bluuebunny/crossref_metadata_2025 huggingface dataset:
The Succinate Receptor Contributes to Obesity‐Induced Diabetes Type‐II and Chronic Kidney Disease
Authors: Carmone Claudia , Robben Joris , van Diepen Janna , Ariza Ana , Devuyst Olivier , Stienstra Rinke , Deen Peter
Published: June 2021

Cell stress leads to cellular release of mitochondrial succinate and activation of its receptor, the SUCNR1, in the renal macula densa is essential for DMI‐related renin release and hypertension. Obesity‐induced DMII and Chronic Kidney Disease (CKD) development is aggravated by hypertension and goes with cell stress in adipose/kidney tissue and macrophages, which express SUCNR1. Here we tested the role of SUCNR1 in obesity‐induced DMII and CKD. Wild‐type and SUCNR1‐/‐ mice fed for 16 weeks with a high fat diet (HFD) revealed a similar gain in total, adipose and kidney weight as compared to low fat diet (LFD) groups, but the gain was higher for liver and heart in wt than SUCNR1‐/‐ mice. Starving glucose levels were similarly increased in both HFD groups, but SUCNR1‐/‐ mice had a better glucose tolerance test response, indicating less insulin resistance in SUCNR1‐/‐ mice. For both HFD groups, blood sodium and urine volumes were similarly reduced, whereas GFR was similarly increased. Importantly, HFD wt mice showed albuminuria and glomerular/interstitial expression of collagen IV, indicative of fibrosis, which was not observed in HFD SUCNR1‐/‐ mice, nor LFD groups. Hypertensive patients and rodent models showed elevated urinary succinate levels, indicating that the renal SUCNR1 is activated in hypertension.

Together, our data reveal that SUCNR1 activation contributes to obesity‐induced DM and CKD development and, if similar in humans, that SUCNR1 blockers may form novel therapeutics for the treatment of these common disorders.
ADAM17‐Mediated Shedding of ACE2 in Pancreatic Beta‐Cells
Authors: Pedersen Kim , Robinson Leonie , Lazartigues Eric
Published: June 2021

Angiotensin‐converting enzyme 2 (ACE2) hydrolyzes angiotensin II. Our laboratory has previously shown that pancreatic ACE2 levels decrease as diabetes progresses and that pancreatic ACE2 gene therapy counteracts development of hyperglycemia in diabetic animal models. As a disintegrin and metalloprotease 17 (ADAM17) is an enzyme that can cleave enzymatically active ACE2 from the cell to the extracellular environment by so‐called shedding, we hypothesize that increased levels of ADAM17 in pancreatic beta‐cells lead to reduced cellular ACE2 levels. To this end, 832/13 cells (rat insulinoma cells derived from pancreatic beta‐cells) were transfected with expression plasmids for ACE2, ADAM17, and a hydrolytically inactive E406A ADAM17 mutant. Using fluorogenic enzyme substrates, we measured shed ACE2 activity after a 24 h incubation as well as cell‐associated ACE2 and ADAM17 activities. For a wide range of ACE2 expression levels, including the ACE2 expression level observed in pancreatic islets, a 4.6‐fold increase in ADAM17 activity had the following significant effects: shed ACE2 activity was increased 2 – 2.7‐fold, cellular ACE2 activity was decreased 33‐47%, and the ratio of shed ACE2/cellular ACE2 was increased 3.4 – 4.1‐fold. Adjusting for transfection efficiency, we further determined that the cellular ACE2 activity can be described as a power function of the ADAM17 activity with exponent ‐0.29 ±0.04. We conclude that ADAM17‐mediated shedding of ACE2 has the potential to decrease cellular ACE2 levels in pancreatic beta‐cells. More studies are underway to assess the role of this mechanism in diabetes. Support: NIH: GM103424, AHA: 12EIA8030004.
Using Social Media as an Educational Tool: The Potential Role of Twitter in Enhancing the Student Learning Experience in Neuro/Anatomy
Authors: Hennessy Catherine , Border Scott
Published: June 2021

Background

Since the rise in tuition fees the value of the student experience has become more important than ever. Difficult areas of medical degree programmes like neuroanatomy can often leave students feeling disengaged and unsupported. More recently the use of social media, such as Twitter has been used in higher education to increase engagement and offer a supportive online community for the learning of challenging subjects. At the University of Southampton, we incorporated the use of Twitter as a way of supporting students learning on a neuroanatomy module to see how it impacted upon their engagement and learning experience.

Aims

To investigate if Twitter can be used to engage and support medical students while learning neuroanatomy and to identify how it is used by students.

Method

The nlm2soton hashtag was created and was displayed (via a widget) on the University's Virtual Learning Environment (Blackboard) for a cohort of 203 BM5 Year 2 medical students studying neuroanatomy. Student usage was tracked to measure levels of engagement throughout the course.

Results

62% of the cohort viewed the widget with on average 30 hits per day. A 16% increase in the widget's daily hits coincided with the January revision period. 33% of the cohort tweeted or favoured tweets which were themed as follows: Shared learning (29%), Morale boosts (28%), Questions (23%), Worries (16%) and Information (4%).

