Protective effects of apigenin on the brain transcriptome with aging.

Brain aging is associated with reduced cognitive function that increases the risk for dementia. Apigenin is a bioactive plant compound that inhibits cellular aging processes and could protect against age-related cognitive dysfunction, but its mechanisms of action in the brain have not been comprehensively studied. We characterized brain transcriptome changes in young and old mice treated with apigenin in drinking water. We observed improved learning/memory in old treated mice, and our transcriptome analyses indicated that differentially expressed genes with aging and apigenin were primarily related to immune responses, inflammation, and cytokine regulation. Moreover, we found that genes/transcripts that were increased in old vs. young mice but downregulated with apigenin treatment in old animals were associated with immune activation/inflammation, whereas transcripts that were reduced with aging but increased with apigenin were related neuronal function and signaling. We also found that these transcriptome differences with aging and apigenin treatment were driven in part by glial cells. To follow up on these in vivo transcriptome findings, we studied aged astrocytes in vitro, and we found that apigenin reduced markers of inflammation and cellular senescence in these cells. Collectively, our data suggest that apigenin may protect against age-related cognitive dysfunction by suppressing neuro-inflammatory processes.

ADAR1 suppression causes interferon signaling and transposable element transcript accumulation in human astrocytes.

Neuroinflammation is a central mechanism of brain aging and Alzheimer's disease (AD), but the exact causes of age- and AD-related neuroinflammation are incompletely understood. One potential modulator of neuroinflammation is the enzyme adenosine deaminase acting on RNA 1 (ADAR1), which regulates the accumulation of endogenous double-stranded RNA (dsRNA), a pro-inflammatory/innate immune activator. However, the role of ADAR1 and its transcriptomic targets in astrocytes, key mediators of neuroinflammation, have not been comprehensively investigated. Here, we knock down ADAR1 in primary human astrocytes via siRNA transfection and use transcriptomics (RNA-seq) to show that this results in: (1) increased expression of type I interferon and pro-inflammatory signaling pathways and (2) an accumulation of transposable element (TE) transcripts with the potential to form dsRNA. We also show that our findings may be clinically relevant, as ADAR1 gene expression declines with brain aging and AD in humans, and this is associated with a similar increase in TE transcripts. Together, our results suggest an important role for ADAR1 in preventing pro-inflammatory activation of astrocytes in response to endogenous dsRNA with aging and AD.

The reverse transcriptase inhibitor 3TC protects against age-related cognitive dysfunction.

Aging is the primary risk factor for most neurodegenerative diseases, including Alzheimer's disease. Major hallmarks of brain aging include neuroinflammation/immune activation and reduced neuronal health/function. These processes contribute to cognitive dysfunction (a key risk factor for Alzheimer's disease), but their upstream causes are incompletely understood. Age-related increases in transposable element (TE) transcripts might contribute to reduced cognitive function with brain aging, as the reverse transcriptase inhibitor 3TC reduces inflammation in peripheral tissues and TE transcripts have been linked with tau pathology in Alzheimer's disease. However, the effects of 3TC on cognitive function with aging have not been investigated. Here, in support of a role for TE transcripts in brain aging/cognitive decline, we show that 3TC: (a) improves cognitive function and reduces neuroinflammation in old wild-type mice; (b) preserves neuronal health with aging in mice and Caenorhabditis elegans; and (c) enhances cognitive function in a mouse model of tauopathy. We also provide insight on potential underlying mechanisms, as well as evidence of translational relevance for these observations by showing that TE transcripts accumulate with brain aging in humans, and that these age-related increases intersect with those observed in Alzheimer's disease. Collectively, our results suggest that TE transcript accumulation during aging may contribute to cognitive decline and neurodegeneration, and that targeting these events with reverse transcriptase inhibitors like 3TC could be a viable therapeutic strategy.

Farm Dinner Theater: Testing an innovative health and safety intervention among older farmers and their families.

PURPOSE: The effectiveness of a novel intervention for increasing health and safety behaviors of older farmers was tested. Blending didactic and readers' theater techniques, Farm Dinner Theater (FDT) engages farmers in discussions of health and safety in a nonthreatening social atmosphere supportive of potential changes. METHODS: Through community collaborations, farmers 45 years and older were recruited in 8 communities for the FDT. For each site, 3 scripts were prepared highlighting health and safety issues especially relevant for older farmers. The brief plays were performed in a dinner theater format, with group discussion following each play. Printed educational packets (EPs) addressing the same topics were mailed to comparison groups of participants in 9 communities. In telephone interviews conducted 2 weeks and 2 months later, 870 participants (553 FDT and 317 EP) reported health and safety-related changes they had made in their farm operations. FINDINGS: FDT participants were more likely than EP participants to report having made any changes and reported making more changes on both the 2-week and 2-month follow-up assessments. This outcome occurred when analyzing all farms and when considering only farms with at least 1 participant who spent 10 or more hours per week farming. CONCLUSIONS: FDT is a fun, relaxing intervention; it is acceptable to farming communities; and it is more effective in producing health and safety-related changes than the common approach of providing printed materials. FDT not only had a greater impact than EP, but it has the potential to reach larger audiences due to its greater appeal.

