bluuebunny/crossref_metadata_2025 huggingface dataset:
Acetylation of Mitochondrial Proteins in the Heart And Skeletal Muscle of Aged Rats
Authors: Javadova Leyla , Jang Sehwan , Soto Hernandez Jessica , Javadov Sabzali , Escobales Nelson
Published: June 2021

Acetylation of proteins plays a crucial role in pathogenesis of cardiac diseases and aging. ROS accumulation under oxidative stress increases protein acetylation due to inactivation of NAD+‐dependent deacetylases known as sirtuins. We investigated the effect of the newly developed mitochondrial‐targeted ROS scavenger, XJB‐5‐131 (XJB) on acetylation of mitochondrial proteins and SIRT3 in adult (6 mo) and aged (30 mo) rats subjected to ex‐vivo global ischemia‐reperfusion (IR). We hypothesized that XJB decreases the acetylation of mitochondrial proteins and increases the level of SIRT3 in aged rat hearts following IR. Acetylated proteins and SIRT3 levels were determined in cardiac mitochondria using acetyl‐lysine and SIRT3 antibodies. Mitochondria of aged hearts demonstrated a 58% (P<0.038) increase in protein acetylation compared to adult rats after IR. XJB reduced acetylation of mitochondrial proteins in aged hearts whereas no significant effect was observed in adult rats. Moreover, SIRT3 increased 37% (P<0.045 vs. untreated) in aged animals treated withXJB. Analysis of the gastrocnemius muscle (no IR) did not demonstrate significant alterations in protein acetylation and SIRT3 levels in mitochondria in adult and aged rats treated with or without XJB. In conclusion, the mitochondrial‐targeted ROS scavenger, XJB decreases the acetylation of mitochondrial proteins and increases mitochondrial SIRT3 in aged rat hearts following IR. This suggests that XJB could be of therapeutic use to reduce the progression of cardiac diseases with aging.

Supported by the APS/NHLBI (1 R25 HL115473‐01) STRIDE Undergraduate Summer Research Fellowship (L.J.), the NHLBI‐NIH grant SC1HL118669 (S.J.) and the UPR MSC.
Myofibroblastic Differentiation of Human Skeletal Muscle‐Derived Progenitors Is Inhibited by Pirfenidone
Authors: Alinejad Yasaman , Downey Jennifer , Drouin Genevieve , Morand Meggie , Daviau Alex , Despatis Marc‐Antoine , Birot Olivier , Balg Frederic , Faucheux Nathalie , Grenier Guillaume
Published: June 2021

We identified a population within the human skeletal muscle (CD90+) capable of differentiating into myofibroblasts, the most important cells involved in fibrosis development, after stimulation with transforming growth factorbeta (TGFβ). Our objective was to characterize these progenitors and to evaluate the potential of Pirfenidone, a drug currently used for the treatment of idiopathic pulmonary fibrosis, to inhibit their myofibroblastic differentiation. Myofibroblastic differentiation was assessed with or without Pirfenidone treatment by measuring the expression of α‐smooth muscle actin (αSMA) and collagen type I at gene and protein levels as well as contractility. Pirfenidone inhibited the myofibroblastic differentiation as shown by a decrease of αSMA and collagen expression, lowered contractility and an inhibition of pro‐fibrotic genes. Suppression of Smad‐2 and ‐3 phosphorylation was shown to be involved as a mechanism through which Pirfenidone hindered the formation of myofibroblasts. Identifying myofibroblast progenitors in human skeletal muscle and showing the anti‐fibrotic effects of Pirfenidone is a step forward to better understand and treat muscle fibrosis observed in several muscle regenerative disorders.
Membrane‐Stabilizing Copolymers Confer Protection to Dystrophic Skeletal Muscle in vitro and in vivo
Authors: Houang Evelyne , Haman Karen , Filareto Antonio , Perlingeiro Rita , Bates Frank , Lowe Dawn , Metzger Joseph
Published: June 2021

Muscle membrane instability is a hallmark of Duchenne Muscular Dystrophy, a disease that results in skeletal muscle weakness and cardiomyopathy. Poloxamer 188 (P188) is a membrane stabilizer that has been shown by us and others to protect the dystrophic myocardium under physiological stress but its effects on the skeletal myopathy have been less clear to date. P188 belongs to the tri‐block copolymer family, which comprises molecules made of a hydrophobic polypropylene oxide (PPO) core flanked by linear chains of hydrophilic polyethylene oxide (PEO) moieties. These exist at various sizes and PPO/PEO ratios and it is unclear what structural properties of P188 confer its membrane protecting functionality. Mechanistic knowledge is requisite for a deeper understanding of membrane protection by copolymers. We show that P188 at concentrations protective for dystrophic cardiac myocytes is also efficacious in stabilizing membranes of dystrophic skeletal muscle cells in vitro suggesting that delivery limits P188 efficacy in vivo. We show here that P188′s efficacy in protecting dystrophic mdx mice limb muscle from lengthening injury in vivo is critically dependent on delivery route. We also show that extended tri‐block copolymers can provide increased potency. Systematic optimization of tri‐block copolymer delivery, dosing and structure offers a unique therapeutic strategy to protect both dystrophic cardiac and skeletal muscle in vivo. Funded by MDA, NIH and AHA.
Angiotensin Converting Enzyme (ACE) Site‐directed Mutations Designed to Study the Enzyme Interaction with its Specific Inhibitors
Authors: Aragão Danielle , Pereira Larissa , Affonso Regina , Reis Rosana , Casarini Dulce
Published: June 2021

