bluuebunny/crossref_metadata_2025 huggingface dataset:
Dietary supplementation with tart cherries for prevention of inflammation‐associated colorectal cancer in mice
Authors: Hunter Ashli , Larson Deanna , Phatak Sumira , Hintze Korry , Benninghoff Abby
Published: June 2021

The cherry fruit is a nutrient‐dense food with comparatively low caloric content and significant amounts of key nutrients and bioactive food chemicals. Much of the health benefit of cherries is attributed to their high amounts of anthocyanins, which have anti‐oxidant and anti‐cancer properties that contribute to changes in cell signaling pathways involved in inflammation, carcinogenesis and angiogenesis. In this project, we aimed to determine whether dietary supplementation with tart cherries prevents colon tumor development in mice consuming a Western diet compared to a prudent diet. Previously, our research team developed the Total Western Diet (TWD) for mice to emulate typical U.S. nutrition with respect to macro‐ (sugars, fats, and protein) and micronutrient (vitamin and mineral) contents (Hintze, et al. 2012 J Ag Food Chem 60(27): 6736–6742). Incorporating the TWD in pre‐clinical studies allows for the analysis of the impact of dietary bioactives or functional foods on tumor development in a physiological environment that reflects nutritional patterns of the average American. We hypothesized that dietary supplementation with freeze‐dried whole tart cherries would suppress development of colon tumors in a model of inflammation‐associated colorectal cancer. A 2×2 factorial design was employed, whereby mice were fed either AIN93G (optimized for rodent health) or the TWD, each with and without Montmorency tart cherry powder added to the diet for a total anthocyanin content of 188 mg/kg diet. Mice were initiated with 10 mg/kg azoxymethane and provided 1% dextran sodium sulfate (DSS) in their drinking water for 4 weeks to promote colonic inflammation and tumorigenesis. Necropsy and tumor assessment were performed after 15 weeks of treatment. TWD consumption markedly enhanced colitis (40‐fold increase in disease activity) and tumor multiplicity (near 6‐fold increase) compared to consumption of the AIN93G diet. Supplementation with tart cherry powder caused a significant 40% reduction (P<0.05) in tumor incidence in mice fed AIN93G, whereas tart cherries had no effect on tumor incidence in mice fed TWD. However, tart cherry powder supplementation did not significantly affect tumor multiplicity or tumor size in mice fed either basal diet. Moreover, addition of the tart cherry supplement did not significantly affect colitis disease activity. These data contrast with a prior observation by our group that green tea supplementation was effective at reducing development of aberrant crypts, but only in mice fed TWD. Collectively, these observations point to important interactions between basal diets and dietary bioactive supplements and underscore the need for careful consideration of the role of basal diet in dietary chemoprevention studies in rodents.

Support or Funding Information

Support was provided by the Utah Agricultural Experiment Station (project UTA‐01178) and USDA NIFA Grant No. 2014‐67017‐21755 to A.B.
Calculation of Retention Factors for Flavonoids in Cooked Broccoli
Authors: Wu Xianli , Zhao Yang , Bhagwat Seema , Haytowitz David B , Harnly James M , Pehrsson Pamela R , Chen Pei
Published: June 2021

Thermal processes such as cooking have a large influence on flavonoids in foods, which further impact the accuracy of developing food flavonoid database and the estimation of their dietary intake. The objective of this study was to determine how common cooking methods alter complex flavonoids in broccoli, and to compare the effects of different cooking and calculating methods for estimating retention factors. Fresh broccoli samples were purchased from local grocery chains and were cooked by three common ways (boiling, steaming and microwaving). Flavonoids were analyzed by HPLC‐MS/MS. Eight major kaempferol (Km) tri‐ or tetra‐glycosides and one quercetin tri‐glycoside were identified and quantified in raw and cooked broccoli. Retention factors were calculated on individual flavonoids based on the dry weight; they ranged widely from 33.9% to 237.2%, depending on the chemical structure and cooking method. Contents of certain Km glycosides elevated after cooking, probably due to the increased release from cells or from binding with other components. In addition, different calculation methods to generate an overall retention factor for multiple flavonoids with the same aglycone were compared. Among the three methods, namely “retention factor by aglycone”, “retention factor by weight” and “retention factor by average”, the “retention factor by aglycone” was shown to be an appropriate method. The retention factors by aglycone for Km glycosides in broccoli was calculated as 83.9% for boiling, 131.6% for steaming and 136.1% for microwaving.

Support or Funding Information

NIH Agreement 58‐1235‐3‐126 and USDA
Vasopressin‐Altered Glycemic Control May Lead to Metabolic Disorders of Severe Hemorrhagic Shock
Authors: Uyehara Catherine F T , Wetstein Paul J , Murata Lee‐Ann M , Ichimura Wayne M , Hernandez Claudia A , Richards Carly R , McMurray Robert C , Kajiura Lauren N , Wong Sara A
Published: June 2021

