Search

Purpose: This study aimed to translate and cross-culturally adapt the "Voice-related Experiences of Nonbinary Individuals" (VENI) to Brazilian Portuguese (BP)., Methods: Cross-cultural adaptation was performed based on the combined guidelines of the World Health Organization's (WHO) Translation Recommendations and the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN). The process included five stages: a) Translation of the instrument into BP by a translator specialized in the construct and a non-specialist, both native BP speakers and fluent in English; b) Synthesis of the two translations by consensus; c) Back-translation by a translator specialized in the construct and a non-specialist, both native English speakers and fluent in BP; d) Analysis by a committee of five speech-language pathologists voice specialist and the creation of the final version; e) Pre-testing with 21 individuals from the target population, conducted virtually., Results: During the translation stage, there were disagreements regarding the title, instructions, response key, and 15 items. In the back-translation stage, there were discrepancies in the format of 12 items and the content of four items. The expert committee's analysis led to changes in the title, instructions, one option in the response key, and eight items to meet the equivalence criteria. In the pre-test, a significantly higher proportion of usual responses to the instrument was observed when compared to the non-applicable option; this is frequently observed in instrument adaptations., Conclusion: The cross-cultural adaptation of VENI into Brazilian Portuguese was successful, resulting in the "Experiências relacionadas à Voz de Pessoas Não Binárias - VENI-Br" version.

Cerebellar dysfunction has been linked to autism spectrum disorders (ASDs). Although cerebellar pathology has been observed in individuals with fragile X syndrome (FXS) and in mouse models of the disorder, a cerebellar functional contribution to ASD-relevant behaviors in FXS has yet to be fully characterized. In this study, we demonstrate a critical cerebellar role for Fmr1 (fragile X messenger ribonucleoprotein 1) in ASD-relevant behaviors. First, we identify reduced social behaviors, sensory hypersensitivity, and cerebellar dysfunction, with loss of cerebellar Fmr1. We then demonstrate that cerebellar-specific expression of Fmr1 is sufficient to impact social, sensory, cerebellar dysfunction, and cerebro-cortical hyperexcitability phenotypes observed in global Fmr1 mutants. Moreover, we demonstrate that targeting the ASD-implicated cerebellar region Crus1 ameliorates behaviors in both cerebellar-specific and global Fmr1 mutants. Together, these results demonstrate a critical role for the cerebellar contribution to FXS-related behaviors, with implications for future therapeutic strategies., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The time of day strongly influences adaptive behaviors like long-term memory, but the correlating synaptic and molecular mechanisms remain unclear. The circadian clock comprises a canonical transcription-translation feedback loop (TTFL) strictly dependent on the BMAL1 transcription factor. We report that BMAL1 rhythmically localizes to hippocampal synapses in a manner dependent on its phosphorylation at Ser 42 [pBMAL1(S42)]. pBMAL1(S42) regulates the autophosphorylation of synaptic CaMKIIα and circadian rhythms of CaMKIIα-dependent molecular interactions and LTP but not global rest/activity behavior. Therefore, our results suggest a model in which repurposing of the clock protein BMAL1 to synapses locally gates the circadian timing of plasticity.

Transgender individuals may seek a variety of gender-affirming health and educational services, including voice modification from speech-language pathologists. Measuring the client's self-perception of their communication experiences is crucial for providing client-centered services and measuring outcomes. However, there is currently no validated assessment tool for the nonbinary population, a part of the transgender population. This study explores the voice-related concerns and experiences among the nonbinary population to create a valid measure of their self-perception of voice. Ten nonbinary individuals were surveyed about their voice-related concerns and experiences. A thematic analysis of the responses led to the development of the questionnaire, titled the Voice-related Experiences of Nonbinary Individuals. The questionnaire was systematically evaluated for its content validity by a panel of speech-language pathologist experts in transgender voice services. Outcomes of this analysis supported the measure's content validity and motivated further revisions. This is the first assessment tool that measures self-perception of voice and voice-related experiences for nonbinary individuals. Initial psychometric testing supported its content validity and further research is needed for large-scale testing of validity and reliability., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

BARLEY B-RECOMBINANT/BASIC PENTACYSTEINE (BBR/BPC) family members are plant-specific GAGA-motif binding factors (GAFs) controlling multiple developmental processes of growth and propagation. BPCs recruit histone remodeling factors for transcriptional repression of downstream targets. It has been revealed that BPCs have an overlapping and antagonistic relationship in regulating development. In this study, we showed disturbances interfering with the homeostasis of BPC expressions impede growth and development. The ectopic expression of BPC3 results in the daily growth defect shown by higher-order bpc mutants. Oscillations of multiple circadian clock genes are phase-delayed in the quadruple mutant of bpc1 bpc2 bpc4 bpc6 ( bpc1,2,4,6 ). By introducing the overexpression of BPC3 into wild-type Arabidopsis, we found that BPC3 is a repressor participating in its repression and repressing multiple regulators essential to the circadian clock. However, the induction of BPC3 overexpression did not fully replicate clock defects shown by the quadruple mutant, indicating that in addition to the BPC3 antagonization, BPC members also cofunction in the circadian clock regulation. A leaf edge defect similar to that shown by bpc1,2,4,6 is also observed under BPC3 induction, accompanied by repression of a subset of TCPs required for the edge formation. This proves that BPC3 is a repressor that must be confined during the vegetative phase. Our findings demonstrate that BPCs form a meticulous repressor network for restricting their repressive functions to molecular mechanisms controlling plant growth and development., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lee, Tsai, Huang and Tsai.)

Targeted therapies for epilepsies associated with the mTORC1 signaling negative regulator GATOR1 are lacking. NPRL2 is a subunit of the GATOR1 complex and mutations in GATOR1 subunits, including NPRL2 , are associated with epilepsy. To delineate the mechanisms underlying NPRL2-related epilepsies, we created a mouse ( Mus musculus ) model with neocortical loss of Nprl2 . Mutant mice have increased mTORC1 signaling and exhibit spontaneous seizures. They also display abnormal synaptic function characterized by increased evoked and spontaneous EPSC and decreased evoked and spontaneous IPSC frequencies, respectively. Proteomic and metabolomics studies of Nprl2 mutants revealed alterations in known epilepsy-implicated proteins and metabolic pathways, including increases in the neurotransmitter, glycine. Furthermore, glycine actions on the NMDA receptor contribute to the electrophysiological and survival phenotypes of these mice. Taken together, in this neuronal Nprl2 model, we delineate underlying molecular, metabolic, and electrophysiological mechanisms contributing to mTORC1-related epilepsy, providing potential therapeutic targets for epilepsy., Competing Interests: The authors declare no competing interests., (© 2022 The Authors.)

