bluuebunny/crossref_metadata_2025_split huggingface dataset:
CALERIE II: the effect of 25% calorie restriction over two years on cognitive function (629.7)
Authors: Scott Tammy , Das Sai , Martin Corby , Stewart Tiffany , Williamson Donald , Stein Rick , Bhapkar Manjushri , Pieper Carl , Rochon James , Roberts Susan 
Published: June 2021

Calorie restriction (CR) extends lifespan in a range of animal models and potentially decreases disease risk factors in humans. It is unclear, however, how CR impacts cognition; a negative outcome could decrease the feasibility and practicality of CR for health improvement. Previous studies in both animal models and humans have provided inconsistent findings reporting either positive, negative, or no effects. Our objective was to study the effect of CR on cognition during a 2‐year, multi‐center, randomized controlled trial. The analysis population was comprised of 218 healthy normal‐ and over‐weight adult volunteers who were enrolled into the CALERIE study, were randomized 2:1 into a 25% CR or an Ad Libitum control group, and began intervention. Cognition was measured through a computerized battery of tests (reaction time, attention/vigilance, verbal and visual memory, working memory, and executive function) at baseline, and 6‐, 12‐, and 24‐month follow‐up. Analysis was on an intention‐to‐treat basis, with models adjusted for study site, sex, baseline BMI stratum (18.5 ‐ 24.9 kg/m2 and 25 ‐ 28.9 kg/m2), baseline scores, age and education. Our results showed no consistent main effect of study intervention for any of the cognitive tests, nor a significant interaction between intervention and BMI stratum. Our null findings suggest that cognitive outcome is not a limitation for the use of CR for health improvement.Grant Funding Source: Supported by: USDA agreement No. 58‐1950‐0‐014 and NIA grant No. U01AG022132
A calcium and vitamin D fortified food product improves bone adaptation during military training (634.3)
Authors: Gaffney‐Stomberg Erin , Lutz Laura , Hughes Julie , Murphy Nancy , Marchitelli Louis , Cable Sonya , Young Andrew , McClung James 
Published: June 2021

Stress fracture incidence during military training is high. Prior work suggests calcium (Ca) and vitamin D (vit D) intakes above the RDA may reduce fracture incidence in female trainees. How Ca and vit D affect measures of bone density and strength during initial military training (IMT) is not known. This randomized, double‐blind, placebo‐controlled trial was conducted to determine whether Ca and vit D (2000 mg and 800 IU) delivered as 2 snack bars daily throughout 9 wks of IMT improved trainee bone health. Measures of bone density pre‐ and post‐IMT and strength were assessed using peripheral quantitative computed tomography (n=20 men, n=27 women). Tibia scans were performed on the non‐dominant leg at 4, 14 and 66% of the segment length proximal to the distal end plate. Several parameters increased during training including: trabecular volumetric bone mineral density (vBMD) and bone strength index at the 4% site, cortical vBMD at the 14% and 66% sites, and stress strain index at the 66% site suggesting bone strength improved during IMT (all P<0.05). Those who received Ca and vit D had greater increases in total vBMD at the 4% site (3.0 ± 3.3 vs. 1.2 ± 2.4%; P<0.05) as well as cortical thickness (1.9 ± 2.2 vs. 0.6 ± 1.8%; P<0.05) and bone mineral content (1.6 ± 1.6 vs 0.6 ± 1.8%; P<0.05) at the 14% site. These data indicate that Ca and vit D intakes above the RDA may support bone health during periods of high turnover such as IMT.Grant Funding Source: Research supported by: ORISE and USAMRMC.
Umbilical cord coiling in adolescent and multiples pregnancies: associations with iron status (636.4)
Authors: Durlacher Jocelyn , Katzman Philip , Lee Sunmin , Guillet Ronnie , Pressman Eva , Cooper Elizabeth , O'Brien Kimberly 
Published: June 2021

