bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of mitochondrial complex I inhibition on Ca2+ transients in pulmonary microvascular endothelium (1176.2)
Authors: Townsley Mary , Phillips Vantel , Cioffi Donna , Merker Marilyn , Francis Michael , Taylor Mark
Published: June 2021

In intact rat lung, we have shown that the decrease in lung ATP and endothelial barrier integrity resulting from rotenone‐induced mitochondrial complex I (CI) inhibition are prevented by the quinone CoQ1 (Free Radic Biol Med. doi: 10.1016/j.freeradbiomed.2013.07.040). To test whether impact of CI inhibition on Ca2+ handling might contribute, we evaluated Ca2+ dynamics using confocal microscopy and automated region of interest (ROI) detection and event tracking software in confluent monolayers of Fluo 4‐AM loaded rat pulmonary microvascular endothelial cell (PMVEC), in low glucose (0.2mM) HEPES buffer (25 °C) to limit glycolysis. Ca2+ transients were assessed at 1) baseline, 2) after vehicle, rotenone (0.5 µM) or rotenone + CoQ1 (10 µM), and 3) during activation of transient receptor potential vanilloid 4 channels with 4α‐phorbol 12,13‐didecanoate (4αPDD, 5 µM). Rotenone depressed the number of 4αPDD‐induced Ca2+ events/100 cells/sec, compared to vehicle or rotenone + CoQ1 (p<0.05, 2‐way ANOVA with Bonferroni post hoc tests), but did not significantly impact Ca2+ signal amplitude or spread. The addition of CoQ1 concomitant with rotenone limited both the duration and decay (sec) of Ca2+ signals compared to vehicle or rotenone alone (p<0.05). These data suggest that while CI inhibition does not break down structured endothelial Ca2+ domains in PMVEC, it blunts recovery of Ca2+ transients after TRPV4 activation.
K252a inhibits carotid body growth but not oxygen sensitivity (1177.2)
Authors: Bavis Ryan , Logan Sarah , Blegen Halward , Fallon Sarah
Published: June 2021

Brain‐derived neurotrophic factor (BDNF) supports innervation of the carotid body by afferent neurons (Hertzberg et al., Dev. Biol. 166:801‐811, 1994). Carotid body glomus cells express TrkB receptors as well, but the role of BDNF in carotid body growth and O2 sensitivity has not been studied. Neonatal rats were injected with the TrkB antagonist K252a (100 µg kg‐1, i.p.) or vehicle (25% DMSO) twice daily on postnatal days P0‐P6 and studied on P7. Carotid body volume was decreased by 35% after chronic K252a (P<0.001). However, single‐unit chemoafferent responses to 5% O2, measured in vitro, were unaffected by K252a administration. Ventilatory responses to 12% O2, measured by head‐body plethysmography, were also normal. Similar results were obtained for hypoxic chemoafferent and ventilatory responses after acute K252a administration. These data suggest that BDNF regulates carotid body growth but does not modulate glomus cell O2 sensitivity.

Grant Funding Source: Supported by NIH grant P20 GM‐103423 (Maine INBRE)
The problem of suicides in Semipalatinsk region (Republic of Kazakhstan) (1179.4)
Authors: Danbayev Serik , Tell Damilya
Published: June 2021

The analysis of the data on prevalence and structure of suicides in modern conditions of Semipalatinsk region testifies to practically unprece¬dented wave of increase of frequency of suicides in all groups of the population, frequency of suicide attempts accompanying with the most expressed growth in efficient groups of the population. The usual situation, thus, demands immediate actions on activation of preventive work of suicidologic serv¬ices. Constant active preventive and rehabilitation work is necessary for maintenance of reduction of a level of suicides, prevention of attempts of suicides, including repeated. In structure of suicidologic services joint functioning doctors and specialised departments of suicidologist and the social ‐ psy‐chological help for adult population, a psychiatric hospital are necessary. The special attention is nec¬essary for giving formation children's and teenage suicidologic services as in a significant part of cases of attempt of suicide to Semipalatinsk are made by teenagers. The society is interested in elimination of any exhibiting of suicides, and there was a requirement of deep knowledge suicides and management by it. In this plan the large interest represents an opportu¬nity of exercise of relative research of prevalence, frame, causes and socio‐economic consequences of suicides in various regions of Republic Kazakhstan with the purpose of the further development and expansion of frames, capable to carry out effective preventive, therapeutic and rehabilitational measures for downstroke of a level of suicidality in scales of all state. The given direction of scientific ‐ practical development should become one of the priorities in social medicine and organization of public health service in the republic. The basic share of service falls to studing of the social ‐ psychological help which provide realization rehabilitation programs and serve initial references and directions of doctors of general medical networks.
Vitamin D and the breastfed infant: family physicians’ recommendations (118.5)
Authors: Cozine Elizabeth , Umaretiya Puja , Thacher Tom , Maxson Julie , Oberhelman Sara
Published: June 2021

The American Academy of Pediatrics (AAP) recommends that all breastfed infants be supplemented with 400 IU of vitamin D daily, beginning soon after birth. We surveyed all Family Medicine providers at a single, academic medical institution regarding their perceptions and practices of infant vitamin D supplementation. Of 99 surveys solicited, 56 (57%) responded. Respondents were aware of the AAP recommendation with 52 (93%) correctly identifying the AAP’s recommended dose. The self‐reported median (interquartile range) proportion of visits in which the provider recommended supplementation to exclusively or partially breastfed infants were 80% (50 ‐ 97%) and 50% (25 ‐ 80%), respectively. The most common reason (82%) for recommending supplementation was “to follow the AAP recommendations.” Thirty (54%) reported recommending vitamin D supplementation within the first two weeks of life. Of all respondents, 49 (88%) recommend infant vitamin D drops as the route of supplementation. Finally, 49 (88%) respondents would prefer to supplement the mother instead of the infant or offer the parents a choice if this were an adequate and safe option for vitamin D supplementation, and 17 (30%) would prefer monthly to daily supplementation. In conclusion, Family Medicine providers are aware of current AAP recommendations, but vary in their practices; they are open to maternal vitamin D supplementation as an alternative option.
Mechanistic insights into osmosensing in the PVN (1182.2)
Authors: Feetham Claire , Barrett‐Jolley Richard
Published: June 2021

