Reasonable adjustments to the application of the comprehensive care standard within an Australian mainstream internal medicine outpatient clinic attended by adults with Down syndrome.

Background: The Australian Commission on Safety and Quality in Health Care recommends the development of reasonable adjustments to Comprehensive Care Standard to better suit the needs of people with intellectual disability.

Method: An audit of adults with Down syndrome attending a mainstream internal medicine outpatient clinic was undertaken to describe their biopsychosocial profile, identify previously developed reasonable adjustments to clinical service and to consider their alignment with comprehensive care.

Results: Of 54 adults, 31 (57%) male, average age 36 years (17.

Pain management challenges in a patient with mucopolysaccharidosis IVA.

It is important to consider all potential pain management modalities including alternative treatment on managing complex pain presentations. Acupuncture is a treatment modality that may result in reduction of pain in patients with significant medical comorbidities due to MPS IVA.

A system for developing reasonable adjustments to the application of the National Safety and Quality Health Service Standards for adult patients with intellectual disability in Australian hospital settings.

The Australian Commission of Safety and Quality in Health Care mandates the application of the eight National Safety and Quality Health Service Standards to minimise high-risk adverse events in hospital settings for all Australian patients. It acknowledges that adults with intellectual disability require reasonable adjustments to the application of the standards to optimise the impact of the quality and safety measures for this group. The paper proposes a system whereby reasonable adjustments can be developed for this population.

Transgenic mice overexpressing mutant TDP-43 show aberrant splicing of neurological disorders-associated gene prior to onset of motor symptoms.

Mutations in TDP-43 are known to cause Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD). TDP-43 binds to and regulates splicing of several RNA including . Zmynd11 is a transcriptional repressor and a potential E3 ubiquitin ligase family member, known for its role in neuron and muscle differentiation.

Palliative care for adults with intellectual disability.

Contemporary disability principles and values suggest that adults with intellectual disability should be able to access and participate in any mainstream service rather than having a separate service for them. In the case of healthcare services, achievement of optimal access to and participation in healthcare by adults with intellectual disability requires the presence of both adequate disability supports for the person and reasonable adjustments to generic health systems to enable a person-centred approach to care. Development of an interface between people with lived experience of intellectual disability, disability and health sectors help clarify the required nature of disability supports and types of adjustments to mainstream health services.

PGRMC1 effects on metabolism, genomic mutation and CpG methylation imply crucial roles in animal biology and disease.

Background: Progesterone receptor membrane component 1 (PGRMC1) is often elevated in cancers, and exists in alternative states of phosphorylation. A motif centered on PGRMC1 Y180 was evolutionarily acquired concurrently with the embryological gastrulation organizer that orchestrates vertebrate tissue differentiation.

Results: Here, we show that mutagenic manipulation of PGRMC1 phosphorylation alters cell metabolism, genomic stability, and CpG methylation.

National Disability Insurance Scheme, health, hospitals and adults with intellectual disability.

Preventable poor health outcomes for adults with intellectual disability in health settings have been known about for years. Subsequent analysis and the sorts of reasonable adjustments required in health and disability support settings to address these health gaps are well described, but have not really been embedded in practice in any significant way in either setting. As far as health is concerned, implementation of the National Disability Insurance Scheme (NDIS, the Scheme) affords an opportunity to recognise individual needs of people with intellectual disability to provide reasonable and necessary functional support for access to mainstream health services, to build capacity of mainstream health providers to supply services and to increase individual capacity to access services.

Whole-exome sequencing in amyotrophic lateral sclerosis suggests NEK1 is a risk gene in Chinese.

Background: Amyotrophic lateral sclerosis (ALS) is a progressive neurological disease characterised by the degeneration of motor neurons, which are responsible for voluntary movement. There remains limited understanding of disease aetiology, with median survival of ALS of three years and no effective treatment. Identifying genes that contribute to ALS susceptibility is an important step towards understanding aetiology.

Cross-ethnic meta-analysis identifies association of the GPX3-TNIP1 locus with amyotrophic lateral sclerosis.

Cross-ethnic genetic studies can leverage power from differences in disease epidemiology and population-specific genetic architecture. In particular, the differences in linkage disequilibrium and allele frequency patterns across ethnic groups may increase gene-mapping resolution. Here we use cross-ethnic genetic data in sporadic amyotrophic lateral sclerosis (ALS), an adult-onset, rapidly progressing neurodegenerative disease.

A Methodological Approach to Small Area Estimation for the Behavioral Risk Factor Surveillance System.

Public health researchers have used a class of statistical methods to calculate prevalence estimates for small geographic areas with few direct observations. Many researchers have used Behavioral Risk Factor Surveillance System (BRFSS) data as a basis for their models. The aims of this study were to 1) describe a new BRFSS small area estimation (SAE) method and 2) investigate the internal and external validity of the BRFSS SAEs it produced.

Multiplex families with epilepsy: Success of clinical and molecular genetic characterization.

Objective: To analyze the clinical syndromes and inheritance patterns of multiplex families with epilepsy toward the ultimate aim of uncovering the underlying molecular genetic basis.

Methods: Following the referral of families with 2 or more relatives with epilepsy, individuals were classified into epilepsy syndromes. Families were classified into syndromes where at least 2 family members had a specific diagnosis.

ALS-associated TDP-43 induces endoplasmic reticulum stress, which drives cytoplasmic TDP-43 accumulation and stress granule formation.

In amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration, TAR DNA binding protein 43 (TDP-43) accumulates in the cytoplasm of affected neurons and glia, where it associates with stress granules (SGs) and forms large inclusions. SGs form in response to cellular stress, including endoplasmic reticulum (ER) stress, which is induced in both familial and sporadic forms of ALS. Here we demonstrate that pharmacological induction of ER stress causes TDP-43 to accumulate in the cytoplasm, where TDP-43 also associates with SGs.

