The ubiquitin ligase RFWD3 is required for translesion DNA synthesis.

Lesions on DNA uncouple DNA synthesis from the replisome, generating stretches of unreplicated single-stranded DNA (ssDNA) behind the replication fork. These ssDNA gaps need to be filled in to complete DNA duplication. Gap-filling synthesis involves either translesion DNA synthesis (TLS) or template switching (TS). Controlling these processes, ubiquitylated PCNA recruits many proteins that dictate pathway choice, but the enzymes regulating PCNA ubiquitylation in vertebrates remain poorly defined. Here we report that the E3 ubiquitin ligase RFWD3 promotes ubiquitylation of proteins on ssDNA. The absence of RFWD3 leads to a profound defect in recruitment of key repair and signaling factors to damaged chromatin. As a result, PCNA ubiquitylation is inhibited without RFWD3, and TLS across different DNA lesions is drastically impaired. We propose that RFWD3 is an essential coordinator of the response to ssDNA gaps, where it promotes ubiquitylation to drive recruitment of effectors of PCNA ubiquitylation and DNA damage bypass.

SCAI promotes error-free repair of DNA interstrand crosslinks via the Fanconi anemia pathway.

DNA interstrand crosslinks (ICLs) are cytotoxic lesions that threaten genome integrity. The Fanconi anemia (FA) pathway orchestrates ICL repair during DNA replication, with ubiquitylated FANCI-FANCD2 (ID2) marking the activation step that triggers incisions on DNA to unhook the ICL. Restoration of intact DNA requires the coordinated actions of polymerase ζ (Polζ)-mediated translesion synthesis (TLS) and homologous recombination (HR). While the proteins mediating FA pathway activation have been well characterized, the effectors regulating repair pathway choice to promote error-free ICL resolution remain poorly defined. Here, we uncover an indispensable role of SCAI in ensuring error-free ICL repair upon activation of the FA pathway. We show that SCAI forms a complex with Polζ and localizes to ICLs during DNA replication. SCAI-deficient cells are exquisitely sensitive to ICL-inducing drugs and display major hallmarks of FA gene inactivation. In the absence of SCAI, HR-mediated ICL repair is defective, and breaks are instead re-ligated by polymerase θ-dependent microhomology-mediated end-joining, generating deletions spanning the ICL site and radial chromosomes. Our work establishes SCAI as an integral FA pathway component, acting at the interface between TLS and HR to promote error-free ICL repair.

Survivors of infant atypical teratoid/rhabdoid tumors present with severely impaired cognitive functions especially for fluid intelligence and visual processing: data from the German brain tumor studies.

BACKGROUND: The contribution of tumor type, multimodal treatment, and other patient-related factors upon long-term cognitive sequelae in infant brain tumor survivors remains undefined. We add our retrospective analysis of neuropsychological and quality of survival (QoS) outcome data of survivors of atypical teratoid/rhabdoid tumors (ATRT) and extracranial malignant rhabdoid tumors of the soft tissues (eMRT) and kidneys (RTK) treated within the same framework. Neuropsychological data from children with ATRT were compared to data from children with non-irradiated low-grade glioma (LGG). PATIENTS AND METHODS: Following surgery, patients (0-36 months at diagnosis) had received radio-chemotherapy (up to 54 Gy; ATRT: n = 13; eMRT/RTK: n = 7), chemotherapy only (LGG: n = 4; eMRT/RTK: n = 1) or had been observed (LGG: n = 11). Neuropsychological evaluation employing comparable tests was performed at median 6.8 years (ATRT), 6.6 years (eMRT/RTK), and 5.2 years (LGG) post diagnosis. RESULTS: We detected sequelae in various domains for all tumor types. Group comparison showed impairments, specifically in fluid intelligence (p = .041; d = 1.11) and visual processing (p = .001; d = 2.09) in ATRT patients when compared to LGG patients. Results for psychomotor speed and attention abilities were significantly below the norm for both groups (p < .001-.019; d = 0.79-1.90). Diagnosis predicted impairments of cognitive outcome, while sex- and age-related variables did not. QoS outcome for all rhabdoid patients displayed impairments mainly in social (p = .008; d = 0.74) and school functioning (p = .048; d = 0.67), as well as lower overall scores in psychosocial functioning (p = .023; d = 0.78) and quality of life (p = .006; d = 0.79) compared to healthy controls. CONCLUSION: Survivors of infant ATRT experience various late effects in cognition and QoS following multimodal treatment, while infant LGG patients without radiotherapy demonstrated comparable impairments in psychomotor and attention abilities. Early onset and multimodal treatment of rhabdoid tumors require close monitoring of neuropsychological and QoS sequelae.