The cerebellum has been increasingly implicated in autism spectrum disorder (ASD) with many ASD-linked genes impacting both cerebellar function and development. However, the precise timing and critical periods of when abnormal cerebellar neurodevelopment contributes to ASD-relevant behaviors remains poorly understood. In this study, we identify a critical period for the development of ASD-relevant behaviors in a cerebellar male mouse model of tuberous sclerosis complex (TSC), by using the mechanistic target of rapamycin (mTOR) inhibitor, rapamycin, to pharmacologically inhibit dysregulated downstream signaling. We find independent critical periods during which abnormal ASD-relevant behaviors develop for the two core ASD diagnostic criteria, social impairments and behavioral flexibility, and delineate an anatomic, physiological, and behavioral framework. These findings not only further our understanding of the genetic mechanisms underlying the timing of ASD-relevant behaviors but also have the capacity to inform potential therapies to optimize treatment interventions. SIGNIFICANCE STATEMENT No targeted treatments currently exist for autism spectrum disorder (ASD). This complex developmental disorder has established links to genetic and circuit aberrations, yet the precise timing and coordination of these underlying mechanisms that contribute to the spectrum of physiological and behavioral abnormalities remains unclear. Cerebellar pathology is consistently seen in ASD individuals; therefore, we sought to identify the specific windows for cerebellar involvement in the development of ASD-relevant behaviors. Using pharmacologic treatment paradigms, we outline distinct critical periods of developmental vulnerability for ASD-relevant social and inflexible behaviors. From this study, we posit a refined window of time during which ASD symptoms develop that will inform therapeutic timing., (Copyright © 2022 the authors.)

Social interactions involve processes ranging from face recognition to understanding others' intentions. To guide appropriate behavior in a given context, social interactions rely on accurately predicting the outcomes of one's actions and the thoughts of others. Because social interactions are inherently dynamic, these predictions must be continuously adapted. The neural correlates of social processing have largely focused on emotion, mentalizing, and reward networks, without integration of systems involved in prediction. The cerebellum forms predictive models to calibrate movements and adapt them to changing situations, and cerebellar predictive modeling is thought to extend to nonmotor behaviors. Primary cerebellar dysfunction can produce social deficits, and atypical cerebellar structure and function are reported in autism, which is characterized by social communication challenges and atypical predictive processing. We examine the evidence that cerebellar-mediated predictions and adaptation play important roles in social processes and argue that disruptions in these processes contribute to autism.

Autism spectrum disorders (ASD) are highly prevalent neurodevelopmental disorders; however, the neurobiological mechanisms underlying disordered behavior in ASD remain poorly understood. Notably, individuals with ASD have demonstrated difficulties generating implicitly derived behavioral predictions and adaptations. Although many brain regions are involved in these processes, the cerebellum contributes an outsized role to these behavioral functions. Consistent with this prominent role, cerebellar dysfunction has been increasingly implicated in ASD. In this review, we will utilize the foundational, theoretical contributions of the late neuroscientist Masao Ito to establish an internal model framework for the cerebellar contribution to ASD-relevant behavioral predictions and adaptations. Additionally, we will also explore and then apply his key experimental contributions towards an improved, mechanistic understanding of the contribution of cerebellar dysfunction to ASD., (Copyright © 2020 IBRO. Published by Elsevier Ltd. All rights reserved.)

Cerebellar dysfunction has been demonstrated in autism spectrum disorders (ASDs); however, the circuits underlying cerebellar contributions to ASD-relevant behaviors remain unknown. In this study, we demonstrated functional connectivity between the cerebellum and the medial prefrontal cortex (mPFC) in mice; showed that the mPFC mediates cerebellum-regulated social and repetitive/inflexible behaviors; and showed disruptions in connectivity between these regions in multiple mouse models of ASD-linked genes and in individuals with ASD. We delineated a circuit from cerebellar cortical areas Right crus 1 (Rcrus1) and posterior vermis through the cerebellar nuclei and ventromedial thalamus and culminating in the mPFC. Modulation of this circuit induced social deficits and repetitive behaviors, whereas activation of Purkinje cells (PCs) in Rcrus1 and posterior vermis improved social preference impairments and repetitive/inflexible behaviors, respectively, in male PC-Tsc1 mutant mice. These data raise the possibility that these circuits might provide neuromodulatory targets for the treatment of ASD.

Dysregulated mTOR contributes to neurodevelopmental dysfunction. A new study (Chen et al., 2019) demonstrates that suppression of mTORC2, not mTORC1, ameliorates survival, seizures, and abnormal behaviors in a Pten mutant model, highlighting mTORC2 as a potential therapeutic target in mTORopathies., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: The study examined the relationship between word-form similarity network (phonological neighborhood) and stuttering occurrence in spontaneous speech in adults. The study asked whether neighborhood characteristics, including the number of neighbors (neighborhood density) and the average word frequency among neighbors (neighborhood frequency), differentiate stuttered from fluent words within spontaneous speech samples, and more specifically, whether neighborhood characteristics facilitate speech fluency in adults who stutter., Method: Spontaneous speech samples were collected from 14 adults who stutter, including 7 with mild stuttering and 7 with severe stuttering. Each stuttered word was matched with a fluently produced word within the sample, controlling for multiple lexical factors. Neighborhood density and neighborhood frequency were compared between the stuttered and matched fluent words., Results: Adults stuttered on words with lower neighborhood density, compared to fluently produced words, with similar patterns in the two severity subgroups. There appeared to be a marginal difference between single-syllable whole-word repetition and the other stuttering typologies., Conclusion: Neighborhood density facilitates fluent word production in spontaneous speech in adults who stutter, regardless of stuttering severity. This finding adds to the evidence supporting that phonological encoding plays a role in stuttering in naturalistic, spontaneous speech in adults., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Despite a prevalence exceeding 1%, mechanisms underlying autism spectrum disorders (ASDs) are poorly understood, and targeted therapies and guiding parameters are urgently needed. We recently demonstrated that cerebellar dysfunction is sufficient to generate autistic-like behaviors in a mouse model of tuberous sclerosis complex (TSC). Here, using the mechanistic target of rapamycin (mTOR)-specific inhibitor rapamycin, we define distinct sensitive periods for treatment of autistic-like behaviors with sensitive periods extending into adulthood for social behaviors. We identify cellular and electrophysiological parameters that may contribute to behavioral rescue, with rescue of Purkinje cell survival and excitability corresponding to social behavioral rescue. In addition, using anatomic and diffusion-based MRI, we identify structural changes in cerebellar domains implicated in ASD that correlate with sensitive periods of specific autism-like behaviors. These findings thus not only define treatment parameters into adulthood, but also support a mechanistic basis for the targeted rescue of autism-related behaviors., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

A new C-glycosyl flavone, Chrysin-8-C-(2″-O-β-6-deoxy-glucopyranosyl)-β-D-glucopyranoside (1), a new neolignan glycoside, citrusin G (2), as well as 15 known compounds (3-17) were isolated from the peel of Passiflora edulis Sims. The structure determinations were primarily based on comprehensive spectroscopic analyses, and the absolute configuration of 2 were unequivocally determined by the CD experiment and chemical transformation. Compound 1 represents the rare examples of the flavonoid featuring a deoxy glucose sugar moiety. Compounds 5, 7 and 9 exhibited moderate inhibitory effects on nitric oxide (NO) production stimulated by lipopolysaccharide (LPS) in RAW 264.7 cells, with IC 50 values of 34.92, 16.12 and 26.67 μM, respectively.