Metabolic disorders associated with trauma and hemorrhage typically follow an early hyperglycemic reflex aimed at increasing brain blood glucose in the face of oxygen debt. The hyperglycemic reflex is believed to be initiated by hypoxia‐induced carotidbody stimulation via a vasopressin (VP) V1a receptor mechanism. We hypothesized that elevated circulating VP levels released in response to severe shock contribute not only to restoring blood pressure, but may also prolong altered glycemic control. Thus, we examined VP influence on glucose regulation after severe oxygen debt from hemorrhagic shock using Yorkshire cross pigs (n=29, body weight 31.1+0.3 kg). Rapid hemorrhage (30 ml/kg bloodshed over 20 minutes) was induced to cause a 50% drop in mean arterial pressure and an oxygen debt of 68+5 ml/kg. Blood glucose levels rose from 124+10 mg/dl at baseline to 174+10mg/dl after hemorrhage (p<0.01), with accompanying increases in VP, epinephrine, glucagon, and insulin. Relationships between blood glucose, VP, epinephrine, glucagon, insulin, pancreatic blood flow and liver blood flow were examined. Multiple regression analysis of glycemic control from baseline through the end of hemorrhage indicated that glucose levels were strongly associated with VP and epinephrine, and inversely related to glucagon which correlated with VP (p<0.01). VP and pancreatic blood flow remained negatively correlated in all phases of baseline, hemorrhage and resuscitation with exogenous VP (30 ng/kg/min i.v., n=7). Thus pancreatic blood flow was significantly lower (p<0.01) with VP‐treated pigs (0.14+0.02 ml/kg/min) than in pigs that were resuscitated with normal saline where pancreatic blood flow (0.36+0.04ml/kg/min, n=10) did not further decrease. Exogenous VP during resuscitation also stimulated liver blood flow, and seemed to keep glucagon from decreasing despite the decreased pancreatic blood flow. VP did not affect insulin levels. Results suggest that VP mediates a hyperglycemic response in severe hemorrhagic shock via influence on glucagon secretion. If hyperglycemia continues beyond this acute response to hemorrhage, long‐term metabolic disorders could develop which would lead to tissue oxidative damage and contribute to trauma‐induced multisystem organ failure. Strategies for critical care management of hemorrhagic shock need to incorporate understanding of VP‐induced metabolic alterations of glycemic control.

Support or Funding Information

This project was supported by U.S. Army Medical Research and Materiel Command Congressionally Directed Medical Research Program grant #DAMD17‐03‐1‐0072. The views expressed in this abstract are those of the authors and do not reflect the official policy or position of the Department of the Army, Department of Defense, or the U.S. Government.
Ontogeny of breathing pattern and ventilatory chemosensitivity in altricial red‐winged blackbird (Agelaius phoenixes) nestlings
Authors: Dzialowski Edward M , Sirsat Tushar S. , Sirsat Sarah K.G. , Price Edwin
Published: June 2021

Altricial bird species, like the red‐winged blackbird, hatch at an immature level of functional maturity with very limited aerobic capacity. Over the next 9 days, red‐winged blackbirds develop increased metabolic capacity and fledge. Metabolic capacity is limited in the early neonate and the ontogeny of the ventilator chemosensitivity is unknown. Here we examined developmental changes in chemosensitivity of tidal volume (VT), breathing frequency (f), minute ventilation (VE), and whole‐animal oxygen consumption (Vo2) from hatching to fledging in the red‐winged blackbird on days 3, 5, 7, and 9 days post hatching (dph) in response to hypercapnia (2 and 4% CO2) and hypoxia (15 and 10% O2). The barometric technique was used to estimate VT. Under control conditions, there was a developmental increase in VE with age that was due in part to increased VT with age. All ages exhibited a hypercapnic and hypoxic chemosensitivity. In response to hypercapnia, the 3 dph neonates increased VE by increasing both f and VT. From 5 dph on, the hypercapnic increase in VE was accounted for by increases in VT and not f. In response to hypoxia, all ages exhibited an increase in f at 10% O2, while VT decreased in older animals. This resulted in an increased VE at 3 dph with no change in VE at the later ages. Chemosensitivity in response to O2 and CO2 appear to mature early in the neonatal red‐winged blackbird, well before they are able to increase Vo2 in response to cooling.

Support or Funding Information

National Science Foundation IOS‐1146758
Postnatal Muscle Growth Is Dependent on Satellite Cell Proliferation Which Demonstrates A Specific Requirement for Dietary Protein
Authors: Fiorotto Marta L. , Columbus Daniel A. , Steinhoff‐Wagner Julia , Suryawan Agus , Nguyen Hanh V. , Davis Teresa A.
Published: June 2021

Extrauterine growth faltering is a serious problem for premature neonates due in large part to insufficient nutrient intake secondary to physiological immaturity and feeding intolerance. Growth of lean mass is especially compromised in these patients due to poor muscle growth. In neonates, short‐term supplementation with leucine of a reduced protein, but energy adequate, feed promoted muscle protein synthesis by stimulating mTORC1 activity similar to feeding a high protein feed. Whether sustained long‐term leucine supplementation of a protein limiting diet can enhance muscle growth is unknown. Five‐d‐old pigs (n = 8–11/diet) were fed by gastric catheter a milk replacement diet with either a high protein (HP) or restricted protein (RP) content or RP supplemented with leucine to the same level as in the HP diet (RPL); all feeds were isocaloric. Pigs were fed every 4 h for 21 d. BrdU (25 mg/(kg.d)) was given as an i.v. bolus every 12 hrs over 3 d from day 6. After 21 d, longissimus dorsi muscle was collected and muscle mass, BrdU+ myonuclei and sublaminal Pax7+ nuclear frequency in muscle cross‐sections were quantified (>1000 fibers/pig). Average fiber cross‐sectional area (CSA) was correlated (r=0.83, P=0.001) with muscle weight and was lower in RP compared to HP pigs (P=0.01), with no improvement in muscle mass with leucine supplementation. Total myonuclear number/fiber also was lower in RP and RPL compared to HP (P=0.01) and was correlated to CSA (r=0.77; P=0.001), with no difference in nuclear domain size (fiber CSA/myonucleus) among groups. There were 40% fewer Pax7+ nuclei in RP and RPL than HP muscles (P=0.001) and their frequency was predictive of myonuclear number/fiber (r=0.79, P=0.001). RP and RPL muscle on average had 30% fewer BrdU+ myonuclei than HP (P=0.003) muscle; the average number of myonuclei per fiber was correlated to the number of BrdU+ nuclei (r=0.76; P=0.001) and the average ratio was similar among groups. The results demonstrate that in the immature muscle fiber hypertrophy is dependent on sustained satellite cell proliferation and myonuclear accretion. This process is highly sensitive to protein intake even when concurrent energy and leucine intakes are optimized for growth.

