Browsing by Author "Grootveld, Martin"
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Item Metadata only Benchtop Low-Frequency 60 MHz NMR Analysis of Urine: A Comparative Metabolomics Investigation(MDPI, 2020-04-16) Leenders, Justine; Grootveld, Martin; Percival, Benita; Gibson, Miles; Casanova, Federico; Wilson, Philippe B.Metabolomics techniques are now applied in numerous fields, with the ability to provide information concerning a large number of metabolites from a single sample in a short timeframe. Although high-frequency (HF) nuclear magnetic resonance (NMR) analysis represents a common method of choice to perform such studies, few investigations employing low-frequency (LF) NMR spectrometers have yet been published. Herein, we apply and contrast LF and HF 1H-NMR metabolomics approaches to the study of urine samples collected from type 2 diabetic patients (T2D), and apply a comparative investigation with healthy controls. Additionally, we explore the capabilities of LF 1H-1H 2D correlation spectroscopy (COSY) experiments regarding the determination of metabolites, their resolution and associated analyses in human urine samples. T2D samples were readily distinguishable from controls, with several metabolites, particularly glucose, being associated with this distinction. Comparable results were obtained with HF and LF spectrometers. Linear correlation analyses were performed to derive relationships between the intensities of 1D and 2D resonances of several metabolites, and R2 values obtained were able to confirm these, an observation attesting to the validity of employing 2D LF experiments for future applications in metabolomics studies. Our data suggest that LF spectrometers may prove to be easy-to-use, compact and inexpensive tools to perform routine metabolomics analyses in laboratories and ‘point-of-care’ sites. Furthermore, the quality of 2D spectra obtained from these instruments in half an hour would broaden the horizon of their potential applications.Item Open Access Characterisation of Actions of p-menthane-3,8 diol (PMD) Repellent Formulations against Aedes aegypti mosquitoes(Oxford University Press, 2020-06-15) Goodyer, Larry; Grootveld, Martin; Deobhankar, Kedar; Debboun, Mustapha; Philip, ManjuBackground Characterisation of mosquito repellents using arm-in-cage tests are performed by assessing the ED95, half-life and complete protection times (CPT). This study fully characterises p-menthane-3,8 diol PMD which has not been widely studied, and a long-acting formulation containing a PMD-vanillin composite. Method A series of arm in cage tests against Aedes aegypti aegypti (Dipera-Culicidae) strain mosquitoes were devised using 6 volunteers to estimate CPT or 10 to estimate the effective dose (ED95) and half-life for three repellents: 20% DEET, 30% PMD and a novel 30% PMD-vanillin formulation. Non-linear Regression analysis was used to characterise the relationship between applied dose and CPT. were also estimated Results PMD and DEET showed a very similar log dose relationship to CPT; however, the PMD-vanillin formulation exhibited a sigmoidal ‘S-shape’ relationship. This resulted in a 1.5 times higher CPT for PMD-vanillin compared to that of 20% DEET when applied at a dose of 1.6mg/cm2, but little difference at lower doses of 0.8-1mg/cm2. The ED95 value for the 30% PMD and PMD-vanillin formulations were 0.25 and 0.24 mg/cm2 respectively, these being higher than that for 20% DEET (0.09 mg/cm2). The half-lives for 30% PMD and 20% DEET were similar (2.23 vs. 2.74 hrs.), but longer for the PMD-vanillin formulations (3.8 hrs.). Conclusion Such a full characterisation for other repellent formulations, particularly those claiming extended longevity, should be conducted in order to identify differences at various applied doses.Item Metadata only Comparative 1H NMR-Based Chemometric Evaluations of the Time-Dependent Generation of Aldehydic Lipid Oxidation Products in Culinary Oils Exposed to Laboratory-Simulated Shallow Frying Episodes: Differential Patterns Observed for Omega-3 Fatty Acid-Containing Soybean Oils(MDPI, 2021-10-17) Wann, Angela; Percival, Benita; Woodason, Kate; Gibson, Miles; Vincent, Siany; Grootveld, MartinSoybean oil is the second most exported oil from the United States and South America, and is widely marketed as a cooking oil product containing numerous health benefits for human consumers. However, culinary oils with high polyunsaturated fatty acid (PUFA) contents, are known to produce high quantities of lipid oxidation products (LOPs), including toxic aldehydes upon exposure to high-temperature frying episodes. Previous studies have demonstrated causal links between aldehyde ingestion and inhalation with deleterious health perturbations, including mutagenic and carcinogenic effects, along with cardiovascular and teratogenic actions. In this study, aldehydic LOPs were detected and quantified in commercially available samples of soybean, avocado, corn and extra-virgin olive oil products before and after their exposure to laboratory-simulated laboratory frying episodes (LSSFEs) using high-resolution 1H nuclear magnetic resonance (NMR) analysis. Results acquired demonstrated that PUFA-rich soybean and corn oils gave rise to the highest concentrations of oil aldehydes from the thermo-oxidation of unsaturated fatty