Publications by authors named "Harvey Ho"

38 Publications

Global sensitivity analysis of a single-cell HBV model for viral dynamics in the liver.

Infect Dis Model 2021 27;6:1220-1235. Epub 2021 Oct 27.

York University, Canada.

The predictive accuracy of mathematical models representing anything ranging from the meteorological to the biological system profoundly depends on the quality of model parameters derived from experimental data. Hence, robust sensitivity analysis (SA) of these critical model parameters aids in sifting the influential from the negligible out of typically vast parameter regimes, thus illuminating key components of the system under study. We here move beyond traditional local sensitivity analysis to the adoption of global SA techniques. Partial rank correlation coefficient (PRCC) based on Latin hypercube sampling is compared with the variance-based Sobol method. We selected for this SA investigation an infection model for the hepatitis-B virus (HBV) that describes infection dynamics and clearance of HBV in the liver [Murray & Goyal, 2015]. The model tracks viral particles such as the tenacious and nearly ineradicable covalently closed circular DNA (cccDNA) embedded in infected nuclei and an HBV protein known as p36. Our application of these SA methods to the HBV model illuminates, especially over time, the quantitative relationships between cccDNA synthesis rate and p36 synthesis and export. Our results reinforce previous observations that the viral protein, p36, is by far the most influential factor for cccDNA replication. Moreover, both methods are capable of finding crucial parameters of the model. Though the Sobol method is independent of model structure (e.g., linearity and monotonicity) and well suited for SA, our results ensure that LHS-PRCC suffices for SA of a non-linear model if it is monotonic.
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http://dx.doi.org/10.1016/j.idm.2021.10.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8573155PMC
October 2021

Effect of Anastomosis Angles on Retrograde Perfusion and Hemodynamics of Hybrid Treatment for Thoracoabdominal Aortic Aneurysm.

Ann Vasc Surg 2021 Oct 12. Epub 2021 Oct 12.

Department of Applied Mechanics, Sichuan University, Chengdu, China.. Electronic address:

Background: Hemodynamic effects on the retrograde visceral reconstruction (RVR) for thoracoabdominal aortic aneurysms treatment by anastomotic angle remains unclear. This study aims to qualitatively and quantitatively investigate the effects of different anastomotic angles on hemodynamics and patency.

Methods: Three RVR models with 45°, 60° and 90° anastomotic angles were reconstructed respectively by manipulating apostoperative patient-specific model. The manipulated models of the RVRs were numerically simulated and analyzed in terms of hemodynamics including theinstant and cumulative patency, flow pattern and indicators based on wall shear stress (WSS).

Results: Although a smaller anastomotic angle may decrease the patency rate of common iliac arteries, it can improve the visceral perfusion during a cardiac cycle. More importantly, RVR with the smallest anastomotic angle experienced a minimal low time-averaged wall shear stress, high oscillatory shear index and relative residence time in the anastomosis region, whereas the largest anastomotic angle can introduce more unfavorable WSS in the graft trunk. Furthermore, a spiral flow pattern was observed in the proximal graft trunk of all three models, where no high-risk shear distribution was detected in this region.

Conclusion: A smaller anastomotic angle may have more benefits of hemodynamic environment in RVR, especially the WSS distribution and flow pattern in the graft trunk. We may also suggest that additional stents or an extended cuff for the graft can be used to induce spiral flow intentionally, which can further improve local hemodynamic environment and long-term prognosis.
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http://dx.doi.org/10.1016/j.avsg.2021.08.009DOI Listing
October 2021

Physiologically Based Pharmacokinetic Modelling for Nicotine and Cotinine Clearance in Pregnant Women.

Front Pharmacol 2021 20;12:688597. Epub 2021 Jul 20.

National Institute for Health Innovation, The University of Auckland, Auckland, New Zealand.

Physiologically based pharmacokinetic (PBPK) models for the absorption, disposition, metabolism and excretion (ADME) of nicotine and its major metabolite cotinine in pregnant women (p-PBPK) are rare. The aim of this short research report is to present a p-PBPK model and its simulations for nicotine and cotinine clearance. The maternal-placental-fetal compartments of the p-PBPK model contain a total of 16 compartments representing major maternal and fetal organs and tissue groups. Qualitative and quantitative data of nicotine and cotinine disposition and clearance have been incorporated into pharmacokinetic parameters. The p-PBPK model reproduced the higher clearance rates of nicotine and cotinine in pregnant women than non-pregnant women. Temporal profiles for their disposition in organs such as the brain were also simulated. Nicotine concentration reaches its maximum value within 2 min after an intravenous injection. The proposed p-PBPK model produces results consistent with available data sources. Further pharmacokinetic experiments are required to calibrate clearance parameters for individual organs, and for the fetus.
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http://dx.doi.org/10.3389/fphar.2021.688597DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8329445PMC
July 2021

Distribution and variation in proteins of casein micellar fractions response to heat-treatment from five dairy species.

Food Chem 2021 Dec 20;365:130640. Epub 2021 Jul 20.

