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1.  Recovery, Dependence or Death After Discharge 
doi:10.1007/s11606-012-2310-3
PMCID: PMC3579963  PMID: 23435831
2.  ACTIVITY ENERGY EXPENDITURE AND INCIDENT COGNITIVE IMPAIRMENT IN OLDER ADULTS 
Archives of internal medicine  2011;171(14):1251-1257.
Introduction
Studies suggest that physically active people have reduced risk of incident cognitive impairment in late life. However, these studies are limited by reliance on subjective self-reports of physical activity, which only moderately correlate to objective measures and often exclude activity not readily quantifiable by frequency and duration. The objective of this study was to investigate the relationship between activity energy expenditure (AEE), an objective measure of total activity, and incidence of cognitive impairment.
Methods
We calculated AEE as 90% of total energy expenditure (assessed over two weeks using doubly-labeled water) minus resting metabolic rate (measured using indirect calorimetry) in 197 men and women (mean 74.8 years) who were free of mobility and cognitive impairments at study baseline (1998–2000). Cognitive function was assessed at baseline and 2 or 5 years later using the Modified Mini-Mental State Examination (3MS). Cognitive impairment was defined as a decline of >1.0 SD (9 points) between baseline and follow-up.
Results
After adjustment for baseline 3MS, demographics, fat free mass, sleep duration, self-reported health, and diabetes, older adults in the highest sex-specific tertile of AEE had lower odds of incident cognitive impairment than those in the lowest tertile (OR, 95% CI 0.09, 0.01–0.79). There was also a significant dose response between AEE and incidence of cognitive impairment (p-for-trend over tertiles=0.05).
Conclusions
These findings indicate that greater activity energy expenditure may be protective against cognitive impairment in a dose-response manner. The significance of overall activity in contrast to vigorous or light activity should be determined.
doi:10.1001/archinternmed.2011.277
PMCID: PMC3923462  PMID: 21771893
3.  Prediction of Recovery, Dependence or Death in Elders Who Become Disabled During Hospitalization 
ABSTRACT
BACKGROUND
Many older adults become dependent in one or more activities of daily living (ADLs: dressing, bathing, transferring, eating, toileting) when hospitalized, and their prognosis after discharge is unclear.
OBJECTIVE
To develop a prognostic index to estimate one-year probabilities of recovery, dependence or death in older hospitalized patients who are discharged with incident ADL dependence.
DESIGN
Retrospective cohort study.
PARTICIPANTS
449 adults aged ≥ 70 years hospitalized for acute illness and discharged with incident ADL dependence.
MAIN MEASURES
Potential predictors included demographics (age, sex, race, education, marital status), functional measures (ADL dependencies, instrumental activities of daily living [IADL] dependencies, walking ability), chronic conditions (e.g., congestive heart failure, dementia, cancer), reason for admission (e.g., neurologic, cardiovascular), and laboratory values (creatinine, albumin, hematocrit). Multinomial logistic regression was used to develop a prognostic index for estimating the probabilities of recovery, disability or death over 1 year. Discrimination of the index was assessed for each outcome based on the c statistic.
KEY RESULTS
During the year following hospitalization, 36 % of patients recovered, 27 % remained dependent and 37 % died. Key predictors of recovery, dependence or death were age, sex, number of IADL dependencies 2 weeks prior to admission, number of ADL dependencies at discharge, dementia, cancer, number of other chronic conditions, reason for admission, and creatinine levels. The final prognostic index had good to excellent discrimination for all three outcomes based on the c statistic (recovery: 0.81, dependence: 0.72, death: 0.78).
CONCLUSIONS
This index accurately estimated the probabilities of recovery, dependence or death in adults aged 70 years or older who were discharged with incident disability following hospitalization. This tool may be useful in clinical settings to guide care discussions and inform decision-making related to post-hospitalization care.
doi:10.1007/s11606-012-2226-y
PMCID: PMC3614138  PMID: 23054919
functional status; disability; mortality; hospitalization; prognosis
4.  Acute Care For Elders Units Produced Shorter Hospital Stays At Lower Cost While Maintaining Patients’ Functional Status 
Health affairs (Project Hope)  2012;31(6):10.1377/hlthaff.2012.0142.
