Role of the dental hospital-based paediatric liaison nurse in safeguarding children

Aim: Service evaluation of our dental hospital paediatric liaison nursing (DH-PLN) service which provides an additional route for information sharing about safeguarding concerns via an agreed pathway for two-way communication with public health nurses. Method: Retrospective analysis of clinical records of all children referred by DH teams to PLN in the three months October-December 2016. Results: One hundred and four children were referred; mean age was 6.2 years, 89.4% from Index of Multiple Deprivation (IMD) quintiles 4 and 5, and 70.2% were attending for dental general anaesthesia. The most common referral reason was dental neglect in 66.3%, followed by missed appointments in 50.0%. The PLN checked child health databases and shared information with health visitors and school nurses (46.2% and 53.8% respectively). Feedback retrieved included known child maltreatment risk factors in 7.7%. This prompted additional child protection referrals to children's social services for seven children (6.7%). Dental outcomes six months later were: treatment complete in 50.0%, treatment ongoing 28.8%, discharged to original referrer with treatment incomplete in 21.1%. Conclusion: This DH-PLN service promotes integrated multidisciplinary working, helping overcome barriers to dentistry's involvement in safeguarding. It facilitates more accurate assessments of risk of harm to children receiving dental care and prompts additional child protection referrals to social services

A Role for the Vacuolating Cytotoxin, VacA, in Colonization and Helicobacter pylori-Induced Metaplasia in the Stomach

Carriage of Helicobacter pylori strains producing more active (s1/i1) forms of VacA is strongly associated with gas-tric adenocarcinoma. To our knowledge, we are the first to determine effects of different polymorphic forms of VacA on inflammation and metaplasia in the mouse stomach. Bacteria producing the less active s2/i2 form of VacA colonized mice more efficiently than mutants null for VacA or producing more active forms of it, providing the first evidence of a positive role for the minimally active s2/i2 toxin. Strains producing more active toxin forms induced more severe and extensive metaplasia and in flammation in the mouse stomach than strains producing weakly active (s2/i2) toxin. We also examined the association in humans, controlling for cag PAI status. In human gastric biopsy specimens, the vacA i1 allele was strongly associated with precancerous intestinal metaplasia, with almost complete absence of intestinal metaplasia in subjects infected with i2-type strains, even in a vacA s1, cagA+ background

Change in Oral Health-Related Quality of Life Following Minimally Invasive Aesthetic Treatment for Children with Molar Incisor Hypomineralisation: A Prospective Study

Molar incisor hypomineralisation (MIH) is a common enamel condition, presenting with incisor opacities, which may be of psychosocial concern to children. This clinical study sought to determine whether minimally invasive treatment, aiming to improve incisor aesthetics, would also improve children's oral health-related quality of life (OHRQoL). 111 MIH patients, aged 7⁻16 years, referred to a UK Dental Hospital, were invited to complete the Child Oral Health Impact Profile (C-OHIP-SF19) prior to any intervention (T₀) and again at one-month following the intervention (T₁) for MIH. Treatment regimens included one or more of the following: Microabrasion; resin infiltration; tooth whitening; resin composite restoration. Data were obtained for 93 children with a mean age of 11 years. Mean total C-OHIP-SF19 score at T₀ was 47.00 (SD = 9.29; range = 0⁻76) and this increased significantly at T₁ to 58.24 (SD = 9.42; range = 0⁻76; p < 0.001, paired t-test), indicating a marked improvement in self-reported OHRQoL. There were no statistically significant differences according to gender. This is the first study to show that simple, minimally invasive dental treatment, to reduce the visibility of enamel opacities, in MIH, can have a positive impact on children's wellbeing

Determinants of children’s oral health-related quality of life following aesthetic treatment of enamel opacities

Objectives To identify clinical and psychosocial predictors of oral health-related quality of life (OHRQoL) in children with molar incisor hypomineralisation (MIH) following aesthetic treatment of incisor opacities. Methods Participants were 7- to 16-year-old children referred to a UK Dental Hospital for management of incisor opacities. Prior to treatment (To), participants completed validated questionnaires to assess OHRQoL and overall health status (C−OHIP-SF19), and self-concept (Harter’s Self-Perception Profile for Children [SPPC]). Interventions for MIH included microabrasion, resin infiltration, tooth whitening or composite resin restoration. Children were reviewed after six months (T1) when they re-completed the C−OHIP-SF19 and SPPC questionnaires. The relationships of predictors with improvement of children’s OHRQoL (T1-To) and children’s overall health status at T1 were assessed using linear and ordinal logistic regression respectively, guided by the Wilson and Cleary’s theoretical model. Results Of 103 participants, 86 were reviewed at T1 (83.5 % completion rate). Their mean age was 11-years (range = 7−16) and 60 % were female. Total and domain OHRQoL scores significantly increased (improved OHRQoL) following MIH treatment. There was a significant positive change in SPPC physical appearance subscale score between To and T1. A higher number of anterior teeth requiring aesthetic treatment were associated with poor improvement of socio-emotional wellbeing at T1 (Coef =-0.43). Higher self-concept at To was associated with greater improvement of socio-emotional wellbeing at T1 (ß = 3.44). Greater orthodontic treatment need (i.e. higher IOTN-AC score) at T0 was linked to worse overall oral health at T1 (OR = 0.43). Conclusions Psychosocial factors and dental clinical characteristics were associated with change in children’s OHRQoL following minimal interventions for incisor opacities. Clinical significance MIH is a common condition and clinicians should be aware of the negative impacts some children experience, particularly those with multiple anterior opacities, poor tooth alignment and low self-concept. However, simple, minimally invasive treatments can provide good clinical and psychosocial outcomes and should be offered to children reporting negative effects