College of Food Science and Engineering, Qingdao Agricultural University, Qingdao 266109, Shandong, China. Electronic address:

Casein micelles (CMs) contribute to the physicochemical properties and stability of milk. However, how the proteome of CMs changes following heat treatment has not been elucidated. Here, changes in the proteins of CMs in samples of Holstein, buffalo, yak, goat, and camel milk following heat treatment were investigated using a LC-MS/MS approach. According to the hierarchical clustering results, Holstein, yak, and buffalo milk samples had similar CMs protein components, followed by goat and camel milk samples. Changes in lipoprotein lipase and α-lactalbumin in CMs were dependent on the intensity of heat treatment and were similar among the studied species, whereas changes in κ-casein, lactoferrin, and apolipoprotein A-I differed among different types of milk. These results provide information on the distribution and variations of the proteomes of CMs following heat treatment, which will assist in the identification of proteins that are dissociated and attached to CMs from different dairy species during heat treatment.
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http://dx.doi.org/10.1016/j.foodchem.2021.130640DOI Listing
December 2021

Prevalence, Drug Resistance, and Virulence Genes of Potential Pathogenic Bacteria in Pasteurized Milk of Chinese Fresh Milk Bar.

J Food Prot 2021 Nov;84(11):1863-1867

College of Food Science and Engineering, Qingdao Agricultural University, Qingdao 266109, Shandong, People's Republic of China.

Fresh Milk Bar (FMB), an emerging dairy retail franchise, is used to instantly produce and sell pasteurized milk and other dairy products in China. However, the quality and safety of pasteurized milk in FMB have received little attention. The objective of this study was to investigate the prevalence, antimicrobial resistance, and virulence genes of Escherichia coli, Staphylococcus aureus, and Streptococcus in 205 pasteurized milk samples collected from FMBs in China. Four (2.0%) isolates of E. coli, seven (3.4%) isolates of S. aureus, and three (1.5%) isolates of Streptococcus agalactiae were isolated and identified. The E. coli isolates were resistant to amikacin (100%), streptomycin (50%), and tetracycline (50%). Their detected resistance genes include aac(3)-III (75%), blaTEM (25%), aadA (25%), aac(3)-II (25%), catI (25%), and qnrB (25%). The S. aureus isolates were mainly resistant to penicillin G (71.4%), trimethoprim-sulfamethoxazole (71.4%), kanamycin (57.1%), gentamicin (57.1%), amikacin (57.1%), and clindamycin (57.1%). blaZ (42.9%), mecA (28.6%), ermB (14.3%), and ermC (14.3%) were detected as their resistance genes. The Streptococcus strains were mainly resistant to tetracycline (66.7%) and contained the resistance genes pbp2b (33.3%) and tetM (33.3%). The virulence genes eae and stx2 were only found in one E. coli strain (25%), sec was detected in two S. aureus strains (28.6%), and bca was detected in one S. agalactiae strain (33.3%). The results of this study indicate that bacteria with drug resistance and virulence genes isolated from the pasteurized milk of FMB are a potential risk to consumers' health.
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http://dx.doi.org/10.4315/JFP-21-094DOI Listing
November 2021

Virtual Lobule Models Are the Key for Multiscale Biomechanical and Pharmacological Modeling for the Liver.

Authors:
Harvey Ho En Zhang

Front Physiol 2020 2;11:1061. Epub 2020 Sep 2.

Chongqing Institute for Food and Drug Control, Chongqing City, China.

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http://dx.doi.org/10.3389/fphys.2020.01061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7492636PMC
September 2020

A Pilot Study on Secondhand Smoke Exposure Among Pregnant Women in Chongqing, China: A Combined Questionnaire, Saliva Cotinine Test, and Ultrasound Flow Index Analysis.

Front Public Health 2020 29;8:290. Epub 2020 Jul 29.

Chongqing Health Center for Women and Children, Chongqing, China.

The aim of the study was to gain updated data on SHS exposure among pregnant women in Chongqing city, one of the four municipalities of China. Pregnant women attending routine ultrasound checks at an obstetrics and gynecology center voluntarily participated in the survey of SHS exposure. Some participants were also invited to have saliva cotinine tests using a NicAlert kit. The pulsatility index (PI) of the umbilical artery was compared between the SHS and non-SHS groups. A total of 548 pregnant women (74.82 and 25.18% at 12 and 24 weeks' gestation, respectively) participated in the survey from July to November 2019. SHS exposure was reported by 29.44% of participants. "Workplace" was listed as the top location for SHS exposure. Twenty-three of the 31 participants who tested cotinine-negative in their saliva samples self-reported SHS exposure in the survey questionnaire. However, two of the eight participants who tested cotinine-positive in their saliva samples self-reported SHS-exposure negative. The mean PI in the SHS group is higher than that in the non-SHS group (1.10 vs. 1.02) in fetuses at 24 weeks' gestation. However, the PI may not be suitable as an index for SHS exposure at 12 weeks' gestation due to frequent absent or reversed diastolic flow. The first survey on SHS exposure in pregnant women that combines a questionnaire, saliva cotinine tests, and ultrasound flow index analysis has been performed in China and provided valuable data for ensuing studies.
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http://dx.doi.org/10.3389/fpubh.2020.00290DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7438839PMC
May 2021

Survey of Aflatoxin M1 in Commercial Liquid Milk Products in China.

