Many males with FXS meet criteria for ASD. This study was designed to (1) describe ASD symptoms in adolescent and young adult males with FXS (
n
= 44) and (2) evaluate the contributions to ASD ...severity of cognitive, language, and psychiatric factors, as well as FMRP (the protein deficient in FXS). A few ASD symptoms on the ADOS-2 were universal in the sample. There was less impairment in restricted and repetitive behaviors (RRB) than in the social affective (SA) domain. The best predictor of overall ASD severity and SA severity was expressive syntactic ability. RRB severity was best predicted by the psychiatric factors. Implications for clinical practice and for understanding the ASD comorbidity in FXS are discussed.
Although the cellular mechanisms responsible for the pathogenesis of autism are not understood, a growing number of studies have suggested that localized inflammation of the central nervous system ...(CNS) may contribute to the development of autism. Recent evidence shows that IL-6 has a crucial role in the development and plasticity of CNS.
Immunohistochemistry studies were employed to detect the IL-6 expression in the cerebellum of study subjects. In vitro adenoviral gene delivery approach was used to over-express IL-6 in cultured cerebellar granule cells. Cell adhesion and migration assays, DiI labeling, TO-PRO-3 staining and immunofluorescence were used to examine cell adhesion and migration, dendritic spine morphology, cell apoptosis and synaptic protein expression respectively.
In this study, we found that IL-6 was significantly increased in the cerebellum of autistic subjects. We investigated how IL-6 affects neural cell development and function by transfecting cultured mouse cerebellar granule cells with an IL-6 viral expression vector. We demonstrated that IL-6 over-expression in granule cells caused impairments in granule cell adhesion and migration but had little effect on the formation of dendritic spines or granule cell apoptosis. However, IL-6 over-expression stimulated the formation of granule cell excitatory synapses, without affecting inhibitory synapses.
Our results provide further evidence that aberrant IL-6 may be associated with autism. In addition, our results suggest that the elevated IL-6 in the autistic brain could alter neural cell adhesion, migration and also cause an imbalance of excitatory and inhibitory circuits. Thus, increased IL-6 expression may be partially responsible for the pathogenesis of autism.
Factor analysis is a multivariate statistical approach commonly used in psychology, education, and more recently in the health-related professions. This paper will attempt to provide novice ...researchers with a simplified approach to undertaking exploratory factor analysis (EFA). As the paramedic body of knowledge continues to grow, indeed into scale and instrument psychometrics, it is timely that an uncomplicated article such as this be offered to the paramedic readership both nationally and internationally. Factor analysis is an important tool that can be used in the development, refinement, and evaluation of tests, scales, and measures that can be used in education and clinical contexts by paramedics. The objective of the paper is to provide an exploratory factor analysis protocol, offering potential researchers with an empirically-supported systematic approach that simplifies the many guidelines and options associated with completing EFA.
Hutchinson-Gilford progeria syndrome is an ultrarare segmental premature aging disease resulting in early death from heart attack or stroke. There is no approved treatment, but starting in 2007, ...several recent single-arm clinical trials administered inhibitors of protein farnesylation aimed at reducing toxicity of the disease-producing protein progerin. No study assessed whether treatments influence patient survival. The key elements necessary for this analysis are a robust natural history of survival and comparison with a sufficiently large patient population that has been treated for a sufficient time period with disease-targeting medications.
We generated Kaplan-Meier survival analyses for the largest untreated Hutchinson-Gilford progeria syndrome cohort to date. Mean survival was 14.6 years. Comparing survival for treated versus age- and sex-matched untreated cohorts, hazard ratio was 0.13 (95% confidence interval, 0.04-0.37; P<0.001) with median follow-up of 5.3 years from time of treatment initiation. There were 21 of 43 deaths in untreated versus 5 of 43 deaths among treated subjects. Treatment increased mean survival by 1.6 years.
This study provides a robust untreated disease survival profile that can be used for comparisons now and in the future to assess changes in survival with treatments for Hutchinson-Gilford progeria syndrome. The current comparisons estimating increased survival with protein farnesylation inhibitors provide the first evidence of treatments influencing survival for this fatal disease.
http://www.clinicaltrials.gov. Unique Indentifiers: NCT00425607, NCT00879034, and NCT00916747.
•Multiomics were applied to study premature utero-contraction in sPTB.•Genomic variants in the sarcomere gene TTN were identified in sPTB.•Epigenetic regulation of long non-coding RNAs were ...identified in gene TPM3.•Methylomic profiles were identified in sarcomeric genes/loci.•Differential expression of transcripts associates with premature utero-contraction.