ACE is considered a key enzyme of the renin angiotensin system (RAS), which is involved in blood pressure regulation and electrolyte and fluid homeostasis. ACE is responsible for generating the most important vasoconstrictor peptide of the RAS, angiotensin II. The use of ACE inhibitors and antagonists of angiotensin II receptors are strategies for the treatment of hypertension. Considering its physiological importance, ACE has being the target of many studies which seek for better understanding of its structure and its interaction with specific inhibitors. The aim of this study is the development of site‐directed mutations in order to investigate whether modifications in the target amino acid residues may compromise the enzyme/inhibitor interaction through the purification and characterization of ACE mutants. The target amino acid residues were chosen based on the structural studies of the enzyme and are strong candidates for interaction with ACE inhibitors. Oligonucleotides for the change of the target amino acids were synthesized to the complementary strands containing the desired mutation of the coding region and were expressed in mammal cells using pcDNA plasmid containing human ACE cDNA. PCR reactions were performed in order to promote the site‐directed mutations. The DNA purified from transformed bacteria was sequenced to analyze the success of the mutation. The development of these site‐directed mutations and further biochemical characterization of purified ACE mutants could highlight the importance of these amino acid residues for the activity and/or function of the enzyme, possibly contributing to further identification of new ACE inhibitors. Supported by CAPES and FAPESP.
Modifying Portapres™ Technology for Continuous Noninvasive Blood Pressure Measurements in the Hyperbaric Chamber
Authors: van der Bel René , Sliggers Bart , van Houwelingen Marc , van Lieshout Johannes , Stok Wim , van Hulst Rob , Krediet C
Published: June 2021

For various (patho‐)physiological human study designs it would desirable to have a safe, noninvasive continuous blood pressure measurement for use under hyperbaric conditions. For this purpose we present the modifications to the Portapres™ system (Model 1) and its preliminary validation.

The Portapres™ system was systematically analyzed according to “failure mode and effects analysis” principles. We identified possible failure modes related to pressure resistance and fire hazard in a hyperbaric and oxygen enriched environment, and adapted the device accordingly. 1) the carbon brush pump was replaced by a pressure reducing valve to be connected to a pressurized air supply. 2) gas‐filled electrolytic capacitors were replaced for solid equivalents. 3) the power supply was modified to fit the low voltage supply in the hyperbaric chamber.

Preliminary validation of the modified system was performed in 5 healthy volunteers: against a standard Finapres® device (n=5) there was concurrence between measurements under normobaric conditions, with non‐significant (p > 0.2) mean differences of 1.03 and 4.93 mmHg in systolic and diastolic blood pressure. Hyperbaric measurements proceeded without problems in two of the healthy volunteers.

The modified system seems to provide safe and reliable measurements both under normo‐ and hyperbaric conditions. Further validation is warranted.
Quantitative Assessment of the Coupling of Theoretical Fibroblast and Cardiomyocyte Models
Authors: Liu Fusheng , Wang Pengfei , Xu Feng , Lu Tianjian , Elson Elliot , Wakatsuki Tetsuro , Genin Guy , Carlson Brian
Published: June 2021

Methodologies for creating engineered heart tissue (EHT) constructs by co‐culturing cardiomyocytes and fibroblasts are currently used as an in vitro platform to understand native heart tissue function. However a careful evaluation of how closely EHTs mimic native tissue is still needed and can be facilitated by an approach combining both theoretical and experimental analysis. These theoretical analyses are previously developed computational models of cardiomyocyte and fibroblast electrophysiology and ion handling. In these models contrasting results have been shown for how coupling of cardiomyocytes to fibroblast affects cardiomyocyte action potential duration (APD). Here we show that this result is a function of the type of cardiomyocyte the fibroblast is coupled to and more specifically is linked to the magnitude of the cardiomyocyte transient outward K+current. In addition, we observe that two very different formulations of fibroblast electrophysiology yield similar results when coupled to a human cardiomyocyte and that APD is increased by ~20% when slow delayed rectifier K+is blocked but this increase is eliminated resulting in a ~6% decrease in APD when the human cardiomyocyte is coupled to two fibroblasts. This finding suggests the influence of fibroblasts on cardiomyocytes should not be ignored when using EHTs as an in vitro testing platform. Supported by NIH R01 HL109505 03.
Partial Reduction in Cardiac Sialylation Contributes to Dilated Cardiomyopathy and Heart Failure
Authors: Deng Wei , Ednie Andrew , Bennett Eric
Published: June 2021

Dilated cardiomyopathy (DCM) leads to heart failure (HF) and is often associated with life‐threatening arrhythmias. Protein glycosylation is altered in DCM and with DCM risk factors. Patients with congenital disorders of glycosylation often present with DCM and related arrhythmias. We previously showed that gene deletion of the sialyltransferase, ST3Gal4, results in partial reduction in cardiac sialylation, altered cardiac Nav gating, and increased susceptibility to arrhythmias. Here, we investigated the impact of ST3Gal4 gene deletion on cardiac performance. Anomalous ECGs, including prolonged QT and corrected QT intervals, were recorded in ST3Gal4‐/‐ male mice. One‐year old ST3Gal4‐/‐ mice developed left ventricle (LV) dilation as evidenced by significantly increased LV end‐diastolic volume (EDV) and a significantly thinner LV posterior wall compared to wild type (WT). Transverse aortic constriction (TAC) was used as a stressor on 16‐20 week old animals. TAC'd ST3Gal4‐/‐ hearts decompensated rapidly, presenting by week 3 post‐surgery with significant LV dilation and reduced systolic function (together indicating HF) compared to TAC'd WT littermates (ejection fraction, EF%, ST3Gal4‐/‐= 35.3 ± 3.6%, WT = 48.3 ± 3.5%, p<0.05; EDV(µl), ST3Gal4‐/‐= 103 ± 4.6, WT = 79 ± 5.7, n = 7‐10; p<0.01). Thus, gene deletion of ST3Gal4 results in aberrant electrical signaling and to the later onset of apparent DCM. The DCM phenotype was more pronounced with stress in ST3Gal4‐/‐mice, presenting with HF by week three following pressure‐overload induction. Thus, partial reduction of sialylation contributes to aberrant cardiac electrical signaling and performance with the functional phenotype exacerbated under stress conditions that lead to the rapid onset of HF.
Differences in Correlates of Energy Balance in Normal Weight, Overweight and Obese Adults
Authors: Drenowatz Clemens , Jakicic John , Blair Steven , Hebert James , Hand Gregory
Published: June 2021

