Telehealth Versus Face-to-Face Fine Motor and Social Communication Interventions for Children With Autism Spectrum Disorder: Efficacy, Fidelity, Acceptability, and Feasibility.

IMPORTANCE: The efficacy of telehealth (TH) interventions needs to be studied. OBJECTIVE: To compare the efficacy, fidelity, acceptability, and feasibility of face-to-face (F2F) versus TH seated play (SP) interventions among children with autism spectrum disorder (ASD). DESIGN: As part of a larger randomized controlled trial, children were assigned to the SP group and received TH and F2F interventions over 8 wk using a pretest-posttest study design. SETTING: A research lab or through videoconferencing. PARTICIPANTS: Fifteen children with ASD (ages 5-14 yr) were randomly assigned to the SP group and received the intervention F2F or through TH. INTERVENTION: Children received 16 SP intervention sessions (2 sessions per week for 8 wk). OUTCOMES AND MEASURES: Pretests and posttests included standardized fine motor assessments. Video coding compared socially directed verbalization during training sessions. Parents and trainers provided feedback on their experiences. RESULTS: Seven children received the intervention F2F, whereas 8 received TH intervention. Children in both subgroups showed similar training improvements in fine motor skills and socially directed verbalizations (ps > .01). Parents rated both interventions as acceptable and feasible; however, they reported longer preparation time and effort during TH interventions (ps < .01). Trainers reported greater parental involvement but more communication and technological issues during TH interventions. Fidelity checks indicated fewer reinforcements during TH versus F2F sessions. CONCLUSIONS AND RELEVANCE: TH intervention is feasible and effective in improving fine motor and social communication performance. Clinicians should reduce parental burden and overcome technological issues. What This Article Adds: This study confirmed the efficacy, fidelity, acceptability, and feasibility of delivering seated play, standard of care interventions for children with autism spectrum disorder via telehealth. However, clinicians should work on reducing parental burden and overcoming communication and technological issues related to telehealth.

Using Telehealth to Conduct Family-Centered, Movement Intervention Research in Children With Autism Spectrum Disorder During the COVID-19 Pandemic.

PURPOSE: After the COVID-19 pandemic, several randomized controlled trials came to a halt; however, we chose to reinvent our study and shifted to a home-based, telehealth intervention delivery format to support children with autism spectrum disorder and their families. Children with autism spectrum disorder have social communication impairments as well as perceptuomotor and cognitive comorbidities. Continued access to care is crucial for their long-term development. METHODS: We created a general movement intervention to target strength, endurance, executive functioning, and social skills through goal-directed games and activities delivered using a telehealth intervention model. FINDINGS: Our family-centered approach allowed for collaboration between trainers and caregivers and made it easy for families to replicate training activities at home. CONCLUSIONS: While more studies comparing telehealth and face-to-face interventions are needed, we encourage researchers and clinicians to consider family-centered telehealth as a valid and feasible intervention delivery method, to increase the likelihood of carryover of skills into the daily lives of children and ultimately enhance their long-term development.

Protective Effect of a Fucose-Rich Fucoidan Isolated from Saccharina japonica against Ultraviolet B-Induced Photodamage In Vitro in Human Keratinocytes and In Vivo in Zebrafish.

A fucose-rich fucoidan was purified from brown seaweed Saccharina japonica, of which the UVB protective effect was investigated in vitro in keratinocytes of HaCaT cells and in vivo in zebrafish. The intracellular reactive oxygen species levels and the viability of UVB-irradiated HaCaT cells were determined. The results indicate that the purified fucoidan significantly reduced the intracellular reactive oxygen species levels and improved the viability of UVB-irradiated HaCaT cells. Furthermore, the purified fucoidan remarkably decreased the apoptosis by regulating the expressions of Bax/Bcl-xL and cleaved caspase-3 in UVB-irradiated HaCaT cells in a dose-dependent manner. In addition, the in vivo UV protective effect of the purified fucoidan was investigated using a zebrafish model. It significantly reduced the intracellular reactive oxygen species level, the cell death, the NO production, and the lipid peroxidation in UVB-irradiated zebrafish in a dose-dependent manner. These results suggest that purified fucoidan has a great potential to be developed as a natural anti-UVB agent applied in the cosmetic industry.

