Search

Abstract Objective Duchenne muscular dystrophy (DMD) is a progressive muscular disease characterized by chronic cycles of inflammatory and necrotic processes. Prostaglandin D2 (PGD2) is produced by hematopoietic PGD synthase (HPGDS), which is pathologically implicated in muscle necrosis. This randomized, double‐blind, placebo‐controlled early phase 2 study (NCT02752048) aimed to assess the efficacy and safety of the novel selective HPGDS inhibitor, TAS‐205, with exploratory measures in male DMD patients aged ≥5 years. Methods Patients were randomized 1:1:1 to receive low‐dose TAS‐205 (6.67–13.33 mg/kg/dose), high‐dose TAS‐205 (13.33–26.67 mg/kg/dose), or placebo. The primary endpoint was the change from baseline in a 6‐minute walk distance (6MWD) at Week 24. Results Thirty‐six patients were enrolled, of whom 35 patients were analysed for safety. The mean (standard error) changes from baseline to Week 24 in 6MWD were −17.0 (17.6) m in the placebo group (n = 10), −3.5 (20.3) m in the TAS‐205 low‐dose group (n = 11), and −7.5 (11.2) m in the TAS‐205 high‐dose group (n = 11). The mean (95% confidence interval) difference from the placebo group was 13.5 (−43.3 to 70.2) m in the TAS‐205 low‐dose group and 9.5 (−33.3 to 52.4) m in the TAS‐205 high‐dose group. No obvious differences were observed in the incidences of adverse events between treatment groups. No adverse drug reactions specific to TAS‐205 treatment were observed. Interpretation The HPGDS inhibitor TAS‐205 showed a favorable safety profile in DMD patients. Further research is required to examine the effectiveness of TAS‐205 in a larger trial.

This study investigated whether the motor execution process of one finger movement in response to a start cue is influenced by the participation of another finger movement and whether the process of the finger movement is dependent on the movement direction. The participants performed a simple reaction time (RT) task, the abduction or flexion of one (index or little finger) or two fingers (index and little fingers). The RT of the prime mover for the finger abduction was significantly longer than that for the flexion, indicating that the time taken for the motor execution of the finger response is dependent on the movement direction. The RT of the prime mover was prolonged when the abduction of another finger, whose RT was longer than the flexion, was added. This caused closer RTs between the prime movers for a two-finger response compared with the RTs for a one finger response. The absolute difference in the RT between the index and little finger responses became smaller when two fingers responded together compared with one finger response. Those results are well explained by a view that the common motor drive triggers the prime movers when two fingers move together in response to a start cue.

The present study investigated whether the long-interval interhemispheric inhibition (LIHI) is induced by the transcranial magnetic stimulation over the primary sensory area (S1-TMS) without activation of the conditioning side of the primary motor area (M1) contributing to the contralateral motor evoked potential (MEP), whether the S1-TMS-induced LIHI is dependent on the status of the S1 modulated by the tactile input, and whether the pathways mediating the LIHI are different from those mediating the M1-TMS-induced LIHI. In order to give the TMS over the S1 without eliciting the MEP, the intensity of the S1-TMS was adjusted to be the sub-motor-threshold level and the trials with the MEP response elicited by the S1-TMS were discarded online. The LIHI was induced by the S1-TMS given 40 ms before the test TMS in the participants with the attenuation of the tactile perception of the digit stimulation (TPDS) induced by the S1-TMS, indicating that the LIHI is induced by the S1-TMS without activation of the conditioning side of the M1 contributing to the contralateral MEP in the participants in which the pathways mediating the TPDS is sensitive to the S1-TMS. The S1-TMS-induced LIHI was positively correlated with the attenuation of the TPDS induced by the S1-TMS, indicating that the S1-TMS-induced LIHI is dependent on the effect of the S1-TMS on the pathways mediating the TPDS at the S1. In another experiment, the effect of the digit stimulation given before the conditioning TMS on the S1- or M1-TMS-induced LIHI was examined. The digit stimulation produces tactile input to the S1 causing change in the status of the S1. The S1-TMS-induced LIHI was enhanced when the S1-TMS was given in the period in which the tactile afferent volley produced by the digit stimulation just arrived at the S1, while the LIHI induced by above-motor-threshold TMS over the contralateral M1 was not enhanced by the tactile input. Thus, the S1-TMS-induced LIHI is dependent on the status of the S1 modulated by the tactile input, and the pathways mediating the sub-motor-threshold S1-TMS-induced LIHI are not the same as the pathways mediating the above-motor-threshold M1-TMS-induced LIHI.

Immature stages of Laccobius (Laccobius) kunashiricus Shatrovskiy, 1984 are described based on specimens reared from adults collected in the fi eld. The egg-case, all larval instars and pupa are described in detail, including primary and secondary chaetotaxy of the larval head. The biology of the species was observed and is briefl y discussed. We also summarize the knowledge of immature stages of Laccobius Erichson, 1837 and provide a key to identify larvae of the known Laccobiini genera. [ABSTRACT FROM AUTHOR]

Immature stages of Laccobius (Laccobius) kunashiricus Shatrovskiy, 1984 are described based on specimens reared from adults collected in the field. The egg-case, all larval instars and pupa are described in detail, including primary and secondary chaetotaxy of the larval head. The biology of the species was observed and is briefly discussed. We also summarize the knowledge of immature stages of Laccobius Erichson, 1837 and provide a key to identify larvae of the known Laccobiini genera. [ABSTRACT FROM AUTHOR]