Biomedical subjects

Elizabeth Moore

Publications and source records attributed to Elizabeth Moore.

12 recordsLinked to original sources

PubMed2024

Free-water: A promising structural biomarker for cognitive decline in aging and mild cognitive impairment.

Diffusion MRI derived free-water (FW) metrics show promise in predicting cognitive impairment and decline in aging and Alzheimer's disease (AD). FW is sensitive to subtle changes in brain microstructure, so it is possible these measures may be more sensitive than traditional structural neuroimaging biomarkers. In this study, we examined the associations among FW metrics (measured in the hippocampus and two AD signature meta-ROIs) with cognitive performance, and compared FW findings to those from more traditional neuroimaging biomarkers of AD. We leveraged data from a longitudinal cohort (nparticipants = 296, nobservations = 870, age at baseline: 73 ± 7 years, 40% mild cognitive impairment [MCI]) of older adults who underwent serial neuropsychological assessment (episodic memory, information processing speed, executive function, language, and visuospatial skills) and brain MRI over a maximum of four time points, including baseline (n = 284), 18-month (n = 246), 3-year (n = 215), and 5-year (n = 125) visits. The mean follow-up period was 2.8 ± 1.3 years. Structural MRI was used to quantify hippocampal volume, in addition to Schwarz and McEvoy AD Signatures. FW and FW-corrected fractional anisotropy (FAFWcorr) were quantified in the hippocampus (hippocampal FW) and the AD signature areas (SchwarzFW, McEvoyFW) from diffusion-weighted (dMRI) images using bi-tensor modeling (FW elimination and mapping method). Linear regression assessed the association of each biomarker with baseline cognitive performance. Additionally, linear mixed-effects regression assessed the association between baseline biomarker values and longitudinal cognitive performance. A subsequent competitive model analysis was conducted on both baseline and longitudinal data to determine how much additional variance in cognitive performance was explained by each biomarker compared to the covariate only model, which included age, sex, race/ethnicity, apolipoprotein-ε4 status, cognitive status, and modified Framingham Stroke Risk Profile scores. All analyses were corrected for multiple comparisons using an FDR procedure. Cross-sectional results indicate that hippocampal volume, hippocampal FW, Schwarz and McEvoy AD Signatures, and the SchwarzFW and McEvoyFW metrics are all significantly associated with memory performance. Baseline competitive model analyses showed that the McEvoy AD Signature and SchwarzFW explain the most unique variance beyond covariates for memory (ΔRadj 2 = 3.47 ± 1.65%) and executive function (ΔRadj 2 = 2.43 ± 1.63%), respectively. Longitudinal models revealed that hippocampal FW explained substantial unique variance for memory performance (ΔRadj 2 = 8.13 ± 1.25%), and outperformed all other biomarkers examined in predicting memory decline (pFDR = 1.95 x 10-11). This study shows that hippocampal FW is a sensitive biomarker for cognitive impairment and decline, and provides strong evidence for further exploration of this measure in aging and AD.

Alzheimer’s disease (AD)↗

PubMed2007

Identification of a novel targeting sequence for regulated secretion in the serine protease inhibitor neuroserpin.

Ns (neuroserpin) is a member of the serpin (serine protease inhibitor) gene family that is primarily expressed within the central nervous system. Its principal target protease is tPA (tissue plasminogen activator), which is thought to contribute to synaptic plasticity and to be secreted in a stimulus-dependent manner. In the present study, we demonstrate in primary neuronal cultures that Ns co-localizes in LDCVs (large dense core vesicles) with the regulated secretory protein chromogranin B. We also show that Ns secretion is regulated and can be specifically induced 4-fold by secretagogue treatment. A novel 13-amino-acid sorting signal located at the C-terminus of Ns is identified that is both necessary and sufficient to target Ns to the regulated secretion pathway. Its deletion renders Ns no longer responsive to secretagogue stimulation, whereas PAI-Ns [Ns (neuroserpin)-PAI-1 (plasminogen activator inhibitor-1) chimaera appending the last 13 residues of Ns sequence to the C-terminus of PAI-1] shifts PAI-1 secretion into a regulated secretory pathway.

