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Senescence is an anti-tumour mechanism and hallmark of cancer. Loss or mutation of key senescence effectors, such as p16INK4A, are frequently observed in cancer. Intriguingly, some human tumours are both proliferative and senescent-marker positive (Sen-Mark+). Here, we explore this paradox, focusing on the prognostic consequences and the current challenges in classifying these cells. We discuss future strategies for Sen-Mark+ cell detection together with emerging opportunities to exploit senescence for cancer., (© 2024. The Author(s).)

Oncolytic viruses are being tested in clinical trials, including in women with ovarian cancer. We use a drug-repurposing approach to identify existing drugs that enhance the activity of oncolytic adenoviruses. This reveals that carvedilol, a β-arrestin-biased β-blocker, synergises with both wild-type adenovirus and the E1A-CR2-deleted oncolytic adenovirus, dl922-947. Synergy is not due to β-adrenergic blockade but is dependent on β-arrestins and is reversed by β-arrestin CRISPR gene editing. Co-treatment with dl922-947 and carvedilol causes increased viral DNA replication, greater viral protein expression and higher titres of infectious viral particles. Carvedilol also enhances viral efficacy in orthotopic, intraperitoneal murine models, achieving more rapid tumour clearance than virus alone. Increased anti-cancer activity is associated with an intratumoural inflammatory cell infiltrate and systemic cytokine release. In summary, carvedilol augments the activity of oncolytic adenoviruses via β-arrestins to re-wire cytokine networks and innate immunity and could therefore improve oncolytic viruses for cancer patient treatment., (© 2022. The Author(s).)

Objectives: Variants in DLX3 cause tricho-dento-osseous syndrome (TDO, MIM #190320), a systemic condition with hair, nail and bony changes, taurodontism and amelogenesis imperfecta (AI), inherited in an autosomal dominant fashion. Different variants found within this gene are associated with different phenotypic presentations. To date, six different DLX3 variants have been reported in TDO. The aim of this paper was to explore and discuss three recently uncovered new variants in DLX3., Subjects and Methods: Whole-exome sequencing identified a new DLX3 variant in one family, recruited as part of an ongoing study of genetic variants associated with AI. Targeted clinical exome sequencing of two further families revealed another new variant of DLX3 and complete heterozygous deletion of DLX3. For all three families, the phenotypes were shown to consist of AI and taurodontism, together with other attenuated features of TDO., Results: c.574delG p.(E192Rfs*66), c.476G>T (p.R159L) and a heterozygous deletion of the entire DLX3 coding region were identified in our families., Conclusion: These previously unreported variants add to the growing literature surrounding AI, allowing for more accurate genetic testing and better understanding of the associated clinical consequences., (© 2018 The Authors Oral Diseases Published by John Wiley & Sons Ltd. All rights reserved.)

Aims: This study examined the problems encountered by children with autism spectrum disorder (ASD), when accessing dental care., Study Design: This was a cross-sectional, case-control questionnaire study., Methods: A piloted questionnaire was developed to identify the main barriers to dental care experienced by patients with ASD in Hull and East Riding. The study group was comprised of parents/carers of children with ASD, and the control group was comprised of parents/carers of age matched healthy, neurotypical children., Statistics: Results were analysed using Chi-square and Fisher's exact tests where appropriate. Significance was deemed at p < 0.05. Ordinal data was presented using medians and 25th and 75th centiles and compared using Mann-Whitney U test., Methods: A piloted questionnaire was developed to identify the main barriers to dental care experienced by patients with ASD in Hull and East Riding. The study group was comprised of parents/carers of children with ASD, and the control group was comprised of parents/carers of age matched healthy, neurotypical children., Results: 112 subjects completed the questionnaire. There was no significant difference in accessing dental care between study and control groups (p = 0.051), although access was perceived as more difficult in the ASD group (p < 0.001). There was a significantly greater perceived difficulty in travelling to the dental surgery in the ASD group. Predicted negative behaviours were more frequent in the ASD group. All suggested interventions were predicted to be helpful in a significantly greater proportion of the ASD group., Conclusion: Difficulties exist for children with ASD in accessing dental care in the Hull and East Riding area.

