Efficient translesion replication in the absence of Escherichia coli Umu proteins and 3′–5′ exonuclease proofreading function

Translesion replication (TR) past a cyclobutane pyrimidine dimer in Escherichia coli normally requires the UmuD′₂C complex, RecA protein, and DNA polymerase III holoenzyme (pol III). However, we find that efficient TR can occur in the absence of the Umu proteins if the 3′–5′ exonuclease proofreading activity of the pol III -subunit also is disabled. TR was measured in isogenic uvrA6 ΔumuDC strains carrying the dominant negative dnaQ allele, mutD5, or ΔdnaQ spq-2 mutations by transfecting them with single-stranded M13-based vectors containing a specifically located cis-syn T–T dimer. As expected, little TR was observed in the ΔumuDC dnaQ⁺ strain. Surprisingly, 26% TR occurred in UV-irradiated ΔumuDC mutD5 cells, one-half the frequency found in a uvrA6 umuDC⁺mutD5 strain. lexA3 (Ind⁻) derivatives of the strains showed that this TR was contingent on two inducible functions, one LexA-dependent, responsible for ≈70% of the TR, and another LexA-independent, responsible for the remaining ≈30%. Curiously, the ΔumuDC ΔdnaQ spq-2 strain exhibited only the LexA-independent level of TR. The cause of this result appears to be the spq-2 allele, a dnaE mutation required for viability in ΔdnaQ strains, since introduction of spq-2 into the ΔumuDC mutD5 strain also reduces the frequency of TR to the LexA-independent level. The molecular mechanism responsible for the LexA-independent TR is unknown but may be related to the UVM phenomenon [Palejwala, V. A., Wang, G. E., Murphy, H. S. & Humayun, M. Z. (1995) J. Bacteriol. 177, 6041–6048]. LexA-dependent TR does not result from the induction of pol II, since TR in the ΔumuDC mutD5 strain is unchanged by introduction of a ΔpolB mutation.     

National Patterns of Risk-Standardized Mortality and Readmission After Hospitalization for Acute Myocardial Infarction,Heart Failure,and Pneumonia: Update on Publicly Reported Outcomes Measures Based on the 2013 Release

BACKGROUND

The Centers for Medicare & Medicaid Services publicly reports risk-standardized mortality rates (RSMRs) within 30-days of admission and, in 2013, risk-standardized unplanned readmission rates (RSRRs) within 30-days of discharge for patients hospitalized with acute myocardial infarction (AMI), heart failure (HF), and pneumonia. Current publicly reported data do not focus on variation in national results or annual changes.

OBJECTIVE

Describe U.S. hospital performance on AMI, HF, and pneumonia mortality and updated readmission measures to provide perspective on national performance variation.

DESIGN

To identify recent changes and variation in national hospital-level mortality and readmission for AMI, HF, and pneumonia, we performed cross-sectional panel analyses of national hospital performance on publicly reported measures.

PARTICIPANTS

Fee-for-service Medicare and Veterans Health Administration beneficiaries, 65 years or older, hospitalized with principal discharge diagnoses of AMI, HF, or pneumonia between July 2009 and June 2012. RSMRs/RSRRs were calculated using hierarchical logistic models risk-adjusted for age, sex, comorbidities, and patients’ clustering among hospitals.

Results

Median (range) RSMRs for AMI, HF, and pneumonia were 15.1% (9.4–21.0%), 11.3% (6.4–17.9%), and 11.4% (6.5–24.5%), respectively. Median (range) RSRRs for AMI, HF, and pneumonia were 18.2% (14.4–24.3%), 22.9% (17.1–30.7%), and 17.5% (13.6–24.0%), respectively. Median RSMRs declined for AMI (15.5% in 2009–2010, 15.4% in 2010–2011, 14.7% in 2011–2012) and remained similar for HF (11.5% in 2009–2010, 11.9% in 2010–2011, 11.7% in 2011–2012) and pneumonia (11.8% in 2009–2010, 11.9% in 2010–2011, 11.6% in 2011–2012). Median hospital-level RSRRs declined: AMI (18.5% in 2009–2010, 18.5% in 2010–2011, 17.7% in 2011–2012), HF (23.3% in 2009–2010, 23.1% in 2010–2011, 22.5% in 2011–2012), and pneumonia (17.7% in 2009–2010, 17.6% in 2010–2011, 17.3% in 2011–2012).