Amino Acid Sequence↗

PubMed2007

Mental health screening in schools.

BACKGROUND: This article discusses the importance of screening students in schools for emotional/behavioral problems. METHODS: Elements relevant to planning and implementing effective mental health screening in schools are considered. Screening in schools is linked to a broader national agenda to improve the mental health of children and adolescents. Strategies for systematic planning for mental health screening in schools are presented. RESULTS: Mental health screening in schools is a very important, yet sensitive, agenda that is in its very early stages. Careful planning and implementation of mental health screening in schools offers a number of benefits including enhancing outreach and help to youth in need, and mobilizing school and community efforts to promote student mental health while reducing barriers to their learning. CONCLUSIONS: When implemented with appropriate family, school, and community involvement, mental health screening in schools has the potential to be a cornerstone of a transformed mental health system. Screening, as part of a coordinated and comprehensive school mental health program, complements the mission of schools, identifies youth in need, links them to effective services, and contributes to positive educational outcomes valued by families, schools, and communities.

Adolescent↗

PubMed2006

Brutal neglect: Australian rural women's access to health services.

Access to health services in rural Australia has been particularly problematic because of the vast geographical areas and the sparse population distribution across the inland. The focus on health servicing has been very much on primary health care with most attention being giving to the distribution of doctors in rural Australia. This study takes a closer look at rural health servicing through the eyes of women in rural Australia. Drawing on a survey of 820 women, the study revealed that a focus on primary health care may be resulting in a lack of attention to women's health in areas, such as maternity models of care, domestic violence and mental health. The study also reveals the disquiet of Australian rural women at the poor state of health services.

Adolescent↗

PubMed2006

The President's New Freedom Commission: capitalizing on opportunities to advance school-based mental health services.

The report from President George W. Bush's New Freedom Commission on Mental Health (NFC), Achieving the Promise: Transforming Mental Health Care in America(2003), proposes goals and recommendations for improving mental health services. This report has significant implications for the delivery of mental health services through the schools. A focused discussion of the potential opportunities and challenges of implementing NFC recommendations related to school-based mental health is presented. Strategies for addressing five key areas at the intersection of school mental health and the Commission's recommendations include: stigma reduction, suicide prevention, expansion and improvement of school mental health, and screening and treatment of co-occurring mental health and substance abuse disorders.

Advisory Committees↗

PubMed2006

Skin prick testing to food allergens in breast-fed young infants with moderate to severe atopic dermatitis.

SUMMARY The role of food allergy in atopic dermatitis is controversial. This study presents results of skin prick tests to 31 different food allergens in a selected population of predominantly breast-fed young infants who had moderate to severe generalized atopic dermatitis. Of the 59 infants (22 female, mean age 26.5 weeks) tested, 54 infants (91.5%) had positive responses to one or more foods, 53 infants (90%) were positive to one or more of the five common food allergens (egg white, cow's milk, peanuts, wheat or soy) and 80% were positive to egg white, which was by far the most common positive test. A total of 37 infants had strongly positive responses to one or more foods, with 33 of these 37 having strongly positive responses to egg white. The significance of these responses is discussed. It is concluded that positive skin prick tests to foods, particularly to egg white, are very common in this selected population of breast-fed infants with moderate to severe atopic dermatitis.

Age Factors↗

PubMed2006

Enhancing No Child Left Behind-School mental health connections.

