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Aim the main aim of this study was to examine the usability of a new dietary measure among a high caries population and examine whether reported food intake, when weighted by frequency and cariogenicity, was associated with increased caries rates within a high caries population. Key method Two hundred and eighteen children with caries were examined using standard caries diagnostic criteria. The examinations were carried out by a single calibrated dental examiner. A food frequency table was completed by the parents of each participant and this was analysed by weighting foods’ cariogenic potential by the frequency of consumption, and summing the product. The total cariogenicity score for each child was then plotted against its dmft and dt and correlation coefficients were calculated. Result the mean cariogenicity score using this new measure was 71.02, with a range of 31.96 to 135.24. The standard deviation was 16.72. Total cariogenicity scores using the new measure and dmft were weakly correlated, with the Pearson correlation co-efficient being 0.130 and for dt 0.131. These correlations did not reach significance. Conclusion The study has demonstrated that in children with caries, reported food intake (when weighted by frequency and cariogenicity) and caries are only weakly and non-significantly associated. Dietary intake, when measured in a way, which takes account of all food groups, was therefore not strongly associated with caries when measured on an individual level.

Objective: To identify the relative influence of home and school environments on children's caries experience in both the primary and secondary dentitions. Setting The north west of England. Method: Data were used from surveys of 5- and 12-year-old children in the north west of England. Super Profiles was used to categorise children into four groups based on the areas in which their home address and school were located. Differences in dental caries experience were examined using t-tests with Bonferroni modification to the p-value. Results: Five-year-old children living in deprived areas and attending schools in deprived areas, and those living in a deprived area but attending a school in an affluent area had significantly (p<0.05) more disease than children from affluent areas who attended schools in deprived areas and those from affluent areas who attended schools in affluent areas. The situation in 12-year-olds differed, those living in deprived areas and attending schools in deprived areas having significantly (p<0.05) more disease than children from the other three groups. Conclusions: The results suggest that the main influence on dental disease experience in both 5- and 12-year-olds is the home environment. The results have implications for the planning of health promotion interventions. [ABSTRACT FROM AUTHOR]

The aim of this study was to develop an instrument to measure an individual's value of the appearance of their anterior teeth. Structured interviews were carried out using the Index of Orthodontic Treatment Need (IOTN) as a basis for time trade-offs and visual analogue utility measurement. The subjects of the study were forty-five 11-14 year-old children at new patient consultation with an orthodontist (seekers) and forty-five 11-14-year-old children in school (non-seekers). It was possible to derive utility values using the techniques adopted. The seekers and non-seekers of treatment had significantly different utility values for anterior tooth appearance { P <0.05, Mann-Whitney). This study suggests that it is possible to develop utilities that reflect how patients value the appearance of anterior teeth. These utilities had a predictive validity in that there were significant differences in seekers' and non-seekers' utility values. The seekers placed a higher value than non-seekers on the desirability of a good aesthetic appearance. [ABSTRACT FROM AUTHOR]

The Neuropeptide S system, consisting of the 20-amino acid peptide neuropeptide S (NPS) and its G-protein coupled receptor (NPSR), modulates arousal, wakefulness, anxiety, and fear-extinction in mice. In addition, recent evidence indicates that the NPS system attenuates stress-dependent impairment of fear extinction, and that NPS-expressing neurons in close proximity to the locus coeruleus (pericoerulear, periLC) region are activated by stress. Furthermore, periLC NPS neurons receive afferents from neurons of the centrolateral nucleus of the amygdala (CeL), of which a substantial population expresses the kappa opioid receptor (KOR) ligand precursor prodynorphin. This study aims to identify the effect of the dynorphinergic system on NPS neurons in the periLC via pre- and postsynaptic mechanisms. Using electrophysiological recordings in mouse brain slices, we provide evidence that NPS neurons in the periLC region are directly inhibited by dynorphin A via activation of κ-opioid receptor 1 (KOR1) and a subsequent increase of potassium conductances. Thus, the dynorphinergic system is suited to inactivate NPS neurons in the periLC. In addition to this direct, somatic effect, dynorphin A reduces the efficacy of GABAergic synapses on NPS neurons via KOR1 and KOR2. In conclusion, the present study provides evidence for the interaction of the NPS and the kappa opioid system in the periLC. Therefore, the endogenous opioid dynorphin is suited to inhibit NPS neurons with a subsequent decrease in NPS release in putative target regions leading to a variety of physiological consequences such as increased anxiety or vulnerability to stress exposure.

Intercellular communication between different cell types in solid tumors contributes to tumor growth and metastatic dissemination. The secretome of cancer-associated fibroblasts (CAFs) plays major roles in these processes. Using human mammary CAFs, we showed that CAFs with a myofibroblast phenotype released extracellular vesicles that transferred proteins to endothelial cells (ECs) that affected their interaction with immune cells. Mass spectrometry-based proteomics identified proteins transferred from CAFs to ECs, which included plasma membrane receptors. Using THY1 as an example of a transferred plasma membrane-bound protein, we showed that CAF-derived proteins increased the adhesion of a monocyte cell line to ECs. CAFs produced high amounts of matrix-bound EVs, which were the primary vehicles of protein transfer. Hence, our work paves the way for future studies that investigate how CAF-derived matrix-bound EVs influence tumor pathology by regulating the function of neighboring cancer, stromal, and immune cells.

