Copy-number variants in the contactin-5 gene are a potential risk factor for autism spectrum disorder

BackgroundContactin-5 (CNTN5) is a candidate risk gene for autism spectrum disorder (ASD). Previous attempts to associate CNTN5 CNVs with ASD-susceptibility were limited by insufficient statistical power. Here, we aim to clarify the putative association between CNTN5 CNVs and ASD-risk using large-scale case-control analyses.MethodA CNTN5 CNV, shared by four brothers in a multiplex family with ASD, was initially identified. We calculated the prevalence and transmission of CNTN5 CNVs in cases across five ASD cohorts (n=15,784). Second, we compared the prevalence of CNTN5 CNVs in cases to their unaffected siblings (n=4,996). Third, we assessed the enrichment of CNTN5 CNVs in cases to extrafamilial controls across three cohorts (n=24,886) and the UK Biobank (n = 459,862). Finally, we evaluated the clinical impact of CNTN5 CNVs in a broad neurodevelopmental disorder cohort and the DECIPHER database.ResultsMost (96.7%) CNTN5 CNV deletions (0.193%) and duplications (0.03%) in cases were inherited by a parent that transmitted the variant to their affected and unaffected children at the same rate. We identified a significant enrichment of intronic CNTN5 CNV deletions in cases compared to extrafamilial controls (0.178% versus 0.019%; p-value=1.68E-05; OR:8.51; 95%CI=[2.58-44.21]). There was no difference in CNTN5 CNV enrichment between cases and individuals with NDDs.ConclusionsIntronic CNTN5 CNV deletions are rare, inherited, and intermediate effect size ASD-susceptibility variants that may also confer risk for other neuropsychiatric disorders. We offer a framework to characterize candidate variants that may not be detected through small-scale approaches to implicate intermediate effect size variants in the etiology of ASD.     

Meaningful engagement of the patient in rare cancer research: sarcoma as an exemplar

Patient advocates who understand scientific methods and proper research processes can bring valuable perspectives to modern research. This is particularly important in rare cancers like sarcoma as each patient becomes a precious source of information to better diagnose, understand the biology and the effect of treatment. Reviewing approaches used by other cancer patient advocates can provide valuable insights to develop effective research advocates in rare cancers such as sarcoma.     

Chinese expert consensus on the clinical applications of aminolevulinic acid-based photodynamic therapy in female lower genital tract diseases (2022)

IntroductionWith the younger onset age of female lower genital tract diseases, there are increasing demands for protecting organ and tissue structures to preserve fertility and, therefore, effective fertility-sparing treatments that cause minimal normal tissue damage and less adverse reactions are urgently needed.ObjectiveThis study is aimed at reviewing information and achieving consensus on recommendations on the clinical applications of aminolevulinic acid-based photodynamic therapy (ALA-PDT) in female lower genital tract diseases.MethodsMembers of the expert panel held online and in-person meetings to discuss and revise drafts created by the steering committee based on the literature review and the clinical experiences of the expert panel. Opinions of the experts were transcribed and discussed in detail to ensure that the consensus statement best reflects the current advances in the field and the experts’ view.ResultsAfter numerous rounds of meetings, experts unanimously agreed on the importance of ALA-PDT in the treatment of cervical squamous intraepithelial lesions (SIL), vaginal SIL, vulvar SIL, vulvar lichen sclerosus (VLS), and condyloma acuminatumon (CA). Experts also reached consensus on the recommended treatment regimen and treatment methods.ConclusionThis consensus aimed to provide practical basis and guidance for the clinical applications of ALA-PDT in female lower genital tract diseases in China. Of note, this is the only expert consensus prepared by board-certified specialists in gynecology and obstetrics in China. More evidence-based clinical studies should be made to update and expand the current recommendations.     

Autism spectrum disorder is associated with an increased risk of development of underweight in children and adolescents: A systematic review and meta-analysis

Background & AimsMultiple observational studies have examined the association between autism spectrum disorder (ASD) and underweight, yet the evidence remains ambiguous. We examined the pooled prevalence and relative risk of developing underweight among children with ASD in a systematic review and meta-analysis and examined the effects of potential risk factors in a meta-regression.MethodsProQuest, PubMed, Scopus and Web of Science databases were systematically searched and screened per the PRISMA guidelines. DerSimonian–Laird random-effects meta-analyses were performed using the ‘meta’ package in R to determine the pooled prevalence and the relative risk of underweight among children with ASD. Meta-regression analyses examined the moderator effects of risk factors.ResultsUnderweight had a prevalence of 6.5% (95% CI, 5.1–8.2) among children with ASD overall (29 study groups). Children with ASD possessed a 28.5% (8 studies) greater risk of being underweight vs. neurotypical controls. Meta-regression analyses revealed that non-Caucasian origin and male sex may increase the risk of being underweight in children with ASD.ConclusionsChildren with ASD seem to be at an increased risk of being underweight, which may further impair the clinical outcomes and quality of life. Clinicians need to vigilantly monitor weight and height among children with ASD to prevent underweight and associated complications. Future studies should aim to establish factors that may contribute to the development of underweight among children with ASD.     