Acute Care for Elders Units offer enhanced care for older adults in specially designed hospital units. The care is delivered by interdisciplinary teams, which can include geriatricians, advanced practice nurses, social workers, pharmacists, and physical therapists. In a randomized controlled trial of 1,632 elderly patients, length-of-stay was significantly shorter—6.7 days per patient versus 7.3 days per patient—among those receiving care in the Acute Care for Elders Unit compared to usual care. This difference produced lower total inpatient costs—$9,477 per patient versus $10,451 per patient—while maintaining patients’ functional abilities and not increasing hospital readmission rates. The practices of Acute Care for Elders Units, and the principles they embody, can provide hospitals with effective strategies for lowering costs while preserving quality of care for hospitalized elders.
doi:10.1377/hlthaff.2012.0142
PMCID: PMC3870859  PMID: 22665834
5.  Development and Validation of a Questionnaire to Detect Behavior Change in Multiple Advance Care Planning Behaviors 
PLoS ONE  2013;8(9):e72465.
Introduction
Advance directives have traditionally been considered the gold standard for advance care planning. However, recent evidence suggests that advance care planning involves a series of multiple discrete behaviors for which people are in varying stages of behavior change. The goal of our study was to develop and validate a survey to measure the full advance care planning process.
Methods
The Advance Care Planning Engagement Survey assesses “Process Measures” of factors known from Behavior Change Theory to affect behavior (knowledge, contemplation, self-efficacy, and readiness, using 5-point Likert scales) and “Action Measures” (yes/no) of multiple behaviors related to surrogate decision makers, values and quality of life, flexibility for surrogate decision making, and informed decision making. We administered surveys at baseline and 1 week later to 50 diverse, older adults from San Francisco hospitals. Internal consistency reliability of Process Measures was assessed using Cronbach's alpha (only continuous variables) and test-retest reliability of Process and Action Measures was examined using intraclass correlations. For discriminant validity, we compared Process and Action Measure scores between this cohort and 20 healthy college students (mean age 23.2 years, SD 2.7).
Results
Mean age was 69.3 (SD 10.5) and 42% were non-White. The survey took a mean of 21.4 minutes (±6.2) to administer. The survey had good internal consistency (Process Measures Cronbach's alpha, 0.94) and test-retest reliability (Process Measures intraclass correlation, 0.70; Action Measures, 0.87). Both Process and Action Measure scores were higher in the older than younger group, p<.001.
Conclusion
A new Advance Care Planning Engagement Survey that measures behavior change (knowledge, contemplation, self-efficacy, and readiness) and multiple advance care planning actions demonstrates good reliability and validity. Further research is needed to assess whether survey scores improve in response to advance care planning interventions and whether scores are associated with receipt of care consistent with one's wishes.
doi:10.1371/journal.pone.0072465
PMCID: PMC3764010  PMID: 24039772
6.  Dysthymia and Depression Increase Risk of Dementia and Mortality among Older Veterans 
Objective
To determine if less severe depression spectrum diagnoses such as dysthymia, as well as depression, are associated with risk of developing dementia and mortality in a “real world” setting.
Design
Retrospective cohort study conducted using the Department of Veterans Affairs (VA) National Patient Care Database (1997-2007).
Setting
VA medical centers in the United States.
Participants
A total of 281,540 veterans 55 years and older without dementia at study baseline (1997-2000).
Measurements
Depression status and incident dementia were ascertained from ICD-9 codes during study baseline (1997-2000) and follow-up (2001-2007), respectively. Mortality was ascertained by time of death dates in the VA Vital Status File.
Results
Ten percent of veterans had baseline diagnosis of depression and nearly 1% had dysthymia. The unadjusted incidence of dementia was 11.2% in veterans with depression, 10.2% with dysthymia and 6.4% with neither. After adjusting for demographics and comorbidities, patients diagnosed with dysthymia or depression were twice as likely to develop incident dementia compared to those with no dysthymia/depression (adjusted dysthymia hazard ratio [HR]: 1.96, 95% confidence interval [CI]: 1.71-2.25; and depression HR: 2.18, 95% CI: 2.08-2.28). Dysthymia and depression also were associated with increased risk of death (31.6% dysthymia and 32.9% depression vs 28.5% neither; adjusted dysthymia HR: 1.41, 95% CI: 1.31-1.53; and depression HR: 1.47, 95% CI: 1.43-1.51).