Support or Funding Information

Studies were funded by NIH grants: HD072891, AR 46308, AR44474; USDA NIFA 2013‐67015‐20438; USDA/ARS/CSREES 6250‐51000‐55
Maternal Choline Supplementation Modulates Maternal and Fetal Choline Metabolism and Downregulates Inflammatory Gene Expression in a Mouse Model of Placental Insufficiency
Authors: King Julia H , Kwan Sze Ting (Cecilia) , Yan Jian , Jiang Xinyin , Fomin Vladislav G , Roberson Mark S , Caudill Marie A
Published: June 2021

A properly functioning placenta allows efficient transfer of nutrients from mother to fetus and promotes fetal growth. Decreased placental efficiency is commonly associated with intrauterine growth restriction, preeclampsia, and miscarriage. Choline is an essential nutrient that is a precursor for several molecules with crucial roles in fetal development: betaine, an osmolyte and methyl donor; acetylcholine, a neurotransmitter and signaling molecule; and phosphatidylcholine (PC), the most prevalent membrane phospholipid. We previously showed that maternal choline supplementation (MCS) in the Dlx3+/− mouse, a model of placental insufficiency, increases fetal growth in early gestation and lowers expression of pro‐angiogenic genes implicated in preeclampsia. To explore the mechanisms contributing to these effects, we measured choline metabolites in the maternal liver and placentas of Dlx3+/− female mice consuming 1X (control), 2X or 4X the recommended intake levels of choline during gestation. Additionally, we measured expression of inflammatory genes that are elevated in preeclampsia and indicative of placental dysfunction. Dams were sacrificed at embryonic days E10.5, E12.5, E15.5, and E18.5. Data were analyzed using linear mixed models with dam as a random factor. MCS increased betaine concentrations in the maternal liver at all four time points (p<.01) and prevented a decline in maternal hepatic betaine stores in late pregnancy. 4X choline also increased phosphocholine, a precursor of PC, at E15.5 (p=.014), and decreased glycerophosphocholine, a product of PC breakdown, at E12.5 (p=.025). In the placenta, MCS increased betaine concentrations at E10.5 and 12.5 (p=.005 and .041, respectively). These data suggest that effects of MCS may be primarily driven by betaine, potentially through increased supply of methyl groups for one‐carbon reactions including DNA methylation. This is supported by data demonstrating widespread effects of choline on gene expression. In Dlx3+/− placentas, choline decreased (p<0.05) expression of pro‐inflammatory genes Il1b (at E12.5, 15.5 and 18.5), Tnf‐α (at E12.5) and NfκB (at E15.5). Further studies are ongoing to identify downstream effects of increased betaine on placental DNA methylation and growth factor signaling pathways.

Support or Funding Information

Funding provided by USDA‐NIFA 2012‐67017‐30176
Dietary Tomato Powder Inhibits Hepatic Steatosis, Inflammation and Tumorigenesis in Beta‐carotene‐15, 15′‐oxygenase (BCO1) and Beta‐carotene‐9, 10′‐oxygenase (BCO2) Double Knockout Mice
Authors: Li Cheng‐Chung , Liu Chun , Hu Kangquan , Smith Donald E. , von Lintig Johannes , Wang Xiang‐Dong
Published: June 2021

Consumption of tomatoes and tomato products which are rich in lycopene, is associated with a decreased risk of chronic disease. Lycopene can be cleaved by beta‐carotene‐15, 15′‐oxygenase (BCO1) and beta‐carotene‐9′, 10′‐oxygenase (BCO2) to produce biological active apolycopenoids. We have recently shown that lycopene and apolycopenoid have different mechanisms of protection against high fat diet (HFD)‐induced hepatic steatosis and hepatocellular carcinoma (HCC) development in BCO2 knockout (KO) mice (Ip, 2014, 2015). Since apolycopenoids also exist in tomato and tomato products (Kopec, 2010), the present investigation examined whether or not the whole tomato (tomato powder, TP) can inhibit HFD‐induced hepatic steatosis, inflammation and HCC in the absence of both BCO1/BCO2 in mice.

BCO1/BCO2 double KO mice were injected with a carcinogen (diethylnitrosamine, i.p. 25 mg/kg body weight) at 2 weeks of age. At the age of 6 weeks, the mice were randomly assigned to either the HFD (n=9, 60% of energy as fat) feeding alone group or the HFD feeding with TP supplementation (n=9, HFD+TP, 41.8 g TP/kg diet, equivalent to 36 mg lycopene/day in human, which is 3–4 times higher than the average intake of lycopene) for 24 weeks. BCO1/BCO2 double KO mice (n=9) of the same age were fed with a chow diet as the control group.