A Step Toward Identifying Sources of Medical Errors: Modeling Standards of Care Deviations for Different Disease States.

Objective: To examine the feasibility of utilizing electronic health records (EHR) to determine a metric for identifying physician diagnostic and treatment deviations in standards of care for different disease states. Methods: A Boolean-rule-based model compared deviations in standards of care across four disease states: diabetes, cardiovascular disease, asthma, and rheumatoid arthritis. This metric was used to identify the relationship between physician deviations in standards of care procedures, before and after diagnosis, for 76 internal medicine physicians. Results: The Boolean-rule-based model identified patterns of standards of care deviation for the physicians before diagnosis and during treatment. The deviations identified for each of the four disease states were then related to Continuing Medical Education courses that could support further training. The rule-based model was extended and improved by including system and process aspects of medical care that are not specifically related to the physician, yet potentially have an impact on the physician's decision to deviate from the standards of care. Conclusion: The Boolean-rule-based approach provided a means to systematically mine EHRs and use these data to assess deviations in standards of care that could identify quality of care issues stemming from system processes or the need for specific CME for a physician.

Perspectives on Active Video Gaming as a New Frontier in Accessible Physical Activity for Youth With Physical Disabilities.

This perspective article explores the utility of active video gaming as a means of reducing sedentary behavior and increasing physical activity among youth with physical disabilities and limitations in lower extremity function who typically are excluded from mainstream exercise options. Youth with physical disabilities are disproportionately affected by health problems that result from sedentary behavior, lack of physical activity, and low fitness levels. Physical, programmatic, and attitudinal barriers have a synergistic and compounded impact on youths' ability to participate in physical activity. A recent health and wellness task force recommendation from the American Physical Therapy Association's Section on Pediatrics supports analyzing individualized health behaviors and preferences that are designed to improve fitness, physical activity, and participation in pediatric rehabilitation. This recommendation represents an opportunity to explore nontraditional options to maximize effectiveness and sustainability of pediatric rehabilitation techniques for youth with disabilities who could best benefit from customized programming. One new frontier in promoting physical activity and addressing common physical activity barriers for youth with physical disabilities is active video games (AVGs), which have received growing attention as a promising strategy for promoting health and fitness in children with and without disabilities. The purpose of this article is to discuss the potential for AVGs as an accessible option to increase physical activity participation for youth with physical disabilities and limitations in lower extremity function. A conceptual model on the use of AVGs to increase physical activity participation for youth with physical disabilities is introduced, and future research potential is discussed, including a development project for game controller adaptations within the Rehabilitation Engineering Research Center on Interactive Exercise Technologies and Exercise Physiology for People With Disabilities (RERC RecTech) at the University of Alabama at Birmingham (UAB)/Lakeshore Foundation Research Collaborative.

User-centered virtual environment design for virtual rehabilitation.

BACKGROUND: As physical and cognitive rehabilitation protocols utilizing virtual environments transition from single applications to comprehensive rehabilitation programs there is a need for a new design cycle methodology. Current human-computer interaction designs focus on usability without benchmarking technology within a user-in-the-loop design cycle. The field of virtual rehabilitation is unique in that determining the efficacy of this genre of computer-aided therapies requires prior knowledge of technology issues that may confound patient outcome measures. Benchmarking the technology (e.g., displays or data gloves) using healthy controls may provide a means of characterizing the "normal" performance range of the virtual rehabilitation system. This standard not only allows therapists to select appropriate technology for use with their patient populations, it also allows them to account for technology limitations when assessing treatment efficacy. METHODS: An overview of the proposed user-centered design cycle is given. Comparisons of two optical see-through head-worn displays provide an example of benchmarking techniques. Benchmarks were obtained using a novel vision test capable of measuring a user's stereoacuity while wearing different types of head-worn displays. Results from healthy participants who performed both virtual and real-world versions of the stereoacuity test are discussed with respect to virtual rehabilitation design. RESULTS: The user-centered design cycle argues for benchmarking to precede virtual environment construction, especially for therapeutic applications. Results from real-world testing illustrate the general limitations in stereoacuity attained when viewing content using a head-worn display. Further, the stereoacuity vision benchmark test highlights differences in user performance when utilizing a similar style of head-worn display. These results support the need for including benchmarks as a means of better understanding user outcomes, especially for patient populations. CONCLUSIONS: The stereoacuity testing confirms that without benchmarking in the design cycle poor user performance could be misconstrued as resulting from the participant's injury state. Thus, a user-centered design cycle that includes benchmarking for the different sensory modalities is recommended for accurate interpretation of the efficacy of the virtual environment based rehabilitation programs.

