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Objectives: To synthesize and appraise the evidence regarding the relationship between food insecurity and behaviours associated with dental caries development in adults and children in high-income countries., Methods: A systematic review including observational studies assessing the association between food insecurity and selected dietary (free sugar consumption) and non-dietary factors (tooth brushing frequency; use of fluoridated toothpaste; dental visiting; oral hygiene aids; type of toothbrush used; interdental cleaning frequency and mouthwash use) related to dental caries development in adults and children in high-income countries. Studies specifically looking at food insecurity during the COVID-19 pandemic were excluded. Searches were performed in MEDLINE, Embase, Global Health and Scopus from inception to 25 May 2023. Two authors screened the search results, extracted data and appraised the studies independently and in duplicate. Study quality was assessed using the Newcastle-Ottawa Scale (with modifications for cross-sectional studies). Vote counting and harvest plots provided the basis for evidence synthesis., Results: Searches identified 880 references, which led to the inclusion of 71 studies with a total of 526 860 participants. The majority were cross-sectional studies, conducted in the USA and reported free sugar consumption. Evidence for the association between food insecurity and free sugar intake from 4 cohort studies and 61 cross-sectional studies including 336 585 participants was equivocal, particularly in the sugar-sweetened beverage (SSB) consumption post-hoc subgroup, where 20 out of 46 studies reported higher SSB consumption in food insecure individuals. There was consistent, but limited, evidence for reduced dental visiting in adults experiencing food insecurity compared to food secure adults from 3 cross-sectional studies including 52 173 participants. The relationship between food insecurity and dental visiting in children was less clear (3 cross-sectional studies, 138 102 participants). A single cross-sectional study of 3275 children reported an association between food insecurity and reported failure to toothbrush the previous day., Conclusions: This review did not identify clear associations between food insecurity and behaviours commonly implicated in the development of dental caries that would explain why individuals experiencing food insecurity are more likely to have dental caries than those who have food security. There was some evidence of decreased dental visiting in adults experiencing food insecurity. Common methodological weaknesses across the evidence base related to the selection of participants or control of potentially confounding variables. Consequently, the quality of evidence for all outcomes was downgraded to very low. More research is needed to explore access to oral hygiene products and household environments conducive to habitual oral self-care in food insecure populations., (© 2024 The Authors. Community Dentistry and Oral Epidemiology published by John Wiley & Sons Ltd.)

Objectives This analysis aimed to: i) review how patient dental charges (PDCs) changed over time in England, Scotland and Wales; ii) determine how these changes relate to a) inflation and b) minimum wages; and iii) how the charges have varied in the devolved administrations.Methods Data were obtained from NHS and Office for National Statistics (ONS) records and historical valuations of the national living wage (NLW). General inflation was calculated using the ONS Consumer Price Index.Results PDCs differed significantly between countries in relation to cost; which aspects of dental care require a charge; and value of payments (p <0.001). PDCs in England for simple, intermediate and more complex care rose from £15.90, £43.60 and £194.00 in 2007, to £25.80, £70.70 and £306.80 in 2023. Adjusted for inflation, the 2007 prices equate to £25.53, £70.02 and £311.55, demonstrating that the relative costs have remained constant in England. In Wales, 2007 prices (inflation-adjusted):2023 prices for the three complexities of treatment were £19.27:£14.80, £62.23:£47.33 and £284.25:£204.43. In Scotland, PDCs for the four treatment items fell marginally when adjusted for inflation. The ratio of PDC:NLW fell by an average of 13.8% in England and 30.7% in Wales.Conclusions There has been significant variation in the approach to PDCs across Great Britain both in terms of nominal costs and the degree to which these have kept pace with inflation., (© 2024. The Author(s).)

The genetic code consists of 61 codons coding for 20 amino acids. These codons are recognized by transfer RNAs (tRNAs) that bind to specific codons during protein synthesis. All organisms utilize less than all 61 possible anticodons due to base pair wobble: the ability to have a mismatch with a codon at its third nucleotide. Previous studies observed a correlation between the tRNA pool of bacteria and the temperature of their respective environments. However, it is unclear if these patterns represent biological adaptations to maintain the efficiency and accuracy of protein synthesis in different environments. A mechanistic mathematical model of mRNA translation is used to quantify the expected elongation rates and error rate for each codon based on an organism's tRNA pool. A comparative analysis across a range of bacteria that accounts for covariance due to shared ancestry is performed to quantify the impact of environmental temperature on the evolution of the tRNA pool. We find that thermophiles generally have more anticodons represented in their tRNA pool than mesophiles or psychrophiles. Based on our model, this increased diversity is expected to lead to increased missense errors. The implications of this for protein evolution in thermophiles are discussed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for Molecular Biology and Evolution.)