Cardiovascular disease is linked to disturbed osmosensing; effecting sympathetic activity, blood pressure and heart rate. The hypothalamus maintains plasma osmolality within a narrow range. The mechanisms are so far unknown; the paraventricular nucleus (PVN) may play a role. The transient receptor potential channel (TRPV4) and calcium activated potassium channels (KCa) are possible candidates for osmosensing. Having previously shown coupling of these channels in PVN neuron regulation in response to osmotic challenge, we wanted to further investigate the mechanisms responsible. Using cell‐attached patch clamp electrophysiology a population of ion channels were identified with a mean slope unitary conductance of 57±7pS and reversal potential of ‐5±3mV (n=6). The channel had a mean open probability (Po) of 0.1±0.0 at ‐40mV; increased by 48±9% (n=4) with the TRPV4 agonist 4αPDD. In isolated cells a resting membrane potential of ‐54±5mV and capacitance of 31±2pS were seen and a depolarisation of 11±2mV observed with 4αPDD (n=4;p<0.05). To investigate intracellular [Ca2+] by activation of TRPV4, [Ca2+] was measured using Fura‐2AM. 4αPDD caused a significant transient increase of 45±12nM (n=6;p<0.005). We have uncovered a potential mechanism for osmosensing within the PVN involving TRPV4 and KCa coupling. Targeting these ion channels may provide novel therapies for cardiovascular disease.
Spinal cord injury and disruption of extrinsic sympathetic control of cerebral vasculature does not significantly alter cerebrovascular reactivity to carbon dioxide (1183.10)
Authors: Inskip Jessica , Ravensbergen Rianne , O'Connor Shawn , Claydon Victoria
Published: June 2021

The role of the autonomic nervous system in the control of the cerebral circulation has been widely debated. Individuals with spinal cord injury (SCI), who have damage to sympathetic pathways, provide a unique opportunity to study cerebrovascular control in the absence of extrinsic sympathetic control. Here we studied cerebrovascular reactivity to CO2 in individuals with chronic SCI (both with and without damage to sympathetic pathways) and neurologically intact controls.

A range of CO2 levels was obtained by voluntary hyperventilation and hypoventilation, with increased inspired CO2, during normoxia (controlled on a breath‐by‐breath basis using dynamic end‐tidal forcing). Supine middle cerebral artery velocity (MCAv), inspired and expired O2 and CO2 were recorded continuously.

Compared to controls, individuals with autonomically complete SCI had reduced supine end‐tidal CO2 (36.6 ± 1.5 mmHg) and MCAv (53.4 ± 3.3 cm/s) compared to controls (40.5 ± 0.9 mmHg, p=0.05; 76.8 ± 6.0 cm/s, p<0.05). However, no significant difference in cerebrovascular reactivity to CO2 were observed between groups: disruption of extrinsic sympathetic neural control of the cerebral vasculature in individuals with complete autonomic SCI did not significantly alter the sensitivity or operating point of cerebrovascular reactivity to CO2.

Grant Funding Source: Supported by the Heart and Stroke Foundation of B.C. and Yukon (V.E.C.)
Effects of physical exertion and heat on cerebrovascular response in professional firefighters (1183.4)
Authors: Neary J. Patrick , Butz Matthew , Dahlstrom Barclay , Smirl Jonathan , Bishop Scott
Published: June 2021

Firefighting is a physically demanding occupation and a number of factors can compromise the firefighter’s (FF) health during duty, including inadequate cerebral blood flow (CBF) regulation. We hypothesized that dynamic cerebral pressure‐flow relationships will be altered in FF in response to acute physical exertion in the heat. Seven firefighters (age=30.8 ± 10.3 yrs) performed 30 minutes of treadmill walking at 65% of heart rate maximum in full turn‐out gear in an environmental chamber at 39°C. Testing involved: 5 minutes squat‐stand maneuvers at 0.05 Hz performed before and after the 30 minute treadmill test. CBF velocity was monitored in the middle cerebral artery (MCAv) using transcranial Doppler, blood pressure (BP) was recorded continuously using finger plethysmography, and 3‐lead electrocardiography recorded heart rate. Transfer function analysis (TFA) was used to determine the autoregulatory metrics. The results showed that the driven TFA metrics were not significantly different (p<0.05) pre‐ to post‐exercise for coherence (0.991 ± 0.007 vs 0.966 ± 0.037), gain (0.62 ± 0.15 vs 0.582 ± 0.199 cm/s/mmHg) and phase (0.634 ± 0.20 vs 0.612 ± 0.32 Rad), and power spectral density for both MCAv (22954.1 ± 11271.2 vs 24958.1 ± 13909.4 cm/s2) and BP (56121.0 ± 16177.9 vs 62612.6 ± 23002.4 mmHg2). In conclusion, the cerebral pressure ‐ flow relationship in FF was unaltered pre‐ to post‐ moderate exercise in the heat.
Comparison of autoregulatory indexes on spontaneous variations with linear support vector machines (1184.9)
Authors: Chacon Max , Bello Felipe , Jara José , Panerai Ronney
Published: June 2021

Comparison of Autoregulatory Indexes on Spontaneous Variations with Linear Support Vector MachinesMax Chacón1, Felipe Bello1, JL Jara1, Ronney B. Panerai2: 1Departamento de Ingeniería Informática, Universidad de Santiago de Chile, Avda. Ecuador 3659, 9170124, Santiago, Chile. 2Department of Cardiovascular Science, Leicester University, Clinical Sciences Wing, Glenfield General Hospital, Leicester, LE3 9QP, UK.

