bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chemical Tools for Studying the Activation of the Intracellular Innate Immune Protein Nod2
Authors: Grimes Catherine , Melnyk James 
Published: June 2021

Chronic inflammatory disorders, such as Inflammatory Bowel Disease, arise from an inappropriate immune response to bacteria. In order to treat these diseases, we need a better understanding of how the innate immune system senses and responds to bacteria. It has long been known that muramyl dipeptide (MDP,Figure 1), a fragment of bacterial cell wall (peptidoglycan), is able to generate an immune response. Recently, it has been shown that the intracellular, mammalian protein Nod2 is involved in sensing the presence of MDP in the cell, leading to activation of the synthesis of inflammatory molecules. Nod2 is an important protein to human health, as mutations in the gene have shown an increased incidence of Crohn's disease.The mechanism of activation of the Nod2 signaling pathway by MDP is not understood. For example, it is not known if MDP directly interacts with Nod2. We have taken a chemical biological approach to this problem by synthesizing tagged versions of MDP. This tool was then utilized to probe for an interaction between Nod2 and MDP. We describe the development of a variety of binding assays and present a model for Nod2 activation via MDP. Our approach has led to a deeper understanding of the biophysical mechanisms used by the innate immune system to sense bacteria.
Metabolic Complexity of Aggressive Primary and Metastatic Brain Tumors Beyond the Warburg Effect: What Substrates are Fueling the Citric Acid Cycle?
Authors: Maher Elizabeth 
Published: June 2021

BackgroundGlioblastomas and brain metastases are aggressive, highly proliferative tumors with short survival times. 13C‐NMR analysis of resected tumors from brain tumor patients infused with 13C‐glucose at the time of surgery established that oxidation of glucose was occurring simultaneously with high lactate production. While it was clear that the citric acid cycle was actively metabolizing glucose, there were carbons in the acetyl‐CoA pool that could not be attributed to infused 13C‐glucose. The tumors were metabolizing another substrate(s), identified as the 'substrate gap' (Maher et al., 2012). Since astrocytes, the presumptive cell of origin of glioblastomas, use acetate as a major energy substrate, we investigated whether the tumors were capable of oxidizing acetate. Brain metastases, tumors derived from organs that do not normally oxidize acetate were studied to determine whether altered substrate choice is cell type dependent or a property of brain tumors. Methods: For these studies we used our human orthotopic tumor mouse models of glioblastoma and brain metastases from non‐small cell lung cancer, breast cancer, renal cell carcinoma, melanoma and endometrial cancer, which have remarkable fidelity to the human tumor from which they were derived. The orthotopic tumors are passaged in the brain, without adaptation to culture. We co‐infused [1,2‐13C]acetate and [1,6‐13C]glucose for 2 hours in tumor‐bearing mice and then analyzed the resected tumor by 13C‐NMR. In addition, we infused [1,2‐13C]acetate in patients during surgery after obtained informed consent on an IRB‐approved protocol. The 13C‐NMR results from the resected tumors were compared to the prior human studies of infused 13C‐glucose and to the results in the orthotopic mice. Results: The orthotopic tumors from the glioblastomas and brain metastases all have the capacity to oxidize acetate and do so simultaneously with glucose oxidation. We have validated this finding in patients with glioblastoma and brain metastases.ConclusionsTogether the data demonstrate a strikingly common metabolic phenotype in these diverse brain tumors that includes the ability to oxidize acetate in the citric acid cycle. It is unclear at present whether this represents an adaptation to meet the high bioenergetic demands of growth in the brain, is a general characteristic of metastatic tumors, or a basic feature of malignant transformation. Evaluation of human primary tumors in vivo will help to address this question.
Effect of the Intake of High‐SDS Product on Metabolic and Inflammatory Markers in Healthy Subjects with High Metabolic Risk
Authors: Meynier Alexandra , Lambert‐Porcheron Stéphanie , Normand Sylvie , Roth Hubert , Laville Martine , Vinoy Sophie 
Published: June 2021

