Mitochondrial Trafficking of MLKL, Bak/Bax, and Drp1 Is Mediated by RIP1 and ROS which Leads to Decreased Mitochondrial Membrane Integrity during the Hyperglycemic Shift to Necroptosis.

Apoptosis and necroptosis overlap in their initial signaling but diverge to produce non-inflammatory and pro-inflammatory outcomes, respectively. High glucose pushes signaling in favor of necroptosis producing a hyperglycemic shift from apoptosis to necroptosis. This shift depends on receptor-interacting protein 1 (RIP1) and mitochondrial reactive oxygen species (ROS). Here, we show that RIP1, mixed lineage kinase domain-like (MLKL) protein, Bcl-2 agonist/killer (Bak), Bcl-2 associated x (Bax) protein, and dynamin-related protein 1 (Drp1) traffic to the mitochondria in high glucose. RIP1 and MLKL appear in the mitochondria in their activated, phosphorylated states while Drp1 appears in its activated, dephosphorylated state in high glucose. Mitochondrial trafficking is prevented in rip1 KO cells and upon treatment with N-acetylcysteine. Induction of ROS replicated the mitochondrial trafficking seen in high glucose. MLKL forms high MW oligomers in the outer and inner mitochondrial membranes while Bak and Bax form high MW oligomers in the outer mitochondrial membrane in high glucose, suggesting pore formation. MLKL, Bax, and Drp1 promoted cytochrome c release from the mitochondria as well as a decrease in mitochondrial membrane potential in high glucose. These results indicate that mitochondrial trafficking of RIP1, MLKL, Bak, Bax, and Drp1 are key events in the hyperglycemic shift from apoptosis to necroptosis. This is also the first report to show oligomerization of MLKL in the inner and outer mitochondrial membranes and dependence of mitochondrial permeability on MLKL.

Adverse Childhood Experiences among a Community of Resilient Centenarians and Seniors: Implications for a Chronic Disease Prevention Framework.

CONTEXT: Research has linked adverse childhood experiences (ACEs) with chronic disease in adults and diminished life span. Adverse biological embedding of ACEs potentially occurs through inflammatory mechanisms; inflammatory marker alterations are identified as candidate biomarkers for mediating health consequences. Lifestyle practices of residents of California's Loma Linda Blue Zone, one of five worldwide longevity hotspots, may provide insight into inflammation remediation and chronic disease prevention. Little research has been done on centenarians' early-life experiences or on ACEs in a longevity community. OBJECTIVE: To interview centenarians and seniors in this region regarding their childhood experiences to inform chronic disease prevention frameworks. DESIGN: Qualitative study of Loma Linda Blue Zone community members. Childhood exposures and practices were assessed using focus groups and semistructured key informant interviews, with open-ended questions on general hardships and ACEs and supplemented with lifestyle and resiliency factor questions. Data were audiorecorded and transcribed. Integrative grounded theory methods guided coding and theming. MAIN OUTCOME MEASURES: Exposure to ACEs and practice of resiliency factors. RESULTS: Participants (7 centenarians and 29 seniors) reported exposure to multiple ACEs (domains: Economic deprivation, family dysfunction, and community violence). Community members reported practicing resiliency factors, each with anti-inflammatory properties suggesting mitigation of ACE-related toxic stress. CONCLUSION: This is one of the first studies of its kind to identify a community of resilient members despite their tremendous burden of ACEs. Embedding the identified resiliency factors into chronic disease prevention frameworks has potential for mitigating systemic inflammation, alleviating chronic disease burden, and promoting a culture of health.

Strategic Partnerships for Change in an Environmental Justice Community: The ENRRICH Study.

