Analysis of the association between salivary proteins and oral mucositis in patients with head and neck cancer undergoing IMRT: a longitudinal study.

INTRODUCTION: This longitudinal study assessed the association between salivary protein composition and the clinical onset/severity of oral mucositis (OM) in patients with head and neck tumours treated with intensity-modulated-radiotherapy (IMRT). METHODS: Saliva samples/clinical data were obtained from 40 head and neck cancer patients treated at Guy's Hospital before -IMRT(T0) and after-IMRT (T1 = 6 m, T2 = 12 m) (ethics approval/consent). Salivary flow rate, total protein concentration, and secretion rate were determined from saliva samples and compared with pre-treatment values. OM was assessed, total/specific salivary proteins, including mucin 5B and 7, IgA, cystatin-S, albumin, and α-amylase, were quantified. RESULTS: 95% patients experienced OM during IMRT, with 33 subjects reaching grade 2&3. At T1, there was a significant reduction in salivary flow rate, total protein secretion rate, α-amylase and cystatin-S compared to baseline. Remarkably IMRT did not significantly alter mucin 5B and 7, or the IgA secretion rate at any time point. At T1, all the analyzed proteins were associated with the OM outcomes. In addition, there was a significant inverse correlation between IgA concentration at T0 and the severity of OM during IMRT. CONCLUSION: This study revealed significant associations between several salivary proteins and OM in patients with head and neck cancer undergoing IMRT. Further longitudinal studies are needed to confirm these results. CLINICAL SIGNIFICANCE: The study contributes to the understanding of certain salivary proteins association with OM. This could be the first step towards identifying potential salivary markers that could offer perspectives for personalized medicine approaches to improve their quality of life (QoL). RESEARCH QUESTION: What is the association between salivary proteins and the occurrence and severity of OM in head and neck cancer patients? AIM: To assess the association between salivary protein composition with the clinical onset/severity of oral mucositis (OM) in head and neck cancer patients treated with intensity modulated radiotherapy. NULL HYPOTHESIS: There is no association between salivary proteins and onset/severity of OM in HNC patients.

Do Tooth Loss and Dentures Cause Body Image Disturbance?

PURPOSE: To investigate the psychologic morbidities associated with tooth loss despite treatment with technically successful dentures. MATERIALS AND METHODS: This cross-sectional questionnaire-based study compared the psychologic disturbance and functional difficulties in two groups: individuals with tooth loss who wore optimal-quality removable dentures (test group), and individuals with tooth loss who did not wear dentures (control group). The questionnaire used was developed and validated previously. The short-form revised Eysenck personality questionnaire was also used to assess the relationship with personality traits. A total of 138 participants were recruited (denture group = 70; control group = 68). RESULTS: There was a significant difference in body image dissatisfaction between the groups (χ2 = 7.72, P value = .005). The denture group had 5.75-times higher probability than the control group of suffering from body image disturbance. Older patients were predicted to have 75% less probability of body image disturbance (OR = 0.25), and men were predicted to have up to 70% less disturbance (OR = 0.3). As for psychologic morbidities, participants in both groups presented with somatic symptoms related to depression or anxiety, which were nearly double that expected in the general population (15.7% and 7.8%, respectively). Furthermore, participants who complained about body image impairment were more likely to have higher scores on the neuroticism scale (OR = 3.64). CONCLUSION: Tooth loss and dentures could be associated with body image dissatisfaction and psychologic morbidity. Planning for patient-centered care is paramount prior to extracting any teeth and providing replacement options.

The need for early Kasai portoenterostomy: a Western Pediatric Surgery Research Consortium study.

