A major T cell antigen of Mycobacterium leprae is a 10-kD heat-shock cognate protein.

Several mycobacterial antigens, identified by monoclonal antibodies and patient sera, have been found to be homologous to stress or heat-shock proteins (hsp) defined in Escherichia coli and yeast. A major antigen recognized by most Mycobacterium leprae-reactive human T cell lines and cell wall-reactive T cell clones is a 10-kD protein that has now been cloned and sequenced. The predicted amino acid sequence of this protein is 44% homologous to the hsp 10 (GroES) of E. coli. The purified native and recombinant 10-kD protein was found to be a stronger stimulator of peripheral blood T cell proliferation than other native and recombinant M. leprae proteins tested. The degree of reactivity paralleled the response to intact M. leprae throughout the spectrum of leprosy. Limiting-dilution analysis of peripheral blood lymphocytes from a patient contact and a tuberculoid patient indicated that approximately one third of M. leprae-reactive T cell precursors responded to the 10-kD antigen. T cell lines derived from lepromin skin tests were strongly responsive to the 10-kD protein. T cell clones reactive to both the purified native and recombinant 10-kD antigens recognized M. leprae-specific epitopes as well as epitopes crossreactive with the cognate antigen of M. tuberculosis. Further, the purified hsp 10 elicited strong delayed-type hypersensitivity reactions in guinea pigs sensitized to M. leprae. The strong T cell responses against the M. leprae 10-kD protein suggest a role for this heat-shock cognate protein in the protective/resistant responses to infection

Neurological complications following extrusion of sodium hypochlorite solution during root canal treatment.

AIM: To report the presentation and management of two cases with neurological complications secondary to the extrusion of sodium hypochlorite solution into the facial soft tissues during root canal treatment. SUMMARY: The clinical features, with particular emphasis on nerve deficit following inadvertent extrusion of sodium hypochlorite, are discussed and its management highlighted. Early and aggressive treatment is advocated following such incidents in order to reduce potentially serious complications. KEY LEARNING POINTS: *Neurological sequelae can follow inadvertent hypochlorite extrusion. *Early recognition may avert a potentially more serious outcome. *Active hospital treatment including intravenous steroids and antibiotics is recommended

Atypical features in pleomorphic adenoma--a clinicopathologic study and implications for management.

Pleomorphic adenoma is the most common salivary gland neoplasm and infrequently undergoes malignant transformation. Carcinoma ex pleomorphic adenoma is typically an infiltrative neoplasm with features of cellular pleomorphism, high mitotic activity, peri-neural and vascular invasion. More recently, sub-groups of pleomorphic adenoma have been described exhibiting vascular invasion and features of malignancy without evidence of extra-capsular extension. There is little information in the literature regarding how these different histological variants influence clinical presentation and outcome following primary treatment. Following a review of 100 consecutive pleomorphic adenomas removed from the major salivary glands, 4 cases with atypical histological features were found. Three tumours exhibited features of dysplasia/carcinoma without evidence of extra-capsular invasion and a further case demonstrated benign vascular invasion. There were no clinical features suggestive of the atypical nature of these neoplasms, though fine needle aspiration cytology (FNAC) was suspicious of a malignancy in 2 cases and CT scan in 1 case. Patients underwent a superficial parotidectomy or submandibular gland excision based on the location of the lesion. All lesions were completely excised and there were no recurrences in this series

Diclofenac Mouthwash as a potential therapy for reducing pain and discomfort in chemo-radiotherapy-induced oral mucositis

AIMS: Oral and/or oropharyngeal acute mucositis during and after chemo-radiotherapy (chemo-RT) for head and neck squamous cell carcinoma (HNSCC) can be extremely painful, sometimes requiring nasogastric feeding to enable adequate nutrition. The MASCC/ISOO evidence- based guidelines recommend benzydamine mouthwash for mucositis prevention in RT (recently updated to include chemo-RT), and a Cochrane systematic review found other agents to be effective in prophylaxis. Diclofenac mouthwash is licenced for painful oral mucosal inflammatory conditions but to our knowledge has not been assessed in chemo-RT associated oral mucositis. METHOD: A clinical observation and service evaluation study in 10 patients undergoing chemo-RT for HNSCC to assess the potential value of diclofenac mouthwash (0.74mg/ml) in reducing symptoms. Patients used 20ml of mouthwash up to 4 times a day starting in week 3 (of a 6 week course of treatment), recording pain and discomfort scores using a visual analogue scale on days 0, 1,7 and 14 (until the end of week 4). As per our current clinical practice, oral mucositis was not clinically scored as an outcome. Statistical analysis was performed using a one-way ANOVA. RESULTS: Using diclofenac mouthwash, 9/10 patients experienced pain score reduction from day 0 (mean score 6.75 +/- SD 1.83) to day 2 (5.05 +/- SD 1.62) and day 14 (4.09 +/- SD 1.96). CONCLUSIONS: Diclofenac mouthwash may be beneficial for managing chemo-RT-induced oral mucositis. While a prospective randomised clinical trial is needed, it can be prescribed for this condition within its current licence

Role of salivary transcriptomics as potential biomarkers in oral cancer: A systematic review

