bluuebunny/crossref_metadata_2025 huggingface dataset:
Biology of the lumbar zygapophyseal joint and its clinical implications
Authors: Cramer Gregory D
Published: November 2023

This session will begin with a brief review of relevant clinical anatomy (including microscopic anatomy) of the lumbar zygapophyseal (Z, facet) joints. The results of a series of mechanisms‐based, proof of concept, animal and human studies will then be summarized. The studies were designed to investigate a fundamental hypothesis of a beneficial effect of spinal manipulation (SM). Briefly, the hypothesis states that the Z joints, which are known pain generators, become hypomobile for a variety of reasons and that connective tissue adhesions develop in these hypomobile Z joints. SM is hypothesized to gap the Z joint facet surfaces, which re‐establishes normal joint movement by, in part, breaking up or preventing the formation of the joint adhesions. Our previous work identified time dependent Z joint adhesions and degenerative changes following induced spinal hypomobility in a rat model. Important to subsequent studies, such Z joint changes are thought to be accompanied by crepitus (joint sounds). In concurrent research, we assessed healthy human subjects (n=64) and subjects with acute and subacute LBP (n=112). We found that the lumbar Z joints gapped during both side‐posture positioning and during SM, and the joints gapped significantly more during SM (following two weeks of treatment for LBP subjects). We then used accelerometers to assess the vibrations associated with Z joint gapping induced cavitation during SM and side‐posture positioning. We identified the specific lumbar Z joints or sacroiliac joints from which cavitations originated during lumbar SM (n=30) and non‐SM controls (n=10) and found a positive correlation between cavitation and Z joint gapping. More recently we assessed healthy (n=5) and low back pain (LBP, n=5) subjects from 3 different age groups (18–25, 26–45, and 46–65 years) to evaluate Z joint crepitus during full ranges of motion before and after SM. This was done to determine the feasibility of using crepitus as a potential biomarker for Z joint hypomobility. In this pilot study, crepitus prevalence increased with age, was higher in LBP than healthy subjects, and overall decreased following SM. We concluded that crepitus assessment using accelerometers has the potential of being an outcome measure for assessing Z joint function during movement and the effects of LBP treatments (e.g., SM) on Z joint function. The session will conclude with a brief discussion of future research planned to further assess non‐invasive, acoustic measures of Z joint function. When combined with imaging (e.g., US) and measures of pain and function, such acoustic measures could help evaluate the relationships among Z joint degeneration and various treatment methods.

Support or Funding Information

NIH/NCCIH grants 1‐3R01 AT000123
Hedgehog Signaling in Cardiac Development and Disease
Authors: Moskowitz Ivan
Published: November 2023

Congenital Heart Disease (CHD), malformations of the heart present at birth, is the most common class of life‐threatening birth defect. Atrioventricular septal defects (AVSDs) are a common and serious form of CHD in humans, comprising 5–10% of all CHD cases and a greater proportion of those requiring surgical correction. Gaining a mechanistic understanding of atrioventricular septation is an essential goal for improving clinical approaches to structural heart disease. Whereas the canonical view of atrioventricular septation was based on intracardiac events centered at the endocardial cushion, recent work demonstrates that cilia‐required Sonic hedgehog (Shh) signaling in the Second Heart Field, outside of the heart proper, drives atrioventricular septation. We harness our new understanding of atrioventricular septation to address the molecular developmental mechanisms underlying ASVDs in more detail. Hh signaling is transduced by the GLI family of transcription factors (TFs). We have previously described a genetic interaction between the cardiogenic TF TBX5 and GLI TFs in the SHF that promotes atrioventricular septation. These studies suggest that Hh signaling‐dependent GLI TFs and cardiogenic TFs co‐regulate a gene regulatory network critical for the specification of atrial septum progenitors. We will present new data that test predictions of this model.

Support or Funding Information

This work has been supported by grants from the NIH (R01 HL092153 and R01HL124836) and AHA (13EIA14690081)
The Role of Long Non‐Coding RNAs in Nuclear Organization and Disease
Authors: Spector David L.
Published: November 2023

Genome‐wide analyses have identified approximately 16,000 human long non‐coding RNA (lncRNA) genes representing approximately 27% of annotated human genes. LncRNAs tend to localize to cell nuclei implying roles in gene expression and/or nuclear organization. While the number of currently annotated lncRNA genes is close to the number of protein‐coding genes we know relatively little in regard to the molecular mechanisms by which these RNA molecules exert their functions. I will discuss an interesting mouse (19qA) and human (11q13.1) genomic region that harbors 2 lncRNA genes, Neat1 and Malat1. Evidence will be presented for an architectural role of Neat1 in the establishment and maintenance of a nuclear domain called paraspeckles, and Malat1 in regulating gene expression and RNA splicing in breast cancer progression.

