Protocol for the Systematic Fixation, Circuit-Based Sampling, and Qualitative and Quantitative Neuropathological Analysis of Human Brain Tissue.

Human brain tissue has long been a critical resource for neuroanatomy and neuropathology, but with the advent of advanced imaging and molecular sequencing techniques, it has become possible to use human brain tissue to study, in great detail, the structural, molecular, and even functional underpinnings of human brain disease. In the century following the first description of Alzheimer's disease (AD), numerous technological advances applied to human tissue have enabled novel diagnostic approaches using diverse physical and molecular biomarkers, and many drug therapies have been tested in clinical trials (Schachter and Davis, Dialogues Clin Neurosci 2:91-100, 2000). The methods for brain procurement and tissue stabilization have remained somewhat consistently focused on formalin fixation and freezing. Although these methods have enabled research protocols of multiple modalities, new, more advanced technologies demand improved methodologies for the procurement, characterization, stabilization, and preparation of both normal and diseased human brain tissues. Here, we describe our current protocols for the procurement and characterization of fixed brain tissue, to enable systematic and precisely targeted diagnoses, and describe the novel, quantitative molecular, and neuroanatomical studies that broadly expand the use of formalin-fixed, paraffin-embedded (FFPE) tissue that will further our understanding of the mechanisms underlying human neuropathologies.

Neuropathological and transcriptomic characteristics of the aged brain.

As more people live longer, age-related neurodegenerative diseases are an increasingly important societal health issue. Treatments targeting specific pathologies such as amyloid beta in Alzheimer's disease (AD) have not led to effective treatments, and there is increasing evidence of a disconnect between traditional pathology and cognitive abilities with advancing age, indicative of individual variation in resilience to pathology. Here, we generated a comprehensive neuropathological, molecular, and transcriptomic characterization of hippocampus and two regions cortex in 107 aged donors (median = 90) from the Adult Changes in Thought (ACT) study as a freely-available resource (http://aging.brain-map.org/). We confirm established associations between AD pathology and dementia, albeit with increased, presumably aging-related variability, and identify sets of co-expressed genes correlated with pathological tau and inflammation markers. Finally, we demonstrate a relationship between dementia and RNA quality, and find common gene signatures, highlighting the importance of properly controlling for RNA quality when studying dementia.

Home Improvement in HIV Primary Care: Investigating the Patient-Centered Medical Home Model for People Living with HIV/AIDS.

This article details the processes and findings of a 3-year demonstration project implementing population health management and the Patient-Centered Medical Home (PCMH) model in 3 community health centers in Alameda County, California. The article provides a first look at the PCMH Continuum, a tool for aiding staff in conceptualizing and implementing complex organizational change. Findings of the project evaluation also are shared, comprising a road map for other organizations looking to implement population health management, panel management, and PCMH. The article reflects on lessons learned and best practices from the demonstration project.

Alcohol coverage in California newspapers: frequency, prominence, and framing.

The purpose of this study was to investigate the nature and extent of alcohol coverage in California newspapers by examining the frequency, positioning, and framing of alcohol-related articles. A content analysis assessed the frequency and nature of alcohol references in news content drawn from a random sample of nine California newspaper issues from September 1997 to June 1998. The study findings indicate that alcohol is mentioned at least once a day in daily newspapers with more frequent mention in smaller newspapers. Alcohol is most often discussed in relation to trauma or in the context of promoting alcohol consumption. Articles on trauma and driving while intoxicated receive more prominence than other stories mentioning alcohol. Despite the relative frequency of alcohol content in trauma news, these stories are rarely framed with any sort of health context. Public health advocates should work toward increasing the frequency and improving the framing of alcohol in newspaper coverage.

Independent evaluation of the California Tobacco Control Program: relationships between program exposure and outcomes, 1996-1998.

OBJECTIVES: This study sought to determine the effects of the California Tobacco Control Program on tobacco-related attitudes and behaviors. METHODS: In 1996 and 1998, a telephone survey was conducted among adults in randomly selected households in 18 California counties. Tenth-grade youths in 84 randomly selected high schools completed a written survey. In analyses conducted at the county level, differences in outcomes were regressed on an index of program exposure. RESULTS: Among adults, program exposure was associated with decreased smoking prevalence rates, increased no-smoking policies in homes, and decreased violations of workplace no-smoking policies. Among youths, there was no effect of program exposure on outcomes. CONCLUSIONS: These results suggest that the California Tobacco Control Program may have reduced adult smoking prevalence rates and exposure to environmental tobacco smoke.