Linear Support Vector Machines (lSVMs) were used to model the relationship between signals of spontaneous variations in arterial blood pressure (ABP) and cerebral blood flow velocity (CBFV) of 16 healthy subjects in two capnic conditions: normocapnia and hypercapnia (5% CO2). Each model was trained with a section of 2.5 m of the recorded signals and evaluated by means of correlation analysis on another 2.5 m section. Signals were sampled at 0,6 s.

The classic index of autoregulation (ARI) and a recently‐proposed index, named model‐free ARI (mfARI), were calculated for the step response of the models. Paired tests were applied to determine significant differences between capnic conditions and between indexes. Sensitivity and Specificity were also estimated considering that subjects in hypercapnia should exhibit impaired autoregulation and a normality threshold of 5 for both indexes.

Table 1 summarizes the results. Both indexes found significant differences between capnic conditions. mfARI values were significantly lower than ARI values for subject in hypercapnia, and yielded a more balanced discrimination between normal and abnormal autoregulation.

Tabla 1: Results

Normocapniamean index
Hypercapniamean index
Diff. between capnic states
Sensitivity
Specificity

Correlation coeff.
0.593
0.662

ARI
6.288
5.400
p=0.019
92%
50%

mfARI
5.863
3.305
p=0.001
69%
75%

Diff. between indices
p=0.055
p<0.001
Perfection of blood donors selection process organization in Kazakhstan (1185.2)
Authors: Magzumova R. , Turgambayeva A. , Omarova A. , Omarkulov B. , Alihanova K. , Kulov D.
Published: June 2021

Currently, there are not normative‐legal acts regulating informative cooperation of these organizations in Kazakhstan. We carried out content‐analysis of productive activity indicators for 2008‐2012 years in seventeen Blood Centers of Donorshipindicators: the number of removed handling at the stage before blood donorship.

Specific density of absolute rejectsin general numberof Transfusions increased to 1, 24% in 2012compared with 2008 in comparative measures in Kazakhstan.

Specific densityof rejects on hemotransmissible infections composes 7, 0% in 2012 on the average in The Republic of Kazakhstan.

Strong insignificant growth of the number of rejection on the stage before blood donorshipis noted. Average index composed 14, 2% in 2008, 15, 4% in 2009,15, 6% in 2010,and 15, 8% in 2011.

Thus, on the basis of data,obtained in the result of analysis of efficiency of blood donors selection process organization on the stage before blood donorship, we made plan of priority directions on perfection of donorship of blood and its components in Blood Service of Kazakhstan; it is appropriately to develop the national standards of donors selection, based on epidemiology data on the country and on population segment; for information obtaining about persons not subject to participating in a donorshipit is legislatively to define the order of cooperation between concerned parties.
Ways to improve labarotory services of dermavenerologic institutions in Astana (1185.6)
Authors: Danbayeva Zh.
Published: June 2021

The construction of Astana attracts a large army of people from all regions of Kazakhstan, as well as people from other countries who come here hoping to get a job.It should be noted that the population growth inevitably causes social problems related to health.In 65% of sexually transmitted diseases infected people are younger than 35 years old. The influx of migrants to the capital has a significant impact on the epidemiological situation.Rhythm of work does not give people a timely manner to address specific medical care, which leads to the development of women's and men's sexual dysfunction, infertility, chronic inflammatory processes.It should be noted that the number of infected people are asymptomatic disease, so these patients do not receive treatment and can infect other people through sexual contact. In Astana there is a functioning Centre of Dermatology and prevention of sexually transmitted diseases, which conducts specialized treatment of dermatological and venereal diseases, using specific and modern methods of laboratory diagnosis of sexually transmitted diseases. The dermatovenereologic institution of Astana has 4 laboratories, and 2 of them are centralized: bacteriological and PCR and laboratory immunoassay. At present, the priority method for fast and qualitative detection of sexually transmitted infections are the methods of gene diagnostics, immunofluorescence, which is responsible PCR and immunodiagnostic laboratory, where the survey is conducted of sexually transmitted infections by PCR in real time, FATand ELISA.PCR and immunodiagnostic laboratory are equipped with modern facilities: a high‐speed microcentrifuge, mikrotsentrifuge‐vorteks, a programmable thermostat cycler,thermal cycler, a constant current source, electrophoresis chamber, UV transilluminator, fluorescence microscope, etc. Research by PCR, ELISA and FAT can efficiently and comprehensively examine the patient.
Understanding decision moments in infant feeding trajectories to improve interventions (119.4)
Authors: Zongrone A.A. , Menon P , Roopnaraine T , Bhuiyan M.I. , Pelto G.H. , Constas M , Rasmussen K.M. , Saha K.K. , Stoltzfus R.J.
Published: June 2021