Conclusions

We report the first national unplanned readmission results demonstrating declining rates for all three conditions between 2009–2012. Simultaneously, AMI mortality continued to decline, pneumonia mortality was stable, and HF mortality experienced a small increase.     

Self-Management: A Comprehensive Approach to Management of Chronic Conditions

For both clinical and economic reasons, the increasing number of persons living with chronic conditions represents a public health issue of growing importance. Emphasizing patient responsibility, and acting in concert with the provider community, self-management represents a promising strategy for treating chronic conditions—moving beyond education to teaching individuals to actively identify challenges and solve problems associated with their illness. Self-management also shows potential as an effective paradigm across the prevention spectrum (primary, secondary, and tertiary) by establishing a pattern for health early in life and providing strategies for mitigating illness and managing it in later life. We suggest ways to advance research methods and practical applications of self-management as steps in its future development and implementation.Improvements in health care have resulted in greater numbers of people living with multiple chronic conditions for longer periods of time. With this change, chronic illness is now a major focus of health care.1 At the same time, increased attention has been concentrated on approaches to manage chronic symptoms to maintain patient independence and quality of life over longer periods of time. Approaches to managing chronic illness are shifting from the traditional provider–patient relationship to a paradigm in which individuals with chronic conditions play a key role in guiding their care, in partnership with health care providers.2,3Many prevalent chronic conditions, such as heart disease, diabetes, and arthritis, though unique in their own attributes and demands, share common challenges associated with their management. These include dealing with symptoms and disability; monitoring physical indicators; managing complex medication regimens; maintaining proper levels of nutrition, diet, and exercise; adjusting to the psychological and social demands, including difficult lifestyle adjustments; and engaging in effective interactions with health care providers.4,5The identification and elaboration of common patient-centric strategies to deal with these challenges is the focus of the field of self-management.6,7 Regardless of the chronic condition, the development of a generic set of skills has proven successful in allowing individuals to effectively manage their illness and improve health outcomes.8 A 2010 report by the Department of Health and Human Services included self-management as one of 4 goals in a strategic framework for improving the health status of individuals with multiple chronic conditions.9 More recently, the 2012 Institute of Medicine report “Living Well With Chronic Illness: A Call for Public Health Action” included self-management10 as one of several models of living well interventions, noting that self-management programs instill individual responsibility and offer tools for patients to use in caring for their chronic illness.10There is increasing recognition that chronic illness, including its prevention, treatment and management, represents a public health as well as a clinical issue.11,12 Indeed, the Institute of Medicine report noted that a population health perspective for developing strategies, interventions, and policies to combat chronic illness is critical.10 Community-based self-management intervention programs are one aspect of a population-based approach addressing the larger public health problem of chronic conditions in the United States and across the globe. There is an extensive body of literature related to self-management of chronic conditions, but our intent with this article is not to provide a comprehensive review, but rather to highlight the unique contribution of nurse scientists to the field.Nursing science has enhanced the care of individual patients and has tested interventions that can be scaled up for implementation at the population level. We present examples of nursing science that demonstrate effectiveness, promise sustainability and scalability, and set the foundation for implementing wide-reaching public health actions for managing chronic illness.12There is increased awareness of the need to promote conceptual clarity regarding self-management and its integration into clinical practice. Equally important is the requirement to develop more sophisticated models of self-management, tailored to various health conditions and situations. Fundamental to the development of such models and their practical application is the need to conduct research that informs self-management practice and contributes to health policy.The nursing community, comprising both researchers and clinicians, plays a crucial role in efforts to provide the evidence base for innovative self-management practices, and is ideally positioned to implement those advances in a practical manner. Over the course of its history, the National Institute of Nursing Research (NINR) at the National Institutes of Health (NIH) has promoted self-management science as one of its core areas of investigation, supporting research to improve and manage symptoms of acute and chronic illness.13 Recognizing that self-management represents a topic of ever-increasing importance, a goal of NINR is to advance the science of self-management and, ultimately, disseminate results widely for translation into clinical practice.Recently, a group of nurse scientist leaders assembled to discuss “The Science of Chronic Illness Self-Management” as the topic of the 2013 National Nursing Research Roundtable. The Roundtable is an annual meeting with the purpose of providing a regular forum of communication about the direction and conduct of nursing research. Discussions from this year’s meeting resulted in a set of recommended areas of focus and approaches to advance the field and practice of self-management (see the box on this page).

