Cross-sectional audit assessing the quality of dried bloodspot specimens received by UK metabolic biochemistry laboratories for the biochemical monitoring of individuals with Phenylketonuria.

Background: Sapropterin has been approved as a treatment option for individuals with Phenylketonuria in the United Kingdom. Individuals are assessed as responsive to Sapropterin by a ≥30% reduction in Phenylalanine (Phe) concentrations using dried blood spot (DBS) specimens. DBS quality is critical for accurate and precise measurement of Phe.

Supportive Care for Dementia: A Replicable Model to Reduce Neurobehavioral Symptoms, Caregiver Stress, and Hospitalizations, and Increase Hospice Referrals.

This report describes a hospice-supported no-fee program to support patients living with all levels of dementia and their caregivers. Our medical system struggles to serve the rapidly increasing numbers of patients with dementia. Hospice of the Valley developed a low-cost six-month program to reduce caregiver stress and reduce neurobehavioral disturbances of patients living with dementia, reduce costs for insurers, and increase hospice referrals.

Rigor and reproducibility in analysis of rodent behavior utilizing the forelimb reaching task following a cervical spinal cord injury.

Spinal cord injury (SCI) research with animals aims to understand the neurophysiological responses resultant of injury and to identify effective interventions that can translate into clinical treatments in the future. Consistent and reliable assessments to properly measure outcomes are essential to achieve this aim and avoid issues with reproducibility. The objective of this study was to establish a baseline for implementing the forelimb reaching task (FRT) assessment and analysis that increased reproducibility of our studies.

Neural Stimulation and Molecular Mechanisms of Plasticity and Regeneration: A Review.

Neural stimulation modulates the depolarization of neurons, thereby triggering activity-associated mechanisms of neuronal plasticity. Activity-associated mechanisms in turn play a major role in post-mitotic structure and function of adult neurons. Our understanding of the interactions between neuronal behavior, patterns of neural activity, and the surrounding environment is evolving at a rapid pace.

A Model Hospice Inpatient Unit Specializing in Patients Living with Advanced Dementia.

This report describes a pilot hospice inpatient unit dedicated to individuals experiencing distressing behaviors from dementia. Patients with dementia who experience distressing symptoms cannot be well managed on typical inpatient units. Hospice of the Valley selected one unit to dedicate to dementia care.

Enhancing cancer immunotherapy through nanotechnology-mediated tumor infiltration and activation of immune cells.

Cancer immunotherapy has become arguably the most promising advancement in cancer research and therapy in recent years. The efficacy of cancer immunotherapy is critically dependent on specific physiological and physical processes - collectively referred to as transport barriers - including the activation of T cells by antigen presenting cells, T cells migration to and penetration into the tumor microenvironment, and movement of nutrients and other immune cells through the tumor microenvironment. Nanotechnology-based approaches have great potential to help overcome these transport barriers.

Functional Assessment and Intervention by Nursing Assistants in Hospice and Palliative Care Inpatient Care Settings: A Quality Improvement Pilot Study.

This study assessed the impact of a nursing assistant-led functional intervention in an urban hospice. Thirty-three patients participated. A physical therapist trained 4 nursing assistants to assess 4 basic functional activities at admission and discharge and to provide daily activity training to intervention group participants.

Activity and social behavior in a complex environment in rats neonatally exposed to alcohol.

Environmental complexity (EC) is a powerful, stimulating paradigm that engages animals through a variety of sensory and motor pathways. Exposure to EC (30 days) following 12 days of wheel running preserves hippocampal neuroplasticity in male rats neonatally exposed to alcohol during the third-trimester equivalent (binge-like exposure on postnatal days [PD] 4-9). The current experiment investigates the importance of various components of EC (physical activity, exploration, social interaction, novelty) and examines whether neonatal alcohol exposure affects how male rats interact with their environment and other male rats.

The role of ABCA1 gene sequence variants on risk of Alzheimer's disease.

The ATP-binding cassette, sub-family A, member 1 gene (ABCA1) is a candidate risk gene for late onset Alzheimer's disease (LOAD) as a consequence of its role in cholesterol transport and metabolism, which is implicated in LOAD risk. ABCA1 has been shown in mouse models to enable the clearance of amyloid-β peptide from the brain, through its role in the lipidation of apolipoprotein (APOE). Although recent large scale genome wide association studies (GWAS) have failed to find significant associations with common genetic variants in this gene and LOAD, rare variants in ABCA1 have been shown to influence plasma high-density lipoprotein cholesterol levels.

