bluuebunny/crossref_metadata_2025 huggingface dataset:
The impact of pre-existing conditions and perceived health status on mental health during the COVID-19 pandemic
Authors: Buneviciene Inesa , Bunevicius Romas , Bagdonas Sarunas , Bunevicius Adomas
Published: June 2021

Background

Patients with pre-existing conditions and poor health status are vulnerable for adverse health sequalae during the COVID-19 pandemic. We investigated the association of pre-existing medical conditions and self-perceived health status with the risk of mental health complications during the COVID-19 pandemic.

Methods

In October—December, 2020, 1036 respondents completed online survey that included assessment of pre-existing conditions, self-perceived health status, depressive (Patient Health Questionnaire-8 score ≥ 10), anxiety (Generalized Anxiety Disorders-7 score ≥ 10) and post-traumatic stress (Impact of Events Scale Revised) symptoms, alcohol use (AUDIT), and COVID-19 fear (COVID-19 Fears Questionnaires for Chronic Medical Conditions).

Results

Study participants were predominantly women (83%), younger than 61 years of age (94%). Thirty-six percent of respondents had a pre-existing condition and 5% considered their health status as bad or very bad. Pre-existing conditions and poor perceived health status were associated with increased risk for moderate to severe depressive and anxiety symptoms, fear of COVID-19 and post-traumatic stress symptoms, independently from respondents’ age, gender, living area, smoking status, exercise, alcohol consumption and diet.

Conclusions

Pre-existing medical conditions and poor perceived health status are associated with increased risk of poor mental health status during the COVID-19 pandemic.
TEVA UK LIMITED v GILEAD SCIENCES, INC
Authors:   Court of Appeal
Published: June 2021

H1 Supplementary protection certificates – Anti-retroviral medication – Validity – Combination of active ingredients – Construction of art. 3(a) of the SPC Regulation – Whether product “protected by the basic patent in force” – Whether extent of protection the relevant test – Issue referred to Court of Justice – Interpretation and application of judgment of Court of Justice – Appeal to Court of Appeal
Phosphorus Supply Does Not Affect Fusarium Crown Rot of Winter Wheat
Authors: Hagerty C. H. , McLaughlin K. R. , Kroese D. R. , Lutcher L. K.
Published: June 2021

Fusarium crown rot (FCR) is a major limitation to the wheat (Triticum aestivum L.) industry in the inland Pacific Northwest, United States. Genetic resistance to FCR is poorly understood and major gene resistance is not available in adapted cultivars. Chemical control is ineffective and crop rotations, which disrupt cycles of the disease, are not feasible in the region’s precipitation-limited climate. Cultural control methods are the only realistic option for farmers who struggle to minimize the impact of this disease. It is well established that FCR is favored by moisture-limited environments and an oversupply of plant-available nitrogen in soil. Effects of the supply of phosphorus in soil have not been clearly delineated. We conducted a 2-year FCR experiment at two locations in the low-precipitation zone (<30 cm) of north-central Oregon. Phosphorus fertilizer was applied in-furrow with phosphorus (P) at rates of 0, 5, and 15 kg ha−1, to plots planted with either a hard red or soft white winter wheat cultivar. The P at 15 kg ha−1 application rate increased tissue phosphorus concentration, early-season dry matter, and phosphorus uptake at both locations and both years of this study. Phosphorus treatment had no effect on grain yield, protein, or test weight. Phosphorus had no effect on the severity of FCR. This research improved our knowledge of cultural management boundaries as they relate to the control of FCR.

[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Surprising phospholipid specificity of two blood clotting proteins: factor VII and protein C
Authors: Tavoosi Narjes , Morrissey James H.
Published: June 2021

Phospholipid membranes are an important part of the blood clotting cascade and can alter rates of clotting reactions depending on their phospholipid composition. Seven proteins in blood clotting bind reversibly to phospholipid membranes through γ‐carboxyglutamate‐rich (GLA) domains. Although the GLA domains of these proteins are very similar structurally, their membrane binding affinities vary by almost three orders of magnitude. We employed surface plasmon resonance binding studies and enzymatic assays to systematically investigate the phospholipid specificity of these seven GLA domains. It has long been thought that GLA domains bind preferentially to bilayers containing phosphatidylserine (PS), but we found, surprisingly, that two of the GLA domain‐containing blood clotting proteins (factor VII and protein C) bound preferentially to membranes containing phosphatidic acid (PA) or phosphatidylinositol phosphate (PIP), compared to PS. Furthermore, PA and PIP strongly enhanced the enzymatic activities of factor VIIa and activated protein C. Incidentally, of the seven blood clotting proteins with GLA domains, factor VII and protein C are known to have the lowest binding affinities for PS‐ membranes. Our findings provide new insights into the membrane binding mechanism for these two medically important GLA domain‐containing clotting proteins, through PA‐ and PIP‐specific binding interactions.
A Moderate‐Fat Diet with Pistachios Lowers Small‐Dense LDL and Improves Markers of Insulin Sensitivity in Subjects with Moderately‐Elevated Cholesterol Levels
Authors: Holligan Simone , West Sheila G. , Gebauer Sarah K. , Kay Colin D. , Kris‐Etherton Penny M.
Published: June 2021