acids, whereas monounsaturated fatty acid (MUFA)-laden avocado and olive oils were much more resistant to this peroxidation process, as expected. Multivariate chemometrics analyses provided evidence that an orthogonal component pattern of aldehydic LOPs featuring low-molecular-mass n-alkanals such as propanal, and 4-oxo-alkanals, arises from thermo-oxidation of the ω-3 fatty acid (FA) linolenic acid (present in soybean oils at levels of ca. 7% (w/w)), was able to at least partially distinguish this oil from corresponding samples of thermally-stressed corn oil. Despite having a similar total PUFA level, corn oil has only a negligible ω-3 FA content, and therefore generated significantly lower levels of these two aldehyde classes. In view of the adverse health effects associated with dietary LOP ingestion, alternative methodologies for the incorporation of soybean oils within high-temperature frying practices are proposed.Item Open Access Computational Simulation of 1H NMR Profiles of Complex Biofluid Analyte Mixtures at Differential Operating Frequencies: Applications to Low-Field Benchtop Spectra(Wiley, 2021-11-30) Edgar, Mark; Kuhn, Stefan; Page, Georgina; Grootveld, MartinEstimations of accurate and reliable NMR chemical shift values, coupling patterns and constants within a reasonable timeframe remain significantly challenging, and the unavailability of reliable software strategies for the prediction of low-field (e.g., 60 MHz) spectra from those acquired at higher operating frequencies hampers their direct comparison. Hence, this study explored the applications of accessible software options for predicting these parameters in the 1H NMR profiles of analytes as a function of magnetic field strength; this was performed for individual analytes and also for complex biofluid matrices featured in metabolomics investigations. For this purpose, results from the very first successful experimental acquisition and simulation of the 1H NMR profiles of intact human salivary supernatant samples on a 60 MHz benchtop spectrometer were evaluated. Using salivary metabolite concentrations determined at 400 MHz, it was demonstrated that simulation of the low-field spectra of five biomolecules with the most prominent 1H resonances detectable allowed multiple component fits to be applied to experimental spectra. Hence, these salivary 1H NMR profiles could be successfully predicted throughout the 45–600 MHz operating frequency range. With the exception of propionate resonance multiplets, which revealed more complex coupling patterns at low field and required more astute computational and fitting options, valuable quantitative metabolomics data on salivary acetate, formate, methanol and glycine could be attained from low-field spectrometres. These studies are both timely and pertinent in view of the recent advancement of low-field benchtop NMR facilities for diagnostically significant biomarker tracking in biofluids. Experiments performed with added ammonium chloride to facilitate the release of salivary metabolites from biopolymer binding sites provided evidence that a small but nevertheless significant proportion of propionate, but not lactate, was bound to such sites, an observation of much relevance to biomolecule quantification in salivary metabolomics investigations.Item Open Access Current Concepts of Laser–Oral Tissue Interaction.(MDPI, 2020-06-28) Parker, Steven; Anagnostaki, Eugenia; Mylona, Valina; Cronshaw, Mark; Lynch, Edward; Grootveld, MartinFundamental to the adjunctive use of laser photonic energy for delivering therapy and tissue management, is the ability of the incident energy to be absorbed by target tissues. The aim of this review is to examine the differential performance of the separate components of oral hard and soft tissues when exposed to laser photonic irradiance of variable wavelengths and power values. Through an examination of peer-reviewed published data and materials, the interaction of laser photonic energy and target tissues are explored in detail. Varying laser wavelength emissions relative to anatomical structures explores the ability to optimise laser–tissue interactions, and also identifies possible risk scenarios as they apply to adjacent non-target structures. The concepts and practical aspects of laser photonic energy interactions with target oral tissues are clearly demonstrated. Emphasis was placed on optimising the minimum level of laser power delivery in order to achieve a desired tissue effect, whilst minimising the risk or outcome of collateral tissue damage.Item Metadata only Editorial: Dietary Lipid Oxidation and Fried Food Toxicology(Frontiers, 2022-03-04) Grootveld, Martin; Addis, Paul Bradley; Le Gresley, AdamMankind is facing some difficult challenges and decisions. Indeed, our recently evidenced vulnerability to emergent viruses and how they can best be defended against; whether or not it is wise to totally move to a “carbon-free” world economy; and should we switch from animal foods to plant-based “fake meats,” to name but a few. The human condition, as affected by diet, has been debated for more than a century. It is therefore crucial that decisions made on future human health prospects, and the global environment, are based on sound scientific principles, and not simply to impart an economic advantage of one particular