Behavioral interventions have been used to improve infant and young child feeding (IYCF) with varying success. “Decision moments” (DMs), critical junctures at which caregivers make choices about IYCF are often key intervention targets. The behavior resulting from DMs determines what and how children are fed and thus their longitudinal pattern of feeding or “IYCF trajectory.” In the context of the Alive & Thrive process evaluation in Bangladesh, we aimed to understand behavior at these critical junctures by identifying DMs, characterizing and describing “IYCF trajectory” patterns, and examining the influence of maternal and household capacities (M&HCaps). We conducted longitudinal, in‐depth qualitative interviews (n=89 interviews in n=17 households) with mothers, fathers and grandmothers when the index child was 0‐6 and 7‐11 mo old. NVivo v10 was used for coding and analysis. Households were classified into 9 “IYCF trajectory” patterns based on a biomedical paradigm. “IYCF trajectory” patterns varied widely. DMs clustered at several times: after birth, and at 3‐4, 5‐6, 6‐7, and 7‐8 mo. The most influential M&HCaps included financial and material resources, time, social support, supportive advice and beliefs. We conclude that DMs cluster at multiple times during IYCF trajectories, there is no single normative “IYCF trajectory” that characterizes the population, and interventions to influence critical DMs must identify and remedy inadequate M&HCaps.

Grant Funding Source: Alive & Thrive, funded by the Bill & Melinda Gates Foundation & managed by FHI360; NIH(5T32HD007331)
Sun exposure and vitamin D supplementation in relation to the vitamin D status of breastfeeding mothers and infants in the Global Exploration of Human Milk study (119.8)
Authors: Dawodu Adekunle , Herbers Patricia , Davidson Barbara , Woo Jessica , Morrow Ardythe
Published: June 2021

Vitamin D (vD) deficiency in breastfeeding (BF) infants is reported worldwide, but comparison of its global prevalence and risk factors in BF women and their infants is scarce.

The prevalence of and risk factors for vD deficiency was determined in a cohort of BF mothers and their infants in Mexico City, Mexico, Latitude 19 N, Shanghai, China, Latitude 31 N and Cincinnati, Ohio Latitude 39 N.

360 mother‐infant pairs from the three sites were enrolled in the Global Exploration of Human Milk study. All delivered at term, planned to provide breast milk for at least 3 months. Serum 25(OH)D was measured in all mothers at 4 wks and in a subset of 47 Cincinnati, 35 Shanghai and 45 Mexican infants matched for fall and winter seasons and seen at 26 wks of life. Data were recorded prospectively on vD supplementation and sun exposures (sun index). vD deficiency was defined as serum 25(OH)D <50nmol/L.

At 4 wks postpartum, mean maternal serum 25(OH)D differed (p<0.001) by site, ranging from 70.2 nmol/L in Cincinnati (n=119), to 48.6 nmol/L in Shanghai (n=112), and 48.2 nmol/L in Mexico City (n=113). vD deficiency was identified in 17%, 52% and 62% of Cincinnati, Shanghai and Mexican mothers, respectively (p<0.001). Regression analysis found vD supplementation (p<0.001), sun index (p=0.036), season (p=0.002), and education (p<0.001) to be independent predictors of maternal vD status. At 26 wks of age, mean 25(OH)D was higher in Shanghai (95.3 nmol/L) than Cincinnati (68.3 nmol/L) and Mexico infants (44.0 nmol/L), p<0.001. vD deficiency was found in 6%, 28%, and 62% of Shanghai, Cincinnati, and Mexican infants, respectively (p<0.001). Regression analysis showed sun index (p=0.03), season (p=0.001), formula feeding (p=0.01), and higher maternal 25(OH)D (p=0.03) to predict higher infant vD status.

Vitamin D deficiency is common in BF mothers and infants worldwide, though the prevalence in diverse populations depends on sun exposure and vD supplementation behaviors. Greater attention to improve vD status is warranted.
Effect of eating frequency on evening meal energy intake (120.4)
Authors: Raynor Hollie , Collier J. Jason , Gellar Lauren , Zhao Ling , Chen Guoxun
Published: June 2021

Little experimental research has examined the effect of eating frequency (EF) on energy intake. This study tested two EF prescriptions, MEAL and GRAZE, on energy intake during an ad lib evening meal. Twelve, healthy, normal‐weight, unrestrained, regularly active participants (22.7 +/‐ 4.2 yrs, 22.4 +/‐ 1.0 kg/m2, 58.3% female, 83.3% white) completed two, counterbalanced, EF conditions. Participants were given identical types and amounts of food to eat prior to an evening meal, providing 60% of estimated energy needs. All provided food was consumed between 7 am and 5 pm, in two bouts (MEAL) and in five bouts (GRAZE). Energy consumed during an ad lib 30‐min evening meal was determined by measuring the weight of food eaten. Hunger and fullness were measured by 100 mm visual analogue scales prior to and after the meal. A repeated measures ANOVA, controlling for condition order and objectively measured moderate‐to vigorous‐intensity physical activity, found MEAL ate less meal energy than GRAZE (839.1 +/‐ 290.0 kcal vs. 875.2 +/‐ 277.1 kcal, p < 0.01). Hunger was lower after than before the meal (62.1 +/‐ 18.5 mm vs. 9.8 +/‐ 8.4 mm, p < 0.05), with no condition difference. No difference in fullness in pre‐ and post‐meal measures or by condition occurred. Eating less frequently, as compared to more frequently, produced lower evening meal intake, with no differences in hunger and fullness ratings. Reduced evening meal consumption may be a consequence of reduced food cue exposure earlier in the day.

Grant Funding Source: Supported by University of Tennessee
The effects of high or low iron status and male or female sex on the non‐transferrin‐bound iron response to oral iron supplementation (122.8)
Authors: Orozco Monica , Solomons Noel , Romero‐Abal Maria Eugenia , Samayoa Gabriela , Weiss Günter , Schümann Klaus
Published: June 2021

Background: Fe status determines intestinal Fe‐absorption and internal metabolism. Recently, sex‐associated effects on Fe handling have been suggested as well. These hold implications for prophylactic or therapeutic oral Fe supplementation.