Cerebellar abnormalities, particularly in Right Crus I (RCrusI), are consistently reported in autism spectrum disorders (ASD). Although RCrusI is functionally connected with ASD-implicated circuits, the contribution of RCrusI dysfunction to ASD remains unclear. Here neuromodulation of RCrusI in neurotypical humans resulted in altered functional connectivity with the inferior parietal lobule, and children with ASD showed atypical functional connectivity in this circuit. Atypical RCrusI-inferior parietal lobule structural connectivity was also evident in the Purkinje neuron (PN) TscI ASD mouse model. Additionally, chemogenetically mediated inhibition of RCrusI PN activity in mice was sufficient to generate ASD-related social, repetitive, and restricted behaviors, while stimulation of RCrusI PNs rescued social impairment in the PN TscI ASD mouse model. Together, these studies reveal important roles for RCrusI in ASD-related behaviors. Further, the rescue of social behaviors in an ASD mouse model suggests that investigation of the therapeutic potential of cerebellar neuromodulation in ASD may be warranted.

Tuberous sclerosis complex (TSC) is a neurodevelopmental disorder characterized by mutations in either the TSC1 or TSC2 genes, whose products form a critical inhibitor of the mechanistic target of rapamycin (mTOR). Loss of TSC1/2 gene function renders an mTOR-overactivated state. Clinically, TSC manifests with epilepsy, intellectual disability, autism, and sleep dysfunction. Here, we report that mouse models of TSC have abnormal circadian rhythms. We show that mTOR regulates the proteostasis of the core clock protein BMAL1, affecting its translation, degradation, and subcellular localization. This results in elevated levels of BMAL1 and a dysfunctional clock that displays abnormal timekeeping under constant conditions and exaggerated responses to phase resetting. Genetically lowering the dose of BMAL1 rescues circadian behavioral phenotypes in TSC mouse models. These findings indicate that BMAL1 deregulation is a feature of the mTOR-activated state and suggest a molecular mechanism for mitigating circadian phenotypes in a neurodevelopmental disorder., (Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.)

Here, we report that long-term stable and efficient organic solar cells (OSCs) can be obtained through the following strategies: i) combination of rapid-drying blade-coating deposition with an appropriate thermal annealing treatment to obtain an optimized morphology of the active layer; ii) insertion of interfacial layers to optimize the interfacial properties. The resulting devices based on poly[4,8-bis(5-(2-ethylhexyl)thiophen-2-yl)benzo[1,2-b;4,5-b']dithiophene-2,6-diyl-alt-(4-(2-ethylhexyl)-3-fluorothieno[3,4-b]thiophene-2-carboxylate-2,6-diyl)] (PBDTTT-EFT):[6,6]-phenyl C 71 butyric acid methyl ester (PC 71 BM) blend as the active layer exhibits a power conversion efficiency (PCE) up to 9.57 %, which represents the highest efficiency ever reported for blade-coated OSCs. Importantly, the conventional structure devices based on poly(3-hexylthiophene) (P3HT):phenyl-C 61 -butyric acid methyl ester (PCBM) blend can retain approximately 65 % of their initial PCE for almost 2 years under operating conditions, which is the best result ever reported for long-term stable OSCs under operational conditions. More encouragingly, long-term stable large-area OSCs (active area=216 cm 2 ) based on P3HT:PCBM blend are also demonstrated. Our findings represent an important step toward the development of large-area OSCs with high performance and long-term stability., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Heat shock protein 90 (HSP90), which is expressed in cancer cells, profoundly affects progression, invasion, and metastasis. However, to our knowledge, in East Asia, the correlation between the expression of HSP90 and clinicopathological variables has seldom been discussed. We therefore investigated this and its prognostic value in 36 patients newly diagnosed with oral squamous cell carcinoma (SCC) in northern Taiwan. Samples of tumour and normal samples from the patients were compared immunohistochemically. HSP90 was expressed mainly in the samples of tumour, and was significantly higher in these than in the normal epithelium (p<0.001). Metastases to the lymph nodes in the 36 patients also correlated with expression of HSP90. Correlation between expression of HSP90 and the size of the tumour or pathological staging was not significant, but strong expression correlated with poor survival. In general, expression was low among our samples (30/36). It was significantly higher in the tumour samples than in normal samples, and correlated with metastases to lymph nodes in the neck., (Copyright © 2017. Published by Elsevier Ltd.)

Purpose: The study examined whether semantic and phonological encoding processes were capacity demanding, involving the central cognitive mechanism, in adults who do and do not stutter (AWS and NS) to better understand the role of cognitive demand in linguistic processing and stuttering. We asked (a) whether the two linguistic processes in AWS are capacity demanding, which can temporally disrupt the processing of a concurrent nonlinguistic task, and (b) whether AWS and NS show similar patterns of temporal disruption in the two processes., Method: Twenty AWS and 20 matched NS participated in the study. We examined semantic interference and phonological facilitation effects, using the picture-word interference paradigm, under concurrent and sequential processing of a secondary, nonlinguistic task., Results: Both AWS and NS showed statistically significant semantic interference and phonological facilitation effects, and both effects caused temporal disruption to the processing of a secondary task to the predicted extent., Conclusions: The observed result patterns in both AWS and NS suggest that both semantic and phonological encoding processes are capacity demanding and can be vulnerable to concurrent processing demands. This finding on NS is inconsistent with the current literature on young, fluent adults and warrants further investigation.

Autism is a prevalent neurodevelopmental disorder whose origins are not well understood. Cerebellar involvement has been implicated in the pathogenesis of autism spectrum disorders with increasing evidence from both clinical studies and animal models supporting an important role for cerebellar dysfunction in autism spectrum disorders. This article discusses the various cerebellar contributions to autism spectrum disorders. Both clinical and preclinical studies are discussed and future research directions highlighted., (Copyright © 2016. Published by Elsevier Ltd.)