Background: Bacterial surface glycans are assembled by glycosyltransferases (GTs) that transfer sugar monomers to long-chained lipid carriers. Most bacteria employ the 55-carbon chain undecaprenyl phosphate (Und-P) to scaffold glycan assembly. The amount of Und-P available for glycan synthesis is thought to be limited by the rate of Und-P synthesis and by competition for Und-P between phosphoglycosyl transferases (PGTs) and GTs that prime glycan assembly (which we collectively refer to as PGT/GTs). While decreasing Und-P availability disrupts glycan synthesis and promotes cell death, less is known about the effects of increased Und-P availability., Results: To determine if cells can maintain higher Und-P levels, we first reduced intracellular competition for Und-P by deleting all known non-essential PGT/GTs in the Gram-negative bacterium Escherichia coli (hereafter called ΔPGT/GT cells). We then increased the rate of Und-P synthesis in ΔPGT/GT cells by overexpressing the Und-P(P) synthase uppS from a plasmid (puppS). Und-P quantitation revealed that ΔPGT/GT/puppS cells can be induced to maintain 3-fold more Und-P than wild type cells. Next, we determined how increasing Und-P availability affects glycan expression. Interestingly, increasing Und-P availability increased endogenous and recombinant glycan expression. In particular, ΔPGT/GT/puppS cells could be induced to express 7-fold more capsule from Streptococcus pneumoniae serotype 4 than traditional E. coli cells used to express recombinant glycans., Conclusions: We demonstrate that the biotechnology standard bacterium E. coli can be engineered to maintain higher levels of Und-P. The results also strongly suggest that Und-P pathways can be engineered to increase the expression of potentially any Und-P-dependent polymer. Given that many bacterial glycans are central to the production of vaccines, diagnostics, and therapeutics, increasing Und-P availability should be a foremost consideration when designing bacterial glycan expression systems., (© 2024. The Author(s).)

Proline is a nonessential amino acid, and its metabolism has been implicated in numerous malignancies. Together with a direct role in regulating cancer cells' proliferation and survival, proline metabolism plays active roles in shaping the tumor microenvironment (TME). Cancer-associated fibroblasts (CAFs) display high rates of proline biosynthesis to support the production of collagen for the extracellular matrix (ECM). Indeed, impaired proline metabolism in CAFs results in reduced collagen deposition and compromises the growth and metastatic spread of cancer. Moreover, the rate of proline metabolism regulates intracellular reactive oxygen species (ROS) levels, which influence the production and release of cytokines from cancer cells, contributing toward an immune-permissive TME. Hence, targeting proline metabolism is a promising anticancer strategy that could improve patients' outcome and response to immunotherapy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

High-grade serous (HGS) ovarian cancer is the most lethal gynaecological disease in the world and metastases is a major cause. The omentum is the preferential metastatic site in HGS ovarian cancer patients and in vitro models that recapitulate the original environment of this organ at cellular and molecular level are being developed to study basic mechanisms that underpin this disease. The tumour extracellular matrix (ECM) plays active roles in HGS ovarian cancer pathology and response to therapy. However, most of the current in vitro models use matrices of animal origin and that do not recapitulate the complexity of the tumour ECM in patients. Here, we have developed omentum gel (OmGel), a matrix made from tumour-associated omental tissue of HGS ovarian cancer patients that has unprecedented similarity to the ECM of HGS omental tumours and is simple to prepare. When used in 2D and 3D in vitro assays to assess cancer cell functions relevant to metastatic ovarian cancer, OmGel performs as well as or better than the widely use Matrigel and does not induce additional phenotypic changes to ovarian cancer cells. Surprisingly, OmGel promotes pronounced morphological changes in cancer associated fibroblasts (CAFs). These changes were associated with the upregulation of proteins that define subsets of CAFs in tumour patient samples, highlighting the importance of using clinically and physiologically relevant matrices for in vitro studies. Hence, OmGel provides a step forward to study the biology of HGS omental metastasis. Metastasis in the omentum are also typical of other cancer types, particularly gastric cancer, implying the relevance of OmGel to study the biology of other highly lethal cancers., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