OBJECTIVE. This study compared normal weight, overweight and obese adults on energy expenditure (EE), energy intake (EI) and diet quality.

METHODS. The analysis included data from 430 adults (27±4 years; 49% male) who were classified as normal weight, overweight, or obese based on BMI. Body weight and height was measured according to standard procedures and percent body fat was determined based on dual x‐ray absorptiometry. EE was assessed via the SenseWear Armband® over a period of 10 days. EI and diet quality were calculated from multiple 24‐hour recalls.

RESULTS. %BF increased with increased BMI (p<.001). Weight adjusted EI and total daily EE were significantly lower in overweight and obese adults compared to their normal weight peers (p<.001) and obese women had a lower diet quality (p=.006). Overweight and obese adults had a higher proportion of EE in sedentary and in light PA (p<.001), while the proportion of EE in moderate‐to‐vigorous PA (MVPA) was lower compared to their normal weight peers (p<.001). The inverse relationship between BMI or %BF and EE in MVPA was stronger than the positive association between BMI or %BF and EE in sedentary or light PA (rMVPA= ‐.51 to ‐.66 vs. rSedentary= .33 to .52 / rlight= .36 to .47; p<.001).

CONCLUSIONS

These findings emphasize that MVPA is an important determinant in weight management.

Funding for this project was provided through an unrestricted grant from The Coca‐Cola Company.
Penetrating the Glycan Shield on HIV‐1
Authors: Kwong Peter
Published: June 2021

The HIV‐1 envelope spike, the sole target of virus‐directed neutralizing antibodies, is covered by a dense array of N‐linked glycans, which comprises rough half its molecular weight. Because these glycan are generated by self‐biosynthetic machinery, the human immune system can only recognize them as non‐self if they are arranged either in a unique cluster of glycans (such as the triple glycan cluster recognized by antibody 2G12) or as part of a glyco‐peptide epitope (such as observed with antibodies PG9 or 35O22). For the few surfaces on HIV‐1 that are glycan‐free, such as that recognized by the CD4 receptor, antibodies need to contend with the dense glycan that surrounds the site. Here we use crystal structures of a soluble trimeric form HIV‐1 (SOSIP.664) to investigate requirement for penetration to the nominally glycan‐free site of CD4 attachment. We analyze the crystal structure of a fully glycosylated HIV‐1 Env trimer to gain insight into the degree that surrounding N‐linked glycan sterically cover the CD4‐binding site. We also analyze crystal structures of trimeric HIV‐1 Env with antibody VRC01, a CD4‐binding‐site directed antibody capable of neutralizing ~90% of HIV‐1 isolates. The double head of a human antibody, a consequence of the heavy chain‐light chain pairing, appears to be sterically constrained relative to the single‐headed llama vHH antibodies. The vaccine implications of these findings will be discussed.
Osteophytes for Neophytes‐Geriatric MSK Anatomy for Health Care Students
Authors: Dalley Arthur
Published: June 2021

The anatomy presented in most anatomy courses and anatomical atlases is prime of life anatomy—generally that of the child‐bearing years, usually featuring the most common variation. Anatomy outside this age range can vary considerably, but is still “normal anatomy.” Neonates and children are not miniature adults. Likewise, anatomical changes occur with aging of the musculoskeletal system and should be anticipated in examining (physically or radiographically) older patients. Although common (“normal”) at this age, these age‐related findings are not necessarily subclinical. They may produce complaints and require further examination to determine an appropriate level of clinical intervention. Anatomical changes may require alteration of lifestyle, and often increase vulnerability to injury or dysfunction. Examples are altered body stature, form and proportion, decreased bone and muscle mass, osteophyte formation, cartilage dehydration and degeneration, and diminished range of movement at joints. In view of changing demographics, students should gain awareness of typical anatomy during advanced age. These changes are apparent in the aged body donors utilized for dissection, often causing discrepancies between what the atlas shows and the cadaver reveals, making anatomy lab a prime site for gaining awareness of gerontological anatomy. Unfortunately, decreased lab hours in the curriculum often exclude exploration and consideration beyond defined core information.
A Systematic Review of the Literature on Intermittent Fasting for Weight Management
Authors: Hankey Catherine , Klukowska Dominika , Lean Michael
Published: June 2021