Duchenne muscular dystrophy is caused by mutations in the DYSTROPHIN gene. Although primarily associated with muscle wasting, a significant portion of patients (approximately 25%) are also diagnosed with autism spectrum disorder. We describe social behavioral deficits in dystrophin-deficient mice and present evidence of cerebellar deficits in cGMP production. We demonstrate therapeutic potential for selective inhibitors of the cGMP-specific PDE5A and PDE9A enzymes to restore social behaviors in dystrophin-deficient mice., Competing Interests: LMK is a consultant for Pfizer, Summit Corporation PLC and Sarepta Therapeutics for muscle disease drug therapies. MTP, CAM, all hold equity in Pfizer. MTP is a current employee of Autism Speaks. RJK is a consultant for Ironwood Pharmaceuticals. CJS, JFH and ELPC are employees of Pfizer. MS is on the Scientific Advisory Board of Sage Therapeutics and has received research support from Novartis and Shire. The remaining authors declare no conflict of interest.

Purpose: Little is known about whether buccal mucosa elasticity influences the determination of surgical margins for buccal carcinomas. This study investigated whether there is a difference in elasticity of the buccal mucosa in patients with buccal carcinoma compared with controls without the disease., Patients and Methods: A case-and-control study comprised of patients with buccal carcinoma and controls without the disease was conducted. In each patient, 2 gutta-percha points were attached to the buccal mucosa horizontally and examined twice by lateral cephalometry, once with the mouth closed and once during maximal mouth opening (MMO). Changes in distance between the gutta-percha points were used as a measurement of buccal elasticity. Information on age, alcohol consumption, betel nut chewing, smoking habits, oral submucosa fibrosis (OSF), temporomandibular joint (TMJ) subluxation, and interincisal distance at MMO (IDMMO) was collected. The results were analyzed using independent-sample and paired-sample t tests., Results: Ten patients with buccal carcinoma and another 11 patients without buccal carcinoma were enrolled in this study. There was a significant increase in magnification percentage in patients with carcinoma (32.35%; P < .001) during MMO. Magnification of the comparison group during MMO measured 51.55%, also a significant increase (P < .001). Betel nut chewing significantly decreased mucosa elasticity; magnification was 29.20% (P = .013). Magnification was significantly higher in patients with TMJ subluxation (54.50%; P = .041) than in the controls. Age, alcohol consumption, smoking, OSF, and IDMMO did not affect buccal mucosa elasticity., Conclusions: Buccal mucosa elasticity increased considerably at MMO in patients with buccal carcinoma. This elasticity should be taken into account when calculating adequate surgical margins for transoral resection of buccal carcinoma., (Copyright © 2016 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

In this work, we investigate blade-coated organic interlayers at the rear surface of hybrid organic-silicon photovoltaics based on two small molecules: Tris(8-hydroxyquinolinato) aluminium (Alq(3)) and 1,3-bis(2-(4-tert-butylphenyl)-1,3,4-oxadiazol-5-yl) benzene (OXD-7). In particular, soluble Alq(3) resulting in a uniform thin film with a root-mean-square roughness < 0.2nm is demonstrated for the first time. Both devices with the Alq(3) and OXD-7 interlayers show notable enhancement in the open-circuit voltage and fill-factor, leading to a net efficiency increase by over 2% from the reference, up to 11.8% and 12.5% respectively. The capacitance-voltage characteristics confirm the role of the small-molecule interlayers resembling a thin interfacial oxide layer for the Al-Si Schottky barrier to enhance the built-in potential and facilitate charge transport. Moreover, the Alq(3) interlayer in optimized devices exhibits isolated phases with a large surface roughness, in contrast to the OXD-7 which forms a continuous uniform thin film. The distinct morphological differences between the two interlayers further suggest different enhancement mechanisms and hence offer versatile functionalities to the advent of hybrid organic-silicon photovoltaics.

Sensory integration difficulties have been reported in autism, but their underlying brain-circuit mechanisms are underexplored. Using five autism-related mouse models, Shank3+/ΔC, Mecp2(R308/Y), Cntnap2-/-, L7-Tsc1 (L7/Pcp2(Cre)::Tsc1(flox/+)), and patDp(15q11-13)/+, we report specific perturbations in delay eyeblink conditioning, a form of associative sensory learning requiring cerebellar plasticity. By distinguishing perturbations in the probability and characteristics of learned responses, we found that probability was reduced in Cntnap2-/-, patDp(15q11-13)/+, and L7/Pcp2(Cre)::Tsc1(flox/+), which are associated with Purkinje-cell/deep-nuclear gene expression, along with Shank3+/ΔC. Amplitudes were smaller in L7/Pcp2(Cre)::Tsc1(flox/+) as well as Shank3+/ΔC and Mecp2(R308/Y), which are associated with granule cell pathway expression. Shank3+/ΔC and Mecp2(R308/Y) also showed aberrant response timing and reduced Purkinje-cell dendritic spine density. Overall, our observations are potentially accounted for by defects in instructed learning in the olivocerebellar loop and response representation in the granule cell pathway. Our findings indicate that defects in associative temporal binding of sensory events are widespread in autism mouse models.

Tuberous sclerosis complex (TSC) is a disorder arising from mutation in the TSC1 or TSC2 gene, characterized by the development of hamartomas in various organs and neurological manifestations including epilepsy, intellectual disability and autism. TSC1/2 protein complex negatively regulates the mammalian target of rapamycin complex 1 (mTORC1) a master regulator of protein synthesis, cell growth and autophagy. Autophagy is a cellular quality-control process that sequesters cytosolic material in double membrane vesicles called autophagosomes and degrades it in autolysosomes. Previous studies in dividing cells have shown that mTORC1 blocks autophagy through inhibition of Unc-51-like-kinase1/2 (ULK1/2). Despite the fact that autophagy plays critical roles in neuronal homeostasis, little is known on the regulation of autophagy in neurons. Here we show that unlike in non-neuronal cells, Tsc2-deficient neurons have increased autolysosome accumulation and autophagic flux despite mTORC1-dependent inhibition of ULK1. Our data demonstrate that loss of Tsc2 results in autophagic activity via AMPK-dependent activation of ULK1. Thus, in Tsc2-knockdown neurons AMPK activation is the dominant regulator of autophagy. Notably, increased AMPK activity and autophagy activation are also found in the brains of Tsc1-conditional mouse models and in cortical tubers resected from TSC patients. Together, our findings indicate that neuronal Tsc1/2 complex activity is required for the coordinated regulation of autophagy by AMPK. By uncovering the autophagy dysfunction associated with Tsc2 loss in neurons, our work sheds light on a previously uncharacterized cellular mechanism that contributes to altered neuronal homeostasis in TSC disease., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by tumor growth and neuropsychological symptoms such as autistic behavior, developmental delay, and epilepsy. While research has shed light on the biochemical and genetic etiology of TSC, the pathogenesis of the neurologic and behavioral manifestations remains poorly understood. TSC patients have a greatly increased risk of developmental delay and autism spectrum disorder, rendering the relationship between the two sets of symptoms an extremely pertinent issue for clinicians. We have expanded on previous observations of aberrant vocalizations in Tsc2 (+/-) mice by testing vocalization output and developmental milestones systematically during the early postnatal period. In this study, we have demonstrated that Tsc2 haploinsufficiency in either dams or their pups results in a pattern of developmental delay in sensorimotor milestones and ultrasonic vocalizations.

