bluuebunny/crossref_metadata_2025 huggingface dataset:
How probiotics impact on immunological parameters in rainbow trout (Oncorhynchus mykiss)? A systematic review and meta‐analysis
Authors: Rahimi Ruhollah , Mirahmadi Seyedeh Atefeh , Hajirezaee Saeed , Fallah Aziz A.
Published: June 2021

Probiotics are microbial cells with multifunctional properties including immunostimulatory function in their host. Today, probiotics are widely used for controlling diseases in aquaculture, especially for rainbow trout, Oncorhynchus mykiss, as the most important commercial cold‐water fish in the world. So far, many studies have been conducted on the effect of probiotics on the immune system of rainbow trout, but due to different experimental conditions, these results are different and sometimes inconsistent. Therefore, the aim of the present study was to perform a systematic review and meta‐analysis to eliminate inconsistencies and to clarify the results related to some immune parameters in rainbow trout. This study is the first meta‐analysis study of probiotic‐induced effects on the immune system of rainbow trout. In order to perform meta‐analysis, four Internet databases, PubMed, Scopus, ISI Web of Science and Google Scholar were systematically searched until 27/03/2020 and after receiving related articles, effect sizes related to 10 outcomes including serum and plasma lysozyme activity, ACH50 activity, Ig activity, serum complement activity, phagocytosis activity, serum total protein activity and respiratory burst activity were evaluated by SMD and Hedges' g statistic and 95% CI was calculated from a random effects model. The SYRCL’S risk of bias tool for animal study was also used to assess the quality of the studies. Meta‐analysis was performed for 36 studies by 499 experiments. The effect of probiotics on immunity components was as follows: serum lysozyme activity (p < 0.05), plasma lysozyme activity (p > 0.05), Serum ACH50 activity (p < 0.05), Plasma ACH50 activity (p < 0.05), serum immunoglobulin activity (p < 0.05), plasma immunoglobulin activity (p < 0.05), total serum protein activity (p < 0.05), serum complement activity (p < 0.05), phagocytic activity (p < 0.05) and respiratory burst activity (p > 0.05). In conclusion, the results of the present study showed that, except plasma lysozyme activity and burst activity, probiotics could enhance immune system of rainbow trout.
From the scriptural to the virtual: Indonesian engineering students responses to the digitalization of Islamic education
Authors: Pabbajah Mustaqim , Jubba Hasse , Abdullah Irwan , Pabbajah M. Taufiq Hidayat , Juhansar
Published: June 2021

Digitization has transformed how religion is studied, with religious education shifting from text‐based (scriptural) to media‐based (virtual). This study seeks to understand how Muslim young adults in Indonesia have responded to the digitization of Islamic education, examining not only trends in digitals religious education, but also their implications for Islamic education. It employs a qualitative descriptive approach, using observation, interviews, and focus group discussions to collect data. It finds that religious education has transformed from face‐to‐face discussions with religious scholars into mediated online interactions. This has resulted from three factors: the ease and affordability of online religious media, the cost and time efficiency inherent to online media, and the diversity and comprehensiveness of available digital media. This study recommends that future researchers investigate how online media can be used to promote a deeper religious understanding.
Implementation of Pharmacist-Driven Antifungal Stewardship Program in a Tertiary Care Hospital
Authors: Kara Emre , Metan Gokhan , Bayraktar-Ekincioglu Aygin , Gulmez Dolunay , Arikan-Akdagli Sevtap , Demirkazik Figen , Akova Murat , Unal Serhat , Uzun Omrum
Published: June 2021

Antifungal stewardship (AFS) is recommended to reduce the inappropriate use of antifungal drugs. In this study, the role of AFS in providing appropriate antifungal therapy was evaluated.
Hydrostatic anorectal injury caused by fall from jet-ski
Authors: Litmanovich Adi , Nordkin Dmitri , Vakarev Anna , Waksman Igor
Published: June 2021

A 14-year-old girl, a rear seat passenger on a jet-ski not wearing suitable protective gear, was ‘jumping’ waves at a low velocity when she was ejected backwards off the vehicle, suffering a complex and unusual hydrostatic perineal injury as a result of the high-pressure water stream propelling the jet-ski. She presented to the emergency room with rectal bleeding and perineal and abdominal pain. Initial investigations revealed signs of anorectal injury and both intraperitoneal and extraperitoneal free air and fluid, suggesting a possible rectal perforation. Proctoscopy confirmed the primary diagnosis and exploratory laparotomy revealed an intraperitoneal tear in the rectal wall. The tear was repaired, and protective loop colostomy was performed. Initial results of anal manometry, transrectal ultrasound and anal electromyography were unfavourable. However, 17 months after pelvic floor physiotherapy and biofeedback, the colostomy was reversed, and her continence has returned to her normal (preinjury) state.
Acanthamoebascleral abscess reoccurring after penetrating keratoplasty
Authors: Barnett Brad , McCloskey Kyle
Published: June 2021

Two months following penetrating keratoplasty forAcanthamoebakeratitis, a 76-year-old man was referred due to inability to wean high-dose topical steroids. Despite a very healthy graft and minimal pain, a scleral abscess involving three clock hours of the superior conjunctiva was present. The patient underwent conjunctival and scleral excision of the area of apparent infection with adjuvant mitomycin C and double freeze–thaw cryotherapy treatment followed by amniotic membrane graft. Recurrence was confirmed with PCR. Following a multimonth regimen of oral voriconazole and topical polyhexamethylene biguanide, chlorhexidine and moxifloxacin, the patient was weaned from all anti-infectious agents. After cataract surgery and scleral lens fitting, the patient is now 20/20 in the affected eye. This case highlights the need for judicious use of immunosuppressive agents as well as the necessary vigilance to monitor for recurrence withAcanthamoebainfection. It also represents the first reported use of adjuvant mitomycin C and double freeze–thaw cryotherapy for treatment ofAcanthamoebascleral abscess.
Young stroke due to pulmonary arteriovenous malformation
Authors: Sen Gautam , Lwin Myo T , Smith Lindsay , Weir Nicolas
Published: June 2021

