bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bone Geometry and Trabecular and Cortical Microarchitecture are Altered by Type 2 Diabetes, but not Insulin Resistance, in the Hyperphagic OLETF Rat
Authors: Dirkes Rebecca K. , Ortinau Laura C. , Richard Matthew W. , Linden Melissa A. , Rector R. Scott , Hinton Pamela S. 
Published: November 2023

Recently, fragility fracture has been added to the list of type 2 diabetes (T2D) complications. The purpose of this study was to determine the effects of insulin resistance (IR) and T2D on bone outcomes using the hyperphagic Otsuka Long‐Evans Tokushima Fatty (OLETF) rat model of T2D. Long‐Evans Tokushima Otsuka (LETO) and calorically restricted (CR; ~30% reduction vs. OLETF) OLETF rats weight‐matched to the LETO controls were used as lean, normoglycemic controls. The skeletal effects of IR and T2D were evaluated in 20‐ and 40‐week old male OLETF rats. Femur geometry and trabecular and cortical microarchitecture were analyzed using mCT. Cortical bone strength was analyzed by torsional loading of the femur to failure. The effects of IR and T2D on bone outcomes were compared using a two‐way (group, age) ANOVA; body weight (BW) was included as a covariate for body‐size‐dependent outcomes. As expected, the hyperphagic OLETF rats had significantly greater BW than controls. Blood glucose and insulin confirmed that OLETF rats were hyperglycemic and hyperinsulinemic at 20 weeks and at 40 weeks were hypoinsulinemic due to β‐cell dysfunction. At 20 weeks, only the cortical‐to‐total area ratio (Ct.Ar/Tt.Ar) was greater in IR OLETF versus CR controls. However, at 40 weeks bone geometry, microarchitecture, and biomechanical properties differed between OLETF rats and LETO and CR controls. OLETF rats had significantly shorter femur length than LETO and CR controls. Total cross‐sectional area and cortical area were greater in T2D OLETF rats versus LETO and CR controls. Ct.Ar/Tt.Ar and polar moment of inertia were greater in OLETF compared with CR. OLETF rats showed a greater increase in trabecular spacing and greater decreases in connectivity density from 20 to 40 weeks compared with LETO and CR controls; at 40 weeks T2D OLETF rats had reduced percent bone volume. T2D OLETF rats did not show the age‐related decline in torsional stiffness (Ks) observed in controls. Relative to CR, OLETF rats had a greater decline in ultimate tensile strength (Su), and at 40 weeks OLETF rats had reduced shear modulus of elasticity (G). In summary, bone geometry, trabecular and cortical microarchitecture, and biomechanical properties are altered by T2D, but not IR, in the hyperphagic OLETF rat relative to lean controls. The results of this study suggest that early identification and treatment of T2D might reduce the skeletal complications associated with hyperglycemia and β‐cell dysfunction.Support or Funding InformationThis work was funded by the VA Career Development Award and the Department of Nutrition and Exercise Physiology at the University of Missouri.
Efficacy of a Novel Food Fortification System to Combat Vitamin D Deficiency in rats
Authors: ALMAJWAL ALI M , Abulmeaty Mahmoud , Andrade Juan 
Published: November 2023

Background and aim of the workFortification of foodstuffs has proven effective in preventing micronutrient deficiencies. Dairy products are fortified in Saudi Arabia, but still vitamin D (VD) deficiency is highly prevalent. Therefore, development of sable and effective alternative micronutrient delivery technologies is required. The aim of this study is to test the efficacy of the novel vitamin D‐Nanoemulsion (VDN) developed by sonication and pH‐shifting of pea protein in vitamin D deficient rats.MethodsA total number of 35 healthy adult male albino young rats were used. Rats shortly after weaning (3–4 weeks old, weight 78.70±10.2 g) were divided primarily into two groups: rats of the C group (n=7) were fed on normal balanced growth diet. The remaining rats (n=28) were fed on vitamin D‐deficient, normal calcium and phosphorus diet for 6 weeks. Vitamin D deficient rats were subdivided into: T1 group (n=7) which treated with vitamin D‐Nanoemulsion (3 ml of VDN containing 27 ug/ml VD3) for 1 week. T2 group (n=7) that treated with vitamin D3 in oil (3ml of 27 ug/ml VD3), C1 group (n=7) that treated with 3 ml of Nanoemulsion without VD, and C2 group (n=7) that treated with canola oil without vitamin D for 1 week. Plasma 25 hydroxy vitamin D3 (25OHVD), parathyroid hormone (PTH), calcium (Ca), phosphorus (P) levels and activity of alkaline phosphatase (ALP) enzyme were estimated and femur bone used to prepare histopathological sections. Image J software was used to measure the histomorphometric changes. Paired T test and ANOVA with post hoc test were used to test statistical significance.ResultsSignificant increase of 25 hydroxyvitamin D3 after VDN treatment in T1 group (34.38±7.00 vs 14.65±1.29, P<0.01). Comparison of VDN with VD treated groups revealed significant changes of PTH, Ca, P, & LAP levels (25.22±14.26 vs 86.05±9.67, 9.64±0.60 vs 5.32±1.28, 3.65±0.71 vs1.33±0.32 & 72.37±30.97 vs 182.62±61.83, respectively). In addition, there was a significant improvement of osteoid area and reduction of trabecular separation of the bone sections.ConclusionsMicronutrient delivery technologies such as VDN is a successful delivery system in improvement of bone status in vitamin D deficient rats. Further research should be conducted about the safety and possibility of use in human.Support or Funding InformationThe Project was funded by the National Plan for Science, Technology, and Innovation (MAARIFAH), King Abdulaziz City for Science and Technology, Kingdom of Saudi Arabia, Award Number (12NAN2576‐02)
Consumption of S‐allylcysteine from garlic prevents ischemic injuries by augmentation of neovasculogenesis
Authors: Tang Feng‐Yao , Syu Jia‐Ning , Chiang En‐Pei Isabel 
Published: November 2023