A Pilot Study Comparing the Efficacy, Fidelity, Acceptability, and Feasibility of Telehealth and Face-to-Face Creative Movement Interventions in Children with Autism Spectrum Disorder.

Aims: We compared the efficacy, fidelity, acceptability, and feasibility of a creative movement (CM) intervention for children with autism spectrum disorder (ASD), delivered face-to-face (F2F) or through telehealth (TH). Methods: Fifteen children with ASD received the CM intervention F2F or through TH. Motor assessments were used to evaluate effects of F2F and TH interventions on children's motor skills, while video coding was used to assess affect, socially directed verbalization, interpersonal synchrony, and motor coordination during training. Stakeholder feedback and training fidelity data on the intervention were also collected. Results: Children in both subgroups showed similar baseline performance and training-related improvements in motor skills, positive/interested affect, socially directed verbalization, interpersonal synchrony, and dual/multilimb coordination. Parents in the TH subgroup considered the intervention feasible and acceptable; however, they reported greater effort to supervise and redirect their child's attention compared to the F2F subgroup. Trainers for the TH subgroup reported more communication difficulties, technological issues, and longer session lengths, but found greater parental involvement compared to the F2F subgroup. Conclusions: CM interventions are consistent, acceptable, feasible, and effective in improving social, behavioral-affective, and motor skills of children with ASD, regardless of the method of delivery. Clinicians should make efforts to reduce communication/technological issues and parental burden when delivering CM interventions through TH. ClinicalTrials.Gov Study ID-NCT04258254.

Developmental Differences in Reaching-and-Placing Movement and Its Potential in Classifying Children with and without Autism Spectrum Disorder: Deep Learning Approach.

Autism Spectrum Disorder (ASD) is among the most prevalent neurodevelopmental disorders, yet the current diagnostic procedures rely on behavioral analyses and interviews and lack objective screening methods. This study seeks to address this gap by integrating upper limb kinematics and deep learning methods to identify potential biomarkers that could be validated in younger age groups in the future to enhance the identification of ASD. Forty-one school-age children, with and without an ASD diagnosis (Mean age ± SE = 10.3 ± 0.4; 12 Females), participated in the study. A single Inertial Measurement Unit (IMU) was affixed to the child's wrist as they engaged in a continuous reaching and placing task. Deep learning techniques were employed to classify children with and without ASD. Our findings suggest delays in motor planning and control in school-age children compared to healthy adults. Compared to TD children, children with ASD exhibited poor motor planning and control as seen by greater number of movement units, more movement overshooting, and prolonged time to peak velocity/acceleration. Compensatory movement strategies such as greater velocity and acceleration were also seen in the ASD group. More importantly, using Multilayer Perceptron (MLP) model, we demonstrated an accuracy of ~ 78.1% in classifying children with and without ASD. These findings underscore the potential use of studying upper limb movement kinematics during goal-directed arm movements and deep learning methods as valuable tools for classifying and, consequently, aiding in the diagnosis and early identification of ASD upon further validation in younger children.

fNIRS-Based Differences in Cortical Activation during Tool Use, Pantomimed Actions, and Meaningless Actions between Children with and without Autism Spectrum Disorder (ASD).

