bluuebunny/crossref_metadata_2025 huggingface dataset:
Carbon metabolism of parasitic protozoa: strategies for surviving in intracellular niches
Authors: McConville Malcolm , Saunders Eleanor , Sernee Fleur , Blume Martin , Kloehn Joachim , Ralton Julie
Published: November 2023

Many parasitic protozoa, including Plasmodium spp, Toxoplasma gondii and Leishmania spp, proliferate within intracellular niches in their mammalian hosts. Despite many decades of research, we still have an incomplete understanding of the physiological state and metabolism of these intracellular stages and their capacity to adapt to different growth conditions during infection. This information is crucial for understanding the molecular basis of host‐parasite interactions, parasite responses to drugs, and for developing new anti‐parasitic therapies. While genome‐wide reconstructions have defined many aspects of parasite metabolism, more than half of the protein‐encoding genes have unknown function or have inferred functions from other highly divergent eukaryotic organisms. In order to experimentally validate the operation of predicted pathways, as well as to identify new/unanticipated metabolic pathways in these organisms, we have combined comprehensive metabolomic profiling approaches with 13C‐ and 2H‐stable isotope labeling approaches and imaging mass spectrometry. These studies have highlighted aspects of central carbon metabolism in intracellular parasite stages that have diverged from comparable pathways in the mammalian host. In particular we have identified a number of regulatory mechanisms that involve energy‐wasting futile cycles that appear to be critical for parasite growth and survival. These studies suggest that parasite central carbon metabolism may harbor a number of potential new drug targets.

Support or Funding Information

This work was supported by the Australian National Health and Medical Research Council
Dissecting the role of the Rad51 paralogs during double‐strand break repair
Authors: Bernstein Kara , McClendon Tiffany B , Sullivan Meghan R , Godin Stephen K , Gaines William , Sung Patrick , Yanowitz Judith
Published: November 2023

Double‐strand breaks (DSBs) are one of the most cytotoxic forms of DNA damage. Defects in DSB repair are associated with cancer predisposition, as well as, several heritable diseases including Fanconi anemia. Our work has centered around Rad51 paralog function during DSB repair. Importantly, mutations in the human Rad51 paralogs are found in tumors and also lead to Fanconi anemia. Due to the embryonic lethality of the mouse knockout models and the low abundance and insolubility of the human proteins, there is very limited understanding as to how the Rad51 paralogs function to maintain genomic integrity. To circumvent these obstacles, we are studying the role of a unique Rad51 paralog‐containing complex, called the Shu complex, in the budding yeast S. cerevisiae and the nematode C. elegans. Although the Shu complex was discovered 10 years ago and is critical for DSB repair, its molecular function has remained elusive. We discovered that the yeast Shu complex is highly conserved from archaea through humans. Furthermore, we have identified direct physical interacting partners of the yeast and worm Shu complex and to show that these interactions are necessary and sufficient for the biological efficacy of the Shu complex during DSB repair. We define a molecular role for the yeast and worm Shu complexes in Rad51 presynaptic filament assembly, and thus for the first time gained insight into its mechanistic function. Our work has important implications for how the Rad51 paralogs and the human Shu complex function to prevent tumorigenesis and Fanconi anemia.

Support or Funding Information

This work was supported by the National Institutes of Health (GM088413 and ES024872) to K.A.B.
Observations on the Cellular Dynamics of a Metabolic Complex, the Purinosome
Authors: Benkovic Stephen , Chan Chung Yu (Keith) , Kim Doory , Pedley Anthony , Zhuang Xiaowei
Published: November 2023

For several decades sequential metabolic enzymes had long been hypothesized to form multi‐enzyme complexes in cells to regulate metabolic flux. Single molecular fluorescence imaging in live cells of the six human enzymes involved in de novo purine biosynthesis uncovered the reversible formation of a metabolic multi‐enzyme complex, the “purinosome”. Purinosome formation was found to be sensitive to changes in purine demands and assisted by molecular chaperones. In cells lacking purine salvage enzymes, purinosome levels were enhanced. Despite the transient nature of this complex, the flux through the de novo pathway was increased in cells containing a high density of purinosomes, which is consistent with its function. Imaging experiments revealed the proximity of these complexes near mitochondria and along microtubules. The question then is to what extent are there relationships between these subcellular structures and the purinosome? I will discuss imaging analyses that explain the cellular dynamics of the purinosome near these structures in hopes to further understand how a cell responds to purine demand to fulfill its metabolic requirements.

Support or Funding Information

National Institutes of Health, #GM024129
Sphingosine‐1‐Phosphate: A Bridge From Bench To Clinic
Authors: Spiegel Sarah
Published: November 2023

There is growing evidence that sphingosine‐1‐phosphate (S1P), a bioactive sphingolipid signaling molecule formed inside cells by sphingosine kinases (SphK1 and SphK2), regulates many physiological processes involved in obesity, inflammation and breast cancer. Patients with breast cancer have elevated levels of SphK1 that correlate with poor prognosis. Although most of the actions of S1P are mediated via specific receptors (S1PR1‐5), we have shown that nuclear S1P formed by SphK2 is an endogenous inhibitor of histone deacetylases (HDACs). Obesity, that is now endemic, increases breast cancer risk and is associated with worse prognosis, which may be due in part to chronic inflammation induced by obesity, the high frequency of triple negative breast cancer (TNBC), and ineffective hormonal therapy. This lecture will be highlight the role of the SphK/S1P/S1PR axis in obesity promoted breast cancer progression, and explain its involvement in a feed‐forward amplification loop leading to activation of the master transcription factors NF‐kB and STAT3. Focus will also be on a new mechanism of action in cancer of the pro‐drug FTY720/fingolimod that is approved for treatment of multiple sclerosis. The sphingosine analogue FYY720 is phosphorylated in the nucleus by SphK2 to the active form FTY720‐P that like S1P binds and inhibits class I HDACs. Finally, new therapeutic approaches that target the S1P axis for treatment of hormonal therapy resistant breast cancer will be discussed.