ObjectivesThe comparison of metabolic and inflammatory responses following the ingestion of cereal products high in Slowly Digestible Starch (SDS) was studied in subjects with impaired glucose tolerance.MethodsIn a cross‐over design, 20 (13F/7M) healthy overweight subjects with high metabolic risk participated to 3 sessions: one session testing a glucose solution (54g which is the amount of carbohydrates provided by the two other breakfasts), two sessions testing either a biscuit high in SDS or a rusk without SDS with 250 mL of semi‐skimmed milk and a hot beverage. The 2 sessions with cereal products followed a 3‐week period where the corresponding cereal product was daily consumed. Glycemia, insulinemia, blood lipid profile and markers for inflammation and oxidative stress were followed during a 240‐minute postprandial period.ResultsGlycemic responses following both cereal products were lower compared to glucose solution. iAUC(0‐120 min) glycemia was significantly lower (‐32 %) following the breakfast with biscuit high in SDS compared to rusk without SDS. The insulinemic response was also lower following the breakfast with the biscuit compared to the 2 other sessions. No significant difference was observed between the 2 groups with cereal products for blood lipid profile and for the makers of inflammation and oxidative stress.ConclusionBreakfast with a high‐SDS biscuit led to lower glycemic and insulinemic responses compared to breakfast including a rusk with no SDS in subjects with high metabolic risk. The ingestion for 3 weeks of the cereal products did not modified fasting and postprandial markers of inflammation and oxidative stress.
Development of a Formal Protocol to Map the Community Food Environment Using Direct Observation: a Case Study in Urban Guatemala
Authors: Garcia Rosario , Kanter Rebecca , Fuentes Déborah , Burgunder Lauren , Scieszka Laura , Díaz Ruiz Elena , Andringa Sygrit , Browne Lauren , Polanco Ana , Solomons Noel 
Published: June 2021

BackgroundMeasures of the community nutrition environment are important to understanding the food environment, which affects individual diet.ObjectiveTo develop a formal protocol to improve the reliability of using direct observation to map the food environment in Guatemala.MethodsFour teams of two raters were asked to walk two thoroughfares in urban Quetzaltenango, Guatemala. Each team consisted of one rater from Guatemala and one non‐Guatemalan. All teams read the mapping protocol and explored the area prior to mapping. Data was collected in a step‐wise fashion. The first team collected data and revised the mapping protocol that was then utilized by the next team. The validity of direct observation in mapping a community food environment in Quetzaltenango was determined by comparing the inter‐team concordance on each subsequent use of the protocol; and compared to data previously collected without a protocol.ResultsThe inter‐team reliability improved with the use of a formal protocol and mixed‐ethnicity teams. On one street, the inter‐team reliability improved to 76% using the revised protocol from 67% with the original protocol; compared to 60% without a protocol. On the other street in which 40% of the food establishments were mobile vendors, the improvement in inter‐team reliability was modest.ConclusionsIn Guatemala, street‐mapping correspondence saturates at a certain point with or without considering the ambulatory aspects of carts and street vendors. A formal protocol and mixed teams that include a rater native to the country of interest improve the use of direct observation as a reliable low‐cost method to map the community food environment.
Glycemic Index and Glycemic Load and Liver Enzyme Activity
Authors: Chiavaroli Laura , Augustin Livia , Ireland Christopher , Mirrahimi Arash , Sievenpiper John , Kendall Cyril , Jenkins David 
Published: June 2021

ObjectiveThe relationship between non‐alcoholic fatty liver disease (NAFL) and insulin resistance, suggests that dietary interventions to reduce postprandial glycemia and insulin demand, i.e. low glycemic index (GI) and low glycemic load (GL) diets, may be relevant to NAFL.
MethodsLiver enzymes (ALT and AST) were measured in two 3‐month clinical trials of low GI or GL versus control (high cereal fiber) diets in participants with type 2 diabetes (n=212). Baseline liver enzymes were also measured in three additional studies of type 2 diabetes (n=299). ResultsIn study 1, the low GI diet resulted in significant reductions in both liver enzymes with a greater reduction for AST when compared to the control diet (P<0.05). In study 2, the low GL diet demonstrated significant reductions in both liver enzymes, while the control diet significantly reduced AST. However, the reductions in AST were significantly greater on the low GL diet compared to control (P<0.05). Using baseline data from studies 1 and 2 as well as 3 additional studies, baseline correlations between liver enzymes and markers of metabolic syndrome revealed significant positive correlations for both AST and ALT with diastolic blood pressure and with triglycerides, and for ALT with fasting glucose, HbA1c and systolic blood pressure (P<0.05). Of the dietary factors correlated with liver enzymes, only dietary cholesterol was positively associated with AST and ALT (P<0.05). ConclusionLower GI and GL diets improved liver enzymes and thus may play a role in reducing the risk of NAFL. Funding: Barilla
Plan for the Registered Dietitian Identification and Documentation of Adult Inpatients
Authors: Browning Maria , Roberts Beth , Kingery Joanna , Carter Kimberly , Hines Courtney , Gardus‐Pizlo Irmina , Roberts Scott 
Published: June 2021