RADX interacts with single-stranded DNA to promote replication fork stability.

Single-stranded DNA (ssDNA) regions form as an intermediate in many DNA-associated transactions. Multiple cellular proteins interact with ssDNA via the oligonucleotide/oligosaccharide-binding (OB) fold domain. The heterotrimeric, multi-OB fold domain-containing Replication Protein A (RPA) complex has an essential genome maintenance role, protecting ssDNA regions from nucleolytic degradation and providing a recruitment platform for proteins involved in responses to replication stress and DNA damage. Here, we identify the uncharacterized protein RADX (CXorf57) as an ssDNA-binding factor in human cells. RADX binds ssDNA via an N-terminal OB fold cluster, which mediates its recruitment to sites of replication stress. Deregulation of RADX expression and ssDNA binding leads to enhanced replication fork stalling and degradation, and we provide evidence that a balanced interplay between RADX and RPA ssDNA-binding activities is critical for avoiding these defects. Our findings establish RADX as an important component of cellular pathways that promote DNA replication integrity under basal and stressful conditions by means of multiple ssDNA-binding proteins.

The impact and importance of place on health for young people of Pasifika descent in Queensland, Australia: a qualitative study towards developing meaningful health equity indicators.

BACKGROUND: Health equity is a priority in the global sustainable development agenda. Available health equity indicators often focus on health outcomes, access to healthcare, risk factors and determinants such as income, education, and gender. Less attention has been given to other social determinants, including those related to place and ethnicity. Measures such as income, education, and gender, however, may not provide policy-makers with sufficient information to redress inequities. In this paper, we begin to develop health equity indicators for young Pasifika peoples in Logan, Queensland, Australia. While health data on Pasifika young people in Queensland is scant, available data suggests significant inequalities. The purpose of the study was to develop an understanding of the drivers of these disparities through the lens of the social determinants of health, to create health equity indicators. METHODS: Following meetings with community stakeholders to develop respectful and collaborative partnership processes, we took a youth participatory action research approach. Six peer researchers (3 male, 3 female) were recruited from the Logan area for the project. Following training, the peer researchers undertook 31 qualitative interviews with young Pasifika (16-24 years old). Data was manually analysed, coded and grouped into themes to develop the draft indicators. Interviews used the culturally appropriate Talanoa storytelling approach. RESULTS: Six key themes were identified from the interviews and were used to develop example indicators related to: spiritual and socio-cultural dimensions, place, access to culturally responsive services, economic and material dimensions and political dimensions. The results demonstrate health inequities experienced by Pasifika populations are strongly linked to place and their economic, social and cultural position. CONCLUSIONS: This study emphasises the need to understand the multiplicity of place-based factors that interact in complex ways to shape health inequities for young Pasifika peoples. It highlights health equity indicators must go beyond healthcare services, outcomes and a limited number of objective determinants, to include a more holistic focus. Starting to measure health and wellbeing via the lens of the social determinants of health will help to identify where policy-makers and programmes can intervene to begin to more adequately address inequities.

Evaluation of the Good Start Program: a healthy eating and physical activity intervention for Maori and Pacific Islander children living in Queensland, Australia.