Support or Funding Information

Supported by NIH grants RO1CA061774 and RO1GM043880 and the Department of Defense BCRP program award W81XWH‐14‐1‐0086.
Eukaryotic transcription mechanisms: from nuclear RNA polymerases to general initiation factors, gene‐specific activators, coactivators and chromatin
Authors: Roeder Robert G.
Published: November 2023

Transcriptional regulation underlies key events in development, differentiation, homeostasis and cell growth and transformation. The last 45 years have revealed an extraordinary complexity to the eukaryotic transcription machinery, far beyond that evident in prokaryotes, as well as diverse regulatory mechanisms. Our own biochemical studies over this period led to the discovery of (i) three nuclear RNA polymerases (Pols I, II and III) with distinct subunit compositions and functions, (ii) cognate general initiation factors that are essential for RNA polymerase recruitment and initiation, (iii) the first gene‐specific transcriptional activator (and prototype zinc finger protein) in eukaryotes, (iv) diverse general and cell‐specific coactivators and (v) underlying mechanisms of action1. Notably, our early demonstration of robust, accurate in vitro transcription of cell‐specific genes (assayed as DNA templates) by Pol II and corresponding (ubiquitous) general initiation factors also led to the prediction of a general repression mechanism, later identified primarily as assembly into chromatin, and gene/tissue‐specific factors, many examples of which now exist, that could selectively reverse this repression. Our more recent studies have emphasized mechanistic analyses of transcriptional coactivators in biochemically defined cell‐free systems reconstituted with purified factors and either DNA templates (to analyze coactivators, such as the 30‐subunit Mediator and the TAF subunits of TFIID, that directly link activators to Pol II and cognate initiation factors) or with recombinant chromatin templates (to analyze the functions of histone modifying factors that act indirectly on the transcription machinery). Among other significant findings, these studies have (i) provided important insights into mechanisms underlying Mediator recruitment (interactions with enhancer‐bound activators) and subsequent functions, (ii) provided the first evidence that specific histone modifications are causal for (rather than simply correlated with) transcriptional activation, (iii) established direct synergistic functions of diverse histone modifying factors, through new mechanisms, in transcription and (iv) established a novel mechanism for activation of higher order (condensed) linker histone H1‐containing chromatin. Selected aspects of this work will be discussed.
New mode of EGF receptor transactivation: regulated ligand delivery
Authors: Coffey Robert J. , Cao Zheng , Singh Bhuminder
Published: November 2023

EGF receptor (EGFR) transactivation is achieved by GPCR‐mediated, metalloprotease‐dependent cell surface cleavage of an EGFR ligand whereupon soluble ligand binds and activates the receptor. NKD2, a basolateral sorting adaptor for the EGFR ligand TGF‐α, is phosphorylated at S223 by protein kinase A (PKA) in cells stimulated by forskolin or the GPCR agonist VIP. This phosphorylation stabilizes NKD2, ensuring efficient delivery of TGF‐α to the cell surface for its subsequent cleavage by metalloproteases. PKA‐mediated NKD2 phosphorylation is facilitated by smAKAP, an A Kinase Anchoring Protein with no known previous function. Thus, PKA‐mediated efficient delivery of TGF‐α to the cell surfaces in response to GPCR agonist stimulation represents a new mode of EGFR transactivation that occurs proximal to metalloprotease‐activated ligand cleavage.
Spatial Correlation of Constitutive HER2 Activities with Cell Membrane Deformation
Authors: Chung Inhee
Published: November 2023

Approximately 20% of breast cancers (BC) are characterized by gene amplification and overexpression of the HER2 receptor tyrosine kinase. These tumors are clinically classified as HER2 “positive”, and they grow faster and more aggressively than tumors with normal HER2 levels. The poor prognosis for this BC subset is related to the constitutive activation of HER2 that results from its overexpression. However, how this activation occurs is not yet clear. In contrast to other closely related receptors, HER2 does not require ligand binding or conformational changes for activation. To gain a better understanding of this process, we developed a single molecule optical tracking method that can separate the diffusion states of individual HER2s that relate to their activation on living cells. We found that slow diffusion of HER2 correlates with the receptor activation. Using this information we constructed a map of the locations of “active” HER2s on the cell surface. We observed that at any given time, a greater fraction of HER2s were in “active” states in high HER2 expressing cells compared with cells that express lower levels. Interestingly, a large fraction of active HER2s were associated with the deformed membrane structures that are prevalent on cells that overexpress HER2s. This suggests that the membrane deformations caused by HER2 overexpression create localized conditions that enable constitutive receptor activation to take place.
Mitochondrial Protonophores For Treatment of NAFLD/NASH and Type 2 Diabetes
Authors: Shulman Gerald I
Published: November 2023

