bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of 1 year of alternate day fasting versus daily calorie restriction on type 2 diabetes risk
Authors: Kroeger Cynthia , Trapanowski John , Barnosky Adrienne , Klempel Monica , Varady Krista
Published: June 2021

Alternate day fasting (ADF) is effective for weight loss and cardio‐protection, but its effect on type 2 diabetes (T2D) risk remains unclear. Moreover, whether ADF produces greater reductions in T2D risk versus daily calorie restriction (CR) is also unknown. Accordingly, this study compared the effect ADF versus CR on T2D risk indicators. Obese subjects (n = 48) were randomized to: 1) ADF (75% restriction fast day alternated with ad libitum feed day), or 2) CR (25% restriction everyday), for a 6‐month weight loss period followed by a 6‐month weight maintenance period. Body weight, fat mass, and visceral fat mass decreased similarly (P < 0.01) in the ADF (7 ± 1 kg; 5 ± 1 kg; 0.4 ± 0.1 kg) and CR group (7 ± 1 kg; 5 ± 1 kg; 0.4 ± 0.1 kg) during the weight loss period, and remained stable during the weight maintenance period. Fat free mass did not change throughout the study. Glucose remained unchanged. Insulin decreased (P < 0.05) by ADF only (7 ± 4 uIU/ml) with weight loss, and was sustained with weight maintenance. HOMA‐IR remained unchanged in both groups. Resistin, an adipokine involved in insulin resistance, decreased (P < 0.05) by ADF (2 ± 2 ng/ml) and CR (4 ± 1 ng/ml) with weight loss, and was sustained with weight maintenance. Thus, ADF and CR produce mild but comparable reductions in T2D risk, which are sustained with weight maintenance.
Effects of Elevating Colonic Propionate on Liver Fat Content in Adults with Non‐Alcoholic Fatty Liver Disease
Authors: Chambers Edward , Viardot Alexander , Psichas Arianna , Morrison Douglas , Murphy Kevin , Zac‐Varghese Sagen , Preston Tom , Tedford Catriona , Bell Jimmy , Thomas Louise , Dhillo Waljit , Bloom Stephen , Frost Gary
Published: June 2021

Non‐alcoholic fatty liver disease (NAFLD) is reported in 20% of adults worldwide, a condition associated with an increased risk of developing type 2 diabetes. Positive physiological effects have been linked with the production of short chain fatty acids (SCFA) by colonic fermentation of dietary fiber, including reductions in hepatic fat content. We have developed a novel inulin‐propionate ester (IPE), whereby the SCFA propionate is bound to the dietary fiber inulin. The bound propionate is only released through fermentation in the colon and we hypothesized that long term elevations in colonic propionate production would reduce liver fat in adults with NAFLD. Sixteen participants (40‐65 years) were recruited and intrahepatocellular lipid (IHCL) was determined using 1H‐MRS. All participants were identified as having NAFLD on the basis of a liver fat content >5%. Participants were provided with either 10 g/day IPE (n=11) or 10 g/day inulin control (n=5) to add to their normal diet for a 24 week period. In the IPE group a significant reduction in IHCL content post‐intervention was observed (22.1±9.6% to 15.9±7.1%; P=0.038). This effect was not found in the inulin control group (19.1±6.2% to 18.7±4.2%; P=0.576). Targeting increased colonic propionate levels may offer a public health solution to the increased prevalence of NAFLD and warrants further investigation.
Bile Acids Promote Diethylnitrosamine‐induced Hepatocellular Carcinoma via Increased Inflammatory Signaling.
Authors: Apte Udayan , Sun Lina , Borude Prachi , Bhushan Bharat , Manley Michael , Li Hua
Published: June 2021

Hepatocellular carcinoma (HCC) is the most common hepatic malignancy and the third leading cause of cancer related deaths. Previous studies have implicated bile acids in pathogenesis of HCC but the mechanisms are not known. We investigated the mechanisms of bile acid‐mediated promotion of HCC using a diethylnitrosamine (DEN)‐mediated initiation‐cholic acid (CA)‐induced tumor promotion protocol in mice. The data show that 0.2% CA treatment resulted in 3‐fold increase in number and size of DEN‐induced liver tumors. All tumors observed in DEN‐treated mice were well‐differentiated HCCs. Microarray based global gene expression studies combined with Ingenuity Pathway Analysis revealed NF‐κB pathway as the main signaling pathways activated in the DEN‐treated 0.2% CA‐fed livers. Further studies showed significantly higher TNFα, IL‐1β, MCP‐1 mRNA, a significant increase in total and phosphorylated‐p65 and phosphorylated IκBa (degradation form) and higher EGR1 mRNA and protein in livers of DEN‐treated 0.2% CA‐fed mice. Interestingly, total bile acid quantification revealed increase in hepatic and serum bile acids in both DEN‐treated and DEN‐treated 0.2% CA‐fed mice, which was higher in the latter group. Finally, quantification of total serum bile acids in normal, cirrhotic and HCC human samples revealed increased bile acids in serum of cirrhotic and HCC patients. Taken together, these data indicate that bile acids are mechanistically involved pathogenesis of HCC and may promote HCC formation via activation of inflammatory signaling.
Profiling of Human Milk miRNA
Authors: Hassiotou Foteini , Alsaweed Mohammed , Savigni Donna , Lai Ching Tat , Hartmann Peter , Geddes Donna
Published: June 2021

