Embedding patient and public involvement into a doctoral study: developing a point-of-care HIV testing intervention for dental settings.

Introduction: Patient and Public Involvement (PPI) can have a positive impact on research. PPI can make research more meaningful and appropriate as well as preventing research waste. For decades, patient advocates with HIV have played a key part in public health and research. This article presents the PPI activity undertaken during a doctoral study. The aim of this article is to demonstrate how PPI was embedded into a doctoral study that explored the feasibility of HIV testing in dental settings. Methods: Patients and the public were invited to be involved with the feasibility study through various organisations and charities. A comprehensive PPI activity strategy was devised, and appropriate funding was obtained. Patients and the public were predominantly consulted or collaboratively involved with several aspects of the study. Findings: Patients and the public positively contributed to the intervention development and the resources supporting its implementation. As a result, the study resources (i.e., questionnaire and information leaflets) were easier to read, and the intervention was more appropriate to the needs of patients. Furthermore, the training and focus groups conducted with dental patients and people with HIV benefitted from input of people with lived experience. Conclusions: PPI can be embedded within doctoral studies provided there is sufficient funding, flexibility, and supervisory support. However, PPI activity may be impacted by limited resource and a priori research protocol and funding agreements.

Cachexia and head and neck squamous cell carcinoma: A scoping review.

OBJECTIVE: The objective of this paper was to provide an understanding of cachexia in relation to oral squamous cell carcinoma relevant to oral health care. The paper is a scoping review of aspects of the clinical presentation, aetiology and management of cachexia in relation to oral health and oral health care. METHODS: A combined search of MEDLINE and EMBASE databases (via OVID) was conducted using the terms ([Head and Neck] OR [Oral Squamous Cell Carcinoma]) AND (Cachexia). Duplicates were removed and results were subsequently limited to studies published between 2000 and 2023, humans and English language. After screening and full-text assessment a total number of 87 studies were included in the review. RESULTS: It is evident that cachexia is a not uncommon feature of patients with advanced malignancy of the head and neck driven by a multitude of mechanisms, induced by the tumour itself, that lead to reduced nutritional intake, increased metabolism and loss of adipose and skeletal tissue. CONCLUSION: While a variety of nutritional, physical, psychological and pharmacological interventions may improve quality and duration of life, ultimately the diagnosis of cachexia in relation to head and neck cancer remains an indicator of poor life expectancy.

The role of clay minerals in the preservation of Precambrian organic-walled microfossils.

Precambrian organic-walled microfossils (OWMs) are primarily preserved in mudstones and shales that are low in total organic carbon (TOC). Recent work suggests that high TOC may hinder OWM preservation, perhaps because it interferes with chemical interactions involving certain clay minerals that inhibit the decay of microorganisms. To test if clay mineralogy controls OWM preservation, and if TOC moderates the effect of clay minerals, we compared OWM preservational quality (measured by pitting on fossil surfaces and the deterioration of wall margins) to TOC, total clay, and specific clay mineral concentrations in 78 shale samples from 11 lithologic units ranging in age from ca. 1650 to 650 million years ago. We found that the probability of finding well-preserved microfossils positively correlates with total clay concentrations and confirmed that it negatively correlates with TOC concentrations. However, we found no evidence that TOC influences the effect of clay mineral concentrations on OWM preservation, supporting an independent role of both factors on preservation. Within the total clay fraction, well-preserved microfossils are more likely to occur in shales with high illite concentrations and low berthierine/chamosite concentrations; however, the magnitude of their effect on preservation is small. Therefore, there is little evidence that bulk clay chemistry is important in OWM preservation. Instead, we propose that OWM preservation is largely regulated by physical properties that isolate organic remains from microbial degradation such as food scarcity (low TOC) and low sediment permeability (high total clay content): low TOC increases the diffusive distances between potential carbon sources and heterotrophic microbes (or their degradative enzymes), while high clay concentrations reduce sediment pore space, thereby limiting the diffusion of oxidants and degradative enzymes to the sites of decay.

Color, composition, and thermal environment of Kuiper Belt object (486958) Arrokoth.

The outer Solar System object (486958) Arrokoth (provisional designation 2014 MU69) has been largely undisturbed since its formation. We studied its surface composition using data collected by the New Horizons spacecraft. Methanol ice is present along with organic material, which may have formed through irradiation of simple molecules. Water ice was not detected. This composition indicates hydrogenation of carbon monoxide-rich ice and/or energetic processing of methane condensed on water ice grains in the cold, outer edge of the early Solar System. There are only small regional variations in color and spectra across the surface, which suggests that Arrokoth formed from a homogeneous or well-mixed reservoir of solids. Microwave thermal emission from the winter night side is consistent with a mean brightness temperature of 29 ± 5 kelvin.

