The diabetes management experiences questionnaire: Psychometric validation among adults with type 1 diabetes.

AIMS: To examine the psychometric properties of the Diabetes Management Experiences Questionnaire (DME-Q). Adapted from the validated Glucose Monitoring Experiences Questionnaire, the DME-Q captures satisfaction with diabetes management irrespective of treatment modalities. METHODS: The DME-Q was completed by adults with type 1 diabetes as part of a randomized controlled trial comparing hybrid closed loop (HCL) to standard therapy. Most psychometric properties were examined with pre-randomization data (n = 149); responsiveness was examined using baseline and 26-week follow-up data (n = 120). RESULTS: Pre-randomization, participants' mean age was 44 ± 12 years, 52% were women. HbA1c was 61 ± 11 mmol/mol (7.8 ± 1.0%), diabetes duration was 24 ± 12 years and 47% used an insulin pump prior to the trial. A forced three-factor analysis revealed three expected domains, that is, 'Convenience', 'Effectiveness' and 'Intrusiveness', and a forced one-factor solution was also satisfactory. Internal consistency reliability was strong for the three subscales ( α range = 0.74-0.84) and 'Total satisfaction' ( α = 0.85). Convergent validity was demonstrated with moderate correlations between DME-Q 'Total satisfaction' and diabetes distress (PAID: rs = -0.57) and treatment satisfaction (DTSQ; rs = 0.58). Divergent validity was demonstrated with a weak correlation with prospective/retrospective memory (PRMQ: rs = -0.16 and - 0.13 respectively). Responsiveness was demonstrated, as participants randomized to HCL had higher 'Effectiveness' and 'Total satisfaction' scores than those randomized to standard therapy. CONCLUSIONS: The 22-item DME-Q is a brief, acceptable, reliable measure with satisfactory structural and construct validity, which is responsive to intervention. The DME-Q is likely to be useful for evaluation of new pharmaceutical agents and technologies in research and clinical settings.

Bringing an end to diabetes stigma and discrimination: an international consensus statement on evidence and recommendations.

People with diabetes often encounter stigma (ie, negative social judgments, stereotypes, prejudice), which can adversely affect emotional, mental, and physical health; self-care, access to optimal health care; and social and professional opportunities. To accelerate an end to diabetes stigma and discrimination, an international multidisciplinary expert panel (n=51 members, from 18 countries) conducted rapid reviews and participated in a three-round Delphi survey process. We achieved consensus on 25 statements of evidence and 24 statements of recommendations. The consensus is that diabetes stigma is driven primarily by blame, perceptions of burden or sickness, invisibility, and fear or disgust. On average, four in five adults with diabetes experience diabetes stigma and one in five experience discrimination (ie, unfair and prejudicial treatment) due to diabetes, such as in health care, education, and employment. Diabetes stigma and discrimination are harmful, unacceptable, unethical, and counterproductive. Collective leadership is needed to proactively challenge, and bring an end to, diabetes stigma and discrimination. Consequently, we achieved unanimous consensus on a pledge to end diabetes stigma and discrimination.

Feasibility and acceptability of 'low-intensity mental health support via a telehealth-enabled network' for adults with type 1 and type 2 diabetes: the LISTEN pilot study.

BACKGROUND: This study examined the feasibility and acceptability of the low-intensity mental health support via telehealth-enabled network (LISTEN) intervention, for adults with diabetes, facilitated by diabetes health professionals (HPs). METHODS: LISTEN training. Three HPs participated in three half-day online workshops and applied their learnings during training cases (maximum four). Competency was assessed with a validated tool and achieved 'satisfactory' ratings for three consecutive sessions. LISTEN pilot. A single-group, pre-post study (up to four LISTEN sessions) with online assessments at baseline, post-intervention, and 4-week follow-up. Eligible participants were adults with type 1 or type 2 diabetes, with diabetes distress, but excluded if they had moderate/severe depressive and/or anxiety symptoms. Feasibility was assessed via recruitment and session completion rates. Acceptability was assessed with post-intervention self-report data. Changes in diabetes distress and general emotional well-being from baseline (T1) were explored at post-intervention (T2) and at 4-week follow-up (T3). RESULTS: Two HPs achieved competency (median training case sessions required: 7) and progressed to deliver LISTEN in the pilot study. In the pilot, N = 16 adults (Med [IQR] age: 60 [37-73] years; 13 women) with diabetes participated (median sessions per participant: 2). Twelve participants (75%) completed the post-intervention assessment (T2): 92% endorsed the number of sessions offered as 'just right', 75% felt comfortable talking with the HP, and 67% were satisfied with LISTEN. Perceived limitations were the structured format and narrow scope of problems addressed. Diabetes distress scores were lower post-intervention. CONCLUSIONS: This pilot demonstrates the feasibility of training HPs to deliver LISTEN, and the acceptability and potential benefits of LISTEN for adults with diabetes. The findings highlight adaptations that may enhance the delivery of, and satisfaction with, LISTEN that will be tested in a hybrid type 1 effectiveness-implementation trial.

