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The Repurposing of Ivermectin for Malaria: A Prospective Pharmacokinetics-Based Virtual Clinical Trials Assessment of Dosing Regimen Options

Badhan R, Zakaria Z, Olafuyi O

J Pharm Sci, 2018 08;107(8):2236-2250.
PMID: 29626533 DOI: 10.1016/j.xphs.2018.03.026

Ivermectin has demonstrated many successes in the treatment of a range of nematode infections. Considering the increase in malaria resistance, attention has turned toward ivermectin as a candidate for repurposing for malaria. This study developed and validated an ivermectin physiology-based pharmacokinetic model in healthy adults (20-50 years), pediatric (3-5 years/15-25 kg) subjects, and a representative adult malaria population group (Thailand). Dosing optimization demonstrating a twice-daily dose for 3- or 5-day regimens would provide a time above the LC50 of more than 7 days for adult and pediatric subjects. Furthermore, to address the occurrence of CYP450 induction that is often encountered with antiretroviral agents, simulated drug-drug interaction studies with efavirenz highlighted that a 1-mg/kg once-daily dose for 5 days would counteract the increased ivermectin hepatic clearance and enable a time above LC50 of 138.8 h in adults and 141.2 h in pediatric subjects. It was also demonstrated that dosage regimen design would require consideration of the age-weight geographical relationship of the subjects, with a dosage regimen for a representative Thailand population group requiring at least a single daily dose for 5 days to maintain ivermectin plasma concentrations and a time above LC50 similar to that in healthy adults.

Matched MeSH terms: Models, Biological
Fulltext Primary stability recognition of the newly designed cementless femoral stem using digital signal processing

Baharuddin MY, Salleh ShH, Hamedi M, Zulkifly AH, Lee MH, Mohd Noor A, et al.

Biomed Res Int, 2014;2014:478248.
PMID: 24800230 DOI: 10.1155/2014/478248

Stress shielding and micromotion are two major issues which determine the success of newly designed cementless femoral stems. The correlation of experimental validation with finite element analysis (FEA) is commonly used to evaluate the stress distribution and fixation stability of the stem within the femoral canal. This paper focused on the applications of feature extraction and pattern recognition using support vector machine (SVM) to determine the primary stability of the implant. We measured strain with triaxial rosette at the metaphyseal region and micromotion with linear variable direct transducer proximally and distally using composite femora. The root mean squares technique is used to feed the classifier which provides maximum likelihood estimation of amplitude, and radial basis function is used as the kernel parameter which mapped the datasets into separable hyperplanes. The results showed 100% pattern recognition accuracy using SVM for both strain and micromotion. This indicates that DSP could be applied in determining the femoral stem primary stability with high pattern recognition accuracy in biomechanical testing.

Matched MeSH terms: Models, Biological*
Fulltext Real-time gas identification by analyzing the transient response of capillary-attached conductive gas sensor

Bahraminejad B, Basri S, Isa M, Hambli Z

Sensors (Basel), 2010;10(6):5359-77.
PMID: 22219666 DOI: 10.3390/s100605359

In this study, the ability of the Capillary-attached conductive gas sensor (CGS) in real-time gas identification was investigated. The structure of the prototype fabricated CGS is presented. Portions were selected from the beginning of the CGS transient response including the first 11 samples to the first 100 samples. Different feature extraction and classification methods were applied on the selected portions. Validation of methods was evaluated to study the ability of an early portion of the CGS transient response in target gas (TG) identification. Experimental results proved that applying extracted features from an early part of the CGS transient response along with a classifier can distinguish short-chain alcohols from each other perfectly. Decreasing time of exposition in the interaction between target gas and sensing element improved the reliability of the sensor. Classification rate was also improved and time of identification was decreased. Moreover, the results indicated the optimum interval of the early transient response of the CGS for selecting portions to achieve the best classification rates.