BACKGROUND: Reducing the prevalence of obesity and chronic disease are important priorities. Maori and Pacific Islander communities living in Australia have higher rates of obesity and chronic disease than the wider Australian population. This study aims to assess the effectiveness of the Good Start program, which aims to improve knowledge, attitudes and practices related to healthy eating and physical activity amongst Maori and Pacific Islander communities living in Queensland. METHODS: The intervention was delivered to children aged 6-19 years (N = 375) in schools by multicultural health workers. Class activities focused on one message each term related to healthy eating and physical activity using methods such as cooking sessions and cultural dance. The evaluation approach was a quantitative uncontrolled pre-post design. Data were collected each term pre- and post-intervention using a short questionnaire. RESULTS: There were significant increases in knowledge of correct servings of fruit and vegetables, knowledge of sugar and caffeine content of common sugar-sweetened drinks, recognition of the consequences of marketing and upsizing, and the importance of controlling portion size (all P < 0.05). There was also increases in knowledge of physical activity recommendations (P < 0.001), as well as the importance of physical activity for preventing heart disease (P < 0.001) and improving self-esteem (P < 0.001). In terms of attitudes, there were significant improvements in some attitudes to vegetables (P = 0.02), and sugar-sweetened drinks (P < 0.05). In terms of practices and behaviours, although the reported intake of vegetables increased significantly (P < 0.001), the proportion of children eating discretionary foods regularly did not change significantly, suggesting that modifying the program with an increased emphasis on reducing intake of junk food may be beneficial. CONCLUSION: The study has shown that the Good Start Program was effective in engaging children from Maori and Pacific Island backgrounds and in improving knowledge, and some attitudes and practices, related to healthy eating and physical activity. The evaluation contributes valuable information about components and impacts of this type of intervention, and considerations relevant to this population in order to successfully change behaviours and reduce the burden of chronic disease.

Perspectives of key stakeholders and experts in infant feeding on the implementation of the Australian National Breastfeeding Strategy 2010-2015.

Breastfeeding is widely accepted as an important public health issue for babies and their mothers. Yet, despite this, Australia continues to struggle with reaching global targets for breastfeeding indicators. In 2007, the Best Start Parliamentary Inquiry Report was released and set the stage for the Australian National Breastfeeding Strategy [2010-2015), which was announced in November 2009, with the vision to increase Australia's breastfeeding rates of infants at 6 months of age and beyond. The aim of this research project was to explore the perspectives of key stakeholders in the field of infant feeding in Australia on the implementation of the strategy, barriers and enablers to its successful implementation and actions that were still needed. Using qualitative research methods of in-depth, semi-structured interviews and thematic analysis, this study identifies main themes of these perceptions about the strategy implementation and some recommendations for future strategies and further research. The main themes identified were initial opinions of the strategy as a blueprint for action, the strategy as a driver for action, lessons learned and recommendations for the future. For success in improving implementation of national breastfeeding strategies, it is recommended that Australia establish an independent breastfeeding/infant feeding committee, increase the political prioritisation of issues surrounding infant feeding and strengthen the regulation of the marketing of breastmilk substitutes.

The effect of zinc supplementation on body composition and hormone levels related to adiposity among children: a systematic review.

OBJECTIVE: To provide a comprehensive synthesis of the effects of Zn supplementation on childhood body composition and adiposity-related hormone levels. DESIGN: Five electronic databases were searched for randomized controlled trials of Zn supplementation studies published before 28 February 2015. No statistical pooling of results was carried out due to diversity in study designs. SETTING: Community- or hospital-based, from fourteen developing and developed countries. SUBJECTS: Children and adolescents aged 0 to 10 years. RESULTS: Seven of the fourteen studies reported an overall or subgroup effect of Zn supplementation on at least one parameter of body composition, when determined by anthropometric measurements (increased mid upper-arm circumference, triceps skinfold, subscapular skinfold and mid upper-arm muscle area, and decreased BMI). Three out of the fourteen studies reported increased mean value of total body water estimated by bio-impedance analysis and increased fat-free mass estimated by dual energy X-ray absorptiometry and by total body water. Zn supplementation was associated with increased fat-free mass among stunted children. One study found supplementation decreased leptin and insulin concentrations. CONCLUSIONS: Due to the use of anthropometry when determining body composition, a majority of the studies could not accurately address whether alterations in the fat and/or fat-free mass components of the body were responsible for the observed changes in body composition. The effect of Zn supplementation on body composition is not consistent but may modify fat-free mass among children with pre-existing growth failure.

Dietary habits of Samoan adults in an urban Australian setting: a cross-sectional study.