DNA variation in the SNAP25 gene confers risk to ADHD and is associated with reduced expression in prefrontal cortex.

Background: The Coloboma mouse carries a ∼2 cM deletion encompassing the SNAP25 gene and has a hyperactive phenotype similar to that of ADHD. Such mice are 3 fold more active compared to their control littermates. Genetic association studies support a role for allelic variants of the human SNAP25 gene in predisposing to ADHD.

Identification of RNA bound to the TDP-43 ribonucleoprotein complex in the adult mouse brain.

Cytoplasmic inclusions containing TDP-43 are a pathological hallmark of several neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. TDP-43 is an RNA binding protein involved in gene regulation through control of RNA transcription, splicing and transport. However, the function of TDP-43 in the nervous system is largely unknown and its role in the pathogenesis of ALS is unclear.

A high density linkage disequilibrium mapping in 14 noradrenergic genes: evidence of association between SLC6A2, ADRA1B and ADHD.

Pharmacological evidence suggests the importance of noradrenergic and other monoaminergic neurotransmitters in the aetiology and treatment of attention deficit hyperactivity disorder (ADHD). Until recently, the genes of the noradrenergic pathway were not intensively investigated in ADHD compared to dopaminergic and serotonergic candidates. In this study, 91 SNP markers of 14 noradrenergic genes (an average density of one SNP per 4.

The COMT Val158 allele is associated with impaired delayed-match-to-sample performance in ADHD.

Background: This study explored the association between three measures of working memory ability and genetic variation in a range of catecholamine genes in a sample of children with ADHD.

Methods: One hundred and eighteen children with ADHD performed three working memory measures taken from the CANTAB battery (Spatial Span, Delayed-match-to-sample, and Spatial Working Memory). Associations between performance on working memory measures and allelic variation in catecholamine genes (including those for the noradrenaline transporter [NET1], the dopamine D4 and D2 receptor genes [DRD4; DRD2], the gene encoding dopamine beta hydroxylase [DBH] and catechol-O-methyl transferase [COMT]) were investigated using regression models that controlled for age, IQ, gender and medication status on the day of test.

Magnetic resonance microimaging of the spinal cord in the SOD1 mouse model of amyotrophic lateral sclerosis detects motor nerve root degeneration.

Amyotrophic lateral sclerosis (ALS) is characterized by selective degeneration of motor neurons. Current imaging studies have concentrated on areas of the brain and spinal cord that contain mixed populations of sensory and motor neurons. In this study, ex vivo magnetic resonance microimaging (MRM) was used to separate motor and sensory components by visualizing individual dorsal and ventral roots in fixed spinal cords.

What can we learn from study of Alzheimer's disease in patients with Down syndrome for early-onset Alzheimer's disease in the general population?

The clinical and scientific study of dementia in adults with Down syndrome led to the development of the amyloid hypothesis as a fundamental concept in Alzheimer's disease pathogenesis. The journey started with the discovery of the structure and metabolic processing of β-amyloid brain deposits associated with Alzheimer's dementia in adults with Down syndrome, and then the prediction and confirmation of the amyloid precursor protein gene on chromosome 21. The processes and genes responsible for tau hyperphosphorylation contributing to toxic brain deposits were additionally identified.

Non-invasive diffusion tensor imaging detects white matter degeneration in the spinal cord of a mouse model of amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is characterized by selective degeneration of motor neurons. Here we examine the ability of magnetic resonance imaging (MRI) to measure axonal degeneration in the lumbar spinal cord of the SOD1 mouse model of ALS. Diffusion tensor imaging (DTI) was successful in detecting axonal spinal cord damage in vivo.

A homozygous mutation in human PRICKLE1 causes an autosomal-recessive progressive myoclonus epilepsy-ataxia syndrome.

Progressive myoclonus epilepsy (PME) is a syndrome characterized by myoclonic seizures (lightning-like jerks), generalized convulsive seizures, and varying degrees of neurological decline, especially ataxia and dementia. Previously, we characterized three pedigrees of individuals with PME and ataxia, where either clinical features or linkage mapping excluded known PME loci. This report identifies a mutation in PRICKLE1 (also known as RILP for REST/NRSF interacting LIM domain protein) in all three of these pedigrees.

Priapism, ecstasy, and marijuana: is there a connection?

Priapism is a urological emergency with multiple aetiologies including drug induced. Currently, there have been no reports of priapism induced by the combination of ecstasy and marijuana. We speculated on the potential mechanisms for acute drug-induced priapism resulting from ingestion of these two common illicit drugs.

Latent stem and progenitor cells in the hippocampus are activated by neural excitation.

The regulated production of neurons in the hippocampus throughout life underpins important brain functions such as learning and memory. Surprisingly, however, studies have so far failed to identify a resident hippocampal stem cell capable of providing the renewable source of these neurons. Here, we report that depolarizing levels of KCl produce a threefold increase in the number of neurospheres generated from the adult mouse hippocampus.

Audit of cardiovascular disease risk factors among supported adults with intellectual disability attending an ageing clinic.

Background: Little is known about the cardiovascular disease (CVD) risk factor profile for older adults with intellectual disability (ID). As many CVD risk factors are treatable by lifestyle changes, confirmation of the risk factor profile for older adults with ID could substantially impact upon preventive health practices for this group.

Method: Medical charts of all adults aged 40 years or over attending a specialised ageing clinic for adults with ID between January 2002 and June 2005 were reviewed.