bluuebunny/crossref_metadata_2025 huggingface dataset:
Small extracellular vesicles from human adipose-derived mesenchymal stromal cells: a potential promoter of fat graft survival
Authors: Chen Aizhen , Tang Shijie , He Jiawei , Li Xiangyu , Peng Guohao , Zhang Haoruo , Chen Jinghua , Chen Liangwan , Chen Xiaosong
Published: May 2021

Background

Small extracellular vesicles (sEVs) with genetic information secreted by cells play a crucial role in the cellular microenvironment. In this study, our purpose is to explore the characteristics of the small extracellular vesicles of human adipose-derived mesenchymal stromal cells (hADMSC-sEVs) and studied the role of hADMSC-sEVs in improving the survival rate of grafted fat.

Methods

In the present study, we used the transmission electron microscopy, nano-tracking analysis, nanoflow surface protein analysis, and zeta potential value to identify sEVs. SEVs’ trajectory was traced dynamically to verify whether hADMSC-sEVs can be internalized into human umbilical vein endothelial cells (HUVECs) in vitro at different times. The angiogenic property of hADMSC-sEVs was observed by measuring the volume, weight, and histological analysis of the grafted fats in nude mouse models.

Results

Our research showed that the hADMSC-sEVs were sEVs with double-layer membrane structure and the diameter of which is within 30–150 nm. hADMSC-sEVs exert biological influence mainly through internalization into cells. Compared with the control group, the hADMSC-sEVs group had a significantly higher survival rate of grafted fat, morphological integrity, and a lower degree of inflammation and fibrosis. And immunohistochemistry showed that hADMSC-sEVs significantly increased the neovascularisation and the expression of CD34, VEGFR2, and Ki-67 in the graft tissue.

Conclusions

As a potential nanomaterial, hADMSC-sEVs have been explored in the field of cell-free application of stem cell technology. hADMSC-sEVs promoted the survival of grafted fats by promoting the formation of new blood vessels, which is another promising progress in the field of regenerative medicine. We believe that hADMSC-sEVs will have a broad application prospect in the field of regenerative medicine in the future.
Consecutive daily administration of intratracheal surfactant and human umbilical cord-derived mesenchymal stem cells attenuates hyperoxia-induced lung injury in neonatal rats
Authors: Chou Hsiu-Chu , Chang Chien-Hsiang , Chen Chien-Han , Lin Willie , Chen Chung-Ming
Published: May 2021

Background

Surfactant therapy is a standard of care for preterm infants with respiratory distress and reduces the incidence of death and bronchopulmonary dysplasia in these patients. Our previous study found that mesenchymal stem cells (MSCs) attenuated hyperoxia-induced lung injury and the combination therapy of surfactant and human umbilical cord-derived MSCs (hUC-MSCs) did not have additive effects on hyperoxia-induced lung injury in neonatal rats. The aim is to evaluate the effects of 2 consecutive days of intratracheal administration of surfactant and hUC-MSCs on hyperoxia-induced lung injury.

Methods

Neonatal Sprague Dawley rats were reared in either room air (RA) or hyperoxia (85% O2) from postnatal days 1 to 14. On postnatal day 4, the rats received intratracheal injections of either 20 μL of normal saline (NS) or 20 μL of surfactant. On postnatal day 5, the rats reared in RA received intratracheal NS, and the rats reared in O2 received intratracheal NS or hUC-MSCs (3 × 104 or 3 × 105 cells). Six study groups were examined: RA + NS + NS, RA + surfactant + NS, O2 + NS + NS, O2 + surfactant + NS, O2 + surfactant + hUC-MSCs (3 × 104 cells), and O2 + surfactant + hUC-MSCs (3 × 105 cells). The lungs were excised for histological, western blot, and cytokine analyses.

Results

The rats reared in hyperoxia and treated with NS yielded significantly higher mean linear intercepts (MLIs) and interleukin (IL)-1β and IL-6 levels and significantly lower vascular endothelial growth factors (VEGFs), platelet-derived growth factor protein expression, and vascular density than did those reared in RA and treated with NS or surfactant. The lowered MLIs and cytokines and the increased VEGF expression and vascular density indicated that the surfactant and surfactant + hUC-MSCs (3 × 104 cells) treatment attenuated hyperoxia-induced lung injury. The surfactant + hUC-MSCs (3 × 105 cells) group exhibited a significantly lower MLI and significantly higher VEGF expression and vascular density than the surfactant + hUC-MSCs (3 × 104 cells) group did.

Conclusions

Consecutive daily administration of intratracheal surfactant and hUC-MSCs can be an effective regimen for treating hyperoxia-induced lung injury in neonates.
Conversion of stem cells from apical papilla into endothelial cells by small molecules and growth factors
Authors: Yi Baicheng , Ding Tian , Jiang Shan , Gong Ting , Chopra Hitesh , Sha Ou , Dissanayaka Waruna Lakmal , Ge Shaohua , Zhang Chengfei
Published: May 2021

Objectives

Recently, a new strategy has been developed to directly reprogram one cell type towards another targeted cell type using small molecule compounds. Human fibroblasts have been chemically reprogrammed into neuronal cells, Schwann cells and cardiomyocyte-like cells by different small molecule combinations. This study aimed to explore whether stem cells from apical papilla (SCAP) could be reprogrammed into endothelial cells (ECs) using the same strategy.