Support or Funding Information

D.L.S. is supported by NIGMS 42694 and NCI 5PO1CA013106□Project 3
Understanding and modeling aging
Authors: Brunet Anne
Published: November 2023

Age is the greatest risk factor for most diseases, including neurodegenerative diseases, cardiovascular diseases, cancer, metabolic disorders, diabetes, and autoimmune diseases. However, our understanding of aging is still rudimentary because aging is an extraordinarily complex process that defies many conventional rules in biology. My lab aims to discover new, fundamental principles of aging regulation that can ultimately be translated to humans. We have broken new ground by pioneering the naturally short‐lived African killifish as a new model to study aging and diseases in the context of aging in vertebrates. This new model has allowed us to generate a high throughput platform to not only model diseases by also screen for the impact of genetic pathways and chemical compounds on disease. In addition to developing this fish, my lab is also using C. elegans and mice, as well as cells from mice and humans, to identify genetic and epigenetic mechanisms involved in the regulation of lifespan and understand their mode of action. This approach has already generated new insights on the epigenetic regulation of aging. Our work has the promise to transform our understanding of why aging is at the heart of so many human diseases.
Bacterial metabolism and antibiotic efficacy
Authors: Collins James J
Published: November 2023

In this talk, we will highlight recent work in network biology aimed at elucidating the mechanisms of action of antibacterials and bacterial responses to antibiotic treatment. Of note, we highlight recent work showing that antibiotics perturb the metabolic state of bacteria and that the metabolic state of bacteria impacts antibiotic We discuss how the insights arising from these studies can be harnessed to create more effective antibiotics and innovative antibacterial therapies to treat resistant and persistent infections.
Context‐specific action of ribosomal antibiotics
Authors: Vazquez‐Laslop Nora , Mankin Alexander
Published: November 2023

Ribosomes are the makers of all cellular proteins and one of the preferred targets of clinically important antibacterials. Polymerization of amino acids into polypeptides occurs at the peptidyl transferase center (PTC), which resides in the large subunit of the ribosome. The nascent protein is then threaded through the exit tunnel in its way out to the cytoplasm. The classic natural compound chloramphenicol and the synthetic antibiotic linezolid specifically bind to the PTC, hindering accommodation of the aminoacylated tRNA substrate, and thus inhibiting formation of peptide bonds. Antibiotics belonging to the macrolide family, such as the natural erythromycin and the semisynthetic ketolides, partially block the exit tunnel, obstructing the passage of the nascent peptide. The classic models for the action of PTC‐ or exit tunnel‐targeting antibiotics have suggested that inhibition of protein synthesis occurs indiscriminately. However, the ribosome profiling analysis of the global translation of bacteria exposed to the drugs and biochemical experiments in cell free systems have revealed that these compounds stall translation in a context specific manner. The PTC‐ and exit tunnel‐targeting compounds show different specificities but, in both cases, the context is dictated by the sequence of the nascent protein. Our findings demonstrate that the protein residing in the exit tunnel influences the properties of the PTC, including its ability to bind inhibitors of translation. Therefore, the mechanism of action of antibiotics is directly affected by the functional link between the exit tunnel and the catalytic core of the ribosome. Non‐universal inhibition of protein synthesis may also apply to other classes of ribosomal‐targeting drugs. Development of antibiotics with improved antibacterial activity may depend on our understanding of their context specific mode of action.

Support or Funding Information

National Institutes of Health Grant R01GM106386

National Institutes of Health Grant AI125518

Melinta Therapeutics

Cempra Pharmaceuticals
Maximizing career and professional development during doctoral training
Authors: Feeney Shea E.
Published: November 2023

Over the last few decades the number of STEM doctorate recipients has been consistently increasing while at odds with the drastic employment shift away from the previous archetype career pathway of tenured faculty. Where once research mentors at an academic institution could provide career mentoring for the large majority of their students they can no longer fully serve this role with the rising number of students seeking employment outside of the academic sector. It is clear that we have a growing gap in career and professional development training as some reports suggest that more than half of graduate and early postdoctoral trainees have undefined career interests. This problem is further compounded with a rapid increase in the number of recent doctoral students that have yet to secure employment or a post‐doctoral position. Arguably then, doctoral training is not evolving to equip trainees with the necessary resources for career planning and professional development needed for the diverse career paths available to scientists. A cross‐country comparison and evaluation of efficacy of current practices and programs available to doctoral students for career and professional development will be presented in order to drive an informed restructuring of current training practices so that we can best assist our trainees for the next step—securing a career.
MAPK substrate phosphoproteomics screen identifies GRAB as a novel MKP‐5‐regulated MAPK substrate
Authors: Bennett Anton M.
Published: November 2023

The mitogen‐activated protein kinases (MAPKs) have been shown to regulate skeletal muscle function. Previously, we showed that MAPK phosphatase‐5 (MKP5) negatively regulates regeneration of skeletal muscle through inhibition of p38 MAPK and c‐Jun N‐terminal kinase (JNK) activities. However, the identity and contribution of MKP5‐dependent MAPK targets in the regulation of skeletal muscle function and regenerative myogenesis has not been established. In order to identify MKP5‐dependent MAPK substrates in skeletal muscle, we performed a global differential phospho‐MAPK substrate screen in regenerating skeletal muscles of wild type and Mkp5−/− mice. The results of this screen identified several MKP5‐dependent MAPK substrates that were differentially phosphorylated during muscle regeneration. We discovered a novel MKP5‐regulated MAPK substrate, called guanine nucleotide exchange factor for Rab3A (GRAB) that was hyper phosphorylated by 8‐fold in skeletal muscles of Mkp5−/− mice as compared with wild type mice. We identified that GRAB serine 169 is a novel site of phosphorylation mediated by JNK. Myoblasts overexpressing a phosphorylation‐defective mutant of GRAB (GRAB‐S169A) did not impair myoblast proliferation but inhibited the ability of C2C12 myoblasts to differentiate. We found that GRAB phosphorylation at Ser169 was required for the secretion of the pro‐myogenic cytokine interleukin 6 (IL‐6). Consistent with this observation, MKP5‐deficient mice exhibited increased circulating expression of IL‐6 as compared with wild type mice. Collectively, these data demonstrate a novel mechanism whereby MKP5‐mediated regulation of MAPK activity negatively regulates phosphorylation of GRAB which in turn is responsible for the secretion of the pro‐myogenic cytokine, IL‐6. These data are consistent with the notion that MKP5 serves as an essential regulator of MAPK‐dependent signaling in skeletal muscle.