J Food Prot 2021 Feb;84(2):200-203

College of Food Science and Engineering, Qingdao Agricultural University, Qingdao 266109, Shandong, People's Republic of China.

Abstract: The objective of this study was to investigate the occurrence of aflatoxin M1 (AFM1) in Chinese liquid milk products. A total of 190 liquid milk samples, including 168 ultrahigh-temperature-treated milk samples and 22 pasteurized milk (PM) samples, were collected in August 2019. A screening assay with the Charm rapid test kit and a confirmation method with high-performance liquid chromatography were used for AFM1 analysis. Nine (4.74%) samples were screened positive, of which 5 (2.11%) samples were confirmed with concentration levels of 0.022 to 0.049 μg/kg. The AFM1 levels confirmed were all below the maximum residue levels set by China, the European Union, the United States, and the Codex Alimentarius Commission. The detection rate of AFM1 in domestic milk samples was 3.39%, while no AFM1 was detected in samples of imported milk. The prevalences of AFM1 detected in three groups of brands were as follows: group I, the major brands of China, 2.70%; group II, the local city domestic brands, 4.55%; and group III, the brands imported into China, 0. The detection rate of AFM1 was significantly higher in PM samples (9.09%) than in ultrahigh-temperature-treated samples (1.19%) (P < 0.05). Although the residue level of AFM1 did not exceed the maximum residue levels in any of the samples, the higher detection rate in local Chinese brands, especially in PM samples, deserves the attention of the Chinese government and consumers.

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http://dx.doi.org/10.4315/JFP-20-159DOI Listing
February 2021

Patient-Specific Blood Flow Analysis for Cerebral Arteriovenous Malformation Based on Digital Subtraction Angiography Images.

Front Bioeng Biotechnol 2020 23;8:775. Epub 2020 Jul 23.

Auckland Bioengineering Institute, The University of Auckland, Auckland, New Zealand.

Real-time digital subtraction angiography (DSA) is capable of revealing the cerebral vascular morphology and blood flow perfusion patterns of arterial venous malformations (AVMs). In this study, we analyze the DSA images of a subject-specific left posterior AVM case and customize a generic electric analog model for cerebral circulation accordingly. The generic model consists of electronic components representing 49 major cerebral arteries and veins, and yields their blood pressure and flow rate profiles. The model was adapted by incorporating the supplying and draining patterns of the AVM to simulate some typical AVM features such as the blood "steal" syndrome, where the flow rate in the left posterior artery increases by almost three times (∼300 ml/min vs 100 ml/min) compared with the healthy case. Meanwhile, the flow rate to the right posterior artery is reduced to ∼30 ml/min from 100 ml/min despite the presence of an autoregulation mechanism in the model. In addition, the blood pressure in the draining veins is increased from 9 to 22 mmHg, and the blood pressure in the feeding arteries is reduced from 85 to 30 mmHg due to the fistula effects of the AVM. In summary, a first DSA-based AVM model has been developed. More subject-specific AVM cases are required to apply the presented model, and data are used to validate the simulation results.
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http://dx.doi.org/10.3389/fbioe.2020.00775DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7390970PMC
July 2020

Ventricular Septal Rupture After Blunt Chest Trauma in an Infant: A Case Report and Mini-Review.

Front Pediatr 2020 19;8:316. Epub 2020 Jun 19.

Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Infection and Immunity, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorder, Chongqing, China.

Ventricular septal rupture (VSR) due to blunt chest trauma (BCT) is rare in infants. Traumatic VSR should be considered in infants with acute congestive cardiac failure following blunt trauma to the chest. Echocardiography is the method of choice for diagnosis and guiding the management of VSR. In this case report, we present a case of VSR caused by BCT in a 1-year and 9-month-old infant, who was diagnosed by emergency bedside echocardiography. We also provide a mini-review of literatures on BCT-induced VSR in children.
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http://dx.doi.org/10.3389/fped.2020.00316DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7325629PMC
June 2020

Occurrence, Antimicrobial Resistance Patterns, and Genetic Characterization of Isolated from Raw Milk in the Dairy Farms over Two Seasons in China.

Microb Drug Resist 2021 Jan 4;27(1):99-110. Epub 2020 Jun 4.

College of Food Science and Engineering, Qingdao Agricultural University, Qingdao City, China.

This study investigated the occurrence and resistance rates of strains isolated from raw milk in the dairy farms over two seasons (spring and autumn) and across four regions that included 11 provinces in China. In total, 750 raw milk samples from the 405 dairy farms were collected. Fifteen antimicrobial agents were tested for antimicrobial resistance via disk diffusion tests, and PCR tests were performed to identify drug resistance genes of isolates. Out of 750 samples, 276 (36.8%) were positive for , with 150 (41.1%) being positive in spring and 126 (32.7%) being positive in autumn. The occurrence rate of in northeastern China (45%) was higher than that in western China (33%) and southern China (31.9%), respectively, and the rate significantly ( < 0.05) differed from those of western China and southern China. Of 276 isolates, 261 (94.6%) strains were resistant to more than 1 antimicrobial drug, and 193 (69.9%) strains were multidrug resistant. The Z (46.3%), (35.5%), and (27.2%) genes were detected at a high frequency in the strains. Our data revealed a variation ( < 0.05) in the resistance patterns in the different regions and across the two seasons. The occurrence and drug resistance rates of isolated from raw milk obtained from dairy farms may still cause severe problems in China.
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http://dx.doi.org/10.1089/mdr.2019.0358DOI Listing
January 2021

An rat liver atlas.