Daily calorie restriction is the most common weight loss approach. However, intermittent calorie restriction or fasting (ICR) is an approach promoted widely in the media, though not new, but an established ritual of many religions. Studies which examined the use of ICR for weight management were sought. Three databases were searched: Science Direct, PubMed and Cochrane Library between 1975 to 2014. Inclusion criteria comprised; human studies, cyclic/periodic calorie restriction, duration >2 weeks, randomised trial design initial reported body weight or BMI >22kg/m2 and weight change. The review identified 7 studies which used ICR strategies for both weight loss and maintenance, of which 6 were considered for analysis due to a duplication of data reporting. All studies included overweight or obese participants and were heterogeneous in duration and sample size. Three studies focused on weight loss while 3 others focused on both weight loss and weight maintenance. Weekly fasting periods differed, 3 studies used 2 ICR days per week, 1 used 4 days, another used 1 day and 3 used a mixture of 2 and 5 fasting days weekly. Six studies reported mean weight loss of 2.6% after first month, 5.8% after 2 months, 6.4% after 3 months and 8.9% after 6 months of weight loss and further mean weight loss of 8.2% after a month of weight maintenance. The impact of ICR interventions on blood pressure and insulin sensitivity was recorded. All studies reported a decrease in blood pressure up to 4% and 4 reported decreased insulin concentrations with 3 reaching the reference range. Attrition rates were lower than seen in many studies of weight management, at around 20%. Current research evidence to estimate the impact of ICR is limited. Findings are indicative, sample sizes small and further research justified.
Energy Density and Adherence as Predictors of Weight Loss in the POUNDS LOST Study
Authors: Champagne Catherine , Burton Jeffrey , DeCesare Laura , Johnson Callie , Talbot Grace , Sacks Frank , Bray George
Published: June 2021

The composition of the best weight loss diet continues to be controversial. The POUNDS LOST Trial studied 4 diet treatments containing low or high fat (LF, HF) and average or high protein (AP, HP). Participants (n=811) from sites in Boston and Baton Rouge were randomized and 50% completed extensive dietary interviews. The purpose of this study was to review energy density associated with weight loss considering all foods and beverages and to evaluate weight loss relative to adherence. Energy density was calculated as kcal/g of food and beverages. Adherence was defined as consuming within ±5% of both fat and protein content of the prescribed diet. Weight loss and dietary data were evaluated at 6 and 24 months (6M, 24M) among adherers and non‐adherers. Overall, a reduction in energy density was associated with weight loss regardless of diet group (p=0.0176). While there were not significant differences in mean weight change across the diet groups, there were significant effects of change in energy density on change in weight within the HP/LF (p=0.0249) and AP/HF (p=0.0146) diet groups. Weight loss among adherers was greater than non‐adherers at 6M for the HP/LF (p=0.0155) and AP/HF (p=0.0008), but not significantly different for the other two diet groups. The LF group had the highest percentage of adhering participants at 6M, but the lowest at 24M suggesting LF diets may be more difficult to follow. Energy density appears to be related to weight loss though weight loss did not appear to be different among the groups. Especially at 6 months, greater weight loss is associated with greater adherence, but weight loss will continue if adherence is sustained.
Mechanisms need not be molecular ‐ tissue‐level mechanisms for drug‐induced changes to bone mechanical properties
Authors: Allen Matthew
Published: June 2021

Several pharmacological agents exist that effectively reduce fracture risk in various at‐risk populations. The most common class of agents, anti‐remodeling drugs, are known to target osteoclast‐mediated bone resorption as their main cellular mechanism of action. But for some anti‐remodeling agents, there is more to the story. Using imaging, histological, and mechanical assays, a novel mechanism of action for one particular anti‐remodeling agent, Raloxifene, has been uncovered that appears to have nothing to do with cellular activity or regulation yet helps make sense of clinical findings.
Breastmilk Vitamin B12 Concentration is Low among Women in Western Kenya and is Not Associated with Animal Source Food Intake or Food Insecurity
Authors: Williams Anne , Chantry Caroline , Young Sera , Null Clair , Stewart Christine
Published: June 2021

Breastmilk (BM) vitamin B12 concentration varies with maternal diet, and may be inadequate in regions where animal source food (ASF) consumption is infrequent. Our objective was to measure B12 in mature BM, and examine associations with food insecurity (FI) and recent ASF intake.

Between June and Aug 2014, 160 women 1‐6 mo postpartum (PP) in W. Kenya hand expressed BM one minute into a feed, following 90‐minutes of observed non‐breastfeeding. Vitamin B12 was measured using a competitive protein‐binding assay, which has been validated for BM. Food intake in the last week was measured using a food frequency questionnaire (FFQ). An ASF score was based on frequency of 10 items on the 7‐day FFQ (range 0‐70).

Mean (SD) age, mo PP, and parity were 26 (6) yr, 3.7(1.4), and 3.7(2.0), respectively. Median (Q1,Q3) B12 concentration was 151 (78,247) pmol/L; 87% were <330 pmol/L, the estimated adequate level. Moderate FI prevalence was 34%; the ASF score ranged from 0‐30 (M (Q1,Q3) = 9 (5,13)). Controlling for age, education, parity, SES, dietary diversity and mo PP, FI and ASF score were not significantly associated with BM B12. Although not statistically significant, there was a trend for older mothers (p=0.09) to have higher BM B12.