Support or Funding Information

NIH/NIAMS RO1 AR066601
Genetic analysis of pathogenesis in Toxoplasma gondii
Authors: Sibley L. David
Published: November 2023

Toxoplasma gondii is a widespread parasite of animals that also causes opportunistic infections in humans. Forward genetic mapping studies and comparative genomic analyses of diverse strains have collectively demonstrated that virulence is largely mediated by expansion of several families of secretory pathogenesis determinants (SPDs). Among these are secreted effectors that bind to host transcription factors to disrupt host gene expression. For example, the recently described Inhibitor of STAT1 Transcription (TgIST) blocks the effect of interferon gamma, which is normally mediated by this host transcription factor. TgIST is secreted across the parasitophorous vacuole by a parasite‐encoded export pathway on the vacuole membrane. Within the host cell, TgIST binds to active phosphorylated STAT1 homodimers that are found tightly bound to promoter elements in nucleus, yet paradoxically transcription is blocked. Biochemical studies revealed that TgIST works by recruiting the Nucleosome Remodeling and Repressive complex (NuRD), which modifies chromatin to suppress gene expression. TgIST is predicted to be a highly unstructured protein, suggesting it recognizes its binding partners through induced fit – a property shared by many transcriptional co‐factors. TgIST is conserved among all strains of T. gondii and it mediates repression of type I, II and III interferons, thus dampening immunity. These studies reveal the molecular mechanism of how SPDs mediate changes in host gene expression to block innate immunity and contribute to pathogenesis.

Support or Funding Information

Supported by grants from the NIH.
Metabolic and transcriptional alterations observed in the early stages of cardiac substrate switching hint at novel mTOR‐regulated hypertrophy signaling pathways
Authors: Pascual Florencia , Schisler Jonathan C. , Grevengoed Trisha J. , Coleman Rosalind A.
Published: November 2023

Cardiomyocyte‐specific deficiency of long‐chain acyl‐CoA synthetase 1 (Acsl1H−/−) results in a block in FA oxidation, rendering the heart dependent on the oxidation of glucose for contractile energy. Ten weeks after temporally‐induced Acsl1 inactivation, knockout hearts exhibit a 90% reduction in total ACSL activity and FA oxidation, and a compensatory increase in glucose uptake, as well as the development of mTOR‐mediated hypertrophy and diastolic dysfunction. Concomitant treatment with the mTOR inhibitor rapamycin for 10 weeks prevents cardiac hypertrophy due to the attenuation in the abnormal expression of hypertrophy‐associated genes as well as a block in ventricular S6K phosphorylation, suggesting heart‐specific mTOR signaling. The current work examines the early changes in gene expression, metabolites, and cardiac function as the Acsl1‐deficient heart adapts to the loss of FA substrate. Two weeks after cardiac‐specific Acsl1 ablation, ACSL activity decreased 60% and glucose and FA uptake were markedly altered, consistent with a shift toward glycolytic oxidation. Strikingly, this partial inhibition of FA activation was sufficient to elicit cardiac hypertrophy, the development of which was reversed by concomitant rapamycin treatment. No significant changes were observed in plasma glucose, NEFA, free glycerol or TAG, indicating that systemic metabolic homeostasis was not affected by short‐term cardiac Acsl1 deficiency. However, rapamycin‐responsive changes to the metabolic fingerprint and transcriptional response of Acsl1H−/− hearts were observed, many of which were unique to the two week time point. Notably, alterations in the rapamycin‐sensitive mTOR genes identified in the ten week cardiac Acsl1 inactivation model were not evident at two weeks, despite the observed development of cardiac hypertrophy in both temporal knockout models. In addition, changes in expression of fibrosis genes were detected only in the short‐term Acsl1 abrogation model. Taken as a whole, these results support the notion that cardiac hypertrophy can develop via a novel pathway. Additional analyses of microarray and metabolomic data, as well as histological studies of fibrosis and hypertrophy, will allow us to elucidate the interrelationship between hypertrophy, cardiac dysfunction, and substrate use in heart.

Support or Funding Information

Supported by DK59935 and a grant from the American Heart Association 12GRNT12030144.
Diet Quality Declines and Differs by Race in Early Childhood
Authors: Reynolds Kelly Anne , Kalkwarf Heidi , Summer Suzanne , Khoury Phil , Gavin Marcia , Woo Jessica G
Published: November 2023

Introduction

Diet quality is an important determinant of health in children, but little is known about how diet quality progresses during early childhood. We hypothesized that overall diet quality, assessed by the 2010 Healthy Eating Index, would decline during early childhood.

Methods

Three hundred seventy‐two (372) healthy 3‐year‐old children were recruited from the Greater Cincinnati area and assessed every 4 months until age 7 at in‐person clinical visits, for a total of 13 visits. Parents completed 3‐day diet diaries at each visit which were analyzed for nutrient composition using the Nutrition Data Systems for Research system (NDSR). The 2010 Healthy Eating Index (HEI) total and food‐group component scores were calculated and averaged by year of study. Longitudinal mixed modeling was used to evaluate longitudinal trends.

