bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heat Stress‐induced Insulin Sensitivity in Oxidative Skeletal Muscle
Authors: Ganesan Shanthi , Pearce Sarah , Summers Corey , Gabler Nicholas , Valentine Rudy , Baumgard Lance , Rhoads Robert , Selsby Joshua 
Published: June 2021

Heat‐related complications continue to be a major health concern for humans and animals and lead to potentially life‐threatening conditions ranging from heat exhaustion, heat stroke and even death. Heat stress have been shown to alter metabolic and energetic parameters in mammals and may alter glucose metabolism and insulin sensitivity. Therefore, the purpose of this investigation was to determine the extent to which short‐term HS altered markers of insulin signaling in oxidative skeletal muscle. To address this, crossbred gilts (n=8/group) were assigned to thermoneutral (TN; 24° C), HS (37° C), or pair‐fed to HS and kept under TN conditions (PFTN) groups for 12 hours. Following treatment, animals were euthanized and the semitendinosus red (STR) was recovered. HS‐induced changes were not caused by reduced feed intake as TN and PFTN were similar for nearly all measures. Twelve hours of HS increased insulin receptor protein abundance by 54% (p<0.05) and phosphorylated insulin receptor substrate (pIRS1S307) by 56% (p<0.05) compared to TN. Phosphorylation of IRS1 at this site is a negative regulator of insulin signaling. Relative protein abundance and phosphorylation of phosphoinositide 3‐kinase (PI3K) and 3‐phosphoinositide dependent protein kinase‐1 (PDK1) were similar between groups. Phosphorylation of protein kinase B (pAKTs473) was decreased by 53% (p<0.05) in HS compared to TN, which indicates that insulin signaling was suppressed through pIRS1. Conversely, HS increased phosphorylation of protein kinase C (PKC)λ/ζ and pPKCδ protein abundance by 128% and 205%, respectively, compared to TN which are known to stimulate pIRS1S307. Sarcolemma glucose transporter‐4 (Glut4) was decreased by 47% (p<0.05) in HS group compared to TN suggesting reduced glucose uptake. These data suggest that HS induces insulin sensititvity by disturbing insulin signaling via an AKT‐mediated pathway.Support or Funding InformationThis work is supported by USDA grants 2014‐67015‐21627 and 2011‐67003‐30007
Impaired Mitochondrial Clearance Contributes to Heat Stress‐mediated Muscle Dysfunction
Authors: Ganesan Shanthi , Summers Corey , Pearce Sarah , Gabler Nicholas , Valentine Rudy , Baumgard Lance , Rhoads Robert , Selsby Joshua 
Published: June 2021

Prolonged exposure to high temperatures can result in heat stress (HS), which is characterized by morbidities and mortality in humans and animals and appears to cause organ‐specific injury and dysfunction. We have previously found increased free radical injury in skeletal muscle following 24 hours of HS. The purpose of this investigation was to determine the extent to which short‐term HS caused muscle dysfunction in oxidative skeletal muscle. We hypothesized that in oxidative muscle 12 hours of HS would lead to free radical injury, apoptosis, autophagy, and decreased mitochondrial content compared to muscle from thermoneutral (TN) animals. To address this hypothesis, crossbred gilts (n=8/group) were assigned to three groups: TN (24° C), HS (37° C), or pair‐fed to heat stress (PFTN; 24° C) for 12 hours. Following treatment, animals were euthanized and the semitendinosus red (STR) was recovered. TN and PFTN were similar for nearly all measures indicating changes caused by HS were not due to reduced feed intake but due to the hyperthermic environment. The relative abundance of malondialdehyde modified proteins was increased by 36% in HS (p<0.05) compared to TN, which was matched by an inadequate antioxidant response including a 48% and 170% increase in superoxide dismutase (SOD) I and II relative protein abundance, respectively, and a 26% increase in total SOD activity but a 40% reduction in catalase activity in HS compared to TN. Further, HS caused a 103% increase in caspase 3 activation and tended to increase BCL2‐Associated X Protein by 40% (p<0.06) and apoptotic protease activating factor 1 by 66% (p<0.06) indicating increased apoptotic signaling. Despite increased initiation, autophagy appeared to be inhibited by HS as the microtubule‐associated protein A/B‐light chain 3 II/I ratio was decreased by 53% and sequestosome‐1(p62) protein abundance was increased by 40% in HS compared to TN. Markers of mitochondrial content cytochrome c, cytochrome c oxidase IV, voltage dependent anion channel, pyruvate dehydrogenase and prohibitins 1 were increased in HS compared to TN. Increased mitochondrial content is likely reflective of a combination of increased accumulation of damaged mitochondria that fail to be cleared via autophagy and mitochondrial biogenesis. We postulate that in oxidative skeletal muscle HS‐mediated mitochondrial dysfunction is allowed to persist due to a failure of autophagy to clear damaged mitochondria, which results in increased oxidative stress and apoptotic signaling. These data demonstrate widespread aberrant intracellular signaling caused by HS that implicate impaired autophagy as a key feature in HS‐mediated muscle dysfunctionSupport or Funding InformationThis work supported by USDA grants 2014‐67015‐21627 and 2011‐67003‐30007.
Frank‐Starling Responses during Heat Stress in Healthy Aged Humans
Authors: Gagnon Daniel , Romero Steven A , Ngo Hai , Sarma Satyam , Cornwell William K , Poh Paula YS , Stoller Douglas , Levine Benjamin D , Crandall Craig G 
Published: June 2021

