bluuebunny/crossref_metadata_2025 huggingface dataset:
3R, 3′R zeaxanthin Protects Retina from Photo‐Oxidative Damage: in vivo model
Authors: Sahin Nurhan , Akdemir Fatih , Orhan Cemal , Tuzcu Mehmet , Yilmaz Ismet , Juturu Vijaya
Published: November 2023

Objective

3R, 3′R zeaxanthin is one of the three principle carotenoids in the eye and supports eye health and visual function as a potent antioxidant and protector of lipid membranes against singlet oxygen and free radicals. RR‐zeaxanthin works synergistically with the other macular carotenoids to absorb a broader spectrum of high‐energy blue light to protect against photo‐induced oxidative damage. We tested this hypothesis to determine the effects of 3R, 3′R zeaxanthin (OmniXan®, OMX) in ocular tissues and plasma in age‐related macular degeneration (AMD) of rats exposed to dark and intense light

Methods

Male Wistar male rats (age: 8 weeks, weight: 180 ± 20 g) were housed in a controlled environment with a 12:12‐h light‐dark cycle at 22°C and provided with rat chow and water ad libitum. All experiments were conducted under the National Institutes of Health's Guidelines for the Care and Use of Laboratory Animals and approved by the Ethics Committee of the Inonu University. After providing compliance with the conditions of the laboratory, rats were randomly divided into treatment groups and exposed to Group I (A & B+/− 100 mg/kg BW OMX); 12 h light and 12 dark], Intense light [Gr II (A & B)+/100 mg/kg BW OMX) LED] 24h, Intense light [Gr III (A & B) +/− 100 mg/kg BW OMX) IL, LED] 16h and 8h dark adaptation for 60 days. Vision and brain health markers such as Rhodopsin (Rho) Rod arrestin (Sag), G Protein Subunit Alpha Transducin 1 Gnat1, nuclear factor‐kappa B NFkB, neural cell adhesion molecule NCAM, growth‐associated protein‐43 GAP43, glial fibrillary acid protein (GFAP), nuclear factor (erythroid‐derived 2)‐like 2 Nrf2 and Heme oxygenase 1 (HO‐1) were analyzed. Oxidative stress and anti ‐inflammatory markers were analyzed. The data were analyzed using the GLM procedure of SAS (SAS Institute: SAS User's Guide). The treatments were compared using ANOVA and student's unpaired t test; P < 0.05 was considered statistically significant.

Results

OMX administration significantly alleviated oxidative stress and improved Rho, Rod arrestin (Sag), Gnat1, NCAM, GAP43, Nrf2 and HO‐1 in retinal tissues. SOD and GSH‐Px improved with OMX. No gross lesions, no mortality and no adverse events were observed.

Conclusion

These observations suggest that OMX may be considered to prevent photoreceptor cell degeneration.

Support or Funding Information

Omni Active Health Technologies Ltd. India.
Genistein in Combination with Sulforaphane for the Treatment of Type 2 Diabetes
Authors: Liu Dongmin , Wang Aihua , Liu Jing , Alkhalidy Hana , Zhen Wei , Moore William
Published: November 2023

Insulin resistance and loss of functional beta‐cell mass are hallmarks for the pathogenesis of type 2 diabetes (T2D). Therefore, the search for agents that simultaneously reverse these two defects could be a more effective strategy to treat T2D. We recently reported that dietary provision of genistein (0.5 g/kg diet) preserved pancreatic b‐cell mass and ameliorated hyperglycemia in diabetic mice. Here, we found that sulforaphane (0.25 g/kg diet), a small molecule derived from cruciferous vegetables prevented insulin resistance in diet‐induced obese mice. Notably, oral administration of genistein in combination with sulforaphane completely normalized hyperglycemia and insulin sensitivity in middle‐aged obese diabetic mice. Ex vivo, genistein directly promoted viability of cultured human and mouse islets chronically exposed to palmitate (0.5 mM) and high glucose (HG, 20 mM). On molecular levels, genistein activates GPR30, which subsequently induces the Gαs/cAMP/PKA/CREB pathway essential for promoting beta cell survival. Consistently, oral administration of genistein (50 mg/kg body weight) mitigated STZ‐induced hyperglycemia in WT but not in GPR30 KO diabetic mice. Moreover, we show that sulforaphane promoted mitochondrial function, enhanced pyruvate and fatty acid oxidation, and increased glucose uptake in primary human muscle cells. These results demonstrate for the first time that the combination of phytonutrient genistein and sulforaphane with complimentary mechanisms of actions may have considerable potential for preventing and treating T2D.

Support or Funding Information

The work was supported by grants from NCCIH of NIH (1R01AT007077, 1R01AT007566) and the American Diabetes Association Diabetes Basic Research Award (7‐11‐BS‐84).
Effect of Sulfur‐Containing Compounds on Hydrogen Sulfide Production in THP‐1 Differentiated Macrophages
Authors: Rodrigues Camila , Fereyduni Ehsan , Grenning Alexander J , Rowe Cheryl A , Percival Susan S
Published: November 2023