Results

The population was 52% (195/372) male, 78% (290/372) white and 83% (308/372) completed the final visit. HEI total scores at age 3 were poor (mean±SE: 45.2±0.4) and declined significantly between ages 3–7 (p<0.0001). None of the participants had “good” quality diet (HEI>80) at any point in the study. HEI total scores differed by race, with white children having significantly higher scores (p=0.05, Figure 1). HEI component scores showed a mixed pattern, with some significantly improving (protein [Figure 2], vegetables and fatty acids), some significantly worsening (dairy, refined grains, sodium, whole fruit and total fruit); other component scores did not change. Differences by race also varied, with African‐Americans having consistently better scores for vegetables, greens and beans, protein and fatty acids (all p<0.0001, Figure 2), while white children had better scores for dairy, sodium and refined grains (all p<0.0005).

Conclusions

The average HEI scores for young children showed poor baseline diet quality at age 3 that became gradually worse throughout early childhood. The varying patterns in HEI component scores indicate specific areas of focus for early dietary intervention, which may differ by race.
Macronutrient composition of early childhood diet is associated with growth and adiposity
Authors: Voortman Trudy , Braun Kim V.E. , Jaddoe Vincent W.V. , Franco Oscar H.
Published: November 2023

Background

Previous studies suggest that high protein intake in infancy leads to a higher body mass index. However, it is not clear whether lean or fat mass are affected and what the role is of the other macronutrients in the diet. We examined associations of macronutrient composition of the diet in early childhood with growth and detailed measures of body composition up to the age of 9 years.

Methods

This study was performed among 3,564 children participating in a population‐based cohort study in the Netherlands. Dietary intake was assessed with food‐frequency questionnaires at age 1 year. We calculated intakes of total protein and protein from different sources; of total carbohydrates, fiber, polysaccharides, monosaccharides and disaccharides; and of total, saturated, monounsaturated and polyunsaturated fat. Height and weight were repeatedly measured between the ages of 1 and 9 years. Fat and fat‐free mass were measured at 6 and 9 years using dual X‐ray absorptiometry. We calculated age‐ and sex‐specific SD scores for height, weight, body mass index (BMI), fat‐mass index (FMI), and fat‐free mass index (FFMI). Macronutrient intakes were expressed in energy percentages and entered in multivariable linear mixed models in which we examined different macronutrient replacement effects. Models were adjusted for maternal age, education, BMI, and smoking and for child's sex, age, ethnicity, birth weight, having received breastfeeding, diet quality, television watching, and playing sports.

Results

Mean (±SD) macronutrient intakes were 12.9 (±2.4) E% from protein, 28.6 (±5.6) E% from fat, and 58.4 (±5.9) E% from carbohydrates. Results from multivariable models showed that higher intake of total and animal protein (both dairy and non‐dairy) was associated with a higher height, weight and BMI up to the age of 9 years, irrespective of whether it was replacing carbohydrates or fats in the diet. Further analyses showed that the positive association with BMI was completely explained by a higher FMI, and not by FFMI. In multivariable models, no significant associations were observed for any of the other macronutrients.

Conclusions

Our results suggest that high protein intake, particularly animal protein, in early childhood is associated with a higher body fat mass, but not fat‐free mass. Future studies are needed to examine the optimal range of protein intake and macronutrient composition of the diet for infants and young children.
Misreporting of energy intake in multicenter study in Latin America population: results from the Latin American Study of Nutrition and Health (ELANS)
Authors: Previdelli Agatha , Gómez Georgina , Kovalskys Irina , Fisberg Mauro , Cortés Yadira , Herrera‐Cuenca Marianella , Yépez Martha , Pareja Rossina , Rigotti Attilio , Guajardo Viviana , Zimberg Iona
Published: November 2023

Object

The study aimed to evaluate the prevalence and associated factors of under‐reporter (UR) and over‐reporter (OR) of energy intake (EI) in Latin American (LA) adolescents and adults participating in the ELANS study.

Methods

Multicenter cross‐sectional study including a representative sample of urban population from eight LA countries (Argentina, Brazil, Chile, Colombia, Costa Rica, Ecuador, Peru and Venezuela). Two 24‐h dietary recalls and physical activity data using IPAQ‐long version questionnaire were collected from 9218 participants (15–65 years old). Misreporting was identified using ±1.5SD cut‐off points to statistically compare reported EI with predicted total energy expenditure. Associations between misreporting of EI and covariates were examined by Chi‐square test (p<0.05).

Results

In average, 13% were UR and 14% were OR. Chile had the highest percentage of UR (22%), the lowest percentage of OR (7%) and showed the highest obesity prevalence. Peru showed the lowest percentage of UR (5%) and Ecuador the highest percentage of OR (20%). We found no differences between the prevalence of misreporting and sex. Individuals with lower educations showed the highest percentage of misreporting (UR=14%, OR=15%). We observed more UR and fewer OR among overweight and obese subjects. UR was associated with higher weight, waist and neck circumference and body mass index (p<0.05). Also, UR was significantly associated with lower intake of energy, fats and carbohydrates, and higher protein intake. In relation to plausible respondents, EI on average was 32% lower in UR and 43% higher in OR. Proportion of UR was higher in older group (15%), widowers (19%), high socioeconomic level (15%), undefined race (18%), physically active (14%) and obese (21%). The proportion of OR was higher in adolescents (21%), single (16%), low socioeconomic level (15%), non‐Caucasian (16%), physically active (15%) and underweight (37%).

