Publications by authors named "Mike Milward"

15 Publications

  • Page 1 of 1

The oral health and periodontal diseases awareness and knowledge in the Iraqi population: Online-based survey.

Clin Exp Dent Res 2020 10 26;6(5):519-528. Epub 2020 Jun 26.

College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.

Objectives: This study aimed to evaluate oral health (OH) and periodontal diseases (PD) awareness in the Iraqi population.

Material And Methods: This study was a questionnaire-based online survey of two weeks duration. The questionnaire was built using a Google platform and was distributed randomly via social media (Facebook and Telegram). The questionnaire consisted of a demographic data section and two other main sections for the evaluation of OH and PD awareness. Each response was marked with "1" for a positive answer and "0" for the other answers. For each respondent, answers were summed to give an overall score. The frequency of positive responses was used to determine the association of awareness with demographic data and the level of awareness into low, moderate, and high levels.

Results: A total of 1,465 were included in the final analysis after application of exclusion criteria. The respondents showed significantly higher levels of awareness about PD (mean ± SD = 3.66 ± 1.42) than OH awareness (mean ± SD = 2.19 ± 1.29). Analysis of data showed that OH awareness was mainly associated with high degree holders (OR 1.851) and age > 45 years (OR 1.730). However, PD awareness did not show any evident association with demographic variables investigated. In general, the respondents exhibited low levels of OH knowledge and low to moderate level of PD knowledge.

Conclusions: Despite limitations, this study revealed inappropriate levels of OH and PD awareness and knowledge in the Iraqi population and provided the baseline data necessary for the development of Governmental educational programs and health awareness campaigns which are highly suggested particularly focusing on the primary and high schools, in an attempt to improve the levels of awareness.
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http://dx.doi.org/10.1002/cre2.304DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7545227PMC
October 2020

A randomized double-blind clinical trial to evaluate the efficacy of chlorhexidine, antioxidant, and hyaluronic acid mouthwashes in the management of biofilm-induced gingivitis.

Int J Dent Hyg 2020 Aug 20;18(3):268-277. Epub 2020 Mar 20.

College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.

Objectives: To investigate the antiplaque and antigingivitis efficacy in addition to evaluating side effects and subjects' perceptions of three commercially available mouthwashes.

Methods: This study was a double-blind, parallel, and short-term trial. A total of 75 dental students with biofilm-induced gingivitis were included in the final analysis of the current study. Clinical parameters (plaque index and bleeding on probing) and the staining effect were measured at baseline and after 7 days. In addition, a VAS-based assessment questionnaire was completed by the participants.

Results: All interventions significantly reduced plaque scores, but chlorhexidine (CHX) had a significantly higher effect than the hyaluronic acid (HA) and antioxidant mouthwashes. However, all mouthwashes significantly reduced the total bleeding scores to <10% in 53% of the patients, compared to the baseline record. Additionally, teeth underwent shade changes in association with all interventions by the end of the study. Analysis of feedback about the mouthwashes showed that the participants seemed to prefer the HA mouthwash over the other mouthwashes.

Conclusions: CHX remains the most effective antiplaque mouthwash although HA and antioxidants are as effective as CHX in reducing bleeding. In addition, based on its better acceptance by the participants, HA is potentially a good alternative to CHX.
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http://dx.doi.org/10.1111/idh.12432DOI Listing
August 2020

Periodontal diagnosis in the context of the BSP implementation plan for the 2017 classification system of periodontal diseases and conditions: presentation of a patient with severe periodontitis following successful periodontal therapy and supportive periodontal treatment.

Br Dent J 2019 Mar;226(6):411-413

Department of Oral Surgery, The School of Dentistry, University of Birmingham, Birmingham, UK.

Case report A case of a 59-year-old female patient who attended with a history of periodontitis, who had been successfully treated and maintained for several years, is described. Following a full periodontal assessment, the patient was diagnosed with 'generalised periodontitis; stage IV; grade C; currently stable'.Conclusion The present case report exemplifies the use of the 2017 classification system in a successfully treated and well-maintained patient whose treatment need is supportive periodontal treatment. It recognises the fact that, by staging and grading, the patient is a high-risk periodontitis patient due to historical disease experience, but also that following successful therapy and maintenance she is currently 'stable' with no need for active periodontal therapy.
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http://dx.doi.org/10.1038/s41415-019-0143-8DOI Listing
March 2019

Periodontal diagnosis in the context of the BSP implementation plan for the 2017 classification system of periodontal diseases and conditions: presentation of a patient with a history of periodontal treatment.