Young patients presenting with cryptogenic stroke should be investigated for cardiac and extra-cardiac sources of emboli. We present a patient who was investigated for a cardiac source of emboli, following multiple ischaemic strokes and migraine with aura over a period of 17 years. The events were initially thought to be related to a patent foramen ovale (PFO) on bubble contrast echocardiography, however, due to an unusual flow pattern to the left heart, she underwent a CT angiogram to exclude intrapulmonary shunting. This confirmed the presence of a moderate sized congenital pulmonary arteriovenous fistula in the left lung. Transcatheter occlusion of the vascular malformation has resolution of her symptoms. Bubble contrast echocardiography is routinely used to diagnose a PFO in these cases, but extreme caution is required during the procedure to differentiate the pattern of flow seen in patients with a pulmonary arteriovenous malformation.
Fulminant granulomatosis with polyangiitis presenting with diffuse alveolar haemorrhage following COVID-19
Authors: Lind Eric , Jameson Andrew , Kurban Esaw
Published: June 2021

A 40-year-old man developed granulomatosis with polyangiitis (GPA) following a mild case of COVID-19. Initially, he experienced mild migrating joint pain for 2 months prior to testing positive for SARS-CoV-2 but dramatically worsened following resolution of his infection. The pain continued to progress until he suddenly develope haemoptysis, prompting him to present to a local hospital. The diagnosis of diffuse alveolar haemorrhage secondary to GPA was confirmed with labs, imaging and histopathology. Precipitous deterioration of GPA with concurrent COVID-19 infection indicates a possible temporal relationship. Since the onset of the pandemic, SARS-CoV-2 has been anecdotally associated with the development of various connective tissue disorders. The overlapping clinical presentations and similar appearance on lung imaging present clinicians with a diagnostic challenge. This underscores the importance of having a high index of suspicion of autoimmune diagnoses in patients who present with new or worsening findings following a COVID-19 infection.
Analysis of the effect of superheavy load vehicles: a review of current criteria
Authors: Pérez-González Erdrick Leandro , Bilodeau Jean-Pascal , Doré Guy
Published: June 2021

The analysis of damage caused by vehicles with atypical load magnitudes and axle conditions on flexible pavements is challenging for engineers. This analysis determines whether the road network’s use by this type of vehicle is authorized or denied. Consequently, it is a fundamental part of the planning and final cost estimation associated with transporting specific loads. In the literature available, different approaches are presented to address this problem. In this paper, the background in these approaches is presented, and their advantages and limitations are discussed. A compilation of different criteria can cover the aspects relevant to this type of analysis more broadly. However, some conceptual weaknesses can be identified in some currently available standards, leaving room for future research to improve how the effect of superheavy vehicles is analyzed.
Inverse complements and strongly unit regular elements
Authors: Kelathaya Umashankara , Varkady Savitha , Karantha Manjunatha Prasad
Published: June 2021

In this paper, the notion of “strongly unit regular element”, for which every reflexive generalized inverse is associated with an inverse complement, is introduced. Noting that every strongly unit regular element is unit regular, some characterizations of unit regular elements are obtained in terms of inverse complements and with the help of minus partial order. Unit generalized inverses of given unit regular element are characterized as sum of reflexive generalized inverses and the generators of its annihilators. Surprisingly, it has been observed that the class of strongly regular elements and unit regular elements are the same. Also, several classes of generalized inverses are characterized in terms of inverse complements.
Potential and Comparative Tablet Disintegrant Properties of Pectin Obtained from Five Okra Genotypes in Ghana
Authors: Owusu Frederick William Akuffo , Boakye-Gyasi Mariam El , Agbenorhevi Jacob Kwaku , Bayor Marcel Tunkumgnen , Ofori-Kwakye Kwabena
Published: June 2021

Okra pectin has been studied as a potential excipient in tablet formulations for pharmaceutical industries. Okra is widely grown and available in Ghana and other parts of the world. The prospective use of pectin from okra genotypes grown in Ghana as tablet disintegrants has not been reported. This study aims to determine the potential and comparative disintegrating properties of pectin from five okra genotypes (Abelmoschus esculentus L.) in Ghana using uncoated immediate release paracetamol tablet formulations. The yield of the pectin from the various genotypes ranged between 6.12 and 18.84% w/w. The extracted pectins had pH ranging from slightly acidic to almost neutral (6.39–6.92). Pectin from the various genotypes exhibited good swelling indexes (˃200%), varying solubility in different solvents, and low moisture content (˂20%). Elemental analysis of the extracted pectin from the various genotypes revealed very low levels of toxic metals and micronutrients. Pectin from the various genotypes was evaluated as disintegrants within concentrations of 5–10% w/w (F1–F18). Their disintegrating properties were compared to that of maize starch BP. All the formulated batches of uncoated immediate release paracetamol tablets (F1–F18) passed the following: uniformity of weight test, uniformity of dimensions, hardness, friability (˂1%), and drug content (95–105%). Significant differences (p≤0.05) were observed between the hardness of the maize starch tablets and tablets formulated from pectin of the various genotypes. Pectin from all genotypes other than PC5 exhibited good disintegrating properties (DT ˂ 15 min) and subsequently passed the dissolution profile test (≥70% release in 45 minutes). Tablets formulated with PC5 as disintegrants at all concentrations (5% w/w (F5), 7.5% w/w (F11), and 10% w/w (F17)) failed the disintegration and dissolution tests. Ultimately, pectins extracted from PC1, PC2, PC3, and PC4 can be commercially exploited as disintegrants in immediate release tablets.
The Aqueous Extract of Eucommia Leaves Promotes Proliferation, Differentiation, and Mineralization of Osteoblast-Like MC3T3-E1 Cells
Authors: Guan Mengqi , Pan Daian , Zhang Mei , Leng Xiangyang , Yao Baojin
Published: June 2021