BackgroundStudies suggest that a low level of circulating human endothelial progenitor cells (hEPCs) is a risk factor of ischemic injuries and coronary artery disease (CAD). Consumption of S‐allylcysteine (SAC) is known to prevent CAD. However, the protective effects of SAC on the ischemic injuries are not yet clear.ObjectiveWe examined whether SAC could prevent ischemic injuries through EPC‐mediated neovasculogenesis.ResultsThe results demonstrate that SAC significantly enhances the neovasculogenesis of hEPCs in vitro. The molecular mechanisms for SAC enhancement of neovasculogenesis include the activation of Akt/endothelial nitric oxide synthase (eNOS) signaling cascades. SAC increased the expression of c‐kit, β‐catenin, cyclin D1 and CDK4 proteins in hEPCs. Daily intake of SAC at dosages of 0.2 and 2 mg/per kg body weight (BW) significantly enhanced c‐kit protein levels in vivo.ConclusionDietary consumption of SAC prevents ischemic injuries by inducing neovasculogenesis in experimental models.
A Double‐Blind, Randomized Human Trial To Evaluate The Safety, Tolerability, And Host Response To Lactobacillus johnsonii N6.2
Authors: Lorca Graciela L , Marcial Guillermo G. , Ford Amanda L , Haller Michael J , Gonzalez Claudio F , Dahl Wendy J 
Published: November 2023

Several human trials have successfully showed oral Lactobacillus supplementation alleviates symptoms of disorders ranging from asthma to irritable bowel syndrome. It is increasingly clear that the gut environment may play a central role in the development of Type 1 Diabetes (T1D); however, the use of bacteria to alleviate the onset of this disease has been restricted to studies in rodent models. To date, the ability of a Lactobacillus probiotic to prevent T1D onset in humans has not been evaluated. We isolated and characterized L. johnsonii N6.2, which mitigated the onset of T1D when administered to Biobreeding diabetes‐prone rats. We determined that L. johnsonii N6.2 alters the activity of intestinal indoleamine 2,3‐dioxygenase‐1 (IDO), correlating with a Th17 bias in the mesenteric lymph nodes of animals protected from T1D onset. Translating this work toward the prevention of T1D in humans required a pilot study in healthy individuals. We performed a human trial to evaluate the safety, tolerability, and general response to consumption of this microorganism in healthy individuals (n=42; F=30, M=12; 23.2±5.5 y). The 13‐week study was divided into three phases: 1‐week pre‐baseline, 8‐week intervention (1 capsule/d of L. johnsonii N6.2 at 1010 CFU or placebo), and 4‐week wash‐out. Blood and fecal samples were collected and analyzed throughout the study. Stool samples were plated to determine transit survival of L. johnsonii N6.2. The administration of the probiotic did not modify the hemogram and chemistry profiles of participants suggesting general safety. The levels of tryptophan metabolites were determined in serum throughout the study. It was found that in participants who consumed L. johnsonii, the serum levels of kynurenine were decreased while increased amounts of tryptophan were observed. These results are in agreement with observations in rodent models of T1D. The results obtained from this pilot study will provide a solid foundation for the approval of an investigation into prevention of T1D onset by L. johnsonii N6.2 consumption in an at‐risk human population.Support or Funding InformationJuvenile Diabetes Research Foundation
Sex Differences in the Relationships Between Body Composition and Postoperative Outcomes in Patients Undergoing Hepatic Resection for Benign and Malignant Neoplasms
Authors: Tauscher Robert , Yin Wu , Idrees Kamran , Silver Heidi 
Published: November 2023