We evaluated the dose‐response effects of pistachios over 4 weeks, on markers of insulin sensitivity in individuals (N=28) with moderately elevated LDL‐C (>; 110 mg/dl). Three test diets (SFA ≈ 8%; cholesterol < 300 mg/dl) were fed in this crossover study: control (25% total fat); 10% of energy from pistachios (1PD; 32–63 g; 30% total fat); or 20% of energy from pistachios (2PD; 63–126 g; 34% total fat). A Western run‐in diet (35% total fat, 11% SFA) was fed for 2 weeks; subjects had a mean BMI of 26.8 ± 0.7 kg/m2 and were weight stable while on the study. There was a significant diet effect on small‐dense LDL (sdLDL) levels (P = 0.001); sdLDL decreased on the 2PD versus the 1PD (P = 0.03) and the 2PD versus control (P = 0.001). There also was a significant diet effect for the TG/HDL‐C ratio (P = 0.041), with a significant reduction on the 2PD versus control (P = 0.036). Reductions in sdLDL levels were significantly correlated with reductions in TG levels (r = 0.424; P = 0.025); changes were calculated as the difference between baseline and post 2PD treatment. There were no significant diet effects for HDL‐C levels when comparing the pistachio diets to control, but there were trends for diet effects on increasing levels of functional α‐1 (P = 0.073) and α‐2 (P = 0.056) HDL particles. Pistachio inclusion in a moderate‐fat diet (≈ 35%) favorably affects insulin sensitivity and contributes to a beneficial cardio‐metabolic profile.

Grant Funding Source: American Pistachio Growers
Efficacy of different schemes of supplementation with micronutrient powders on anemia and micronutrient status in infants
Authors: Zavaleta Nelly , Loza David , Egoavil Patricia , Sánchez Jorge , Mosqueira Roberto , Neufeld Lynnette
Published: June 2021

Objective

To compare the efficacy of different dosing and duration schemes for micronutrient powders on anemia, and micronutrient status. We supplemented a group of 400 infants 6–11 months old, living in the northern highlands of Peru, with powder micronutrients containing iron, zinc, vitamin A, vitamin C and folic acid. Children were randomly assigned to 4 supplementation groups: a) 6 months daily supplementation; b) 6 months intermittent; c) 12 months daily and; d) 12 months intermittent supplementation, supplements were provided monthly at the baby well visit. At entry and after supplementation scheme, hemoglobin and micronutrient status were measured. We found baseline anemia 73%, 71%, 73% and 76% respectively (p=0.885); at 6 months supplementation anemia was reduced to 40%, 40%, 34% and 52% respectively (p=0.086). Initial mean hemoglobin values were 116, 117, 117, and 115 g/L respectively. At 6 months mean hemoglobin values were 125, 123, 126 and 122 g/L. During the first 6 months of supplementation with micronutrient powders, the results suggest that all groups benefitted from supplementation, without large differences between them. After 6 months, the prevalence of anemia was still high. Supported by Micronutrient Initiative, Canada.
Glutamate receptor activation in the rostral ventrolateral medulla (RVLM) mediates the sympathetic response to increased cerebrospinal fluid (CSF) sodium concentration
Authors: Lang Susan M , Stocker Sean D
Published: June 2021

Compelling evidence indicates increased CSF sodium concentration elevates sympathetic nerve activity (SNA) and arterial blood pressure (ABP) in salt‐sensitive hypertension. RVLM neurons project to the spinal cord and regulate SNA and ABP under a number of physiological challenges and pathophysiological states. Therefore, we hypothesized that RVLM neurons mediate the sympathoexcitatory response to increased CSF sodium. Inactin‐anesthetized, male Sprague‐Dawley rats (n=5/group) were infused with 1M NaCl (5 μL/10 min) or artificial CSF in the lateral ventricle and then received an RVLM injection (60 nL) of CSF or the ionotropic glutamate receptor antagonist kynurenic acid (KYN, 25 mM). Infusion of 1M NaCl significantly increased lumbar SNA (112±1%, P<0.05) and ABP (Δ: 9±1 mmHg, P<0.05). RVLM injection of KYN significantly attenuated (P<0.05) the increase in lumbar SNA (101±3%) and mean ABP (Δ: 1±2 mmHg). In addition, in vivo single‐unit recordings demonstrate that infusion of 1M NaCl increased discharge in 60% (3/5) of spinally‐projecting, barosensitive RVLM neurons (2.1±0.4 to 5.8±0.2 Hz, P<0.05). These findings suggest increased CSF sodium activates RVLM neurons to elevate SNA and ABP.
Neuroprotective Activity of Berberis aristata against 6‐OHDA Induced Parkinson's Disease Model
Authors: Magnnavar Chandrashekhar V , Panji Avinash S , Chinnam Sowmya
Published: June 2021

Objective

Traditionally, the plant is used for various diseases, including neuronal disorders. To evaluate the neuroprotective activity of Berberis aristata DC.against 6‐OHDA Parkinson's disease in rat model.

Materials and methods

Parkinson's disease was induced by the striatal 6‐OHDA lesions. The behavioral assessments such as spontaneous locomotor activity, muscular coordination, and open field were studied along with antioxidant enzymatic and non‐enzymatic levels were estimated. Striatal infraction area, volume, estimation of Dopamine level was done by LC/MS/MS method. The histophathological studies were performed.

Results

The Berberis aristata DC. methanol extract showed anti‐Parkinson's disease activity by increase in behavioural activity and muscular coordination, decrease in clockwise rotation and in biochemical estimation there was significant decrease in lipid peroxidation (LPO) and increase in superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and total thiols levels in extract treated groups as compared to control group. Striatal infraction area and volume was significantly reduced in extract treated groups as compared to control group.