The vast majority of women had BM B12 concentrations currently considered inadequate, suggesting that ASF intake in this population may be insufficient among breastfeeding mothers. Neither FI nor frequency of ASF intake over the last week was associated with BM B12 concentration among women in W. Kenya.
Oral S‐adenosylmethionine (SAM) Administration Increases Whole Brain Concentrations of Dopamine and Norepinephrine in Rats
Authors: Schalinske Kevin , Smazal Anne
Published: June 2021

S‐adenosylmethionine (SAM) is an over‐the‐counter supplement marketed at improving mood and overall mental health. Although well known for decades to be an antidepressant, very little data exists with respect to the impact of oral SAM administration on whole brain concentrations of specific neurotransmitters. Male Sprague‐Dawley rats were fed a AIN93 diet and provided a daily oral supplement of SAM (10 mg/ kg bwt), a level that is comparable to the recommended dosage for humans. After 20 d of treatment, rats were killed and whole brain samples were analyzed for the concentration of dopamine, norepinephrine, and serotonin, as well as their respective transporters. Oral SAM supplementation increased the intracellular concentration of SAM in the liver and brain approximately 2‐ and 4‐fold respectively. S‐adenosylhomocysteine (SAH) concentrations were significantly elevated by oral SAM treatment in the brain, but were not affected in liver tissue. For whole brain tissue, SAM also markedly increased the concentration of dopamine and norepinephrine 15‐fold and 50%, respectively, whereas it did not have a statistically significant impact on serotonin concentrations. Moreover, SAM administration was without effect on the concentrations of the transporters for dopamine, norepinephrine, or serotonin. Therefore, oral daily provision of SAM to rats at a dosage recommended for humans dramatically increased the intracellular concentrations of specific neurotransmitters, dopamine in particular. The significant increase in brain SAH concentrations may result in the allosteric inhibition of a number of SAM‐dependent methyltransferases that function to metabolize dopamine and norepinephrine, thereby elevating their tissue concentrations.
Linoleic and α‐Linolenic Acid Prevent Insulin Resistance in Obese Zucker Rats but have Different Impacts on Skeletal Muscle Metabolism
Authors: Holloway Graham , Matravadia Sarthak , Herbst Eric , Jain Swati , Chabowski Adrian , Mutch David
Published: June 2021

The use of long‐chain polyunsaturated fatty acids (LC‐PUFAs) to prevent the development of insulin resistance (IR) has recently gained considerable interest. However, the roles of essential PUFAs (i.e., linoleic acid, LA; α‐linolenic acid, ALA) remain poorly understood. We investigated the efficacy of diets enriched with either LA or ALA on preventing IR in obese Zucker rats. After the 12‐wk intervention, both LA‐ and ALA‐enriched diets protected against IR compared to obese control animals. The maintenance of whole‐body glucose homeostasis was linked to the preservation of muscle‐specific insulin sensitivity. LA and ALA differentially regulated markers of skeletal muscle mitochondrial content, respiratory function and H2O2 emission. However, both LA and ALA prevented increases in 4‐HNE content (i.e., a marker of oxidative stress) compared to obese control animals. Collectively, the protective effects of LA and ALA appear independent of mitochondrial bioenergetics, but may involve improvements in oxidative stress. Subsequent lipid profiling in skeletal muscle by gas chromatography revealed that LA and ALA increased omega‐6 and omega‐3 PUFA content, as expected. However, diacylglycerol (DAG) and ceramide accumulation was similar between obese control, LA and ALA groups; suggesting that preservation of skeletal muscle insulin sensitivity occurred independent of changes in reactive lipid content. Overall, LA and ALA are efficacious in preventing obesity‐related IR, but further work is necessary to elucidate the mechanism(s) of action.

Grant Funding Source: Supported by OMAFRA
Low calorie sweetener and macronutrient intake in the US adult population:NHANES 2007‐2010
Authors: Hunt Kelly , Malek Angela , DellaValle Diane , Greenberg Danielle , St. Peter John , Marriott Bernadette
Published: June 2021

The effectiveness of Low Calorie Sweeteners (LCS) for weight management is an area of debate but data on their use is lacking. Prevalence of LCS and macronutrient intake among US adults (19+y;n=9634, N=213,173,877) was determined using both NHANES 2007‐2010 nonconsecutive 24 hr dietary recalls and the National Cancer Institute usual intake method. We categorized individuals into LCS usage groups as zero LCS use (56%; NO), LCS use 1‐2x/2 day (23%; LO), or LCS use 蠅3x/2 day (21%; HI) based on use of LCS in foods, beverages, and condiments. Those in the highest LCS group, when compared to those who did not use LCS, were more likely to be: female, non‐Hispanic white, age 51‐70y, college educated, of higher income or BMI >30 kg/m2 (all p<0.001).

Mean ± SEM daily intake by LCS group adjusted for age, racial‐ethnic group and sex

No LCS
LO LCS
HI LCS

Energy (kcal)
2254 ± 31
2120±32
2081±33

Carbohydrate (gm)
278.7 ±3.1
255.0±3.3
239.0±3.2

Protein (gm)
81.7± 1.6
80.6±1.7
82.8±2.0

Total Fat (gm)
83.1±1.7
80.7±1.6
83.8±1.9

Total Sugars (gm)
133.5±2.4
115.1±1.7
99.3±2.0

Dietary Fiber (gm)
15.8±0.5
16.8±0.5
16.9±0.5

Those who reported the higher LCS use evidenced mean total daily intake that was lower in total energy, carbohydrate, and sugar intake than those who did not use LCS. These data are consistent with available published randomized controlled trials on the impact of use of LCS in weight management and underscore the need for future research in this area. Research Support: PepsiCo, Inc. Global R&D
Shelter Expenditures Increase Vulnerability to Household Food Insecurity
Authors: Fafard Andree‐Anne , Tarasuk Valerie
Published: June 2021

Objective

Income is a strong predictor of food insecurity, but the income necessary for food security is a function of household expenditures. The objective of this study is to characterize the relationship between income, shelter expenditures and food insecurity in Canada.

