114 research outputs found
Pathways to Care of Maine Youth with Psychosis
Study clinicians conducted semi-structured interviews to identify the timing and steps of each person’s Pathway to Care (PtC).https://knowledgeconnection.mainehealth.org/lambrew-retreat-2023/1028/thumbnail.jp
Considerations and strategies for incorporating lived experience in mental health research
Introduction: Incorporating lived experience in mental health research deserves special focus due to the unique stigma faced by those with lived experience and the unique gap between the experience and expression of mental health struggle.https://knowledgeconnection.mainehealth.org/lambrew-retreat-2023/1029/thumbnail.jp
COVID-19 and depression and anxiety screening in primary care
Introduction:
• The COVID-19 pandemic had a severe effect on mental health, heightening the prevalence and severity of anxiety and depression amongst the general population in rural and non-rural areas, particularly youth.
• Most reports draw from available data from mental health referrals, hospitalizations, suicides, and other incident data
• There is limited longitudinal information from general population samples using standardized mental health assessments.https://knowledgeconnection.mainehealth.org/lambrew-retreat-2023/1027/thumbnail.jp
Most Colorectal Cancer Survivors Live a Large Proportion of Their Remaining Life in Good Health
Purpose Colorectal cancer (CRC) diagnosis reduces life expectancy and decreases patients’ well-being. We sought to assess the determinants of health and functional status and estimate the proportion of remaining life that CRC survivors would spend in good health. Methods Using Sullivan method, healthy life expectancy was calculated based on survival data of 14,849 CRC survivors within a population-based cancer registry in southern Netherlands and quality of life information among a random sample of these survivors (n = 1,291). Results: Overall, albeit short life expectancy (LE at age 50 = 12 years for males and 13 years for females), most CRC survivors spent a large proportion of their remaining life in good health (74 and 77 %, for males and females, respectively). Long-term survivors may expect to live a normal life span (LE at age 50 = 30 years) and spent a large proportion of the remaining life in good health (78 %). In distinction, those with stage IV CRC had less than 2 years to live and spent more than half of their remaining life in poor health. Conclusions: Most CRC patients may expect no compromise on living a healthy life, underlining the importance of early detection. On the other hand, the high proportion of non-healthy years among stage IV CRC survivors confirms the importance of early detection and palliative care. Electronic supplementary material The online version of this article (doi:10.1007/s10552-012-0010-2) contains supplementary material, which is available to authorized users
Syntheses and characterization of three-and five-coordinate copper(II) complexes based on SNS pincer ligand precursors
A series of tridentate pincer ligands, each possessing two sulfur- and one nitrogen-donor functionalities (SNS), based on a bis-imidazolyl precursor were metallated with CuCl2 to give new tridentate SNS pincer copper(II) complexes [(SNS)CuCl2]. These purple complexes exhibit a five-coordinate pseudo-square pyramidal geometry at the copper center. The [(SNS)CuCl2] complexes were characterized with single crystal X-ray diffraction, electrospray mass spectrometry, EPR spectroscopy, attenuated total reflectance infrared spectroscopy, UV–Vis spectroscopy, cyclic voltammetry, and elemental analysis. The EPR spectra are consistent with typical anisotropic Cu(II) signals with four hyperfine splittings in the lower-field region (g||). Various electronic transitions are apparent in the UV–Vis spectra of the complexes and originate from d-to-d transitions or various charge transfer transitions. We preformed computational studies to understand the influence that structural constraints internal to our tridentate SNS ligand precursors have on the oxidation state of the resulting bound copper complex. We have determined that a d9 copper(II) metal center is better situated than a d10 copper(I) center to bind our tridentate SNS ligand set when it does not contain an internal CH2 group. Without this methylene linker, the SNS ligand forces the N and S atoms into a T-shaped arrangement about the metal center
Evidence for involvement of GNB1L in autism
Structural variations in the chromosome 22q11.2 region mediated by nonallelic homologous recombination result in 22q11.2 deletion (del22q11.2) and 22q11.2 duplication (dup22q11.2) syndromes. The majority of del22q11.2 cases have facial and cardiac malformations, immunologic impairments, specific cognitive profile and increased risk for schizophrenia and autism spectrum disorders (ASDs). The phenotype of dup22q11.2 is frequently without physical features but includes the spectrum of neurocognitive abnormalities. Although there is substantial evidence that haploinsufficiency for TBX1 plays a role in the physical features of del22q11.2, it is not known which gene(s) in the critical 1.5 Mb region are responsible for the observed spectrum of behavioral phenotypes. We identified an individual with a balanced translocation 46,XY,t(1;22)(p36.1;q11.2) and a behavioral phenotype characterized by cognitive impairment, autism, and schizophrenia in the absence of congenital malformations. Using somatic cell hybrids and comparative genomic hybridization (CGH) we mapped the chromosome-22 breakpoint within intron 7 of the GNB1L gene. Copy number evaluations and direct DNA sequencing of GNB1L in 271 schizophrenia and 513 autism cases revealed dup22q11.2 in two families with autism and private GNB1L missense variants in conserved residues in three families (P = 0.036). The identified missense variants affect residues in the WD40 repeat domains and are predicted to have deleterious effects on the protein. Prior studies provided evidence that GNB1L may have a role in schizophrenia. Our findings support involvement of GNB1L in ASDs as well. © 2011 Wiley Periodicals, Inc