Children with autism spectrum disorder (ASD) have difficulties with tool use and pantomime actions. The current study utilized functional near-infrared spectroscopy (fNIRS) to examine the neural mechanisms underlying these gestural difficulties. Thirty-one children with and without ASD (age (mean ± SE) = 11.0 ± 0.6) completed a naturalistic peg-hammering task using an actual hammer (hammer condition), pantomiming hammering actions (pantomime condition), and performing meaningless actions with similar joint motions (meaningless condition). Children with ASD exhibited poor praxis performance (praxis error: TD = 17.9 ± 1.7; ASD = 27.0 ± 2.6, p < 0.01), which was significantly correlated with their cortical activation (R = 0.257 to 0.543). Both groups showed left-lateralized activation, but children with ASD demonstrated more bilateral activation during all gestural conditions. Compared to typically developing children, children with ASD showed hyperactivation of the inferior parietal lobe and hypoactivation of the middle/inferior frontal and middle/superior temporal regions. Our findings indicate intact technical reasoning (typical left-IPL activation) but atypical visuospatial and proprioceptive processing (hyperactivation of the right IPL) during tool use in children with ASD. These results have important implications for clinicians and researchers, who should focus on facilitating/reducing the burden of visuospatial and proprioceptive processing in children with ASD. Additionally, fNIRS-related biomarkers could be used for early identification through early object play/tool use and to examine neural effects following gesture-based interventions.

Autism-Related Differences in Cortical Activation When Observing, Producing, and Imitating Communicative Gestures: An fNIRS Study.

Children with autism spectrum disorder (ASD) have difficulties in gestural communication during social interactions. However, the neural mechanisms involved in naturalistic gestural communication remain poorly understood. In this study, cortical activation patterns associated with gestural communication were examined in thirty-two children with and without ASD (mean age: 11.0 years, SE: 0.6 years). Functional near-infrared spectroscopy (fNIRS) was used to record cortical activation while children produced, observed, or imitated communicative gestures. Children with ASD demonstrated more spatial and temporal errors when performing and imitating communicative gestures. Although both typically developing (TD) children and children with ASD showed left-lateralized cortical activation during gesture production, children with ASD showed hyperactivation in the middle/inferior frontal gyrus (MIFG) during observation and imitation, and hypoactivation in the middle/superior temporal gyrus (MSTG) during gesture production compared to their TD peers. More importantly, children with ASD exhibited greater MSTG activation during imitation than during gesture production, suggesting that imitation could be an effective intervention strategy to engage cortical regions crucial for processing and producing gestures. Our study provides valuable insights into the neural mechanisms underlying gestural communication difficulties in ASD, while also identifying potential neurobiomarkers that could serve as objective measures for evaluating intervention effectiveness in children with ASD.

The use of functional near-infrared spectroscopy in tracking neurodevelopmental trajectories in infants and children with or without developmental disorders: a systematic review.

Understanding the neurodevelopmental trajectories of infants and children is essential for the early identification of neurodevelopmental disorders, elucidating the neural mechanisms underlying the disorders, and predicting developmental outcomes. Functional Near-Infrared Spectroscopy (fNIRS) is an infant-friendly neuroimaging tool that enables the monitoring of cerebral hemodynamic responses from the neonatal period. Due to its advantages, fNIRS is a promising tool for studying neurodevelopmental trajectories. Although many researchers have used fNIRS to study neural development in infants/children and have reported important findings, there is a lack of synthesized evidence for using fNIRS to track neurodevelopmental trajectories in infants and children. The current systematic review summarized 84 original fNIRS studies and showed a general trend of age-related increase in network integration and segregation, interhemispheric connectivity, leftward asymmetry, and differences in phase oscillation during resting-state. Moreover, typically developing infants and children showed a developmental trend of more localized and differentiated activation when processing visual, auditory, and tactile information, suggesting more mature and specialized sensory networks. Later in life, children switched from recruiting bilateral auditory to a left-lateralized language circuit when processing social auditory and language information and showed increased prefrontal activation during executive functioning tasks. The developmental trajectories are different in children with developmental disorders, with infants at risk for autism spectrum disorder showing initial overconnectivity followed by underconnectivity during resting-state; and children with attention-deficit/hyperactivity disorders showing lower prefrontal cortex activation during executive functioning tasks compared to their typically developing peers throughout childhood. The current systematic review supports the use of fNIRS in tracking the neurodevelopmental trajectories in children. More longitudinal studies are needed to validate the neurodevelopmental trajectories and explore the use of these neurobiomarkers for the early identification of developmental disorders and in tracking the effects of interventions.