Conclusions
Findings suggest that older adults with dysthymia or depression need to be monitored closely for adverse outcomes. Future studies should determine whether treatment of depression spectrum disorders may reduce risk of these outcomes.
doi:10.1097/JGP.0b013e31822001c1
PMCID: PMC3229643  PMID: 21597358
Dysthymia; Depression; Dementia; Mortality
7.  Secondhand Smoke, Vascular Disease, and Dementia Incidence: Findings From the Cardiovascular Health Cognition Study 
American Journal of Epidemiology  2010;171(3):292-302.
Recent studies have found that smoking is associated with an increased risk of dementia, but the effects of secondhand smoke (SHS) on dementia risk are not known to have previously been studied. The authors used Cox proportional hazards marginal structural models to examine the association between self-reported lifetime household SHS exposure and risk of incident dementia over 6 years among 970 US participants in the Cardiovascular Health Cognition Study (performed from 1991 to 1999) who were never smokers and were free of clinical cardiovascular disease (CVD), dementia, and mild cognitive impairment at baseline. In addition, because prior studies have found that SHS is associated with increased risk of CVD and that CVD is associated with increased risk of dementia, the authors tested for interactions between SHS and measures of clinical and subclinical CVD on dementia risk. Moderate (16–25 years) and high (>25 years) SHS exposure levels were not independently associated with dementia risk; however, subjects with >25 years of SHS exposure and >25% carotid artery stenosis had a 3-fold increase (hazard ratio = 3.00, 95% confidence interval: 1.03, 9.72) in dementia risk compared with subjects with no/low (0–15 years) SHS exposure and ≤25% carotid artery stenosis. High lifetime SHS exposure may increase the risk of dementia in elderly with undiagnosed CVD.
doi:10.1093/aje/kwp376
PMCID: PMC2878108  PMID: 20051462
aged; dementia; longitudinal studies; models, statistical; tobacco smoke pollution
8.  Mid-life versus late-life depressive symptoms and risk of dementia: Differential effects for Alzheimer’s disease and vascular dementia 
Archives of general psychiatry  2012;69(5):493-498.
Context
Depression and dementia are common in older adults and often co-occur, but it is unclear whether depression is an etiologic risk factor for dementia.
Objective, Design, Setting and Participants
To clarify the timing and etiology of the association, we examined depressive symptoms assessed in mid-life (1964–1973) and late-life (1994–2000) and the risks of dementia, Alzheimer’s disease (AD) and vascular dementia (VaD) (2003–2009) in a retrospective cohort study of 13,535 long-term Kaiser Permanente members. Depressive symptoms were categorized as none, mid-life only, late-life only or both. Cox proportional hazards models (age as time-scale) adjusted for demographics and medical comorbidities were used to examine depressive symptom category and risk of dementia, AD or VaD.
Main Outcome Measure
Any medical record diagnosis of dementia; Neurology clinic diagnosis of AD or VaD.
Results
Subjects had a mean (standard deviation) age of 81 (5) years in 2003; 58% were women and 25% were non-white. Depressive symptoms were present in 14.1% of subjects in mid-life only, 9.2% late-life only, and 4.2% both. Over 6 years, 23.1% were diagnosed with dementia (5.5% AD, 2.3% VaD). The adjusted hazard of dementia was increased by approximately 20% for mid-life depressive symptoms only (Hazard Ratio [95% confidence interval]: 1.19 [1.07, 1.32]), 70% for late-life symptoms only (1.72 [1.54, 1.92]), and 80% for both (1.77 [1.52, 2.06]). When we examined AD and VaD separately, subjects with late-life depressive symptoms only had a two-fold increase in AD risk (2.06 [1.67, 2.55]) whereas subjects with both mid-life and late-life symptoms had more than a three-fold increase in VaD risk (3.51 [2.44, 5.05]).
Conclusions
Depressive symptoms in mid-life or late-life are associated with an increased risk of developing dementia. Depression that begins in late-life may be part of the AD prodrome, while recurrent depression may be etiologically associated with increased risk of VaD.
doi:10.1001/archgenpsychiatry.2011.1481
PMCID: PMC3704214  PMID: 22566581
9.  Physical Activity Over the Life Course and its Association with Cognitive Performance and Impairment in Old Age 
Objective
To determine how physical activity at various ages over the life course is associated with cognitive impairment in late life.
Design
Cross-sectional study
Setting
Four US sites.
Participants
We administered a modified Mini-Mental State Examination (mMMSE) to 9344 women ≥65 years (mean 71.6 years) who self-reported teenage, age 30, age 50, and late life physical activity.