Background: Dental pain can have a detrimental effect on quality of life. Symptomatic apical periodontitis and acute apical abscess are common causes of dental pain and arise from an inflamed or necrotic dental pulp, or infection of the pulpless root canal system. Clinical guidelines recommend that the first-line treatment for these conditions should be removal of the source of inflammation or infection by local operative measures, and that systemic antibiotics are currently only recommended for situations where there is evidence of spreading infection (cellulitis, lymph node involvement, diffuse swelling) or systemic involvement (fever, malaise). Despite this, there is evidence that dentists frequently prescribe antibiotics in the absence of these signs. There is concern that this could contribute to the development of antibiotic-resistant bacteria. This review is the second update of the original version first published in 2014., Objectives: To evaluate the effects of systemic antibiotics provided with or without surgical intervention (such as extraction, incision and drainage of a swelling, or endodontic treatment), with or without analgesics, for symptomatic apical periodontitis and acute apical abscess in adults., Search Methods: We searched Cochrane Oral Health's Trials Register (26 February 2018 (discontinued)), CENTRAL (2022, Issue 10), MEDLINE Ovid (23 November 2022), Embase Ovid (23 November 2022), CINAHL EBSCO (25 November 2022) and two trials registries, and performed a grey literature search. There were no restrictions on language or date of publication., Selection Criteria: Randomised controlled trials of systemic antibiotics in adults with a clinical diagnosis of symptomatic apical periodontitis or acute apical abscess, with or without surgical intervention (considered in this situation to be extraction, incision and drainage, or endodontic treatment) and with or without analgesics., Data Collection and Analysis: Two review authors independently screened the results of the searches against inclusion criteria, extracted data and assessed risk of bias. We used a fixed-effect model in the meta-analysis as there were fewer than four studies. We contacted study authors to request missing information. We used GRADE criteria to assess the certainty of the evidence., Main Results: There was one new completed trial on this topic since the last update in 2018. In total, we included three trials with 134 participants. Systemic antibiotics versus placebo with surgical intervention and analgesics for symptomatic apical periodontitis or acute apical abscess One trial (72 participants) compared the effects of a single preoperative dose of clindamycin versus a matched placebo when provided with a surgical intervention (endodontic chemo-mechanical debridement and filling) and analgesics to adults with symptomatic apical periodontitis. We assessed this study at low risk of bias. There were no differences in participant-reported pain or swelling across trial arms at any time point assessed. The median values for pain (numerical rating scale 0 to 10) were 3.0 in both groups at 24 hours (P = 0.219); 1.0 in the antibiotic group versus 2.0 in the control group at 48 hours (P = 0.242); and 0 in both groups at 72 hours and seven days (P = 0.116 and 0.673, respectively). The risk ratio of swelling when comparing preoperative antibiotic to placebo was 0.50 (95% confidence interval (CI) 0.10 to 2.56; P = 0.41). The certainty of evidence for all outcomes in this comparison was low. Two trials (62 participants) compared the effects of a seven-day course of oral phenoxymethylpenicillin (penicillin VK) versus a matched placebo when provided with a surgical intervention (total or partial endodontic chemo-mechanical debridement) and analgesics to adults with acute apical abscess or symptomatic necrotic tooth. Participants in both trials also received