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Purpose Mounting evidence suggests the gut microbiome influences radiotherapy efficacy and toxicity by modulating immune signalling. However, its contribution to radiotherapy outcomes in head and neck cancer (HNC) is yet to be investigated. This study, therefore, aimed to uncover associations between an individual’s pre-therapy gut microbiota and i) severity of radiotherapy-induced oral mucositis (OM), and ii) recurrence risk in patients with HNC. Methods In this prospective pilot study, 20 patients with HNC scheduled to receive radiotherapy or chemoradiotherapy were recruited. Stool samples were collected before treatment and microbial composition was analysed using 16S rRNA gene sequencing. OM severity was assessed using the NCI-CTCAE scoring system. Patients were also followed for 12 months of treatment completion to assess tumour recurrence. Results Overall, 80% of the patients were male with a median age of 65.5 years. 53% experienced mild/moderate OM while 47% developed severe OM. Further, 18% experienced tumour relapse within 1 year of treatment completion. A pre-treatment microbiota enriched of Eubacterium, Victivallis, and Ruminococcus was associated with severe OM. Conversely, a higher relative abundance of immunomodulatory microbes Faecalibacterium, Prevotella, and Phascolarctobacterium was associated with a lower risk of tumour recurrence. Conclusion Our results indicate that a patient’s gut microbiota composition at the start of treatment is linked to OM severity and recurrence risk. We now seek to validate these findings to determine their ability to predict treatment outcomes in HNC, with the goal of using this data to inform second-generation microbial therapeutics to optimise treatment outcomes for patients with HNC.

Lapatinib, an orally administered small-molecule tyrosine kinase inhibitor (SM-TKI), is an effective treatment for ErbB2-positive breast cancer. However, its efficacy as one of the targeted cancer therapies has been hampered by several adverse effects, especially gastrointestinal toxicity, commonly manifested as diarrhoea. Although it can be generally tolerated, diarrhoea is reported as the most common and most impactful on a patient’s quality of life and associated with treatment interruption. Severe diarrhoea can result in malabsorption, leading to dehydration, fatigue, and even death. ErbB1 is an epidermal growth factor profoundly expressed in normal gut epithelium while lapatinib is a dual ErbB1/ErbB2 tyrosine kinase inhibitor. Thus, ErbB1 inhibition by lapatinib may affect gut homeostasis leading to diarrhoea. Nevertheless, the underlying mechanisms remain unclear. This review article provides evidence of the possible mechanisms of lapatinib-induced diarrhoea that may be related to/or modulated by ErbB1. Insight regarding the involvement of ErbB1 in the pathophysiological changes such as inflammation and intestinal permeability as the underlying cause of diarrhoea is covered in this article.

In 1699, when Williamsburg became the new capital of Virginia, the colony’s plantation economy had begun to incorporate producing wheat into what had been a singular focus on tobacco production. This chapter draws on zooarchaeological and documentary evidence to show how this new capital emerged as part of the transformation of the landscape, from one based on slash-and-burn agriculture and free ranging livestock into a hybrid system that incorporated elements of the mixed husbandry system colonists had known in the Old World. Behavioral studies identify the role livestock played as colonizers, and how, working in tandem with colonists, they produced a free ranging herd system. Data show how ecodynamic relationships between colonists, their livestock, and the agricultural system resulted in transforming the tobacco-focused landscape, one capable of producing commodities for trade and feeding Williamsburg’s emerging population.

Refereed/Peer-reviewed Purpose: Due to its pivotal role in the modulation of immune and inflammatory responses, the gut microbiota has emerged as a key modulator of cancer treatment-induced gastrointestinal mucositis. However, it is not clear yet how it affects radiation therapy-induced oral mucositis (OM). As such, this study aimed to explore the gut microbiota's role in the pathogenesis of radiation-induced OM in rats. Methods and Materials: Male Sprague Dawley rats were treated with 20 Gy x-ray radiation (Rx) delivered to the snout, with or without antibiotic-induced microbiota depletion (AIMD). OM severity was assessed, and tongue tissues were collected on day 9 and 15 postradiation for tissue injury and inflammatory markers assessment. Results: AIMD Rx had a significantly shorter duration of severe OM compared with Rx alone group. Macroscopically, the tongue ulcer-like area was smaller in AIMD+Rx compared with the Rx group. Microscopically, a smaller percentage of the mucosal ulcer was observed in the dorsal tongue of AIMD+Rx compared with the Rx group. AIMD+Rx also had significantly lower levels of interleukin 6, interleukin 1 beta, and toll like receptor 4 in the tongue tissues than the Rx group. Conclusions: The gut microbiota plays a role in OM pathogenesis, mainly in the recovery phase, through the modulation of proinflammatory pathways. Future microbiota-targeted interventions may improve OM in clinical settings.

