Mitochondrial dysfunction abrogates dietary lipid processing in enterocytes.

Digested dietary fats are taken up by enterocytes where they are assembled into pre-chylomicrons in the endoplasmic reticulum followed by transport to the Golgi for maturation and subsequent secretion to the circulation1. The role of mitochondria in dietary lipid processing is unclear. Here we show that mitochondrial dysfunction in enterocytes inhibits chylomicron production and the transport of dietary lipids to peripheral organs. Mice with specific ablation of the mitochondrial aspartyl-tRNA synthetase DARS2 (ref. 2), the respiratory chain subunit SDHA3 or the assembly factor COX10 (ref. 4) in intestinal epithelial cells showed accumulation of large lipid droplets (LDs) in enterocytes of the proximal small intestine and failed to thrive. Feeding a fat-free diet suppressed the build-up of LDs in DARS2-deficient enterocytes, which shows that the accumulating lipids derive mostly from digested fat. Furthermore, metabolic tracing studies revealed an impaired transport of dietary lipids to peripheral organs in mice lacking DARS2 in intestinal epithelial cells. DARS2 deficiency caused a distinct lack of mature chylomicrons concomitant with a progressive dispersal of the Golgi apparatus in proximal enterocytes. This finding suggests that mitochondrial dysfunction results in impaired trafficking of chylomicrons from the endoplasmic reticulum to the Golgi, which in turn leads to storage of dietary lipids in large cytoplasmic LDs. Taken together, these results reveal a role for mitochondria in dietary lipid transport in enterocytes, which might be relevant for understanding the intestinal defects observed in patients with mitochondrial disorders5.

Screening for Impaired Visual Acuity in Older Adults: US Preventive Services Task Force Recommendation Statement.

DESCRIPTION: Update of the US Preventive Services Task Force (USPSTF) recommendation on screening for impaired visual acuity in older adults. METHODS: The USPSTF reviewed the evidence on screening for visual acuity impairment associated with uncorrected refractive error, cataracts, and age-related macular degeneration among adults 65 years or older in the primary care setting; the benefits and harms of screening; the accuracy of screening; and the benefits and harms of treatment of early vision impairment due to uncorrected refractive error, cataracts, and age-related macular degeneration. POPULATION: This recommendation applies to asymptomatic adults 65 years or older who do not present to their primary care clinician with vision problems. RECOMMENDATION: The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for impaired visual acuity in older adults. (I statement).

Screening for Autism Spectrum Disorder in Young Children: US Preventive Services Task Force Recommendation Statement.

DESCRIPTION: New US Preventive Services Task Force (USPSTF) recommendation on screening for autism spectrum disorder (ASD) in young children. METHODS: The USPSTF reviewed the evidence on the accuracy, benefits, and potential harms of brief, formal screening instruments for ASD administered during routine primary care visits and the benefits and potential harms of early behavioral treatment for young children identified with ASD through screening. POPULATION: This recommendation applies to children aged 18 to 30 months who have not been diagnosed with ASD or developmental delay and for whom no concerns of ASD have been raised by parents, other caregivers, or health care professionals. RECOMMENDATION: The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for ASD in young children for whom no concerns of ASD have been raised by their parents or a clinician. (I statement).

Screening for Depression in Adults: US Preventive Services Task Force Recommendation Statement.

DESCRIPTION: Update of the 2009 US Preventive Services Task Force (USPSTF) recommendation on screening for depression in adults. METHODS: The USPSTF reviewed the evidence on the benefits and harms of screening for depression in adult populations, including older adults and pregnant and postpartum women; the accuracy of depression screening instruments; and the benefits and harms of depression treatment in these populations. POPULATION: This recommendation applies to adults 18 years and older. RECOMMENDATION: The USPSTF recommends screening for depression in the general adult population, including pregnant and postpartum women. Screening should be implemented with adequate systems in place to ensure accurate diagnosis, effective treatment, and appropriate follow-up. (B recommendation).

A demonstration of peer support for Ugandan adults with type 2 diabetes.