Objective: To determine whether sex and/or Fe‐status influence the NTBI response to oral Fe.

Methods: 40 subjects ‐‐10 men (LM) and 10 women (LW) with low Fe stores (70 µg ferritin/L) ‐‐ provided blood samples at baseline and at 90, 180 and 270 min after ingesting 100 mg Fe as FeSO4. Fe and NTBI were quantified with ferrozine‐based assay and a fluorometric competitive‐binding assay, respectively.

Responses in serum were estimated as cumulative 3‐h absolute concentrations.

Results: The respective ∑ 3‐h absolute concentrations (in µg/dL) were 820±124, 560±115, 714±61, and 772±198 for serum Fe (p=0.004), and 12±3, 14±4, 16±4, and 11±6 for serum NTBI (p=0.218) for the LM, AM, LW, and AW groups. Two‐way ANOVA interaction‐terms for Fe status and sex were statistically significant for the serum Fe and NTBI responses (p=0.003 and p=0.05).

Conclusion: Among males, the serum Fe uptake response was diminished with adequate Fe status as compared to low status, but a corresponding status‐related differential was not seen among women. The NTBI response was equally mitigated across the entire spectrum of subject groups.

Grant Funding Source: Supported by the Hildegard Grunow Foundation
Dehydroglyasperin C, one of licorice‐derived prenylflavonoids, had antioxidant and cognitive enhancing properties (124.5)
Authors: Seo Ji Yeon
Published: June 2021

Oxidative stress occurs as a result of an imbalance between reactive oxygen species formation and the capacity of antioxidant defenses. The purpose of the present study was to elucidate the antioxidant properties of licorice‐derived prenylflavonoids such as dehydroglyasperin C(DGC), dehydroglyasperin D(DGD) and isoangustone A(IAA). In addition, we investigated the protective effect of DGC from the memory deficits and cognitive function impairment in scopolamine‐induced mice. The learning memory ability of mice was evaluated by passive avoidance test. While the spatial learning and memory abilities of mice were assessed by Y‐maze and Morris water maze tests. We found that DGC improved the cognitive function of mice injected with scopolamine in a dose‐dependent manner. Moreover, DGC recovered the scopolamine‐induced spatial memory deficiency as assessed by Y‐maze test. The inhibitory activity of DGC against acetylcholine esterase present in hippocampus and cerebral cortex extracts was also examined. In conclusion, these results suggest that DGC attenuates scopolamine‐induced memory impairment maybe through enhancement of the cholinergic nervous system via acetylcholine esterase inhibition as well as antioxidative activity.

Grant Funding Source: Supported by NRF‐2010‐0027204 and 2011‐0009782 and IPET (High Value‐added Food TechnologyDevelopment Program, 2012, 112066‐3), S. Korea
Cognition, nutrition and physical function in obese older women (124.7)
Authors: LoBuono Dara , Taetzch Amy , Quintanilla Dinah , Maris Stephen , Letendre Jonathan , Picard Allison , Delmonico Matthew , Xu Furong , Lofgren Ingrid , Mahler Leslie
Published: June 2021

Obese older women are at increased risk of chronic diseases that lifestyle modifications can attenuate. Combined nutrition and physical activity interventions can improve dietary quality and physical function and reduce chronic disease risk, but how cognitive function is associated with these outcomes is unknown. Twenty‐six obese older women (65.3±8.1 years and BMI 38.0 ± 4.6 kg/m2) completed a 12‐week quasi‐experimental community‐based intervention, with a behaviorally‐based modified Dietary Approaches to Stop Hypertension diet, Tai Chi (TC) and resistance training (RT). Seventeen women were in the diet, TC+RT intervention group (EXD) and 9 were in the waiting control group (CON). Cognitive score was assessed via the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Mean baseline RBANS score was 88.1 ± 19.9. The dietary screening tool (DST) was used to assess dietary quality, mean baseline score was 62.3 ± 11.1, which equates to at possible nutrition risk. The short physical performance battery (SPPB) was used to assess physical function; mean baseline score was 8.5±2.6. Baseline RBANS were positively associated with baseline (r=0.39, p=0.03) and post‐intervention SPPB scores (r=0.40, p=0.05) of all participants. Cognitive status is associated with physical function and future research should consider cognitive levels to create appropriate interventions in the community.

Grant Funding Source: College of Environment and Life Sciences Community Access to Research and Extension Services (CELS C
Mothers’ reasons for human milk expression and associations with human milk expression practices (131.3)
Authors: Felice Julia , Rasmussen Kathleen
Published: June 2021

Most breastfeeding (BF) women in the U.S. use human milk (HM) expression (HME), or pumping, to feed HM. HME is used for many reasons that may affect how they implement HME. The characteristics of those who use HME for lactational (L) (engorgement, soreness, low supply), dyadic (D) (nursing unavailable or undesired by mother) or elective (E) (use in solids, emergency stock, donation) reasons are unknown as is whether these types of reasons affect HME practices. To address these issues, we used data from the Infant Feeding Practices Study II cohort of ~3,000 dyads. Among women feeding HM, we used regression analysis to compare (L or D) v. E‐only reasons and found that the (L or D) group was more likely to use HME regularly than the E‐only group (OR 4.15, p = 0.03). Several maternal characteristics predicted both L and D reasons for HME. Cesarean birth and late lactogenesis II onset also predicted L reasons. Mothers who used HME for L reasons v. non‐L reasons had earlier start of regular HME (p = 0.026), which was not significant when adjusted for confounders. Mothers who used HME for D reasons v. non‐D reasons had later start of any HME after adjustment (p < 0.0001). These findings suggest that reasons for HME differ across sociodemographic groups, and may affect the start and regularity of HME. Given the importance of and public health push for HM feeding, and ongoing rise in HME, these phenomena must be explored further.

