Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 7 de 7
Filtrar
1.
J Adv Nurs ; 79(4): 1540-1552, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35864079

RESUMO

AIM: The aim was to discover longitudinal trajectories and patterns of events preceding adolescent-to-mother family violence in a geographic locale in Australia. DESIGN: This was a retrospective case series. METHODS: Routinely collected administrative data were sourced and linked from police and health service electronic records for adolescents born between 1994 and 2006 who had been issued a legal action for a family violence-related offence (n = 775). A time-stamped log of events from birth (where available) was created. Process mining was employed to discover dominant events and trajectories in the log from birth until adolescents' first recorded offence against their mother. RESULTS/FINDINGS: Most adolescents in the case series offended against mothers (63%, n = 486). Trajectory analysis confirmed dominant early childhood events were repeated exposure to parental intimate partner violence (P-IPV), parental drug and/or alcohol use and neglect. During early adolescence, pathways towards adolescent-to-mother violence involved other offending, drug and/or alcohol use and mental health service contact. CONCLUSION: The trajectories evidenced provide a complex picture of the emergence of adolescent-to-mother violence. From an early intervention perspective, it was found that many children and mothers were identifiable from police records in early childhood, at an average age of 35 months. Responses to adolescent family violence need to acknowledge the impact of childhood trauma and emerging mental health problems, along with strategies to mitigate the effect of P-IPV on mother-to-child relationships. IMPACT: This is the first large-scale study to specifically examine trajectories from birth for adolescents who engage in violence towards mothers. The findings have important implications for the design and delivery of early intervention childhood services and interagency collaboration in nursing and midwifery services. In early adolescence, contact with mental health services represents an opportunity for screening and support interventions. This is an important preventive timepoint for family violence, adolescent drug and alcohol use and other offences.


Assuntos
Violência Doméstica , Mães , Humanos , Adolescente , Feminino , Pré-Escolar , Mães/psicologia , Estudos Retrospectivos , Polícia , Transmissão Vertical de Doenças Infecciosas , Serviços de Saúde
2.
Ann Clin Transl Neurol ; 10(5): 686-695, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37026610

RESUMO

Valosin-containing protein (VCP)-associated multisystem proteinopathy (MSP) is a rare genetic disorder with abnormalities in the autophagy pathway leading to various combinations of myopathy, bone diseases, and neurodegeneration. Ninety percent of patients with VCP-associated MSP have myopathy, but there is no consensus-based guideline. The goal of this working group was to develop a best practice set of provisional recommendations for VCP myopathy which can be easily implemented across the globe. As an initiative by Cure VCP Disease Inc., a patient advocacy organization, an online survey was initially conducted to identify the practice gaps in VCP myopathy. All prior published literature on VCP myopathy was reviewed to better understand the different aspects of management of VCP myopathy, and several working group sessions were conducted involving international experts to develop this provisional recommendation. VCP myopathy has a heterogeneous clinical phenotype and should be considered in patients with limb-girdle muscular dystrophy phenotype, or any myopathy with an autosomal dominant pattern of inheritance. Genetic testing is the only definitive way to diagnose VCP myopathy, and single-variant testing in the case of a known familial VCP variant, or multi-gene panel sequencing in undifferentiated cases can be considered. Muscle biopsy is important in cases of diagnostic uncertainty or lack of a definitive pathogenic genetic variant since rimmed vacuoles (present in ~40% cases) are considered a hallmark of VCP myopathy. Electrodiagnostic studies and magnetic resonance imaging can also help rule out disease mimics. Standardized management of VCP myopathy will optimize patient care and help future research initiatives.


Assuntos
Doenças Musculares , Distrofia Muscular do Cíngulo dos Membros , Deficiências na Proteostase , Humanos , Proteína com Valosina/genética , Doenças Musculares/diagnóstico , Doenças Musculares/genética , Doenças Musculares/terapia , Distrofia Muscular do Cíngulo dos Membros/diagnóstico , Distrofia Muscular do Cíngulo dos Membros/genética , Distrofia Muscular do Cíngulo dos Membros/terapia , Fenótipo
3.
Genes (Basel) ; 13(6)2022 05 27.
Artigo em Inglês | MEDLINE | ID: mdl-35741724

RESUMO

In this work, we review clinical features and genetic diagnosis of diseases caused by mutations in the gene encoding valosin-containing protein (VCP/p97), the functionally diverse AAA-ATPase. VCP is crucial to a multitude of cellular functions including protein quality control, stress granule formation and clearance, and genomic integrity functions, among others. Pathogenic mutations in VCP cause multisystem proteinopathy (VCP-MSP), an autosomal dominant, adult-onset disorder causing dysfunction in several tissue types. It can result in complex neurodegenerative conditions including inclusion body myopathy, frontotemporal dementia, amyotrophic lateral sclerosis, or combinations of these. There is also an association with other neurodegenerative phenotypes such as Alzheimer-type dementia and Parkinsonism. Non-neurological presentations include Paget disease of bone and may also include cardiac dysfunction. We provide a detailed discussion of genotype-phenotype correlations, recommendations for genetic diagnosis, and genetic counselling implications of VCP-MSP.


