Background: Children and young adults with JIA have increased levels of poor oral hygiene and dental decay [1].Periodontitis and types of arthritis are linked by similar components of blood cytokine profiles.Good dental health can be directly affected in JIA patients due to physical limitations in upper limb movements making brushing and flossing teeth difficult.An important factor in oral care is good dental hygiene and access to dental health practitioners.NHS advice is that all children should be reviewed by a dentist annually and be offered both sealant of their teeth and fluoride varnish at the appropriate time.Our aim was to establish if our patients had any barriers to accessing dental care.Methods: All patients (age 18 and under) diagnosed with JIA in the paediatric rheumatology clinic over a period of 3 months were asked to complete a dental care questionnaire.Parents completed the questionnaire for their children if necessary.Data were analysed using Excel.Results: 30 questionnaires were completed.Demographics were M:F 1:1.3, all children were diagnosed with JIA, average age 10.5 years with range 2-18.27 children were registered with an NHS dentist with the exception of one child with a private dentist.26 children had seen a dentist at least annually and one child in the past 2 years. 2 children, one aged 16, were not registered with a dentist because their parents didn't think it was important.11 children had 25 fillings in total, 9 of these children were not supervised during dental hygiene.13 children admitted to drinking sugary drinks daily and had 16 dental fillings.None of the children admitted to smoking.Conclusions: Whilst our audit showed that most children were registered with a dentist and were reviewed annually, only 1 child had been offered sealant and fluoride varnish.The NHS advises that children with chronic medical conditions can be seen either by their NHS dentist or by the local Community specialist dental service which can be accessed by referral from their rheumatology department or NHS dentist.None of the children were seen by the specialist dental service.We have developed an information leaflet informing parents and children with JIA of the importance of dental health explaining the benefits of both sealant and fluoride for teeth.

INTRODUCTION: Radiation therapy (RT) is a critical part of the treatment regimen for glioblastoma.However, tumor recurrence after RT is nearly universal.The mechanism of resistance remains elusive.We conducted an RNAi screen to identify the genetic basis of therapeutic failure after RT.METHODS: We investigated the role of chromatin structure glioblastoma therapeutic response via an RNAi screen of 1002 shRNAs directed against 196 genes with known and predicted chromatin-modifying activity for their involvement in DNA damage response.Mechanistic and pathologic correlative experiments were performed using the top candidate.RESULTS: The screen revealed that Brd4, a double bromodomain-containing protein, was a top candidate in the screen.Brd4 knockdown cells displayed altered chromatin structure and enhanced survival after RT, whereas overexpression of Brd4 isoform B resulted in enhanced RT-induced lethality.Further, loss of Brd4 resulted in an increase in both the number and size of RT-induced gH2AX nuclear foci, whereas overexpression of Brd4 isoform B completely suppressed gH2AX formation, despite equivalent double-strand break formation.These results suggest that BRD4 functions as an endogenous inhibitor of chromatin condensation.We showed that this inhibition is mediated through physical interaction with and inhibition of the SMC2 condensin complex.Importantly, high expression of Brd4 isoform B correlated specifically with response to RT in independent specimen collections (p ¼ 0.01).Further, expression of Brd4 isoform B was significantly reduced in recurrent glioblastoma when compared to that in newly diagnosed glioblastoma (p ¼ 0.0003).CONCLUSIONS: These data implicate Brd4 as an endogenous insulator of DNA damage signaling and that expression of Brd4 in glioblastoma can modulate clinical response to DNA-damaging cancer therapy.This finding, along with the recently published driver mutation in the Histone 3.3 gene in pediatric glioblastomas, underscores the importance of chromatin modification in glioblastoma pathogenesis and etiology.