Comput Methods Biomech Biomed Engin 2020 Aug 20;23(10):597-600. Epub 2020 Apr 20.

Auckland Bioengineering Institute, The University of Auckland, New Zealand.

Numerous hepatic function, disease and pharmacological experiments are performed on rat livers. Many of these experiments rely on an accurate understanding of the rat liver anatomy. In this short paper, we present an rat liver atlas which is constructed from the micro-CT images of explanted rat livers. The atlas consists of the parametric mesh for four liver lobes and a paracaval portion. 1D and 3D cubic Hermite mesh are used to represent the rat liver vessels and lobes, respectively. We discuss potential applications that can be performed from the atlas.
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http://dx.doi.org/10.1080/10255842.2020.1754404DOI Listing
August 2020

A Survey of 61 Veterinary Drug Residues in Commercial Liquid Milk Products in China.

J Food Prot 2020 Jul;83(7):1227-1233

College of Food Science and Engineering, Qingdao Agricultural University, Qingdao 266109, Shandong, People's Republic of China (ORCID: https://orcid.org/0000-0003-4485-3331 [R.H.]).

Abstract: To investigate the drug residue status in commercial liquid milk products in China, 190 samples, including ultrahigh temperature milk (n = 168) and pasteurized milk (n = 22) samples, were collected in 2019. Milk samples were analyzed for the presence of any of the 61 veterinary drugs in them by using a screening assay combined with an ultraperformance liquid chromatography-tandem mass spectrometry analysis. Ten (5.26%) samples were found positive for β-lactams, tetracyclines, and aminoglycosides, and six (3.16%) samples were confirmed residual for penicillin G (n = 6; 3.16%), tetracycline (n = 1; 0.53%), and oxytetracycline (n = 1; 0.53%), with the maximum concentration of 2.85, 40.64, and 12.35 μg kg-1, respectively. Drug residue detection rate in group II (4.55%; the local city domestic brands) was higher than that in group I (2.70%; the major brands of China) and group III (2.78%; the imported brands into China) and higher in domestic samples (3.39%) than that in imported samples (2.78%), and higher in pasteurized milk samples (9.09%) than in ultrahigh temperature milk samples (2.38%). All drug residue levels were far below the regulated maximum residue limits. However, based on some veterinary drug residues detected in the samples, there is a potential veterinary drug risk in liquid milk products in the Chinese market, and this situation deserves the attention of governments and consumers.

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http://dx.doi.org/10.4315/JFP-20-048DOI Listing
July 2020

Mathematical Modeling for Hepatitis B Virus: Would Spatial Effects Play a Role and How to Model It?

Front Physiol 2020 25;11:146. Epub 2020 Feb 25.

Department of Mathematics and Statistics, York University, Toronto, ON, Canada.

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http://dx.doi.org/10.3389/fphys.2020.00146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7052012PMC
February 2020

Maternal Smoking Induced Cardiovascular Risks in Fetuses: How Can Models Help?

Front Bioeng Biotechnol 2020 19;8:97. Epub 2020 Feb 19.

Auckland Bioengineering Institute, The University of Auckland, Auckland, New Zealand.

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http://dx.doi.org/10.3389/fbioe.2020.00097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7042462PMC
February 2020

Physicochemical and microstructural attributes of marinated chicken breast influenced by breathing ultrasonic tumbling.

Ultrason Sonochem 2020 Jun 12;64:105022. Epub 2020 Feb 12.

Auckland Bioengineering Institute, The University of Auckland, Auckland, New Zealand.

Currently, the conventional atmospheric pressure-based and vacuum-based tumbling processes have a limited improvement on the chicken characteristic attributes during the marination process. In view of this, through a breathing (pressure change) tumbling strategy, ultrasonication (40 kHz, 140 W) was applied to improve tenderness, taste, and microstructure of chicken by a redesigned tumbler. The results showed that the tumbling with the breathing action and ultrasonication significantly enhanced the marinating absorptivity, tenderness and taste, and accelerated the degradation of myosin light chain. Free peptides (from 1465.9 ± 34.6 to 4725.7 ± 43.2 μg/mL) and amino acids (from 1.503 ± 0.096 to 2.593 ± 0.109 mg/mL) rose evidently for the control and the breathing tumbling treatment assisted by ultrasound respectively. Raman analysis revealed that strength of disulfide bonds declined from 0.731 ± 0.006 to 0.607 ± 0.011 a.u. and the conversion from α-helix (decreased by 67.23%) into β-fold (increased by 1573%) conformation occurred. Low field NMR analysis indicated that the content of immobilized water increased from 77385 ± 14 to 137011 ± 106 au·ms by integral calculus. Scanning and transmission electron microscopies clearly showed a prospective rupture of myofibers, myofibrils, and lysosomes. Overall, as a potential alternative, the breathing ultrasonic tumbling means improved the marinating efficiency and characteristics of marinated chicken breast.
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http://dx.doi.org/10.1016/j.ultsonch.2020.105022DOI Listing
June 2020

A coupled one dimension and transmission line model for arterial flow simulation.

