BACKGROUND & AIMS: :Recent debates in the literature discuss commonalities between Attention-Deficit/Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD) at multiple levels of putative causal networks. This debate requires systematic comparisons between these disorders that have been studied in isolation in the past, employing potential markers of each disorder to be investigated in tandem. The present study, choose superior local processing, typical to ASD, and increased Intra-Subject Variability (ISV), typical to ADHD, for a head-to-head comparison of the two disorders, while also considering the comorbid cases. It directly examined groups of participants aged 10-13 years with ADHD, ASD with (ASD+) or without (ASD-) comorbid ADHD and a typically developing (TD) group (total N = 85). A visual search task consisting of an array of paired words was designed. The participants needed to find the specific pair of words, where the first word in the pair was the cue word. This visual search task was selected to compare these groups on overall search performance and trial-to-trial variability of search performance (i.e., ISV). Additionally, scanpath analysis was also carried out using Recurrence Quantification Analysis (RQA) and the Multi-Match Model. Results show that only the ASD- group exhibited superior search performance; whereas, only the groups with ADHD symptoms showed increased ISV. These findings point towards a double dissociation between ASD and ADHD, and argue against an overlap between ASD and ADHD.

背景与目标： : 文献中最近的辩论在假定的因果网络的多个层面上讨论了注意力缺陷/多动障碍 (ADHD) 和自闭症谱系障碍 (ASD) 之间的共同点。这场辩论需要对过去隔离研究的这些疾病进行系统的比较，并采用每种疾病的潜在标志物进行串联研究。本研究选择了ASD典型的优越局部处理方法和ADHD典型的增加的受试者内变异性 (ISV)，以对两种疾病进行头对头比较，同时还考虑了合并症病例。它直接检查了年龄在10-13岁之间的ADHD，患有 (ASD) 或不患有 (ASD-) 共患ADHD的ASD和典型发育 (TD) 组 (总N = 85) 的参与者组。设计了一个由成对单词数组组成的视觉搜索任务。参与者需要找到特定的单词对，其中该对中的第一个单词是提示单词。选择此视觉搜索任务是为了比较这些组的整体搜索性能和搜索性能 (即ISV) 的试验间差异。此外，还使用递归量化分析 (RQA) 和多匹配模型进行了scanpath分析。结果表明，只有ASD组表现出优异的搜索性能; 而只有具有ADHD症状的组显示ISV增加。这些发现表明ASD和ADHD之间存在双重分离，并反对ASD和ADHD之间存在重叠。

BACKGROUND & AIMS: :Attention-deficit/hyperactivity (ADHD) and autism spectrum (ASD) disorders often co-occur. In both cases, response inhibition deficits and inhibition-related atypical brain activation have been reported, although less consistently in ASD. Research exploring the overlap/distinctiveness between ADHD and ASD has significantly increased in recent years, but direct comparison of the inhibition-related neuronal correlates between these disorders are scarce in the literature. This study aimed at disentangling the shared and specific inhibitory brain dysfunctions in ASD and ADHD. Using functional magnetic resonance imaging (fMRI), brain activity was compared between children with ADHD, ASD and typically developing (TD) children aged 8-12 years during an inhibition stop-signal task, using stringent inclusion criteria. At the behavioural level, only children with ADHD exhibited inhibition deficits when compared with the TD group. Distinct patterns of brain activity were observed during successful inhibition. In children with ADHD, motor inhibition was associated with right inferior parietal activation, whereas right frontal regions were activated in children with ASD. Between-group comparisons disclosed higher middle frontal activation in the ASD group compared with the ADHD and the TD groups. Our results evidence different patterns of activation during inhibition in these two disorders, recruiting different regions of the fronto-parietal network associated to inhibition. Besides brain activity differences, behavioural inhibition deficits found only in children with ADHD further suggest that reactive inhibition is one of the core deficits in ADHD, but not in ASD. Our findings provide further evidence contributing to disentangle the shared and specific inhibitory dysfunctions in ASD and ADHD.