Materials and methods

The expression level of endothelial-specific genes and proteins after chemical induction of SCAP was assessed by RT-PCR, western blotting, flow cytometry and immunofluorescence. The in vitro functions of SCAP-derived chemical-induced endothelial cells (SCAP-ECs) were evaluated by tube-like structure formation assay, acetylated low-density lipoprotein (ac-LDL) uptake and NO secretion detection. The proliferation and the migration ability of SCAP-ECs were evaluated by CCK-8 and Transwell assay. LPS stimulation was used to mimic the inflammatory environment in demonstrating the ability of SCAP-ECs to express adhesion molecules. The in vivo Matrigel plug angiogenesis assay was performed to assess the function of SCAP-ECs in generating vascular structures using the immune-deficient mouse model.

Results

SCAP-ECs expressed upregulated endothelial-specific genes and proteins; displayed endothelial transcriptional networks; exhibited the ability to form functional tubular-like structures, uptake ac-LDL and secrete NO in vitro; and contributed to generate blood vessels in vivo. The SCAP-ECs could also express adhesion molecules in the pro-inflammatory environment and have a similar migration and proliferation ability as HUVECs.

Conclusions

Our study demonstrates that the set of small molecules and growth factors could significantly promote endothelial transdifferentiation of SCAP, which provides a promising candidate cell source for vascular engineering and treatment of ischemic diseases.
Head to head comparison of [99mTc]Tc(CO)3(NTA) and [99mTc]Tc-MAG3 in patients with suspected obstruction
Authors: Taylor Andrew T. , Lipowska Malgorzata , Halkar Raghuveer K.
Published: May 2021

Purpose

99mTc-tricarbonyl-nitrilotriacetic acid, [99mTc]Tc(CO)3(NTA), is a new 99mTc-renal radiopharmaceutical with a clearance equal to that of 131I-ortho-iodohippuran, [131I]I-OIH. Our purpose was to compare the performance of [99mTc]Tc(CO)3(NTA) and [99mTc]Tc-MAG3 in patients with suspected obstruction.

Methods

[99mTc]Tc(CO)3(NTA) was prepared with commercially available NTA ligand and CRS Isolink kit, and isolated by HPLC. Eighteen adult patients referred for diuretic renography received an intravenous injection of approximately 40 mg of furosemide 15 min prior to either [99mTc]Tc(CO)3(NTA) or [99mTc]Tc-MAG3 (mean activity of 47 ± 4.4 MBq). Data were acquired for 24 min followed by an anterior image of the liver and gall bladder and a measure of voided volume. Patients received a second furosemide injection equal to one third of the original dose followed fifteen minutes later by administration of the alternate tracer, mean activity of 320 ± 34 MBq. Clearances were measured using a camera-based technique.

Results

The clearance of NTA was greater than that of MAG3, 331 ± 146 versus 271 ± 105 mL/min/1.73 m2, respectively, p < 0.0001. The kidney to background ratio for NTA was greater than that of MAG3 for both left and right kidneys, p < 0.001; the 20 min/maximum count ratio was significantly less, p < 0.0001. There was no significant difference in the voiding volumes following NTA and MAG3 administration, 598 ± 237 mL versus 498 ± 170 mL, respectively, p = 0.07. Gall bladder activity was not observed with NTA but was present in 6/17 MAG3 studies. Images and renogram curves were comparable except for two patients where the NTA study excluded obstruction but the MAG3 study suggested an indeterminate or obstructed kidney.

Conclusions

Unlike MAG3, NTA is not eliminated via the hepatobiliary track. Moreover, NTA has a higher kidney to background ratio and more rapid clearance than MAG3. These advantages should allow more robust camera-based clearance measurements and may lead to better discrimination between obstructed and non-obstructed kidneys.
Correctness conditions for high-order differential equations with unbounded coefficients
Authors: Ospanov Kordan N.
Published: May 2021

We give some sufficient conditions for the existence and uniqueness of the solution of a higher-order linear differential equation with unbounded coefficients in the Hilbert space. We obtain some estimates for the weighted norms of the solution and its derivatives. Using these estimates, we show the conditions for the compactness of some integral operators associated with the resolvent.
A new method for high-order boundary value problems
Authors: Zhang Yingchao , Mei Liangcai , Lin Yingzhen
Published: May 2021

This paper presents a numerical algorithm for solving high-order BVPs. We introduce the construction method of multiscale orthonormal basis in $W^{m}_{2}[0,1]$

W
2
m

[
0
,
1
]
. Based on the orthonormal basis, the numerical solution of the boundary value problem is obtained by finding the ε-approximate solution. In addition, the convergence order, stability, and time complexity of the method are discussed theoretically. At last, several numerical experiments show the feasibility of the proposed method.
The importance of large-diameter trees to the creation of snag and deadwood biomass
Authors: Lutz James A. , Struckman Soren , Germain Sara J. , Furniss Tucker J.
Published: May 2021

Background

Baseline levels of tree mortality can, over time, contribute to high snag densities and high levels of deadwood (down woody debris) if fire is infrequent and decomposition is slow. Deadwood can be important for tree recruitment, and it plays a major role in terrestrial carbon cycling, but deadwood is rarely examined in a spatially explicit context.

Methods

Between 2011 and 2019, we annually tracked all trees and snags ≥1 cm in diameter and mapped all pieces of deadwood ≥10 cm diameter and ≥1 m in length in 25.6 ha ofTsuga heterophylla/Pseudotsuga menziesiiforest. We analyzed the amount, biomass, and spatial distribution of deadwood, and we assessed how various causes of mortality that contributed uniquely to deadwood creation.