Conclusion

Incorporating the use of Twitter on this module was successful. Although only a third of students contributed their own tweets, almost two‐thirds of the cohort regularly monitored the feed for updates. Sharing learning tips and interestingly, contributions intended to raise spirits were the most common.
How Does Inaccurate Perception of Weight Compared to Actual BMI Status Affect the Diet Score of College Students?
Authors: Querido Jaclyn , Morrell Jesse
Published: June 2021

As self‐perception of health can influence behavior, accurate understanding of weight status may be important for making healthy choices. This study examined the relationship between the accuracy of college students' weight perception, as well as their weight status intentions, to the quality of their diet. Students (n=1330), ages 18‐24, were recruited from the ongoing College Health & Nutrition Assessment Survey at UNH. Perception accuracy was determined by comparing students' self‐identified weight status (overweight, underweight, about right) to their measured BMI. Weight status intentions were evaluated via responses to “What are you trying to do with your weight?” Three day food records evaluated nutrient intake; diet quality was scored via 4‐items. Each item was scored 1‐5; final diet scores ranged 4‐20 with higher scores indicative of a more healthy diet. One‐third of men and one‐quarter of women incorrectly identified their weight status. No significant relationship between weight perception and diet score was seen. No significant differences with men's weight perception and goals were seen; women trying to lose or gain weight had significantly more accurate weight perception than those trying to maintain or do nothing. Men trying to lose weight had significantly lower diet scores than those trying to maintain or gain weight (11.2±3.2 vs. 12.1±3.2 and 12.6±3.2, p<.05). Women trying to lose weight had significantly lower diet scores than those trying to maintain or do nothing (11.7±3.2 vs. 12.5±3.5 and 12.6±3.3, p<.05). Findings suggest that attempts to alter weight may lead to decreased diet scores.
Effect of Coenzyme Q10 Supplementation in Patients with Statin‐related Myalgia
Authors: Mazirka Pavel , Jones Eyone , Strachan Paul , McNurlan Margaret , Lawson William , Caso Giuseppe
Published: June 2021

Statins (Hydroxy‐methylglutaryl CoA reductase inhibitors) are routinely prescribed to treat hypercholesterolemia because they inhibit endogenous cholesterol synthesis but in some patients their use is associated with increased incidence of myalgia and myopathic symptoms. Statins also inhibit the synthesis of CoQ10 and CoQ10 depletion may be a contributing factor to statin‐related myopathy.

The aim of this study was to evaluate the ability of supplementation with coQ10 to reduce muscle symptoms associated with statin use. In a randomized double‐blind placebo controlled trial, statin‐treated patients complaining of myopathic symptoms (i.e. pain, fatigue, weakness) were supplemented with coQ10 (ubiquinol, 300 mg/d) or placebo for 1 month. Muscle pain was assessed before and after supplementation with the validated Brief Pain Inventory, Short Form. Patients in the two groups were comparable for age (55±2 vs. 57±2 y), BMI (31±1 vs. 29±1), gender and statin use. After 1 month of supplementation, CoQ10 plasma levels were significantly elevated in patients treated with CoQ10 (P<0.001). The intensity of pain (i.e. Pain Severity Score, PSS) was significantly reduced both in the CoQ10 (3.78 ± 0.47 vs. 2.72 ± 0.56, n=19) and placebo (3.97 ± 0.39 vs. 1.99 ± 0.46, n=18) groups, P<0.01. However, the changes in PSS before and after intervention were comparable between the two groups. The results of the study suggest that in this population, improvement in statin‐related myalgia with supplementation with CoQ10 was not superior to placebo.

Supported by NIH grants 5R21AT004204 and 5‐MO1‐RR‐10710. CoQ10 was kindly provided by Kaneka Corp. (Pasadena, TX)
Lipid Profile of Male Firefighters in a Northwest Austin Area Fire Department
Authors: Huang Jennifer , Forman Michele , Dong Kane , Pilles Kiona , Mangini Lauren , Stewart Jourdin , Permenter Traci , Bsaibes Stephanie , Hernandez Ladia
Published: June 2021

Background

Cardiovascular disease (CVD) is the leading cause of on‐duty mortality for firefighters since 1977. The primary objective of this project is to examine the distribution of lipids (total cholesterol (TC), high‐density lipoprotein cholesterol (HDL‐C), low‐density lipoprotein cholesterol (LDL‐C), and triglyceride (TG)) in firefighters by CVD risk factors.

Methods

This was a period cross‐sectional study over August and September 2013. Information on 56 male firefighters' demographics, medical history, and lipid profile were collected through self‐administered questionnaires and participants' fasting blood collection at their annual medical examinations. Multivariate generalized linear model was used to investigate the association between lipids and CVD risk factors (age, BMI, fasting blood glucose (FBG), smoker, and hypertension, etc).

Results

Based on the National Cholesterol Education Program Expert Panel ‐ Adult Treatment Panel III, about 75% of the participants did not meet the recommended value for HDL‐C and LDL‐C while about 25% had elevated levels of TC and TG. Adjusting for age and CVD family history, both TC and LDL‐C were inversely associated with BMI and directly associated with FBG. TC was also directly associated with hypertension. HDL‐C was inversely associated with BMI and fat free mass under separate models. Lastly, TG was directly associated with fat free mass and hypertension.

Conclusion

The lipid profile of most firefighters was higher than recommended levels. Traditional CVD risk factors, along with firefighting‐specific activities, should be considered in future wellness programs to help reduce on‐duty CVD events among firefighters.
Using the Socio‐Ecological Framework to determine Breastfeeding Obstacles in a Low‐income Population in Tijuana, Mexico: Individual Factors
Authors: Bueno‐Gutierrez Diana , Chantry Caroline
Published: June 2021

Background

In Mexico, breastfeeding rates are one of the lowest of Latin America, with 14.4% of infants under 6 months being exclusively breastfed. Our objective was to identify the main obstacles to breastfeeding in a low‐income population in Tijuana, Mexico. We assess individual factors in this study, which are those associated directly to the mother, infant and the 'mother‐infant dyad'.