The active form of Helicobacter pylori vacuolating cytotoxin induces decay-accelerating factor CD55 in association with intestinal metaplasia in the human gastric mucosa

High-level expression of decay-accelerating factor, CD55, has previously been found in human gastric cancer (GC) and intestinal metaplasia (IM) tissues. Therapeutic effects of CD55 inhibition in cancer have been reported. However, the role of Helicobacter pylori infection and virulence factors in the induction of CD55 and its association with histological changes of the human gastric mucosa remain incompletely understood. We hypothesised that CD55 would be increased during infection with more virulent strains of H. pylori, and with more marked gastric mucosal pathology. RT-qPCR and immunohistochemical analyses of gastric biopsy samples from 42 H. pylori-infected and 42 uninfected patients revealed that CD55 mRNA and protein were significantly higher in the gastric antrum of H. pylori-infected patients, and this was associated with the presence of IM, but not atrophy, or inflammation. Increased gastric CD55 and IM were both linked with colonisation by vacA i1-type strains independently of cagA status, and in vitro studies using isogenic mutants of vacA confirmed the ability of VacA to induce CD55 and sCD55 in gastric epithelial cell lines. siRNA experiments to investigate the function of H. pylori-induced CD55 showed that CD55 knockdown in gastric epithelial cells partially reduced IL-8 secretion in response to H. pylori, but this was not due to modulation of bacterial adhesion or cytotoxicity. Finally, plasma samples taken from the same patients were analysed for the soluble form of CD55 (sCD55) by ELISA. sCD55 levels were not influenced by IM and did not correlate with gastric CD55 mRNA levels. These results suggest a new link between active vacA i1-type H. pylori, IM, and CD55, and identify CD55 as a molecule of potential interest in the management of IM as well as GC treatment. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland

Helicobacter pylori vacA transcription is genetically-determined and stratifies the level of human gastric inflammation and atrophy

Aims Helicobacter pylori infection is the major cause of peptic ulceration and gastric cancer, and an important virulence determinant is its vacuolating cytotoxin, vacA. Previously, we have described allelic variation in vacA which determines toxin activity and disease risk. We now aimed to quantify vacA mRNA expression in the human stomach, define its genetic determinants and assess how well itpredicted gastric pathology. Methods Gastric biopsies were donated by 39 H. pylori-infected patients attending for endoscopy at Queen’s Medical Centre, Nottingham, UK. Total RNA was extracted, and vacA mRNA quantified by reverse transcriptase quantitative polymerase chain reaction. Separate biopsies were histologically scored for inflammation and atrophy using the updated Sydney system. H. pylori strains were isolated from further biopsies, and the nucleotide sequence upstream of vacA determined. Results vacA mRNA levels in human stomachs varied by two orders of magnitude independently of vacA allelic type. Among vacA i1-type (toxic) strains, increased vacA expression was strongly associated with higher grade gastric inflammation (

Calpain system protein expression in carcinomas of the pancreas, bile duct and ampulla

Background: Pancreatic cancer, including cancer of the ampulla of Vater and bile duct, is very aggressive and has a poor five year survival rate; improved methods of patient stratification are required. Methods: We assessed the expression of calpain-1, calpain-2 and calpastatin in two patient cohorts using immunohistochemistry on tissue microarrays. The first cohort was composed of 68 pancreatic adenocarcinomas and the second cohort was composed of 120 cancers of the bile duct and ampulla. Results: In bile duct and ampullary carcinomas an association was observed between cytoplasmic calpastatin expression and patient age (P = 0.036), and between nuclear calpastatin expression and increased tumour stage (P = 0.026) and the presence of vascular invasion (P = 0.043). In pancreatic cancer, high calpain-2 expression was significantly associated with improved overall survival (P = 0.036), which remained significant in multivariate Cox-regression analysis (hazard ratio = 0.342; 95% confidence interva l = 0.157-0.741; P = 0.007). In cancers of the bile duct and ampulla, low cytoplasmic expression of calpastatin was significantly associated with poor overall survival (P = 0.012), which remained significant in multivariate Cox-regression analysis (hazard ratio = 0.595; 95% confidence interval = 0.365-0.968; P = 0.037). Conclusion: The results suggest that calpain-2 and calpastatin expression is important in pancreatic cancers, influencing disease progression. The findings of this study warrant a larger follow-up study. Keywords: Calpain, Calpastatin, Pancreas, Ampulla, Bile duct, Cance