Int J Numer Method Biomed Eng 2020 04 11;36(4):e3327. Epub 2020 Mar 11.

Auckland Bioengineering Institute, The University of Auckland, Auckland, New Zealand.

A broad choice of numerical schemes and methods currently exists for blood flow simulations. The results rely critically on the prescription of boundary conditions. The outflow boundary condition for a one-dimensional (1D) flow solver is usually prescribed via a Windkessel or lumped parameter model. The weakness of such an approach is the determination of the parameters. In the present work, we use an alternative approach, that is, a reflection coefficient (RC), to lumped parameter models for distal boundary conditions. With such a RC, the number of parameters required is reduced to one. We derive the theoretical foundation for the RC. Specifically, we couple a transmission line theory for peripheral resistance with a 1D arterial flow solver. We apply this method to a healthy and a stenosed virtual aorta, and show this method can reproduce some subtle features in arterial pressure propagation, such as the steepened pressure waveform and the reflection from the stenosed site. In summary, the RC parameter has strong physical implications in the theory of wave propagation and may be used in flow simulations where reflections need to be explicitly modeled. NOVELTY STATEMENT: A novel coupled one-dimensional-transimission line model has been developed in this work with detailed implementations. Only one outflow boundary condition, that is, the refection coefficient is required in the model. Reflections for a pulse wave from aortic terminals as well as from a stenotic site are numerically simulated.
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http://dx.doi.org/10.1002/cnm.3327DOI Listing
April 2020

Analysis of Veterinary Drug Residues in Pasteurized Milk Samples in Chinese Milk Bars.

J Food Prot 2020 Jan 9:204-210. Epub 2020 Jan 9.

College of Food Science and Engineering, Qingdao Agricultural University, Qingdao 266109, Shandong, People's Republic of China (ORCID: https://orcid.org/0000-0003-2110-9008 [R.-W.H.]).

The milk bar is an emerging style of retail business that mainly produces pasteurized milk (PM) and other dairy products on-site in many large cities of the People's Republic of China. To date, no data about veterinary drug residues in PM samples produced from milk bars have been reported. The objective of this study was to investigate the safety of PM from a total of 182 PM samples collected from milk bars from 10 provincial capital cities and to analyze the residues of seven classes of 61 veterinary drugs. First, the chemical components were screened with test kits, and then the positive samples were further confirmed by ultraperformance liquid chromatography-tandem mass spectrometry. The results showed that 15 (8.24%) samples were screened positive for veterinary drugs, and six drugs in 11 (6.04%) samples were confirmed. The veterinary drugs detected were penicillin G (2.20%), tetracycline (1.10%), tylosin (1.10%), amoxicillin (0.55%), oxytetracycline (0.55%), and gentamicin (0.55%), with maximum residue levels of 3.4, 11.9, 28.2, 3.0, 26.9, and 63.5 μg kg, respectively. Veterinary drug residues were detected as positive in 7 of 10 cities, with the highest detection rate as 14.29% in Urumqi. No positive samples were found in the cities of Nanjing, Tianjin, and Nanning. All detected drug levels were far below the maximum residue levels regulated by China, the European Union, and the Codex Alimentarius Commission. This suggests that the overall veterinary drug residues in PM in milk bars reached the safety code of the country. However, potential risks still exist, and continuous attention should be paid to guarantee the safety of this milk product in the future.
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http://dx.doi.org/10.4315/0362-028X.JFP-19-333DOI Listing
January 2020

Modeling the hepatic arterial flow in living liver donor after left hepatectomy and postoperative boundary condition exploration.

Int J Numer Method Biomed Eng 2020 03 26;36(3):e3268. Epub 2019 Dec 26.

Auckland Bioengineering Institute, The University of Auckland, Auckland, New Zealand.

Preoperative and postoperative hepatic perfusion is modeled with one-dimensional (1-D) Navier-Stokes equations. Flow rates obtained from ultrasound (US) data and impedance resulted from structured trees are the inflow and outflow boundary condition (BC), respectively. Structured trees terminate at the size of the arterioles, which can enlarge their size after hepatectomy. In clinical studies, the resistance to pulsatile arterial flow caused by the microvascular bed can be reflected by the resistive index (RI), a frequently used index in assessing arterial resistance. This study uses the RI in a novel manner to conveniently obtain the postoperative outflow impedance from the preoperative impedance. The major emphasis of this study is to devise a model to capture the postoperative hepatic hemodynamics after left hepatectomy. To study this, we build a hepatic network model and analyze its behavior under four different outflow impedance: (a) the same as preoperative impedance; (b) evaluated using the RI and preoperative impedance; (c) computed from structured tree BC with increased radius of terminal vessels; and (d) evaluated using structured tree with both increased radius of root vessel, ie, the outlets of the postoperative hepatic artery, and increased radius of terminal vessels. Our results show that both impedance from (b) and (d) give a physiologically reasonable postoperative hepatic pressure range, while the RI in (b) allows for a fast approximation of postoperative impedance. Since hemodynamics after hepatectomy are not fully understood, the methods used in this study to explore postoperative outflow BC are informative for future models exploring hemodynamic effects of partial hepatectomy.
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http://dx.doi.org/10.1002/cnm.3268DOI Listing
March 2020

Anatomically based simulation of hepatic perfusion in the human liver.

