Neurotrophic properties of leptomeninges

The leptomeninges, consisted of pia mater and arachnoid, cover the surface of brain parenchyma. Leptomeningeal cells produce a number of biologically active proteins, including prostaglandin-D synthase, cyclooxygenase-1, -2, insulin-like growth factor-II, insulin-like growth factor-binding proten-2, and apolipoprotein E, released into the cerebrospinal fluid. The involvement of leptomeninges in neurotrophic, scavenging, and transport activities as well as inflammatory responses, associated with the brain, is reviewed.Biomedical Reviews 1999; 10: 31-36

Pharmacokinetic and pharmacodynamic evaluation of a new sustained-release capsules using starch-sponge matrix (SSM) release system for nifedipine in rats

We conducted a performance assessment study for a new sustained-release capsule including starch-sponge matrix (SSM). The SSM, which is a support medium for drug release, was made from 2.5% cornstarch glue by means of freezing dry method. The SSM capsule was applied for nifedipine (NFP), a calcium channel blocker, and evaluated pharmacokinetic and pharmacodynamic (PK/PD) profiles of NFP after intraduodenal administration of SSM capsules including 2.5 or 5.0 mg of NFP per capsule to rats. Plasma NFP concentrations from the SSM capsules showed dose-dependent increases with a Michaelis-Menten like behavior over 360 minutes after intraduodenal administration. The values of area under the concentration vs. time curve from time zero to 360 min (AUC0-360) of NFP declined in making SSM capsules as compared to control capsules due to a simple physical mixture of NFP and cornstarch, but the values of mean residence time (MRT0-360) extended and abidingness of SSM capsules were admitted with dose-dependent manner. As for a PD parameter, the mean arterial blood pressure (mABP) derived from the SSM capsules showed 15~20% decrease of baseline within 120min after intraduodenal administration, and thereafter the mABP in 2.5 mg SSM capsule was gradually recovered, while a relatively smooth and even change was found in the mABP at 5.0 mg SSM capsule. The relationships between plasma NFP concentration and sampling-time corresponding mABP after intraduodenal administration of SSM capsules showed no rapid change in the mABP, indicating that a sustained-release mechanism due to the SSM functions sufficiently to avoid a fluctuating blood pressure accompanied by going up and down of plasma levels of NFP. The SSM capsules exhibited a sustained-release pharmacokinetics of NFP, and made the fluctuation range with blood pressure small compared to the physical mixture preparations. Thus, it was evidenced that the SSM capsule is useful device to provide a sustained-release systems and optimal therapeutic efficacy of drugs.Keywords: Controlled-release, Cornstarch, Matrix, Nifedipine, Pharmacokinetics, Pharmacodynamics

The Japanese version of the Generalized Problematic Internet Use Scale 2 (GPIUS2): Psychometric evaluation and analysis of the theoretical model

BACKGROUND: The Generalized Problematic Internet Use Scale 2 (GPIUS2) is a self-administered questionnaire that evaluates problematic internet use (PIU) from a multidimensional perspective. We analysed the psychometric properties and adequacy of the theoretical model of Japanese version of the GPIUS2. METHODS: This study included 291 healthy Japanese adults (median age = 25 years; interquartile range 22-43 years; 128 women) who completed the GPIUS2 and several other questionnaires evaluating the degree of PIU, self-esteem, depression, and impulsivity. RESULTS: Exploratory factor analysis (EFA) revealed a similar factor structure between the original and Japanese versions of the GPIUS2, with only minor differences in item composition. Higher-order confirmatory factor analyses revealed a good overall fit for the factorial model suggested by EFA, indicating adequate construct validity. The model showed acceptable internal consistency. Partial correlation analyses between GPIUS2 and other measures, with age as a control variable, revealed good convergent validity. Finally, structural equation modelling showed a good fit to the data, supporting the cognitive-behavioural model of Caplan (2010). CONCLUSIONS: The Japanese version of the GPIUS2 has good psychometric properties and the theoretical model of the original GPIUS2 is applicable to Japanese adults

Structural basis for improved efficacy of therapeutic antibodies on defucosylation of their Fc glycans

Removal of the fucose residue from the N-glycans of the Fc portion of immunoglobulin G (IgG) results in a dramatic enhancement of antibody-dependent cellular cytotoxicity (ADCC) through improved affinity for Fcγ receptor IIIa (FcγRIIIa). Here, we present the 2.2-Å structure of the complex formed between nonfucosylated IgG1-Fc and a soluble form of FcγRIIIa (sFcγRIIIa) with two N-glycosylation sites. The crystal structure shows that one of the two N-glycans of sFcγRIIIa mediates the interaction with nonfucosylated Fc, thereby stabilizing the complex. However, fucosylation of the Fc N-glycans inhibits this interaction, because of steric hindrance, and furthermore, negatively affects the dynamics of the receptor binding site. Our results offer a structural basis for improvement in ADCC of therapeutic antibodies by defucosylation

Calaxin is required for cilia-driven determination of vertebrate laterality

Sasaki, K., Shiba, K., Nakamura, A. et al. Calaxin is required for cilia-driven determination of vertebrate laterality. Commun Biol 2, 226 (2019). https://doi.org/10.1038/s42003-019-0462-

Disconnectivity between Dorsal Raphe Nucleus and Posterior Cingulate Cortex in Later Life Depression