Methods

Data from Canada's 2010 Survey of Household Spending were converted into budget shares (expenditure‐to‐income ratio) for food, utilities and housing (rent or mortgage). Logistic regression was used to assess the relationship between budget shares and food insecurity, defined as any affirmative response to the 10‐item adult food security scale. Among food insecure renters, linear regression was used to test the association between budget shares and severity of food insecurity, defined by a raw score of 1 to 10. All models were adjusted for sociodemographic factors.

Results

Renters were 3 times more likely to be food insecure than homeowners. Having a mortgage doubled the odds of food insecurity for homeowners. For every 1% increase in the proportion of income allocated to utilities, the odds of food insecurity increased by 5.2% for renters and 6.6% for homeowners. The odds of food insecurity also rose with the budget share for rent among renters and with the budget shares for mortgage and food among homeowners, but these effects were much weaker. Among food insecure renters, a 1% increase in the proportion of income allocated to utilities and rent increased the food insecurity raw score by 3.9 and 1.2 points, respectively; food budget share did not affect severity of food insecurity.

Conclusion

Small increments in shelter expenditures, particularly utilities expenses, appear to contribute substantially to the risk of household food insecurity and to severity of food insecurity. Funded by Canadian Institutes of Health Research (115208).
Stakeholders' Perspectives on the Effect of a multi‐level, multi‐sector Intervention on Parent Engagement in and Awareness of Childhood Obesity Prevention and Control
Authors: Ganter Claudia , Aftosmes‐Tobio Alyssa , Chuang Emmeline , Land Thomas , K. Davison Kirsten
Published: June 2021

Methods

We conducted 40 semi‐structured interviews with stakeholders from five community sectors (school, afterschool, WIC, health clinics, Park & Recreation) in two cities participating in the Massachusetts Childhood Obesity Research Demonstration project (MA‐CORD). Interviews were transcribed verbatim, coded using grounded theory, and analyzed in NVivo 10.0.

Results

Stakeholders reported that parent initiative, motivation and willingness to engage in intervention programming had increased since MA‐CORD was launched two years earlier: ”They're more engaged when they come in for the visit…asking questions, asking for brochures, [this] never happened before.” Stakeholders described several mechanisms through which parent engagement and awareness improved. At the family level, stakeholders reported that children “educated” their parents by bringing home healthy messages and behaviors. At the community level, stakeholders noted that cross‐sector strategies have normalized healthy behavior through consistent messaging and visibility of the problem of childhood obesity.

Conclusion

The analysis shows an increase in parent awareness about and engagement with childhood obesity efforts, as reported by stakeholders. Across interviews it became clear that parents want their children to be healthy and progress has been made to engage parents, however parents may not have the means to actualize behavior change. Future interventions in childhood obesity prevention should address parents directly.
Anti‐Atherogenic Effects of Lesion‐Targeted Epigallocatechin Gallate (EGCG) ‐ Loaded Nanoparticles
Authors: Zhang Jia , Nie Shufang , Hossen Md Nazir , Sun Ming , Martinez‐Zaguilan Raul , Sennoune Souad , Wang Shu
Published: June 2021

Objectives

Macrophages are determinant cells for atherosclerotic lesion formation. The objectives of this study were to incorporate macrophage target ligands on the surface of biocompatible and biodegradable epigallocatechin gallate (EGCG)‐loaded nanoparticles (Enano), to evaluate their target specificity to macrophages and anti‐atherogenic effects in vitro and in vivo.

Method

The target specificity to macrophages (in vitro) and to atherosclerotic lesions in low density lipoprotein receptor knockout (LDLr‐/‐) mice was measured using a fluorescence microscopy and IVIS® in vivo imaging system, respectively. Macrophage cholesterol content was determined using a HPLC method, and macrophage monocyte chemoattractant protein 1 (MCP‐1) release was measured using an ELISA kit. After treating LDLr‐/‐ mice with EGCG, untargeted Enano, targeted Enano, void untargeted nano, void targeted nano, or saline via weekly intravenous injection for 20 weeks, atherosclerotic lesion area and inflammatory response were determined.

Results

As compared to untargeted Enano, targeted Enano significantly increased their binding affinity to THP‐1 macrophages, increased macrophage EGCG content and decreased macrophage cholesterol content and macrophage release of MCP‐1

image

The targeted Enano improved the target specificity to atherosclerotic lesions, and decreased atherosclerotic lesion area and inflammatory response in LDLr‐/‐ mice

image

Conclusions

Targeted nanoparticles represent a potential breakthrough in molecular imaging of atherosclerosis and have a potential for the prevention and treatment of atherosclerosis.
Novel Assessment of Built Environment Assets and Barriers to Healthy Eating and Active Living in Rural Communities
Authors: Messing Jennifer , Connor Leah , King Abby , Sheats Jylana , Winter Sandra , Buman Matthew , Seguin Rebecca
Published: June 2021

A community's built environment can influence key health behaviors. Rural populations experience significant health disparities, yet built environment studies in these settings are limited. In this qualitative study, we aimed to understand characteristics of the rural built environment using the Stanford Healthy Neighborhood Discovery Tool, a novel, participatory, tablet‐based assessment tool.

Men (n=10) and women (n=14) aged 39‐89 years (mean, SD = 65±13) were recruited from four rural towns in New York (6 per town). Participants used the Discovery Tool to take pictures and record audio narratives about community features perceived as assets or barriers to healthy eating and active living. Identified assets, barriers, and opportunities for change were discussed during follow‐up focus groups.

