Age-related accumulation of B-1 cell progenitors in mice reflects changes in miR15a/16-1 expression and radioresistance capacity.

Hyperproliferative diseases such as Chronic Lymphocytic Leukemia (CLL) and Systemic Lupus Erythematosus (SLE) are potentially related to some disturbance in the apoptosis pathway, specifically in B-1a cells (CD5+). Accumulation of B-1a cells in lymphoid organs, bone marrow or periphery is observed in some leukemia experimental murine models along aging. It is known that aging also increases the healthy B-1 cell population. However, it is not yet clear if it happens due to self-renewal of mature cells or proliferation of progenitor cells. Herein we demonstrated that the B-1 cell precursor population (B-1p) from bone marrow of middle-aged mice is higher than from young mice. Also, these aged cells are more resistant to irradiation and have downregulation of microRNA15a/16. Alterations in these microRNAs expression and in Bcl-2 regulation were already described in human hematological malignancies and new therapeutically approaches focus on that axis. This finding could explain the early events related to cell transformation during aging and correlate with beginning of symptoms in hyperproliferative diseases. Moreover, studies have already reported these pro-B-1 as a contributor to the origin of other leukemia (Acute Myeloid Leukemia - AML). Our results point to a possible relation between B-1 cell precursors and hyperproliferation during aging. We hypothesized that this population could be maintained until the mature status of the cell or reveal changes that result in re-activation of precursor in adult bone marrow, culminating in accumulation of B-1 cells later. Based on this, B-1 cell progenitor could represent an origin for B cell malignancies and a new candidate target to diagnose and treatments in the future.

Esterification of p-Coumaric Acid Improves the Control over Melanoma Cell Growth.

Previous studies reported that p-coumaric acid modulates melanoma growth. Because the esterification of p-coumaric acid (p-CA) enhanced its activity as an antimelanogenic agent, we aimed to determine the antitumor potential of two derivatives, the ethyl and butyl esters, against the murine B16-F10 and the human SK-MEL-25 melanoma cells. Cell viability was determined in vitro by the lactate dehydrogenase release and violet crystal absorption assays. The cell proliferation rate and cell cycle behavior were determined by the colony formation assay and flow cytometry analysis. Although p-CA, at the concentration of 1 mM, failed to exert a significant antitumor activity, the ethyl and butyl ester derivatives caused substantial tumor cell death at doses < 1 mM. Despite a reduction in their direct cytotoxicity at minor doses, both products controlled the melanoma growth by arresting the cell cycle at the G0/G1 (B16-F10) or S/G2 (SK-MEL-25). Furthermore, the in vivo experiments showed that the butyl ester derivative suppressed the lung B16-F10 burden, compared to the p-CA-treated mice. Thus, the esterification of p-coumaric acid improved the control over the proliferation of murine and human melanoma cells and can be considered an approach for designing novel anticancer agents.

The transcriptome of Cryptosporidium oocysts and intracellular stages.

Human cryptosporidiosis is caused primarily by two species of apicomplexan parasites, Cryptosporidium parvum and C. hominis. Although infection of cell monolayers with sporozoites does not support the complete parasite life cycle, the in vitro system is used to study the asexual phase of multiplication, which consists of two generations of merogony. To better understand host-parasite interaction and to gain insight into gene regulatory processes driving the complex life cycle of Cryptosporidium parasites, we analyzed the transcriptome of C. parvum in oocysts, sporozoites and infected cell monolayers 2-48 h post-infection. Analysis of RNA-Seq data from replicate oocyst, sporozoite and intracellular samples revealed significant differences between transcriptomes expressed outside and inside the host cell. Compared to the transcriptome found in the host cell, the oocyst transcriptome is less diverse. Biological processes significantly over-represented intracellularly relate to biosynthetic processes. Genes significantly overexpressed in oocysts show evidence of specialized functions not found in other Apicomplexa. A more comprehensive view of gene regulation during the Cryptosporidium life cycle will require the analysis of later time points during the infection, particularly of the poorly studied sexual phase of the life cycle.

In our opinion.