PURPOSE: The purpose of this study was to investigate factors impacting transplant-free survival among infants with biliary atresia. METHODS: A multi-institutional, retrospective cohort study was performed at nine tertiary-level children's hospitals in the United States. Infants who underwent Kasai portoenterostomy (KP) from January 2009 to May 2017 were identified. Clinical characteristics included age at time of KP, steroid use, surgical approach, liver pathology, and surgeon experience. Likelihood of transplant-free survival (TFS) was evaluated using logistic regression, adjusting for patient and surgeon-level factors. Secondary outcomes at 1 year included readmission, cholangitis, reoperation, mortality, and biliary clearance. RESULTS: Overall, 223 infants underwent KP, and 91 (40.8%) survived with their native liver. Mean age at surgery was 63.9 days (± 24.7 days). At 1 year, 78.5% experienced readmission, 56.9% developed cholangitis, 3.8% had a surgical revision, and 5 died. Biliary clearance at 3 months was achieved in 76.6%. Controlling for patient and surgeon-level factors, each additional day of age toward operation was associated with a 2% decrease in likelihood of TFS (OR 0.98, 95% CI 0.97-0.99). CONCLUSION: Earlier surgical intervention by Kasai portoenterostomy at tertiary-level centers significantly increases likelihood for TFS. Policy-level interventions to facilitate early screening and surgical referral for infants with biliary atresia are warranted to improve outcomes.

Dentists' perspectives on denture provision after radiotherapy for head and neck cancer: an exploratory study using the theoretical domains framework.

Introduction Patients are often keen to replace their missing teeth after radiotherapy for head and neck cancer (HNC), yet such replacement does not always take place.Aims This study aimed to investigate the influences on dentists' provision of dentures for patients treated with radiotherapy for HNC, including whether risk of osteoradionecrosis (ORN) is a factor influencing intention to provide dentures.Methods An online cross-sectional survey including a case scenario, self-reported behaviour and measures of factors (selected using the theoretical domains framework) that may affect dentists' decisions was completed by general dental practitioners (n = 150) and HNC multidisciplinary team dentists (n = 25) in England.Results Dentists' reluctance to provide dentures for HNC patients post-radiotherapy was often due to concerns about dry mouth and radiation caries rather than risk of ORN. Knowledge of guidelines and beliefs about consequences were independently associated with dentists' intention to replace missing teeth with dentures.Conclusion The likelihood of replacing missing teeth with dentures increased with awareness of clinical guidance on the use of dentures in HNC and that denture provision would have positive consequences that outweigh the costs.

Should the HPV positive oropharyngeal cancer patient be considered for a two-stage dental assessment for their radiation treatment?

Patients due to commence head and neck radiation treatment are expected to undergo a dental assessment and be deemed 'dentally fit'. Though this intervention is welcomed by the dental fraternity it is not without its challenges especially in human papilloma virus (HPV) related oropharyngeal cancer (OPC) which has seen a phenomenal rise over the past decade. This perspective piece presents these challenges and proposes a potential adaption of the dental assessment for HPV OPC patients though not necessarily exclusive to this tumour sub-site.

Dentoalveolar radiation dose following IMRT in oropharyngeal cancer-An observational study.

OBJECTIVES: This observational study aims to determine individual dental doses in oropharyngeal cancer (OPC) patients managed by intensity modulated radiation treatment (IMRT). MATERIALS AND METHODS: OPC patients treated with IMRT had each tooth individually contoured on post-IMRT CT scans. The mean, maximum and minimum doses were calculated per tooth-based upon patient and tumor demographics (tumor size and nodal status). RESULTS: A total of 160 patients were included in this study. Escalating tumor size and nodal status led to an observed increase in Dmean doses to the dentition on the contralateral tumor side. A significant region in both jaws received >30 Gy in this tumor group. CONCLUSION: Tumor demographics were observed to influence RT doses to the dentition and need to be considered when providing a pre-RT dental assessment. The observed dose of >30 Gy in large spans of the dentition and jaws highlights future risk of dental deterioration and ORN with long term survival.

Urea-based amino sugar agent clears murine liver and preserves protein fluorescence and lipophilic dyes.

Five established clearing protocols were compared with a modified and simplified method to determine an optimal clearing reagent for three-dimensionally visualizing fluorophores in the murine liver, a challenging organ to clear. We report successful clearing of whole liver lobes by modification of an established protocol (UbasM) using only Ub-1, a urea-based amino sugar reagent, in a simpler protocol that requires only a 24-h processing time. With Ub-1 alone, we observed sufficiently preserved liver tissue structure in three dimensions along with excellent preservation of fluorophore emissions from endogenous protein reporters and lipophilic tracer dyes. This streamlined technique can be used for 3D cell lineage tracing and fluoroprobe-based reporter gene expression to compare various experimental conditions.