Grant Funding Source: NIH (T32DK007158)
Early formula supplementation and breastfeeding duration (131.4)
Authors: Perrine Cria , Chen Jian , Scanlon Kelley
Published: June 2021

Objective: To describe how supplementation with infant formula in the first two days (F2D) of life is associated with breastfeeding duration in a nationally representative sample of US births.

Methods: We analyzed data from the 2010 birth cohort of the National Immunization Survey. Among infants breastfeeding at 2 days (n=6636), we described prevalence of breastfeeding at 3, 6, and 12 months, by whether the infant received formula in the F2D. We used separate logistic regression models to describe how 2 day supplementation was associated with breastfeeding at each time point, adjusting for maternal socio‐demographic characteristics.

Results: Among breastfeeding infants, 24.2% had been supplemented with formula in the F2D. Infants who had not received formula in the F2D were more likely to be still breastfeeding at 3 (83.8% vs. 75.7%), 6 (67.8% vs. 52.3%), and 12 (37.8% vs. 26.7%, all p<0.01) mo. In adjusted analyses, breastfeeding infants who did not receive formula in the F2D had increased odds of breastfeeding at 3 (OR=1.63, 95% CI: 1.26, 2.10), 6 (OR=1.89, 95% CI: 1.53, 2.35), and 12 (OR=1.62, 95% CI: 1.28, 2.05) mo.

Conclusion: Early supplementation of breastfeeding infants with formula may contribute to earlier cessation of breastfeeding. Improved hospital and professional support may help reduce early supplementation of breastfeeding infants, and thus improve rates of breastfeeding duration.
Maternal upper‐body circumferences predict human milk adiponectin concentration (131.8)
Authors: Minter Anne , Lee Seung‐ , Woo Jessica , Dolan Larry , Morrow Ardythe , Nommsen‐Rivers Laurie
Published: June 2021

Prenatal measures explain little of human milk adiponectin (HMA) variation. We examined whether postpartum metabolic and fat depot measures predict HMA from milk sampled concurrently. Participants underwent a morning oral glucose tolerance test, anthropometry (hip, iliac crest, waist, and under‐breast circumferences; weight and BMI), and breast expression (N=20). Serum insulin, glucose, and total adiponectin were assayed, and insulin sensitivity and secretion were estimated. HMA was assayed using ELISA. Spearman rank coefficients and linear regression were used to examine relations with HMA. Serum adiponectin was the single significant metabolic correlate with HMA (r=0.45, p=0.048). HMA was not significantly correlated with BMI or weight, but became more negatively correlated with fat‐depot specific anthropometry with increasing proximity to the breast: hip (r=‐0.32, p=0.164); iliac crest (r=‐0.46, p=0.039); waist (r=‐0.50, p=0.025); under breast (r=‐0.56, p=0.011). Combined, serum adiponectin and waist circumference predicted 47% of HMA variation (p=0.002). Thus, upper body fat depots may be an important source of HMA independent of circulating adiponectin levels.

Grant Funding Source: NIH 8 ULI TR000077
Evaluating the presence of formal nutrition and physical activity policies in childcare centers in North Carolina (132.1)
Authors: Erinosho Temitope , Mason Kamaria , Morris Ellie , Schwartz Marlene , Ward Dianne
Published: June 2021

This study describes nutrition and physical activity (PA) policies in 50 childcare centers in North Carolina. Directors completed surveys about the presence or absence of policies, and provided copies of their centers’ policy documents. Reviews of these documents showed, 66% had a policy about offering fruits and vegetables for lunch, and 10%, about offering fruits or vegetables for snack. None had policies about limiting sugary drinks. Few centers had policies about limiting milk fat for preschoolers (16%), and type (26%) and amounts (6%) of 100% juice served. Two centers had a policy about making drinking water accessible to children, 33%, about foods allowed for celebrations, and <20%, about caregivers’ behavior at meals (sit, eat with children). Half of the centers had written policies about providing various PA opportunities, and the frequency of outdoor play. Few centers had policies about the provision of structured PA (16%), duration of outdoor play (20%), and a plan for outdoor play in inclement weather (16%). For most policies, directors reported having written policy statements, even though the document reviews showed otherwise. In reporting about policies, it is possible that directors may have been referring to state or federal regulations that may not have been addressed in their centers’ policy documents. Further evaluation is needed to help researchers better understand these inconsistencies.

Funding provided by the Robert Wood Johnson Foundation’s (RWJF) Healthy Eating Research New Connections Program.
Neighborhood vendedores (mobile food vendors) as a dependable source to Mexican‐origin children for after‐school and weekend snacks (132.2)
Authors: Sharkey Joseph , Gomez Melissa
Published: June 2021