Matched MeSH terms: Models, Biological
Biomechanical analysis of rheumatoid arthritis of the wrist joint

Bajuri MN, Kadir MR, Amin IM, Ochsner A

Proc Inst Mech Eng H, 2012 Jul;226(7):510-20.
PMID: 22913098 DOI: 10.1177/0954411912445846

The wrist is the most complex joint for virtual three-dimensional simulations, and the complexity is even more pronounced when dealing with skeletal disorders of the joint such, as rheumatoid arthritis (RA). In order to analyse the biomechanical difference between healthy and diseased joints, three-dimensional models of these two wrist conditions were developed from computed tomography images. These images consist of eight carpal bones, five metacarpal bones, the distal radius and ulna. The cartilages were developed based on the shape of the available articulations and ligaments were simulated via mechanical links. The RA model was developed accurately by simulating all ten common criteria of the disease related to the wrist. Results from the finite element (FE) analyses showed that the RA model produced three times higher contact pressure at the articulations compared to the healthy model. Normal physiological load transfer also changed from predominantly through the radial side to an increased load transfer approximately 5% towards the ulnar. Based on an extensive literature search, this is the first ever reported work that simulates the pathological conditions of the rheumatoid arthritis of the wrist joint.

Matched MeSH terms: Models, Biological*
A hyperelastic fibre-reinforced continuum model of healing tendons with distributed collagen fibre orientations

Bajuri MN, Isaksson H, Eliasson P, Thompson MS

Biomech Model Mechanobiol, 2016 12;15(6):1457-1466.
PMID: 26951049

The healing process of ruptured tendons is problematic due to scar tissue formation and deteriorated material properties, and in some cases, it may take nearly a year to complete. Mechanical loading has been shown to positively influence tendon healing; however, the mechanisms remain unclear. Computational mechanobiology methods employed extensively to model bone healing have achieved high fidelity. This study aimed to investigate whether an established hyperelastic fibre-reinforced continuum model introduced by Gasser, Ogden and Holzapfel (GOH) can be used to capture the mechanical behaviour of the Achilles tendon under loading during discrete timepoints of the healing process and to assess the model's sensitivity to its microstructural parameters. Curve fitting of the GOH model against experimental tensile testing data of rat Achilles tendons at four timepoints during the tendon repair was used and achieved excellent fits ([Formula: see text]). A parametric sensitivity study using a three-level central composite design, which is a fractional factorial design method, showed that the collagen-fibre-related parameters in the GOH model-[Formula: see text] and [Formula: see text]-had almost equal influence on the fitting. This study demonstrates that the GOH hyperelastic fibre-reinforced model is capable of describing the mechanical behaviour of healing tendons and that further experiments should focus on establishing the structural and material parameters of collagen fibres in the healing tissue.

Matched MeSH terms: Models, Biological*
A simplified approach for exit dose in vivo measurements in radiotherapy and its clinical application

Banjade DP, Shrestha SL, Shukri A, Tajuddin AA, Bhat M

Australas Phys Eng Sci Med, 2002 Sep;25(3):110-8.
PMID: 12416587

This is a study using LiF:Mg;Ti thermoluminescent dosimeter (TLD) rods in phantoms to investigate the effect of lack of backscatter on exit dose. Comparing the measured dose with anticipated dose calculated using tissue maximum ratio (TMR) or percentage depth dose (PDD) gives rise to a correction factor. This correction factor may be applied to in-vivo dosimetry results to derive true dose to a point within the patient. Measurements in a specially designed humanoid breast phantom as well as patients undergoing radiotherapy treatment were also been done. TLDs with reproducibility of within +/- 3% (1 SD) are irradiated in a series of measurements for 6 and 10 MV photon beams from a medical linear accelerator. The measured exit doses for the different phantom thickness for 6 MV beams are found to be lowered by 10.9 to 14.0% compared to the dose derived from theoretical estimation (normalized dose at dmax). The same measurements for 10 MV beams are lowered by 9.0 to 13.5%. The variations of measured exit dose for different field sizes are found to be within 2.5%. The exit doses with added backscatter material from 2 mm up to 15 cm, shows gradual increase and the saturated values agreed within 1.5% with the expected results for both beams. The measured exit doses in humanoid breast phantom as well as in the clinical trial on patients undergoing radiotherapy also agreed with the predicted results based on phantom measurements. The authors' viewpoint is that this technique provides sufficient information to design exit surface bolus to restore build down effect in cases where part of the exit surface is being considered as a target volume. It indicates that the technique could be translated for in vivo dose measurements, which may be a conspicuous step of quality assurance in clinical practice.