Methods

We used a socio‐ecological framework to determine factors affecting breastfeeding practices. In four low‐income communities in Tijuana we conducted focus groups and interviews with mothers, fathers, grandparents, and key informants. Interview notes and focus group transcripts were then studied in depth independently by three researchers. The primary analytic technique was constant comparison.

Results

One hundred twenty‐nine subjects participated in this study: six focus groups (n = 53) and 51 interviews among mothers, fathers, and grandparents, as well as 25 interviews among key informants. Main individual obstacles to breastfeeding were perception of inadequate milk, pain, aesthetics, lack of time, comfort, baby's dissatisfaction and breastfeeding maintenance difficulties. Socio‐structural factors such as the biomedical discourse about milk as a product interact with individual factors to impact breastfeeding behavior.

Conclusions

This study showed that women in low‐income communities in Tijuana face multiple obstacles to breastfeeding at the individual level. This information can help to develop culturally‐ appropriate educational material to promote breastfeeding. Additionally, institutional and social structural changes are needed in order to increase breastfeeding rates.
Functional Characterization of Three‐dimensional (3D) Human Liver Tissues Generated by an Automated Bioprinting Platform
Authors: Nguyen Deborah , Robbins Justin , Crogan‐Grundy Candace , Gorgen Vivian , Bangalore Preeti , Perusse Dean , Creasey Olivia , King Shelby , Lin Susan , Khatiwala Chirag , Halberstadt Craig , Presnell Sharon
Published: June 2021

The lack of biological complexity and limited life span of conventional human hepatocyte culture models are major limitations in toxicological research. Recent advances in three‐dimensional (3D) monoculture and co‐culture systems show promise, but may suffer from the lack of reproducibility and spatial control. In this study, we generated 3D human liver tissue mimetics composed of parenchymal and non‐parenchymal cell populations using a proprietary automated 3D fabrication platform. The resulting liver tissues were well organized, containing junctional protein E‐Cadherin between hepatocytes, CD31+ endothelial cell networks and desmin‐positive quiescent stellates. The hepatocytes also demonstrated the ability to store both lipids and glycogen. The tissues actively secreted albumin, cholesterol, fibrinogen, and transferrin into the medium for six weeks. The 3D liver tissues expressed key Phase I enzymes CYP3A4, 2D6, 2B6, 1A2, and 2C9 over 28 days. Basal activity of CYP3A4, as evidenced by the conversion of midazolam to 4‐hydroxymidazolam, was detected throughout the 28 day culture period. In addition, exposure to rifampicin led to an increase in both CYP3A4 mRNA and activity, with 4‐fold induction still evident after 28 days in culture. The 3D liver tissues exhibited a clinically relevant injury response, evidenced by decreased overall viability, to published hepatotoxic agents such as Diclofenac and Troglitazone. These results demonstrate the potential utility of human 3D bioprinted liver tissues in drug discovery and development.

This work was supported with internal funds
Pathological Changes in the Heart of the Strain CUX1 Transgenic Mice
Authors: Fletcher A , Raza F , Buursma J , Livingston S , Kearn D , Herndon B , Vanden Heauvel G , Baybutt R , Molteni A
Published: June 2021

CUX1 is a transcriptional repressor gene in the network controlling G1‐S phase transition. It represses the expression of the cyclin kinase (CK1) inhibitors p21 and p27. Transgenic mice constitutively expressing CUX1 develop multiorgan damage consequent to aberrant p27 expression in the kidneys (polycystic), testes (diminished spermatogenesis), and liver (fibrosis). These mice also present severe pulmonary inflammation, vasculitis, bronchiolitis, bronchiectasis, and fibrosis. This study relates to the damage induced to the heart consequent to the CUX1 expression.

H&E staining of the mice hearts showed extensive myocardial inflammation, interstitial edema, hemorrhages, and increased number of macrophages neutrophils, and lymphocytes. Clusters of myocardial fibers were intensively eosinophilic with nuclear pyknosis and karyolysis suggesting the development of infarctions. A semi‐quantitative evaluation of the histopathological damage made by two pathologists unaware of the slides identity, with damage graded on a scale from 5 (minimal) to 50 (very severe), reported an average value 6.28 + 2.99 for hearts of WTF (controls) vs 22.99 + 3.52 for hearts of CUX1 mice (P< 0.0001). Coronary arteries of the CUX1 mice had a trend indicating medial wall thickening and reduced lumen patency (68% vs 75% of WTF). This data indicates that the damage of the CUX1 mice is also extended to the heart. Additional studies are needed to establish whether such damage is consequent to that of the lungs or originates directly in the organ by p27 effect.
The Effects of a Community‐Based Multi‐lifestyle Intervention on CV Health in Rural Populations
Authors: Lee Kyuwan , DeVallance Evan , Fournier Sara , Brainard Carrie , White Emma , Miller Wayne , Petrone Ashley , Chantler Paul , Dino Geri
Published: June 2021

The rate of cardiovascular diseases (CVD) mortality has decreased over the last few years. However, in rural areas, this reduction is less substantial compared to urban areas despite the effort to translate lifestyle intervention which was successful in urban areas. The purpose of this study is to use community‐based participatory research principles to conduct a pilot study to test the feasibility and acceptability of a lifestyle intervention in a rural community to improve CVD health.