Eucommia leaves are dry leaves of Eucommia ulmoides which have long been considered as a functional health food for the treatment of hypertension, hypercholesterolemia, fatty liver, and osteoporosis. With the recent development of Chinese medicine, Eucommia leaves are widely used for tonifying the kidneys and strengthening bone. However, the specific molecular mechanism of Eucommia leaves for strengthening bone remains largely unknown. Osteoblasts are the main functional cells of bone formation; thus, it is essential to study the effect of Eucommia leaves on osteoblasts to better understand their mechanism of action. In the present study, we prepared an aqueous extract of Eucommia leaves (ELAE) and determined its content by high-performance liquid chromatography (HPLC). The effects of ELAE on MC3T3-E1 cells were investigated by CCK-8 assay, alkaline phosphatase (ALP), and Alizarin red S staining assays, combined with RNA sequencing (RNA-seq) and qRT-PCR validation. We demonstrated that ELAE had a significant promoting effect on the proliferation of MC3T3-E1 cells and significantly enhanced extracellular matrix synthesis and mineralization, which were achieved by regulating various functional genes and related signaling pathways. ELAE significantly increased the expression level of genes promoting cell proliferation, such as Rpl10a, Adnp, Pex1, Inpp4a, Frat2, and Pcdhga1, and reduced the expression level of genes inhibiting cell proliferation, such as Npm1, Eif3e, Cbx3, Psmc6, Fgf7, Fxr1, Ddx3x, Mbnl1, and Cdc27. In addition, ELAE increased the expression level of gene markers in osteoblasts, such as Col5a2, Ubap2l, Dkk3, Foxm1, Col16a1, Col12a1, Usp7, Col4a6, Runx2, Sox4, and Bmp4. Taken together, our results suggest that ELAE could promote osteoblast proliferation, differentiation, and mineralization and prevent osteoblast apoptosis. These findings not only increase our understanding of ELAE on the regulation of bone development but also provide a possible strategy to further study the prevention and treatment of osteogenic related diseases by ELAE.
Linear Programming Model and Online Algorithm for Customer-Centric Train Calendar Generation
Authors: Bosi Tommaso , D’Ariano Andrea
Published: June 2021

An important objective for train operating companies is to let users, especially commuters, directly query the ICT system about trains’ availability calendar, based on an online approach, and give them clear and brief information, expressed through “intelligent” phrases instead of bit maps. This paper provides a linear programming model of this problem and a fast and flexible heuristic algorithm to create descriptive sentences from train calendars. The algorithmic method, based on the “Divide and Conquer” approach, takes the calendar period queried in its whole and divides it into subsets, which are successively processed one by one. The dominant limitation of previous methods is their strong dependence on the size and complexity of instances. On the contrary, our computational findings show that the proposed online algorithm has a very limited and constant computation time, even when increasing the problem complexity, keeping its processing time between 0 and 16 ms, while producing good quality solutions that differ by an average surplus of 0.13 subsentences compared to benchmark state-of-art solutions.
Bmal1 Regulates the Redox Rhythm of HSPB1, and Homooxidized HSPB1 Attenuates the Oxidative Stress Injury of Cardiomyocytes
Authors: Liu Xiehong , Xiao Wen , Jiang Yu , Zou Lianhong , Chen Fang , Xiao Weiwei , Zhang Xingwen , Cao Yan , Xu Lei , Zhu Yimin
Published: June 2021

Oxidative stress is the main cause of acute myocardial infarction (AMI), which is related to the disorder of the regulation of Bmal1 on the redox state. HSPB1 form homologous‐oxidized HSPB1 (homooxidized HSPB1) to resist oxidative damage via S‐thiolated modification. However, it is still unclarified whether there is an interaction between the circadian clock and HSPB1 in myocardial injury. A total of 118 AMI patients admitted and treated in our hospital from Sep. 2019 to Sep. 2020 were selected to detect the plasma HSPB1 expression and the redox state. We divided the AMI patients into three subgroups: morning‐onset AMI (5 : 00 am to 8 : 00 am; Am‐subgroup, n = 38), noon‐onset AMI (12 : 00 pm to 15 : 00; Pm‐subgroup, n = 45), and night‐onset AMI (20 : 00 pm to 23 : 00 pm; Eve‐subgroup, n = 35) according to the circadian rhythm of onset. The Am‐subgroup had remarkably higher cardiac troponin I (cTnI), creatine kinase MB (CK‐MB), and B‐type natriuretic peptide (BNP) but lower left ventricular ejection fraction (LVEF) than the Pm‐subgroup and Eve‐subgroup. Patients complicated with cardiogenic shock were significantly higher in the Am‐subgroup than in the other two groups. The homooxidized HSPB1 in plasma markedly decreased in the Am‐subgroup. The HSPB1C141S mutant accelerated H9c2 cell apoptosis, increased reactive oxygen species (ROS), and decreased reduced‐glutathione (GSH) and the ratio of reduced‐GSH and GSSG during oxidative stress. Importantly, we found that the redox state of HSPB1 was consistent with the oscillatory rhythm of Bmal1 expression in normal C57B/L mice. The circadian rhythm disorder contributed to decrease Bmal1 and homooxidized HSPB1 in cardiomyocytes of C57BL/6 mice. In addition, Bmal1 and homooxidized HSPB1 decreased in neonatal rat cardiomyocytes exposed to H2O2. Knockdown of Bmal1 led to significant attenuation in homooxidized HSPB1 expression, whereas overexpression of Bmal1 increased homooxidized HSPB1 expression in response to H2O2. Our findings indicated that the homooxidized HSPB1 reduced probably the AMI patients’ risk of shock and target organ damage, which was associated with Bmal1 regulating the redox state of HSPB1.
Baseline Values and Kinetics of IL‐6, Procalcitonin, and TNF‐α in Landrace‐Large White Swine Anesthetized with Propofol‐Based Total Intravenous Anesthesia
Authors: Chalkias Athanasios , Spyropoulos Vaios , Georgiou Georgia , Laou Eleni , Koutsovasilis Anastasios , Pantazopoulos Ioannis , Kolonia Konstantina , Vrakas Spyros , Papalois Apostolos , Demeridou Styliani , Gourgoulianis Konstantinos , Dontas Ismene , Kaparos George , Baka Stavroula , Xanthos Theodoros
Published: June 2021