Low-Intensity mental health Support via a Telehealth Enabled Network for adults with diabetes (LISTEN): protocol for a hybrid type 1 effectiveness implementation trial.

BACKGROUND: Mental health problems are common among people with diabetes. However, evidence-based strategies for the prevention and early intervention of emotional problems in people with diabetes are lacking. Our aim is to assess the real-world effectiveness, cost-effectiveness, and implementation of a Low-Intensity mental health Support via a Telehealth Enabled Network (LISTEN), facilitated by diabetes health professionals (HPs). METHODS: A hybrid type I effectiveness-implementation trial, including a two-arm parallel randomised controlled trial, alongside mixed methods process evaluation. Recruited primarily via the National Diabetes Services Scheme, Australian adults with diabetes (N = 454) will be eligible if they are experiencing elevated diabetes distress. Participants are randomised (1:1 ratio) to LISTEN-a brief, low-intensity mental health support program based on a problem-solving therapy framework and delivered via telehealth (intervention) or usual care (web-based resources about diabetes and emotional health). Data are collected via online assessments at baseline (T0), 8 weeks (T1) and 6 months (T2, primary endpoint) follow-up. The primary outcome is between-group differences in diabetes distress at T2. Secondary outcomes include the immediate (T1) and longer-term (T2) effect of the intervention on psychological distress, general emotional well-being, and coping self-efficacy. A within-trial economic evaluation will be conducted. Implementation outcomes will be assessed using mixed methods, according to the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework. Data collection will include qualitative interviews and field notes. DISCUSSION: It is anticipated that LISTEN will reduce diabetes distress among adults with diabetes. The pragmatic trial results will determine whether LISTEN is effective, cost-effective, and should be implemented at scale. Qualitative findings will be used to refine the intervention and implementation strategies as required. TRIAL REGISTRATION: This trial has been registered with the Australian New Zealand Clinical Trials Registry (ACTRN: ACTRN12622000168752) on 1 February, 2022.

Feasibility and acceptability of e-learning to upskill diabetes educators in supporting people experiencing diabetes distress: a pilot randomised controlled trial.

BACKGROUND: Diabetes distress is a commonly experienced negative emotional response to the ongoing burden of diabetes. Holistic diabetes care, including attention to diabetes distress, is recommended in clinical guidelines, yet not routinely implemented. Diabetes health professionals have highlighted lack of training as a barrier to implementation of psychological care. Therefore, we developed an e-learning: 'Diabetes distress e-learning: A course for diabetes educators' to address this need. This pilot study aimed to examine the feasibility of evaluating the e-learning in a randomised controlled trial study, the acceptability of the e-learning to credentialled diabetes educators (CDEs); and preliminary evidence of its effect upon CDEs' diabetes distress-related knowledge, motivation, confidence, behavioural skills, and barriers to implementation. METHODS: A pilot, unblinded, 2-armed, parallel group randomised controlled trial. Participants were recruited during a 4-month timeframe. Eligible participants were CDEs for ≥ 1 year providing care to ≥ 10 adults with type 1 or type 2 diabetes per week. Participants were randomly allocated (1:1 computer automated) to 1 of 2 learning activities: diabetes distress e-learning (intervention) or diabetes distress chapter (active control). They had 4 weeks to access the activity. They completed online surveys at baseline, 2-week and 12-week follow-up. RESULTS: Seventy-four eligible CDEs (36 intervention, 38 active control) participated. At baseline, recognition of the clinical importance of diabetes distress was high but knowledge and confidence to provide support were low-to-moderate. Engagement with learning activities was high (intervention: 83%; active control: 92%). Fifty-five percent returned at least 1 follow-up survey. All 30 intervention participants who returned the 2-week follow-up survey deemed the e-learning high quality and relevant. Systemic barriers (e.g., financial limitations and access to mental health professionals) to supporting people with diabetes distress were common at baseline and follow-up.  CONCLUSIONS: The e-learning was acceptable to CDEs. The study design was feasible but needs modification to improve follow-up survey return. The e-learning showed potential for improving diabetes distress-related knowledge, confidence and asking behaviours, but systemic barriers to implementation remained. Systemic barriers need to be addressed to facilitate implementation of support for diabetes distress in clinical practice. Future larger-scale evaluation of the e-learning is warranted.