oral analgesics. We assessed one study at high risk of bias and the other at unclear risk of bias. There were no differences in participant-reported pain or swelling at any time point assessed. The mean difference for pain (short ordinal numerical scale 0 to 3, where 0 was no pain) was -0.03 (95% CI -0.53 to 0.47) at 24 hours; 0.32 (95% CI -0.22 to 0.86) at 48 hours; and 0.08 (95% CI -0.38 to 0.54) at 72 hours. The standardised mean difference for swelling was 0.27 (95% CI -0.23 to 0.78) at 24 hours; 0.04 (95% CI -0.47 to 0.55) at 48 hours; and 0.02 (95% CI -0.49 to 0.52) at 72 hours. The certainty of evidence for all the outcomes in this comparison was very low. Adverse effects, as reported in two studies, were diarrhoea (one participant in the placebo group), fatigue and reduced energy postoperatively (one participant in the antibiotic group) and dizziness preoperatively (one participant in the antibiotic group). Systemic antibiotics without surgical intervention for adults with symptomatic apical periodontitis or acute apical abscess We found no studies that compared the effects of systemic antibiotics with a matched placebo delivered without a surgical intervention for symptomatic apical periodontitis or acute apical abscess in adults., Authors' Conclusions: The evidence suggests that preoperative clindamycin for adults with symptomatic apical periodontitis results in little to no difference in participant-reported pain or swelling at any of the time points included in this review when provided with chemo-mechanical endodontic debridement and filling under local anaesthesia. The evidence is very uncertain about the effect of postoperative phenoxymethylpenicillin for adults with localised apical abscess or a symptomatic necrotic tooth when provided with chemo-mechanical debridement and oral analgesics. We found no studies which compared the effects of systemic antibiotics with a matched placebo delivered without a surgical intervention for symptomatic apical periodontitis or acute apical abscess in adults., (Copyright © 2024 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Rosenberg AA, Marx A, Bronstein AM (Codon-specific Ramachandran plots show amino acid backbone conformation depends on identity of the translated codon. Nat Commun. 2022:13:2815) recently found a surprising correlation between synonymous codon usage and the dihedral bond angles of the resulting amino acid. However, their analysis did not account for the strongest known correlate of codon usage: gene expression. We re-examined the relationship between bond angles and codon usage by applying the approach of Rosenberg et al. to simulated protein-coding sequences that (i) have random codon usage, (ii) codon usage determined by mutation biases, and (iii) maintain the general relationship between codon usage and gene expression via the assumption of selection-mutation-drift equilibrium. We observed correlations between dihedral bond angle and codon usage when codon usage is entirely random, indicating possible conflation of noise with differences in bond angle distributions between synonymous codons. More relevant to the general analysis of codon usage patterns, we found surprisingly good agreement between the analysis of the real sequences and the analysis of sequences simulated assuming selection-mutation-drift equilibrium, with 91% of significant synonymous codon pairs detected in the former were also detected in the latter. We believe the correlation between codon usage and dihedral bond angles resulted from the variation in codon usage across genes due to the interplay between mutation bias, natural selection for translation efficiency, and gene expression, further underscoring these factors must be controlled for when looking for novel patterns related to codon usage., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for Molecular Biology and Evolution.)