We assessed the feasibility and acceptability using retention and recruitment rate along with CV parameters i.e., Framingham risk score, 6‐min walk test, reactive hyperemia index, carotid thickness, and arterial stiffness, pre and post 10 week intervention.

10 patients with CVD were screened with their family member, yielding 20 individuals screened (recruitment rate 59%). 17 patients were enrolled and retained (retention rate 100%). The 6‐min walk distance significantly (p=0.01) increased (1536±53 to 1651±55) with a tendency of improved HR and diastolic function represented by sub‐endocardial viability ratio after 10 wks intervention, although these parameters did not reach statistical significance. In contrast, there were no significant changes in the other CVD parameters. These findings provide valuable evidence to conduct lifestyle intervention for CVD patients in rural areas.
Cardiomyocyte‐Specific Ablation of the Long‐Chain Fatty Acid Transporter CD36 Accelerates the Progression of Pressure Overload‐Induced Heart Failure in Mice
Authors: Sung Miranda , Byrne Nikole , Levasseur Jody , Masson Grant , Febbraio Maria , Dyck Jason
Published: June 2021

Utilizing an inducible cardiomyocyte‐specific CD36 knockout (icCD36KO) mouse, we investigated the pathophysiological role of myocardial fatty acid transporter CD36 in response to pressure overload and tested whether the ablation of CD36, used as a tool to limit fatty acid uptake and partially inhibit fatty acid oxidation, would be beneficial or detrimental to cardiac function. Wildtype (WT) and icCD36KO mice were subjected to transverse aortic constriction (TAC) surgery to generate pressure overload‐induced cardiac hypertrophy. Following TAC, both WT and icCD36KO mice developed similar degrees of compensatory cardiac hypertrophy in response to pressure overload at 1, 3 and 5 weeks post‐TAC (N=7‐11/group). However, we observed significant systolic dysfunction and reduced ejection fraction (EF) in icCD36KO mice at 5 weeks post‐TAC (%EF: 52.4 ± 2.82 vs. 35.6 ± 3.01; P<0.05). Prior to TAC, cardiac fatty acid oxidation rates were significantly reduced and glucose oxidation rates increased in hearts from icCD36KO compared to WT mice. However, at 5 weeks post‐TAC both glucose and fatty acid oxidation rates were reduced to a similar extent in both WT and icCD36KO mice (N=4). Interestingly, icCD36KO mice fed a diet rich in medium chain fatty acids, which do not require CD36 as a transporter to enter the cardiomyocyte, were protected from TAC‐induced systolic dysfunction (%EF: 45.2 ± 2.67, N=5). In conclusion, these data suggest that limiting fatty acid uptake and partial inhibition of fatty acid oxidation in the heart via CD36 ablation may be detrimental, at least early on during the development of pressure overload‐induced HF.
Effect of Chronic Hypoxia on the Carotid Body Glomus Cell Mitochondrial Response to Acute Hypoxia
Authors: Kim Insook , Carroll John
Published: June 2021

Carotid body (CB) glomus cells depolarize in response to hypoxia, causing a [Ca2+]i increase through activation of voltage‐dependent Ca2+ channels, resulting in neurotransmitter release and carotid sinus nerve excitation. Glomus cell mitochondria are believed to be the site of O2 sensing. Previous work showed that perinatal chronic hypoxia (12% O2) during CB postnatal maturation severely impairs CB glomus cell oxygen sensitivity. It is unknown whether chronic hypoxia (CH) impairs glomus cell mitochondrial O2 sensing vs. downstream elements in the O2 transduction cascade. We therefore studied the effects of CH on [Ca2+]i and mitochondrial membrane potential (Δψm) in response to acute hypoxia, in CB glomus cells from rats exposed to hypoxia (10% O2) for 9‐14 days, starting at postnatal day 16‐18 (OxyCycler). Results show that 1) chronic hypoxia severely reduced glomus cell oxygen responsiveness to acute hypoxia as reflected by [Ca2+]i in ~80% of glomus cells; 2) chronic hypoxia did not affect the glomus cell response to 20mM KCl (a non‐specific depolarizing stimulus); 3) chronic hypoxia did not affect Δψm; 4) The reduced glomus cell oxygen sensitivity recovered after CH exposed rats were returned to room air. These results suggest that CH reversibly impairs glomus cell [Ca2+]i in response to acute hypoxia by a mechanism downstream of mitochondria. (Supported by Arkansas Biosciences Institute funds)
Internal Reliability Estimates of the Lasater Clinical Judgment Rubric Among New-to-Practice Nurses in a Simulated Setting
Authors: Cantrell Mary Ann , Mariani Bette , Lengetti Evelyn
Published: June 2021

Clinical judgment among new-to-practice nurses is critical for safe patient care. The Lasater Clinical Judgment Rubric (LCJR) is a known instrument in undergraduate nursing education research. This study evaluated the internal consistency reliability and changes in the LCJR in a sample of 17 new-to-practice nurses in a simulated setting across four measurements. Cronbach’s alpha reliability for the LCJR was .90. Effect sizes (η2) ranged from .01 to .45, with only the reflecting subscale demonstrating an effect. Study team and study participants’ self-ratings on the LCJR were compared; team members’ ratings were significantly lower than participants’ self-ratings.
Nursing Academic Leadership: An Urgent Workforce Shortage in Nursing Education
Authors: Apen Lynette V. , Rosenblum Ruth , Solvason Nanette , Chan Garrett K.
Published: June 2021

AIM

The aim of the study was to describe the California nursing academic leader workforce shortage, identify succession planning activities, analyze driving and restraining forces of the role, and distinguish critical leadership competencies and onboarding strategies.