The design of an evaluation framework for diabetes self-management education and support programs delivered nationally.

BACKGROUND: The aim of this work was to develop a National Evaluation Framework to facilitate the standardization of delivery, quality, reporting, and evaluation of diabetes education and support programs delivered throughout Australia through the National Diabetes Services Scheme (NDSS). The NDSS is funded by the Australian Government, and provides access to diabetes information, education, support, and subsidized product across diverse settings in each state and territory of Australia through seven independent service-providers. This article reports the approach undertaken to develop the Framework. METHODS: A participatory approach was undertaken, focused on adopting nationally consistent outcomes and indicators, nominating objectives and measurement tools, specifying evaluation processes, and developing quality standards. Existing programs were classified based on related, overarching indicators enabling the adoption of a tiered system of evaluation. RESULTS: Two outcomes (i.e., improved clinical, reduced cost) and four indicators (i.e., improved knowledge and understanding, self-management, self-determination, psychosocial adjustment) were adopted from the Eigenmann and Colagiuri national consensus position statement for diabetes education. This allowed for the identification of objectives (i.e., improved empowerment, reduced distress, autonomy supportive program delivery, consumer satisfaction) and related measurement instruments. Programs were categorized as comprehensive, topic-specific, or basic education, with comprehensive programs allocated to receive the highest-level of evaluation. Eight quality standards were developed, with existing programs tested against those standards. Based on the results of testing, two comprehensive (OzDAFNE for people with type 1 diabetes, DESMOND for people with type 2 diabetes), and eight topic-specific (CarbSmart, ShopSmart, MonitorSmart, FootSmart, MedSmart, Living with Insulin, Insulin Pump Workshop, Ready Set Go - Let's Move) structured diabetes self-management education and support programs were nominated for national delivery. CONCLUSIONS: The National Evaluation Framework has facilitated consistency of program quality, delivery, and evaluation of programs delivered by multiple service providers across diverse contexts. The Framework could be applied by other service providers who facilitate multiple diabetes education and support programs and could be adapted for use in other chronic disease populations where education and support are indicated.

Environmental DNA as Novel Technology: Lessons in Agenda Setting and Framing in News Media.

Environmental DNA (eDNA) is an emerging technology used for understanding ecosystems, environmental change, and stressors. Cellular and extracellular DNA are collected from environmental samples instead of individual wildlife animals, and as such eDNA comes with associated logistical and ethical benefits. It is increasingly being used, yet to date public knowledge and perceptions of eDNA have not been explored. Given that most of the public gathers scientific information from news media sources, this is a logical first place to start. This paper reports on a framing and agenda-setting analysis of news media coverage of eDNA in Canada and the United States from 2000 to 2020. The findings indicate that eDNA is being framed as an emerging and powerful tool, although questions regarding its validity and reliability are raised vis-à-vis identifying the presence of invasive species. Less than half of the news articles analyzed address broader social or ethical issues in relation to eDNA, and the majority focus on the potential financial impacts of eDNA findings on development projects and business interests. The potential ethical advantages of non-lethal sampling methods used via eDNA sampling are not addressed, nor are the potential ethical issues raised by its potential use in bioprospecting, indicating that the current state of agenda setting regarding eDNA in these newspapers is focused on economic impacts, to the exclusion of potential ethical issues. This unfolding news coverage will likely be key to understanding public perceptions of this novel technology.

Developing a novel diabetes distress e-learning program for diabetes educators: an intervention mapping approach.