BACKGROUND: By 2030, 80% of people with diabetes will be living in developing countries. PURPOSE: The purpose of this pre-post quasi-experimental study was to test the feasibility of a peer intervention to improve the following: (1) diabetes self-care behaviors, (2) glycemic control, (3) social support and emotional well-being, (4) linkages to health care providers, and (5) to assess the sustainability of the intervention 18 months later. METHOD: Participants were adults with type 2 diabetes who resided in rural Uganda. Participants (n = 46) attended a 1-day diabetes education program and agreed to make weekly contacts over 4 months with each other by phone or in person to assist with daily management, provide social and emotional support, and encourage appropriate contact with health care providers. RESULTS: Results indicated improvement in glycosylated hemoglobin (A1C), diastolic blood pressure, and eating behaviors. CONCLUSIONS: A short-term peer support program was a feasible intervention to improve diabetes care in rural Uganda. Participants were successfully recruited and retained, and they experienced positive behavioral and physiologic outcomes. Elements of the intervention were sustained 18 months after the intervention.

Mitochondria-originated redox signalling regulates KLF-1 to promote longevity in Caenorhabditis elegans.

Alternations of redox metabolism have been associated with the extension of lifespan in roundworm Caenorhabditis elegans, caused by moderate mitochondrial dysfunction, although the underlying signalling cascades are largely unknown. Previously, we identified transcriptional factor Krüppel-like factor-1 (KLF-1) as the main regulator of cytoprotective longevity-assurance pathways in the C. elegans long-lived mitochondrial mutants. Here, we show that KLF-1 translocation to the nucleus and the activation of the signalling cascade is dependent on the mitochondria-derived hydrogen peroxide (H2O2) produced during late developmental phases where aerobic respiration and somatic mitochondrial biogenesis peak. We further show that mitochondrial-inducible superoxide dismutase-3 (SOD-3), together with voltage-dependent anion channel-1 (VDAC-1), is required for the life-promoting H2O2 signalling that is further regulated by peroxiredoxin-3 (PRDX-3). Increased H2O2 release in the cytoplasm activates the p38 MAPK signalling cascade that induces KLF-1 translocation to the nucleus and the activation of transcription of C. elegans longevity-promoting genes, including cytoprotective cytochrome P450 oxidases. Taken together, our results underline the importance of redox-regulated signalling as the key regulator of longevity-inducing pathways in C. elegans, and position precisely timed mitochondria-derived H2O2 in the middle of it.

Helping persons with multiple chronic conditions overcome barriers to self-management.

ABSTRACT: The prevalence of multiple chronic conditions is growing dramatically, which complicates day-to-day self-management for patients. This article describes the features of multiple chronic conditions, an updated chronic care model, barriers to self-management, and strategies NPs can use to reduce or eliminate barriers to self-management in adults with multiple chronic conditions.

Perceived influences on physical activity and diet in low-income adults from two rural counties.

BACKGROUND: Despite the increased use of ecological models in health behavior research, multilevel influences on health behaviors in rural, low-income people, an aggregate at high risk for sedentary behavior and inadequate diets, have been examined in few studies. OBJECTIVE: The purpose of this study was to describe influences on physical activity and diet in low-income, rural adults. METHOD: A cross-sectional survey was conducted using face-to-face interviews in a convenience sample of 137 low-income Anglo and Latino adults recruited from two rural Wisconsin counties. The survey included questions on health behaviors, self-efficacy, barriers, social support, and community environments. Self-report data on physical activity and fruit and vegetable intake were categorized into outcome variables of meets recommendation or does not meet recommendation. Latent class cluster analysis was used to identify clusters of participants with similar influences on health behaviors, and cluster membership was used as an independent variable in logistic regression of physical activity and diet outcomes. RESULTS: Fifty-two percent of participants met a recommendation for physical activity, but only 8% met their MyPyramid recommendation for fruit and vegetable intake. Participants in the moderate self-efficacy/high safety cluster were significantly more likely than those in the low self-efficacy/moderate safety cluster to meet a recommendation for physical activity (odds ratio = 2.65). For healthy diet, participants in the low barriers cluster were significantly more likely to eat more fruits and vegetables (odds ratio = 4.13) than those in the high barriers cluster. DISCUSSION: People with healthier behaviors were distinguished from those with less healthy behaviors by higher levels of intrapersonal, interpersonal, and community supports. Results support the importance of multilevel approaches to promoting healthy lifestyles in rural, low-income adults.