The No Child Left Behind Act of 2001 was signed into law by President George W. Bush in January 2002 and is regarded as the most significant federal education policy initiative in a generation. The primary focus of the No Child Left Behind Act is on promoting educational success for all children; however, the legislation also contains opportunities to advance school-based mental health. Unfortunately, the complexities of the provisions of the No Child Left Behind Act have made it difficult for educators, stakeholders, and mental health professionals to understand the legal and practical interface between No Child Left Behind and the school mental health movement. Therefore, the goals of this article are to (1) raise awareness about the challenges educators and school mental health professionals face as a result of the implementation of No Child Left Behind and (2) provide ideas and recommendations to advance the interface between No Child Left Behind and school mental health, which will support key provisions of the act and the growth of the field.

Adolescent↗

PubMed2006

The cardiovascular manifestations of Alagille syndrome and JAGI mutations.

Alagille syndrome is an autosomal-dominant disorder characterized by hepatic, cardiac, ocular, skeletal, and facial abnormalities. The disease gene, Jaggedl (JAG]), was identified by molecular analyses of chromosomal alterations involving chromosome 20p. Total gene deletions (3-7%) and intragenic mutations (70%) of JAG] have been identified in Alagille patients. Identifying JAG] mutations is challenging, given its size of 26 exons. Methods to identify both whole-gene deletions and intragenic mutations of JAG] are described in detail, including fluorescence in situ hybridization (FISH), conformation-sensitive gel electrophoresis (CSGE), and complementary DNA (cDNA) sequencing.

Alagille Syndrome↗

PubMed2003

Radiotherapy treatment planning of prostate cancer using magnetic resonance imaging alone.

PURPOSE: Accurate anatomical delineation of the gross tumour volume (GTV) is crucial for effective radiotherapy (RT) treatment of prostate cancers. Although reference to pelvic magnetic resonance (MR) for improved delineation of the prostate is a regular practice in some clinics, MR has not replaced CT due to its geometrical distortions and lack of electron-density information. The possibility and practicality of using MR only for RT treatment planning were studied. MATERIALS AND METHODS: The addition of electron-density information to MR images for conformal radiotherapy (CRT) planning of the prostate was quantified by comparing dose distributions created on the homogeneous density- and bulk-density assigned images to original CT for four patients. To quantify the MR geometrical distortions measurements of a phantom imaged in CT (Siemens Somatom Plus 4) and FLASH 3D T1-weighted MR (1.5 T whole body Siemens Magnetom Vision) were compared. Dose statistics from CRT treatment plans made on CT and MR for five patient data were compared to determine if MR-only treatment plans can be made. RESULTS: The differences between dose-plans on bulk-density assigned images when compared to CT were less than 2% when water and bone values were assigned. Dose differences greater than 2% were observed when images of homogeneous-density assignment were compared to the CT. Phantom measurements showed that the distortions in the FLASH 3D T1-weighted MR averaged 2 mm in the volume of interest for prostate RT planning. For the CT and MR prostate planning study, doses delivered to the planning target volume (PTV) in CT and MR were always inside a 93-107% dose range normalised to the isocentre. Also, the doses to the organs-at-risk in the MR images were similar to the doses delivered to the volumes in the registered CT image when the organ volumes between the two images were similar. CONCLUSIONS: Negligible differences were observed in dose distribution between CRT plans using bone+water CT number bulk-assigned image and original CT. Also, the MR distortions were reduced to negligible amounts using large bandwidth MR sequence for prostate CRT planning. MR treatment planning was demonstrated using a large bandwidth sequence and bulk-assigned images. The development of higher quality, low distortion MR sequence will allow regular practice of this technique.

Feasibility Studies↗

PubMed2003

Progressive ankylosis (Ank) protein is expressed by neurons and Ank immunohistochemical reactivity is increased by limbic seizures.