This presentation will focus on the cellular mechanisms of insulin resistance in humans and the role of ectopic lipid deposits in liver and skeletal muscle in its pathogenesis. Specifically this talk will review recent studies that have implicated diacylglycerol activation of novel PKCs as the molecular trigger for lipid‐induced insulin resistance in these tissues. This talk will also review recent studies that identify the link between adipose tissue inflammation and increased rates of hepatic gluconeogenesis in type 2 diabetes as well as novel mitochondrial protonophore therapies that reverse type 2 diabetes and non alcoholic steatohepatitis through promotion of subtle increases in hepatic mitochondrial inefficiency and reductions in ectopic lipid deposition in liver and skeletal muscle.

Support or Funding Information

This work was supported by grants from NIDDK/NIH: R01 DK‐40936, R01 DK‐49230, the American Diabetes Association and HHMI.
Development of Nonalcoholic Fatty Liver in Superoxide Dismutase‐1 Knockout Mice Was Associated with Altered Expression of Hepatic Fibroblast Growth Factor‐21
Authors: Chakraborty Debrup , Lei Xin Gen
Published: November 2023

Superoxide dismutase‐1 (SOD1) is a well‐known intracellular antioxidant enzyme, and our laboratory has been studying impact and mechanism of the SOD1 knockout on glucose and lipid metabolism in mice. Non‐alcoholic fatty liver disease begins with an excessive accumulation of triglyceride in the liver, a condition that can eventually leads to hepatocyte injury, fibrosis, steatohepatitis, and cirrhosis. In the present study, we found hepatic triglyceride in the SOD1 knockout mice two‐fold higher (P < 0.05, n = 6) than that of their wild‐type controls starting at 3‐wk of age. Hepatic expression of more than 70 key genes related to responses or regulations of oxidative and endoplasmic reticular stresses, glucocorticoid receptor, casein kinase, Wnt, transforming growth factor‐β, caspase 1, and lipid metabolism was compared between the knockout and wildtype mice. Approximately one‐third of these genes were altered (P < 0.05) by the SOD1 knockout over the wild‐type control. Strikingly, the change of fibroblast growth factor‐21 (FGF21) ranked the highest among all the affected genes by the knockout. To determine if there was a cause‐effect relationship between the SOD1 knockout and the change in hepatic FGF21 mRNA levels, we treated primary hepatocytes isolated from the wild‐type mice with the SOD inhibitor (diethyl‐dithio‐carbamic acid at 0 and 50 μM for 6, 12 and 24 h), and found a four‐fold increase (P < 0.05) in FGF21 mRNA level due to the treatment. Subsequently, we injected (intraperitoneal) the SOD1 knockout mice (n = 12, male, 3‐wk old) with the SOD mimic [copper (II) 3, 5‐diisopropylsalicylate hydrate, 30 mg/kg body weight] every other day for 1 wk. The mimic injection resulted in a down‐regulation (P < 0.05) of hepatic FGF21 mRNA compared with the vehicle (80% Phosphate‐buffered saline, 10% Dimethyl sulfoxide and 10% Tween‐80) injection. In conclusion, knockout of SOD1 led to a substantial overexpression of the hepatic FGF21 mRNA, which may serve as one of the mechanisms for the development of non‐alcoholic fatty liver disease in the knockout mice.

Support or Funding Information

Supported in part by a NIH grant DK53018.
Effects of HMB and beta‐alanine co‐supplementation and running wheel activity on skeletal muscle morphometry and metabolomics in aged rats
Authors: Garvey Sean M. , Desai Janish
Published: November 2023

Dietary intervention with either beta‐hydroxy‐beta‐methylbutyrate (HMB) or beta‐alanine (BA) has been shown to improve muscle strength and physical working capacity, respectively, in elderly subjects. We examined the effects of 8 weeks HMB (343 mg/kg bw) and BA (274 mg/kg bw) co‐supplementation (HMB+BA) on skeletal muscle morphometry and metabolomic profiles in aged, male Sprague Dawley rats (22 months), versus AIN‐93M control diet (CTL). Rats were also assigned either continuous voluntary running wheel access (RW+) or cage‐matched without running wheel access (RW‐). Thus, we examined a total of 4 experimental groups (9–10 rats per group). RW activity across the 8 weeks of study was very low across both diet groups, and the HMB+BA diet had no significant effect on RW activity compared to rats fed CTL diet (84 ± 17 m/day vs. 73 ± 16 m/day). The HMB+BA diet also had no significant effects on food intake or body weight in either RW‐ or RW+ rats. Across both RW+ groups, average % body weight change decreased compared to the RW‐ groups (0.2% vs. 6.1%, P<0.00001). RW activity also decreased average weekly food intake by 6.1% (125 ± 2 g vs. 133 ± 2 g, P=0.023). Neither HMB+BA supplementation nor RW activity had significant effects on forelimb grip strength or absolute hindlimb muscle weights (i.e., gastrocnemius, soleus, plantaris). HMB+BA/RW‐ rats showed a trend for increased gastrocnemius myofiber cross‐sectional area (3430 ± 134 μm2 vs. 3802 ± 152 μm2, P=0.084), however with minimal effect on myofiber Feret diameter, relative to CTL/RW‐ rats. Metabolomic profiling highlighted effects of RW activity and HMB+BA diet on carbohydrate and lipid metabolism. In gastrocnemius, RW activity was associated with a decrease in the glycolytic intermediate, fructose‐6‐phosphate, and this effect was more pronounced in combination with the HMB+BA diet. The HMB+BA/RW+ group also showed a significant reduction in pyruvate and citrate, relative to all other groups. Adenine and 2′‐ deoxycytidine levels were also less abundant with the HMB+BA diet. Metabolomic profiling was also carried out on rectus femoris muscle from the RW‐ groups only, and the HMB+BA diet was associated with increased long chain fatty acids (LCFAs), relative to CTL diet. Increased LCFAs may indicate enhanced beta‐oxidation of lipids, and the aforementioned decreases in glycolytic intermediates suggest improved carbohydrate metabolism, as we have previously shown that these biochemicals are more abundant with age in muscle. Altogether, these data suggest that both low‐volume physical activity and HMB+BA co‐supplementation contribute to improved bioenergetics in aging skeletal muscle.