Conclusion

Our study supports other findings that it is important not only to identify individuals that do not accurately report food intake, but also the factors that determine this misreporting, improving the interpretation of diet‐related diseases.

Support or Funding Information

The Coca‐Cola Company
Episodes of Food Insecurity and Linear Growth in Childhood: A Prospective Cohort Study
Authors: Zhu Yeyi , Mangini Lauren D , Dong Yongquan , Forman Michele
Published: November 2023

Objective

Food insecurity prevalence continues to represent a major public health concern in the U.S. A preponderance of evidence has linked food insecurity to childhood morbidity and poor development, yet its association with linear growth in childhood, a period of rapid human growth, remains poorly understood. We aimed to examine the association between household food insecurity and linear growth trajectory from kindergarten through the eighth grade.

Methods

In the prospective Early Childhood Longitudinal Study‐Kindergarten cohort (1998–2007), 5,979 children with complete data on anthropometrics, household food insecurity, and other major socio‐demographic variables at four study waves (spring of kindergarten and third, fifth, and eighth grades) were included. At each wave, household food insecurity was assessed by the validated USDA 18‐item module and anthropometrics were obtained to calculate age‐ and sex‐specific height‐for‐age z‐scores (HAZ). HAZ by sex and food security status (yes vs. no) was examined at each wave. Further, linear mixed‐effects models for repeated measures were fitted to compare HAZ trajectories across number of food insecurity episodes (i.e., 0, 1, 2, ≥3) over the study period.

Results

At each wave, food insecure girls compared to their food secure counterparts were significantly taller at fifth grade but shorter with a marginal significance at eighth grade (P = 0.03 and 0.07, respectively), whereas mean HAZ among boys did not differ by food security status. After adjusting for major sociodemographic variables and child's birthweight, mean HAZ of girls in the food insecurity ≥3 times group was 0.81 SD (95% confidence interval: −1.44, −0.18) lower than HAZ of always food secure girls at kindergarten. From kindergarten through eighth grade, HAZ of girls in the food insecurity ≥3 times group exhibited catch‐up growth after kindergarten with a rate of 0.22 SD/year (95% confidence interval: 0.1, 0.35) on average faster than their always food secure counterparts. HAZ trajectory among boys did not vary by number of food insecurity episodes over the study period, after adjusting for major covariates.

Conclusions

Childhood linear growth trajectory varied by sex and number of household food insecurity episodes. Findings highlight that school‐aged girls were particularly vulnerable to household food insecurity, with a linear growth trajectory characterized by height deficits at eighth grade despite catch‐up growth between kindergarten and fifth grade.
Food insecurity and mental health status: a global analysis of 149 countries
Authors: Jones Andrew D
Published: November 2023

Despite the enormous disease burden caused by common mental disorders worldwide, and the numerous pathways via which food insecurity (FI) may contribute to these disorders, there is limited knowledge outside of high‐income settings about the relation between FI and mental health. The objective of this research was to determine the association of individual‐level food insecurity with mental health status using a global data set. Data were analyzed from the 2014 Gallup World Poll, a nationally representative survey of individuals 15 years and older that is carried out globally using probability sampling in both urban and rural areas. Individual‐level FI was assessed using the Food Insecurity Experience Scale Survey Module for Individuals (FIES SM‐I), a module that assesses respondents' experiences of FI based on domains that are common across cultures and socioeconomic conditions including anxiety, altering the quality of food consumed, and limiting the quantity of food intake. A four‐level categorical variable based on the raw FIES SM‐I score was used in analyses. Two composite indices of mental health with values ranging from 0–100 were used as dependent variables based on self‐reported assessments of recent negative and positive experiences (e.g., worry, sadness, stress, anger, enjoyment, happiness, being treated with respect). Using an aggregated global data set (i.e., 149 countries, 11 world regions, 147,826 individuals), the prevalence of any FI among individuals ranged from 18.3% in East Asia to 76.1% in Sub‐Saharan Africa. Mean respondent age (SD) was 42 years (17) and exactly half of all respondents were adolescent girls or women. In adjusted multiple regression analyses, individual‐level FI was associated with poorer mental health status (regression coefficient (95% CI): mild FI: −8.3 (−9.3, −7.4); moderate FI: −12.6 (−13.8, −11.3); severe FI: −16.2 (−17.9, −14.5); coefficients are relative to a food secure individual). The magnitude of the association between FI and mental health status was greater than that of the socioeconomic variables assessed (e.g., education and employment status of respondent, and annual household income). Regional analyses showed the same dose‐response relation of individual‐level FI with poorer mental health status across all world regions with the exception of the Australia & New Zealand and East Asia regions. No consistent interaction was observed between an individual's sex and FI on the association with mental health status. However, age interacted with FI such that among older individuals the association between FI and mental health was more negative. Though associative in nature, these findings suggest that individual FI status, independent of socioeconomic conditions, may be an important determinant of mental health outcomes across a diversity of global contexts.