Measurements
We used logistic regressions to determine the association between physical activity status at each age and likelihood of cognitive impairment (mMMSE score >1.5SD below the mean, mMMSE≤22). Models were adjusted for age, education, marital status, diabetes, hypertension, depressive symptoms, smoking, and body mass index.
Results
Women who reported being physically active had lower prevalence of cognitive impairment in late life compared to women who were inactive at each time (teenage: 8.5% vs. 16.7%; adjusted Odds Ratio (95% Confidence Interval): 0.65 (0.53–0.80); age 30: 8.9% vs. 12.0%; 0.80 (0.67–0.96); age 50: 8.5% vs. 13.1%; 0.71 (0.59–0.85); old age: 8.2% vs. 15.9%; 0.74 (0.61–0.91)). When the four times were analyzed together, teenage physical activity was most strongly associated with lower odds of late-life cognitive impairment (OR=0.73 (0.58–0.92)). However, women who were physically inactive at teenage and became active in later life had lower risk than those who remained inactive.
Conclusions
Women who reported being physically active at any point over the life course, and especially at teenage, have lower likelihood of cognitive impairment in late life. Interventions should promote physical activity early in life and throughout the life course.
doi:10.1111/j.1532-5415.2010.02903.x
PMCID: PMC3662219  PMID: 20609030
Physical Activity; Exercise; Cognition; Cognitive Impairment; Life Course
10.  Predicting Alzheimer's risk: why and how? 
Because the pathologic processes that underlie Alzheimer's disease (AD) appear to start 10 to 20 years before symptoms develop, there is currently intense interest in developing techniques to accurately predict which individuals are most likely to become symptomatic. Several AD risk prediction strategies - including identification of biomarkers and neuroimaging techniques and development of risk indices that combine traditional and non-traditional risk factors - are being explored. Most AD risk prediction strategies developed to date have had moderate prognostic accuracy but are limited by two key issues. First, they do not explicitly model mortality along with AD risk and, therefore, do not differentiate individuals who are likely to develop symptomatic AD prior to death from those who are likely to die of other causes. This is critically important so that any preventive treatments can be targeted to maximize the potential benefit and minimize the potential harm. Second, AD risk prediction strategies developed to date have not explored the full range of predictive variables (biomarkers, imaging, and traditional and non-traditional risk factors) over the full preclinical period (10 to 20 years). Sophisticated modeling techniques such as hidden Markov models may enable the development of a more comprehensive AD risk prediction algorithm by combining data from multiple cohorts. As the field moves forward, it will be critically important to develop techniques that simultaneously model the risk of mortality as well as the risk of AD over the full preclinical spectrum and to consider the potential harm as well as the benefit of identifying and treating high-risk older patients.
doi:10.1186/alzrt95
PMCID: PMC3308022  PMID: 22126363
12.  Neuropsychiatric Symptoms in Mild Cognitive Impairment: Differences by Subtype and Progression to Dementia 
Background
Neuropsychiatric symptoms (NPS) are common in patients with mild cognitive impairment (MCI). Little is known, however, about how NPS vary by MCI subtype (i.e., amnestic, single domain non-memory, and multiple domain). In addition, it is unclear whether NPS increase risk of progression to dementia. We investigated the distribution of NPS across MCI subtypes and determined whether NPS increase risk of progression to dementia.
Method
Participants were 521 patients diagnosed with MCI at the Alzheimer's Research Centers of California between 1988 and 1999. At baseline, patients were classified into MCI subtypes and were assessed for NPS.
Results
The mean number of NPS was 2.3 (range 0-9.6; 74% had ≥ 1 NPS). Patients with ≥ 4 NPS had more medical comorbidities and greater functional impairment (p ≤ 0.0001 for both). Patients with ≥ 4 NPS were more likely than patients with 0-3 NPS to have amnestic MCI (81% vs. 71%, respectively, p = 0.03), and patients with amnestic MCI were more likely than those with other subtypes to exhibit depressive symptoms. Patients with ≥ 4 NPS had nearly 2.5 times the odds of developing dementia at follow-up than patients with 0-3 NPS (adjusted OR = 2.44, 95% CI 1.07, 5.55).