Support or Funding Information

Funding for this study was provided by Abbott Nutrition.
An integrated nutrition‐sensitive health and agriculture intervention to increase egg consumption among infants and young children in Upper Manya Krobo, Ghana
Authors: Atuobi‐Yeboah Afua , Marquis Grace S , Colecraft Esi , Kanlisi Roland , Aryeetey Richmond , Klevor Moses
Published: November 2023

Poor dietary quality and nutritional status among young children is common in rural low‐income households in Upper Manya Krobo District (UMKD), Ghana. Consumption of animal source foods can improve diet and growth outcomes. The Nutrition Links Project is a 5‐y capacity‐building project to improve nutrition and well‐being of vulnerable populations in UMKD. The project includes a small cluster randomized controlled trial that provides home gardening, health, nutrition education, and poultry entrepreneurial activities for caregivers who had a 0‐to 12‐mo‐old infant and were living in the intervention communities at enrollment (IN; n=102). Caregivers in the control (CT) communities (n=228) receive only the standard‐of‐care for nutrition, health, and agricultural extension provided by government staff. This on‐going study seeks to improve the diets and growth outcomes of young children, partly through increased egg consumption. For this analysis, longitudinal data comparing children's egg consumption during the previous day, were collected from caregivers at baseline and at the first follow‐up [IN (n=102); CT (n=228)], approximately 7 months after the intervention was implemented. At baseline, when infants were 8.7±4.1 mo old, few consumed eggs [IN (15.5%) and CT (20.8%)]. By the first follow‐up, there was a statistically significant difference in the percent of children consuming eggs (IN (28.4%) vs. CT (52.6%); P<0.001). The lower intake of eggs among IN children occurred despite the fact that IN caregivers had an increased access to eggs from the poultry enterprise. The negative effect during the early months of the intervention may reflect caregivers placing greater emphasis on egg sales for income and success of their poultry enterprise rather than home consumption. In‐depth evaluation is needed to better understand caregivers’ behaviours and to determine the project effect on the total diet. Nutrition education activities continue to encourage use of eggs as well as diverse nutrient‐rich foods in UMKD children's diets to ensure the nutrition‐sensitive agriculture intervention achieves the expected objective of improving diets and nutritional status of project participants.

Support or Funding Information

Funded by the Department of Foreign Affairs, Trade, and Development (DFATD) of the Government of Canada
Household Food Insecurity and Hunger in Selected Ethiopian Agricultural Communities: Examination of Supply and Demand Factors
Authors: Zello Gordon A , Ersino Getahun , Henry Carol J , Regassa Nigatu
Published: November 2023

Food insecurity and hunger are major challenges in many Ethiopian communities with repercussions on health and nutrition outcomes in vulnerable household members. Depending on the context, a combination of supply and demand factors, community and institutional factors may affect household food insecurity and hunger. Our objective was to determine the degree of household food insecurity and hunger, and examine the contribution of associated contextual factors, in two rural communities of Ethiopia, namely Halaba and Zeway, located in two adjacent regions of the country (SNNPR and Oromiya Regions, respectively). A sample of 630 households were randomly selected from the two districts, and levels of food insecurity and hunger were measured using the Household Food Insecurity Access Scale and Household Hunger Scale developed by Food and Nutrition Technical Assistant project (United States Agency for International Development). Multiple classification analysis was employed to explore the effects of key demand (e.g. household size, livestock) and supply (e.g. land size, wealth) factors and community (geographic location) as well as institutional (participation in food security programs) factors on food insecurity and hunger. Household food insecurity was unacceptably high in both districts (95% in Halaba & 67% in Zeway). Household hunger was 38% in Halaba and 18% in Zeway. Both food insecurity and hunger were significantly greater in Halaba (p<0.001), indicating an effect of geographic location. Both supply and demand factors were significant in determining household food insecurity and hunger (p<0.01); however, supply factors such as women's access to land, land size and wealth had greater influence than the demand factors. Levels of food insecurity and hunger in both communities were very high and of serious concern. We recommend increasing the food supply, and its subsequent accessibility, for households through enhancing women's access to land, improving income through savings and wealth accumulation, introducing more inclusive programs for women's participation and reducing household work‐burden by significantly enhancing productivity of cultivable land.