ObjectivesTo investigate relationships between skeletal muscle, visceral adipose, and subcutaneous adipose tissue on hospital length of stay (LOS), postoperative complications, ICU stay, and readmissions in male and female patients undergoing hepatic resection.MethodsAll patients undergoing hepatic resection at Vanderbilt University Medical Center between January 2006 and December 2013 were identified (N=449). Of these, only patients with a high‐quality image (low noise) from CT scan within 3 months prior to surgery were included (N=396). From CT, the L3 vertebra axial slice was analyzed for body composition using an automated version of Slice‐O‐Matic software. Images were corrected for attenuation errors by manual adjustments to assure complete quantification of tissues. Electronic medical record review was performed to acquire data for demographics, tumor characteristics, and outcome measures. Univariate and multivariate analyses evaluating potential predictive factors of short‐term outcomes were performed using SPSS version 23.ResultsOf the four body composition variables quantified – skeletal muscle area (SM), visceral adipose tissue area (VAT), subcutaneous adipose tissue area (SAT), and skeletal muscle attenuation (SMA) – having low VAT was significantly associated with worse short‐term outcomes in males. Specifically, low VAT was associated with longer hospital LOS (p=0.007), longer ICU LOS (p=0.01), more post‐operative complications (p=0.07), and more readmissions (p=0.008). Indeed, logistic regression analysis revealed that visceral adiposity is a strong and independent risk factor for ICU stay (p=0.04) and readmissions (p=0.01). Moreover, sex was a strong and independent prognostic factor of readmissions (p=0.002), with males having a greater likelihood of readmission than females. Interestingly, in females we found that low SMA (indicating fatty infiltration of muscle) was significantly associated with worse outcomes, specifically longer hospital LOS (p=0.03), longer ICU LOS (p=0.007), and more post‐operative complications (p=0.09).ConclusionsOverall, the body composition component that was the most robust prognostic factor for adverse short‐term outcomes in patients undergoing hepatic resection was the amount of VAT. In males, increased VAT seems to be protective against adverse short‐term outcomes. However, in females, it appears that low SMA – a reflection of muscle quality – is more associated with adverse short‐term outcomes.
Dietary associations with breast density in women on adjuvant Tamoxifen therapy within the Diindolylmethane Efficacy (DIME) Study
Authors: Strom Meghan , Wertheim Betsy C , Thomson Cynthia A , Maskarinec Gertraud 
Published: November 2023

Breast density (BD) describes the distribution of epithelial and connective versus fatty tissue; higher BD is a predictor of higher breast cancer risk. Tamoxifen (TAM) is a commonly prescribed anti‐estrogen adjuvant cancer treatment to reduce breast cancer risk, partially through modulation of breast density. Dietary components, including fiber, fat, and total energy intake, potentially influence BD. The relationship between dietary intake and BD in women prescribed TAM is not fully understood. We conducted a cross‐sectional analysis using baseline data collected from 130 pre‐ and post‐menopausal women taking TAM and enrolled in the Diindolylmethane Efficacy (DIME) Study. BD was measured from digital mammograms, and participants completed the Arizona Food Frequency Questionnaire to assess dietary intake. Mean BD was 25% ± 15%. Linear regression examining dietary exposures of intake and adjusted for age, time on TAM, menopausal status, and body mass index (BMI) indicated no significant association between BD and total energy intake. No other associations between dietary factors and BD were observed, including total fat, protein, and carbohydrate intake as well as intake of fiber, fruit, vegetables, cruciferous vegetables, and alcohol. Dietary intake shows little association with BD among women taking TAM therapy. Alternate preventive mechanisms for diet in women on TAM therapy should be investigated, including potential effects on estrogen and TAM metabolism.Support or Funding InformationSupported by National Institutes of Health (NIH), National Cancer Institute (NCI) funding under 1R01CA149417‐01A1 (Thomson‐PI) and the University of Arizona Comprehensive Cancer Center Support grant funded by NIH‐NCI grant #CCSG‐CA023074 (Alberts‐PI).
Higher direct bilirubin levels during the second trimester of pregnancy is associated with lower risk of gestational diabetes mellitus
Authors: Liu Chaoqun , Zhong Chunrong , Zhou Xuezhen , Chen Renjuan , Yang Hongying , Xiao Mei , Yang Nianhong 
Published: November 2023