Results

Compared to aboveground woody live biomass of 481 Mg ha−1(from trees ≥10 cm diameter), snag biomass was 74 Mg ha−1and deadwood biomass was 109 Mg ha−1(from boles ≥10 cm diameter). Biomass from large-diameter trees (≥60 cm) accounted for 85%, 88%, and 58%, of trees, snags, and deadwood, respectively. Total aboveground woody live and dead biomass was 668 Mg ha−1. The annual production of downed wood (≥10 cm diameter) from tree boles averaged 4 Mg ha−1yr−1. Woody debris was spatially heterogeneous, varying more than two orders of magnitude from 4 to 587 Mg ha−1at the scale of 20 m × 20 m quadrats. Almost all causes of deadwood creation varied in importance between large-diameter trees and small-diameter trees. Biomass of standing stems and deadwood had weak inverse distributions, reflecting the long period of time required for trees to reach large diameters following antecedent tree mortalities and the centennial scale time required for deadwood decomposition.

Conclusion

Old-growth forests contain large stores of biomass in living trees, as well as in snag and deadwood biomass pools that are stable long after tree death. Ignoring biomass (or carbon) in deadwood pools can lead to substantial underestimations of sequestration and stability.
Movement patterns of juvenile Atlantic tarpon (Megalops atlanticus) in Brewers Bay, St. Thomas, U.S. Virgin Islands
Authors: Duffing Romero Mareike D. , Matley Jordan K. , Luo Jiangang , Ault Jerald S. , Pittman Simon J. , Nemeth Richard S.
Published: May 2021

Background

Atlantic tarpon (Megalops atlanticus) are a highly migratory species ranging along continental and insular coastlines of the Atlantic Ocean. Due to their importance to regional recreational and sport fisheries, research has been focused on large-scale movement patterns of reproductively active adults in areas where they are of high economic value. As a consequence, geographically restricted focus on adults has left significant gaps in our understanding of tarpon biology and their movements, especially for juveniles in remote locations where they are common. Our study focused on small-scale patterns of movement and habitat use of juvenile tarpon using acoustic telemetry in a small bay in St. Thomas, US Virgin Islands.

Results

Four juvenile tarpon (80–95 cm FL) were tracked from September 2015 to February 2018, while an additional eight juveniles (61–94 cm FL) left the study area within 2 days after tagging and were not included in analysis. Four tarpon had > 78% residency and average activity space of 0.76 km2 (range 0.08–1.17 km2) within Brewers Bay (1.8 km2). Their vertical distribution was < 18 m depth with occasional movements to deeper water. Activity was greater during day compared to night, with peaks during crepuscular periods. During the day tarpon used different parts of the bay with consistent overlap around the St. Thomas airport runway and at night tarpon typically remained in a small shallow lagoon. However, when temperatures in the lagoon exceeded 30 °C, tarpon moved to cooler, deeper waters outside the lagoon.

Conclusion

Our results, although limited to only four individuals, provide new baseline data on the movement ecology of juvenile Atlantic tarpon. We showed that juvenile tarpon had high residency within a small bay and relatively stable non-overlapping daytime home ranges, except when seasonally abundant food sources were present. Fine-scale acoustic tracking showed the effects of environmental conditions (i.e., elevated seawater temperature) on tarpon movement and habitat use. These observations highlight the need for more extensive studies of juvenile tarpon across a broader range of their distribution, and compare the similarities and differences in behavior among various size classes of individuals from small juveniles to reproductively mature adults.
Assessing the wellbeing of Chinese university students: validation of a Chinese version of the college student subjective wellbeing questionnaire
Authors: Zhang Yan , Carciofo Richard
Published: May 2021

Background

In response to the rising concern with promoting the wellbeing of university students and relative lack of domain-specific wellbeing measurement instruments in China, the current study aimed to validate a Chinese version of the College Student Subjective Wellbeing Questionnaire (CSSWQ), a 16-item self-report English-language rating scale assessing four aspects of wellbeing (academic satisfaction, academic efficacy, school connectedness, and college gratitude).

Methods

The Chinese translation of the CSSWQ, the Students’ Life Satisfaction Scale, the Positive and Negative Affect Schedule, the 10-Item Big Five Personality Inventory, and demographic questions were completed by 252 Chinese students at a university in Suzhou, China.

Results

Exploratory factor analysis found four factors each with the same four items as in the original English scale. Each subscale showed good internal consistency. Test–retest for a one-month interval showed generally moderate reliability. As predicted, Pearson correlational analysis found positive correlations between the Chinese CSSWQ and life satisfaction, positive affect, extraversion, and GPA, and negative correlations with neuroticism and negative affect. Monthly income had small negative correlations with academic satisfaction and academic efficacy, smoking had a small positive correlation with school connectedness, and exercise had a small positive correlation with academic efficacy.

Conclusion

Data for the Chinese CSSWQ in the current study showed validity and reliability, supporting the use of this instrument as a measurement of college student wellbeing in China.
Empiric use of anticoagulation in hospitalized patients with COVID-19: a propensity score-matched study of risks and benefits
Authors: Yu Bo , Gutierrez Victor Perez , Carlos Alex , Hoge Gregory , Pillai Anjana , Kelly J. Daniel , Menon Vidya
Published: May 2021

Background

Hospitalized patients with COVID-19 demonstrate a higher risk of developing thromboembolism. Anticoagulation (AC) has been proposed for high-risk patients, even without confirmed thromboembolism. However, benefits and risks of AC are not well assessed due to insufficient clinical data. We performed a retrospective analysis of outcomes from AC in a large population of COVID-19 patients.

Methods

We retrospectively reviewed 1189 patients hospitalized for COVID-19 between March 5 and May 15, 2020, with primary outcomes of mortality, invasive mechanical ventilation, and major bleeding. Patients who received therapeutic AC for known indications were excluded. Propensity score matching of baseline characteristics and admission parameters was performed to minimize bias between cohorts.