Healthy aging markedly affects the cardiovascular adjustments to heat stress in humans. In particular, the increase in cardiac output can be attenuated by 50% in older individuals, which has previously been attributed to an inability of the aged to maintain stroke volume when cardiac filling pressures are reduced. In young individuals, a leftward shift in the operating point of the Frank‐Starling response is an important adjustment by which stroke volume is maintained during heat stress. It remains unknown how healthy aging affects the Frank‐Starling response during heat stress. We therefore tested the hypothesis that a leftward shift in the operating point of the Frank‐Starling response is absent in older individuals during whole‐body passive heat stress. Right heart catheterization was performed in 10 aged (A: 70 ± 3 y, 166 ± 9 cm, 68 ± 8 kg, 4 males/6 females) and 12 young (Y: 26 ± 5 y, 165 ± 6 cm, 64 ± 10 kg, 6 males/6 females) healthy individuals to measure pulmonary capillary wedge pressure, cardiac output (thermodilution) and pulmonary artery blood temperature. Heart rate was measured using an electrocardiogram and used to calculate stroke volume. These measurements were obtained at normothermic baseline, as well as at an increase in pulmonary artery blood temperature of 1.5°C achieved through whole‐body passive heat stress. Cardiac output increased in both groups during heat stress (A: 4.5 ± 0.7 to 7.0 ± 0.9 L/min vs. Y: 5.0 ± 0.7 to 9.5 ± 1.1 L/min), the magnitude of which was lower in the aged (P<0.01). Heart rate was similar between groups during heat stress (A: 91 ± 11 vs. Y: 98 ± 14 beats/min, p=0.17) however, the increase from baseline was attenuated in the aged (A: +29 ± 8 vs. Y: +41 ± 9 beats/min, P<0.01). Indicative of a leftward shift in the operating point of the Frank‐Starling response, stroke volume was maintained during heat stress in both groups (A: 74 ± 13 to 78 ± 14 mL/min vs. Y: 89 ± 23 to 99 ± 21 mL/min) despite reductions in pulmonary capillary wedge pressure (A: 9.0 ± 1.9 to 6.6 ± 1.4 mmHg vs. Y: 10.6 ± 1.6 to 6.6 ± 2.0 mmHg). Overall, these results suggest that stroke volume is maintained during whole‐body passive heat stress in healthy aged humans due to an appropriate leftward shift in the Frank‐Starling response. Thus, attenuated increases in cardiac output in the aged while heat stressed are primarily due to attenuated increases in heart rate.Support or Funding InformationFunded by the National Institutes of Health (GM‐068865), Department of Defense (W81XWH‐12‐1‐0152) and ACSM Foundation Research Endowment.
Inactivity‐induced phrenic motor facilitation is initiated though TNF receptor 2 and impaired by TNF receptor 1
Authors: Braegelmann Kendra , Fischer Stephanie , Agbeh Abiye , Baker Tracy 
Published: June 2021

