...in June 2013 the NHLBI initiated collaboration with the ACC and AHA to work with other organizations to complete and publish the guidelines noted above and make them available to the widest ...possible constituency. ...the format of the recommendations differs from other ACC/AHA guidelines. Each recommendation has been mapped from the NHLBI grading format to the ACC/ AHA Classification of Recommendation/Level of Evidence (COR/ LOE) construct (Table 1) and is expressed in both formats. Because of the inherent differences in grading systems and the clinical questions driving the recommendations, alignment between the NHLBI and ACC/AHA formats is in some cases imperfect. According to the 1998 "Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults- The Evidence Report" (5), overweight is defined as a body mass index (BMI) of 25 kg/m2 to 29.9 kg/m2 and obesity as a BMI of >30 kg/m2.
Lipidomics requires the accurate annotation of lipids in complex samples to enable determination of their biological relevance. We demonstrate that unintentional in-source fragmentation (ISF, common ...in lipidomics) generates ions that have identical masses to other lipids. Lysophosphatidylcholines (LPC), for example, generate in-source fragments with the same mass as free fatty acids and lysophosphatidylethanolamines (LPE). The misannotation of in-source fragments as true lipids is particularly insidious in complex matrixes since most masses are initially unannotated and comprehensive lipid standards are unavailable. Indeed, we show such LPE/LPC misannotations are incorporated in the data submitted to the National Institute of Standards and Technology (NIST) interlaboratory comparison exercise. Computer simulations exhaustively identified potential misannotations. The selection of in-source fragments of highly abundant lipids as features, instead of the correct recognition of trace lipids, can potentially lead to (i) missing the biologically relevant lipids (i.e., a false negative) and/or (ii) incorrect assignation of a phenotype to an incorrect lipid (i.e., false positive). When ISF is not eliminated in the negative ion mode, ∼40% of the 100 most abundant masses corresponding to unique phospholipids measured in plasma were artifacts from ISF. We show that chromatographic separation and ion intensity considerations assist in distinguishing precursor ions from in-source fragments, suggesting ISF may be especially problematic when complex samples are analyzed via shotgun lipidomics. We also conduct a systematic evaluation of electrospray ionization (ESI) source parameters on an Exactive equipped with a heated electrospray ionization (HESI-II) source with the objective of obtaining uniformly appropriate source conditions for a wide range of lipids, while, at the same time, reducing in-source fragmentation.
The US faces remarkable food and nutrition challenges. A new federal effort to strengthen and coordinate nutrition research could rapidly generate the evidence base needed to address these multiple ...national challenges. However, the relevant characteristics of such an effort have been uncertain.
Our aim was to provide an objective, informative summary of 1) the mounting diet-related health burdens facing our nation and corresponding economic, health equity, national security, and sustainability implications; 2) the current federal nutrition research landscape and existing mechanisms for its coordination; 3) the opportunities for and potential impact of new fundamental, clinical, public health, food and agricultural, and translational scientific discoveries; and 4) the various options for further strengthening and coordinating federal nutrition research, including corresponding advantages, disadvantages, and potential executive and legislative considerations.
We reviewed government and other published documents on federal nutrition research; held various discussions with expert groups, advocacy organizations, and scientific societies; and held in-person or phone meetings with >50 federal staff in executive and legislative roles, as well as with a variety of other stakeholders in academic, industry, and nongovernment organizations.
Stark national nutrition challenges were identified. More Americans are sick than are healthy, largely from rising diet-related illnesses. These conditions create tremendous strains on productivity, health care costs, health disparities, government budgets, US economic competitiveness, and military readiness. The coronavirus disease 2019 (COVID-19) outbreak has further laid bare these strains, including food insecurity, major diet-related comorbidities for poor outcomes from COVID-19 such as diabetes, hypertension, and obesity, and insufficient surveillance on and coordination of our food system. More than 10 federal departments and agencies currently invest in critical nutrition research, yet with relatively flat investments over several decades. Coordination also remains suboptimal, documented by multiple governmental reports over 50 years. Greater harmonization and expansion of federal investment in nutrition science, not a silo-ing or rearrangement of existing investments, has tremendous potential to generate new discoveries to improve and sustain the health of all Americans. Two identified key strategies to achieve this were as follows: 1) a new authority for robust cross-governmental coordination of nutrition research and other nutrition-related policy and 2) strengthened authority, investment, and coordination for nutrition research within the NIH. These strategies were found to be complementary, together catalyzing important new science, partnerships, coordination, and returns on investment. Additional complementary actions to accelerate federal nutrition research were identified at the USDA.
The need and opportunities for strengthened federal nutrition research are clear, with specific identified options to help create the new leadership, strategic planning, coordination, and investment the nation requires to address the multiple nutrition-related challenges and grasp the opportunities before us.
