Concussion in the UK: a contemporary narrative review.

Concussion has been receiving an increasing amount of media exposure following several high-profile professional sports controversies and multimillion-dollar lawsuits. The potential life-changing sequalae of concussion and the rare, but devasting, second impact syndrome have also gained much attention. Despite this, our knowledge of the pathological processes involved is limited and often extrapolated from research into more severe brain injuries. As there is no objective diagnostic test for concussion. Relying on history and examination only, the diagnosis of concussion has become the rate-limiting step in widening research into the disease. Clinical study protocols therefore frequently exclude the most vulnerable groups of patients such as those with existing cognitive impairment, concurrent intoxication, mental health issues or learning difficulties. This up-to-date narrative review aims to summarize our current concussion knowledge and provides an insight into promising avenues for future research.

Porphyromonas gingivalis Conditioned Medium Induces Amyloidogenic Processing of the Amyloid-ß Protein Precursor upon in vitro Infection of SH-SY5Y Cells.

Background: Cleavage of the amyloid-ß protein precursor (AßPP) mediated by host secretase enzymes, releases several fragments including amyloid-ß (Aß40 and Aß42). Objective: To determine if Porphyromonas gingivalis conditioned medium cleaved AßPP to release Aß40 and Aß42. Methods: The SH-SY5Y cell line was challenged, in vitro, with P. gingivalis (Pg381) conditioned medium in the presence/absence of cytokines. The cells and their supernatants were assessed for AßPP cleavage fragments by immunoblotting and transmission electron microscopy. Results: Western blotting of the cell lysates with the anti-AßPP C-terminal antibody demonstrated variable molecular weight bands corresponding to full length and fragmented AßPP in lanes treated with the following factors: Tryptic soy broth (TSB), Pg381, IL-6, Pg381 + IL-1ß, and Pg381 + TNF-α. The low molecular weight bands corresponding to the C99 dimerized fragment were observed in the Pg381 and interlukin-6 (IL-6) treated groups and were significantly more intense in the presence of Pg381 with either IL-6 or TNF-α. Bands corresponding to the dimerized C83 fragment were observed with cells treated with TNF-α alone and with Pg381 combined with IL-1ß or IL-6 or TNF-α. The anti-Aß antibody detected statistically significant Aß40 and Aß42, levels when these two Aß species were pooled across test samples and compared to the untreated group. Electron microscopic examination of the supernatants demonstrated insoluble Aß40 and Aß42. Conclusion: These observations strongly imply that AßPP is an infection responsive protein cleaved via the amyloidogenic pathway on exposure to conditioned medium and in the presence of pro-inflammatory mediators.

Concussion in Non-athletes: Assessment of Cognition and Symptomatology (CONTACTS) study protocol - an exploratory cohort study investigating the utility of sports concussion assessment tools and salivary microRNAs to diagnose concussion in NHS patients.

INTRODUCTION: Concussion is a complex pathophysiological process with a wide range of non-specific signs and symptoms. There are currently no objective diagnostic tests to identify concussion, and diagnosis relies solely on history and examination. Recent research has identified a unique panel of microRNAs (miRNAs) that distinguish between concussed and non-concussed rugby players. This study aims to assess the diagnostic utility of salivary miRNAs in concussion for a sample of UK National Health Service patients and whether well-established sports-related concussion (SRC) assessment tools may be translated into the emergency department (ED). METHODS AND ANALYSIS: Concussion in Non-athletes: Assessment of Cognition and Symptomatology is a single-centre, prospective, two-phase cohort study. The concussed cohort will consist of participants with maxillofacial trauma and concurrent concussion. The control cohort will consist of participants with isolated limb trauma and no evidence of concussion. Participants will be recruited in the ED and saliva samples will be taken to identify the presence of miRNAs. The SRC assessments being investigated include the Sports Concussion Assessment Test, Fifth Edition (SCAT5), the Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) and the ImPACT Quick. Follow-up will be at 24-48 hours in-hospital and remotely via telephone and email at 14 days and 6 months. ETHICS AND DISSEMINATION: Ethical approval was granted in February 2021 by the West Midlands Coventry & Warwickshire Research Ethics Committee (ref 20/WM/0299). The investigators intend to submit their study findings for publication in peer-reviewed journals and to disseminate study findings via presentation at academic meetings. The results will also form part of a doctorate thesis, registered at the University of Birmingham.

Antimicrobial, Polarizing Light, and Paired Helical Filament Properties of Fragmented Tau Peptides of Selected Putative Gingipains.

