Research gaps and opportunities in precision nutrition: an NIH workshop report.

Precision nutrition is an emerging concept that aims to develop nutrition recommendations tailored to different people's circumstances and biological characteristics. Responses to dietary change and the resulting health outcomes from consuming different diets may vary significantly between people based on interactions between their genetic backgrounds, physiology, microbiome, underlying health status, behaviors, social influences, and environmental exposures. On 11-12 January 2021, the National Institutes of Health convened a workshop entitled "Precision Nutrition: Research Gaps and Opportunities" to bring together experts to discuss the issues involved in better understanding and addressing precision nutrition. The workshop proceeded in 3 parts: part I covered many aspects of genetics and physiology that mediate the links between nutrient intake and health conditions such as cardiovascular disease, Alzheimer disease, and cancer; part II reviewed potential contributors to interindividual variability in dietary exposures and responses such as baseline nutritional status, circadian rhythm/sleep, environmental exposures, sensory properties of food, stress, inflammation, and the social determinants of health; part III presented the need for systems approaches, with new methods and technologies that can facilitate the study and implementation of precision nutrition, and workforce development needed to create a new generation of researchers. The workshop concluded that much research will be needed before more precise nutrition recommendations can be achieved. This includes better understanding and accounting for variables such as age, sex, ethnicity, medical history, genetics, and social and environmental factors. The advent of new methods and technologies and the availability of considerably more data bring tremendous opportunity. However, the field must proceed with appropriate levels of caution and make sure the factors listed above are all considered, and systems approaches and methods are incorporated. It will be important to develop and train an expanded workforce with the goal of reducing health disparities and improving precision nutritional advice for all Americans.

Soluble Receptor for Advanced Glycation End Products (sRAGE) Isoforms Predict Changes in Resting Energy Expenditure in Adults with Obesity during Weight Loss.

Background: Accruing evidence indicates that accumulation of advanced glycation end products (AGEs) and activation of the receptor for AGEs (RAGE) play a significant role in obesity and type 2 diabetes. The concentrations of circulating RAGE isoforms, such as soluble RAGE (sRAGE), cleaved RAGE (cRAGE), and endogenous secretory RAGE (esRAGE), collectively sRAGE isoforms, may be implicit in weight loss and energy compensation resulting from caloric restriction. Objectives: We aimed to evaluate whether baseline concentrations of sRAGE isoforms predicted changes (∆) in body composition [fat mass (FM), fat-free mass (FFM)], resting energy expenditure (REE), and adaptive thermogenesis (AT) during weight loss. Methods: Data were collected during a behavioral weight loss intervention in adults with obesity. At baseline and 3 mo, participants were assessed for body composition (bioelectrical impedance analysis) and REE (indirect calorimetry), and plasma was assayed for concentrations of sRAGE isoforms (sRAGE, esRAGE, cRAGE). AT was calculated using various mathematical models that included measured and predicted REE. A linear regression model that adjusted for age, sex, glycated hemoglobin (HbA1c), and randomization arm was used to test the associations between sRAGE isoforms and metabolic outcomes. Results: Participants (n = 41; 70% female; mean ± SD age: 57 ± 11 y; BMI: 38.7 ± 3.4 kg/m2) experienced modest and variable weight loss over 3 mo. Although baseline sRAGE isoforms did not predict changes in ∆FM or ∆FFM, all baseline sRAGE isoforms were positively associated with ∆REE at 3 mo. Baseline esRAGE was positively associated with AT in some, but not all, AT models. The association between sRAGE isoforms and energy expenditure was independent of HbA1c, suggesting that the relation was unrelated to glycemia. Conclusions: This study demonstrates a novel link between RAGE and energy expenditure in human participants undergoing weight loss.This trial was registered at clinicaltrials.gov as NCT03336411.

Hospital load and increased COVID-19 related mortality in Israel.

The spread of Coronavirus disease 19 (COVID-19) has led to many healthcare systems being overwhelmed by the rapid emergence of new cases. Here, we study the ramifications of hospital load due to COVID-19 morbidity on in-hospital mortality of patients with COVID-19 by analyzing records of all 22,636 COVID-19 patients hospitalized in Israel from mid-July 2020 to mid-January 2021. We show that even under moderately heavy patient load (>500 countrywide hospitalized severely-ill patients; the Israeli Ministry of Health defined 800 severely-ill patients as the maximum capacity allowing adequate treatment), in-hospital mortality rate of patients with COVID-19 significantly increased compared to periods of lower patient load (250-500 severely-ill patients): 14-day mortality rates were 22.1% (Standard Error 3.1%) higher (mid-September to mid-October) and 27.2% (Standard Error 3.3%) higher (mid-December to mid-January). We further show this higher mortality rate cannot be attributed to changes in the patient population during periods of heavier load.