Introduction: Transcriptomes in saliva can be used as potential biomarkers for both diagnostic and response to treatment in oral squamous cell carcinoma (OSCC). In this review, we explored their application in this increasingly common disease. Materials and methods: PubMed, EMBASE, Scopus, Web of Science and grey literature from January 1990 to May 2017 were searched. Two independent reviewers performed the study selection according to eligibility criteria. Results: A total of nine studies were included. Three studies showed increased expression of DUSP1, IL8, IL1B, OAZ1, SAT1, S100P and two showed increased expression of miRNA‐31 among study groups compared to normal healthy controls. The sensitivity ranged from 14% to 100%, while the specificity ranged from 38% to 100%. miRNA‐27b had the highest AUC (write in full) of 0.9643 and DUSP1 had the minimum AUC of 0.41. Conclusion: Salivary transcriptomics may play an effective role as a robust and non‐invasive biomarker sighting tool for the diagnosis and management of OSCC

Induction of fibroblast senescence generates a non-fibrogenic myofibroblast phenotype that differentially impacts on cancer prognosis

Cancer-associated fibroblasts (CAF) remain a poorly characterized, heterogeneous cell population. Here we characterized two previously described tumor-promoting CAF sub-types, smooth muscle actin (SMA)-positive myofibroblasts and senescent fibroblasts, identifying a novel link between the two

Alcohol consumption and lifetime change in cognitive ability:a gene × environment interaction study

Studies of the effect of alcohol consumption on cognitive ability are often confounded. One approach to avoid confounding is the Mendelian randomization design. Here, we used such a design to test the hypothesis that a genetic score for alcohol processing capacity moderates the association between alcohol consumption and lifetime change in cognitive ability. Members of the Lothian Birth Cohort 1936 completed the same test of intelligence at age 11 and 70 years. They were assessed for recent alcohol consumption in later life and genotyped for a set of four single-nucleotide polymorphisms in three alcohol dehydrogenase genes. These variants were unrelated to late-life cognition or to socioeconomic status. We found a significant gene × alcohol consumption interaction on lifetime cognitive change (p = 0.007). Individuals with higher genetic ability to process alcohol showed relative improvements in cognitive ability with more consumption, whereas those with low processing capacity showed a negative relationship between cognitive change and alcohol consumption with more consumption. The effect of alcohol consumption on cognitive change may thus depend on genetic differences in the ability to metabolize alcohol

Fructose transport-deficient Staphylococcus aureus reveals important role of epithelial glucose transporters in limiting sugar-driven bacterial growth in airway surface liquid.

Hyperglycaemia as a result of diabetes mellitus or acute illness is associated with increased susceptibility to respiratory infection with Staphylococcus aureus. Hyperglycaemia increases the concentration of glucose in airway surface liquid (ASL) and promotes the growth of S. aureus in vitro and in vivo. Whether elevation of other sugars in the blood, such as fructose, also results in increased concentrations in ASL is unknown and whether sugars in ASL are directly utilised by S. aureus for growth has not been investigated. We obtained mutant S. aureus JE2 strains with transposon disrupted sugar transport genes. NE768(fruA) exhibited restricted growth in 10 mM fructose. In H441 airway epithelial-bacterial co-culture, elevation of basolateral sugar concentration (5-20 mM) increased the apical growth of JE2. However, sugar-induced growth of NE768(fruA) was significantly less when basolateral fructose rather than glucose was elevated. This is the first experimental evidence to show that S. aureus directly utilises sugars present in the ASL for growth. Interestingly, JE2 growth was promoted less by glucose than fructose. Net transepithelial flux of D-glucose was lower than D-fructose. However, uptake of D-glucose was higher than D-fructose across both apical and basolateral membranes consistent with the presence of GLUT1/10 in the airway epithelium. Therefore, we propose that the preferential uptake of glucose (compared to fructose) limits its accumulation in ASL. Pre-treatment with metformin increased transepithelial resistance and reduced the sugar-dependent growth of S. aureus. Thus, epithelial paracellular permeability and glucose transport mechanisms are vital to maintain low glucose concentration in ASL and limit bacterial nutrient sources as a defence against infection

A hypothetico-deductive approach to assessing the social function of chemical signalling in a non-territorial solitary carnivore

The function of chemical signalling in non-territorial solitary carnivores is still relatively unclear. Studies on territorial solitary and social carnivores have highlighted odour capability and utility, however the social function of chemical signalling in wild carnivore populations operating dominance hierarchy social systems has received little attention. We monitored scent marking and investigatory behaviour of wild brown bears Ursus arctos, to test multiple hypotheses relating to the social function of chemical signalling. Camera traps were stationed facing bear ‘marking trees’ to document behaviour by different age sex classes in different seasons. We found evidence to support the hypothesis that adult males utilise chemical signalling to communicate dominance to other males throughout the non-denning period. Adult females did not appear to utilise marking trees to advertise oestrous state during the breeding season. The function of marking by subadult bears is somewhat unclear, but may be related to the behaviour of adult males. Subadults investigated trees more often than they scent marked during the breeding season, which could be a result of an increased risk from adult males. Females with young showed an increase in marking and investigation of trees outside of the breeding season. We propose the hypothesis that females engage their dependent young with marking trees from a young age, at a relatively ‘safe’ time of year. Memory, experience, and learning at a young age, may all contribute towards odour capabilities in adult bears