Background: There are few contemporary studies on the time taken to complete dental procedures, those most heavily relied on in the United Kingdom date back to 1999., Objectives: This work aimed to establish how long members of the dental team took to complete specific dental procedures, relevant to their scope of practice., Methods: Data were collected via a purposive sample of 96 dentists, dental hygienists/therapists and dental nurses. Via an online survey, participants were asked to state the mean, minimum and maximum time they estimated that they took to complete individual dental procedures., Results: The mean time taken to complete procedures common to both dentists and dental hygienists/therapists ranged from 3.7 to 4 min respectively for clinical note reading prior to seeing patients to 30.1 and 28 min to undertake root surface debridement. There were no significant differences between the time taken by dentists and dental hygienists/therapists to treat adult patients. However, in all but one procedure, dental hygienists/therapists reported taking longer (p = 0.04) to treat child patients., Conclusions: The data provided here represent an up to date assessment of the time taken to complete specific tasks by different members of the dental team. These data will be of value to service planners and commissioners interested in evolving a dental care system that employs a greater degree of skill-mix and preventively oriented care., (© 2023. The Author(s).)

Variation in gene expression across lineages is thought to explain much of the observed phenotypic variation and adaptation. The protein is closer to the target of natural selection but gene expression is typically measured as the amount of mRNA. The broad assumption that mRNA levels are good proxies for protein levels has been undermined by a number of studies reporting moderate or weak correlations between the two measures across species. One biological explanation for this discrepancy is that there has been compensatory evolution between the mRNA level and regulation of translation. However, we do not understand the evolutionary conditions necessary for this to occur nor the expected strength of the correlation between mRNA and protein levels. Here, we develop a theoretical model for the coevolution of mRNA and protein levels and investigate the dynamics of the model over time. We find that compensatory evolution is widespread when there is stabilizing selection on the protein level; this observation held true across a variety of regulatory pathways. When the protein level is under directional selection, the mRNA level of a gene and the translation rate of the same gene were negatively correlated across lineages but positively correlated across genes. These findings help explain results from comparative studies of gene expression and potentially enable researchers to disentangle biological and statistical hypotheses for the mismatch between transcriptomic and proteomic data., (© The Author(s) 2023. Published by Oxford University Press on behalf of Society for Molecular Biology and Evolution.)

A cost-of-living crisis is currently affecting the UK. While this has been explored in terms of the effect on dental practice, the dental implications for patients and for population oral health have not received sufficient attention. This opinion piece discusses how: i) financial pressures leading to hygiene poverty may limit the ability to afford the basic products necessary to maintain oral hygiene; ii) food insecurity is associated with a diet high in sugar and lacking in appropriate nutrition; and iii) reduced disposable income may limit the ability to attend and successfully engage with dental care. The impact of the cost-of-living crisis on the lowest paid members of the dental team is also considered.The most common dental diseases are closely correlated with social and economic deprivation and the points discussed here act as a reminder of how the present financial circumstances have significant potential to widen oral health inequalities., (© 2023. The Author(s), under exclusive licence to the British Dental Association.)

Organisms can adapt to an environment by taking multiple mutational paths. This redundancy at the genetic level, where many mutations have similar phenotypic and fitness effects, can make untangling the molecular mechanisms of complex adaptations difficult. Here, we use the Escherichia coli long-term evolution experiment (LTEE) as a model to address this challenge. To understand how different genomic changes could lead to parallel fitness gains, we characterize the landscape of transcriptional and translational changes across 12 replicate populations evolving in parallel for 50,000 generations. By quantifying absolute changes in mRNA abundances, we show that not only do all evolved lines have more mRNAs but that this increase in mRNA abundance scales with cell size. We also find that despite few shared mutations at the genetic level, clones from replicate populations in the LTEE are remarkably similar in their gene expression patterns at both the transcriptional and translational levels. Furthermore, we show that the majority of the expression changes are due to changes at the transcriptional level with very few translational changes. Finally, we show how mutations in transcriptional regulators lead to consistent and parallel changes in the expression levels of downstream genes. These results deepen our understanding of the molecular mechanisms underlying complex adaptations and provide insights into the repeatability of evolution., Competing Interests: JF, SL, AC, SY No competing interests declared, PS is a scientific advisory board member of Trestle Biosciences and consults for Ribo-Therapeutics. Is also a director at an RNA-therapeutics startup, (© 2022, Favate et al.)

Objective: To describe the development and application of the Assessment of Clinical Oral Risks and Needs (ACORN) stratification tool based on a traffic light system in National Health Service (NHS) general dental services (GDS) Wales, UK., Materials and Methods: This was a secondary analysis of routinely-collected dental care data. All courses of treatment provided in dental practices participating in NHS GDS Reform Programme between July 2018 and September 2019, in which an ACORN assessment and age were recorded were included in the analysis., Results: A total of 236,490 subjects contributed 339,933 courses of treatment during the study period. 'Amber' and 'red' ACORN outcomes were associated with more courses of treatment per annum than 'green' outcomes. Outcomes indicating an increased risk of decay or other dental problems were associated with a greater likelihood of several operative treatment items. Patients at greater risk of poor periodontal health were more likely to receive extractions and dentures than low-risk patients. Patients were most likely to either remain in the same ACORN outcome categories or move to a healthier state between assessments., Conclusion: More research is required to understand the utility of the ACORN tool in risk communication and behaviour change., (Copyright © 2022. Published by Elsevier Ltd.)

