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1.
J Child Health Care ; 26(1): 5-17, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-33570424

RESUMO

Family-centred care (FCC) is recognised as a fundamental practice principle in the delivery of contemporary paediatric allied health care; however, limited evidence exists on how to translate FCC theory into practice for Child Development Services (CDS). This study describes and evaluates parent perceptions of a family-centred model of care at a publicly funded CDS where a care pathway consists of parent orientation-to-service session, integrated transdisciplinary allied health assessment, feedback and goal setting appointments. 15 participants completed a semi-structured in-depth interview and rating scales of service satisfaction. Interview data were audio recorded and transcribed verbatim. Thematic analysis and data triangulation were completed by three investigators to enhance validity and descriptive statistics were identified. The model of care was positively perceived by families, with participants identifying value in communication; fostering of respect and partnership and therapist skills. Service themes that influenced parents' perception of the model included benefits of a holistic approach to care and staffing continuity. Uncertainty of wait list time frames and transition/discharge points were identified as a source of stress by families. This research investigates what components of FCC are meaningful to consumers and considers practical ideas of delivering care within a family-centred framework.


Assuntos
Serviços de Saúde da Criança , Criança , Desenvolvimento Infantil , Comunicação , Humanos , Pais , Satisfação Pessoal , Relações Profissional-Família
2.
Mol Biol Cell ; 32(4): 314-330, 2021 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-33378226

RESUMO

TRIM9 and TRIM67 are neuronally enriched E3 ubiquitin ligases essential for appropriate morphogenesis of cortical and hippocampal neurons and fidelitous responses to the axon guidance cue netrin-1. Deletion of murine Trim9 or Trim67 results in neuroanatomical defects and striking behavioral deficits, particularly in spatial learning and memory. TRIM9 and TRIM67 interact with cytoskeletal and exocytic proteins, but the full interactome is not known. Here we performed the unbiased proximity-dependent biotin identification (BioID) approach to define TRIM9 and TRIM67 protein-protein proximity network in developing cortical neurons and identified putative neuronal TRIM interaction partners. Candidates included cytoskeletal regulators, cytosolic protein transporters, exocytosis and endocytosis regulators, and proteins necessary for synaptic regulation. A subset of high-priority candidates was validated, including Myo16, Coro1A, MAP1B, ExoC1, GRIP1, PRG-1, and KIF1A. For a subset of validated candidates, we utilized total internal reflection fluorescence microscopy to demonstrate dynamic colocalization with TRIM proteins at the axonal periphery, including at the tips of filopodia. Further analysis demonstrated that the RNA interference-based knockdown of the unconventional myosin Myo16 in cortical neurons altered growth cone filopodia density and axonal branching patterns in a TRIM9- and netrin-1-dependent manner. Future analysis of other validated candidates will likely identify novel proteins and mechanisms by which TRIM9 and TRIM67 regulate neuronal form and function. [Media: see text].


Assuntos
Proteínas do Citoesqueleto/metabolismo , Morfogênese/fisiologia , Proteínas do Tecido Nervoso/metabolismo , Proteínas com Motivo Tripartido/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Axônios/metabolismo , Proteínas do Citoesqueleto/genética , Proteínas do Citoesqueleto/fisiologia , Feminino , Cones de Crescimento/metabolismo , Hipocampo/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Morfogênese/genética , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/fisiologia , Neurônios/metabolismo , Mapeamento de Interação de Proteínas/métodos , Mapas de Interação de Proteínas , Pseudópodes/metabolismo , Proteínas com Motivo Tripartido/genética , Proteínas com Motivo Tripartido/fisiologia , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/fisiologia
3.
Mol Psychiatry ; 25(8): 1673-1687, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32099098

RESUMO

To provide insights into the biology of opioid dependence (OD) and opioid use (i.e., exposure, OE), we completed a genome-wide analysis comparing 4503 OD cases, 4173 opioid-exposed controls, and 32,500 opioid-unexposed controls, including participants of European and African descent (EUR and AFR, respectively). Among the variants identified, rs9291211 was associated with OE (exposed vs. unexposed controls; EUR z = -5.39, p = 7.2 × 10-8). This variant regulates the transcriptomic profiles of SLC30A9 and BEND4 in multiple brain tissues and was previously associated with depression, alcohol consumption, and neuroticism. A phenome-wide scan of rs9291211 in the UK Biobank (N > 360,000) found association of this variant with propensity to use dietary supplements (p = 1.68 × 10-8). With respect to the same OE phenotype in the gene-based analysis, we identified SDCCAG8 (EUR + AFR z = 4.69, p = 10-6), which was previously associated with educational attainment, risk-taking behaviors, and schizophrenia. In addition, rs201123820 showed a genome-wide significant difference between OD cases and unexposed controls (AFR z = 5.55, p = 2.9 × 10-8) and a significant association with musculoskeletal disorders in the UK Biobank (p = 4.88 × 10-7). A polygenic risk score (PRS) based on a GWAS of risk-tolerance (n = 466,571) was positively associated with OD (OD vs. unexposed controls, p = 8.1 × 10-5; OD cases vs. exposed controls, p = 0.054) and OE (exposed vs. unexposed controls, p = 3.6 × 10-5). A PRS based on a GWAS of neuroticism (n = 390,278) was positively associated with OD (OD vs. unexposed controls, p = 3.2 × 10-5; OD vs. exposed controls, p = 0.002) but not with OE (p = 0.67). Our analyses highlight the difference between dependence and exposure and the importance of considering the definition of controls in studies of addiction.