The geology and geophysics of Kuiper Belt object (486958) Arrokoth.

The Cold Classical Kuiper Belt, a class of small bodies in undisturbed orbits beyond Neptune, is composed of primitive objects preserving information about Solar System formation. In January 2019, the New Horizons spacecraft flew past one of these objects, the 36-kilometer-long contact binary (486958) Arrokoth (provisional designation 2014 MU69). Images from the flyby show that Arrokoth has no detectable rings, and no satellites (larger than 180 meters in diameter) within a radius of 8000 kilometers. Arrokoth has a lightly cratered, smooth surface with complex geological features, unlike those on previously visited Solar System bodies. The density of impact craters indicates the surface dates from the formation of the Solar System. The two lobes of the contact binary have closely aligned poles and equators, constraining their accretion mechanism.

The solar nebula origin of (486958) Arrokoth, a primordial contact binary in the Kuiper Belt.

The New Horizons spacecraft's encounter with the cold classical Kuiper Belt object (486958) Arrokoth (provisional designation 2014 MU69) revealed a contact-binary planetesimal. We investigated how Arrokoth formed and found that it is the product of a gentle, low-speed merger in the early Solar System. Its two lenticular lobes suggest low-velocity accumulation of numerous smaller planetesimals within a gravitationally collapsing cloud of solid particles. The geometric alignment of the lobes indicates that they were a co-orbiting binary that experienced angular momentum loss and subsequent merger, possibly because of dynamical friction and collisions within the cloud or later gas drag. Arrokoth's contact-binary shape was preserved by the benign dynamical and collisional environment of the cold classical Kuiper Belt and therefore informs the accretion processes that operated in the early Solar System.

Molecular markers relevant to myocardial injury following dental extraction in patients with or without coronary artery disease.

OBJECTIVES: The aim of this study was to characterize biological changes following dental extractions in patients with or without coronary artery disease (CAD). MATERIALS AND METHODS: Forty-five patients (36 males and 9 females) referred for dental extraction underwent treatment and provided blood samples before, immediately after, and 24 h after the procedure. A broad array of biomarkers was employed to assess myocardial injury (highly sensitive troponin T, hs-TnT), bacterial burden (LPS endotoxin activity), and systemic inflammation (CRP, fibrinogen, IFN-γ, IL-1ß, IL-6, IL-8, IL-10, IL-12, and TNF-α). RESULTS: Dental extraction in patients with or without CAD was associated with rises in hs-TnT (p = 0.013), hs-CRP (p < 0.001), fibrinogen (p = 0.005), endotoxin activity (p < 0.001), IFN-γ (p < 0.001), IL-6 (p < 0.001), IL-8 (p = 0.011), and IL-12 (p < 0.001) at 24 h compared with immediately post procedure. Changes in systemic inflammation and endotoxin activity were more evident in those with hs-TnT rise. CONCLUSIONS: Simple dental extractions may cause mild increase in hs-TnT, indicating minor myocardial injury in both patients with or without CAD. Acute systemic inflammation and endotoxemia could represent a possible link between invasive dental treatment and increased risk of acute cardiovascular events. These findings indicate that invasive dental treatment (as simple as a single dental extraction) may impact negatively on clinical outcomes in dental patients, especially those with CAD.

Quantitative CT analysis using functional imaging is superior in describing disease progression in idiopathic pulmonary fibrosis compared to forced vital capacity.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is chronic fibrosing pneumonia with an unpredictable natural disease history. Functional respiratory imaging (FRI) has potential to better characterize this disease. The aim of this study was to identify FRI parameters, which predict FVC decline in patients with IPF. METHODS: An IPF-cohort (treated with pamrevlumab for 48 weeks) was retrospectively studied using FRI. Serial CT's were compared from 66 subjects. Post-hoc analysis was performed using FRI, FVC and mixed effects models. RESULTS: Lung volumes, determined by FRI, correlated with FVC (lower lung volumes with lower FVC) (R2 = 0.61, p < 0.001). A negative correlation was observed between specific image based airway radius (siRADaw) at total lung capacity (TLC) and FVC (R2 = 0.18, p < 0.001). Changes in FVC correlated significantly with changes in lung volumes (R2 = 0.18, p < 0.001) and siRADaw (R2 = 0.15, p = 0.002) at week 24 and 48, with siRADaw being more sensitive to change than FVC. Loss in lobe volumes (R2 = 0.33, p < 0.001), increasing fibrotic tissue (R2 = 0.33, p < 0.001) and airway radius (R2 = 0.28, p < 0.001) at TLC correlated with changes in FVC but these changes already occur in the lower lobes when FVC is still considered normal. CONCLUSION: This study indicates that FRI is a superior tool than FVC in capturing of early and clinically relevant, disease progression in a regional manner.