The misleading statements made in the British Dental Journal in the December 2016 issue relating to dental age assessment are assessed for inaccuracies and negligent omission of the issue of Child Protection. It is emphasised that there is a need for the approach of objective knowledge viz. not influenced by personal feelings or opinions in considering and representing facts. The article by the Chair of the Education, Ethics, and Team Working Group implies that unsatisfactory consent procedures are followed. The DARLInG (Dental Age Research London Information Group) have followed a carefully prescribed procedure that fulfils all the requirements of the advice given by the Consent Committee at King's College Hospital. In addition, the active support in the form of independent support workers and lawyers assisted by interpreters is described. The issue of the lawful use of ionising radiation is described with correct information about where this information can be obtained. The seriously misleading statements made by the Chair of the Education, Ethics and Education Working Group are identified. An unacceptable oversight is the failure of the BDA representatives to draw attention to the need for child protection. The potential benefit of dental age estimation in terms of appropriately providing support for asylum seekers is described.The failure of the BDA Ethics group to be up to date with recent research which shows a high level of certainty in assigning age disputed subjects to above (or below) the 18-year threshold is discussed and the importance of this in reliably determining, in an objective way, the age status of asylum seekers. The incorrect and salacious use of the term 'X-rated' is highlighted and a formal request for its withdrawal has been made.

Periodontal Ligament Visibility (PLV): validation of PLV to determine adult status.

BACKGROUND: Gradual obliteration of the Periodontal Ligament Visibility (PLV) of lower third molars indicates increasing age. This is used to help determine whether or not an age disputed subject is above or below the 18 year threshold. AIM: The main focus was to determine, in test subjects of known age, whether the PLV system used 'blind' is able to reliably indicate whether the subject was a child (age < 18 years) or adult (age > 18). MATERIALS AND METHODS: A total of 250 normal subjects in the age range 16 to 26 years, from the archives of Guy's Hospital in London, UK, were used to validate the system of PLV. The radiographic assessment of PLV1 was used to categorize four grades of PLV. RESULTS: It was found that for both females and males PLV-C and PLV-D gave very high probabilities (p = 1.000) of the test subjects being of adult status. CONCLUSION: Periodontal Ligament Visibility has the potential to play an important part in the assessment of age disputed asylum seekers who look adult and claim to be children.

A method to investigate the shrinkage stress developed by resin-composites bonded to a single flat surface.

OBJECTIVES: To purpose a method for predicting the shrinkage stress development in the adhesive layer of resin-composite cylinders that shrink bonded to a single flat surface, by measuring the deflection of a glass coverslip caused by the shrinkage of the bonded cylinders. The correlation between the volume of the bonded resin-composite and the stress-peak was also investigated. METHODS: A glass coverslip deflection caused by the shrinkage of a bonded resin-composite cylinder (diameter: d=8 mm, 4 mm, or 2 mm, height: h=4 mm, 2 mm, 1 mm, or 0.5 mm) was measured, and the same set-up was simulated by finite element analysis (3D-FEA). Stresses generated in the adhesive layer were plotted versus two geometric variables of the resin-composite cylinder (C-Factor and volume) to verify the existence of correlations between them and stresses. RESULTS: The FEA models were validated. A significant correlation (p<0.01, Pearson's test) between the stress-peak and the coverslip deflection when the resin-composites were grouped by diameter was found for diameters of 2 and 4 mm. The stress-peak of the whole set of data showed a logarithmic correlation with the bonded resin-composite volume (p<0.001, Pearson's test), but did not correlate with the C-Factor. SIGNIFICANCE: The described method should be considered for standardizing the stress generated by the shrinkage of resin-composite blocks bonded to a single flat surface.

Prevalence, intensity and identity of bacteraemia following conservative dental procedures in children.

INTRODUCTION: The aim of this study was to investigate the prevalence, intensity and microbial identity of bacteraemia following conservative dental procedures. The procedures were placement of rubber dam, use of the fast drill, use of the slow drill and placement of a matrix band and wedge. METHOD: Two hundred and five children and adolescents undergoing general anaesthesia for dental treatment at the Eastman Dental Hospital were recruited. Each subject was randomly allocated to one of the procedure groups. A baseline blood sample was taken before any dental treatment was carried out. A second blood sample was taken 30 s after a single conservative procedure. The blood samples were processed using lysis filtration. All bacterial isolates were identified using comparative 16 S ribosomal RNA gene sequencing. Oral Streptococcus spp. and coagulase-negative Staphylococcus spp. were further identified by comparative sodA gene sequencing. RESULTS: The prevalence of bacteraemia was significantly greater following placement of rubber dam (P = 0.01) and placement of matrix band and wedge, compared with baseline. The intensity of bacteraemia was significantly greater following placement of rubber dam (P = 0.001) and placement of matrix band and wedge (P = 0.0001). The most frequently isolated bacteria were Streptococcus spp. (56%), Actinomyces spp. (15%) and coagulase-negative Staphylococcus spp. (15%). CONCLUSION: Conservative dental procedures are a significant cause of bacteraemia.