背景与目标： : 注意力缺陷/多动 (ADHD) 和自闭症谱系 (ASD) 疾病经常同时发生。在这两种情况下，都报道了反应抑制缺陷和与抑制相关的非典型脑激活，尽管在ASD中不太一致。近年来，探索ADHD和ASD之间重叠/独特性的研究已显着增加，但文献中很少直接比较这些疾病之间的抑制相关神经元相关性。这项研究旨在解开ASD和ADHD中共享的和特定的抑制性脑功能障碍。使用功能磁共振成像 (fMRI)，使用严格的纳入标准，比较了ADHD，ASD儿童和8-12岁的典型发育 (TD) 儿童在抑制停止信号任务期间的大脑活动。在行为水平上，与TD组相比，只有ADHD儿童表现出抑制缺陷。在成功抑制过程中观察到不同的大脑活动模式。在患有ADHD的儿童中，运动抑制与右下顶叶激活有关，而在患有ASD的儿童中，右额叶区域被激活。组间比较显示，与ADHD和TD组相比，ASD组的中额激活更高。我们的结果证明，在这两种疾病中，抑制过程中激活的模式不同，募集了与抑制相关的额顶网络的不同区域。除了大脑活动差异外，仅在ADHD儿童中发现的行为抑制缺陷进一步表明，反应抑制是ADHD的核心缺陷之一，而在ASD中却不是。我们的发现提供了进一步的证据，有助于消除ASD和ADHD中共同的和特定的抑制性功能障碍。

BACKGROUND & AIMS: Background:Autism spectrum disorder (ASD) is a neurodevelopmental disorder with a high co-morbidity of epilepsy and associated with hundreds of rare risk factors. NRXN1 deletion is among the commonest rare genetic factors shared by ASD, schizophrenia, intellectual disability, epilepsy, and developmental delay. However, how NRXN1 deletions lead to different clinical symptoms is unknown. Patient-derived cells are essential to investigate the functional consequences of NRXN1 lesions to human neurons in different diseases. Methods:Skin biopsies were donated by five healthy donors and three ASD patients carrying NRXN1α +/- deletions. Seven control and six NRXN1α +/- iPSC lines were derived and differentiated into day 100 cortical excitatory neurons using dual SMAD inhibition. Calcium (Ca2+) imaging was performed using Fluo4-AM, and the properties of Ca2+ transients were compared between two groups of neurons. Transcriptome analysis was carried out to undercover molecular pathways associated with NRXN1α +/- neurons. Results:NRXN1α +/- neurons were found to display altered calcium dynamics, with significantly increased frequency, duration, and amplitude of Ca2+ transients. Whole genome RNA sequencing also revealed altered ion transport and transporter activity, with upregulated voltage-gated calcium channels as one of the most significant pathways in NRXN1α +/- neurons identified by STRING and GSEA analyses. Conclusions:This is the first report to show that human NRXN1α +/- neurons derived from ASD patients' iPSCs present novel phenotypes of upregulated VGCCs and increased Ca2+ transients, which may facilitate the development of drug screening assays for the treatment of ASD.

背景与目标：

BACKGROUND & AIMS: :The main aim of this study was to examine the extent to which affective and cognitive empathy were associated with reactive and proactive aggression, and whether these associations differed between children with an Autism Spectrum Disorder (ASD) and typically developing (TD) children. The study included 133 children (67 ASD, 66 TD, Mage=139 months), who filled out self-report questionnaires. The main findings showed that the association between reactive aggression and affective empathy was negative in TD children, but positive in children with ASD. The outcomes support the idea that a combination of poor emotion regulation and impaired understanding of others' emotions is associated with aggressive behavior in children with ASD.

背景与目标： : 这项研究的主要目的是检查情感和认知同理心与反应性和主动攻击的程度，以及自闭症谱系障碍 (ASD) 儿童和典型发育 (TD) 儿童之间这些关联是否不同。该研究包括133名儿童 (67名ASD，66名TD，法师 = 139个月)，他们填写了自我报告问卷。主要发现表明，反应性攻击与情感移情之间的关联在TD儿童中是负面的，而在ASD儿童中是积极的。结果支持以下观点: 情绪调节不良和对他人情绪的理解受损与ASD儿童的攻击行为有关。

BACKGROUND & AIMS: :This study investigated the relationship between mothers' daily occupational experiences of productivity, restoration and pleasure with their subjective well-being (SWB) and with their child's developmental skills. Forty caregivers parenting young children with autism spectrum disorders served as a convenience sample in this study. Participants rated their occupational experience in a time diary for a 1-week period and rated their SWB on the Positive and Negative Affect Scale and Satisfaction with Life Scale. Their child's occupational performance and development were evaluated using the Pediatric Daily Occupation Scale and Chinese Child Development Inventory. Spearman rank correlations were used to examine the relationship of SWB to these maternal and child factors. Mothers' pleasure levels were associated with two SWB measures: the positive affect and Satisfaction With Life Scale. Restoration levels related to positive affect only. Productivity levels and child factors were not significantly correlated with any of the SWB measures. A larger heterogeneous sample and a longitudinal study design to explore the fluctuation and stability of occupational experiences across time are recommended to examine caregivers' adaptation and/or alterations in SWB while adapting to their child's diagnosis and special needs.