Conjugate vaccines produced either by chemical or biologically conjugation have been demonstrated to be safe and efficacious in protection against several deadly bacterial diseases. However, conjugate vaccine assembly and production have several shortcomings which hinders their wider availability. Here, we developed a tool, Mobile-element Assisted Glycoconjugation by Insertion on Chromosome, MAGIC, a novel biotechnological platform that overcomes the limitations of the current conjugate vaccine design method(s). As a model, we focused our design on a leading bioconjugation method using N-oligosaccharyltransferase (OTase), PglB. The installation of MAGIC led to at least twofold increase in glycoconjugate yield via MAGIC when compared to conventional N-OTase based bioconjugation method(s). Then, we improved MAGIC to (a) allow rapid installation of glycoengineering component(s), (b) omit the usage of antibiotics, (c) reduce the dependence on protein induction agents. Furthermore, we show the modularity of the MAGIC platform in performing glycoengineering in bacterial species that are less genetically tractable than the commonly used Escherichia coli. The MAGIC system promises a rapid, robust and versatile method to develop vaccines against serious bacterial pathogens. We anticipate the utility of the MAGIC platform could enhance vaccines production due to its compatibility with virtually any bioconjugation method, thus expanding vaccine biopreparedness toolbox., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Bicarbonate transport is a pre-existing mechanism of pH regulation in pancreatic ductal cells. In a recent study, Cappellesso et al. demonstrated that pancreatic ductal adenocarcinoma metabolic rewiring creates an acidic environment, enhanced by bicarbonate import into cancer cells via SLC4A4. This acidity favours protumourigenic immunosuppression. Targeting SLC4A4 neutralises environmental pH and restores antitumour immunity, sensitising tumours to immune checkpoint blockade., (© 2023 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Metabolic rewiring is often considered an adaptive pressure limiting metastasis formation; however, some nutrients available at distant organs may inherently promote metastatic growth. We find that the lung and liver are lipid-rich environments. Moreover, we observe that pre-metastatic niche formation increases palmitate availability only in the lung, whereas a high-fat diet increases it in both organs. In line with this, targeting palmitate processing inhibits breast cancer-derived lung metastasis formation. Mechanistically, breast cancer cells use palmitate to synthesize acetyl-CoA in a carnitine palmitoyltransferase 1a-dependent manner. Concomitantly, lysine acetyltransferase 2a expression is promoted by palmitate, linking the available acetyl-CoA to the acetylation of the nuclear factor-kappaB subunit p65. Deletion of lysine acetyltransferase 2a or carnitine palmitoyltransferase 1a reduces metastasis formation in lean and high-fat diet mice, and lung and liver metastases from patients with breast cancer show coexpression of both proteins. In conclusion, palmitate-rich environments foster metastases growth by increasing p65 acetylation, resulting in a pro-metastatic nuclear factor-kappaB signaling., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Elevated production of collagen-rich extracellular matrix is a hallmark of cancer-associated fibroblasts (CAFs) and a central driver of cancer aggressiveness. Here we find that proline, a highly abundant amino acid in collagen proteins, is newly synthesized from glutamine in CAFs to make tumour collagen in breast cancer xenografts. PYCR1 is a key enzyme for proline synthesis and highly expressed in the stroma of breast cancer patients and in CAFs. Reducing PYCR1 levels in CAFs is sufficient to reduce tumour collagen production, tumour growth and metastatic spread in vivo and cancer cell proliferation in vitro. Both collagen and glutamine-derived proline synthesis in CAFs are epigenetically upregulated by increased pyruvate dehydrogenase-derived acetyl-CoA levels. PYCR1 is a cancer cell vulnerability and potential target for therapy; therefore, our work provides evidence that targeting PYCR1 may have the additional benefit of halting the production of a pro-tumorigenic extracellular matrix. Our work unveils new roles for CAF metabolism to support pro-tumorigenic collagen production., (© 2022. The Author(s).)

Background: Glycoengineering, in the biotechnology workhorse bacterium, Escherichia coli, is a rapidly evolving field, particularly for the production of glycoconjugate vaccine candidates (bioconjugation). Efficient production of glycoconjugates requires the coordinated expression within the bacterial cell of three components: a carrier protein, a glycan antigen and a coupling enzyme, in a timely fashion. Thus, the choice of a suitable E. coli host cell is of paramount importance. Microbial chassis engineering has long been used to improve yields of chemicals and biopolymers, but its application to vaccine production is sparse., Results: In this study we have engineered a family of 11 E. coli strains by the removal and/or addition of components rationally selected for enhanced expression of Streptococcus pneumoniae capsular polysaccharides with the scope of increasing yield of pneumococcal conjugate vaccines. Importantly, all strains express a detoxified version of endotoxin, a concerning contaminant of therapeutics produced in bacterial cells. The genomic background of each strain was altered using CRISPR in an iterative fashion to generate strains without antibiotic markers or scar sequences., Conclusions: Amongst the 11 modified strains generated in this study, E. coli Falcon, Peregrine and Sparrowhawk all showed increased production of S. pneumoniae serotype 4 capsule. Eagle (a strain without enterobacterial common antigen, containing a GalNAc epimerase and PglB expressed from the chromosome) and Sparrowhawk (a strain without enterobacterial common antigen, O-antigen ligase and chain length determinant, containing a GalNAc epimerase and chain length regulators from Streptococcus pneumoniae) respectively produced an AcrA-SP4 conjugate with 4 × and 14 × more glycan than that produced in the base strain, W3110. Beyond their application to the production of pneumococcal vaccine candidates, the bank of 11 new strains will be an invaluable resource for the glycoengineering community., (© 2022. The Author(s).)