The Mexican‐origin population is the fastest growing subpopulation in the United States, and at greatest risk for obesity and diabetes. This population growth has been occurring in the burgeoning colonias along the U.S. border with Mexico, especially in Texas and in new destination immigrant communities throughout the U.S. The ready accessibility and utilization of ‘truly’ mobile vendedores (MV) within the community play a role in the types and frequencies of foods marketed to children for purchase after‐school and on weekends. One hundred mother‐child dyads (mother and child 6‐11 years) were recruited by promotora‐researchers from colonias that were spatially selected from four geographic areas in Hidalgo County, TX. Data were collected by trained promotora‐researchers in Spanish during three in‐home visits: survey data and anthropometrics separately for the mother and child from the first visit and dietary recalls from the child during all three visits. Among child participants, 62% were girls; 32% were born in Mexico; 42% were overweight or obese; and 54% reported low or very low food security. Children reported a positive perception of the role of MV as a dependable source of food for the family, convenient source of foods, inexpensive foods, and foods that taste good. Children planned in advance for the MV and purchased food after school and on weekends from the MV who marketed in their colonia. The foods purchased were ice cream, raspas, elotes, candy, and chicharrone. More frequent purchase of foods and beverages by children from MV was associated with greater intakes of total energy (p = 0.004), sodium (p = 0.017), total sugar (p = 0.005), and added sugars (p = 0.017). Findings suggest that strategies for improving the diet of children include neighborhood MV. MV may be a promising venue for increasing neighborhood access to affordable healthy foods in colonia neighborhoods.

Grant Funding Source: Supported by RWJF Healthy Eating Research Program
Role of platelet‐derived growth factor alpha in chronic liver injury (144.4)
Authors: Kikuchi Alexander , Monga Satdarshan
Published: June 2021

Platelet‐derived growth factor α (PDGFRα) is a tyrosine kinase receptor that plays a role in liver development and regeneration and is upregulated in livers of patients with primary biliary cirrhosis as well as a majority of hepatocellular carcinomas (HCC). Whether PDGFRα upregulation in these settings plays a compensatory or a pathological role is unknown. This question has led us to investigate the role of PDGFRα in chronic liver injury and hepatic fibrosis ‐ a pathogenic process that is a precursor to the development of cirrhosis and HCC. In this study we show that PDGFRα is upregulated in murine liver following bile duct ligation, a model of cholestatic liver injury. In addition we show that PDGFRα and one of its ligands, PDGF‐CC, is localized to hepatocytes as well as bile duct epithelial cells. In vivo blockade of PDGFRα in mice using a previously described monoclonal antibody revealed significant attenuation of hepatocellular injury assessed through liver function analysis of animal serum. In contrast, analysis of in situ hepatic collagen deposition in these animals reveals increased fibrosis in animals treated with PDGFRα inhibitor, suggesting that fibrosis and myofibroblast activation occurs independently of hepatocellular injury in this model. These findings point towards a dichotomous contribution of PDGFRα signaling in cholestatic liver injury with opposing effects in parenchymal and non‐parenchymal cell compartments.

Grant Funding Source: T32: HL094295 ANGIOPATHY TRAINING GRANT; R01: DK095498 ROLE OF PDGFRALPHA IN LIVER PATHO‐BIOLOGY
Endotoxin attenuates fibrogenic activity of hepatic stellate cells: a novel mechanism of limiting liver fibrosis (144.5)
Authors: Dangi Anil , Tandon Ashish , Kumar Sudhir , Gandhi Chandrashekhar
Published: June 2021

Chronic liver injury follows tightly regulated sequence involving inflammation, and activation of hepatic stellate cells (HSCs) that gain proliferating and fibrogenic phenotype. Activated HSCs are the primary cells to cause liver fibrosis. Bacterial endotoxin (lipopolysaccharide; LPS) has been shown to promote hepatic fibrosis by modulating TGFβ signaling in quiescent HSCs. However, whether LPS, levels of which are elevated in liver diseases, exerts similar effects on activated HSCs is not known. Here, we found that a single administration of LPS (5 mg/kg; ip) to rats that had developed CCl4‐induced liver fibrosis resulted in significant down‐regulation of α‐smooth muscle actin (α‐SMA; HSC‐activation marker) and type I collagen expression, increased the expression of matrix metalloproteinase 3, and reduced fibrosis as determined by Sirius red staining. LPS also reduced liver injury as indicated by lower serum ALT levels. In culture‐activated HSCs, LPS down‐regulated the expression of α‐SMA, and of TGFβ1 (a potent fibrogenic cytokine) and its receptor, and up‐regulated the expression of TFGβ1 pseudo‐receptor BAMBI. These effects of LPS on HSCs were accompanied by phenotypical alterations (reduced size and α‐SMA) and increased expression of inducible nitric oxide (NO) synthase Furthermore, both in fibrotic liver tissue and cultured HSCs, LPS up‐regulated expression of decorin, which regulates collagen fibrillogenesis, blocks bioactivity of TGFβ1 and exerts protective effect against fibrosis. Our findings suggest that these effects of LPS on activated HSCs may be an intrinsic mechanism of limiting fibrosis in chronic liver disease.
Characterization of group B streptococcal infection of astrocytes and the impact on the blood‐brain barrier (145.8)
Authors: Stoner Terri , Weston Thomas , Trejo JoAnn , Doran Kelly
Published: June 2021

Streptococcus agalactiae (Group B Streptococcus, GBS) is the leading cause of life‐threating meningitis in human newborns. Meningitis is a consequence of neonatal infection at the stage when GBS leaves the bloodstream (bacteremia), crosses the blood‐brain barrier (BBB), and enters the central nervous system (CNS), where the bacteria associates with the meninges. GBS invades the BBB, and the interaction between GBS and astrocytes that physically associate with brain endothelium, have not been described. We hypothesize that human astrocytes play a unique role in GBS infection and the development of meningitis. To address this, we investigated the ability of GBS to interact with human astrocytes in vitro. Wild‐type GBS strains, representing the most clinically dominant serotypes (Ia, Ib, III, and V), were incubated with SVG to determine the levels of both surface‐adherent and intracellular bacteria. All GBS strains were able to adhere and invade astrocyte cells. This was specific to GBS; Streptococcus gordonii and Lactococcus lactis did not invade astrocytes. Wild type GBS also had the ability to persist intracellulary up to 12 hours and intracellular survival was confirmed by Transmission electron Microscopy (TEM). Stimulation of astrocytes with GBS results in IL‐1β and IL‐6 production. GBS intracellular survival and induction of astrocyte, derived cytokines may impact BBB permeability during infection. Understanding the role of astrocytes during GBS infection will provide important information regarding BBB disruption and the development of meningitis.
Aortopathy: a developmental defect with adult pathology? (15.5)
Authors: Riley Ashlie , Krishnamurthy Varun , Maddy Kelsey , Junor Lorain , Biechler Stefanie , Hinton Robert , Goodwin Richard
Published: June 2021