Patterns of non-uniform usage of synonymous codons vary across genes in an organism and between species across all domains of life. This codon usage bias (CUB) is due to a combination of non-adaptive (e.g. mutation biases) and adaptive (e.g. natural selection for translation efficiency/accuracy) evolutionary forces. Most models quantify the effects of mutation bias and selection on CUB assuming uniform mutational and other non-adaptive forces across the genome. However, non-adaptive nucleotide biases can vary within a genome due to processes such as biased gene conversion (BGC), potentially obfuscating signals of selection on codon usage. Moreover, genome-wide estimates of non-adaptive nucleotide biases are lacking for non-model organisms. We combine an unsupervised learning method with a population genetics model of synonymous coding sequence evolution to assess the impact of intragenomic variation in non-adaptive nucleotide bias on quantification of natural selection on synonymous codon usage across 49 Saccharomycotina yeasts. We find that in the absence of a priori information, unsupervised learning can be used to identify genes evolving under different non-adaptive nucleotide biases. We find that the impact of intragenomic variation in non-adaptive nucleotide bias varies widely, even among closely-related species. We show that the overall strength and direction of translational selection can be underestimated by failing to account for intragenomic variation in non-adaptive nucleotide biases. Interestingly, genes falling into clusters identified by machine learning are also physically clustered across chromosomes. Our results indicate the need for more nuanced models of sequence evolution that systematically incorporate the effects of variable non-adaptive nucleotide biases on codon frequencies., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: P.S. is a Scientific Advisory Board member of Trestle Biosciences. P.S. also consults for Ribo-Therapeutics and an unnamed RNA-therapeutics startup.

Background: Codon usage bias (CUB), the non-uniform usage of synonymous codons, occurs across all domains of life. Adaptive CUB is hypothesized to result from various selective pressures, including selection for efficient ribosome elongation, accurate translation, mRNA secondary structure, and/or protein folding. Given the critical link between protein folding and protein function, numerous studies have analyzed the relationship between codon usage and protein structure. The results from these studies have often been contradictory, likely reflecting the differing methods used for measuring codon usage and the failure to appropriately control for confounding factors, such as differences in amino acid usage between protein structures and changes in the frequency of different structures with gene expression., Results: Here we take an explicit population genetics approach to quantify codon-specific shifts in natural selection related to protein structure in S. cerevisiae and E. coli. Unlike other metrics of codon usage, our approach explicitly separates the effects of natural selection, scaled by gene expression, and mutation bias while naturally accounting for a region's amino acid usage. Bayesian model comparisons suggest selection on codon usage varies only slightly between helix, sheet, and coil secondary structures and, similarly, between structured and intrinsically-disordered regions. Similarly, in contrast to prevous findings, we find selection on codon usage only varies slightly at the termini of helices in E. coli. Using simulated data, we show this previous work indicating "non-optimal" codons are enriched at the beginning of helices in S. cerevisiae was due to failure to control for various confounding factors (e.g. amino acid biases, gene expression, etc.), and rather than selection to modulate cotranslational folding., Conclusions: Our results reveal a weak relationship between codon usage and protein structure, indicating that differences in selection on codon usage between structures are slight. In addition to the magnitude of differences in selection between protein structures being slight, the observed shifts appear to be idiosyncratic and largely codon-specific rather than systematic reversals in the nature of selection. Overall, our work demonstrates the statistical power and benefits of studying selective shifts on codon usage or other genomic features from an explicitly evolutionary approach. Limitations of this approach and future potential research avenues are discussed., (© 2022. The Author(s).)

Extracellular vesicles (EVs) may mediate intercellular communication by carrying protein and RNA cargo. The composition, biology, and roles of EVs in physiology and pathology have been primarily studied in the context of biofluids and in cultured mammalian cells. The experimental tractability of C. elegans makes for a powerful in vivo animal system to identify and study EV cargo from its cellular source. We developed an innovative method to label, track, and profile EVs using genetically encoded, fluorescent-tagged EV cargo and conducted a large-scale isolation and proteomic profiling. Nucleic acid binding proteins (∼200) are overrepresented in our dataset. By integrating our EV proteomic dataset with single-cell transcriptomic data, we identified and validated ciliary EV cargo: CD9-like tetraspanin (TSP-6), ectonucleotide pyrophosphatase/phosphodiesterase (ENPP-1), minichromosome maintenance protein (MCM-3), and double-stranded RNA transporter SID-2. C. elegans EVs also harbor RNA, suggesting that EVs may play a role in extracellular RNA-based communication., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Motivation: Ribosome profiling, or Ribo-seq, is the state-of-the-art method for quantifying protein synthesis in living cells. Computational analysis of Ribo-seq data remains challenging due to the complexity of the procedure, as well as variations introduced for specific organisms or specialized analyses., Results: We present riboviz 2, an updated riboviz package, for the comprehensive transcript-centric analysis and visualization of Ribo-seq data. riboviz 2 includes an analysis workflow built on the Nextflow workflow management system for end-to-end processing of Ribo-seq data. riboviz 2 has been extensively tested on diverse species and library preparation strategies, including multiplexed samples. riboviz 2 is flexible and uses open, documented file formats, allowing users to integrate new analyses with the pipeline., Availability and Implementation: riboviz 2 is freely available at github.com/riboviz/riboviz., (© The Author(s) 2022. Published by Oxford University Press.)