Results showed that TP supplementation significantly decreased hepatic steatosis and HCC development (67% reduction in incidence, 83% reduction in multiplicity, and 95% reduction in tumor volume) in BCO1/BCO2 double KO mice, as compared with the mice fed with HFD alone. The protective effects of TP supplementation were associated with 1) decreased hepatic inflammatory foci (89% reduction) and mRNA expressions of pro‐inflammatory biomarkers [interleukin (IL)‐6, IL‐12a, monocyte chemoattractant protein‐1, and inducible NO synthase]; 2) increased mRNA expressions of deacetylase sirtuin 1, sirtuin 3, and nicotinamide phosphoribosyltransferase involving NAD+ production; and 3) restored HFD‐reduced circadian clock gene expressions (circadian locomotor output cycles kaput, period 2, and cryptochrome‐2) to the normal levels of the control group. Taken together, the present study demonstrates that dietary TP can effectively inhibit HFD‐promoted steatosis, inflammation and tumorigenesis in the absence of BCO1/BCO2. The protective effects of TP against HFD‐induced liver injury may involve the regulations of sirtuin deacetylation and its related molecular clock function.

Support or Funding Information

Supported by USDA/NIFA (2015‐67017) and USDA/ARS (58‐1950‐0014)
The Effect of Dietary Protein on Bone during Weight Loss: A Meta‐Analysis and Systematic Review
Authors: Wright Christian S , Li Jia , Campbell Wayne W
Published: June 2021

The pervasiveness of obesity and excess adiposity is an ever prevalent reality amongst US adults, decreasing quality of life and predisposing individuals to metabolic dysfunction. Weight loss is an effective and widely used strategy for decreasing adiposity and improving overall metabolic health. In particular, higher protein weight loss diets (≥25% of energy from protein or ≥1.0 g/kg/day; HP) are shown to retain lean mass and decrease fat mass more than normal protein weight loss diets (<25% of energy from protein or <1.0 g/kg/day; NP). However, weight loss is also shown to significantly decrease bone quantity and the impact of a HP weight loss diet on bone is both unclear and controversial. With individual studies reporting conflicting results, either an exacerbation or an attenuation of weight‐loss induced bone loss with higher protein intakes, a recommendation for total protein intake during weight loss for the preservation of bone health is uncertain. Currently, no comprehensive analyses of randomized controlled trials have investigated the effects of HP weight‐loss diets on bone outcomes. The purpose of this systematic review and meta‐analysis was to assess the effects of HP versus NP weight loss diets (≥12 weeks) on bone mineral density (BMD) and bone mineral content (BMC) in healthy adults (≥19 years old). Two independent researchers collected and assessed a total of 1799 citations spanning the years 1969 to 2015 from multiple literary databases (Pubmed, Cochrane, CINAHL, Scopus, and Web of Science). Out of 1310 abstracts, 108 full articles were acquired for further inspection and 29 met the inclusion criteria for the systematic review. Data from 10 of the 29 studies displaying differences in total protein intake were extracted and a random‐effects model meta‐analysis was conducted (STATA/SE 12 software; StataCorp LP., College Station, TX). Collectively, this systematic review included 1,940 individuals (79.2% women, ~46 years old) actively engaged in a weight loss intervention lasting on average 6.2 ± 4.2 months. Average total protein intake during HP weight‐loss diets was 99.5 ± 13.5g (1.24 ± 0.16 g/kg BW; 26.2 ± 4.4 % of energy from protein), which was largely achieved through the consumption of mixed protein‐rich whole food sources (59% of studies). Though the majority of studies concluded a significant decrease in bone quantity following active weight loss (62%), the current meta‐analysis revealed neither an exacerbation nor an attenuation of bone loss while utilizing a HP weight loss diet (total BMD, p=0.11; total BMC p=0.42). An apparent positive effect was noted for lumbar spine with HP weight loss diets (Lumbar BMD, p=0.053, weighted mean difference: 0.007 g/cm2, 95% CI: −0.001, 0.016). In conclusion, a higher protein weight loss diet is known to favorably influence soft tissue compartments; however it does not appear to influence weight loss induced bone loss.

Support or Funding Information

USDA‐NIFA #2011‐38420‐20038 (WWC)
High‐Calorie Diet Induced Chronic Colonic inflammation: A Human‐Relevant Porcine Model to Assess Whole Food Approach to Reduce Colon Cancer Risk
Authors: Vanamala Jairam , Sido Abigail , Eriksson Elisabeth , Kim Sung Woo , Bhat Vadiraja , Radhakrishnan Sridhar , Reddivari Lavanya
Published: June 2021

Recent studies have shown a critical link between high‐calorie diet (HCD)‐induced chronic inflammation and colon cancer. A recent prospective study revealed a positive association between interleukin‐6 (IL‐6), a pro‐inflammatory cytokine, and colon cancer risk. Recently, we developed a human‐relevant pig model for diet‐induced chronic inflammation where clinical markers of inflammation, calprotectin and LCN‐2, were elevated in colonic digesta and mucosa. In the current study, we hypothesized that HCD will elevate the IL‐6 signaling pathway proteins and these proteins levels will correlate with colon cancer risk (Ki‐67 proliferative index and zone) markers. We further hypothesized that anthocyanin rich purple‐fleshed potatoes suppress IL‐6 pathway proteins and colon cancer risk factors. We observed elevated colonic mucosal IL‐6 expression in HCD‐consuming pigs (3 weeks post‐weaning consumed diets for 13 weeks, n = 8 / group) compared to standard diet (SD, qPCR, P = 0.04) and IL‐6 expression levels strongly correlated with Ki‐67 proliferative index and zone (r = 0.604, 0.743; P = 0.017, 0.002; respectively). LC/MS‐MS‐based proteomic analysis and Ingenuity Pathway Analysis showed that HCD consumption alters IL‐6 signaling pathway proteins (PI3KR4, IL‐1α, Mapk10, Akt3, PIK3CG, PIK3R5, Map2k2). Furthermore, these proteins strongly correlated (r = 0.811, P = 0.001) with Ki‐67 proliferative index/zone. We observed that supplementation of HCD with anthocyanin containing purple‐fleshed potatoes (10% w/w), even after baking, tended to suppress HCD‐elevated IL‐6 expression (P ≤ 0.1) and IL‐6 linked proteins, IL‐1α and Map2k1 (P ≤ 0.1). Our results highlight the importance of IL‐6 signaling in diet‐linked induction/prevention of chronic colonic inflammation/cancer and demonstrate the potential of whole foods as a dietary intervention to counteract chronic inflammation and carcinogenesis using a human‐relevant pig model.