Perspectives on healthy behaviors among low-income Latino and non-Latino adults in two rural counties.

OBJECTIVES: Rural populations and individuals with low incomes are less likely than the general population to achieve recommended levels of physical activity and fruit and vegetable consumption. The purpose of this study was to describe the perspectives of low-income adults in 2 rural Wisconsin counties on the factors that influence physical activity and healthy eating. DESIGN AND SAMPLE: A qualitative descriptive study was conducted using 4 focus groups: 2 in English and 2 in Spanish. A convenience sample (N=20) was recruited. MEASURES: Focus group questions and data analysis were based on an ecological framework. A team of 3 researchers performed content analysis of focus group transcripts. RESULTS: Participants reported individual, social, and community influences on health behaviors. Individual barriers included lack of motivation and lack of knowledge. Participants described the importance of family, friends, and the community social climate for health behaviors. Latinos emphasized the need for resources such as community gardens and public spaces for physical activity, while non-Latinos recommended community education related to healthy eating. CONCLUSIONS: The results suggest that relevant health promotion strategies in rural, low-income populations include multilevel approaches, the development of schools as health promotion resources, and strategies to build social connections among community residents.

A salvage pathway maintains highly functional respiratory complex I.

Regulation of the turnover of complex I (CI), the largest mitochondrial respiratory chain complex, remains enigmatic despite huge advancement in understanding its structure and the assembly. Here, we report that the NADH-oxidizing N-module of CI is turned over at a higher rate and largely independently of the rest of the complex by mitochondrial matrix protease ClpXP, which selectively removes and degrades damaged subunits. The observed mechanism seems to be a safeguard against the accumulation of dysfunctional CI arising from the inactivation of the N-module subunits due to attrition caused by its constant activity under physiological conditions. This CI salvage pathway maintains highly functional CI through a favorable mechanism that demands much lower energetic cost than de novo synthesis and reassembly of the entire CI. Our results also identify ClpXP activity as an unforeseen target for therapeutic interventions in the large group of mitochondrial diseases characterized by the CI instability.

KLF-1 orchestrates a xenobiotic detoxification program essential for longevity of mitochondrial mutants.

Most manipulations that extend lifespan also increase resistance to various stress factors and environmental cues in a range of animals from yeast to mammals. However, the underlying molecular mechanisms regulating stress resistance during aging are still largely unknown. Here we identify Krüppel-like factor 1 (KLF-1) as a mediator of a cytoprotective response that dictates longevity induced by reduced mitochondrial function. A redox-regulated KLF-1 activation and transfer to the nucleus coincides with the peak of somatic mitochondrial biogenesis that occurs around a transition from larval stage L3 to D1. We further show that KLF-1 activates genes involved in the xenobiotic detoxification programme and identified cytochrome P450 oxidases, the KLF-1 main effectors, as longevity-assurance factors of mitochondrial mutants. Collectively, these findings underline the importance of the xenobiotic detoxification in the mitohormetic, longevity assurance pathway and identify KLF-1 as a central factor in orchestrating this response.

Creating a center for global health at the University of Wisconsin-Madison.