Results

The analysis cohort included 973 patients. Forty-four patients who received therapeutic AC for confirmed thromboembolic events and atrial fibrillation were excluded. After propensity score matching, 133 patients received empiric therapeutic AC while 215 received low dose prophylactic AC. Overall, there was no difference in the rate of invasive mechanical ventilation (73.7% versus 65.6%, p = 0.133) or mortality (60.2% versus 60.9%, p = 0.885). However, among patients requiring invasive mechanical ventilation, empiric therapeutic AC was an independent predictor of lower mortality (hazard ratio [HR] 0.476, 95% confidence interval [CI] 0.345–0.657, p < 0.001) with longer median survival (14 days vs 8 days, p < 0.001), but these associations were not observed in the overall cohort (p = 0.063). Additionally, no significant difference in mortality was found between patients receiving empiric therapeutic AC versus prophylactic AC in various subgroups with different D-dimer level cutoffs. Patients who received therapeutic AC showed a higher incidence of major bleeding (13.8% vs 3.9%, p < 0.001). Furthermore, patients with a HAS-BLED score of ≥2 had a higher risk of mortality (HR 1.482, 95% CI 1.110–1.980, p = 0.008), while those with a score of ≥3 had a higher risk of major bleeding (Odds ratio: 1.883, CI: 1.114–3.729, p = 0.016).

Conclusion

Empiric use of therapeutic AC conferred survival benefit to patients requiring invasive mechanical ventilation, but did not show benefit in non-critically ill patients hospitalized for COVID-19. Careful bleeding risk estimation should be pursued before considering escalation of AC intensity.
Seasonal variation of Hedruris dratini (Nematoda) parasitizing Hydromedusa tectifera (Chelidae), with focus on host’s torpor state
Authors: Palumbo Ezequiel , Cassano María Julia , Alcalde Leandro , Diaz Julia Inés
Published: May 2021

Background

The aim of this study was to analyze the seasonal distribution of the nematodeHedruris dratiniparasitizing the South American Snake-necked turtleHydromedusa tectiferaand the amphipodHyalellaspp. in an urban stream. We focused on understand which strategies parasite population displays to get through the host’s hibernation period.

Results

The highest prevalence and abundance ofH. dratiniwere found in summer. The parasitic load was lower in winter, however there were no significant differences when it was compared with autumn and spring. Generalized linear model identified the temperature as a determining factor for the presence of parasites in turtles.

Conclusions

Our results indicate that, beside turtles enter in a diapause state, the life cycle ofH. dratininever stop throughout the year, being a continuous transmission between both the intermediate and final host throughout the year. Turtles feed and become infected with parasite larvae even in winter although with a lower ingestion rate.
Safety of perioperative period in robot-assisted atrial septal defect repair under hyperkalemic arrest
Authors: Miyata Kazuto , Tarui Tatsuya , Shigematsu Sayaka , Ishikawa Norihiko , Watanabe Go
Published: May 2021

Background

Various attempts have been made to meet patient desires, especially among younger and otherwise healthy individuals, for cosmetically satisfying incision with atrial septal defect (ASD) repair. One of procedures was a robotic-assisted totally endoscopic ASD repair via only two ports under hyperkalemic arrest without aortic cross-clamping. This study investigated perioperative management and safety for robotic-assisted total endoscopic ASD repair surgery under hyperkalemic arrest.

Methods

We retrospectively reviewed perioperative management of thirty patients who underwent total endoscopic robot-assisted ASD repair under hyperkalemic arrest. All procedures were performed under general anesthesia using robotic-assisted total endoscopic for ASD repair via two or three ports under hyperkalemic arrest without aortic cross-clamping.

Results

A total of 30 patients (mean age 45 ± 17 years, 8 male, 22 female) underwent successful ASD repair with the total endoscopic robotic-assisted procedures under hyperkalemic arrest.

Hyperkalemic arrest was achieved and maintained by intravenous administration of mean potassium dose of 91±32 mEq (1.4±0.6 mEq/kg) with the lowest bladder temperature was 31.9±1.4 °C during hyperkalemic arrest.

In all cases, serum potassium concentration was <5.0 mEq/L after weaning from cardiopulmonary bypass, although two cases who developed hyperkalemia >6 mEq/L after operation. At other time points, no patient exceeded 6 mEq/L of serum potassium concentration. At admission to the intensive care unit, mean serum creatine phosphokinase-MB level was 32±7mg/dL. There were no cases of arrhythmia or other cardiac complications during recovery.

Conclusions

Perioperative management of robotic-assisted total endoscopic ASD repair under hyperkalemic arrest is safe and is not associated with fatal arrhythmia due to hyperkalemia.
Prevalence of burnout among neurologists in Saudi Arabia
Authors: Al-Qahtani Zina Ali , Alhazzani Adel
Published: May 2021

Background

Burnout is a psychological syndrome defined as emotional exhaustion (EE), depersonalization (DP), and reduced personal accomplishment (PA) secondary to work stress. Burnout is widespread among medical workers. We aim to study the prevalence of burnout among neurologists in Saudi Arabia and describe some related personal and professional factors.

Results

A total of 62 consultants and 34 residents participated in the study. Having long working hours was a high source of stress among most of the participants. Consultants and residents reported high burnout rates in the three domains of the scale. In the emotional and exhaustion domain, more consultants (37.1%) showed high burnout compared to residents (23.5%). Regarding depersonalization domain, more residents (41.2%) showed high burnout compared to consultants (27.4%). Regarding the low personal accomplishment domain, more consultants (77.7%) showed high burnout compared to residents.