Abnormal umbilical cord coiling has been associated with adverse neonatal outcomes. The etiology remains controversial. Perturbations in maternal and neonatal iron (Fe) homeostasis have been associated with abnormal cord coiling. This study was undertaken to examine associations between cord coiling and Fe status, in two obstetric groups at risk for iron deficiency (n=166): pregnant adolescents (蠄18 y, n= 95) and adult women carrying twins (n= 43) and triplets (n= 28). Umbilical cords were classified as hypo, normo, or hyper‐coiled using digital photographs to assess gross appearance after training on degree of coiling of actual cords. Hypo‐coiling and hyper‐coiling were observed in 46% (n=77) and 11.5% (n=19) of the study population. Adolescents with hyper‐coiled cords had lower serum ferritin (SF) (p = 0.01, n=11) and higher ratio of serum transferrin receptor (sTfR) to SF (p = 0.04, n=11) at mid‐gestation (27.7 ± 3.4 wks), and lower cord hepcidin (p= 0.02, n= 17) at birth (39.7± 1.5 wks) compared to teens with normo‐coiled cords (n=25 for SF and sTfR, n= 44 for hepcidin). The prevalence of hypo‐coiling observed among women carrying multiples was at least 3‐fold higher than the prevalence expected in singleton pregnancies. Data analyses for Fe status in multiples pregnancies are in progress. Findings to date suggest that decreased Fe status in adolescents is associated with hyper‐coiling of the umbilical cord.Grant Funding Source: Supported by USDA 2005‐35200; 2008‐01857; the Gerber Foundation
The changing dynamics of maternal nutrition in urban Nepal: findings from a longitudinal study in Bhaktapur (641.17)
Authors: Chandyo Ram , Thorne‐Lyman Andrew , Ulak Manjeswori , Shrestha Prakash , Fawzi Wafaie , Locks Lindsey , Henjum Sigrun , Strand Tor 
Published: June 2021

Nepal is undergoing a nutrition transition in which overweight and obesity are becoming issues of increasing public health concern particularly in the urban, and coexist with undernutrition in the rural communities. More evidence is required to understand the evolution of the rise in overweight in different sub‐populations within Nepal. In 2007‐2008, a representative survey was undertaken among 500 healthy lactating women and their infants, randomly selected in Bhaktapur municipality, Nepal. From these mother‐infant pairs, we collected dietary information and blood samples. Five years later, 325 women and their children were followed up and compared with the baseline data. The prevalence of overweight among the women increased markedly_from 17% to 42%. The prevalence of low BMI (<18.5), which affected 4% of women at baseline decreased to 2%. In apparent contrast to the increased maternal overweight, the prevalence of women with anemia increased in this population (17% in baseline compared with 36% in the follow up survey). In this poster/presentation, we will also examine dietary patterns and factors associated with overweight. Data from our cohort suggests that overweight and obesity is rapidly rising among adults in Nepal.Grant Funding Source: USAID, NUFU and the Research Council of Norway, and the Reiber foundation
Critical role of phosphodiesterase 4 in alcohol induced hepatic steatosis (653.11)
Authors: Avila Diana , Zhang Jingwen , McClain Craig , Barve Shirish , Gobejishvili Leila 
Published: June 2021

Alcohol induced hepatic steatosis is a significant risk factor for progressive liver disease. Cyclic adenosine monophosphate (cAMP) has been shown to play a significant role in the regulation of hepatic lipogenesis. Our recent work demonstrated that cAMP degrading PDE4 enzymes are expressed in the liver. The aim of this study was to examine the effect of alcohol on hepatic PDE4 expression and its potential role in the development of alcoholic steatosis. C57Bl/6 and pde4b knockout (pde4b‐/‐) mice were pair‐fed control or ethanol liquid diets for 4 weeks. One group of mice received rolipram, a PDE4 specific inhibitor. We demonstrated that alcohol feeding leads to an early up‐regulation of PDE4B and D accompanied by increased expression of fatty acid synthase and SREBP‐1. Pde4b‐/‐ mice and mice treated with rolipram were significantly protected from alcohol induced hepatic steatosis. An increase in CYP2E1 expression was similar in wild type and pde4b‐/‐ mice, but was decreased by rolipram. These results indicate that hepatic PDE4B plays a significant role in regulating lipogenesis, whereas PDE4D affects CYP2E1 expression and alcohol metabolism. Taken together, these data suggest that hepatic PDE4 expression is a clinically relevant target, and its inhibition can significantly attenuate the development of alcohol induced hepatic steatosis.Grant Funding Source: Supported by NIH, DOD and Veterans Administration
Attenuation of chronic‐binge alcohol‐induced liver injury by Lactobacillus rhamnosus GG culture supernatant via inhibition of intestinal barrier dysfunction (653.12)
Authors: Zhang Min , Wang Yuhua , Liu Yanlong , Zhao Cuiqing , McClain Craig , Feng Wenke 
Published: June 2021