Matched MeSH terms: Models, Biological
Improvement of production of citric acid from oil palm empty fruit bunches: optimization of media by statistical experimental designs

Bari MN, Alam MZ, Muyibi SA, Jamal P, Abdullah-Al-Mamun

Bioresour Technol, 2009 Jun;100(12):3113-20.
PMID: 19231166 DOI: 10.1016/j.biortech.2009.01.005

A sequential optimization based on statistical design and one-factor-at-a-time (OFAT) method was employed to optimize the media constituents for the improvement of citric acid production from oil palm empty fruit bunches (EFB) through solid state bioconversion using Aspergillus niger IBO-103MNB. The results obtained from the Plackett-Burman design indicated that the co-substrate (sucrose), stimulator (methanol) and minerals (Zn, Cu, Mn and Mg) were found to be the major factors for further optimization. Based on the OFAT method, the selected medium constituents and inoculum concentration were optimized by the central composite design (CCD) under the response surface methodology (RSM). The statistical analysis showed that the optimum media containing 6.4% (w/w) of sucrose, 9% (v/w) of minerals and 15.5% (v/w) of inoculum gave the maximum production of citric acid (337.94 g/kg of dry EFB). The analysis showed that sucrose (p<0.0011) and mineral solution (p<0.0061) were more significant compared to inoculum concentration (p<0.0127) for the citric acid production.

Matched MeSH terms: Models, Biological*
Fulltext Long-term trends in calcifying plankton and pH in the North Sea

Beare D, McQuatters-Gollop A, van der Hammen T, Machiels M, Teoh SJ, Hall-Spencer JM

PLoS One, 2013;8(5):e61175.
PMID: 23658686 DOI: 10.1371/journal.pone.0061175

Relationships between six calcifying plankton groups and pH are explored in a highly biologically productive and data-rich area of the central North Sea using time-series datasets. The long-term trends show that abundances of foraminiferans, coccolithophores, and echinoderm larvae have risen over the last few decades while the abundances of bivalves and pteropods have declined. Despite good coverage of pH data for the study area there is uncertainty over the quality of this historical dataset; pH appears to have been declining since the mid 1990s but there was no statistical connection between the abundance of the calcifying plankton and the pH trends. If there are any effects of pH on calcifying plankton in the North Sea they appear to be masked by the combined effects of other climatic (e.g. temperature), chemical (nutrient concentrations) and biotic (predation) drivers. Certain calcified plankton have proliferated in the central North Sea, and are tolerant of changes in pH that have occurred since the 1950s but bivalve larvae and pteropods have declined. An improved monitoring programme is required as ocean acidification may be occurring at a rate that will exceed the environmental niches of numerous planktonic taxa, testing their capacities for acclimation and genetic adaptation.

Matched MeSH terms: Models, Biological
Influence of alignment of the pyramid on its beneficial effects

Bhat S, Rao G, Murthy KD, Bhat PG

Indian J Exp Biol, 2007 May;45(5):455-8.
PMID: 17569288

The present study was aimed to find out whether a change in the alignment of the pyramid from the north-south axis causes any variation in the effects produced by it on plasma cortisol levels and markers of oxidative stress in erythrocytes of adult-female Wistar rats. Plasma cortisol and erythrocyte TBARS levels were significantly lower whereas erythrocyte GSH was significantly higher in rats kept in pyramid that was aligned on the four cardinal points--north, east, south and west, as compared to normal control rats. Although there was a significant difference in the plasma cortisol level between normal control group and the group of rats kept in randomly aligned pyramid, there was no significant difference between these two groups for the other parameters. Erythrocyte TBARS levels in the group of rats kept in the randomly aligned pyramid was significantly higher than that in the group kept in the magnetically aligned pyramid. The results suggest that the north-south alignment of the pyramid is crucial for its expected effects.