BACKGROUND

Several studies have projected a workforce shortage for nursing academic leaders and studied the leadership competencies and driving and restraining forces impacting the role.

METHOD

The study was a secondary descriptive analysis of an existing cross-sectional needs assessment survey administered to California nursing academic leaders of prelicensure programs.

RESULTS

The results validated an impending workforce shortage for California nurse academic leaders, with 66 percent planning to leave their positions in the next five years and 46 percent not having a succession plan in place.

CONCLUSION

To avoid threatening the success of nursing programs, a sustainable plan to address the workforce shortage of well-prepared academic nurse leaders is urgently needed.
The Application of a Hospital Medical Surge Preparedness Index to Assess National Pandemic and Other Mass Casualty Readiness
Authors: Marcozzi David E. , Pietrobon Ricardo , Lawler James V. , French Michael T. , Mecher Carter , Baehr Nicole E. , Browne Brian J.
Published: June 2021

EXECUTIVE SUMMARY

This article describes the use and findings of the Hospital Medical Surge Preparedness Index (HMSPI) tool to improve the understanding of hospitals’ ability to respond to mass casualty events such as the COVID-19 pandemic. For this investigation, data from the U.S. Census Bureau, the Dartmouth Atlas Project, and the 2005 to 2014 annual surveys of the American Hospital Association (AHA) were analyzed. The HMSPI tool uses variables from the AHA survey and the other two sources to allow facility, county, and referral area index calculations. Using the three data sets, the HMSPI also allows for an index calculation for per capita ratios and by political (state or county) boundaries. In this use case, the results demonstrated increases in county and state HMSPI scores through the period of analysis; however, no statistically significant difference was found in HMSPI scores between 2013 and 2014. The HMSPI builds on the limited scientific foundation of medical surge preparedness and could serve as an objective and standardized measure to assess the nation’s medical readiness for crises such as the COVID-19 pandemic and other large-scale emergencies such as mass shootings. Future studies are encouraged to refine the score, assess the validity of the HMSPI, and evaluate its relevance in response to future legislative and executive policies that affect preparedness measures.
Diameter-Based Volumetric Models May Inadequately Calculate Jugular Paraganglioma Volume Following Sub-Total Resection
Authors: Totten Douglas J. , Sherry Alexander D. , Manzoor Nauman F. , Perkins Elizabeth L. , Cass Nathan D. , Khattab Mohamed H. , Cmelak Anthony J. , Haynes David S. , Aulino Joseph M.
Published: June 2021

Background:

As gross total resection of jugular paragangliomas (JPs) may result in cranial nerve deficits, JPs are increasingly managed with subtotal resection (STR) with postoperative radiological monitoring. However, the validity of commonly used diameter-based models that calculate postoperative volume to determine residual tumor growth is dubious. The purpose of this study was to assess the accuracy of these models compared to manual volumetric slice-by-slice segmentation.

Methods:

A senior neuroradiologist measured volumes via slice-by-slice segmentation of JPs pre- and postoperatively from patients who underwent STR from 2007 to 2019. Volumes from three linear-based models were calculated. Models with absolute percent error (APE) > 20% were considered unsatisfactory based on a common volumetric definition for residual growth. Bland-Altman plots were used to evaluate reproducibility, and Wilcoxon matched-pairs signed rank test evaluated model bias.

Results:

Twenty-one patients were included. Median postoperative APE exceeded the established 20% threshold for each of the volumetric models as cuboidal, ellipsoidal, and spherical model APE were 63%, 28%, and 27%, respectively. The postoperative cuboidal model had significant systematic bias overestimating volume (p = 0.002) whereas the postoperative ellipsoidal and spherical models lacked systematic bias (p = 0.11 and p = 0.82).

Conclusion:

Cuboidal, ellipsoidal, and spherical models do not provide accurate assessments of postoperative JP tumor volume and may result in salvage therapies that are unnecessary or inappropriately withheld due to inaccurate assessment of residual tumor growth. While more time-consuming, slice-by-slice segmentation by an experienced neuroradiologist provides a substantially more accurate and precise measurement of tumor volume that may optimize clinical management.
Assessment of patient mobility improves the risk stratification of triage with the Emergency Severity Index: a prospective cohort study
Authors: Nieves-Ortega Ricardo , Brabrand Mikkel , Dutilh Gilles , Kellett John , Bingisser Roland , Nickel Christian H.
Published: June 2021

Background and importance

Formal triage may assign a low acuity to patients at high risk of deterioration and mortality. A patient’s mobility can be easily assessed at triage.

Objective

To investigate if a simple assessment of mobility at triage can improve the Emergency Severity Index’s (ESI) prediction of adverse outcomes.

Design, setting and participants

Prospective observational study of all patients attending the emergency department (ED) of a single academic hospital in Switzerland over a period of 3 weeks.

Outcome measures and analysis

Triage clinicians classified participants as having normal or impaired mobility at triage. Impaired mobility was defined as the lack of a stable independent gait, regardless of its cause or duration (e.g. any patient who needed help to walk). The primary outcome was 30-day mortality. We performed a survival analysis stratified by mobility and ESI level. We compared the performance of regression models including the ESI alone or in combination with mobility as predictors of mortality using the Bayesian information criterion (BIC).