Commonly reported assets included parks, trails, and seasonal access to local produce. Groups shared frustration over high costs of healthy foods and poor sidewalk and crosswalk conditions. Residents identified numerous opportunities for community improvement projects.

In contrast to Discovery Tool data from urban communities, trails were a commonly mentioned rural asset while trash—a common urban concern—was not raised by our rural residents. Our results support the need for individual community assessments and the importance of hearing residents' perspectives when considering environmental and policy change interventions.

This research was supported by the Bronfenbrenner Center for Translational Research.
Plasma Metabolomics Reveal Longitudinal Changes in Branched‐Chain Amino Acids and other Metabolites during Diabetes Progression in the UCD‐Type‐2‐Diabetes Rat Model
Authors: Piccolo Brian , Graham James , Fiehn Oliver , Havel Peter , Adams Sean
Published: June 2021

Type 2 diabetes mellitus (T2D) causes dysregulation in many metabolic pathways; however, temporal progression of these disturbances has not been fully elucidated. Alterations of branched‐chain amino acids (BCAAs) have been implicated in the diabetes phenotype, but cause‐effect is not established. Using a model that closely resembles T2D in humans, the UCD‐T2DM rat, we utilized metabolomics to assess plasma metabolites in pre‐diabetic rats and after the onset of diabetes at 2‐, 12, and 24 weeks. Partial least squares‐discriminant analysis (PLS‐DA) identified a high number of amino acids that were decreased in plasma at 12‐ and 24‐weeks relative to pre‐diabetic rats. Increased leucine and isoleucine plasma abundances were identified in 24 week diabetic rats only. Plasma BCAAs were inversely related to the decline in the total body weight as diabetes progressed over time. All other amino acids decreased in parallel with the decline in total body weight. TCA cycle intermediates, phenols and glucose derivatives were increased by diabetes at 12‐ and 24‐weeks. These observations indicate that the association between plasma BCAAs and T2D is apparent after the onset of the disease phenotype; thus, a result of T2D. Associations between amino acids and weight suggest that the plasma amino acid profile tracks catabolic changes associated with T2D. Additional metabolites that may provide biomarkers of diabetes progression will also be presented.
A Metabolic Profile of Doctor‐Diagnosed Overweight Children
Authors: Twarog John , Patel Nikita , Zhang Jian
Published: June 2021

Background

The opportunity of early identification of children with weight issues has not yet been fully utilized in the clinical setting. For more effective utilization of office‐based prevention strategies, we conducted this study to identify the metabolic risk factors increasing the likelihood of doctor's early notification of child's weight issue.

Data and Method

We used data collected from six cross‐sectional biennial surveys (National Health and Nutrition Examination Survey, 1999‐2012) with un‐weighted total samples of 14,966 (including 5,617 overweight/obese) children aged 8‐17 years.

Results

Over 85% of the overweight children had been seen by a healthcare provider at least once within the past year, yet only 29.7% (SE=0.83) of all overweight/obese children had been notified as being overweight by the healthcare providers that saw them. The metabolic factor consistently associated with being notified as overweight was BMI equal or above 95 percentile (obese) [OR =5.32 (95%CI=4.17, 6.79) vs. overweight]. Hypertension increased the likelihood of appropriate notification only for boys [4.47 (1.84, 10.9) vs. normal BP]. Compared with overweight peers free of hypertension, hypertensive overweight girls had an equal likelihood of being appropriately notified by their doctor about excessive body weight [1.04 (0.35, 3.13) vs. normal BP].

Conclusions

Severely overweight children were more likely to be notified by a healthcare provider of their unhealthy weight. Comorbidity with hypertension significantly increased the likelihood among boys but not girls. Additional studies are warranted to examine the gender difference and to explore effective strategies to improve the issue of early identification of obesity in a clinical setting.
Apple Consumption Protects Sprague Dawley Rats Against High Fat Diet‐induced Metabolic Disorders Associated With Obesity
Authors: yuan jialing , chew Boon , noratto giuliana
Published: June 2021

Apples contain non‐digestible compounds including fiber and phenolics reported for their benefits associated with prevention of chronic diseases. Our objective was to investigate the effects of apple consumption in prevention of obesity and obesity‐related metabolic disorders in vivo. Freeze dried Granny Smith apple previously identified for its enhanced content of non‐digestible bioactive compounds was used to supplement a high fat diet at 7% (60% calories from fat, HFA), the control HF was supplemented with corn starch to maintain isocaloric diets. Sprague Dawley rats were fed ad libitum for 6 weeks. The collected blood and adipose tissues at the end of study were analyzed for biomarkers of obesity, inflammation, and metabolic disorders using standard analytical procedures.

Results show that body mass index (BMI) data distribution in HFA was below the lower interquartile range of HF group. Adiposity index values were significantly lower in HFA (4.1%) compared to HF group (7.7%). Apple consumption improved significantly glucose tolerance by decreased area under curve in 8% compared to HF. This was correlated with decreased plasma total cholesterol from 190.4 to 159 mg/dL, triglycerides from 72.6 to 54 mg/dL, thiobarbituric acid reactive substances (TBARS) from 71.31 µM to 40.90 µM. Overall, these results strongly indicate that apple consumption can protect from development of metabolic disorders associated with obesity. We are currently investigating the relationship between plasma metabolic and inflammatory makers and changes in fecal bacteria.
Iodized Salt Improves Child's Iodine Status, Mental Development, and Physical Growth in a Cluster Randomized Trial in Ethiopia
Authors: Bougma Karim , Marquis Grace , Aboud Frances , Frongillo Edward , Lemma Tizita , Samuel Aregash
Published: June 2021