Teaching communication skills to hospice teams: comparing the effectiveness of a communication skills laboratory with in-person, second life, and phone role-playing.

Introduction: Communication skills are critical in hospice care but challenging to teach. Therefore, a hospice agency developed a communication skills laboratory for nurses and social workers.

Methods: Learners role-played 3 common hospice scenarios.

Morphological characteristics of motor neurons do not determine their relative susceptibility to degeneration in a mouse model of severe spinal muscular atrophy.

Spinal muscular atrophy (SMA) is a leading genetic cause of infant mortality, resulting primarily from the degeneration and loss of lower motor neurons. Studies using mouse models of SMA have revealed widespread heterogeneity in the susceptibility of individual motor neurons to neurodegeneration, but the underlying reasons remain unclear. Data from related motor neuron diseases, such as amyotrophic lateral sclerosis (ALS), suggest that morphological properties of motor neurons may regulate susceptibility: in ALS larger motor units innervating fast-twitch muscles degenerate first.

Spinal muscular atrophy: going beyond the motor neuron.

Spinal muscular atrophy (SMA) is a neuromuscular disease caused by abnormally low cellular levels of the ubiquitous protein SMN. Traditionally, reduced levels of SMN were thought to cause the selective death of lower motor neurons, leading to denervation and atrophy of skeletal muscles. However, numerous recent studies challenge the notion that SMA is solely a disease of lower motor neurons, indicating that SMA may actually be a multi-system disorder.

Randomized double-blind trial of sublingual atropine vs. placebo for the management of death rattle.

Context: Noisy breathing because of respiratory tract secretions (RTS), often referred to as "death rattle," occurs in up to half of all dying patients. Despite a lack of evidence showing benefit compared with placebo, antimuscarinic medications have been used in an attempt to decrease noise associated with RTS and to decrease family distress.

Objectives: The goal of this study was to compare the efficacy of the antimuscarinic medication atropine with that of placebo in reducing noise associated with death rattle.

The role of ECE1 variants in cognitive ability in old age and Alzheimer's disease risk.

The β-amyloid peptide may play a central role in Alzheimer's disease (AD) pathogenesis. We have evaluated variants in seven Aβ-degrading genes (ACE, ECE1, ECE2, IDE, MME, PLAU, and TF) for association with AD risk in the Genetic and Environmental Risk in Alzheimer's Disease Consortium 1 (GERAD1) cohort, and with three cognitive phenotypes in the Lothian Birth Cohort 1936 (LBC1936), using 128 and 121 SNPs, respectively. In GERAD1, we identified a significant association between a four-SNP intragenic ECE1 haplotype and risk of AD in individuals that carried at least one APOE ε4 allele (P = 0.

The DISC1 promoter: characterization and regulation by FOXP2.

Disrupted in schizophrenia 1 (DISC1) is a leading candidate susceptibility gene for schizophrenia, bipolar disorder and recurrent major depression, which has been implicated in other psychiatric illnesses of neurodevelopmental origin, including autism. DISC1 was initially identified at the breakpoint of a balanced chromosomal translocation, t(1;11) (q42.1;14.

Functional and genetic analysis of haplotypic sequence variation at the nicastrin genomic locus.

Nicastrin (NCSTN) is a component of the γ-secretase complex and therefore potentially a candidate risk gene for Alzheimer's disease. Here, we have developed a novel functional genomics methodology to express common locus haplotypes to assess functional differences. DNA recombination was used to engineer 5 bacterial artificial chromosomes (BACs) to each express a different haplotype of the NCSTN locus.

Housing in environmental complexity following wheel running augments survival of newly generated hippocampal neurons in a rat model of binge alcohol exposure during the third trimester equivalent.

Background: Binge-like alcohol exposure in neonatal rats during the brain growth spurt causes deficits in adult neurogenesis in the hippocampal dentate gyrus (DG). Previous data from our laboratory demonstrated that 12 days of voluntary wheel running (WR) beginning on postnatal day (PD) 30 significantly increased the number of newly generated cells evident in the DG on PD42 in both alcohol-exposed (AE) and control rats, but 30 days later a sustained beneficial effect of WR was evident only in control rats. This study tested the hypothesis that housing rats in environmental complexity (EC) following WR would promote the survival of the newly generated cells stimulated by WR, particularly in AE rats.