Oral health of children with intractable epilepsy attending the UK National Centre for Young People with Epilepsy.

AIM: To investigate the oral health of children with intractable epilepsy attending the UK National Centre for Young People with Epilepsy. STUDY DESIGN AND METHODS: 39 children and adolescents with intractable epilepsy at a residential school, the UK National Centre For Young People With Epilepsy (NCYPE) were age, gender and ethnicity matched with 39 healthy children from local schools in Surrey (England). Dental examinations were completed for indices for both the primary and permanent dentitions comprising decayed, missing and filled teeth and surfaces, plaque index, gingivitis index, developmental enamel defects, and incisor tooth trauma. RESULTS: There was no significant difference in the dmfs, dmft, DMFS or DMFT in the children with epilepsy compared with the controls. There was a significantly greater mean plaque score associated with permanent teeth in the children with epilepsy 68.0 SD+/- 31.5, compared with the control children, 142.9 SD+/- 23.2, p<0.0001. The mean +/- SD gingivitis score was significantly greater in the children with epilepsy 47.9+/-33.8, compared with the control children, 15.85+/-21.8, p<0.001. A significantly greater number of children with epilepsy had experienced anterior tooth trauma, 54% in all, compared with the controls, 12.5% p<0.0001. Although children with epilepsy had greater mean plaque and gingivitis scores, the prevalence of dental caries was low. Children and teenagers with intractable epilepsy were more likely to have sustained dental trauma than controls. CONCLUSIONS: A dental service aimed at early attention to anterior tooth trauma is needed. In addition, there is an ongoing need for improving the oral hygiene of these individuals to prevent the development of periodontal disease in later life.

Dental age assessment (DAA): a simple method for children and emerging adults.

INTRODUCTION: Methods of dental age assessment (DAA) give a wide margin of error and, because third molars are usually excluded, prevent estimation around the age of 18 years. This study extends the use of defined tooth development stages (TDSs) to include third molars. SUBJECTS AND METHODS: Re-use of dental panoramic tomographs (DPTs) and other X-rays taken for clinical use comprised the sample of 1,547 subjects. The radiographic images were then captured in digital format. The TDSs were assessed and the estimated mean age and its standard error were calculated for each TDS. The mathematical technique of meta-analysis was used to provide an estimate of the mean age, with 99% confidence interval, of a new 'test' subject. To assess the accuracy of the method, each of these mean values was then compared with the gold standard of chronological age. RESULTS: On average, estimated dental age (DA) over-estimated chronological age (CA) by 0.29 years, approximately 3(1/2) months. The maximum likely difference between the estimated DA and CA was 1.65 years. CONCLUSION: Estimation of dental age using well defined TDSs, extended to include third molars and combined with the statistical technique of meta-analysis, provides investigators with a rapid and accurate estimation of age.

Duration, prevalence and intensity of bacteraemia after dental extractions in children.

OBJECTIVE: To investigate the duration, prevalence and intensity of bacteraemia after dental extractions in children by comparing within-patient bacteraemia before and after dental extraction. METHODS: Children were randomly allocated to one of 10 postprocedure time groups from 10 s to 60 min. The differences between intensity and prevalence of the bacteraemia at each time after extractions were used to estimate the duration of the bacteraemia. After attainment of general anaesthesia, pre-extraction and postextraction blood samples were processed by broth culture and lysis filtration to isolate and quantify bacteria present in the patients' blood. RESULTS: 500 subjects between 3 and 16 years old were recruited. The estimated duration of bacteraemia was about 11 min. CONCLUSIONS: The duration of bacteraemia after dental extractions is less than previously thought. This has implications for the interpretation of odontogenic bacteraemia studies.