Binge drinking after chronic alcohol consumption is one of the important factors contributing to the progression of hepatic steatosis to steatohepatitis. Our previous study showed that Lactobacillus rhamnosus GG (LGG) culture supernatant (LGGs) ameliorated acute alcohol‐induced liver injury. The present study investigated the effects and potential mechanisms of LGGs on chronic‐binge alcohol‐induced liver injury. Mice were fed Lieber DeCarli diet containing 5% alcohol for 4 weeks, then gavaged single dose of alcohol at 5 g/kg and lasted for 6 hours. Chronic‐binge alcohol exposure induced marked increase in hepatic steatosis and injury, which were attenuated by LGGs supplementation. LGGs application prevented chronic‐binge alcohol‐elevated intestinal permeability and circulating endotoxin level, indicating a beneficial effect of LGGs on intestinal barrier integrity. Further studies demonstrated that the effect of LGGs is through increasing intestinal tight junction proteins and proteins involved in the barrier homeostasis, such as ZO‐1, occludin, p‐glycoprotein, HIF‐2a and intestinal trefoil factor. LGGs also inhibited intestinal microRNA 122a expression, which has been shown to decrease occludin protein translation. In summary, LGGs is effective in preventing chronic‐binge alcohol‐induced liver injury by improving intestinal barrier function.Grant Funding Source: Supported by NIH, DOD and Veterans Administration
Mechanisms for reactive and sustained pressure dilation (677.4)
Authors: Chin Joseph , Land Douglas , Jasperse Samara , Jasperse Jeffrey 
Published: June 2021

We previously found that arteries actively dilate upon return to baseline intraluminal pressure after a brief reduction in pressure (reactive dilation), where the magnitude of dilation is dependent on duration of pressure reduction. We sought to determine the signaling mechanism responsible. Rat soleus feed arteries were isolated and cannulated for in vitro videomicroscopic observation. Pressure was reduced from 115 to 14 cmH2O for 2 min periods followed by a return to 115 cmH2O. Integrin inhibition (0.5 mM RGD peptide) (N=9) reduced reactive dilation (Con: 36.1±3.5%, RGD: 24.2±5.7%). Washing out RGD peptide restored dilation. Specific β3 integrin inhibition (0.5 mM F11 function blocking antibody) (N=7) (blocker) did not reduce reactive dilation. We also examined the initial dilation phase (prior to myogenic constriction) to sustained increases in pressure (80 to 135 cmH2O). Integrin inhibition failed to inhibit dilation, but combined endothelial inhibition (0.3 mM nitroarginine, 0.01 mM indomethacin, and 20 mM K+) reduced dilation (Con: 34.8±8.7%, inhibited: 10.2±3.1%). Combined nitroarginine and 20 mM K+ failed to inhibit dilation. These data suggest that reactive dilation is dependent on non β3 integrins. The data also suggest that initial dilation to sustained pressure increases is partially dependent on prostacyclin and that reactive and sustained pressure dilation utilize different mechanisms.Grant Funding Source: Supported by NSF #DBI‐1062721 and the Seaver Research Council
Gender differences in muscle sympathetic nerve activity and arterial pressure oscillations during progressive central hypovolemia (680.2)
Authors: Carter Robert , Hinojosa‐Laborde Carmen , Convertino Victor 
Published: June 2021

INTRODUCTION: Increased tolerance to central hypovolemia is generally associated with greater oscillatory patterns of mean arterial pressur (MAP) and greater physiological reserve capacity. We tested the hypothesis that women with high tolerance (HT) to hypovolemia would display similar physiological reserve capacity for tachycardia, sympathoexcitation, oscillations in MAP at pre‐syncope compared to men. METHODS: 9 men and 4 women were exposed to progressive lower body negative pressure (LBNP) until presyncope. All subjects were classified as HT because they completed at least ‐60 mmHg level of lower body negative pressure (LBNP). Muscle sympathetic serve activity (MSNA) was measured via microneurography and arterial pressure was measured by photoplethysmography. RESULTS: LBNP time to presyncope was lower (P<0.01) in women (1727±154 sec) than in men (2035±308 sec). At presyncope, MSNA (bursts/min) in men and women was similar (p=0.87). Coincident with smaller stroke volume (SV), women had lower MAP but similar heart rates compared with men. MAP/MSNA coherence was higher (p =0.04) in men (0.77±0.10) than women (0.67±0.04). Women had lower (p =0.06) oscillations in MAP compared to men. CONCLUSIONS: Our data corroborate the hypothesis that lower tolerance in women is not related to differences in sympathoexcitation or tachycardia, but reduced coherence (MSNA/MAP) and lower oscillatory patterns in MAP. Grant Funding Source: Department of Defense
Greater muscle protein synthesis and mitochondrial biogenesis during sprint interval training in males compared with females (702.2)
Authors: Scalzo Rebecca , Peltonen Garrett , Binns Scott , Giordano Gregory , Hartley Dylan , Klochak Anna , Lonac Marc , Paris Hunter , Szallar Steve , Wood Lacey , Peelor Frederick , Price John , Shankaran Shuba , Hellerstein Marc , Bell Christopher , Hamilton Karyn , Miller Benjamin 
Published: June 2021

