Medical Nutrition Education for Health, Not Harm: BMI, Weight Stigma, Eating Disorders, and Social Determinants of Health.

Effective nutrition training is fundamental to medical education. Current training is inadequate and can cause harm to students and patients alike; it leaves physicians unprepared to counsel on nutrition, places undue focus on weight and body mass index (BMI), can exacerbate anti-obesity bias, and increase risk for development of eating disorders, while neglecting social determinants of health and communication skills. Physicians and educators hold positions of influence in society; what we say and how we say it matters. We propose actionable approaches to improve nutrition education to minimize harm and pursue evidence-based, effective, and equitable healthcare.

Dairy purchase behaviors: Increasing understanding of Chinese consumers using a consumer involvement segmentation approach.

Understanding consumers' purchase behaviors is fundamental to the success of the dairy industry. With its economic importance, the Chinese market is critical to dairy producers in most countries around the world. However, understanding consumers in this market is particularly challenging, as these consumers often have a different relationship with dairy products than consumers elsewhere in the world, given the country's historical dairy-related scandals. This special relationship can be characterized by what consumer behavior researchers call "high involvement," indicating that Chinese dairy consumers often attempt to reduce the level of risk associated with buying dairy products. Surprisingly, although this relationship affects several important aspects of purchase behavior, examination of the concept of involvement in the dairy sector has not been widely considered. Of note, there is no understanding of how Chinese consumers vary in their involvement levels and their implications on their dairy purchase behaviors. Nor have there been involvement-based insights provided on how dairy companies can position their marketing strategy to suit the needs of these consumers better. Thus, this study proposes a new approach to understanding Chinese consumer dairy decisions by introducing "consumer involvement" as a segmentation tool through which individuals' behaviors can be predicated according to their involvement profile. Based on an online survey administered in Shanghai using 1,073 dairy consumers, principal component analysis confirmed involvement with dairy is a multidimensional construct with the following 4 factors: pleasure value, symbolic value, risk importance, and risk probability. A 2-step cluster analysis identified 4 consumer clusters based on their involvement profile: face-concerned dairy lover, carefree dairy consumer, cautious dairy lover, and confused dairy consumer. According to a one-way ANOVA test and cross-tabulation with χ2 test, these consumer segments behave differently in relation to the extensiveness of decision making, cue utilization, trust of information sources, and consumption behavior. The outcomes in this paper further explain why efforts to restore consumer trust for dairy products do not work among some consumers, as individuals may exhibit diverse attitudes toward such information due to their heterogeneous involvement levels. The study also provides suggestions for market practitioners and organizations to develop effective target market strategies and policies according to different consumer clusters.

Dietary Supplementation With Medium-Chain Triglycerides Reduces Candida Gastrointestinal Colonization in Preterm Infants.

BACKGROUND: Candida is an important cause of infections in premature infants. Gastrointestinal colonization with Candida is a common site of entry for disseminated disease. The objective of this study was to determine whether a dietary supplement of medium-chain triglycerides (MCTs) reduces Candida colonization in preterm infants. METHODS: Preterm infants with Candida colonization (n = 12) receiving enteral feedings of either infant formula (n = 5) or breast milk (n = 7) were randomized to MCT supplementation (n = 8) or no supplementation (n = 4). Daily stool samples were collected to determine fungal burden during a 3-week study period. Infants in the MCT group received supplementation during 1 week of the study period. The primary outcome was fungal burden during the supplementation period as compared with the periods before and after supplementation. RESULTS: Supplementation of MCT led to a marked increase in MCT intake relative to unsupplemented breast milk or formula as measured by capric acid content. In the treatment group, there was a significant reduction in fungal burden during the supplementation period as compared with the period before supplementation (rate ratio, 0.15; P = 0.02), with a significant increase after supplementation was stopped (rate ratio, 61; P < 0.001). Fungal burden in the control group did not show similar changes. CONCLUSIONS: Dietary supplementation with MCT may be an effective method to reduce Candida colonization in preterm infants.

Fibroblast growth factor receptor is a mechanistic link between visceral adiposity and cancer.