Oral health and caries related microflora in children during the first three months following renal transplantation.

UNLABELLED: There is little information on the oral health of children undergoing renal transplantation during the early transplant period. METHODS: Twenty-four children undergoing renal transplantation aged 4-13.2 years and their matched controls were recruited. The dmfs, dmft, DMFS and DMFT, plaque, gingivitis and gingival enlargement scores were recorded. The oral microflora was sampled and cultured for S. mutans, Lactobacllus species and Candida species. RESULTS: There was a significantly lower mean dmfs (0.3 +/- 0.9; P = 0.03), dmft (0.3 +/- 0.9; P = 0.03), DMFS (2.3 +/- 5.3; P = 0.01) and DMFT (1.5 +/- 2.6; P = 0.02), respectively, in the transplant group. There was a significantly greater mean plaque score (14.7 +/- 11) for the permanent dentition, at baseline only, compared with 90 days post-transplantation (9.4 +/- 10.4; P = 0.02). There was a significantly greater gingival enlargement score (1.8 +/- 1.4; P = 0.04) 90 days post-transplantation compared with baseline. The S. mutans and Lactobacillus counts were significantly lower both at baseline (P = 0.0001 and P = 0.004) and 90 days post-transplantation (P = 0.02; and P = 0.05), respectively, compared with the controls. CONCLUSIONS: The transplant children had less active dental disease than the controls although gingival enlargement needs careful monitoring.

Metastatic infiltration of the dental pulp by medulloblastoma.

Medulloblastoma is an infratentorial primitive neuroectodermal tumour. It is the most commonly occurring brain tumour of childhood, accounting for 15-20% of all paediatric tumours. Extracranial metastasis is rare, but may involve the skeleton. Jaw lesions, however, have never been described. A case is reported of metastases of a medulloblastoma to the jaw including the dental pulp.

Dental disease indices and caries-related microflora in children with glycogen storage disease.

OBJECTIVE: To establish the levels of dental caries, bacterial dental plaque, gingivitis and caries-related microflora in children with glycogen storage disease (GSD). Patients with GSD are treated with regular intakes of glucose polymer and uncooked cornstarch to prevent hypoglycaemia. Dental health data are scarce. STUDY GROUP: The study group comprised 21 children with GSD attending the Great Ormond Street Hospital for Children. OUTCOME MEASURES: These included the number of decayed, missing and filled teeth, and surfaces in both the primary and permanent dentitions, plaque and gingivitis scores. Both plaque and saliva were collected from each child and cultured for Mutans streptococci, Lactobacilli and Candida. RESULTS: The study group included 13 boys and eight girls, aged from 2.7 to 15.5 years. Four of the 21 children had some caries experience. The mean dmft was 0.5 and the mean DMFT, 0.06. Mean plaque and gingivitis scores were 4.8 and 5.9, respectively, for plaque and gingivitis adjacent to the primary teeth, and 11.6 and 12 for those related to permanent teeth. CONCLUSIONS: Only a small proportion of the children had caries experience but most were found to have plaque associated with both primary and permanent teeth. Preventive care should be targeted to improve plaque control thus minimizing the risk of developing periodontal disease as adults.

Dental disease and caries related microflora in children with dystrophic epidermolysis bullosa.

PURPOSE: The purpose of this study was to investigate dental caries, bacterial dental plaque, gingivitis and caries related oral microflora in children with predominantly autosomal recessive Dystrophic Epidermolysis Bullosa (DEB). METHODS: Thirty children with DEB from The Great Ormond Street Hospital for Children and 31 control children matched for age, gender and ethnicity were included in the study. RESULTS: The main findings were: 1. A significantly greater mean dmft in the DEB children (p < 0.05). 2. A significantly greater mean plaque score for the DEB children for both the primary (p < 0.001) and permanent teeth (p < 0.02) compared with the control children. 3. A significantly greater mean gingivitis score for the DEB children for both the primary (p < 0.002) and permanent teeth (p < 0.0001) compared with the control children. 4. A significantly greater salivary total anaerobic count for the control children compared with the DEB children (p < 0.001). CONCLUSIONS: The results reflect the difficulties that children with DEB have with basic oral hygiene procedures combined with slow oral clearance.

The dental health and caries-related microflora in children with craniosynostosis.

