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Background: Incidence of third-generation cephalosporin-resistant (3GCR) Escherichia coli infections has increased in remote Australia from 2012 to 2018., Objectives: To describe the epidemiology of 3GCR E. coli in Central Australia., Methods: A case-control study was conducted in the primary Central Australian hospital. Patient characteristics, antibiotic usage and clinical outcomes were compared between adult hospitalizations with 3GCR and susceptible E. coli isolates in 2018-19. Poisson regression was used to compare the incidence of 3GCR hospitalizations between Indigenous and non-Indigenous individuals. Patient characteristics and antibiotic usage were tested for associations with 3GCR isolates using univariate analysis., Results: A total of 889 E. coli isolates were identified, of which 187 (21%) were 3GCR. The incidence of 3GCR E. coli infection was 2.15 per 1000 person-years, with an incidence rate ratio of 6.8 (95% CI 4.6-10.1) between Indigenous and non-Indigenous individuals. When compared with the control group, 3GCR E. coli infections were associated with a higher Charlson comorbidity index (CCI ≥3 in 30.7% versus 15.0%, P  < 0.001) and were more commonly healthcare associated (52.4% versus 26.7%, P  < 0.001). A higher 1 year mortality was observed in the 3GCR group after adjustment for comorbidity (OR = 4.43, P  = 0.002), but not at 30 days (2.4% versus 0.0%, P  = 0.2). The 3GCR group used more antibiotics in the past 3 months (OR = 5.75, P  < 0.001) and 12 months (OR = 3.65, P  < 0.001)., Conclusions: 3GCR E. coli infections in remote Australia disproportionally affect Indigenous peoples and are associated with a high burden of comorbidities and antibiotic use. Strategies to enhance antimicrobial stewardship should be considered in this remote setting., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Trial Design: This was a randomized, controlled trial designed to compare outcomes between the use of dental and skeletal anchorage, using the Face mask/Alternate Rapid Maxillary Expansion and Contraction (FM/Alt-RAMEC) protocol., Methods and Participants: The study was carried out at Mater Dei Hospital, Malta and included prepubertal skeletal Class III malocclusion patients where the aetiology was primarily maxillary hypoplasia., Interventions: Two groups were assigned. Group I was treated with FM/Alt-RAMEC and group II was treated with skeletally anchored FM/Alt-RAMEC. Wear-time (WT) of the FM was monitored using TheraMon microsensors. Patients were instructed to wear the FM for 12-14 hours/day for 9 months. Changes were evaluated with lateral cephalograms and analysed with Wilcoxon and Mann-Whitney U tests. ANOVA was used to analyse the effect of gender on compliance parameters. Spearman's correlation coefficient was used to assess the correlation between compliance and skeletal changes., Objective: To compare the skeletal and dentoalveolar changes in patients treated with these two protocols., Outcomes: The primary outcome was to assess skeletal and dentoalveolar outcomes in patients treated with skeletally anchored FM/RME and tooth-borne FM/RME; utilizing Alt-RAMEC protocol. The secondary outcome was compliance rate and adherence to FM wear among patients., Randomization: Randomizer software and the sealed envelope technique were used to randomly allocate patients 1:1 into either group I (tooth-borne FM/Alt-RAMEC) or group II (skeletally anchored FM/Alt-RAMEC)., Blinding: It was not possible to blind to treatment allocation, but blinding was used when assessing the outcomes., Results: Numbers randomized and analysed. Thirty-five patients were allocated. Group I consisted of 18 subjects and group II consisted of 17 subjects. One patient in group I dropped out due to illness, so 17 subjects in each group completed the study., Outcomes: Post-treatment changes in group I showed significant increases in SNA (2.10°), ANB (3.90°), Wits (4.70 mm), and overjet (5.40 mm). Group II showed significant increases in ANB (3.10°), Wits (3.20 mm), and overjet (4.50 mm). Wearing time for group I patients was 7.87 ± 2.88 hours/day and for group II was 6.98 ± 2.68 hours/day, with no significant difference between the groups., Limitations: Lack of long-term follow-up post-treatment, making the conclusion applicable only in the short term., Harms: No harm was observed in both groups., Conclusion: Despite the large difference between the measured and the patient-reported daily WT, both tooth-borne and skeletally anchored FM/Alt-RAMEC showed positive, similar, skeletal and dental effects., Clinical Trial Registration: ISRCTN12197405., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Orthodontic Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background and Aim: Postoperative recurrence (POR) following ileocolonic resection is a major concern in patients with Crohn's disease (CD). The role of ustekinumab (UST) in this setting is poorly known., Methods: All consecutive CD patients with a baseline colonoscopy at 6-12 months from ileocolonic resection showing POR (Rutgeerts score ≥ i2) who were treated with UST after the baseline colonoscopy and with an available post-treatment endoscopy, were extracted from the cohort of the Sicilian Network for Inflammatory Bowel Diseases (SN-IBD). The primary outcome was endoscopic success, defined as reduction of at least one point of Rutgeerts score. The secondary outcome was clinical success, assessed at the end of follow-up. Reasons for clinical failure included mild clinical relapse (Harvey-Bradshaw index 5-7), clinically relevant relapse (Harvey-Bradshaw index > 7), and need for new resection., Results: Forty-four patients were included (mean follow-up: 17.8 ± 8.4 months). The baseline postoperative colonoscopy showed severe POR (Rutgeerts score i3 or i4) in 75.0% of patients. The post-treatment colonoscopy was performed after a mean of 14.5 ± 5.5 months following initiation of UST. Endoscopic success was reported in 22 out of 44 (50.0%) patients, of whom 12 (27.3%) achieved a Rutgeerts score i0 or i1. Clinical success at the end of follow-up was reported in 32 out of 44 patients (72.7%); none of the 12 patients with clinical failure had achieved endoscopic success at post-treatment colonoscopy., Conclusions: Ustekinumab could be a promising option for the treatment of POR of CD., (© 2023 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: Epidermolysis bullosa (EB) comprises a group of rare genetic conditions that are characterized by fragility of the skin and mucous membranes and formation of blisters with minor trauma. Severe forms can be life limiting. The palliative care needs of children with severe EB are poorly described. Aim: The aim of this case series was to examine the contribution of a pediatric palliative care service to the complex health care needs of children with severe EB. Methods: We present a case series of five children with severe forms of EB who were known to the state-wide Victorian Paediatric Palliative Care Service, with a discussion of our learnings in caring for these children and their families. Results: Medical treatment decision making in EB provokes complex ethical, psychological, personal, and professional dilemmas. This case series highlights the diversity of management approaches that may be considered, each tailored to the unique context of the child and family.

