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Spouses of Alzheimer’s disease (AD) patients are at higher risk of developing AD dementia, but the reasons and underlying mechanism are unknown. One potential factor is gut microbiota dysbiosis, which has been associated with AD. However, it remains unclear whether the gut microbiota dysbiosis can be transmitted to non-AD individuals and contribute to the development of AD pathogenesis and cognitive impairment. The present study found that co-housing wild-type mice with AD transgenic mice or giving them AD transgenic mice feces caused AD-associated gut microbiota dysbiosis, Tau phosphorylation, and cognitive impairment. Gavage with Lactobacillus and Bifidobacterium restored these changes. The oral and gut microbiota of AD patient partners resembled that of AD patients but differed from healthy controls, indicating the transmission of oral and gut microbiota and its impact on cognitive function. The underlying mechanism of these findings includes that the butyric acid-mediated acetylation of GSK3β at lysine 15 regulated its phosphorylation at serine 9, consequently impacting Tau phosphorylation. These results provide insight into a potential link between gut microbiota dysbiosis and AD and underscore the need for further research in this area.

We study peristaltic flow in a C-shaped compliant tube representing the first section of the small intestine—the duodenum. A benchtop model comprising of a silicone tube filled with a glycerol-water mixture deformed by a rotating roller was created. Particle image velocimetry (PIV) was used to image flow patterns for deformations approximating conditions in the duodenum (contraction amplitude of 34% and wave speed 13 mm/s). Reversed flow was present underneath the roller with fluid moving opposite to the direction of the peristaltic wave propagation. Deformations of the tube were imaged and used to construct a computational fluid dynamics (CFD) model of flow with moving boundaries. The PIV and CFD vorticity and velocity fields were qualitatively similar. The vorticity field was integrated over the imaging region to compute the total circulation and there was on average a 22% difference in the total circulation between the experimental and numerical results. Higher shear rates were observed with water compared to the higher viscosity fluids. This model is a useful tool to study the effect of digesta properties, anatomical variations, and peristaltic contraction patterns on mixing and transport in the duodenum in health and disease.

Background: Sickle cell disease is an inherited disorder associated with chronic haemolysis and anaemia, recurrent episodes of pain and potentially multisystem end-organ damage. A lot less is known about the dental health of these patients. Aims: To explore the incidence of severe dental disease leading to dental extraction in our sickle cell population. Patient/methods: We undertook an audit looking at the rate of dental extractions, as a composite marker of severe dental disease, among sickle cell patients over a 3-month period. The patients were unselected and approached during routine assessments. We analysed both clinical and laboratory data to look for possible associations between dental disease and sickle cell characteristics. Results: 177 patients were interviewed between February 2022 and April 2022. Overall, 71% of the patients had at least one dental extraction with a median number of teeth extracted of three and a median age at first extraction of 26. More than half of the patients stated that they do not have regular dental check-ups. There were no significant associations with the severity of sickle cell phenotype, baseline Hb or markers of haemolysis. Conclusion: A large number of patients with sickle cell disease require dental extractions at a relatively young age. The lack of any correlation with disease severity suggests that poor engagement with dental services and the underestimation of the importance of dental health are the main factors behind the increased prevalence of severe dental disease. Actively enquiring about dental problems should be part of any routine consultation with these patients, both in primary and specialist care.

Sickle cell disease is a multisystem disease associated with episodes of acute illness and progressive organ damage. It is one of the most common severe monogenic disorders worldwide and is now the fastest growing genetic disorder in the UK. Dental awareness of orofacial manifestation varies geographically due to the inheritance pattern and patient population affected by the disease. This article details the epidemiology, pathophysiology and the orofacial manifestations in light of current literature.

Background Guidelines remain unclear over whether patients with early stage oral cancer without overt neck disease benefit from upfront elective neck dissection (END), particularly those with the smallest tumours. Methods We conducted a randomised trial of patients with stage T1/T2 N0 disease, who had their mouth tumour resected either with or without END. Data were also collected from a concurrent cohort of patients who had their preferred surgery. Endpoints included overall survival (OS) and disease-free survival (DFS). We conducted a meta-analysis of all six randomised trials. Results Two hundred fifty randomised and 346 observational cohort patients were studied (27 hospitals). Occult neck disease was found in 19.1% (T1) and 34.7% (T2) patients respectively. Five-year intention-to-treat hazard ratios (HR) were: OS HR = 0.71 (p = 0.18), and DFS HR = 0.66 (p = 0.04). Corresponding per-protocol results were: OS HR = 0.59 (p = 0.054), and DFS HR = 0.56 (p = 0.007). END was effective for small tumours. END patients experienced more facial/neck nerve damage; QoL was largely unaffected. The observational cohort supported the randomised findings. The meta-analysis produced HR OS 0.64 and DFS 0.54 (p Conclusion SEND and the cumulative evidence show that within a generalisable setting oral cancer patients who have an upfront END have a lower risk of death/recurrence, even with small tumours. Clinical Trial Registration NIHR UK Clinical Research Network database ID number: UKCRN 2069 (registered on 17/02/2006), ISCRTN number: 65018995, ClinicalTrials.gov Identifier: NCT00571883.