Improvement in endurance exercise performance in adult humans following sprint interval training (SIT) has been attributed to mitochondrial (mito) biogenesis. However, this conclusion has been inferred from mito biogenic signaling, and not synthesis of new mito protein. Muscle protein synthesis (MPS) and mito biogenic responses to SIT have not been measured, nor have sex‐specific responses. We hypothesized that males and females would have similar rates of MPS, mito biogenesis, and overall individual protein synthetic rates after 9 sessions of SIT. 21 healthy adults (11 male, 10 female, 23±1 years, body mass index: 22.8±0.6 kg/m2; mean±SE) were orally administered deuterium oxide (D2O) for measurements of protein synthetic rates for 4 weeks while completing SIT. Maximal oxygen uptake increased (males from 43.4±2.1 to 44.0±2.3; females from 39.5±0.9 to 42.5±1.3 ml/kg/min; P=0.002) following SIT. MPS was greater in males compared with females in the mixed (150%; P<0.001), cytosolic (135%; P=0.038), and mito (135%; P=0.056) fractions. Kinetic proteomics identified 60 proteins that responded differently to SIT between the sexes (P<0.05); all were greater in males. For the first time, we document greater MPS and mito biogenesis in response to SIT in males compared with females, and present the first data describing the synthetic response of individual proteins in humans during exercise training.Grant Funding Source: Supported by the Office of Naval Research (N00014‐10‐1‐0247)
Towards a molecular understanding of allostasis in free‐ranging marine mammals (703.6)
Authors: Khudyakov Jane , Champagne Cory , Crocker Daniel 
Published: June 2021

Chronic stress negatively affects reproduction and survival of pelagic predators, threatening ecosystem stability. However, our understanding of the stress response in marine mammals is limited and largely based on terrestrial model systems that do not reflect pelagic life history adaptations. We are examining the molecular signature of allostasis in northern elephant seals to develop species‐specific stress diagnostic tools and resolve interactions between the hypothalamic‐pituitary‐adrenal (HPA) axis and other physiological pathways. We conducted stress tests in juvenile elephant seals by intramuscular adrenocorticotropic hormone (ACTH) injection to analyze the magnitude and duration of the HPA axis response. To investigate global gene expression changes in response to a stress challenge, we sequenced RNA isolated from muscle tissue of animals before and after ACTH injection. De novo transcriptome assembly and analysis was performed using the Trinity platform and yielded a reference transcriptome for the northern elephant seal study system. We have identified a number of genes and pathways altered during the stress response in a free‐ranging marine mammal, including several candidate molecular markers of stress. Our data indicate that the magnitude of the stress response to ACTH stimulation provides key information about an animal’s physiological state.Grant Funding Source: Office of Naval Research
Cerebrovascular compliance is not associated with acute mountain sickness following staged ascent to 4300 m (708.3)
Authors: Guerriere Katelyn , Beidleman Beth , Fulco Charles , Kenefick Robert , Staab Janet , Andrew Sean , Muza Stephen 
Published: June 2021