Purpose: To review aspects of the underlying methodological procedures in Atlas Methods of Dental Age Estimation (DAE) research publications. Attention is paid to issues of Reference Data supporting the Atlases, details of analytic procedures in the development of the Atlases, the statistical reporting of results of Age Estimation (AE), the problems of expressing uncertainty, and the viability of conclusions in the reporting of DAE studies., Methods: Research reports utilizing Dental Panoramic Tomographs for creating Reference Data Sets (RDS) were studied to unravel the processes of creating Atlases with a view to determining the appropriate procedures for developing numerical RDS and compiling them into an Atlas format to enable DAE of child subjects without birth records., Results: The five different Atlases reviewed gave several different results in terms of AE. The possible causes of this were discussed - namely inadequate representation of Reference Data (RD) and lack of clarity in expressing uncertainty. It is suggested that the method of compiling Atlases needs to be more clearly defined. The yearly intervals described by some of the Atlases fails to take account of the Uncertainty of Estimates which is usually slightly greater than ±2½ years., Conclusion: The review of published Atlas design papers in the field of DAE shows a number of different study designs, statistical procedures, and presentational styles, particularly with regard to the statistical procedures and findings. These show that Atlas methods can only be accurate to what amounts to at best a year., Recommendations: Atlas methods lack the accuracy and precision of other methods of AE an example of which is the Simple Average Method (SAM). 1 This inherent lack of accuracy must be taken into account when using Atlas methods for AE., Competing Interests: Declaration of competing interest This is to confirm that the above authors declare no conflict of interest in relation to the review articleQuestions of Logic in Atlas Methods of Dental Age Estimation Graham Roberts 2022–08–25., (Crown Copyright © 2023. Published by Elsevier Ltd. All rights reserved.)

Background: The COVID-19 pandemic spread across the globe, including across the Mediterranean basin. This region presents diversity in economy, culture, and societal affairs. We attempted to evaluate the impact of COVID-19 on the population and on the Sustainable Development Goals (SDGs), our aim being to aid in the development of COVID-19 national plans., Methods: Epidemiological data was obtained from 'Our World in Data' databases (January 2020 - July 2021). Case, mortality, and vaccination incidence comparisons were made across neighbouring countries. The SDG index, universal health coverage (UHC) and health workforce targets were collected for each country. Correlations between SDG targets and COVID-19 outcomes were analysed., Results: Similarities in morbidity and mortality outcomes were present across neighbouring countries, with a bidirectional relationship between cumulative fully vaccinated population and infectivity fatality rates. Positive relationships were present between SDG indexes, UHC and health workforces and COVID-19 cases, deaths, and vaccinations., Conclusion: At prima face, high-income countries seem to have sustained worse morbidity and mortality outcomes, despite having had better UHC and a greater health workforce in the pre-COVID-19 era however, one must also consider that factors such as health-seeking behaviour and underdiagnosis may have influenced this. Cross-border infectivity was, however, evident. Pan-Mediterranean action must therefore be taken to ensure COVID-19 transmissibility and mortality are reduced across borders, while ensuring an equitable health outcome across populations., (© 2022 Cuschieri S et al.)

Factors affecting the quality of bowel preparation for colonoscopy in the elderly are not fully known, and current guidelines provide no specific recommendations. This study aimed to assess the difference in bowel cleansing in young and elderly patients and evaluate predictors of bowel cleansing in the elderly. We retrospectively reviewed a prospective cohort of 1289 patients performing colonoscopy after a 1-, 2-, or 4-L PEG-based preparation. All 1289 were included in the analysis. Overall, 44.6% of patients were aged ≥65 years. Cleansing success (CS) was achieved in 77.3% and 70.3% of patients aged <65 years and ≥65 years, respectively. At multivariable analysis, split regimen (OR = 2.43, 95% CI = 1.34−4.38; p = 0.003), adequate cleansing at previous colonoscopy (OR = 2.29, 95% CI = 1.14−4.73; p = 0.02), tolerability score (OR = 1.29, 95% CI = 1.16−1.44; p < 0.001), a low-fiber diet for at least 3 days (OR = 2.45, 95% CI = 1.42−4.24; p = 0.001), and colonoscopy within 5 h after the end of preparation (OR = 2.67, 95% CI = 1.28−5.56; p = 0.008) were independently associated with CS in the elderly. Combining a low-fiber diet for at least 3 days, split preparation, and colonoscopy within 5 h allowed a CS rate above 90% and should always be encouraged. A 1-L PEG-ASC preparation was also associated with greater high-quality cleansing of the right colon and may be preferred.

Introduction: The determination of age of majority (the 18-year-old threshold) using the popular Demirjian tooth staging method is unreliable, so other maturity markers are required. This study examines whether the ratio of the root canal widths (RCW) of the mandibular first, second and third molars is a useful indicator of age., Methods: Nine hundred eighteen dental panoramic radiographs (DPT) were examined and the ratio of the mid-points of the distal roots of the left mandibular first, second and third molars assessed according to the RCW stages as described by Roberts (J Forensic Sci 62:351-354, 2017)., Results: Individuals who had reached stages RCW-A and RCW-B were represented in a wide range of ages spanning the 18-year-old threshold. Individuals who had reached Stage RCW-C were all above the 18-year-old threshold. It was not possible to analyse a large number of DPTs for various reasons., Discussion: Individuals categorised as stage RCW-C may be deemed to have reached the 18-year-old threshold. These results are consistent with other published studies. Variation in root morphology and in the rate of development of the third molar limits the applicability of this method., Conclusions: RCW staging is an accurate method of determining the 18-year-old threshold. Its limited applicability requires the use of substitute markers in a large number of cases., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Celiac disease (CD) is still underestimated. To close this diagnostic gap, the Health Sicilian Authorities have constituted the "Sicilian Network for CD"., Aims: A) To verify the quality of the current diagnostic approach using the data sheet of the Network. B) To evaluate the clinical, serologic and histologic data of new diagnoses in the context of the Network METHODS: We retrospectively evaluated the data collection forms of 369 patients with CD from three Centers within the Sicilian Network. All the Centers used a standard data collection form., Results: A non-classical CD presentation was more frequent than the classical one, anemia being the most frequent symptom (50%). An IBS-like presentation was found in one third of the cases. A diagnostic delay of about 9 years following the onset of symptoms was observed. Almost half of the patients had not undergone multiple duodenal biopsies; unrecommended CD serology assays were prescribed in 59.9% of the cases., Conclusions: The regional data sheets allowed an assessment of the diagnostic delay. We recorded a frequent use of unrecommended tests prescribed before referring patients to the regional Centers. Updating the education of physicians regarding CD is necessary to avoid unwarranted health expenditure., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2021 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: The role of Vedolizumab (VDZ) as therapeutic option for the postoperative recurrence of Crohn's disease (CD) following ileocolonic resection is unknown., Aims: To assess the effectiveness of VDZ in this setting., Methods: All consecutive CD patients with a baseline colonoscopy at 6-12 months from the ileocolonic resection showing postoperative recurrence (Rutgeerts score ≥i2) and treated with VDZ after the baseline colonoscopy were extracted from the cohort of the Sicilian Network for Inflammatory Bowel Diseases (SN-IBD). The primary outcome was endoscopic success, assessed at the first colonoscopy following initiation of VDZ and defined as reduction of at least one point of Rutgeerts score. The secondary outcome was clinical failure, assessed at one year and at the end of follow-up., Results: Fifty-eight patients were included (mean follow-up: 24.8 ± 13.1 months). Endoscopic success was reported in 47.6% of patients. Clinical failure was reported in 19.0% of patients at one year, and in 32.8% of patients at the end of follow-up. A new resection was required in 7 patients (12.1%)., Conclusions: VDZ may be an effective option for the treatment of postoperative recurrence of CD., Competing Interests: Conflict of Interest None declared., (Copyright © 2021 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Dysregulation of Toll-like receptor (TLR) signaling contributes to the pathogenesis of autoimmune diseases. Here, we provide genetic evidence that tankyrase, a member of the poly(ADP-ribose) polymerase (PARP) family, negatively regulates TLR2 signaling. We show that mice lacking tankyrase in myeloid cells developed severe systemic inflammation with high serum inflammatory cytokine levels. We provide mechanistic evidence that tankyrase deficiency resulted in tyrosine phosphorylation and activation of TLR2 and show that phosphorylation of tyrosine 647 within the TIR domain by SRC and SYK kinases was critical for TLR2 stabilization and signaling. Last, we show that the elevated cytokine production and inflammation observed in mice lacking tankyrase in myeloid cells were dependent on the adaptor protein 3BP2, which is required for SRC and SYK activation. These data demonstrate that tankyrase provides a checkpoint on the TLR-mediated innate immune response.

