Urinary Metabolic Distinction of Niemann-Pick Class 1 Disease through the Use of Subgroup Discovery.

In this investigation, we outline the applications of a data mining technique known as Subgroup Discovery (SD) to the analysis of a sample size-limited metabolomics-based dataset. The SD technique utilized a supervised learning strategy, which lies midway between classificational and descriptive criteria, in which given the descriptive property of a dataset (i.e., the response target variable of interest), the primary objective was to discover subgroups with behaviours that are distinguishable from those of the complete set (albeit with a differential statistical distribution). These approaches have, for the first time, been successfully employed for the analysis of aromatic metabolite patterns within an NMR-based urinary dataset collected from a small cohort of patients with the lysosomal storage disorder Niemann-Pick class 1 (NPC1) disease (n = 12) and utilized to distinguish these from a larger number of heterozygous (parental) control participants. These subgroup discovery strategies discovered two different NPC1 disease-specific metabolically sequential rules which permitted the reliable identification of NPC1 patients; the first of these involved 'normal' (intermediate) urinary concentrations of xanthurenate, 4-aminobenzoate, hippurate and quinaldate, and disease-downregulated levels of nicotinate and trigonelline, whereas the second comprised 'normal' 4-aminobenzoate, indoxyl sulphate, hippurate, 3-methylhistidine and quinaldate concentrations, and again downregulated nicotinate and trigonelline levels. Correspondingly, a series of five subgroup rules were generated for the heterozygous carrier control group, and 'biomarkers' featured in these included low histidine, 1-methylnicotinamide and 4-aminobenzoate concentrations, together with 'normal' levels of hippurate, hypoxanthine, quinolinate and hypoxanthine. These significant disease group-specific rules were consistent with imbalances in the combined tryptophan-nicotinamide, tryptophan, kynurenine and tyrosine metabolic pathways, along with dysregulations in those featuring histidine, 3-methylhistidine and 4-hydroxybenzoate. In principle, the novel subgroup discovery approach employed here should also be readily applicable to solving metabolomics-type problems of this nature which feature rare disease classification groupings with only limited patient participant and sample sizes available.

Detection and Quantification of Ammonia as the Ammonium Cation in Human Saliva by 1H NMR: A Promising Probe for Health Status Monitoring, with Special Reference to Cancer.

Ammonia (NH3) has been shown to be a key biomarker for a wide variety of diseases, such as hepatic and chronic kidney diseases (CKD), and cancers. It also has relevance to the oral health research area, and, hence, its determination in appropriate biofluids and tissues is of much importance. However, since it contains exchangeable >N-H protons, its analysis via 1H NMR spectroscopy, which is a widely employed technique in untargeted metabolomic studies, is rendered complicated. In this study, we focused on the 1H NMR analysis of this biomarker in less invasively collected human saliva samples, and we successfully identified and quantified it as ammonium cation (NH4+) in post-collection acidulated forms of this biofluid using both the standard calibration curve and standard addition method (SAM) approaches. For this purpose, n = 27 whole mouth saliva (WMS) samples were provided by healthy human participants, and all donors were required to follow a fasting/oral environment abstention period of 8 h prior to collection. Following acidification (pH 2.00), diluted WMS supernatant samples treated with 10% (v/v) D2O underwent 1H NMR analysis (600 MHz). The acquired results demonstrated that NH4+ can be reliably determined in these supernatants via integration of the central line of its characteristic 1:1:1 intensity triplet resonance (complete spectral range δ = 6.97-7.21 ppm). Experiments performed also demonstrated that any urease-catalysed NH3 generation occurring post-sampling in WMS samples did not affect the results acquired during the usual timespan of laboratory processing required prior to analysis. Further experiments demonstrated that oral mouth-rinsing episodes conducted prior to sample collection, as reported in previous studies, gave rise to major decreases in salivary NH4+ levels thereafter, which renormalised to only 50-60% of their basal control concentrations at the 180-min post-rinsing time point. Therefore, the WMS sample collection method employed significantly affected the absolute levels of this analyte. The LLOD was 60 µmol/L with 128 scans. The mean ± SD salivary NH4+ concentration of WMS supernatants was 11.4 ± 4.5 mmol/L. The potential extension of these analytical strategies to the screening of other metabolites with exchangeable 1H nuclei is discussed, as is their relevance to the monitoring of human disorders involving the excessive generation and/or uptake of cellular/tissue material, or altered homeostasis, in NH3.