Prolonged reductions in synaptic inputs to phrenic motor neurons results in the release of spinal, soluble TNFα (sTNFα) to initiate a long lasting increase in phrenic burst amplitude termed inactivity‐induced phrenic motor facilitation (iPMF). TNFα can activate TNF‐R1 or TNF‐R2, which are two distinct cell surface receptors that tend to initiate discrete signaling cascades. TNF‐R1 mediates the majority of TNFα activity; therefore, we hypothesized sTNFα released within or near the phrenic motor pool in response to reduced activity binds to TNF‐R1 on phrenic motor neurons to initiate iPMF. To test this hypothesis, Harlan Sprague Dawley rats were injected with small interfering RNAs directed against TNF‐R1 or TNF‐R2 in the interpleural space (100pg/side) to selectively reduce TNF‐R1 or TNF‐R2 in phrenic motor neurons. After 3 daily injections of siRNAs, iPMF was measured in anesthetized and ventilated rats for 60min following a prolonged (30min) neural apnea. As expected, control rats receiving injections of non‐targeting siRNA expressed an increase in phrenic burst amplitude for up to 60min following neural apnea (48±15,%baseline), indicating iPMF. Contrary to our hypothesis, knockdown of TNF‐R1 in phrenic motor neurons led to an enhanced iPMF following prolonged neural apnea (80±18,%baseline), whereas knockdown of TNF‐R2 completely abolished the expression of iPMF 60min post neural apnea (−8±5,%baseline,). Collectively, these data suggest that TNF‐R2 signaling in phrenic motor neurons is necessary for iPMF and that TNF‐R1 signaling may initiate mechanisms within phrenic motor neurons that oppose iPMF. Thus, both TNFα receptors may contribute to sculpting phrenic burst amplitude in response to a reduction in respiratory‐related neural inputs.Support or Funding InformationNIH‐HL105501 and DoD SC120226
Discharge of Mid‐Cervical Neurons Following Cervical Spinal Cord Injury
Authors: Patel Shreya , Streeter Kristi , Reier Paul , Baekey David , Fuller David 
Published: June 2021

Prior anatomical and neurophysiologic data suggest that mid‐cervical interneurons may contribute to the control of phrenic motor output after cervical spinal cord injury (cSCI). To explore this possibility, we recorded spinal interneuron bursting patterns and phrenic motor output in rats with chronic cSCI. Twelve weeks following lateral C2 hemi‐section (C2Hx), bilateral phrenic nerve activity was recorded in urethane anesthetized and mechanically ventilated rats (N=5). A multi‐electrode recording array was bilaterally inserted at C4 to enable simultaneous recording of mid‐cervical neuron discharge ipsilateral and contralateral to C2Hx. In this initial evaluation, neuronal discharge patterns were classified as tonic (i.e., active across the entire respiratory cycle) or phasic (i.e., active during only the inspiratory or expiratory phases). Spike triggered averaging of phrenic nerve activity based on discharge of recorded cells was used to identify phrenic motoneurons, all other cells were classified as interneurons for this analysis. Only interneurons (versus motoneurons) were identified in recordings ipsilateral to C2Hx, and these cells primarily burst in a tonic firing pattern (tonic: 91% and phasic: 9% of ipsilateral cells). In contrast, on the contralateral side phrenic motoneurons were readily recorded (26% of contralateral cells) and a greater proportion of phasic interneurons were detected (phasic: 26% and tonic: 48% of contralateral cells). Spike triggered averaging produced no evidence of direct (monosynaptic) coupling between interneurons and either the contra‐ or ipsilateral phrenic motoneuron pool. These preliminary findings confirm altered propriospinal neuron discharge in the ipsilateral vs. contralateral cord immediately caudal to chronic C2Hx injury. The precise role of mid‐cervical propriospinal neurons in respiratory recovery after cSCI remains unclear. Since we did not detect cells that were directly antecedent to the phrenic pool, our data suggest that following cSCI, “connectivity” between respiratory‐modulated spinal interneurons and the phrenic nucleus may involve polysynaptic pathways.Support or Funding InformationFunding: APS Undergraduate Summer Research Fellowship (SP), 1R01NS080180‐01A1 (DF), 1F32NS095620‐01 (KS), and Department of Defense W81XWH‐14‐1‐0625 (PR).
Advancing Systematic Review Methodology to Better Inform Food and Nutrition Policy
Authors: Psota Tricia L. , Spill Maureen , Spahn Joanne , Gungor Darcy , Johns Kirsten , Nadaud Perrine , Wong Yat Ping , Stoody Eve Essery , Rihane Colette 
Published: June 2021