Matched MeSH terms: Models, Biological*
Fulltext Reproductive number of coronavirus: A systematic review and meta-analysis based on global level evidence

Billah MA, Miah MM, Khan MN

PLoS One, 2020;15(11):e0242128.
PMID: 33175914 DOI: 10.1371/journal.pone.0242128

BACKGROUND: The coronavirus (SARS-COV-2) is now a global concern because of its higher transmission capacity and associated adverse consequences including death. The reproductive number of coronavirus provides an estimate of the possible extent of the transmission. This study aims to provide a summary reproductive number of coronavirus based on available global level evidence.
METHODS: A total of three databases were searched on September 15, 2020: PubMed, Web of Science, and Science Direct. The searches were conducted using a pre-specified search strategy to record studies reported the reproductive number of coronavirus from its inception in December 2019. It includes keywords of coronavirus and its reproductive number, which were combined using the Boolean operators (AND, OR). Based on the included studies, we estimated a summary reproductive number by using the meta-analysis. We used narrative synthesis to explain the results of the studies where the reproductive number was reported, however, were not possible to include in the meta-analysis because of the lack of data (mostly due to confidence interval was not reported).
RESULTS: Total of 42 studies included in this review whereas 29 of them were included in the meta-analysis. The estimated summary reproductive number was 2.87 (95% CI, 2.39-3.44). We found evidence of very high heterogeneity (99.5%) of the reproductive number reported in the included studies. Our sub-group analysis was found the significant variations of reproductive number across the country for which it was estimated, method and model that were used to estimate the reproductive number, number of case that was considered to estimate the reproductive number, and the type of reproductive number that was estimated. The highest reproductive number was reported for the Diamond Princess Cruise Ship in Japan (14.8). In the country-level, the higher reproductive number was reported for France (R, 6.32, 95% CI, 5.72-6.99) following Germany (R, 6.07, 95% CI, 5.51-6.69) and Spain (R, 3.56, 95% CI, 1.62-7.82). The higher reproductive number was reported if it was estimated by using the Markov Chain Monte Carlo method (MCMC) method and the Epidemic curve model. We also reported significant heterogeneity of the type of reproductive number- a high-value reported if it was the time-dependent reproductive number.
CONCLUSION: The estimated summary reproductive number indicates an exponential increase of coronavirus infection in the coming days. Comprehensive policies and programs are important to reduce new infections as well as the associated adverse consequences including death.

Matched MeSH terms: Models, Biological
Neuro-fuzzy method for predicting the viability of stem cells treated at different time-concentration conditions

Bindal P, Bindal U, Lin CW, Kasim NHA, Ramasamy TSAP, Dabbagh A, et al.

Technol Health Care, 2017 Dec 04;25(6):1041-1051.
PMID: 28800347 DOI: 10.3233/THC-170922

Dental stem cells isolated for human dental pulp are an excellent source for regenerative medicine and dentistry. Simulation of clinical scenario is one of the crucial challenges for evaluation of the efficacy of DPSCs in various regenerative therapies. In this study we evaluated the viability of DPSCs after treatment with artificial bacterial lipopolysaccharides (LPS) as the main component responsible for inducing inflammatory response in majority of the inflammatory conditions in clinical scenario. Although a number of studies have previously treated stem cells with LPS from bacteria, however the accuracy level of the outcome was not established. Here we have analyzed the outcome using adaptive neuro-fuzzy inferences system (ANFIS) to predict the viability of human DPSCs after treatment with bacterial LPS.

Matched MeSH terms: Models, Biological
Convolution and validation of in vitro-in vivo correlation of water-insoluble sustained-release drug (domperidone) by first-order pharmacokinetic one-compartmental model fitting equation

Bose A, Wui WT

Eur J Drug Metab Pharmacokinet, 2013 Sep;38(3):191-200.
PMID: 23264125 DOI: 10.1007/s13318-012-0116-7