OBJECTIVE: To compare levels of dental caries, bacterial dental plaque, gingivitis, enamel defects, and caries-related microflora in children with and without craniosynostosis. STUDY GROUP: Fifty-seven children with craniosynostosis and their matched controls. OUTCOME MEASURES: The decayed, missing, and filled teeth and surfaces in both the deciduous (dmfs and dmft) and the permanent dentition (DMFS and DMFT). The plaque and gingivitis scores and developmental enamel defects were also recorded. The caries-related microflora was sampled using an alginate swab and the prevalence of Streptococcus mutans and Lactobacillus and Candida species were recorded. RESULTS: The dmfs (p <.02) and dmft (p <.01) were significantly greater in the control children. The plaque score for the deciduous dentition only (p <.02) and also the gingivitis score for the permanent teeth only (p <.008) in the craniosynostosis group were significantly greater. The total aerobic bacterial count (p <.004), anaerobic count (p <.002), and Candida count (p <.05) were significantly greater in the control group. The proportion of S. mutans both as a percentage of the total anaerobic count (p <.04) and the total streptococcal count (p <.05) was significantly greater in the control group.

Dental health indices and caries-related microflora in children with severe haemophilia.

The purpose of this work was to investigate the prevalence of dental caries, bacterial dental plaque, gingivitis, enamel defects and caries- related microflora in children with severe haemophilia. Thirty-eight children with severe haemophilia (factor VIII and IX < 2 U dL(-1)) were recruited from Great Ormond Street Hospital for Children and matched for age, gender and ethnicity with healthy control children from the Eastman Dental Institute. Indices were recorded for decayed, missing, and filled teeth and surfaces in both the deciduous dentition (dmfs/dmft) and the permanent dentition (DMFS/DMFT). The plaque and gingivitis scores and developmental enamel defects were also recorded. The caries-related microflora was sampled and cultured for Streptococcus mutans, and Lactobacilli and Candida species. A significantly greater proportion of children with severe haemophilia were caries-free compared with the controls (36.7% vs. 13.3%; P=0.04). Both the DMFS and DMFT were significantly greater in the controls (3.6 and 2.8, respectively) compared with the haemophilia group, (0.8 and 0.7; P=0.007 and P=0.04). The plaque score for the permanent dentition only was significantly greater for the control children (24.2) compared with the haemophilia group, (10.2; P=0.04). The mean number of colony forming units of S. mutans was significantly greater in the control group compared with the haemophilia group (P=0.05). We conclude that children with severe haemophilia have a significantly lower prevalence of dental caries compared with matched, healthy controls.

Dental procedures in children with severe congenital heart disease: a theoretical analysis of prophylaxis and non-prophylaxis procedures.

OBJECTIVE: To estimate the cumulative exposure to bacteraemia from dental procedures currently recommended for antibiotic prophylaxis and compare this with cumulative exposure from dental procedures not recommended for prophylaxis. DESIGN: Retrospective analysis. SETTING: University and teaching hospital maxillofacial and dental department. PATIENTS: 136 children with severe congenital cardiac disease attending for dental treatment between 1993 and 1998 and for whom full records were available. Each dental procedure was tallied. MAIN OUTCOME MEASURES: Cumulative exposure per annum to "non-prophylaxis procedures"; cumulative exposure per annum to "prophylaxis procedures". RESULTS: Cumulative exposure to bacteraemia from prophylaxis procedures was not significantly greater than from non-prophylaxis procedures. CONCLUSIONS: The data raise important questions about the appropriateness of current guidelines for antibiotic prophylaxis of bacterial endocarditis.

Dental disease indices and caries related oral microflora in children with phenylketonuria.

The purpose of this study was to investigate the dental caries, plaque and gingivitis indices and caries related oral flora in children with classic phenylketonuria. Forty-one children at The Great Ormond Street Hospital for Children and controls were included in the study. The main findings were: No significant difference in the decayed, missing and filled surfaces of the primary and permanent teeth between the phenylketonuria children and the controls. A significantly greater mean plaque score for the control children compared with the phenylketonuria children (p < 0.01) for the permanent teeth only. A significantly greater number of white opacities in the permanent teeth of the phenylketonuria group compared with the control group (p < 0.02). No significant differences in the caries related microflora.