The purpose of the policy was to support the change in procedure to identify and document malnutrition in adult patients admitted to Indiana University Health Methodist Hospital.Retrospective data analysis was used to identify the current state of patients diagnosed with malnutrition at Indiana University Health. Once the new policy was complete and initiated a second data analysis was completed to see if there was a change in the incidence and specificty of the malnutrition diagnosis on patients discharge from IU health Methodist and university hospitals.Intial results indicated that less than 1% of patients discharged form Indiana University Health Methodist in August of 2013 were coded for severe malnutrition or moderate malnutrition. This is significantly less than the predicted 30% of patients in acute care settings. After implementation of the malnturition policy, the incidence of malnutrition diagnosis from August 2014 increase more than 500% to 5%of patients discharged from Indiana University Health Methodist Hospital

August 2013
August 2014
%Change

Severe Protein Calorie Malnutrition
13/2668 (0.5%)
83/2682 (3.1%)
+538%

Moderate Malnutrition
9/2668 (0.34%)
52/2682 (1.9%)
+477%

Although there is still a long way to go in improving the diagnosis of patients with malnutrition, the first month of implementation showed the new policy and procedure to be much more effective in identifying and documenting malnutrition in adult patients hospitalized at Indiana University Health.
Delivery Mode and Neonate Gut Microbiota
Authors: Mueller Noel , Pizoni Aline , Goldani Helena , Werlang Isabel , Matte Ursula , Goldani Marcelo , Shin Hakdong , Dominguez‐Bello M 
Published: June 2021

BackgroundC‐section (CS) babies have elevated risk of obesity, perhaps due to differences in gut microbiota during critical windows of metabolic programming. While known that the newborn gut microbiota differ by delivery mode, it is unclear when these differences emerge.AimsHere we examine how delivery mode is associated with microbiota in neonate 1st (meconium) and 2nd stool.MethodsOur study comprises 62 neonates born by elective CS and 21 by vaginal delivery (VD) from Porto Alegre, Brazil. Bacterial V4 16SrRNA region was sequenced with the Illumina platform. Analyses were performed using QIIME. Linear discriminant analysis (LDA) effect size (LEfSe) method, which integrates statistical significance and biologic relevance, was used to compare the gut microbiota between CS and VD babies.ResultsIn the meconium, there were no differences in microbial diversity or community structure between CS and VD babies. However, in the 2nd stool, compared to CS babies, VD neonates had greater relative abundance of 4 phylotypes, including Bacteroides genus, and lower relative abundance of 19 phylotypes.imageCompared to VD babies, the 2nd stool from CS babies also appeared to have more microbial diversity, but this difference was not statistically significant (p=0.33). Findings were similar across pregnancy weight strata.ConclusionsCS babies have disrupted gut microbiota compared to VD babies, but, in our study, these differences do not emerge until the 2nd stool. Further research is needed to elucidate what determines the microbial composition of meconium, and whether the differences in 2nd stool microbiota by delivery mode have long‐term health consequences.
Relationship between Infant Breast Milk Exposure and Impulse Control during Adolescence
Authors: Darcey Valerie , Stevens Benson , VanMeter John , Rose Emma , Fishbein Diana 
Published: June 2021

Infant diet influences neurodevelopment, yet the direct impact of early diet on neural circuits that underlie impulse control, which are critical for regulating risky behaviors, is not well understood. Here we examined teen prefrontal cortical (PFC) structure and behavioral outcomes in relation to breast milk intake during the first 6 months of lifeParticipants were alcohol‐naïve teens enrolled in a longitudinal neuroimaging study. Mothers completed a survey on infant diet. Exclusively breastfed (BF) were matched to exclusively formula‐fed (F) teens (each N=14).