Breastmilk has been recently identified as a rich source of miRNA with potential regulatory functions in the infant. We compared the miRNA content of breastmilk with that of circulating blood in lactating women, with the aim to shed light into the potential functions of these milk molecules and their origin. Breastmilk and blood samples were collected from 10 mothers in month 2 of lactation. miRNA was analyzed from the cellular and lipid fraction of breastmilk as well as maternal peripheral blood mononucleated cells (PBMCs) and plasma using the TaqMan OpenArray system for 770 different human miRNAs. The total miRNA content of breastmilk and blood was high, particularly in the breastmilk cellular fraction and PBMCs. More than 293 miRNA species were detected in breastmilk cells, 233 in the breastmilk lipids, 169 in blood plasma and 345 in PBMCs. Single correlation analysis showed that within milk cells, milk lipids, and PBMCs, miRNA expression levels were similar among participants. In plasma, marked inter‐individual variation in single miRNA species was observed. Cluster analysis indicated that the miRNA profiles of breastmilk cells and lipids grouped together; however, differences were seen between PBMCs and plasma, with the latter showing the most variable miRNA composition. This study confirms the rich miRNA nature of human breastmilk. Our comparisons between blood and milk miRNA suggest that a proportion of milk miRNA may be derived from the maternal bloodstream, whilst some may originate from the breast epithelium. Given the recently identified stability and function of food‐derived miRNA in regulating mammalian genes, we propose that breastmilk is a rich source of miRNA, which may contribute to early infant development.
Mothers and Others: Designing a Randomized Trial to Prevent Obesity among Infants and Toddlers
Authors: Wasser Heather , Bentley Margaret
Published: June 2021

Background

Despite increases in obesity among children under 2 years, few interventions have targeted this age group. Mothers and Others (M&O) will close this gap by testing the efficacy of a multi‐component obesity prevention intervention versus an attention control (child safety) in promoting healthy weight gain patterns among African‐American (AA) infants. The current study describes the design process and formative research findings.
Methods: Formative data came from 3 sources: existing literature; preliminary longitudinal cohort of 217 AA mother‐infant dyads; and, 20 semi‐structured interviews with AA moms, dads and grandmothers.
Results: The trial will be conducted among 468 AA mothers recruited through antenatal clinics. Intervention mothers will identify a study partner to participate with her. Delivery channels include face‐to‐face peer counseling through 6 home visits, support from a lactation consultant, 6 newsletters, and twice weekly text messages. Outcomes include differences in weight‐for‐length z‐scores at 18 months (main outcome) and breastfeeding, healthy complementary feeding, age‐appropriate sleep duration and lower levels of television and electronic media exposure (secondary outcomes). Formative feedback was generally positive, with target participants also requesting information on postpartum weight loss, depression, maternal sleep, father‐infant bonding and maintaining intimate relationships.

Discussion

M&O contains several innovations, including beginning during a ‘teachable’ moment, pregnancy; active engagement of multiple caregivers; and use of text messaging. If successful, M&O will have high public health relevance for future obesity‐prevention efforts aimed at children less than 2 years.

Funding: NIH/NICHD
Induction of differentiation of small intestinal enterocyte cells by maltooligosaccharides
Authors: Chegeni Mohammad , Hamaker Bruce
Published: June 2021

Maltose and maltooligosaccharides are the primary products from starch digestion by pancreatic α‐ amylase and are major substrates for enterocyte intestinal α‐glucosidases. We have recently shown that maltooligosaccharides act as signal molecules to stimulate the maturation and trafficking of disaccharidases for their subsequent digestion. As this finding is potentially indicative of a maltooligosaccharides sensing ability by enterocytes, it suggests another control glycemic response. It appears also that maltooligosaccharides may signal other events in small intestine enterocytes. Culture‐related conditions (e.g. glucose concentration) have been known to alter physical barrier properties of Caco‐2 cell monolayers, which predominantly affects transepithelial transport of solutes permeating the cell barrier. Transepithelial electrical resistance experiments have been conducted to measure the integrity of monolayer of intestinal epithelial cells in response to maltooligosaccharides. Results showed higher resistance related to reduced permeability in cells treated with maltose. In addition to barrier function of small intestine enterocytes, metabolomics study was conducted using high‐resolution 1H NMR. Results showed that concentration of metabolite profiles which are known to be as markers for cell differentiation increase in Caco‐2 cells treated with different types of maltooligosaccharides compare to glucose and sucrose. Thus, maltooligosaccharides appear to signal intestinal enterocytes cells to promote faster cell differentiation.
Effects of Short Chain Fatty Acids on Glucose and Lipid metabolism in Adipocytes
Authors: Mora Silvia , Fullerton Robert
Published: June 2021

Short chain fatty acids (SCFA) are major products of bacterial fermentation by gut microbiota. Recent literature suggests that microbiota contribute to regulate glucose homeostasis and insulin sensitivity in the host. The purpose of the study was to determine whether the SCFAs acetate, butyrate and propionate impact on glucose and lipid metabolism and insulin signalling in adipose cells in vitro. We cultured differentiated 3T3L1 adipocytes in the presence of acetate, butyrate or propionate for 48 hours. We determined glucose transporter expression and activation of insulin signalling cascades by western blotting. We measured insulin‐stimulated 2‐deoxyglucose uptake and determined total Triglyceride content and expression and activation of Hormone Sensitive lipase (HSL) and Adipose Triglyceride Lipase (ATGL) by western blotting. None of the SCFAs had an effect on Glut1 or Glut4 glucose transporter expression or elicited an effect on basal or insulin‐stimulated glucose uptake. Insulin‐mediated activation of AKT and ERK were similar to that obtained in control untreated cells. While acetate and propionate did not have any effect in total triglyceride accumulation compared to control cells, butyrate treated cells showed lower lipid content compared to untreated cells. Butyrate treated cells showed increased levels of phosphorylated HSL (Ser 660) in basal state (no insulin) whereas the response to insulin was similar to that of untreated cells. We did not detect any changes in the expression levels of HSL, but cells treated with butyrate had increased ATGL levels compared to untreated cells. These data suggests that SCFA do not directly modify glucose uptake, and that butyrate but not other SCFA reduces lipid content by increasing the basal activity of HSL and expression of ATGL in adipocytes.
Predictors of Adherence to Preconception and Prenatal Micronutrient Supplementation in Vietnam
Authors: Gonzalez‐Casanova Ines , Nguyen Phuong , Harding Kim , Reinhart Greg , Nguyen Hieu , Truong Truong , Pham Hoa , Nguyen Son , Martorell Reynaldo , Ramakrishnan Usha
Published: June 2021