Support or Funding Information

The data for this study were made available by the Food and Agriculture Organization of the United Nations Voices of the Hungry Project.
Compensatory Autonomic Modulations Mediate Hypohydration Related Changes in Brain Functioning and Mood
Authors: Young Hayley Anne , Johnston Stephen , Benton David
Published: November 2023

It is commonly assumed that relatively small changes in hydration (<1% of body mass) are readily compensated by homeostatic mechanisms such that they are of little functional consequence. Nonetheless an emerging literature suggests that minor hypohydration can influence cognition and mood; indeed it is possible that homeostatic autonomic adaptations mediate these effects. The aim was to determine if drinking water, when mildly hypohydrated, effects brain functioning and mood and to explore the mechanistic role of autonomic and interoceptive processing. On two mornings participants were exposed to a temperature of 30°C for four hours and either did or did not drink two 150ml glasses of water during that time. At the end of the morning they completed an fMRI protocol during which they completed a modified Paced Auditory Serial Addition Test. They had their heart rate variability measured, rated their thirst, mood and task difficulty. Changes in body temperature, fluid loss and urine osmolality were also monitored. Drinking water resulted in a greater BOLD activity in the orbito‐frontal cortex, ventral cingulate gyrus, dorsal cingulate cortex, hypothalamus, amygdala, right striatum, post‐central gyrus and superior parietal cortex. These activations were associated with increased heart rate variability, lower perceived effort and a better mood. These data support a model whereby autonomic regulatory and interoceptive processes contribute to the cognitive and affective consequences of hypohydration.

Support or Funding Information

This research was funded by PepsiCo Inc.
Differences in the transcriptome of responders and non‐responders on glucose metabolism markers after fish oil supplementation
Authors: Tejero M Elizabeth , López‐Martínez Mónica E. , Cardenas‐Ovando Roberto A. , Escareño Claudia Rangel , Binia Aristea , Vargas‐Martinez Carolina , Ancira Monica , Gámez‐Valdez Eli , Martinez‐Soria Diana , Medina Leticia Sebastian , Angeles‐Quezada Adriana , Gonzalez‐Alberto Rocio , Fernández Silvia , Martínez‐Conde Diego , Hernández‐Morán Brianda , Ramirez‐Solano Marisol , Rubio‐Aliaga Isabel , Vadillo‐Ortega Felipe , Kussmann Martin , Zolezzi Irma Silva
Published: November 2023

An intervention study conducted in young Mexican adults showed significant improvement of the supplementation with fish oil (FO) on glucose metabolism. Differences in the response among subjects were observed. Gene expression in peripheral blood mononuclear cells (PBMC) has been used as a proxy of the effect of nutritional interventions in other tissues. We compared the changes in the transcriptome of PBMC induced by FO supplementation (2.7 g of DHA + EPA during six weeks) in subjects with contrasting responses in fasting insulin concentrations. Participants with the largest decrease (group A, n=16) in fasting insulin (5.64 mg/dL ± 6.87) and the largest increase (group B, n=16) in fasting insulin (−5.96mg/dL ± 6.59) were selected, and pair‐matched by age, sex, change in ω3 index and BMI. RNA analysis was conducted using high throughput RNA sequencing (Illumina). Data analysis included data preprocessing, mapping, assembly of transcripts, differential expression of gene and pathway analysis. Differences were observed between groups at baseline in 68 genes. After 6 weeks of intervention 49 genes changed in group A while 14 genes changed in group B, and 258 genes showed significant difference between groups (p<0.05; 75 genes upregulated, 183 genes downregulated). Transcripts with the most significant changes between groups are CXCL2 (FC = −1.95 p=0.015) IL‐1β (FC=−1.82, p=0.021), NR4A3 (FC=−1.82, p=0.016), which are related with inflammatory response and glucose metabolism. These findings suggest that the reduction in insulin concentrations is associated with the decrease of the expression of genes related to inflammatory pathways in PBMC.

Support or Funding Information

NESTEC & INMEGEN
Identifying feasible ways for cafeteria operators to comply with calorie and sodium nutrition standards in hospitals
Authors: Lee‐Kwan Seung Hee , Onufrak Steve , Simon Caitlin
Published: November 2023

Implementing nutrition standards for foods sold in public food service venues such as hospitals is a public health strategy to improve diet quality and prevent chronic diseases for employees and visitors. However, no studies have examined the nutrition quality of foods offered in hospitals implementing Partnership for a Healthier America (PHA) Hospital Healthier Food Imitative (HHFI) nutrition standards. To aid food service venues trying to implement similar requirements, study objectives were to 1) examine the percentage of entrees and sides meeting PHA HHFI calorie and sodium standards and 2) identify the food categories that most often met the standards. We used data on two days (i.e., breakfast, lunch, and dinner) of cafeteria entrée and side offerings from 63 U.S. based hospitals that participated in PHA HHFI during 2012–2013. We calculated 1) percentage of entrees and side dishes that met HHFI calorie and sodium standards both overall and by hospital and food category and 2) rank food entrée and side categories with the highest of percentage of items meeting these requirements. A total of 3,975 entrees and 13,541 sides were identified as reported by cafeteria managers or nutritionists; 85% of entrees and 77% of sides met calorie requirements of <525 kcal and ≤175 kcal, respectively. A total of 56% of entrees and 75% of sides met sodium requirements of <600 mg and ≤200 mg, respectively. For entrees, the range that met the calorie requirements at each hospital was 52%–100% (median=88%) and 22%–86% (median=54%) for sodium. The range of sides that met calorie requirements at each hospital was 42%–93% (median=74%) and 25%–85% (median=75%) for sodium. Food categories with the highest percentage of entrees meeting calorie requirements were dairy protein combinations with fruits or grain (e.g., yogurt cups with granola and fruits), chicken or turkey based entrees, and breakfast omelets; and for sides were fruits, vegetable dishes, and yogurts. The categories with the highest percentage of entrees that did not meet the calorie requirement were pizza and Mexican entrees, and for sides were pancakes/waffles and cookies/pastries. The top three food categories meeting sodium requirements for entrees were hot/cold cereal, fish dishes, and dairy protein combo with fruits or grain; and for sides were fruits, yogurt, frozen dairy items. For sodium, top categories that did not meet the requirements for entrees were pizza, chicken entrée, and soups, and for sides were Asian dishes, stew or soup, and pancake or waffles. These findings can help inform the development of strategies to aid food service venues in understanding the landscape of food offerings and help them successfully implement nutrition standards.
Development of a Healthy Eating Pattern for the Revision of Canada's Food Guide
Authors: Elvidge Lisa‐Anne , Davis Karelyn , Esslinger Krista Anne , St‐Pierre Sylvie
Published: November 2023