Homo sapiens harbor trillions of microbes, whose microbial metagenome (collective genome of a microbial community) using omic validation interrogation tools is estimated to be at least 100-fold that ...of human cells, which comprise 23,000 genes. This article highlights some of the current progress and open questions in nutrition-related areas of microbiome research. It also underscores the metabolic capabilities of microbial fermentation on nutritional substrates that require further mechanistic understanding and systems biology approaches of studying functional interactions between diet composition, gut microbiota, and host metabolism. Questions surrounding bacterial fermentation and degradation of dietary constituents (particularly by Firmicutes and Bacteroidetes) and deciphering how microbial encoding of enzymes and derived metabolites affect recovery of dietary energy by the host are more complex than previously thought. Moreover, it is essential to understand to what extent the intestinal microbiota is subject to dietary control and to integrate these data with functional metabolic signatures and biomarkers. Many lines of research have demonstrated the significant role of the gut microbiota in human physiology and disease. Probiotic and prebiotic products are proliferating in the market in response to consumer demand, and the science and technology around these products are progressing rapidly. With high-throughput molecular technologies driving the science, studying the bidirectional interactions of host-microbial cometabolism, epithelial cell maturation, shaping of innate immune development, normal vs. dysfunctional nutrient absorption and processing, and the complex signaling pathways involved is now possible. Substantiating the safety and mechanisms of action of probiotic/prebiotic formulations is critical. Beneficial modulation of the human microbiota by using these nutritional and biotherapeutic strategies holds considerable promise as next-generation drugs, vaccinomics, and metabolic agents and in novel food discovery.
Context:
The effect of obesity and concomitant insulin resistance on pubertal development is incompletely elucidated.
Objective:
To determine how measures of adiposity and insulin resistance are ...associated with pubertal maturation in boys and girls.
Setting and Design:
Breast and pubic hair Tanner stage and testicular volume by orchidometry were determined by physical examination in 1066 children. Ovarian volume was estimated by trans-abdominal ultrasound. Fat mass, skeletal age, and fasting serum for insulin and glucose, total T, estradiol, estrone, dehydroepiandrosterone-sulfate, and androstenedione were measured at the National Institutes of Health Clinical Research Center. Convenience sample; 52% obese, 59% female.
Results:
Logistic regression identified a significant interaction between sex and obesity for prediction of pubertal development (P ≤ .01). There was a negative association between boys' testicular volume and body mass index (BMI)/fat mass but a positive association between girls' breast stage and BMI/fat mass. Ovarian volume in girls was positively associated with insulin resistance but not with BMI/fat mass. There was a positive association between obesity and measures of estrogen exposure (breast development and skeletal age) in both sexes. Positive correlations were seen for girls between BMI and pubic hair development and between insulin resistance and T production, whereas adiposity was negatively associated with pubic hair in boys.
Conclusions:
Significant sexual dimorphisms in the manifestations of pubertal development are seen in obese girls and boys. Two known effects of obesity, increased peripheral conversion of low-potency androgens to estrogens by adipose tissue-aromatase and increased insulin resistance, may be in large part responsible for these differences.
OBJECTIVE: The purpose of this study was to determine whether having childhood depressive symptoms is a risk factor that prospectively predicts impairment in glucose homeostasis. RESEARCH DESIGN AND ...METHODS: A non–treatment-seeking sample of 115 children (aged 5–13 years), oversampled for being at risk for adult obesity, was assessed at baseline and again approximately 6 years later. Children self-reported depressive symptoms using the Children’s Depression Inventory at baseline. Insulin resistance was assessed at baseline and follow-up with the homeostasis model assessment of insulin resistance index (HOMA-IR). RESULTS: Children’s depressive symptoms were a significant predictor of follow-up HOMA-IR, fasting insulin, and fasting glucose in models accounting for baseline HOMA-IR, insulin, or glucose values; sex; race; baseline age; baseline BMI; change in BMI at follow-up; family history of type 2 diabetes; and time in the study (P < 0.01). CONCLUSIONS: In this study, depressive symptomatology at baseline predicted the progression of insulin resistance during child and adolescent development independent of changes in BMI. Research is needed to determine whether early intervention to decrease elevated depressive symptoms in youth ameliorates later development of insulin resistance and lessens the risk of type 2 diabetes.
Context: Some studies suggest the presence of metabolic syndrome before adulthood may identify those at high risk for later cardiovascular morbidity, but there are few data examining the reliability ...of pediatric metabolic syndrome.
Objective: To examine the short- and long-term stability of pediatric metabolic syndrome.
Design: Metabolic syndrome was defined as having at least three of the following: waist circumference, blood pressure, and fasting serum triglycerides in the 90th or higher percentile for age/sex; high-density lipoprotein-cholesterol 10th or lower percentile for age/sex; and fasting serum glucose of at least 100 mg/dl. Short-term metabolic syndrome stability (repeated measurements within 60 d) was assessed in obese youth ages 6–17 yr. Long-term metabolic syndrome stability (repeated measurements more than 1.5 yr apart) was studied in 146 obese and nonobese children age 6–12 yr at baseline.
Patients and Setting: Convenience samples of obese and nonobese youth ages 6–17 yr participating in research studies were collected at a clinical research hospital.
Results: Short-term metabolic syndrome stability (repeat measurements performed 19.7 ± 13.1 d apart) was assessed in 220 children. The diagnosis of metabolic syndrome was unstable in 31.6% of cases. At their short-term follow-up visit, incidence of metabolic syndrome among participants who did not have metabolic syndrome at baseline was 24%. In the long term (repeat measurements performed 5.6 ± 1.9 yr apart), the diagnosis of metabolic syndrome was unstable in 45.5% of cases.
Conclusions: Cutoff-point-based definitions for pediatric metabolic syndrome have substantial instability in the short and long term. The value of making a cutoff-point-based diagnosis of metabolic syndrome during childhood or adolescence remains in question.
Cut-point-based definitions for pediatric metabolic syndrome have substantial instability in the short- and long-term that may limit the value of making this diagnosis.
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