The experimental study presents a brief and comprehensive perspective on the methods of developing a Level A in vitro-in vivo correlation (IVIVC) for extended oral dosage forms of water-insoluble drug domperidone. The study also evaluates the validity and predictability of in vitro-in vivo correlation using the convolution technique by one-compartmental first-order kinetic equation. The IVIVC can be substituted as a surrogate for in vivo bioavailability study for the documentation of bioequivalence studies as mandatory from any regulatory authorities. The in vitro drug release studies for different formulations (fast, moderate, slow) were conducted in different dissolution mediums. The f (2) metric (similarity factor) was used to analyze the dissolution data for determination of the most discriminating dissolution method. The in vivo pharmacokinetics parameters of all the formulations were determined by using liquid chromatography mass spectrometry (LC/MS) methods. The absorption rate constant and percentage of absorption of drugs at different time intervals were calculated by using data convolution. In vitro drug release and in vivo absorption correlation were found to be a linear correlation model, which was developed by using percent absorbed drug release versus percent drug dissolved from the three formulations. Internal and external validation was performed to validate the IVIVC. Predicted domperidone concentrations were obtained by convolution technique using first-order one-compartmental fitting equation. Prediction errors estimated for C (max) and AUC (0-infinity) were found to be within the limit.

Matched MeSH terms: Models, Biological
Fulltext Subcellular localization and interactions among rubber particle proteins from Hevea brasiliensis

Brown D, Feeney M, Ahmadi M, Lonoce C, Sajari R, Di Cola A, et al.

J Exp Bot, 2017 Nov 02;68(18):5045-5055.
PMID: 29036360 DOI: 10.1093/jxb/erx331

Natural rubber (polyisoprene) from the rubber tree Hevea brasiliensis is synthesized by specialized cells called laticifers. It is not clear how rubber particles arise, although one hypothesis is that they derive from the endoplasmic reticulum (ER) membrane. Here we cloned the genes encoding four key proteins found in association with rubber particles and studied their intracellular localization by transient expression in Nicotiana benthamiana leaves. We show that, while the cis-prenyltransferase (CPT), responsible for the synthesis of long polyisoprene chains, is a soluble, cytosolic protein, other rubber particle proteins such as rubber elongation factor (REF), small rubber particle protein (SRPP) and Hevea rubber transferase 1-REF bridging protein (HRBP) are associated with the endoplasmic reticulum (ER). We also show that SRPP can recruit CPT to the ER and that interaction of CPT with HRBP leads to both proteins relocating to the plasma membrane. We discuss these results in the context of the biogenesis of rubber particles.

Matched MeSH terms: Models, Biological
Fulltext Integrating HIV pre-exposure prophylaxis and harm reduction among men who have sex with men and transgender women to address intersecting harms associated with stimulant use: a modelling study

Bórquez A, Rich K, Farrell M, Degenhardt L, McKetin R, Tran LT, et al.

J Int AIDS Soc, 2020 Jun;23 Suppl 1(Suppl 1):e25495.
PMID: 32562365 DOI: 10.1002/jia2.25495

INTRODUCTION: Among men who have sex with men (MSM) and transgender women (TW), stimulant use is high and has been associated with an increased risk of HIV infection, suicide and cardiovascular disease (CVD) mortality. We used epidemic modelling to investigate these intersecting health harms among MSM/TW in Lima, Peru and assess whether they could be mitigated by prioritizing HIV pre-exposure prophylaxis (PrEP) and harm reduction interventions among MSM/TW who use stimulants.
METHODS: We adapted a dynamic model of HIV transmission among MSM/TW in Lima to incorporate stimulant use and increased HIV risk, suicide and CVD mortality. Among 6% to 24% of MSM/TW using stimulants (mostly cocaine), we modelled an increased risk of unprotected anal sex (RR = 1.35 [95%CI: 1.17 to 1.57]) obtained from local data, and increased risk of suicide (SMR = 6.26 [95%CI: 2.84 to 13.80]) and CVD (SMR = 1.83 [95%CI: 0.39 to 8.57]) mortality associated with cocaine use based on a global systematic review. We estimated the proportion of health harms occurring among MSM/TW who use stimulants in the next year (01-2020/01-2021). We also investigated the 10-year impact (01-2020/01-2030) of: (1) PrEP prioritization for stimulant-using MSM/TW compared to random allocation, and (2) integrating PrEP with a theoretical intervention halving stimulant-associated risk.
RESULTS: MSM/TW in Lima will experience high HIV incidence, suicide mortality and CVD mortality (1.6/100 py, and 0.018/100 py, 0.13/100 py respectively) in 2020. Despite stimulant using MSM/TW comprising an estimated 9.5% (95%CI: 7.8 to 11.5) of all MSM/TW, in the next year, 11% 95%CI (i.e. 2.5% to 97.5% percentile) 10% to 13%) of new HIV infections, 39% (95%CI: 18% to 60%) of suicides and 15% (95%CI: 3% to 44%) of CVD deaths could occur among this group. Scaling up PrEP among all stimulant using MSM/TW could prevent 19% (95%CI: 11% to 31%) more HIV infections over 10 years compared to random allocation. Integrating PrEP and an intervention to halve stimulant-associated risks could reduce new HIV infections by 20% (95%CI: 10% to 37%), suicide deaths by 14% (95%CI: 5% to 27%) and CVD deaths by 3% (95%CI: 0% to 16%) over a decade.
CONCLUSIONS: MSM/TW who use stimulants experience a disproportionate burden of health harms. Prioritizing PrEP based on stimulant use, in addition to sexual behaviour/gender identity criteria, could increase its impact. Integrated substance use, harm reduction, mental health and HIV care among MSM/TW is needed.