Epidemiological evidence implicates excess adipose tissue in increasing cancer risk. Despite a steeply rising global prevalence of obesity, how adiposity contributes to transformation (stage a non-tumorigenic cell undergoes to become malignant) is unknown. To determine the factors in adipose tissue that stimulate transformation, we used a novel ex vivo system of visceral adipose tissue (VAT)-condition medium-stimulated epithelial cell growth in soft agar. To extend this system in vivo, we used a murine lipectomy model of ultraviolet light B-induced, VAT-promoted skin tumor formation. We found that VAT from mice and obese human donors stimulated growth in soft agar of non-tumorigenic epithelial cells. The difference in VAT activity was associated with fibroblast growth factor-2 (FGF2) levels. Moreover, human and mouse VAT failed to stimulate growth in soft of agar in cells deficient in FGFR-1 (FGF2 receptor). We also demonstrated that circulating levels of FGF2 were associated with non-melanoma tumor formation in vivo. These data implicate FGF2 as a major factor VAT releases to transform epithelial cells-a novel, potential pathway of VAT-enhanced tumorigenesis. Strategies designed to deplete VAT stores of FGF2 or inhibit FGFR-1 in abdominally obese individuals may be important cancer prevention strategies as well as adjuvant therapies for improving outcomes.

Manipulation of Host Diet To Reduce Gastrointestinal Colonization by the Opportunistic Pathogen Candida albicans.

Candida albicans, the most common human fungal pathogen, can cause systemic infections with a mortality rate of ~40%. Infections arise from colonization of the gastrointestinal (GI) tract, where C. albicans is part of the normal microflora. Reducing colonization in at-risk patients using antifungal drugs prevents C. albicans-associated mortalities. C. albicans provides a clinically relevant system for studying the relationship between diet and the microbiota as it relates to commensalism and pathogenicity. As a first step toward a dietary intervention to reduce C. albicans GI colonization, we investigated the impact of dietary lipids on murine colonization by C. albicans. Coconut oil and its constituent fatty acids have antifungal activity in vitro; we hypothesized that dietary coconut oil would reduce GI colonization by C. albicans. Colonization was lower in mice fed a coconut oil-rich diet than in mice fed diets rich in beef tallow or soybean oil. Switching beef tallow-fed mice to a coconut oil diet reduced preexisting colonization. Coconut oil reduced colonization even when the diet also contained beef tallow. Dietary coconut oil also altered the metabolic program of colonizing C. albicans cells. Long-chain fatty acids were less abundant in the cecal contents of coconut oil-fed mice than in the cecal contents of beef tallow-fed mice; the expression of genes involved in fatty acid utilization was lower in C. albicans from coconut oil-fed mice than in C. albicans from beef tallow-fed mice. Extrapolating to humans, these findings suggest that coconut oil could become the first dietary intervention to reduce C. albicans GI colonization. IMPORTANCE Candida albicans, the most common human fungal pathogen, can cause infections with a mortality rate of ~40%. C. albicans is part of the normal gut flora, but when a patient's immune system is compromised, it can leave the gut and cause infections. By reducing the amount of C. albicans in the gut of susceptible patients, infections (and the resulting fatalities) can be prevented. Currently, this is done using antimicrobial drugs; to "preserve" drugs for treating infections, we looked for a dietary change to reduce the amount of C. albicans in the gut. Using a mouse model, we showed that adding coconut oil to the diet could become the first drug-free way to reduce C. albicans in the gut. More broadly, this model lets us study the interactions between our diet and the microbes in our body and the reasons why some of those microbes, under certain conditions, cause disease. Podcast: A podcast concerning this article is available.

Transcriptional Profiling of Candida albicans in the Host.

Gene expression profiling has become an important tool for determining gene functions, performing phenotypic analysis, and quantifying the differential expression of individual transcripts under various conditions. Candida albicans gene expression is highly responsive to environmental conditions and rapidly adapts to various niches within the host. Here, we describe a mouse model of gastrointestinal colonization with C. albicans, the measurement of colonization in fecal pellets, and the collection of samples for transcriptional profiling. We describe how to extract and purify RNA suitable for analysis via RT-qPCR or microarray.

Validation of the completeness and accuracy of the Northern Ireland Cancer Registry.

BACKGROUND: It has been suggested that inaccuracies in cancer registries are distorting UK survival statistics. This study compared the Northern Ireland Cancer Registry (NICR) database of living patients, with independent data held by Northern Ireland's General Practitioners (GPs) to compare and validate the recorded diagnoses and dates held by the registry. METHODS: All 387 GP practice managers were invited to participate. 100 practices (25.84%) responded. Comparisons were made for 17,102 patients, equivalent to 29.08% of the living patients (58,798) extracted from the NICR between 1993 and 2010. RESULTS: There were no significant differences (p>0.05) between the responding and nonresponding GP patient profiles for age, marital status or deprivation score. However, the responding GPs included more female patients (p=0.02). NICR data accuracy was high, 0.08% of GP cancer patients (n=15) were not included in registry records and 0.02% (n=2) had a diagnosis date which varied more than 2 weeks from GP records (3 weeks and 5 months). The NICR had recorded two different tumour types and three different tumour statuses (benign vs. malignant) to the GPs. CONCLUSION: This comparison demonstrates a high level of accuracy within the NICR and that the survival statistics based on this data can be relied upon.