The baseline levels of various inflammatory mediators and their changes during anesthesia in swine are not known. The aim of this animal study was to measure the baseline values and kinetics of interleukin‐6, procalcitonin, and tumor necrosis factor‐alpha in healthy Landrace‐Large White swine anesthetized with propofol‐based total intravenous anesthesia. We included 8 healthy male pigs with an average weight of 19 ± 2 kg (aged 10‐15 weeks) that were subjected to propofol‐based total intravenous anesthesia for 8 hours. Complete blood count, serum chemistry, and serum levels of interleukin‐6, procalcitonin, and tumor necrosis factor‐alpha were analyzed, and serum levels were quantified hourly. Blood was also collected for bacterial culturing. Baseline values of interleukin‐6 and procalcitonin were 18 pg/ml and 21 ng/ml, respectively, while tumor necrosis factor‐alpha was not detectable during collection of baseline samples. A statistically significant difference was observed in interleukin‐6 levels between time points (p < 0.0001). Procalcitonin increased with time, but there were no significant differences between time points (p = 0.152). Tumor necrosis factor‐alpha increased until the 3rd hour of propofol‐based total intravenous anesthesia, while after the 4th hour, it gradually decreased, reaching its baseline undetectable values by the 7th hour (p < 0.001). Our results can serve as the basis for further translational research.
Cell Area-Based Method for Analyzing the Coverage Capacity of Satellite Constellations
Authors: Song Zhiming , Liu Haidong , Dai Guangming , Wang Maocai , Chen Xiaoyu
Published: June 2021

Constellation-to-ground coverage analysis is an important problem in practical satellite applications. The classical net point method is one of the most commonly used algorithms in resolving this problem, indicating that the computation efficiency significantly depends on the high-precision requirement. On this basis, an improved cell area-based method is proposed in this paper, in which a cell is used as the basic analytical unit. By calculating the accuracy area of a cell that is partly contained by the ground region or partly covered by the constellation, the accurate coverage area can be obtained accordingly. Experiments simulating different types of coverage problems are conducted, and the results reveal the correctness and high efficiency of the proposed analytical method.
Service Migration Policy Optimization considering User Mobility for E-Healthcare Applications
Authors: Zhao Xuhui , Liu Jianghui , Ji Baofeng , Wang Lin
Published: June 2021

Mobile edge computing (MEC) is an emerging technology that provides cloud services at the edge of network to enable latency-critical and resource-intensive E-healthcare applications. User mobility is common in MEC. User mobility can result in an interruption of ongoing edge services and a dramatic drop in quality of service. Service migration has a great potential to address the issues and brings inevitable cost for the system. In this paper, we propose a service migration solution based on migration zone and formulate service migration cost with a comprehensive model that captures the key challenges. Then, we formulate service migration problem into Markov decision process to obtain optimal service migration policies that decide where to migrate in a limited area. We propose three algorithms to resolve the optimization problem given by the formulated model. Finally, we demonstrate the performance of our proposed algorithms by carrying out extensive experiments. We show that the proposed service migration approach reduces the total cost by up to 3 times compared to no migration and outperforms the general solution in terms of the total expected reward.
Clinical and Surgical Outcome of a Supplementary Multifocal Intraocular Lens Implanted with a Bag-In-the-Lens Intraocular Lens: 5-Year Follow-Up
Authors: Verdonck Thomas , Werner Liliana , Ní Dhubhghaill Sorcha , Tassignon Marie-José
Published: June 2021

Introduction: To assess the postoperative outcome and patient-reported satisfaction, spectacle independence, and dysphotopsia after implantation with the mutifocal Rayner Sulcoflex supplementary intraocular lens (sIOL). Materials and Methods: We analyzed the outcome of all patients implanted with a multifocal sIOL between 2009 and 2011. In all cases, the sIOL was the Rayner Sulcoflex IOL (type 653F) and the primary IOL was a bag-in-the-lens (BIL) IOL. The data were obtained through a retrospective analysis of the patient records and by means of a questionnaire, 5 years after sIOL implantation. Results: This study included 31 eyes of 20 patients. In 13 eyes, the sIOL needed explantation (n = 13, 41.94%). Dysphotopsia is a frequent complaint (12/15 patients: 80.0%) after sIOL implantation. In 13 out of 31 eyes (41.94%), pigment deposits were found on the sIOL with variable clinical complaints. Five eyes required additional surgery because of clinically significant deposits. Discussion/Conclusion: Patients with a multifocal sIOL in combination with a BIL implantation have a higher incidence of dysphotopsia compared to previously published studies. Dysphotopsia was the main complaint and reason for explantation. We encountered a high incidence of pigmented IOL deposits. The sIOLs can be safely removed even years after implantation.
Elevated Levels of Homocysteinesulfinic Acid in the Plasma of Patients with Amyotrophic Lateral Sclerosis: A Potential Source of Excitotoxicity?
Authors: Lee Aven , Arachchige Buddhika Jayakody , Henderson Robert , Aylward James , McCombe Pamela Ann
Published: June 2021