We examined predictors of adherence to preconception and prenatal micronutrient supplementation, using data from a randomized controlled trial in rural Vietnam. 5011 women of reproductive age were randomized to receive weekly PRECONCEPT supplements containing either: Folic Acid, Iron and Folic Acid (IFA), or Multiple Micronutrients. Women who became pregnant (1744) received daily prenatal IFA (GESTCARE) supplements through delivery. Monitors visited women's homes every 14 d to deliver supplements and record consumption and side effects. 59% and 75% consumed all the tablets that they received for PRECONCEPT and GESTCARE, respectively. In logistic regression analyses, women anemic at baseline (OR, 95% CI=1.25, 1.06 1.47), farmers (OR, 95% CI=1.28, 1.07 1.53), and minority ethnicity (OR, 95% CI=1.50, 1.31 1.71) were more likely to have lower adherence to PRECONCEPT supplements and minority ethnicity with lower adherence to GESTCARE (OR, 95% CI=1.33, 1.01 1.77). There were no differences by type of supplement. Parity, body mass index, side effects, and education did not predict adherence (p>0.05). Adherence to preconception and prenatal supplementation was high among women from a rural province of Vietnam. Lower adherence in vulnerable groups suggests a need to develop tailored behavior change interventions to accompany micronutrient supplementation in this population. Funded by the Micronutrient Initiative and the Mathile Institute.
Sanguinarine instead of Tryptophan on Growth and Metabolism of Pig under Conditions of Lower‐protein Diets
Authors: Xi He , Shirui Zhang , Long Yue , Qian Lin
Published: June 2021

The experiment was conducted to investigate the effect of sanguinarine on the growth performance of pigs under the conditions of lower‐protein diets. 192 healthy Duroc×Landrace×Large pigs with average body weight of 25 kg were randomly selected and allocated to 4 groups, 6 replicates in each group and 8 pigs in each replicate.The group I to IV were separately feeding with lower‐protein diet, lower‐protein without tryptophan diet, lower‐protein without tryptophan but with sanguinarine diet and basal diet. The experiment consisted of two stages according the weight about 25‐60 kg and 60‐100 kg.

Results showed that: 1)There were no significant difference on growth performance of the whole period among each group (P>0.05). 2) The serum tryptophan levels of group III was always higher than group II(P<0.05), but there was no significant difference between the four groups (P>0.05). 3) Caecum sections' skatole was lowest in group III, but there was no significant difference among all the groups (P>0.05). In the colon, the contents of skatole of group II and group III were significantly lower than groupIand group IV(P<0.05).The activity of tryptophan decarboxylase (TDC) in the jejunal and ileum which from group III was lower than group II (P>0.05),and there were no significant difference among those groups.

In general, the sanguinarine showed no difference on the growth performance of pigs. And sanguinarine couldn't affect the skatole which comes from the tryptophan metabolite. It showed that the sanguinarine could improve the content of tryptophan in the serum, and influence the activity of the tryptophan decarboxylase in pigs' gut, all this could be beneficial to the synthesis of protein.
The Impact of Tubaramure, a Food‐Assisted Integrated Health and Nutrition Program in Burundi, on Children's Development
Authors: Olney Deanna , Leroy Jef , Bliznashka Lilia , Ruel Marie
Published: June 2021

Tubaramure is a food‐assisted integrated health and nutrition program that targets pregnant women and their children up to 2 y of age (first 1000 d). Program beneficiaries received monthly food rations (corn‐soy blend and oil) and attended bi‐monthly nutrition and health education sessions and preventive health visits. We evaluated the program's impact over 2 y using a cross‐sectional cluster randomized controlled study. Sixty villages were assigned to one of 4 study groups that received benefits for different durations: T24: pregnancy up to 24 m; T18: pregnancy to 18 m; TNFP: same as T24, but without food rations during pregnancy; and Control. We estimated the program's impact on children's motor (30 milestones) and language (21 milestones) development in three age groups (4‐11 m, 12‐17 m and 18‐24 m).

Tubaramure had statistically significant positive impacts on children's motor and language development although the pattern of impacts varied by age. The program led to higher achieved motor milestones among children aged 12‐17 m in the TNFP and T18 groups compared to control (1.2 and 0.8 milestones, respectively). No effect was found in T24. Tubaramure positively impacted language development among children 12‐17 m in the TNFP and T18 groups (0.9 and 0.8 milestones, respectively) and among children 18‐24 m in the T18 and T24 groups (0.8 and 1.6 milestones, respectively). There were no significant program impacts on motor or language development among children aged 4‐11 m. Tubaramure had a significant impact on motor development around the age when children obtain bipedal locomotion and on language development as they gain more language skills.