BACKGROUND: San Bernardino, California, is home to the San Bernardino Railyard (SBR), a major commerce hub with high associated air-pollution, identified as an environmental justice (EJ) issue by local community and air quality agencies. Alarmingly, one elementary school is located only a few hundred yards from SBR. METHODS: The school, university researchers, and a local community-based organization (CBO) established a partnership to assess potential adverse health impacts in the children and develop interventions and mitigation plans. RESULTS: Study results comparing target school with a demographically matched school verified community concerns finding significantly poorer respiratory health in children attending school near the railyard. Partners are working with local and state collaboratives, the school board, and funding agencies to address the resulting needs of children through education, mitigation, and prevention in an environment where necessary systems changes involving the railyard are elusive. CONCLUSIONS: This paper shares lessons learned in moving toward change when addressing an EJ community's health challenges.

Experiences of a rail yard community: life is hard.

Community groups and local air pollution control agencies have identified the San Bernardino Railyard (SBR) as a significant public health and environmental justice issue. In response, the authors conducted a comprehensive study with community members living in close proximity to the rail yard. The purpose of this article is to share the community's perceptions about the rail yard and ideas on sustainable change. A qualitative study using key informant interviews and focus group discussions was conducted and resulted in four emerging themes. Themes emerged as follows: "health as an unattainable value," "air quality challenges," "rail yard pros and cons," and "violence and unemployment ripple effect." Community participants expressed concern for poor air quality, but other challenges took priority. The authors' findings suggest that future mitigation work to reduce air pollution exposure should not only focus on reducing risk from air pollution but address significant co-occurring community challenges. A "Health in All Policies" approach is warranted in addressing impacted communities in close proximity to the goods movement industry.

Making human subject protection training community responsive: experiences delivering on the community-based participatory research promise.

BACKGROUND: A community-based participatory research (CBPR) approach was used by the California-based Environmental Railyard Research (ENRRICH) Study, a partnership between scientists from Loma Linda University (LLU) and a local community organization, with the aim of assessing the health effects of exposure to emissions from a rail yard on a community. METHODS/RESULTS: To allow meaningful community participation in all study activities and comply with institutional review board (IRB) requirements, all participants involved needed to be properly trained and certified in the ethical conduct of human subjects (HS) research. Existing IRB training materials and the conventional certification methods designed for university scientists are not well-suited for community members who often face educational as well as language barriers. CONCLUSION: The purpose of this article is to share experiences in developing and implementing a customized human subject research curriculum, which was community responsive and addressed IRB requirements.

Analysis of international content of ranked nursing journals in 2005 using ex post facto design.

AIM: The purpose of this study was to examine articles in ISI-ranked nursing journals and to analyse the articles and journals, using definitions of international and article content. BACKGROUND: Growing emphasis on global health includes attention on international nursing literature. Contributions from Latin America and Africa have been reported. Attention to ranked nursing journals to support scholarship in global health is needed. METHOD: Using an ex post facto design, characteristics of 2827 articles, authors and journals of 32 ranked nursing journals for the year 2005 were analysed between June 2006 and June 2007. Using definitions of international and of article content, research questions were analysed statistically. FINDINGS: (a) 928 (32·8%) articles were international; (b) 2016 (71·3%) articles were empirical or scholarly; (c) 826 (89·3%) articles reflecting international content were scholarly or empirical; (d) among international articles more were empirical (66·3 % vs. 32·8 %; χ(2) ((1)) = 283·6, P < 0·001); (e) among non-international articles more were scholarly (29·2 % vs. 22·7 %; χ(2) ((1)) = 15·85, P < 0·001; 22·7 %); (f) 1004 (78·0 %) articles were international, based on author characteristics; (f) 20 (62·5 %) journals were led by an international editorial team; and (g) international journals had more international articles (3·6 % vs. 29·2 %; χ(2) ((1)) = 175·75, P < 0·001) and higher impact factors than non-international journals (t = -14·43, P < 0·001). CONCLUSION: Articles with empirical content appear more frequently in international journals. Results indicate the need to examine the international relevance of the nursing literature.

Online survey of nursing journal peer reviewers: indicators of quality in manuscripts.