Evidence for open or closed exposure of palatally displaced canines is equivocal, but this study sheds light on new facets which may influence the method of choice. The aim of this article is to give a short perspective on this field, highlight the merits of a study published in this issue of the European Journal of Orthodontics by Björksved et al. the study, place the findings into context and show how it may influence clinical practice., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Orthodontic Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Introduction: Delayed tooth eruption is often seen in patients with palatally displaced canines (PDC), but there is controversy over whether tooth formation is also delayed. This study attempts to elucidate the answer by addressing methodological shortcomings in previous studies., Methods: Archived records were searched, and 100 patients (aged 8-16 years) with unilateral PDC were identified. Records of 50 women and 50 men were matched for age and sex with unaffected controls. The exclusion criteria included hypodontia. Dental age (DA) was calculated using the population-specific Maltese database and subtracted from the chronological age (CA). Nonparametric tests were used to compare CA-DA in patients with PDC and controls to determine the DA of end-of-series teeth., Results: No statistically significant difference with CA-DA between patients with PDC and controls was found. In addition, there were no particular teeth significantly delayed in development., Conclusions: Unilateral PDC does not affect dental developmental age, and the end-of-series teeth investigated show no delay in development., (Copyright © 2021 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.)

Background: No data on the recently introduced infliximab (IFX) biosimilar SB2 in inflammatory bowel disease (IBD) are available., Methods: The Sicilian Prospective Observational Study of Patients With IBD Treated With Infliximab Biosimilar SB2 is a multicenter, observational, prospective study performed among the cohort of the Sicilian Network for Inflammatory Bowel Disease. All consecutive IBD patients starting the IFX biosimilar SB2 from its introduction in Sicily (March 2018) to September 2019 (18 months) were enrolled., Results: Two hundred seventy-six patients (Crohn disease: 49.3%, ulcerative colitis: 50.7%) were included: 127 (46.0%) were naïve to IFX and naïve to anti-tumor necrosis factor medications (anti-TNFs), 65 (23.5%) were naïve to IFX and previously exposed to anti-TNFs, 17 (6.2%) were switched from an IFX originator to SB2, 43 (15.6%) were switched from the biosimilar CT-P13 to SB2, and 24 (8.7%) were multiply switched (from IFX originator to CT-P13 to SB2). The cumulative number of infusions of SB2 was 1798, and the total follow-up time was 182.7 patient-years. Sixty-seven serious adverse events occurred in 57 patients (20.7%; incidence rate: 36.7 per 100 patient-year), and 31 of these events caused the withdrawal of the drug. The effectiveness after 8 weeks of treatment was evaluated in patients naïve to IFX (n = 192): 110 patients (57.3%) had steroid-free remission, while 56 patients had no response (29.2%). At the end of follow-up, 72 patients (26.1%) interrupted the treatment, without significant differences in treatment persistency estimations between the five groups (log-rank P = 0.15)., Conclusions: The safety and effectiveness of SB2 seem to be overall similar to those reported for the IFX originator and CT-P13., (© 2020 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background and Aim: There are no head-to-head randomized controlled trials between biologics in Crohn's disease (CD). We aimed to perform a multicenter, real-life comparison of the effectiveness of vedolizumab (VDZ) and adalimumab (ADA) in CD., Methods: Data of consecutive patients with CD treated with VDZ and ADA from January 2016 to April 2019 were extracted from the cohort of the Sicilian Network for Inflammatory Bowel Disease. The effectiveness was evaluated at 12, 52 weeks, and as failure-free survival at the end of follow up. Propensity score analysis was performed using the inverse probability of treatment weighting method., Results: Five hundred eighty-five treatments (VDZ: n = 277; ADA: n = 308) were included (median follow-up: 56.0 weeks). After 12 weeks, a clinical response was achieved in 64.3% patients treated with VDZ and in 83.1% patients treated with ADA (odds ratio [OR] 0.65, 95% confidence interval [CI] 0.38-1.10, P = 0.107), while at 52 weeks, a clinical response was observed in 54.0% patients treated with VDZ and in 69.1% patients treated with ADA (OR 0.77, 95% CI 0.45-1.31, P = 0.336). Cox survival analysis weighted for propensity score showed no significant difference in the probability of failure-free survival between the two drugs (hazard ratio = 1.20, 95% CI 0.83-1.74, P = 0.340). Post-treatment endoscopic response and mucosal healing rates were similar between the two groups (endoscopic response: 35.3% for VDZ and 25.5% for ADA, P = 0.15; mucosal healing: 31.8% for VDZ and 33.8% for ADA, P = 0.85)., Conclusions: In the first study comparing VDZ and ADA in CD via propensity score analysis, the drugs showed comparable effectiveness and a similar safety profile., (© 2020 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: No real-life study on the comparative effectiveness of Vedolizumab (VDZ), Adalimumab (ADA), and Golimumab (GOL) in ulcerative colitis (UC) is currently available., Aims: To compare the effectiveness of the three biologics in consecutive patients with UC., Methods: A three-arms propensity score-adjusted analysis was performed using the Inverse Probability of Treatment Weighting method., Results: 463 treatments (VDZ: n = 187; ADA: n = 168; GOL: n = 108) were included (median follow-up: 47.6 weeks). At 12 weeks (n = 463), a steroid-free remission was reported in 24.1% patients in the VDZ group, in 33.3% patients in the ADA group, and in 30.6% patients in the GOL group (p = n.s. for all comparisons). At 52 weeks (n = 377), a steroid-free remission was reported in 51.5% patients in the VDZ group, in 31.2% patients in the ADA group, and in 29.4% patients in the GOL group (p = 0.002 for VDZ vs. ADA, p = 0.001 for VDZ vs. GOL, p = n.s. for ADA vs. GOL). Cox survival analysis demonstrated that patients treated with VDZ had reduced probability of treatment discontinuation compared to those treated with ADA (HR: 0.42, 95% CI 0.28-0.64, p < 0.001) and GOL (HR: 0.30, 95% CI 0.19-0.46, p < 0.001), while patients treated with ADA had reduced risk of treatment discontinuation compared to those treated with GOL (HR: 0.71, 95% CI 0.50-1.00, p = 0.048)., Conclusions: VDZ was superior to ADA and GOL at 52 weeks and as treatment persistence, while ADA showed a superior treatment persistence compared to GOL., Competing Interests: Declaration of Competing Interest Fabio Salvatore Macaluso served as an advisory board member and/or received lecture grants from AbbVie, Biogen, MSD, and Takeda Pharmaceuticals. Maria Cappello served as an advisory board member for AbbVie, MSD, Takeda Pharmaceuticals, and received lecture grants from AbbVie, MSD, Chiesi, and Takeda Pharmaceuticals. Filippo Mocciaro served as an advisory board member for AbbVie and MSD Pharmaceuticals, and received lecture grants from AbbVie, MSD and Takeda Pharmaceuticals. Sara Renna served as an advisory board member for AbbVie and MSD Pharmaceuticals, and received lecture grants from AbbVie, MSD and Takeda Pharmaceuticals Ambrogio Orlando served as an advisory board member for AbbVie, MSD, Janssen, Pfizer, Takeda Pharmaceuticals, and received lecture grants from AbbVie, MSD, Sofar, Chiesi, Janssen, Pfizer, and Takeda Pharmaceuticals., (Copyright © 2020 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: Biologically naïve patients with inflammatory bowel disease treated with vedolizumab (VDZ) are largely underrepresented in real-world cohorts. A multi-centre, observational cohort study was performed on the effectiveness and safety of VDZ in biologically naïve subjects with Crohn's disease (CD) and ulcerative colitis (UC)., Methods: Data of consecutive biologically naïve patients with CD and UC treated with VDZ from July 2016 to December 2019 were extracted from the cohort of the Sicilian Network for Inflammatory Bowel Disease., Results: A total of 172 consecutive patients (CD: N  = 88; UC: N  = 84; median age 66.0 years) were included, with a median follow-up of 58.8 weeks. After 14 weeks, a clinical response was reported in 68.2% of patients with CD and 67.9% of patients with UC treated with VDZ, including 45.5% patients in the CD group and 46.4% patients in the UC group who achieved steroid-free remission. After 52 weeks, a clinical response was reported in 77.4% of CD and in 73.8% of UC patients treated with VDZ, including 59.7% patients in the CD group and 60.7% patients in the UC group who achieved steroid-free remission., Conclusions: This study demonstrates the effectiveness and safety of VDZ as a first-line biological, particularly among elderly patients.