Photothermal Effects of High-Energy Photobiomodulation Therapies: An In Vitro Investigation.

The 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.

High-resolution 1H NMR analysis of continuous and discontinuous thermo-oxidative susceptibility of culinary oils during frying at 180 °C.

Lipid oxidations products (LOPs) are reactive mutagenic and carcinogenic species known to be generated in thermally stressed culinary oils. Mapping the evolution of LOPs in culinary oils exposed to standard frying practices - both continuous and discontinuous thermo-oxidation - at 180 °C is vital to our understanding of these processes, and to the development of scientific solutions for their effective suppression. Modifications in the chemical compositions of the thermo-oxidised oils were analysed using a high-resolution proton nuclear magnetic resonance (1H NMR) technique. Research findings acquired showed that polyunsaturated fatty acid (PUFA)-rich culinary oils were the most susceptible to thermo-oxidation. Consistently, coconut oil, which has a very high saturated fatty acid (SFA) content, was highly resistant to the thermo-oxidative methods employed. Furthermore, continuous thermo-oxidation produced greater substantive changes in the oils evaluated than discontinuous episodes. Indeed, for 120 min thermo-oxidation durations, both continuous and discontinuous methods exerted a unique impact on the contents and levels of aldehydic LOPs formed in the oils. This report exposes daily used culinary oils to thermo-oxidation, and therefore, it permits assessments of their peroxidative susceptibilities. It also serves as a reminder to the scientific community to investigate approaches for suppressing toxic LOPs generation in culinary oils exposed to these processes, most notably those involving their reuse.

Low-Field Benchtop NMR Spectroscopy for Quantification of Aldehydic Lipid Oxidation Products in Culinary Oils during Shallow Frying Episodes.

INTRODUCTION: 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,ß-unsaturated classes. The time-dependent production of α,ß-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.

Updates and Original Case Studies Focused on the NMR-Linked Metabolomics Analysis of Human Oral Fluids Part III: Implementations for the Diagnosis of Non-Cancerous Disorders, Both Oral and Systemic.

This communication represents Part III of our series of reports based on the applications of human saliva as a useful and conveniently collectable medium for the discovery, identification and monitoring of biomarkers, which are of some merit for the diagnosis of human diseases. Such biomarkers, or others reflecting the dysfunction of specific disease-associated metabolic pathways, may also be employed for the prognostic pathological tracking of these diseases. Part I of this series set the experimental and logistical groundwork for this report, and the preceding paper, Part II, featured the applications of newly developed metabolomics technologies to the diagnosis and severity grading of human cancer conditions, both oral and systemic. Clearly, there are many benefits, both scientific and economic, associated with the donation of human saliva samples (usually as whole mouth saliva) from humans consenting to and participating in investigations focused on the discovery of biomolecular markers of diseases. These include usually non-invasive collection protocols, relatively low cost when compared against blood sample collection, and no requirement for clinical supervision during collection episodes. This paper is centred on the employment and value of 'state-of-the-art' metabolomics technologies to the diagnosis and prognosis of a wide range of non-cancerous human diseases. Firstly, these include common oral diseases such as periodontal diseases (from type 1 (gingivitis) to type 4 (advanced periodontitis)), and dental caries. Secondly, a wide range of extra-oral (systemic) conditions are covered, most notably diabetes types 1 and 2, cardiovascular and neurological diseases, and Sjögren's syndrome, along with a series of viral infections, e.g., pharyngitis, influenza, HIV and COVID-19. Since the authors' major research interests lie in the area of the principles and applications of NMR-linked metabolomics techniques, many, but not all, of the studies reviewed were conducted using these technologies, with special attention being given to recommended protocols for their operation and management, for example, satisfactory experimental model designs; sample collection and laboratory processing techniques; the selection of sample-specific NMR pulse sequences for saliva analysis; and strategies available for the confirmation of resonance assignments for both endogenous and exogenous molecules in this biofluid. This article also features an original case study, which is focussed on the use of NMR-based salivary metabolomics techniques to provide some key biomarkers for the diagnosis of pharyngitis, and an example of how to 'police' such studies and to recognise participants who perceive that they actually have this disorder but do not from their metabolic profiles and multivariate analysis pattern-based clusterings. The biochemical and clinical significance of these multidimensional metabolomics investigations are discussed in detail.