OBJECTIVE: To describe key characteristics of the dietary habits of Samoans residing in Logan, Queensland and to compare these characteristics with comparable populations. DESIGN: Dietary intake was measured using a self-administered structured questionnaire between December 2012 and March 2013. Demographic characteristics included age and sex. Questionnaire results were compared with data from samples of Brisbane residents of similar social and economic characteristics and Pacific Islanders in New Zealand. The association between demographic characteristics and diet was investigated. SETTING: Logan, Queensland, Australia. SUBJECTS: Samoans aged 16 years and older. RESULTS: A total of 207 Samoans participated, ninety-six (46 %) of whom were male. Of the participants, seventy-nine (38 %) were aged 16-29 years, sixty-three (30 %) were aged 30-49 years and sixty-five (31 %) were aged ≥50 years. Younger adults were significantly more likely to eat hamburgers, pizza, cakes, savoury pastries, potato crisps, sweets and soft drinks (all variables P<0·001). Among Samoans, 44·7 % consumed two or more pieces of fruit daily, compared with 43·8 % of comparable Brisbane residents (relative risk=1·0; 95 % CI 0·8, 1·2). Three or more servings of vegetables each day were consumed by 9·2 % of Samoans compared with 36·6 % of comparable Brisbane residents (relative risk=3·8; 95 % CI 2·5, 6·0). CONCLUSIONS: Samoans are consuming significantly fewer vegetables and more discretionary foods than other populations. Socio-economic factors, length of stay in Australia and cultural practices may impact upon Samoans' diets. Further comprehensive studies on Samoans' dietary habits in Australia are recommended.

Breastfeeding experiences of Aboriginal and Torres Strait Islander mothers in an urban setting in Brisbane.

STUDY AIM: This study examined urban Aboriginal and Torres Strait Islander mothers' breastfeeding experiences to inform support for mothers and their families. STUDY DESIGN: The research took a strengths approach, using qualitative methodology. Twenty semi-structured in-depth face-to-face interviews were conducted and analysed thematically. SETTING AND PARTICIPANTS: Indigenous mothers of infants 3 to 12 months were recruited through a Brisbane Indigenous health service. KEY FINDINGS: All mothers recounted considerable physical and emotional energy invested in breastfeeding. Although early introduction of formula made sense for some mothers under stressful circumstances, timely pro-breastfeeding support from family and health professionals facilitated continued breastfeeding. Professional and social/family contacts play key roles in steering infant feeding outcomes. CONCLUSIONS: Mothers' experiences strongly influence infant feeding strategies. Aboriginal and Torres Strait Islander community strengths are underutilised in supporting breastfeeding mothers. FUTURE IMPLICATIONS: Indigenous mothers, family and community strengths present points for engagement in future breastfeeding promotion and support initiatives.

Re-imagining the 'social' in the nutrition sciences.

OBJECTIVE: In response to The New Nutrition Science Project's Giessen Declaration, we provide here a case for a more fully described and integrated 'social' dimension within the nutrition sciences. DESIGN: This paper explores what we mean when we argue for socially engaged nutrition sciences (SENS), and describes the disciplinary fields, epistemologies and methodologies that contribute to SENS' potential rich diversity and value. Additionally, the current positioning of 'social nutrition' research within the nutrition sciences is critiqued. RESULTS: There is fairly broad acceptance of the 'social' as an important contributor to successful public health nutrition situation analyses, intervention planning and implementation. However, we assert that the 'social' is not merely a contributor, the usual position, but is central. Implications for policy and practice that could follow from this shift in approach are outlined. CONCLUSIONS: We call for researchers, educators, policy makers and practitioners alike to re-imagine the role and purpose of social science enquiry that could enable the delivery of more socially engaged nutrition sciences.

The Fatty Liver Assessment in Germany (FLAG) cohort study identifies large heterogeneity in NAFLD care.

