Uremic pruritus is a very common and frustrating condition for both patients and clinicians because no treatment has been demonstrated to be effective in relieving the itch. In this report, nalfurafine, a new -opioid receptor agonist, was used to treat uremic pruritus in patients who were undergoing routine hemodialysis. Two multicenter, randomized, double-blind, placebocontrolled studies enrolled 144 patients with uremic pruritus to postdialysis intravenous treatment with either nalfurafine or placebo for 2 to 4 wk. A meta-analysis approach was used to assess the efficacy of nalfurafine. Statistically significant reductions in worst itching (P ‫؍‬ 0.0212), itching intensity (P ‫؍‬ 0.0410), and sleep disturbances (P ‫؍‬ 0.0003) were noted in the nalfurafine group as compared with placebo. Improvements in itching (P ‫؍‬ 0.0025) and excoriations (P ‫؍‬ 0.0060) were noted for the nalfurafine-treated patients. Nalfurafine showed similar types and incidences of drug-related adverse events as did placebo. Nalfurafine was shown to be an effective and safe compound for use in this severely ill patient population. U remic pruritus has a major impact on the quality of life in patients who already have a compromised lifestyle (1-5). It is, of itself, not a life-threatening condition; however, it is known to contribute to an increase in morbidity (6) and mortality (7) of uremic patients. The only current definitive treatment for uremic pruritus is successful renal transplantation (8). Increasing the dialysis dose as well as implementing other therapeutic measures to lessen the symptoms, some as extraordinary as acupressure, (9) have provided only limited effectiveness in dialysis patients.Stimulation of the -opioid receptor in the brain and/or peripheral nerve endings by its agonists, such as morphine, can result in itching (10 -12). -Opioid receptor antagonists can inhibit itching induced by substance P (13). -Opioid stimulation inhibits -receptor effects both centrally and peripherally (11). Nalfurafine, a new -opioid receptor agonist, was effective in reducing the scratching behavior induced by an injection of substance P in the mouse model (13,14). From these findings, it was hypothesized that uremic pruritus could be triggered and sustained by the release of substance P (15). This led to the studies in the treatment of uremic pruritus using nalfurafine. Materials and Methods Study Design and TreatmentsTwo multicenter, randomized, double-blind, placebo-controlled clinical studies were performed with the common objective of assessing the efficacy and the safety of nalfurafine, as compared with placebo, in the treatment of uremic pruritus. The inclusion and exclusion criteria and the evaluations, methods of evaluations, and times of evaluations were the same in both studies.Patients were males and females who were at least 18 yr of age and undergoing routine hemodialysis secondary to ESRD and had severe, uncontrolled pruritus caused only by ESRD. Female patients were not of childbearing potential or were using an acceptab...

A comparative analysis of animal behavior (e.g., male vs. female groups) has been widely used to elucidate behavior specific to one group since pre-Darwinian times. However, big data generated by new sensing technologies, e.g., GPS, makes it difficult for them to contrast group differences manually. This study introduces DeepHL, a deep learning-assisted platform for the comparative analysis of animal movement data, i.e., trajectories. This software uses a deep neural network based on an attention mechanism to automatically detect segments in trajectories that are characteristic of one group. It then highlights these segments in visualized trajectories, enabling biologists to focus on these segments, and helps them reveal the underlying meaning of the highlighted segments to facilitate formulating new hypotheses. We tested the platform on a variety of trajectories of worms, insects, mice, bears, and seabirds across a scale from millimeters to hundreds of kilometers, revealing new movement features of these animals.

Multiple mazes are routinely used to test the performance of animals because each has disadvantages inherent to its shape. However, the maze shape cannot be flexibly and rapidly reproduced in a repeatable and scalable way in a single environment. Here, to overcome the lack of flexibility, scalability, reproducibility, and repeatability, we develop a reconfigurable maze system that consists of interlocking runways and an array of accompanying parts. It allows experimenters to rapidly and flexibly configure a variety of maze structures along the grid pattern in a repeatable and scalable manner. Spatial navigational behavior and hippocampal place coding were not impaired by the interlocking mechanism. As a proof-of-principle demonstration, we demonstrate that the maze morphing induces location remapping of the spatial receptive field. The reconfigurable maze thus provides flexibility, scalability, repeatability, and reproducibility, therefore facilitating consistent investigation into the neuronal substrates for learning and memory and allowing screening for behavioral phenotypes.

Animals exhibit remarkable navigation abilities as if they have an internal compass. Head direction (HD) cells encoding the animal’s heading azimuth are found in the brain of several animal species; the HD cell signals are dependent on the vestibular nuclei, where magnetic responsive cells are present in birds. However, it is difficult to determine whether HD cell signals drive the compass orientation in animals, as they do not necessarily rely on the magnetic compass under all circumstances. Recording of HD cell activities from the medial pallium of shearwater chicks ( Calonectris leucomelas ) just before their first migration, during which they strongly rely on compass orientation, revealed that shearwater HD cells prefer a north orientation. The preference remained stable regardless of geolocations and environmental cues, suggesting the existence of a magnetic compass regulated by internally generated HD signals. Our findings provide insight into the integration of the direction and magnetoreception senses.

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