Aim: To examine the anxiety levels of children referred for dental general anaesthesia and their parents at various key points of the referral and anaesthetic procedure., Methods: Structured interviews and anxiety measures were conducted with 50 children attending the Department of Paediatric Dentistry, Leeds Dental Institute, and progressing to general anaesthetic (GA) and their parents. Interviews were conducted with parents and children prior to initial assessment, following assessment and prior to a GA. Anxiety was measured at each interview, using the Visual Analogue Scale for parents and the Venham's Picture test for children. A fourth telephone interview was conducted with parents one week after the GA when the degree of upset caused to parents and children by the procedure was evaluated., Results: Anxiety of children remained constant at each interview. Parent and child anxiety were not related. There was a rise in parent anxiety following initial assessment in those families attending in response to a routine referral and progressing to GA (p<0.05). There was a further rise in parent anxiety in these families immediately prior to the GA itself (p<0.001). Parent upset was strongly related to their anxiety at each of the three interviews prior to the GA (p<0.01, 0.05 and 0.001 respectively) and to the distress of their child (p<0.02). Child distress was strongly related to anxiety at each of the three interviews prior to the GA., Conclusion: The anxiety levels of children did not appear to change throughout the whole GA assessment and treatment process. Parent anxiety rose significantly following assessment and again just prior to the GA. Factors contributing to parent upset post treatment were child upset and pre treatment parent anxiety levels. Children who were most anxious prior to GA found the procedure most distressing.

This case illustrates the management of multiple dental anomalies in a young patient, which included anomalies of number and morphology. Although individually these anomalies are not uncommon, the combination is unusual and highlights the importance of careful clinical and radiographic examination of patients with dental anomalies.

Dental erosion is becoming a major dental problem in both children and adults. The aim of this study was to measure the salivary flow rates, buffering capacity and mutans streptococci counts in children with erosion, and compare them to age- and sex-matched caries-free and caries-active individuals to establish which factors may be important in erosion. The study was conducted as a case-control study with standard methods of salivary and mutans streptococci measurement. The results showed significant differences for mutans streptococci counts (p = 0.05), unstimulated and stimulated salivary pH and buffering capacity (p = 0.001). These results suggest that although individuals with erosion have caries experience similar to a caries-free individual, their salivary characteristics more closely match those of a caries-active subject. The tests described are simple to carry out and may be useful in explaining individual patient susceptibility.

This article seeks to aid the busy dentist by providing a basic guide to treating fractured and traumatized primary teeth and soft tissues. Simple guidelines for a step-by-step approach to the efficient care of traumatized primary teeth are given.

Gastroesophageal reflux (GOR) is often a self-limiting condition but nevertheless is a common cause of morbidity in childhood. Studies of adult patients with hiatus hernias and GOR have suggested that there is an increased incidence of dental erosion in these individuals. The aim of this study was to investigate the relationship between dental erosion and GOR in children. Fifty-three children aged 2 to 16 yr (mean 4.9 yr) with moderate to severe GOR, defined by pH monitoring, were examined for dental erosion. A questionnaire investigating dietary habits, other relevant medical conditions, and erosion risk factors was also completed. Results showed that the prevalence of dental erosion was low, when compared with the UK National Survey, with only 9 (17%) children showing any signs of erosion, and of these only one had erosion involving dentine. These results suggest that dental erosion may not be as great a problem in children with GOR as it is in adults. It may be that refluxing is limited to the oesophagus, and further work is needed to investigate those children that positively reflux into the mouth.

Animal bites and stings may not figure highly in the differential diagnosis of facial swelling in the United Kingdom but should be considered in those who have been in a tropical area. This case report documents details of the presentation and investigation of a case of jellyfish sting that appeared as a facial swelling in a 4-year-old girl who had recently been on holiday in Greece. The report emphasizes the requirement to consider unusual aetiological factors in cases of facial swelling.