Alzheimer's disease and age-related macular degeneration have different genetic models for complement gene variation.

Alzheimer's disease (AD) and age-related macular degeneration (AMD) are both neurodegenerative disorders which share common pathological and biochemical features of the complement pathway. The aim of this study was to investigate whether there is an association between well replicated AMD genetic risk factors and AD. A large cohort of AD (n = 3898) patients and controls were genotyped for single nucleotide polymorphisms (SNPs) in the complement factor H (CFH), the Age-related maculopathy susceptibility protein 2 (ARMS2) the complement component 2 (C2), the complement factor B (CFB), and the complement component 3 (C3) genes.

Alzheimer's disease risk factor complement receptor 1 is associated with depression.

Variation in the complement receptor 1 gene (CR1) has been identified in recent genome-wide association studies as a risk factor for Alzheimer's disease. Here, we show that two Alzheimer's disease-associated CR1 variants, rs6656401 and rs3818361, are associated with major recurrent depression in females in a population-based cohort using individuals from the Generation Scotland: Scottish Family Health Study.

Long-term consequences of developmental alcohol exposure on brain structure and function: therapeutic benefits of physical activity.

Developmental alcohol exposure both early in life and during adolescence can have a devastating impact on normal brain structure and functioning, leading to behavioral and cognitive impairments that persist throughout the lifespan. This review discusses human work as well as animal models used to investigate the effect of alcohol exposure at various time points during development, as well as specific behavioral and neuroanatomical deficits caused by alcohol exposure. Further, cellular and molecular mediators contributing to these alcohol-induced changes are examined, such as neurotrophic factors and apoptotic markers.

Alzheimer's disease genes are associated with measures of cognitive ageing in the lothian birth cohorts of 1921 and 1936.

Alzheimer's disease patients have deficits in specific cognitive domains, and susceptibility genes for this disease may influence human cognition in nondemented individuals. To evaluate the role of Alzheimer's disease-linked genetic variation on cognition and normal cognitive ageing, we investigated two Scottish cohorts for which assessments in major cognitive domains are available: the Lothian Birth Cohort of 1921 and the Lothian Birth Cohort of 1936, consisting of 505 and 998 individuals, respectively. 158 SNPs from eleven genes were evaluated.

Deep sequencing of the Nicastrin gene in pooled DNA, the identification of genetic variants that affect risk of Alzheimer's disease.

Nicastrin is an obligatory component of the γ-secretase; the enzyme complex that leads to the production of Aβ fragments critically central to the pathogenesis of Alzheimer's disease (AD). Analyses of the effects of common variation in this gene on risk for late onset AD have been inconclusive. We investigated the effect of rare variation in the coding regions of the Nicastrin gene in a cohort of AD patients and matched controls using an innovative pooling approach and next generation sequencing.

Association of serotonin and dopamine gene pathways with behavioral subphenotypes in dementia.

Genetic association studies investigating the association between genes of serotonergic and dopaminergic systems and behavioral and psychological symptoms in dementia (BPSD) are contradictory. We have utilized 1008 probable Alzheimer's disease (AD) patients from the UK and used the 12-item Neuropsychiatric Inventory. We applied a multiple indicators-multiple causes (MIMIC) approach to investigate the effect of 11 polymorphisms on the 4 behavioral subphenotypes "psychosis", "moods", "agitation", and "behavioural dyscontrol".

Postnatal binge-like alcohol exposure decreases dendritic complexity while increasing the density of mature spines in mPFC Layer II/III pyramidal neurons.

Prenatal exposure to alcohol in humans can result in a wide range of deficits collectively referred to as fetal alcohol spectrum disorders. Of these deficits, cognitive impairments are among the most debilitating and long-lasting. Specifically, cognitive impairments in executive functioning suggest damage to the prefrontal cortex (PFC).

Cytokines and IGF-I in delirious and non-delirious acutely ill older medical inpatients.

Background: therapeutic use of cytokines can induce delirium, and delirium often occurs during infections associated with elevated levels of cytokines. This study examined the association of demographic, clinical and biological factors (IL-1alpha, IL-1beta, IL-1RA, IL-6, TNF-alpha, IFN-gamma, LIF, IGF-I, APOE genotype) with the presence and severity of delirium.

Methods: in an observational prospective longitudinal study, patients aged 70+ were recruited from an elderly medical unit and assessed every 3-4 days (maximum assessments 4).