BACKGROUND & AIMS: NAFLD is a growing health concern. The aim of the Fatty Liver Assessment in Germany (FLAG) study was to assess disease burden and provide data on the standard of care from secondary care. METHODS: The FLAG study is an observational real-world study in patients with NAFLD enrolled at 13 centres across Germany. Severity of disease was assessed by non-invasive surrogate scores and data recorded at baseline and 12 months. RESULTS: In this study, 507 patients (mean age 53 years; 47% women) were enrolled. According to fibrosis-4 index, 64%, 26%, and 10% of the patients had no significant fibrosis, indeterminate stage, and advanced fibrosis, respectively. Patients with advanced fibrosis were older, had higher waist circumferences, and higher aspartate aminotransferase and gamma-glutamyltransferase as well as ferritin levels. The prevalence of obesity, arterial hypertension, and type 2 diabetes increased with fibrosis stages. Standard of care included physical exercise >2 times per week in 17% (no significant fibrosis), 19% (indeterminate), and 6% (advanced fibrosis) of patients. Medication with either vitamin E, silymarin, or ursodeoxycholic acid was reported in 5%. Approximately 25% of the patients received nutritional counselling. According to the FibroScan-AST score, 17% of patients presented with progressive non-alcoholic steatohepatitis (n = 107). On follow-up at year 1 (n = 117), weight loss occurred in 47% of patients, of whom 17% lost more than 5% of body weight. In the weight loss group, alanine aminotransferase activities were reduced by 20%. CONCLUSIONS: This is the first report on NAFLD from a secondary-care real-world cohort in Germany. Every 10th patient presented with advanced fibrosis at baseline. Management consisted of best supportive care and lifestyle recommendations. The data highlight the urgent need for systematic health agenda in NAFLD patients. LAY SUMMARY: FLAG is a real-world cohort study that examined the liver disease burden in secondary and tertiary care. Herein, 10% of patients referred to secondary care for NAFLD exhibited advanced liver disease, whilst 64% had no significant liver scarring. These findings underline the urgent need to define patient referral pathways for suspected liver disease.

Using systems thinking and the Intervention Level Framework to analyse public health planning for complex problems: Otitis media in Aboriginal and Torres Strait Islander children.

BACKGROUND: Middle ear disease (otitis media) is endemic among Aboriginal and Torres Strait Islander children in Australia and represents an important cause of hearing loss. The disease is the result of a mix of biological, environmental and host risk factors that interact in complex, non-linear ways along a dynamic continuum. As such, it is generally recognised that a holistic, systems approach is required to reverse the high rates of otitis media in Aboriginal and Torres Strait Islander children. The objective of this paper is to examine the alignment between efforts designed to address otitis media in Aboriginal and Torres Strait Islander children in Queensland, Australia and core concepts of systems thinking. This paper's overall purpose is to identify which combination of activities, and at which level, hold the potential to facilitate systems changes to better support ear health among Aboriginal and Torres Strait Islander children. METHODS: We began with a review of documents identified in consultation with stakeholders and an online search. In addition, key informants were invited to participate in an online survey and a face-to-face or phone interview. Qualitative interviews using a semi-structured interview guide were used to explore survey responses in more depth. We also undertook interviews at the community level to elicit a diverse range of views. Ideas, statements or activities reported in the documents and interviews as being performed under the Intervention Level Framework were identified using qualitative thematic and content analysis. A quantitative descriptive analysis was also undertaken, whereby data was extracted into an Excel spreadsheet and coded under the relevant strategic directions and performance indicators of the Framework. Subsequently, we coded activities against the five-level intervention framework developed by Malhi and colleagues, that is: 1) paradigm; 2) goals; 3) system structure; 4) feedback and delays; and 5) structural elements. RESULTS: Overall, twenty documents were reviewed. We examined surveys and interviews with six key informants. Twenty-four individual and 3 group interviews were conducted across central and community level informants. One hundred and four items were coded from the 20 documents and 156 items from interview data. For both data sets, the majority of activities were coded at the structural elements level. The results suggested three key areas where further work is needed to drive sustained improvements: 1) build the governance structures needed for paradigm shift to achieve a multi-sectoral approach; 2) develop shared system level goals; 3) develop system-wide feedback processes. CONCLUSIONS: Sustained progress in improving ear health within Aboriginal and Torres Strait Islander children requires a holistic, system-wide approach. To advance such work, governance structures for multi-sectoral collaboration including the development of joint goals and monitoring and feedback are required. Intervening at these higher leverage points could have a profound effect on persistent public health issues.

Beverage consumption in Australian children.

