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Abstract Background In parts of Great Britain and Ireland, Eurasian badgers (Meles meles) constitute a reservoir of Mycobacterium bovis infection and a potential source of infection for cattle. In vitro diagnostic tests for live badgers are an important component of strategies to control TB in this species. Immunological tests have been developed for badgers, although little is known about the influence of the age of the animal on test performance. To address this, we evaluated the performance of three immunological tests for badgers with respect to the age of the animal: the Brock Test and BrockTB STAT-PAK® serological tests and the recently developed interferon-gamma enzyme immunoassay (IFNγ EIA). Data published elsewhere suggested that seropositivity was associated with more progressive forms of TB in the badger. To gain further evidence for this, we used longitudinal data from a well-studied population of badgers to test for an association between the sensitivity of the Brock Test and the duration of TB infection. Results Sensitivity of the two serological tests was approximately 54% for both cubs and adults. Sensitivity of the IFNγ EIA was lower in cubs (57%) compared with adults (85%) when a common cut-off value was used to define test positivity. Taking data from the cubs alone, the IFNγ EIA cut-off value could be adjusted to increase the sensitivity to 71% with no loss in specificity. As a general observation, specificity of all tests was higher in cubs, although only significantly so in the case of the Brock Test. Using logistic regression analysis to adjust for age, sensitivity of the Brock Test was significantly lower at first culture positive event (58%), but increased to >80% as infection progressed. Conclusion These data suggest that serodiagnosis could be a valuable tool for detecting a higher proportion of badgers with the greatest probability of transmitting infection. The age category of the badger appeared to exert little influence on the performance of the serological tests. Although data were only available for the IFNγ EIA in a small number of cubs, reduced sensitivity of the test in these individuals suggests a lower cut-off may be needed when testing younger animals.

Sarah Carpenter and Meg Twycross, Masks and Masking in Medieval and Early, Tudor England, Studies in Performance and Early Modern Drama (Aldershot: Ashgate, 2002). 418 pp.; 32 plates, 14 figures. [...]

Objective: The purpose of this study was to estimate prevalence/severity of self-reported trismus, determine association with quality of life (QOL), and examine clinical risk factors in a large population of patients treated for oropharyngeal cancer. Materials and methods: A cross-sectional survivorship survey was conducted among patients who completed definitive treatment for oropharyngeal carcinoma, disease-free ≥ 1-year post-treatment (median survival, 7 years among 892 survivors). Associations between trismus and QOL were also analyzed using MDASI-HN, EQ-5D, and MDADI. Dietary and feeding tube status were also correlated to trismus status. Results: Trismus was self-reported in 31%. Severity of trismus positively correlated (r = 0.29) with higher mean interference scores reflecting a moderate association with quality of life (p < 0.0001). There was a negative correlation for MDADI composite scores (r = − 0.33) indicating increased perceived dysphagia related to trismus severity (p < 0.0001). EQ-5D VAS scores were also negatively correlated with trismus severity (r = − 0.26, p < 0.0001). Larger T-stage (p ≤ 0.001), larger nodal stage (p = 0.03), tumor sub-site (p = 0.05), and concurrent chemoradiation (p = 0.01) associated with increased prevalence of trismus. Diet negatively correlated (r = − 0.27) with trismus severity (p = < 0.0001), and survivors with severe trismus were also more likely to be feeding tube-dependent. Conclusion: Severity of trismus appears to negatively impact quality of life and associate with various adverse functional outcomes in long-term oropharyngeal cancer survivorship. Trismus remains associated with advanced disease stages, tumor sub-site (tonsil), and addition of chemotherapy. Further investigation is merited for the dose-effect relationship to the muscles of mastication. [ABSTRACT FROM AUTHOR]