Background: Although the role of vitamin D deficiency in causing osteomalacia is well recognised, there is limited evidence to suggest that vitamin D deficiency is associated with osteoporosis. One community based study has suggested a reduction in bone density in females with low vitamin D levels, while another has shown no effect of isolated vitamin D deficiency on population fracture rates. We aimed to assess bone density in a cohort of women with low vitamin D levels but no other identified risk factors for osteoporosis. We wished to see if there was any relationship between the two, in order to clarify whether measurement of vitamin D was justified in aiding selection of patients for DXA, and whether DXA was justified in patients found to have isolated vitamin D deficiency. Methods: We identified 70 women referred to an open access DXA scanning service by their GP with low vitamin D levels (under 48 nmol/l) as their only risk factor. We performed DXA of hip and spine and recorded the absolute bone density and Z scores for each patient, together with their vitamin D levels. We calculated the mean (SD) values for Z score at hip and spine, and compared these to a control group of women referred for baseline DXA prior to commencing aromatase inhibitors for breast cancer. We also compared the results with those obtained from the rest of the GP database for women referred up with a 10 year risk of osteoporotic fractures calculated at over 10% using FRAX. These statistical comparisons were made using unpaired Students t test. Mean values for Z scores at hip and spine were calculated and compared within the index group for those with vitamin D levels above and below 20 nmol/l using Students t test. Correlation coefficients between vitamin D levels and Z scores at hip and spine were also calculated for the index group. Results: Mean (SD) values for Z scores in the hip and spine for patients with isolated vitamin D deficiency were +0.30 (0.87) and +0.46 (0.92) respectively. These were not significantly different from controls whose corresponding values were +0.17 (0.34) and +0.49 (0.45). By contrast, patients with a 10 year risk of fracture of over 10% had lower values at hip −0.01 (0.07) and spine −0.13 (0.09) [p = 0.01]. Mean Z scores for those with very low vitamin D levels (under 20 nmol/l) were not significantly different at either site when compared to those with less severe deficiency (20-48 nmol/l) [p = 0.26]. There was no correlation between vitamin D levels and Z scores at hip or spine [r = 0.01] Conclusions: There was no overall decrease in bone density associated with low vitamin D levels in women in our study. There is no evidence to support the routine measurement of vitamin D to select patients for DXA scanning. There is no reason to perform DXA scans in those patients who have an isolated vitamin D deficiency in the absence of defined risk factors for osteoporosis. Disclosure statement: The authors have declared no conflicts of interest.

SummaryWe present a consensus document on the diagnosis and management of C1 inhibitor deficiency, a syndrome characterized clinically by recurrent episodes of angio-oedema. In hereditary angio-oedema, a rare autosomal dominant condition, C1 inhibitor function is reduced due to impaired transcription or production of non-functional protein. The diagnosis is confirmed by the presence of a low serum C4 and absent or greatly reduced C1 inhibitor level or function. The condition can cause fatal laryngeal oedema and features indistinguishable from gastrointestinal tract obstruction. Attacks can be precipitated by trauma, infection and other stimulants. Treatment is graded according to response and the clinical site of swelling. Acute treatment for severe attack is by infusion of C1 inhibitor concentrate and for minor attack attenuated androgens and/or tranexamic acid. Prophylactic treatment is by attenuated androgens and/or tranexamic acid. There are a number of new products in trial, including genetically engineered C1 esterase inhibitor, kallikrein inhibitor and bradykinin B2 receptor antagonist. Individual sections provide special advice with respect to diagnosis, management (prophylaxis and emergency care), special situations (childhood, pregnancy, contraception, travel and dental care) and service specification.

We present a consensus document on the diagnosis and management of C1 inhibitor deficiency, a syndrome characterized clinically by recurrent episodes of angio-oedema. In hereditary angio-oedema, a rare autosomal dominant condition, C1 inhibitor function is reduced due to impaired transcription or production of non-functional protein. The diagnosis is confirmed by the presence of a low serum C4 and absent or greatly reduced C1 inhibitor level or function. The condition can cause fatal laryngeal oedema and features indistinguishable from gastrointestinal tract obstruction. Attacks can be precipitated by trauma, infection and other stimulants. Treatment is graded according to response and the clinical site of swelling. Acute treatment for severe attack is by infusion of C1 inhibitor concentrate and for minor attack attenuated androgens and/or tranexamic acid. Prophylactic treatment is by attenuated androgens and/or tranexamic acid. There are a number of new products in trial, including genetically engineered C1 esterase inhibitor, kallikrein inhibitor and bradykinin B2 receptor antagonist. Individual sections provide special advice with respect to diagnosis, management (prophylaxis and emergency care), special situations (childhood, pregnancy, contraception, travel and dental care) and service specification.