Int J Numer Method Biomed Eng 2019 09 31;35(9):e3229. Epub 2019 Jul 31.

Auckland Bioengineering Institute, The University of Auckland, Auckland, New Zealand.

Liver structures of a healthy subject are digitised and segmented from computed tomography (CT) images, and hepatic perfusion is modelled in the hepatic artery and portal vein of the healthy subject with structured tree-based outflow boundary conditions. This self-similar structured tree is widely used in the literature, eg, blood flow simulation in larger systemic arteries and cerebral circulation, and is used in this study to model the effect of the smaller hepatic arteries and arterioles, as well as the smaller hepatic portal veins and portal venules. Physiologically reasonable results are obtained. Since the structured tree terminates at the size of the microvasculature system in liver lobules, the structured tree boundary condition will enable the proposed organ-level model of hepatic arterial flow to be easily connected to tissue-level models of liver lobules. Blood flow in the hepatic vein is also modelled in this subject with three-element Windkessel model as outflow boundary conditions. The benefit of integrating the perfusion in all hepatic vascular vessels is that it helps us analyse some complicated clinical phenomenon more efficiently, eg, one possible application is to obtain the portal pressure gradient (PPG) to help examine the reliability of hepatic venous pressure gradient (HVPG) as an indirect measure of portal pressure. Moreover, since four to six generations of hepatic vessels, which are sufficient for liver classification analysis, were employed in the model, this study is setting the computational foundation of a potentially handy surgical tool.
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http://dx.doi.org/10.1002/cnm.3229DOI Listing
September 2019

A computational model for hepatotoxicity by coupling drug transport and acetaminophen metabolism equations.

Int J Numer Method Biomed Eng 2019 09 28;35(9):e3234. Epub 2019 Jul 28.

Auckland Bioengineering Institute, The University of Auckland, Auckland, New Zealand.

The spatial distributions of cytochrome P450 (CYP450) and glutathione (GSH) in liver lobules determine the heterogeneous hepatotoxicity of acetaminophen (APAP). Their interplay in conjunction with blood flow is not well understood. In this paper, we integrate a cellular APAP metabolism model with a sinusoidal blood flow to simulate the temporal-spatial patterns of APAP-induced hepatotoxicity. The heterogeneous distribution of CYP450 and GSH is modeled by linearly varying their reaction rates along the portal triad to the central vein axis of a sinusoid. We found that the spatial distribution of GSH, glutathione S-transferases (GSTs), and CYP450 all contributes to the high acetaminophen protein adduct formation at zone 3 of the lobules. The reversed spatial gradients of CYP450 and GSH cause quick depletion of GSH, which is further accelerated by the distribution of GST. The hepatic flow congestion and hyperperfusion however do not seem to play a significant role in the zonal hepatotoxicity. The simulation results may be useful for understanding the APAP-induced hepatotoxicity and associated pharmaceutical treatment.
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http://dx.doi.org/10.1002/cnm.3234DOI Listing
September 2019

Hemodynamic aspects of the Budd-Chiari syndrome of the liver: A computational model study.

Authors:
Harvey Ho Chen Qiu

Med Eng Phys 2019 07 9;69:134-139. Epub 2019 May 9.

Department of Physiology, School of Medical Sciences, The University of Auckland, Auckland 1010, New Zealand.

Budd-Chiari syndrome (BCS) is a rare liver disease characterised by the obstruction of draining hepatic veins, and subsequent reduced blood return to the heart. Although many clinical BCS studies have been reported, few studies have quantified the associated changes that occur in the entire hepatic circulation. In this communication, we present an electrical analog model of the hepatic circulation that incorporates the Hepatic Arterial Buffer Response (HABR) mechanism in both the left and right lobes. Using this model we can simulate the hepatic flow under both normal and acute BCS conditions. The model can capture subtle features in the hepatic circulation, such as reduced total portal flow but increased arterial flow under BCS. This observation was previously reported in literature and may have clinical implications. As such, we suggest the presented model could be used for the analysis of systematic haemodynamic changes of BCS and therefore may be useful in supporting clinical interventions.
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http://dx.doi.org/10.1016/j.medengphy.2019.04.010DOI Listing
July 2019

A spatial-temporal model for zonal hepatotoxicity of acetaminophen.

Drug Metab Pharmacokinet 2019 Feb 8;34(1):71-77. Epub 2018 Oct 8.