Hydrogen sulfide (H2S) is considered the third endogenous gaseous signaling transmitter. The H2S has been described as a target molecule for therapies on specific diseases, such as cardiovascular diseases and inflammatory processes. Garlic and glutathione (GSH) are examples of sulfur‐containing compounds that have been shown to modulate H2S production in erythrocytes and other specialized cells. However, such evidence has never been described in immune cells. Therefore, the aim of this study was to investigate the effect of aged garlic extract (AGE) and GSH on H2S production in macrophages. THP‐1 monocytes (0.7×106) were differentiated into macrophages using phorbol 12‐myristate 13‐acetate in a 96‐well plate. Once differentiated, the cells were pre‐incubated at 37°C in a humidified 5% CO2 atmosphere for 30 minutes with a fluorescent turn‐on H2S‐responsive probe (DP‐NBD – 150uM), synthesized according to Zhang et al. (2015). The cells were treated for 24 hours with GYY4137 (300uM), GSH (1mM), AGE (100mg/ml) or GSH+AGE. Cells were also treated for 24 hours with GSH and then 3 hours with AGE. The H2S production was identified using a fluorescent microscope and the fluorescence of DP‐NBD recorded. After the 24 hour incubation, GSH and AGE treatments alone had no effect on H2S production compared to non‐treated cells. Moreover, in the GSH (24 hours) + AGE (3 hours) treatment, the fluorescence intensity also did not differ from non‐treated cells. However, when the macrophages were incubated with GSH+AGE at the same time, the fluorescence was higher than non‐treated cells and comparable to the positive control. In conclusion, incubation with GSH and AGE together increased H2S production in THP‐1 differentiated macrophages after 24 hours of treatment, but this effect was not observed in the individual treatments. These results demonstrate a possible interaction between GSH and AGE in immune cells.

Support or Funding Information

UF/IFAS Agriculture Experiment Station
Dietary Supplement Items on Commonly Used Food Frequency Questionnaires
Authors: Rios‐Avila Luisa , Dwyer Johanna , Costello Rebecca , Potischman Nancy
Published: November 2023

For some nutrients, dietary supplements (DS) contribute substantially to total intakes, and thus assessment of DS use is important. Most large epidemiological studies use food frequency questionnaires (FFQ) to obtain information about DS intake. However, the various FFQs enquire about different DS and use differing methods for assigning values for nutrients and other bioactive constituents in the products. In addition, FFQs differ in the questions about frequencies, duration and dosages of DS, making comparisons of intakes across studies difficult. Inconsistencies in the literature relating DS usage with particular outcomes may be partly due to differences in assessment of DS in these questionnaires. We examined commonly used FFQs available for general use in large epidemiological cohorts including the Diet History Questionnaire II, the Willett questionnaire, the Block questionnaire 2014 full‐length FFQ + physical activity screener, the Women's Health Initiative FFQ, the Vitamins and Lifestyle FFQ and the Multiethnic Cohort Study FFQ and their additional supplement questionnaire used to validate their FFQ supplement data. In addition to the studies mentioned, these questionnaires have been used in large prospective studies including the Nurses' Health Study, the Health Professionals Follow‐Up Study, the Women's Health Study, the Sister Study, the Cancer Prevention Study II Nutrition Survey, and the AARP cohort study. This analysis compared differences and similarities on items querying DS use. The FFQs differed on number of DS with lists varying from 3 to 49 supplements; type of supplement (e.g. One FFQ did not ask about multivitamin with minerals, four did not ask about herbal/botanical, and two did not ask about non‐vitamin/non‐mineral supplements); dosages (Six of the FFQs asked for dosages only for specific nutrients such as vitamin C, vitamin E, vitamin D, and calcium); and frequency and duration categories of use (e.g. Two FFQs did not ask how often DS are used, two asked for seasonal use only for vitamin A, C and D, and only four asked how often herbal/botanical supplements are used). Information on the DS database used to estimate nutrients from supplements on FFQs was also obtained. In summary, all FFQs included questions to determine the use of multivitamins, single vitamins, and single minerals, but differed in the inclusion or exclusion of other types including multivitamins with minerals or other combinations, herbal/botanical, and non‐vitamin/non‐mineral supplements. Moreover, FFQs differed in the number of DS supplements listed, dosage for all DS listed, and frequency and duration of use for some of the DS including herbal/botanical supplements.

Support or Funding Information

Office of Dietary Supplements, NIH
Objectively Collected Weight Data and Long‐Term Outcomes: Analysis of Data From 90,000 Users of the Withings Smart Scale
Authors: Wilkinson Lua Juliet , Levitsky David
Published: November 2023

Importance

Frequent self‐weighing is a low‐intensity strategy that is associated with weight loss and/or weight maintenance in adults. Internet connected scales create a unique opportunity to study self‐weighing behaviors and weight outcomes over long periods.

Objective

To examine associations between body weight and self‐weighing over 5 years in a cohort of Withings Smart Scale users.

Data source

A de‐identified commercial dataset was obtained at no cost by contacting (via email found on the company's website) the Withings company.

Design and Methods

This is a retrospective cohort study. All participants over age 18 and with BMIs above 15 using the scale worldwide between April 2009 and December 2015 were included. We performed descriptive analysis to explore weight trends. Multivariate logistic regression models were created to assess association of weight maintenance or loss to self‐weighing.

Results

A total of 91,814 participants were included in the analysis. Baseline BMI was 27.91±4.95 for males and 24.18±4.95 for females. 66.7% lost or maintained their weight while they were using the scale (median 1,717; interquartile range = 334). Overall weight change was ‐ 0.09±7.62kg of baseline body weight; mean weights per week was 1.75 ± 1.44. Making a desired weight loss goal was the most important factor for successful weight loss or maintenance (OR = 1.72; 95% CI = 1.66–1.77, p <0.001), followed by frequent weighing (≥ weekly) (OR = 1.11; 95% CI = 1.08–1.14; p <0.001).

Conclusion

In this cohort of adults using a commercially available smart scale, making a weight loss target and frequent self‐weighing are significantly associated with weight loss and/or maintenance. This study is just one example of many of the clinical utility that objective weight data from a large commercial data set may offer.