Systematic reviews critically assess research studies relevant to a particular research question. The USDA's Nutrition Evidence Library (NEL) utilizes state‐of‐the‐art methodology to conduct systematic reviews evaluating scientific evidence related to food and nutrition to answer questions that inform federal policies and programs, such as the Dietary Guidelines for Americans. The NEL has continually advanced its process to stay at the forefront of the systematic review field. However, the key steps of the NEL process remain the same, including: 1) developing systematic review questions; 2) searching, screening, and sorting the literature; 3) extracting data and assessing the risk of bias of the research; 4) describing and synthesizing the evidence; 5) developing conclusion statements and grading the evidence; and 6) identifying research recommendations. Advancements to the NEL process include: 1) integrating broader input to develop, refine, and prioritize systematic review questions; 2) incorporating key definitions and confounders into the analytic framework, a visual representation of the systematic review project; 3) developing a standard inclusion/exclusion template to promote consistency across reviews and expanding the inclusion/exclusion criteria list; 4) conducting a duplication assessment to determine if other high‐quality systematic reviews exist which answer the prioritized questions; 5) combining title and abstract screening; 6) integrating dual‐screening of the literature; 7) revising the quality assessment tool to be tailored by study design and to focus on internal validity assessment, opposed to study quality; 8) revising the NEL grading rubric used to grade the totality of the evidence; 9) integrating a step to define research recommendations as a component of the evidence review, opposed to after the process; and 10) creating technical abstracts and plain‐language summaries that summarize the completed systematic reviews. In addition to process improvements, the NEL has enriched the training of experts with whom it works to streamline the conducting of systematic reviews. Also, the NEL has expanded its website by including additional systematic review materials, which increases the transparency of the process and makes nutrition research publicly available. NEL systematic reviews will be used to illustrate these improvements and to facilitate discussions which can contribute to advancing systematic review methodology for the field of nutrition science. Furthermore, future directions for advancement, such as leveraging research recommendations better, will be explored.Support or Funding InformationUSDA
Children Are Eating Savory Snack Foods: What We Eat in America, NHANES 2011–2012
Authors: Rhodes Donna G , Clemens John C , Hymes Melanie A , Moshfegh Alanna J 
Published: June 2021

The savory snack market is over $28 billion yearly and advertising often targets children; however, data are limited on the consumption of such products among children. This research examined the percentage of U.S. children who consumed chips, flavored snacks, popcorn and pretzels (referred to here as savory snack foods) on a given day during 2011–2012. The studysample included nationally representative data from individuals aged 2–19 years(n=3132), participating in What We Eat in America (WWEIA), NHANES2011–2012. Dietary intake data, obtained from an in‐person 24‐hour recall, were collected using the interviewer‐administered 5‐step USDA Automated Multiple‐Pass Method. The WWEIA Food Categories were used to estimate the percentages of children who consumed potato chips, tortilla/corn/otherchips, popcorn, and pretzels/snack mix at least once, any time during the intake day. Overall, 43.9 ± 1.6% (mean ±SE) of children consumed savory snack foods on any given day. Among race/ethnicity groups, a greater percentage of non‐Hispanic black children (50.4± 2.9%) consumed savory snack foods on a day compared to non‐Hispanic white (44.0± 2.5%), Hispanic (42.5 ± 2.2%) or non‐Hispanic Asian (40.1 ± 3.3%) children. By age group, the percentage consuming was40.5% (2–5 yr), 47.8% (6–11 yr) and 42.8% (12–19 yr). With respect to amount consumed, mean intake of savory snack foods among consumers increased with age: 27 ± 3g, 38 ± 3g and 48 ± 3g among children2–5 yr, 6–11 yr and 12–19 yr, respectively. Overall, on the day consumed, they contributed 10% of total energy and7% of total sodium; mean energy was 199 kcal and mean sodium was 230mg. The results of this research highlight the wide‐spread consumption of savory snack foods by children of all ages and race/ethnic backgrounds.Support or Funding InformationUSDA, ARS
Development and Evaluation of the Transdisciplinary Obesity Prevention Research Sciences Program
Authors: Teegarden Dorothy , Bowers Jill , Hammons Amber , Destefano Lizanne , Garcia Gabriella , Koester Brenda , Parker Loran , Childress Amy , Fiese Barbara 
Published: June 2021

The Transdisciplinary Obesity Prevention Research Sciences Program (TOPRS) is an applied research methods curriculum for undergraduates on the causes and consequences of childhood obesity that has been developed by a multidisciplinary team from the University of Illinois at Urbana‐Champaign, Purdue University, and California State University‐Fresno. To address the need of the contemporary workforce the course has been developed to integrate transdisciplinary approaches 1) to knowledge about the causes, consequences and correlates of obesity from an ecological framework from cell to society, 2) hands‐on research experience, and 3) a professional development series. The program development was an iterative process of integrating rigorous evaluation results with curriculum design. The class format is a “flipped” version with students viewing 10 minute lectures and class time spent in interactive discussions and activities focusing on research design and methodologies. The lectures are presented by national experts in nutritional sciences, animal science, child development, family science, early care and education, community health, and public health. The professional development activities reinforce leadership and team building skills. The pilot evaluation revealed students’ (N = 53) increased knowledge related to obesity causes and consequences. Students increased in their research‐related abilities and reported having a better understanding of the research process. Furthermore, students increased in self‐confidence in their research skills and their intention to choose a research‐oriented career by the end of the program. Finally, the program strengthened students’ understanding of the importance of collaboration and teamwork. Additionally, the program helped students understand the importance of interdisciplinary approaches by increasing appreciation of the complexity of obesity prevention. In conclusion, the innovative curriculum development will be available for use, and also represents a model for integrative, interdisciplinary program development.Support or Funding InformationThis material is based upon work that is supported by the National Institute of Food and Agriculture, U.S. Department of Agriculture.
Nutrimetabolomics fingerprinting to identify biomarkers of whole grain wheat intake
Authors: Sang Shengmin , Zhu Yingdong , Sha Wei , Wang Pei 
Published: June 2021