A functional portrait of Med7 and the mediator complex in Candida albicans.

Mediator is a multi-subunit protein complex that regulates gene expression in eukaryotes by integrating physiological and developmental signals and transmitting them to the general RNA polymerase II machinery. We examined, in the fungal pathogen Candida albicans, a set of conditional alleles of genes encoding Mediator subunits of the head, middle, and tail modules that were found to be essential in the related ascomycete Saccharomyces cerevisiae. Intriguingly, while the Med4, 8, 10, 11, 14, 17, 21 and 22 subunits were essential in both fungi, the structurally highly conserved Med7 subunit was apparently non-essential in C. albicans. While loss of CaMed7 did not lead to loss of viability under normal growth conditions, it dramatically influenced the pathogen's ability to grow in different carbon sources, to form hyphae and biofilms, and to colonize the gastrointestinal tracts of mice. We used epitope tagging and location profiling of the Med7 subunit to examine the distribution of the DNA sites bound by Mediator during growth in either the yeast or the hyphal form, two distinct morphologies characterized by different transcription profiles. We observed a core set of 200 genes bound by Med7 under both conditions; this core set is expanded moderately during yeast growth, but is expanded considerably during hyphal growth, supporting the idea that Mediator binding correlates with changes in transcriptional activity and that this binding is condition specific. Med7 bound not only in the promoter regions of active genes but also within coding regions and at the 3' ends of genes. By combining genome-wide location profiling, expression analyses and phenotyping, we have identified different Med7p-influenced regulons including genes related to glycolysis and the Filamentous Growth Regulator family. In the absence of Med7, the ribosomal regulon is de-repressed, suggesting Med7 is involved in central aspects of growth control.

Pediatric ergot alkaloid exposures reported to the California Poison Control System: 1997-2008.

CONTEXT: The risk of toxicity from exposure to ergot alkaloid-containing medications in children is uncertain. Due to the alarming historical experience with severe toxicity and the syndrome of ergotism from natural and synthetic ergot alkaloids, triage recommendations for pediatric exposures to medicinal agents containing ergot alkaloids may be inappropriate and inconsistent. OBJECTIVES: The goal of this study was to describe the clinical effects of unintentional ergot alkaloid exposures in children and to identify the need for hospitalization in these cases. METHODS: This was a retrospective cohort study of all pediatric (< 7 years old) ergot alkaloid exposures reported to the California Poison Control System (CPCS) from 1997 to 2008. Case narratives were reviewed and assessed for patient demographics, ergot alkaloid agent and dose, route of and reason for exposure, symptoms, therapy, hospitalization period, and final outcome. RESULTS: Of the 374 cases, 353 met the inclusion criteria. The median age was 24 months (Range: 7-72 months) with more than 99% oral route of exposure. The most frequent clinical effect was gastrointestinal distress (16%), followed by lethargy (5%). Two cases with significant vascular and CNS symptoms were identified, both with complete recovery. For symptomatic patients, all symptoms were there at time of initial presentation. The majority, 62%, of all patients were treated in the hospital setting. The median length of hospital stay was 4 h (Range: 1-36 h). Ergot exposures had a similar number of serious outcomes (moderate or worse effects) compared to all other pediatric poisonings reported to the CPCS during the study period (odds ratio [OR], 0.98; 95% confidence interval [CI], 0.25-3.95), but were associated with a disproportionately higher number of hospitalizations (OR, 13.8; 95% CI, 11.1-17.1). CONCLUSIONS: Pediatric ergot exposures were associated with few transient adverse effects but multiple hospitalizations. Rare cases of significant toxicity associated with methylergonovine exposures were found. Current poison control send-in protocols and emergency department (ED) guidelines should consider home management and short ED stays as opposed to lengthy critical care bed admissions.

Basal subtype, as approximated by triple-negative phenotype, is associated with locoregional recurrence in a case-control study of women with 0-3 positive lymph nodes after mastectomy.

