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Scapsipedus icipe Hugel and Tanga (Orthoptera: Gryllidae) is a newly described edible cricket species. Although, there is substantial interest in mass production of S. icipe for human food and animal feed, no information exists on the impact of temperature on their bionomics. Temperature-dependent development, survival, reproductive and life table parameters of S. icipe was generated and integrated into advanced Insect Life Cycle Modeling software to describe relative S. icipe population increase and spatial spread based on nine constant temperature conditions. We examined model predictions and implications for S. icipe potential distribution in Africa under current and future climate. These regions where entomophagy is widely practiced have distinctly different climates. Our results showed that S. icipe eggs were unable to hatch at 10 and 40°C, while emerged nymphs failed to complete development at 15°C. The developmental time of S. icipe was observed to decrease with increased in temperature. The lowest developmental threshold temperatures estimated using linear regressions was 14.3, 12.67 and 19.12°C and the thermal constants for development were 185.2, 1111.1- and 40.7-degree days (DD) for egg, nymph and pre-adult stages, respectively. The highest total fecundity (3416 individuals/female/generation), intrinsic rate of natural increase (0.075 days), net reproductive rate (1330.8 female/female/generation) and shortest doubling time (9.2 days) was recorded at 30°C. The regions predicted to be suitable by the model suggest that S. icipe is tolerant to a wider range of climatic conditions. Our findings provide for the first-time important information on the impact of temperature on the biology, establishment and spread of S. icipe across the Africa continent. The prospect of edible S. icipe production to become a new sector in food and feed industry is discussed.

Scapsipedus icipe Hugel and Tanga (Orthoptera: Gryllidae) is a newly described edible cricket species. Although, there is substantial interest in mass production of S. icipe for human food and animal feed, no information exists on the impact of temperature on their bionomics. Temperature-dependent development, survival, reproductive and life table parameters of S. icipe was generated and integrated into advanced Insect Life Cycle Modeling software to describe relative S. icipe population increase and spatial spread based on nine constant temperature conditions. We examined model predictions and implications for S. icipe potential distribution in Africa under current and future climate. These regions where entomophagy is widely practiced have distinctly different climates. Our results showed that S. icipe eggs were unable to hatch at 10 and 40°C, while emerged nymphs failed to complete development at 15°C. The developmental time of S. icipe was observed to decrease with increased in temperature. The lowest developmental threshold temperatures estimated using linear regressions was 14.3, 12.67 and 19.12°C and the thermal constants for development were 185.2, 1111.1- and 40.7-degree days (DD) for egg, nymph and pre-adult stages, respectively. The highest total fecundity (3416 individuals/female/generation), intrinsic rate of natural increase (0.075 days), net reproductive rate (1330.8 female/female/generation) and shortest doubling time (9.2 days) was recorded at 30°C. The regions predicted to be suitable by the model suggest that S. icipe is tolerant to a wider range of climatic conditions. Our findings provide for the first-time important information on the impact of temperature on the biology, establishment and spread of S. icipe across the Africa continent. The prospect of edible S. icipe production to become a new sector in food and feed industry is discussed. [ABSTRACT FROM AUTHOR]