Pre-radiotherapy dental status of oropharyngeal cancer patients based on HPV status in a novel radiation era.

Objectives Among common head and neck cancers (HNCs), oropharyngeal cancer (OPC) patients have been identified as having a better dentition than many other tumour subsites. OPC consists of human papillomavirus (HPV)-positive and negative groups with different prognosis. The purpose of this study is to explore the presenting dental status of OPC patients based on HPV status at the pre-radiotherapy phase.Materials and methods The study reviewed the dental panoramic radiographs of OPC patients seen at a dedicated pre-radiotherapy dental assessment clinic from 2011-2017. Only patients planned for intensity-modulated radiotherapy treatment were included within this study. Relevant dental and oncological data were collected.Results A total of 316 patients with known HPV status (215 positive; 101 negative) were included for analysis. HPV-positive patients had significantly more teeth on attendance than HPV-negative patients (22.3 vs 19.0, p = 0.0000) and horizontal bone loss was less severe compared to HPV-negative patients (p = 0.0000). HPV-positive males and patients in the 55-64 decade presented with the best and most complex dentition.Conclusion The rise of OPC with the prospect of long survival, particularly in HPV-positive patients, requires a dentition with adequate function and subsequent maintenance. The current study demonstrated that these patients have a complex dentition presenting new challenges to the dentist. This may explain in part the elevated osteoradionecrosis rate seen in this tumour group.

Use of dentures, receipt of information, quality of life, and oral function following radiotherapy for head and neck cancer.

BACKGROUND: Teeth with a poor prognosis are often extracted prior to radiotherapy for head and neck cancer (HNC) in order to help prevent the need for dental treatment after radiotherapy that might in turn lead to the development of osteoradionecrosis. However, the details and impact of replacing missing teeth after radiotherapy for HNC have received little attention, especially from the patients' perspective. AIMS: This study aimed to assess the use, satisfaction, and impact of denture use following radiotherapy for HNC. The study also sought to determine patients' satisfaction with information about replacing their missing teeth postradiotherapy. Finally, this study also aimed to assess interest in replacing missing teeth for those who had not done so. METHODS: A structured, validated, and reliable questionnaire was sent to HNC patients who had received radiotherapy and had missing teeth at the time of discharge. In addition to demographic details and self-reported oral hygiene, the questionnaire included questions on use of (or interest in) dentures, satisfaction with dentures, satisfaction with information about replacing missing teeth, QoL as measured by two questions from the short version of WHOQoL-BREF, and oral functioning as measured by BCSQ-H&N. Demographic details and clinical details were extracted from the hospital records. RESULTS: N = 80 (24%) returned a completed questionnaire. Participants had an average of 12 missing teeth (SD = 8.05). Most (n = 60, 75%) had not replaced their missing teeth. Of these, 35 (58%) were very or extremely interested in doing so. For HNC survivors who wore dentures, there was variable satisfaction and a number of side-effects of wearing dentures. Satisfaction with information about replacing missing teeth was low. There was no statistical difference in QoL or oral functioning between participants who wore dentures and participants who did not wear dentures. However, those with dentures reported fewer problems with carrying out daily routines as measured by the oral functioning tool. CONCLUSIONS: QoL and oral functioning were similar regardless of denture use, highlighting reduced oral function in both those with and without dentures. In those who had not replaced their missing teeth, there was substantial interest in doing so and thus may be an unmet need. The dental team could offer HNC survivors more support after radiotherapy and following denture provision to improve information about denture use and increase satisfaction with dentures.

Prominin-1-expressing hepatic progenitor cells induce fibrogenesis in murine cholestatic liver injury.