Br Dent J 2019 02;226(4):265-267

Department of Oral Surgery, The School of Dentistry, University of Birmingham, Birmingham, UK.

This case report is the fourth in a series that illustrates the application of the BSP implementation plan for diagnosing periodontitis patients according to the 2017 classification. It demonstrates the diagnostic approach and disease classification for a previously treated patient who presented with a diagnosis of unstable generalised periodontitis; stage IV, grade C. We describe a case of a 49-year-old patient who attended with a history of periodontal treatment over several years. Following a full periodontal assessment, the patient was diagnosed with 'generalised periodontitis; stage IV, grade C; currently unstable'. This case report presents an example of how to classify and diagnose a patient using the 2017 classification system and highlights challenges with the application of the new classification in patients with a previous history of periodontal therapy.
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http://dx.doi.org/10.1038/s41415-019-0015-2DOI Listing
February 2019

Differential responses of myoblasts and myotubes to photobiomodulation are associated with mitochondrial number.

J Biophotonics 2019 06 20;12(6):e201800411. Epub 2019 Feb 20.

School of Dentistry, College of Medical and Dental Sciences, Institute of Clinical Sciences, University of Birmingham, Birmingham, UK.

Objective: Photobiomodulation (PBM) is the application of light to promote tissue healing. Current indications suggest PBM induces its beneficial effects in vivo through upregulation of mitochondrial activity. However, how mitochondrial content influences such PBM responses have yet to be evaluated. Hence, the current study assessed the biological response of cells to PBM with varying mitochondrial contents.

Methods: DNA was isolated from myoblasts and myotubes (differentiated myoblasts), and mitochondrial DNA (mtDNA) was amplified and quantified using a microplate assay. Cells were seeded in 96-wellplates, incubated overnight and subsequently irradiated using a light-emitting diode array (400, 450, 525, 660, 740, 810, 830 and white light, 24 mW/cm , 30-240 seconds, 0.72-5.76J/cm ). The effects of PBM on markers of mitochondrial activity including reactive-oxygen-species and real-time mitochondrial respiration (Seahorse XFe96) assays were assessed 8 hours post-irradiation. Datasets were analysed using general linear model followed by one-way analysis of variance (and post hoc-Tukey tests); P = 0.05).

Results: Myotubes exhibited mtDNA levels 86% greater than myoblasts (P < 0.001). Irradiation of myotubes at 400, 450 or 810 nm induced 53%, 29% and 47% increases (relative to non-irradiated control) in maximal respiratory rates, respectively (P < 0.001). Conversely, irradiation of myoblasts at 400 or 450 nm had no significant effect on maximal respiratory rates.

Conclusion: This study suggests that mitochondrial content may influence cellular responses to PBM and as such explain the variability of PBM responses seen in the literature.
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http://dx.doi.org/10.1002/jbio.201800411DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7065641PMC
June 2019

Characterization, Quantification, and Visualization of Neutrophil Extracellular Traps.

Methods Mol Biol 2017 ;1537:481-497

Institute of Clinical Sciences, College of Medical and Dental Sciences, The School of Dentistry, University of Birmingham, 5 Mill Pool Way, Edgbaston, Birmingham, B5 7EG, UK.

Following the discovery of neutrophil extracellular traps (NETs) in 2004 by Brinkmann and colleagues, there has been extensive research into the role of NETs in a number of inflammatory diseases, including periodontitis. This chapter describes the current methods for the isolation of peripheral blood neutrophils for subsequent NET experiments, including approaches to quantify and visualize NET production, the ability of NETs to entrap and kill bacteria, and the removal of NETs by nuclease-containing plasma.
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http://dx.doi.org/10.1007/978-1-4939-6685-1_29DOI Listing
January 2018

Oral Epithelial Cell Culture Model for Studying the Pathogenesis of Chronic Inflammatory Disease.

Methods Mol Biol 2017 ;1537:381-401

Institute of Clinical Sciences, College of Medical and Dental Sciences, The School of Dentistry, University of Birmingham, 5 Mill Pool Way, Edgbaston, Birmingham, B5 7EG, UK.

The interactions between bacteria, epithelium, and neutrophilic polymorphonuclear leukocytes (neutrophils) are the key to the initiation and progression of many chronic inflammatory-immune diseases. In addition, all can be influenced by external factors, such as micronutrients, thereby providing potentially novel approaches to therapy. This chapter will therefore provide detailed methods for core techniques involved in studying cellular and molecular epithelial responses to a bacterial challenge in relation to chronic inflammatory disease pathogenesis and therapy.
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http://dx.doi.org/10.1007/978-1-4939-6685-1_22DOI Listing
January 2018

Antioxidant Micronutrients and Oxidative Stress Biomarkers.