Support or Funding Information

Dr Wilkinson is supported by Grant Number T32DK062710 from the National Institute of Diabetes and Digestive and Kidney Diseases.
Pasta Consumption in American Children and Adolescents is Associated with Greater Daily Intake of Shortfall Nutrients as Defined by the 2015–2020 Dietary Guidelines, Improved Diet Quality and Lower Added Sugar Intake
Authors: Papanikolaou Yanni
Published: November 2023

Pasta remains a popular food choice with American children and adolescents, but limited data is available on the nutritional relevance of pasta consumption. The purpose of this study was to examine associations between pasta consumption, shortfall nutrient intakes as defined by the 2015–2020 Dietary Guidelines for Americans (2015–2020 DG), and diet quality in comparison to non‐pasta consumption in US children and adolescents 2–18 years‐old; N=323). A secondary analyses was completed using datasets from What We Eat in America, the dietary component of the National Health and Nutrition Examination Survey, 2001–2012. Diet quality was measured using USDA's Healthy Eating Index‐2010. Pasta consumption was defined as all dry domestic and imported pasta/noodle varieties made with only wheat and no egg. No significant differences were seen in energy intake when comparing adult pasta consumers vs. non‐consumers (2029±52 vs. 1985±9 kcal/d). When considering 2015–2020 DG shortfall nutrients, pasta consumption was significantly associated with increased intake of dietary fiber (16±0.6 vs. 13±0.1 g/d, p<0.0001), folate, DFE (701±30 vs. 528±5 μg/d, p<0.0001), iron (15.8±0.5 vs. 14.4±0.1 mg/d, p=0.01), magnesium (249±7 vs. 231±1 mg/d, p=0.006), and vitamin E as α‐tocopherol (7.1±0.4 vs. 6.0±0.1 mg/d, p=0.012), in comparison to non‐pasta consumption. No significant associations were seen for vitamins A and D, calcium, and potassium intake. Of nutrients to limit, adults consuming pasta had significantly lower saturated fat (23±1 vs. 26±0.2 g/d, p=0.007) and total fat (66±2.4 vs. 73±0.5 g/d, p=0.009) intake, while no differences were observed for sodium, total and added sugar intake compared to non‐pasta consumption. Pasta consumers had a significantly better diet quality compared to non‐pasta consumers (48.6±1.0 vs. 45.5±0.2, p=0.0021). No significant associations were seen with body weight, waist circumference and body mass index. Pasta consumption in children and adolescents was associated with a better diet quality as measured by USDA's Healthy Eating Index‐2010, improved 2015 DG shortfall nutrient intakes and lower intake of nutrients to limit (saturated and total fat), relative to non‐pasta consumption.

Support or Funding Information

This study was supported by the National Pasta Association.
Blood lead, iron deficiency and attentional ADHD symptoms in Uruguayan first‐graders
Authors: Barg Gabriel , Queirolo Elena I , Mañay Nelly , Peregalli Fabiana , Kordas Katarzyna
Published: November 2023

The combined effect of iron deficiency and lead exposure on attentional ADHD symptoms is not well studied. We investigated the associations among blood lead level (BLL), iron deficiency (ID, serum ferritin <15 μg/L) and inattention/cognitive problems (I/CP‐measured by the Conners Teacher Rating Scale) in a cross‐sectional study of first‐grade children (n=257, age 6.7±0.5 years, 55.6% boys) from Montevideo, Uruguay. Aspects of children's attention (ex., attention shifting) were measured by teacher reports on the BRIEF questionnaire. Generalized linear models (GLM) accounting for the school‐based cluster design and adjusting for maternal education and employment, parental smoking, household crowding and SES, as well as child's general intelligence and attention problems were used to model the association of BLL and ID with I/CP scores. Mean of BLL was 4.19±2.2 μg/dL, 39% of children had ID and 25% had mild to severe inattention problems (I/CP > 60 T score). BLL and serum ferritin were not independently associated with I/CP. However, in children with ID, BLL was associated with more problematic I/CP scores (0.32±0.14, p=0.026). This was not observed among non‐ID children (0.09 ±0.08, p=0.239). General intelligence and maternal education were protective factors against I/CP (both at p<0.000). The ability to shift attention, commonly beneficial for cognitive performance, was negatively associated with I/CP in children with ID, presumably by ID's negative effect on the ability to control the attentional focus. In sum, our early findings suggest an adverse effect of the combination of ID and higher BLLs on sustained attention, a key competence for learning and socialization.

Support or Funding Information

NIEHS R21ES16523, R21ES019949
NUTRITIONAL STATUS OF BRAZILIAN CHILDREN FROM ACRE AND RIO GRANDE DO SUL STATES ASSISTED BY “BOLSA FAMÍLIA” PROGRAM.
Authors: BORTOLINI MIGUEL JUNIOR SORDI , Freitas Anderson Gonçalves , de Lima Diego Gonçalves , Silva Carolina Freitas , Bortolini Cristiane Soares Ferreira , de Abreu Luiz Carlos , de Oliveira Meneguetti Dionatas Ulises , Silva Romeu Paulo Martins
Published: November 2023

Objective

To compare the nutritional status of children from two Brazilian states assisted by “Bolsa Família” program using SISVAN WEB.

Methods

Descriptive and retrospective epidemiological study were conducted using a secondary database evaluating the nutritional status of children aged five to ten years old receiving economical support by the “Bolsa Familia” Program (PBF) from 2011 to 2015 in Acre (AC) and Rio Grande do Sul (RS) states of Brazil. The data from AC (94.865 children) and RS (342.462 children) states were collected from an open database platform, SISVAN WEB platform. Anthropometric index of body mass index‐age (BMI/age) were used to data classification.