背景与目标： : 这项研究调查了母亲日常的生产力，恢复和愉悦的职业经历与主观幸福感 (SWB) 以及孩子的发展技能之间的关系。在这项研究中，有40名照顾者为自闭症谱系障碍的幼儿做父母作为方便样本。参与者在1周的时间日记中对他们的职业经历进行了评估，并根据正面和负面影响量表以及对生活量表的满意度对他们的SWB进行了评估。使用儿科日常职业量表和中国儿童发展量表评估其儿童的职业表现和发育。Spearman等级相关性用于检查SWB与这些母婴因素的关系。母亲的愉悦水平与两个SWB指标相关: 积极影响和对生活量表的满意度。仅与积极影响相关的恢复水平。生产力水平和儿童因素与任何SWB指标都没有显着相关。建议使用较大的异质样本和纵向研究设计来探索职业经历的时间波动和稳定性，以检查照顾者在SWB中的适应和/或改变，同时适应孩子的诊断和特殊需求。

BACKGROUND & AIMS: BACKGROUND:Deficits in perception and production of vocal pitch are often observed in people with autism spectrum disorder (ASD), but the neural basis of these deficits is unknown. In magnetoencephalogram (MEG), spectrally complex periodic sounds trigger two continuous neural responses-the auditory steady state response (ASSR) and the sustained field (SF). It has been shown that the SF in neurotypical individuals is associated with low-level analysis of pitch in the 'pitch processing center' of the Heschl's gyrus. Therefore, alternations in this auditory response may reflect atypical processing of vocal pitch. The SF, however, has never been studied in people with ASD. METHODS:We used MEG and individual brain models to investigate the ASSR and SF evoked by monaural 40 Hz click trains in boys with ASD (N = 35) and neurotypical (NT) boys (N = 35) aged 7-12-years. RESULTS:In agreement with the previous research in adults, the cortical sources of the SF in children were located in the left and right Heschl's gyri, anterolateral to those of the ASSR. In both groups, the SF and ASSR dominated in the right hemisphere and were higher in the hemisphere contralateral to the stimulated ear. The ASSR increased with age in both NT and ASD children and did not differ between the groups. The SF amplitude did not significantly change between the ages of 7 and 12 years. It was moderately attenuated in both hemispheres and was markedly delayed and displaced in the left hemisphere in boys with ASD. The SF delay in participants with ASD was present irrespective of their intelligence level and severity of autism symptoms. LIMITATIONS:We did not test the language abilities of our participants. Therefore, the link between SF and processing of vocal pitch in children with ASD remains speculative. CONCLUSION:Children with ASD demonstrate atypical processing of spectrally complex periodic sound at the level of the core auditory cortex of the left-hemisphere. The observed neural deficit may contribute to speech perception difficulties experienced by children with ASD, including their poor perception and production of linguistic prosody.

背景与目标：

BACKGROUND & AIMS: :Ethical considerations preclude the biopsy of normal human myocardium. As a consequence, morphological investigations of diseased human heart muscle are hampered by a lack of suitable normal control tissue. The left ventricular (LV) myocardium of patients with isolated secundum atrial septal defect (ASD) is considered to be normal. This study was designed to investigate the possibility that the fine-structure of LV myofibres in hearts with ASD could be used as normal controls for myofibre pathomorphology. Wedge biopsies from the LV of four adults undergoing elective surgery for the repair of ASD were examined by light and electron microscopy. Bivariant myofibre morphometry showed that the LV myocardium of one specimen was 'normal' while three specimens exhibited varying degrees of hypertrophy. There was a correlation between the diameter (FD) and morphology of individual myofibres within and between specimens. In general, myofibres with FD less than 25 microns were similar in fine-structural appearance to those described as morphologically normal in animal models whereas those with FD greater than 25 microns exhibited hypertrophic features that increased in 'severity' with increase in myofibre size. It is proposed that although the LV myocardium in ASD may be mildly hypertrophied, myofibres with FD less than 25 microns are probably normal and may be used as fine-structural controls for myofibre pathomorphology in hearts suspected of disease.