Chikungunya fever: General and oral healthcare implications.

Chikungunya virus (CHIKV) was first isolated in humans in 1952, following an epidemic in Tanzania. The origin of the name means "to bend forward or become contorted," in reference to the posture adopted by patients due to the joint pain that occurs during the infection. Epidemiology data suggest that by the end of 2015, about 1.6 million people had been infected with CHIKV. The acute period of the disease is characterized by high fever, myalgia, joint pain, and severe and disabling polyarthritis, sometimes accompanied by headache, backache, and maculopapular rash, predominantly on the thorax. Around half of the patients will progress to the subacute and chronic phases, that is manifested by persistent polyarthritis/polyarthralgia, accompanied by morning stiffness and fatigue, which could remain for years. Oral features may include gingivitis possibly as a consequence of arthralgia of the hands leading to limited oral health measures as well as burning sensation and oral mucosal ulceration. Treatment in the acute phase includes acetaminophen, and weak opioids (tramadol or codeine) should be used in cases of severe or refractory pain. For patients who have progressed to the subacute stage and who have not had notable benefit from common analgesics or opioids, NSAIDs, or adjunctive pain medications (anticonvulsants or antidepressants) may be of benefit. In patients with moderate-to-severe musculoskeletal pain or in those who cannot be given or tolerate NSIADs or opiates, prednisolone should be prescribed.

Establishing a clinical phenotype for cachexia in end stage kidney disease - study protocol.

BACKGROUND: Surveys using traditional measures of nutritional status indicate that muscle wasting is common among persons with end-stage kidney disease (ESKD). Up to 75% of adults undergoing maintenance dialysis show some evidence of muscle wasting. ESKD is associated with an increase in inflammatory cytokines and can result in cachexia, with the loss of muscle and fat stores. At present, only limited data are available on the classification of wasting experienced by persons with ESKD. Individuals with ESKD often exhibit symptoms of anorexia, loss of lean muscle mass and altered energy expenditure. These symptoms are consistent with the syndrome of cachexia observed in other chronic diseases, such as cancer, heart failure, and acquired immune deficiency syndrome. While definitions of cachexia have been developed for some diseases, such as cardiac failure and cancer, no specific cachexia definition has been established for chronic kidney disease. The importance of developing a definition of cachexia in a population with ESKD is underscored by the negative impact that symptoms of cachexia have on quality of life and the association of cachexia with a substantially increased risk of premature mortality. The aim of this study is to determine the clinical phenotype of cachexia specific to individuals with ESKD. METHODS: A longitudinal study which will recruit adult patients with ESKD receiving haemodialysis attending a Regional Nephrology Unit within the United Kingdom. Patients will be followed 2 monthly over 12 months and measurements of weight; lean muscle mass (bioelectrical impedance, mid upper arm muscle circumference and tricep skin fold thickness); muscle strength (hand held dynamometer), fatigue, anorexia and quality of life collected. We will determine if they experience (and to what degree) the known characteristics associated with cachexia. DISCUSSION: Cachexia is a debilitating condition associated with an extremely poor outcome. Definitions of cachexia in chronic illnesses are required to reflect specific nuances associated with each disease. These discrete cachexia definitions help with the precision of research and the subsequent clinical interventions to improve outcomes for patients suffering from cachexia. The absence of a definition for cachexia in an ESKD population makes it particularly difficult to study the incidence of cachexia or potential treatments, as there are no standardised inclusion criteria for patients with ESKD who have cachexia. Outcomes from this study will provide much needed data to inform development and testing of potential treatment modalities, aimed at enhancing current clinical practice, policy and education.

Oral manifestations of systemic disease.

While the majority of disorders of the mouth are centred upon the direct action of plaque, the oral tissues can be subject to change or damage as a consequence of disease that predominantly affects other body systems. Such oral manifestations of systemic disease can be highly variable in both frequency and presentation. As lifespan increases and medical care becomes ever more complex and effective it is likely that the numbers of individuals with oral manifestations of systemic disease will continue to rise. The present article provides a succinct review of oral manifestations of systemic disease. In view of this article being part of a wider BDJ themed issue on the subject of oral medicine, this review focuses upon oral mucosal and salivary gland disorders that may arise as a consequence of systemic disease.