Main results

2523 patients were included in the study and 880 (34.9%) had impaired mobility. Patients with impaired mobility had a lower median 30-day survival in ESI levels 1–3. Survival of patients with normal mobility was similar regardless of their ESI level.

Conclusion

The assessment of mobility at triage improves the ESI algorithm’s risk stratification.
Threshold Analysis of the Cost-effectiveness of Endoscopic Ultrasound in Patients at High Risk for Pancreatic Ductal Adenocarcinoma
Authors: Kumar Shria , Saumoy Monica , Oh Aaron , Schneider Yecheskel , Brand Randall E. , Chak Amitabh , Ginsberg Gregory G. , Kochman Michael L. , Canto Marcia Irene , Goggins Michael Gilbert , Hur Chin , Kastrinos Fay , Katona Bryson W. , Rustgi Anil K.
Published: June 2021

Objectives

Data from the International Cancer of the Pancreas Screening Consortium studies have demonstrated that screening for pancreatic ductal adenocarcinoma can be effective and that surveillance improves survival in high-risk individuals. Endoscopic ultrasound (EUS) and cross-sectional imaging are both used, although there is some suggestion that EUS is superior. Demonstration of the cost-effectiveness of screening is important to implement screening in high-risk groups.

Methods

Results from centers with EUS-predominant screening were pooled to evaluate efficacy of index EUS in screening. A decision analysis model simulated the outcome of high-risk patients who undergo screening and evaluated the parameters that would make screening cost-effective at a US $100,000 per quality-adjusted life-year willingness to pay.

Results

One-time index EUS has a sensitivity of 71.25% and specificity of 99.82% to detection to detect high-risk lesions. Screening with index EUS was cost-effective, particularly at lifetime pancreatic cancer probabilities of greater than 10.8%, or at lower probabilities if life expectancy after resection of a lesion that was at least 16 years, and if missed, lesion rates on index EUS are 5% or less.

Conclusions

Pancreatic cancer screening can be cost-effective through index EUS, particularly for those individuals at high-lifetime risk of cancer.
Functional Outcomes of Nerve Allografts Seeded with Undifferentiated and Differentiated Mesenchymal Stem Cells in a Rat Sciatic Nerve Defect Model
Authors: Mathot Femke , Saffari Tiam M. , Rbia Nadia , Nijhuis Tim H. J. , Bishop Allen T. , Hovius Steven E. R. , Shin Alexander Y.
Published: June 2021

Background:

Mesenchymal stem cells have the potential to produce neurotrophic growth factors and establish a supportive microenvironment for neural regeneration. The purpose of this study was to determine the effect of undifferentiated and differentiated mesenchymal stem cells dynamically seeded onto decellularized nerve allografts on functional outcomes when used in peripheral nerve repair.

Methods:

In 80 Lewis rats, a 10-mm sciatic nerve defect was reconstructed with (1) autograft, (2) decellularized allograft, (3) decellularized allograft seeded with undifferentiated mesenchymal stem cells, or (4) decellularized allograft seeded with mesenchymal stem cells differentiated into Schwann cell–like cells. Nerve regeneration was evaluated over time by cross-sectional tibial muscle ultrasound measurements, and at 12 and 16 weeks by isometric tetanic force measurements, compound muscle action potentials, muscle mass, histology, and immunofluorescence analyses.

Results:

At 12 weeks, undifferentiated mesenchymal stem cells significantly improved isometric tetanic force measurement and compound muscle action potential outcomes compared to decellularized allograft alone, whereas differentiated mesenchymal stem cells significantly improved compound muscle action potential outcomes. The autografts outperformed both stem cell groups histologically at 12 weeks. At 16 weeks, functional outcomes normalized between groups. At both time points, the effect of undifferentiated versus differentiated mesenchymal stem cells was not significantly different.

Conclusions:

Undifferentiated and differentiated mesenchymal stem cells significantly improved functional outcomes of decellularized allografts at 12 weeks and were similar to autograft results in the majority of measurements. At 16 weeks, outcomes normalized as expected. Although differences between both cell types were not statistically significant, undifferentiated mesenchymal stem cells improved functional outcomes of decellularized nerve allografts to a greater extent and had practical benefits for clinical translation by limiting preparation time and costs.
Mesenteric Panniculitis Can Be Diagnosed by Examination and Cured by Comprehensive Therapy
Authors: Zhao Li , Xie Dajiang
Published: June 2021

Mesenteric panniculitis is a rare, slowly progressive, benign, and chronic fibrous inflammatory disease that affects the adipose tissue of the mesentery. In the present study, we aim to investigate its clinical presentations, computed tomography/sonography scan features, effectiveness of the treatment, and overall prognosis. We investigated various presentations, etiologies, diagnostic approaches, potential treatment modalities, and overall prognosis of mesenteric panniculitis. We present one case of mesenteric panniculitis with abdominal pain, which underwent steroid treatment regimens subsequently and gained weight moderately. An abdomen and pelvis cavity computed tomography scan showed misty mesentery, an ill-defined increase in the density of the peritoneal fat at the base of the mesentery with few small associated lymph nodes. The appearance is that of a panniculitis. His symptoms gradually decreased in intensity and disappeared totally within 1 month after oral prednisone 40 mg per day and moderate gain weight. Computed tomography scan features of the disease have recently been delineated clearly. Standard treatment strategy does not exist, and the current ways mainly consist of immunosuppressor or anti-inflammation agents. Overall prognosis is usually good and recurrence seems to be rare.
Controlling the adhesive pull-off force via the change of contact geometry
Authors: Argatov I. I.
Published: June 2021

A first-order asymptotic analysis of the Griffith energy balance in the Johnson–Kendall–Roberts model of adhesive contact under non-symmetric perturbation of the contact geometry is presented. The pull-off force is evaluated in explicit form. A particular case of adhesive contact between a relatively stiff sphere and an elastic half-space is considered under the assumption that the sphere geometry is changed by the application of an arbitrary lateral normal surface loading. The effect of the sphere Poisson’s ratio on controlling the adhesive pull-off force is considered.