Auckland Bioengineering Institute, The University of Auckland, New Zealand. Electronic address:

The metabolism zonation in liver lobules is well known yet its incorporation into the mathematical models of acetaminophen (APAP) metabolism is still primitive - only the oxidation pathway via reaction with the cytochrome P450 (CYP450) has been considered, yet the zonal heterogeneity exhibits in all three pathways including sulphation, glucuronidation and oxidation. In this paper we present a novel computational method where an intracellular APAP metabolism model is integrated into a Finite Element Model (FEM) of sinusoids, and the zonal heterogeneity in three metabolism pathways are all incorporated. We demonstrate that the degradation of APAP, detoxification via glutathione (GSH) and the formation of hepatotoxicity, are all affected profoundly by the zonal difference. Specifically, glucuronidation plays a major role in the degradation of APAP. Generation of GSH, its conjugation with the toxic NAPQI and the spatial distribution of CYP450 combined together determine the toxicity of APAP. We suggest that the current platform be used for further hepatotoxicity study of APAP by incorporating other heterogeneity factors.
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http://dx.doi.org/10.1016/j.dmpk.2018.09.266DOI Listing
February 2019

Quantification of in vivo gastric fluid volume in Bama miniature pigs in fasted state.

Biopharm Drug Dispos 2018 Sep 18;39(8):403-407. Epub 2018 Sep 18.

Agricultural Bio-pharmaceutical Laboratory, Qingdao Agricultural University, Qingdao, 266109, China.

Although the study of bioequivalence waivers in humans is already well-established, their application and translation into animals, which are complicated by differences in physiology, have only recently become subjects of interest. The main purpose of this paper is to quantify the liquid volume affecting drug dissolution in pig stomachs. We used magnetic resonance imaging (MRI) to scan 18 Bama miniature pigs weighing 15, 30 or 50 kg. Amira 6.0.1 software was used for 3D image processing. We found that the gastric fluid volume had a linear relationship with the weight of pig (R  = 0.9935) over this weight range. The pig weight, therefore, could be used as a surrogate for the fasted gastric fluid volume. After combining data of gastric fluid secretion and drinking water volumes, our results could be used as a reference for the evaluation of oral drug absorption in pigs.
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http://dx.doi.org/10.1002/bdd.2155DOI Listing
September 2018

A multi-scale spatial model of hepatitis-B viral dynamics.

PLoS One 2017 7;12(12):e0188209. Epub 2017 Dec 7.

Auckland Bioengineering Institute, University of Auckland, Auckland, New Zealand.

Chronic hepatitis B viral infection (HBV) afflicts around 250 million individuals globally and few options for treatment exist. Once infected, the virus entrenches itself in the liver with a notoriously resilient colonisation of viral DNA (covalently-closed circular DNA, cccDNA). The majority of infections are cleared, yet we do not understand why 5% of adult immune responses fail leading to the chronic state with its collateral morbid effects such as cirrhosis and eventual hepatic carcinoma. The liver environment exhibits particularly complex spatial structures for metabolic processing and corresponding distributions of nutrients and transporters that may influence successful HBV entrenchment. We assembled a multi-scaled mathematical model of the fundamental hepatic processing unit, the sinusoid, into a whole-liver representation to investigate the impact of this intrinsic spatial heterogeneity on the HBV dynamic. Our results suggest HBV may be exploiting spatial aspects of the liver environment. We distributed increased HBV replication rates coincident with elevated levels of nutrients in the sinusoid entry point (the periportal region) in tandem with similar distributions of hepatocyte transporters key to HBV invasion (e.g., the sodium-taurocholate cotransporting polypeptide or NTCP), or immune system activity. According to our results, such co-alignment of spatial distributions may contribute to persistence of HBV infections, depending on spatial distributions and intensity of immune response as well. Moreover, inspired by previous HBV models and experimentalist suggestions of extra-hepatic HBV replication, we tested in our model influence of HBV blood replication and observe an overall nominal effect on persistent liver infection. Regardless, we confirm prior results showing a solo cccDNA is sufficient to re-infect an entire liver, with corresponding concerns for transplantation and treatment.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0188209PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5720747PMC
January 2018

Roadmap for cardiovascular circulation model.

J Physiol 2016 12 29;594(23):6909-6928. Epub 2016 Sep 29.

Auckland Bioengineering Institute, University of Auckland, Auckland, New Zealand.

Computational models of many aspects of the mammalian cardiovascular circulation have been developed. Indeed, along with orthopaedics, this area of physiology is one that has attracted much interest from engineers, presumably because the equations governing blood flow in the vascular system are well understood and can be solved with well-established numerical techniques. Unfortunately, there have been only a few attempts to create a comprehensive public domain resource for cardiovascular researchers. In this paper we propose a roadmap for developing an open source cardiovascular circulation model. The model should be registered to the musculo-skeletal system. The computational infrastructure for the cardiovascular model should provide for near real-time computation of blood flow and pressure in all parts of the body. The model should deal with vascular beds in all tissues, and the computational infrastructure for the model should provide links into CellML models of cell function and tissue function. In this work we review the literature associated with 1D blood flow modelling in the cardiovascular system, discuss model encoding standards, software and a model repository. We then describe the coordinate systems used to define the vascular geometry, derive the equations and discuss the implementation of these coupled equations in the open source computational software OpenCMISS. Finally, some preliminary results are presented and plans outlined for the next steps in the development of the model, the computational software and the graphical user interface for accessing the model.
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http://dx.doi.org/10.1113/JP272660DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5134416PMC
December 2016

Fast blood-flow simulation for large arterial trees containing thousands of vessels.