Funded by USAID's Food and Nutrition Technical Assistance Project & CGIAR Research Program on A4NH, led by IFPRI.
Effect of Small‐Quantity Lipid‐Based Nutrient Supplement (SQ‐LNS) on Breast Milk Vitamin A Concentration among Ghanaian Women
Authors: Klevor Moses , Haskell Marjorie , Lartey Anna , Adu‐Afarwuah Seth , Zeilani Mamane , Dewey Kathryn
Published: June 2021

Background

Vitamin A deficiency remains a global public health problem.

Design

Women 蠄 20 weeks of gestation (N=1,320) were randomly assigned to receive either a multiple micronutrient supplement (MMN) providing 18 micronutrients including 800 µg RE vitamin A or SQ‐LNS with the same nutrients as the MMN group, plus four minerals and macronutrients contributing 118 kcal daily until 6 months postpartum; a control group received iron and folic acid only (IFA) during pregnancy and a placebo during the first 6 months postpartum. Breast milk samples collected at 6 months postpartum were analyzed for retinol and fat concentrations in a subsample of 756 women.

Results

Average ± SD breast milk retinol concentration, per gram of fat, was 56.3 ± 2.1 nmol/g; there were no significant differences between groups [IFA (n=243) 59.1 ± 2.8, MMN (n=260) 55.4 ± 2.5, LNS (n=253) 54.7 ± 2.5 nmol/g fat; p=0.45], regardless of whether the woman had or had not received a high‐dose vitamin A supplement (200, 000 IU) soon after childbirth.

About 17% of participants had low milk retinol (蠄 28 nmol/g fat), whereas we estimated that 36% of infants were potentially receiving vitamin A at levels above the Tolerable Upper Level (UL, 600 µg RAE/day).

Conclusion

Daily low dose vitamin A supplementation did not increase breast milk vitamin A levels in this sample of Ghanaian women. Women in this population may have had adequate dietary vitamin A intake.
The impact of Tubaramure, a food‐assisted integrated health and nutrition program in Burundi, on maternal and child anemia
Authors: Leroy Jef , Olney Deanna , Ruel Marie
Published: June 2021

Tubaramure is a food‐assisted, preventive maternal and child health and nutrition (MCHN) program targeted to pregnant women and their child 0‐2 y of age (first 1000 days) in two highly food insecure provinces in Burundi. Monthly food rations include corn‐soy‐blend (CSB) and vit A‐ and D‐fortified oil. We evaluated the program's impact using a cluster randomized controlled study, where 60 villages were assigned to: T24: benefits during pregnancy up to 24 m; T18: pregnancy up to 18 m; TNFP: same as T24, but without food rations during pregnancy; and Control. We estimated the program's impact on Hb and anemia in children 0‐24 m and their mothers using double difference estimates with repeated cross‐sectional data at baseline (BL) and 2 y later (EL). We used mixed methods to document pathways of impact.

Mean Hb was significantly lower at EL compared to BL in children (0.8 g/dL) and their mothers (0.7 g/dL), but the program had a significant protective effect. Compared to control, Hb in beneficiary children dropped 0.3‐0.5 g/dL less; in mothers 0‐3 m post‐partum, anemia increased 24‐39 pp less. Impact pathway analyses suggest that impacts were achieved through positive changes among children in dietary diversity, intake of Fe‐rich foods, bednet use, and lower morbidity; among mothers, bednet use appears to be part of the pathway. Differences between treatment groups will be discussed. This theory‐based impact evaluation demonstrated the effectiveness of a preventive food assisted MCHN program on children's HB and maternal anemia and highlighted the contribution of different program inputs in achieving this impact.

Funded by USAID's Food and Nutrition Technical Assistance Project & CGIAR Research Program on Agriculture for Nutrition and Health (A4NH), led by IFPRI.
The Recruitment of the Transcription Factor YY1 to DNA Damage Sites in Human Cells
Authors: Tesfazghi Merih , Riman Sarah , Alexander karen , Rizkallah Raed , Hurt Myra
Published: June 2021

Our DNA is under continuous stress by endogenous and exogenous attacks such as genotoxic chemicals, ionizing radiation, and metabolic products. DNA damage is extremely detrimental, even a single unrepaired damage is sufficient to kill a cell. Cells mobilize a tightly regulated complex repair signaling pathway to either mend or remove the damaged DNA and avoid harmful consequences such as malignant transformation and genome instability syndromes. Here, for the first time, we show the rapid and transient recruitment of the transcription factor YY1 to laser induced damage sites in live human cells in real time, suggesting the early and direct role of YY1 in DNA repair. Use of a panel of YY1 deletion constructs reveal that part of the C‐terminus of the protein is required for the damage response and identified the repair response domain. Our findings provide first evidence for the early and potentially direct role of YY1 in DNA repair. To advance insight into the contribution of YY1 in DNA damage response, we continue to investigate the role of YY1 and its regulation in real time using different knockout human cells, inhibitors, and RNAi technology. Our findings will ultimately provide evidence on the mechanistic role of YY1 in DNA repair and further our understanding in the role of YY1 in genome integrity and maintenance.
The Risk of Overweight and Insufficient Dietary Intake among Children in Low‐income Family in South Korea
Authors: Min Jungwon , Lee Jeong‐rim , Lim Hyunjung
Published: June 2021