It is not uncommon for patients with odontogenic and non-odontogenic infection to present in general dental practice. Untreated infection can lead to life-threatening sepsis. This article aims to advise general dental practitioners on the relevance of sepsis and highlight the recent published NICE guidelines for interpretation in the dental setting. Sepsis is defined as a life-threatening organ dysfunction due to a deregulated host response to infection. It is paramount for dental professionals to understand head and neck infection, underlying systemic infection and concepts of fascial space infection. It is also essential to know the warning signs or ‘red flags’ of emerging sepsis. CPD/Clinical Relevance: Following the recent published NICE guidelines and public awareness campaigns regarding sepsis, it is vitally important to raise awareness of the potential for sepsis to be identified in the general dental practice setting.

Material removal at the sub-micron level has been a topic of interest in the past few years, particularly with respect to the fabrication of miniaturized devices. While numerous techniques have been developed and refined from their larger meso-scale counterparts (e.g. polishing), most have inherent limitations (such as the introduction of scratches from polishing) which may render these processes to be less attractive. In this work, a novel non-contact technique (where the machining tool is not in contact with the workpiece [1-4]) of using electrokinetic phenomenon for precise material removal (a.k.a electrokinetic material removal process) at rates in the order of nanometers/min is introduced. The technique involves movements of abrasive particles in a fluidic flow, under the influence of an AC electric field with a DC offset, to collide with the surface of the material to achieve material removal. Results showed that the technique is feasible in achieving material removal up to a depth of several hundred nanometers. Parametric studies on the material removal, which include material removal rate (MRR) and surface roughness (SR), were carried out and documented. A semi-empirical model on the material removal rate (MRR) was subsequently proposed after the dominating material removal mechanism was identified. The model was further validated with additional experimental results to show its predictive capability. With no chemicals involved in the process, the technique offers the further attraction of being a benign nano-manufacturing process with potential usage in the microelectromechanical systems (MEMS) areas. DOCTOR OF PHILOSOPHY (MAE)

Infant oral mutilation (IOM) is a primitive traditional practice involving the 'gouging out' of an infant's healthy primary tooth germs. This can lead to transmission of blood-borne diseases such as HIV/ AIDS, septicaemia and death. Other complications include eradication and/ or malformation of the child's permanent dentition. IOM is usually performed by village healers in low income countries as an accepted remedy for common childhood illness. The gingival swelling of the unerupted teeth is mistakenly thought to indicate the presence of 'tooth worms'. Crude methods to remove these are employed using unsterile tools. IOM has been reported in many African countries. More recently, some immigrants living in high income countries, such as the UK, have shown signs of IOM. Our aim is to raise awareness among clinicians about the existence of IOM practice being carried out among respective African immigrant groups. We encourage clinicians, particularly those working with paediatric patients to inform parents and carers of children with a history of IOM about the risks and consequences. As part of child safeguarding policies, dental practitioners and health care professionals should intervene if they are aware of any perceived plan that IOM is to be carried out in the future.

This is a retrospective review of 24 elderly patients with upper cervical adjacent segment disease (ASD) after anterior cervical discectomy and fusion (ACDF), treated with posterior cervical fusion (PCF) and stabilized with cages placed bilaterally in the facets. Eight out of 24 patients had PCF with laminectomy (PCLF). Length of stay for PCF alone cohort was 30 ± 11 h, operative time was 44 ± 11 min and estimated blood loss was 46 ± 26 cc. In the PCLF cohort, hospital length of stay was 73 ± 32 h, operative time was 92 ± 18 min, and blood loss was 155 ± 58 cc. The pooled sample showed significant decreases in mean NDI and VAS for neck and arm pain at each follow-up visit (6 weeks, 3, 6, 12 months) compared to baseline (p 0.0001). All 19 patients that returned for an additional visit, after 12 months visit, continued to report an improvement over the baseline VAS and NDI scores. For those patients treated with PCLF, Nurick scores improved by more than one point in 62% of patients. The overall fusion rate was 96%, including all 16 patients treated with PCF alone (fusion defined as less than 2 mm interspinous movement on dynamic X-ray), and in 7 out of 8 patients treated with PCLF (fusion defined as less than 3 degrees angulation). There was one asymptomatic non-union. There were no significant changes in the overall cervical lordosis (p = 0.436) or segmental lordosis (p = 0.449), and no device-related complications.