Objectives: Excitotoxicity is thought to be involved in the pathogenesis of amyotrophic lateral sclerosis (ALS). One possible source of excitotoxicity is the presence of sulphur amino acids (SAAs). In the brain of subjects with ALS, there are increased levels of taurine. In the metabolism of methionine to taurine, excitatory sulphur amino acids (SAAs) are formed. These could potentially contribute to excitotoxicity in ALS. The present study has examined whether plasma levels of SAAs in 38 ALS patients differ from those of 30 healthy controls. Methods: Plasma levels of SAAs were measured by liquid chromatography mass spectrometry. Results: There were no significant changes in plasma cysteic acid, cysteine sulfinic acid, and homocysteic acid in ALS patients compared to healthy subjects. Significant elevations in plasma homocysteinesulfinic acid (HCSA) levels (p < 0.0001) were observed in the ALS patients (75.91 ± 15.38 nM) compared to healthy controls (54.06 ± 8.503 nM); 50% of the ALS patients had HCSA levels that were 1.5–2-folds higher than those of controls. Plasma levels of HCSA differed significantly (p = 0.0440) between patients with bulbar onset and spinal onset (68.57 ± 14.20 vs. 79.30 ± 14.95 nM, respectively). Conclusion: HCSA is elevated in the blood of subjects with ALS. Since HCSA can be transported from the blood to the CNS by active transport, has neurotransmitter properties, and can activate synaptic receptors including NMDAR and metabotropic glutamate receptor, it is possible that increases in HCSA could influence glutamatergic neurotransmission and potentially contribute to excitotoxicity in some ALS patients.
A problemática da tradução dos upanixades
Authors: Botelho Octavio Da Cunha
Published: June 2021

Este estudo pretende apontar os problemas na tradução dos textos upanixádicos, quer no meio religioso ou acadêmico. Ademais, apresentar algumas soluções para estas dificuldades alcançadas até ago- ra, devido, principalmente, às contribuições acadêmicas e filológicas.
Três poemas sobre o Gazel
Authors: Amâncio Moacir
Published: June 2021

A figura do efebo (o gazel) é aqui apresentada na tradução de três poemas de dois autores judeus medievais da Espanha: Shemuel haNaguid e Iehudá haLevi. São vistos como textos que enriquecem a obra dos respectivos poetas, na perspectiva rigorosamente literária.
Abstract 454: High Density Lipoprotein Proteome Dynamics is Altered in Non-alcoholic Fatty Liver Disease
Authors: Kasumov Takhar
Published: June 2021

Objectives:
Nonalcoholic fatty liver disease (NAFLD) is associated with an increased rate of cardiovascular disease (CVD) related mortality. HDL protects against CVD through reverse cholesterol transport, anti-oxidant and anti-inflammatory functions. HDL functions and the proteome composition are altered in CVD. We used
2
H
2
O metabolic labeling approach to test hypothesis that altered HDL proteome dynamics is involved in HDL dysfunction in NAFLD.

Methods:
The kinetics of HDL proteins were measured in patients NAFLD (n=12) and healthy controls (n=8). Each subject consumed
2
H
2
O in their drinking water and blood samples were collected at different time points during one week.
2
H-enrichment of tryptic peptides from HDL proteins were analyzed by mass spectrometry. Oxidase activity of HDL-associated ceruloplasmin (Cp) and HDL’s inflammatory index were quantified using spectrophotometric assays.

Results:
Compared to control, NAFLD had higher BMI, Hba1c, HOMA-IR, plasma AST, ALT and triglycerides, but similar LDL and HDL cholesterol. NAFLD also had higher inflammatory index (1.8±0.5 vs 1.2±0.2 RUF/mgHDLc/min, p<0.05) and oxidase activity of Cp (93.7±61.2 vs 61.2 U/L, p<0.005). This was associated with increased serum actvity of MPO (6.2±1.2 vs 8.4±1.6, p<0.05), a nutrophile-derived protein involved in HDL dysfunction. HDL
NAFLD
was significantly enriched with proteins involved in the acute phase response (complement 3, Cp) but depleted in apoAII and PON1. These changes were associated with increased fractional catabolic rates (FCRs) of apoAI (1.6±0.2 vs 1.1±0.3 %/h), apoAII (1.6±0.2 vs 1.1±0.3 %/h), apoAIV (2.6±0.8 vs 3.9±0.7%/h) and increased relative production rate (RPR) of complement 3 (>4 fold). Oxidase activity of Cp was positively associated with FCR of apoAI (r=0.53, p=0.002) and RPR of C3 (r=0.32, p=0.03).