Results

By analyzing the period from 2011 to 2015, it was found that the average prevalence of eutrophic children aged five to ten years old were respectively 70.42% and 61.28% in AC and RS states; Acre's overweight (Ow) children archived 13.06% (AC) and 19.48% (RS) and the prevalence was of obesity (Ob) was 5.08% (AC) and 9.36% (RS); Severe obesity (SO) was 4.02% (AC) and 6.92% (RS).

Conclusions

Overweight and obesity in Brazilian children assisted by PBF has grown in the past five years in both states. Notably RS state had greater amount of Ow, Ob and SO compared to AC one. We hypnotized that it could occurred because the nutritional transition from RS is already more advanced than AC state. Future studies should be applied to research this matter.

Support or Funding Information

FUNDAÇÃO DE AMPARO A PESQUISA DO ESTADO DO ACRE (FAPAC)
Maternal Weight Over Successive Pregnancies and Breastfeeding Initiation, Duration and Exclusivity
Authors: Metallinos‐Katsaras Elizabeth , Siu Elizabeth Colavito , Colchamiro Rachel
Published: November 2023

Maternal overweight and obesity have been shown to adversely affect breastfeeding success. This study aims to examine the relationship between maternal weight status over the course of 2 successive pregnancies and breastfeeding initiation, duration and exclusivity among a low income diverse sample. Mothers enrolled in Massachusetts WIC (2001–2009) with two consecutive (linked) pregnancies were included. Only those with singleton, full term, live, adequate‐birth‐weight infants and with complete breastfeeding (2nd birth) and covariate (n=10,157)) data were included. Maternal weight status was examined using the following variables: change in weight classification between pregnancies 1–2 using pre‐pregnancy weight (none, decrease, increase), 2nd pre‐pregnancy weight status (underweight, normal weight, overweight, obese) and gestational weight gain (IOM 2009 recommendations) during the second pregnancy. Breastfeeding outcomes were initiation, duration and whether or not infants were exclusively breastfed for at least 4 weeks. Covariates included the following: race/Hispanic ethnicity, maternal age and education, first pregnancy breastfeeding initiation/duration, timing of WIC entry, smoking post‐partum. Multivariate Logistic Regression was used to examine associations with breastfeeding initiation, and exclusivity, while General Linear Model Regression was used to examine breastfeeding duration. The sample was diverse (52.4% nonwhite) with a mean age of 24.5 years (SD=5.0). At the start of their second pregnancy, 50.7% of women were overweight or obese; 28.1% of women shifted to a higher weight status classification between their 1st and 2nd pregnancies, while 5.0% shifted to a lower weight class. After the second pregnancy, 58.6% initiated breastfeeding; mean breastfeeding duration was 9.0 weeks among initiators (SD=15.9). Weight gain during pregnancy was not associated with any of the breastfeeding outcomes, however, 2nd pregnancy's pre‐pregnancy weight status, and change in weight class category were. Women who were obese prior to their second pregnancy were 24% less likely to initiate breastfeeding (AOR(95%CI))=0.76 (0.67–0.87) than those normal weight. Those whose weight class declined between pregnancies were 30% more likely to initiate breastfeeding (AOR=1.30 95% CI=1.03–1.64) than those whose weight status stayed the same. Mothers who were obese, breastfed for a shorter duration (p<.05) than those who were overweight (12.2 vs. 13.9 weeks), or normal weight (13.2 weeks). Obese mothers were less likely to exclusively breastfeed for at least four weeks compared to normal weight mothers (AOR=0.57, p < .05). No associations were found with other weight status categories. Both weight status prior to pregnancy and changes over subsequent pregnancies appear to be associated with breastfeeding success in a low income diverse population.

Support or Funding Information

No support.
Maternal Low‐Protein Diet During Gestation Gender‐Selectively Induces Amino Acid Response Pathway and Autophagy in the Liver of Offspring Rats
Authors: Cai Mingzhu , Wang Huan , Pan Yuan‐Xiang
Published: November 2023

Maternal protein deficiency during pregnancy is associated with metabolic responses, including the activation of amino acid response (AAR) pathway. Amino acid starvation induces the AAR pathway through eIF2α phosphorylation and induction of ATF4 expression, which potentially play a crucial role in autophagy related gene expression program. The present study investigates the impact of maternal protein deficiency on the AAR pathway and autophagy in offspring. In this study, pregnant Sprague‐Dawley rats were fed either a control diet (GC group, 18% energy from protein) or a low‐protein diet (GLP group, 8.5% energy from protein) during gestation period followed by the control diet during lactation. Offspring consumed the same control diet post‐weaning from postnatal day 21. Liver tissue was collected at postnatal day 38 from the offspring. mRNA expression of AAR pathway‐ and autophagy‐ related genes was analyzed in the liver tissue from both male and female offspring. The maternal low‐protein diet significantly induced mRNA expression of the AAR pathway related genes including Asns, Atf3, Chop and Snat2 in liver tissue of female offspring, but not in male offspring. Moreover, gene expression of autophagy related genes including LC3a, Binp3 and Atg4b was increased significantly only in the female offspring by gestational low‐protein diet. The interactions between the two critical stress‐response pathways were further investigated to illustrate the differences in responding to maternal dietary restriction between the male and female offspring. Overall, our data demonstrated that maternal protein deficiency during gestation differentially programs AAR pathway and autophagy in the liver of male and female offspring rats.
Milk Production in Mothers with and without Signs of Insulin Resistance
Authors: Nommsen‐Rivers Laurie Ann , Riddle Sarah Ann , Thompson Amy , Ward Laura , Wagner Erin
Published: November 2023