This article is part of a discussion meeting issue ‘A cracking approach to inventing new tough materials: fracture stranger than friction’.
Deceased donor kidney degradomics indicates cytoskeletal proteolytic alterations impacting post-transplant function
Authors: Vaughan Rebecca H. , Kresse Jean-Claude , Farmer Louise K. , Thézénas Marie L. , Kessler Benedikt M. , Lindeman Jan H. N. , Sharples Edward J , Welsh Gavin I. , Nørregaard Rikke , Ploeg Rutger J. , Kaisar Maria E.
Published: June 2021

Background

In brain death, cerebral injury contributes to systemic biological dysregulation, causing significant cellular stress in donor kidneys that adversely impacts the quality of grafts. Here, we hypothesized that DBD kidneys may undergo proteolytic processes that renders grafts susceptible to post-transplant dysfunction.

Material & Methods

Using mass spectrometry and immunoblotting analyses, we profiled degradation patterns of cytoskeletal proteins in deceased (n=55) and living (n=10) donor kidneys.

Results

We found that in DBD kidneys, key podocyte cytoskeletal proteins had been proteolytically cleaved. Generated degradation profiles were not associated to donor related demographic and clinical factors but were associated to suboptimal post-transplant function. Strikingly, α-actinin -4 and Talin-1 degradation profiles were not observed in circulatory-death or living-donor kidneys. As Talin-1 is a specific proteolytic target of Calpain-1, we investigated a potential trigger of Calpain activation and Talin-1 degradation using ex-vivo precision-cut human kidney slices and in-vitro immortalised human podocytes. Notably, we found that Transforming-Growth Factor-β (TGF-β) activated Calpain-1 and proteolytically cleaved Talin-1 to generate distinct peptide fragments. These peptide fragments were of similar size and matched the degradation patterns observed in DBD kidneys. Talin-1 degradation was prevented in vitro by Calpain-1 inhibition.

Conclusions

Here, we provide initial evidence that DBD kidneys are susceptible to cytoskeletal protein degradation that impacts posttransplant kidney function. Subsequent studies should aim to further investigate the link between brain death and activation of proteolytic pathways exploring new therapeutic opportunities.
Neutrophil Lymphocyte Ratio as a Predictor of Glucocorticoid Effectiveness in Covid-19 Treatment
Authors: Lengerich Benjamin J. , Caruana Rich , Peysakhovich Alex , Horwitz Leora , Aphinayanaphongs Yin
Published: June 2021

Glucocorticoids have been shown to improve outcomes of patients with severe cases of Covid-19. However, criteria for prescribing glucocorticoids are currently limited. To identify potential for targeting, we perform an observational analysis of mortality of hospitalized patients. Our results agree with current clinical understanding that glucocorticoids benefit patients with severe cases of Covid-19, and that elevated Neutrophil/Lymphocyte Ratio (NLR) is associated with mortality. Furthermore, our results suggest that glucocorticoids could be targeted to patients with elevated NLR (especially in the range 6-25) at time of admission. Finally, we note there are also high-risk patients with low NLR, suggesting varying presentations of severe Covid-19.
Comparing azithromycin to amoxicillin in the management of uncomplicated severe acute malnutrition in Burkina Faso: a pilot randomized trial
Authors: O’Brien Kieran S. , Sié Ali , Dah Clarisse , Ourohire Millogo , Ouédraogo Moussa , Boudo Valentin , Arzika Ahmed M. , Lebas Elodie , Nyatigo Fanice , Godwin William W. , Kelly J. Daniel , Arnold Benjamin F. , Oldenburg Catherine E.
Published: June 2021

Introduction

Given the potential for asymptomatic infection in children with uncomplicated severe acute malnutrition (SAM), the World Health Organization recommends a broad-spectrum antibiotic like amoxicillin. Azithromycin is a promising alternative to amoxicillin as it can be administered as a single dose and has efficacy against several pathogens involved in the burden of infectious disease and mortality in this population. In this pilot study, we aimed to establish the feasibility of a larger randomized controlled trial and to provide preliminary evidence comparing the effect of azithromycin to amoxicillin on weight gain in children with uncomplicated SAM.

Methods

This pilot randomized trial enrolled children 6-59 months old with uncomplicated SAM at 6 healthcare centers in Burkina Faso. Participants were randomized to a single dose of azithromycin or a 7-day course of amoxicillin. All participants received ready-to-use therapeutic food and were followed weekly until nutritional recovery and again at 8 weeks. The primary feasibility outcomes included enrollment potential, refusals, and loss to follow-up. The primary clinical outcome was weight gain (g/kg/day) over the 8-week period. Outcome assessors were masked.

Results

Between June and October 2020, 312 children were screened, 301 were enrolled with 0 refusals, and 282 (93.6%) completed the 8-week visit. Average weight gain was 2.5 g/kg/day (SD 2.0) in the azithromycin group and 2.6 (SD) 1.7) in the amoxicillin group (Mean Difference - 0.1, 95% CI -0.5 to 0.3, P = 0.63). Fewer adverse events were reported in the azithromycin group (Risk Ratio 0.50, 95% CI 0.31 to 0.82, P = 0.006).