Interface carrier recombination currently hinders the performance of hybrid organic-silicon heterojunction solar cells for high-efficiency low-cost photovoltaics. Here, we introduce an intermediate 1,1-bis[(di-4-tolylamino)phenyl]cyclohexane (TAPC) layer into hybrid heterojunction solar cells based on silicon nanowires (SiNWs) and conjugate polymer poly(3,4-ethylenedioxy-thiophene):poly(styrenesulfonate) (PEDOT:PSS). The highest power conversion efficiency reaches a record 13.01%, which is largely ascribed to the modified organic surface morphology and suppressed saturation current that boost the open-circuit voltage and fill factor. We show that the insertion of TAPC increases the minority carrier lifetime because of an energy offset at the heterojunction interface. Furthermore, X-ray photoemission spectroscopy reveals that TAPC can effectively block the strong oxidation reaction occurring between PEDOT:PSS and silicon, which improves the device characteristics and assurances for reliability. These learnings point toward future directions for versatile interface engineering techniques for the attainment of highly efficient hybrid photovoltaics.

The cerebellum plays an important role in motor learning and cognition, and structural cerebellar abnormalities have been associated with cognitive impairment. In tuberous sclerosis complex, neurologic outcome is highly variable, and no consistent imaging or pathologic determinant of cognition has been firmly established. The cerebellum calls for specific attention because mouse models of tuberous sclerosis complex have demonstrated a loss of cerebellar Purkinje cells, and cases of human histologic data have demonstrated a similar loss in patients. We hypothesized that there might be a common cerebellar finding in tuberous sclerosis complex that could be measured as morphometric changes with magnetic resonance imaging. Using a robust, automated image analysis procedure, we studied 36 patients with tuberous sclerosis complex and age-matched control subjects and observed significant volume loss among patients in the cerebellar cortices and vermis. Furthermore, this effect was strongest in a subgroup of 19 patients with a known, pathogenic mutation of the tuberous sclerosis 2 gene and impacted all cerebellar structures. We conclude that patients with tuberous sclerosis complex exhibit volume loss in the cerebellum, and this loss is larger and more widespread in patients with a tuberous sclerosis 2 mutation., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Mammalian target of rapamycin (mTOR) signaling has been shown to be deregulated in a number of genetic, neurodevelopmental disorders including Tuberous Sclerosis Complex, Neurofibromatosis, Fragile X, and Rett syndromes. As a result, mTOR inhibitors, such as rapamycin and its analogs, offer potential therapeutic avenues for these disorders. Some of these disorders-such as Tuberous Sclerosis Complex-can be diagnosed prenatally. Thus, prenatal administration of these inhibitors could potentially prevent the development of the devastating symptoms associated with these disorders. To assess the possible detrimental effects of prenatal rapamycin treatment, we evaluated both early and late behavioral effects of a single rapamycin treatment at embryonic day 16.5 in wildtype C57Bl/6 mice. This treatment adversely impacted early developmental milestones as well as motor function in adult animals. Rapamycin also resulted in anxiety-like behaviors during both early development and adulthood but did not affect adult social behaviors. Together, these results indicate that a single, prenatal rapamycin treatment not only adversely affects early postnatal development but also results in long lasting negative effects, persisting into adulthood. These findings are of importance in considering prenatal administration of rapamycin and related drugs in the treatment of patients with neurogenetic, neurodevelopmental disorders.

Tuberous sclerosis complex (TSC) is a neurodevelopmental disorder with prominent brain manifestations due to mutations in either TSC1 or TSC2. Here, we describe novel mouse brain models of TSC generated using conditional hypomorphic and null alleles of Tsc2 combined with the neuron-specific synapsin I cre (SynIcre) allele. This allelic series of homozygous conditional hypomorphic alleles (Tsc2(c-del3/c-del3)SynICre(+)) and heterozygote null/conditional hypomorphic alleles (Tsc2(k/c-del3)SynICre(+)) achieves a graded reduction in expression of Tsc2 in neurons in vivo. The mice demonstrate a progressive neurologic phenotype including hunchback, hind limb clasp, reduced survival and brain and cortical neuron enlargement that correlates with a graded reduction in expression of Tsc2 in the two sets of mice. Both models also showed behavioral abnormalities in anxiety, social interaction and learning assays, which correlated with Tsc2 protein levels as well. The observations demonstrate that there are graded biochemical, cellular and clinical/behavioral effects that are proportional to the extent of reduction in Tsc2 expression in neurons. Further, they suggest that some patients with milder manifestations of TSC may be due to persistent low-level expression of functional protein from their mutant allele. In addition, they point to the potential clinical benefit of strategies to raise TSC2 protein expression from the wild-type allele by even modest amounts.

Autism spectrum disorders (ASDs) are highly prevalent neurodevelopmental disorders, but the underlying pathogenesis remains poorly understood. Recent studies have implicated the cerebellum in these disorders, with post-mortem studies in ASD patients showing cerebellar Purkinje cell (PC) loss, and isolated cerebellar injury has been associated with a higher incidence of ASDs. However, the extent of cerebellar contribution to the pathogenesis of ASDs remains unclear. Tuberous sclerosis complex (TSC) is a genetic disorder with high rates of comorbid ASDs that result from mutation of either TSC1 or TSC2, whose protein products dimerize and negatively regulate mammalian target of rapamycin (mTOR) signalling. TSC is an intriguing model to investigate the cerebellar contribution to the underlying pathogenesis of ASDs, as recent studies in TSC patients demonstrate cerebellar pathology and correlate cerebellar pathology with increased ASD symptomatology. Functional imaging also shows that TSC patients with ASDs display hypermetabolism in deep cerebellar structures, compared to TSC patients without ASDs. However, the roles of Tsc1 and the sequelae of Tsc1 dysfunction in the cerebellum have not been investigated so far. Here we show that both heterozygous and homozygous loss of Tsc1 in mouse cerebellar PCs results in autistic-like behaviours, including abnormal social interaction, repetitive behaviour and vocalizations, in addition to decreased PC excitability. Treatment of mutant mice with the mTOR inhibitor, rapamycin, prevented the pathological and behavioural deficits. These findings demonstrate new roles for Tsc1 in PC function and define a molecular basis for a cerebellar contribution to cognitive disorders such as autism.