BACKGROUND/OBJECTIVES: While beverages are an important dietary source of water and some essential nutrients, consumption of sweet beverages has increasingly been linked to adverse health outcomes. Currently there is a paucity of longitudinal consumption data on beverage consumption in Australian children. SUBJECTS/METHODS: The Longitudinal Study of Australian Children has run biennially since 2004. Twenty four-hour recall data collected over 6 waves from the birth cohort (aged 0-1 year at baseline) was analysed and demographics were assessed for associations. RESULTS: Five thousand one hundred and seven children participated at baseline, with a 71-90% retention of participants at each wave. Water consumption remained consistent with age over time, with more than 90% consuming more than one glass in the last 24-h. Proportions of fruit juice consumers decreased overall. Soft drink and cordial consumer proportions increased from 1% (0-1 year), to 28% (2 years) and 43% (10 years). Between 2 and 10 years, proportions of consumption of full-cream milk decreased by 8% and for skim milk this proportion increased by 51%. High proportions of consumers of soft drink/cordial was significantly associated with older children, males, children with a medical condition, living in a rural area, low socio-economic status and Indigenous Australians. CONCLUSIONS: Water consumption remained consistently high across the ages, while fruit juice was commonly introduced into the diet early childhood. While proportions of fruit juice consumers decreased after the age of 2 years, proportions of soft drink consumers increased. The findings from this study should assist with surveillance data and inform policy and interventions aimed at reducing consumption of sweet beverages.

'Hey, We Are the Best Ones at Dealing with Our Own': Embedding a Culturally Competent Program for Maori and Pacific Island Children into a Mainstream Health Service in Queensland, Australia.

OBJECTIVE: We present the results of one component of an external evaluation of Good Start Program (GSP), a community-based program for the prevention of chronic disease among Maori and Pacific Island (MPI) communities living in the state of Queensland, Australia. DESIGN: An evaluation of the GSP was undertaken using a mixed methods approach. This paper reports on the qualitative component where interview and focus group data was collected, using Talanoa, a culturally tailored research methodology. Respondents included school students, community groups, teachers and parents, as well as the Good Start implementation team. RESULT(S): The five broad themes that emerged from this evaluation related to (i) components of cultural-competence and (ii) perceived impact of the program. The views of all participants reinforced the importance of culturally appropriate programs and highlighted how the multicultural health workers (MHWs) contributed to the program's perceived success. The challenges in understanding restrictions of the mainstream health service framework were noted indicating the need for it to be flexible in incorporating culturally appropriate components if a program was to be embraced. CONCLUSION: The qualitative evaluation of the GSP suggests that culturally tailored programs, delivered by MHWs, have the potential to impact positively on community-level behavioural changes that improve health. These findings, supported by studies from other countries, contribute to the evidence that cultural-tailoring of programs is critical for ensuring that culturally appropriate initiatives are embedded in health care systems that support multicultural communities. Embedding includes the development of culturally appropriate policies, a culturally competent workforce and long-term funding to support culturally competent initiatives.

Open-Minded Midwifes, Literate Butchers, and Greedy Hooligans-The Independent Contributions of Stereotype Valence and Consistency on Evaluative Judgments.

Do people evaluate an open-minded midwife less positively than a caring midwife? Both open-minded and caring are generally seen as positive attributes. However, consistency varies-the attribute caring is consistent with the midwife stereotype while open-minded is not. In general, both stimulus valence and consistency can influence evaluations. Six experiments investigated the respective influence of valence and consistency on evaluative judgments in the domain of stereotyping. In an impression formation paradigm, valence and consistency of stereotypic information about target persons were manipulated orthogonally and spontaneous evaluations of these target persons were measured. Valence reliably influenced evaluations. However, for strongly valenced stereotypes, no effect of consistency was observed. Parameters possibly preventing the occurrence of consistency effects were ruled out, specifically, valence of inconsistent attributes, processing priority of category information, and impression formation instructions. However, consistency had subtle effects on evaluative judgments if the information about a target person was not strongly valenced and experimental conditions were optimal. Concluding, in principle, both stereotype valence and consistency can play a role in evaluative judgments of stereotypic target persons. However, the more subtle influence of consistency does not seem to substantially influence evaluations of stereotyped target persons. Implications for fluency research and stereotype disconfirmation are discussed.

Charting Availability of Processed and Unprocessed Foods in School Neighbourhood Nutrition Environments in an Urban Australian Setting.

School Neighbourhood Nutrition Environments (SNNEs) can facilitate or impede healthy eating. This study describes the SNNEs surrounding 6 Good Start Program (GSP) schools in 5 suburbs in Logan, Queensland. Relative density of healthy and unhealthy food outlets was calculated for SNNEs surrounding GSP (6) and non-GSP (10) schools within the 5 suburbs. Relative accessibility of minimally processed and highly processed food and drink in SNNEs of the 6 GSP schools was determined using shelf measurements of snack foods. Unhealthy outlets greatly outnumber healthy outlets (mean relative density 15.6%, median 19.1%). The majority of outlets stock predominantly highly processed food and drink. Study areas are dominated by unhealthy food outlets and highly processed food.