Background: The effectiveness of Ustekinumab (UST) on Crohn's disease (CD)-associated spondyloarthropathy (SpA) is currently unknown., Research Design and Methods: All consecutive CD patients with active SpA at the initiation of the treatment with UST were extracted from the cohort of the Sicilian Network for Inflammatory Bowel Diseases (SN-IBD). The primary outcome was the articular response at 8 and 24 weeks, defined as the disappearance of objective signs of arthritis (swelling and/or articular stiffness) and resolution of pain., Results: Thirty CD patients with active SpA at the initiation of the treatment with UST were assessed. At 24 weeks, 13 patients (43.3%) had an articular response, including 10/18 patients (55.5%) with peripheral SpA and 3/9 patients (33.3%) with axial and peripheral SpA. No patient with axial SpA experienced an articular response. The drop of mean as Harvey-Bradshaw Index values from baseline to week 24 was higher in patients with articular response compared with non-responders (3.8 ± 2.4 vs. 1.3 ± 2.8, p = 0.02)., Conclusions: Our real-world, multicentre experience showed that UST was able to obtain a response on articular symptoms in nearly half of the patients with CD and active SpA after 24 weeks of treatment.

Background: The effectiveness of colonoscopy strictly depends on adequate bowel cleansing. Recently, a 1 L polyethylene glycol plus ascorbate (PEG-ASC) solution (Plenvu; Norgine, Harefield, United Kingdom) has been introduced on the evidence of three phase-3 randomized controlled trials, but it had never been tested in the real-life., Aim: To assess the effectiveness and tolerability of the 1 L preparation compared to 4 L and 2 L- PEG solutions in a real-life setting., Methods: All patients undergoing a screening or diagnostic colonoscopy after a 4, 2 or 1 L PEG preparation, were consecutively enrolled in 5 Italian centers from September 2018 to February 2019. The primary endpoints of the study were the assessment of bowel cleansing success and high-quality cleansing of the right colon. The secondary endpoints were the evaluation of tolerability, adherence and safety of the different bowel preparations. Bowel cleansing was assessed through the Boston Bowel Preparation Scale. Adherence was defined as consumption of at least 75% of each dose, while tolerability was evaluated through a semi-quantitative scale. Safety was systematically monitored through adverse events reporting., Results: Overall, 1289 met the inclusion criteria and were enrolled in the study. Of these, 490 patients performed a 4 L-PEG preparation (Selgesse ® ), 566 a 2 L-PEG cleansing (Moviprep ® or Clensia ® ) and 233 a 1 L-PEG preparation (Plenvu ® ). Bowel cleansing by Boston Bowel Preparation Scale was 6.5 ± 1.5 overall and 6.3 ± 1.5, 6.2 ± 1.5, 7.3 ± 1.5 ( P < 0.001) in the subgroups of 4 L, 2 L and 1 L-PEG preparation, respectively. Cleansing success was achieved in 72.4%, 74.1% and 90.1% ( P < 0.001), while a high-quality cleansing of the right colon in 15.9%, 12.0% and 41.4% ( P < 0.001) for 4 L, 2 L and 1 L-PEG preparation groups, respectively. The 1 L preparation was the most tolerated compared to the 2 and 4 L-PEG solutions in the absence of serious adverse events within any of the three groups. Multiple regression models confirmed 1 L PEG-ASC preparation as an independent predictor of overall cleansing success, high-quality cleansing of the right colon and of tolerability., Conclusion: This study supports the effectiveness and tolerability of 1 L PEG-ASC, also showing it is an independent predictor of overall cleansing success, high-quality cleansing of the right colon and of tolerability., Competing Interests: Conflict-of-interest statement: The authors have no proprietary, financial, professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of this manuscript., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Introduction: The determination of age of majority (the 18-year-old threshold) using the popular Demirjian tooth staging method is unreliable, so other maturity markers are required. This study examines whether the Root Pulp Visibility (RPV) of the mandibular third molar is a useful indicator of age., Methods: One thousand six dental panoramic radiographs (DPTs) were examined and the left mandibular third molar assessed according to the RPV stages using the method of Olze et al. (Int J Legal Med 124:183-186, 2010) as modified by Lucas et al. (Forensic Sci Int 270:98-102, 2017). Six hundred sixty-two DPTs, 288 males and 374 females, satisfied the inclusion criteria., Results: Individuals who had reached stages RPV-A and RPV-B were represented in a wide range of ages spanning the 18-year-old threshold. Individuals who had reached stages RPV-C and RPV-D were all above the 18-year-old threshold. It was not possible to analyse a large number of DPTs for various reasons., Discussion: Individuals whose mandibular third molar exhibited stages RPV-C and RPV-D may be deemed to have reached the age of majority. These results are consistent with other published studies. Variation in the rate of development of the third molar limits the applicability of this method., Conclusions: RPV staging is an accurate method of determining the 18-year-old threshold. Substitute methods are required in a large number of cases.