Background: Some aspects regarding the use of antiplatelet agents after coil embolization for subarachnoid hemorrhage during admission remain unclear. This study used diagnostic procedure combination (DPC) data to investigate the safety and prognostic effects of aspirin monotherapy and aspirin and P2Y12 inhibitor combination therapy on bleeding events., Methods: This cross-sectional study used Japanese DPC data to assess patients who were hospitalized with subarachnoid hemorrhage and received aspirin monotherapy and aspirin and P2Y12 inhibitor combination therapy between April 2016 and March 2020 (n = 4421). The aspirin monotherapy (A group, n = 2848) and aspirin and P2Y12 inhibitor combination therapy (AP group, n = 1573) groups were compared. The primary and secondary endpoints were the incidence of bleeding events and proportion of patients with a modified Rankin Scale (mRS) score ≤ 2 at discharge, respectively. Data was analyzed using multivariable adjusted logistic regression (significance level, 5%)., Results: The adjusted odds ratio in AP group, with A group as the reference, for bleeding events and the proportion of patients with mRS score ≤ 2 at discharge were 0.97 (95% confidence interval [95% CI]: 0.75-1.26, p = 0.839) and 1.09 (95% CI: 0.92-1.29, p = 0.302), respectively., Conclusions: There are no differences in the incidence of bleeding events or good clinical outcomes (mRS score ≤ 2 at discharge) between aspirin monotherapy and aspirin and P2Y12 inhibitor combination therapy., Competing Interests: Declarations. Funding: This study did not receive any specific grants from funding agencies in the public, commercial, or not-for-profit sectors. Conflicts of interest: Hiroshi Magara is an employee of Nxera Pharmaceuticals Japan Ltd. The other authors declare no conflicts of interest. Availability of data and materials: The data that support the findings of this study are not openly available due to reasons of sensitivity but are available from the corresponding author upon reasonable request. Ethics approval: The study protocol was approved by the Ethics Review Board of the Tokyo Medical and Dental University (approval number: M2000-788-33). This study involved secondary analyses of a claims database and did not directly involve participants. We did not involve patients in designing the research question, outcome measures, interpretation, or writing the results of this study. The participants were given the opportunity to opt out via the study website. Consent to Participate: The ethics review board of the Tokyo Medical and Dental University waived the need for informed consent because the study design involving secondary analyses of a claims database and did not directly involve participants (designing the research question, selecting the outcome measures, and interpreting and writing the results of this study). Participants were given the opportunity to opt out via the study website. Consent for publication: Not applicable. Code availability: Not applicable. Authors’ Contributions: Hiroshi Magara and Yuri Nakamura were responsible for conceptualization, methodology, data curation, writing: original draft preparation, visualization, and investigation; Takuaki Tani and Shinobu Imai were responsible for conceptualization, methodology, data analysis and writing: reviewing and editing; Anna Kiyomi and Kensuke Yoshida were responsible for conceptualization, methodology, and writing: reviewing and editing; Kiyohide Fushimi was responsible for conceptualization, data acquisition, and writing: reviewing and editing; and Munetoshi Sugiura was responsible for conceptualization, methodology, writing: reviewing and editing, and supervision. All the authors have read and approved the final version of the manuscript., (© 2024. The Author(s).)

Background: Fasudil and ozagrel are drugs with the same indications for the treatment of cerebral vasospasm in Japan. However, there have been no definitive conclusions on the clinical efficacy of fasudil hydrochloride and ozagrel sodium monotherapy or their combination. Therefore, we aimed to investigate the effectiveness of the combined administration of fasudil hydrochloride and ozagrel sodium in Japanese patients with subarachnoid hemorrhage (SAH)., Methods: This cross-sectional study used Diagnosis Procedure Combination data to assess patients who were hospitalized with SAH and received fasudil hydrochloride or ozagrel sodium between April 2016 and March 2020 (n = 17,346). The participants were divided into three groups based on the treatment received: fasudil hydrochloride monotherapy (F group, n = 10,484), ozagrel sodium monotherapy (O group, n = 465), and fasudil hydrochloride and ozagrel sodium combination therapy (FO group, n = 6,397). The primary outcome was in-hospital mortality. Multivariable adjusted logistic regression analysis (significance level, 5%) was used for data analyses., Results: The results of the multivariable analysis, adjusted for factors considered to impact prognosis, showed that the adjusted odds ratio (OR) with the F group as the reference for in-hospital mortality was 0.94 in the FO group (95% confidence interval [CI]: 0.81-1.08, p = 0.355), with no differences compared to the F group., Conclusion: Fasudil hydrochloride and ozagrel sodium had different mechanisms of action, suggesting a synergistic effect of combination therapy. However, a comparison of fasudil hydrochloride monotherapy and combination therapy of fasudil hydrochloride and ozagrel sodium showed no difference in the prognostic effect. Therefore, it was suggested that fasudil hydrochloride monotherapy may be sufficient., (© 2024. The Author(s).)