BACKGROUND: Tau is an established substrate for gingipains secreted by Porphyromonas gingivalis. Hyperphosphorylation of tau and neurofibrillary tangle (NFT) formation is a defining lesion of Alzheimer's disease (AD) where NFT distribution is related to Braak stage and disease severity. OBJECTIVE: To assess gingipains'-fragmented tau peptides for their antimicrobial properties and for the likelihood of paired helical/straight filament (PHF/SF) formation with implications for the NFT lesion. METHODS: Seven non-phosphorylated (A-G) and three phosphorylated (A-C) tau peptides, were tested for antimicrobial properties against P. gingivalis. Polarizing light properties were determined using Congo Red staining. Secondary and tertiary structures of peptides B-F were determined using transmission electron microscopy (TEM) and circular dichroism (CD) was undertaken for the soluble peptides A in phosphorylated and non-phosphorylated states. RESULTS: Phosphorylated tau peptide A displayed a significant effect against planktonic P. gingivalis. The CD results demonstrated that both peptides A, in phosphorylated and non-phosphorylated states, in aqueous solution, adopted mainly ß-type structures. Non-phosphorylated peptides B-F and phosphorylated peptides B-C were insoluble and fibrillar under the TEM. The secondary and tertiary structures of the non-phosphorylated peptide B demonstrated fewer helical twists, whereas peptide C displayed significantly more helical twists along the whole fiber(s) length following its phosphorylation. CONCLUSION: Phosphorylated peptide A reduced P. gingivalis viability. CD spectroscopy demonstrated the phosphorylated and the non-phosphorylated peptide A predominantly formed from ß-sheet structures in aqueous solution with potential antimicrobial activity. Phosphorylation of tau peptides physically changed their tertiary structure into PHFs with potential for self-aggregation and binding to the NFT lesion.

Periodontitis as a Risk Factor for Alzheimer's Disease: The Experimental Journey So Far, with Hope of Therapy.

Periodontitis and Alzheimer's disease (AD) exist globally within the adult population. Given that the risk of AD incidence doubles within 10 years from the time of periodontal disease diagnosis, there is a window of opportunity for slowing down or preventing AD by risk-reduction-based intervention. Literature appraisal on the shared risk factors of these diseases suggests a shift to a healthy lifestyle would be beneficial. Generalised (chronic) periodontitis with an established dysbiotic polymicrobial aetiology affects the tooth supporting tissues with eventual tooth loss. The cause of AD remains unknown, however two neurohistopathological lesions - amyloid-beta plaques and neurofibrillary tangles, together with the clinical history, provide AD diagnosis at autopsy. Historically, prominence was given to the two hallmark lesions but now emphasis is placed on cerebral inflammation and what triggers it. Low socioeconomic status promotes poor lifestyles that compromise oral and personal hygiene along with reliance on poor dietary intake. Taken together with advancing age and a declining immune protection, these risk factors may negatively impact on periodontitis and AD. These factors also provide a tangible solution to controlling pathogenic bacteria indigenous to the oral and gastrointestinal tract microbioes in vulnerable subjects. The focus here is on Porphyromonas gingivalis, one of several important bacterial pathogens associated with both periodontitis and AD. Recent research has enabled advances in our knowledge of the armoury of P. gingivalis via reproduction of all clinical and neuropathological hallmark lesions of AD and chronic periodontal disease in vitro and in vivo experimental models, thus paving the way for better future management.

Ex vivo Detection of Amyloid-ß in Naturally Formed Oral Biofilm.

Background: Oral infection has been implicated in the possible etiology of Alzheimer's disease. Objective: To detect amyloid-ß (Aß) within microbial biofilms. Methods: Freshly extracted teeth (N = 87) with periodontal disease were separated into Group A (N = 11), with primary root canal infection and Group B (N = 21) with failed endodontic treatment identified by the presence of, gutta percha root filling. Biofilm characteristics were observed by scanning electron microscopy (SEM). Demineralized paraffin wax embedded tooth sections and mineralized calculus biofilm were immunostained with the anti-Aß antibody. The gutta perchas were processed either for on-section acrylic resin tissue immunocolloidal gold silver staining (IGSS) using the anti-Aß antibody or in Araldite resin for ultrastructure. Results: SEM demonstrated calculus and gutta percha in situ harboring a polymicrobial biofilm featuring extracellular polymeric substance (EPS) and water channels. Immunohistochemistry on rehydrated paraffin wax tooth sections from Group A, demonstrated Aß staining on external (calculus and plaque) and all intracanal infected regions. In Group B, the gutta percha biofilm IGSS gave an inconclusive result for Aß. Transmission electron microscopy of selected teeth with infected intra-canals (Group A) and 20% of gutta percha biofilm (Group B) EPS contained electron dense fibrils of variable sizes, some of which were typical of human Aß fibrils. Conclusion: This study detected both soluble and insoluble Aß fibrils within the EPS of periodontal and endodontic natural biofilm, strongly suggesting its role as an antimicrobial peptide in combatting local infection, with potential risk for cross-seeding into the brain for AD development.