Maternal obesity is associated with shortened breastfeeding duration. Insulin resistance is a physiologic hallmark of obesity and may underlie lactation difficulties in obese and other insulin resistant mothers. Our objective is to compare 24‐hour milk production in mothers with signs of insulin resistance (IR) versus those without. We examined baseline data from the MALMS study, a randomized placebo‐controlled trial of metformin to augment low milk supply. Baseline eligibility includes: mother 1–8 weeks postpartum, healthy term infant that is currently requiring formula supplement to achieve sufficient growth, but mother has strong desire to improve breast milk production. Mothers fitting this description were referred to the study by area health care providers. At baseline, all women complete a weighed record of milk production over 24 hours and undergo evaluation for trial eligibility, including the following signs of IR: fasting plasma glucose ≥ 95 mg/dL, abdominal obesity, recent gestational diabetes, or polycystic ovary syndrome. We compared relative ranking of baseline 24‐hour milk production in IR versus no IR groups, and then in obese versus non‐obese groups, with the Wilcoxon test. Of 48 women who completed baseline measurements, 33 (69%) exhibited signs of IR. Mean age (±SD) of mother (31±5 years) and infant (4±2 weeks) did not differ between groups, but BMI was significantly higher in the IR group (36.9z±7.9 versus 25.4±3.6 kg/m2, P<0.001). Relative ranking of milk production was significantly lower in IR versus no‐IR: Median [interquartile range], 216[158–332] versus 377[294–598], P=0.004. Differences were less pronounced when milk output rankings were compared for obese versus non‐obese, P=0.05. While suboptimal lactation management may have contributed to low production at Baseline in some participants, our results point to an additional deficit associated with IR.

Support or Funding Information

NIH 5 K12 HD051953 (PI, Tsevat, University of Cincinnati), Bridging Interdisciplinary Research Careers in Women's Health (BIRCWH award to LN‐R)
A Meatless Monday Evaluation and Best Practices Guide for Reducing Meat Consumption in Food Service Institutions: A Qualitative Study
Authors: Chan Mandy , Ramsing Rebecca
Published: November 2023

Meatless Monday began in 2003 as an effort to reduce meat consumption, aiming to improve the sustainability of our food system and benefit human health. Until recently, there has been little evaluation of the program and a lack of consensus regarding implementation best practices. The Center for Livable Future and Bon Appétit Management Company (BAMCO) partnered to evaluate Meatless Monday implementation and create a Meatless Monday Best Practices Guide. We conducted qualitative interviews with 16 participants from 12 BAMCO sites (primarily college/university settings) across the United States. Participants included general managers, marketing managers, sustainability staff, and executive and sous chefs. We utilized HyperRESEARCH to code and analyze common themes. Promising practices included increasing choice, not completely eliminating meat, and investing more time and creativity into preparing plant‐based foods. Food service staff were more likely to contribute to the success of programs if they created and actively promoted flavorful, appealing plant‐based dishes. A challenge included pushback from students (particularly athletes) and leadership staff when sites initially eliminated meat completely. Sites responded to pushback by incorporating student feedback, including increasing choice and eliminating meat only at one station within a dining facility. Additionally, there was a need for education regarding Meatless Monday's messaging and protein content in plant‐based foods. A majority of sites collaborated with student groups that were often involved in promoting the campaigns. Students were more receptive to a campaign if they saw colleagues represent the cause. Overall, sites that were adaptive to challenges and consistent in their implementation were most successful. We observed a growth in adopting meat reduction strategies in efforts to improve human health and the sustainability of our food system. This qualitative research adds context to previous quantitative research, provides a narrative of strategies that can be tailored to different food service institutions, and promotes individual and institutional change in meat consumption.
Mitigating climate change with a carbon tax on foods: What are the ethical implications?
Authors: Downs Shauna , Fox Elizabeth L , Fanzo Jessica
Published: November 2023

The global production of food is responsible for approximately 30% of all greenhouse gas emissions, a significant portion of which can be attributed to red meat. As the global population and growth in per capita income increases, the demand for red meat will continue to rise putting further pressure on the planet. Numerous recent studies have explored the environmental and health impacts of different diets and have identified red meat (and beef in particular) as one of the key contributors to greenhouse gas emissions and adverse health outcomes. Shifting dietary patterns to reduce red meat intakes could help reduce greenhouse gas emission and improve health outcomes. In exploring strategies to mitigate such environmental and health impacts for current and future generations, a number of policy recommendations have been proposed. One popular proposal is carbon taxation of foods that capture the actual environmental cost of producing and consuming such foods. In Denmark, a carbon tax on red meat was recently proposed to help curb emissions and reduce population intakes. However, such recommendations are wrought with ethical dilemmas. Using an ethics framework for public health developed by Kass (2001), we critically analyzed the proposal of carbon taxation for its public health and environmental goals, potential burdens and minimization of burdens, fairness of distribution, and implications for individuals' autonomy. We determine that the distribution of burden resulting from such policies is inequitable and regressive, having negative tradeoffs for low‐income stakeholders and individuals from low‐income countries. We also determine that the potential burden and autonomy of future generations is not evenly distributed. Current policy proposals aimed at enhancing the sustainability of our diets often result in unethical tradeoffs. Policymakers and key stakeholders should consider the ethical dimensions of interventions and policies promoting sustainable diets, and should consider who bears the weight of such policy decisions before enacting them.