Globalization, migration, and widespread health disparities call for interdisciplinary approaches to improve health care at home and abroad. Health professions students are pursuing study abroad in increasing numbers, and universities are responding with programs to address these needs. The University of Wisconsin (UW)-Madison schools of medicine and public health, nursing, pharmacy, veterinary medicine, and the division of international studies have created an interdisciplinary center for global health (CGH). The CGH provides health professions and graduate students with courses, field experiences, and a new Certificate in Global Health. Educational programs have catalyzed a network of enthusiastic UW global health scholars. Partnerships with colleagues in less economically developed countries provide the foundation for education, research, and service programs. Participants have collaborated to improve the education of health professionals and nutrition in Uganda; explore the interplay between culture, community development, and health in Ecuador; improve animal health and address domestic violence in Mexico; and examine successful public health efforts in Thailand. These programs supply students with opportunities to understand the complex determinants of health and structure of health systems, develop adaptability and cross-cultural communication skills, experience learning and working in interdisciplinary teams, and promote equity and reduce health disparities at home and abroad. Based on the principles of equity, sustainability, and reciprocity, the CGH provides a strong foundation to address global health challenges through networking and collaboration among students, staff, and faculty within the UW and beyond.

U.S. Preventive Services Task Force Methods to Communicate and Disseminate Clinical Preventive Services Recommendations.

The U.S. Preventive Services Task Force (USPSTF) issues evidence-based screening and prevention recommendations, and key to this task is dissemination and implementation of these recommendations. The Task Force has recommendations for more than 84 topics; each USPSTF Recommendation Statement includes a letter grade, a topline summary to guide clinician interpretation in practice, and a summary of gaps in evidence to help catalyze clinically relevant research. The USPSTF aims to update existing topics regularly and considers new topics to add each year. Clearly communicating and disseminating each recommendation is a critical task to ensure maximum benefit from use of the recommendations. The primary USPSTF audience is primary care clinicians. Over time, other audiences have become interested in the USPSTF and these entities have broad and diverse needs, necessitating a range of communication platforms and approaches. This includes engagement with and input from topic experts, primary care and federal partners, and the public to help shape the development of the recommendations. It also includes engagement of partners to disseminate USPSTF recommendations to help ensure that the primary care workforce remains up-to-date on USPSTF recommendations. This paper outlines the approaches used by the USPSTF to both solicit input (e.g., public comment periods), as well as to facilitate dissemination of its recommendations to help improve the health of all Americans (e.g., web-based and mobile application tools, journal publications, and annual reports to Congress).

A training program for diabetes care in Vietnam.

PURPOSE: This article will describe a project designed to enhance the knowledge and skills of Vietnamese nurses and physicians to improve diabetes care. METHODS: Strategies used to achieve these goals included training in behavioral and educational approaches and physical assessment skills. RESULTS: Six-month follow-up reports on the outcomes of diabetes education projects and institutional strategies for diabetes education will be presented. CONCLUSIONS: The skills and knowledge provided through this project will prepare nurses to assume a greater role in health care teams for diabetes care in Vietnam.

Predictors of fat intake behavior differ between normal-weight and obese WIC mothers.

PURPOSE: To determine whether predictors of fat intake behavior were the same for normal-weight and obese WIC mothers when applying the PRECEDE-PROCEED model and to identify predictors for each group. DESIGN: Proportional stratified convenience sampling. SUBJECTS: Five hundred eighty-one nonpregnant, black and white normal-weight (n = 180) or obese (n = 401) women. SETTINGS: The Special Supplemental Nutrition Program for Women, Infants and Children in six counties in southern Wisconsin. MEASURES: The independent variables were predisposing, enabling, and reinforcing factors. Predisposing factors included beliefs in diet and health, beliefs in diet and body shape, health concerns in food choice, health concerns in nutrition, and eating habits. Enabling factors were cost of food, availability of time to prepare food, and accessibility to purchase food. Reinforcing factors were weight control intentions, sensory appeal, and mood. The dependent variable was fat intake behavior. Structural equation modeling was performed. RESULTS: When controlling for covariates, certain factors affectingfat intake behavior differed between the normal-weight and the obese groups. For the normal-weight group, only reinforcing factors were positively associated with fat intake behavior For the obese group, reinforcing and enabling, but not predisposing, factors were positively associated with fat intake behavior. CONCLUSIONS: Interventions to modify low-income women's fat intake behavior might benefit from targeting behavioral predictors that differ with body size. Messages that emphasize weight control intentions, sensory appeal, and mood are likely to affect both normalweight and obese women. Information about cost of food, availability of time to prepare food, and accessibility to purchase food is likely to be more effective with obese women.