Updates and Original Case Studies Focused on the NMR-Linked Metabolomics Analysis of Human Oral Fluids Part II: Applications to the Diagnosis and Prognostic Monitoring of Oral and Systemic Cancers.

Human saliva offers many advantages over other biofluids regarding its use and value as a bioanalytical medium for the identification and prognostic monitoring of human diseases, mainly because its collection is largely non-invasive, is relatively cheap, and does not require any major clinical supervision, nor supervisory input. Indeed, participants donating this biofluid for such purposes, including the identification, validation and quantification of surrogate biomarkers, may easily self-collect such samples in their homes following the provision of full collection details to them by researchers. In this report, the authors have focused on the applications of metabolomics technologies to the diagnosis and progressive severity monitoring of human cancer conditions, firstly oral cancers (e.g., oral cavity squamous cell carcinoma), and secondly extra-oral (systemic) cancers such as lung, breast and prostate cancers. For each publication reviewed, the authors provide a detailed evaluation and critical appraisal of the experimental design, sample size, ease of sample collection (usually but not exclusively as whole mouth saliva (WMS)), their transport, length of storage and preparation for analysis. Moreover, recommended protocols for the optimisation of NMR pulse sequences for analysis, along with the application of methods and techniques for verifying and resonance assignments and validating the quantification of biomolecules responsible, are critically considered. In view of the authors' specialisms and research interests, the majority of these investigations were conducted using NMR-based metabolomics techniques. The extension of these studies to determinations of metabolic pathways which have been pathologically disturbed in these diseases is also assessed here and reviewed. Where available, data for the monitoring of patients' responses to chemotherapeutic treatments, and in one case, radiotherapy, are also evaluated herein. Additionally, a novel case study featured evaluates the molecular nature, levels and diagnostic potential of 1H NMR-detectable salivary 'acute-phase' glycoprotein carbohydrate side chains, and/or their monomeric saccharide derivatives, as biomarkers for cancer and inflammatory conditions.

Application of data augmentation techniques towards metabolomics.

Niemann-Pick Class 1 (NPC1) disease is a rare and debilitating neurodegenerative lysosomal storage disease (LSD). Metabolomics datasets of NPC1 patients available to perform this type of analysis are often limited in the number of samples and severely unbalanced. In order to improve the predictive capability and identify new biomarkers in an NPC1 disease urinary dataset, data augmentation (DA) techniques based on computational intelligence have been employed to create synthetic samples, i.e. the addition of noise, oversampling techniques and conditional generative adversarial networks. These techniques have been used to evaluate their predictive capacities on a set of urine samples donated by 13 untreated NPC1 disease and 47 heterozygous (parental) carrier control participants. Results on the prediction have also been obtained using different machine learning classification models and the partial least squares techniques. These results provide strong evidence for the ability of DA techniques to generate good quality synthetic data. Results acquired show increases in sensitivity of 20%-50%, an F1 score of 6%-30%, and a predictive capacity of 0.3 (out of 1). Additionally, more conventional forms of multivariate data analysis have been employed. These have allowed the detection of unusual urinary metabolite profiles, and the identification of biomarkers through the use of synthetically augmented datasets. Results indicate that urinary branched-chain amino acids such as valine, 3-aminoisobutyrate and quinolinate, may be employable as valuable biomarkers for the diagnosis and prognostic monitoring of NPC1 disease.