Support or Funding Information

This project does not have funding.
Analyzing Short Term Protein Oxidation Provides Evidence about Its Role in Whole Body Protein Metabolism
Authors: Reckman Gerlof , Priebe Marion , Koehorst Martijn , Boer Theo , Vonk Roel J
Published: November 2023

INTRODUCTION

Protein intake has been suggested to play an important role in development of obesity; on one hand in newborn, where excess protein intake might stimulate development of obesity in later life (Kirchberg et al. 2014). On the other hand, protein consumption is promoted for weight management (Martens et al. 2014). At present, no formal recommendations for the upper limit of protein intake have been presented. Information about rate‐limiting steps in protein catabolism is scarce. We therefore studied the role of protein oxidation in this process.

OBJECTIVES

To monitor protein oxidation we have developed a non‐invasive natural enriched 13C‐protein breath test using naturally enriched 13C‐milk protein (fractions). We used this technique to analyze the kinetics of protein oxidation and its interfering factors.

METHOD/DESIGN

The breath test was preceded by an overnight fast. After consuming the substrate, dissolved in 500 ml water, breath samples were collected up to 330 minutes and analyzed by Isotope Ratio Mass Spectrometry for the 13CO2:12CO2 ratio.

RESULTS

Whey was oxidized for 28.6% ± 6.8% (mean ± SD) after 240 minutes, compared to 22.9% ± 6.2% for glucose in the same period. Postprandial oxidation kinetics of glucose and whey started to diverge after 70 min after which whey was being oxidized faster than glucose.

Different doses of milk protein (10, 30, 50, 60, 70 g) were oxidized for 15.3, 24.2, 22.3, 21.5 and 14.5% respectively. Maximal milk protein oxidation was measured during the 60 g dose at a rate of 0.062 g/min, leading to a maximal oxidation capacity of 1.3 g/kg bodyweight/day.

Combining protein (30 g 13C‐whey) with carbohydrates (30 g non‐labeled glucose) resulted in two‐fold increase in oxidation of 13C‐whey compared to oxidation of 13C‐whey alone. A three‐fold increase in oxidation of 13C‐glucose was measured when non‐labeled whey was added compared to oxidation of 13C‐glucose alone.

CONCLUSIONS

Whey is oxidized faster than glucose from 70 min onwards, which seem to suggest that stomach emptying was not the cause of the difference in oxidation. The interaction of whey and glucose suggest that the oxidation of whey is not driven by energy demand. The stimulating effect of glucose might hint to the involvement of insulin. Oxidation of whey protein is quantitatively of high importance and not down regulated by concomitant administration of other substrates. Analyzing biological variations in acute protein oxidation in defining the upper limit of intake, seem to be relevant.

Support or Funding Information

The 13C‐milk substrates were provided by Hanze Nutrition BV.
Lack of Arginase II Spares Arginine and Restores Growth in Mice
Authors: Marini Juan C. , Mohammad Mahmoud A. , Didelija Inka C.
Published: November 2023

Arginine (Arg) is an essential amino acid for growth in C57BL/6 (BL6) mice, but not for Swiss mice. BL6 mice fed an Arg free diet after weaning fail to achieve maximal growth rate due to limited endogenous de novo Arg synthesis. In contrast, Swiss mice have a greater synthesis of citrulline and Arg and thus do not require dietary Arg. Alternatively, reducing Arg disposal has the potential to increase Arg availability and increase growth rate. To test this hypothesis, mice lacking arginase II were studied during the post‐weaning period. Arginase II ko (ARGII, n= 20) and wild type (WT, n= 20) male littermates were weaned at 21 d of age. After a 3 d adaptation period to a powder standard diet, mice were fed either an Arg‐free or Arg sufficient diet (8 g Arg/kg diet) for 3 weeks. Mice were weighed twice a week to monitor growth. The data generated was analyzed using a logistic model for growth (A‐B*exp(‐k*time), where A is the mature weight, (A‐B) is the initial weight and k is the growth constant). At the end of the feeding trial, [13CD4] citrulline and [15N2] arginine were infused in fasted mice to determine the flux of Arg and de novo Arg synthesis rate. ARGII mice were slightly heavier than their WT littermates (A‐B= 15.5 vs 14.2 g, respectively) at the beginning of the feeding trial on d 24, but without reaching significance (P = 0.15). No genotype or dietary Arg intake effect was detected for the asymptotic mature weight of these mice (A= 25.9±1 g). Both ARGII mice and mice fed the Arg sufficient diet grew faster (k; P < 0.001) than WT mice and mice fed the Arg free diet, respectively. At the end of the trial ARGII mice fed the Arg free diet achieved a similar body weight than WT mice fed the Arg sufficient diet (21.3 vs 21.8 g, respectively; P = 0.94). ARGII mice had greater plasma Arg concentration (100 vs 79 μmol/L; P < 0.001) and fluxes (460 vs 390 μmol•kg−1•h−1; P < 0.001) than WT mice; there was no dietary treatment effect for these parameters (P > 0.6). Citrulline production was greater in WT mice (95 vs 86 μmol•kg−1•h−1; P < 0.01) and in mice fed the Arg‐free diet (98 vs 84 μmol•kg−1•h−1; P < 0.001). However, this did not translate in a higher de novo Arg synthesis rate (78 μmol•kg−1•h−1; P >0.05). In conclusion, ARGII mice have greater Arg availability (Arg flux and plasma concentration) than their WT counterparts. This higher Arg availability allows ARGII mice to grow in an Arg‐free diet and achieve a growth rate similar to WT mice fed an Arg sufficient diet. This work shows that reducing the disposal rate of Arg through limiting arginase activity abolishes the dietary requirement for Arg for growth in BL mice.