Conclusion

Residents and consultant neurologists showed high burnout rates, and results can be used as a baseline guidance to assist in reducing burnout by improving job satisfaction and working environment among neurologists.
Indoor navigation: state of the art and future trends
Authors: El-Sheimy Naser , Li You
Published: May 2021

This paper reviews the state of the art and future trends of indoor Positioning, Localization, and Navigation (PLAN). It covers the requirements, the main players, sensors, and techniques for indoor PLAN. Other than the navigation sensors such as Inertial Navigation System (INS) and Global Navigation Satellite System (GNSS), the environmental-perception sensors such as High-Definition map (HD map), Light Detection and Ranging (LiDAR), camera, the fifth generation of mobile network communication technology (5G), and Internet-of-Things (IoT) signals are becoming important aiding sensors for PLAN. The PLAN systems are expected to be more intelligent and robust under the emergence of more advanced sensors, multi-platform/multi-device/multi-sensor information fusion, self-learning systems, and the integration with artificial intelligence, 5G, IoT, and edge/fog computing.
Bioanalysis in the Age of New Drug Modalities
Authors: Shi Jing , Chen Xuesong , Diao Jianbo , Jiang Liying , Li Lan , Li Stephen , Liang Wenzhong , Jin Xiaoying , Wang Yonghui , Wong Colton , Zhang Xiaolong Tom , Tse Francis L.S.
Published: May 2021

In the absence of regulatory guidelines for the bioanalysis of new drug modalities, many of which contain multiple functional domains, bioanalytical strategies have been carefully designed to characterize the intact drug and each functional domain in terms of quantity, functionality, biotransformation, and immunogenicity. The present review focuses on the bioanalytical challenges and considerations for RNA-based drugs, bispecific antibodies and multi-domain protein therapeutics, prodrugs, gene and cell therapies, and fusion proteins. Methods ranging from the conventional ligand binding assays and liquid chromatography-mass spectrometry assays to quantitative polymerase chain reaction or flow cytometry often used for oligonucleotides and cell and gene therapies are discussed. Best practices for method selection and validation are proposed as well as a future perspective to address the bioanalytical needs of complex modalities.
Gut Microbiome and Intestinal Permeability Are Promising Targets for Treating Nonalcoholic Fatty Liver Disease
Authors: Heshmati Hassan Massoud
Published: May 2021

Background: Nonalcoholic fatty liver disease (NAFLD) is a leading liver disease worldwide with a prevalence of approximately 24% among adult population. It is a spectrum of liver disorders ranging from simple steatosis to nonalcoholic steatohepatitis (NASH). Obesity, insulin resistance, inflammation, disrupted gut microbiome (dysbiosis), and increased intestinal permeability (“leaky gut”) are important risk factors associated with and/or contributing to NAFLD. In the absence of specific drugs to treat NAFLD, management relies mainly on lifestyle changes (diet and exercise). Gut microbiome and intestinal permeability are becoming promising targets for the treatment of several diseases including NAFLD. Methods: A systematic search of literature was conducted using the search terms nonalcoholic fatty liver disease, obesity, insulin resistance, inflammation, gut microbiome, intestinal permeability, and targeted therapy. Results: Several clinical studies have shown the association of qualitative and quantitative changes in gut microbiome (e.g., increased Lactobacillus and Gram-negative bacteria) with NAFLD and its severity. The increased gut microbiome taxa may produce more short-chain fatty acids (SCFAs), alcohol, and lipopolysaccharides (LPS). Increased SCFAs, alcohol, and LPS (endotoxins) associated with increased intestinal permeability are implicated in the pathogenesis of NAFLD and its evolution to NASH (promotion of obesity and inflammation). Gut microbiome and intestinal permeability can be modified with diet, prebiotics, probiotics, synbiotics, and fecal microbiota transplantation. A high-fiber diet for 6 months in NAFLD subjects caused a decrease in intestinal permeability (as assessed by serum zonulin) and a reduction of liver enzymes and fatty liver. Treatment with a prebiotic (oligofructose) for 8 weeks in NASH subjects showed a significant decrease in markers of liver inflammation. Administration of probiotics (e.g., Lactobacillus, Bifidobacterium, and VSL#3) for 8 to 16 weeks in NAFLD subjects had several beneficial effects including reduction of liver enzymes and fatty liver. Clinical studies using fecal microbiota transplantation in NAFLD subjects are currently ongoing. To optimize the efficacy of therapies using prebiotics, probiotics, synbiotics, and fecal microbiota transplantation in NAFLD subjects, focus should be on the altered gut microbiome taxa responsible for high SCFAs, alcohol, and LPS production. Conclusion: NAFLD is the most common chronic liver disease. NAFLD subjects have disrupted gut microbiome associated with increased intestinal permeability. In addition to weight loss (when excess body weight is present), targeting gut microbiome and intestinal permeability with diet, prebiotics, probiotics, synbiotics, and fecal microbiota transplantation represents a promising novel approach in the treatment of NAFLD.
Human Visceral Adipose Tissue (VAT) Inflammation Is Not Associated With Perforin Deficiency in Type 2 Diabetes Mellitus (DM) Subjects as Compared to Health Controls
Authors: Shukla Ravindra Kumar , Choudhary Ramkaran , Lodha Mahendra , Rodha Mahaveer singh , Bajpai Nitin , Purohit Purvi , Sharma Praveen , Garg M K
Published: May 2021