Conclusions:
HDL dysfunction in NASH could be related to the altered turnover of HDL proteins, including increased degradation of apoAI, apoAII, apoAIV and increased production of C3.
Abstract 02: Effect of Airway Insertion First-Pass Success Upon Patient Outcomes in the Pragmatic Airway Resuscitation Trial
Authors: Lesnick Jason , Zhang Yefei , Moore Justin X , Daya Mohamud R , Jarvis Jeffrey W , Nichol Graham , Carlson Jestin N , Klug Cameron D , Schmicker Robert , Dennis David , Idris Ahamed H , Sopko George , Doshi Pratik , Madden Eric , Wang Henry E
Published: June 2021

Introduction:
The multicenter Pragmatic Airway Resuscitation Trial (PART) demonstrated better adult out-of-hospital cardiac arrest (OHCA) outcomes with initial laryngeal tube (LT) insertion than endotracheal intubation (ETI) airway management. While emphasized in clinical practice, the effect of advanced airway insertion first-pass success (FPS) upon outcomes after OHCA is unknown. We sought to determine the direct and indirect mediating effects of LT and ETI FPS upon adult OHCA in a secondary analysis of PART. HYPOTHESES: 1) FPS associated with adult OHCA outcomes. 2) FPS mediates (explains) the association between airway type (LT vs. ETI) and adult OHCA outcomes.

Methods:
We defined FPS as successful LT insertion or ETI on the first attempt as reported by EMS personnel. We examined the outcomes return of spontaneous circulation (ROSC), 72-hour survival, hospital survival, and hospital survival with favorable neurologic function (MRS ≤3). Using multivariable GEE, we determined the association between FPS and outcomes after OHCA, adjusting for age, sex, witnessed arrest status, bystander CPR, initial rhythm, and trial randomization. Using the method of Baron and Kenny, we used mediation analysis to explain the contribution of FPS towards differences in OHCA outcomes between LT and ETI.

Results:
Of 3,004 patients enrolled in the trial, 1,423 received LT, 1,227 received ETI, 354 received bag-valve-mask ventilation only. FPS was: LT 90.3% and ETI 51.5%. FPS was associated with increased ROSC (adjusted OR 1.36, 95% CI 1.04-1.78) and 72h survival (1.45; 1.20-1.74) but not hospital survival (0.94; 0.67-1.31) or hospital survival with favorable neurologic function (0.70; 0.40-1.23). FPS had a strong mediating effect on the OHCA outcome differences between LT and ETI; 72h survival (74% mediated); ROSC (53% mediated); hospital survival (52% mediated); hospital survival with favorable neurologic status (35% mediated).

Conclusion:
In adult with OHCA, airway insertion FPS is associated with increased ROSC and 72h survival. Differences in OHCA outcomes between LT and ETI are largely explained by differences in FPS. EMS personnel should emphasize FPS in the advanced airway management of OHCA.
Abstract 104: Metabolic Effect of Temperature Manipulation in Healthy Individuals
Authors: Rittenberger Jon C , Flickinger Katharyn , Hopkins David , Elmer Jonathan , Guyette Frank , Dezfulian Cameron , Weissman Alexandra
Published: June 2021

Introduction:
Temperature manipulation to decrease metabolism is commonly after acute brain injury. Preclinical data suggest metabolism decreases 7-8% for each degree C drop in core temperature. We hypothesized similar results would be found in healthy individuals.

Methods:
Following informed consent and physical screening, we administered a 1mcg/kg bolus of dexmedetomidine followed by 20cc/kg of cold (4C) saline bolus. We cooled subjects using surface pads (emcools (Austria)). Dexmedetomidine infusion was titrated to effect (max dose <1.5mcg/kg/hr). We recorded vital signs, Richmond Agitation Sedation Scale, Bedside Shivering Assessment Scale and sensation of cold every 15 minutes. We measured resting metabolism at baseline and after each 1 C decrease in temperature thereafter using indirect calorimetry and a ventilated canopy system. We analyzed data using analysis of variance.

Results:
Median age in the 9 enrolled subjects was 30 (SD 10) years and most (78%) were male. Median height was 173 (IQR 168, 180) cm and median weight was 77 (IQR 72, 83) kg. Baseline VO2 was 3.4 (IQR 3.0, 3.8) ml/kg/min and baseline energy expenditure was 1692 (IQR 1579, 1845) kcal/day. Both VO2 and energy expenditure decreased with core temperature (p=0.017 and p=0.027) (Table).

Conclusion:
Metabolic rate decreases with core temperature manipulation. The largest change occurs between 37C and 36C with smaller changes thereafter.
Abstract 112: Survival of In-Hospital Cardiac Arrest Patients Before and After the Implementation of the Act on Decisions on Life-Sustaining Treatment; The Well-Dying Law
Authors: Chae Minjung K , Jeong Chae-Won , Lee Sung Eun
Published: June 2021

Objective:
The act on decisions on life-sustaining treatment; the well-dying law(WDL) was implemented in Korea since February of 2018 so that a patient may cease with dignity in his or her death bed. However in the contrary, we have observed increase of in-hospital cardiac arrest patients resulting in poor outcomes due to strict regulations of withdrawal of life support. The objective of this study is to analyze the survival of in-hospital cardiac arrest patients before and after implementation of the WDL.

Methods:
We retrospectively reviewed our in-hospital cardiac arrest data registry from our in-hospital cardiac arrest committee and electronic medical records. Baseline characteristics, cardiac arrest variables and cardiac arrest outcomes were compared before and after the implementation of the WDL. Multivariate logistic regression was done to analyze the association of the implementation of the WDL and return of spontaneous circulation(ROSC) of in-hospital cardiac arrest patients.

Results:
There were 183 patients before and 346 patients after the implementation of the WDL. ROSC (158[45.7%] vs. 115[62.8%]), 24 hour survival (60[17.3%] vs. 53[29.0%]) and survival discharge (29[8.4%] vs. 25[13.7%]) was lower in the after period versus the before period. In the multivariate logistic regression analysis implementation of the WDL was associated with lower ROSC (Odds ratio 0.56, 95% Confidence interval 0.37-0.85, p<0.01) and lower survival at 24 hours (Odds ratio 0.53, 95% Confidence interval 0.31-0.93, p=0.03).

