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Ann Arbor, MI, United States

Sun L.Y.,University of Michigan | Bokov A.F.,University of Texas Health Science Center at San Antonio | Richardson A.,University of Texas Health Science Center at San Antonio | Miller R.A.,University of Michigan | Miller R.A.,Ann Arbor Veterans Affairs Medical Center
FASEB Journal | Year: 2011

Multiple stress resistance pathways were evaluated in the liver of Ames dwarf mice before and after exposure to the oxidative toxin diquat, seeking clues to the exceptional longevity conferred by this mutation. Before diquat treatment, Ames dwarf mice, compared with nonmutant littermate controls, had 2- to 6-fold higher levels of expression of mRNAs for immediate early genes and 2- to 5-fold higher levels of mRNAs for genes dependent on the transcription factor Nrf2. Diquat led to a 2-fold increase in phosphorylation of the stress kinase ERK in control (but not Ames dwarf) mice and to a 50% increase in phosphorylation of the kinase JNK2 in Ames dwarf (but not control) mice. Diquat induction of Nrf2 protein was higher in dwarf mice than in controls. Of 6 Nrf2-responsive genes evaluated, 4 (HMOX, NQO-1, MT-1, and MT-2) remained 2- to 10-fold lower in control than in dwarf liver after diquat, and the other 2 (GCLM and TXNRD) reached levels already seen in dwarf liver at baseline. Thus, livers of Ames dwarf mice differ systematically from controls in multiple stress resistance pathways before and after exposure to diquat, suggesting mechanisms for stress resistance and extended longevity in Ames dwarf mice. © FASEB. Source


Shin L.M.,Tufts University | Shin L.M.,Harvard University | Liberzon I.,Ann Arbor Veterans Affairs Medical Center | Liberzon I.,University of Michigan
Neuropsychopharmacology | Year: 2010

Anxiety disorders are a significant problem in the community, and recent neuroimaging research has focused on determining the brain circuits that underlie them. Research on the neurocircuitry of anxiety disorders has its roots in the study of fear circuits in animal models and the study of brain responses to emotional stimuli in healthy humans. We review this research, as well as neuroimaging studies of anxiety disorders. In general, these studies have reported relatively heightened amygdala activation in response to disorder-relevant stimuli in post-traumatic stress disorder, social phobia, and specific phobia. Activation in the insular cortex appears to be heightened in many of the anxiety disorders. Unlike other anxiety disorders, post-traumatic stress disorder is associated with diminished responsivity in the rostral anterior cingulate cortex and adjacent ventral medial prefrontal cortex. Additional research will be needed to (1) clarify the exact role of each component of the fear circuitry in the anxiety disorders, (2) determine whether functional abnormalities identified in the anxiety disorders represent acquired signs of the disorders or vulnerability factors that increase the risk of developing them, (3) link the findings of functional neuroimaging studies with those of neurochemistry studies, and (4) use functional neuroimaging to predict treatment response and assess treatment-related changes in brain function. © 2010 Nature Publishing Group All rights reserved. Source


Perlman R.L.,Ann Arbor Veterans Affairs Medical Center | Perlman R.L.,University of Michigan | Rao P.S.,University of Michigan
Drugs and Aging | Year: 2014

Kidney transplantation is currently the best treatment for end-stage renal disease, both in terms of mortality benefit and quality of life (QOL). Elderly patients are a rapidly growing subset of the kidney transplant waiting list. While it is clear that elderly individuals have a mortality benefit from kidney transplant, it is less clear how to make sure these individuals benefit from optimal QOL following transplant. Several studies demonstrate superiority of some immunosuppressive regimens over others in the QOL domain. Tacrolimus has been shown to be associated with better QOL than cyclosporine (ciclosporin), as has corticosteroid-free immunosuppressive regimens. Similarly, patients on drug regimens, which tend to lessen the side effects, report better QOL. However, these studies are observational or cross-sectional and not focused exclusively on the elderly patient. More studies are needed to determine optimal immunosuppression regimens for elderly individuals. Additionally, further studies on determinants of QOL in elderly kidney transplant recipients are also needed. © 2014 Springer International Publishing Switzerland. Source


Beck J.M.,Ann Arbor Veterans Affairs Medical Center | Beck J.M.,University of Michigan | Young V.B.,University of Michigan | Huffnagle G.B.,University of Michigan
Translational Research | Year: 2012

Investigation of the lung microbiome is a relatively new field. Although the lungs were classically believed to be sterile, recently published investigations have identified microbial communities in the lungs of healthy humans. At the present time, there are significant methodologic and technical hurdles that must be addressed in ongoing investigations, including distinguishing the microbiota of the upper and lower respiratory tracts. However, characterization of the lung microbiome is likely to provide important pathogenic insights into cystic fibrosis, respiratory disease of the newborn, chronic obstructive pulmonary disease, and asthma. In addition to characterization of the lung microbiome, the microbiota of the gastrointestinal tract have profound influence on the development and maintenance of lung immunity and inflammation. Further study of gastrointestinal-respiratory interactions is likely to yield important insights into the pathogenesis of pulmonary diseases, including asthma. As this field advances over the next several years, we anticipate that studies using larger cohorts, multicenter designs, and longitudinal sampling will add to our knowledge and understanding of the lung microbiome. © 2012 Mosby, Inc. All rights reserved. Source


Meddings J.,University of Michigan | Saint S.,University of Michigan | Saint S.,Ann Arbor Veterans Affairs Medical Center | McMahon Jr. L.F.,University of Michigan
Infection Control and Hospital Epidemiology | Year: 2010

OBJECTIVE. To evaluate whether hospital-acquired catheter-associated urinary tract infections (CA-UTIs) are accurately documented in discharge records with the use of International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes so that nonpayment is triggered, as mandated by the Centers for Medicare and Medicaid Services (CMS) Hospital-Acquired Conditions Initiative. METHODS. We conducted a retrospective medical record review of 80 randomly selected adult discharges from May 2006 through September 2007 from the University of Michigan Health System (UMHS) with secondary-diagnosis urinary tract infections (UTIs). One physician-abstractor reviewed each record to categorize UTIs as catheter associated and/or hospital acquired; these results (considered "gold standard") were compared with diagnosis codes assigned by hospital coders. Annual use of the catheter association code (996.64) by UMHS coders was compared with state and US rates by using Healthcare Cost and Utilization Project data. RESULTS. Patient mean age was 58 years; 56 (70%) were women; median length of hospital stay was 6 days; 50 patients (62%) used urinary catheters during hospitalization. Hospital coders had listed 20 secondary-diagnosis UTIs (25%) as hospital acquired, whereas physician-abstractors indicated that 37 (46%) were hospital acquired. Hospital coders had identified no CA-UTIs (code 996.64 was never used), whereas physician-abstractors identified 36 CA-UTIs (45%; 28 hospital acquired and 8 present on admission). Catheter use often was evident only from nursing notes, which, unlike physician notes, cannot be used by coders to assign discharge codes. State and US annual rates of 996.64 coding (~1% of secondary-diagnosis UTIs) were similar to those at UMHS. CONCLUSIONS. Hospital coders rarely use the catheter association code needed to identify CA-UTI among secondary-diagnosis UTIs. Coders often listed a UTI as present on admission, although the medical record indicated that it was hospital acquired. Because coding of hospital-acquired CA-UTI seems to be fraught with error, nonpayment according to CMS policy may not reliably occur. © 2010 by The Society for Healthcare Epidemiology of America. All rights reserved. Source

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