背景与目标： 伦理考虑排除了正常人心肌的活检。结果，由于缺乏合适的正常对照组织，阻碍了患病人心肌的形态学研究。孤立的继发性房间隔缺损 (ASD) 患者的左心室 (LV) 心肌被认为是正常的。这项研究旨在研究ASD心脏中LV肌纤维的精细结构可以用作肌纤维病理形态学的正常对照的可能性。通过光学和电子显微镜检查了四名接受择期手术以修复ASD的成年人的LV的楔形活检。双变型肌纤维形态测定表明，一个标本的LV心肌是 “正常的”，而三个标本则表现出不同程度的肥大。标本内部和之间的单个肌纤维的直径 (FD) 与形态之间存在相关性。通常，FD小于25微米的肌纤维在精细结构外观上与动物模型中描述为形态正常的肌纤维相似，而FD大于25微米的肌纤维表现出肥厚特征，随着肌纤维大小的增加，其 “严重” 增加。有人提出，尽管ASD中的LV心肌可能轻度肥大，但FD小于25微米的肌纤维可能是正常的，可以用作怀疑有疾病的心脏中肌纤维病理形态的精细结构对照。

BACKGROUND & AIMS: :Autism spectrum disorder (ASD) is a debilitating brain illness causing social deficits, delayed development and repetitive behaviors. ASD is a heritable neurodevelopmental disorder with poorly understood and complex etiology. The central dopaminergic system is strongly implicated in ASD pathogenesis. Genes encoding various elements of this system (including dopamine receptors, the dopamine transporter or enzymes of synthesis and catabolism) have been linked to ASD. Here, we comprehensively evaluate known molecular interactors of dopaminergic genes, and identify their potential molecular partners within up/down-steam signaling pathways associated with dopamine. These in silico analyses allowed us to construct a map of molecular pathways, regulated by dopamine and involved in ASD. Clustering these pathways reveals groups of genes associated with dopamine metabolism, encoding proteins that control dopamine neurotransmission, cytoskeletal processes, synaptic release, Ca(2+) signaling, as well as the adenosine, glutamatergic and gamma-aminobutyric systems. Overall, our analyses emphasize the important role of the dopaminergic system in ASD, and implicate several cellular signaling processes in its pathogenesis.

背景与目标： 自闭症谱系障碍 (ASD) 是一种使人衰弱的脑部疾病，会导致社会缺陷，发育延迟和重复行为。ASD是一种遗传性神经发育障碍，病因尚不清楚且复杂。中枢多巴胺能系统与ASD发病机制密切相关。编码该系统各种元素的基因 (包括多巴胺受体，多巴胺转运蛋白或合成和分解代谢的酶) 已与ASD相关。在这里，我们全面评估多巴胺能基因的已知分子相互作用，并在与多巴胺相关的上/下蒸汽信号通路中确定其潜在的分子伙伴。这些计算机分析使我们能够构建由多巴胺调节并参与ASD的分子途径图。对这些途径进行聚类揭示了与多巴胺代谢相关的基因组，编码控制多巴胺神经传递，细胞骨架过程，突触释放，Ca(2) 信号传导以及腺苷，谷氨酸能和 γ-氨基丁酸系统的蛋白质。总的来说，我们的分析强调了多巴胺能系统在ASD中的重要作用，并暗示了其发病机理中的几个细胞信号过程。

BACKGROUND & AIMS: :We compared the effects of 8-weeks of rhythm and robotic interventions with those of a comparison, standard-of-care intervention, on the spontaneous and responsive social attention patterns of school-age children with Autism Spectrum Disorder. Attention patterns were examined within a standardized pretest/posttest measure of joint attention (JA) and a training-specific social attention measure during early, mid, and late training sessions. The rhythm and comparison groups demonstrated improvements in JA. Social attention was greater in the rhythm followed by the robot and lastly the comparison group. The robot and comparison groups spent maximum time fixating on the robot and objects, respectively. Across sessions, the robot group decreased attention to the robot and increased attention to elsewhere. Overall, rhythmic movement contexts afford sustained social monitoring in children with autism.