industry or corporation over another. The historic view that saturated fat and cholesterol are linked to cardiovascular disease (CVD), has experienced a significant evolution. Cholesterol is now considered not to represent a serious dietary issue, according to the American Heart Association (1). Likewise, the extreme resistance of saturated fat to lipid oxidation, and the lack of hypercholesterolemic effects of some saturated fatty acids, has led to a less severe attitude being expressed by many researchers (1). These new conclusions raise the question of what dietary components are related to human CVD and other pathologies? One clearly valuable answer to this question is afforded by groups of publications focused on fried food toxicology. It is interesting and perhaps significant that a recent review has summarized intelligibly, the massive amount of evidence adversely implicating omega-6 rich vegetable oils in the development, progression and pathogenesis of human CVDs (2), citing the fact that the introduction of soybean oil in the USA coincides clearly with an increased incidence of this non communicable chronic disease (NCD). Animal fat consumption has been declining for more than a century, beginning at the same time period that vegetable oil intake began to significantly increase. Interestingly, the authors of Ref. (2) cite the oxidized linoleic acid hypothesis, naming compounds which they specify as causative agents, particularly linoleoylglycerol oxidation products. This hypothesis coincides with the primary focus of the following papers-namely, radical-induced lipid oxidation is a serious health issue for the world’s human population and this subject has been “flying under the radar” for far too long.Item Metadata only Evaluations of the Peroxidative Susceptibilities of Cod Liver Oils by a 1H NMR Analysis Strategy: Peroxidative Resistivity of a Natural Collagenous and Biogenic Amine-Rich Fermented Product(MDPI, 2020-03-12) Percival, Benita; Wann, Angela; Zbasnik, Richard; Schelgel, Vicki; Edgar, Mark; Ampem, Gilbert; Le Gresley, Adam; Wilson, Philippe B.; Naughton, Declan; Grootveld, Martin; Zhang, JieHigh-resolution 1H nuclear magnetic resonance (NMR) analysis was employed to molecularly screen the lipid, lipid oxidation product (LOP), and antioxidant compositions of four natural (unrefined) cod liver oil (CLO) products. Products 1–3 were non-fermented CLOs, whilst Product 4 was isolated from pre-fermented cod livers. Supporting analytical data that were acquired included biogenic amine, flavanone, tannin, phenolic antioxidant, α-tocopherol, and oxygen radical absorbance capacity (ORAC) determinations by recommended HPLC, LC/MS/MS, or spectrophotometric methods. SDS-PAGE, HPLC, and 1H NMR analyses investigated and determined collagenous antioxidants and their molecular mass ranges. 1H NMR analysis of aldehydic LOPs was employed to explore the susceptibilities/resistivities of each CLO product to peroxidation that is induced by thermal stressing episodes (TSEs) at 180°C, or following prolonged (42 day) storage episodes at 4 and 23 °C. Product 4 displayed extremely high ORAC values, which were much greater than those of Products 1–3, and that were predominantly ascribable to significant levels of peroxidation-blocking and/or aldehyde-consuming collagenous polypeptides/peptides and ammoniacal agents therein. Significantly lower levels of toxic aldehydes were generated in the pre-fermented Product 4 during exposure to TSEs, or the above long-term storage episodes. These results confirmed the enhanced peroxidative resistivity of a fermented, antioxidant-fortified natural CLO product over those of non-fermented unrefined products. Product 4: Green Pasture Blue Ice™ Fermented Cod Liver Oil.Item Metadata only Evidence-Based Challenges to the Continued Recommendation and Use of Peroxidatively-Susceptible Polyunsaturated Fatty Acid-Rich Culinary Oils for High-Temperature Frying Practises: Experimental Revelations Focused on Toxic Aldehydic Lipid Oxidation Products(Frontiers, 2022-01-05) Grootveld, MartinIn this manuscript, a series of research reports focused on dietary lipid oxidation products (LOPs), their toxicities and adverse health effects are critically reviewed in order to present a challenge to the mindset supporting, or strongly supporting, the notion that polyunsaturated fatty acid-laden frying oils are “safe” to use for high-temperature frying practises. The generation, physiological fates, and toxicities of less commonly known or documented LOPs, such as epoxy-fatty acids, are also considered. Primarily, an introduction to the sequential autocatalytic peroxidative degradation of unsaturated fatty acids (UFAs) occurring during frying episodes is described, as are the potential adverse health effects posed by the dietary consumption of aldehydic and other LOP toxins formed. In continuance, statistics on the dietary consumption of fried foods by humans are reviewed, with a special consideration of French fries. Subsequently, estimates of human dietary aldehyde intake are critically explored, which unfortunately are limited to acrolein and other lower homologues such as acetaldehyde and formaldehyde. However, a full update on estimates of quantities derived from fried food sources is provided here. Further items reviewed include the biochemical