Cholestatic liver injury is associated with intrahepatic biliary fibrosis, which can progress to cirrhosis. Resident hepatic progenitor cells (HPCs) expressing Prominin-1 (Prom1 or CD133) become activated and participate in the expansion of cholangiocytes known as the ductular reaction. Previously, we demonstrated that in biliary atresia, Prom1(+) HPCs are present within developing fibrosis and that null mutation of Prom1 significantly abrogates fibrogenesis. Here, we hypothesized that these activated Prom1-expressing HPCs promote fibrogenesis in cholestatic liver injury. Using Prom1CreERT2-nLacZ/+ ;Rosa26Lsl-GFP/+ mice, we traced the fate of Prom1-expressing HPCs in the growth of the neonatal and adult livers and in biliary fibrosis induced by bile duct ligation (BDL). Prom1-expressing cell lineage labeling with Green Fluorescent Protein (GFP) on postnatal day 1 exhibited an expanded population as well as bipotent differentiation potential toward both hepatocytes and cholangiocytes at postnatal day 35. However, in the adult liver, they lost hepatocyte differentiation potential. Upon cholestatic liver injury, adult Prom1-expressing HPCs gave rise to both PROM1(+) and PROM1(-) cholangiocytes contributing to ductular reaction without hepatocyte or myofibroblast differentiation. RNA-sequencing analysis of GFP(+) Prom1-expressing HPC lineage revealed a persistent cholangiocyte phenotype and evidence of Transforming Growth Factor-ß pathway activation. When Prom1-expressing cells were ablated with induced Diphtheria toxin in Prom1CreERT-nLacZ/+ ;Rosa26DTA/+ mice, we observed a decrease in ductular reactions and biliary fibrosis typically present in BDL as well as decreased expression of numerous fibrogenic gene markers. Our data indicate that Prom1-expressing HPCs promote biliary fibrosis associated with activation of myofibroblasts in cholestatic liver injury.

Denture use and dental risk factors associated developing osteoradionecrosis after head and neck radiotherapy: A retrospective analysis of hospital records.

OBJECTIVES: This study aimed to assess the association between denture use and occurrence of osteoradionecrosis (ORN) following radiotherapy for head and neck cancer (HNC). MATERIALS AND METHODS: Medical records of 439 HNC patients treated with radiotherapy at Guy's & St Thomas' NHS Foundation Trust (London, UK) (2014-2019) who had missing teeth at the time of discharge were reviewed. Descriptive statistics were used to summarise the participant characteristics and outcome measures. Logistic regression analysis was used to identify factors associated with occurrence of ORN. RESULTS: Patients had an average of 14 missing teeth and 39 % wore dentures. Twenty-two (5 %) developed ORN. Out of 22 who developed ORN, 11 (50 %) wore dentures. Of these, 5 patients developed ORN in areas contacted by dentures. Denture use was not significantly associated with the occurrence of ORN (OR = 1.94; 95%CI = 0.79-4.81; p-value = 0.150). Longer duration of radiotherapy (OR =1.03; 95%CI = 1.00-1.06; p-value= 0.048) and more missing teeth in the lower anterior area (OR = 1.11; 95%CI = 1.01-1.22; p-value = 0.024) were significantly associated with the development of ORN. CONCLUSIONS: Within the limitations of this single-centre study in which few patients developed ORN, denture use may not be a risk factor for ORN following radiotherapy for HNC. This is likely to be the case if dentures are well-fitting and not causing sores or irritation. CLINICAL SIGNIFICANCE: Replacement of the missing teeth with dentures in HNC patients post-radiotherapy may be a suitable choice for many HNC survivors. However, a powered study in a large cohort that includes clinical evaluation of dentures and the quality of fit alongside denture wearing experience would be useful to further assess the impact of denture use on the development of ORN.

Developing a questionnaire to measure psychological disturbance associated with tooth loss.

OBJECTIVES: To develop and validate a self-reporting measure to assess the psychological disturbance in adult patients with tooth loss and dentures Methods: Ethical approval obtained from the Health Research Authority NHS England (Ref:17/NI/0098). 128 participants (100 patients - 28 clinicians) were recruited to participate in the development and validation of the questionnaire. Inclusion criteria included adults (age ≥18) with tooth loss/dentures. Exclusion criteria included patients with a history of psychotic mental illness or patients who had treatment with dental implants. The development processes included: Phase 1. Development of questionnaire: describing the aims/target population of the questionnaire, generating a pool of items, defining the constructs to be measured, adapting psychological morbidity screening tools, Items reduction and producing a preliminary questionnaire. Phase 2. Validation of questionnaire: content validation, face validation, establishing construct validity, pilot testing and establishing reliability. RESULTS: Face and content validation indicated that the questionnaire was an appropriate tool to measure the impact of tooth loss and related psychological morbidities. Reliability analysis (Test re-test reliability/internal consistency) indicated the questionnaire has satisfactory reliability (correlation >0.7). Testing the theoretical hypothesis structure of the impact of tooth loss has also enhanced the construct validity of the questionnaire (domains correlated mildly (r>5 & <3) to strongly (r>5). Pilot testing confirmed the scale adequacy and wording clarity (>90 % of respondents). Results indicated that the developed questionnaire has adequate psychometric properties. CONCLUSION: A disease-specific measure that assesses the psychological impact of tooth loss and the effectiveness of interventions (i.e. dentures) has been developed and validated. CLINICAL SIGNIFICANT: A patient outcome measure was developed which could be used to assess the psychological impact of tooth loss and compare the effectiveness of various interventions like dentures and implants.