Patient-reported outcome measures in recurrent aphthous stomatitis: A critical assessment of quality properties.

OBJECTIVES: To analyse the range of existing patient-reported outcome measures (PROMs) used in studies of recurrent aphthous stomatitis (RAS) and to evaluate their quality properties via the assessment of psychometric properties and interpretability. MATERIALS AND METHODS: Electronic databases were searched to identify relevant publications related to PROMs used in RAS. Publications were selected based on predefined criteria. All identified PROMs were then classified by measuring concepts and assessed for instrument characteristics and evidence for quality properties for RAS patients. RESULTS: Twenty-eight PROMs were used in studies of RAS patients. Instruments focused upon oral symptoms (n = 4), psychosocial status (n = 15) and quality of life (n = 9). Five PROMs (Oral Health-related Quality of Life-UK, Chronic Oral Mucosal Disease Questionnaire, Oral Health Impact Profile-14, Medical Outcome Study Short Form-36 and Mumcu's composite index) were found to have some evidence of psychometric performance. No PROMs showed evidence for interpretability of their scores in RAS patients. CONCLUSION: There was a wide range of PROMs used in clinical studies of RAS. The majority of these PROMs lack evidence of measurement properties and interpretability for RAS patients. Further studies are required to confirm whether these instruments are suitable and useful for this patient group.

Changes in brain-behavior relationships following a 3-month pilot cognitive intervention program for adults with traumatic brain injury.

Facilitating functional recovery following brain injury is a key goal of neurorehabilitation. Direct, objective measures of changes in the brain are critical to understanding how and when meaningful changes occur, however, assessing neuroplasticity using brain based results remains a significant challenge. Little is known about the underlying changes in functional brain networks that correlate with cognitive outcomes in traumatic brain injury (TBI). The purpose of this pilot study was to assess the feasibility of an intensive three month cognitive intervention program in individuals with chronic TBI and to evaluate the effects of this intervention on brain-behavioral relationships. We used tools from graph theory to evaluate changes in global and local brain network features prior to and following cognitive intervention. Network metrics were calculated from resting state electroencephalographic (EEG) recordings from 10 adult participants with mild to severe brain injury and 11 age and gender matched healthy controls. Local graph metrics showed hyper-connectivity in the right inferior frontal gyrus and hypo-connectivity in the left inferior frontal gyrus in the TBI group at baseline in comparison with the control group. Following the intervention, there was a statistically significant increase in the composite cognitive score in the TBI participants and a statistically significant decrease in functional connectivity in the right inferior frontal gyrus. In addition, there was evidence of changes in the brain-behavior relationships following intervention. The results from this pilot study provide preliminary evidence for functional network reorganization that parallels cognitive improvements after cognitive rehabilitation in individuals with chronic TBI.

Early Adhesion of Candida albicans onto Dental Acrylic Surfaces.

Denture-associated stomatitis is a common candidal infection that may give rise to painful oral symptoms, as well as be a reservoir for infection at other sites of the body. As poly (methyl methacrylate) (PMMA) remains the main material employed in the fabrication of dentures, the aim of this research was to evaluate the adhesion of Candida albicans cells onto PMMA surfaces by employing an atomic force microscopy (AFM) single-cell force spectroscopy (SCFS) technique. For experiments, tipless AFM cantilevers were functionalized with PMMA microspheres and probed against C. albicans cells immobilized onto biopolymer-coated substrates. Both a laboratory strain and a clinical isolate of C. albicans were used for SCFS experiments. Scanning electron microscopy (SEM) and AFM imaging of C. albicans confirmed the polymorphic behavior of both strains, which was dependent on growth culture conditions. AFM force-spectroscopy results showed that the adhesion of C. albicans to PMMA is morphology dependent, as hyphal tubes had increased adhesion compared with yeast cells ( P < 0.05). C. albicans budding mother cells were found to be nonadherent, which contrasts with the increased adhesion observed in the tube region. Comparison between strains demonstrated increased adhesion forces for a clinical isolate compared with the lab strain. The clinical isolate also had increased survival in blood and reduced sensitivity to complement opsonization, providing additional evidence of strain-dependent differences in Candida-host interactions that may affect virulence. In conclusion, PMMA-modified AFM probes have shown to be a reliable technique to characterize the adhesion of C. albicans to acrylic surfaces.

Time to onset of bisphosphonate-related osteonecrosis of the jaws: a multicentre retrospective cohort study.

