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Aim: Adverse childhood experiences are potentially traumatic events with long-lasting effects on the health and well-being of patients with autism spectrum disorder (ASD). It is important to clarify which types of long-lasting autism-related symptoms are influenced by childhood experiences to design future intervention studies. However, few studies have examined the association between childhood experiences and autistic symptoms in large samples of adults with ASD and individuals with typical development (TD). In this study, we evaluate the effects of adverse childhood experiences on multiple ASD phenotypes among both individuals with ASD and those with TD., Method: We combined questionnaire evaluations; Childhood Abuse and Trauma Scale, the Japanese version of the Autism-Spectrum Quotient, Conners' Adult ADHD Rating Scale, the Japanese version of the Impact of Event Scale-Revised, and the Japanese version of the Adolescent/Adult Sensory Profile., Results: Individuals with ASD and those with TD (n = 205 and 104, respectively) were included. There were significant correlations between the extent of adverse childhood experiences and severity of attention-deficit/hyperactivity disorder symptoms, posttraumatic stress disorder symptoms, and hypersensitivity in both participants with ASD and those with TD. By contrast, ASD core symptoms showed no significant correlation with adverse childhood experiences in either group. These results remained consistent after adjusting for age, sex, and the estimated intelligence quotient., Conclusion: These findings suggest the need for a detailed disentanglement of ASD-related core and peripheral symptoms of adverse childhood experiences, which may help to appropriately set outcomes for future early interventions for the childhood experiences of individuals with ASD., (© 2024 The Author(s). Psychiatry and Clinical Neurosciences published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology.)

Visuospatial working memory (vsWM), which is impaired in schizophrenia (SZ), is mediated by multiple cortical regions including the primary (V1) and association (V2) visual, posterior parietal (PPC) and dorsolateral prefrontal (DLPFC) cortices. In these regions, parvalbumin (PV) or somatostatin (SST) GABA neurons are altered in SZ as reflected in lower levels of activity-regulated transcripts. As PV and SST neurons receive excitatory inputs from neighboring pyramidal neurons, we hypothesized that levels of activity-regulated transcripts are also lower in pyramidal neurons in these regions. Thus, we quantified levels of four activity-regulated, pyramidal neuron-selective transcripts, namely adenylate cyclase-activating polypeptide-1 (ADCYAP1), brain-derived neurotrophic factor (BDNF), neuronal pentraxin-2 (NPTX2) and neuritin-1 (NRN1) mRNAs, in V1, V2, PPC and DLPFC from unaffected comparison and SZ individuals. In SZ, BDNF and NPTX2 mRNA levels were lower across all four regions, whereas ADCYAP1 and NRN1 mRNA levels were lower in V1 and V2. The regional pattern of deficits in BDNF and NPTX2 mRNAs was similar to that in transcripts in PV and SST neurons in SZ. These findings suggest that lower activity of pyramidal neurons expressing BDNF and/or NPTX2 mRNAs might contribute to alterations in PV and SST neurons across the vsWM network in SZ., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2024. Published by Elsevier B.V.)

Background/aims: This study aimed to examine the synergistic effect of independent risk factors on post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP)., Methods: This multicenter retrospective study included 1,273 patients with native papillae who underwent ERCP for bile duct stones in Japan. Independent PEP risk factors were identified using univariate and multivariate analyses. Significant risk factors for PEP in the multivariate analysis were included in the final analysis to examine the synergistic effect of independent risk factors for PEP., Results: PEP occurred in 45 of 1,273 patients (3.5%). Three factors including difficult cannulation ≥10 minutes, pancreatic injection, and normal serum bilirubin level were included in the final analysis. The incidences of PEP in patients with zero, one, two, and three factors were 0.5% (2/388), 1.9% (9/465), 6.0% (17/285), and 12.6% (17/135), respectively. With increasing risk factors for PEP, the incidence of PEP significantly increased (1 factor vs. 2 factors, p=0.006; 2 factors vs. 3 factors, p=0.033)., Conclusions: As the number of risk factors for PEP increases, the risk of PEP may not be additive; however, it may multiply. Thus, aggressive prophylaxis for PEP is strongly recommended in patients with multiple risk factors.