Nursing journal peer reviewers (N = 1,675) completed a 69-item online survey that assessed their views on manuscripts' contributions to nursing, priorities in writing reviews, use of journal impact factor, and other areas related to indicators of quality. They reported using contribution to knowledge or research evidence, topic of current interest, and newly emerging area as indicators of a manuscript's contribution to nursing. In writing their reviews, research rigor and clinical relevance of the manuscript were high priorities. Those familiar with the concept of impact factor were significantly more often not nurses; not United States residents; involved in research; and most often reviewed for journals that published only research or a scholarly mix of research, reviews, policy, and theory. When judging a paper's contribution, nursing journal peer reviewers weigh both research and clinical interests. Most reviewers do not use impact factors and place clinical considerations ahead of impact factors.

Ethical concerns of nursing reviewers: an international survey.

Editors of scientific literature rely heavily on peer reviewers to evaluate the integrity of research conduct and validity of findings in manuscript submissions. The purpose of this study was to describe the ethical concerns of reviewers of nursing journals. This descriptive cross-sectional study was an anonymous online survey. The findings reported here were part of a larger investigation of experiences of reviewers. Fifty-two editors of nursing journals (six outside the USA) agreed to invite their review panels to participate. A 69-item forced-choice and open-ended survey developed by the authors based on the literature was pilot tested with 18 reviewers before being entered into SurveyMonkey(TM). A total of 1675 reviewers responded with useable surveys. Six questions elicited responses about ethical issues, such as conflict of interest, protection of human research participants, plagiarism, duplicate publication, misrepresentation of data and 'other'. The reviewers indicated whether they had experienced such a concern and notified the editor, and how satisfied they were with the outcome. They provided specific examples. Approximately 20% of the reviewers had experienced various ethical dilemmas. Although the majority reported their concerns to the editor, not all did so, and not all were satisfied with the outcomes. The most commonly reported concern perceived was inadequate protection of human participants. The least common was plagiarism, but this was most often reported to the editor and least often led to a satisfactory outcome. Qualitative responses at the end of the survey indicate this lack of satisfaction was most commonly related to feedback provided on resolution by the editor. The findings from this study suggest several areas that editors should note, including follow up with reviewers when they identify ethical concerns about a manuscript.

Scientific and statistical reviews of manuscripts submitted to Nursing Research: Comparison of completeness, quality, and usefulness.

Sound statistical analysis is fundamental to high-quality reporting of quantitative studies. Peer review are also important in determining whether statistical procedures in submitted manuscripts are appropriate and effectively reported. However, the quality of statistical reviews of manuscripts submitted to nursing journals has not been previously evaluated. The purpose of this project was to compare the content and quality of statistical and scientific (general) reviews of manuscripts submitted to Nursing Research. The General Assessment of Reviews of Nursing Research (GARNR) and the Statistical Assessment of Reviews of Nursing Research (SARNR) were used to evaluate 105 reviews of 35 manuscripts assigned to both scientific and statistical review between August 2007 and February 2009. Scientific reviews were rated as more comprehensive, but most did not evaluate statistical aspects of a manuscript. Statistical reviews were more likely to identify fatal flaws, were generally rated higher in overall usefulness to the editor in making a decision on whether to publish, and were rated as more useful to authors for improving a manuscript. Statistical and scientific reviews are complementary and both are necessary. More thorough integration of substantive and methodological content in reviews of quantitative studies has potential for even greater leverage of effort and improved quality of nursing research reports.

Peer reviewer training and editor support: results from an international survey of nursing peer reviewers.

TOPIC: Nursing journals depend on the services of peer reviewers for their expertise in research and clinical practice. Although some research has been done with peer reviewers of biomedical journals, to date, our knowledge about reviewers of nursing journals is minimal. METHODS: In this international survey of 1,675 reviewers for 41 nursing journals, reviewers were asked 69 questions about their experiences reviewing for professional nursing journals. This article examines their answers to the survey questions about training to become reviewers and the support they receive from editors. RESULTS: Results showed that 65% wanted formal training, although only about 30% received such training in the form of orientation, manuals, practice reviews, or workshops. For most peer reviewers, it took one to five reviews before they felt comfortable with the process, although some commented that, "I still question my reviews" and "It took a few years." In this sample, 31% reported getting feedback from editors about their reviews, but 87% wanted feedback. Most (80%) wanted to see the other reviews of the manuscripts they reviewed, although only about 45% actually saw them. Reviewers reported that the editor had been helpful to them by providing feedback, demonstrating appreciation of their efforts, mentoring, and being available. CONCLUSIONS: We concluded from this research that many reviewers' needs for training and support are not being met and that both reviewers and nursing editors could profit from a better understanding of the process. Editors could consider instituting programs of orientation, training, and support such as feedback on reviews, making other reviews available, and feedback on final disposition of manuscripts. Reviewers should consider discussing these issues with editors to make their needs for feedback and training known. Intervention studies to examine the effects of such programs on reviewer satisfaction could ultimately strengthen the nursing literature.