Conclusion

The methanol extract of Berberis aristata DC.showed potent neuroprotective activity against 6‐OHDA induced Parkinson's disease in rat model.
Renal responses to short term non‐pressor AngII ± intrarenal RAS blockade in rats
Authors: Nguyen Mien Thi Xuan , Han Julie , McDonough Alicia A.
Published: June 2021

Long term (14d) AngII infusion augments intrarenal AngII production and raises blood pressure; ACE inhibition (ACEi) blunts both responses. This study aimed to determine 1) the renal responses to a short term (3 d) non‐pressor dose of AngII and 2) whether the responses were blunted by ACEi treatment implicating local AngII production. Male Sprague‐Dawley rats were infused via osmotic minipumps with either vehicle (control) or AngII (200 ng/kg/min) ± the ACEi enalapril (30 mg/kg/day in drinking water). There were no significant differences in body weight gain, overnight urine volume, or urinary Na and K excretion among the groups. Abundance of renal transporters was determined by quantitative immunoblot, and normalized to control values, defined as 1.0.

Control
AngII
AngII + enalapril

Cortex
NHE3 total
1.00 ± 0.05
1.51 ± 0.14*
1.37 ± 0.02*

NHE3‐P
1.00 ± 0.07
1.37 ± 0.09
1.45 ± 0.13*

NKCC total
1.00 ± 0.09
1.70 ± 0.23*
1.57 ± 0.11

NKCC‐P
1.00 ± 0.17
1.96 ± 0.20*
2.13 ± 0.17*

NCC total
1.00 ± 0.05
1.33 ± 0.08*
1.12 ± 0.03

NCCpS71
1.00 ± 0.07
1.29 ± 0.09*
1.01 ± 0.04

SPAK total
1.00 ± 0.19
2.71 ± 0.55*
2.87 ± 0.40*

Medulla
NKCC total
1.00 ± 0.04
0.70 ± 0.05*
0.75 ± 0.07*

NKCC‐P
1.00 ± 0.03
0.82 ± 0.11
1.22 ± 0.28

SPAK total
1.00 ± 0.02
0.99 ± 0.06
0.98 ± 0.03

p<0.05 vs. control.

Conclusion

1) 3 d AngII infusion increases cortical NHE3, NKCC, NCC and SPAK while decreasing medullary NKCC abundance. 2) Blocking intrarenal RAS with enalapril blunted the effects of AngII infusion on NCC total, NCCp, and NKCC indicating these are early targets of intrarenal RAS stimulation and, thus, intrarenal ACE inhibition. NIH R01 DK 083785.
Americans consume less added sugars and solid fats and consume more whole grains and oils: changes from 2003‐04 to 2009‐10 (369.2)
Authors: Bowman Shanthy , Friday James , Thoerig Rachel , Clemens John , Moshfegh Alanna
Published: June 2021

The 2010 Dietary Guidelines for Americans (DGA) provide recommendations on how much to eat from nutritious food groups such as whole grains, vegetables, fruits, lean protein foods, dairy, and oils while placing limits on added sugars and solid fats that are sources of empty calories. The research objective was to identify changes in the intakes of DGA food groups from 2003‐04 and 2009‐10. The What We Eat in America, National Health and Nutrition Examination Survey 2003‐04 and 2009‐10, day 1 dietary data were used for the study. The mean intake estimates of individuals, ages 2 years and over, were compared. A 33% increase in the whole grains (0.6 vs. 0.8 oz. eq.) and 8% reduction in refined grains (6.3 vs. 5.8 oz. eq.) intakes were noted. The mean intakes of solid fats decreased by 23% from 48g to 37g; and added sugars decreased by 14% from 88g to 76g. The mean intake of oils increased from 19g to 22g. The mean total vegetable intake decreased by 0.2 cup equivalents (1.6 vs. 1.4 cup eq.) in the time period studied. Total fruit intake did not change appreciably (1.0 vs. 1.1 cup eq.). The study showed that Americans consumed lower amounts of empty calories by reducing added sugars and solid fats in the diet. They replaced foods containing solid fats with foods containing oils. Nevertheless, in 2009‐10, American’s intakes of nutritious foods such as whole grains and vegetables were much below the 2010 DGA recommendations.
Localization and expression profile of activator of G‐protein signaling proteins in the kidney (690.6)
Authors: Lenarczyk Marek , Regner Kevin , Park Frank
Published: June 2021

Activator of G‐protein signaling (AGS) are a family of accessory proteins that regulate heterotrimeric G‐protein function in a receptor‐independent mechanism. Recent studies in our lab have identified a crucial role for AGS3/GPSM1 in the recovery of the renal epithelial cells following acute kidney injury. Under normal conditions, AGS3/GPSM1 is exclusively expressed in the distal and collecting ducts. Following ischemia‐reperfusion injury, AGS3/GPSM1 is induced in the proximal tubules in the outer medulla, which is a highly sensitive site of injury due to ischemia. To determine whether other AGS proteins are expressed and may demonstrate biological activity during acute kidney injury, this study was designed to localize AGS proteins within the kidney using immunohistochemistry, and also determine the renal expression profile using quantitative RT‐PCR of all 13 known AGS proteins during quiescence and following an injury response. AGS1 was found to be predominantly localized to the proximal tubule in the renal cortex and outer medulla from mice, whereas AGS3, 5, and 8 were exclusively localized to the distal and collecting ducts in rat kidneys. In rat kidneys following ischemia‐reperfusion injury, AGS1 and AGS7 were both dramatically increased after 24 hours by 6‐7 fold, and slowly decreased towards normal (sham) levels at 72 and 168 hours after reperfusion. Messenger RNA levels of AGS4, 8, 9, 10, 11 and 12 were decreased by 40‐90% in the ischemia‐reperfusion injured kidneys compared to their sham (time‐control) kidneys at 24 hours, which tended to return towards normal (sham) levels by 168 hours after reperfusion. This study provides new information as to the site of synthesis of AGS protein, and could shed new light on their potential roles during normal and pathologic conditions in the kidney.