The dorsal raphe nucleus (DRN) has been repeatedly implicated as having a significant relationship with depression, along with its serotoninergic innervation. However, functional connectivity of the DRN in depression is not well understood. The current study aimed to isolate functional connectivity of the DRN distinct in later life depression (LLD) compared to a healthy age-matched population. Resting state functional magnetic resonance imaging (rsfMRI) data from 95 participants (33 LLD and 62 healthy) were collected to examine functional connectivity from the DRN to the whole brain in voxel-wise fashion. The posterior cingulate cortex (PCC) bilaterally showed significantly smaller connectivity in the LLD group than the control group. The DRN to PCC connectivity did not show any association with the depressive status. The findings implicate that the LLD involves disruption of serotoninergic input to the PCC, which has been suggested to be a part of the reduced default mode network in depression

Very rare solitary primary peripheral nerve onset cytotoxic molecule-positive peripheral T-cell lymphoma (PTCL)

Here we present the first report of solitary primary peripheral nerve onset cytotoxic molecule (CM)-positive peripheral T-cell lymphoma (PTCL) diagnosed after nerve biopsy. An 84-year-old female with rheumatoid arthritis (RA) complained of asymmetric severe tenderness in her upper limbs. The biopsy pathology revealed a direct invasion of CM-positive PTCL. When RA patients complain of numbness, tenderness, or weakness, lymphomatic peripheral nerve invasion should be considered

An international cross-sectional investigation on social media, fitspiration content exposure, and related risks during the COVID-19 self-isolation period.

With the global COVID-19 pandemic, governments from many countries in the world implemented various restrictions to prevent the SARS-Cov-2 virus's spread, including social distancing measures, quarantine, in-home lockdown, and the closure of services and public spaces. This led to an in-creased use of social media platforms to make people feel more connected, but also to maintain physical activity while self-isolating. Concerns about physical appearance and the desire to keep or reach a muscular and toned ideal body, might have further reinforced the engagement in fitness-related social media activities, like sharing progresses in training achievements or following more fitness contents on popular profiles. To better understand the underlying relation among these factors, the present study investigates 729 responses to the Exercise Addiction Inventory (EAI), the Appearance Anxiety Inventory (AAI), the Self-Compassion Scale (SCS) and their association to social media usage and compares the results cross-culturally in five countries (Spain, Lithuania, United Kingdom, Japan, and Hungary). Findings highlight significant differences between males and females, espe-cially in regard to the time spent online (U = 477.5, p = 0.036). Greater levels of appearance anxiety were associated with the exposure to fitness-related contents on social media. These results strongly confirm the previously highlighted association between fitspiration media and body image anxiety predominantly in females. Clinical implications and future considerations in terms of prevention and treatment in a situation of global emergency are also discussed

Compulsive sexual behavior disorder in 42 countries: Insights from the International Sex Survey and introduction of standardized assessment tools

© 2023 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC), https://creativecommons.org/licenses/by-nc/4.0/Background and aims Despite its inclusion in the 11th revision of the International Classification of Diseases, there is a virtual paucity of high-quality scientific evidence about compulsive sexual behavior disorder (CSBD), especially in underrepresented and underserved populations. Therefore, we comprehensively examined CSBD across 42 countries, genders, and sexual orientations, and validated the original (CSBD-19) and short (CSBD-7) versions of the Compulsive Sexual Behavior Disorder Scale to provide standardized, state-of-the-art screening tools for research and clinical practice. Method Using data from the International Sex Survey (N = 82,243; Mage = 32.39 years, SD = 12.52), we evaluated the psychometric properties of the CSBD-19 and CSBD-7 and compared CSBD across 42 countries, three genders, eight sexual orientations, and individuals with low vs. high risk of experiencing CSBD. Results A total of 4.8% of the participants were at high risk of experiencing CSBD. Country- and gender-based differences were observed, while no sexual-orientation-based differences were present in CSBD levels. Only 14% of individuals with CSBD have ever sought treatment for this disorder, with an additional 33% not having sought treatment because of various reasons. Both versions of the scale demonstrated excellent validity and reliability. Discussion and conclusions This study contributes to a better understanding of CSBD in underrepresented and underserved populations and facilitates its identification in diverse populations by providing freely accessible ICD-11-based screening tools in 26 languages. The findings may also serve as a crucial building block to stimulate research into evidence-based, culturally sensitive prevention and intervention strategies for CSBD that are currently missing from the literature.Peer reviewe

ペプチド転移酵素Sortase A が触媒するtranspeptidation 反応に対するCa2＋濃度、反応温度、E105点変異、外因性金属イオンの効果に関する研究

Sortase A is a transpetidase from Staphylococcus aureus that recognizes five specific amino acid sequences, LPETG, and binds them to polyglycine on the cell wall surface, immobilizing the target protein on the cell wall surface. Sortase A contains one Ca2＋ as a co-factor in its structure, and Ca2＋ plays an important role in the enzymatic reaction. First, the time course of the enzymatic reaction, the optimal Ca2＋ concentration, and the optimal reaction temperature were investigated using wild-type Sortase A. Next, we focused on E105, an amino acid residue that has been reported to play an important role in Ca2＋ binding. We prepared point mutants in which E105 was replaced with non-coordinating Ala residues and coordinating amino acid residues (Asp, Cys, His) with Lewis base moieties on the side chains and examined the enzymatic reaction in the presence of Ca2＋ and its cognate elements, Mg2＋ and Sr2＋.The result was the clarification of the optimal Ca2＋ concentration and the optimal reaction temperature range for the enzymatic reaction. In the case of Ca2＋ in the wild-type and E105 mutants, the reactivity was WT ≈ E105D＜E105C＜E105A＜E105H, indicating that the enzymatic reaction is affected by the Lewis basicity of the ligand and the steric structure of the side chain. For Sr2＋, the same trend of reactivity as Ca2＋ was observed, but the overall reactivity decreased. However, for Mg2＋, reactivity was significantly decreased in all cases, indicating the significant effect of ionic radius on the enzymatic reaction.論