高校学报微信平台传播力的影响因素研究

【目的】 对高校学报微信平台传播力的影响因素进行分析,提出期刊提升传播力的建议。【方法】 以国内已开通微信公众号的62种CSSCI高校学报和45种CSCD高校学报为分析对象,通过使用有序Logit模型分别对2020年3月1日至2020年8月1日在微信公众号上发布的1396篇、540篇推文的传播效果进行实证分析。【结果】 CSSCI高校学报的文本编排方式、互动次数、图片数量、目次或摘要的展示方式、所在城市水平、学校知名度与传播效果呈显著正相关,而发文数量、认证情况、关键词、外部链接等与传播力呈负相关。而CSCD高校学报的关键词、编排方式、文章长度、菜单数量、活跃度与阅读量呈正相关,呈现方式、交流互动等变量与阅读量呈负相关。【结论】 从4V营销理论的差异化、功能化、附加价值、共鸣这4个维度提出提升高校学报微信平台传播力的建议。     

Pharmacokinetic analyses using absorption kinetics in low-alcohol dose cases of drunken driving

In Japan, low-alcohol dose cases of drunken driving, where drivers drink just before getting behind the wheel, are increasing for expert witnesses since the penalties for drunken driving have become stricter. Widmark’s equation has generally been used for the pharmacokinetic analysis of blood alcohol concentration, which encompasses the one-compartment model with zero-order elimination kinetics but ignores absorption kinetics. We therefore propose that the formula might not be applicable to the analysis of low-alcohol dose cases of drunken driving because the issue is focused on the absorption phase. In this paper, we present two representative low-alcohol dose cases, which were analyzed using the one-compartment model with first-order absorption and zero-order elimination kinetics. This formula is thought to be more suitable and useful for medicolegal practice than Widmark’s formula.     

Childhood parental bonding affects adulthood trait anxiety through self-esteem

IntroductionThe association between trait anxiety and parental bonding has been suggested. However, the mechanism remains uncertain and there is no study focused on general adult population. We investigated the association and the mechanism between childhood parental bonding and adulthood trait anxiety in the general adult population.Material and methodsA cross-sectional retrospective survey was conducted in 2014 with 853 adult volunteers from the general population. The Parental Bonding Instrument, Rosenberg Self-Esteem Scale, and State-Trait Anxiety Inventory Form Y (STAI-Y) were self-administered. Structural equation modelling was used for the analysis.ResultsChildhood parental bonding affected adulthood trait anxiety indirectly mediated by self-esteem. Trait anxiety was decreased by parental care and increased by parental overprotection through self-esteem. This model explained 51.1% of the variability in STAI-Y trait anxiety scores.ConclusionsThis study suggests an important role of self-esteem as a mediator between childhood parental bonding and adulthood trait anxiety.     

Chronic Stress Influences Sexual Motivation and Causes Damage to Testicular Cells in Male Rats

IntroductionThe suppressing effects of chronic stress on sexual desire have long been noted. Yet the biological mechanisms underlying such effects, especially at the level of cellular biology of testicular cells, have not been fully investigated.AimIn the present study, we used a chronic unpredictable mild stress model to examine the association between chronic stress and structural alterations in the male reproductive system.Main Outcome MeasuresThe main outcome measures were the structural changes in sperm cells and Leydig cells of male rats. We used Agmo and Ellingsen's procedure to study partner preference behavior and observed the morphology of Leydig cells and germ cells in the control and stress groups.MethodsOur methods included histology, electron microscopy, and animal behavior tests.ResultsThe results showed that after 5 weeks of chronic stress exposure, partner preference behavior was impaired, the total surface area of Leydig cells and the number and diameter of seminiferous tubules decreased significantly, and the number and size of Leydig cells, as well as the number and the short‐axis diameter of spermatogenic cells, also decreased. At the ultrastructural level, transmission electron microscopy revealed that the basement membranes of seminiferous tubules in stressed rats was far thinner, had a low density, and was uneven in thickness compared with the normal group, with enhanced apoptosis in germ cells.ConclusionWe conclude that chronic stress can trigger organic damage to testicular cells in male rats. Hou G, Xiong W, Wang M, Chen X, and Yuan T‐F. Chronic stress influences sexual motivation and causes damage to testicular cells in male rats. J Sex Med 2014;11:653–663.     

Rifampicin inhibits rotenone-induced microglial inflammation via enhancement of autophagy

Mitochondrial and autophagic dysfunction, as well as neuroinflammation, are associated with the pathophysiology of Parkinson's disease (PD). Rotenone, an inhibitor of mitochondrial complex I, has been associated as an environmental neurotoxin related to PD. Our previous studies reported that rifampicin inhibited microglia activation and production of proinflammatory mediators induced by rotenone, but the precise mechanism has not been completely elucidated. BV2 cells were pretreated for 2 h with rifampicin followed by 0.1 μM rotenone, alone or in combination with chloroquine. Here, we demonstrate that rifampicin pretreatment alleviated rotenone induced release of IL-1β and IL-6, and its effects were suppressed when autophagy was inhibited by chloroquine. Moreover, preconditioning with 50 μM rifampicin significantly increased viability of SH-SY5Y cells cocultured with rotenone-treated BV2 cells in the transwell coculture system. Chloroquine partially abolished the neuroprotective effects of rifampicin pretreatment. Rifampicin pretreatment significantly reversed rotenone-induced mitochondrial membrane potential reduction and reactive oxygen species accumulation. We suggest that the mechanism for rifampicin-mediated anti-inflammatory and antioxidant effects is the enhancement of autophagy. Indeed, the ratio of LC3-II/LC3-I in rifampicin-pretreated BV2 cells was significantly higher than that in cells without pretreatment. Fluorescence and electron microscopy analyses indicate an increase of lysosomes colocalized with mitochondria in cells pretreated with rifampicin, which confirms that the damaged mitochondria were cleared through autophagy (mitophagy). Taken together, the data provide further evidence that rifampicin exerts neuroprotection against rotenone-induced microglia inflammation, partially through the autophagy pathway. Modulation of autophagy by rifampicin is a novel therapeutic strategy for PD.