The production of conjugate vaccines within an E. coli (Escherichia coli) host provides an inexhaustible supply without the need for culture of pathogenic organisms. The machinery for expression of glycan and acceptor protein, as well as the coupling enzyme, are all housed within the E. coli chassis, meaning that there are no additional steps required for individual purification and chemical conjugation of components. In addition, there are far fewer purification steps necessary to obtain a purified glycoconjugate for use in vaccine testing. Here we describe production and purification of a HIS-tagged Campylobacter jejuni AcrA protein conjugated to Streptococcus pneumoniae serotype 4 capsule., (© 2022. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Fibroblasts are a major non-neoplastic component of solid tumors, yet it is unclear whether they promote or oppose cancer. In this issue of Cancer Cell, Hutton et al. report two distinct fibroblast subpopulations that are defined by a single marker, one subpopulation that is tumor permissive and the other that is tumor suppressive and supports anti-tumor immunity., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Cancer associated fibroblasts (CAFs) are a major component of the tumour microenvironment in most tumours, and are key mediators of the response to tissue damage caused by tumour growth and invasion, contributing to the observation that tumours behave as 'wounds that do not heal'. CAFs have been shown to play a supporting role in all stages of tumour progression, and this is dependent on the highly secretory phenotype CAFs develop upon activation, of which extracellular matrix (ECM) production is a key element. A collagen rich, stromal ECM has been shown to influence tumour growth and metastasis, exclude immune cells and impede drug delivery, and is associated with poor prognosis in many cancers. CAFs also extensively remodel their metabolism to support cancer cells, however, it is becoming clear that metabolic rewiring also supports intrinsic functions of activated fibroblasts, such as increased ECM production. In this review, we summarise how fibroblasts metabolically regulate ECM production, focussing on collagen production, at the transcriptional, translational and post-translational level, and discuss how this can provide possible strategies for effectively targeting CAF activation and formation of a tumour-promoting stroma., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Kay, Koulouras and Zanivan.)

Protein Glycan Coupling Technology (PGCT) uses purposely modified bacterial cells to produce recombinant glycoconjugate vaccines. This vaccine platform holds great potential in this context, namely due to its modular nature, the simplified production process in comparison to traditional chemical conjugation methods, and its amenability to scaled-up operations. As a result, a considerable reduction in production time and cost is expected, making PGCT-made vaccines a suitable vaccine technology for low-middle income countries, where vaccine coverage remains predominantly low and inconsistent. This work aims to develop an integrated whole-process automated platform for the screening of PGCT-made glycoconjugate vaccine candidates. The successful translation of a bench scale process for glycoconjugate production to a microscale automated setting was achieved. This was integrated with a numerical computational software that allowed hands-free operation and a platform adaptable to biological variation over the course of a production process. Platform robustness was proven with both technical and biological replicates and subsequently the platform was used to screen for the most favourable conditions for production of a pneumococcal serotype 4 vaccine candidate. This work establishes an effective automated platform that enabled the identification of the most suitable E. coli strain and genetic constructs to be used in ongoing early phase research and be further brought into preclinical trials.

Data sources PubMed, the Cochrane Oral Health Group Trials Register and Embase. Additionally, issues of the following journals between 2000 and April 2019 were hand-searched: Journal of Clinical Periodontology, Journal of Periodontology, International Journal of Periodontology and Restorative Dentistry, European Journal of Oral Implantology, Journal of Oral and Maxillofacial Surgery, Clinical Implant Dentistry and Related Research, and Clinical Oral Implants Research.Study selection Only randomised controlled trials (RCTs) involving soft tissue augmentation at dental implant sites were considered for inclusion. The selection was restricted to RCTs published in English language with at least ten patients per group and a minimum follow-up period of three months. A PICO method was used to organise the inclusion criteria and soft tissue augmentations were clustered into three groups; that is, before prosthetic treatment, after prosthetic treatment and at immediate implant placement.Data extraction and synthesis The screening of titles and abstracts was carried out by two reviewers and disagreements were moderated by a third reviewer. Eligibility was determined using full texts and data were extracted using purposefully designed forms. The Cochrane handbook for systematic reviews of interventions toolkit was used to assess the risk of bias. The studies were grouped according to the type of intervention and subjected to quantitative data synthesis. Continuous outcome measures were assessed using random-effects meta-analyses and pooled estimates were expressed as weighted mean differences (MDs) along with 95% confidence intervals (CIs).Results Following initial electronic and hand-searches, 2,119 studies were screened for title and abstract, and 32 studies were considered for full-text screening. Only 14 RCTs met the inclusion criteria and the remaining 18 studies were excluded from the systematic review. The included studies described soft tissue augmentation for 538 implants placed in 475 patients. Three studies (68 patients; 78 implants) reported improved soft tissue thickness with xenogenic collagen matrix (XCM) augmentation compared to no augmentation at the implant sites before prosthetic treatment (high/unclear risk of bias). One study (28 patients; 41 implants) reported improved height of keratinised tissue (KT) and marginal bone levels (MBLs) with free gingival graft (FGG) compared to no augmentation at the implant sites after prosthetic treatment (unclear risk of bias). Three RCTs (126 patients; 126 implants) focused on connective tissue grafting (CTG) and bone grafting versus no grafting in conjunction with immediate implant placement after tooth extraction (unclear risk of bias). There was no difference in MBLs in any of the studies, while one study showed superior soft tissue thickness (STT). Four RCTs (129 patients; 133 implants) compared different augmentation techniques before prosthetic treatment. Only one study showed improved STT with CTG compared to XCM (low risk of bias). Finally, three RCTs (124 patients; 160 implants) compared different augmentation techniques after prosthetic treatment (high/unclear risk of bias). FGG was observed to be superior to acellular dermal matrix (ADM) and vestibuloplasty to improve KT. Meta-analyses did not favour CTG to improve MBLs at extraction sites but CTG was superior to XCM to improve STT before prosthetic treatment.Conclusions Notwithstanding the limitations of the systematic review, soft tissue augmentation significantly enhances the amount of soft tissue at the implant site. CTG at the extraction site also improves subsequent bone level of the implants. Moreover, CTG before prosthetic treatment is superior to XCM to improve thickness of peri-implant soft tissues. However, these findings are based on short-term follow-up and future studies with improved methodology are required to establish the long-term benefits of soft tissue augmentation at the dental implant sites.