A case control study to investigate the effects of denture wear on residual alveolar ridge resorption in edentulous patients.

OBJECTIVES: To investigate the effect of complete denture wearing on residual ridge resorption in edentulous patient compared with edentulous patient who never wore dentures. METHODS: Patients who had been edentulous for at least five year who had never worn dentures successfully were matched to edentulous denture wearing control patients. To control for factors possibly associated with alveolar ridge resorption patients who had been rendered edentulous in one arch before the other, smokers, those taking steroids, bisphosphonates, with histories of autoimmune diseases, diabetes mellitus or osteoporosis at any time during their period of edentulousness were excluded. Case and control groups were matched for age, sex and time since being rendered edentulous. Statistical analyses were undertaken using Person's Chi squared (X2) test and Fisher's exact test. RESULTS: 30 edentulous patients who had not worn dentures for at least five years were identified and matched with 30 controls. All control patients were the same age ± 2 years and had been edentulous for the same number of years ± 2 years of their respective controls. There was no significant difference between age and time since being rendered edentulous between case and control. Denture wearers had significantly more maxillary and mandibular residual alveolar ridge resorption than did non denture wearers. Severe ridge resorption was mostly confined to the denture wearing group. CONCLUSION: Patients wearing complete dentures for more than 5 years had significantly more residual alveolar ridge resorption than was found in non-denture wearing edentulous patients.

Presenting pre-radiotherapy dental status of head and neck cancer patients in the novel radiation era.

Objectives Dental assessment remains a key intervention for head and neck cancer (HNC) patients pre-radiotherapy (RT). The purpose of this study was to identify the variation in dental status of patients pre-treatment, with respect to population and oncological demographics.Materials and methods The study reviewed dental panoramic radiographs of HNC patients seen on a dedicated pre-RT dental clinic from 2011-2017. Only patients who had undergone intensity-modulated radiotherapy treatment were included within this study. Relevant dental and oncological data were collected.Results A total of 886 patients were included in this study, with oropharyngeal cancer constituting 36% of the cohort. The average number of teeth in HNC patients was <21 at the pre-RT phase, which is below the recognised threshold for a functional dentition. Smoking status has a significant impact on overall DMFT (decay/missing/filled teeth), severity of horizontal bone loss and the number of third molars present (p <0.001). In the latter, males had a higher mean number of third molars compared to females (p <0.005). Comparing dental status of patients based on their tumour sub-site identified significant (p <0.0005) variation in all aforementioned categories.Conclusion There are distinct differences in the dental health of HNC patients due to commence RT, compared to the general population. It varies by cancer sub-site and this should be taken into consideration at dental assessment to tailor a dental care plan to the needs of the individual. Consideration should be given to balancing masticatory function against the risks of osteoradionecrosis on the background of increasingly extended survivorship.

Assessment of Psychological Disturbance in Patients with Tooth Loss: A Systematic Review of Assessment Tools.