Grant Funding Source: Supported by National Institutes of Health
Functional connectivity between Bötzinger complex glycinergic neurons and parafacial late‐expiratory neurons for expiratory and sympathetic control (712.17)
Authors: Moraes David , Abdala Ana , Machado Benedito , Paton Julian
Published: June 2021

Our computational model predicts that post‐inspiratory (post‐I) neurons expressing the glycine transporter 2 (GLYT2) located in the Bötzinger Complex (BötC) suppress generation of abdominal and sympathetic late‐expiratory (late‐E) activities in eucapnia. Hypercapnia allows parafacial late‐E neurons to escape this inhibition. To test functional connectivity between glycinergic BötC and late‐E neurons, we used cell‐type specific viral vector expression of channelrhodopsin (ChETA) or hallorhodopsin (eNpHR3.0) to excite/inhibit GLTY2 neurons in the BötC of rats. Intracellular recordings of parafacial late‐E neurons (n=9) confirmed that inhibition during post‐I prevents generation of late‐E activity under eucapnia. eNpHR3.0‐mediated inhibition of GLYT2 neurons in the BötC evoked abdominal and sympathetic late‐E activities and increased arterial pressure (n=4).In contrast, ChETA‐mediated excitation of GLYT2 neurons in the BötC abolished the CO2‐induced abdominal and sympathetic late‐E activities (n=4), due to inhibition of parafacial late‐E neurons (n=3). These results indicate an emergence of parafacial late‐E activity with hypercapnia which is normally suppressed by BötC glycinergic neurons.

Grant Funding Source: Supported by NIH R01 NS069220 and FAPESP
Consumption of almonds is associated with increased nutrient intake, better diet quality, and better physiological status in adult participants (19+ y) from the NHANES (2001‐2010) (810.17)
Authors: Papanikolaou Yanni , O’Neil Carol , Nicklas Theresa , Fulgoni Victor
Published: June 2021

The association of almond consumption with nutrient intake, dietary quality, and physiological parameters was examined in adults 19+ yrs (n=24,808) using NHANES (2001‐2010). Consumers (n=395) were defined as those who had any amount of almonds/almond butter during the first 24‐hr diet recall. ANOVA (covariate adjusted) were conducted using appropriate sample weights. Diet quality was calculated using the Healthy Eating Index‐2010 (HEI). Energy intake (2287±52 v 2176±9 kcal/d) was higher (p<0.05) in consumers than in non‐consumers. Protein (91±1.7 v 83±0.3 g/d), dietary fiber (22.1±0.7 v 15.9±0.1 g/d), PUFA (20.8±0.9 v 17.4±0.1 g/d), MUFA (35.1±0.6 v 30.2±0.1 g/d), vitamin A (740±36 v 620±7 RAE mcg/d), vitamin E (15.6±0.7 v 7.3±0.1 mg AT/d), magnesium (406±11 v 291±2 mg/d), potassium (3118±73 v 2719±12 mg/d), and iron (17.1±0.6 v 15.6±0.1 mg/d) intake was higher in consumers while SFA (22.4±0.7 v 26.6±0.1 g/d) and added sugars (14.5±0.8 v 19.2±0.2 tsp/d) were lower. Consumers had higher HEI scores (62.5±0.9 v 46.6±0.2). BMI (27.1±0.3 v 28.5±0.1), waist circumference (94.1±0.9 v 97.5±0.2 cm), and LDL (110±2.9 v 117±0.5 mg/dl) were lower in consumers. Consumers were 27% less likely to be overweight or obese, had a 35% reduced risk of increased waist size and were 44% less likely to have elevated LDL. Almond consumption was associated with better nutrient intake, diet quality, and physiological parameters in adults.

Grant Funding Source: Supported by the Almond Board of California and USDA
Implications of virtual reality technology in nutrition intervention (811.28)
Authors: Meng Yu , Wong Siew Sun
Published: June 2021

This era is rich in digital information. Health‐related communications and information acquisition among the younger generation increasingly involve social media, mobile technology, intelligent sensing, and immersive technology. Community‐based interventions are also exploring the use of technology. Virtual reality (VR) technology has been used in social and behavioral research in many domains. It showed potentials in supporting positive behavioral changes. This article reviews 5 published literatures featuring nutrition education interventions in VR to promote healthy eating among adults and youth. Despite limited interventions, some showed positive outcomes. In 2 of the studies, VR‐enhanced devices were effective in improving adult participants’ adherence to weight loss behaviors, and decreased social bias in self‐reporting diet records. However, the effectiveness of VR in 1 of weight management studies was inconsistent probably due to lack of supporting theories, less well‐constructed study designs, and/or negative aspects, such as motion sickness, in virtual learning environments. In addition to health promotion, weight management, and weight loss, research is needed to evaluate VR effectiveness in obesity prevention. It is recommended that future trials use randomized control trials with larger sample population over a longer period of intervention.

Grant Funding Source: PacificSource Healthcare
Almond supplementation without dietary advice significantly reduces C‐reactive protein in subjects with poorly‐controlled type 2 diabetes (830.24)
Authors: Sweazea Karen , Johnston Carol , Ricklefs Kristin , Petersen Katherine , Alanbagy Samer
Published: June 2021

The national cost of diabetes exceeds $174 billion annually in the United States. Heart disease and stroke are the primary causes of morbidity and mortality among people with type 2 diabetes (T2D). The objective of this 12‐week randomized, parallel‐arm controlled study was to determine if almond supplementation (1.5 oz/d) to a routine diet would improve diabetic and cardiovascular risk markers in subjects with T2D who are not currently taking insulin (n=11) compared to matched controls with T2D (n=10). Inclusion criteria stipulated that subjects have poorly‐controlled diabetes as characterized by HbA1c values between 6.5‐9.0%. While the results showed no significant difference in nutrient intake of subjects in the two groups, those in the almond‐treated group tended to consume fewer carbohydrates (p=0.073). There were no significant differences in plasma markers of glucose regulation or oxidative stress between subjects in the two groups, whereas the inflammatory biomarker C‐reactive protein (CRP) was significantly reduced in subjects who consumed almonds (‐1.2% vs. 4.33%, p=0.029). Therefore, daily almond consumption in the absence of other dietary or physical activity modifications is beneficial for reducing inflammation in subjects with poorly‐controlled T2D.