Objective: Examine the endogenous relationship between uncompensated care and hospital patient experience scores., Data Sources/study Setting: The Hospital Consumer Assessment of Healthcare Providers and Systems Survey, CMS Healthcare Cost Report Information System, and the US Census Bureau., Study Design: The exogenous change in uncompensated care caused by the 2014 Medicaid expansion was exploited to measure the effect of uncompensated care on patient experience scores using a 2SLS regression with instrumental variables approach., Data Collection/extraction Methods: U.S. general, short-term hospitals whose DSH status remained constant and had nonmissing data for 2011-2015, which totaled 969 unique hospitals per year., Principal Findings: The effect of uncompensated care on patient experience was in the predicted direction, with three of the 10 measures being statistically significant. A one percentage point increase in uncompensated care costs resulted in a 0.25-0.50 percentage point decrease in select patient experience scores., Conclusions: Results indicate a weak relationship between uncompensated care and patient experience scores, as a reduction in uncompensated care is related to quality improvement for some hospitals. These findings have implications for hospitals as they navigate changing reimbursement structures and policy makers considering changes to Obama-era health care reforms., (© Health Research and Educational Trust.)

Introduction: Colorectal cancer (CRC) is a major health-care problem all over the world and CRC screening is effective in reducing mortality and increasing the 5-year survival. Colonoscopy has a central role in CRC screening. It can be performed as a primary test, as a recall policy after a positive result of another screening test, and for surveillance. Since effectiveness of endoscopic screening depends on adequate detection and removal of colonic polyps, consistent quality measures, which are useful in enhancing the diagnostic yield of examination, are essential. Areas covered: The aim of this review is to analyze current evidence from literature supporting quality measures able to refine endoscopic screening of colorectal cancer. Expert commentary: Quality measures namely a) time slot allotted to colonoscopy, b) assessment of indication, c) bowel preparation, d) Cecal intubation, e) withdrawal time, f) adenoma detection rate, g) proper management of lesions (polypectomy technique, polyps retrieval rate and tattooing of resection sites), and h) adequate follow-up intervals play a key role in identifying malignant and at-risk lesions and improving the outcome of screening. Adherence to these quality measures is critical to maximize the effectiveness of CRC screening, as well as, a proper technique of colonoscopy and a quality report of the procedure. Among all recommended measures, adenoma detection rate is the most important and must be kept above the recommended quality threshold by all physicians practicing in the setting of screening.

Objective: To estimate the effect of the first full year of the ACA Medicaid expansion on hospital provision of uncompensated care, with special attention paid to hospitals that treat a disproportionate share of low-income patients., Data Sources: Data from a balanced panel of short-term, general, nonfederal, Medicare-certified hospitals were obtained from Medicare cost reports from 2011 to 2014., Study Design/study Setting: A series of difference-in-differences analyses were performed using hospitals in nonexpansion states as the control group. The dependent variable is hospital provision of uncompensated care., Data Collection/extraction Methods: The data were downloaded from the National Bureau of Economic Research website., Principal Findings: The Medicaid expansion significantly reduced hospital provision of uncompensated care in 2014. In particular, within expansion states, DSH hospitals saw reductions beyond those experienced by non-DSH hospitals., Conclusions: Evidence from this study indicates that the Medicaid expansion served to widen an already broad gap in provision of uncompensated care between hospitals in expansion and nonexpansion states. In addition, within expansion states, variation in uncompensated care between hospitals that treat a disproportionate share of low-income patients and those that do not was reduced, with the former experiencing significantly larger reductions. Lawmakers considering expanding Medicaid and those deciding appropriate levels of DSH payments should consider these findings., (© Health Research and Educational Trust.)

Introduction: An extended family presenting with several members affected by developmentally missing teeth was investigated by analysis of the MSX1 and PAX9 genes., Materials and Methods: Saliva samples were collected and DNA extracted. Primers were designed to span the exons and intron-exon junctions of the MSX1 and PAX9 genes. These primers were optimised using gradient Polymerase Chain Reaction. The amplified fragments were sent for Sanger sequencing RESULTS: a novel heterozygote missense mutation in exon 3 of PAX9 (c.296G > C, p.A99P), was found in two severely affected members of the family as well as a potentially pathogenic heterozygote variant (c.119C > G, p.A40G) in exon 1 of the MSX1 gene., Conclusion: The PAX9 A99P mutation is in the DNA binding domain and is predicted to be pathogenic., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Muscle weakness is a risk factor for mortality in hemodialysis (HD) patients. Muscle strength measurements are routinely used as a screening tool but depend on patient cooperation and motivation. We wished to determine whether measuring maximal voluntary muscle strength was affected by patient self-reported distress., Methods: We measured pinch strength (PS) and handgrip strength (HGS) in 382 adult HD patients with a corresponding self-reported distress thermometer (DT) scores. Postdialysis body composition measurements were made using multifrequency bioelectrical assessments and patients assessed for frailty., Results: Mean age was 66.4 ± 14.9 years, with 238 males (62%), 48% diabetic, and dialysis vintage 36 (15-75) months. The mean DT score was 4.4 ± 3.3, with a frailty score of 4.6 ± 1.5. On multivariable analysis, DT scores were associated with frailty (β = 0.35, P = .003), prescription of aspirin for cardiac disease (β = 1.0, P = .004), lean body mass (β = 0.04, P = .004), and negatively with age (β = -0.05, P < .001), hematocrit (β = -8.2, P = .004), and maximum PS (β = -1.4, P = .003)., Conclusion: Paradoxically higher self-reported DT scores were associated with younger age and lean body mass. As such, younger healthier, rather than more comorbid, patients may have greater expectations for their health and therefore report more distress. We found no association between DT scores and HGS, and as such, although HGS is a voluntary test, it appears to be a robust test independent of patient stresses. However, PS was lower in patients with higher DT scores, and as such, greater care may be required in interpreting these measurements.

