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1 Intrathecal (i.t.) administration of nociceptin and high doses of morphine induced allodynia in response to innocuous tactile stimuli, and i.t. nociceptin evoked hyperalgesia in response to noxious thermal stimuli in conscious mice. Here we have characterized the nociceptin-induced allodynia and compared it with the morphine-induced allodynia and the nociceptin-evoked hyperalgesia. 2 Nociceptin-induced allodynia was evoked by the ®rst stimulus 5 min after i.t. injection, reached a maximum at 10 min, and continued for a 50 min experimental period. Dose-dependency of the allodynia showed a bell-shaped pattern from 50 pg to 5 ng kg 71 , and the maximum e ect was observed at 2.5 ng kg 71 . 3 Morphine-induced allodynia reached the maximum e ect at 15 min and declined progressively until cessation by 40 ± 50 min. The dose-response curve showed a bell-shaped pattern, similar to that induced by nociceptin, with a maximum e ect at 0.5 mg kg 71 , ®ve orders of magnitude higher than that of nociceptin. 4 The allodynia evoked by nociceptin and morphine were dose-dependently blocked by glycine, D(7)-2-amino-5-phosphonovaleric acid (D-AP5, an N-methyl-D-aspartate (NMDA) receptor antagonist), g-Dglutamylaminomethyl sulphonic acid (GAMS, a non-NMDA receptor antagonist) and methylene blue (a soluble guanylate cyclase inhibitor), but were not a ected by muscimol (a g-aminobutyric acid A (GABA A ) receptor agonist) and baclofen (a GABA B receptor agonist). 5 Morphine did not inhibit forskolin-stimulated cyclicAMP formation in cultured cells expressing the nociceptin receptor. 6 Nociceptin-induced hyperalgesia was evoked 10 ± 15 min after i.t. injection. Nociceptin produced a monophasic hyperalgesic action over a wide range of doses from 5 fg to 50 ng kg 71 . The nociceptininduced hyperalgesia was blocked by glycine only among the agents examined. 7 None of the pain responses evoked by nociceptin and morphine were blocked by naloxone. 8 These results demonstrate that, whereas the mechanisms of the nociceptin-induced allodynia and hyperalgesia are evidently distinct, they involve a common neurochemical event beginning with the disinhibition of the inhibitory glycinergic response. Morphine may induce allodynia through a pathway common to nociceptin, but the nociceptin receptor does not mediate the action of high doses of morphine.

The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2020 (J‐SSCG 2020), a Japanese‐specific set of clinical practice guidelines for sepsis and septic shock created as revised from J‐SSCG 2016 jointly by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine, was first released in September 2020 and published in February 2021. An English‐language version of these guidelines was created based on the contents of the original Japanese‐language version. The purpose of this guideline is to assist medical staff in making appropriate decisions to improve the prognosis of patients undergoing treatment for sepsis and septic shock. We aimed to provide high‐quality guidelines that are easy to use and understand for specialists, general clinicians, and multidisciplinary medical professionals. J‐SSCG 2016 took up new subjects that were not present in SSCG 2016 (e.g., ICU‐acquired weakness [ICU‐AW], post‐intensive care syndrome [PICS], and body temperature management). The J‐SSCG 2020 covered a total of 22 areas with four additional new areas (patient‐ and family‐centered care, sepsis treatment system, neuro‐intensive treatment, and stress ulcers). A total of 118 important clinical issues (clinical questions, CQs) were extracted regardless of the presence or absence of evidence. These CQs also include those that have been given particular focus within Japan. This is a large‐scale guideline covering multiple fields; thus, in addition to the 25 committee members, we had the participation and support of a total of 226 members who are professionals (physicians, nurses, physiotherapists, clinical engineers, and pharmacists) and medical workers with a history of sepsis or critical illness. The GRADE method was adopted for making recommendations, and the modified Delphi method was used to determine recommendations by voting from all committee members. As a result, 79 GRADE‐based recommendations, 5 Good Practice Statements (GPS), 18 expert consensuses, 27 answers to background questions (BQs), and summaries of definitions and diagnosis of sepsis were created as responses to 118 CQs. We also incorporated visual information for each CQ according to the time course of treatment, and we will also distribute this as an app. The J‐SSCG 2020 is expected to be widely used as a useful bedside guideline in the field of sepsis treatment both in Japan and overseas involving multiple disciplines.

(Ca1- x Nd2 x /3)TiO3 sintered samples are fabricated with 0≦x≦1 and the crystal structure and dielectric properties are investigated. It is shown that (Ca1- x Nd2 x /3)TiO3 has an orthorhombic GdFeO3-type structure for 0≦x≦0.69 and an La2/3TiO3-type double-layered perovskite structure for 0.78≦x≦0.93. High ε and high f Q values are obtained for the GdFeO3 phase of (Ca1- x Nd2 x /3)TiO3, e.g., ε=108 and f Q=17200 GHz for x=0.39. On the other hand, for the La2/3TiO3 phase, ε is between 80 and 100 and f Q is below 1000 GHz.