ABSTRACT
Melanoma Differentiation-Associated protein 5 (MDA5) is a member of the retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) family, which is a cytosolic pattern recognition receptor that detects viral nucleic acids. Here we show an Mda5-dependent response to rhabdovirus infection in vivo using a dominant-negative mda5 transgenic zebrafish. Dominant-negative mda5 zebrafish embryos displayed an impaired antiviral immune response compared to wild-type counterparts that can be rescued by recombinant full-length Mda5. To our knowledge, we have generated the first dominant-negative mda5 transgenic zebrafish and demonstrated a critical role for Mda5 in the antiviral response to rhabdovirus.
Subject(s)
DEAD-box RNA Helicases/metabolism , Receptors, Pattern Recognition/metabolism , Rhabdoviridae Infections/immunology , Rhabdoviridae/immunology , Zebrafish Proteins/metabolism , Zebrafish/immunology , Animals , Animals, Genetically Modified , DEAD-box RNA Helicases/genetics , DEAD-box RNA Helicases/immunology , Immunity, Active/genetics , Interferon Type I/metabolism , Mutation/genetics , Receptors, Pattern Recognition/genetics , Receptors, Pattern Recognition/immunology , Transgenes/genetics , Viral Load/genetics , Zebrafish Proteins/genetics , Zebrafish Proteins/immunologyABSTRACT
A randomized trial of falls prevention program that addressed home safety, exercise, and behavioral risks was conducted with 3,182 independently living HMO members age 65 and older. The intervention decreased the odds of falling by 0.85, but only reduced the average number of falls among those who fell by 7%. The effect was strongest among men age 75 and older. The likelihood of avoiding falls requiring medical treatment was not significantly affected by the intervention. We conclude that the intervention dose was not of sufficient intensity or duration to have a marked protective effect on older persons. Future research should focus on more intensive intervention approaches because serious falls do not appear to be amendable to low-intensity environment/behavioral efforts.
Subject(s)
Accidental Falls/prevention & control , Health Education , Wounds and Injuries/prevention & control , Accidental Falls/statistics & numerical data , Aged , Aged, 80 and over , Female , Health Behavior , Humans , Male , Multivariate Analysis , Risk Factors , SafetyABSTRACT
The Seniors' Program for Injury Control and Education (SPICE) examines the effects of exercise and physical fitness on falls and related injuries among older persons. The design is a two-group, randomized trial with 2 years of follow-up. The study is at Northwest Region of Kaiser Permanente (NWKP), a large hospital-based prepaid group practice HMO in Portland, OR. The participants are 1,323 community-living persons 65 years or older who are enrolled in NWKP and are at moderate risk of falling. A multifaceted intervention strategy uses a group approach to falls and injury prevention which includes moderate intensity endurance-building exercise (walking), strength and balance training, home safety improvements, and mental practice. Sessions of 20-25 participants are led by two nurses. Participants set their own realistic goals for exercising to accommodate to differing functional abilities and baseline conditioning. The control group receives usual care from the HMO. Participants report all falls for 2 years after randomization. Outcome measures include health status, physical functioning, falls, and fall-related medical care use and cost. If SPICE is effective, cost-effectiveness analysis will examine the relative efficiency of SPICE versus other successful FICSIT interventions. Thus far, recruitment and intervention compliance goals have been met from a population of frail elderly HMO members.