Grant Funding Source: Supported by the Almond Board of California.
The 4F peptide significantly decreases intestinal oxidized fatty acids (835.1)
Authors: Dadgostar Amir , Vazirian Samra , Farah Kassra , Faraz Marya
Published: June 2021

Background: We recently reported that the intestine maybe a major site of action for the peptide regardless of the route of administration. In the present study we sought to examine this hypothesis .

Methods: LDLR null mice (6 ‐ 7 months old) were fed a Western Diet (WD) and were given drinking water with or without D‐4F at a concentration of 50 υg/mL. After 2 weeks the mice were anesthetized and perfused for 10 min through the left ventricle with ice cold saline containing 2mM EDTA and 20 μM BHT to wash the organs free of blood. The intestinal lumen was thoroughly washed with the perfusion solution and enterocytes were isolated and disrupted in the presence of potent antioxidants and protease inhibitors. Lipids were extracted and determined by LC‐ESI‐MS/MS. Results: D‐4F significantly reduced the enterocyte content of 5‐HETE, 12‐HETE, 15‐HETE, 9‐HODE, and 13‐HODE (p = 0.015; p = 0.014; p = 0.015; p = 0.034; p = 0.024, respectively). D‐4F also reduced the fecal content of 5‐HETE, 12‐HETE, 15‐HETE, 9‐HODE, and 13‐HODE (p = 0.014; p = 0.044; p = 0.051; p = 0.031; p = 0.034, respectively). Conclusion: 4F significantly reduces intestinal oxidized fatty acids consistent with the hypothesis that the intestine is a major site of action for the peptide.

Grant Funding Source: NIH
Mir‐126 dependent alteration of angiogenesis contributes to right ventricle failure in pulmonary arterial hypertension (868.2)
Authors: Potus Francois , Graydon Colin , Breuils Bonnet Sandra , Paulin Roxane , Michelakis Evangelos , Provencher Steeve , Bonnet sebastien
Published: June 2021

Right Ventricular Failure (RVF) is the most important predictor of both morbidity and mortality in pulmonary arterial hypertension (PAH). PAH hypertrophied RV is relatively ischemic, potentially because of angiogenesis defect. miR‐126 (pro‐angiogenic miRNA), triggers VEGF pathway by inhibiting SPRED‐1, have emerged as critical actor of angiogenesis. We hypothesized that specific miR‐126 downregulation will promote RV ischemia and the transition from compensated (CRV) to a decompensated (DRV) RV. We studied free RV wall tissue from humans with normal RV functions, CRV and PAH (DRV). As expected, compared to both control and CRV, DRV has decreased miR‐126 (qRT‐PCR) and microvessels density (CD31 immunofluorescence) creating an imbalance between O2 demand and delivery. Interestingly, under the same conditions, miR‐126 expression did not fall in LV. miR‐126 downregulation in DRV increases SPRED‐1 thus decreasing VEGF pathway. Finally, in endothelial cells isolated from human RV, miR‐126 up‐regulation using mimic increased angiogenesis in a PAH model (matrigel assay) while downregulation of miR‐126 (antagomir) in control or CRV mimicked PAH phenotype by decreasing angiogenesis. We demonstrated for the first time that the specific RV downregulation of miR‐126 contributes to ischemic status of the DRV. Targeting miR‐126 represents a new avenue of investigation in preventing and reversing failing RV.
Aerobic exercise in pregnant Latina women: effect on metabolic and body composition outcomes. A randomized clinical trial (886.6)
Authors: Ramirez Velez Robinson
Published: June 2021

PURPOSE: A prospective randomized controlled trial was designed to assess the benefits of aerobic exercise during pregnancy, using a fitness regimen based on the 2008 Physical Activity Guidelines for Americans for exercise during pregnancy.

METHODS: The study included Sixty‐seven nulliparous in gestational week 16‐20. The experimental group completed a 3‐month supervised exercise program, commencing at 16 to 20 weeks of gestation. Each session included walking(10‐min), aerobic exercise(30‐min) and stretching(10‐min). The control group continued usual activities and performed no specific exercise. The primary outcomes were changes on blood lipids, insulin sensitivity(HOMA‐IR) and body composition(body fat/skinfold thicknesses).

RESULTS: At the end of the 3‐month program, there was no difference in the change in blood lipids: total cholesterol ‐6 mg/dL, LDL ‐8 mg/dL, glucose 0.3 mg/dL, insulin ‐2 mU/L and HOMA‐IR ‐0.9. Triglycerides and VLDL were significantly lower in the experimental group by ‐28 mg/mL and ‐6 mg/dL, respectively, P<0.05. The experimental group showed lower values of body fat and skinfold thicknesses than did the control group, but these differentials were non‐significant.