reactivities, metabolism and volatilities of aldehydic LOPs (the latter of which is of critical importance regarding the adverse health effects mediated by the inhalation of cooking/frying oil fumes); their toxicological actions, including sections focussed on governmental health authority tolerable daily intakes, delivery methods and routes employed for assessing such effects in animal model systems, along with problems encountered with the Cramer classification of such toxins. The mutagenicities, genotoxicities, and carcinogenic potential of aldehydes are then reviewed in some detail, and following this the physiological concentrations of aldehydes and their likely dietary sources are considered. Finally, conclusions from this study are drawn, with special reference to requirements for (1) the establishment of tolerable daily intake (TDI) values for a much wider range of aldehydic LOPs, and (2) the performance of future nutritional and epidemiological trials to explore associations between their dietary intake and the incidence and severity of non-communicable chronic diseases (NCDs).Item Metadata only Extensive Chemometric Investigations of Distinctive Patterns and Levels of Biogenic Amines in Fermented Foods: Human Health Implications(MDPI, 2020-12-05) Grootveld, Martin; Percival, Benita; Zhang, JieAlthough biogenic amines (BAs) present in fermented foods exert important health-promoting and physiological function support roles, their excessive ingestion can give rise to deleterious toxicological effects. Therefore, here we have screened the BA contents and supporting food quality indices of a series of fermented food products using a multianalyte-chemometrics strategy. A liquid chromatographic triple quadrupole mass spectrometric (LC-MS/MS) technique was utilized for the simultaneous multicomponent analysis of 8 different BAs, and titratable acidity, pH, total lipid content, and thiobarbituric acid-reactive substances (TBARS) values were also determined. Rigorous univariate and multivariate (MV) chemometric data analysis strategies were employed to evaluate results acquired. Almost all foods analyzed had individual and total BA contents that were within recommended limits. The chemometrics methods applied were useful for recognizing characteristic patterns of BA analytes and food quality measures between some fermented food classes, and for assessing their inter-relationships and potential metabolic sources. MV analysis of constant sum-normalized BA profile data demonstrated characteristic signatures for cheese (cadaverine only), fermented cod liver oil (2-phenylethylamine, tyramine, and tryptamine), and wine/vinegar products (putrescine, spermidine, and spermine). In conclusion, this LC-MS/MS-linked chemometrics approach was valuable for (1) contrasting and distinguishing BA catabolite signatures between differing fermented foods, and (2) exploring and evaluating the health benefits and/or possible adverse public health risks of such products.Item Embargo The Influence of Delivery Power Losses and Full Operating Parametry on the Effectiveness of Diode Visible – Near Infra-red (445 - 1064nm) Laser Therapy in Dentistry – A Multi-Center Investigation(Springer, 2022-01-14) Parker, Steven; Cronshaw, Mark; Grootveld, Martin; Anagnostaki, Eugenia; Mylona, Valina; Chala, Marianna; George, Roy; Walsh, LaurenceThe development of protocols for laser-assisted therapy demands strict compliance with comprehensive operating parametry. The purpose of this investigation was to examine the accuracy of correlation between laser control panel and fibre emission power values in a selection of diode dental lasers. Through retrospective analysis using successive systematic review and meta-analysis, it is clear that there is inconsistency in the details, and possible inaccuracies in laser power applied and associated computed data. Through a multi-centre investigation, 38 semi-conductor (“diode”) dental laser units were chosen, with emission wavelengths ranging from 445 to 1064 nm. Each unit had been recently serviced according to manufacturer’s recommendations, and delivery fibre assembly checked for patency and correct alignment with the parent laser unit. Subject to the output capacity of each laser, four average power values were chosen using the laser control panel—100 mW, 500 mW, 1.0 W, and 2.0 W. Using a calibrated power meter, the post-fbre emission power value was measured, and a percentage power loss calculated. For each emission, a series of six measurements were made and analysed to investigate sources of power losses along the delivery fibre, and to evaluate the precision of power loss determinations. Statistical analysis of a dataset comprising % deviations from power setting levels was performed using a factorial ANOVA model, and this demonstrated very highly significant differences between devices tested and emission power levels applied (p<10–142 and<10–52 respectively). The devices emission power interaction effect was also markedly significant (p<10–66), and this confirmed that differences observed in these deviations for each prior power setting parameter were dependent on the device employed for delivery. Power losses were found to be negatively related to power settings applied. Significant differences have emerged to recommend the need to standardize