Support or Funding Information

The research was supported by the International Development Research Centre (IDRC) and the Department of Foreign Affairs Trade and Development (DFATD), Government of Canada, through the Canadian International Food Security Research Fund (CIFSRF).
Association of Fathers’ Income and Education Level with Childhood Obesity Risk Factors in Preschool Age Children
Authors: Vollmer Rachel Lynn , Kari Adamsons , Foster Jaime S , Mobley Amy R
Published: November 2023

The aims of this study were to determine if certain characteristics (income and educational level) of fathers with preschool age children were associated with 1) paternal feeding practices, 2) child BMI z‐score, 3) child diet quality, 4) paternal concern for and perception of child weight, and 5) paternal perception of the role of the father in the family (ROF) and at mealtimes (ROFM). Biological fathers of preschoolers (n=150) were interviewed individually to measure feeding practices (Child Feeding Questionnaire), child diet quality (24‐hour dietary recall, Healthy Eating Index‐2010), role of the father in the family and at mealtimes (Role of the Father and Role of the Father at Mealtimes Questionnaire). Each preschool child's height and weight was also measured and BMI z‐score calculated. Linear regression was used to test each study aim. Most fathers in this sample had either some college education (31.3%) or a 4‐year degree or higher (50.7%) and were low‐income (52.7%). Being a low‐income father, above and beyond education level, race, and ethnicity, was associated with higher pressure to eat (β = −.697, p = .007), higher child BMI z‐score (β = −.483, p = .034), and higher perceived child weight (β = −.270, p = .001). Education level, above and beyond income level, race, and ethnicity, was negatively associated with ROF (β = −.818, p = .037) and ROFM (β = −1.517, p = .006) scores, indicating that fathers who had lower education levels thought the father should be more involved in the family and at mealtimes compared to fathers with higher education levels. Higher education levels were also associated with higher child diet quality scores (β = 5.263, p = .003), while controlling for income, race, and ethnicity. These results indicate that low‐income fathers and fathers with a lower education level may benefit from interventions or policy changes focusing on positive child feeding practices and providing a healthy diet for their preschool age child, respectively, that could, in turn, positively influence child weight status in this higher risk population.

Support or Funding Information

University of Connecticut Center for Health, Intervention, and Prevention
Parental intention to engage in healthier beverage practices: effects of gain‐ versus loss‐framed messages
Authors: Zahid Arwa , Reicks Marla
Published: November 2023

Energy imbalance from excessive sugar‐sweetened beverage (SSB) consumption may lead to adverse health consequences in childhood and later in adulthood. The purpose of this study was to test effects of message framing (gain‐ or loss‐framed) on behavioral intention of parents to role model healthful beverage intake and to make healthful beverages available in the home for a child (6–12 years). Two messages embedded in still images were tested for each behavior, one gain‐framed and one loss‐framed, in a between subjects, posttest only study. A survey was administered to 380 parents at the Minnesota State Fair 2015 to assess usual beverage intake, home beverage availability, and to test the effects of message framing on behavioral intention (scale of 1 to 4 where 1 = not at all and 4 = a lot). The majority of parents were white (90.7%), women (79.7%), employed full time (72.9%), and had a 4 year degree college (70.5%); mean age was 42.0 years. A manipulation check with 75 parents showed that a majority perceived the messages to be framed according to the intended valence. Higher home availability of less healthy beverages and frequency of soda intake was correlated with lower parental intention to make healthy beverages available or to role model intake of healthy beverages, regardless of message valence. A higher number of parents indicated that the gain‐framed versus the loss‐framed messages would motivate them (some and a lot) to make healthful beverages available at home (73.2% vs. 65.8%) and to role model healthful beverage intake for their children (76.1% vs. 64.0%). The gain‐framed message (M=3.06, SD= 0.90) produced significantly (p<.002) greater intention to make healthful beverages available in the home than the loss‐framed message (M=2.93, SD= 0.96). The gain‐framed message (M=3.10, SD= 0.85) also produced significantly greater intention (p<.0001) to role model healthful beverage intake for their children than the loss‐framed message (M=2.81, SD= 1.03). Based on these results, a parent intervention program using gain‐framed messages will be developed and implemented to decrease intake of SSBs by children. Decreased intake of SSBs may positively affect weight status as well as nutrient quality of the diet.

Support or Funding Information

Minnesota Agricultural Experiment Station
Protein intake and risk of hip fractures in post menopausal women and men over 50 years
Authors: Fung Teresa , Willett Walter , Feskanich Diane
Published: November 2023

Background

The relationship between protein intake and fracture risk is unclear. In addition, few studies have examined the contribution or association of specific protein sources with hip fractures among men.

Objective

To examine association between intake of total and specific sources of protein and hip fracture risk in postmenopausal women and men over 50 years of age.

Methods

Data from 74,540 women in the Nurses’ Health Study followed between 1980 and 2012, and 35,451 men from the Health Professionals Follow‐up Study followed between 1986 and 2012 were used for this analysis. Health and lifestyle information, and hip fractures were self reported on biennial questionnaires. Protein was assessed approximately every four years with a food frequency questionnaire. Relative risks (RR) were computed for hip fracture by quintiles of total, animal, dairy, and plant protein intake using Cox proportional hazards models, adjusting for potential confounders.