Evaluating Feasible and Referable Behavioral Counseling Interventions.

The U.S. Preventive Services Task Force (USPTF) recognizes that behaviors have a major impact on health and well-being. Currently, the USPSTF has 11 behavioral counseling intervention (BCI) recommendations. These BCIs can be delivered in a primary care setting or patients can be referred to other clinical or community programs. Unfortunately, many recommended BCIs are infrequently and ineffectually delivered, suggesting that more evidence is needed to understand which BCIs are feasible and referable. In response, the USPSTF convened an expert forum in 2013 to inform the evaluation of BCI feasibility. This manuscript reports on findings from the forum and proposes that researchers use several frameworks to help clinicians and the USPSTF evaluate which BCIs work under usual conditions. A key recommendation for BCI researchers is to use frameworks whose components can support dissemination and implementation efforts. These frameworks include the Template for Intervention Description and Replication (TIDieR), which helps describe the essential components of an intervention, and pragmatic frameworks like Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) or Pragmatic-Explanatory Continuum Indicator Summary (PRECIS), which help to report study design elements and outcomes. These frameworks can both guide the design of more-feasible BCIs and produce clearer feasibility evidence. Critical evidence gaps include a better understanding of which patients will benefit from a BCI, how flexible interventions can be without compromising effectiveness, required clinician expertise, necessary intervention intensity and follow-up, impact of patient and clinician intervention adherence, optimal conditions for BCI delivery, and how new care models will influence BCI feasibility.

Organization of the mitochondrial genomes of whiteflies, aphids, and psyllids (Hemiptera, Sternorrhyncha).

BACKGROUND: With some exceptions, mitochondria within the class Insecta have the same gene content, and generally, a similar gene order allowing the proposal of an ancestral gene order. The principal exceptions are several orders within the Hemipteroid assemblage including the order Thysanoptera, a sister group of the order Hemiptera. Within the Hemiptera, there are available a number of completely sequenced mitochondrial genomes that have a gene order similar to that of the proposed ancestor. None, however, are available from the suborder Sternorryncha that includes whiteflies, psyllids and aphids. RESULTS: We have determined the complete nucleotide sequence of the mitochondrial genomes of six species of whiteflies, one psyllid and one aphid. Two species of whiteflies, one psyllid and one aphid have mitochondrial genomes with a gene order very similar to that of the proposed insect ancestor. The remaining four species of whiteflies had variations in the gene order. In all cases, there was the excision of a DNA fragment encoding for cytochrome oxidase subunit III(COIII)-tRNAgly-NADH dehydrogenase subunit 3(ND3)-tRNAala-tRNAarg-tRNAasn from the ancestral position between genes for ATP synthase subunit 6 and NADH dehydrogenase subunit 5. Based on the position in which all or part of this fragment was inserted, the mitochondria could be subdivided into four different gene arrangement types. PCR amplification spanning from COIII to genes outside the inserted region and sequence determination of the resulting fragments, indicated that different whitefly species could be placed into one of these arrangement types. A phylogenetic analysis of 19 whitefly species based on genes for mitochondrial cytochrome b, NADH dehydrogenase subunit 1, and 16S ribosomal DNA as well as cospeciating endosymbiont 16S and 23S ribosomal DNA indicated a clustering of species that corresponded to the gene arrangement types. CONCLUSIONS: In whiteflies, the region of the mitochondrial genome consisting of genes encoding for COIII-tRNAgly-ND3-tRNAala-tRNAarg-tRNAasn can be transposed from its ancestral position to four different locations on the mitochondrial genome. Related species within clusters established by phylogenetic analysis of host and endosymbiont genes have the same mitochondrial gene arrangement indicating a transposition in the ancestor of these clusters.

Cancer prevention services and physician consensus in primary care group practices.