a minimum set of parameters that should form the basis of comparative research into laser–tissue interactions, both in vitro and in vivo.Item Open Access Laser-Assisted aPDT Protocols in Randomized Controlled Clinical Trials in Dentistry: A Systematic Review(MDPI, 2020-09-22) Mylona, Valina; Anagnostaki, Eugenia; Parker, Steven; Cronshaw, Mark; Lynch, Edward; Grootveld, MartinBackground: Antimicrobial photodynamic therapy (aPDT) has been proposed as an effective alternative method for the adjunctive treatment of all classes of oral infections. The multifactorial nature of its mechanism of action correlates with various influencing factors, involving parameters concerning both the photosensitizer and the light delivery system. This study aims to critically evaluate the recorded parameters of aPDT applications that use lasers as the light source in randomized clinical trials in dentistry. Methods: PubMedandCochrane search engineswere used to identifyhuman clinical trials of aPDT therapy in dentistry. After applying specific keywords, additional filters, inclusion and exclusion criteria, the initial number of 7744 articles was reduced to 38. Results: Almost one-half of the articles presented incomplete parameters, whilst the others had different protocols, even with the same photosensitizer and for the same field of application. Conclusions: No safe recommendation for aPDT protocols can be extrapolated for clinical use. Further research investigations should be performed with clear protocols, so that standardization for their potential dental applications can be achieved.Item Metadata only Low-Field Benchtop NMR Spectroscopy for Quantification of Aldehydic Lipid Oxidation Products in Culinary Oils during Shallow Frying Episodes(MDPI, 2023-03-15) Gibson, Miles; Percival, Benita; Edgar, Mark; Grootveld, MartinIntroduction: Toxic aldehydic lipid oxidation products (LOPs) arise from the thermo-oxidative deterioration of unsaturated fatty acids present in heated culinary oils when exposed to high-temperature frying episodes, and currently these effects represent a major public health concern. Objectives: In this study, we investigated the applications of low-field (LF), benchtop NMR analysis to detect and quantify toxic aldehyde species in culinary oils following their exposure to laboratory-simulated shallow frying episodes (LSSFEs) at 180 °C. Four culinary oils of variable fatty acid (FA) composition were investigated to determine the analytical capabilities of the LF NMR instrument. Oil samples were also analysed using a medium-field (400 MHz) NMR facility for comparative purposes. Results: Aldehydes were quantified as total saturated and total α,β-unsaturated classes. The time-dependent production of α,β-unsaturated aldehydes decreased in the order chia > rapeseed ≈ soybean > olive oils, as might be expected from their polyunsaturated and monounsaturated FA (PUFA and MUFA, respectively) contents. A similar but inequivalent trend was found for saturated aldehyde concentrations. These data strongly correlated with medium-field 1H NMR data obtained, although LF-determined levels were significantly lower in view of its inability to detect or quantify the more minor oxygenated aldehydic LOPs present. Lower limit of detection (LLOD) values for this spectrometer were 0.19 and 0.18 mmol/mol FA for n-hexanal and trans-2-octenal, respectively. Aldehydic lipid hydroperoxide precursors of aldehydic LOPs were also detectable in LF spectra. Conclusions: We therefore conclude that there is scope for application of these smaller, near-portable NMR facilities for commercial or ‘on-site’ quality control determination of toxic aldehydic LOPs in thermally stressed frying oils.Item Metadata only Photobiomodulation and Oral Mucositis: A Systematic Review(MDPI, 2020-08-05) Cronshaw, Mark; Parker, Steven; Anagnostaki, Eugenia; Mylona, Valina; Lynch, Edward; Grootveld, MartinOral mucositis (OM) is a debilitating complication of chemotherapy, and head and neck radiotherapy. In an effort to offer the best possible advice within the limitations of published research, a systematic review with an extended discussion and commentary on dosimetry and dose delivery is presented. Using keywords as listed, Pubmed, Google Scholar and Cochrane databases were searched during a period extending from 1995 to 2019. A total of 782 abstracts were identified. A total of 50 papers were analysed, and of these, 29 satisfied criteria required for systematic review in accordance with an optimized PRISMA statement. Clinical outcome as reported was subject to analysis with respect to time of intervention, incidence and severity of oral mucositis, and pain amelioration, and a comprehensive combined univariate and multivariate statistical analysis of the methods employed was performed. Recommendations are made with respect to the timing of the intervention. Moreover, there is an extended discussion available on the treatment care rationale of photobiomodulation (PBM), and its adjunctive association with OM. In conclusion, early prophylactic application offers clear advantages in clinical management. The many studies and associated variables and covariables assessed here revealed a choice of delivery techniques, associated wavelengths and many further indices to consider with regard to the accomplishment of optical parameters. It is therefore our recommendation that clinicians use PBM as a therapy with a full and proper understanding and training in order to optimise the clinical effects achievable.Item Open Access Photobiomodulation Delivery Parameters in Dentistry: An Evidence based Approach.