We compare different radiotherapy techniques-helical tomotherapy (tomotherapy), step-and-shoot IMRT (IMRT), and 3-dimensional conformal radiotherapy (3DCRT)-for patients with mid-distal esophageal carcinoma on the basis of dosimetric analysis. Six patients with locally advanced mid-distal esophageal carcinoma were treated with neoadjuvant chemoradiation followed by surgery. Radiotherapy included 50 Gy to gross planning target volume (PTV) and 45 Gy to elective PTV in 25 fractions. Tomotherapy, IMRT, and 3DCRT plans were generated. Dose-volume histograms (DVHs), homogeneity index (HI), volumes of lung receiving more than 10, 15, or 20 Gy (V(10), V(15), V(20)), and volumes of heart receiving more than 30 or 45 Gy (V(30), V(45)) were determined. Statistical analysis was performed by paired t-tests. By isodose distributions and DVHs, tomotherapy plans showed sharper dose gradients, more conformal coverage, and better HI for both gross and elective PTVs compared with IMRT or 3DCRT plans. Mean V(20) of lung was significantly reduced in tomotherapy plans. However, tomotherapy and IMRT plans resulted in larger V(10) of lung compared to 3DCRT plans. The heart was significantly spared in tomotherapy and IMRT plans compared to 3DCRT plans in terms of V(30) and V(45). We conclude that tomotherapy plans are superior in terms of target conformity, dose homogeneity, and V(20) of lung.

Background: To study ground reaction force (GRF) patterns in stroke patients with various degrees of motor recovery, using plantar dynamic analysis., Methods: Forty-three people with hemiplegic stroke and 20 healthy subjects were enrolled in the study. Motor impairment (motor recovery and muscle tone) and plantar dynamic data (GRF patterns, peak pressure, and walking speeds) were analyzed. GRF patterns were categorized into four patterns based on the force magnitude (spatial features) through time (temporal features) of the vertical GRF. Then stroke patients were classified into good (patterns III and IV) and poor groups (patterns I and II)., Results: Patients with hemiplegic stroke showed characteristic GRF patterns which could be categorized from bimodal (pattern IV) to pathological shapes (I-III). The peak pressures on the paretic side in the metatarsal and toe areas were reduced in stroke patients compared with those in healthy subjects. Walking speeds were higher in the good group than in the poor group (p < 0.05). The peak pressures on both sides in the metatarsal and midfoot areas were lower in the poor group than in the good group (p < 0.05). GRF patterns were highly correlated with walking speeds (r = 0.92, p < 0.01). GRF patterns and walking speeds were positively correlated with motor recovery of knee movement (r > 0.4, p < 0.01), but not with hip and ankle movement or muscle tone in the lower limb., Conclusions: GRF patterns, correlated with walking speeds, indicate underlying motor control of hemiplegic or hemiparetic gait. Knee motor control may be the most important factor in determining walking performance. Plantar dynamic analysis could allow clinicians an alternative assessment in detecting gait changes and planning therapeutic strategies in stroke patients.

Care of patients with panic disorder has raised quality-of-life (QOL) issues. The purpose of this study was to identify the level of QOL in patients with panic disorder and to examine the relationships between QOL and adverse effects of medication, social support, course of illness, psychopathology, and demographic characteristics. We recruited 57 patients with panic disorder from outpatient psychiatric clinics. We measured their QOL levels with the Short Form of the World Health Organization Questionnaire on Quality of Life-Taiwan Version (the WHOQOL-BREF Taiwan version) and examined the correlates of QOL. The analysis revealed that multiple factors were associated with poor QOL in patients with panic disorder, including severe adverse effects of medication for panic disorder, perceived low social support, severe current panic symptoms, total Beck Depression Inventory-II (BDI-II) score>/=17, young age, being unmarried, and early onset of panic disorder. The QOL of patients with panic disorder was correlated to multiple factors that were specific to individual subjects and influenced by interactions with treatment and the social environment. The results provide screening factors so that clinicians can intervene to improve QOL for their patients with panic disorder.

Objective: To investigate the effectiveness of a universal integrated pointing device apparatus (IPDA), which can integrate numerous commercial pointing devices and can be controlled by various combinations of available movements, for people with cervical spinal cord injury (SCI) who cannot operate standard computer pointing devices., Design: An exploratory quasi-experimental design. All subjects were required to perform specific mouse-operating (continuous-clicking, target-acquisition, drag-and-drop) tasks. People with SCI received clinical assessments and were classified into 2 groups based on pointing device used: group A, who used standard mouse devices, and group B (IPDA combinations), who were unable to use standard mouse devices. The measures of group A and group B were compared., Setting: Rehabilitation science center of a medical institution., Participants: Thirty-seven people with high cervical SCI and 30 able-bodied subjects., Intervention: The IPDA., Main Outcome Measures: The efficiency of the people with SCI in each mouse-operation task was expressed as a percentage of that for able-bodied subjects (%NL)., Results: Group B displayed similar operational efficiency in performing the drag-and-drop tasks ( approximately 30% NL) to group A, although they exhibited worse efficiency than group A in performing the other tasks (P<.05). Operational efficiencies of all tasks had negative relationships with age by using linear regression analysis (adjusted r(2)>.36, P<.001). The use of pointing devices was associated with American Spinal Injury Association Impairment Scale (P<.001), completeness (P<.001), and muscle strength (P<.01), particularly finger flexor muscle strength, but not with neurologic level or muscle tone., Conclusions: The IPDA could help most people with high cervical SCI who could not use commercial mouse devices to achieve acceptable operational efficiencies. Pointing devices were assigned based on the underlying SCI severity and muscle strength, particularly finger flexor muscle strength.