A study was carried out to compare the effectiveness of two doses of temazepam elixir for the behaviour management of paediatric dental patients. Twenty-two children aged 2-5 years (mean 4.06 years), classified as ASA Class I and II (American Society of Anesthesiologists Classification), were assigned to receive either 0.3 or 0.5 mg/kg temazepam elixir in a double-blind randomized cross-over study. All treatment sessions were videotaped and rated independently by three paediatric dentists for the degree of crying, movement, sleep and overall behaviour at 15-minute intervals while being treated. The results showed no statistically significant differences between the two doses.

Thirty children diagnosed as suffering from acute lymphoblastic leukaemia were followed up for between 6 months and 1 year during their treatment for the disease. Dental examinations were carried out at approximately monthly intervals for caries, gingival condition, plaque and calculus. The results showed a significant deterioration in gingival condition, but there were no significant changes in the amounts of plaque and calculus. No new carious lesions developed in any of the children's teeth during the study period.

Thirty-four children with diagnosed cases of acute leukemias and being treated with cytotoxic chemotherapy at St James' Hospital, Leeds, were followed for between 6 months and 1 year to determine the changes in their oral microflora. They were examined before treatment commenced and then at monthly intervals. Swabs were taken from the oral cavity to test for the presence or absence of bacteria and Candida. Saliva samples were also used to assess the levels of Streptococcus mutans in the mouth. Sensitivity tests were carried out to assess the effect of the cytotoxic agents on the oral flora. All children received prophylactic nystatin and chlorhexidine gluconate mouthrinses four times daily for the whole period of the study. There was significant difference (p < 0.0001) for counts of S. mutans at different treatment stages. Sensitivity tests showed that S. mutans was sensitive to the cytotoxic drug daunorubicin, and this drug was probably responsible for the fall in S. mutans counts. A significant difference was also found in the types of bacteria isolated between the study and reference groups, but there was no change in the composition of the flora in the study group during treatment. These bacteria were also found to mirror those cultured from routine blood samples in children with acute leukemia.

A total of 1,974 primary molar teeth from the skeletal remains of 373 children from Prehistoric times to the 18th century were examined for caries prevalence and site characteristics. Results showed that caries in primary teeth was initiated more often at the cemento-enamel junction than the contact point in most time periods and that caries prevalence values recorded were comparable to those in other reports based upon much smaller sample sizes. Caries prevalence and site characteristics for primary molar teeth were found to be similar to those of permanent dentitions of corresponding periods, a finding that contradicts many previous studies. This study showed a higher caries prevalence in primary molars during the Romano-British period than recorded previously.

This research studied an association between dental caries prevalence in the primary dentition and cribra orbitale, an indicator of nutritional stress in archeological populations. Skeletal remains of 221 British children (Pre-Roman to Late Medieval) were examined, of whom 100 had orbital material available. Dental caries, as dmfs, was related to the presence of cribra orbitale (none, slight, moderate, or severe). Thus, data for 50 children showed a statistically significant association (P less than 0.005) between caries prevalence and cribra orbitale using the Fisher Exact Test, suggesting that nutritional stress is an associated factor in caries etiology in children.

A review of 80 children treated under general anesthesia for comprehensive dental treatment between 1984 and 1987 inclusive was carried out to assess the effectiveness of this type of care. A minimum 2-year follow-up period was used. This approach allowed the dentition to be restored in one visit. Preventive care and 'behaviour shaping' could then begin at subsequent visits to the dental clinic. It was found that 80% of the children needing further treatment at a later date accepted local anaesthesia and treatment in the normal way. Full coverage stainless steel crowns were significantly more successful (3% failure rate) than amalgam or composite restorations (29% failure rate). Vital pulpotomies also showed only a 2% failure rate.