Background/Objectives: Faecal microbiota transplant (FMT) is a powerful tool used to connect changes in gut microbial composition with a variety of disease states and pathologies. While FMT enables potential causal relationships to be identified, the experimental details reported in preclinical FMT protocols are highly inconsistent and/or incomplete. This limitation reflects a current lack of authoritative guidance on reporting standards which would facilitate replication efforts and ultimately reproducible science. We therefore systematically reviewed all FMT protocols used in mouse models with the goal of formulating recommendations on the reporting of preclinical FMT protocols. Methods: Search strategies were applied across three databases (PubMed, EMBASE and Ovid Medline) until June 30, 2020. Data related to donor attributes, stool collection, processing/storage, recipient preparation, administration and quality control were extracted.Results: A total of 1753 papers were identified, with 241 identified for data extraction and analysis. Of the papers included, 92.5% reported a positive outcome with FMT intervention. However, the vast majority of studies failed to address core methodological aspects including the use of anaerobic conditions (91.7% of papers lacked information), storage (49.4%), homogenisation (33.6%), concentration (31.5%), volume (19.9%) and administration route (5.3%). To address these reporting limitations, we developed the Guidelines for Reporting Animal Faecal Transplant (GRAFT) that guide reporting standards for preclinical FMT. Conclusion: The GRAFT recommendations will enable robust reporting of preclinical FMT design, and facilitate high quality peer review, improving the rigour and translation of knowledge gained through preclinical FMT studies.

Gold Standards Framework (GSF) is a systematic, evidence based approach to optimise care for all patients approaching the end of life, delivered by generalist frontline care providers. There is evidence that 30% of adult hospital inpatients are in the last year of life (Clarke et al. 2014). The specialist palliative care team have completed a yearly audit to establish the percentage of adult inpatients on a particular date in June, who died during the following 12 months. The overall percentage is 33 percent of adult inpatients on the 3rd June 2018 had died within 1 year. Therefore, this data supported the published evidence and also supported the wards with the GSF implementation programme. Over the last 2 years the wards have engaged with six workshops and developed care plans based on national documentation for Gold Standards Framework Green, Amber and Red. The front runner wards ‘‘ elderly care, stroke and CCU have completed the requirements for accreditation and have been awarded GSF accreditation in August 2020. CCU is the first in the country to be GSF accredited. The improvements across these wards include the following which we were able to demonstrate through a GSF log data collection system: Increasing recognition of patients in the last year of life Increasing number of these patients offered advance care planning Increasing number of dying patients supported with Priorities for care of the dying person communication document Reduced length of stay for fast track patients The wards requested that the recording of GSF was available via the EPR system which has been achieved thanks to support from IT and allows staff to view patients that have been identified as GSF and if they have had an advance care plan offer or priorities for care communication document commenced. Furthermore, when a patient is re-admitted their previous GSF status will be visible on the tracking board. We are also able to record preferred place of death with documents on the EPR and are currently working with IT to enable reporting of achievement of preferred place on discharge and death. March - April 2020 as we all know have been unprecedented times with COVID-19. Our data offers assurance that the GSF has continued to be embedded across the hospital and patients are being identified as GSF which will include the use of appropriate care plans and enable the development of an individual plan of care. We have also demonstrated increasing number of patients identified for GSF and died on the wards with a reduction in the number of MET calls.