CONCLUSION: The potential public health benefits of exercise are too great and this study supports existing guidelines indicating that Latina women may begin or maintain an exercise program during pregnancy.
Kimchi fermented in a kimchi refrigerator showed enhanced anti‐cancer effects on human leukemia and gastric cancer cells (LB405)
Authors: Park Ki‐Bum , Oh Suk‐Heung , Kim Nam‐Suk , Oh Chan‐Ho , Jeon Jong‐In
Published: June 2021

In this study we investigated the anticancer effects of Kimchi (DV) extract obtained from Baechu kimchi fermented and stored in a kimchi refrigerator for 21 days. The DV kimchi extract contained higher levels of ornithine compared with control kimchi (DS) extract obtained from standard storage condition. The DV kimchi significantly inhibited the proliferation of both AGS (human, gastric adenocarcinoma) and HL‐60 (human, acute promyelocytic leukemia) cell lines. The DV kimchi extract treatment lead to increased apoptosis and decreased mitochondrial transmembrane potential in the cultured HL‐60 leukemia cells. In addition, the treatments resulted in increased expression of the p53 gene in cultured AGS gastric adenocarcinoma cells. On the other hand, the DS kimchi treatments showed relatively a small effect on the cancer cell growth prevention, apoptosis, and mitochondrial transmembrane potential at the similar concentration ranges of kimchi extract. These results suggest that, the consumption of DV kimchi could be more beneficial in promoting apoptosis and retarding the proliferation of cancer cells compared to the DS kimchi. This research was funded by WiniaMando Inc.
Novel bitter taste receptor ligands elicit G protein‐dependent negative inotropic effects in mouse heart (LB572)
Authors: Foster Simon , Blank Kristina , See Hoe Louise , Behrens Maik , Meyerhof Wolfgang , Peart Jason , Thomas Walter
Published: June 2021

G protein‐coupled receptors (GPCRs) are key mediators in cardiovascular physiology, yet frontline therapies for heart disease only target a small fraction of the cardiac GPCR repertoire. Moreover, there is emerging evidence that GPCRs implicated in taste (TIR and T2Rs) have specific functions beyond the oral cavity. Our recent description of these receptors in heart foreshadows a novel role for previously unappreciated cardiac GPCRs. Here, we sought to identify novel ligands for cardiac‐T2Rs and investigate their effects on murine cardiac function ex vivo. Five T2Rs cloned from rat heart, were screened against a panel of 102 natural or synthetic bitter chemicals in a heterologous expression system. After validating putative T2R ligands for receptor and concentration‐dependence, three novel ligands for T2R108, T2R137 and T2R143 were then tested in Langendorff perfused mouse hearts (isolated from 8 week old male C57BL/6 mice). All T2R ligands tested exhibited concentration‐dependent effects on cardiac function. Furthermore, the biphasic change of aortic pressure with sodium benzoate and the ~40% sodium thiocyanate‐mediated decrease in left ventricular developed pressure were both abrogated in the presence of Gαi and Gβγ inhibitors (pertussis toxin, 100 µg/kg i.p. 24 hr prior to isolation and gallein, 10 µM infusion, respectively). This study represents the first demonstration of profound T2R ligand‐induced, G protein‐dependent effects on mouse heart function. Future work will focus on the delineation of specific receptor‐dependent responses of these ligands.

Grant Funding Source: Supported by Australian National Health and Medical Research Council (NHMRC) (1024726) and the National Heart Foundation of Australia (G‐12B‐6532)
Using the NCSBN Transition to Specific Practice Competency Tool to Develop a Multiple Patient Simulation
Authors: Dunderdale Joanne O. , Kostovich Carol T.
Published: June 2021

Because of complexities of clinical practice and limitations in the clinical setting, prelicensure nursing students may not develop competencies necessary for safe entry into practice. Multiple patient simulation (MPS) is an effective teaching strategy to gain these competencies. The National Council of State Boards of Nursing Transition to Practice Specific Competency Tool was used to assess and identify gaps in students’ knowledge and skills when designing an MPS. This unique approach allowed faculty to customize the MPS to meet the needs of students and potentially increase their readiness for practice.
Using Simulation to Assess Nurse Practitioner Education
Authors: Knopp Andrea , Graham Amy , Stowell Sarah , Schubert Carolynn
Published: June 2021

Resource restraints and the movement toward competency-based education encourage exploration of innovative simulation experiences in advanced practice registered nurse education. Building upon existing best practices in simulation development, this pilot project explores opportunities and challenges translating these practices to the advanced practice registered nurse context. Innovations focused on using a competency-based framework, developing a competency-based evaluation tool, and providing feedback from faculty and standardized patients. Lessons learned from this experience inform recommendations for how to design instructional experiences and provide formative methods of feedback for nurse practitioner student assessment.
COVID-19 pneumonia
Authors: Avadhani Amita , Cardinale Maria , Akintade Bimbola
Published: June 2021

COVID-19-associated pneumonia is a complex acute care diagnosis that requires careful evaluation and management. This article includes pertinent recommendations for management of acutely ill patients with COVID-19 pneumonia.
Development and implementation of a trauma team education program in Georgetown, Guyana
Authors: Ramirez Rick , Cook Courtney , Van Meter Jessica
Published: June 2021

Trauma teams without structured team training demonstrate impaired team dynamics, which can cause delays in patient care, leading to poor patient outcomes. Improving team dynamics leads to better communication, reduced errors, and enhanced patient care. Evidence-based trauma team training was implemented and delivered within a resource-restricted ED.
Does Size Matter for Female Continuous-flow LVAD Recipients? A Translational Approach to a Decade Long Question
Authors: Anne Dual Seraina , Nayak Aditi , Hu Yingtian , Schmid Daners Marianne , Morris Alanna A. , Cowger Jennifer
Published: June 2021