Matched MeSH terms: Models, Biological
Fulltext Roles of Sema4D and Plexin-B1 in tumor progression

Ch'ng ES, Kumanogoh A

Mol. Cancer, 2010;9:251.
PMID: 20858260 DOI: 10.1186/1476-4598-9-251

Sema4D, also known as CD100, is a protein belonging to class IV semaphorin. Its physiologic roles in the immune and nervous systems have been extensively explored. However, the roles of Sema4D have extended beyond these traditionally studied territories. Via interaction with its high affinity receptor Plexin-B1, Sema4D-Plexin-B1 involvement in tumor progression is strongly implied. Here, we critically review and delineate the Sema4D-Plexin-B1 interaction in many facets of tumor progression: tumor angiogenesis, regulation of tumor-associated macrophages and control of invasive growth. We correlate the in vitro and in vivo experimental data with the clinical study outcomes, and present a molecular mechanistic basis accounting for the intriguingly contradicting results from these recent studies.

Matched MeSH terms: Models, Biological
Fulltext Multipurpose contrast enhancement on epiphyseal plates and ossification centers for bone age assessment

Chai HY, Swee TT, Seng GH, Wee LK

Biomed Eng Online, 2013;12:27.
PMID: 23565999 DOI: 10.1186/1475-925X-12-27

The high variations of background luminance, low contrast and excessively enhanced contrast of hand bone radiograph often impede the bone age assessment rating system in evaluating the degree of epiphyseal plates and ossification centers development. The Global Histogram equalization (GHE) has been the most frequently adopted image contrast enhancement technique but the performance is not satisfying. A brightness and detail preserving histogram equalization method with good contrast enhancement effect has been a goal of much recent research in histogram equalization. Nevertheless, producing a well-balanced histogram equalized radiograph in terms of its brightness preservation, detail preservation and contrast enhancement is deemed to be a daunting task.

Matched MeSH terms: Models, Biological
Fulltext The biological seal of the implant-soft tissue interface evaluated in a tissue-engineered oral mucosal model

Chai WL, Brook IM, Palmquist A, van Noort R, Moharamzadeh K

J R Soc Interface, 2012 Dec 7;9(77):3528-38.
PMID: 22915635 DOI: 10.1098/rsif.2012.0507

For dental implants, it is vital that an initial soft tissue seal is achieved as this helps to stabilize and preserve the peri-implant tissues during the restorative stages following placement. The study of the implant-soft tissue interface is usually undertaken in animal models. We have developed an in vitro three-dimensional tissue-engineered oral mucosal model (3D OMM), which lends itself to the study of the implant-soft tissue interface as it has been shown that cells from the three-dimensional OMM attach onto titanium (Ti) surfaces forming a biological seal (BS). This study compares the quality of the BS achieved using the three-dimensional OMM for four types of Ti surfaces: polished, machined, sandblasted and anodized (TiUnite). The BS was evaluated quantitatively by permeability and cell attachment tests. Tritiated water (HTO) was used as the tracing agent for the permeability test. At the end of the permeability test, the Ti discs were removed from the three-dimensional OMM and an Alamar Blue assay was used for the measurement of residual cells attached to the Ti discs. The penetration of the HTO through the BS for the four types of Ti surfaces was not significantly different, and there was no significant difference in the viability of residual cells that attached to the Ti surfaces. The BS of the tissue-engineered oral mucosa around the four types of Ti surface topographies was not significantly different.