Assuntos
Analgésicos Opioides/administração & dosagem , Comportamento Aditivo/genética , Predisposição Genética para Doença/genética , Variação Genética/genética , Estudo de Associação Genômica Ampla , Genômica , Transtornos Relacionados ao Uso de Opioides/genética , Analgésicos Opioides/farmacologia , Feminino , Genoma Humano/genética , Humanos , Masculino , Herança Multifatorial/genética
4.
Transl Psychiatry ; 9(1): 269, 2019 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-31636251

RESUMO

Cannabis use and disorders (CUD) are influenced by multiple genetic variants of small effect and by the psychosocial environment. However, this information has not been effectively incorporated into studies of gene-environment interaction (GxE). Polygenic risk scores (PRS) that aggregate the effects of genetic variants can aid in identifying the links between genetic risk and psychosocial factors. Using data from the Pasman et al. GWAS of cannabis use (meta-analysis of data from the International Cannabis Consortium and UK Biobank), we constructed PRS in the Collaborative Study on the Genetics of Alcoholism (COGA) participants of European (N: 7591) and African (N: 3359) ancestry. The primary analyses included only individuals of European ancestry, reflecting the ancestral composition of the discovery GWAS from which the PRS was derived. Secondary analyses included the African ancestry sample. Associations of PRS with cannabis use and DSM-5 CUD symptom count (CUDsx) and interactions with trauma exposure and frequency of religious service attendance were examined. Models were adjusted for sex, birth cohort, genotype array, and ancestry. Robustness models were adjusted for cross-term interactions. Higher PRS were associated with a greater likelihood of cannabis use and with CUDsx among participants of European ancestry (p < 0.05 and p < 0.1 thresholds, respectively). PRS only influenced cannabis use among those exposed to trauma (R2: 0.011 among the trauma exposed vs. R2: 0.002 in unexposed). PRS less consistently influenced cannabis use among those who attend religious services less frequently; PRS × religious service attendance effects were attenuated when cross-term interactions with ancestry and sex were included in the model. Polygenic liability to cannabis use was related to cannabis use and, less robustly, progression to symptoms of CUD. This study provides the first evidence of PRS × trauma for cannabis use and demonstrates that ignoring important aspects of the psychosocial environment may mask genetic influences on polygenic traits.


Assuntos
Cannabis , Predisposição Genética para Doença , Uso da Maconha/genética , Herança Multifatorial , Influência dos Pares , Espiritualidade , Violência , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , População Negra , Criança , Feminino , Interação Gene-Ambiente , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , População Branca , Adulto Jovem
5.
Vet Anaesth Analg ; 45(6): 871-875, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30305232

RESUMO

OBJECTIVE: This study evaluated the spread of a two-point transversus abdominis plane (TAP) injection in canine cadavers. Compared with previous techniques, the two-point TAP injection was developed to increase the consistency of local anaesthetic spread to the nerve segments T11, T12, L1, L2 and L3. STUDY DESIGN: Prospective experimental trial. ANIMALS: Five fresh canine cadavers. METHODS: Two-point TAP injections were performed under ultrasound guidance by a single trained individual in canine cadavers (15.7-43.0 kg). Each hemi-abdomen was infiltrated and evaluated independently for a total of 10 evaluations of the technique. The first injection was performed at the level of the costo-chondral junction of the thirteenth rib, and the second injection was performed cranial to the tuber coxae. Each injection comprised 0.3 mL kg-1 methylene blue solution (0.0015 mg mL-1). Ten minutes after the injections, abdominal wall dissection was performed, and any nerves stained for a minimum of 10 mm along their long axis were identified and recorded. RESULTS: During all injections, separation of the internal oblique and transversus abdominis muscles was observed on ultrasound. On dissection, branches of T12, T13, L1, L2 and L3 were adequately stained in 30%, 100%, 100%, 90% and 90% of injections, respectively. No staining of branches of T11 occurred in any of the cadavers. In one hemi-abdomen, branches of L1 and L3, but not L2, were stained. CONCLUSIONS AND CLINICAL RELEVANCE: This study indicates that the two-point TAP injection delivers consistent dye dispersion to adequately stain branches of T13, L1, L2 and L3, with no coverage of T11 and poor coverage of T12, in fresh canine cadavers. An in vivo study using local anaesthetic should be performed to evaluate the analgesic efficacy of this technique in mid to caudal abdominal surgeries.


Assuntos
Músculos Abdominais , Anestesia Local/veterinária , Injeções Intramusculares/veterinária , Ultrassonografia de Intervenção/veterinária , Anestesia Local/métodos , Animais , Cadáver , Cães , Feminino , Injeções Intramusculares/métodos , Masculino , Projetos Piloto , Estudos Prospectivos , Ultrassonografia de Intervenção/métodos
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