We hypothesized that a reduction in cerebrovascular compliance (∆V), due to cerebral edema, would be associated with acute mountain sickness (AMS) following staged ascent to 4300 m. Forty‐five unacclimatized men and women (mean±SD; 24±5 yr) were exposed to 48 h at a staging altitude at or above 2500 m followed by 24 h at 4300 m. AMS was assessed using the Environmental Symptoms Questionnaire. Near‐infrared spectroscopy was used to assess ∆V within the right frontal lobe via calculation of change in relative total hemoglobin concentration from resting baseline to peak value during a valsalva maneuver to a fixed pressure. Hemoglobin and hematocrit were measured to calculate changes in plasma volume (PV). All assessments were completed at rest in the morning at sea level (SL) and after 24 hours at 4300 m (HA). AMS severity increased (P<0.001) from SL (0.07±0.15) to HA (0.44±0.43). ∆V also increased (P<0.001) from SL (3.08±0.35) to HA (4.60±0.49). PV decreased (P<0.001) from SL to HA (‐17.3±7.1%). No relationship was found between the change in ∆V from SL to HA and the change in AMS severity (r=0.04;p=0.78), but the change in ∆V was significantly associated with the % change in PV (r=0.34;p=0.01). We conclude that ∆V was not related to AMS, potentially caused by cerebral edema, but rather hemoconcentration following staged ascent to 4300 m. Funding: USAMRMC. Authors’ views not official US Army or DOD policy.Grant Funding Source: Supported by USAMRMC
Ascending projections of the nucleus retroambiguus target key areas of the ponto‐medullary respiratory network (714.1)
Authors: Jones Sarah , Stanic Davor , Dutschmann Mathias 
Published: June 2021

Purpose: We aim to elucidate the role and contribution of the nucleus retroambiguus (NRA) in the generation of respiratory rhythm. We previously identified a putative rhythmogenic area 1.5 mm caudal to obex, destruction of which abolished respiratory rhythm in the in‐situ perfused brainstem‐spinal cord preparation of rat. Histological analysis indicated that the putative rhythmogenic cell population resides at the planar level of the pyramidal decussation, therefore likely to overlap with the NRA. We investigated possible involvement of the NRA in rhythm generation by mapping its neuronal connectivity in rat. Methods: Anterograde neuronal tracer, biotinylated dextran amine, was injected into the NRA. Respiratory areas in which labelled terminal fields were seen were injected with retrograde tracer Fast Blue in subsequent experiments. Results: Anterograde tracing from the NRA revealed dense clusters of labelled nerve terminals within important respiratory nuclei including the pre‐Bötzinger complex (PBC), parafacial respiratory group (pFRG) and Kölliker Fuse nucleus (KF). Injection of retrograde tracer into PBC, KF and pFRG show clusters of retrogradely labelled cell bodies in the NRA. Conclusion: Our data provides the anatomical framework for a rhythmogenic role of the NRA within the respiratory network.Grant Funding Source: ARC
Increased cardiac output, not pulmonary artery systolic pressure, increases blood flow through intrapulmonary arteriovenous anastomoses and impairs pulmonary gas exchange efficiency (717.2)
Authors: Elliott Jonathan , Duke Joseph , Futral Joel , Goodman Randall , Hawn Jerold , Lovering Andrew 
Published: June 2021

Sources of venous admixture (QVA/QT) that impair pulmonary gas exchange efficiency, defined by an increased alveolar‐arterial PO2 difference (AaDO2), are ventilation‐perfusion inequality (VA/Q), diffusion limitation, and shunt. Blood flow through intrapulmonary arteriovenous anastomoses (QIPAVA) increases QVA/QT and the AaDO2. However, it is unclear whether increased cardiac output (QT) or pulmonary artery systolic pressure (PASP) cause the increase in QIPAVA. We hypothesized that an increase in QT alone would increase QIPAVA resulting in an increased AaDO2 at rest breathing room air and 40% O2 to prevent contributions from diffusion and VA/Q. Epinephrine, i.v. at 320 ng/kg/min (EPI), and low dose epinephrine (80 ng/kg/min) combined with 2 mg of atropine (EPI+ATR) were used in healthy human subjects (n=5) to increase QT. When breathing either room air or 40% O2, EPI and EPI+ATR increased QT, (measured by acetylene uptake) from 7.8±1.0 to 13.3±3.4 L/min. Only EPI significantly increased PASP (to 54±14 mmHg), measured with ultrasound, but not with EPI+ATR (to 39±5 mmHg). However, EPI and EPI+ATR, breathing either room air or 40% O2 resulted in equal QIPAVA detected with saline contrast echocardiography. Furthermore, with EPI and EPI+ATR, the AaDO2 increased significantly when breathing either room air or 40% O2. Consistent with our data above, the calculated QVA/QT required to account for the entire AaDO2 was 2.4±0.4% with EPI and EPI+ATR, breathing either room air or 40% O2. We conclude that increased QT alone significantly increases QIPAVA and AaDO2 in healthy humans.Grant Funding Source: Supported by: Department of Defense #W81XWH‐10‐2‐0114, AHA Predoctoral Fellowship