Chronic sclerosing sialadenitis, also known as Küttner’s tumour, is a chronic inflammatory condition affecting the salivary glands. We present the case of an arteriovenous vascular malformation (AVM) of the right submandibular gland mimicking a Küttner’s tumour on ultrasound scan in a 63-year-old woman. Examination revealed a 2 cm firm, mobile, non-pulsatile, right-sided submandibular mass with no overlying skin changes but with mild tenderness to palpation. Histological appearances revealed an AVM associated with localised fatty metaplasia and glandular atrophy. Although rare, AVMs should be considered a differential diagnosis for a submandibular gland mass that gives unclear or unusual radiological appearances.

Urologic patients receiving bone-targeted therapies are at risk of developing osteonecrosis of the jaw (ONJ). ONJ has historically been associated with bisphosphonate therapy. More recently, RANK-Ligand inhibitors (denosumab) have also been used to reduce the risk of skeletal-related events in patients who have advanced cancers with bone metastases. More than 65% of men with metastatic prostate cancer and nearly 75% of women with metastatic breast cancer are affected by bone metastases. The literature has described ONJ associated with bisphosphonate therapy as bisphosphonate-related osteonecrosis of the jaw (BRONJ). However, with evidence also linking the use of RANK-Ligand inhibitors with osteonecrosis of the jaw, we advocate use of the term "anti-bone resorption therapy-related osteonecrosis of the jaw" (ABRT-ONJ). The term "medication-related osteonecrosis of the jaw" (MRONJ) is now becoming more widespread. There is not a universally accepted definition of ABRT-ONJ, which may have hindered recognition and reporting of the condition. In Part I of this article, a review of current knowledge around the etiology of ABRT-ONJ and incidence data are provided. In Part II, we provide an audit of ONJ in a nurse consultant-led bone support clinic. In the article, we refer to zoledronic acid because this is the bisphosphonate of choice for use in men with prostate cancer in the United Kingdom.

Men who receive bone-targeted therapy for metastatic prostate cancer are at increased risk of osteonecrosis of the jaw (ONJ). Development of ONJ has been associated with the administration of bone-targeted therapies in association with other risk factors. ONJ can be distressing for a patient because it can cause pain, risk of jaw fracture, body image disturbance, difficultly eating, and difficulty maintaining good oral hygiene. The aim of this article is to report results of an audit of prior assessment by oral and maxillofacial surgeons (OMFS) before initiation of bone-targeted therapies and whether it may reduce the risk of ONJ in patients receiving bone-targeted therapies for advanced cancers.

Diseases of the thyroid are common in the developed and developing world. We retrospectively compared surgical pathologies, types of thyroidectomy, and postoperative complications between 2 case series, one from the Mercy Ships in West Africa with 87 patients, and the other from London in the United Kingdom with 120 patients. In both, the most common operation was hemithyroidectomy, and nodular hyperplasia was the most common disease. The postoperative complication rate of sero-haematoma was comparable with large international series.

Acute angioedema attacks are conventionally treated with antihistamines and steroids, in line with a presumed mechanism of disease involving overwhelming mast-cell degranulation. This approach overlooks a small but important minority of cases in which attacks are bradykinin driven and exhibit poor responsiveness to steroid or anti-histamine therapy. These patients may have a family history of angioedema (hereditary angioedema), or a past medical history including B-cell lymphoproliferative disorders or autoimmune disease (acquired angioedema). Rather than steroid therapy, they respond to administration of a bradykinin inhibitor, or more commonly, a C1 esterase inhibitor substitute, to control acute symptoms and reduce the probability of invasive airway insertion. In the long-term, they require C1 esterase inhibitor sparing therapy and a treat-the-cause approach to reduce the risk of recurrent attacks. We present here a case of a middle-aged woman who presented with recurrent angioedema of initially uncertain aetiology.