Support or Funding Information

NIH R01 GM108940
Lipidomic profiling of erythocytes in septic patients revels novel biomarkers
Authors: Mecatti Giovana Colozza , Messias Marcia Cristina Fernandes , Angolini Célio Fernando Figueiredo , de Oliveira Carvalho Patricia
Published: November 2023

Sepsis is common and often deadly. It remains the primary cause of death from infection, despite modern medicine. The identification of reliable diagnostic biomarkers for the early detection of this disease is critical and may reduce the mortality rate as it could allow early treatments. The present study deals with the plasma and red cells blood lipidome profiling of patients diagnosed with sepsis and septic shock and aimed to find possible sepsis biomarkers using GC and ESI‐MS (q‐ToF). The data was treated with multivariate data analysis, including principal component analysis (PCA) and (orthogonal) partial least squared discriminant analysis ((O)PLS‐DA). Potential biomarkers including lysophosphatidylcholines (lyso‐PCs) and sphingomyelin (SMs) with specific fatty acid chains were identified. Lyso‐PCs and SMs were down‐regulated whereas saturated and unsaturated phosphatidylcholine (PCs) were up‐regulated in the plasma and erythrocytes of septic patients, which is evidence for deregulated activity of phospholipases. An increase of oleic acid (C18:1 n‐9) accompanied by a decrease in the unsaturation index as well as in the abundances of n‐3 polyunsaturated fatty acids (n‐3 PUFA) was observed in erythrocytes phospholipids patients as compared with healthy controls. This study thus provides new insights into underlying sepsis lipids pathophysiology which may serve clinical diagnosis

Support or Funding Information

FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo)
Heparanase contributes to idiopathic pulmonary fibrosis via regulation of A20/TNFAIP3 expression
Authors: Yang Yimu , Lara Abigail , Rutebemberwa Alleluiah , Schmidt Eric
Published: November 2023

We have previously demonstrated that heparanase, a mammalian endoglycosidase that cleaves the extracellular glycosaminoglycan heparan sulfate (HS), is activated during acute lung inflammation, contributing to the acute respiratory distress syndrome. The impact of heparanase on chronic lung injury (such as idiopathic pulmonary fibrosis, IPF) is uncertain. We found increased heparanase expression within the lungs of patients with severe IPF, co‐localized with clusters of pathologically‐activated myofibroblasts. Similar heparanase induction was noted in a bleomycin mouse model of pulmonary fibrosis. Proliferation of myofibroblasts during Idiopathic Pulmonary Fibrosis (IPF) has been attributed to increased resistance to apoptosis. To determine effect of heparanase on apoptosis, normal human lung fibroblasts (HLF) were treated with heparanase, TGFβ1 (a pro‐fibrotic mediator), CXCL10 (anti‐fibrotic chemokine) or combinations thereof for 48 hours. We measured gene expression of A20/TNFAIP3, an anti‐apoptotic protein which protects cells from TNF‐induced cell death. A20/TNFAIP3 expression was increased in heparanase‐treated human lung fibroblasts. Heparanase‐induced A20/TNFAIP3 expression was augmented by CXCL10, and abolished by TGFb1. Pharmacological inhibition of heparanase activity did not change A20/TNFAIP3 expression, suggesting that heparanase may regulate A20/TNFAIP3 expression via non‐enzymatic effects. Taken together, these findings suggest that heparanase induction may promote fibroblast survival and pathological collagen deposition in IPF.

Support or Funding Information

R01 HL125371
Effect of Losartan on 2 Types of Macrophages in a Chronic Rat Model of Fat Embolism
Authors: Arif D. , Khalafi F. , Siddiqi A. , Philips S. , Said A. , Ponnapureddy R. , Tappeta K. , Poisner A. , Hamidpour S. , Molteni A.
Published: November 2023

Introduction

In a rat model of pulmonary fat embolism (FE) using triolein (T), we showed that the long term histopathological effects of T‐induced FE extend to 10 weeks, are inhibited by losartan (LOS), an angiotensin II type one receptor blocker, and augmented by a second hit with LPS (1,2). We also observed that mast cell (MC) numbers increased in T‐treated rats vs. saline controls and even more when LPS was added to T. This MC increase was blocked by losartan treatment. LOS or LPS alone did not increase the MC number (3). In view of mast cells' interaction with macrophages in the inflammatory process leading to fibrosis, we extended our study to the identification of macrophages in the same organ.

Methods

Thirty‐six Sprague Dawley rats were treated with T (0.2 ml i.v.) or saline. After 6 weeks, half of the groups were given saline or LPS 0.1 mL (3 mg/kg) i.p. followed one hour later with saline or LOS (10 mg/kg i.p.), and then by LOS in the drinking water (50 mg/L). 4 weeks later (10 weeks after T), the rats were necropsied after isoflurane anesthesia. Lungs were fixed in 10% formalin and stained with H&E for morphometric scoring, Masson Trichrome for fibrosis and CD68 for macrophage counts. Two pathologists unaware of the slides' identity took 10 photographs at random in each slide at 400× and counted the macrophage number.

Results

As reported previously, T injection induced severe fibrosis, even more marked by LPS addition. LOS reduced the damage (4). Two types of macrophages were observed: one with compact cytoplasm and with similar size of mast cells, the second one with a larger vacuolated cytoplasm. Contrarily to what was observed for mast cells (3) no increase was seen for the small macrophages nor LOS reduced their number. Large vacuolated macrophages however were markedly increased vs controls in T + saline and LPS + saline groups (p<0.05 and p<0.01). LOS reduced the number in all groups with exception of the LPS + LOS. Contrarily to the increase seen both with T + saline and LPS + saline and the losartan effect, the group receiving both T + LPS in saline treatment did not show any increase. The findings suggest the existence of different cellular responses to the inflammatory and fibrotic stimuli given to the animals.