Introduction Measuring performance in End of Life Care within an acute setting is a complex and difficult task. GSF implementation within a hospital setting can improve quality of care, patient satisfaction and an increase in advance care planning. This study aims to show how by developing an internal hospital application and protocol for GSF patients, improved data collection can be transformed from data into intelligence and impact on delivery of high quality, individualised end of life care. Methods Most wards within Dudley had different ways of capturing GSF identified patients and recorded information manually. Informatics and the Specialist Palliative Care team developed an internal application to monitor all patient admissions against a GSF outcome and to provide additional information such as preferred place of care and ACP. This provided the ward with a visual management tool, easily identifying end of life patients and the ability to capture essential end of life metrics. Results Since the launch of this application, analysis of the data has demonstrated an increase in the percentage of adult inpatients assessed for GSF and currently using this information for targeted education and learning. As of the 30th September 2019, the three front runner wards had a combined assessment rate of 90.2% Through this log, other metrics broken down by ward include identification rate, percentage of patients who achieve their preferred place of care and how many have an individualised plan of care in place or offered ACP. Conclusion Initial results indicate that having an electronic centralised database for monitoring GSF outcomes provides a platform to scrutinise key metrics for end of life care, which enable the wards and specialist palliative care team to ensure high quality end of life care is achieved.

Primary care clinicians suggest that staff education is needed to increase chlamydia testing appropriately.To determine if interactive workshops and modified laboratory request forms could increase testing and case detection.Prospective cluster randomized controlled study, using modified Zelen's design, examining the effect of workshops and modified request forms on primary care clinicians' chlamydia specimen submission and case positivity rate.82 general practices in six geographical clusters within five primary care trusts (PCTs) in Gloucestershire and County Durham and Darlington.Practices within geographical clusters were randomly assigned to workshops on chlamydia or a control consisting of comparable workshops on the management of urinary symptoms, held in PCT-protected learning time. Half the practices were randomized to receive modified laboratory request forms. Staff were unaware that they were part of a study.Interactive workshops increased chlamydia testing in 16- to 24-year-old women by 33% in intervention practices compared to controls with effect persisting at 10 months (P = 0.003). No associated rise in the number of chlamydia infections was detected (P = 0.91), suggesting that increased testing may have occurred in a lower risk population. Modified forms did not change test submission (P = 0.75).Interactive workshops for general practices can be used to successfully increase chlamydia-testing rates. Chlamydia detection rates will need to be monitored as this type of educational programme may not increase absolute numbers of chlamydia infections detected, if patients at lower risk of infection are inappropriately tested. Other interventions may need to be combined with the workshops, to reach sufficiently high chlamydia screening rates to significantly reduce prevalence of chlamydial infection.

This work was undertaken to investigate the effects of various dietary carotenoid sources on the skin pigmentation in a marine teleost, the gilthead seabream (Sparus aurata). In a first trial, homogenous groups of seabream (initial mean body weight: 150 g) were fed, for 9 weeks, one of three diets containing 40 mg/kg of astaxanthin in three different forms: as biomass of laboratory produced Haematococcus pluvialis (LHP), as a commercial source of H. pluvialis (NR) and as synthetic astaxanthin (AST). A control diet (C) without added astaxanthin was also tested. In a second trial, fish (initial mean body weight: 97 g) were fed diets containing 40 mg/kg of each of the following synthetic carotenoids: astaxanthin (Ast), canthaxanthin (Cant), apocarotenoic acid ethyl ester (Z) and lutein (L). At the beginning and every 3 weeks until the end of the experiments, samples of skin from three different skin body locations (forefront, operculum, and along the dorsal fin), and of dorsal muscle and plasma, were withdrawn from five fish per group for subsequent analysis of total carotenoid content and carotenoid composition. Neither growth nor feed efficiency were significantly affected by dietary treatments. In both trials, the dietary carotenoid supplementation increased total carotenoid content in all skin zones sampled, but had no effect on the muscle pigment content. The carotenoid concentration was highest in the skin at the forefront area of the fish, irrespective of the carotenoid source fed. In trial I, the total carotenoid content in the plasma was not affected by the various dietary carotenoid sources, but the plasma astaxanthin content in fish fed diet AST was significantly higher than in fish fed any other experimental diets. In trial II, after 6 weeks of feeding, there were no major differences in the skin carotenoid concentration between fish fed the various diets, but the highest values were observed in fish fed diets Cant and L. Lutein esters and epilutein esters represented almost the totality of the pigments present in the skin samples of seabream, irrespective of the sampling zone. The plasma carotenoid composition was closely related to the carotenoid composition of the diets, irrespective of the dietary carotenoid source fed. However, given that the total carotenoid concentration of the skin and its composition were not significantly affected by the various dietary pigment sources within the constraints tested, it is still difficult to ascertain with absolute certainty the effectiveness of modulating the skin pigmentation in gilthead seabream by dietary means.