Aims

Obesity prevalence has increased steadily in Asian countries. Especially low‐income child is known as vulnerable to obesity due to the limited access to affordable foods and health care. To identify the health and nutrition condition of low‐income children in South Korea, data from the fifth Korean National Health and Nutrition Survey(2010‐2012) was used. Methods: To define the risk of children's health and nutrition status, we adapted the classifications of the Korean family income level(The National Statistical Office, 2012), Korean child standard growth charts(KCDC, 2007), and Korean nutrition intake standards(The Korean Nutrition Society, 2010). Data from age 1 to age 5(n=2,272,243) were analyzed by survey module in SAS. Results: The children's overweight risk decreased by family income. 13.6% children in family with the minimum cost of living were over 95percentile in BMI. However their undergrowth(<5percentile in BMI) rate is the lower(2.2%) compared with other income groups. Those children in the lowest income group had the highest percent of inadequate intake of carbohydrate and fat among children(52.4%, 44.0%). They also had largest rate of insufficient intakes in Vitamin A(37.5%), B1(20.0%), B2(23.9%), Niacin(29.5%), Vitamin C(43.1%), Calcium(64.7%), and iron(41.2%).

Conclusions

For the healthy growth among children in low‐income families in South Korea the accessibility of healthy foods and health care are need to be secured.
Design and Characterization of a Multicellular, Three‐Dimensional (3D) Tissue Model of the Human Kidney Proximal Tubule
Authors: King Shelby , Creasey Olivia , Presnell Sharon , Nguyen Deborah
Published: June 2021

Renal toxicity is a major cause of drug attrition at the clinical trial stage, and the primary site of this toxicity is within the proximal tubule. Conventional renal cell culture models lack the complexity of native tissue and thus have a limited capacity for predicting tissue‐level responses. In addition, the predictive potential of pre‐clinical animal trials is limited due to species‐specific differences between human and animal renal functions, including differential sensitivity to insults. We designed and fabricated a human three‐dimensional (3D) tissue model of the tubulointerstitial interface in which human renal interstitial tissue is supporting proximal tubule epithelial cells to facilitate their optimal morphology and function. Histological characterization demonstrated that the interstitial layer is viable and well organized, containing well‐developed CD31+ endothelial cell networks. Method optimization resulted in the formation of a polarized layer of renal epithelium on top of the interstitial layer, and formation of a basement membrane between the layers. Gene expression analysis showed that the renal tissues expressed key enzymes involved in metabolism and protein processing (CYPs, renin‐angiotensin system), suggesting that physiologic function is retained. These bioprinted human tissues may provide an opportunity to accurately study how compounds affect the renal proximal tubule as well as modeling pathogenic processes that involve tubular transport, cell‐cell interactions, and the development of tubulointerstitial fibrosis.

This work was supported with internal funds.
Genetic Regulation of Endothelial Responses to Exercise Training
Authors: Kim Seung , Avila Joshua , Massett Michael
Published: June 2021

Exercise training improves endothelial function in a duration and intensity‐dependent manner. The aim of this study was to characterize the genetic contribution to phenotypic variation in endothelial adaptation to exercise training. Concentration response curves to acetylcholine (ACh) and sodium nitroprusside (SNP) in isolated thoracic aortas from male mice (n ∼ 6/group/strain, 12 wks) from 26 inbred strains were obtained after moderate intensity continuous training (MOD) or sedentary controls (SED) for 4 weeks. Endothelium‐dependent relaxation to ACh (EDR) in SED mice varied by ~2 fold between two strains having the highest and lowest responses. However, only A/J and NON showed greater EDR in MOD mice compared to SED. Responses to SNP were similar among strains and between groups. These results imply that MOD for 4 weeks might not be sufficient to stimulate changes in endothelial function. Thus, a follow‐up study was conducted to examine the effects of different training modes (intensity and duration) on EDR in 4 selected inbred strains (NON, 129S1, C57BL6, SJL). Male mice from each strain were assigned into 6 groups (n = 6/group): SED, MOD or high intensity interval training for 4 or 8 weeks. Concentration response curves to ACh and SNP were measured after training. There was a significant interaction between strain and training mode for EDR. In 129S1 and C57BL6 mice, exercise training had no effect on EDR. EDR in NON was greater in 4 wk‐trained mice of either intensity, but not 8 wk, compared with SED. Interestingly, EDR was lower in 4wk‐high intensity interval trained‐SJL compared to SED. Responses to SNP were similar across all mice. These data indicate that there is a complex interactive effect between genetic background and training mode on endothelial function.

Supported by NIH grant HL085918 to MPM
Relationship between oxidant-antioxidant status and hypercoagulobility indices in children with iron deficiency anaemia
Authors: Özdemir Zeynep Canan , Çolak Emine , Kar Yeter Düzenli , Özen Hülya , Bör Özcan
Published: June 2021

Oxidative stress is a potential mechanism involved in the pathogenesis of iron deficiency anaemia (IDA). Although a tendency for hypercoagulability has been reported in IDA, its underlying mechanism is yet to be elucidated. This study investigated the probable relationship between oxidative stress and hypercoagulability in children with IDA.

This study included 57 children diagnosed with IDA (IDA group) between October 2016 and October 2017 in addition to 48 healthy children (control group). The maximum clot firmness (MCF) index, and clot formation time (CFT) index, which are indicators of hypercoagulability in rotational thromboelastometry assays [intrinsic TEM (INTEM) and extrinsic TEM (EXTEM)] derived from our previous study, were recorded. Total oxidant status (TOS), total antioxidant capacity (TAC) and oxidative stress index (OSI) were analysed from serum samples of the individuals.

