1. Gholizadeh S, Arsenault J, Xuan IC, Pacey LK, Hampson DR. {{Reduced Phenotypic Severity Following Adeno-Associated Virus Mediated Fmr1 Gene Delivery in Fragile X Mice}}. {Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology}. 2014 Jul 7.
Fragile X syndrome is a neurodevelopmental disorder caused by a trinucleotide repeat expansion in the FMR1 gene that codes for Fragile X Mental Retardation Protein (FMRP). To determine if FMRP expression in the central nervous system could reverse phenotypic deficits in the Fmr1 knockout mouse model of fragile X, we used a single-stranded adeno-associated viral vector (AAV) with viral capsids from serotype 9 that contained a major isoform of FMRP. FMRP transgene expression was driven by the neuron-selective synapsin-1 promoter. The vector was delivered to the brain via a single bilateral intra-cerebroventricular injection into neonatal Fmr1 knockout mice and transgene expression and behavioral assessments were conducted 22-26 and 50-56 days post-injection. Western blotting and immunocytochemical analyses of AAV-FMRP injected mice revealed FMRP expression in the striatum, hippocampus, retrosplenial cortex and cingulate cortex. Cellular expression was selective for neurons and reached approximately 50% of wild-type levels in the hippocampus and cortex at 56 days post-injection. The pathologically elevated repetitive behavior and the deficit in social dominance behavior seen in PBS-injected Fmr1 knockout mice were reversed in AAV-FMRP injected mice. These results provide the first proof-of-principle that gene therapy can correct specific behavioral abnormalities in the mouse model of fragile X syndrome.Neuropsychopharmacology accepted article preview online, 07 July 2014; doi:10.1038/npp.2014.167.
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2. Kotey S, Ertel K, Whitcomb B. {{Co-occurrence of Autism and Asthma in a Nationally-Representative Sample of Children in the United States}}. {Journal of autism and developmental disorders}. 2014 Jul 6.
Few large epidemiological studies have examined the co-occurrence of autism and asthma. We performed a cross-sectional study to examine this association using the 2007 National Survey of Children’s Health dataset (n = 77,951). We controlled for confounders and tested for autism-secondhand smoke interaction. Prevalence of asthma and autism were 14.5 % (n = 11,335) and 1.81 % (n = 1,412) respectively. Unadjusted odds ratio (OR) for asthma among autistic children was 1.35 (95 % CI 1.18-1.55). Adjusting for covariates (age, gender, body mass index, race, brain injury, secondhand smoke and socio-economic status) attenuated the OR to 1.19 (95 % CI 1.03-1.36). Autism-secondhand smoke interaction was insignificant (p = 0.38). Asthma is approximately 35 % more common in autistic children; screening may be an efficient approach to reduce risk of morbidity due to asthma.
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3. McStay RL, Trembath D, Dissanayake C. {{Stress and Family Quality of Life in Parents of Children with Autism Spectrum Disorder: Parent Gender and the Double ABCX Model}}. {Journal of autism and developmental disorders}. 2014 Jul 6.
Past research has supported the utility of the Double ABCX model of family adaptation for parents raising a child with autism spectrum disorder (ASD). What remains unclear is the impact of family-related variables on outcomes in both mothers and fathers within the same family. We explored the potential predictors of maternal and paternal stress and family quality of life in an Australian sample of 196 parents of children with ASD aged 3-16 years. Using a cross-sectional design, parents completed questionnaires assessing factors within the Double ABCX model attributed to family adaptation. Findings provide further evidence of the negative impact of child externalising behaviours and highlight the importance of family sense of coherence on positive parental outcomes.
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4. Nadal-Desbarats L, Aidoud N, Emond P, Blasco H, Filipiak I, Sarda P, Bonnet-Brilhault F, Mavel S, Andres CR. {{Combined 1H-NMR and 1H-13C HSQC-NMR to improve urinary screening in autism spectrum disorders}}. {The Analyst}. 2014 Jul 7;139(13):3460-8.
Autism spectrum disorders (ASD) are neurodevelopmental diseases with complex genetic and environmental etiological factors. Although genetic causes play a significant part in the etiology of ASD, metabolic disturbances may also play a causal role or modulate the clinical features of ASD. The number of ASD studies involving metabolomics is increasing, and sometime with conflicting findings. We assessed the metabolomics profiling of urine samples to determine a comprehensive biochemical signature of ASD. Furthermore, to date no study has combined metabolic profiles obtained from different analytical techniques to distinguish patient with ASD from healthy individuals. We obtained (1)H-NMR spectra and 2D (1)H-(13)C HSQC NMR spectra from urine samples of patients with ASD or healthy controls. We analyzed these spectra by multivariate statistical data analysis. The OPLS-DA model obtained from (1)H NMR spectra showed a good discrimination between ASD samples and non-ASD samples (R(2)Y(cum) = 0.70 and Q(2) = 0.51). Combining the (1)H NMR spectra and the 2D (1)H-(13)C HSQC NMR spectra increased the overall quality and predictive value of the OPLS-DA model (R(2)Y(cum) = 0.84 and Q(2) = 0.71), leading to a better sensitivity and specificity. Urinary excretion of succinate, glutamate and 3-methyl-histidine differed significantly between ASD and non-ASD samples. Urinary screening of children with neurodevelopmental disorders by combining NMR spectroscopies (1D and 2D) in multivariate analysis is a better sensitive and a straightforward method that could help the diagnosis ASD.
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5. Quint EH. {{Menstrual and Reproductive Issues in Adolescents With Physical and Developmental Disabilities}}. {Obstetrics and gynecology}. 2014 Jul 7.
Most obstetrician-gynecologists will encounter adolescents with disabilities in their practice, because developmental and physical disabilities are common in young patients (8.4%). Reproductive health issues such as puberty, sexuality, and menstruation can be more complicated for teenagers with disabilities and their families as a result of concerns surrounding menstrual hygiene, abuse risk, vulnerability, changes in seizure pattern, and altered mood. Teenagers with disabilities have gynecologic health care needs similar to those of their peers as well as unique needs related to their physical and cognitive issues. The gynecologic health visit for a teenager with disabilities should include an evaluation of the teenager’s reproductive knowledge as well as an assessment of her abuse and coercion risk and her ability to consent to sexual activity. The menstrual history is focused on the effects of menstrual cycles on her daily life. Diagnostic testing is not different from other adolescents. Hormonal treatment is often requested by the patient and her family to alleviate abnormal bleeding, cyclic mood changes, dysmenorrhea, or a combination of these, to assist with menstrual hygiene, and to provide contraception. Menstrual manipulation can be used to induce complete amenorrhea, regulate cycles, or decrease regular menstrual flow. However, treatment risks and side effects may have a different effect on the lives of these adolescents. The comfort level of health care providers to respond to the special concerns of adolescents with disabilities is low, and several barriers exist. This review addresses the complex issues of puberty, menstruation, sexuality, abuse, and safety highlighting the distinctive needs of this population. The options and decisions around menstrual manipulation are highlighted in detail.