Support or Funding Information

Catherine T. Geldmacher Foundation St. Louis, MO
The Assessment of Clinically Relevant Extracellular Matrix Markers in a Bleomycin‐Induced Mouse Model of Lung Fibrosis
Authors: Young Alan , Nath Puneeta , Leeming Diana , Karsdal Morten , Brockbank Sarah , Rider David , Cruwys Simon
Published: November 2023

The bleomycin‐induced lung fibrosis model is routinely used to investigate efficacy of potential therapies for treating idiopathic pulmonary fibrosis (IPF). The aim here was to characterize a bleomycin model over an extended time course and correlate inflammation, lung function changes, collagen deposition and pathology with systemic markers reflecting extracellular matrix (ECM) metabolism assessed by MMP derived collagen fragments (C1M, C3M); markers associated with the diagnosis and prognosis of human idiopathic pulmonary fibrosis (IPF) (Jenkins et al, Lancet Respir Med 2015).

Methods

C57BL/6J mice were anaesthetized and dosed with bleomycin (BLM) intratracheally (0.03 units/mouse). Control animals received saline. Animals were observed daily and bodyweight measured from D3. Lung function was assessed on days −1, 3, 7, 14, 21, 28, 35, 42 and 56. Animals were sacrificed on days 3, 7, 14, 21, 28, 35, 42, and 56 and serum samples taken. Markers of the formation and degradation of collagen type I (C1M) and collagen type III (C3M) were measured. Lungs from separate cohorts were lavaged for mediator and inflammatory cell analysis, then perfused and snap‐frozen for determination of hydroxyproline and protein levels. Another cohort had their lungs inflated with phosphate buffered formalin and used for histopathological analysis (including Modified Ashcroft score) and subsequent image analysis.

Results

BLM elicited a decrease in bodyweight, peaking on D7. BLM induced lung inflammation within the BALF with increases in neutrophils (peaking at D7, +135% p<0.05), lymphocytes (peaking at D14, +5240% p<0.0001) and macrophages (peaking at D21, +134%, p<0.05). Lung wet weight also increased following BLM‐administration, peaking on D14 (+44%, p<0.0001). There were observable BLM‐induced changes in lung function (peaking at D7), which were fully resolved by D21. Levels of hydroxyproline were elevated from D21 onwards (+63%, p<0.05). Pathology also increased over this time period, with a clear inflammatory response being seen at D7 and D14 and fibrotic lesions increasing in severity and prevalence from D21. The ECM degradation biomarker C1M was elevated in serum on D7 and 14 (+32%, p<0.01), with C3M increasing on D7,14 and 21 (+15–25%, all p< 0.05). These biomarkers were not observed in other models of inflammation (e.g., LPS‐induced lung inflammation).

These data suggest that in this BLM‐induced lung fibrosis model, there is an early inflammatory phase, followed by a generation of fibrosis and collagen deposition. Clinically relevant biomarkers associated with diagnosis and progression of IPF can be measured in this model and may improve the predictability and translatability of such models when considering assessment of novel mechanisms and compounds

Support or Funding Information

Charles River, Nordic Biosciences and Grunenthal
Influenza A infection decrease the population of tissue resident alveolar macrophages
Authors: Gonzalez‐Gonzalez Francisco , McQuattie‐Pimentel Alexandra , Soberanes Saul , Casalino‐Matsuda Marina , Chi Monica , Piseaux Raul , Sporn Peter , Budinger Scott
Published: November 2023

Rationale

Influenza A pneumonia is the most common cause of death from an infectious agent and can become an important contributor to overall mortality during pandemics. Severe influenza A pneumonia results in the development of the acute respiratory distress syndrome, which is the proximal cause of death in most of these patients. It is now recognized that alveolar macrophages represent a heterogeneous population of cells. Tissue resident alveolar macrophages are long lived, self‐renewing cells with developmental origins outside of the bone marrow. During infection, monocytes are recruited to the lung where they differentiate into alveolar macrophages. The role and fate of these different macrophage populations during the course of influenza A pneumonia is not known.

Hypothesis

Influenza A infection results in the replacement of tissue resident alveolar macrophages with monocyte derived cells that persist after injury.

Methods

We infected ten to twelve week old C57Bl/6 mice intratracheally with lethal and sublethal doses of influenza A/WSN/33. We analyzed inflammatory cell populations in lung digests at different time points after the influenza A infection using multi‐color flow cytometry. We developed a shielded bone marrow chimera system to unambiguously identify tissue resident and alveolar macrophage populations during the development and resolution of influenza A infection.

Results

In the early stages of influenza A infection, tissue‐resident alveolar macrophages could be readily distinguished from monocyte‐derived cells using flow cytometry. Tissue‐resident alveolar macrophages were rapidly depleted during influenza A infection accompanied by an influx of monocyte derived cells into the lung. Using bone marrow chimeric mice generated with lung protection followed by myeloablation, we observed that monocyte derived cells persisted in the lung after the resolution of infection for as long as 10 months but could no longer be distinguished from tissue resident cells on the basis of flow cytometry.

Conclusions

Influenza A infection results in the dose‐dependent depletion of tissue resident alveolar macrophages in the lung. Whether this results from direct infection by the influenza A virus or secondary effects related to lung tissue destruction and inflammation is not clear. Monocytes recruited to the lung during influenza A infection differentiate into alveolar macrophages in the local microenvironment of the lung and persist long after the resolution of infection. Our results suggest that severe influenza infection results in permanent changes in tissue resident alveolar macrophage ontogeny.