BackgroundBilirubin concentrations have been recently reported to be negatively associated type 2 diabetes mellitus (T2DM). We examined the association between bilirubin concentrations and gestational diabetes mellitus (GDM).MethodsIn a prospective cohort study (Tongji Maternal and Child Health Cohort, TMCHC), 1739 pregnant women were recruited prior to 16 weeks of gestation and were followed up until delivery. The value of bilirubin was tested and oral glucose tolerance test (OGTT) was conducted to screen GDM. The relationship between serum total bilirubin (TB) concentration and gestational weeks was studied by two‐piecewise linear regression. A subsample of 822 participants with serum bilirubin test during 12 to 22 weeks gestation was conducted to research the association between serum bilirubin levels and risk of GDM by multiple linear regressions and logistic regression.ResultsGDM developed in 9.9% of the participants (172 of 1793). A nonlinear relationship between serum total bilirubin and the gestational week was exhibited through the scatterplot smoothing after adjusted for BMI, age supplements intake, sleep quality, smoking, and alcohol intake. Two‐piecewise linear regression analyses demonstrated threshold effect between serum total bilirubin and the gestational week from 2493 tests of 1739 participants. Serum total bilirubin levels decreased with gestational week up to the turning point 25.6 (β=−0.008, p<0.001). When the gestational weeks exceeded 25.6, TB level was increased slightly (β=0.002, p=0.004).The unadjusted logistic regression analysis indicate that the risk for the development of GDM was lower in the highest tertile of serum direct bilirubin concentrations than that in the lowest tertile (RR, 0.64; 95%CI, 0.44 to 0.95). After adjusting for BMI and age, the RR remains 0.66 ( 95%CI, 0.44 to 0.97). After further adjusting for SBP, DBP, smoking, alcohol intake, sleep quality, and family history of diabetes, hypertension and obesity, the RR was 0.65 ( 95%CI, 0.44 to 0.96). Serum total and indirect bilirubin levels were slightly association with the incidence of GDM. In adjusted logistic regression analysis, highest tertile of serum total bilirubin concentrations has lower risk for the development of GDM than the lowest (RR, 0.87; 95%CI, 0.73 to 1.03). After adjusted for BMI, age and other confounders, the RR was 0.88 (95%CI, 0.70 to 1.12).ConclusionsThe results suggested that higher maternal serum direct bilirubin during second trimester of pregnancy could be a protective factor for the development of GDM later.Support or Funding InformationNational Program on Basic Research Project of China: NO.2013FY114200
The thyroid hormone T4 improve antioxidant capability and regulate type II and type III deiodinase activity in MIN6 cell in vitro culture
Authors: Tang Xue , Wang Fei , Le Guowei , Shi Yonghui 
Published: November 2023

The objective of our study is to analyze whether thyroxine (T4) could maintain the redox homeostasis and insulin secretion function of pancreatic β cells under H2O2‐induced oxidative stress. MIN6 cells were treated with/without H2O2 (200μM) for 6h and exposed to T4 (10−5M, 10−6M and 10−7M) for 48 h. Viable cells were harvested, and dichloro‐dihydro‐fluorescein diacetate (DCFH‐DA) was used to detect reactive oxygen species (ROS) level; glutathione (GSH) and glutathione disulphide (GSSG) ratio, total antioxidant capacity (T‐AOC) and malandialdehyde (MDA) level were assayed with the appropriate test kits; cell viability was determined by MTT assay; the activity of type II and type III deiodinase (D2 and D3), conversation rate of T4 to T3 and insulin secretion were also measured in the present study. The results showed that H2O2 induced ROS production and cell death, and induced adverse affects in relation to antioxidant defense systems and insulin secretion. These changes were restored by T4 incubation in a dose‐dependent manner. Moreover, T4 increased the conversation rate of T4 to T3 by regulating D2 and D3 activity. These findings indicates that protective effects of T4 on redox homeostasis and insulin secretion may be related about its role in regulating the antioxidant capacity and D2 and D3 activity.Support or Funding InformationThe present study was supported by the 12th Five‐Year Plan for for Science and Technology Development (No. 2012BAD33B05)
INTRAUTERINE THERAPY OF INTRAUTERINE GROWTH RESTRICTION
Authors: Gumus Hatice Gulcin , Illa Miriam , Pla Laura , Crispi Fatima , Gratacos Eduard 
Published: November 2023