Immunohistochemical expression of mitochondrial membrane complexes (MMCs) I, III, IV and V in malignant and benign periampullary epithelium: a potential target for drug therapy of periampullary cancer?

<p>Abstract</p> <p>Background</p> <p>Mitochondrial membrane complexes (MMCs) are key mediators of cellular oxidative phosphorylation, and inhibiting them could lead to cell death. No published data are available on the relative abundance of MMCs in different periampullary cancers. Therefore, we studied the expression profile of MMCs I, III, IV and V in periampullary cancers, reactive pancreatitis, normal pancreas and chronic pancreatitis.</p> <p>Methods</p> <p>This was a retrospective study on tissue microarrays constructed from formalin-fixed paraffin-embedded tissue from 126 consecutive patients (cancer = 104, chronic pancreatitis = 22) undergoing pancreatic resections between June 2001 and June 2006. 78 specimens of chronic pancreatitis tissue were obtained adjacent to areas of cancer. Normal pancreatic tissue was obtained from the resection specimens in a total of 30 patients. Metastatic tumours in 61 regional lymph nodes from 61 patients were also studied.</p> <p>Results</p> <p>MMCs I, III, IV and V were highly expressed (p < 0.05) in all primary periampullary cancers compared with metastatic lymph nodes and adjacent benign pancreas. MMCs III, IV and V were highly expressed in all cancers regardless of type compared with chronic pancreatitis (p < 0.05). Higher expression of MMCs I and V was associated with better survival and may, in part, relate to lower expression of these MMCs in poorly differentiated tumours compared with well and moderately differentiated tumours.</p> <p>Conclusions</p> <p>Differential expression of MMCs III, IV and V in primary periampullary cancers compared with adjacent benign periampullary tissue and chronic pancreatitis is a novel finding, which may render them attractive anticancer targets.</p

Structure and Luminescence Properties of Eu3+-Doped Cubic Mesoporous Silica Thin Films

Eu3+ ions-doped cubic mesoporous silica thin films with a thickness of about 205 nm were prepared on silicon and glass substrates using triblock copolymer as a structure-directing agent using sol–gel spin-coating and calcination processes. X-ray diffraction and transmission electron microscopy analysis show that the mesoporous silica thin films have a highly ordered body-centered cubic mesoporous structure. High Eu3+ ion loading and high temperature calcination do not destroy the ordered cubic mesoporous structure of the mesoporous silica thin films. Photoluminescence spectra show two characteristic emission peaks corresponding to the transitions of5D0-7F1 and 5D0-7F2 of Eu3+ ions located in low symmetry sites in mesoporous silica thin films. With the Eu/Si molar ratio increasing to 3.41%, the luminescence intensity of the Eu3+ ions-doped mesoporous silica thin films increases linearly with increasing Eu3+ concentration

The SNAT4 isoform of the system A amino acid transporter is functional in human placental microvillous plasma membrane

Placental system A activity is important for the supply of neutral amino acids needed for fetal growth. There are three system A isoforms: SNAT1, SNAT2 and SNAT4, but the contribution of each to system A-mediated transport is unknown. Here, we have used immunohistochemistry to demonstrate that all three isoforms are present in the syncytiotrophoblast suggesting each plays a role in amino acid transport across the placenta. We next tested the hypothesis that the SNAT4 isoform is functional in microvillous plasma membrane vesicles (MVM) from normal human placenta using a method which exploits the unique property of SNAT4 to transport both cationic amino acids as well as the system A-specific substrate MeAIB. The data show that SNAT4 contribution to system A-specific amino acid transport across MVM is higher in first trimester placenta compared to term (approx. 70% and 33%, respectively, P < 0.01). Further experiments performed under more physiological conditions using intact placental villous fragments suggest a contribution of SNAT4 to system A activity in first trimester placenta but minimal contribution at term. In agreement, Western blotting revealed that SNAT4 protein expression is higher in first trimester MVM compared to term (P < 0.05). This study provides the first evidence of SNAT4 activity in human placenta and demonstrates the contribution of SNAT4 to system A-mediated transport decreases between first trimester and term: our data lead us to speculate that at later stages of gestation SNAT1 and/or SNAT2 are more important for the supply of amino acids required for normal fetal growth