Conclusions

No differences were found in weight gain between groups. Given the ability to administer a single dose and the potential for fewer adverse events, azithromycin may be an alternative to amoxicillin for uncomplicated SAM. With strong enrollment and follow-up, a larger trial in this setting is feasible.
Antibody neutralization to SARS-CoV-2 and variants after one year in Wuhan
Authors: Liu Qianyun , Xiong Qing , Mei Fanghua , Ma Chengbao , Zhang Zhen , Hu Bing , Xu Junqiang , Jiang Yongzhong , Zhan Faxian , Chen Xianying , Guo Ming , Wang Xin , Fang Yaohui , Shen Shu , Liu Yingle , Liu Fang , Zhou Li , Xu Ke , Ke Changwen , Deng Fei , Cai Kun , Yan Huan , Chen Yu , Lan Ke
Published: June 2021

Most COVID-19 patients can build effective humoral immunity against SARS-CoV-2 after recovery(1, 2). However, it remains unknown how long the protection can maintain and how efficiently it can protect people from the reinfection of the emerging SARS-CoV-2 variants. Here we evaluated the sera from 248 COVID-19 convalescents around one year post-infection in Wuhan, the earliest epicenter of SARS-CoV-2. We demonstrated that the SARS-CoV-2 immunoglobulin G (IgG) maintains at a high level and potently neutralizes the infection of the original strain (WT) and the B.1.1.7 variant in most patients. However, they showed varying degrees of efficacy reduction against the other variants of concern (P.1, B.1.525, and especially B.1.351) in a patient-specific manner. Mutations in RBD including K417N, E484K, and E484Q/L452R (B.1.617) remarkably impair the neutralizing activity of the convalescents’ sera. Encouragingly, we found that a small fraction of patients’ sera showed broad neutralization potency to multiple variants and mutants, suggesting the existence of broadly neutralizing antibodies recognizing the epitopes beyond the mutation sites. Our results suggest that the SARS-CoV-2 vaccination effectiveness relies more on the timely re-administration of the epitope-updated vaccine than the durability of the neutralizing antibodies.
Blood metabolites predicting Mild Cognitive Impairment in the Study of Latinos-Investigation of Neurocognitive Aging (HCHS/SOL)
Authors: He Shan , Granot-Hershkovitz Einat , Zhang Ying , Bressler Jan , Tarraf Wassim , Yu Bing , Huang Tianyi , Zeng Donglin , Wassertheil-Smoller Sylvia , Lamar Melissa , Daviglus Martha , Marquine Maria J , Cai Jianwen , Mosley Thomas , Kaplan Robert , Boerwinkle Eric , Fornage Myriam , DeCarli Charles , Kristal Bruce , Gonzalez Hector M , Sofer Tamar
Published: June 2021

INTRODUCTION

Blood metabolomics-based biomarkers may be useful to predict measures of neurocognitive aging.

METHODS

We tested the association between 707 blood metabolites measured in 1,451 participants from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), with MCI and global cognitive change assessed seven years later. We further used Lasso penalized regression to construct a metabolomics risk score (MRS) that predicts MCI, potentially identifying a different set of metabolites than those discovered in individual-metabolite analysis.

RESULTS

We identified 20 metabolites associated with MCI and/or global cognitive change. Six of them were novel and 14 were previously reported as associated with neurocognitive aging outcomes. The MCI MRS comprised 61 metabolites and improved prediction accuracy from 84% (minimally adjusted model) to 89% in the entire dataset and from 75% to 87% among APOE-ε4 carriers.

DISCUSSION

Blood metabolites may serve as biomarkers identifying individuals at risk for MCI among U.S. Hispanics/Latinos.
Localization of planteose hydrolysis during seed germination of Orobanche minor
Authors: Okazawa Atsushi , Baba Atsuya , Okano Hikaru , Tokunaga Tomoya , Nakaue Tsubasa , Ogawa Takumi , Shimma Shuichi , Sugimoto Yukihiro , Ohta Daisaku
Published: June 2021

Root parasitic weeds of the Orobanchaceae, such as witchweeds (Striga spp.) and broomrapes (Orobanche and Phelipanche spp.), cause serious losses in agriculture worldwide. No practical method to control these parasitic weeds has been developed to date. Understanding the characteristic physiological processes in the life cycles of root parasitic weeds is particularly important to identify specific targets for growth modulators. In our previous study, planteose metabolism was revealed to be activated soon after the perception of strigolactones in germinating seeds of O. minor. Nojirimycin inhibited planteose metabolism and impeded seed germination of O. minor, indicating that planteose metabolism is a possible target for root parasitic weed control. In the present study, we investigated the distribution of planteose in dry seeds of O. minor by matrix-assisted laser desorption/ionization–mass spectrometry imaging. Planteose was detected in tissues surrounding—but not within—the embryo, supporting its suggested role as a storage carbohydrate. Biochemical assays and molecular characterization of an α-galactosidase family member, OmAGAL2, indicated the enzyme is involved in planteose hydrolysis in the apoplast around the embryo after the perception of strigolactones to provide the embryo with essential hexoses for germination. These results indicated that OmAGAL2 is a potential molecular target for root parasitic weed control.

Highlight

Planteose accumulated in tissues surrounding the embryo in Orobanche minor dry seeds and was indicated to be hydrolyzed in the apoplast around the embryo by α-galactosidase during germination.