Revisiting Fluoride in the Twenty-First Century: Safety and Efficacy Considerations.

Over 100 years of scientific literature is available which describes the long relationship between dentistry and the many possible applications of fluoride anion (F-) as successful therapeutic strategies. To date, systemic introduction of fluoride via water, milk and salt fluoridation, and fluoride-containing tablets, has been employed. Post-eruption topical fluoride products have also been introduced, such as fluoridated toothpaste, along with fluoride-containing rinses and varnishes. Importantly, a recent addition to the available armamentarium of fluoride therapeutics now exists in the form of metal ion-fluorido adducts, most especially silver(I)-diammine fluoride (SDF). In view of its high level of therapeutic success, very recently this agent was added to the World Health Authority's (WHO's) list of essential medicines available for the treatment and prevention of tooth decay. Overall, this current state of affairs merits a major review of all these fluoride-containing therapeutic compounds, together with their risks and benefits, both individually and collectively. In this study, a simple graphical tool has been developed for the rapid "on-site" evaluation of fluoride intake with respect to a range of oral healthcare products and body mass index is presented as a gauge of safety for the risk of fluoride toxicity in individual patients. This exposition commences with (a) an account of the history and value of fluoride therapeutics in clinical dentistry, including applications of monofluorophosphate and stannous fluoride; (b) an evaluation of the toxicological activities of fluoride, together with a summary of any reports, albeit very rare ones, arising from its clinically-driven overuse; (c) a history of the development, molecular structure, mechanisms of action, and therapeutic applications of SDF, including a summary of any possible toxic activities and effects arising from silver(I) ion rather than fluoride itself; and (d) the establishment of a working relationship between fluoride exposure and toxicity, with special reference to the instigation of newly-developed tabular/graphical reference guidelines for use by dental clinicians who employ fluoride-rich products in their practices. Particular attention is given to the oral care and treatment options of pediatric patients. In conclusion, applications of this unique monitoring tool may serve as a valuable toxicity guide for dental practitioners.

Nuclear Magnetic Resonance Spectroscopic Analysis of the Evolution of Peroxidation Products Arising from Culinary Oils Exposed to Thermal Oxidation: An Investigation Employing 1H and 1H-1H COSY and TOCSY Techniques.

Scientific warnings on the deleterious health effects exerted by dietary lipid oxidation products (LOPs) present in thermally stressed culinary oils have, to date, not received adequate attention given that there has been an increase in the use and consumption of such oil products in everyday life. In this study, high-resolution 1H nuclear magnetic resonance (NMR) analysis was used to characterize and map chemical modifications to fatty acid (FA) acyl groups and the evolution of LOPs in saturated fatty acid (SFA)-rich ghee, monounsaturated fatty acid (MUFA)-rich groundnut, extra virgin olive, and macadamia oils, along with polyunsaturated fatty acid (PUFA)-rich sesame, corn and walnut oils, which were all thermally stressed at 180 °C, continuously and discontinuously for 300 and 480 min, respectively. Results acquired revealed that PUFA-rich culinary oils were more susceptible to thermo-oxidative stress than the others tested, as expected. However, ghee and macadamia oil both generated only low levels of toxic LOPs, and these results demonstrated a striking similarity. Furthermore, at the 120 min thermo-oxidation time-point, the discontinuous thermo-oxidation episodes produced higher concentrations of aldehydic LOPs than those produced during continuous thermo-oxidation sessions for the same duration. On completion of the thermo-oxidation period, a higher level of triacylglycerol chain degradation, and hence, higher concentrations of aldehydes, were registered in culinary oils thermally stressed continuously over those found in discontinuous thermo-oxidized oils. These findings may be crucial in setting targets and developing scientific methods for the suppression of LOPs in thermo-oxidized oils.

Effects of Methylphenidate on the Dopamine Transporter and Beyond.