(Mary Ann Liebert Inc, 2022-01-13) Parker, Steven; Cronshaw, Mark; Grootveld, MartinNotwithstanding around 50 years of continued research, and with an ascending level of current research submissions, there is at present no agreed methodology and process to adopted treatment protocols. Dosimetry at target tissue level is, however, largely agreed, and more recent proposals have promoted the concept of a multiphasic dose–response to clinical outcomes [1]. Higher dosimetry appears to be the most effective for analgesia, and a lower dose bracket for the growth-promoting and optimal tissue healing benefits associated with tissue regeneration and the resolution of inflammation [2–6]. There is, however, no agreement with respect to wavelengths adopted, spectral emission modes, optical beam spatial profiles, and the optical surface spot size, together with the inter-relationship of these variables to optimize therapy outcome. Further, energy delivery to subsurface targets has proven to be a significant challenge, with the requirement for the operator to deliver a meaningful photonic dose to target through overlying anisotropic multiple layers of variable tissue types [7–9]. However, despite the many difficulties that have been encountered by researchers and clinicians alike, there is considerable interest in harnessing the proven benefits of photobiomodulation (PBM) as a therapy. This has led the authors to consider broadly and as widely as possible within the prior published evidence base factors that can more consistently lead to reduced operator errors and a higher level of research and clinical endeavor outcomes. For the purpose of this study, the authors considered that a prime objective in maintaining the sustainability of evidence-based data is to mandate a full description of laser operating parameters, both those concerning control panel running parameters and computed data relating to photonic dose. In this regard, the authors conducted an audit of published randomized clinical trial (RCT)-level articles that formed the basis of five recent systematic reviews. Within a total of 141 published articles, a selection of criteria that contributed to a ‘‘risk of bias’’ determination was examined. From this, it is asserted that the high level of absence of some basic values of photonic energy delivery renders cause for concern regarding the scientific rigor of conclusions obtained in such studies.Item Metadata only Photobiomodulation Dose Parameters in Dentistry: A Systematic Review and Meta-Analysis(MDPI, 2020-10-06) Cronshaw, Mark; Parker, Steven; Anagnostaki, Eugenia; Mylona, Valina; Lynch, Edward; Grootveld, MartinObjective: This systematic review and meta-analysis of published randomized controlled trials examines a possible relationship between optical spot size at surface tissue, irradiance, radiant exposure, total energy delivered, operator technique and reported clinical outcomes. Background: Clinical photobiomodulation (PBM) therapy has achieved a high level of evidence-based acceptance in the mitigation of oral mucositis associated with cancer radiotherapy and chemotherapy, and supportive clinical research in relation to orthodontic tooth movement, oral medical conditions, including burning mouth syndrome, xerostomia and lichen planus. Inconsistent outcomes have been reported not withstanding a substantial body of primary supportive research from clinical, in vitro and animal studies. Materials and Methods: PubMed, Cochrane Database of Reviews and Google Scholar search engines were applied to identify human clinical trials of PBM therapy in clinical dentistry. A total of 766 articles between February 2009 and June 2020 were identified and following a full text evaluation, 38 papers with sufficient data to permit analyses are included in this investigation. Results: Following a detailed assessment of potential factors that may have an influence in clinical outcome, a clear trend is apparent associating optical spot size to a positive or negative effect. Furthermore, there is a clear difference in the reported results in relation to total energy applied, delivery techniques and optical parameters, which merits further investigation. Factorial statistical analyses identified an association between smaller optical surface applications and an overall lower level of reported clinical success in treating superficial and deeper targets, and correspondingly sub-surface larger target tissues were found to be more responsive to therapy by use of a larger optical surface spot size. Moreover, use of multiple small diameter probe applications was found to provide inconsistent results. Conclusions: Many factors can confound clinical success including variations in anatomy, site location, clinical condition and subject individuality. To achieve higher levels of predictable outcome, a mature appreciation of these factors, plus an expanded understanding of laser parametry, tissue volume and target depth to deliver an adequate dose within current recommended guidelines, is