Phospholipase A2 (PLA2) injured lymphatic endothelial cells leading to progression of secondary lymphoedema.

Secondary lymphoedema is one of the common complications after lymph node dissection for gynecologic malignancies and breast cancer. In this study, the relationship between PLA2 and postoperative lymphoedema in cancer at the molecular level has been explored through transcriptomics and metabolomic assays. Transcriptome sequencing technology, as well as metabolomic assays, were utilized to explore the expression of PLA2 in lymphoedema patients, and search for potential pathways in the pathogenesis and exacerbation mechanism of lymphoedema. The effect of sPLA2 on human lymphatic endothelial cells was investigated by culturing human lymphatic endothelial cells. Secretory phospholipases A2 (sPLA2) showed high expression levels in lymphoedema tissues, however, cytoplasmic phospholipases A2 (cPLA2), showed low expression in lymphoedema, as demonstrated by RT-qPCR. By culturing human lymphatic vascular endothelial cells, the study found that sPLA2 causes HLEC vacuolization and has an inhibitory effect on HLEC proliferation and migration. By detecting sPLA2 in the serum of lymphoedema patients and analyzing clinical data, it was found that sPLA2 was positively correlated with the severity of lymphoedema. Secretory Phospholipase A2 (sPLA2) is highly expressed in lymphoedema tissue, damages lymphatic vessel endothelial cells, is strongly associated with disease severity, and can be used as a potential predictor of disease severity.Abbreviations: PLA2: Phospholipase A2; DEGs: differentially expressed genes; DMP: differential metabolic production.

Simultaneous multimodal fNIRS-EEG recordings reveal new insights in neural activity during motor execution, observation, and imagery.

Motor execution, observation, and imagery are important skills used in motor learning and rehabilitation. The neural mechanisms underlying these cognitive-motor processes are still poorly understood. We used a simultaneous recording of functional near-infrared spectroscopy (fNIRS) and electroencephalogram (EEG) to elucidate the differences in neural activity across three conditions requiring these processes. Additionally, we used a new method called structured sparse multiset Canonical Correlation Analysis (ssmCCA) to fuse the fNIRS and EEG data and determine the brain regions of neural activity consistently detected by both modalities. Unimodal analyses revealed differentiated activation between conditions; however, the activated regions did not fully overlap across the two modalities (fNIRS: left angular gyrus, right supramarginal gyrus, as well as right superior and inferior parietal lobes; EEG: bilateral central, right frontal, and parietal). These discrepancies might be because fNIRS and EEG detect different signals. Using fused fNIRS-EEG data, we consistently found activation over the left inferior parietal lobe, superior marginal gyrus, and post-central gyrus during all three conditions, suggesting that our multimodal approach identifies a shared neural region associated with the Action Observation Network (AON). This study highlights the strengths of using the multimodal fNIRS-EEG fusion technique for studying AON. Neural researchers should consider using the multimodal approach to validate their findings.

Cortical activation during cooperative joint actions and competition in children with and without an autism spectrum condition (ASC): an fNIRS study.

Children with an Autism Spectrum Condition (ASC) have social communication and perceptuomotor difficulties that affect their ability to engage in dyadic play. In this study, we compared spatio-temporal errors and fNIRS-related cortical activation between children with and without an ASC during a Lincoln Log dyadic game requiring them to play leader or follower roles, move in synchrony or while taking turns, and move cooperatively or competitively with an adult partner. Children with an ASC had greater motor, planning, and spatial errors and took longer to complete the building tasks compared to typically developing (TD) children. Children with an ASC had lower superior temporal sulcus (STS) activation during Turn-take and Compete, and greater Inferior Parietal Lobe (IPL) activation during Lead and Turn-take compared to TD children. As dyadic play demands increased, TD children showed greater STS activation during Turn-take (vs. Synchrony) and Compete (vs. Cooperate) whereas children with an ASC showed greater IPL activation during Lead and Compete (vs. Cooperate). Our findings suggest that children with an ASC rely on self-generated action plans (i.e., increased IPL activation) more than relying on their partner's action cues (i.e., reduced STS activation) when engaging in dyadic play including joint actions and competition.