Increased whole grain (WG) consumption has been inversely associated with the risk for developing some diet‐related disorders, such as type 2 diabetes, obesity, cancer, and cardiovascular diseases. Many epidemiological studies, however, have failed to generate consistent results on this topic due to a lack of accurate tools to assess dietary intake of whole grains. Nutritional epidemiology research needs more reliable and quantitative methods for measuring dietary intake of specific foods. Using a targeted LC/MS based metabolomic approach, we established the metabolic fingerprints of the major phytochemicals in WG wheat in human urine including metabolites of alkylresorcinols, benzoxazinoids, lignans, and phytosterols, as well as microbial‐derived metabolites. Using a non‐targeted LC/MS based global metabolomic approach, we investigated the impact of WG wheat bread intake on the endogenous urinary metabolome. Metabolic profiling revealed a number of differences relating to the consumption of WG wheat bread vs. refined grain wheat bread, such as 3,5‐dihydroxybenzoic acid, 2‐aminophenol sulfate, ferulic acid 4‐sulfate, 2‐acetamidophenol sulfate, and cysteine. Using the targeted and non‐targeted nutrimetabolomic approaches, we are able to develop multiple metabolites as the potential biomerkers of WG wheat intake.Support or Funding InformationUSDA‐NIFA grant 2012‐38821‐20012 to S. Sang
Physical Activity Level, Modeling, and Importance to Mothers of Preschool Children
Authors: Martin‐Biggers Jennifer T , Quick Virginia , Worobey John , Byrd‐Bredbenner Carol 
Published: June 2021

Physical activity (PA) is an important component of obesity prevention for children and adults. This study compared maternal and child PA levels, maternal modeling of PA, and importance mothers place on PA for herself and her child to maternal and child BMI categories. Survey participants (n=550) were 72% white and 37% had a college degree or higher. Categorizing mothers by weight status indicated that 26%, 23%, 21%, and 30%, were underweight/low normal weight (BMI<22.5), high normal weight (BMI≥22.5 to <25), overweight (BMI ≥25 to <30), or obese (BMI≥30), respectively. Mean maternal PA levels were low (15.44±9.98SD; 0–42 point scale), with obese mothers (n=165) scoring significantly lower than underweight/low normal weight mothers (14.20±9.91SD vs 17.17±10.47SD, p=0.018). Using a 5‐point 2‐item scale, mothers indicated they felt modeling PA behaviors to their children was important and modeled PA 3.08±1.22SD days a week in the past month. Compared to both categories of normal weight mothers, obese mothers placed significantly less importance on modeling PA behaviors (3.91±0.89SD vs 4.24±0.84SD and 4.32±0.69SD, p<0.001) to their children and spent significantly fewer days a week in the last month modeling PA behaviors (2.80±1.23SD vs 3.35±1.14SD and 3.21±1.25SD, p<0.001). Mothers placed less importance on PA for themselves than for their children (mean 3.49±0.97SD vs 3.83±0.87SD, on a 5‐point scale). Obese mothers placed significantly less importance on PA for themselves than mothers in all other weight categories. PA level of participants’ children was moderate (26.19±11.42SD, 0–42 point scale). No significant differences were found among child BMI categories and child PA levels. The importance mothers placed on modeling PA and importance placed on PA for their children did not differ among child BMI weight categories. Mothers of overweight children reported modeling PA behaviors significantly more days per week than mothers with middle normal weight (25th to 74th percentile) children (3.41±1.27SD vs 2.85±1.17SD). The importance mothers placed on their own PA was lower among mothers of underweight children and tended to increase as child BMI increased. Findings suggest that mothers of obese children may be more sensitive to the importance of modeling PA and its importance to health. Encouragement of all parents to promote PA and model PA behaviors to children is important for obesity prevention.Support or Funding InformationUSDA NIFA #2011‐68001‐30170