Spontaneous preterm birth is a syndrome with clinical and genetic heterogeneity. Few studies have focused on the genetic and epigenetic defects and pathogenic mechanisms associated with premature uterine contraction in spontaneous preterm birth. The objective of this study was to investigate the (epi)genetic variations associated with premature uterine contraction of spontaneous preterm birth. A systems biology approach with an integrated multiomic study was employed. Biobanked pregnancy tissues selected from a pregnancy cohort were subjected to genomic, transcriptomic, methylomic, and proteomic studies, with a focus on genetic loci/genes related to uterine muscle contraction, specifically, genes associated with sarcomeres and desmosomes. Thirteen single nucleotide variations and pathogenic variants were identified in the sarcomere gene, TTN, which encodes the protein Titin, from 146 women with spontaneous preterm labor. Differential expression profiles of five long non-coding RNAs were identified from loci that overlap with four sarcomeric genes. Longitudinally, the long non-coding RNA of gene TPM3 that encodes the protein tropomysin 3 was found to significantly regulate the mRNA of TPM3 in the placenta, compared to maternal blood. The majority of genome methylation profiles related to premature uterine contraction were also identified in the CpG promoters of sarcomeric genes/loci. Differential expression profiles of mRNAs associated with premature uterine contraction showed 22 genes associated with sarcomeres and three with desmosomes. The results demonstrated that premature uterine contraction was associated mainly with pathogenic variants of the TTN gene and with transcriptomic variations of sarcomeric premature uterine contraction genes. This association is likely regulated by epigenetic factors, including methylation and long non-coding RNAs.
Purpose: In this study, the authors examined the impact of sampling context on multiple aspects of expressive language in male participants with fragile X syndrome in comparison to male participants ...with Down syndrome or typical development. Method: Participants with fragile X syndrome (n = 27), ages 10-17 years, were matched groupwise on nonverbal mental age to adolescents with Down syndrome (n = 15) and typically developing 3- to 6-year-olds (n = 15). Language sampling contexts were an interview-style conversation and narration of a wordless book, with scripted examiner behavior. Language was assessed in terms of amount of talk, mean length of communication unit (MLCU), lexical diversity, fluency, and intelligibility. Results: Participants with fragile X syndrome had lower MLCU and lexical diversity than did participants with typical development. Participants with Down syndrome produced yet lower MLCU. A differential effect of context among those with fragile X syndrome, Down syndrome, and typical development emerged for the number of attempts per minute, MLCU, and fluency. For participants with fragile X syndrome, autism symptom severity related to the number of utterances produced in conversation. Aspects of examiner behavior related to participant performance. Conclusion: Sampling context characteristics should be considered when assessing expressive language in individuals with neurodevelopmental disabilities.
Maternal nutrients play critical roles in modulating epigenetic events and exert long-term influences on the progeny’s health. Folic acid (FA) supplementation during pregnancy has decreased the ...incidence of neural tube defects in newborns, but the influence of high doses of maternal FA supplementation on infants’ brain development is unclear. The present study was aimed at investigating the effects of a high dose of gestational FA on the expression of genes in the cerebral hemispheres (CHs) of 1-day-old pups. One week prior to mating and throughout the entire period of gestation, female C57BL/6J mice were fed a diet, containing FA at either 2 mg/kg (control diet (CD)) or 20 mg/kg (high maternal folic acid (HMFA)). At postnatal day 1, pups from different dams were sacrificed and CH tissues were collected. Quantitative RT-PCR and Western blot analysis confirmed sex-specific alterations in the expression of several genes that modulate various cellular functions (
P
< 0.05) in pups from the HMFA group. Genomic DNA methylation analysis showed no difference in the level of overall methylation in pups from the HMFA group. These findings demonstrate that HMFA supplementation alters offsprings’ CH gene expression in a sex-specific manner. These changes may influence infants’ brain development.