Comput Methods Biomech Biomed Engin 2017 Feb 4;20(2):160-170. Epub 2016 Jul 4.

a Bioengineering Institute, University of Auckland , Auckland , New Zealand.

Blood flow modelling has previously been successfully carried out in arterial trees to study pulse wave propagation using nonlinear or linear flow solvers. However, the number of vessels used in the simulations seldom grows over a few hundred. The aim of this work is to present a computationally efficient solver coupled with highly detailed arterial trees containing thousands of vessels. The core of the solver is based on a modified transmission line method, which exploits the analogy between electrical current in finite-length conductors and blood flow in vessels. The viscoelastic behaviour of the arterial-wall is taken into account using a complex elastic modulus. The flow is solved vessel by vessel in the frequency domain and the calculated output pressure is then used as an input boundary condition for daughter vessels. The computational results yield pulsatile blood pressure and flow rate for every segment in the tree. This solver is coupled with large arterial trees generated from a three-dimensional constrained constructive optimisation algorithm. The tree contains thousands of blood vessels with radii spanning ~1 mm in the root artery to ~30 μm in leaf vessels. The computation takes seconds to complete for a vasculature of 2048 vessels and less than 2 min for a vasculature of 4096 vessels on a desktop computer.
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http://dx.doi.org/10.1080/10255842.2016.1207170DOI Listing
February 2017

AneuSearch: a software prototype for intracranial aneurysm searching and clinical decision support.

Int J Comput Assist Radiol Surg 2014 Nov 3;9(6):997-1004. Epub 2014 Apr 3.

Department of Neurosurgery, Mianyang Central Hospital, Mianyang City, Sichuan Province, China.

Purpose: Clinical decisions for treating intracranial aneurysms (IA) require integrating information in various forms and from multiple sources. We aim to establish a framework namely AneuSearch to integrate relevant information in IA management and also allow for efficient IA searching based on carefully designed criteria.

Methods: The backbone of AneuSearch is an open-source three-tier DICOM image management system called DCM4Chee, which is a Java implementation for PACS. A supplementary database (AneuSearchDB) was developed to contain morphological features, hemodynamic and histological data. The relational tables in AneuSearchDB correspond to the most fundamental questions raised by neurosurgeons during IA treatment. The system was developed through collaborations between bioengineers and neurosurgeons.

Results: The prototype software has been deployed to computers in a Mianyang Central Hospital in China. Currently, the system contains the data of 105 IA patients, seven hemodynamic simulation results and nine histological section images. This system was queried as per given criteria and can also provide blood flow data after running an external computational fluid dynamics software.

Conclusions: The prototype software provides a novel tool to IA management. Future works include incorporating IA treatment criteria in IA rupture risk assessment.
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http://dx.doi.org/10.1007/s11548-014-0996-xDOI Listing
November 2014

Blood flow simulation for the liver after a virtual right lobe hepatectomy.

Med Image Comput Comput Assist Interv 2012 ;15(Pt 3):525-32

Bioengineering Institute, University of Auckland, New Zealand.

In this paper we present a hybrid OD-3D modeling method to investigate the hepatic flow in a virtual right lobe hepatectomy (RLH), the surgical procedure for adult-to-adult living donor liver transplanation (LDLT). The 3D method is employed to simulate complex 3D flow in the portal vein, and the OD model is used to study the systemic hepatic circulation. In particular, we quantify the flow velocity and wall shear stress (WSS) in the left portal vein which increase dramatically post-RLH, and also simulate the essential hepatic distribution features in a healthy adult pre- and post-procedure. We further predict the arterial flow in the remnant left liver, which would decrease due to a hepatic arterial buffer response (HABR) effect. Finally we discuss the physiological significance of these phenomena, and the potential of this hybrid modeling approach.
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http://dx.doi.org/10.1007/978-3-642-33454-2_65DOI Listing
January 2013

Modeling the hepatic arterial buffer response in the liver.

Med Eng Phys 2013 Aug 15;35(8):1053-8. Epub 2012 Nov 15.

Bioengineering Institute, University of Auckland, New Zealand.

In this paper we present an electrical analog model for the hepatic arterial buffer response (HABR), an intrinsic regulation mechanism in the liver whereby the arterial flow counteracts the changes in portal venous flow. The model itself is a substantial simplification of a previously published model, with nonlinear arterial and portal resistors introduced to account for the dynamic HABR effects. We calibrate the baseline model using published hemodynamic data, and then perform a virtual portal occlusion simulation where the portal vein is half or fully occluded. The simulation results, which suggest that the increased arterial flow cannot fully compensate lost portal perfusion, are consistent with clinical reports and animal model findings. Since HABR functions in both the whole liver and liver graft after transplantation, we also simulate blood flow in a virtual right-lobe graft by adjusting the electronic component parameters in the electric circuit, and our model is able to reproduce the portal venous hyperperfusion and hepatic arterial hypoperfusion conditions due to the HABR effects.
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http://dx.doi.org/10.1016/j.medengphy.2012.10.008DOI Listing
August 2013
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