Methods Mol Biol 2017 ;1537:61-77

School of Dentistry, Institute of Clinical Sciences, Collegeof Medical and Dental Sciences, University of Birmingham, 5 Mill Pool Way, Edgbaston, Birmingham, B5 7EG, UK.

Chronic inflammatory diseases are the major causes of mortality in humans and recent research has improved our understanding of the major impact of life-style factors upon inflammatory diseases and conditions. One of the most influential of these is nutrition, which may drive both pro-inflammatory as well as anti-inflammatory cascades at molecular and cellular levels. There are a variety of model systems that may be employed to investigate the impact of micronutrients and macronutrients upon inflammatory pathways, many of which operate through oxidative stress, either at the level of controlling the redox state of the cell and downstream redox-regulated gene transcription factors, and other acting as free radical generating or scavenging agents. This chapter focuses upon biological sample preparation prior to assay and details methods for analyzing certain antioxidant micronutrients and biomarkers of oxidative stress.
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http://dx.doi.org/10.1007/978-1-4939-6685-1_4DOI Listing
January 2018

Peripheral blood neutrophil extracellular trap production and degradation in chronic periodontitis.

J Clin Periodontol 2016 12 27;43(12):1041-1049. Epub 2016 Oct 27.

Periodontal Research Group and MRC Centre for Immune Regulation, School of Dentistry, University of Birmingham, UK and Birmingham Community Healthcare Trust, 5 Mill Pool Way, Birmingham, B5 7EG, UK.

Aims: To investigate ex vivo peripheral neutrophil extracellular trap (NET) production and their subsequent degradation by plasma in chronic periodontitis patients, and periodontally and systemically healthy-matched controls.

Materials And Methods: Chronic periodontitis patient and control (n = 40 pairs) peripheral blood neutrophils (PBN) were stimulated for NET quantification. A subset of patients received non-surgical periodontal therapy (n = 19) and NETs were quantified 3 months later alongside controls. Blood plasma was collected from patients and controls to quantify plasma-induced NET degradation (n = 19 pairs). Subsequent experiments quantified plasma concentrations of DNase-1, immunoglobulin G (IgG), free light chains (FLCs), and cystatin C.

Results: No differences were observed in NET production between patients and controls. However, NET production decreased significantly in patients post-treatment. Plasma NET degradation was significantly lower in patients than controls, which may be due to significantly reduced DNase-1 levels as demonstrated, or potentially due to elevated IgG/FLC concentrations in patients. NET degradation post-periodontal treatment was comparable between patients and controls.

Conclusions: NET production was comparable between patients and controls; however, non-surgical therapy causes attenuated NETs. NET degradation by plasma is impaired in untreated chronic periodontitis, potentially increasing the chronic NET burden, which may enhance antimicrobial function, or conversely, increase the risk of autoimmune/inflammatory responses.
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http://dx.doi.org/10.1111/jcpe.12628DOI Listing
December 2016

Differential activation of neutrophil extracellular traps by specific periodontal bacteria.

Free Radic Biol Med 2014 Oct 10;75 Suppl 1:S53. Epub 2014 Dec 10.

University of Birmingham (Dental School), Medical and Dental School, UK.

Periodontitis is a chronic inflammatory disease initiated by periodontal pathogens. Neutrophils play a pivotal role within the periodontal lesion, where they have a cytotoxic arsenal at their disposal, including Reactive oxygen species (ROS) and release of neutrophil extracellular trap (NETs). ROS production is essential for NET release and neutrophils in periodontitis patients are hyperactive and hyper-reactive with regard to ROS release (Matthews 2007), which may lead to disease progression. Here we characterise NET and ROS release in response to specific periodontal bacteria. Peripheral blood neutrophils were incubated with a panel of bacteria, including F. nucleatum and C. gingivalis. Neutrophil total ROS and superoxide release were measured (2hours) by luminol and lucigenin-enhanced chemiluminescence respectively. NET release was assayed by incubating the cells with bacteria for 4hours and fluorometrically quantifying NET DNA with sytox green (Palmer 2012). In all assays phorbol myristate acetate [PMA] was used as a positive control. Relative to unstimulated neutrophils S. Gordinii, F. nucleatum, V. parvula and A. viscosus stimulated significantly greater total ROS release (n=5, p=<0.05). S. Gordinii and V. parvula (n=5, p=<0.05) also stimulated significantly higher levels of superoxide.Bacterial stimulation of NETs (n=5) showed marked heterogeneity, with F. nucleatum and S. Gordinii stimulating higher levels of NETs than other species. Collectively, these data demonstrate variability between periodontal bacteria in their ability to stimulate neutrophil total ROS production, superoxide and NET responses. This variability may contribute to altered NET production in-vivo by specific periodontal bacteria and may contribute to the pathogenesis of periodontitis. Mechanisms may include bacterial avoidance of NET stimulation and thus persistence of infection, or excess NET release with associated autoimmunity.
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http://dx.doi.org/10.1016/j.freeradbiomed.2014.10.827DOI Listing
October 2014