Introduction: Role of T cells in VAT inflammation is poorly characterised. Perforin deficiency is associated with autoimmune inflammatory diseases like Hemophagocytosis Lymphohistiocytosis,as also in context of type 1 DM pathogenesis. Data from animal models suggest that perforin deficiency leads to VAT inflammation1Objective: We hypothesized CD8+/perf+ and CD56+/perf+ cells to be decreased in type 2 DM as compared to healthy controls. The present study also explored the difference in activation of T/NK cells between two groups Methods: 2×2 cm omental tissue was obtained from subjects undergoing elective abdominal surgery. The sample was transported in RPMI solution and stored in -80 ℃. Processing involved thawing, incubation at 37.6 ℃ for 24 hours with type IV Collagenase (1 mg/ml, Sigma Aldrich) 1ml/g of tissue,centrifuge (32g for 10 min at 10℃). The resultant Stromal Vascular fraction (SVF) was suspended in phosphate buffer saline (PBS), passed through cell strainer to make single cell suspension. It was again centrifuged and tagged with CD markers of interest. Fc block was added and single cell solution with FACS fluid prepared. It was run in BD CANTO-2 flow cytometer as described2Results: Of seventeen samples analysed, twelve samples of type 2 diabetes subjects were compared with five healthy controls. All results are presented in median. The diabetics had higher HbA1c (8.1 % vs 6%), higher BMI (28 kg/m2 vs 24 kg/m2), hsCRP(2.1 mg/dl Vs 0.9 mg/dl) but there was no difference in HOMA-Ir (5 vs 5.2 mU/L/mg/dl). The percentage of CD4+ + CD8+ cells/g of VAT was similar in both cases and control (20 × 103 Vs 23× 103). CD8+/CD45+/perf+ and CD56+/CD45+/perf+ could not be identified in any of the samples. Although CD8+/CD45+/perf-- and CD56+/CD45+/perf-- cells were identified. Next, we analysed the same cells for cytotoxic activation by 107a. The percentage of 107a positivity was low in CD 8+ (7% and 4 % respectively in cases and control) and CD 56+ cells (10% and 9 % respectively in cases and control),Although clinically type 2 DM subjects were obese and had inflammation (i.e higher hsCRP), there was no difference in VAT activation of immune cells studied. Also, we could not delineate perforin in any of the samples. Conclusion: Taken together this work suggests VAT T cell immune milieu in human Type 2 DM is different from mouse model. It is neither characterised by perforin deficiency nor activation of T cell/NK cell. This study points towards the probability that, the role of T cell/NK cells in human VAT infiltration could be fundamentally different from mice models. Further studies should be focussed on functional characteristics of these cells and interaction with VAT macrophages. References 1. Xavier S. Revelo et al Diabetes 2015;64:90–103 2. Wetzels S et al J Vis Exp. 2018 Mar 6;(133):57319.
Is Insulin Resistance at Baseline a Predictor of Weight Loss After Bariatric Surgery?
Authors: Borges-Canha Marta , Neves João Sérgio , Mendonça Fernando , Silva Maria Manuel , Costa Cláudia , Cabral Pedro , Guerreiro Vanessa , Lourenço Rita , Meira Patrícia , Salazar Cristina Daniela , Ferreira Maria João , Pedro Jorge , Sande Ana , Belo Sandra , Souto Selma S B , Lau Eva , Freitas Paula , Carvalho Davide
Published: May 2021

Background: Obesity is a multifactorial disease that is strongly associated to other metabolic disorders, such as insulin resistance and type 2 diabetes. Bariatric surgery is nowadays considered the most effective treatment of morbid obesity. The role of insulin resistance (IR) in weight loss after bariatric surgery is highly unknown.

Aim: To evaluate the association between Insulin Resistance (IR) and percentage of excess weight loss (EWL%) one, two, three and four years after bariatric surgery in patients with morbid obesity. Methods: Retrospective longitudinal study in patients with morbid obesity followed in our centre between January 2010 and July 2018 were included. Patients were excluded if they had diabetes. We evaluated baseline Homeostatic Model Assessment of IR (HOMA-IR), Homeostatic Model Assessment of β-cell function (HOMA-beta), Quantitative Insulin Sensitivity Check Index (QUICKI) and Matsuda and DeFronzo index, and performed a linear regression concerning each year’s EWL%.

Results: After applying the exclusion criteria, 1723 patients were included in this analysis. The logarithm of HOMA-beta was negatively associated with EWL% at second-, third- and fourth-years post-surgery (β=-1.04 [-1.82 to -0.26], p<0.01; β=-1.16 [-2.13 to -0.19], p=0.02; β=-1.29 [-2.64 to 0.06], p=0.061, respectively), adjusting for age, sex, body mass index and type of surgery. This was not observed in the first-year post-surgery nor for the other indexes. Glycaemia at baseline was also positively associated to EWL% at second- and third-years post-surgery.

Conclusion: IR at baseline seems to be associated to long term weight loss, explicitly after the first year post bariatric surgery.
Low Health Literate State Does Not Negatively Affect Final Weight Loss After a Laparoscopic Gastric Bypass Procedure
Authors: Twickler Theodorus Bartholomeus , Marije Dubbelman , Feskens Pierre , van den Broek Jos
Published: May 2021