Insertions and deletions (InDels) are frequently observed in natural protein evolution, yet their potential remains untapped in laboratory evolution. Here we introduce a transposon-based mutagenesis approach (TRIAD) to generate libraries of random variants with short in-frame InDels, and screen TRIAD libraries to evolve a promiscuous arylesterase activity in a phosphotriesterase. The evolution exhibits features that differ from previous point mutagenesis campaigns: while the average activity of TRIAD variants is more compromised, a larger proportion has successfully adapted for the activity. Different functional profiles emerge: (i) both strong and weak trade-off between activities are observed; (ii) trade-off is more severe (20- to 35-fold increased k cat /K M in arylesterase with 60-400-fold decreases in phosphotriesterase activity) and (iii) improvements are present in k cat rather than just in K M , suggesting adaptive solutions. These distinct features make TRIAD an alternative to widely used point mutagenesis, accessing functional innovations and traversing unexplored fitness landscape regions.

Cohort selection The study cohort was selected through screening of electronic records of all patients rehabilitated with interforaminal implants and implant-supported fixed complete dental prostheses (IFCDPs) over an 11-year period at the Tufts University School of Dental Medicine. Evaluation was based on medical and dental history; clinical oral examination of hard and soft tissues; and radiographic examination during a single visit.Data analysis Survival and failure rates of implants and prostheses were recorded based on predefined criteria. Along with descriptive statistics, the observed annual incidence, and the estimated five- and ten-year biologic and technical complications were computed with 95% confidence intervals.Results The study cohort included 41 patients with an average age of 65.8 years (range = 39 to 88 years) and comprised 19 females and 22 males. A total of 359 moderately rough surface dental implants (Nobel Biocare, Straumann, Biomet 3i) were used to rehabilitate 36 cement-retained and 19 screw-retained metal-ceramic IFCDPs in maxilla (N = 32) mandible (N = 23). The mean observation times for implants and prostheses were 5 and 7.5 years, respectively. Two implant failures in a single patient were recorded 11 years post-insertion, yielding an implant survival rate of 99.4%. The cumulative prostheses survival rate was 98.2% (100% at five years and 92.9% at ten years). Biologic and/or technical complications were associated with all 55 prostheses. Among major complications, the most frequent biologic complication was peri-implantitis while porcelain fractures were the most common technical complication. The cumulative rates of 'prostheses free of biologic complications' were 50.4% (95% CI: 36.4% to 63.0%) at five years and 10.1% (95% CI: 3.5% to 20.8%) at ten years. The cumulative rates for 'prosthesis free of technical complications' were 56.4% (95% CI: 41.7% to 68.8%) at five years and 9.8% (95% CI: 3.2% to 21.0%) at ten years.Conclusions Metal-ceramic implant-supported fixed full arch dental prostheses show high survival rates at five-year follow-up, including an implant survival rate of 99.4% and prosthesis survival rate of 98.2%. However biological and technical complications were observed in 47.1% and 42%, respectively.

Introduction Oral disease in very young children is far more common among children in deprived and vulnerable families than among their peer group. Such children are at the highest risk of requiring a general anaesthetic for removal of decayed primary teeth.Aim This study aimed to create new knowledge about how best to promote oral health among a target population, about who very little is established with regard to how to successfully intervene to improve long-term oral health.Method Phase one of the study developed a logic model, and phase two delivered an oral health-promoting intervention by working with the Family Nurse Partnership. The social and empirical acceptability of the intervention was explored, and the attributes needed by people delivering such an intervention were investigated in-depth.Results The thematic analysis of phase one data produced seven key themes which appeared to influence parents' ability and willingness to accept an oral health intervention aimed at their infants. These were: their personal experiences, current oral health knowledge, desire for dental care for their child, the timing of an intervention, their perception of difficulties, family norms and the level of trust developed.Conclusion It is possible to motivate the most vulnerable families to establish behaviours which are conducive to good oral health, and that intervention is feasible and appropriate if a trusting relationship is adopted by the deliverer of the intervention. Families were successful in adopting oral health behaviours and visiting dental services when such circumstances were established.

Data sources PubMed, CINAHL, and Cochrane databases.Study selection Papers reporting a primary study with any population, one or both genders specified, participants of any age, incidence of any cancer subsite of HN, and UADT reported as the health outcome, frequency of dental visits/check-ups prior to the diagnosis of one of these cancers (assessed as the exposure), and availability of sufficient data to estimate the measure of association, ie, unadjusted odds ratio (OR) along with its corresponding 95% confidence interval (CI).Data extraction and synthesis Two reviewers independently screened the title and abstract of the identified citations. Full texts of citations judged as potentially eligible were acquired by at least one of the two reviewers. Thereafter, both the reviewers used a standardised and pilot-tested form to independently screen every full text for eligibility. Methodological quality of the studies was assessed using the quality assessment tool for quantitative studies developed by the Effective Public Health Practice Project (EPHPP)Results After initial search of 1377 studies, thirty-eight articles were included in the analysis for systemic review including 32 case-control and six other design studies not limited to cross-sectional, observational, case-series, and screening. Finally, twenty-six case-control studies were included in the meta-analysis. Subgroup analyses of studies in meta-analysis showed the overall pooled estimate risk was (OR 2.01; 95% CI 1.76 to 2.30, P <0.001). The test for heterogeneity produced Tau square of 0.00, Q = 36.33, I2 = 31.76%, test for overall effect z = 9.24, (P <0.001). No publication bias was observed in the meta analysis. Conclusions Individuals with never/irregular/not frequent dental visits are more likely to be incident cases of HNCs/UADT cancers. Targeted education to alert those at risk about OCs and other HNCs, and the warning signs, and better training coupled with opportunistic oral cavity examinations by dentists could reduce the burden of this disease.