Diabetes distress is a common negative emotional response to the ongoing burden of living with diabetes. Elevated diabetes distress is associated with impaired diabetes self-management and quality of life yet rarely identified and addressed in clinical practice. Health professionals report numerous barriers to the provision of care for diabetes distress, including lack of skills and confidence, but few diabetes distress training opportunities exist. The purpose of this paper is to describe how we utilized Intervention Mapping to plan the development, implementation, and evaluation of a novel diabetes distress e-learning program for diabetes educators, to meet a well-documented need and significant gap in diabetes care. A multidisciplinary team (combining expertise in research, health and clinical psychology, diabetes education, nursing, tertiary education, and website architecture) developed a diabetes distress e-learning program. We followed a six-step process (logic model of the problem, program outcomes and objectives, program design, program production, program implementation plan, and evaluation plan) known as Intervention Mapping. The program is underpinned by educational and psychological theory, including Bloom's Taxonomy of Educational Objectives and social cognitive theory. We developed a short (estimated 4 h) e-learning program for diabetes educators, which draws on the content of the Diabetes and Emotional Health handbook and toolkit. It integrates a 7As model, which provides a stepwise approach to identifying and addressing diabetes distress. Our diabetes distress e-learning program has been developed systematically, guided by an Intervention Mapping approach. In the next phase of the project, we will trial the e-learning.

Adults With Diabetes Distress Often Want to Talk With Their Health Professionals About It: Findings From an Audit of 4 Australian Specialist Diabetes Clinics.

OBJECTIVES: In an unselected clinical sample, we aimed to: 1) investigate the willingness of adults with diabetes to talk with their health professional(s) about their feelings and experiences living with diabetes, 2) assess the prevalence of impaired general emotional well-being and severe diabetes distress and 3) examine whether willingness to talk related to general and/or diabetes-specific emotional well-being. METHODS: Unselected adults with type 1 diabetes (T1D) or type 2 diabetes (T2D) attending 4 Australian specialist diabetes clinics completed surveys about their experiences of, and preferences for, talking with their diabetes health professional(s) about their feelings and personal experiences of diabetes. They indicated preferred topics to discuss from a list and completed validated measures of emotional well-being (World Health Organisation-5 Well-being Index) and diabetes distress (Problem Areas In Diabetes scale). RESULTS: Among 682 participants (T1D, n=440; T2D, n=142), one-fourth of adults with T1D and nearly half with T2D wanted to talk with their health professional about their "feelings and personal experience of living with diabetes," with >50% reported having been asked. The most commonly selected topic was "How diabetes affects my mood" (T1D, 35%; T2D, 37%). Impaired emotional well-being (T1D, 33%; T2D, 39%) and severe diabetes distress (T1D, 17%; T2D, 25%) were prevalent. Those willing to talk had greater diabetes distress. CONCLUSIONS: In this study we show that many adults with T1D and T2D both need and want to talk to their diabetes health professionals about the emotional impact of diabetes. Those who were most willing to have this conversation were most in need of emotional support.

The Diabetes and Emotional Health Handbook and Toolkit for Health Professionals Supporting Adults With Type 1 and Type 2 Diabetes: Formative Evaluation.

BACKGROUND: Health professionals have expressed unmet needs, including lacking the skills, confidence, training, and resources needed to properly attend to the psychological needs of people with diabetes. OBJECTIVE: Informed by needs assessments, this study aimed to develop practical, evidence-based resources to support health professionals to address the emotional needs of adults with type 1 or type 2 diabetes. METHODS: We developed a new handbook and toolkit informed by formative evaluation, including literature reviews, stakeholder consultation and review, and a qualitative study. In the qualitative study, health professionals participated in interviews after reading sections of the handbook and toolkit. RESULTS: The literature review uncovered that psychological problems are common among adults with diabetes, but health professionals lack resources to provide related support. We planned and drafted resources to fill this unmet need, guided by stakeholder consultation and an Expert Reference Group (ERG). Before finalizing the resources, we implemented feedback received from stakeholders (ERG, health professionals, academics, and people with diabetes). The resulting resources were the practical, evidence-based Diabetes and Emotional Health handbook and toolkit. A total of 19 health professionals took part in the qualitative study about the handbook and toolkit. They viewed the resources favorably, felt empowered to support people with diabetes experiencing psychological problems, and felt motivated to share the resources with others. Some gave examples of how they had used the handbook in clinical practice. A perceived highlight was the inclusion of a process model outlining 7 steps for identifying and supporting people with emotional problems: the 7 A's model. With funding from the National Diabetes Services Scheme (NDSS), more than 2400 copies of Diabetes and Emotional Health have been distributed. It is freely available on the Web. The NDSS is an initiative of the Australian Government administered with the assistance of Diabetes Australia. CONCLUSIONS: The new evidence-based resources are perceived by stakeholders as effective aids to assist health professionals in providing emotional support to adults with diabetes. The 7 A's model may have clinical utility for routine monitoring of other psychological and health-related problems, as part of person-centered clinical care.

