Neuroimaging of tissue microstructure as a marker of neurodegeneration in the AT(N) framework: defining abnormal neurodegeneration and improving prediction of clinical status

Background: Alzheimer’s disease involves accumulating amyloid (A) and tau (T) pathology, and progressive neurodegeneration (N), leading to the development of the AD clinical syndrome. While several markers of N have been proposed, efforts to define normal vs. abnormal neurodegeneration based on neuroimaging have been limited. Sensitive markers that may account for or predict cognitive dysfunction for individuals in early disease stages are critical. Methods: Participants (n = 296) defined on A and T status and spanning the AD-clinical continuum underwent multi-shell diffusion-weighted magnetic resonance imaging to generate Neurite Orientation Dispersion and Density Imaging (NODDI) metrics, which were tested as markers of N. To better define N, we developed age- and sex-adjusted robust z-score values to quantify normal and AD-associated (abnormal) neurodegeneration in both cortical gray matter and subcortical white matter regions of interest. We used general logistic regression with receiver operating characteristic (ROC) and area under the curve (AUC) analysis to test whether NODDI metrics improved diagnostic accuracy compared to models that only relied on cerebrospinal fluid (CSF) A and T status (alone and in combination). Results: Using internal robust norms, we found that NODDI metrics correlate with worsening cognitive status and that NODDI captures early, AD neurodegenerative pathology in the gray matter of cognitively unimpaired, but A/T biomarker-positive, individuals. NODDI metrics utilized together with A and T status improved diagnostic prediction accuracy of AD clinical status, compared with models using CSF A and T status alone. Conclusion: Using a robust norms approach, we show that abnormal AD-related neurodegeneration can be detected among cognitively unimpaired individuals. Metrics derived from diffusion-weighted imaging are potential sensitive markers of N and could be considered for trial enrichment and as outcomes in clinical trials. However, given the small sample sizes, the exploratory nature of the work must be acknowledged

Pioglitazone Prevents Capillary Rarefaction in Streptozotocin-Diabetic Rats Independently of Glucose Control and Vascular Endothelial Growth Factor Expression

Background/Aims: Reduction of capillary network density occurs early in the development of metabolic syndrome and may be relevant for the precipitation of diabetes. Agonists of the peroxisome proliferator-activated receptor (PPAR)-gamma transcription factor are vasculoprotective, but their capacity for structural preservation of the microcirculation is unclear. Methods: Male Wistar rats were rendered diabetic by streptozotocin and treated with pioglitazone in chow for up to 12 weeks. Capillary density was determined in heart and skeletal muscle after platelet endothelial cell adhesion molecule-1 (PECAM-1) immunostaining. Hallmarks of apoptosis and angiogenesis were determined. Results: Capillary density deteriorated progressively in the presence of hyperglycemia (from 971/mm(2) to 475/mm(2) in quadriceps muscle during 13 weeks). Pioglitazone did not influence plasma glucose, left ventricular weight, or body weight but nearly doubled absolute and relative capillary densities compared to untreated controls (1.2 vs. 0.6 capillaries/myocyte in heart and 1.5 vs. 0.9 capillaries/myocyte in quadriceps muscle) after 13 weeks of diabetes. No antiapoptotic or angiogenic influence of pioglitazone was detected while a reduced expression of hypoxia-inducible factor-3 alpha and PPAR coactivator-1 alpha (PGC-1 alpha) mRNA as well as vascular endothelial growth factor (VEGF) protein possibly occurred as a consequence of improved vascularization. Conclusion: Pioglitazone preserves microvascular structure in diabetes independently of improvements in glycemic control and by a mechanism unrelated to VEGF-mediated angiogenesis. Copyright (C) 2012 S. Karger AG, Base

Linking public health agencies and hospitals for improved emergency preparedness: North Carolina's public health epidemiologist program