Conclusion
NPS are common in MCI patients. Those with an elevated number of NPS may be more likely to have the amnestic subtype of MCI, and depression may be more common in amnestic MCI than in other subtypes. An elevated number of NPS may increase risk of progression to dementia for patients with MCI.
doi:10.1002/gps.2187
PMCID: PMC2735341  PMID: 19140134
Mild cognitive impairment; neuropsychiatric symptoms; dementia
13.  Computer-Based Cognitive Training for Mild Cognitive Impairment: Results from a Pilot Randomized, Controlled Trial 
We performed a pilot randomized, controlled trial of intensive, computer-based cognitive training in 47 subjects with mild cognitive impairment (MCI). The intervention group performed exercises specifically designed to improve auditory processing speed and accuracy for 100 minutes/day, 5 days/week for 6 weeks; the control group performed more passive computer activities (reading, listening, visuospatial game) for similar amounts of time. Subjects had a mean age of 74 years and 60% were men; 77% successfully completed training. On our primary outcome, Repeatable Battery for Assessment of Neuropsychological Status (RBANS) total scores improved 0.36 standard deviations (SD) in the intervention group (p=0.097) compared to 0.03 SD in the control group (p=0.88) for a non-significant difference between the groups of 0.33 SD (p=0.26). On 12 secondary outcome measures, most differences between the groups were not statistically significant. However, we observed a pattern in which effect sizes for verbal learning and memory measures tended to favor the intervention group while effect sizes for language and visuospatial function measures tended to favor the control group, which raises the possibility that these training programs may have domain-specific effects. We conclude that intensive, computer-based mental activity is feasible in subjects with MCI and that larger trials are warranted.
doi:10.1097/WAD.0b013e31819c6137
PMCID: PMC2760033  PMID: 19812460
human; aged; cognition; cognitive rehabilitation; memory; neuropsychological tests; randomized controlled trial; mild cognitive impairment
14.  Predicting dementia: role of dementia risk indices 
Future neurology  2009;4(5):555-560.
There are currently more than 5 million people in the USA living with Alzheimer’s disease and other forms of dementia, and prevalence is expected to triple over the next 40 years. As new strategies for prevention and treatment are developed, it will be critically important to be able to identify older adults who do not currently have dementia but have a high risk of developing symptoms within a few years so that they can be targeted for monitoring, prevention and early treatment. In other fields, prognostic models and risk indices are often used to identify high-risk individuals (e.g., Framingham Heart Index and Breast Cancer Risk Assessment Tool). The objective of this paper is to describe the development of Dementia Risk Indices and to discuss the potential for these tools to be incorporated into clinical and research settings for the identification of individuals with a high risk of dementia.
doi:10.2217/fnl.09.43
PMCID: PMC2805956  PMID: 20161571
dementia; prevention; risk assessment; risk factors
15.  Cognition in Older Women: The Importance of Daytime Movement 
OBJECTIVES
To determine whether an objective measure of daytime movement is associated with better cognitive function in women in their 80s.
DESIGN, SETTING AND PARTICIPANTS
Cross-sectional study of 2,736 older women without evidence of dementia participating in a study of health and aging.
MEASUREMENTS
Daytime movement was assessed with actigraphy—a watch-like device that objectively quantifies accelerometer motion—over a mean of 3.0 ± 0.8 days. Cognitive function was measured by the Trail-Making Test, Part B (Trails B) and the Mini-Mental State Examination (MMSE). Cognitive impairment was defined as performing > 1.5 standard deviations (SD) worse than the mean on a given test.
RESULTS
Women had a mean age of 83 ± 4 years; 10% were African American. After adjustment for age, race and education, women in the highest versus lowest movement quartiles had better mean cognitive test scores (20 seconds [0.3 SD] faster on Trails B and 0.3 [0.2 SD] points higher on MMSE, both p<0.001) and were less likely to be cognitively impaired (Odds Ratio [95% Confidence Interval]: 0.61 [0.41 to 0.92] for Trails B and 0.68 [0.44 to 1.07] for MMSE). Associations were similar in different subgroups and were independent of self-reported walking, medical comorbidities, physical function and other healthy behaviors.
CONCLUSION
Daytime movement as measured objectively using actigraphy was associated with better cognitive function and lower odds of cognitive impairment in women in their 80s. Additional studies are needed to clarify the direction of the association and to explore potential mechanisms.
doi:10.1111/j.1532-5415.2008.01841.x
PMCID: PMC2680379  PMID: 18662201
movement; exercise; activity; cognition; risk factor
16.  An Advance Directive Redesigned to Meet the Literacy Level of Most Adults: A Randomized Trial 
Patient education and counseling  2007;69(1-3):165-195.