背景与目标： : 我们比较了8周的节律和机器人干预与比较的护理标准干预对自闭症谱系障碍学龄儿童自发和反应迅速的社会注意模式的影响。在早期，中期和晚期培训课程中，在标准化的联合注意力 (JA) 前测试/后测试措施和针对特定培训的社会注意力措施中检查了注意力模式。节奏和比较组显示了JA的改善。机器人，最后是比较组的节奏，社会关注度更高。机器人和比较组分别花费最大时间固定在机器人和物体上。在整个会议期间，机器人小组减少了对机器人的关注，并增加了对其他地方的关注。总体而言，有节奏的运动环境为自闭症儿童提供了持续的社会监测。

BACKGROUND & AIMS: :The current manuscript is the second in a mini-series of manuscripts reporting the effects of alternative, movement-based, rhythm and robotic interventions on the social communication skills of 36 school-age children with ASD. This pilot randomized controlled trial compared the effects of 8-weeks of rhythm and robotic interventions to those of a standard-of-care, comparison intervention. The first manuscript reported intervention effects on the spontaneous and responsive social attention skills of children. In this manuscript, we report intervention effects on the spontaneous and responsive verbal communication skills of children. Communication skills were assessed within a standardized test of responsive communication during the pretest and posttest as well as using training-specific measures of social verbalization during early, mid, and late training sessions. The rhythm and comparison groups improved on the standardized test in the posttest compared to the pretest. The rhythm and robot groups increased levels of social verbalization across training sessions. Movement-based and stationary contexts afforded different types and amounts of communication in children with ASD. Overall, movement-based interventions are a promising tool to enhance verbal and non-verbal communication skills in children with ASD.

背景与目标： : 当前的手稿是小型手稿系列中的第二篇，报告了替代，基于运动，节奏和机器人干预对36名ASD学龄儿童的社会沟通技巧的影响。这项随机对照试验比较了8周节律和机器人干预与标准护理比较干预的效果。第一篇手稿报告了干预对儿童自发和反应迅速的社会注意技能的影响。在本手稿中，我们报告了干预对儿童自发和反应灵敏的口头交流技巧的影响。在前测试和后测试期间的响应式沟通标准化测试中评估了沟通技巧，并在早期，中期和后期培训期间使用了针对特定培训的社交语言化措施。与前测相比，后测中的标准化测试的节奏和比较组有所改善。节奏和机器人组在整个培训课程中提高了社交表达水平。基于运动和静止的环境为ASD儿童提供了不同类型和数量的交流。总体而言，基于运动的干预措施是增强ASD儿童的言语和非语言交流技能的有前途的工具。

BACKGROUND & AIMS: :Individuals with autism may engage in sexual behavior at inappropriate times and/or in inappropriate places. The current study investigated the effects of response interruption and redirection (RIRD) and response interruption (RI) on public masturbation (PM) of children and adolescents with autism. Initial assessments showed that PM was maintained by automatic reinforcement. During the treatment evaluation phase, we compared RIRD and RI to determine whether either procedure was successful in decreasing the duration of PM. In the RIRD condition, contingent on the occurrence of any PM the participant completed physical activities involving both hands (e.g., moving chairs, touching toes). In the RI condition, the therapist interrupted all instances of PM using physical and verbal prompts (e.g., saying in a neutral tone, "Stop that" and moving hands away from genitals). Both procedures were effective in decreasing the duration of PM but RI required fewer resources and less time. Clinical implications and suggestions for future research are reviewed.

背景与目标： : 自闭症患者可能会在不适当的时间和/或不适当的地方进行性行为。当前的研究调查了自闭症儿童和青少年的反应中断和重定向 (RIRD) 和反应中断 (RI) 对公共手淫 (PM) 的影响。初步评估显示，PM通过自动加固进行维护。在治疗评估阶段，我们比较了RIRD和RI，以确定两种手术是否成功减少了PM的持续时间。在RIRD条件下，取决于任何PM的发生，参与者完成了涉及双手的身体活动 (例如，移动椅子，触摸脚趾)。在RI条件下，治疗师使用物理和口头提示 (例如，以中性语气说 “停止” 并将手从生殖器上移开) 中断了所有PM实例。这两种方法都可以有效地减少PM的持续时间，但是RI需要更少的资源和更少的时间。回顾了临床意义和对未来研究的建议。