Inhibition of the Alzheimer's disease associated protein β-site amyloid precursor protein cleaving enzyme-1 (BACE1) remains a potential avenue for treatment of this disease. The cellular thermal shift assay (CETSA) is an attractive method of screening for protein binding molecules due to its ability to detect intracellular binding while avoiding the need to purify the protein in question. Here, the CETSA was carried out using the known BACE1 inhibitor verubecestat, where an increase in Tagg to 53.27 ± 0.89 °C from 49.53 ± 0.69 °C was observed. Three test compounds from the ChemBridge DiverSet compound library, identified to bind BACE1 using differential scanning fluorimetry, were then screened using the CETSA. Only compound C34 yielded a significant increase in Tagg (p value ≤ 0.05), indicative of intracellular binding. This is the first description of the cellular thermal shift assay being used to detect BACE1 binding molecules, with one novel BACE1 binding molecule being validated. [ABSTRACT FROM AUTHOR]

Abstract Background It would be useful to have psychometrically-sound measures of dental fear for Hispanics, who comprise the largest ethnic minority in the United States. We report on the psychometric properties of Spanish-language versions of two common adult measures of dental fear (Modified Dental Anxiety Scale, MDAS; Dental Fear Survey, DFS), as well as a measure of fear of dental injections (Needle Survey, NS). Methods Spanish versions of the measures were administered to 213 adults attending Hispanic cultural festivals, 31 students (who took the questionnaire twice, for test-retest reliability), and 100 patients at a dental clinic. We also administered the questionnaire to 136 English-speaking adults at the Hispanic festivals and 58 English-speaking students at the same college where we recruited the Spanish-speaking students, to compare the performance of the English and Spanish measures in the same populations. Results The internal reliabilities of the Spanish MDAS ranged from 0.80 to 0.85. Values for the DFS ranged from 0.92 to 0.96, and values for the NS ranged from 0.92 to 0.94. The test-retest reliabilities (intra-class correlations) for the three measures were 0.69, 0.86, and 0.94 for the MDAS, DFS, and NS, respectively. The three measures showed moderate correlations with one another in all three samples, providing evidence for construct validity. Patients with higher scores on the measures were rated as being more anxious during dental procedures. Similar internal reliabilities and correlations were found in the English-version analyses. The test-retest values were also similar in the English students for the DFS and NS; however, the English test-retest value for the MDAS was better than that found in the Spanish students. Conclusion We found evidence for the internal reliability, construct validity, and criterion validity for the Spanish versions of the three measures, and evidence for the test-retest reliability of the Spanish versions of the DFS and NS.

The function of perseverative speech for an adult man who had been diagnosed with autism and mental retardation was examined. Results showed that verbal perseverations were maintained by social attention. An intervention consisting of differential reinforcement of appropriate verbal responses and extinction of perseverative verbal responding was effective in decreasing verbal perseverations. DESCRIPTORS: verbal perseverations, functional analysis, autism

According to the entrainment hypothesis, traditional migratory routes develop in fish populations through social interactions. First-time migrants learn migratory routes by following experienced conspecifics and, by repeating the migration, contribute to guiding future cohorts along the same route. The loss of collective memory of migratory routes may be a precursor to fisheries collapse. The survival value of entrainment has not been convincingly demonstrated, and this possibly explains why there has not been greater interest in this putative migratory mechanism. I propose that the relative frequency of demonstrators of alternative contingents provides information to first-time migrants on relative survival rates. Using simulation, I show that a population in which contingent adoption is regulated by entrainment can achieve higher overall survival rates than a comparable population with fixed rates of contingent adoption in the situation where mortality rates differ among contingents. In certain cases, the advantage could be even larger in the presence of fishing mortality. I also compare the responses of the entrainment-based and fixed-rate migration populations in a scenario intended to mimic the cessation of fishing after a period of high fishing mortality, such as might occur after the collapse of a fishery. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance is of growing concern in human and animal health. The aim of this study was to raise awareness and perception of risk of infection-related behaviours during routine preparation for veterinary surgery. We took a multi-disciplinary and multi-method approach to 'make visible, the invisible' by illustrating how microbial contamination can be spread during the preparation process for surgical procedures. The design-led visualization approach enhanced inter-disciplinary team and workshop participant contributions during the co-development of an innovative digital tool to support training for veterinary practitioners and students. After experiencing the intervention, 92% of 51 participants agreed to change their behaviour and stated an intention to implement an infection control behaviour that aligned with training objectives. The 3D graphics enhanced the delivery of training content by making difficult and abstract contamination concepts easy to understand. A similar approach could be taken for human health applications. [ABSTRACT FROM AUTHOR]