The aim of this study is to determine the predictive critical value of the Glasgow Coma Scale for use as a determinant of outcome for children with traumatic brain injuries. A total of 309 children, aged 2-10 years, were enrolled in this study. Each subject underwent the following assessments: Glasgow Coma Scale; clinical data; brain computed tomography; and Glasgow Outcome Scale assessments. The receiver operating characteristic curve indicated that a critical point of the Glasgow Coma Scale set at 5 was most strongly correlated with outcome of pediatric traumatic brain injury. Subarachnoid hemorrhage with brain swelling and edema, subdural, intracerebral hemorrhage, and basal ganglion lesions were associated with severe injury and poor outcome (P < 0.05). However, cortical lesions did not affect injury severity and outcome. In injuries associated with traumatic brain injuries, only chest trauma had a tendency to be associated with poor outcome (P < 0.05). Of the factors analyzed, the score of the Glasgow Coma Scale was the most effective predictor for outcome in pediatric traumatic brain injury. Furthermore, the predictive critical score of the Glasgow Coma Scale should be set at 5 for pediatric traumatic brain injury. The computed tomographic findings also were important in determining injury severity and predicting outcome.

Erythropoietin (EPO) is the principal growth factor regulating the production of red blood cells. Recent studies demonstrated that exogenous EPO acts as a neuroprotectant and regulates neurogenesis. Using a genetic approach, we evaluate the roles of endogenous EPO and its classical receptor (EPOR) in mammalian neurogenesis. We demonstrate severe and identical embryonic neurogenesis defects in animals null for either the Epo or EpoR gene, suggesting that the classical EPOR is essential for EPO action during embryonic neurogenesis. Furthermore, by generating conditional EpoR knock-down animals, we demonstrate that brain-specific deletion of EpoR leads to significantly reduced cell proliferation in the subventricular zone and impaired post-stroke neurogenesis. EpoR conditional knockdown leads to a specific deficit in post-stroke neurogenesis through impaired migration of neuroblasts to the peri-infarct cortex. Our results suggest that both EPO and EPOR are essential for early embryonic neural development and that the classical EPOR is important for adult neurogenesis and for migration of regenerating neurons during post-injury recovery.

Objective: To assess the effectiveness of neuromuscular electrical stimulation (NMES) on cough capacity and prevention of pulmonary complication in patients with acute cervical cord injury., Design: A randomized controlled trial., Subjects: Twenty-six tetraplegic patients with cervical spinal cord injury, 13 in the NMES therapy group and 13 in the control group., Methods: NMES was applied to the clavicular portion of the pectoralis major and abdominal muscle. Pulmonary function tests were performed before and after therapy, and at 3 months and 6 months follow-up. The pulmonary complications in this 6-month follow-up period were also recorded., Results: After the 4-week therapy, and at 3 months and 6 months follow-up testing, patients in the NMES therapy group displayed significant improvement in their peak expiratory flow, forced expiratory volume in 1 second, forced vital capacity, maximal expiratory pressure and maximal inspiratory pressure, compared with those in the control group (p<0.05). Patients in the NMES therapy group also had fewer pulmonary complications in the follow-up period., Conclusion: NMES over the pectoralis and abdominal muscles might improve cough capacity and pulmonary function in cervical spinal cord injury with tetraplegia. This improvement might last for 6 months. With this improvement, pulmonary complications were reduced.

Purpose: To describe a novel and straightforward conformal avoidance intensity-modulated radiation therapy (IMRT) technique for coverage of pelvis and inguinal/femoral nodes and to compare the dosimetry of the new method with that of other traditional methods of radiation treatment., Methods and Materials: Data of 2 patients with anal cancer were used as example cases to illustrate details and advantages of conformal avoidance IMRT technique. Conventional photons with enface electrons design was created first, thereby providing "outermost boundaries" defined as planning target volume (PTV) for subsequent conformal avoidance IMRT design. Organs at risk (OARs), including femoral head and neck and external genitalia, were contoured as conformal avoidance structures. A step-and-shoot inverse IMRT planning was subsequently generated. For dosimetric comparison, a recently published technique by modified segmental boost was also generated. These treatment techniques were evaluated by dose-volume histogram (DVH) of PTV and OARs. Dose profiles at four different depths from each treatment planning were generated for comparison., Results: The DVH of PTV showed that coverage of the PTV was comparable among three treatment techniques. Percent volume of PTV receiving more than 90% prescription dose was in the range 94-98% for the three treatment techniques, and all had only 0-2% of PTV receiving more than 110% of prescription dose. The DVH of OARs confirmed that both femoral head and neck and external genitalia could be spared well by conformal avoidance IMRT as compared with the other two techniques. Although greater inhomogeneity of dose distribution within the PTV was noted by conformal avoidance IMRT technique, as shown by dose profiles at four different depths, the maximum doses at different depths were less than 115%, which was comparable to those planned by modified segmental boost technique. Planning by photons and enface electrons technique, however, showed a greater dose variation up to 134% of the prescription dose at 1.5 cm depth along photon-electron match-line., Conclusions: To cover pelvis and inguinal/femoral nodes, conformal avoidance IMRT is technically simple to simulate, plan, and execute. Dosimetric study has demonstrated that it achieves comparable PTV coverage compared with other approaches while at the same time significantly sparing the surrounding OARs.

Objective: To assess the balance function of hemiplegic stroke patients and to investigate whether visual feedback rhythmic weight-shift training following acute stroke can decrease falls among patients with hemiplegic stroke., Design: A prospective study, using a Balance Master., Setting: Hospital-based rehabilitation units., Subjects: Fifty-two hemiplegic stroke patients (28 in the training group and 24 in the control group)., Interventions: Conventional stroke rehabilitation programme plus visual feedback rhythmic weight-shift training. Training effect was evaluated by assessing the static and dynamic balance performance as well as comparing the occurrence of falls in the training and control groups at six-month follow-up., Main Measures: Occurrence of falls; static balance in different sensory conditions; and dynamic balance performance, including on-axis velocity and directional control during rhythmic weight-shift., Results: Significant improvement in dynamic balance performance was found in hemiplegic patients in the training group. The improvement was sustained for six months. With regarding to static balance function, no significant improvement was found. At six-month follow-up, 5 of 28 patients (17.8%) in the training group had fallen, compared with 10 of 24 patients (41.7%) in the control group. The occurrence of falls decreased, although not statistically significantly (p=0.059)., Conclusions: Visual feedback rhythmic weight-shift training may improve dynamic balance function for hemiplegic stroke patients. The effects of training may be sustained for six months. The occurrence of falls decreased in the training group, but not statistically significantly.