essential.Item Embargo Photobiomodulation Effects on Periodontal Ligament Stem Cells: A Systematic Review of In Vitro Studies(Bentham Science Publishers, 2022-04-12) Mylona, Valina; Anagnostaki, Eugenia; Chiniforush, Nasim; Barikani, Hamidreza; Lynch, Edward; Grootveld, MartinBackground: Stem cell therapy has been considered to play a paramount role in the treatment modalities available for regenerative dentistry. The established beneficial effects of photobiomodulation (PBM) at the cellular level have led to the combined use of these two factors (PBM and stem cells). The main goal of this study was firstly to critically appraise the effects of PBM on periodontal ligament stem cells (PDLSCs), and secondly to explore the most effective PBM protocols applied. Methods: Pubmed, Cochrane, Scopus, Science Direct, and Google Scholar search engines were used to identify experimental in vitro studies in which PBM was applied to cultured PDLSCs. After applying specific keywords, additional filters, and inclusion/exclusion criteria, a preliminary number of 245 articles were narrowed down to 11 in which lasers and LEDs were used within the 630 - 1064 nm wavelength range. Selected articles were further assessed by three independent reviewers for strict compliance with PRISMA guidelines, and a modified Cochrane risk of bias to determine eligibility. Statistical Analysis: The dataset analysed was extracted from the studies with sufficient and clearly pre- sented PBM protocols. Simple univariate regression analysis was performed to explore the significance of contributions of potential quantitative predictor variables toward study outcomes, and a one-way ANOVA model was employed for testing differences between the laser or LED sources of the treatments. The sig- nificance level for testing was set at α = 0.05. Results: The proliferation rate, osteogenic differentiation, and expression of different indicative genes for osteogenesis and inflammation suppression were found to be positively affected by the application of various types of lasers and LEDs. With regard to the PBM protocol, only the wavelength variable ap- peared to affect the treatment outcome; indeed, the 940 nm wavelength parameter was found not to exert a favourable effect. Conclusions: Photobiomodulation can enhance the stemness and differentiation capacities of periodontal ligament stem cells. Therefore, for PBM protocols, there remains no consensus amongst the scientific community. Statistical analyses performed here indicated that the employment of a near-infrared (NIR) wavelength of 940 nm may not yield a significant favourable outcome, although those within the 630 - 830 nm range did so. Concerning the fluence, it should not exceed 8 J/cm2 when therapy is applied by LED devices, and 4 J/cm2 when applied by lasers, respectively.Item Metadata only Photothermal Effects of High-Energy Photobiomodulation Therapies: An In Vitro Investigation(MDPI, 2023-06-04) Cronshaw, Mark; Parker, Steven; Grootveld, Martin; Lynch, EdwardThe purpose of this study was to investigate photothermal aspects of photobiomodulation therapies (PBMT) in vitro to assist in the development of safe clinical parameters with respect to higher-power devices with large surface applicators. Laser wavelengths in the range of 650 nm–1064 nm were investigated using a thermal camera. Thermographic measures of surface and sub-surface temperature variations of similar lean porcine muscle tissue samples were recorded for a series of calibrated experiments. A thermal comparison was then made between Flat-top and Gaussian beam spatial distribution devices. Outcome data were subjected to statistical analysis using an ANOVA model. Results acquired at similar parameters of irradiance indicated that the application of the 980 nm wavelength was associated with the highest rise in temperature, which decreased with other wavelengths in the order 980 > 1064 ≈ 650 >>> 810 nm (p < 5 × 10−20). All wavelengths assessed were associated with a significant temperature increase, and with the exception of 810 nm, all exceeded the threshold of a 6 °C rise within the prescribed parameter limits. Optical scanning by movement of the applied source over a relevant area was found to offer effective mitigation of these temperature increases. An extended discussion is presented, analysing the clinical significance of the study outcomes. Recommendations are made within the limits of this in vitro study in order to assist future clinical investigations.Item Metadata only Potential Advantages of Peroxoborates and Their Ester Adducts Over Hydrogen Peroxide as Therapeutic Agents in Oral Healthcare Products: Chemical/Biochemical Reactivity Considerations In Vitro, Ex Vivo And In Vivo(MDPI, 2020-08-07) Grootveld, Martin; Lynch, Edward; Page, Georgina; Chan, W.; Percival, Benita; Anagnostaki, Eugenia; Mylona, Valina; Bordin-Aykroyd, Sonia; Grootveld, KerryPeroxides present in oral healthcare products generally exert favourable protective activities against the development and progression of tooth decay, plaque, gingivitis, and halitosis, etc. However, despite the high level of research focus on hydrogen and carbamide peroxides as therapeutically active (and tooth-whitening) agents, to date the use of alternative chemical forms of peroxides such as peroxoborates for these purposes has