Assuntos
Esclerose Lateral Amiotrófica , Demência Frontotemporal , Osteíte Deformante , Proteína com Valosina , Esclerose Lateral Amiotrófica/genética , Demência Frontotemporal/diagnóstico , Demência Frontotemporal/genética , Demência Frontotemporal/patologia , Humanos , Mutação , Osteíte Deformante/diagnóstico , Osteíte Deformante/genética , Osteíte Deformante/patologia , Proteína com Valosina/genética
4.
Orphanet J Rare Dis ; 17(1): 23, 2022 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-35093159

RESUMO

Valosin-containing protein (VCP) associated multisystem proteinopathy (MSP) is a rare inherited disorder that may result in multisystem involvement of varying phenotypes including inclusion body myopathy, Paget's disease of bone (PDB), frontotemporal dementia (FTD), parkinsonism, and amyotrophic lateral sclerosis (ALS), among others. An international multidisciplinary consortium of 40+ experts in neuromuscular disease, dementia, movement disorders, psychology, cardiology, pulmonology, physical therapy, occupational therapy, speech and language pathology, nutrition, genetics, integrative medicine, and endocrinology were convened by the patient advocacy organization, Cure VCP Disease, in December 2020 to develop a standard of care for this heterogeneous and under-diagnosed disease. To achieve this goal, working groups collaborated to generate expert consensus recommendations in 10 key areas: genetic diagnosis, myopathy, FTD, PDB, ALS, Charcot Marie Tooth disease (CMT), parkinsonism, cardiomyopathy, pulmonology, supportive therapies, nutrition and supplements, and mental health. In April 2021, facilitated discussion of each working group's conclusions with consensus building techniques enabled final agreement on the proposed standard of care for VCP patients. Timely referral to a specialty neuromuscular center is recommended to aid in efficient diagnosis of VCP MSP via single-gene testing in the case of a known familial VCP variant, or multi-gene panel sequencing in undifferentiated cases. Additionally, regular and ongoing multidisciplinary team follow up is essential for proactive screening and management of secondary complications. The goal of our consortium is to raise awareness of VCP MSP, expedite the time to accurate diagnosis, define gaps and inequities in patient care, initiate appropriate pharmacotherapies and supportive therapies for optimal management, and elevate the recommended best practices guidelines for multidisciplinary care internationally.


Assuntos
Esclerose Lateral Amiotrófica , Miosite de Corpos de Inclusão , Osteíte Deformante , Esclerose Lateral Amiotrófica/genética , Proteínas de Ciclo Celular/genética , Humanos , Mutação , Osteíte Deformante/genética , Padrão de Cuidado , Proteína com Valosina/genética
5.
Orphanet J Rare Dis ; 15(1): 267, 2020 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-32993728

RESUMO

BACKGROUND: Dominant mutations in valosin-containing protein (VCP) gene cause an adult onset inclusion body myopathy, Paget's disease of bone, and frontotemporal dementia also termed multisystem proteinopathy (MSP). The genotype-phenotype relationships in VCP-related MSP are still being defined; in order to understand this better, we investigated the phenotypic diversity and patterns of weakness in the Cure VCP Disease Patient Registry. METHODS: Cure VCP Disease, Inc. was founded in 2018 for the purpose of connecting patients with VCP gene mutations and researchers to help advance treatments and cures. Cure VCP Disease Patient Registry is maintained by Coordination of Rare Diseases at Sanford. The results of two questionnaires with a 5-point Likert scale questions regarding to patients' disease onset, symptoms, and daily life were obtained from 59 participants (28 males and 31 females) between June 2018 and May 2020. Independent of the registry, 22 patients were examined at the Cure VCP Disease annual patient conference in 2019. RESULTS: In the questionnaires of the registry, fifty-three patients (90%) reported that they were with inclusion body myopathy, 17 patients (29%) with Paget's disease of bone, eight patients (14%) with dementia, two patients (3%) with amyotrophic lateral sclerosis, and a patient with parkinsonism. Thirteen patients (22%) reported dysphagia and 25 patients (42%) reported dyspnea on exertion. A self-reported functional rating scale for motor function identified challenges with sit to stand (72%), walking (67%), and climbing stairs (85%). Thirty-five (59%) patients in the registry answered that their quality of life is more than good. As for the weakness pattern of the 22 patients who were evaluated at the Cure VCP Disease annual conference, 50% of patients had facial weakness, 55% had scapular winging, 68% had upper proximal weakness, 41% had upper distal weakness, 77% had lower proximal, and 64% had lower distal weakness. CONCLUSIONS: The Cure VCP Disease Patient Registry is useful for deepening the understanding of patient daily life, which would be a basis to develop appropriate clinical outcome measures. The registry data is consistent with previous studies evaluating VCP patients in the clinical setting. Patient advocacy groups are essential in developing and maintaining disease registries.