Support or Funding Information

National Research Initiative Grant 2009‐55200‐05197 from the USDA National Institute for Food and Agriculture (2009–2012)
Impact of cranberry on gut microbiota in a colon carcinogenesis mouse model
Authors: Cai Xiaokun , Sun Jin , Qi Ce , Gu Min , Goulette Timothy , Wu Xian , Song Mingyue , You Xiaomeng , Sela David , Neto Catherine , Xiao Hang
Published: June 2021

Accumulating evidence showed that microbiota play important roles in colonic inflammation and inflammation‐associated colon carcinogenesis. Fruits and vegetable are know to have protective effects against colon carcinogenesis. In this study, we studied the protective effects of whole cranberry powder against inflammation‐associated colon carcinogenesis in mice treated with azoxymethane (AOM) and dextran sulfate sodium (DSS), and its impact on gut microbiota. Whole cranberry powder was administered to mice through diet at 1.5% w/w for 20 week. Our results demonstrated that treatment with cranberry powder significantly reduced the incidence and multiplicity of colon tumors. These protective effects were associated with decreased inflammation and increased apoptosis in the colonic tumors. Using Miseq sequencing and qPCR, we analyzed the composition of fecal microbiota of the mice. Compared to that of the negative control group, fecal microbiota of AOM/DSS‐treated mice showed relative abundance shifts, alterations in the abundance of Clostridiales and Bacteroidales, and an increase of the low abundant Enterobacteriales and Deferribacterales. Dietary treatment with whole cranberry powder reversed aforementioned alterations in the fecal microbiota of AOM/DSS‐treated mice. Moreover, whole cranberry powder also increased the number of Bifidobacteriales and Lactobacillus in the fecal microbiota. These composition alterations induced by whole cranberry powder were associated with suppressed colonic inflammation and carcinogenesis. In conclusion, our results demonstrated that whole cranberry powder modulated the composition of gut microbiota in AOM/DSS‐treated mice, which may contribute to its anti‐inflammatory and anti‐carcinogenic effects in the colon.

Support or Funding Information

This study was partially supported by fund from USDA
Characterization of the Unique Viscoelastic Properties of the Mitral Valve Anterior Leaflet
Authors: Figueroa Lysmarie , Brazile Bryn , Lin Sallie , Nelson Brandon , Liao Jun
Published: June 2021

The most common mitral valve (MV) disease is the MV regurgitation, in which the anterior leaflet and the posterior leaflet cannot coapt well and hence result in the leaking of blood from the left ventricle to the left atrium during the systolic phase. The treatment options include MV replacement and repair. In order to develop a bioprosthetic or a tissue engineered mitral valve leaflets that behaves similarly to the native MV, the mechanical properties of the native MV leaflets must be well understood (Grashow et al., 2006). In this study, we aim to characterize the unique viscoelastic properties of mitral valve anterior leaflet by studying the mechanical behavior of the tissue in regards to stress‐relaxation, creep, and tissue failure. Mitral valve anterior leaflets (MVAL) of porcine specimens were obtained from a local abattoir. These specimens were then further dissected in the circumferential direction into a dog‐bone shape samples for mechanical testing at a target load level of 600 grams. The testing protocol for each sample was performed as follows: after preconditioning, leaflet tissue was subjected to (1) stress‐relaxation for 15 minutes, followed by (2) creep for 15 minutes, and finally (3) the sample is ultimately pulled to failure. All testing was performed in a PBS bath using a Test Resources uniaxial testing machine. We observed a normal degree of stress relaxation similar to other types of collagenous tissues (~30% – 50%), but negligible creep. Understanding the unique viscoelastic properties of the native MV leaflets at different loading levels would help to better design bioprosthetics or tissue engineered mitral valves that mimics the natural design and the optimal tissue behavior.

Support or Funding Information

This research was funded by the National Science Foundation Award No. DMR‐1359437 at the Agricultural and Biological Engineering Department at Mississippi State University.

Special thanks to Sourav Patnaik and Xiaodan Shi for their contribution to the project and to the UPR‐PRISE Program NIH Grant #R25GM096955 for funding and supporting its students through participation in research experiences during their summer internships
Management of Distal Radius Fractures in Adolescent Patients
Authors: Greig Danielle , Silva Mauricio
Published: June 2021

Background:

While management recommendations for distal radius fractures in both young and skeletally mature patients have been generally well-established, controversy still exists regarding optimal management in adolescent patients approaching skeletal maturity. Thus, the goal of this review is to analyze relevant literature and provide expert recommendations regarding the management of distal radius fractures in this patient population.

Methods:

A PubMed search was performed to identify literature pertaining to distal radius fractures in adolescent patients, defined as 11 to 14 years in girls and 13 to 15 years in boys. Relevant articles were selected and summarized.