Utilization of biologic skin substitutes for the management of soft tissue defects as an alternative to autologous skin grafts has expanded over the past 2 decades. The purpose of this case series study was to report our experience with Integra® bilayer wound matrix for reconstruction of intraoral oncologic defects. Case records of 6 patients with intraoral oncologic defects reconstructed with Integra® bilayer wound matrix were retrospectively reviewed. The surgical defect location, size, and time to removal of surgical splint varied. Clinically, normal oral epithelialization was noted for all patients. One patient demonstrated a small area of dehiscence and bone exposure after adjuvant radiation therapy which resolved with minimal intervention. Integra bilayer wound matrix is a viable and versatile option for reconstruction of intraoral oncologic surgical defects. Further exploration of wound healing with Integra® matrix, surgical techniques, and cost‐effectiveness is advocated. [ABSTRACT FROM AUTHOR]

Increase of antimicrobial resistance (AMR) is a global threat to health. The AMR profile of bacteria isolated from domesticated animals and free-ranging wildlife has been studied, but there are relatively few studies of bacteria isolated from captive wild animals. Understanding the dynamics of AMR in different populations is key to minimizing emergence of resistance and to preserve the efficacy of antimicrobials. In this study, fecal samples were collected from 17 species of healthy ungulates from a zoological collection in southeast England, which yielded 39 Escherichia coli and 55 Enterococcus spp. isolates for further analysis. Antibiotic sensitivity was investigated using agar disk diffusion. Escherichia coli isolates were resistant to a range of antibiotics, with resistance to ampicillin being the most common (28%). All E. coli isolates were susceptible to apramycin, enrofloxacin, chloramphenicol, and florfenicol. None tested positive for extended-spectrum beta-lactamase or AmpC activity. Seven of 39 (18%) E. coli isolates were resistant to three or more antibiotic classes. The E. coli isolates were further analyzed using multilocus sequence typing, which identified four pairs of identical sequence type isolates and 27 diverse strains. The Enterococcus spp. isolates were resistant to a range of antibiotics, with resistance to cefpodoxime seen in 95% of isolates. All Enterococcus spp. isolates were susceptible to ampicillin, gentamicin, chloramphenicol, and vancomycin. This study identified multidrug-resistant phenotypes in enterobacterial isolates that were like those commonly found in domestic ungulates. There was no apparent spatial clustering of the resistance profiles within the zoo. Review of the medical records of individual animals showed no direct relation to the AMR profiles observed. Observed resistance to antibiotics rarely or never used may have been due to coselection or directly acquired from other sources. [ABSTRACT FROM AUTHOR]

Purpose: Many head and neck cancer patients who receive radiation therapy experience radiation-induced dysgeusia (RID), which has no standard treatment. The only supplement controlled clinical trials have evaluated for the treatment of RID is zinc. However, the results of these and other studies investigating the use of zinc for RID have been inconsistent. To assess the validity of zinc as a treatment for RID, we conducted a systematic literature search and performed a meta-analysis to determine the extent to which zinc affects RID incidence and the degree to which ongoing RID responds to zinc. Methods: We searched the Ovid MEDLINE, Ovid Embase, PubMed, and Cochrane Library databases to identify studies investigating the use of zinc-based therapy for RID in head and neck cancer patients treated with radiation that were published between January 1, 2003, and November 9, 2017. Using American Society of Clinical Oncology criteria, we selected studies with a high level of evidence for inclusion in the meta-analysis. Results: Of the 32 full-text articles eligible for inclusion, three were included in the final review and meta-analysis. The meta-analysis showed that, compared with placebo, zinc reduces the incidence of RID (risk ratio, 0.72; 95% confidence interval, 0.67–0.92) but does not improve taste acuity more rapidly following radiation therapy (risk ratio, 2.58; 95% confidence interval, 0.97–6.88). Conclusion: Our findings indicate that zinc-based therapy reduces the incidence of RID but has a minimal effect on ongoing RID. Our findings also highlight the need for additional evidence-based research on this topic. [ABSTRACT FROM AUTHOR]