Assuntos
Demência Frontotemporal , Miosite de Corpos de Inclusão , Osteíte Deformante , Adulto , Feminino , Humanos , Masculino , Mutação/genética , Miosite de Corpos de Inclusão/genética , Osteíte Deformante/genética , Fenótipo , Qualidade de Vida , Sistema de Registros , Proteína com Valosina/genética
6.
Gene ; 298(2): 173-82, 2002 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-12426105

RESUMO

We have cloned the promoter regions of two Xenopus laevis genes, Prph2 (also called RDS) and red cone opsin (RCO) using a polymerase chain reaction-based gene-walking method. The proteins coded by these genes are expressed exclusively in retinal photoreceptors. Although these promoter sequences are evolutionarily distant from previously described homologues, potentially informative similarities were noted that suggest conserved binding sites of the transcription factors Crx and Rx. The promoters were tested for function in transgenic X. laevis. RCO-driven expression was restricted to cones and pinealocytes, while the Prph2 promoter drove expression of a reporter green fluorescent protein transgene in both rod and cone photoreceptors, as well as low levels of expression in muscle tissue. This is the first description of transgene expression driven by a Prph2 promoter homologue from any species. In combination with the previously reported X. laevis opsin and arrestin promoters, these sequences will facilitate the development and analysis of X. laevis models of inherited retinal degeneration.


Assuntos
Proteínas de Filamentos Intermediários/genética , Glicoproteínas de Membrana , Proteínas do Tecido Nervoso/genética , Células Fotorreceptoras de Vertebrados/metabolismo , Regiões Promotoras Genéticas/genética , Opsinas de Bastonetes/genética , Transgenes/genética , Xenopus laevis/genética , Animais , Animais Geneticamente Modificados , Sequência de Bases , Clonagem Molecular , Expressão Gênica , Proteínas de Fluorescência Verde , Proteínas Luminescentes/genética , Microscopia de Fluorescência , Dados de Sequência Molecular , Periferinas , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas Recombinantes de Fusão/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Proteínas de Xenopus
7.
Genome Res ; 14(10B): 2121-7, 2004 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-15489334

RESUMO

The National Institutes of Health's Mammalian Gene Collection (MGC) project was designed to generate and sequence a publicly accessible cDNA resource containing a complete open reading frame (ORF) for every human and mouse gene. The project initially used a random strategy to select clones from a large number of cDNA libraries from diverse tissues. Candidate clones were chosen based on 5'-EST sequences, and then fully sequenced to high accuracy and analyzed by algorithms developed for this project. Currently, more than 11,000 human and 10,000 mouse genes are represented in MGC by at least one clone with a full ORF. The random selection approach is now reaching a saturation point, and a transition to protocols targeted at the missing transcripts is now required to complete the mouse and human collections. Comparison of the sequence of the MGC clones to reference genome sequences reveals that most cDNA clones are of very high sequence quality, although it is likely that some cDNAs may carry missense variants as a consequence of experimental artifact, such as PCR, cloning, or reverse transcriptase errors. Recently, a rat cDNA component was added to the project, and ongoing frog (Xenopus) and zebrafish (Danio) cDNA projects were expanded to take advantage of the high-throughput MGC pipeline.


Assuntos
Clonagem Molecular/métodos , DNA Complementar , Biblioteca Gênica , Fases de Leitura Aberta/fisiologia , Animais , Biologia Computacional , Primers do DNA , DNA Complementar/genética , DNA Complementar/metabolismo , Humanos , Camundongos , National Institutes of Health (U.S.) , Ratos , Estados Unidos , Xenopus laevis/genética , Peixe-Zebra/genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA