronic insomnia disorder is common and associated with reduced quality of life. Benzodiazepine hypnotics are commonly prescribed for insomnia, but have potential side effects such as concentration impairment, somnolence, and dependence. Lemborexant (LEM) is an orexin receptor antagonist considered to have fewer side effects than benzodiazepine hypnotics. This study evaluated the effect of LEM on sleep in detail and examined whether benzodiazepine hypnotics can be gradually tapered by adding LEM. Methods: We retrospectively examined the effectiveness of LEM in 28 outpatients with insomnia. Insomnia symptoms were assessed using the Athens Insomnia Scale (AIS) before and after LEM administration. We also attempted to taper benzodiazepine hypnotics and assessed benzodiazepine dose using diazepam equivalents for some patients taking benzodiazepine hypnotics. Wilcoxon's signed-rank test was used for statistical analysis. Results: The mean AIS score was significantly improved after LEM treatment (8.7 ± 5.2 vs. 3.8 ± 3.3; P < 0.01). Among the AIS subitems, significant improvement was observed for six items: sleep induction, awakenings during the night, sleep quality, well-being, functioning capacity, and sleepiness during the day. The mean benzodiazepine dose was significantly lower after LEM treatment (4.6 ± 5.0 mg vs. 2.1 ± 3.3 mg; P < 0.01). Conclusions: This study indicated the potential of LEM for improving insomnia and reducing benzodiazepine dose.

Evaluation of dye decolorization using anaerobic granular sludge from an expanded granular sludge bed based on spectrometric and microbiome analyses.

The decolorization of 11 dyes by granular sludge from an anaerobic expanded granular sludge bed (EGSB) reactor was evaluated. Biological decolorization of Reactive Red 21, 23, and 180, and Reactive Yellow 15, 17, and 23 in model textile wastewater was observed for the first time after a 7-day incubation (over 94% decolorization). According to the sequencing analysis of 16S rRNA gene amplicons from EGSB granular sludge, the operational taxonomic unit related to Paludibacter propionicigenes showed the highest increase in relative abundance ratios in the presence of dyes (7.12 times on average over 11 dyes) compared to those without dyes.

Associative anticipatory learning and control of the cerebellar cortex based on the spike-timing-dependent plasticity of the parallel fiber-Purkinje cell synapses.

Time delays are inevitable in the neural processing of sensorimotor systems; small delays can cause severe damage to movement accuracy and stability. It is strongly suggested that the cerebellum compensates for delays in neural signal processing and performs predictive control. Neural computational theories have explored concepts of the internal models of control objects-believed to avoid delays by providing internal feedback information-although there has been no clear relevance to neural processing. The timing-dependent plasticity of parallel fiber-Purkinje cell synapses is well known. The long-term depression of the synapse is observed when parallel fiber activation precedes climbing fiber activation within -50-300 ms, and is the greatest within 50-200 ms. This paper presents a theory that this temporal difference of 50-200 ms is the basis for an associative anticipation of as many milliseconds. Associative learning can theoretically connect an input signal to a desired signal; therefore, a 50-200 ms earlier input signal can be connected to a desired output signal through temporary asymmetric plasticity. After learning is completed, an input signal generates a desired output signal that appears 50-200 ms later. For the associative learning of temporally continuous signals, this study integrates the universal function approximation capability of the cerebellar cortex model and temporally asymmetric synaptic plasticity to create the theory of associative anticipatory learning of the cerebellum. The effective motor control of this learning is demonstrated by adaptively stabilizing an inverted pendulum with a delay similar to that done by humans.

Effects of supplemental ß-carotene on colostral immunoglobulin and plasma ß-carotene and immunoglobulin in Japanese Black cows.

Data from 26 Japanese Black cows were collected to clarify the effects of supplemental ß-carotene on colostral immunoglobulin (Ig) and plasma ß-carotene and Ig in the cows. Cows were assigned to control or ß-carotene groups from 21 days before the expected calving date to 60 days after parturition. Supplemental ß-carotene was provided at 500 mg/day in the ß-carotene group. Supplemental ß-carotene drastically increased plasma ß-carotene concentrations in the cows from parturition to 60 days after parturition, and plasma ß-carotene concentrations in the control and ß-carotene groups at parturition were 202 and 452 µg/dl, respectively. Supplemental ß-carotene had no effects on plasma IgG1 , IgA or IgM concentrations at parturition. Supplemental ß-carotene increased colostral IgG1 concentrations in the cows, but colostral ß-carotene, IgA and IgM concentrations were not affected by supplemental ß-carotene. These results indicate that supplemental ß-carotene is effective to enhance colostral IgG1 concentrations and plasma ß-carotene concentrations in Japanese Black cows.

Effects of ß-carotene-enriched dry carrots on ß-carotene status and colostral immunoglobulin in ß-carotene-deficient Japanese Black cows.

Data from 18 ß-carotene-deficient Japanese Black cows were collected to clarify the effects of feeding ß-carotene-enriched dry carrots on ß-carotene status and colostral immunoglobulin (Ig) in cows. Cows were assigned to control or carrot groups from 3 weeks before the expected calving date to parturition, and supplemental ß-carotene from dry carrots was 138 mg/day in the carrot group. Plasma ß-carotene concentrations in the control and carrot groups at parturition were 95 and 120 µg/dL, and feeding dry carrots slightly improved plasma ß-carotene at parturition. Feeding dry carrots increased colostral IgA concentrations in cows and tended to increase colostral IgG1 , but colostral IgM, IgG2 , ß-carotene and vitamin A were not affected by the treatment. Feeding dry carrots had no effects on plasma IgG1 , IgA and IgM concentrations in cows, but plasma IgG1 concentrations decreased rapidly from 3 weeks before the expected calving date to parturition. These results indicate that feeding ß-carotene-enriched dry carrots is effective to enhance colostral IgA and IgG1 concentrations in ß-carotene-deficient cows.

A theory of cerebellar cortex and adaptive motor control based on two types of universal function approximation capability.

Lesions of the cerebellum result in large errors in movements. The cerebellum adaptively controls the strength and timing of motor command signals depending on the internal and external environments of movements. The present theory describes how the cerebellar cortex can control signals for accurate and timed movements. A model network of the cerebellar Golgi and granule cells is shown to be equivalent to a multiple-input (from mossy fibers) hierarchical neural network with a single hidden layer of threshold units (granule cells) that receive a common recurrent inhibition (from a Golgi cell). The weighted sum of the hidden unit signals (Purkinje cell output) is theoretically analyzed regarding the capability of the network to perform two types of universal function approximation. The hidden units begin firing as the excitatory inputs exceed the recurrent inhibition. This simple threshold feature leads to the first approximation theory, and the network final output can be any continuous function of the multiple inputs. When the input is constant, this output becomes stationary. However, when the recurrent unit activity is triggered to decrease or the recurrent inhibition is triggered to increase through a certain mechanism (metabotropic modulation or extrasynaptic spillover), the network can generate any continuous signals for a prolonged period of change in the activity of recurrent signals, as the second approximation theory shows. By incorporating the cerebellar capability of two such types of approximations to a motor system, in which learning proceeds through repeated movement trials with accompanying corrections, accurate and timed responses for reaching the target can be adaptively acquired. Simple models of motor control can solve the motor error vs. sensory error problem, as well as the structural aspects of credit (or error) assignment problem. Two physiological experiments are proposed for examining the delay and trace conditioning of eyelid responses, as well as saccade adaptation, to investigate this novel idea of cerebellar processing.

Organoclays in water cause expansion that facilitates caffeine adsorption.

This study investigates the adsorption of caffeine in water on organically modified clays (a natural montmorillonite and synthetic saponite, which are smectite group of layered clay minerals). The organoclays were prepared by cation-exchange reactions of benzylammonium and neostigmine with interlayer exchangeable cations in the clay minerals. Although less caffeine was uptaken on neostigmine-modified clays than on raw clay minerals, uptake was increased by adding benzylammonium to the clays. The adsorption equilibrium constant was considerably higher on benzylammonium-modified saponite (containing small quantities of intercalated benzylammonium) than on its montmorillonite counterpart. These observations suggest that decreasing the size and number of intercalated cations enlarges the siloxane surface area available for caffeine adsorption. When the benzylammonium-smectite powders were immersed in water, the intercalated water molecules expanded the interlayer space. Addition of caffeine to the aqueous dispersion further expanded the benzylammonium-montmorillonite system but showed no effect on benzylammonium-saponite. We assume that intercalated water molecules were exchanged with caffeine molecules. By intercalating benzylammonium into smectites, we have potentially created an adaptable two-dimensional nanospace that sequesters caffeine from aqueous media.

New supervised learning theory applied to cerebellar modeling for suppression of variability of saccade end points.

A new supervised learning theory is proposed for a hierarchical neural network with a single hidden layer of threshold units, which can approximate any continuous transformation, and applied to a cerebellar function to suppress the end-point variability of saccades. In motor systems, feedback control can reduce noise effects if the noise is added in a pathway from a motor center to a peripheral effector; however, it cannot reduce noise effects if the noise is generated in the motor center itself: a new control scheme is necessary for such noise. The cerebellar cortex is well known as a supervised learning system, and a novel theory of cerebellar cortical function developed in this study can explain the capability of the cerebellum to feedforwardly reduce noise effects, such as end-point variability of saccades. This theory assumes that a Golgi-granule cell system can encode the strength of a mossy fiber input as the state of neuronal activity of parallel fibers. By combining these parallel fiber signals with appropriate connection weights to produce a Purkinje cell output, an arbitrary continuous input-output relationship can be obtained. By incorporating such flexible computation and learning ability in a process of saccadic gain adaptation, a new control scheme in which the cerebellar cortex feedforwardly suppresses the end-point variability when it detects a variation in saccadic commands can be devised. Computer simulation confirmed the efficiency of such learning and showed a reduction in the variability of saccadic end points, similar to results obtained from experimental data.

Efficacy and safety of pramipexole in Japanese patients with primary restless legs syndrome: A polysomnographic randomized, double-blind, placebo-controlled study.