Neural Effects of Physical Activity and Movement Interventions in Individuals With Developmental Disabilities-A Systematic Review.

Individuals with developmental disabilities present with perceptuo-motor, social communication, and cognitive impairments that often relate to underlying atypical brain structure and functioning. Physical activity/movement interventions improve behavioral performance of individuals with and without developmental disabilities. Majority of the evidence on potential neural mechanisms explaining the impact of physical activity/movement interventions is based on studies in individuals with typical development; there is a dearth of systematic reviews synthesizing the neural effects of physical activity/movement interventions in individuals with developmental disabilities. In this systematic review, we have gathered evidence on the neural effects of physical activity/movement interventions from 32 papers reporting substantial neural effects and behavioral improvements in individuals with developmental disabilities. Chronic intervention effects (multiple sessions) were greater than acute intervention effects (single session). Specifically, using electroencephalogram, functional magnetic resonance imaging, diffusion tensor imaging, and functional near-infrared spectroscopy, studies found physical activity/movement intervention-related changes in neural activity, indicating normalization of cortical arousal in individuals with attention-deficit /hyperactivity disorder (ADHD), increased social brain connectivity in individuals with autism spectrum disorder (ASD), and more efficient executive functioning processes in individuals with a wide range of other developmental disabilities. Despite promising results, more research is clearly needed in this area with larger sample sizes, using standardized neuroimaging tools/variables, and across multiple diagnoses to further explore the neural mechanisms underlying physical activity/movement interventions and to replicate findings from the present review.

Bioinformatics analysis of inflammation and oncology in pulmonary lymphangioleiomyomatosis.

This study investigates the molecular markers and biological pathways of pulmonary lymphangioleiomyomatosis. We analyzed 2 gene expression profiles in the gene expression omnibus Gene Expression Omnibus database for normal lung tissue and lymphangioleiomyomatosis and identified differential expressed genes in pulmonary lymphangioleiomyomatosis. Ninety-one differentially expressed genes were identified, including 36 upregulated genes and 55 downregulated genes. Hub genes and pathogenic pathways associated with disease development were subsequently identified by enrichment analysis and protein-protein interaction network. Analysis showed that differential expressed genes are mainly involved in the biological behavior of tumor cell proliferation and invasion as well as the inflammatory response. We have identified 10 hub genes in the protein-protein interaction network. Hub genes play an important role in the proliferation and inflammatory response involved in tumor cell proliferation. This study deepens the understanding of lymphangioleiomyomatosis disease and provides a biological basis for further clinical diagnosis and treatment.

Effects of Creative Movement Therapies on Social Communication, Behavioral-Affective, Sensorimotor, Cognitive, and Functional Participation Skills of Individuals With Autism Spectrum Disorder: A Systematic Review.

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder affecting multiple developmental domains including social communication, behavioral-affective, sensorimotor, and cognitive systems. There is growing evidence for the use of holistic, whole-body, Creative Movement Therapies (CMT) such as music, dance, yoga, theater, and martial arts in addressing the multisystem impairments in ASD. We conducted a comprehensive quantitative and qualitative review of the evidence to date on the effects of CMT on multiple systems in individuals with ASD. The strongest evidence, both in terms of quantity and quality, exists for music and martial arts-based interventions followed by yoga and theater, with very limited research on dance-based approaches. Our review of 72 studies (N = 1,939 participants) across participants with ASD ranging from 3 to 65 years of age suggests that at present there is consistent evidence from high quality studies for small-to-large sized improvements in social communication skills following music and martial arts therapies and medium-to-large improvements in motor and cognitive skills following yoga and martial arts training, with insufficient evidence to date for gains in affective, sensory, and functional participation domains following CMT. Although promising, our review serves as a call for more rigorous high-quality research to assess the multisystem effects of CMT in ASD. Based on the existing literature, we discuss implications of our findings for autism researchers and also provide evidence-based guidelines for clinicians to incorporate CMT approaches in their plan of care for individuals with ASD.