In IDA group, OSI and TOS levels were higher and TAC level was lower compared to the control group (P < 0.001, for all). The EXTEM and INTEM MCF in the IDA group was higher than in the control group, while the INTEM CFT was lower than in the control group (P < 0.001, P < 0.001, P < 0.05, published data).TOS and OSI had a negative correlation with INTEM CFT (r:−0.361, P < 0.001 and r:−0.333, P = 0.001) and a positive correlation with INTEM MCF (r:+0.420, P < 0.001 and r:+0.367, P < 0.001) and EXTEM MCF (r:+0.476, P < 0.001 and r:+0.403, P < 0.001). However, TAC demonstrated no correlation with CFT and MCF index.

The oxidant–antioxidant balance is disrupted in favour of oxidative stress in children with IDA. In addition, TOS and OSI, which are parameters of oxidative stress, are correlated with CFT and MCF indices. Oxidative stress appears to be an important factor for the development of tendency to hypercoagulability in IDA.
The Anorexia Nervosa Care Pathway: Closing the Treatment Gap to Improve Care for Patients Admitted to Medical Hospitals
Authors: Allen Kathryn , Brien Kate O , O’Reilly Marese K , Henderson Deirbhile , Toole Aoibhlinn O , MacHale Siobhan , Boland Karen
Published: June 2021

Introduction

Medical complications of malnutrition and refeeding account for approximately half of deaths in anorexia nervosa (AN). The AN Care Pathway (ANCP) was introduced at our institution in 2016 to improve quality of care of patients admitted for medical observation and management. We report results from our review of medical complications and report the impact and adoption of the ANCP.

Methods

The ANCP was developed in response to a need to improve quality of medical monitoring of patients with severe AN using Squire Guidelines and the Plan-Do-Study-Act cycle. All patients admitted to a medical hospital with AN between 2010-2020 were included after hospital inpatient enquiry and medical records were reviewed. Descriptive statistics were calculated using Stata (Statcorp).

Results

Fifty-one patients (63 admissions) were included. Median BMI was 13.8 kg/m (11.9-22.5). After ANCP implementation in 2016, compliance with recommended daily ECG, thiamine and blood tests improved from 30% (n=8/27) to 86% (n=21/36). We report a high rate of medical complications of severe AN including anaemia (n=24, 47%), neutropoenia (n=18, 35%), abnormal liver bloods (n=15, 29%) and half developed refeeding syndrome. One-third patients had cardiovascular compromise including reduced cardiac contractility (n=13, 25%), pericardial effusion (n=7, 14%) and one death. Low BMI was associated with cardiovascular complications (mean BMI 13.5 kg/m vs 15.5 kg/m, p=0.01) and neutropoenia (mean BMI 13.4 kg/m vs 15.4 kg/m, p=0.02).

Conclusion

Introduction of the ANCP improved quality of care during medical stabilisation. We report a high rate of medical complications of severe AN in patients admitted to a medical hospital. Use of multidisciplinary care protocols may contribute to quality improvement and improved consistency of care for this vulnerable population.
Psychological impact of home confinement due to coronavirus disease on medical students and its relationship with cognitive emotion regulation
Authors: Saguem Bochra Nourhene , Braham Amel , Romdhane Islem , Ben Nasr Selma
Published: June 2021

Purpose

This paper aims to assess the psychological impact of home confinement in Tunisian medical students and analyze the relationship between psychopathology and cognitive emotion regulation strategies.

Design/methodology/approach

In total, 251 medical students who have been in home confinement accepted to participate in an online questionnaire survey. They completed depression, anxiety and stress scale, beck hopelessness scale and cognitive emotion regulation questionnaire.

Findings

Moderate to extremely severe levels of depression, anxiety and stress were reported by 57.4%, 51.0% and 31.4% of medical students, respectively. Based on the cut-off value of nine, 31.1% of the participants showed high levels of hopelessness. Hierarchical regression analysis identified four cognitive emotion regulation strategies as significant independent contributors to psychopathology above and beyond home confinement related variables. Self-blame positively predicted stress. Catastrophizing positively predicted anxiety and hopelessness. Refocusing on planning negatively predicted anxiety. Positive reappraisal negatively predicted hopelessness.

Practical implications

Cognitive emotion regulation strategies may constitute a valuable target of preventive and interventional measures to improve medical students’ mental health.

Originality/value

A unique feature of this study is the demonstration of the important role played by cognitive emotion regulation strategies in predicting anxiety, stress and hopelessness in medical students. In the context of mandatory home confinement, these cognitive strategies were significant predictors of psychopathology above and beyond home confinement related variables.
Human iPSC‐derived neural precursor cells differentiate into multiple cell types to delay disease progression following transplantation into YAC128 Huntington's disease mouse model
Authors: Park Hyun Jung , Jeon Juhyun , Choi Jiwoo , Kim Ji Yeon , Kim Hyun Sook , Huh Ji Young , Goldman Steven A. , Song Jihwan
Published: June 2021

Objectives

To investigate whether human HLA‐homozygous induced pluripotent stem cell (iPSC)‐derived neural precursor cells (iPSC‐NPCs) can provide functional benefits in Huntington’s disease (HD), we transplanted them into the YAC128 transgenic HD mouse model.

Materials and Methods

CHAi001‐A, an HLA‐homozygous iPSC line (A*33:03‐B*44:03‐DRB1*13:02), was differentiated into neural precursor cells, and then, they were transplanted into 6 months‐old YAC128 mice. Various behavioural and histological analyses were performed for five months after transplantation.