Matched MeSH terms: Models, Biological*
Ultrastructural analysis of implant-soft tissue interface on a three dimensional tissue-engineered oral mucosal model

Chai WL, Brook IM, Emanuelsson L, Palmquist A, van Noort R, Moharamzadeh K

J Biomed Mater Res A, 2012 Feb;100(2):269-77.
PMID: 22045611 DOI: 10.1002/jbm.a.33245

A three dimensional tissue-engineered human oral mucosal model (3D OMM) used in the investigation of implant-soft tissue interface was recently reported. The aim of this study was to examine the ultrastructural features of soft tissue attachment to various titanium (Ti) implant surfaces based on the 3D OMM. Two techniques, that is, focus ion beam (FIB) and electropolishing techniques were used to prepare specimens for transmission electron microscopic (TEM) analysis of the interface. The 3D OM consisting of both epithelial and connective tissue layers was constructed by co-culturing human oral keratinocytes and fibroblasts onto an acellular dermis scaffold. Four types of Ti surface topographies were tested: polished, machined (turned), sandblasted, and TiUnite. The specimens were then processed for TEM examination using FIB (Ti remained) and electropolishing (Ti removed) techniques. The FIB sections showed some artifact and lack of details of ultrastructural features. In contrast, the ultrathin sections prepared from the electropolishing technique showed a residual Ti oxide layer, which preserved the details for intact ultrastructural interface analysis. There was evidence of hemidesmosome-like structures at the interface on the four types of Ti surfaces, which suggests that the tissue-engineered oral mucosa formed epithelial attachments on the Ti surfaces.

Matched MeSH terms: Models, Biological
A standard quantitative method to measure acid tolerance of probiotic cells

Chan ES, Lee PP, Ravindra P, Krishnaiah K, Voo WP

Appl Microbiol Biotechnol, 2010 Mar;86(1):385-91.
PMID: 20033402 DOI: 10.1007/s00253-009-2384-y

The aim of this work was to develop a standard quantitative method to measure the acid tolerance of probiotic cells when exposed to a simulated gastric fluid. Three model strains of different cell concentrations were exposed to a standard simulated gastric fluid of fixed volume. The fluid pH ranged from pH 1.5 to 2.5. In general, the death kinetics followed an exponential trend. The overall death constant, k (d), for all strains was found to be in a power relationship with the pH value and the initial cell concentration, and it can be expressed as k(d)=k(AII) (pH(-9.0)N(0)(-0.19)) where k (AII) is defined as the acid intolerance indicator and N (0) is the initial cell concentration (CFU/ml). This equation was validated with the experimental data with an average R (2) of 0.98. The acid intolerance of cells can be quantitatively expressed by the k (AII) values, where higher value indicates higher intolerance. In conclusion, a standard quantitative method has been developed to measure the acid tolerance of probiotic cells. This could facilitate the selection of probiotic strains and processing technologies.

Matched MeSH terms: Models, Biological
Sensitivity of thermophysiological models of cryoablation to the thermal and biophysical properties of tissues

Chan JY, Ooi EH

Cryobiology, 2016 12;73(3):304-315.
PMID: 27789380 DOI: 10.1016/j.cryobiol.2016.10.006

Advancement in biomedical simulation and imaging modality have catalysed the development of in silico predictive models for cryoablation. However, one of the main challenges in ensuring the accuracy of the model prediction is the use of proper thermal and biophysical properties of the patient. These properties are difficult to measure clinically and thus, represent significant uncertainty that can affect the model prediction. Motivated by this, a sensitivity analysis is carried out to identify the model parameters that have the most significant impact on the lesion size during cryoablation. The study is initially carried out using the Morris method to screen for the most dominant parameters. Once determined, analysis of variance (ANOVA) is performed to quantitatively rank the order of importance of each parameter and their interactions. Results from the sensitivity analysis revealed that blood perfusion, water transport and ice nucleation parameters are critical in predicting the lesion size, suggesting that the acquisition of these parameters should be prioritised to ensure the accuracy of the model prediction.

Matched MeSH terms: Models, Biological*

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