Results

There were 2156 incidents of hip fractures in women and 590 fractures in men. Among women, there was no association between hip fractures and intake of total and animal protein. However, there was a significant inverse trend with dairy protein (RR comparing quintile 5 vs quintile 1=0.89, 95% CI=0.83–1.02, p trend=0.03) and a marginally significant inverse trend with plant protein (RR=0.86, 95% CI=0.72–1.01, p trend=0.05). Among men, we observed a significant inverse association with total (RR=0.72, 95% CI=0.52–0.99, p trend=0.01) and animal protein intake (RR=0.77, 95% CI=0.56–1.07, p trend=0.006), but no association with dairy or plant protein. When total protein intake was categorized in women according to the quintile ranges in men, a significant inverse association appeared (RR for ≥100g vs <70g intake=0.81, 95% CI=0.53–1.23, p trend=0.03). Examination of specific sources including animal flesh, dairy, nuts and legumes did not result in any clear trends of association.

Conclusion

Higher protein intake was not associated with an increased risk of hip fractures in post menopausal women or men 50 years old or above. On the other hand, higher intake of certain protein sources may be associated with a lower risk of hip fractures.

Support or Funding Information

NIH grants: CA87969, HL60712, and AG30521
Vitamin D and Ovarian Reserve and Fecundability among Women with Proven Fecundity
Authors: Mumford Sunni Lyn , Silver Robert , Sjaarda Lindsey A , Galai Noya , Stanford Joseph , Lynch Anne , Lesher Laurie , Perkins Neil , Wactawski‐Wende Jean , Garbose Rebecca , Kim Keewan , Michels Kara , Schisterman Enrique
Published: November 2023

Objective

Vitamin D is associated with markers of ovarian reserve in women of advanced reproductive age and in vitro studies suggest that vitamin D may influence anti‐mullerian hormone (AMH). Higher vitamin D levels are also associated with improved IVF outcomes in some studies. However, less is understood regarding associations with ovarian reserve or time to pregnancy among younger women or women without a history of infertility. Our purpose was to assess the relationships between vitamin D and AMH and fecundability among women with proven fecundity.

Design

Secondary analysis of the EAGeR Trial, a multicenter, block‐randomized, double‐blind, placebo‐controlled clinical trial to evaluate the effect of preconception‐initiated daily low dose aspirin on reproductive outcomes in women with a history of pregnancy loss and normal fecundity.

Methods

Participants were attempting pregnancy, aged 18–40 years, with 1–2 prior pregnancy losses and no history of infertility. We assessed 25‐OH vitamin D and AMH in serum at baseline (not pregnant) among 1185 women. AMH levels were log‐transformed for normality. Linear regression was used to estimate associations between vitamin D and AMH concentrations adjusting for age, body mass index, race, season, physical activity, and number of prior losses. Time to hCG detected pregnancy was assessed using Cox proportional hazard regression models for discrete survival time, accounting for left truncation and right censoring, to estimate fecundability odds ratios (FOR), adjusting for the same factors.

Results

A total of 163 women (13.8%) had deficient vitamin D levels (<20 ng/mL). Overall, vitamin D levels were not associated with AMH (percent change −1.6, 95% confidence interval [CI] −5.3%, 2.3% per 10 ng/mL). Vitamin D deficiency was also not associated with AMH (deficient: adjusted geometric mean AMH 2.51, 95% CI 2.20, 2.85 vs. inadequate/sufficient: 2.74, 95% CI 2.60, 2.89). There also were no significant associations observed between overall vitamin D levels or deficiency and fecundability (FOR 1.09, 95% CI 0.84, 1.42 comparing deficient vs. inadequate/sufficient) after adjustment.

Conclusions

Vitamin D was not associated with AMH, time to pregnancy, or fecundability among women with proven fecundity. These results suggest that vitamin D is not associated with ovarian reserve or fecundability and that vitamin D supplementation may offer little clinical benefit for improving markers of ovarian reserve and fecundity.

Support or Funding Information

Intramural Research Program, DIPHR, NICHD, NIH
A Short‐Term Transition from a High‐Fat Diet to a Normal‐Fat Diet Before Pregnancy Exacerbates Female Mouse Offspring Obesity
Authors: Xie Linglin , Fu Qiang , Olson Patrick , Zhang Ke
Published: November 2023

Background/Objectives

Recent findings have highlighted the detrimental influence of maternal over‐nutrition and obesity on fetal development and early life development. However, there are no evidence‐based guidelines regarding the optimal strategy for dietary intervention prior to pregnancy.

Subjects/Methods

We used a murine model to study whether switching from a high‐fat diet to a normal‐fat diet (H1N group) 1 week before pregnancy could lead to in utero reprogramming of female offspring obesity; comparator groups were offspring given a consistent maternal high‐fat diet (HF group) or normal‐fat diet (NF group) until weaning. After weaning, all female offspring were given the high‐fat diet for either 9 or 12 weeks before killed humanely.