Results:

Distal radius fractures demonstrate significant potential for remodeling of angular deformity and bayonet apposition, even in patients older than 12 years of age. Rotational forearm range of motion and functional outcomes are acceptable with up to 15 degrees of residual angulation. Closed reduction and percutaneous pinning reduces fracture redisplacement but has a high associated complication rate. There is no literature comparing plate versus pin fixation of distal radius fractures in the pediatric population, but in adults plate fixation is associated with higher cost with no improvement in long-term functional outcomes.

Conclusions:

Remodeling can still be expected to occur in adolescent patients, and even with residual deformity functional outcomes after distal radius fractures are excellent. Up to 15 degrees of residual angulation can be accepted before considering operative management. Smooth pins should be considered over plates as first-line operative management for unstable fractures that fail nonoperative treatment.
Proximal Humerus Fractures: What Alignment is Acceptable in Children 10 and Up?
Authors: Shahriar Rajin , Hosseinzadeh Pooya
Published: June 2021

Background:

Fractures of the proximal humerus in skeletally immature patients are rare, and even rarer still in individuals approaching skeletal maturity. Concepts regarding remodeling potential, amount of deformity and functional demands can guide our treatment decision making, but criteria are poorly defined. The purpose of this manuscript is to discuss the issues and the best available evidence.

Methods:

A search of the English literature was carried out using PubMed to identify papers on the topic of proximal humerus fractures in skeletally immature individuals.

Results:

The literature available on the topic of pediatric proximal humerus fractures is limited, especially regarding fractures in patients approaching skeletal maturity. Certainly, as the remodeling potential decreases and the amount of deformity and functional demand increase, the need for operative treatment increases. The exact tolerances and criteria have not been established. A variety of surgical techniques exist, and have been shown to be helpful.

Conclusions:

Operative treatment may be necessary in individuals approaching skeletal maturity. Concepts discussed in this paper regarding remodeling, amount of deformity and functional demand may help the surgeon to make appropriate treatment decisions. Future prospective comparative studies which are pending will hopefully shed further light on this matter.
When Should Instrumentation to the Pelvis be Considered in Minimally Ambulatory Adolescents With Neuromuscular Scoliosis?
Authors: Douleh Diana G. , Greig Danielle , Thompson Rachel , Garg Sumeet
Published: June 2021

Introduction:

The goal of neuromuscular scoliosis (NMS) surgery is to improve sitting balance, facilitate daily care, and alleviate pain. In nonambulatory patients, where sitting balance is key, fusion to the pelvis is usually required. However, in minimally ambulatory patients, fusion to the pelvis remains controversial, and there is considerable practice variability in this patient population. The purpose of this study is to evaluate and summarize the available evidence regarding fusion constructs in minimally ambulatory patients with NMS and to provide expert opinion regarding when fusion to the pelvis should be considered.

Methods:

A search of the English literature was performed using PubMed to identify papers pertaining to patients with NMS treated with instrumented posterior spinal fusion. Papers published before 2000, case reports, and level V evidence were excluded.

Results:

The authors identified 8 studies for review. The majority included both nonambulatory and minimally ambulatory patients. Structured review of the literature demonstrated fusion to the pelvis may allow for greater curve and pelvic obliquity correction, but it is also associated with increased blood loss and operative time. There is no evidence that fusing to the pelvis decreases ambulatory status in minimally ambulatory patients.

Conclusions:

In minimally ambulatory patients with NMS, fusion short of the pelvis may be considered in patients with adequate head control without the presence of hip subluxation or dislocation and when pelvic obliquity is <15 degrees. Fusion to the pelvis is recommended in patients who do not meet these criteria.
Fine particulate pollution concentration in Addis Ababa exceeds the WHO guideline value
Authors: Kumie Abera , Worku Alemayehu , Tazu Zelalem , Tefera Worku , Asfaw Araya , Boja Getu , Mekashu Molla , Siraw Dawit , Teferra Solomon , Zacharias Kristin , Patz Jonathan , Samet Jonathan , Berhane Kiros
Published: June 2021

Background:

Real-time monitoring of fine particulate matter (PM2.5) concentrations and assessing the health impact are limited in Ethiopia. The objective of this study is to describe current levels of PM2.5 air pollution in Addis Ababa and examine temporal patterns and to consider the health impact of current PM2.5 exposure levels.

Methods:

PM2.5 concentrations were measured using a centrally-located Beta Attenuator Monitor (BAM-1022) for 3 years (1 April 2017 to 31 March 2020), with data downloaded biweekly. Deaths attributable to current PM2.5 concentration levels were estimated using the AirQ+ tool. The daily average was estimated using hourly data.

Results:

The daily mean (SD) PM2.5 concentration was 42.4 µg/m3 (15.98). Two daily extremes were observed: morning (high) and afternoon (low). Sundays had the lowest PM2.5 concentration, while Mondays to Thursdays saw a continuous increase; Fridays showed the highest concentration. Seasons showed marked variation, with the highest values during the wet season. Concentration spikes reflected periods of intensive fuel combustion. A total of 502 deaths (4.44%) were attributable to current air pollution levels referenced to the 35 µg/m3 WHO interim target annual level and 2,043 (17.7%) at the WHO 10 µg/m3 annual guideline.

Conclusion:

PM2.5 daily levels were 1.7 times higher than the WHO-recommended 24-hour guideline. The current annual mean PM2.5 concentration results in a substantial burden of attributable deaths compared to an annual mean of 10 µg/m3. The high PM2.5 level and its variability across days and seasons calls for citywide interventions to promote clean air.
Regional Variation of Early-onset Neonatal Group B Streptococcal Disease Prevention Strategies in Mainland China
Authors: Wang Yan , Zhao Yangyu , Zou Liying , Qiao Jie , Benitz William E.
Published: June 2021

Background:

Prevention strategies can reduce the incidence of early-onset group B Streptococcus (GBS) neonatal sepsis (EOGBS). Rates of GBS colonization and infection vary among regions within China. China has not adopted a unified prevention strategy.