Exclusive Breastfed (BF)
Exclusive Formula (F)
p (2‐tailed)

Matched characteristics

N
14
14
‐‐

Age (years)
12.5+0.6
12.2+0.9
NS

Gender (% female)
64.3%
64.3%
NS

Race (% Caucasian)
35.7%
35.7%
NS

Maternal education (% &amp;gt; high school education)
64.3%
64.3%
NS

Other characteristics

Maternal age at delivery (years)
31.9+4.7
34.0+6.8
NS

Teen BMI (kg/m2)
19.2+3.9
22.9+5.2
0.042

Teen birth weight (oz.)
118.1+29.7
117.3+19.8
NS

Teen birth length (inches)
20.2+1.5
20.7+1.2
NS

Impulsivity and risk‐taking were assessed via Go/No‐go and Wheel of Fortune tasks. Parents rated teens on the BRIEF Inhibition subscale. PFC gray matter volumes (GMV) were derived from 3T T1 MPRAGE images. Images meeting quality standards (11 BF; 10 F) were analyzed via VBM.Compared to BF teens, F teens were less inhibited and tended toward greater impulsivity, but did not differ in risky choices. There was a trend toward interaction of group and GMV in the middle orbital gyrus predicting risky choices in F teens.

Exclusive Breastfed (BF)
Exclusive Formula (F)
p (2‐tailed)

BRIEF‐Inhibition score
12.9+3.1
16.1+3.9
0.021

Go/No‐Go (% commission errors)
45.0+16.5
55.3+13.7
0.084

Wheel of Fortune (average % high risk selections)
51.0+6.0
49.0+6.0
NS

Average GMV in Frontal Middle Orbital Gyrus, R (BA11)
0.23+0.02
0.22+0.02
NS

imageThis preliminary analysis suggests exclusive breast milk in the first 6 months of life facilitates impulse control years later. In contrast, exclusive formula diet may influence neurodevelopment in a manner that predicts risky choices. Determining how this complex relationship is mediated by dietary factors that benefit brain maturation and mitigate risk taking may improve health outcomes.
Epigenetic Mechanisms by Which Chemoprotective Natural Compounds Promote RXR/FXR Signaling and Reduce Colon Cancer Progression
Authors: Triff Karen , Knight Jason , Ivanov Ivan , Zhou Beiyan , Chapkin Robert 
Published: June 2021

Chemoprotective natural compounds include amphiphilic n‐3 polyunsaturated fatty acids (PUFA) found in fish oil, and butyrate, a histone deacetylase inhibitor, generated in the colonic lumen via the fermentation of fiber by gut microbes. Using preclinical models, we have demonstrated that n‐3 PUFA and butyrate synergistically reduce colon tumor development by increasing targeted apoptosis of DNA damaged cells, thus reducing tumorigenesis. Therefore, we assessed epigenetic reprogramming using high‐resolution transcriptome and chromatin state maps from epithelial cells isolated from rats injected with a colon‐specific carcinogen (AOM) and fed a combination of fermentable fiber (butyrate) plus n‐3 PUFA vs control.Colonocyte transcriptional profile analysis (RNA‐Seq and ChIP‐Seq) of n‐3 PUFA/butyrate vs control rats at the cancer progression stage, 10 wks post AOM exposure, revealed 26 differentially expressed genes related to the RXR/FXR signaling (IPA pathway analysis p<0.001). Differential H3K9ac occupancy concurrent with the induced pathway genes included hepatic transport proteins (ABCA1 and ABCA2), metabolizing enzymes (CYP2B6, GSTA3), biosynthesis enzymes (CYP7A1), RXR ligand synthesis (ALDH8), and nuclear hormone receptor (FXR) linked to increased metabolism, transport and biosynthesis of lipid, bile acid and xenobiotics. In conclusion, we propose that the chemoprotective effects of n‐3 PUFA/butyrate combination during cancer progression include activated transcription and chromatin acetylation of RXR/FXR function and lipid metabolism associated genes.
Bouts of sedentary time and cardiovascular risk factors in children
Authors: Oken Emily , CANTORAL Alejandra , Thompson Jennifer , Baccarelli Andrea , Svensson Katherine , Tellez‐Rojo Marta M , Wright Robert O 
Published: June 2021