Conclusion:
Implementation of the WDL was associated with lower ROSC and lower survival at 24 hours in in-hospital cardiac arrest patients.
Abstract 124: A Machine-Learning Based Shock Advice Algorithm for Reliable Rhythm Diagnosis During Out-Of-Hospital Cardiac Arrest
Authors: Alonso Erik , Irusta Unai , Aramendi Elisabete , Chicote Beatriz , Corcuera Carlos , Larrea Andima , Veintemillas Jose , Olabarria Mikel , Alonso Daniel
Published: June 2021

Introduction:
In out-of-hospital cardiac arrest (OHCA) a reliable rhythm diagnosis by the automated external defibrillator (AED) allows for the delivery of correct therapy, a prompt defibrillation for shockable rhythms and resuming cardiopulmonary resuscitation for non-shockable rhythms. The aim of this study was to develop a machine-learning (ML) based shock advice algorithm (SAA) for reliable rhythm diagnosis during OHCA.

Materials and methods:
The study analyzed data from 853 OHCA patients treated with AEDs by the basic life support personnel in the Basque Health service (Osakidetza, Basque Country, Spain) between 2013 and 2015. The datased used in the study contained 4212 5-s ECG segments, 489 shockable and 3723 non-shockable, annotated by consensus between six clinicians. The dataset was split patient-wise into training (60%) and test (40%) sets. Each ECG segment was preprocessed and 15 well-known waveform features were computed. The SAA was composed of two blocks. First, a low electrical activity (LEA) detector based on the power of the ECG for a prompt diagnosis of asystole. Second, a shock/no-shock ML algorithm based on a hidden Markov model that made the shock/no-shock classification of those segments not detected as asystole by the LEA detector. The training set was used to select the most discriminative features and develop/optimize the SAA. The test set was used to measure the performance of the method in terms of sensitivity (SE) and specificity (SP), and to compare it with the performance of a commercial AED. This procedure was repeated 50 times to estimate the distributions of the performance metrics.

Results:
The method showed a mean (SD) SE and SP of 97.7% (1.0) and 99.1% (0.4), respectively. While the commercial AED presented a SE and SP of 94.2% (1.3) and 99.8% (0.1).

Conclusions:
Both methods were compliant with the American Heart Association’s requirements (SE>90% and SP>95%). However, our ML approach outperformed the SAA of the commercial AED, increasing the SE in 3.5-points with a decrease in SP of 0.7-points. Therefore, a ML based SAA algorithm can accurately make shock/no-shock diagnoses during OHCA and might improve the performance of current algorithms.
Abstract 155: Elevated Risk of Venous Thromboembolism in Patients Undergoing Targeted Temperature Management After Cardiac Arrest
Authors: Sharma Toishi , Kunkes Jordan , Ibrahim Waleed , Sullivan David O , Fernandez Antonio B
Published: June 2021

Introduction:
Therapeutic hypothermia (TH) reduces mortality and improves neurological outcomes after cardiac arrest. Cardiac arrest is considered a pro-thrombotic state. Endovascular cooling catheters may increase the risk of thrombosis. Therapeutic hypothermia (TH), however, increases fibrinolysis. These opposing effects may expose patients to both bleeding and venous thromboembolic risk during and after therapeutic hypothermia. The net effect in these patientsremains largely unexplored. Moreover, the exact rate of venous thromboembolism (VTE) is uncertain in these patients. We sought to determine the incidence and potential predictors of VTE in patients undergoing TH after cardiac arrest and compare it to a control group with similar risk of VTE.

Methods:
Single center retrospective analysis. Participants were age ≥18 years old, admitted to Hartford Hospital with out-of-hospital or in-hospital cardiac arrest, underwent TH between January 1, 2007 and April 30, 2019 with endovascular cooling catheter. A total of 562 patients who underwent TH (Study group) were compared to 304 matchedpatientstreated in the medical ICU with a diagnosis of ARDS (control group). This control group was based on presumed similarities in factors affecting VTE: intensive care setting, immobility, length of stay and likely presence of central venous catheters.

Results:
Patients who underwent TH had a significantly higher rate of VTE (6.6% vs 4.6%, p=0.006) and deep vein thrombosis (DVT) (2.3% vs 1.3%, p=0.011) when compared to control group. The rate of pulmonary embolism was higher in the TH group, but this was not statistically significant (2.5% and 1.0%, p=0.128). In multivariate analysis age, gender, race and hospital length of stay were not associated with development of VTE in the study group.

Conclusion:
Patients undergoing TH after cardiac arrest have statistically higher incidence of VTE and DVT compared to patients with ARDS. This risk is independent of age, gender, race or length of stay. Further research into additional independent predictors of VTE and DVT in this population may eventually guide the management and potential future interventions.
Abstract 157: The Association Between Serum Magnesium Levels and Qt Interval Duration During Therapeutic Hypothermia and its Effects on Neurological Outcomes
Authors: Kumar Manish , Perucki William , Hiendlmayr Brett , O’Sullivan David , Mazigh Silya , Fernandez Antonio B
Published: June 2021

Introduction:
Sudden cardiac arrest is a major cause of mortality in the United States and globally. Therapeutic hypothermia (TH) has demonstrated success in improving neurological outcomes in post-cardiac arrest patients. TH causes several physiologic ECG changes, including QTc prolongation. TH also decreases serum magnesium levels. These changes may lead to malignant ventricular arrhythmia and poor neurological outcome. We aimed to evaluate the association between the QTc interval during TH, magnesium levels, and neurologic outcomes.