In past years, the cell-sheet construct has spurred wide interest in regenerative medicine, especially for reconstructive surgery procedures. The development of diversified technologies combining adipose tissue-derived stromal cells (ADSCs) with various biomaterials has led to the construction of numerous types of tissue-engineered substitutes, such as bone, cartilage, and adipose tissues from rodent, porcine, or human ADSCs. Extended esophageal endoscopic submucosal dissection (ESD) is responsible for esophageal stricture formation. Stricture prevention remains challenging, with no efficient treatments available. Previous studies reported the effectiveness of mucosal cell-sheet transplantation in a canine model and in humans. ADSCs are attributed anti-inflammatory properties, local immune modulating effects, neovascularization induction, and differentiation abilities into mesenchymal and non-mesenchymal lineages. This original study describes the endoscopic transplantation of an ADSC tissue-engineered construct to prevent esophageal stricture in a swine model. The ADSC construct was composed of two allogenic ADSC sheets layered upon each other on a paper support membrane. The ADSCs were labeled with the PKH67 fluorophore to allow probe-based confocal laser endomicroscopy (pCLE) monitoring. On the day of transplantation, a 5-cm and hemi-circumferential ESD known to induce esophageal stricture was performed. Animals were immediately endoscopically transplanted with 4 ADSC constructs. The complete adhesion of the ADSC constructs was obtained after 10 min of gentle application. Animals were sacrificed on day 28. All animals were successfully transplanted. Transplantation was confirmed on day 3 with a positive pCLE evaluation. Compared to transplanted animals, control animals developed severe strictures, with major fibrotic tissue development, more frequent alimentary trouble, and reduced weight gain. In our model, the transplantation of allogenic ADSCs, organized in double cell sheets, after extended ESD was successful and strongly associated with a lower esophageal stricture rate.

The purpose of this study was to validate a Reference Data Set, developed from the radiographic archives of the Dental Department, Mater Dei Hospital, Malta, for Dental Age Estimation of the Maltese population and to assess the accuracy of the method. Dental Panoramic Tomograms of 100 male and 100 females were selected. Tooth Development Stages were recorded for all 16 permanent teeth on the left and both third molars on the right. Summary and percentile data were calculated for each Tooth Development Stage and the Dental Age of each subject estimated using the unweighted average method. The distribution of the differences between the Dental and Chronological age was analysed. There was no statistically significant difference between the means of the Dental and Chronological ages and the mean differences were within acceptable limits. The conclusion was that the Dataset is valid for the Maltese population and the method used gives adequate accuracy., (Copyright © 2016 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.)

Unlabelled: Background Chlamydia and gonorrhoea are the two most common sexually transmissible infections (STI) among men who have sex with men (MSM) worldwide. Infections at the pharynx and rectum are usually asymptomatic; however, the natural history of these infections remains unknown. The aim of this study is to estimate the duration of both infections at the extragenital sites from published epidemiological cohort studies., Methods: English peer-reviewed articles were searched from 1 January 2000 to 12 March 2015 in three electronic databases (MEDLINE, EMBASE and Cochrane Central). The prevalence-to-incidence ratio from each study was calculated to reflect the duration of each infection. This review followed the PRISMA guidelines and was registered in PROSPERO (CRD42014007087)., Results: There were 2585 records identified, with 1721 abstracts and 52 full-text articles screened, resulting in four studies fulfilling the inclusion criteria. Pharyngeal gonorrhoea (114-138 days) had a shorter duration of infection than rectal gonorrhoea (346 days). In addition, chlamydia had a longer duration of infection at the pharynx (667 days) and rectum (579 days) compared with gonorrhoea infection., Conclusions: Gonorrhoea has a shorter duration of infection than chlamydia, suggesting that annual STI screening will be more effective at diagnosing chlamydia than gonorrhoea. The current STI guidelines recommend screening gonorrhoea and chlamydia at least once a year in MSM; it would only detect ~30% of incident pharyngeal gonorrhoea cases, with a mean duration of 4 months.

The purpose of this study was to develop and validate a Reference Data Set for Dental Age Assessment of the Maltese population and compare the mean Age of Attainment to a UK Caucasian Reference Data Set. The Maltese Reference Data Set was developed from 1593 Dental Panoramic Tomograms of patients aged between 4 and 26 years, taken from the radiographic archives of the Dental Department, Mater Dei Hospital, Malta. Tooth Development Stages were recorded for all 16 maxillary and mandibular permanent teeth on the left side and both permanent third molars on the right, according to Demirjian's staging method. Summary and percentile data were calculated for each Tooth Development Stage, including the mean Age of Attainment. These means were used to estimate the Dental Age of each subject in the study sample using the simple unweighted average method. The estimated Dental Age was compared to the gold standard of the Chronological Age. Comparison of the Maltese and UK Caucasian Reference Data Set was by a series of t-tests, carried out for each paired Tooth Development Stage by gender. The mean Age of Attainment was slightly higher for the Maltese than the UK Caucasians in both males and females. However there was no statistically significant difference between the Chronological Age and Dental Age for either sex., (Copyright © 2016 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.)

Background & Aims: Extended esophageal endoscopic submucosal dissection (ESD) is highly responsible for esophageal stricture. We conducted a comparative study in a porcine model to evaluate the effectiveness of adipose tissue-derived stromal cell (ADSC) double cell sheet transplantation., Methods: Twelve female pigs were treated with 5 cm long hemi-circumferential ESD and randomized in two groups. ADSC group (n = 6) received 4 double cell sheets of allogenic ADSC on a paper support membrane and control group (n = 6) received 4 paper support membranes. ADSC were labelled with PKH-67 fluorophore to allow probe-based confocal laser endomicroscopie (pCLE) monitoring. After 28 days follow-up, animals were sacrificed. At days 3, 14 and 28, endoscopic evaluation with pCLE and esophagography were performed., Results: One animal from the control group was excluded (anesthetic complication). Animals from ADSC group showed less frequent alimentary trouble (17% vs 80%; P = 0.08) and higher gain weight on day 28. pCLE demonstrated a compatible cell signal in 4 animals of the ADSC group at day 3. In ADSC group, endoscopy showed that 1 out of 6 (17%) animals developed a severe esophageal stricture comparatively to 100% (5/5) in the control group; P = 0.015. Esophagography demonstrated a decreased degree of stricture in the ADSC group on day 14 (44% vs 81%; P = 0.017) and day 28 (46% vs 90%; P = 0.035). Histological analysis showed a decreased fibrosis development in the ADSC group, in terms of surface (9.7 vs 26.1 mm²; P = 0.017) and maximal depth (1.6 vs 3.2 mm; P = 0.052)., Conclusion: In this model, transplantation of allogenic ADSC organized in double cell sheets after extended esophegeal ESD is strongly associated with a lower esophageal stricture's rate.