Methods:

To assess strategies to reduce EOGBS in China, models were developed to quantify residual EOGBS rates with intrapartum antibiotic prophylaxis in infants ≥ 35 weeks’ gestation in risk factor-based and antepartum screening-based strategies. Maternal GBS colonization rates and EOGBS incidence in 3 regions of China (A: Xiamen of Fujian province, B: Shanghai and C: Liuzhou of Guangxi province) were estimated from published data.

Results:

Estimates for GBS colonization and attack rates were 21.6%, 11.7% and 6.1% and 1.79, 1.79 and 0.58 per 1000 live births for regions A, B and C, respectively. Modeling predicted that strategies including screening cultures beginning at 36 weeks’ gestation and intrapartum antibiotic prophylaxis in 90% of eligible parturients could reduce EOGBS incidence to 0.44, 0.50 and 0.16 per 1000 live births in these regions. In region C, the expected EOGBS rate could be reduced to 0.28 per 1000 using a risk factor-based strategy.

Conclusions:

Different strategies for preventing EOGBS may be needed in different regions of mainland China. Screening strategies may be most appropriate in regions with higher attack rates, even with moderate levels of maternal GBS colonization. In areas with low attack rates, risk factor strategies that reduce morbidity by at least one-third may suffice.
Intrinsic attention to pain is associated with a pronociceptive phenotype
Authors: Adams Greig , Harrison Richard , Gandhi Wiebke , van Reekum Carien M. , Salomons Tim V.
Published: June 2021

Introduction:

Evidence suggests that attention to pain is a product of both incoming sensory signals and cognitive evaluation of a stimulus. Intrinsic attention to pain (IAP) is a measure that captures an individual's natural tendency to attend to a painful stimulus and may be important in understanding why pain disrupts cognitive functioning in some individuals more than others.

Objective:

In this study, we explored the extent to which IAP was associated with the modulation of incoming sensory signals characteristic of a pronociceptive phenotype: temporal summation (TS) and conditioned pain modulation (CPM).

Method:

44 healthy participants (23 female; Mage=23.57, S.D.=5.50) were assessed on IAP, TS and CPM.

Results:

We found that IAP was positively correlated with TS and CPM. A regression model showed that TS and CPM explained 39% of the variance in IAP scores. Both mechanisms seem to contribute independently to the propensity to attend to pain.

Conclusion:

These findings highlight that modulatory mechanisms at the spinal/supraspinal level exert a strong influence on an individual's ability to disengage from pain.
Best practices for virtual care to support youth with chronic pain and their families: a rapid systematic review to inform health care and policy during COVID-19 and beyond
Authors: Birnie Kathryn A. , Killackey Tieghan , Stinson Jennifer , Noel Melanie , Lorenzetti Diane L. , Marianayagam Justina , Jordan Isabel , Jordan Evie , Neville Alexandra , Pavlova Maria , Campbell Fiona , Lalloo Chitra
Published: June 2021

The COVID-19 pandemic has acutely challenged health systems and catalyzed the need for widescale virtual care and digital solutions across all areas of health, including pediatric chronic pain. The objective of this rapid systematic review was to identify recommendations, guidelines, and/or best practices for using virtual care to support youth with chronic pain and their families (CRD42020184498). MEDLINE, CINAHL, Embase, APA PsychINFO, and Web of Science were searched the week of May 25, 2020, for English language peer-reviewed articles published since 2010 that (1) discussed children and adolescents aged <18 years reporting any type of chronic pain (ie, pain lasting >3 months); (2) focused on any type of virtual care (eg, telephone, telehealth, telemedicine, mHealth, eHealth, online, or digital); and (3) reported on guidelines, best practices, considerations, or recommendations for virtual care. Abstract and full text screening and data extraction were performed in duplicate. Meta-ethnography was used to synthesize concepts across articles. Of 4161 unique records screened, 16 were included addressing diverse virtual care and pediatric chronic pain conditions. Four key themes were identified: (1) opportunities to better leverage virtual care, (2) direct effective implementation of virtual care, (3) selection of virtual care platforms, and (4) gaps in need of further consideration when using virtual care to support youth with chronic pain and their families. No existing guidelines for virtual care for pediatric chronic pain were identified; however, best practices for virtual care were identified and should be used by health professionals, decision makers, and policymakers in implementing virtual care.
Introduction: the mathematics of energy systems
Authors: Mancarella Pierluigi , Moriarty John , Philpott Andy , Veraart Almut , Zachary Stan , Zwart Bert
Published: June 2021

The urgent need to decarbonize energy systems gives rise to many challenging areas of interdisciplinary research, bringing together mathematicians, physicists, engineers and economists. Renewable generation, especially wind and solar, is inherently highly variable and difficult to predict. The need to keep power and energy systems balanced on a second-by-second basis gives rise to problems of control and optimization, together with those of the management of liberalized energy markets. On the longer time scales of planning and investment, there are problems of physical and economic design. The papers in the present issue are written by some of the participants in a programme on the mathematics of energy systems which took place at the Isaac Newton Institute for Mathematical Sciences in Cambridge from January to May 2019—see
http://www.newton.ac.uk/event/mes
.