Purpose: This study aimed to assess dentists' views of the utility of an unrestored shortened dental arch (SDA) compared to the utility of various prosthetic treatment options., Materials and Methods: A total of 142 dentists working at four sites in Riyadh, Saudi Arabia, were interviewed and presented with 18 scenarios for patients of different ages with SDAs that lost molar teeth. Participants were asked to indicate on a standardized visual analog scale (VAS) how they would value the health of the patient's mouth if the SDAs were left unrestored or restored with five prosthetic dental restorations., Results: With a utility value of 0.0 representing the worst possible health state for a mouth and 1.0 representing the best, dentists' mean utility value for unrestored SDAs was 0.43 (standard deviation [SD] = 0.28). For implant-supported fixed dental prostheses (ISFDPs), cobalt-chromium removable partial dentures (RPDs), acrylic RPDs, cantilever conventional fixed dental prostheses (CFDPs), and cantilever resin-bonded fixed dental prostheses (RBFDPs), the mean utility values were 0.64 (SD = 0.27), 0.54 (SD = 0.20), 0.48 (SD = 0.20), 0.42 (SD = 0.28), and 0.39 (SD = 0.27), respectively. Neither patient age nor dentists' clinical experience had an impact on dentists' perceptions of the utility of unrestored SDAs and outcomes of this treatment concept (P > .01)., Conclusion: Restoration of SDAs by ISFDPs received the highest utility value among the surveyed group of dentists. Although the assigned value for unrestored SDAs was low, this value was comparable to the value of SDAs that were restored by acrylic RPDs or cantilever FDPs of either type.

Streptococcus pneumoniae is the leading cause of bacterial pneumonia. Although this is a vaccine preventable disease, S. pneumoniae still causes over 1 million deaths per year, mainly in children under the age of five. The biggest disease burden is in the developing world, which is mainly due to unavailability of vaccines due to their high costs. Protein polysaccharide conjugate vaccines are given routinely in the developed world to children to induce a protective antibody response against S. pneumoniae. One of these vaccines is Prevnar13, which targets 13 of the 95 known capsular types. Current vaccine production requires growth of large amounts of the 13 serotypes, and isolation of the capsular polysaccharide that is then chemically coupled to a protein, such as the diphtheria toxoid CRM 197, in a multistep expensive procedure. In this study, we design, purify and produce novel recombinant pneumococcal protein polysaccharide conjugate vaccines in Escherichia coli, which act as mini factories for the low-cost production of conjugate vaccines. Recombinant vaccine efficacy was tested in a murine model of pneumococcal pneumonia; ability to protect against invasive disease was compared to that of Prevnar13. This study provides the first proof of principle that protein polysaccharide conjugate vaccines produced in E. coli can be used to prevent pneumococcal infection. Vaccines produced in this manner may provide a low-cost alternative to the current vaccine production methodology., (Copyright © 2018. Published by Elsevier Ltd.)

Aims: The aim of this study was to develop a valid and reliable scale to measure preparedness of new dental graduates., Methods: The scale development and validation was carried out using the Rasch measurement model. Following a pilot and pre-testing of the scale, a national study was undertaken with undergraduate students from all dental schools as well as foundation dentists in UK., Results: To examine the internal validity of the scale, we conducted a Rasch analysis. External validity of the scale was checked through validation with a range of stakeholders. An excellent fit to the Rasch model provided evidence of internal construct validity. The scale demonstrated invariance, ordered thresholds and lack of differential item functioning. Unidimensionality of the scale was confirmed by independent t-tests. The PSI value was 0.877, indicating a good degree of person separation and internal consistency. Test-retest reliability of the scale was also established., Conclusions: The preparedness scale developed in this project reflects innovative research using a systematic approach and employment of modern psychometric methods. The scale can be used for assessment of the preparedness of undergraduate students by dental educators and potential employers as well as by the student for self-assessment., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Tumor progression alters the composition and physical properties of the extracellular matrix. Particularly, increased matrix stiffness has profound effects on tumor growth and metastasis. While endothelial cells are key players in cancer progression, the influence of tumor stiffness on the endothelium and the impact on metastasis is unknown. Through quantitative mass spectrometry, we find that the matricellular protein CCN1/CYR61 is highly regulated by stiffness in endothelial cells. We show that stiffness-induced CCN1 activates β-catenin nuclear translocation and signaling and that this contributes to upregulate N-cadherin levels on the surface of the endothelium, in vitro This facilitates N-cadherin-dependent cancer cell-endothelium interaction. Using intravital imaging, we show that knockout of Ccn1 in endothelial cells inhibits melanoma cancer cell binding to the blood vessels, a critical step in cancer cell transit through the vasculature to metastasize. Targeting stiffness-induced changes in the vasculature, such as CCN1, is therefore a potential yet unappreciated mechanism to impair metastasis., (© 2017 Cancer Research UK Beatson Institute. Published under the terms of the CC BY 4.0 license.)