BACKGROUND: We conducted a randomized clinical trial of interventions to achieve physician consensus, practice changes, and patient activation designed to help primary care group practices enhance the delivery of cancer prevention and screening services. METHODS: In each of 42 primary care practices in 1991 to 1994, we studied approximately 60 patients per physician who were between the ages 53 and 64. Data sources included patient and physician questionnaires, medical record audits of consenting patients for evidence of 11 cancer prevention services during the previous 3 years, and telephone interviews with key practice personnel. RESULTS: None of the interventions was associated with significant changes in frequency of services or procedures received or provided. Increased frequencies of services overall and of specific activities were associated with HMO membership or insurance coverage for six screening procedures. Patient reports of clinic staff recommendations to have each of six screening procedures were specifically associated with higher frequencies of services (P = 0.001). CONCLUSIONS: Demonstration of intervention impact may have been limited because the rates of prevention services were significantly higher in this study than have been reported elsewhere. These results might be explained by selection biases inherent in studying patients with a regular provider, overall practice trends for changes in provision of the studied services, and the study methods.

Development of an instrument to assess predisposing, enabling, and reinforcing constructs associated with fat intake behaviors of low-income mothers.

OBJECTIVE: To establish reliability and construct and discriminant validity of selected factors adapted from the Health and Taste Attitudes Questionnaire developed in Finland and the Food Choice Questionnaire developed in England for use with low-income mothers in the United States. DESIGN: Cross-sectional. SETTING: Head Start and the Special Supplemental Nutrition Program for Women, Infants and Children sites in south-central Wisconsin. PARTICIPANTS: A convenience sample of 211 nonpregnant non-Hispanic black and white women. VARIABLES MEASURED: Predisposing, enabling, and reinforcing constructs of the PRECEDE-PROCEED model. ANALYSIS: Factor analyses. RESULTS: After modification, the resulting measurement models of predisposing, enabling, and reinforcing constructs demonstrated good reliability and construct and discriminant validity. These models showed excellent model fit (chi-square/df range 1.5-2.0, root mean square error of approximate range.05-.07, non-normed fit index range.97-1.0, comparative fit index range.98-1.0, incremental fit index range.98-1.0), with all factor loadings significant (P <.001). Items previously developed with European adults demonstrated different pattern structures in predisposing and enabling constructs but the same structures for reinforcing construct when applied to low-income mothers in the United States. CONCLUSION AND IMPLICATION: This modified instrument provides a tool for researchers and educators to further explore factors affecting fat intake behaviors in low-income mothers.

Development and validation of a self-efficacy measure for fat intake behaviors of low-income women.

OBJECTIVE: To develop a valid self-efficacy measure for eating low-fat diets in low-income women. DESIGN: Cognitive interviews followed by self-administered questionnaires. PARTICIPANTS/SETTINGS: 206 (6 + 200) nonpregnant black and white women participating in Head Start and the Special Supplemental Nutrition Program for Women, Infants and Children (WIC) in Wisconsin. VARIABLES MEASURES: A 13-item self-efficacy measure for eating low-fat diets. ANALYSIS: Content analysis and factor analyses. RESULTS: After cognitive interviews, 3 items were removed from a draft instrument. Factor analyses were carried out using data from 200 questionnaires that were randomly selected from a pool of 487 respondents: 100 for exploratory factor analysis (EFA) and 100 for confirmatory factor analysis (CFA). Based on EFA, the 10-item pool was further reduced to 8 items, and 3 domains emerged: negative affect, positive affect, and availability. The results of CFA showed excellent model fit to the data (chi 2/df = 1.2, non-normed fit index = 1.0, comparative fit index = 1.0, incremental fit index = 1.0, root mean square error of approximate =.046). This measure demonstrated excellent reliabilities (Cronbach alpha : .82-.92; composite reliability: .92-.99) and construct and convergent validities. CONCLUSIONS AND IMPLICATIONS: Information obtained from this revised instrument can be used among low-income women to measure self-efficacy for eating low-fat diets. This is an important step in developing more targeted and thus more effective education messages to help low-income women modify their fat intake behaviors.