Aim: To compare the developmental dental anomalies associated with maxillary canine-first premolar (MxCP1) transposition and those of palatally displaced canine (PDC) with each other and with the background prevalence in the Maltese population in order to elucidate whether the two conditions have similar or differing genetic backgrounds., Materials and Methods: Dental records of 477 subjects with PDC, 57 subjects with MxCP1, and a control group of 500 subjects with no history of a PDC or tooth transposition were compared for canine eruption anomalies and hypodontia., Results: A high frequency of bilateral occurrence was present for both canine malpositions and when unilateral, a trend to right-sided occurrence was evident. The occurrence of transpositions in the PDC group and of PDC in the MxCP1 group was higher than expected. The prevalence of incisor hypodontia was significantly higher in subjects with PDC and MxCP1, as compared to the control group., Limitations: The size of the MxCP1 group is relatively small. The study population is a small isolated Caucasian population and the results may not be applicable to other populations., Conclusions: There is no significant difference between the MxCP1 and PDC groups in the prevalence or distribution of hypodontia and each of these groups exhibits a higher prevalence of the other canine anomaly. These findings support the theory that PDC and MxCP1 form part of a group of interrelated dental anomalies that share a common genetic basis., (© The Author 2015. Published by Oxford University Press on behalf of the European Orthodontic Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The resistance of Helicobacter pylori strains to clarithromycin is increasing in several developed countries and their association with a genetic pattern circulation has been variously explained as related to different geographical areas. In this study we have reported: the prevalence of the resistance of H. pylori, isolated in Sicily, to clarithromycin; the principal point of mutation associated with this resistance; and the more frequent association between resistance to clarithromycin and cagA, the EPIYA motif, and the vacA and oipA genes. Resistance to clarithromycin was detected in 25% of cases, the main genetic mutation involved being A2143G. The cagA gene was present in 48% of cases and the distribution of the EPIYA motif was: ABC in 35 cases; ABCC in 8 cases; ABCCC in 2 cases; ABC-ABCC in 2 cases; and ABC-ABCC-ABCCC in 1 case. Regarding the vacA allele, an s1i1m1 combination was detected in 35% of cases, s1i1m2 in 12 %, s1i2m2 in 12%, s2i2m2 in 40%, and a double s1m1-m2 mosaic in 1% of cases. The status of the oipA gene was 'off' in 45% of cases and 'on' in 55%. Resistance to clarithromycin was found to be high in Sicily, but no correlation was found among resistance to clarithromycin, the vacA gene and oipA status; a higher correlation was observed between resistant strains and cagA-negative strains.

The aim of this study was to investigate and compare the inheritance pattern and prevalence of inheritable dental anomalies in a sample of patients with maxillary canine-first premolar transposition and their first-degree relatives with a sample of palatally displaced canine families. Thirty-five consecutive maxillary canine-first premolar transposition probands and 111 first-degree relatives were matched to 35 consecutive palatally displaced canine probands and 115 first-degree relatives. These were assessed for palatally displaced canines and incisor-premolar hypodontia. Parental age at birth of the proband was also noted. The results revealed that (i) there is no difference in the overall prevalence of palatally displaced canine or incisor-premolar hypodontia between the groups of relatives; (ii) first-degree relatives of bilateral palatally displaced canine probands have a higher prevalence of palatally displaced canine and incisor-premolar hypodontia than those with unilateral palatally displaced canine; and (iii) maternal age at birth of the maxillary canine-first premolar transposition probands was significantly higher than that of the palatally displaced canine probands. The results suggest that maxillary canine-first premolar transposition and palatally displaced canine are unlikely to be different genetic entities and also indicate environmental or epigenetic influences on dental development.

Objective: Candida colonization is a consequence of orthodontic treatment and can lead to oral candidosis as a complication of maxillary removable appliance treatment. During orthodontic treatment, it is important to minimize colonization to prevent active infection that could consequently interfere with treatment. Hygiene is the most important factor in managing colonization; in this study, the efficacy of NitrAdine to reduce Candida was tested., Method and Materials: A randomized, double-blind, placebo-controlled trial was performed. Ninety-two patients 11 to 14 years of age were recruited at the Children's and the University Dental Clinics at Mater Dei Hospital, Tal-Qroqq, Msida, Malta. Forty-four patients used the product with NitrAdine, while 48 patients used a placebo. Sampling employing the imprint technique was performed before and after the product was used. Brilliance Candida agar was used for cultures and identification. Further identification was performed using Auxacolor 2 when required., Results: The control group had a statistically significant increase in Candida during treatment, while the experimental group had a nonstatistically significant decrease., Conclusion: It was concluded that NitrAdine may reduce the Candida burden in maxillary removable appliances. Larger sample sizes are needed to achieve statistical significance.

Objective: to evaluate the efficiency of NitrAdine (MSI Laboratories) tablets in the reduction of oral Candida levels, biofilm formation, and appliance odor in maxillary removable orthodontic appliance wearers., Method and Materials: seventy children between 11 and 15 years of age undergoing maxillary removable appliance treatment were assigned via a double-blind randomized method to the experimental or placebo arm of the study. One milliliter of unstimulated saliva was collected at the beginning of the experiment and 6 weeks later after treatment of the maxillary removable appliance with NitrAdine tablets. Samples were cultured on chromogenic Candida agar, and the number of colony-forming units per mL of saliva (CFU mL-1) was determined., Results: there was no significant difference in salivary Candida levels before or after treatment with NitrAdine tablets. There was a significant drop in plaque accumulation on the appliance and a significant amelioration in appliance odor. There was a small, nonsignificant drop in individuals exhibiting counts of 400 CFU mL-1 or more in the experimental group and a nonsignificant increase in the number of new species in the placebo group., Conclusions: NitrAdine tablets are effective in reducing plaque accumulation and appliance odor during maxillary removable appliance treatment. Further in vivo studies are required to determine the efficacy and exact protocol for NitrAdine tablets in appliance disinfection.

Objective: This study investigated the effects of trauma to primary teeth, related by age at the time of injury and type of injury sustained, to the frequency and type of developmental disturbances in the permanent successor teeth in a representative population of Maltese children., Method and Materials: Thirty-two children with 67 traumatized primary teeth were examined and any developmental disturbances of the corresponding permanent teeth recorded., Results: Altogether, 52.2% of the permanent teeth exhibited developmental disturbances following trauma to their primary predecessors. The highest frequency of malformations was found following subluxation injuries. Intrusion injuries were associated with the most severe malformations. Age at the time of trauma to the primary dentition was a principal factor in the risk and severity of malformations developing in the permanent successors., Conclusion: The extent of malformation of the developing tooth germ was highly related to its developmental stage and to the severity and type of trauma sustained by the primary incisor.

The aims of this study were to investigate the association of unerupted incisors with other dental anomalies and to indicate the aetiological and clinical relevance of such associations. Forty-one patients with unerupted incisors were examined. The group comprised 30 males and 11 females, ranging in age from 7 to 39 years. The patients were assessed for nine dental anomalies: hyperdontia, hypodontia, microdontia, enamel hypoplasia, infraocclusion of the primary molars and ectopia of the canines, premolars, first permanent molars, and second permanent molars. The patients were matched with respect to age and gender to 41 consecutively selected control subjects with similar selection criteria but no history of problems with incisor eruption. The prevalence rates of the dental anomalies in association with failure of eruption of incisors were compared to the reference rates in the control group by means of Pearson chi-square tests. The results of this study revealed that unerupted incisors were more frequent in males than in females. A statistically significant association (P = 0.006) was found between unerupted incisors and other inherited dental anomalies, namely ectopic teeth, hyperdontia, and enamel hypoplasia. Unerupted incisors may be considered part of a spectrum of inheritable dental anomalies.