OBJECTIVES: Osteonecrosis of the jaw (ONJ) is a potentially severe adverse effect of bisphosphonates (BP). Although the risk of ONJ increases with increasing duration of BP treatment, there are currently no reliable estimates of the ONJ time to onset (TTO). The objective of this study was to estimate the TTO and associated risk factors in BP-treated patients. SUBJECTS AND METHODS: Retrospective analysis of data from 22 secondary care centres in seven countries relevant to 349 patients who developed BP-related ONJ between 2004 and 2012. RESULTS: The median (95%CI) TTO was 6.0 years in patients treated with alendronate (n = 88) and 2.2 years in those treated with zoledronate (n = 218). Multivariable Cox regression showed that dentoalveolar surgery was inversely associated, and the use of antiangiogenics directly associated, with the TTO in patients with cancer treated with zoledronate. CONCLUSIONS: The incidence of ONJ increases with the duration of BP therapy, with notable differences observed with respect to BP type and potency, route of administration and underlying disease. When data are stratified by BP type, a time of 6.0 and 2.2 years of oral alendronate and intravenous zoledronate therapy, respectively, is required for 50% of patients to develop ONJ. After stratification by disease, a time of 5.3 and 2.2 years of BP therapy is required for 50% of patients with osteoporosis and cancer, respectively, to develop ONJ. These findings have significant implications for the design of future clinical studies and the development of risk-reduction strategies aimed at either assessing or modulating the risk of ONJ associated with BP.

The formation of Charon's red poles from seasonally cold-trapped volatiles.

A unique feature of Pluto's large satellite Charon is its dark red northern polar cap. Similar colours on Pluto's surface have been attributed to tholin-like organic macromolecules produced by energetic radiation processing of hydrocarbons. The polar location on Charon implicates the temperature extremes that result from Charon's high obliquity and long seasons in the production of this material. The escape of Pluto's atmosphere provides a potential feedstock for a complex chemistry. Gas from Pluto that is transiently cold-trapped and processed at Charon's winter pole was proposed as an explanation for the dark coloration on the basis of an image of Charon's northern hemisphere, but not modelled quantitatively. Here we report images of the southern hemisphere illuminated by Pluto-shine and also images taken during the approach phase that show the northern polar cap over a range of longitudes. We model the surface thermal environment on Charon and the supply and temporary cold-trapping of material escaping from Pluto, as well as the photolytic processing of this material into more complex and less volatile molecules while cold-trapped. The model results are consistent with the proposed mechanism for producing the observed colour pattern on Charon.

Transplacental passage of clindamycin from mother to neonate.

OBJECTIVE: To evaluate maternal and neonatal cord blood levels at delivery in patients receiving 900 mg of clindamycin intravenous (IV) every 8 h. STUDY DESIGN: Prospective study consented every mother that entered labor with a positive group B streptococcal culture, a high-risk penicillin allergy, and sensitivity to clindamycin and erythromycin. Maternal and cord blood clindamycin levels were obtained at delivery. Time from last dose completion to delivery, number of doses administered and body mass index (BMI) were assessed. RESULTS: Twenty-three patients were consented. All maternal clindamycin values were therapeutic and 22 (96%) of the 23 cord blood samples were therapeutic. The mean maternal level was of 4.46 µg ml-1 (range of 0.7 to 8.4 µg ml-1). The mean cord blood level was 3.35 µg ml-1 (range of <0.5 to 6.4 µg ml-1). CONCLUSION: These data show that the current dosing recommendation of 900 mg of clindamycin IV every 8 h produces therapeutic maternal and cord blood levels.

The geology of Pluto and Charon through the eyes of New Horizons.

NASA's New Horizons spacecraft has revealed the complex geology of Pluto and Charon. Pluto's encounter hemisphere shows ongoing surface geological activity centered on a vast basin containing a thick layer of volatile ices that appears to be involved in convection and advection, with a crater retention age no greater than ~10 million years. Surrounding terrains show active glacial flow, apparent transport and rotation of large buoyant water-ice crustal blocks, and pitting, the latter likely caused by sublimation erosion and/or collapse. More enigmatic features include tall mounds with central depressions that are conceivably cryovolcanic and ridges with complex bladed textures. Pluto also has ancient cratered terrains up to ~4 billion years old that are extensionally faulted and extensively mantled and perhaps eroded by glacial or other processes. Charon does not appear to be currently active, but experienced major extensional tectonism and resurfacing (probably cryovolcanic) nearly 4 billion years ago. Impact crater populations on Pluto and Charon are not consistent with the steepest impactor size-frequency distributions proposed for the Kuiper belt.