Food, eating and body image in the lives of low socioeconomic status rural Mexican women living in Queretaro State, Mexico.

Qualitative research using semi-structured interviews and key informant interviews were used to explore how women from low socioeconomic rural households in Queretaro State, Mexico perceived and reacted to their obesogenic environment. Reduced availability of healthy food options and household financial constraints along with reduced agency of women in this setting were factors that limited women's ability to access and consume diets consistent with the promotion of good health. The cultural values that emphasised obesity as a desirable state for women and the women's social networks that promoted these values were also identified as playing a role in reinforcing certain behaviours. Public health advocates wanting to design interventions in such settings need to be sensitive to the cultural as well as the environmental context described for rural Mexican women.

Hypoglycemia in patients with diabetes who are fasting for laboratory blood tests: the Cape Girardeau Hypoglycemia En Route Prevention Program.

OBJECTIVE: Patients with diabetes are routinely asked to fast for laboratory tests. If not properly prepared, they may be at risk for hypoglycemia, which may result in traffic accidents while driving en route to and from laboratory facilities. We undertook this study to evaluate the magnitude of this overlooked problem, and to evaluate the effectiveness of a prevention program implemented in our clinic. METHODS: A retrospective study consisting of chart reviews and telephone interviews of consecutive hypoglycemic events (blood glucose level < 70 mg/dL). The study cohorts, A and B, were extracted from our central laboratory database. Cohort A (from January 2008-September 2009) consisted of patients prior to--and cohort B (from October 2009-June 2011) subsequent to--the implementation of a prevention program involving blood glucose monitoring and adjustment of antidiabetic medications. Duration of each cohort was 21 months. For the purpose of this article, we use the acronym FEEHD (fasting-evoked en-route hypoglycemia in diabetes) to describe this overlooked form of hypoglycemia. RESULTS: Of a total of 1801 blood glucose test results retrieved, cohort A included a total of 55 hypoglycemic events in 51 patients (4 patients with 2 events each). Cohort B included a total of 23 hypoglycemic events in 22 patients (with 1 patient sustaining 2 events) out of a total of 2561 blood glucose test results retrieved. In cohort A, of 35 patients on antidiabetic medications who recalled fasting or probably fasting, there were 39 hypoglycemic events (2.2% frequency), compared with 18 events (0.7% frequency) in 17 patients in cohort B. This indicates a 68% risk reduction. The frequency of critical hypoglycemia (< 50 mg/dL) was more significantly reduced, from 11 events (0.6%) to 2 events (0.07%), indicating a risk reduction of 88%. CONCLUSION: This study showed a 68% risk reduction of FEEHD with implementation of the prevention program, and an 88% reduction of severe FEEHD (blood glucose level < 50 mg/dL). Reporting on the first prevention program of its kind, this is the first study to evaluate an overlooked safety problem in diabetes management. Clinicians should consider if fasting laboratory tests are in fact necessary, and when ordered, clinicians should properly instruct their patients on adequate blood glucose monitoring and adjustment of antidiabetic medications. We present the guidelines that proved effective in our program to help patients with diabetes and their clinicians avert this potentially harmful complication.

Unbiased reconstruction of a mammalian transcriptional network mediating pathogen responses.

Models of mammalian regulatory networks controlling gene expression have been inferred from genomic data but have largely not been validated. We present an unbiased strategy to systematically perturb candidate regulators and monitor cellular transcriptional responses. We applied this approach to derive regulatory networks that control the transcriptional response of mouse primary dendritic cells to pathogens. Our approach revealed the regulatory functions of 125 transcription factors, chromatin modifiers, and RNA binding proteins, which enabled the construction of a network model consisting of 24 core regulators and 76 fine-tuners that help to explain how pathogen-sensing pathways achieve specificity. This study establishes a broadly applicable, comprehensive, and unbiased approach to reveal the wiring and functions of a regulatory network controlling a major transcriptional response in primary mammalian cells.