Females have increased risk of right-ventricular failure (RVF) and 3 month mortality after left-ventricular assist device (LVAD) implantation. In this translational study, we tested the hypothesis that sex differences in outcomes are driven by pump-induced LV size-volume mismatch, due to a negative impact on interventricular septal (IVS) interdependence. Adult continuous-flow LVAD recipients from the International Society For Heart And Lung Transplantation Mechanically Assisted Circulatory Support registry (n = 15,498) were studied to determine association of female sex with outcomes of 3 month mortality and RVF. Female sex was associated with smaller preimplant left-ventricular end-diastolic diameter (6.5 vs. 6.9 cm, p < 0.001), increased 3 month mortality (odds ratio [OR]: 1.42, p < 0.001) and RVF (OR: 1.18, p = 0.005). Smaller left-ventricular end-diastolic diameter was associated with worse outcomes after LVAD implantation (OR for mortality: 1.20, p < 0.001; RVF: 1.09, p < 0.001), and attenuated the association of female sex with these outcomes. In test bench heart phantoms (n = 4), the IVSs of smaller hearts demonstrated abnormal leftward shift earlier than larger hearts (volume change at IVS shift: 40 [95% confidence interval: 30–52] vs. 50 [95% confidence interval: 48–69] ml). Smaller LV size partially mediates worse post-LVAD outcomes for female patients, due to lower volume thresholds for adverse IVS shifting.
Prediction of Bloodstream Infection in Pediatric Acute Leukemia by Microbiota and Volatile Organic Compounds Analysis
Authors: van de Velde Mirjam E. , el Hassani Sofia el Manouni , Kaspers Gert Jan L. , Broertjes Jorrit , Benninga Marc A. , de Boer Nanne K.H. , Budding Andries E. , de Meij Tim G.J.
Published: June 2021

Introduction:

Bloodstream infections (BSIs) cause treatment-related mortality in pediatric acute leukemia. We explored the potential of intestinal microbiota and fecal volatile organic compounds (VOCs) analyses to predict BSI.

Methods:

In this case-control study, fecal samples of pediatric acute leukemia patients were collected. Microbiota composition and fecal VOC profiles of BSI cases and matched non-BSI controls were compared.

Results:

In total, 6 patients were included, of which 1 developed BSI and 1 neutropenic fever. Both showed reduced microbial diversity and stability of Bacteroidetes. In the BSI case, Pantoea was identified 15 days before BSI. Significant differences in fecal VOC profiles were measured between the case and controls.

Conclusion:

Microbiota and fecal VOC could serve as biomarkers to predict BSI in pediatric leukemia.
Hodgkin Lymphoma–related Vanishing Bile Duct Syndrome Cholestasis Resolved After Chemotherapy
Authors: Gonzalez Rafael , Parmar Pooja , Hardee Steven , Chang-Halpenny Christine , Titapiwatanakun Ruetima , Tcheng Wendy , Au Yeung Karla , Fernández Karen S.
Published: June 2021

Vanishing bile duct syndrome is a rare paraneoplastic syndrome occasionally seen in pediatric Hodgkin lymphoma. It is usually regarded as a fatal disorder. Here, we present a case of vanishing bile duct syndrome cholestasis related to Hodgkin lymphoma that resolved after chemotherapy and radiation.
COVID-19-related Gastrointestinal Bleeding in a Pediatric Patient With ALL
Authors: Wojciechowska Małgorzata , Renke Joanna , Irga-Jaworska Ninela
Published: June 2021

Coronavirus disease 2019 (COVID-19) is a contagious disease caused by severe acute respiratory syndrome coronavirus-2. Patients with hematologic malignancies have been shown to have higher risk of mortality due to COVID-19 than reported in the general adult population. Reports on acute lymphoblastic leukemia and COVID in children are scarce. We present a case of an 11-year-old male patient undergoing treatment for B-cell acute lymphoblastic leukemia with an atypical course of COVID-19. The patient received a positive result of the syndrome coronavirus-2 polymerase chain reaction test performed due to epidemiologic reasons. The chemotherapy was continued since the patient had no clinical signs of COVID-19. The disease started with intensive gastrointestinal bleeding, followed by severe respiratory tract infection over 2 weeks later.
Multisystem Inflammatory Syndrome in Children During Induction Chemotherapy in a Newly Diagnosed Pediatric Acute Myeloid Leukemia and Concurrent COVID-19
Authors: Tekle-Yohannes Girmay H. , Mann Esther , Miller Michal A.
Published: June 2021

A 15-year-old male presented with fatigue and weight loss for 1 month, petechiae and bruising for 2 weeks. He was diagnosed with concurrent new acute myeloid leukemia and coronavirus disease 2019. He was febrile and chest computed tomography scan showed ground glass opacities. Fever resolved after 4 days. Polymerase chain reaction test for coronavirus disease 2019 became negative after 2 days. Induction chemotherapy was initiated on day 8 and was complicated by multisystem inflammatory syndrome in children. The multisystem inflammatory syndrome in children was managed with symptomatic treatment and continued chemotherapy. Patient recovered and end of induction bone marrow showed remission of the leukemia.
Use of Pegfilgrastim in Japanese Pediatric Patients With Solid Tumors: A Retrospective Analysis
Authors: Saito Yoshimasa , Kumamoto Tadashi , Yamaguchi Masakazu , Ogawa Chitose , Kato Masashi
Published: June 2021

There are no detailed analyses of regarding pegfilgrastim usage in Japanese pediatric solid tumor patients. The approved dose of pegfilgrastim in Japan is 3.6 mg. We retrospectively evaluated the incidence of dose delays and dose reductions due to neutropenia in pediatric patients with solid tumors receiving chemotherapy with pegfilgrastim between 2015 and 2018. The effects of the timing of pegfilgrastim administration were evaluated. In chemotherapies administered every 2 and 3 weeks, prolongation of chemotherapy cycles was analyzed. Fifty-nine patients received chemotherapy with prophylactic pegfilgrastim for a total 247 cycles. No significant incidence of dose delays was observed with pegfilgrastim administration during the first 1 to 3 days after chemotherapy. When 77 cycles in 2-week regimens were compared with 166 cycles in 3-week regimens, mean cycle durations were 15.19±2.06 and 21.97±2.88 days, respectively (P<0.001). A total of 77 chemotherapy cycles administered every 14 days were subdivided. The incidence of dose delays in pediatric patients receiving chemotherapy for 5 consecutive days was similar to that for 1 day and 2 consecutive days. Pegfilgrastim prophylaxis could be of use for Japanese pediatric patients with solid tumors receiving chemotherapy, including administration every 2 weeks. Its use aids in maintaining the chemotherapy schedule.
Low-Field Magnetic Resonance Imaging
Authors: Heiss Rafael , Nagel Armin M. , Laun Frederik B. , Uder Michael , Bickelhaupt Sebastian
Published: June 2021