Short report on research trends during the COVID-19 pandemic and use of telehealth interventions and remote brain research in children with autism spectrum disorder.

LAY ABSTRACT: The COVID-19 pandemic has caused disruption in F2F healthcare delivery and neuroimaging research, especially when involving vulnerable populations such as children with autism spectrum disorder. Given the easy access to multiple video conferencing platforms, many healthcare services have moved to an online delivery format (i.e. telehealth). It is important to monitor the behavioral and neural effects of telehealth interventions and resume neuroimaging research while adopting public health safety protocols to control the risk of COVID-19 transmission. We summarize existing safety protocols and our own experience from in-person functional near-infrared spectroscopy neuroimaging data collection (on-site, at home, and in outdoor settings), as well as potential opportunities of using online data sharing and low-cost, remote neuroimaging/electrophysiological techniques to continue brain research during the pandemic.

Movement kinematics and cortical activation in children with and without autism spectrum disorder during sway synchrony tasks: an fNIRS study.

Children with Autism Spectrum Disorder (ASD) have difficulties with socially embedded movements such as imitation and interpersonal synchrony (IPS); however, related movement characteristics and underlying neural mechanisms are not well understood. This study compared the movement characteristics and cortical activation patterns of children with and without ASD during a whole-body, sway synchrony task when different levels of social information were provided. Thirty children with and without ASD (mean age: 12.6 years, SE: 0.6 years) participated. Movement kinematics and fNIRS-based cortical activation were recorded when the child observed an adult tester sway side to side, when they swayed solo, or when they swayed face to face with the tester with or without fingertips touching (i.e., IPS). Children with ASD showed reduced synchrony and smaller sway amplitude compared to typically developing children without ASD. They showed reduced cortical activation over the inferior frontal gyrus and superior temporal sulcus during IPS and did not show significant increase in cortical activation when more social information was provided. The cortical activation findings were significantly associated with IPS behaviors and social communication performance. The ASD-related neurobiomarkers identified in our study could be used as objective measures to evaluate intervention effects in children with ASD.

Looking Back at the Next 40 Years of ASD Neuroscience Research.

During the last 40 years, neuroscience has become one of the most central and most productive approaches to investigating autism. In this commentary, we assemble a group of established investigators and trainees to review key advances and anticipated developments in neuroscience research across five modalities most commonly employed in autism research: magnetic resonance imaging, functional near infrared spectroscopy, positron emission tomography, electroencephalography, and transcranial magnetic stimulation. Broadly, neuroscience research has provided important insights into brain systems involved in autism but not yet mechanistic understanding. Methodological advancements are expected to proffer deeper understanding of neural circuitry associated with function and dysfunction during the next 40 years.

Deep conservation of prion-like composition in the eukaryotic prion-former Pub1/Tia1 family and its relatives.