Results

Motor and cognitive functions were significantly improved in transplanted animals. Cells transplanted in the striatum showed multipotential differentiation. Five months after transplantation, the donor cells had differentiated into neurons, oligodendrocytes and astrocytes. Transplantation restored DARPP‐32 expression, synaptophysin density, myelin basic protein expression in the corpus callosum and astrocyte function.

Conclusion

Altogether, these results strongly suggest that iPSC‐NPCs transplantation induces neuroprotection and functional recovery in a mouse model of HD and should be taken forward for clinical trials in HD patients.
Fluorescence Assay for Tolyporphins Amidst Abundant Chlorophyll in Crude Cyanobacterial Extracts
Authors: Nguyen Kathy‐Uyen , Zhang Ran , Taniguchi Masahiko , Lindsey Jonathan S.
Published: June 2021

Tolyporphins are distinctive tetrapyrrole natural products found singularly in a filamentous cyanobacterial‐microbial holobiont (termed HT‐58‐2) from Micronesia. The absorption and fluorescence features of tolyporphins resemble those of chlorophyll a, complicating direct analysis of culture samples. Treatment of the crude (unfractionated) organic extract (CH2Cl2/2‐propanol, 1:1) of HT‐58‐2 cultures with NaBH4 in methanol causes reduction of the peripheral ketone auxochromes, whereupon tolyporphins (predominantly 7,17‐dioxobacteriochlorins) exhibit a bathochromic shift (λabs ˜ 676 → ˜ 700 nm) and chlorophyll a (a 131‐oxochlorin) exhibits a hypsochromic shift (λabs 665 → 634 nm). Fluorescence excitation spectroscopy (at 368 and 491 nm with λem 710 nm) enabled detection of reduced tolyporphins amidst abundant reduced chlorophyll a (1:19 ratio), a detection sensitivity >5 times that without reduction. The resulting assay combines simple sample preparation from non‐axenic cultures at microscale quantities (2 mL, 2 μm), absence of any fractionation procedures, and fluorescence detection. Tolyporphins were readily detected in cultures of HT‐58‐2 at reasonable growth periods in the absence of environmental stressors, which was not possible previously.
Voxel-Based Adaptive Toolpath Planning using GPU for Freeform Surface Machining
Authors: Kukreja Aman , Dhanda Mandeep , Pande Sanjay
Published: June 2021

Today freeform surfaces are widely used on products in automobile, aerospace, and die/molds industries, which are generally manufactured using multi-axis CNC machines. Frequent changes in the design of products necessitate creation of CNC part programs which need fast and accurate toolpath generation methods. Traditional toolpath generation methods involve complex computations and are unable to consider multiple surface patches together. The voxel-based CAD model provides the ability to represent the multi-patch surfaces in a discretized manner which can be processed using an advanced parallel computing framework for accurate tool path planning. This paper presents a new method to generate an adaptive Iso-planar toolpath for a 3-axis CNC machine using the voxel-based part model. The algorithm is designed to work on a Graphics Processing Unit (GPU) that allows parallel processing for faster toolpath generation. The proposed approach consists of two main steps, an algorithm to generate gouge free cutter location points from the voxel-based CAD model and an algorithm to find out sidestep and forward step from those cutter location points to create the final CNC tool path. A new image-processing technique has been proposed to identify gouge by detecting the shadow surface voxels and their intersection with the cutting tool. The developed system was extensively tested and compared with the various reported toolpath planning strategies for machining complex freeform surface parts. The results show that the developed method is computationally efficient, robust, and accurate in generating adaptive planar toolpath.
Investigation of electrical properties of peald-deposited Ti/Al2O3/Al/Si MIM capacitors
Authors: Patil Sumit , Barhate Viral , Mahajan Ashok , Xu Haoyu , Rasadujjaman Mohammad , Zhang Jing
Published: June 2021

MIM devices fabricated with 10-nm thickness of Al2O3 high-[Formula: see text] thin film deposited using plasma-enhanced atomic layer deposition (PEALD) system on Al-coated Si substrate were investigated. The structural, morphological and electrical properties of Ti/Al2O3/Al/Si MIM capacitors as-deposited and post-deposition annealed (PDA) at different temperatures were studied and compared. Al2O3 thin films were investigated using atomic force microscopy (AFM) and X-ray diffraction (XRD) and Ti/Al2O3/Al/Si MIM capacitors were characterized by current–voltage ([Formula: see text]–[Formula: see text] and capacitance–voltage ([Formula: see text]–[Formula: see text] measurements. The stable phase formation of Ti/Al2O3/Al/Si MIM capacitor provides the lowest leakage current density in the range of nA/cm2 for as-deposited and annealed films.
Application of response surface methodology to investigate nano-finishing of the silicon wafer
Authors: Mosavat Mohammad , Rahimi Abdolreza
Published: June 2021

The aim of this research is study the effect of polishing factors to the reduction ratio rate in surface roughness (%[Formula: see text] during the Magnetic Abrasive Finishing (MAF) process using Response Surface Methodology (RSM). The parameters studied were machining gap, rotational speed, abrasive size and magnetic abrasive particle (MAP) size. Quadratic models were developed by applying Box–Behnken Design (BBD). Also, experiments were carried out on the silicon wafer and results of surface roughness data were analyzed by using analysis of variance (ANOVA) and significant factors were identified. According to our findings, the maximum %[Formula: see text] value and the best surface roughness of silicon wafer achieved 3.70 and 51 nm, respectively.
Detection and Characterization of Hidden Crack Inside a Stainless Steel Material Using Shear Vertical Waves and PLSR Technique
Authors: Boughedda Houssem , Hacib Tarik , Le bihan Yann , Sadou Hakim , Acikgoz Hulusi
Published: June 2021