The dopamine transporter (DAT) is the main target of methylphenidate (MPH), which remains the number one drug prescribed worldwide for the treatment of Attention-Deficit Hyperactivity Disorder (ADHD). In addition, abnormalities of the DAT have been widely associated with ADHD. Based on clinical and preclinical studies, the direction of DAT abnormalities in ADHD are, however, still unclear. Moreover, chronic treatment of MPH has been shown to increase brain DAT expression in both animals and ADHD patients, suggesting that findings of overexpressed levels of DAT in ADHD patients are possibly attributable to the effects of long-term MPH treatment rather than the pathology of the condition itself. In this chapter, we will discuss some of the effects exerted by MPH, which are related to its actions on catecholamine protein targets and brain metabolites, together with genes and proteins mediating neuronal plasticity. For this purpose, we present data from biochemical, proton nuclear magnetic resonance spectroscopy (1H-NMR) and gene/protein expression studies. Overall, results of the studies discussed in this chapter show that MPH has a complex biological/pharmacological action well beyond the DAT.

Photobiomodulation effects on periodontal ligament stem cells: A systematic review of in-vitro studies.

BACKGROUND: 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 was 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 presented PBM protocols. Simple univariate regression analysis was performed to explore the significance of contributions of potential quantitative predictor variables towards study outcomes, and a one-way ANOVA model was employed for testing differences between the laser or LED sources of the treatments. The significance 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 appeared 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.

The influence of delivery power losses and full operating parametry on the effectiveness of diode visible-near infra-red (445-1064 nm) laser therapy in dentistry-a multi-centre investigation.

The 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-fibre 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.

Supplement therapy with apelin for improving the TSH level and lipid disorders in PTU-induced hypothyroid rats.

Hyperlipidemia is a common metabolic disorder in the general population, which may arise in hypothyroidism. Apelin is an endogenous ligand that acts as an adiponectin, and is involved in energy storage and metabolism. This study evaluated the effects of apelin administration per se or in combination with T4 on the serum level of thyroid-stimulating hormone (TSH), body weight, and lipid profile, along with the serum level of apelin, and its mRNA expression in heart, in 6-propyl-2-thiouracil (PTU)-induced hypothyroid rats. Male Wistar rats were assigned to five different groups: control, H (hypothyroid), H+A, H+T, and H+A+T. All groups except the control one received PTU (0.05%) in the drinking water for 6 weeks. In addition to PTU, the H+A, H+T, and H+A+T groups received apelin (200 µg/kg/day, i.p.), l-thyroxin (T4) (20 µg/kg/day, via gavage tube), and apelin+T4 during the last 14 days of the trial, respectively. A combined application of T4 and apelin in the H+A+T group effectively diminished mean TSH level, low-density-lipoprotein cholesterol/high-density-lipoprotein cholesterol ratio, and atherogenic index in these animals when compared with these values for the H group. Coadministration of apelin with T4 may offer valuable therapeutic benefits, specifically lowering blood plasma TSH, lipid disorder, and atherosclerosis biomarkers in PTU-induced hypothyroid rats.

The impact of partial oil substitution and trace metal ions on the evolution of peroxidation products in thermally stressed culinary oils.

Suppressing toxic aldehydic lipid oxidation product (LOP) generation in culinary oils is now considered vital, since the deleterious effects arising from their ingestion are implicated in a wide range of disease conditions. Partial substitution involves the replenishment of thermally-stressed culinary oils with corresponding unheated ones. This technique was tested by employing 10%, 25%, 50%, and 75% (v/v) partial substitutions of coconut, olive, rapeseed, and sunflower oils at 180℃ for a 300 min continuous thermo-oxidation duration. Oil samples were analysed by proton nuclear magnetic resonance (1H NMR) spectroscopy. Trace metal levels, including oxidation-reduction (redox)-active metal ions credited with enhancing cooking oil oxidation were also analysed using inductively coupled plasma-optical emission spectroscopy (ICP-OES). As expected, the degree of oil unsaturation, and the % partial substitutions significantly influenced their susceptibility to thermo-oxidation. In view of the very low polyunsaturated fatty acid (PUFA) and monounsaturated fatty acid (MUFA) contents of coconut oil, both the class and concentrations of evolved LOPs were found to be least affected by this partial substitution process. Aldehydic LOPs were greatly suppressed in partially-substituted rapeseed oil. The % suppression activity of LOPs evaluated for the partially substituted oils were generally high making partial oil substitutions an effective chemical-free method in suppressing LOPs at both industrial and commercial levels. In general, the % partial oil substitutions were directly related to the dilution effect observed for LOPs quantified in the oils. Furthermore, trace metal ion concentrations measured in the culinary oils did not influence the evolution of LOPs in the oils.