BACKGROUND & AIMS: :Amorphous solid dispersions (ASDs) are often used for formulating poorly water-soluble active pharmaceutical ingredients (APIs). In an ASD, the amorphous API is embedded in a suitable matrix excipient in order to stabilize the amorphous state and control the dissolution performance. ASDs can be prepared by commonly dissolving the API and the polymer in a suitable organic solvent which is evaporated afterward (e.g., via spray drying) aiming at a homogeneous API distribution in the polymer matrix. Sometimes, unexpected solvent influences on the heterogeneity of the dry ASD are observed. Thermodynamic predictions using the Perturbed-Chain Statistical Associating Fluid Theory combined with experimental investigations via Raman spectroscopy, differential scanning calorimetry, and microscopy performed in this work revealed the amorphous phase separation (APS) between the solvent and the polymer as causing the ASD heterogeneities. It will be shown that thermodynamic modeling allows for identifying appropriate solvents that will neither show APS with the polymeric excipient nor at any time of the drying process of ASD formulations.

背景与目标： : 无定形固体分散体 (asd) 通常用于配制水溶性差的活性药物成分 (api)。在ASD中，将无定形API嵌入合适的基质赋形剂中，以稳定无定形状态并控制溶解性能。ASDs可以通过通常将API和聚合物溶解在合适的有机溶剂中制备，所述有机溶剂随后 (例如，通过喷雾干燥) 蒸发，以使API在聚合物基质中均匀分布。有时，会观察到意外的溶剂对干燥ASD的异质性的影响。使用扰动链统计关联流体理论进行的热力学预测，结合拉曼光谱，差示扫描量热法和显微镜的实验研究，在这项工作中进行了研究，揭示了溶剂和聚合物之间的非晶相分离 (APS) 导致ASD异质性。将表明，热力学模型允许鉴定合适的溶剂，这些溶剂既不会显示带有聚合物赋形剂的APS，也不会在ASD制剂的干燥过程的任何时间显示APS。

BACKGROUND & AIMS: :There is limited research regarding the effectiveness of community-based services for young adults with autism spectrum disorder (ASD) as they transition out of school and enter a more autonomous life stage. This study utilized a two-phase, mixed methods design to determine the feasibility and participant acceptability of a protocol developed to standardize an assessment of program effectiveness for young adults with ASD at a community-based center. Field notes, participant interviews, and clinical observations were combined with descriptive analysis of participant survey responses. This study offers insights into the process of effective outcomes measurement for young adults with ASD participating in community-based programs. Administration of the study's protocol is feasible; however, alternative methods of data collection should continue to be explored. Furthermore, research in the form of a pilot study is needed to further determine the protocol's facility for assessing program outcomes in young adults with ASD.

背景与目标： : 关于针对自闭症谱系障碍 (ASD) 的年轻人的社区服务的有效性的研究有限，因为他们从学校过渡到进入更自主的生活阶段。这项研究采用了两阶段的混合方法设计，以确定开发的协议的可行性和参与者的可接受性，该协议旨在标准化社区中心对患有ASD的年轻人的计划有效性评估。现场笔记，参与者访谈和临床观察与参与者调查答复的描述性分析相结合。这项研究为参加社区计划的ASD年轻人提供了有效结果测量过程的见解。研究方案的管理是可行的; 但是，应继续探索其他数据收集方法。此外，还需要以试点研究的形式进行研究，以进一步确定该方案用于评估患有ASD的年轻人的计划结果的工具。