received only scant attention. Intriguingly, peroxoborate and its esters with polyols, such as glycerol, have a very diverse chemistry/biochemistry in aqueous solution, for which there is an increasing amount of evidence that it remains distinctive from that of hydrogen peroxide; such properties include self-associative and hydrolytic equilibria, and their abilities to participate in electrophile- or nucleophile-scavenging, metal ion-complexing, redox and free radical reactions, for example. Therefore, the purpose of this detailed commentary is to evaluate both differences and similarities between the molecular/biomolecular reactivities of peroxoborate species and hydrogen peroxide in vitro, ex-vivo and in vivo. It encompasses brief sectional accounts regarding the molecular heterogeneity of peroxoborates, the release of bioactive agents therefrom, and their oxidative attack on oral cavity biomolecules (the nucleophilic or electrophilic character of these oxidations are discussed). Further areas explored are the abilities of borates and peroxoborates to enhance the solubility of iron ions in aqueous solution, their involvements in free radical biochemistry (particularly the complexation of oxygen radical-promoting transition metal ions by, and antioxidant properties of, peroxoborate-polyol ester adducts), and the specific inhibition of protease enzymes. Further aspects focus on the tooth-whitening, oral malodor neutralizing, and potential mutagenic and genotoxic properties of peroxoborates, along with possible mechanisms for these processes. The abilities of peroxoborates, and peroxides in general, to modulate the activities of inflammatory mediators and vitamins, antioxidant or otherwise, are also explored.Item Metadata only Potential Adverse Public Health Effects Afforded by the Ingestion of Dietary Lipid Oxidation Product Toxins: Significance of Fried Food Sources(MDPI, 2020-04-01) Grootveld, Martin; Percival, Benita; Leenders, Justine; Wilson, Philippe B.Exposure of polyunsaturated fatty acid (PUFA)-rich culinary oils (COs) to high temperature frying practices generates high concentrations of cytotoxic and genotoxic lipid oxidation products (LOPs) via oxygen-fueled, recycling peroxidative bursts. These toxins, including aldehydes and epoxy-fatty acids, readily penetrate into fried foods and hence are available for human consumption; therefore, they may pose substantial health hazards. Although previous reports have claimed health benefits offered by the use of PUFA-laden COs for frying purposes, these may be erroneous in view of their failure to consider the negating adverse public health threats presented by food-transferable LOPs therein. When absorbed from the gastrointestinal (GI) system into the systemic circulation, such LOPs may significantly contribute to enhanced risks of chronic non-communicable diseases (NCDs), e.g. , cancer, along with cardiovascular and neurological diseases. Herein, we provide a comprehensive rationale relating to the public health threats posed by the dietary ingestion of LOPs in fried foods. We begin with an introduction to sequential lipid peroxidation processes, describing the noxious effects of LOP toxins generated therefrom. We continue to discuss GI system interactions, the metabolism and biotransformation of primary lipid hydroperoxide LOPs and their secondary products, and the toxicological properties of these agents, prior to providing a narrative on chemically-reactive, secondary aldehydic LOPs available for human ingestion. In view of a range of previous studies focused on their deleterious health effects in animal and cellular model systems, some emphasis is placed on the physiological fate of the more prevalent and toxic α,β-unsaturated aldehydes. We conclude with a description of targeted nutritional and interventional strategies, whilst highlighting the urgent and unmet clinical need for nutritional and epidemiological trials probing relationships between the incidence of NCDs, and the frequency and estimated quantities of dietary LOP intake.Item Metadata only Real-World Evaluation of Lipid Oxidation Products and Trace Metals in French Fries From Two Chain Fast-Food Restaurants(Frontiers, 2021-02-05) Ampem, Gilbert; Le Gresley, Adam; Grootveld, Martin; Naughton, Declan; De Mars, SimonDifferences in lipid oxidation products (LOPs) and trace metal concentrations of French fry samples found between two global chain fast-food restaurants in the UK were investigated using high-resolution proton nuclear magnetic resonance (1H NMR) and inductively coupled plasma-optical emission spectrometry (ICP-OES) analyses, respectively, of extracts derived therefrom. Over the course of 3 days and 3 different diurnal time periods, samples of French fries (FFs) were analyzed, and comparisons of two different oil extraction methods were undertaken for the two restaurants involved. The magnitude of concentrations of LOPs extracted from FFs is discussed. Significant differences between 6/7 aldehyde classifications, and aluminum, manganese, vanadium, lead, iron, copper and nickel levels between samples from the two restaurants are also reported. Redox-active transition and further trace metal concentrations inversely correlated with FF oil sample LOP contents; this suggested an antioxidant rather than a pro-oxidant role for them.