The effectiveness of iodized salt programs to improve mental development and physical growth has not been studied in children < 36 months. Using a cluster randomized design, 1835 infants 5‐11 mo old were enrolled in 60 villages in Amhara, Ethiopia. Following salt iodization legislation, iodized salt was forced early into the markets of 30 villages (intervention, I) before it became available in the 30 control (C) villages. The two groups were similar at baseline. Children (85% of the baseline sample) were re‐assessed at age 20‐29 mo. Treatment effects were analyzed using linear mixed models. The median endline urinary iodine concentration (UIC) was significantly higher in group I (161.6 vs 124.0 µg/L; p<0.001). Group I had significantly higher scores at reassessment on three of the four Bayley‐III subscales: cognitive (std mean 6.40 vs 6.14; p<0.05), receptive language (std mean 7.19 vs 6.92; p<0.05), and fine motor (std mean 7.97 vs 7.59; p<0.05). Moderator analysis indicated that length‐for‐age in children was higher in group I for those with high household assets. UIC was higher in I vs C children with an unschooled mother, unimproved water, and no recent illness. These results support universal salt iodization to improve children's life. [Funded by Micronutrient Initiative, Canada]
Inflammatory leukocytes exhibit distinct rhythms in their recruitment to arteries and veins
Authors: de Juan Alba , Druzd David , Kraus Kerstin , Scheiermann Christoph
Published: June 2021

Acute cardiovascular complications occur predominantly at the onset of the behavioral activity phase and are the major cause of death in humans. Recent evidence points to a critical role for rhythmic leukocyte recruitment in the onset of vascular diseases. Whether rhythmically distinct leukocyte interactions between arteries and veins can drive vessel‐type‐specific cardiovascular complications is unknown. Here, we demonstrate rhythmic differences in the ability of leukocytes to adhere to arteries and veins in an acute inflammatory scenario. Using TNFα in combination with i.v. injected fluorescent antibodies, we performed in vivo imaging analyses of the carotid artery and the jugular vein of the same mice at different time points. Our data indicate that leukocyte recruitment to the jugular vein followed a robust rhythm (~3‐fold difference between day and night) whereas leukocyte adhesion to the carotid artery exhibited an altered oscillatory pattern. While similar circadian rhythmicity was detected in the expression of CD11b integrin levels on leukocytes adherent to both artery and vein, we observed an inverse oscillation in the expression of ICAM‐1 and VCAM‐1 between endothelial cells of these vessels. Altered rhythmicity resulted in a heightened susceptibility to vaso‐occlusion at different times (vein: 10 min at Zeitgeber time (ZT, time after light onset) 2 vs 5 min at ZT8; artery: 11 min at ZT2 vs 20 min at ZT8). Together, our data indicate distinct mechanisms that induce rhythmic leukocyte recruitment to arteries and veins and their potential implications in driving time‐of‐day‐dependent cardiovascular complications.

Funded by the Emmy‐Noether‐Program of the German Research Foundation (DFG)
Roles of podoplanin positive cells in wound healing of the mouse tongue
Authors: Shimizu Kazuhiko , Arimura Yutaka , Ezaki Taichi
Published: June 2021

Recently, we have reported that a large number of stromal cells appeared in wound areas and became positive for podoplanin (PDPN), known as a lymphatic endothelial marker. In this study, we characterized the PDPN+ cells appearing during wound healing in the mouse tongue to clarify their roles in tissue repair. We made a 1mm‐deep laceration on the tongue of C57BL/6 mice under anesthesia. Tongues were excised and then snap‐frozen at various times after injury. Their cryosections of 10‐14 µm thickness were made for various morphological analyses. The epithelium completely healed by day5 after injury. The granulation was formed in the submucus where many PDPN+ cells with active fibroblast‐like morphology were populated and formed fine meshworks in stead of lymphatic vessels. To examine the functional roles of PDPN+ cells, sections were multiple immunostained for PDPN in combination with CD68, collagen type IV, CCL2 and MMP9. Most of PDPN+ cells co‐expressed CCL2 during wound healing and many CD68+ cells migrated around the PDPN+ cells. And PDPN+ cells were stretched processes towards collagen type IV+ epithelial basement membrane. In addition, these PDPN+ cells expressed MMP9 and the cell projections seemed to penetrate through the collagen type IV+ basement membrane. These results suggest that the PDPN+ cells may have some roles in wound healing of the mouse tongue by recruiting other cells such as CD68+ cells with CCL2 and by expressing MMP9 for remodeling the tissue.
Discourse perspectives on learning anatomy by whole‐body dissection
Authors: Bazira Peter
Published: June 2021

The place and role of whole body dissection in medical education, and whether or not dissection is an efficient means of learning clinically relevant anatomy, is at the core of many debates in the literature. This study aimed to discursively evaluate what was being learned during the course of whole body dissection. Fourth year medical students on an intensive advanced clinical anatomy course completely dissected a cadaver following a standard dissecting manual, recording all anatomical variations and pathological findings, and reconstructing the ante‐mortem presentation of the deceased. The conversations of these students during the course of dissection were recorded, transcribed, coded and subjected to discourse analysis. There was a diachronic transition from narrative to academic discourse (argumentation, descriptive, expository), and evidence of an ontological trinity (cadaver‐disease‐person) in the discourse. Whole body dissection was found to be an efficient medium for the recall and consolidation of basic and clinical science knowledge; for contextualization of anatomical and pathological findings; for the expression of clinical reasoning skills; and for discussion of relevant professional and ethical issues.