Recommended Areas of Focus and Approaches to Advancing Self-Management

Characteristics of U.S. Veterans Who Begin and Complete Prolonged Exposure and Cognitive Processing Therapy for PTSD

This retrospective chart‐review study examined patient‐level correlates of initiation and completion of evidence‐based psychotherapy (EBP) for posttraumatic stress disorder (PTSD) among treatment‐seeking U.S. veterans. We identified all patients (N = 796) in a large Veterans Affairs PTSD and anxiety clinic who attended at least 1 individual psychotherapy appointment with 1 of 8 providers trained in EBP. Within this group, 91 patients (11.4%) began EBP (either Cognitive Processing Therapy or Prolonged Exposure) and 59 patients (7.9%) completed EBP. The medical records of all EBP patients (n = 91) and a provider‐matched sample of patients who received another form of individual psychotherapy (n = 66) were reviewed by 4 independent raters. Logistic regression analyses revealed that Iraq and Afghanistan veterans were less likely to begin EBP than veterans from other service eras, OR = 0.48, 95% CI = [0.24, 0.94], and veterans who were service connected for PTSD were more likely than veterans without service connection to begin EBP, OR = 2.33, 95% CI = [1.09, 5.03]. Among those who began EBP, Iraq and Afghanistan veteran status, OR = 0.09, 95% CI = [0.03, 0.30], and a history of psychiatric inpatient hospitalization, OR = 0.13, 95% CI = [0.03, 0.54], were associated with decreased likelihood of EBP completion.     

Respiratory chain deficiency in aged spinal motor neurons

Sarcopenia, muscle wasting, and strength decline with age, is an important cause of loss of mobility in the elderly individuals. The underlying mechanisms are uncertain but likely to involve defects of motor nerve, neuromuscular junction, and muscle. Loss of motor neurons with age and subsequent denervation of skeletal muscle has been recognized as one of the contributing factors. This study investigated aspects of mitochondrial biology in spinal motor neurons from elderly subjects. We found that protein components of complex I of mitochondrial respiratory chain were reduced or absent in a proportion of aged motor neurons–a phenomenon not observed in fetal tissue. Further investigation showed that complex I-deficient cells had reduced mitochondrial DNA content and smaller soma size. We propose that mitochondrial dysfunction in these motor neurons could lead to the cell loss and ultimately denervation of muscle fibers.     

Improving sensitivity of cervical cytology by removal of cervical secretions before sampling: a prospective study in Mexico

Sensitivity of cervical cytology is suboptimal, especially in developing countries such as Mexico, despite available guidelines aimed at improving this. When obtaining cervical samples, whether the samples are taken from the transformation zone and whether abnormal cells are missing must be considered. Cervical secretions (CS) are always present in variable proportions, and when cleaning the cervix, better samples may be obtained. In this study, we analyzed samples obtained with or without cleaning the cervix, and compared their contents in order to determine the sensitivity and specificity of these two methods. Methods: Of 500 patients who underwent cytology and colposcopy, 271 (54.2%) required a second opinion due to a diagnosis of cervical intraepithelial neoplasia (CIN). CS was removed and compared with the clean, second sample (SS) using in both liquid-based cytology. The quality of samples according to the Bethesda System, the presence of CIN, and inflammatory reactions were recorded. The sensitivity and specificity were calculated using biopsy as the gold standard. Results: The SS resulted in a higher proportion of adequate samples being obtained (97.6% vs. 44.8%), and in increased sensitivity (88.2% vs. 58.8%). CIN was detected in the SS 26% more often than in the CS (34 vs. 27 samples), whereas inflammatory reactions were noted more often in the CS (91.4% vs. 74%). Conclusion: Cervical sampling including CS results in lower sensitivity and CIN detection rates, and in more inflammatory reactions. By excluding CS from cervical samples, the sensitivity could be improved and the false negative rate could be reduced.