IntroductionSedentary behavior is being widely recognized as a factor independently associated with several health outcomes. The aim of the present study was to examine the association between measured sedentary activity and cardiovascular risk factors in children between 4 and 5 years old. Methods: In a subsample of 132 children of the PRGRESS cohort in Mexico City, bouts of sedentary time were measured with an accelerometer for seven days, and the following biomarkers were determined: glucose, triglycerides, total‐cholesterol, HDL‐Cholesterol and LDL‐Cholesterol. Linear regression models were performed to estimate the association between bouts of sedentary time and the anthropometric and biochemical variables. Models were adjusted by sex, age in months, energy intake, BMI Z‐score and moderate physical activityResultsThe mean of sedentary bouts was 7.9 per day (SD +2.45), for each bout of sedentary time blood glucose and LDL‐cholesterol significantly increased (b= 0.90mg/dL, CI: .05, 1.74 and b=3.89mg/dl, CI: 0.67, 7.12 respectively); also as the bouts increased total‐cholesterol and triglycerides increased as well, although these association were not statistically significant (β= 3.23, CI: ‐0.59,7.05 and β=3.26, CI: ‐1.03, 7.55, respectively).ConclusionThe number of bouts of sedentary time was associated with cardiovascular risk factors independently of moderate physical activity.
Social Support and Sabotage: The Influence of Relationships on Health Eating and Physical Activity Behaviors in Rural Adults
Authors: Sriram Urshila , Morgan Emily , Graham Meredith , Folta Sara , Nelson Miriam , Paul Lynn , Kenkel Donald , Seguin Rebecca 
Published: June 2021

Social environments exert an important influence on nutrition and physical activity behaviors, yet few studies have examined the meaning of social ties in relation to the health of rural communities. This work explored how social relationships influence the adoption and maintenance of health‐related behaviors among midlife and older rural adults. Seventeen focus groups were conducted with 126 sedentary, overweight/obese adults aged 40‐91 years residing in government designated “medically underserved” rural Montana towns (average population <3,000). Groups were stratified by age (40‐64 and 蠅64) and gender. Transcripts were examined thematically according to social facilitators and barriers to healthy eating and physical activity. Results indicated that social ties had both health‐promoting and health‐damaging effects. Support from and accountability to family and friends were common facilitators of behavior change and maintenance. However, expectations to conform to social norms in these isolated communities often hindered healthy eating and physical activity. Participants reported feeling that ingrained ideas of what constituted a meal (e.g. meat and potatoes) and obligations to eat at social gatherings were barriers to adopting/maintaining healthier eating. These findings suggest that interventions targeting adults in rural settings need to consider the impact of social relationships in both supporting and sabotaging health behavior change and maintenance strategiesFunded by NIH/NHLBI, R01 HL120702‐01.
An Evaluation of Two Methods to Measure Hemoglobin Concentration among Women with Genetic Hemoglobin Disorders in Cambodia: A Method‐Comparison Study
Authors: Karakochuk Crystal , Janmohamed Amynah , Whitfield Kyly , Barr Susan , Vercauteren Suzanne , Kroeun Hou , Talukder Aminuzzaman , McLean Judy , Green Timothy 
Published: June 2021

Genetic hemoglobin (Hb) E variants are common in Cambodia and result in an altered and unstable Hb molecule. There are no known studies on the accuracy of Hb measurement using these methods in individuals with Hb E variants.MethodsWe measured Hb concentration in capillary blood using a hemoglobinometer (HemoCue) and in venous blood using a hematology analyzer (Sysmex XT‐1800i) in 420 Cambodian women (18‐45 y).ResultsBias and concordance appeared similar between methods among women with no Hb disorders (n=195, bias=2.5, pc=0.68), women with Hb E variants (n=133, bias=2.5, pc=0.78), and women with other Hb variants (n=92, bias=2.7, pc=0.73). The overall bias (difference in Hb means between methods) was 2.6 g/L , resulting in a difference in anemia prevalence of 11.5% (Hemocue 41% vs. Sysmex 29.5%, p <0.001). Based on concordance plots, the HemoCue device appears to underestimate Hb concentrations in capillary blood as compared to Sysmex (venous blood) at lower Hb concentrations, and to overestimate Hb concentrations in capillary blood as compared to Sysmex at higher Hb concentrations.ConclusionsBias and concordance were similar among all groups, suggesting the two methods were comparable in measuring Hb among women in all groups. We highlight the bias between the two methods to caution programming staff, researchers, and policy makers in the interpretation of data and the impact that even a small bias can have on anemia prevalence rates.