PURPOSE: Basal subtype, as approximated by the triple-negative phenotype (ER-PR-Her2-), has correlated with higher LRR in recent studies. Indications for postmastectomy RT (PMRT) in women with 0-3 positive lymph nodes remain unclear. We evaluated the importance of biologic subtype in a cohort of women with LRR after mastectomy. METHODS: We identified 22 women with 0-3 positive lymph nodes at our institution who were initially treated with mastectomy (without post-mastectomy radiation), suffered LRRs, and had paraffin-embedded tissue blocks from the primary mastectomy specimen available for staining. None of these women received PMRT. We case-control matched these to 29 women with 0-3 positive nodes who had mastectomy (no PMRT) and remained without evidence of disease at last follow-up and had available primary specimens for processing. We matched controls for age (±3 years) and follow-up duration (<5 year vs. more). Paraffin-embedded specimens were used to construct a triple-redundant tissue microarray. We used conditional logistic regressions to study the association between each predictor and LRR. Results were summarized based on odds ratio (OR). RESULTS: On univariate analysis, ER+, PR+, or the combination was strongly associated with lower odds of LRR. Basal subtype, as approximated by ER-PR-Her2- (TN), was associated with higher LRR (OR 8.5, p = 0.048). Use of chemotherapy also was associated with lower LRR (OR 0.126, p = 0.0073). CONCLUSIONS: Our data are concordant with reports from others demonstrating that TN phenotype is associated with higher LRR and can be considered along with other predictors of LRR when selecting women for PMRT.

Baking soda misuse as a home remedy: case experience of the California Poison Control System.

WHAT IS KNOWN AND OBJECTIVE: Baking soda is a common household product promoted by the manufacturer as an antacid. It contains sodium bicarbonate and has the potential for significant toxicity when ingested in excessive amounts. Characterizing the patterns and outcomes from the misuse of baking soda as a home remedy can guide the clinical assessment and preventative counselling of patients at risk for use of this product. METHODS: We conducted a retrospective review of all symptomatic cases involving ingestion and misuse of a baking soda powder product that were reported to the California Poison Control System between the years 2000 and 2012. RESULTS AND DISCUSSION: Of the 192 cases we identified, 55·8% were female, ages ranged 2 months to 79 years, and the most common reasons for misuse included antacid (60·4%), 'beat a urine drug test' (11·5%) and treat a UTI (4·7%). Most cases (55·2%) had significant symptoms warranting a medical evaluation, whereas 12 patients required hospital admission developed either electrolyte imbalances, metabolic alkalosis or respiratory depression. WHAT IS NEW AND CONCLUSION: Misuse of baking soda can result in serious electrolyte and acid/base imbalances. Patients at highest risk of toxicity may include those who chronically use an antacid, those who use the method to 'beat' urine drug screens, pregnant women and young children. Self-treatment with baking soda as a home remedy may also mask or delay medical care thereby complicating or exacerbating an existing medical problem. We suggest that healthcare providers counsel high-risk patients about the potential complications of misuse of baking soda as a home remedy.

Shaping the Future of Research: a perspective from junior scientists.

The landscape of scientific research and funding is in flux as a result of tight budgets, evolving models of both publishing and evaluation, and questions about training and workforce stability. As future leaders, junior scientists are uniquely poised to shape the culture and practice of science in response to these challenges. A group of postdocs in the Boston area who are invested in improving the scientific endeavor, planned a symposium held on October 2 (nd) and 3 (rd), 2014, as a way to join the discussion about the future of US biomedical research. Here we present a report of the proceedings of participant-driven workshops and the organizers' synthesis of the outcomes.

Induction of the RNA regulator LIN28A is required for the growth and pathogenesis of RESTless breast tumors.

The transcription factor RE1 silencing transcription factor (REST) is lost in approximately 20% of breast cancers. Although it is known that these RESTless tumors are highly aggressive and include all tumor subtypes, the underlying tumorigenic mechanisms remain unknown. In this study, we show that loss of REST results in upregulation of LIN28A, a known promoter of tumor development, in breast cancer cell lines and human breast tumors. We found that LIN28A was a direct transcriptional target of REST in cancer cells and that loss of REST resulted in increased LIN28A expression and enhanced tumor growth both in vitro and in vivo, effects that were dependent on heightened LIN28A expression. Tumors lacking REST expression were locally invasive, consistent with the increased lymph node involvement observed in human RESTless tumors. Clinically, human RESTless breast tumors also displayed significantly enhanced LIN28A expression when compared with non-RESTless tumors. Our findings therefore show a critical role for the REST-LIN28A axis in tumor aggression and suggest a causative relationship between REST loss and tumorigenicity in vivo.