Complementary therapy use by patients with cancer is highly prevalent, although little is known about the optimal model of integration with conventional care. This study explored patient preferences regarding integration in an Australian context.Cancer patients participated in focus groups conducted by an experienced facilitator. Transcripts of discussions were subjected to thematic analysis.Fourteen female and four male patients took part in eight focus groups. Eleven had received conventional cancer treatment for early-stage disease, and seven for advanced stage. Participants had sound understanding of the distinction between complementary and alternative medicines. There were differing views on whether complementary therapy and conventional cancer services should be colocated. Some participants described colocation as discordant with their reasons for using complementary therapy. Participants valued guidance from oncology health professionals regarding complementary therapy that was tailored to their individual needs. In addition to medical oncologists, nursing staff and affiliated complementary therapists were considered to be appropriate sources for guidance. Additional themes identified in the analysis were also informative: patients achieve autonomy and self-expression through complementary therapies; the knowledge and attitudes of health professionals and limited consultation time are barriers to integration; self-funding of complementary therapies is acceptable to participants.The study findings suggest that while patients have diverse views regarding the optimal integration model, there is no strong preference for geographic colocation of complementary therapy with conventional cancer care. Patients valued personalized information and guidance regarding complementary therapy from health professionals involved in their cancer care.

This work explores archaeological age data and their ability to identify shifts in animal husbandry that are the direct result of changes that occurred in Boston during the 18th century, when the city’s population was growing and the regions’ market system was evolving into a well-developed market system. Archaeological age data illustrate two important points: first, that households living in urban communities were enmeshed in economic trade systems, and second, that patterns evident in the archaeological record are, to a greater extent than often presumed, the result of large-scale distribution systems rather than variability related to household rank and ethnic affiliation.

The faunal assemblages from the Central Artery project offer a wonderful opportunity to investigate diet, economic choice, and husbandry in early New England. But finely stratified deposits, such as the Cross Street Back Lot privy, also allow detailed comparisons that provide evidence of variability that can be glossed over when discussing regional subsistence patterns. Some of this variability, and how it can be seen or not seen, is studied using the traditional tools of modern zooarchaeology, and integrated, using the careful controls provided by the stratification, with artifactual and environmental evidence.

Urine is the most common microbiology laboratory specimen. Submissions increase annually by 5-10%, and many specimens may be unnecessary.To assess the impact of guidance, implemented by interactive workshops and reinforced with modified request forms, on specimen submission.This was a prospective randomized controlled study with modified Zelen design. The study population comprised five primary care trusts (PCTs) in Gloucestershire/County Durham/Darlington, containing 82 general practices in six geographical clusters. The six clusters were randomly assigned to urine workshop covering submission in the elderly, adults and children or a control workshop. Within these groups, half the practices were randomized to receive modified laboratory forms emphasizing the workshop messages. Practices were not aware of the study.Workshops lead to a 12% reduction in urine submissions from 16- to 64-year olds, which persisted for the 15 months but had no effect on bacteriuria rate. Workshops had no significant effect in the elderly or children. Modified forms were not associated with any reduction in submissions but were associated with an 11% reduction in detection of significant bacteriuria in 16- to 64-year olds.The 12% decrease in urine submissions from 16- to 64-year olds, attained with workshops, may help counter relentlessly rising test submissions. Modified forms are currently not worth pursuing. When educational workshops are used across PCTs to change practice, the change in test submission is smaller than attained in educational initiatives involving volunteers. Workshops may be more effective if they also discuss urine submissions from asymptomatic patients and are directed at high testing practices and care homes.

The case is described of a 30-year-old man who presented to the Army Medical Services with a pyogenic liver abscess from which methicillin resistant Staphylococcus aureus (MRSA) was isolated.

Problems in integrating documentary, architectural, and archaeological data are discussed first in terms of defining the archaeological context of a farmsite occupied by the Mott family for over 250 years, and then integrating zooarchaeological data with agricultural economics and foodway patterns. The social context of one unit, a cellar filled in the 1730’s, is established as being that of the family of Jacob Mott II. This context is then used in conjunction with zooarchaeological data and information drawn from the probate inventory of Jacob II on animal husbandry to determine uses of animals, agricultural economics, and foodways on a family farmstead. Proportions of domestic animals present on the Mott farm in 1736 are established from the probate inventory and are then compared with proportions of animals determined from the archaeological record. Discrepancies between the two sources are explained in terms of varying uses of sheep, pig, and cattle.