Porphyromonas gingivalis (W83) Infection Induces Alzheimer's Disease-Like Pathophysiology in Obese and Diabetic Mice.

BACKGROUND: Periodontal disease(s) and metabolic illnesses negatively impact the quality of life and, eventually mental health. OBJECTIVE: This study investigated the effect of Porphyromonas gingivalis (W83) oral infection on the development of Alzheimer's disease (AD) pathophysiology in a wild-type obese, diabetic (db/db) mouse model. METHODS: The db/db mice were either orally infected with P. gingivalis and Fusobacterium nucleatum or sham infected for 16 weeks. The presence of amyloid-ß (Aß) and neurofibrillary tangles (NFTs) were assessed using a silver impregnation technique and subsequently by immunohistochemistry for tau and neuroinflammation. The mRNA abundance of a panel of 184 genes was performed using quantitative real-time PCR, and the differentially expressed genes were analyzed by Ingenuity Pathway Analysis. RESULTS: While no Aß plaques and NFTs were evident by silver impregnation, immunohistochemistry (glial cell markers) of the P. gingivalis-infected mice tissue sections exhibited neuroinflammation in the form of reactive microglia and astrocytes. Anti-tau immunopositivity, in addition to cells, was prominent in thickened axons of hippocampal CA neurons. The mRNA abundance of crucial genes in the insulin signaling pathway (INSR, IGF1, IRS, IDE, PIK3R, SGK1, GYS, GSK3B, AKT1) were upregulated, potentially exacerbating insulin resistance in the brain by P. gingivalis oral infection. Increased mRNA abundance of several kinases, membrane receptors, transcription factors, and pro-inflammatory mediators indicated hyperactivation of intracellular cascades with potential for tau phosphorylation and Aß release in the same infection group. CONCLUSION: P. gingivalis W83 infection of db/db mice provides a disease co-morbidity model with the potential to reproduce AD pathophysiology with induced periodontal disease.

Endodontic Management of Traumatised Permanent Anterior Teeth.

Traumatised permanent anterior teeth can require endodontic treatment which may be immediate as part of acute trauma management, or delayed due to the development of sequelae. This paper will enable clinical decision making by exploring a range of situations in which endodontic treatment may be indicated, and also offer practical advice regarding effective endodontic treatment for paediatric dental trauma patients.Endodontic treatment of traumatised permanent teeth in paediatric patients is often challenging. However, with timely decision making and appropriate treatment, these teeth can often last throughout childhood and adolescence thus ensuring that a young patient does not have the social burden of a missing tooth and needing a prosthesis, and has the maximum restorative options available to them as they enter adulthood.

Porphyromonas gingivalis is a Strong Risk Factor for Alzheimer's Disease.

Porphyromonas gingivalis (P. gingivalis) is one of the several important bacterial pathogens associated with the sporadic Alzheimer's disease (AD). Different serotypes are either capsulated or are non-capsulated. It has been demonstrated that P. gingivalis (non-capsulated) can reproduce the neurodegenerative AD-like changes in vitro, and a capsular P. gingivalis (strain W83) could reproduce the cardinal hallmark lesions of AD in a wild-type mouse model. All P. gingivalis forms express proteolytically active proteases that enable cleavage of the amyloid-ß protin precursor (AßPP) and tau resulting in the formation of amyloid-ß and neurofibrillary tangles. Tau is an established substrate for gingipains, which can cleave tau into various peptides. Some of the P. gingivalis fragmented tau protein peptides contain "VQIINK" and "VQIVYK" hexapeptide motifs which map to the flanking regions of the microtubule binding domains and are also found in paired helical filaments that form NFTs. P. gingivalis can induce peripheral inflammation in periodontitis and can also initiate signaling pathways that activate kinases, which in turn, phosphorylate neuronal tau. Periodontal disease related inflammation has metabolic implications for an individual's peripheral and brain health as patients suffering from generalized periodontitis often have related co-morbidities and are "at risk" of developing AD. The aim here is to discuss the role of P. gingivalis behind such associations with the backdrop of huge efforts to test P. gingivalis virulence factors clinically (GAIN Trial: Phase 2/3 Study of COR388 in Subjects with AD) with inhibitors, which may lead to an intervention by reducing the pathogenic bacterial load.

In real life: evaluating primary care-based undergraduate dental education in Northwest England.