Aortopathy is a subclinical disease characterized by aortic dilation, which can result in aortic dissection and/or aortic aneurysm. Hallmarks of aortopathy include vascular smooth muscle cell (VSMC) and elastin fiber misregulation. Elastin hemizygous (Eln+/‐) mice have a thickened and altered arterial wall structure, specifically, aortic root distension and an increase in VSMC layers along the ascending aorta. We hypothesize that aortopathy has a congenital basis with the associated defects originating in the cardiac neural crest (CNC) aorta. Aortic tissues from adult and aged wild type (WT) and Eln+/‐ mice were examined to detect anatomic and/or developmental variation. Sonic Hedgehog (a marker of CNC derived cells), SM22 (a marker of VSMCs), aggrecan and biglycan (proteoglycan markers) were utilized in a novel 3D reconstructive manner to discern spatial and temporal localization. Quantification of these findings revealed that cardiac neural crest‐derived aorta tissue is spatiotemporally associated with VSMC abnormalities, maladaptive matrix remodeling with differential proteoglycan misexpression, and biomechanical dysfunction suggesting a primary role in the development of aortopathy.

Grant Funding Source: This study was supported by the AHA 11PRE7210044 (VKK), and the National Institutes of Health HL0851
l‐Citrulline protects from kidney damage in STZ‐diabetic rodents (151.10)
Authors: Romero‐Lucas Maritza , Yao Lin , Lucas Rudolf , Caldwell Robert , Bagi Zsolt
Published: June 2021

Rationale. Diabetic nephropathy (DN) is a major cause of end‐stage renal disease. Hypercatabolic states are a common feature of chronic diseases such as diabetes mellitus (DM), and are accompanied by an increase of circulating inflammatory cytokines. Therefore, amino acid supplementation may be effective in counteracting the metabolic consequences of DM, including DN.

Aims. To investigate whether L‐citrulline (L‐cit) supplementation represents a safe intervention in DN, and to assess the effects of L‐cit on the inflammatory profile observed in DM.

Methods. STZ‐C57BL6 mice and rats received L‐cit or vehicle supplemented in the drinking water (50 mg/kg/day). Human glomerular endothelial cells (HGEC) were exposed to high glucose (HG, 25 mM)‐supplemented medium.

Results. L‐cit supplementation markedly reduced urinary albumin excretion (µg/day, C=141.4 ± 23.8; STZ= 807.2 ± 205.1 p<0.001 vs C; L‐cit‐STZ= 193.4 ± 109.8 p<0.05 vs STZ), tubulo‐interstitial collagen deposition, and kidney hypertrophy observed in untreated STZ‐mice and rats. These effects were accompanied by enhanced plasma levels of the anti‐inflammatory cytokine IL‐10, and an increased expression of a marker of an anti‐inflammatory phenotype arginase II in proximal tubules. L‐cit also restored NO/ROS balance and barrier function in HG‐treated HGEC.

Conclusions. L‐cit supplementation is beneficial in preserving the nephron function in STZ‐rodent models. This effect may be due to L‐citrulline’s abilities to establish an anti‐inflammatory response in the proximal tubules and in the circulation. L‐cit also protects the glomerular barrier function from hyperpermeability and NO/ROS imbalance.

Grant Funding Source: Supported by NIH HL104126
Giardia cathepsin B cysteine proteases degrade interleukin‐8 and attenuate interleukin‐8‐induced neutrophil chemotaxis (152.2)
Authors: Cotton James , Bhargava Amol , Ferraz Jose , Yates Robin , Beck Paul , Buret Andre
Published: June 2021

New therapeutic approaches for gastrointestinal inflammatory disorders are sorely needed. Children infected with the protozoan parasite Giardia duodenalis exhibit attenuated gut inflammatory responses via unknown mechanisms. The Giardia genome contains 9 cathepsin B (catB) proteases with anti‐inflammatory potential. Objectives. Using complimentary models of human intestinal biopsies, mice, and human enterocytes in vitro, to determine if Giardia infections attenuate Clostridium difficile toxin‐induced colitis, and if Giardia trophozoites attenuate interleukin‐8 (CXCL8) secretion from intestinal epithelial cells. Results. Reduced neutrophil (PMN) recruitment was observed in Giardia‐infected mice following rectal administration of C. difficile toxins. Co‐incubation of Giardia trophozoites with human small intestinal mucosal biopsy tissues ex vivo, or in vitro Caco‐2 monolayers resulted in attenuated of IL‐1β‐ or Salmonella‐induced CXCL8 secretion via catB‐mediated degradation of CXCL8. Giardia catB proteases also attenuated CXCL8‐induced PMN chemotaxis. Conclusion. Giardia trophozoites secrete catB proteases that degrade CXCL8 and attenuate CXCL8‐induced PMN chemotaxis. Parasitic protease‐mediated reduction of PMN’s may offer a promising therapeutic avenue for intestinal inflammatory disorders. Funding provided by NSERC, AIHS, and CCFC.