Pub1 protein is an important RNA-binding protein functional in stress granule assembly in budding yeast Saccharomyces cerevisiae and, as its co-ortholog Tia1, in humans. It is unique among proteins in evidencing prion-like aggregation in both its yeast and human forms. Previously, we noted that Pub1/Tia1 was the only protein linked to human disease that has prion-like character and and has demonstrated such aggregation in both species. Thus, we were motivated to probe further into the evolution of the Pub1/Tia1 family (and its close relative Nam8 and its orthologs) to gain a picture of how such a protein has evolved over deep evolutionary time since the last common ancestor of eukaryotes. Here, we discover that the prion-like composition of this protein family is deeply conserved across eukaryotes, as is the prion-like composition of its close relative Nam8/Ngr1. A sizeable minority of protein orthologs have multiple prion-like domains within their sequences (6-20% depending on criteria). The number of RNA-binding RRM domains is conserved at three copies over >86% of the Pub1 family (>71% of the Nam8 family), but proteins with just one or two RRM domains occur frequently in some clades, indicating that these are not due to annotation errors. Overall, our results indicate that a basic scaffold comprising three RNA-binding domains and at least one prion-like region has been largely conserved since the last common ancestor of eukaryotes, providing further evidence that prion-like aggregation may be a very ancient and conserved phenomenon for certain specific proteins.

Differences in cortical activation patterns during action observation, action execution, and interpersonal synchrony between children with or without autism spectrum disorder (ASD): An fNIRS pilot study.

Engaging in socially embedded actions such as imitation and interpersonal synchrony facilitates relationships with peers and caregivers. Imitation and interpersonal synchrony impairments of children with Autism Spectrum Disorder (ASD) might contribute to their difficulties in connecting and learning from others. Previous fMRI studies investigated cortical activation in children with ASD during finger/hand movement imitation; however, we do not know whether these findings generalize to naturalistic face-to-face imitation/interpersonal synchrony tasks. Using functional near infrared spectroscopy (fNIRS), the current study assessed the cortical activation of children with and without ASD during a face-to-face interpersonal synchrony task. Fourteen children with ASD and 17 typically developing (TD) children completed three conditions: a) Watch-observed an adult clean up blocks; b) Do-cleaned up the blocks on their own; and c) Together-synchronized their block clean up actions to that of an adult. Children with ASD showed lower spatial and temporal synchrony accuracies but intact motor accuracy during the Together/interpersonal synchrony condition. In terms of cortical activation, children with ASD had hypoactivation in the middle and inferior frontal gyri (MIFG) as well as middle and superior temporal gyri (MSTG) while showing hyperactivation in the inferior parietal cortices/lobule (IPL) compared to the TD children. During the Together condition, the TD children showed bilaterally symmetrical activation whereas children with ASD showed more left-lateralized activation over MIFG and right-lateralized activation over MSTG. Additionally, using ADOS scores, in children with ASD greater social affect impairment was associated with lower activation in the left MIFG and more repetitive behavior impairment was associated with greater activation over bilateral MSTG. In children with ASD better communication performance on the VABS was associated with greater MIFG and/or MSTG activation. We identified objective neural biomarkers that could be utilized as outcome predictors or treatment response indicators in future intervention studies.

Mouse tail models of secondary lymphedema: fibrosis gradually worsens and is irreversible.

Although the mouse tail model of secondary lymphedema has been widely used in research, our knowledge regarding some of the characteristic changes in this model is lacking. Therefore, in the current study, we aimed to identify pathologic changes after surgery. Tail lymphedema was created in C57BL/6J mice by disconnecting both superficial and deep lymphatic vessels. The surgery resulted in chronic edema formation with the proliferation of subcutaneous adipose tissue, deposition of fibrotic tissue, and gradual increase in CD4+ T lymphocyte infiltration. Furthermore, dramatic expansion and an increased number of lymphatic vessels were observed postoperatively. Lymphatic reflux was established at least 8 weeks after surgery, as evidenced by staining of the scar from the surgical excision. In addition, tissue fibrosis was irreversible, although CD4+ T cell infiltration, tail swelling, and subcutaneous adipose hyperplasia were alleviated over time. We also show that necrosis could be effectively avoided by paying attention to several details in the modeling process. As animal models play a key role in exploring the pathophysiology of disease, our findings provide strong support for the study of lymphedema. The irreversibility of fibrosis suggests the importance of treating lymphedema by preventing fibrosis development.