Results

H1N treatment did not result in maternal weight loss before pregnancy. NF offspring were neither obese nor glucose‐intolerant during the entire experimental period. H1N offspring were most obese after the 12‐week postweaning HF diet and displayed glucose intolerance earlier than HF offspring. Our mechanistic study showed reduced adipocyte IRS1 and hepatic IRS2 expression and increased adipocyte p‐Ser636/639 and p‐Ser612 of H1N or HF offspring than in NF offspring. Among all groups, the H1N offspring had lowest level of IRS1 and the highest levels of p‐Ser636/639 and p‐Ser612 in gonadal adipocyte. In addition, H1N offspring further reduced expression of Glut4 and Glut2, versus those of HF offspring which was lower than NF offspring. There were also enhanced expression of genes inhibiting glycogenesis and decreased hepatic glycogen in H1N versus HF or NF offspring. Furthermore, we showed extremely higher expression of lipogenesis and adipogenesis genes in gonadal adipocytes of H1N offspring comparing to all other groups.

Conclusion

Our results suggest that a transition from a high‐fat diet to a normal‐fat diet shortly before pregnancy, without resulting in maternal weight loss, is not necessarily beneficial and may have deleterious effects on offspring.

Support or Funding Information

This project was supported by grants from the National Institutes of Health (NIH‐1R15HL117238 to LX and National Center for Research Resources, 5P20RR016471‐12/8 P20 GM103442‐12 to LX and KZ) and the American Heart Association (Scientist Development Grant13SDG14650009 to LX).
Disparities in the Incidence of Hypertension in Youth
Authors: Koebnick Corinna , Daley Matthew F , Mohan Yasmina D , Reynolds Kristi , Li Xia , Sidell Margo A , Porter Amy H , Handler Joel , Daniels Stephen R , Kuizon Beatriz D
Published: November 2023

Background

While racial disparities in adult hypertension incidence are well established, our knowledge is limited regarding at what age these disparities begin. Data on predictors for the incidence of hypertension in youth is scant.

Study Design

For this population‐based cohort of youth in southern California, members of a health plan between 3 and 17 years of age and without hypertension (n = 279,708) were passively followed. Blood pressure (BP) and baseline body mass index were extracted from electronic health records. We classified BP using the definitions of the Fourth Report (NHBPEP 2005) and JNC8. Relative risks (RR and 95%CI) are presented mutually adjusted for race, sex, age and socioeconomic status.

Results

The cohort was racially/ethnically diverse (52.5% Hispanic, 9.9% Black, 7.4% Asian). During 1,124,912 person‐years of follow‐up (over a median of 5.0 years), we identified 9,158 youth with incident hypertension at a mean age of 12.0 years (SD ± 4.3 years). The crude incidence rate of hypertension was 81 cases per 10,000 person‐years. The RR of hypertension was 0.83 (95%CI 0.80–0.87) for girls compared to boys. Compared to non‐Hispanic whites, the RR of hypertension was 1.00 (0.95–1.05) for Hispanics, 0.98 (0.91–1.06) in non‐Hispanic Blacks, 0.95 (0.87–1.03) in Asian/Pacific Islanders. For youth with low socioeconomic status indicated by state‐subsidized health coverage the RR was 1.12 (1.06–1.18).

Conclusion

In this large multiethnic, population‐based cohort of youth, sex and socioeconomic status but not race/ethnicity were associated with the risk of hypertension.

Support or Funding Information

Kaiser Permanente Direct Community Benefit Funds
Iron Status and Regulation in High‐Risk Pregnant African American Women
Authors: Welke Lauren
Published: November 2023

Iron is essential across the lifecycle but is critical during pregnancy. African American (AA) women are more likely to be iron deficient (ID) during pregnancy and classified as having a high‐risk pregnancy due to factors including existing medical conditions and obesity. Such conditions can also compromise maternal iron metabolism due to inflammation‐induced overexpression of the iron‐regulatory peptide hormone hepcidin. The aim of this study was to examine iron status and regulation during the 2nd and 3rd trimester of pregnancy in AA women classified as a high‐risk pregnancy.

Methods

Non‐fasting venous blood was drawn at 22 and 32 weeks gestation for the assessment of iron status, hepcidin, and inflammation. Anthropometric and survey data was also obtained. Ferritin < 15.0 and < 30.0 ng/ml (to account for inflammatory effects on ferritin) was used to define iron deficiency. Descriptive statistics were calculated and changes in the clinical parameters between the 2nd and 3rd trimester were evaluated via paired t‐test.

Results

Forty seven women, mean age 28 (± 6.6) years and pre‐pregnancy BMI of 32.6 (± 11.6) kg/m2 were recruited. Mean habitual dietary iron intake was 38 mg/day. Between the 2nd and 3rd trimester, significant (p < 0.05) declines in serum iron, ferritin, transferrin saturation, hepcidin, and C‐reactive protein were observed. During the 2nd trimester, 28% of women were ID increasing to 50% in the 3rd trimester based on ferritin < 15.0 ng/ml. When using a ferritin cut‐point of < 30.0 ng/ml, 68% and 87% of women were classified as ID, respectively.

Conclusion

Maternal iron deficiency was prevalent among these high‐risk pregnant AA women. Although hepcidin declined significantly between trimesters, concentrations in this cohort were higher than previously reported in healthy pregnancy suggesting decreased maternal iron bioavailability. Because elevated maternal hepcidin may impair dietary iron absorption, further research is warranted in this high‐risk group.