Sulforaphane restores cellular glutathione levels and reduces chronic periodontitis neutrophil hyperactivity in vitro.

PLoS One 2013 24;8(6):e66407. Epub 2013 Jun 24.

Life and Health Sciences, Aston Research Centre for Healthy Ageing, Aston University, Birmingham, United Kingdom.

The production of high levels of reactive oxygen species by neutrophils is associated with the local and systemic destructive phenotype found in the chronic inflammatory disease periodontitis. In the present study, we investigated the ability of sulforaphane (SFN) to restore cellular glutathione levels and reduce the hyperactivity of circulating neutrophils associated with chronic periodontitis. Using differentiated HL60 cells as a neutrophil model, here we show that generation of extracellular O2 (. -) by the nicotinamide adenine dinucleotide (NADPH) oxidase complex is increased by intracellular glutathione depletion. This may be attributed to the upregulation of thiol regulated acid sphingomyelinase driven lipid raft formation. Intracellular glutathione was also lower in primary neutrophils from periodontitis patients and, consistent with our previous findings, patients neutrophils were hyper-reactive to stimuli. The activity of nuclear factor erythroid-2-related factor 2 (Nrf2), a master regulator of the antioxidant response, is impaired in circulating neutrophils from chronic periodontitis patients. Although patients' neutrophils exhibit a low reduced glutathione (GSH)/oxidised glutathione (GSSG) ratio and a higher total Nrf2 level, the DNA-binding activity of nuclear Nrf2 remained unchanged relative to healthy controls and had reduced expression of glutamate cysteine ligase catalytic (GCLC), and modifier (GCLM) subunit mRNAs, compared to periodontally healthy subjects neutrophils. Pre-treatment with SFN increased expression of GCLC and GCM, improved intracellular GSH/GSSG ratios and reduced agonist-activated extracellular O2 (. -) production in both dHL60 and primary neutrophils from patients with periodontitis and controls. These findings suggest that a deficiency in Nrf2-dependent pathways may underpin susceptibility to hyper-reactivity in circulating primary neutrophils during chronic periodontitis.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0066407PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3691189PMC
March 2014

Mapping biological to clinical phenotypes during the development (21 days) and resolution (21 days) of experimental gingivitis.

J Clin Periodontol 2012 Feb 12;39(2):123-31. Epub 2011 Dec 12.

Unilever Oral Care, Bebington, UK.

Aim: To characterize and map temporal changes in the biological and clinical phenotype during a 21-day experimental gingivitis study.

Materials And Methods: Experimental gingivitis was induced over 21 days in healthy human volunteers (n = 56), after which normal brushing was resumed (resolution phase). Gingival and plaque indices were assessed. Gingival crevicular fluid was collected from four paired test and contra-lateral control sites in each volunteer during induction (Days 0, 7, 14 and 21) and resolution (Days 28 and 42) of experimental gingivitis. Fluid volumes were measured and a single analyte was quantified from each site-specific, 30s sample. Data were evaluated by analysis of repeated measurements and paired sample tests.

Results: Clinical indices and gingival crevicular fluid volumes at test sites increased from Day 0, peaking at Day 21 (test/control differences all p < 0.0001) and decreased back to control levels by Day 28. Levels of four inflammatory markers showed similar patterns, with significant differences between test and control apparent at Day 7 (substance P, cathepsin G, interleukin-1β, elastase: all p < 0.03) and peaking at Day 21 (all p < 0.002). Levels of α-1-antitrypsin showed no pattern.

Conclusions: Levels of substance P, cathepsin G, interleukin-1β and neutrophil elastase act as objective biomarkers of gingival inflammation induction and resolution that typically precede phenotypical changes.
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http://dx.doi.org/10.1111/j.1600-051X.2011.01825.xDOI Listing
February 2012

Management of periodontal disease in general dental practice.