BACKGROUND & AIMS: AIMS:Atrial fibrillation and flutter remain an important cause of morbidity in adults with atrial septal defect (ASD). This study aimed at investigating predictors for late (≥ 1 month after repair) atrial arrhythmia. METHODS:Patients who underwent ASD closure after the age of 18 years, were selected through the databases of three medical centres in Belgium. Preprocedural, periprocedural and follow-up data were extracted. Univariate and multivariate Cox-regression analysis was performed. Kaplan-Meier analysis was performed for any independent predictor of late atrial arrhythmia. RESULTS:A total of 155 patients (38 men and 117 women) was included. Twenty-four patients (median age 48.3 years, range 19.9-79.8) underwent surgical and 131 (median age 57.6 years, range 18.2-86.9) underwent transcatheter closure. Thirty-nine patients (25.2%) presented with late atrial arrhythmia. Male gender (P = 0.008), creatinine (P = 0.002), atrial arrhythmia before (P < 0.0001) and within 1 month after repair (P = 0.001) and a mean pulmonary artery pressure (mPAP) ≥ 25 mmHg (P < 0.0001) correlated with late atrial arrhythmia in univariate Cox-regression analysis. Multivariate analysis showed that mPAP ≥ 25 mm Hg (HR 3.72; 95%CI 1.82-7.59; P < 0.0001) and the presence of atrial arrhythmia before (HR 3.22; 95%CI 1.56-6.66; P = 0.002) and within 1 month after repair (HR 2.08; 95%CI 2.08-15.92; P = 0.001) were predictive of late atrial arrhythmia. Kaplan-Meier analysis showed that patients with a mPAP ≥ 25 mm Hg had a higher risk at developing late atrial arrhythmia (P < 0.0001). CONCLUSION:In patients with ASD type secundum, a mPAP ≥ 25 mmHg is an independent predictor of late atrial arrhythmia. The presence of pulmonary hypertension before repair should raise awareness for atrial arrhythmias and may be used to guide therapy.

背景与目标：

BACKGROUND & AIMS: :Autism spectrum disorder (ASD) is a neurodevelopmental disorder with complex aetiology and phenotypes. Phosphodiesterase-10A (PDE10A) inhibition has shown to provide benefits in various brain conditions. We investigated the role of a PDE10A inhibitor, papaverine on core phenotypes in prenatal-valproic acid (Pre-VPA) model of ASD. In order to identify probable mechanisms involved, the effects on several protein markers of neuronal function such as, neurogenesis-DCX, neuronal survival-BDNF, synaptic transmission-synapsin-IIa, neuronal transcription factor-pCREB, neuronal inflammation (IL-6, IL-10 and TNF-α) and neuronal oxidative stress (TBARS and GSH) were studied in frontal cortex, cerebellum, hippocampus and striatum. Pre-VPA induced impairments in social behaviour, presence of repetitive behaviour, hyper-locomotion, anxiety, and diminished nociception were studied in male Albino Wistar rats. Administration of papaverine to Pre-VPA animals resulted in improvements of social behaviour, corrected repetitive behaviour, anxiety, locomotor, and nociceptive changes. Also, papaverine resulted in a significant increase in the levels of BDNF, synapsin-IIa, DCX, pCREB, IL-10 and GSH along with significant decrease in TNF-α, IL-6 and TBARS in different brain areas of Pre-VPA group. Finally, high association between behavioural parameters and biochemical parameters was observed upon Pearson's correlation analysis. Papaverine, administration rectified core behavioural phenotype of ASD, possibly by altering protein markers associated with neuronal survival, neurogenesis, neuronal transcription factor, neuronal transmission, neuronal inflammation, and neuronal oxidative stress. Implicating PDE10A as a possible target for furthering our understanding of ASD phenotypes.

背景与目标： 自闭症谱系障碍 (ASD) 是一种具有复杂病因和表型的神经发育障碍。Phosphodiesterase-10A (PDE10A) 抑制已显示在各种大脑条件下提供益处。我们研究了PDE10A抑制剂罂粟碱对ASD产前丙戊酸 (Pre-VPA) 模型核心表型的作用。为了确定可能涉及的机制，对神经元功能的几种蛋白质标志物的影响，例如，神经发生-DCX，神经元存活-BDNF，突触传递-突触素-IIa，神经元转录因子-pCREB，神经元炎症 (IL-6，在额叶皮层，小脑，海马和纹状体中研究了IL-10和TNF-α) 和神经元氧化应激 (TBARS和GSH)。在雄性白化病Wistar大鼠中研究了VPA前引起的社交行为障碍，重复行为的存在，过度运动，焦虑和伤害感受减弱。对VPA前动物施用罂粟碱可改善社交行为，纠正重复行为，焦虑，运动能力和伤害性变化。此外，罂粟碱导致前VPA组不同脑区域的BDNF，synapsin-IIa，DCX，pCREB，IL-10和GSH的水平显着增加，同时TNF-α，IL-6和TBARS显着降低。最后，通过Pearson相关分析，观察到行为参数与生化参数之间的高度关联。罂粟碱，给药可能通过改变与神经元存活，神经发生，神经元转录因子，神经元传递，神经元炎症和神经元氧化应激相关的蛋白质标记物来纠正ASD的核心行为表型。暗示PDE10A是进一步了解ASD表型的可能靶标。