We report direct observation by electron holography of the spin polarization of electrons in a vacuum region around a charged SiO2 wire coated with Pt-Pd. Irradiating the SiO2 wire with 300 keV electrons caused the wire to become positively charged due to the emission of secondary electrons. The spin polarization of these electrons interacting with the charged wire was observed in situ using a phase reconstruction process under an external magnetic field. The magnetic field of the spin-polarized electrons was simulated taking into account the distribution of secondary electrons and the effect of the external magnetic field., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Japanese Society of Microscopy.)

A secondary electron (SE) energy analyzer was developed for a transmission electron microscope. The analyzer comprises a microchannel plate (MCP) for detecting electrons, a coil for collecting SEs emitted from the specimen, a tube for reducing the number of backscattered electrons incident on the MCP, and a retarding mesh for selecting the energy of SEs incident on the MCP. The detection of the SEs associated with charging phenomena around a charged specimen was attempted by performing electron holography and SE spectroscopy using the energy analyzer. The results suggest that it is possible to obtain the energy spectra of SEs using the analyzer and the charging states of a specimen by electron holography simultaneously.

Rolofylline is a potent, selective adenosine A1 receptor antagonist that was under development for the treatment of patients with acute congestive heart failure and renal impairment. Rolofylline is metabolized primarily to the pharmacologically active M1-trans and M1-cis metabolites (metabolites) by cytochrome P450 (CYP) 3A4. The aim of this investigation was to provide a pharmacokinetic (PK) model for rolofylline and metabolites following intravenous administration to healthy volunteers. Data included for this investigation came from a randomized, double-blind, dose-escalation trial in four groups of healthy volunteers (N=36) where single doses of rolofylline, spanning 1 to 60 mg ,were infused over 1-2 h. The rolofylline and metabolite data were analyzed simultaneously using NONMEM. The simultaneous PK model comprised, in part, a two-compartment linear PK model for rolofylline, with estimates of clearance and volume of distribution at steady-state of 24.4 L/h and 239 L, respectively. In addition, the final PK model contained provisions for both conversion of rolofylline to metabolites and stereochemical conversion of M1-trans to M1-cis. Accordingly, the final model captured known aspects of rolofylline metabolism and was capable of simultaneously describing the PK of rolofylline and metabolites in healthy volunteers.

Objective: The efficacy of antihistamines in perennial allergic rhinitis in children has been evaluated in studies using active comparators, whereas placebo-controlled studies are very few. A randomized, multicenter, double-blind, parallel-group clinical study was carried out to evaluate the dose-response relationship and superiority of olopatadine hydrochloride over placebo in children aged 7 to 16 years with perennial allergic rhinitis., Methods: Subjects received twice daily treatment for two weeks with either olopatadine 2.5 mg, 5 mg or placebo after a one-week observation period. Efficacy was assessed based on the diary card score the subject (or guardian) recorded., Results: Of the 302 subjects randomized, two were excluded from analysis: one did not receive treatment; the other was not monitored for efficacy parameters. The remaining 300 subjects (97 in the placebo group, 103 in the olopatadine 2.5-mg group and 100 in the olopatadine 5-mg group) constituted the full analysis set (FAS) for the efficacy analysis. As a primary endpoint, the total three nasal symptom score (for sneezing, rhinorrhea and nasal congestion) at final assessment was compared with baseline or the score obtained in the observation period. The change from baseline was then tested using analysis of covariance (ANCOVA) with the baseline score as covariate. Williams' test was applied to the least squares means estimated from this ANCOVA model for each treatment group, resulting in showing the monotonicity Williams' test assumed. The total three nasal symptom score significantly improved in the 5-mg group compared with the placebo group (p = 0.019). In contrast, the 2.5-mg group did not differ statistically from the placebo group. Adverse events occurred in 33.7% (33/98 subjects) in the placebo group, 35.9% (37/103 subjects) in the 2.5-mg group and 35.0% (35/100 subjects) in the 5-mg group. There were no serious or severe adverse events., Conclusions: Olopatadine hydrochloride 5 mg twice daily is an effective and safe treatment for perennial allergic rhinitis in children.