Methods:
We reviewed the electrocardiograms of 366 patients who underwent TH at various intervals corresponding to pre-cooling, maintenance of targeted temperature management, and rewarming periods. We reviewed the change in the corrected QT segment (QTc) and evaluated their relationship with the patients’ magnesium levels and neurologic outcomes.

Results:
71.3% of the patients had a significant increase in QTc interval defined as >60 ms or any QTc>500 ms during TH. Patients with persistent prolongation of QTc after rewarming had poor neurological outcomes (p<0.05). Magnesium level showed a positive correlation with QTc interval at presentation (R=0.240, p<0.05) and at 48 hours (R=0.225, p= <0.05). Patients who had poor neurological outcomes tended to have higher magnesium levels at presentation (p<0.05). The majority of patients who received supplemental Mg did not have any significant change in their QTc.

Conclusion:
TH is independently associated with QTc prolongation. Patients with a persistent increase in QTc interval during the rewarming phase should be promptly evaluated for QTc-prolonging factors given its association with worse neurological outcomes. The inverse correlation between magnesium levels and poor neurological outcomes deserves further investigation.
Abstract 158: Association Between Initial Body Temperature and Neurologic Outcomes of Out-Of-Hospital Cardiac Arrest Undergoing Targeted Temperature Management
Authors: Kim Jong Hwan , Park Jeong Ho , Lee Sun Young , Shin Sang Do , Pak Jieun , Kim Tae Han
Published: June 2021

Objectives:
Targeted temperature management (TTM) is the core post-resuscitation care to minimize neurologic deficit after out-of-hospital cardiac arrest (OHCA). Uncontrolled body temperature of patients may reflect the thermoregulation ability which can be associated with neurologic damage during arrest. The aim of this study was to investigate the association between initial body temperature (BT) and neurologic outcomes in OHCA patients who underwent TTM.

Methods:
We used nationwide OHCA database from January 2016 to December 2017. Adult OHCA patients with presumed cardiac etiology who underwent TTM after return-of-spontaneous circulation (ROSC) were included. The main exposure was a BT at initiation of TTM which was categorized into 3 groups: low (-35.5°c), middle(35.6°c-37.4°c), and high BT (37.5°c-). The primary outcome was good neurologic outcome (cerebral performance categories (CPC) 1 or 2). Adjusted ratios (AORs) and 95% confidence intervals (CIs) were estimated to evaluate association between initial BT of TTM and outcome in multivariable logistic regression model. Stratified subgroup analyses were according to the target temperature of TTM (hypothermia vs normothermia).

Results:
Of a total of 744 patients, 208 (28.0%) patients were low initial BT group and 471 (63.3%) patients were normal initial BT group and 65 (8.7%) patients were high initial BT group. Good neurological recovery rate was 13.9% in low initial BT group, 41.8% in middle initial BT group and 36.9% in high initial BT group. The adjusted odds ratios for good neurologic recovery were 0.281 (95% confidence interval [CI] 0.17-0.47) in low BT group and 0.65 (95% CI 0.34-1.27) in high BT group compared with normal initial BT group. Similar results were also found regardless of target temperature of TTM.

Conclusion:
Low initial BT of TTM was associated with unfavorable neurologic recovery for OHCA patients who underwent TTM after ROSC.
Abstract 167: Epinephrine Plus Chest Compressions May Be Superior to Epinephrine Alone in a Hypoxia-Induced Porcine Model of Lifeless Shock
Authors: Teran Felipe , Centeno Claire , Lindqwister Alex L , Hunckler William J , Landis William , Moodie Karen L , Abella Benjamin S , Paradis Norman A
Published: June 2021

Background:
Lifeless shock (LS) (previously called EMD and pseudo-PEA) is a global hypotensive ischemic state with retained coordinated myocardial contractile activity and an organized ECG. We have previously described our hypoxic LS model. The role of standard external chest compressions remains unclear in the setting of LS and its associated intrinsic hemodynamics. Although it is known the patients with LS have better prognosis compared to PEA, it is unclear what is the best treatment strategy. Prior work has shown that chest compressions (CC) when synchronized with native systole results in significant hemodynamic improvement, most notably coronary perfusion pressure (CPP), and hence it is plausible that standard dyssynchronous CC may be detrimental to hemodynamics. Furthermore, retrospective clinical data has shown that LS patients treated with vasopressors and no CC, may have better outcomes. We compared epinephrine only versus epinephrine and chest compression, in a porcine model of LS.

Methods:
Our porcine model of hypoxic LS has previously been described. We randomized pigs to episodes of LS treated with epinephrine only (control) (0.0015 mg/kg) versus epinephrine plus standard external chest compressions (intervention). Animals were endotracheally intubated and mechanically ventilated, and the fraction of inspired oxygen (FiO
2
) was gradually lowered from room air (20-30% O
2
) to a target FiO
2
of 3-7% O
2
. This target FiO
2
was maintained until the systolic blood pressure (SBP) dropped to 30 mmHg for 30 seconds, or the animal became bradycardic (HR less than 40), which was defined as the start of LS. FiO
2
was then raised to 100%, and then animal would receive control or intervention. Return of spontaneous circulation (ROSC) was defined as SBP 60 mmHg, stable after 2 minutes.

Results:
Twenty-six episodes of LS in 11 animals received epinephrine only control and 21 episodes the epinephrine plus chest compression intervention. The rates of ROSC in two minutes or less were 5/26 (19%) in the control arm vs 14/21 (67%) in the intervention arm (P=0.001;95% CI 19.7 %-67.2%).

Conclusions:
In a swine model of hypoxia induced LS, epinephrine plus CPR may be superior to epinephrine alone.