Prevalence and impact on quality of life of lower urinary tract symptoms among a sample of employed women in Taipei: a questionnaire survey.

BACKGROUND: Previous studies about the prevalence and impact of lower urinary tract symptoms (LUTS) were focused on urinary incontinence or overactive bladder in the general population. Little research has been focused on the role that the workplace has in employed women's experiences with LUTS or the impact of LUTS on their health-related quality of life (HRQL). OBJECTIVES: To estimate the prevalence of LUTS among employed female nurses in Taipei and to compare the HRQL for nurses with and without LUTS. DESIGN: This study was a cross-sectional, questionnaire survey. SETTINGS: Three medical centers and five regional hospitals in Taipei were selected randomly. PARTICIPANTS: In the selected hospitals, 1065 female nurses were selected randomly. Data analyses were based on 907 usable surveys. All participants were native Taiwanese; most of the female nurses were 26-35 years of age (mean=31.02, SD=6.32), had normal body mass index, and had never given birth. Most nurses' bladder habits were poor or very poor and their personal habits of fluid consumption at work were inadequate. METHODS: Data were collected using the Taiwan Nurse Bladder Survey and the Short Form 36 Taiwan version. Chi-square tests were used to compare the prevalence rates of different LUTS for nurses in different age groups. Student's t-tests were conducted to compare the mean scores of HRQL for nurses with and without LUTS. RESULTS: Based on 907 usable surveys, 590 (65.0%) experienced at least one type of LUTS. The prevalence for different LUTS ranged from 8.0% to 46.5%. Nurses who reported LUTS also reported lower HRQL, more so on physical health than mental health, than nurses who did not report LUTS. CONCLUSIONS: Although most of the nurses in this study were young (< or =35 years) and nulliparous, LUTS were common among this group. The high prevalence rate of LUTS leads to concerns about nurses' possible dysfunctional voiding patterns and possible effects of working environment and poor bladder and personal habits on LUTS. Study results showed a possible negative impact of LUTS on nurses' physical health. Designing a continence-related education program for this group is essential for delivering information about LUTS prevention and management.

Quality of manuscript reviews in nursing research.

Dissemination of research findings through publication of results in peer reviewed journals is the gold standard in nursing science. Yet, little is known about quality of manuscript reviews or factors associated with review quality. The purpose of this project was to refine a methodology for assessing quality of reviews and then to evaluate review quality. We created a continuous quality improvement process to assess the narrative portion of 464 reviews of 203 manuscripts submitted to Nursing Research from August 2006-July 2007. The General Assessment of Reviews of Nursing Research (GARNR) was developed to measure quality. Inter-rater reliability of the average of 2 raters' scores was satisfactory for most items and the scales. Quality was better for technical (design and methods) rather than background (theory and review of literature) aspects of a manuscript. Based on assessment of global quality, 18.9% of the reviews were deemed poor or inadequate. On average, statistical reviews were rated more highly than regular reviews, and reviewers from research intensive institutions wrote higher quality reviews than others. Recommendations for monitoring quality in the review process and guidelines for preparation of the review narrative to improve quality are made.

Experience, time investment, and motivators of nursing journal peer reviewers.