Magnetic resonance imaging (MRI) plays a pivotal role in diagnostic imaging. In today's clinical environment, scanners with field strengths of 1.5 to 3 T are most commonly used. However, recent technological advancements might help to augment the clinical usage and availability of MRI via the introduction of high-performance low-field MRI systems (ranging from ~0.1–0.55 T in current systems). The combination of low field strength and high-performance hardware is characterized by increased flexibility, excellent quality of results, and reduced cost. This review discusses the multifaceted potential advantages of a new generation of high-performance low-field MRI systems and presents the potential impact of such systems in terms of socioeconomic benefits as well as positive effects on patient care.
Early Prehospital Tranexamic Acid Following Injury Is Associated With a 30-day Survival Benefit
Authors: Li Shimena R. , Guyette Francis , Brown Joshua , Zenati Mazen , Reitz Katherine M. , Eastridge Brian , Nirula Raminder , Vercruysse Gary A. , O’Keeffe Terence , Joseph Bellal , Neal Matthew D. , Zuckerbraun Brian S. , Sperry Jason L.
Published: June 2021

Objective:

We sought to characterize the timing of administration of prehospital tranexamic acid (TXA) and associated outcome benefits.

Background:

TXA has been shown to be safe in the prehospital setting post-injury.

Methods:

We performed a secondary analysis of a recent prehospital randomized TXA clinical trial in injured patients. Those who received prehospital TXA within 1 hour (EARLY) from time of injury were compared to those who received prehospital TXA beyond 1 hour (DELAYED). We included patients with a shock index of >0.9. Primary outcome was 30-day mortality. Kaplan-Meier and Cox Hazard regression were utilized to characterize mortality relationships.

Results:

EARLY and DELAYED patients had similar demographics, injury characteristics, and shock severity but DELAYED patients had greater prehospital resuscitation requirements and longer prehospital times. Stratified Kaplan-Meier analysis demonstrated significant separation for EARLY patients (N = 238, log-rank chi-square test, 4.99; P = 0.03) with no separation for DELAYED patients (N = 238, log-rank chi-square test, 0.04; P = 0.83). Stratified Cox Hazard regression verified, after controlling for confounders, that EARLY TXA was associated with a 65% lower independent hazard for 30-day mortality [hazard ratio (HR) 0.35, 95% confidence interval (CI) 0.19–0.65, P = 0.001] with no independent survival benefit found in DELAYED patients (HR 1.00, 95% CI 0.63–1.60, P = 0.999). EARLY TXA patients had lower incidence of multiple organ failure and 6-hour and 24-hour transfusion requirements compared to placebo.

Conclusions:

Administration of prehospital TXA within 1 hour from injury in patients at risk of hemorrhage is associated with 30-day survival benefit, lower incidence of multiple organ failure, and lower transfusion requirements.
Variation in radiation dosing among pediatric trauma patients undergoing head computed tomography scan
Authors: LaQuaglia Michael J. , Anderson Melissa , Goodhue Catherine J. , Bautista-Durand Maria , Spurrier Ryan , Ourshalimian Shadassa , Lai Lillian , Stanley Philip , Chaudhari Pradip P. , Bliss David
Published: June 2021

BACKGROUND

When head injured children undergo head computed tomography (CT), radiation dosing can vary considerably between institutions, potentially exposing children to excess radiation, increasing risk for malignancies later in life. We compared radiation delivery from head CTs at a level 1 pediatric trauma center (PTC) versus scans performed at referring adult general hospitals (AGHs). We hypothesized that children at our PTC receive a significantly lower radiation dose than children who underwent CT at AGHs for similar injury profiles.

METHODS

We retrospectively reviewed the charts of all patients younger than 18 years who underwent CT for head injury at our PTC or at an AGH before transfer between January 1 and December 31, 2019. We analyzed demographic and clinical data. Our primary outcome was head CT radiation dose, as calculated by volumetric CT dose index (CTDIvol) and dose-length product (DLP; the product of CTDIvol and scan length). We used unadjusted bivariate and multivariable linear regression (adjusting for age, weight, sex) to compare doses between Children’s Hospital Los Angeles and AGHs.

RESULTS

Of 429 scans reviewed, 193 were performed at our PTC, while 236 were performed at AGHs. Mean radiation dose administered was significantly lower at our PTC compared with AGHs (CTDIvol 20.3/DLP 408.7 vs. CTDIvol 30.6/DLP 533, p < 0.0001). This was true whether the AGH was a trauma center or not. After adjusting for covariates, findings were similar for both CTDIvol and DLP. Patients who underwent initial CT at an AGH and then underwent a second CT at our PTC received less radiation for the second CT (CTDIvol 25.6 vs. 36.5, p < 0.0001).

CONCLUSIONS

Head-injured children consistently receive a lower radiation dose when undergoing initial head CT at a PTC compared with AGHs. This provides a basis for programs aimed at establishing protocols to deliver only as much radiation as necessary to children undergoing head CT.

LEVEL OF EVIDENCE

Care Management/Therapeutic, level IV.