Transcription fidelity: New paradigms in epigenetic inheritance, genome instability and disease.

RNA transcription errors are transient, yet frequent, events that do have consequences for the cell. However, until recently we lacked the tools to empirically measure and study these errors. Advances in RNA library preparation and next generation sequencing (NGS) have allowed the spectrum of transcription errors to be empirically measured over the entire transcriptome and in nascent transcripts. Combining these powerful methods with forward and reverse genetic strategies has refined our understanding of transcription factors known to enhance RNA accuracy and will enable the discovery of new candidates. Furthermore, these approaches will shed additional light on the complex interplay between transcription fidelity and other DNA transactions, such as replication and repair, and explore a role for transcription errors in cellular evolution and disease.

How Acts of Infidelity Promote DNA Break Repair: Collision and Collusion Between DNA Repair and Transcription.

Transcription is a fundamental cellular process and the first step in gene regulation. Although RNA polymerase (RNAP) is highly processive, in growing cells the progression of transcription can be hindered by obstacles on the DNA template, such as damaged DNA. The authors recent findings highlight a trade-off between transcription fidelity and DNA break repair. While a lot of work has focused on the interaction between transcription and nucleotide excision repair, less is known about how transcription influences the repair of DNA breaks. The authors suggest that when the cell experiences stress from DNA breaks, the control of RNAP processivity affects the balance between preserving transcription integrity and DNA repair. Here, how the conflict between transcription and DNA double-strand break (DSB) repair threatens the integrity of both RNA and DNA are discussed. In reviewing this field, the authors speculate on cellular paradigms where this equilibrium is well sustained, and instances where the maintenance of transcription fidelity is favored over genome stability.

Transcription infidelity and genome integrity: the parallax view.

It was recently shown that removal of GreA, a transcription fidelity factor, enhances DNA break repair. This counterintuitive result, arising from unresolved backtracked RNA polymerase impeding DNA resection and thereby facilitating RecA-loading, leads to an interesting corollary: error-free full-length transcripts and broken chromosomes. Therefore, transcription fidelity may compromise genomic integrity.

DksA and ppGpp Regulate the σS Stress Response by Activating Promoters for the Small RNA DsrA and the Anti-Adapter Protein IraP.

σS is an alternative sigma factor, encoded by the rpoS gene, that redirects cellular transcription to a large family of genes in response to stressful environmental signals. This so-called σS general stress response is necessary for survival in many bacterial species and is controlled by a complex, multifactorial pathway that regulates σS levels transcriptionally, translationally, and posttranslationally in Escherichia coli It was shown previously that the transcription factor DksA and its cofactor, ppGpp, are among the many factors governing σS synthesis, thus playing an important role in activation of the σS stress response. However, the mechanisms responsible for the effects of DksA and ppGpp have not been elucidated fully. We describe here how DksA and ppGpp directly activate the promoters for the anti-adaptor protein IraP and the small regulatory RNA DsrA, thereby indirectly influencing σS levels. In addition, based on effects of DksAN88I, a previously identified DksA variant with increased affinity for RNA polymerase (RNAP), we show that DksA can increase σS activity by another indirect mechanism. We propose that by reducing rRNA transcription, DksA and ppGpp increase the availability of core RNAP for binding to σS and also increase transcription from other promoters, including PdsrA and PiraP By improving the translation and stabilization of σS, as well as the ability of other promoters to compete for RNAP, DksA and ppGpp contribute to the switch in the transcription program needed for stress adaptation.IMPORTANCE Bacteria spend relatively little time in log phase outside the optimized environment found in a laboratory. They have evolved to make the most of alternating feast and famine conditions by seamlessly transitioning between rapid growth and stationary phase, a lower metabolic mode that is crucial for long-term survival. One of the key regulators of the switch in gene expression that characterizes stationary phase is the alternative sigma factor σS Understanding the factors governing σS activity is central to unraveling the complexities of growth, adaptation to stress, and pathogenesis. Here, we describe three mechanisms by which the RNA polymerase binding factor DksA and the second messenger ppGpp regulate σS levels.