Introduction: Prolonged, 4-day (96 h) measurement by the wireless Bravo system provides an opportunity to assess the variance, diagnostic reproducibility, and yield of 24- and 48-h pH and symptom association studies., Method: Retrospective analysis of 83 patients with suspected reflux symptoms undergoing wireless pH monitoring with the intention of 96-h measurement. Study periods were classified based on esophageal acid exposure, the DeMeester score (DMS), and the association of reflux events and symptoms (symptom index). The technical success of prolonged pH recording and diagnostic accuracy of 24-, 48-, and 72-h pH studies compared to the 96-h "gold standard" were assessed., Results: Prolonged Bravo pH studies were possible and well tolerated in routine clinical practice. Complete 96-h recordings were available for 34/83 (41%) patients. Variation in pH measurements reduced with increasing study duration (24-h 45%vs 48-h 27%, P<0.01), but no change in reflux severity over time was observed (ANOVA, P=ns). Abnormal acid exposure was found in 7 (19%) on every test day and 21 (58%) on at least one of four test days. A diagnosis consistent with the 96-h "gold standard" was present in 22 (63%), 29 (83%), and 32 (91%) patients for 24-, 48-, and 72-h test periods, respectively, with a significant improvement of diagnostic sensitivity with study duration (P<0.01). Similar findings were present for symptom association., Conclusion: Increasing the duration of pH studies progressively improves measurement variance and the diagnostic reproducibility of reflux studies. Future studies must address the impact of prolonged pH studies on clinical management.

Transmigrated teeth are rare, though reports have increased with the advent of panoramic radiography. Ectopic eruption of canines and other dental anomalies as retained deciduous teeth and supernumerary teeth have a genetic etiology and may be linked. A case report is presented which exhibits transmigration of both a mandibular canine and lateral incisor as well as the presence of a supplemental premolar and retained deciduous molar roots. The possible etiology of these abnormalities is discussed.

The Runx2 gene is a master transcription factor of bone and plays a role in all stages of bone formation. It is essential for the initial commitment of mesenchymal cells to the osteoblastic lineage and also controls the proliferation, differentiation, and maintenance of these cells. Control is complex, with involvement of a multitude of factors, thereby regulating the expression and activity of this gene both temporally and spatially. The use of multiple promoters and alternative splicing of exons further extends its diversity of actions. RUNX2 is also essential for the later stages of tooth formation, is intimately involved in the development of calcified tooth tissue, and exerts an influence on proliferation of the dental lamina. Furthermore, RUNX2 regulates the alveolar remodelling process essential for tooth eruption and may play a role in the maintenance of the periodontal ligament. In this article, the structure of Runx2 is described. The control and function of the gene and its product are discussed, with special reference to developing tooth tissues, in an attempt to elucidate the role of this gene in the development of the teeth and supporting structures.

The aims of the study were to analyse the records of 26 subjects (18 females, eight males) with maxillary canine-first premolar transposition (Mx.C.P1) together with 160 subjects with a palatally displaced canine (PDC) to determine the pattern of tooth agenesis in these cases and to compare them with similar samples reported in the literature. A strong association between Mx.C.P1, lateral incisor and lower second premolar agenesis was found, with a 20 per cent prevalence of lateral incisor agenesis and a 24 per cent prevalence of lower second premolar agenesis. There was a lesser association with third molar (M.3) agenesis, with a prevalence of 52.2 per cent. Weaker associations were found for a PDC, with a prevalence of 5 per cent for lateral incisor agenesis. The prevalence of lower second premolar (5 per cent) and M.3 (27.5 per cent) agenesis approached reference values. Evidence for the implication of the MSX1 or PAX9 genes in the aetiology of PDC was weak.

Transmigration of the mandibular permanent canine is a rare event, the etiology of which is not clear. We present five cases of transmigrated mandibular canines together with a review of the literature, a discussion of the etiology, and the treatment options.

In the Maltese islands, soil is one of the most threatened natural resources, being continuously exposed to a multitude of climatic, environmental, and man-induced impacts. The changes in agricultural practices as well as increases in urban development have intensified environmental problems and have accentuated the pressures on agricultural land and fragile semi-natural ecosystems. Between 1956 and 2001, the total agricultural land declined from 20,433 ha to 10,713 ha, however, during the same period, the irrigated land as a percentage of total agricultural land increased from 3.9% to 10.7%. The poor quality of irrigation water sources, and the supply of treated sewage effluent with a high level of salts, contribute to a significant salt input. The extent of salt-affected soils in the Maltese islands is not well-documented, however, field observations and technical reports indicate that soil salinity is a potential constraint for agricultural production. This article gives a comparative review of the salinity status of soils in three case study areas in Malta, the agricultural dryland at Ghammieri, the intensively cultivated irrigated valley of Pwales, and the agricultural land irrigated with treated sewage effluent of the Sant Antnin Sewage Treatment Plant in the South-East of Malta. This analysis is provided in the context of the environmental impact of irrigation on soil quality in the Maltese islands.

Thiazolidinediones are oral insulin-sensitizing agents that may be useful for the treatment of non-insulin-dependent diabetes mellitus (NIDDM). BRL 49653 ameliorates insulin resistance and improves glucoregulation in high-fat-fed (HF) rats. It is known that thiazolidinediones bind to the peroxisome proliferator-activated receptor (PPAR gamma) in fat cells, but the extent to which the improved glucoregulation and hypolipidemic effects relate to adipose tissue requires clarification. We therefore examined BRL 49653 effects on lipid metabolism in HF and control (high-starch-fed [HS]) rats. The diet period was 3 weeks, with BRL 49653 (10 mumol/kg/d) or vehicle gavage administered over the last 4 days. Studies were performed on animals in the conscious fasted state. In HF rats, rate constants governing 3H-palmitate clearance were unaffected by BRL 49653. This finding, taken with a concurrent decrease of fasting plasma nonesterified fatty acids (NEFA) (P < .01, ANOVA), demonstrated that systemic NEFA supply and hence absolute utilization are reduced by BRL 49653. Hepatic triglyceride (TG) production (HTGP) assessed using Triton WR1339 was unaffected by diet or BRL 49653. In liver, BRL 49653 increased insulin-stimulated conversion of glucose into fatty acid in both HF (by 270%) and HS (by 30%) groups (P < .05). Relative to HS rats, HF animals had substantially elevated levels of muscle diglyceride (diacylglycerol[DG] by 240%, P < .001). BRL 49653 significantly reduced muscle DG in HF (by 30%, P < .05) but not in HS rats. The agent did not reduce the intake of dietary lipid. In conclusion, these results are consistent with a primary action of BRL 49653 in adipose tissue to conserve lipid by reducing systemic lipid supply and subsequent utilization. The parallel effects of diet and BRL 49653 treatment on insulin resistance and muscle acylglyceride levels support the involvement of local lipid oversupply in the generation of muscle insulin resistance.

The neuropathological diagnosis of infections by non conventional agents relies on four lesions: astrocytic gliosis (cell hypertrophy and proliferation) usually contrasting with absent mononuclear cell infiltrates (lymphocytes, monocytes-macrophages, and/or microglia) revealed by conventional techniques, and neuronal loss in the most affected areas are little specific findings. Amyloid plaques that are inconstantly found, and spongiosis of gray matter, a characteristic and very frequent finding, are most specific. PrP immunohistochemistry brings additional data. The main diagnostic difficulties are emphasized, and guidelines for Pathological studies are recalled.