BackgroundIntrauterine growth restriction (IUGR) is one of the most prevalent causes of fetal mortality and fetal morbidity, affecting up to 10% of all births and it is associated with increased risk of neurological, cardiovascular and metabolic diseases later in life. Even though numerous studies intended to find a therapy for IUGR, no standard therapy for IUGR has been established so far.ObjectiveTo examine the effect of an intrauterine nutritional therapy in the IUGR rabbit model in terms of survival and birth weight.MethodsIUGR was surgically induced in pregnant rabbits (n=16) at gestational age 25 by ligating 40–50%of uteroplacental vessels of each gestational sac in both uterine horns. At the same moment, fetal injections of Total Parenteral Nutrition solution (TPN) was administered into the amniotic sac of IUGR fetuses (n=90) in one horn, whereas sham injection was performed in the contralateral horn (n=86). Five days after, a cesarean section was performed obtaining treated and non‐treated IUGR animals.ResultsSurvival rate of treated IUGR animals were significantly higher than the non‐treated IUGR animals (61.5% and 41.9% respectively, p=0.013). Birth weight were similar between groups (38.4 g ± 9.3 SD vs. 36.2 g ± 8.5 SD, p=0.49, treated vs. non‐treated IUGR respectively,).ConclusionOur data suggests that TPN solution directly administrated to the IUGR animals at the time of IUGR induction could increases the survival rate, with no difference in birth weight. Further studies are needed in order to confirm the results and try to fully evaluate the potential benefits of such strategy in promoting fetal survival.Support or Funding InformationThis study was partly supported by grants from Ministerio de Economia y Competitividad (ref. SAF2012‐37196); the Instituto de Salud Carlos III (ref. (PI12/00851) integrado en el Plan Nacional de I+D+I y cofinanciado por el ISCIII‐Subdirección General de Evaluación y el Fondo Europeo de Desarrollo Regional (FEDER) “Otra manera de hacer Europa”; Obra Social “la Caixa” (Barcelona, Spain); and AGAUR 2014 SGR grant n&[ordm] 928 (Barcelona, Spain). HGG has also been funded with support of the Erasmus + Programme of the European Union (Framework Agreement number: 2013‐0040). This publication reflects the views only of the author, and the Commission cannot be held responsible for any use which may be made of the information contained therein.
Impact of High‐Flavanol and High‐Theobromine Chocolate Consumption on Lipid Profile in Women at Risk of Preeclampsia: a Double Blind Randomized Clinical Trial
Authors: Lebel Élise Lavoie , Leblanc Vicky , Giguère Yves , Babar Asma , Marc Isabelle , Lemieux Simone , Belkacem Abdous , Bujold Emmanuel , Sidi Elhadji Anassour Laouan , Bazinet Laurent , Dodin Sylvie 
Published: November 2023

Despite discrepancy among results in the literature, flavanol‐rich chocolate consumption during pregnancy could have beneficial effects on the risk of preeclampsia (PE) through improvement of blood pressure and endothelial function. Theobromine, a major constituent of dark chocolate, also possesses vasodilatation properties. However, to our knowledge, no study has investigated the effect of high‐flavanol and high‐theobromine chocolate consumption on lipid profile in pregnant women at risk of PE.ObjectiveTo assess the impact of high‐flavanol and high‐theobromine chocolate consumption on lipid profile in pregnant women at risk of PE.MethodsA single‐center randomized controlled trial was conducted in women with singleton pregnancy between 11 and 14 weeks gestation. Uterine artery Doppler was performed and women with bilateral diastolic notches and either a uterine artery pulsatility index (PI) >95th percentile on one side and/or bilateral PI>50th percentile were considered as potentially eligible for randomization. A total of 131 pregnant women were randomly assigned to either high‐flavanol, high theobromine (HFHT) or low‐flavanol, low‐theobromine (LFLT) chocolate groups. Women had to consume a total of 30 g of chocolate on a daily basis for 12 weeks. Fasting blood samples and anthropometric variables were measured at baseline and at 12 weeks.ResultsA significant group by time interaction was observed for triglyceride concentrations (p=0.006), with a more pronounced increase in the LFLT group (increases of 0.6 mmol/L in HFHT versus 0.8 mmol/L in LFLT). Significant time effects were observed in total‐C, LDL‐C, HDL‐C and total‐C on HDL‐C ratio (p< 0.0001), with similar increases in both HFHT and LFLT chocolate groups. A significant group by time interaction was noted for body weight (p=0.03), with a greater weight gain in the HFHT group.ConclusionOur results suggest that consumption of HFHT chocolate could have beneficial effects on triglyceride concentrations in pregnant women at risk of PE.Support or Funding InformationThis research project was supported by Canadian Institute of Health Research by the Jeanne and Jean‐Louis Lévesque Perinatal Research Chair at Laval University.