Autism is characterized by a broad spectrum of clinical manifestations including qualitative impairments in social interactions and communication, and repetitive and stereotyped patterns of behavior. ...Abnormal acceleration of brain growth in early childhood, signs of slower growth of neurons, and minicolumn developmental abnormalities suggest multiregional alterations. The aim of this study was to detect the patterns of focal qualitative developmental defects and to identify brain regions that are prone to developmental alterations in autism. Formalin-fixed brain hemispheres of 13 autistic (4–60 years of age) and 14 age-matched control subjects were embedded in celloidin and cut into 200-μm-thick coronal sections, which were stained with cresyl violet and used for neuropathological evaluation. Thickening of the subependymal cell layer in two brains and subependymal nodular dysplasia in one brain is indicative of active neurogenesis in two autistic children. Subcortical, periventricular, hippocampal and cerebellar heterotopias detected in the brains of four autistic subjects (31%) reflect abnormal neuronal migration. Multifocal cerebral dysplasia resulted in local distortion of the cytoarchitecture of the neocortex in four brains (31%), of the entorhinal cortex in two brains (15%), of the cornu Ammonis in four brains and of the dentate gyrus in two brains. Cerebellar flocculonodular dysplasia detected in six subjects (46%), focal dysplasia in the vermis in one case, and hypoplasia in one subject indicate local failure of cerebellar development in 62% of autistic subjects. Detection of flocculonodular dysplasia in only one control subject and of a broad spectrum of focal qualitative neuropathological developmental changes in 12 of 13 examined brains of autistic subjects (92%) reflects multiregional dysregulation of neurogenesis, neuronal migration and maturation in autism, which may contribute to the heterogeneity of the clinical phenotype.
Purpose: The validity, responsiveness, and clinical utility of the Canadian Occupational Performance Measure was investigated when used in a sub-acute setting.
Materials and Methods: Fifty older ...adults (mean age 78.2 years, Standard Deviation = 7.2; 64% female) completed the Canadian Occupational Performance Measure, Functional Independence Measure and the Short-Form 36 Health Questionnaire. The Canadian Occupational Performance Measure was correlated with the Functional Independence Measure and Short-Form 36 Health Questionnaire and the admission and discharge Canadian Occupational Performance Measure Performance and Satisfaction scores were compared for significant differences. Qualitative interviews with were completed with six older adults and six occupational therapists to explore the utility of the Canadian Occupational Performance Measure.
Results: The Canadian Occupational Performance Measure Satisfaction scale was significantly associated with the Functional Independence Measure and Short-Form 36 Health Questionnaire. Significant differences were found between the admission and discharge Canadian Occupational Performance Measure Performance and Satisfaction scale scores. From both the clients' and therapists' perspectives, four key qualitative themes emerged: (1) "Likes" about the Canadian Occupational Performance Measure; (2) Effects on practice; (3) Utility; and (4) Future use.
Conclusions: This study provides evidence of the Canadian Occupational Performance Measure's validity, responsiveness and clinical utility when used in a sub-acute setting.
Implications for rehabilitation
The Canadian Occupational Performance Measure appears able to effectively evaluate the outcomes of occupational therapy interventions, including in sub-acute rehabilitation settings. It is an individualized outcome measure where clients are responsible for measuring their own progress and meaningful outcomes from therapy.
Evidence of the Canadian Occupational Performance Measure's convergent validity, predictive validity and responsiveness to change was found which contributes to the body of knowledge of its psychometric properties.
From a qualitative perspective, the Canadian Occupational Performance Measure was found to improve clinical decision making, facilitating client engagement, formulating clear treatment goals and making therapy more meaningful for clients.
•All thermal treatments reduced pathogenic and indicator bacteria on fresh beef.•Treatment time for 6 s at 71°C effectively reduced pathogens on fresh beef.•Cascade e-ion plasma could be an effective ...thermal intervention for fresh beef.
Thermal treatment interventions consistently provide effective pathogen reductions. However, the cost of maintaining high temperature of 95°C in order to raise the surface temperature of carcasses to 82°C is very expensive. Therefore, beef processors need to identify thermal application times and temperatures that optimize the treatment effects with less maintenance cost. The objectives of this study were to determine the efficacy of hot water or steam at 71°C for 6 s and cascade e-ion plasma treatment for 2 s in reducing pathogens on the surface of fresh beef compared to the thermal treatment at 82°C for 15 s. Hot water at 71°C for 6 s reduced Escherichia coli O157:H7 and Salmonella by 2.38 and 2.48 log CFU/cm2, while steam treatment at 71°C for 6 s reduced E. coli O157:H7 and Salmonella by 2.94 and 3.06 log CFU/cm2, respectively. Cascade e-ion plasma treatment for 2 s reduced E. coli O157:H7 on surface of fresh beef by 1.89 log CFU/cm2. The findings indicate that short treatment time with appropriate temperature could serve as an effective carcass intervention to improve the safety of fresh beef.
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