Pneumothorax influenced 3D lung deformations.

In this paper we propose a method to simulate morphological changes caused by both closed and tension pneumothorax. We consider a clinical parameter, the pneumothorax-index (i.e., the degree of lung collapse), as the input to the simulation. Specifically, such an index constitutes a key parameter to the computation of the changes in size and shape of the affected lung. Once the index is obtained, the increase in ventilation rate and the change in the pressure-volume relationship of the affected lung are then computed. For tension pneumothorax, the air continuously flows into the pleural cavity and thus every exhalation is followed by the changes seen for a closed pneumothorax, until the affected lung collapses. The subsequent closure of pulmonary veins and resulting hyper expansion of the apposing lung is also presented. Results show a real-time visualization of closed and tension pneumothorax using a high-resolution 3D model obtained from a normal human subject.

Peer review committee is learning laboratory.

The peer review process benefits dentists, their patients and the volunteers who conduct the process and learn its most valuable lessons. These lessons are to keep impeccable records, charge reasonable fees while maintaining high standards, make sure treatment plans are appropriate, refrain from disparaging the work of colleagues, and be an effective communicator.

Aspergilosis broncopulmonar: consideraciones sobre 122 casos con serología positiva para Aspergillus fumigatus / Bronchopulmonar aspergillosis: 122 cases diagnosed by serological tests for A. fumigatus

Se presenta el análisis de 122 casos de aspergilosis broncopulmonar diagnosticados entre los años 1990 y 1994, en el Departamento de Micología del Instituto Nacional de Higiene y Medicina Tropical de Guayaquil. Todos ellos presentaban anticuerpos frente al antígeno de A. fumigatus demostrables por inmunodifusión por la técnica de Ouchterlony. El estudio micológico en muestras de esputo fue realizado en 60 enfermos. Se señalan los parámetros considerados para el diagnóstico, las lesiones radiológicas observadas y los tratamientos instituídos

Aspergilosis broncopulmonar: consideraciones sobre 122 casos con serología positiva para Aspergillus fumigatus / Bronchopulmonar aspergillosis: 122 cases diagnosed by serological tests for A. fumigatus

Se presenta el análisis de 122 casos de aspergilosis broncopulmonar diagnosticados entre los años 1990 y 1994, en el Departamento de Micología del Instituto Nacional de Higiene y Medicina Tropical de Guayaquil. Todos ellos presentaban anticuerpos frente al antígeno de A. fumigatus demostrables por inmunodifusión por la técnica de Ouchterlony. El estudio micológico en muestras de esputo fue realizado en 60 enfermos. Se señalan los parámetros considerados para el diagnóstico, las lesiones radiológicas observadas y los tratamientos instituídos (AU)

[Multiple simultaneous stratigraphy. Results with a 5-plane system for pediatric use]. / Stratigrafia multipla simultanea. Risultati di un sistema a 5 strati per uso pediatrico.

The authors report the results of a five-layer simultaneous multisection tomographic technique to be used in pediatric radiology, based on an appropriately selected series of Trimax rare-earth intensifying screens arranged in progressive speed order. The technique has been so far employed with excellent results in 100 children, especially during IVP, when X-ray examination is very frequently disturbed by ileocolic gas. The many advantages of the technique are emphasized: a) all sections are perfectly parallel and simultaneous, in the same respiratory phase and body position; b) film density is practically identical in all sections; c) there is considerable saving in time, machine consumption, and radiation dose.

[Nonketotic hyperosmolar coma. Clinical aspects and treatment in 12 cases]. / Il coma iperosmolare non chetosico. Aspetti clinici e trattamento in 12 casi.

Non-ketotic hyperosmolar diabetic coma is a complication of diabetes characterised by extreme dehydration, plasmatic hyperosmolarity and the absence of ketosis. The mortality rate is very high, especially in elderly subjects with type II diabetes. A personal series of 12 cases is reported with an assessment of general features, triggering factors, biochemical parameters at onset and treatment given. The data confirm reports in the literature and the results show the therapeutic superiority of continuous endovenous infusions of insulin at 3-10 mu/hour over other treatment protocols.