PURPOSE: To describe nursing journal reviewers' professional backgrounds, reviewing experience, time investment, and perceptions of their role. DESIGN: Exploratory descriptive cross-sectional study. METHODS: A 69-question survey containing both fixed-option and open-ended questions and accessed via the World Wide Web was completed by 1,675 nursing journal reviewers who had been invited to participate by editors of 52 nursing journals. FINDINGS: Participants were from 44 countries, with 74% from the US, and 90% were nurses. The majority were doctorally prepared academics who were involved in research. They reported spending an average of 5 hours on each critique and completed an average of 7-8 reviews per year. The most common reason reported for becoming involved was personal contact with an editor. Lack of time because of competing work commitments was the most commonly cited barrier to reviewing and negative aspect of the role. The most common positive aspect was keeping up to date with the field. CONCLUSIONS: Nursing journal peer reviewers express rewards and challenges similar to those reported elsewhere for biomedical journal reviewers. Based on these findings, editors might consider new approaches to recruiting and supporting reviewers, and potential reviewers might gain insight into the role. Support of these distinguished scholars in this important role is critical to sustain the quality of scholarship that informs nursing practice, education, and research. CLINICAL RELEVANCE: Clinicians, researchers, and educators who rely on the quality of the articles published in nursing journals can learn from this survey about the background and experiences of those who protect that quality by providing expert feedback to authors and editors.

Blinding in peer review: the preferences of reviewers for nursing journals.

AIM: This paper is a report of a study to assess the beliefs and preferences of reviewers for nursing journals about blinding of authors to reviewers, reviewers to authors, neither or both. BACKGROUND: Blinding of author and reviewer names in the manuscript review process has been of interest to nursing editors, but reports that are based on data rather than simply opinion concern the editorial practices of biomedical rather than nursing journals. There has been no study of nursing journal reviewer beliefs and preferences related to blinding. METHOD: A descriptive web-based survey was conducted. The sample included 1675 anonymous reviewers, recruited through 52 editors of nursing journals from their review panels. Data were collected in 2007. FINDINGS: Double-blinding of reviews was the most common method reported. Ninety per cent of respondents reported that the papers they received to review did not include author names. When author names were blinded, 62% of reviewers could not identify the authors of papers; another 17% could identify authors < or =10% of the time. Double-blinding was the method preferred by 93.6% of reviewers, although some identified some advantages to an unblinded open review process. CONCLUSION: Nursing journal reviewers are generally very satisfied with double-blinding and believe it contributes to the quality of papers published. Editors or editorial boards interested in a more open review process could consider alternatives such as offering authors and reviewers the option to unblind themselves. Simply announcing that the review process will henceforth be unblinded would probably lead to loss of reviewers.

Factors related to lower urinary tract symptoms among a sample of employed women in Taipei.

AIM: To identify factors associated with lower urinary tract symptoms (LUTS) among female elementary school teachers in Taipei. METHODS: This study is a cross-sectional, descriptive study. A total of 520 surveys were distributed to 26 elementary schools in Taipei. Logistic regression was used to identify possible factors related to individual LUTS. RESULTS: Study results were based on the information provided by 445 participants. Of the 445 teachers, 293 (65.8%) experienced at least one type of LUTS. Factors associated with urinary incontinence were body mass index (BMI), vaginal delivery, obstetric and/or gynecological surgery, bladder habits, and job control. Increased daytime urinary frequency was associated with chronic cough and chronic constipation. Bladder habits, straining to lift heavy objects at work and chronic constipation were associated with urgency. Nocturia was associated with age and caffeine consumption while intermittent stream was associated with the presence of a family history of LUTS and chronic constipation. Bladder habits and regular exercise were associated with weak urinary stream. Incomplete emptying was more likely to occur in teachers with chronic constipation and in those who did not exercise regularly. CONCLUSION: All the LUTS under logistic regression analyses were associated with 1-3 modifiable factors. Identification of these modifiable contributing factors may be useful to health care providers. Education of women may include the importance of maintaining normal body weight, good bladder/bowel habits, and regular exercise, treating chronic cough, decreasing daily caffeine consumption, and implementing feasible environmental modifications in employment settings.