The transcription fidelity factor GreA impedes DNA break repair.

Homologous recombination repairs DNA double-strand breaks and must function even on actively transcribed DNA. Because break repair prevents chromosome loss, the completion of repair is expected to outweigh the transcription of broken templates. However, the interplay between DNA break repair and transcription processivity is unclear. Here we show that the transcription factor GreA inhibits break repair in Escherichia coli. GreA restarts backtracked RNA polymerase and hence promotes transcription fidelity. We report that removal of GreA results in markedly enhanced break repair via the classic RecBCD-RecA pathway. Using a deep-sequencing method to measure chromosomal exonucleolytic degradation, we demonstrate that the absence of GreA limits RecBCD-mediated resection. Our findings suggest that increased RNA polymerase backtracking promotes break repair by instigating RecA loading by RecBCD, without the influence of canonical Chi signals. The idea that backtracked RNA polymerase can stimulate recombination presents a DNA transaction conundrum: a transcription fidelity factor that compromises genomic integrity.

Validation of the WHO-5 as a first-step screening instrument for depression in adults with diabetes: Results from Diabetes MILES - Australia.

AIMS: Screening for depression is recommended internationally. The World Health Organization's 5-item Well-being Index (WHO-5) is used clinically to screen for depression but its empirical suitability for this purpose is not well documented. We investigated the psychometric properties of the WHO-5 and its suitability for identifying likely depression in Australian adults with diabetes. METHODS: The Diabetes MILES - Australia study dataset provided a sample of N=3249 who completed the WHO-5 (positively-worded 5-item measure of emotional well-being) and the PHQ-9 (9-item measure of depressive symptoms). Analyses were conducted for the full sample, and separately by diabetes type and treatment (type 1, non-insulin-treated type 2, and insulin-treated type 2 diabetes). Construct (convergent and factorial) validity and reliability of the WHO-5 were examined. ROC analyses were used to examine the sensitivity and specificity of the WHO-5 as a depression screening instrument, comparing two commonly used WHO-5 cut-off values (≤7 and <13) with the PHQ-9. RESULTS: For the whole sample, the WHO-5 demonstrated satisfactory internal consistency reliability (α=0.90) and convergent validity with the PHQ-9 (r=-0.73, p<0.001). Confirmatory factor analysis partially supported factorial validity: Χ2(5)=834.94, p<0.001; RMSEA=0.23, 90% CI 0.21-0.24; CFI=0.98, TLI=0.96; factor loadings=0.78-0.92. The AUC was 0.87 (95% CI: 0.86-0.89, p<0.001). The sensitivity/specificity of the WHO-5 for detecting likely depression was 0.44/0.96 for the ≤7 cut-off, and 0.79/0.79 for the <13 cut-off, with similar findings by diabetes type and treatment. CONCLUSIONS: These findings support use of a WHO-5 cut-point of <13 to identify likely depression in Australian adults with diabetes, regardless of type/treatment.

Holliday junction trap shows how cells use recombination and a junction-guardian role of RecQ helicase.