Aim To explore how working at dental education centres (DECs), away from the university campus, has influenced the attitudes of dental students towards providing dental care in a primary setting, and whether students feel that this model of dental education meets their perceived training needs.Design Exploratory, qualitative interview study.Methods Semi-structured interviews with five fourth BDS students, analysed using thematic analysis.Results The main theme identified was 'real life dentistry', as students described how their clinical experiences and the teaching at DECs would prepare them for life as a general dental practitioner. Students felt they had a positive impact on their patients, and although some felt they could not comment on the impact to the community, others thought that this was likely to be positive.Conclusion Students believed they experienced 'real life dentistry' which would prepare them well for their foundation year and future practice. They also believed they had a positive impact on their patients.

The Emergency Treatment of Traumatised Permanent Anterior Teeth in Children and Adolescents.

This article aims to provide a practical clinician's guide to assessing and diagnosing dental trauma involving permanent teeth in children and young people, and for carrying out appropriate, guideline supported acute management. Timely referral to specialist paediatric dental services is crucial in more complex trauma presentations and will lead to improved outcomes for the dentition. Appropriate acute management by the primary clinician optimises the prognosis of any traumatised tooth and this article will focus on the emergency treatment of the traumatised permanent tooth.

How Danish dentists and dental hygienists handle their role in child abuse and neglect matters.

OBJECTIVE: The objective of this study was to identify how the dental team perceives its role in safeguarding children, to identify barriers to referral to social services, to compare data with data previously reported from Denmark, and to assess if increased focus on safeguarding children has had an effect on how the dental team handles its responsibility to refer to social services. MATERIAL AND METHODS: The study is based on a Danish version of a questionnaire previously used in Scotland and Denmark. The questionnaire was sent to a random sample of the Danish dental team. RESULTS: The number of returned questionnaires was 964 (67.0%) with valid data. Of these, 40.8% had had a suspicion of child abuse or neglect and 50.0% had referred their concern to social services. Frequently reported barriers to referral were uncertainty about observations, signs, and symptoms of abuse and neglect, and uncertainty about referral procedures. A total of 84 (8.9%) of the respondents had received both undergraduate and postgraduate training on the topic, and 64.4% of the respondents found that the dental staff could recognize signs and symptoms of abuse and neglect. CONCLUSION: Findings suggest a continuous need for a focus on the awareness and training of the Danish dental staff on the important topic of child abuse and neglect.

The seroprevalence of hepatitis C virus infection among children and their mothers attending for dental care in Glasgow, Scotland, United Kingdom.

This paper describes a voluntary anonymous survey to investigate the seroprevalence of Hepatitis C (HCV) in children in Glasgow, UK attending a Dental Hospital and the proportion of HCV positive mothers who have a child who is HCV seropositive. The study was undertaken among children and accompanying parents and household contacts attending a general anaesthetic assessment clinic at Glasgow Dental Hospital and School. Children were asked to provide an oral fluid specimen for HCV testing. Accompanying adults were asked to provide demographic data on the child and information on familial risk factors for HCV infection using a standardised questionnaire. Birth mothers were also asked to provide an oral fluid specimen. Specimens and questionnaires were linked by a unique anonymous study number. Between June 2009 and December 2011, samples were collected from 2141 children and 1698 mothers. None of the samples from the children were HCV seropositive but 16 (0.9%, 95% CI 0.6-1.5%) of the specimens from mothers were HCV antibody positive. In summary, the prevalence of HCV seropositivity in the birth mothers of the children was similar to that estimated in the general population served by the hospital and showed no evidence of mother-to-child transmission of HCV.

Use of Vandetanib in Metastatic Medullary Carcinoma of Thyroid in a Pediatric Patient With Multiple Endocrine Neoplasia 2B.

We describe a child with advanced, metastatic, inoperable medullary carcinoma of thyroid associated with multiple endocrine neoplasia 2B and rearranged during transfection mutation with a positive response to vandetanib treatment. He responded well with a fall in calcitonin levels and a reduction in size of the thyroid malignancy, lymph nodes, and pulmonary metastases. He has been on vandetanib for 4 years with good clinical and biochemical response. Vandetanib has a role in the treatment of patients including children with inoperable locally advanced and metastatic medullary carcinoma of thyroid. More information is needed on its use in children and long-term outcome.

The Francis Report--Why it Matters to the Dental Team.

The Francis Report into the deaths at Mid-Staffordshire NHS Trust highlighted the problems facing the NHS when patients, families, clinicians and nurses are not heard, and where the management, leadership and ensuing culture are focused on the system's business, not patient care. This paper, the first in a series based on the implications of the Francis Report, provides the background and context for the subsequent 'perspective' articles from a range of relevant stakeholders and care-providers. The overriding message is that in all areas of healthcare, dentistry included, the quality of patient care, especially patient safety, must be placed above all other aims. Clinical Relevance: The overriding importance of patient-centredness and quality of care, above all other aims, is the key message of clinical relevance from the Francis Report.