Industrial equipment can be exposed to various types of damage during their long exploitation in harsh environments which might lead to corrosion cracking. Typically, a hidden crack is very dangerous since it is difficult to be detected by Non-Destructive Testing (NDT) techniques. Moreover, the integrity requirements of metallic structures cannot be satisfied by simply detecting the existence of cracks. However, the quantitative description of the cracks is still an issue that should be solved. This paper introduces a new approach to estimate the dimensions of hidden cracks inside a stainless steel plate based on Shear Vertical (SV) waves generated by an Electromagnetic Acoustic Transducer (EMAT). The Finite Elements Method (FEM) has been used to model the acquired signal by EMAT. Then, the characterization of hidden cracks is carried out by combining two methods; Time-of-Flight (ToF) technique that has been used to evaluate the crack height, and the Partial Least Square Regression (PLSR) method that has been used to estimate the crack width. The obtained results demonstrate the efficiency and the reliability of the adopted approach concerning the quantitative evaluation of the crack dimensions.
From Bioorganic Models to Cells
Authors: Benkovic Stephen J.
Published: June 2021

I endeavor to share how various choices—some deliberate, some unconscious—and the unmistakable influence of many others shaped my scientific pursuits. I am fascinated by how two long-term, major streams of my research, DNA replication and purine biosynthesis, have merged with unexpected interconnections. If I have imparted to many of the talented individuals who have passed through my lab a degree of my passion for uncloaking the mysteries hidden in scientific research and an understanding of the honesty and rigor it demands and its impact on the world community, then my mentorship has been successful.
From an Incidental Finding to an Emergent Treatment: A Case Report of a Hepatic Adenomatosis and Large Ruptured Hepatic Adenoma
Authors: Mironova Maria , Mahdi Mohammed K. , Bhatia Jyoti , Nielson Rosemarie C. , Doria Cataldo
Published: June 2021

Introduction. Hepatic adenoma is an uncommon benign liver tumor presenting as solitary lesions or even rarely as hepatic adenomatosis. Large lesions carry a risk of rupture, hemorrhage, and malignant transformation. This case report aims to increase awareness about risk factors for hepatic adenomas, considering the increasing prevalence of obesity and the widespread use of oral contraceptive pills. Case Presentation. A 20-year-old obese female who was taking oral contraceptive pills for seven years presented to the emergency department with vomiting and abdominal pain caused by gastroenteritis. On imaging, multiple hepatic adenomas, including two lesions 6 and 9 cm in diameter, were incidentally found. During the hospitalization, the patient suddenly developed acute anemia and rupture of the largest lesion, which was promptly treated with arterial embolization. Discussion. Obesity and exposure to hormones are well-known risk factors for hepatic adenomas. The incidence of hepatic adenomas is steadily increasing because of the prevalence of obesity, especially among females. Lifestyle interventions for weight loss and discontinuation of oral contraceptive pills are considered a conservative treatment of hepatic adenomas. Large lesions possess the risk of malignant transformation and rupture and require surgical excision.
Current and Future Projections of Amyotrophic Lateral Sclerosis in the United States Using Administrative Claims Data
Authors: Miller Chris , Apple Stephen , Paige Jeremy S. , Grabowsky Tara , Shukla Oodaye , Agnese Wendy , Merrill Charlotte
Published: June 2021

Background: Various methodologies have been reported to assess the real-world epidemiology of amyotrophic lateral sclerosis (ALS) in the United States. The aim of this study was to estimate the prevalence, incidence, and geographical distribution of ALS using administrative claims data and to model future trends in ALS epidemiology. Methods: We performed a retrospective analysis of deidentified administrative claims data for >100 million patients, using 2 separate databases (IBM MarketScan Research Databases and Symphony Health Integrated DataVerse [IDV]), to identify patients with ALS. We evaluated disease prevalence, annual incidence, age- and population-controlled geographical distribution, and expected future trends. Results: From 2013 to 2017, we identified 7,316 and 35,208 ALS patients from the MarketScan databases and IDV, respectively. Average annual incidence estimates were 1.48 and 1.37 per 100,000 and point prevalence estimates were 6.85 and 5.16 per 100,000 and in the United States for the MarketScan databases and IDV, respectively. Predictive modeling estimates are reported out to the year 2060 and demonstrate an increasing trend in both incident and prevalent cases. Conclusions: This study provides incidence and prevalence estimates as well as geographical distribution for what the authors believe to be the largest ALS population studied to date. By using 2 separate administrative claims data sets, confidence in our estimates is increased. Future projections based on either database demonstrate an increase in ALS cases, which has also been seen in other large-scale ALS studies. These results can be used to help improve the allocation of healthcare resources in the future.
Laser Surgery of Extensive Homogeneous Oral Leukoplakia Histologically Suggestive of Proliferative Type: A Case Report
Authors: Azevedo Luciane , Tuma Mariana , Orsini Suzana , Migliari Dante
Published: June 2021

Oral leukoplakia (OL) has the potential for malignant transformation; unfortunately, there are no strategies to prevent this possible outcome. Surgical intervention has been reported to be effective in reducing but not eliminating the risk of malignant transformation. Meta-analyses have reported that patients who underwent excision of OL lesions had a significantly lower chance of malignant transformation than those whose lesions were not excised. The present study aimed to report a case of successful management of extensive OL using a high-power laser. The patient has been under periodic monitoring, and we aim to continue the follow-up as long as possible. Recurrence or signs of malignancy were not observed at the 2-year follow-up.