Global analysis of in vivo Foxa2-binding sites in mouse adult liver using massively parallel sequencing
Foxa2 (HNF3β) is a one of three, closely related transcription factors that are critical to the development and function of the mouse liver. We have used chromatin immunoprecipitation and massively parallel Illumina 1G sequencing (ChIP–Seq) to create a genome-wide profile of in vivo Foxa2-binding sites in the adult liver. More than 65% of the ∼11.5 k genomic sites associated with Foxa2 binding, mapped to extended gene regions of annotated genes, while more than 30% of intragenic sites were located within first introns. 20.5% of all sites were further than 50 kb from any annotated gene, suggesting an association with novel gene regions. QPCR analysis demonstrated a strong positive correlation between peak height and fold enrichment for Foxa2-binding sites. We measured the relationship between Foxa2 and liver gene expression by overlapping Foxa2-binding sites with a SAGE transcriptome profile, and found that 43.5% of genes expressed in the liver were also associated with Foxa2 binding. We also identified potential Foxa2-interacting transcription factors whose motifs were enriched near Foxa2-binding sites. Our comprehensive results for in vivo Foxa2-binding sites in the mouse liver will contribute to resolving transcriptional regulatory networks that are important for adult liver function
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Resting state EEG in youth with ASD: age, sex, and relation to phenotype
Background
Identification of ASD biomarkers is a key priority for understanding etiology, facilitating early diagnosis, monitoring developmental trajectories, and targeting treatment efforts. Efforts have included exploration of resting state encephalography (EEG), which has a variety of relevant neurodevelopmental correlates and can be collected with minimal burden. However, EEG biomarkers may not be equally valid across the autism spectrum, as ASD is strikingly heterogeneous and individual differences may moderate EEG-behavior associations. Biological sex is a particularly important potential moderator, as females with ASD appear to differ from males with ASD in important ways that may influence biomarker accuracy.
Methods
We examined effects of biological sex, age, and ASD diagnosis on resting state EEG among a large, sex-balanced sample of youth with (N = 142, 43% female) and without (N = 138, 49% female) ASD collected across four research sites. Absolute power was extracted across five frequency bands and nine brain regions, and effects of sex, age, and diagnosis were analyzed using mixed-effects linear regression models. Exploratory partial correlations were computed to examine EEG-behavior associations in ASD, with emphasis on possible sex differences in associations.
Results
Decreased EEG power across multiple frequencies was associated with female sex and older age. Youth with ASD displayed decreased alpha power relative to peers without ASD, suggesting increased neural activation during rest. Associations between EEG and behavior varied by sex. Whereas power across various frequencies correlated with social skills, nonverbal IQ, and repetitive behavior for males with ASD, no such associations were observed for females with ASD.
Conclusions
Research using EEG as a possible ASD biomarker must consider individual differences among participants, as these features influence baseline EEG measures and moderate associations between EEG and important behavioral outcomes. Failure to consider factors such as biological sex in such research risks defining biomarkers that misrepresent females with ASD, hindering understanding of the neurobiology, development, and intervention response of this important population
Pathogenic SPTBN1 variants cause an autosomal dominant neurodevelopmental syndrome
SPTBN1 mutations cause a neurodevelopmental syndrome characterized by intellectual disability, language and motor delays, autism, seizures and other features. The variants disrupt beta II-spectrin function and disturb cytoskeletal organization and dynamics. SPTBN1 encodes beta II-spectrin, the ubiquitously expressed beta-spectrin that forms micrometer-scale networks associated with plasma membranes. Mice deficient in neuronal beta II-spectrin have defects in cortical organization, developmental delay and behavioral deficiencies. These phenotypes, while less severe, are observed in haploinsufficient animals, suggesting that individuals carrying heterozygous SPTBN1 variants may also show measurable compromise of neural development and function. Here we identify heterozygous SPTBN1 variants in 29 individuals with developmental, language and motor delays;mild to severe intellectual disability;autistic features;seizures;behavioral and movement abnormalities;hypotonia;and variable dysmorphic facial features. We show that these SPTBN1 variants lead to effects that affect beta II-spectrin stability, disrupt binding to key molecular partners, and disturb cytoskeleton organization and dynamics. Our studies define SPTBN1 variants as the genetic basis of a neurodevelopmental syndrome, expand the set of spectrinopathies affecting the brain and underscore the critical role of beta II-spectrin in the central nervous system
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