Photobiomodulation Delivery Parameters in Dentistry: An Evidence-Based Approach.

Background: Dosimetry at a level of 2-8 J/cm2 at target cellular level has been accepted to represent the optimum range for the stimulatory benefits associated with photobiomodulation therapies. However, it has been proposed that a higher bracket of 10-30 J/cm2 at target tissue level may represent a good and effective range for analgesia, accompanied by at-distance regional anti-inflammatory effects. However, although this provides a useful guideline, transforming recommendations into a translatable and repeatable clinical skill have to date proven elusive. Methods: Based on prior publications of systematic reviews by the authors, key factors have been identified, associated with reported clinical and in vitro and in vivo animal studies that can support outcome success or null responses. Drawn from five recently published systematic reviews, an analysis of an extended published evidence base indicates that research methodology should embrace a mature understanding of terminology, a requirement for consistent metered energy delivery, and an appreciation of optical transport techniques. Results: Using models derived from orthodontics and oncology, evidence-based optimal delivery parameters and techniques are presented. Within the confines of the accepted inclusion criteria, a modified Cochrane risk of bias tool has been applied and the parameters extracted from the included studies were subjected to a meta-analysis. This demonstrated a low risk of bias from the studies included with a multivariate and/or univariate statistical analysis that supports the author's evidence-based determinations. The adoption of a surface optical spot size of >1 cm2 demonstrated a high degree of success in managing both superficial as well as subsurface pathologies in oral care. Also, the timing of the intervention with conditioning before or at the same time as a potentially traumatic cellular event was found to be a significant signal of outcome success. An extended commentary explores the benefits and disadvantages of scanning techniques. Conclusions: The extracted clinical data are cross-referenced to the mechanisms suggested for photobiomodulation therapies from the authors' own current in vitro research, and proposals are made for some possible lines of approach in future research and clinical trials.

Computational simulation of 1 H NMR profiles of complex biofluid analyte mixtures at differential operating frequencies: Applications to low-field benchtop spectra.

Estimations 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 1 H 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 1 H 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 1 H resonances detectable allowed multiple component fits to be applied to experimental spectra. Hence, these salivary 1 H 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.

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.

Soybean 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.

The Role of Polydimethylsiloxane in Suppressing the Evolution of Lipid Oxidation Products in Thermo-Oxidised Sunflower Oil: Influence of Stirring Processes.

Suppressing the evolution of lipid oxidation products (LOPs) in commercially available culinary oils is considered to represent a valuable health-promoting incentive since these agents have cytotoxic and genotoxic properties and have been implicated in the pathogenesis of several chronic disease states. One agent used to suppress LOPs formation is polydimethylsiloxane (PDMS). In this study, proton nuclear magnetic resonance (1H NMR) analysis was employed to evaluating the influence of increasing PDMS concentrations (6.25 × 10-7, 1.0 × 10-5, 0.025, 0.05, 0.1, 0.5, 1.0, 5.0, and 10.0 ppm) in either stirred or unstirred refined sunflower oil exposed to thermal stressing episodes continuously at 180°C for 300 min with no oil replenishment. Results acquired showed that the extent of blockage of LOPs generation was correlated with increasing concentrations of PDMS. The minimal level of added PDMS required to provide a statistically significant protective role for both stirred and unstirred culinary oils when exposed to high frying temperatures was only 6.25 × 10-7 ppm. Furthermore, stirring at 250 rpm was experimentally determined to reduce the functional role PDMS. This is vital in a real world setting since the boiling process of frying may ultimately reduce the LOPs suppression activity of PDMS.