Ank is a 492-amino acid multipass transmembrane protein involved in the regulation of extracellular inorganic pyrophosphate levels and the control of tissue calcification. Previous Northern blot hybridization experiments revealed that Ank mRNA was expressed in the brain, but there have been no reports describing the anatomical sites or specific cell types in the brain that express Ank protein. In this study, we demonstrate that Ank is expressed primarily in human brain neurons, with the highest levels of expression observed in the thalamus, the III and V cortical layers, the Purkinje cells of the cerebellum, clusters of cells in the dorsal portion of the pons and midbrain, and neurons of the anterior horn of the spinal cord. In primary mouse neuronal cell cultures, Ank is detected on both the cell body and on cell extensions, mainly dendrites. In the rat brain, Ank mRNA is expressed at relatively high levels in the thalamus, midbrain, and spinal cord, and the Ank protein expression pattern is similar to that observed in the human brain. Finally, we observed a significant increase in Ank immunoreactivity in the rat amygdala, the CA-2 and CA-3 layers of the hippocampus, and the cerebral cortex after the induction of seizure activity. Ank regulation of ATP and/or inorganic pyrophosphate release from neurons may function to modulate the membrane excitability and cell death associated with seizure activity.

Adult↗

PubMed2002

Regulation of seizure spreading by neuroserpin and tissue-type plasminogen activator is plasminogen-independent.

Tissue-type plasminogen activator (tPA) is a highly specific serine proteinase expressed in the CNS during events that require neuronal plasticity. In this study we demonstrate that endogenous tPA mediates the progression of kainic acid-induced (KA-induced) seizures by promoting the synchronization of neuronal activity required for seizure spreading, and that, unlike KA-induced cell death, this activity is plasminogen-independent. Specifically, seizure induction by KA injection into the amygdala induces tPA activity and cell death in both hippocampi, and unilateral treatment of rats with neuroserpin, a natural inhibitor of tPA in the brain, enhances neuronal survival in both hippocampi. Inhibition of tPA within the hippocampus by neuroserpin treatment does not prevent seizure onset but instead markedly delays the progression of seizure activity in both rats and wild-type mice. In tPA-deficient mice, seizure progression is significantly delayed, and neuroserpin treatment does not further delay seizure spreading. In contrast, plasminogen-deficient mice show a pattern of seizure spreading and a response to neuroserpin that is similar to that of wild-type animals. These findings indicate that tPA acts on a substrate other than plasminogen and that the effects of neuroserpin on seizure progression and neuronal cell survival are mediated through the inhibition of tPA.

Amygdala↗

PubMedDate not supplied

Evaluation of a re-training program for older drivers.

BACKGROUND: Some older drivers may have a higher crash risk than others. Because many of these drivers have not received formal driving training, we evaluated the effectiveness of a re-training program for older drivers as it is currently being offered. Specifically, we examined if older drivers who received the training would have better scores on a driving evaluation than drivers who did not receive the training. METHODS: We used a randomized controlled trial. Participants first took part in on-road driving evaluations (possible scores ranged from 0 to 100), after which they were block randomized into training (treatment) or waiting (control) groups based on the driving evaluation results, age, and sex. Individuals in the treatment group attended driver re-training sessions, and were tested once more with the on-road test. Those in the control group completed their second driving evaluation and were then offered the re-training sessions. The second evaluations took place approximately two months after the first evaluations. RESULTS: Sixty-five participants completed two driving evaluations. Despite the overall improvement in driving scores (3.73, SD = 6.87, p = 0.001), we found no statistically significant difference between the control and treatment groups. The mean improvement for the control group was 3.46 (SD=6.72) compared to 4.02 (SD=7.11) for the treatment group (p = 0.747). Drivers' age was related to overall driving scores (r = -0.55, p = 0.001) but not changes between the first and second evaluations (r = 0.01, p = 0.955). INTERPRETATION: Although we have not demonstrated a statistically significant impact of the intervention, the overall increase suggests that an initial driving evaluation may underestimate the actual driving ability of many older drivers. Furthermore, although older drivers may have lower driving scores initially, they have the ability to improve on these scores. These findings should encourage us to explore diverse approaches to improve driving safety.

Accident Prevention↗