Dent Update 2010 Jun;37(5):310-2, 314-6, 319-20

Eastman Dental Hospital, Birmingham, UK.

Unlabelled: This paper reviews the important parameters deemed useful in the diagnosis and management of periodontal disease in general dental practice. We aim to highlight the importance of these when making a diagnosis and the necessary treatment undertaken in general dental practice before considering referral to specialist services. We also provide guidelines to assist the referral of patients for periodontal treatment in specialist care settings.

Clinical Relevance: This paper provides the knowledge base to facilitate correct management of periodontal disease in dental practice.
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http://dx.doi.org/10.12968/denu.2010.37.5.310DOI Listing
June 2010

Competency assessment for infection control in the undergraduate dental curriculum.

Eur J Dent Educ 2007 Aug;11(3):148-54

School of Dentistry, University of Birmingham, St Chads Queensway, Birmingham, UK.

Objectives: This study aimed at investigating the introduction of an infection control competency assessment on undergraduate dental student's awareness and knowledge of infection control.

Method: A short course, including an introductory lecture and a three component competency based assessment exercise testing student's knowledge and ability in infection control measures was incorporated into the previously established training programme. The assessment exercises included a written test of students' knowledge of the Infection Control Policy, a unit management exercise and a hand hygiene assessment. The infection control competency was initially incorporated into the final term of the second year in 2004 and is now an established part of the 5-year dental undergraduate degree programme. Re-assessments were scheduled (at the start of third year) for students failing to meet the required standard as successful completion of this course was compulsory prior to students being allowed to treat their first patients. Student performance over the last 2 years on this course and during their first year on clinic were analysed to determine potential improvements in student knowledge and application in infection control. Examination results from the year 3, infection control spot test were compared with those of earlier years. In addition, the opinions, as assessed by questionnaire analysis, of dental staff and students on the infection control competency were obtained.

Results: All students successfully completed the infection control competency (either at first or second attempt) and were subsequently allowed to enter clinical training in year 3. Significant improvements were seen in students passing the course at their initial attempt, 42% and 78%, in the 2004 and 2005 academic years, respectively. Also subsequent testing of these students during their first year on clinic showed marked increases in awareness and knowledge of the infection control protocols. Staff and student feedback on this course was also found to be highly supportive of the introduction of the infection control competency.

Conclusion: Incorporation of additional formal pre-clinical teaching and introduction of an infection competency potentially provides enduring knowledge and clinical application benefits.
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http://dx.doi.org/10.1111/j.1600-0579.2007.00439.xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7194216PMC
August 2007

The prevalence of inflammatory periodontitis is negatively associated with serum antioxidant concentrations.

J Nutr 2007 Mar;137(3):657-64

Periodontal Research Group, University of Birmingham, School of Dentistry, St. Chads Queensway, Birmingham, B4 6NN, UK.

Chronic periodontitis is an inflammatory disease that affects the supporting tissues of the teeth. It is initiated by specific bacteria within the plaque biofilm and progresses due to an abnormal inflammatory-immune response to those bacteria. Periodontitis is the major cause of tooth loss and is also significantly associated with an increased risk of stroke, type-2 diabetes and atheromatous heart disease. Oxidative stress is reported in periodontitis both locally and peripherally (serum), providing potential mechanistic links between periodontitis and systemic inflammatory diseases. It is therefore important to examine serum antioxidant concentrations in periodontal health/disease, both at an individual species and total antioxidant (TAOC) level. To determine whether serum antioxidant concentrations were associated with altered relative risk for periodontitis, we used multiple logistic regression for dual case definitions (both mild and severe disease) of periodontitis in an analysis of 11,480 NHANES III adult participants (>20 y of age). Serum concentrations of vitamin C, bilirubin, and TAOC were inversely associated with periodontitis, the association being stronger in severe disease. Vitamin C and TAOC remained protective in never-smokers. Higher serum antioxidant concentrations were associated with lower odds ratios for severe periodontitis of 0.53 (CI, 0.42,0.68) for vitamin C, 0.65 (0.49,0.93) for bilirubin, and 0.63 (0.47,0.85) for TAOC. In the subpopulation of never-smokers, the protective effect was more pronounced: 0.38 (0.26,0.63, vitamin C) and 0.55 (0.33,0.93, TAOC). Increased serum antioxidant concentrations are associated with a reduced relative risk of periodontitis even in never-smokers.
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http://dx.doi.org/10.1093/jn/137.3.657DOI Listing
March 2007