OBJECTIVE: To evaluate the efficacy of pramipexole on polysomnographic measures, patient ratings and a clinical rating in Japanese patients with primary restless legs syndrome (RLS). METHODS: Patients with moderate to severe RLS having periodic limb movements in bed index (PLMI)>or=5 were randomly assigned to receive pramipexole or placebo in a 6-week, double-blind, placebo-controlled study with forced titration from 0.125 to 0.75mg/day. Both polysomnography (PSG) and the suggested immobilization test (SIT) were performed at baseline and 6weeks after starting treatment. RESULTS: The analysis of covariance of log-transformed PLMI showed that the adjusted means at the end of study were significantly smaller in the pramipexole group than in the placebo group (p=0.0019). In all patients, variables on SIT did not show any differences between the two groups, whereas a significant improvement was shown in the pramipexole group compared with the placebo group for patients with a SIT-PLM index at baseline >or=15. Pramipexole group showed a significant reduction in the International Restless Legs Syndrome Study Group rating scale (IRLS; p=0.0005), a significant improvement in both Patient Global Impression (PGI; p<0.0001) and Clinical Global Impressions (CGI-I; p=0.0488), and a significantly greater mean reduction in the Pittsburgh Sleep Quality Index (PSQI; p=0.0016), when compared with those of placebo group at week 6. CONCLUSIONS: Pramipexole is highly efficacious in the reduction of PLMI and in the improvement of subjective severity of RLS and subjective sleep disturbance caused by the disorder.

Some perspectives on saccade adaptation.

The saccadic system is an ideal model for the study of how the brain optimizes its motor behavior. Here we review some recent research that points to exciting new areas of investigation relative to the multiple time scales of and the influence of context and consolidation on motor learning. These findings suggest new ways of thinking about the processes that underlie the short-term adaptive mechanisms that maintain accuracy of eye movements and so ensure optimal vision.

The effect of one-dose package on medication adherence for the elderly care in Japan.

UNLABELLED: Deterioration of the medication adherence for elderly could result in wasteful medical expenditure in a long-term span as well as aggravating the patient's medical condition. OBJECTIVE: This study surveyed the effect of one-dose package medication made up by a pharmacist on the patient's behavior towards medication, what is expected to be one of the measures to improve the medication adherence for elderly. METHODS: With support activity of the Pharmacist Association in Ueda-city in Nagano Prefecture, Japan, the survey form of one-dose package was sent to 86 pharmacy directors located in Ueda-city. RESULTS: The most frequent reasons of one dose packaging was "Patient's request" though, "Large number of doses", "Prevent the improper drug use" and "Improved medication adherence" which is considered that the pharmacists are willing to utilize one dose package for patient's care in order to improve the medication adherence were chosen as well. The influences of one dose package for patient's medication adherence were very positive, and most answers indicated that medication adherence was improved. CONCLUSION: It is noticed that the pharmacists were willing to dispense one dose packaging by own decision, not physician's order, in order to improve the medication adherence, prevent improper drug use and optimize the medication therapy. It is also noticed that there are great improvement of patient's compliance by one dose package, and patients felt advantage to reduce the improper drug use as well.

Feed-forward associative learning for volitional movement control.

One of the most difficult problems in motor learning is determining the source of a learning signal, sometimes called an error signal. This problem is hidden in the adaptations of simple reflexive movements by attributing its source to sensory organs. The feed-forward associative motor learning theory proposed here attributes the source to the movement system itself. When a subject performs a corrective movement after his primary movement, the proposed neural learning device learns to associate the primary motor command with the corrective motor command by using a place-coding system. In the subsequent trials, the primary movement will involve a correction due to the participation of this mechanism, thus resulting in better performance. The theory assumes three conditions, namely, that a motor center and the learning device share the same place-encoded motor information; the motor center issues a command and a learning signal simultaneously from the same unit; and a learning signal issued with a corrective command has a heterosynaptic interaction with the previous primary command. The cerebellum is a reasonable candidate for the device satisfying these conditions. The reaction time of a corrective movement, usually 100-300 ms, almost satisfies the coincidence condition for long-term depression of the granule-to-Purkinje synapses. As an application, this theory is demonstrated to account for behavioral results regarding saccadic adaptation.

Selective and delay adaptation of human saccades.

The consistently triggered step back of a target during primary saccades of a human subject induced a gradual change in gain, the ratio of the saccade amplitude to the target eccentricity. After a few hundred trials, subjects were able to foveate the displaced target in a single saccade. Presentation of a displaced target showed that human memory guided saccades have gain adaptation just like the well-established adaptation of visually guided saccades. Examining the transfer of adaptation between the memory guided saccade and two other types of visually guided saccades showed that each saccade transferred a 10-25% adapted gain change to the other saccades. However, any pair of the three saccades acquired different gains by adaptation in the same horizontal direction simultaneously, hence each saccade had adaptive capability independent of the others. Adaptation took place even when the appearance of a displaced target was delayed by 400-600 ms from the end of a primary saccade. These findings have important implications about the adaptation, particularly the location and temporal property of the adaptive mechanism in saccade generation.