Weight loss surgery is an effective treatment in patients with morbid obesity, but its benefit depends on self-care management afterwards Self-care management is partly influenced by individual’s health literacy. The level of individual’s health literate state (HLS) could determine the person’s health behavior with a subsequent effect on final weight loss We therefore hypothesized that a low HLS may result in a worse post-bariatric surgery outcome (final weight loss) compared to them with a high HLS. A retrospective study was performed including 78 patients (male vs female: 23% vs 77%, respectively; mean age 43 years (SD 12)) who underwent a laparoscopic gastric bypass (LGB) procedure. All patients were invited to perform in a review in which HLS was estimated using Rapid Estimate of Adult Literacy in Medicine- Dutch (REALM-D) and Newest Vital Sign- Dutch (NVS-D) questionnaires. Anthropometric information, such as weight at 0, 3, 6 9 and 12 months after surgery, was collected. Mean preoperative weight was 128.0 kg (SD 21.1) and patients had an average weight loss of 42.2 kg (SD 12.0) after 12 months. Almost half of the population (49%) was low educated, 38% had medium education and 13% was high educated. Of all patients, 22% had an inadequate HLS, according to the REALM-D. Following the NVS-D, 14% was characterized with an inadequate HLS. Patients with an inadequate HLS had an average weight loss of 40.2 kg (SD 13.8) or 31.5% (SD 8.1), while patients with an adequate HLS had an average weight loss of 42.8 kg (SD 11.4 or 33.3 % (SD 6.6). Following the NVS-D, preoperative weight was 123.6 (SD 20.5) for patients with an inadequate HLS and 128.7 (SD 21.1) for patients with an adequate HLS. Patients with an inadequate HLS had an average weight loss of 39.8 kg (SD 14.2) or 31.5% (SD 8.5), patients with an adequate HLS had an average weight loss of 42.6 kg (SD 11.6) or 33.1 % (SD 6.7). This reduce after 12 months did not significantly differ between patients with an inadequate and adequate HLS according to the REALM-D (B = - 1.806, P = 0.350) and NVS-D (B= -0.357, P = 0.885) after correction for age, gender and preoperative weightWeight reduction did not significantly differ between patients with inadequate or adequate health literacy levels, one year after LGB.
Prevalence of Childhood Obesity in the United States 1999 - 2018: A 20-Year Analysis
Authors: Li Hang Long , Tsoi Man Fung , Feng Qi , Cheung Ching-Lung , Cheung Tommy , Cheung Bernard M Y
Published: May 2021

Introduction: Obesity is a public health crisis in the US. Childhood obesity is associated with multiple comorbidities in the adulthood, including metabolic syndrome, cardiovascular diseases, and premature death. A recent study found that the prevalence of childhood obesity varied according to age and ethnicity. This study aims to evaluate the long-term trends and the underexplored socioeconomic factors associated with childhood obesity.

Method: From the US National Health and Nutrition Examination Survey from 1999 to 2018, 35 907 children aged 2–19 with body mass index (BMI) data were included. Prevalence of obesity and severe obesity, defined as BMI ≥95th percentile and ≥120% of 95th percentile of US Centers for Disease Control and Prevention growth charts, respectively. Trends in prevalence of obesity and subgroup analyses according to age group, sex, ethnicity, language used in interview, household education level, and household income level, were analyzed. Data analysis was performed using the R statistical package “survey” (version 3.6.3).

Results: The prevalence of obesity and severe obesity increased from 14.7 [95% CI: 12.9–17.0] % to 19.2 [17.2–21.0] % and 3.9 [2.9–5.0] % to 6.1 [4.8–8.0] % in 1999–2018, respectively (p=0.001 and p=0.014 for obesity and severe obesity, respectively). In 2017–8, the prevalence of obesity among children from Spanish-speaking households was 24.4 [22.4–27.0] %, higher than children from English-speaking households (p=0.027). Children from households with high education level and high income level had a lower prevalence of obesity compared to those with low education level and low income level (p=0.003 and p=0.002 for education level and income level, respectively). Compared to girls, boys had higher prevalence of obesity (p=0.002) and severe obesity (p=0.004).

Conclusion: The prevalence of childhood obesity in America kept increasing during the period 1999–2018 despite various public health initiatives. The problem is worse in children with lower socioeconomic status, and in children from Spanish-speaking households. Public health interventions are urgently needed to halt the rising trend of childhood obesity, and measures specifically catering to children from Spanish-speaking families should be put in place.
The Absence of Cortisol Awakening Response Is Associated With Personality Traits in Bariatric Women
Authors: Ostinelli Giada , Pelletier Melissa , Iceta Sylvain , Michaud Andreanne , Begin Catherine , Tchernof Andre
Published: May 2021

Background: There is a large body of evidence linking obesity to the HPA axis and cortisol secretion or metabolism. Early work hypothesized that obesity onset may be associated with over-activation of the HPA axis, causing an extenuation of the system. The cortisol awakening response (CAR) has been suggested to be a reliable marker of HPA axis activity and has already been examined in samples of individuals with obesity. Our objective was to compare individuals showing a morning cortisol peak (CAR responders) from those who did not (non-responders) and identify possible metabolic or psychological differences among these two groups. Our hypothesis was that the two groups differed in the level of anxiety and aspects of their personality rather than in their metabolic profile. Methods: CAR response was determined using a baseline to peak cut-off of 2.5 nM. Nine CAR non-responder women awaiting bariatric surgery (BMI: 50.8 ± 4.6 kg/m2) were compared to 9 sex- and age-matched CAR responders (BMI: 48.1 ± 5.9 kg/m2). Participants collected salivary cortisol upon awakening as well as 15, 30 minutes after and responded to psychological questionnaires that measured anxiety (State and trait anxiety inventory questionnaire) and personality traits (Temperament and character inventory). Results: Non-responders were all non-diabetic women aged 37 ± 8 years. There was no significant difference between CAR responders and non-responders in terms of BMI or waist circumference. No difference was found in metabolic variables such as glycaemia or the lipid profile. As expected, non-responders had a significantly lower CAR AUCi when compared to responders (p<0.001). However there was no difference in awakening cortisol concentration. Despite our hypothesis, no significant difference was found in general level of anxiety between the two groups. Finally, we analyzed aspects of human personality. We found that CAR responders scored significantly higher in character traits such as self-directedness (p=0.02), cooperativeness (p=0.03) and self-transcendence (p<0.01). Conclusion: The CAR differences in women with severe obesity are not associated with adiposity. Our data show that non-responders exhibit traits related to reduced self-determination and responsibility but also lower level of self-consciousness and helpfulness, which could be associated with a reduction in patient compliance and possibly less weight loss after surgery.
Trends in the Racial and Ethnic Disparity and Predictors of Hepatic Steatosis: Data From NHANES III and NHANES 2017–2018
Authors: Shaheen Magda , Pan Deyu , Schrode Katrina , Kermah Dulcie , Najjar Sonia Michael , Friedman Theodore C
Published: May 2021