Background: Autism is a pervasive developmental disorder, characterized by pervasive impairment in several areas of development, including social interactions and communication skills. The purpose of this study was to investigate the development profiles and determine the relationship of social function with motor and speech functions in children with autism., Methods: We collected the medical records of 32 children with autism. We used the Chinese Children Developmental Inventory (CCDI) to assess eight functional domains including: gross motor (GM), fine motor (FM), expressive language (EL), concept comprehension (CC), social comprehension (SC), self help (SH), personal social (PS), and general development (GD). The children were classified into group A if the PS development quotient (DQ) was equal to or higher than 50%, or they were classified into group B if the PSDQ was lower than 50%. We compared the DQ between the two groups. A value of p < 0.05 was considered statistically significant., Results: The developmental functions, including motor, speech, and self help functions in the autism group with high social function were better than those in the autism group with low social function. The DQs of all developmental function in group A (60-88%) were higher than those in group B (28-57%) (p < 0.01). The gross motor and fine motor functions were better than speech and social function by 20 to 37% in both groups. Correlation analysis among developmental functions showed significant correlation (r=0.46-0.94, p<0.01). Using a stepwise linear regression test, the PS function was highly correlated with SC (r2=0.832, p <0.001)., Conclusions: Autism is a multifaceted and disproportional developmental disorder. Social communication may play the dominant role in determining the social functions in children with autism.

Objective: To describe the characteristics of leg muscle activation patterns in hemiplegic stroke patients during the movement of rising from a chair and to determine the differences of leg muscle activation patterns between stroke fallers and nonfallers., Design: Subjects stood up from an armless chair at a comfortable, self-paced speed. Leg muscle activation time and patterns during the sit-to-stand movement were analyzed using multichannel surface electromyography and a force platform. The differences between stroke fallers and nonfallers were compared., Results: The mean onset time of muscle activity in the affected limbs of stroke fallers was markedly delayed for the tibialis anterior muscle and earlier for the soleus muscle. The muscle activation patterns in the affected side of the stroke fallers exhibited a wide range of variation. Seventy percent of our stroke fallers exhibited no or merely low-amplitude activity in their tibialis anterior muscle when the patients were rising from a chair. Half of the stroke fallers exhibited premature or excessive activation of their soleus muscle when the rising activity was initiated., Conclusions: Stroke patients who exhibited no or low-amplitude muscle activity in the tibialis anterior, associated with premature or excessive activation of the soleus muscle in their hemiplegic limbs, when rising from a chair were prone to falling. The compensatory excessive tibialis anterior and quadriceps muscle activation in the unaffected limbs of stroke patients might have a role in preventing them from falling.

Laurence-Moon-Biedl syndrome is an autosomal recessive disorder characterized by retinitis pigmentosa, obesity, polydactyly, hypogenitalism, mental retardation, and renal abnormalities. We report the linguistic and gait disorders in a child with Laurence-Moon-Biedl syndrome associated with left temporal and parietal hypoplasia as determined by magnetic resonance imaging. Our patient was mildly mentally retarded, scoring better on the performance subtest than on the verbal subtest. He received serial assessments for developmental, language, speech, and gait functions, before and after rehabilitation, at age 4.5 and 6 yr, respectively. After comprehensive rehabilitation, the boy achieved improvement in speech, language, fine motor, and gait functions. Early comprehensive rehabilitation programs seem beneficial for improving functional development for children with Laurence-Moon-Biedl syndrome.

Thymocyte development is a non-cell-autonomous process that requires signals provided by the thymic stroma. Bone morphogenetic proteins (BMPs) and fibroblast growth factors (FGFs) derived from thymic stroma have been implicated as possible regulators of T-cell development. Using thymic organ culture, this study demonstrates that both BMP4 and FGF7/FGF10 arrest early T-cell development at the CD4-CD8-CD44+CD25- (double-negative 1 [DN1]) population and at the CD4-CD8- double-negative (DN) to CD4+CD8+ double-positive (DP) transition in a stromal compartment-dependent manner. Furthermore, BMP4 functions upstream of FGF7/FGF10, as the effects of BMP can be suppressed by cotreatment with an FGF receptor antagonist. BMP4 also acts directly on the thymic stroma to up-regulate the stroma-specific transcription factor Foxn1 and stroma-expressed chemokines. Taken together, the data in this report demonstrate that BMP acts upstream of FGF in the regulation of early T-cell development and that BMP4 acts primarily through the thymic stroma, thereby altering the thymic microenvironment and affecting thymopoiesis.

Objective: Gait patterns vary among stroke patients. This study attempted to discover gait performance with compensatory adaptations in stroke patients with different degrees of motor recovery., Design: Data were gathered from 35 stroke patients and 15 healthy subjects. Gait performance and motor recovery were assessed 6 mos after stroke. Stroke patients further were divided into poor and good groups. The walking velocity was correlated with Brunnström's stages, and the temporal stride and motion variables of the two groups were compared., Results: Walking velocity was positively correlated with the Brunnström's stages of the proximal lower limb. The poor group displayed slower walking velocity and shorter single-support time compared with the good group. Both groups displayed low maximum excursion of hip extension and ankle plantarflexion during the stance phase and low maximum excursion of hip and knee flexion and ankle dorsiflexion during the swing phase. Moreover, both groups displayed excessive pelvic tilts during the stance and swing phases. However, the poor group displayed different pelvic motion and timing sequences to each peak joint angle from normal subjects and the good group. Peak hip and knee angles of the affected limb during the stance phase occurred almost simultaneously in this group., Conclusions: Selective control of the proximal lower limb may be the main determinant of walking velocity. The compensatory adaptations were similar, except for pelvic motion, in stroke patients with different levels of motor recovery, whereas the poor group walked with synergistic mass patterns and reduced stability.

Objective: We investigated the correlation between movement patterns, measured by polyelectromyography (PEMG), and clinical motor manifestations in children with cerebral palsy., Design: Subjects included 53 children with spastic cerebral palsy (diplegic [n = 43] and quadriplegic [n = 10] groups) and 18 normal children. All children underwent PEMG assessments, recorded from pairs of flexor/extensor muscles during voluntary movement. We correlated PEMG patterns with clinical motor assessments, including muscle tone, range of motion, and ambulatory and functional capacities in the children with cerebral palsy., Results: Children with cerebral palsy exhibited four distinct PEMG patterns, ranging from partial reciprocal to complete synchrony. Lower PEMG pattern scores were significantly associated with better ambulatory (rho = 0.88, P < 0.01) and functional (rho = 0.78, P < 0.01) capacities. PEMG patterns also had weakly positive relationships with muscle tone (rho > 0.33, P < 0.01) and range of motion of both lower limbs (rho > 0.31, P < 0.01). Most children of spastic diplegia with PEMG patterns II and III had independent ambulatory capacities and mild limitation of functional capacity, whereas most children with pattern of IV and V had no ambulatory abilities and no independent functional capacities (P < 0.01)., Conclusions: These findings suggest that PEMG patterns correlate with clinical motor deficits and may allow us to plan treatment strategies based on underlying motor control in cerebral palsy.