PURPOSE: To systematically review the available evidence on screening tools to detect the psychological disturbance in patients with tooth loss and technically successful removable dentures (partial and complete). MATERIALS AND METHODS: The study protocol was registered with the National Institute of Health Research Database (I.D. CRD42017082125). The PICOS tool (patients, intervention, control, outcomes measure, and study design) was used to formulate an effective search strategy. Participants were adults (≥ 18), who were edentulous or had significant tooth loss (< 9 remaining teeth). The intervention included undergoing replacement with technically successful dentures (partial or complete). A control group of adults were either edentulous or had significant tooth loss and without dentures. Outcomes included assessing psychological disturbance due to treatment with dentures or due to no treatment using a validated tool. A structured search strategy was used to complete a standard systematic search of the electronic database without any date limit and/or language restriction. Only quantitative studies using a validated measuring tool to screen for psychological distress in adults with significant tooth loss were included. Two authors independently assessed the risk of bias in the included studies. Data homogeneity was assessed in regards to the screening tools to measure psychological disturbance following the management of tooth loss with dentures. The significant level was set at 0.05, using IBM SPSS Statistics 24.0 (SPSS Inc., New York, NY). The psychometric properties and the validation processes of the screening tools were assessed. RESULTS: From the original 3510 studies identified, only eight studies were found to meet the inclusion criteria. All eight studies used the same questionnaire to screen for the emotional distress of tooth loss. In addition, one study also used the Patient Health Questionnaire-9 (PHQ-9) to screen for the association of depression with tooth loss. Six studies suggested that a significant number of patients have difficulties in accepting tooth loss, were less confident, and had emotional distress related to tooth loss. However, two studies reported no significant link. All studies found a marked impact on functional activities and social interaction. However, four studies had a potentially biased selection process, and the questionnaire used was assessed to be at high-risk of measurement bias, as the development and validation process was not clear. There was also a lack of well-defined control groups in all studies. CONCLUSION: Tooth loss could cause psychological disturbance in some patients. To date, there is a lack of available tools that are suitable to screen and measure psychological disturbance in patients with tooth loss. Additional research is required to develop tools to identify and measure such impact and to recommend suitable interventions when needed.

Symptomatic catheter-associated thrombosis in pediatric trauma patients: Choose your access wisely.

BACKGROUND: Traumatic injury and the presence of a central venous catheter are 2 of the strongest risk factors for venous thromboembolism in children. The purpose of this study was to determine the incidence of symptomatic, catheter-associated thrombosis in critically injured children. We hypothesized that femoral venous catheters are associated with a greater rate of thrombotic complications when compared with all other central venous access points. METHODS: We reviewed a retrospective cohort (2006-2016) of injured children (≤18 years) admitted to a pediatric intensive care unit with central access placed ≤7 days from admission. Symptomatic, catheter-associated thrombosis was determined by radiographic evidence. Poisson regression was used to compare the incidence of catheter-associated thrombosis per 1,000 catheter days between femoral and nonfemoral catheters. All comparisons were 2-tailed with α = 0.05. RESULTS: We examined 209 pediatric trauma patients with central access (65% femoral, 19% subclavian, 11% arm vein, and 5% internal jugular). Femoral catheters were removed earlier (median [interquartile range] 4 [2-7] vs 8 [3-12] days, P < .001) and were larger in diameter (5 Fr [4-7] vs 4 Fr [4-4], P < .001) when compared with all other catheters. Catheter-associated thrombosis was more frequent in femoral versus nonfemoral catheters (18.4 vs 3.5 per 1,000 catheter days, P = .01). CONCLUSION: Femoral venous catheters are associated with a greater incidence of symptomatic, catheter-associated thrombosis in pediatric trauma patients. When central venous access is indicated for injured children, the femoral site should be avoided. If a femoral venous catheter is necessary, use of a smaller catheter should be considered.

Volume Assessment of the Effect of Obturators on Facial Form Following Surgery for Head and Neck Cancer Using Stereophotogrammetry.