Hepatic steatosis is a serious problem worldwide and it affects Hispanics at a higher rate than Blacks. This disparity is an important public health problem. The purpose of this study was to examine the trend in the racial/ethnic disparity of hepatic steatosis among a representative sample of the U.S. adult ≥20 years old in two time-periods. Data from the National Health and Nutrition Examination Survey (NHANES) III (1988–1994) and NHANES 2017–2018 were analyzed. The sample size in the two respective cycles was 13,910 and 5,492 respectively. Hepatic steatosis in NHANES III was diagnosed using ultrasound while in NHANES 2017–2018, fibroscan was used. We analyzed the data using bivariate Chi square, and multiple logistic regression to adjusting for confounding variables and considering the design and sample weights. In both time-periods, Mexican American had the highest prevalence of hepatic steatosis (28% in NHANES III and 43% in NHANES 2017–2018) compared to the other racial/ethnic groups (p<0.05). In the adjusted logistic regression model, relative to the white population, Mexican-Americans had 40% higher odds of hepatic steatosis in NHANES III (adjusted odds ratio [AOR]=1.4, 95% confidence level [CL]=1.1–1.9, p<0.05) and 200% higher odds of hepatic steatosis in NHANES 2017–2018 (AOR=2.0, 95% CL=1.3–3.1, p<0.05). The common predictors of hepatic steatosis in the two time periods were gender, high waist-to-hip ratio, borderline and high levels of triglyceride, and prediabetes and diabetes as diagnosed by HbA1c (p<0.05). For CRP, independent of the method used, mild and significant inflammation were predictors of hepatic steatosis (p<0.05). In NHANES 2017–2018, participants ≥ 65 years (compared to 20–34 years of age) and Blacks (relative to Whites) had a lower chance of hepatic steatosis in the adjusted regression model (p<0.05), and those inactive (relative to those who met the physical activity guideline) had a higher chance of hepatic steatosis (p<0.05). The increased prevalence of hepatic steatosis in 2017–2018 compared to 1988–1994, may be related to the obesity epidemic, although differences in methodological factors may also play a role. Our study indicated that the racial/ethnic disparity in hepatic steatosis especially among Mexican American persisted over time. Future work is needed to explore the persistence of the racial/ethnic disparity of hepatic steatosis and its underlying mechanisms.
Acquired Brain Injury-Induced Hyperphagia and Obesity, Successfully Treated With a GLP-1 Agonist
Authors: Ngu Michael , Blocher Nissa , Segal Miriam
Published: May 2021

Background: Several Glucagon-like peptides 1 (GLP-1s) were approved since 2005 for the treatment of DM & obesity. Their usefulness in other conditions is not well studied. We present two cases of hyperphagia after TBI successfully treated with GLP-1 agonists. Clinical cases: Case 1: A 54-year-old female with a history of multiple traumatic brain injuries (multiple falls and a ski accident) complained of years of insatiable hunger leading to hyperphagia and over 20 pounds weight gain. With tremendous will-power, she avoided additional weight gain by adopting a strict meal-plan and increasing her water intake (10–12 liters a day) to relieve her hunger. She sipped so much water, that her sodium remained 123 - 133 mmol/L (ref: 135–146) with dilute urine. Initial tests revealed: IGF-1 315 ng/ml (52–328), FSH 77.5 mIU/ml (23–116.3), LH 24.3 mIU/ml (14.2–52.3), prolactin 17.1 ng.ml (10–54.7), estradiol 17 (<31), TSH 1.09mIU/ml (0.45–4.5), FT4 1.0 ng/dl(0.8–1.8), all within the normal limit for her age. Semaglutide 0.25mg/week was started and increased to 0.5mg/week. Within the first six months of treatment, she experienced 22 pounds of weight loss, hunger relief, less water sipping behavior, and more enjoyment of food. Her sodium rose to 137 mmol/L. Case 2: A 40-year-old female, s/p craniectomy and aneurysm clipping due to intracranial hemorrhage complicated by an ischemic stroke developed sudden, documented, 45-pound weight gain over thirteen months despite aggressive lifestyle modification attempts. Initial labs revealed: TSH 1.33 mIU/ml (0.45–4.5), FT4 1.22 ng/dl (0.8–1.8), midnight salivary cortisol 0.03 mcg/dl (<0.09), ruling out hypothyroidism and Cushing syndrome. Liraglutide 1.8mg/day was started and has resulted to date in 26 pounds (11.8% of maximum weight) by 9 months with an associated decrease in subjective hunger. Conclusion: Hyperphagia can be seen in brain injury, in response to some medications, and some genetic conditions, like Prader-Willi. The exact mechanisms are not clear am may be multifactorial. In the case of brain injury, proposed mechanisms include insatiable hunger due to ventromedial hypothalamic or brain stem dysfunction, or disinhibition and poor impulse control due to frontal lobe injury. GLP-1’s may act on the causal mechanism for increased hunger, or it may result in clinical improvement through a parallel pathway. More studies are warranted to investigate the application of GLP-1’s to hyperphagia.