A rapid, sensitive and specific assay method has been developed to determine plasma concentrations of olopatadine hydrochloride (A) and its metabolites, M1 (B), M2 (C) and M3 (D), using high-performance liquid chromatography with electrospray ionization tandem mass spectrometry (LC-ESI-MS-MS). Olopatadine, its metabolites, and internal standard, KF11796 (E), were separated from plasma using solid-phase extraction (Bond Elut C18 cartridge). The eluate was dried, reconstituted and injected into the LC-ESI-MS-MS system. The calibration curves showed good linearity over the ranges 1-200 ng/ml for olopatadine and M3, and 2-100 ng/ml for M1 and M2, and the method was thoroughly validated and applied to the determination of olopatadine and its metabolites in plasma collected during Phase I clinical trials. Furthermore, the assay values were compared with those determined by the radioimmunoassay method, which has been routinely used to determine olopatadine in plasma.

A highly sensitive and specific determination method of a new calcium antagonist, benidipine hydrochloride, in human plasma has been developed using capillary column gas chromatography with negative ion chemical ionization mass spectrometry. A deuterated analogue of benidipine hydrochloride was used as an internal standard. Benidipine hydrochloride was extracted from plasma with diethyl ether under basic conditions, back-extracted with 0.5 M sulphuric acid, and reextracted with diethyl ether under basic conditions. For gas chromatography, a solventless injection port was used, and the whole extract was injected. Fragment ions at m/z 488 (benidipine) and m/z 493 (internal standard) were used as monitoring ions for selected-ion monitoring. The detection limit was 0.02 ng/ml with 0.5 ml of plasma. The coefficient of variation of intra-day assay was 17.4% and 12.1% at the 0.02 and 0.1 ng/ml levels, respectively. This method has made it possible to detect the plasma level of unchanged drug up to 12 h after an 8-mg oral dose of benidipine hydrochloride to humans.

The stereoselective pharmacokinetics of suprofen enantiomers has been studied in humans by means of stable isotope-labeled pseudoracemate-diastereomer methodology. After a single oral dose of a near equimolar mixture of unlabeled-(R)-(-)- and [2H3]-(S)-(+)-suprofen [or unlabeled-(S)- and [2H3]-(R)-suprofen] to three healthy male subjects, the plasma concentrations of drug were determined by a stereospecific gas chromatography-mass spectrometry method. Racemic [2H7]suprofen was used as an internal standard. The method involved chiral derivatization with (S)-(-)-1-(naphthyl)ethylamine to form the diastereomeric amide. The plasma concentrations were consistently higher for the (R)-isomer than the (S)-isomer. No significant difference in the elimination half-life of the enantiomers was observed. An average of 6.8% of an administered dose of the (R)-isomer was stereospecifically inverted to the (S)-isomer. There was no measurable inversion of the (S)- to (R)-isomer. The present stable isotope-labeled pseudoracemate-diastereomer methodology has made it possible to evaluate the pharmacokinetics of each enantiomer, including the estimation of chiral inversion after administration of the racemic mixture.

A method for the stereoselective assay of the (+)- and (-)-enantiomers of suprofen and [2H3]suprofen in human plasma was developed using gas chromatography-mass spectrometry-selected-ion monitoring. (+/-)-[2H7]Suprofen was used as an internal standard. The method involved diethyl ether extraction and chiral derivatization with S-(-)-1-(naphthyl)ethylamine to form diastereomeric amide. The diastereoisomers were separated on a capillary gas chromatograph-mass spectrometer. Quantitation was achieved by selected-ion monitoring of the quasi-molecular ions of the diastereoisomers. The sensitivity, specificity, accuracy and reproducibility of the method were demonstrated to be satisfactory for application to pharmacokinetic studies of suprofen enantiomers.