Objectives The objective of this study was to systematically review the evidence regarding the use of motivational interviewing in the context of general dental practice, in order that practitioners can decide whether it might be an important skill to develop within their practices.Data sources The results reported in this study form part of a larger systematic review which sought to identify whether oral health promotion within dental practice is effective and how its effects can be optimised. Here, we focus on the papers describing motivational interviewing in dental practice published since 1994. The systematic review included searches of 20 online resources (including Ovid Medline and Embase).Data selection Papers which were not about oral health promotion and did not apply the behavioural and psychological theories, which underpin motivational interviewing, were excluded.Data synthesis This review included eight papers all of which were considered to be of robust quality, in terms of their research methods and seven of which were considered to offer externally valid findings. Five described randomised controlled trials and all of these RCTs demonstrated that interventions including motivational interviewing had a positive effect on oral health and health behaviour.Conclusions This review shows that the motivational interviewing technique, which is based on the concept of autonomy support, has potential for helping patients with poor oral health. Training in motivational interviewing for dental personnel could be a very useful addition to the skill set of practitioners and dental teams.

Currently, Streptococcus pneumoniae is responsible for over 14 million cases of pneumonia worldwide annually, and over 1 million deaths, the majority of them children. The major determinant for pathogenesis is a polysaccharide capsule that is variable and is used to distinguish strains based on their serotype. The capsule forms the basis of the pneumococcal polysaccharide vaccine (PPV23) that contains purified capsular polysaccharide from 23 serotypes, and the pneumococcal conjugate vaccine (PCV13), containing 13 common serotypes conjugated to CRM197 (mutant diphtheria toxin). Purified capsule from S. pneumoniae is required for pneumococcal conjugate vaccine production, and costs can be prohibitively high, limiting accessibility of the vaccine in low-income countries. In this study, we demonstrate the recombinant expression of the capsule-encoding locus from four different serotypes of S. pneumoniae within Escherichia coli. Furthermore, we attempt to identify the minimum set of genes necessary to reliably and efficiently express these capsules heterologously. These E. coli strains could be used to produce a supply of S. pneumoniae serotype-specific capsules without the need to culture pathogenic bacteria. Additionally, these strains could be applied to synthetic glycobiological applications: recombinant vaccine production using E. coli outer membrane vesicles or coupling to proteins using protein glycan coupling technology.

Objective: To examine the disutility of tooth loss. It compared how people value their teeth in two countries which are culturally similar in order to explore the effect of culture on self-perceptions of oral health., Basic Research Design: Cross sectional study., Participants: Participants were recruited from subjects attending two hospitals in Turkey and in Iran., Interventions: Nineteen descriptions of mouths with varying degrees and types of tooth loss were presented to the participants. They were shown mouth models of partially edentate dentitions and the teeth missing were explained in relation to the participants own mouth. The participants were specifically asked to consider the role their teeth played in function (chewing), communication (speech) and aesthetics (looks) along with "all the other things that make your mouth important"., Main Outcome Measures: The participants were asked to indicate on a visual analogue scale how they would value the health of their mouth if they lost the tooth/teeth described and the resultant space was left unrestored., Results: Overall 152 subjects participated, 78 in Turkey and 74 in Iran with 83 being female and 69 male. Their mean age was 29.5 years (SD 9.3), 62.5% had experienced tooth loss and 37.5% had complete (or completely restored) dentitions. Although there were no differences between the two countries in the degree of utility people attached to anterior teeth, Turkish participants attached significantly more disutility than Iranians to the loss of premolar and molar teeth (p < 0.003)., Conclusion: Country of origin had an influence on the value placed on certain parts of the dentition and this effect is independent of the number of missing teeth, gender and age. This implies that attitudes to oral health are influenced by prevalent cultural attitudes more than by function.

Objective. This study aimed to investigate the impact of subject age, gender, and arch length on dentists' attitudes towards unrestored shortened dental arches. Materials and Methods. 93 Syrian dentists were interviewed and presented with 24 scenarios for male and female subjects of different ages and shortened dental arches of varying length. Participants were asked to indicate on a standardized visual analogue scale how they would value the health of the mouth if the posterior space was left unrestored. Results. A value of 0.0 represented the worst possible health state for a mouth and 1.0 represented the best. The highest mean value (0.73) was assigned to a shortened dental arch with missing second molar teeth in the mouth of a 70-year-old subject. A 35-year-old female subject with an extremely shortened dental arch (all molar and premolar teeth are missing) attracted the lowest mean value (0.26). The statistical analysis indicated a significant decrease in the value placed on unrestored shortened dental arches as the number of remaining teeth decreased (p < 0.008). While subject gender had almost no impact on dentists' attitudes towards shortened dental arches, the scenarios for the older shortened dental arch subjects attracted significantly higher values compared to the scenarios for the younger subjects (p < 0.017). Conclusion. Subject age and arch length affect dentists' attitudes towards shortened dental arches, but subject gender does not.