Health Canada develops evidence‐based guidance on healthy eating. Canada's Food Guide is currently under revision and Health Canada is exploring an expanded food pattern modelling methodology to develop a revised healthy eating pattern. The objective of this presentation is to share Health Canada's draft modelling methodology.

Food pattern modelling is the process of adjusting daily amounts of foods from different categories to meet specific criteria, such as meeting nutrient intake goals, limiting nutrients of concern or ensuring inclusion of foods associated with positive health outcomes. Food pattern modelling was used to develop the healthy eating pattern in the previous (2007) version of Canada's Food Guide and will be used again during this revision.

To help inform the draft methodology, a literature review was conducted to describe and compare statistical modelling methods used internationally in the development of dietary patterns, primarily since the 2007 Canadian food guide was released. Results of the review indicate that while different countries used various approaches, many similarities were found in terms of the overall steps taken to develop recommended dietary patterns. Differences included how energy levels were considered, whether or not to include guidance on discretionary calories, and modelling of additional patterns to highlight certain food groups that reduce chronic disease risks.

The review identified techniques and ideas on how Canada's modeling approach could be expanded and improved. This information was integrated in the proposed modelling methodology that Health Canada is putting forward. This presentation will highlight the key steps and important considerations while developing the revised healthy eating pattern.

This session will give attendees the opportunity to ask questions and provide feed‐back on the proposed modeling approach.
Comparison of the inhibitory potential of anthocyanin‐rich plant extracts on colon cancer cell proliferation and their mechanism of action in vitro
Authors: Mazewski Candice , Liang Katie , de Mejia Elvira Gonzalez
Published: November 2023

Foods associated with lowering risk of colorectal cancer include fruits, vegetables, and whole cereals and legumes. Anthocyanins (ANC), pigments in the flavonoid class, have shown potential to provide various health benefits, including prevention and suppression of colon cancer. The objective of this study was to evaluate the anti‐proliferative effect of ANC‐rich extracts from a variety of plant sources on HCT‐116 and HT‐29 human colorectal cancer cells in comparison to oxaliplatin and to investigate the mechanism of action. Eleven extracts were tested on both cell lines which consisted of fruits (red and purple grape), vegetables (sweet purple potato and purple carrot), legumes (black and purple bean, black lentil and black peanut), and cereals (sorghum, black rice and blue wheat). An accelerated solvent extraction system was used for anthocyanin extraction at 50 °C from each material; only water was used as solvent for extraction. The chemical composition of the extracts was compared through HPLC, mass spectrometry, total ANC and phenolic concentration, as well as color parameters such as hue, and chroma. The effect of chemical composition was correlated with anti‐proliferative capabilities. Total ANC concentrations of all extracts ranged from 0 to 287.5 mg cyanidin 3‐O‐glucoside (C3G) equivalent/g dry extract and total polyphenols from 47.3 to 382.3 mg gallic acid/g dry extract. There was a strong correlation between HCT‐116 and HT‐29 cell inhibition and total polyphenols (r=0.87 and 0.77, respectively), as well as with hue (r=−0.81 and −0.58, respectively). HPLC profiles were very distinctive for all extracts, predominating in C3G, peonidin 3‐O‐glucoside, and delphinidin 3‐O‐glucoside. The three most potent extracts were selected to perform further mechanistic studies: black lentil (BL), sorghum (SH), and red grape (RG). On HCT‐116 cells, the IC50 values for BL, SH, and RG were 0.9±0.1, 1.0±0.1, and 1.5±0.1 mg/mL (p<0.05), respectively, and on HT‐29 cells, they were 1.4±0.1, 1.7±0.1, and 2.0±0.2 mg/mL, respectively (p<0.05). For all extracts and oxaliplatin, the IC50 for HCT‐116 cells were lower than HT‐29 cells. The extracts showed important changes on markers of apoptosis such as Bcl‐2, survivin, livin, and TNF‐α. The results of the present study suggest that BL, SH, and RG extracts exhibit a potential to inhibit human colon cancer proliferation in vitro, possibly through promotion of apoptosis. They also indicated that there were potential correlations between chemical composition and human colon cancer cell inhibition.
E4orf1 Protein Requires the Distal but not Proximal Insulin Signaling to Enhance Glut4 Translocation
Authors: Shastri Anuradha , Peddibhotla Swetha , Feizy Zahra , Hegde Vijay , Dhurandhar Nikhil V
Published: November 2023