Microglia and brain-derived neurotrophic factor (BDNF) are essential for the neuroplasticity that characterizes critical developmental periods. The experience-dependent development of social behaviors-associated with the medial prefrontal cortex (mPFC)-has a critical period during the juvenile period in mice. However, whether microglia and BDNF affect social development remains unclear. Herein, we aimed to elucidate the effects of microglia-derived BDNF on social behaviors and mPFC development. Mice that underwent social isolation during p21-p35 had increased Bdnf in the microglia accompanied by reduced adulthood sociability. Additionally, transgenic mice overexpressing microglial Bdnf-regulated using doxycycline at different time points-underwent behavioral, electrophysiological, and gene expression analyses. In these mice, long-term overexpression of microglial BDNF impaired sociability and excessive mPFC inhibitory neuronal circuit activity. However, administering doxycycline to normalize BDNF from p21 normalized sociability and electrophysiological function in the mPFC, whereas normalizing BDNF from later ages (p45-p50) did not normalize electrophysiological abnormalities in the mPFC, despite the improved sociability. To evaluate the possible role of BDNF in human sociability, we analyzed the relationship between adverse childhood experiences and BDNF expression in human macrophages, a possible proxy for microglia. Results show that adverse childhood experiences positively correlated with BDNF expression in M2 but not M1 macrophages. In summary, our study demonstrated the influence of microglial BDNF on the development of experience-dependent social behaviors in mice, emphasizing its specific impact on the maturation of mPFC function, particularly during the juvenile period. Furthermore, our results propose a translational implication by suggesting a potential link between BDNF secretion from macrophages and childhood experiences in humans., (© 2024. The Author(s).)

Background: Dislocation is a major complication of total hip arthroplasty (THA). The modular femoral neck system provides practical advantages by allowing adjustment of neck version and length in the presence of intraoperative instability. Anatomical studies have identified morphological differences in the hip joint between men and women. Despite sex-based differences in hip morphology, it remains unclear whether such differences affect neck selectivity in THA using a modular neck system and whether this approach achieves anatomical reconstruction, thereby reducing complications such as dislocation. This study aimed to investigate gender differences in neck selectivity in THA with the modular neck system and assess the clinical impact of the modular neck system., Methods: A total of 163 THAs using a modular neck system were included in this study. Data on the type of modular neck and intraoperative range of motion (ROM) were retrieved from patient records. Pre- and post-operative leg length differences (LLD) were examined as part of the radiographic assessment. Dislocation was investigated as a postoperative complication., Results: Neck selectivity did not significantly differ between men and women. The comparison of pre- and post-operative LLD revealed a tendency for varus necks to improve LLD more than version-controlled necks. Furthermore, no significant correlation was found between intraoperative ROM and neck selectivity, or postoperative dislocation and neck selectivity., Conclusions: This study on THA with a modular neck system provided valuable insights into sex-based differences in neck selectivity and highlighted the potential benefits of the modular neck system in addressing LLD and preventing postoperative dislocation., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: A growing body of evidence suggests that immune dysfunction and inflammation in the peripheral tissues as well as the central nervous system are associated with the neurodevelopmental deficits observed in autism spectrum disorder (ASD). Elevated expression of pro-inflammatory cytokines in the plasma, serum, and peripheral blood mononuclear cells of ASD has been reported. These cytokine expression levels are associated with the severity of behavioral impairments and symptoms in ASD. In a prior study, our group reported that tumor necrosis factor-α (TNF-α) expression in granulocyte-macrophage colony-stimulating factor-induced macrophages (GM-CSF MΦ) and the TNF-α expression ratio in GM-CSF MΦ/M-CSF MΦ (macrophage colony-stimulating factor-induced macrophages) was markedly higher in individuals with ASD than in typically developed (TD) individuals. However, the mechanisms of how the macrophages and the highly expressed cytokines affect neurons remain to be addressed., Methods: To elucidate the effect of macrophages on human neurons, we used a co-culture system of control human-induced pluripotent stem cell-derived neurons and differentiated macrophages obtained from the peripheral blood mononuclear cells of five TD individuals and five individuals with ASD. All participants were male and ethnically Japanese., Results: Our results of co-culture experiments showed that GM-CSF MΦ affect the dendritic outgrowth of neurons through the secretion of pro-inflammatory cytokines, interleukin-1α and TNF-α. Macrophages derived from individuals with ASD exerted more severe effects than those derived from TD individuals., Limitations: The main limitations of our study were the small sample size with a gender bias toward males, the use of artificially polarized macrophages, and the inability to directly observe the interaction between neurons and macrophages from the same individuals., Conclusions: Our co-culture system revealed the non-cell autonomous adverse effects of GM-CSF MΦ in individuals with ASD on neurons, mediated by interleukin-1α and TNF-α. These results may support the immune dysfunction hypothesis of ASD, providing new insights into its pathology., (© 2024. The Author(s).)

A diphosphene ligand possessing a PP bond and a phosphineborane moiety in its molecule was synthesized. The reaction of the new bidentate diphosphene-phosphineborane ligand with [Rh(cod) 2 ]BF 4 provided a cationic diphosphene-rhodium complex with cis -coordination through the η 1 -PP and η 2 -BH 3 moieties. The complex was applied to the coupling reaction of benzimidazole with cyclohexylallene. The complex also underwent a ligand exchange reaction with N-donor reagents such as N -methylpyrrolidine and N , N , N , N -tetramethylethylenediamine. In particular, the addition reaction of pyridine with the rhodium complex provided an equilibrium mixture of the rhodium complex, pyridine, the diphosphene-phosphineborane ligand, and [Rh(pyridine) 2 (cod)]BF 4 .