Objective
To determine whether an advance directive redesigned to meet most adults’ literacy needs (5th grade reading level with graphics) was more useful for advance care planning than a standard form (>12th grade level).
Methods
We enrolled 205 English and Spanish-speaking patients, aged ≥ 50 years from an urban, general medicine clinic. We randomized participants to review either form. Main outcomes included acceptability and usefulness in advance care planning. Participants then reviewed the alternate form; we assessed form preference and six-month completion rates.
Results
40% of enrolled participants had limited literacy. Compared to the standard form, the redesigned form was rated higher for acceptability and usefulness in care planning, P≤0.03, particularly for limited literacy participants (P for interaction ≤ 0.07). The redesigned form was preferred by 73% of participants. More participants randomized to the redesigned form completed an advance directive at six months (19% vs. 8%, P=0.03); of these, 95% completed the redesigned form.
Conclusions
The redesigned advance directive was rated more acceptable and useful for advance care planning and was preferred over a standard form. It also resulted in higher six month completion rates.
Practice Implications
An advance directive redesigned to meet most adults’ literacy needs may better enable patients to engage in advance care planning.
doi:10.1016/j.pec.2007.08.015
PMCID: PMC2257986  PMID: 17942272
advance directive; health literacy; communication; decision-making; ethics; health disparities
17.  Use of a Modified Informed Consent Process among Vulnerable Patients: A Descriptive Study 
BACKGROUND
Little is known about patient characteristics associated with comprehension of consent information, and whether modifications to the consent process can promote understanding.
OBJECTIVE
To describe a modified research consent process, and determine whether literacy and demographic characteristics are associated with understanding consent information.
DESIGN
Descriptive study of a modified consent process: consent form (written at a sixth-grade level) read to participants, combined with 7 comprehension questions and targeted education, repeated until comprehension achieved (teach-to-goal).
PARTICIPANTS
Two hundred and four ethnically diverse subjects, aged ≥50, consenting for a trial to improve the forms used for advance directives.
MEASUREMENTS
Number of passes through the consent process required to achieve complete comprehension. Literacy assessed in English and Spanish with the Short Form Test of Functional Health Literacy in Adults (scores 0 to 36).
RESULTS
Participants had a mean age of 61 years and 40% had limited literacy (s-TOHFLA<23). Only 28% of subjects answered all comprehension questions correctly on the first pass. After adjustment, lower literacy (P=.04) and being black (P=.03) were associated with requiring more passes through the consent process. Not speaking English as a primary language was associated with requiring more passes through the consent process in bivariate analyses (P<.01), but not in multivariable analyses (P>.05). After the second pass, most subjects (80%) answered all questions correctly. With a teach-to-goal strategy, 98% of participants who engaged in the consent process achieved complete comprehension.
CONCLUSIONS
Lower literacy and minority status are important determinants of understanding consent information. Using a modified consent process, little additional education was required to achieve complete comprehension, regardless of literacy or language barriers.
doi:10.1111/j.1525-1497.2006.00535.x
PMCID: PMC1831581  PMID: 16881949
informed consent; health literacy; communication; vulnerable populations; ethics
18.  Gene-Targeted Mice Lacking the Trex1 (DNase III) 3′→5′ DNA Exonuclease Develop Inflammatory Myocarditis 
Molecular and Cellular Biology  2004;24(15):6719-6727.
TREX1, originally designated DNase III, was isolated as a major nuclear DNA-specific 3′→5′ exonuclease that is widely distributed in both proliferating and nonproliferating mammalian tissues. The cognate cDNA shows homology to the editing subunit of the Escherichia coli replicative DNA polymerase III holoenzyme and encodes an exonuclease which was able to serve a DNA-editing function in vitro, promoting rejoining of a 3′ mismatched residue in a reconstituted DNA base excision repair system. Here we report the generation of gene-targeted Trex1−/− mice. The null mice are viable and do not show the increase in spontaneous mutation frequency or cancer incidence that would be predicted if Trex1 served an obligatory role of editing mismatched 3′ termini generated during DNA repair or DNA replication in vivo. Unexpectedly, Trex1−/− mice exhibit a dramatically reduced survival and develop inflammatory myocarditis leading to progressive, often dilated, cardiomyopathy and circulatory failure.
doi:10.1128/MCB.24.15.6719-6727.2004
PMCID: PMC444847  PMID: 15254239

Results 1-18 (18)