Background

Cellular action of insulin consists of proximal and distal signaling. The proximal signaling includes binding of insulin to its receptor and activation of insulin receptor substrates (IRS). Distal signaling includes the activation of phosphatidyl inositol 3‐kinase by IRS leading to the up‐regulation of AKT followed by membrane translocation of Glut4 to promote cellular glucose uptake. Type 2 diabetes is often linked with impaired proximal insulin signaling. Hence, an agent that enhances cellular glucose uptake independent of proximal insulin signaling would be desirable for improving glycemic control. The E4orf1 peptide (E4) derived from human adenovirus 36 may be such a candidate, which promotes cellular glucose uptake in vitro and in vivo, independent of insulin, but by recruiting insulin signaling pathway. Previous data suggested that E4 bypasses a part of insulin signaling to upregulate cellular glucose uptake. Here, we tested if E4orf1 requires the distal but not proximal insulin signaling to enhance Glut4 translocation.

Method

Murine 3T3‐L1 cells inducibly expressing E4 or a null vector (NV) were treated with inhibitor of insulin receptor (S961), inhibitor of IGF‐1 (Picropodophyllin, PPP), PPP+S961, or PI3K inhibitor (Wortmannin, WM). PPP and S961 were used to block the proximal insulin signaling and WM was used to block the distal insulin signaling. Exposure to inhibitors was 2 h, except WM for 30 min. In the final 20 min of treatment, cells were exposed to 0 or 100 nM insulin.

Results

In NV cells, if the proximal or distal insulin signaling was blocked, insulin could not increase pAKT protein abundance or Glut4 translocation, determined by western blotting and FACS analysis respectively. Whereas, in the absence of insulin, E4 cells significantly increased pAKT levels and GLUT4 translocation with or without the blockage of proximal insulin signaling. However, treatment with WM completely blocked E4 stimulation of pAkt and GLUT4 translocation.

Conclusions

E4 bypasses the proximal insulin signaling but uses the distal insulin signaling to activate pAkt and in turn Glut4 translocation to improve cellular glucose uptake. E4 offers a promising template to improve glycemic control when the proximal insulin signaling is impaired.

Support or Funding Information

Funded by Vital Health Interventions.
High‐sucrose Diet Time‐dependently Changes Hepatic Endoplasmic Reticulum Stress from an Adaptive to Pro‐apoptotic Pattern in Young Mice
Authors: de Andrade Paes Antonio Marcus , Flister Karla Frida Torres , dos Santos Pâmela Costa , Pinto Bruno Araújo Serra , Vale Caroline Castro , Kajihara Daniela , Laurindo Francisco Rafael Martins , França Lucas Martins
Published: November 2023

The relationship between excessive nutrient intake and hepatic endoplasmic reticulum stress (ER stress) is well stablished. However, mechanisms underlying the progression from adaptive to apoptotic pattern are still unclear. This study sought to investigate the effects of high‐sucrose diet on metabolic disorders associated to hepatic ER stress. Weaned Swiss mice received standard chow (CTR) or high‐sucrose diet (HSD; 25% sucrose) for distinct periods of 30 (CTR30 and HSD30) and 60 (CTR60 and HSD60) days. Weight gain, food intake, feed efficiency and Lee index (LI) were measured for obesity development assessment. At each treatment end, glucose (GTT) and insulin (ITT) tolerance tests were performed. Blood, white adipose tissue (WAT) depots and liver were collected upon euthanasia of anesthetized animals. Serum glucose (GL), triglycerides (TG), total cholesterol (TC) and free fatty acids (FFA) levels were determined. WAT depots were weighed and their lipolytic activity assessed. Hepatic tissue was used to determine the lipid profile and gene expression of ER stress (ATF6, IRE1α, PERK, GRP78, PDI, NRF2) and pro‐apoptotic (CHOP and caspase 2) markers. Only HSD60 showed higher weight gain (8%), LI (3%) and feed efficiency (31%), as compared to CTR60. WAT was 2‐fold higher in HSD60 than in HSD30, whereas both of them were significantly higher than their controls. Lipolytic activity under isoproterenol‐stimulation was 40% lower in HSD60. Serum GL and TC were increased in 20 and 40%, respectively, in both HSD groups. However, TG (43%) and FFA (25%) were increased only in HSD60. Area under the curve of GTT was augmented in both HSD30 (14%) and HSD60 (41%), as compared to their controls. Whereas only HSD60 presented reduced kITT (37%) and increase TyG (8%). Total fat liver content was increased in 22 and 61% for HSD30 and HSD60, respectively. On the other hand, hepatic TG was augmented only in HSD60 (69%). HSD30 presented increased hepatic gene expression of GRP78 (57%), PERK (83%), IRE1α (49%), ATF6 (70%), PDI (41%) and NRF2 (32%), and reduced expression of CHOP (39%). An opposite pattern was found in HSD60, with reduced expression of PERK (34%), IRE1α (52%), ATF6 (36%) and PDI (46%), and increase expression of CHOP (72%). Notwithstanding, caspase‐2 expression did not change in any group. Therefore, our data suggest the HSD intake for up to 60 days after weaning rapidly promotes metabolic disorders associate to early onset of hepatic ER stress, which promptly progress from an adaptive to a pro‐apoptotic pattern.

Support or Funding Information

FAPEMA, CNPq, CAPES and UFMA.