A Minimalistic Resource Allocation Model to Explain Ubiquitous Increase in Protein Expression with Growth Rate.

Most proteins show changes in level across growth conditions. Many of these changes seem to be coordinated with the specific growth rate rather than the growth environment or the protein function. Although cellular growth rates, gene expression levels and gene regulation have been at the center of biological research for decades, there are only a few models giving a base line prediction of the dependence of the proteome fraction occupied by a gene with the specific growth rate. We present a simple model that predicts a widely coordinated increase in the fraction of many proteins out of the proteome, proportionally with the growth rate. The model reveals how passive redistribution of resources, due to active regulation of only a few proteins, can have proteome wide effects that are quantitatively predictable. Our model provides a potential explanation for why and how such a coordinated response of a large fraction of the proteome to the specific growth rate arises under different environmental conditions. The simplicity of our model can also be useful by serving as a baseline null hypothesis in the search for active regulation. We exemplify the usage of the model by analyzing the relationship between growth rate and proteome composition for the model microorganism E.coli as reflected in recent proteomics data sets spanning various growth conditions. We find that the fraction out of the proteome of a large number of proteins, and from different cellular processes, increases proportionally with the growth rate. Notably, ribosomal proteins, which have been previously reported to increase in fraction with growth rate, are only a small part of this group of proteins. We suggest that, although the fractions of many proteins change with the growth rate, such changes may be partially driven by a global effect, not necessarily requiring specific cellular control mechanisms.

Overlapping codes within protein-coding sequences.

Genomes encode multiple signals, raising the question of how these different codes are organized along the linear genome sequence. Within protein-coding regions, the redundancy of the genetic code can, in principle, allow for the overlapping encoding of signals in addition to the amino acid sequence, but it is not known to what extent genomes exploit this potential and, if so, for what purpose. Here, we systematically explore whether protein-coding regions accommodate overlapping codes, by comparing the number of occurrences of each possible short sequence within the protein-coding regions of over 700 species from viruses to plants, to the same number in randomizations that preserve amino acid sequence and codon bias. We find that coding regions across all phyla encode additional information, with bacteria carrying more information than eukaryotes. The detailed signals consist of both known and potentially novel codes, including position-dependent secondary RNA structure, bacteria-specific depletion of transcription and translation initiation signals, and eukaryote-specific enrichment of microRNA target sites. Our results suggest that genomes may have evolved to encode extensive overlapping information within protein-coding regions.

Preferentially quantized linker DNA lengths in Saccharomyces cerevisiae.

The exact lengths of linker DNAs connecting adjacent nucleosomes specify the intrinsic three-dimensional structures of eukaryotic chromatin fibers. Some studies suggest that linker DNA lengths preferentially occur at certain quantized values, differing one from another by integral multiples of the DNA helical repeat, approximately 10 bp; however, studies in the literature are inconsistent. Here, we investigate linker DNA length distributions in the yeast Saccharomyces cerevisiae genome, using two novel methods: a Fourier analysis of genomic dinucleotide periodicities adjacent to experimentally mapped nucleosomes and a duration hidden Markov model applied to experimentally defined dinucleosomes. Both methods reveal that linker DNA lengths in yeast are preferentially periodic at the DNA helical repeat ( approximately 10 bp), obeying the forms 10n+5 bp (integer n). This 10 bp periodicity implies an ordered superhelical intrinsic structure for the average chromatin fiber in yeast.

Perianesthetic dental injuries: analysis of incident reports.

STUDY OBJECTIVE: To conduct a retrospective analysis of incident reports concerning dental injury, the most common cause for litigation against anesthesiologists, to determine specific risk factors that will help in formulating a risk reduction strategy for this clinical problem. DESIGN: Retrospective chart review of a large professional liability insurer. INTERVENTIONS: Of 40 hospitals that report to the MRM Co. as part of the professional liability insurance, during the years 1992-1999, 18 hospitals reported dental injury. A Maxillofacial surgeon (GN) and an anesthesiologist (ES), using a structured form, reviewed the reports. Evaluation of the cost of injury was determined from the patient's claims or from an evaluation of rehabilitation plan constructed by the maxillofacial surgery consultants to the company. MEASUREMENTS AND MAIN RESULTS: There were 203 incidents due to dental injury. The patients were most commonly in their 5(th) to 7(th) decade. Eighty six percent of the injured teeth were the upper incisors. Lower incisors were more likely to be injured during an urgent intubation, or due to airway manipulation other than intubation. (i.e., oral airway insertion) In only 38 (18.6%) cases was there a previous assessment of an expected difficult intubation. Dentition was judged to be pathological in 32% of the patients. CONCLUSIONS: In elective intubation, the teeth most likely to be injured are the upper incisors, in patients aged 50-70 years. In most cases dental injury is not associated with a pre-event prediction of difficult intubation.