This paper describes the process set up by the BDA and the Shirley Glasstone Hughes (SGH) Trust as a result of their will to involve dental practitioners in dental research prioritisation, so that funding could be directed towards research that practitioners would find useful. The paper considers the technical, operational and economic feasibility of using an online system to determine the research priorities of primary care practitioners and describes the extent to which the system worked in practice. The aim of the work described was to ensure that the research commissioned by SGH Trust actually served practitioners' needs and promotes the use of evidence in general dental practice.

Aims: The aims of this study were to articulate the concept of preparedness of dental graduates for foundation training programme in the United Kingdom and identify the essential attributes of preparedness., Methods: A qualitative approach using semi-structured interviews was used to explore the concept of preparedness. The study was carried out in the South West region of England. Participants were recruited from a range of stakeholders in dental education and foundation training using purposive sampling. Participants were recruited using email through appropriate professional channels. Stakeholders included dental students (DS), dental academics (DA), foundation dental practitioners (FDP), foundation trainers (FT), general dental practitioners (GDP) and a postgraduate dental deanery representative (DDR). Interviews were transcribed verbatim and data were imported into NVivo 9 and analysed thematically., Results: Sixteen interviews were carried out with representation from all stakeholder groups. Participants expressed their views on a range of issues related to the preparedness of dental graduates., Conclusions: This study provides useful insights into the concept of preparedness as perceived by the stakeholders. The findings of this study may offer clarity on the essential attributes required by dental graduates upon entry into foundation training.

This paper describes the historical origins and purpose of 'evidence-based practice' and describes the barriers to the growth of evidence-based practice within dentistry. It describes a new research agenda-setting process for dentistry, which includes identifying and prioritising the topics of most relevance to the work of primary dental care practitioners. By undertaking the work described in this paper we were striving to make research more relevant to the day to day decisions made by dentists in practice by introducing a new process, the intention being to promote and promulgate the practice of evidence-based dentistry.

Objectives: The objectives of this study are to study how tooth loss affects the utility of the dentition from both patient and professional perspectives and to compare patient and professional utility values., Methods: One hundred six patients and 118 dentists were asked to read 19 different written scenarios accompanied by visual images and models, describing mouths with missing teeth, and to indicate on a visual analog scale the value of that oral health state., Results: Both groups of participants attached the greatest utility to missing incisor teeth and disutility of tooth loss decreased as the tooth in question became nearer the back of the mouth. When dentist and patient utility values for the loss of different tooth types were compared, using independent t-tests, differences were statistically significant for only one tooth loss scenario - the loss of upper canines., Conclusions: The patient and professional groups valued tooth loss scenarios in a similar way. This finding is contrary to the majority of previous studies comparing patient and professional utilities., (© 2013 American Association of Public Health Dentistry.)

This study investigated a method of measuring oral health, as opposed to measuring disease. The objective was to compare DMF score and whole mouth utility scores to a patient-reported outcome measure (PROM). Disutility values for lost and restored teeth were used to weight the decayed, missing and filled teeths(DMFTs) of 10 adult patients. This gave two whole mouth utility scores (WMU). These scores were then compared with a patient-reported oral health outcome measure recorded by the use of a visual analogue scale (VAS). The anchors for the VAS were 'my mouth could not be worse' and 'my mouth could not be better'. There was a positive correlation (r = 0.6457) between WMU1 and the patient-reported outcome measure (P < 0.05) and a negative correlation (r = -0.8383) between WMU1 and DMFT which was significant at the P < 0.01 level. There was a statistically significant positive correlation of r = 0.7926 between WMU2 and the patient-reported outcome measure (P < 0.01) and a negative correlation (r = -0.9393) between WMU2 and DMFT (P < 0.01). The Pearson's correlation between DMFT and the patient-reported outcome measure was -0.8757, which was significant at the 0.01 level. Patient reports of their perceived level of health correlate well with DMFT scores. Weighting DMFT scores according to the differential values assigned to missing, or missing and filled, teeth does not increase the degree of correlation between the measure and the patients' personal quantification of their oral health. Decayed, missing and filled teeth therefore seems to adequately capture the patient's sense of well-being., (© 2013 John Wiley & Sons Ltd.)

Introduction: In a new enquiry-based learning dental curriculum, problem-based learning (PBL) was chosen as a central methodology because it promotes a collaborative and constructive approach to learning. However, inevitably, some groups function worse than others. This study explores the relationship between group functionality and individuals' results on knowledge-based assessment. It also sought to establish whether using the Belbin team role theory could improve group functionality., Methods: Students completed the Belbin team role inventory that assigns individuals to a team role type and were allocated to either an ideal Belbin group or a control group. To evaluate the functionality of the groups, Macgowan's group engagement measure was completed after 18 and 31 weeks for each student by their group facilitator. The scores were summed and averaged giving a group engagement score for each group. Relationships between group engagement, individual performance in assessment in weeks 18 and 31 and Belbin and non-Belbin teams were investigated., Results: Individual group engagement scores and performance in the knowledge tests had a statistically significant positive relationship despite the small number of students involved (62). However, no correlation was shown between Belbin groups and group engagement scores., Conclusions: Those students who engaged most with the PBL process performed markedly better in assessments of knowledge. Using Belbin's team role theory to place students in PBL groups in an effort to increase group functionality had no effect when compared with non-Belbin control groups., (© 2011 John Wiley & Sons A/S.)