The transcription factor REST is lost in aggressive breast cancer.

The function of the tumor suppressor RE1 silencing transcription factor (REST) is lost in colon and small cell lung cancers and is known to induce anchorage-independent growth in human mammary epithelial cells. However, nothing is currently known about the role of this tumor suppressor in breast cancer. Here, we test the hypothesis that loss of REST function plays a role in breast cancer. To assay breast tumors for REST function, we developed a 24-gene signature composed of direct targets of the transcriptional repressor. Using the 24- gene signature, we identified a previously undefined RESTless breast tumor subtype. Using gene set enrichment analysis, we confirmed the aberrant expression of REST target genes in the REST-less tumors, including neuronal gene targets of REST that are normally not expressed outside the nervous system. Examination of REST mRNA identified a truncated splice variant of REST present in the REST-less tumor population, but not other tumors. Histological analysis of 182 outcome-associated breast tumor tissues also identified a subpopulation of tumors that lack full-length, functional REST and over-express the neuroendocrine marker and REST target gene Chromogranin A. Importantly, patients whose tumors were found to be REST-less using either the 24-gene signature or histology had significantly poorer prognosis and were more than twice as likely to undergo disease recurrence within the first 3 years after diagnosis. We show here that REST function is lost in breast cancer, at least in part via an alternative splicing mechanism. Patients with REST-less breast cancer undergo significantly more early disease recurrence than those with fully functional REST, regardless of estrogen receptor or HER2 status. Importantly, REST status may serve as a predictor of poor prognosis, helping to untangle the heterogeneity inherent in disease course and response to treatment. Additionally, the alternative splicing observed in REST-less breast cancer is an attractive therapeutic target.

Alternative models for telephone response to pediatric poisonings.

BACKGROUND: Poison Control Centers (PCCs) provide telephone consultations to manage poisonings. They are threatened with funding loss. Policy decision-makers have requested an evaluation of alternate models for telephone management of poisonings. OBJECTIVE: We examined the feasibility of alternative models for the telephone management of poisonings from the public. METHODS: Alternative models evaluated included emergency medical dispatchers (EMDs), advice nurses (RNs), and poison information providers (PIPs) to manage real and hypothetical poisonings with protocols or computerized references (Poisindex) with and without PCC backup. RESULTS: EMDs and RNs with a structured protocol and access to a PCC specialist were able to manage a small subset of poisoning calls. EMDs and RNs managed 6% and 12% of poisoning calls respectively. Non-protocol management of hypothetical cases using Poisindex resulted in mismanagement of cases and longer periods of time to manage cases. PIPs within a PCC were able to manage a substantially greater proportion of calls, but had a significant portion of non-productive time waiting for a PCC call. CONCLUSION: EMDs, RNs, and technician-level PIPs can manage a subset of poisoning cases using structured protocols. Alternative providers were dependent on PCC staff for consultation of the majority of poisoning calls. There are several obstacles to these models and their cost-effectiveness needs to be determined. These studies were the basis of a new staffing model with the integration of PIPs into the call response system in California.

Diabetic and endocrine emergencies.

Endocrine emergencies constitute only a small percentage of the emergency workload of general doctors, comprising about 1.5% of all hospital admission in England in 2004-5. Most of these are diabetes related with the remaining conditions totalling a few hundred cases at most. Hence any individual doctor might not have sufficient exposure to be confident in their management. This review discusses the management of diabetic ketoacidosis, hyperosmolar hyperglycaemic state, hypoglycaemia, hypercalcaemia, thyroid storm, myxoedema coma, acute adrenal insufficiency, phaeochromocytoma hypertensive crisis and pituitary apoplexy in the adult population.

Integrating decision tools for the sustainable management of land contamination.

The approach to taking decisions on the management of land contamination has changed markedly over 30 years. Change has been rapid with policy makers and regulators, practitioners and researchers having to keep pace with new technologies, assessment criteria and diagnostic methods for their measurement, techniques for risk analysis and the frameworks that support decision-makers in their efforts to regenerate historically contaminated land. Having progressed from simple hazard assessment through to 'sustainability appraisal' we might now consider piecing together the experience of decision-making for managing land contamination. Here, we critically review recent developments with a view to considering how better decisions can be made by integrating the decision tools available. We are concerned with the practicality of approach and the issues that arise for practitioners as decision criteria are broadened.