DNA repair by homologous recombination (HR) underpins cell survival and fuels genome instability, cancer, and evolution. However, the main kinds and sources of DNA damage repaired by HR in somatic cells and the roles of important HR proteins remain elusive. We present engineered proteins that trap, map, and quantify Holliday junctions (HJs), a central DNA intermediate in HR, based on catalytically deficient mutant RuvC protein of Escherichia coli. We use RuvCDefGFP (RDG) to map genomic footprints of HR at defined DNA breaks in E. coli and demonstrate genome-scale directionality of double-strand break (DSB) repair along the chromosome. Unexpectedly, most spontaneous HR-HJ foci are instigated, not by DSBs, but rather by single-stranded DNA damage generated by replication. We show that RecQ, the E. coli ortholog of five human cancer proteins, nonredundantly promotes HR-HJ formation in single cells and, in a novel junction-guardian role, also prevents apparent non-HR-HJs promoted by RecA overproduction. We propose that one or more human RecQ orthologs may act similarly in human cancers overexpressing the RecA ortholog RAD51 and find that cancer genome expression data implicate the orthologs BLM and RECQL4 in conjunction with EME1 and GEN1 as probable HJ reducers in such cancers. Our results support RecA-overproducing E. coli as a model of the many human tumors with up-regulated RAD51 and provide the first glimpses of important, previously elusive reaction intermediates in DNA replication and repair in single living cells.

DksA involvement in transcription fidelity buffers stochastic epigenetic change.

DksA is an auxiliary transcription factor that interacts with RNA polymerase and influences gene expression. Depending on the promoter, DksA can be a positive or negative regulator of transcription initiation. Moreover, DksA has a substantial effect on transcription elongation where it prevents the collision of transcription and replication machineries, plays a key role in maintaining transcription elongation when translation and transcription are uncoupled and has been shown to be involved in transcription fidelity. Here, we assessed the role of DksA in transcription fidelity by monitoring stochastic epigenetic switching in the lac operon (with and without an error-prone transcription slippage sequence), partial phenotypic suppression of a lacZ nonsense allele, as well as monitoring the number of lacI mRNA transcripts produced in the presence and absence of DksA via an operon fusion and single molecule fluorescent in situ hybridization studies. We present data showing that DksA acts to maintain transcription fidelity in vivo and the role of DksA seems to be distinct from that of the GreA and GreB transcription fidelity factors.

The Healthy Migrant Families Initiative: development of a culturally competent obesity prevention intervention for African migrants.

BACKGROUND: Although obesity among immigrants remains an important area of study given the increasing migrant population in Australia and other developed countries, research on factors amenable to intervention is sparse. The aim of the study was to develop a culturally-competent obesity prevention program for sub-Saharan African (SSA) families with children aged 12-17 years using a community-partnered participatory approach. METHODS: A community-partnered participatory approach that allowed the intervention to be developed in collaborative partnership with communities was used. Three pilot studies were carried out in 2008 and 2009 which included focus groups, interviews, and workshops with SSA parents, teenagers and health professionals, and emerging themes were used to inform the intervention content. A cultural competence framework containing 10 strategies was developed to inform the development of the program. Using findings from our scoping research, together with community consultations through the African Review Panel, a draft program outline (skeleton) was developed and presented in two separate community forums with SSA community members and health professionals working with SSA communities in Melbourne. RESULTS: The 'Healthy Migrant Families Initiative (HMFI): Challenges and Choices' program was developed and designed to assist African families in their transition to life in a new country. The program consists of nine sessions, each approximately 1 1/2 hours in length, which are divided into two modules based on the topic. The first module 'Healthy lifestyles in a new culture' (5 sessions) focuses on healthy eating, active living and healthy body weight. The second module 'Healthy families in a new culture' (4 sessions) focuses on parenting, communication and problem solving. The sessions are designed for a group setting (6-12 people per group), as many of the program activities are discussion-based, supported by session materials and program resources. CONCLUSION: Strong partnerships and participation by SSA migrant communities enabled the design of a culturally competent and evidence-based intervention that addresses obesity prevention through a focus on healthy lifestyles and healthy families. Program implementation and evaluation will further inform obesity prevention interventions for ethnic minorities and disadvantaged communities.

Lost in transcription: transient errors in information transfer.

Errors in information transfer from DNA to RNA to protein are inevitable. Here, we focus on errors that occur in nascent transcripts during transcription, epimutations. Recent approaches using novel cDNA library preparation and next-generation sequencing begin to directly determine the rate of epimutation and allow analysis of the epimutational spectrum of transcription errors, the type and sequence context of the errors produced in a transcript by an RNA polymerase. The phenotypic consequences of transcription errors have been assessed using both forward and reverse epimutation systems. These studies reveal that transient transcription errors can produce a modification of cell phenotype, partial phenotypic suppression of a mutant allele, and a heritable change in cell phenotype, epigenetic switching in a bistable gene network.