Arguably the largest source of REED material of their kind so far collected, the accounts of Durham's medieval monastic community provide evidence for plays, music, and performers from around the palatinate, including payments to istriones, joculatores, and ministralli performing for various occasions. With accountancy material, however, it can be difficult deciding if individual entries represent evidence of performers or performances per se, or what the nature of any performance might have been. This essay examines these issues in Durham's accountancy records, looking particularly at Finchale Priory's so-called 'playerchambre': instances in which evidence of 'performance' is uncertain and/or only determinable by wider consideration of context. [ABSTRACT FROM AUTHOR]

Aims Cardiovascular side effects caused by non-steroidal anti-inflammatory drugs (NSAIDs), which all inhibit cyclooxygenase (COX)-2, have prevented development of new drugs that target prostaglandins to treat inflammation and cancer. Microsomal prostaglandin E synthase-1 (mPGES-1) inhibitors have efficacy in the NSAID arena but their cardiovascular safety is not known. Our previous work identified asymmetric dimethylarginine (ADMA), an inhibitor of endothelial nitric oxide synthase, as a potential biomarker of cardiovascular toxicity associated with blockade of COX-2. Here, we have used pharmacological tools and genetically modified mice to delineate mPGES-1 and COX-2 in the regulation of ADMA. Methods and results Inhibition of COX-2 but not mPGES-1 deletion resulted in increased plasma ADMA levels. mPGES-1 deletion but not COX-2 inhibition resulted in increased plasma prostacyclin levels. These differences were explained by distinct compartmentalization of COX-2 and mPGES-1 in the kidney. Data from prostanoid synthase/receptor knockout mice showed that the COX-2/ADMA axis is controlled by prostacyclin receptors (IP and PPARβ/δ) and the inhibitory PGE2 receptor EP4, but not other PGE2 receptors. Conclusion These data demonstrate that inhibition of mPGES-1 spares the renal COX-2/ADMA pathway and define mechanistically how COX-2 regulates ADMA. [ABSTRACT FROM AUTHOR]

Purpose: Local/systemic symptoms during cancer therapy may be exacerbated by dysregulated inflammation and its downstream toxic effects. Minocycline can suppress proinflammatory cytokine release; therefore, we investigated its potential to reduce patient-reported symptom severity during radiotherapy (RT) for head and neck cancer (HNC).Methods: Eligible patients for this blinded, placebo-controlled trial were adults with T0-3, N-any, and M0 HNC receiving single-modality RT. Participants were randomized 1:1 to either minocycline (200 mg/day) or placebo during RT. The primary endpoint was the area under the curve (AUC) of 5 prespecified symptoms (pain, fatigue, disturbed sleep, poor appetite, difficulty swallowing/chewing) during RT, assessed with the MD Anderson Symptom Inventory for HNC (MDASI-HN).Results: We analyzed data from 20 evaluable patients per arm. Overall, 75% had oropharyngeal cancer and 78% were male. No grade 3+ adverse events potentially related to study medication were observed. Two minocycline patients required a feeding tube during RT vs 5 placebo patients (P = 0.21). The average daily AUC during RT for the 5 MDASI-HN symptoms was 3.1 (SD = 1.0) for minocycline and 3.7 (SD = 1.7) for placebo (P = 0.16); the 0.37 effect size was less than our 0.70 target. AUC comparisons for several individual symptoms and symptom interference favored minocycline but were not statistically significant. The greatest numerical differences occurred for systemic symptoms, larger toward treatment end, and in early post-RT recovery.Conclusions: Minocycline was feasible, well tolerated, and achieved a positive signal toward reducing patient-reported symptom severity during RT for HNC, particularly for systemic symptoms. This justifies additional study and informs future trial design. [ABSTRACT FROM AUTHOR]