<p>Abstract</p> <p>Background</p> <p>In 2003, 11 public health epidemiologists were placed in North Carolina's largest hospitals to enhance communication between public health agencies and healthcare systems for improved emergency preparedness. We describe the specific services public health epidemiologists provide to local health departments, the North Carolina Division of Public Health, and the hospitals in which they are based, and assess the value of these services to stakeholders.</p> <p>Methods</p> <p>We surveyed and/or interviewed public health epidemiologists, communicable disease nurses based at local health departments, North Carolina Division of Public Health staff, and public health epidemiologists' hospital supervisors to 1) elicit the services provided by public health epidemiologists in daily practice and during emergencies and 2) examine the value of these services. Interviews were transcribed and imported into ATLAS.ti for coding and analysis. Descriptive analyses were performed on quantitative survey data.</p> <p>Results</p> <p>Public health epidemiologists conduct syndromic surveillance of community-acquired infections and potential bioterrorism events, assist local health departments and the North Carolina Division of Public Health with public health investigations, educate clinicians on diseases of public health importance, and enhance communication between hospitals and public health agencies. Stakeholders place on a high value on the unique services provided by public health epidemiologists.</p> <p>Conclusions</p> <p>Public health epidemiologists effectively link public health agencies and hospitals to enhance syndromic surveillance, communicable disease management, and public health emergency preparedness and response. This comprehensive description of the program and its value to stakeholders, both in routine daily practice and in responding to a major public health emergency, can inform other states that may wish to establish a similar program as part of their larger public health emergency preparedness and response system.</p

Cingulate cortex hypoperfusion predicts Alzheimer's disease in mild cognitive impairment

BACKGROUND: Mild cognitive impairment (MCI) was recently described as a heterogeneous group with a variety of clinical outcomes and high risk to develop Alzheimer's disease (AD). Regional cerebral blood flow (rCBF) as measured by single photon emission computed tomography (SPECT) was used to study the heterogeneity of MCI and to look for predictors of future development of AD. METHODS: rCBF was investigated in 54 MCI subjects using Tc-99m hexamethylpropyleneamine oxime (HMPAO). An automated analysis software (BRASS) was applied to analyze the relative blood flow (cerebellar ratios) of 24 cortical regions. After the baseline examination, the subjects were followed clinically for an average of two years. 17 subjects progressed to Alzheimer's disease (PMCI) and 37 subjects remained stable (SMCI). The baseline SPECT ratio values were compared between PMCI and SMCI. Receiver operating characteristic (ROC) analysis was applied for the discrimination of the two subgroups at baseline. RESULTS: The conversion rate of MCI to AD was 13.7% per year. PMCI had a significantly decreased rCBF in the left posterior cingulate cortex, as compared to SMCI. Left posterior cingulate rCBF ratios were entered into a logistic regression model for ROC curve calculation. The area under the ROC curve was 74%–76%, which indicates an acceptable discrimination between PMCI and SMCI at baseline. CONCLUSION: A reduced relative blood flow of the posterior cingulate gyrus could be found at least two years before the patients met the clinical diagnostic criteria of AD

The role of receptivity in the courtship behavior of Podocnemis erythrocephala in captivity

The courtship behavior of Podocnemis erythrocephala (Red-headed Amazon River Turtle) in captivity was studied to examine female receptivity and male response to female rejection. We observed 20 females and 39 males in 150 sessions (3–6 h/day for a total of 450 h). In 36% of the trials, there was no interaction between males and females, and 20% of the trials resulted in copulations. All males introduced into tanks approached females, and eventually there was aggression among the males. In 48% of the experiments, females also searched for or approached males. When males initially approached females, they either accepted the male’s advances (14%), rejected the male passively (38%), or rejected the male aggressively (48%). In 86% of the cases where males were rejected, 4% attempted to approach females again, and in 51% they were ultimately successful

Variance and Autocorrelation of the Spontaneous Slow Brain Activity

Slow (<0.1 Hz) oscillatory activity in the human brain, as measured by functional magnetic imaging, has been used to identify neural networks and their dysfunction in specific brain diseases. Its intrinsic properties may also be useful to investigate brain functions. We investigated the two functional maps: variance and first order autocorrelation coefficient (r1). These two maps had distinct spatial distributions and the values were significantly different among the subdivisions of the precuneus and posterior cingulate cortex that were identified in functional connectivity (FC) studies. The results reinforce the functional segregation of these subdivisions and indicate that the intrinsic properties of the slow brain activity have physiological relevance. Further, we propose a sample size (degree of freedom) correction when assessing the statistical significance of FC strength with r1 values, which enables a better understanding of the network changes related to various brain diseases

A Systematic Review of Music Therapy Practice and Outcomes with Acute Adult Psychiatric In-Patients

PMCID: PMC3732280This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Asteroseismology

Asteroseismology is the determination of the interior structures of stars by using their oscillations as seismic waves. Simple explanations of the astrophysical background and some basic theoretical considerations needed in this rapidly evolving field are followed by introductions to the most important concepts and methods on the basis of example. Previous and potential applications of asteroseismology are reviewed and future trends are attempted to be foreseen.Comment: 38 pages, 13 figures, to appear in: "Planets, Stars and Stellar Systems", eds. T. D. Oswalt et al., Springer Verla