This article is part of the theme issue ‘The mathematics of energy systems’.
Scheduling of energy storage
Authors: Zachary Stan , Tindemans Simon H. , Evans Michael P. , Cruise James R. , Angeli David
Published: June 2021

The increasing reliance on renewable energy generation means that storage may well play a much greater role in the balancing of future electricity systems. We show how heterogeneous stores, differing in capacity and rate constraints, may be optimally, or nearly optimally, scheduled to assist in such balancing, with the aim of minimizing the total imbalance (unserved energy) over any given period of time. It further turns out that in many cases the optimal policies are such that the optimal decision at each point in time is independent of the future evolution of the supply–demand balance in the system, so that these policies remain optimal in a stochastic environment.

This article is part of the theme issue ‘The mathematics of energy systems’.
Large fluctuations in locational marginal prices
Authors: Nesti T. , Moriarty J. , Zocca A. , Zwart B.
Published: June 2021

This paper investigates large fluctuations of locational marginal prices (LMPs) in wholesale energy markets caused by volatile renewable generation profiles. Specifically, we study events of the form

P

(

LMP

∉

∏

i
=
1

n

[

α
i

−

,

α
i

+

]

)

,

where
LMP
is the vector of LMPs at the
n
power grid nodes, and
α
−
,

α

+

∈

R

n

are vectors of price thresholds specifying undesirable price occurrences. By exploiting the structure of the supply–demand matching mechanism in power grids, we look at LMPs as deterministic piecewise affine, possibly discontinuous functions of the stochastic input process, modelling uncontrollable renewable generation. We use techniques from large deviations theory to identify the most likely ways for extreme price spikes to happen, and to rank the nodes of the power grid in terms of their likelihood of experiencing a price spike. Our results are derived in the case of Gaussian fluctuations, and are validated numerically on the IEEE 14-bus test case.

This article is part of the theme issue ‘The mathematics of energy systems’.
Temporal association of reduced serum vitamin D with COVID-19 infection: A single-institution case-control and historical cohort study
Authors: Gupta Diviya , Menon Sahit , Criqui Michael H. , Sun Bryan K.
Published: June 2021

Objectives

Vitamin D supplementation has been proposed for the prevention and treatment of COVID-19, but the relationship between the two is inconclusive: Reduced serum vitamin D may predispose to COVID-19, but it may also be a secondary consequence of infection. The objective of this study was to assess the temporal association between serum vitamin D levels and COVID-19.

Design

A single-institution case-control study and a historical cohort study

Setting

University of California San Diego (UCSD) Health System in San Diego, California

Participants

Patients testing positive for COVID-19 from January 1, 2020 to September 30, 2020 with serum 25-hydroxy-vitamin D (25(OH)D) measured within 180 days of diagnosis. Patients were separated based on whether 25(OH)D was measured before (n=107; “pre-diagnosis”) or after (n=203; “post-diagnosis”) COVID-19 diagnosis. Subjects with 25(OH)D assessments prior to COVID-19 diagnosis were evaluated using a case-control study design, while subjects with 25(OH)D measured after COVID-19 diagnosis were analyzed with a historical cohort study design.

Primary and Secondary Outcome Measures

In the pre-diagnosis study, a conditional logistic regression was performed using COVID-19 infection status as the binary dependent variable. In the post-diagnosis study, an ordinary least squares regression was performed using serum 25(OH)D levels as the continuous dependent variable.

Results

Serum 25(OH)D levels were not associated with the odds of subsequently testing positive for COVID-19 (OR 1.00, 95% CI: 0.98 to 1.02, p = 0.982). However, COVID-19 positive individuals had serum 25(OH)D measurements that were lower by 2.70 ng/mL (95% CI: −5.19 to −0.20, p = 0.034) compared to controls.

Conclusions

In our study population, serum 25(OH)D levels were not associated with risk of testing positive for COVID-19 but were reduced in subjects after being diagnosed with COVID-19 infection. These results raise the possibility that reduced serum 25(OH)D may be a consequence and not a cause of COVID-19 infection.
Early Epidemiological Evidence of Public Health Value of WA Notify, a Smartphone-based Exposure Notification Tool: Modeling COVID-19 Cases Averted in Washington State
Authors: Segal Courtney , Zhang Zhehao , Karras Bryant T , Revere Debra , Zane Gregory , Baseman Janet G
Published: June 2021

Background

Secure and anonymous smartphone-based exposure notification tools are recently developed public health interventions that aim to reduce COVID-19 transmission and supplement traditional public health suriveillance. We assessed the impact of Washington State’s exposure notification tool, WA Notify, in mitigating the spread of COVID-19 during its first four months of implementation.

Methods

Due to the constraints of privacy-preservation, aggregate metrics and disparate data sources were utilized to estimate the number of COVID-19 cases averted based on a modelling approach adapted from Wymant et al (2021) using the following parameters: number of notifications generated; the probability that a notified individual goes on to become a case; expected fraction of transmissions preventable by strict quarantine after notification; actual adherence to quarantine; and expected size of the full transmission chain if a contact had not been notified.

Results

The model was run on a range of secondary attack rates (5.1%-13.706%) and quarantine effectiveness (53% and 64%). Assuming a 12.085% secondary attack rate and 53% quarantine effectiveness, the model shows that 5,500 cases (central 95% range of sensitivity analyses 2,800-8,200) were averted statewide during the first four months of its implementation. Based on an estimated COVID-19 case fatality of 1.4%, WA Notify saved 40-115 lives during the study period.

Conclusions

These findings demonstrate the value of exposure notification tools as a novel public health intervention to mitigate the spread of COVID-19 in the U.S. As new variants emerge and non-essential travel bans are lifted, exposure notification tools may continue to play a valuable role in limiting the spread of COVID-19.