Purpose: Patients with skin-penetrating implants sometimes report episodic soft tissue reactions. This pilot clinical trial identified the oral microflora of the peri-implant sulcus of cancer patients with jaw reconstruction and compared sites with and without clinical signs of inflammation. Materials and Methods: Ten patients were selected during routine follow-up of their implant-supported removable prostheses. Eligible patients had at least two intraoral skin-penetrating implants; one showed clinical signs of inflammation with/ without symptoms and the other served as a healthy control site. Eight of the 10 patients had undergone osseocutaneous fibula free flap reconstruction and two had received split-thickness skin grafts on the surface of the native mandible. Subjects were assessed on two visits, 30 to 40 days apart. Subgingival microbial samples were obtained and periodontal pocket depths were measured at the test implant abutment. Between visits, patients followed a strict oral hygiene regimen. Radiographic marginal bone loss around implants was measured using cone beam imaging during the second visit. The microflora were identified after isolation and purification of all growing colonies. Results: The number of different microorganisms ranged from 10 to 21 per site. Among all patients, a total of 47 different microorganisms were identified, but none were considered virulent red-complex periodontal pathogens. By the time of the second visit, after adherence to strict mechanical oral hygiene, the average number of microorganisms per site was reduced through elimination of some species. Almost all subjects had identical microbial species in both sites, but the number of visible colonies was lower at the healthy site. Conclusion: Oral peri-implant epidermal proliferation does not appear to be caused by specific microbial pathogens but is likely related to increased microbial load in the implant sulci. Mechanical oral hygiene improves and maintains healthier peri-implant skin tissues. [ABSTRACT FROM AUTHOR]

Objective: A variety of oral topical agents have been used for prevention and management of radiotherapy-induced adverse effects. The antimicrobial nature of some of the commonly used agents is unknown. The purpose of this study was to evaluate antimicrobial efficacies of various oral topical agents on common microorganisms associated with radiated head and neck cancer patients. Method and Materials: Seven commonly used topical oral agents-0.12% chlorhexidine with alcohol, 0.12% chlorhexidine without alcohol, baking soda-salt rinse, 0.4% stannous fluoride gel, 0.63% stannous fluoride rinse, calcium phosphate mouthrinse, and acemannan hydrogel (aloe vera) rinse-were evaluated in vitro for their antimicrobial efficacies against four common microorganisms. A combination of baking soda-salt rinse and 0.4% stannous fluoride gel was evaluated as the eighth agent. The microorganisms used were Staphylococcus aureus, group B Streptococcus, Escherichia coli, and Candida albicans. An ELISA reader was used to measure the turbidity of microbial culture wells and optical density (OD) values for each of the 960 wells recorded. Mean OD values were rank ordered based on their turbidity. One-way ANOVA with Tukey HSD post hoc analysis was used to study differences in OD values (P < .05). Results: Mean OD values classified for topical agents from lowest to highest were chlorhexidine with alcohol, chlorhexidine without alcohol, baking soda- salt, calcium phosphate rinse, and the combination of baking soda-salt and stannous fluoride gel. Mean OD values classified for microorganisms from lowest to highest were Escherichia coli, Staphylococcus aureus, group B Streptococcus, and Candida albicans. Conclusion: A significant difference among the antimicrobial efficacies of topical agents was evident for each of four microorganisms (P < .05). There was also a significant difference among the antimicrobial efficacies of the same topical agent on the four microorganisms tested (P < .05). [ABSTRACT FROM AUTHOR]