Support or Funding Information

Center for Clinical and Translational Science (UL1RR029879) CCTS Pilot Grant Award, Award Number CCTS08011‐02
Effect of a 1‐Year Walnut Supplementation on Blood Lipids among Older Individuals: Findings from the Walnuts and Healthy Aging (WAHA) study
Authors: Ros Emilio , Rajaram Sujatha , Sala‐Vila Aleix , Serra‐Mir Merce , Valls‐Pedret Cinta , Cofán Montse , Roth Irene , Doménech Monica , Freitas Tania , Calvo Carlos , Haddad Ella , Sabaté Joan
Published: November 2023

Background

In small well‐controlled short‐term feeding studies conducted in middle‐aged adults, nut‐enriched diets have resulted in cholesterol lowering and absence of weight gain compared to control diets. There are no long‐term data on lipid changes when supplementing the diet with nuts in older adults.

Objective

To assess whether adding walnuts to the daily diet of free‐living healthy older adults for 1 year will result in changes in blood lipids compared to the usual diet without nuts.

Design

Within the context of the WAHA study, a two‐center clinical trial aimed at determining the effect of a 2‐year walnut diet on age‐related outcomes, we randomized 707 free‐living older but healthy individuals (352 in Barcelona, 355 in Loma Linda; 67% women, mean age 69 y, mean BMI 27.3 kg/m2) to supplementation of the usual diet with daily doses of walnuts at ≈15% of energy or to usual diet without nuts (control). Participants had frequent (once every two months) assessments by dietitians; no advice was given on total energy/macronutrient intake or food substitution for walnuts. At baseline and 1 year serum lipids were analyzed. Between‐group differences in outcomes were analyzed by analysis of covariance with adjustment for sex, age, center and baseline levels; lipid values were additionally adjusted by changes in statin treatment.

Results

Complete 1‐year data were available for 514 participants (260 walnut diet, 254 control diet). There were 137 participants pending 1‐year assessment and 56 dropouts for various reasons. The walnut diet was well tolerated and the proportion of α‐linolenic acid in red blood cells increased in the walnut group by 0.162% (95% CI, 0.143–0.181) and in the control group by 0.015% (CI, −0.005–0.035) (P<0.001), indicating good compliance with the intervention. Changes in blood lipids were (mean±SEM) −7.5±1.6 versus −0.4±1.6 mg/dL (P=0.003) for total cholesterol, −7.1±1.3 versus −1.1±1.4 mg/dL (P=0.002) for LDL‐cholesterol, and −0.15±0.31 versus −0.05±0.31 (P=0.025) for the total cholesterol/HDL‐cholesterol ratio, in the walnut versus control diets, respectively. No between‐diet differences were observed for triglycerides or HDL‐cholesterol. Lipid effects were similar in the two centers. No differences in body weight was observed between treatments.

Conclusion

Incorporating daily doses of walnuts to the habitual diet of older free‐living individuals for 1 year was well tolerated and resulted in significant LDL‐cholesterol reduction without adverse effects on body weight. Results were similar with a Mediterranean or a Western background diet

Support or Funding Information

The WAHA study is funded by the California Walnut Commission
Snacking Starts Early and Is Prevalent Among Infants, Toddlers and Preschoolers in Mexico
Authors: Deming Denise , Afeiche Myriam , Reidy Kathleen , Eldridge Alison , Villalpando‐Carrión Salvador
Published: November 2023

The aim of this study was to examine snacking patterns among young children living in Mexico. We used data from the 2012 Mexican National Health and Nutrition Survey (ENSANUT 2012) to assess the snacking prevalence, energy intake from snacks and common snacks foods consumed among infants, toddlers and preschoolers (n=2057). Dietary intake interviews (24‐hour recalls) were conducted with parents or caregivers of infants ages 6–11 months (m) (n=229), toddlers 12–23m (n=538) and preschoolers 24–47m (n=1108). Snacking was defined as eating outside of meals (excluding infant feedings), and was self‐reported by parents or caregivers. Most children >11m were snacking on a given day (~82–85%) and consumed snacks more frequently before and after lunch (~55–65%) than before breakfast and after dinner (~20–30%). Snacks contributed ~15% of total energy intake among infants ages 6–11m and ~22% among both toddlers and preschoolers, who consumed ~2 snacks/day (2.2±0.1, and 1.8±0.1, respectively). Energy intake from snacks among consumers increased with age and by the age of 2 years, children consumed on average 392±21 kcals from snacks in a day and about 150–200 kcals per snack occasion. Cookies, salty snacks, fruits, yogurt and cow's milk ranked in the top five most frequently consumed foods during snacking among infants. Fruit, cow's milk, cookies, candy, and salty snacks were the most frequently consumed snacks by toddlers and preschoolers. These findings show that snacking patterns begin in infancy and snacks foods contribute a large percentage to the total caloric intake of young Mexican children and that the quality of some foods consumed as snacks could be improved. Since food preferences and dietary patterns start early in life it is critical to acknowledge the importance of snacking patterns among young Mexican children and the implications for long term health.

Support or Funding Information

Funded by Nestlé Research Center, Lausanne, Switzerland