PURPOSE: To determine if stereophotogrammetry could be used to determine the effects of obturators on facial contour in relation to the measurement of facial volumes. MATERIALS AND METHODS: Stereophotogrammetry images were recorded from 20 subjects with and without their obturators in place. These were converted into a stereolithographic format and overlaid. Registrations were made using the tissues on the normal areas of the face. Difference images were created, enabling surface areas and volumes to be calculated. To assess repeatability of measurement, 2 readings were recorded on each of 2 separate registrations. Data analysis between the sets of readings used correlation coefficients and paired t-tests. Coefficients of repeatability were also calculated. RESULTS: A comparison of readings for the surface areas showed the method of measurement was repeatable with no significant differences between the 2 repeated readings for registration 1 (p = 0.977, coefficient of repeatability = 101 mm2 ), registration 2 (p = 0.085, coefficient of repeatability = 106 mm2 ), and the mean of the two readings for registration 1 compared with registration 2 (p = 0.355, coefficient of repeatability = 103 mm2 ). Similar results were found for the volume measurements with no significant differences between the repeated readings for registration 1 (p = 0.862, coefficient of repeatability = 229 mm3 ), registration 2 (p = 0.200, coefficient of repeatability = 209 mm3 ), and the mean of the 2 readings for registration 1 compared with those for registration 2 (p = 0.131, coefficient of repeatability 339 mm3 ). There was a statistically significant range of volumes that appeared to have been restored by the obturators (p < 0.0005). CONCLUSIONS: Stereophotogrammetry is reliable in assessing the effects of obturators on facial form. In the sample of subjects, obturators generally appeared to be effective in supporting facial tissues following surgical resections of the maxilla and therefore contribute in some degree to the restoration of facial appearance.

Prominin-1 Promotes Biliary Fibrosis Associated With Biliary Atresia.

In patients with biliary atresia (BA), the extent of intrahepatic biliary fibrosis negatively correlates with successful surgical bypass of the congenital cholangiopathy as well as subsequent transplant-free survival. We recently linked the expansion of a population of prominin-1 (Prom1)-expressing hepatic progenitor cells to biliary fibrogenesis. Herein, we hypothesized that Prom1-expressing progenitor cells play a role in BA-associated fibrosis. Rhesus rotavirus (RRV)-mediated experimental BA was induced in newborn mice homozygous for the transgene Prom1cre-ert2-nlacz , which was knocked in to the Prom1 gene locus, thus creating functional Prom1 knockout (KO) mice, and their wildtype (WT) littermates. Clinical data and tissue samples from BA infants from the Childhood Liver Disease Research Consortium were analyzed. Extrahepatic biliary obliteration was present in both WT and KO mice; there was no difference in serum total bilirubin (TBili) levels. The intrahepatic periportal expansion of the PROM1pos cell population, typically observed in RRV-induced BA, was absent in KO mice. RRV-treated KO mice demonstrated significantly fewer cytokeratin-19 (CK19)-positive ductular reactions (P = 0.0004) and significantly less periportal collagen deposition (P = 0.0001) compared with WT. RRV-treated KO mice expressed significantly less integrin-ß6, which encodes a key biliary-specific subunit of a transforming growth factor (TGF) ß activator (P = 0.0004). Infants with successful biliary drainage (Tbili ≤1.5 mg/dL within 3 months postoperatively), which is highly predictive of increased transplant-free survival, expressed significantly less hepatic PROM1, CK19, and COLLAGEN-1α compared with those with TBili >1.5 (P < 0.05). Conclusion: Prom1 plays an important role in biliary fibrogenesis, in part through integrin-mediated TGF pathway activation.

An investigation into the prevalence of combination syndrome.

OBJECTIVES: To investigate the prevalence of Combination Syndrome, and to investigate if provision of a mandibular removable partial denture has any influence on the prevalence of Combination Syndrome. METHOD: Patients attending Kings College London Dental Institute, Guys Hospital who wore maxillary conventional complete dentures opposing mandibular anterior teeth only, with or without mandibular partial dentures were examined by one examiner. Oral health, residual alveolar ridge and denture quality were assessed. Features putatively associated with Combination Syndrome were recorded. Patient ratings of dentures were recorded. RESULTS: 99 patients were recruited who were wearing maxillary removable complete dentures opposing only mandibular anterior teeth. Of these, 64 patients wore mandibular removable partial dentures and 35 patients did not. Only 8 patients displayed two features of Combination Syndrome and 38 patients displayed one feature of Combination Syndrome, excessive resorption of the anterior maxillary sextant. These findings are not compatible with previous research which suggested that the five features of Combination Syndrome were prevalent in patients wearing maxillary complete dentures opposing mandibular anterior teeth. CONCLUSIONS: Evidence supporting the existence of Combination Syndrome was not discovered in this research. Prevalence of Combination Syndrome appeared to be low or non-existent. Patient treatment modalities and teaching in relation to Combination Syndrome may need to be modified.