Introduction Patients are sensitive to both the frequency and costs of dental recall visits. Shared decision making (SDM) is a principle of patient-centred care, advocated by the National Institute for Health and Care Excellence and policymakers, whereby joint decisions are made between clinicians and patients.Aims To explore NHS dentists' and patients' attitudes towards SDM in decisions about recall interval.Methods Semi-structured telephone interviews were conducted with 25 NHS patients and 25 NHS general dental practitioners in Wales, UK. Transcripts were thematically analysed.Results While many patients would be happy to accept changes to their recall interval, most wanted to be seen at least annually. Most patients were willing to be guided by their dentist in decisions about recall interval, as long as consideration was given to issues such as time, travel and cost. This contrasted with the desire to actively participate in decisions about operative treatment. Although the dentists' understanding of SDM varied, practitioners considered it important to involve patients in decisions about their care. However, dentists perceived that time, patient anxiety and concerns about potential adverse outcomes were barriers to the use of SDM.Conclusions Since there is uncertainty about the most clinically effective and cost-effective dental recall strategy, patient preference may play a role in these decisions., (© 2022. The Author(s), under exclusive licence to the British Dental Association.)

Introduction The National Institute for Health and Care Excellence (NICE) Guideline CG19 recommends that the intervals between oral health reviews should be tailored to patients' disease risk. However, evidence suggests that most patients still attend at six-monthly intervals.Aim To explore facilitators and barriers to the implementation of CG19 in general dental practice.Methods Semi-structured telephone interviews were conducted with 25 NHS general dental practitioners (GDPs) in Wales, UK. Transcripts were thematically analysed.Results Dentists described integrating information on clinical risk, patients' social and dental history, and professional judgement when making decisions about recall interval. Although most GDPs reported routinely using risk-based recall intervals, a number of barriers exist to recall intervals at the extremes of the NICE recommendations. Many practitioners were unwilling to extend recall intervals to 24 months, even for the lowest-risk patients. Conversely, dentists described how it could be challenging to secure the agreement of high-risk patients to three-month recalls. In addition, time and workload pressures, the need to meet contractual obligations, pressure from contracting organisations and the fear of litigation also influenced the implementation of risk-based recalls.Conclusions Although awareness of the NICE Guideline CG19 was high, there is a need to explore how risk-based recalls may be best supported through contractual mechanisms., (© 2022. The Author(s).)

The emergence of ribosome profiling as a tool for measuring the translatome has provided researchers with valuable insights into the post-transcriptional regulation of gene expression. Despite the biological insights and technical improvements made since the technique was initially described by Ingolia et al. (Science 324(5924):218-223, 2009), ribosome profiling measurements and subsequent data analysis remain challenging. Here, we describe our lab's protocol for performing ribosome profiling in bacteria, yeast, and mammalian cells. This protocol has integrated elements from three published ribosome profiling methods. In addition, we describe a tool called RiboViz (Carja et al., BMC Bioinformatics 18:461, 2017) ( https://github.com/riboviz/riboviz ) for the analysis and visualization of ribosome profiling data. Given raw sequencing reads and transcriptome information (e.g., FASTA, GFF) for a species, RiboViz performs the necessary pre-processing and mapping of the raw sequencing reads. RiboViz also provides the user with various quality control visualizations., (© 2022. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Chemical modifications of RNA 5'-ends enable "epitranscriptomic" regulation, influencing multiple aspects of RNA fate. In transcription initiation, a large inventory of substrates compete with nucleoside triphosphates for use as initiating entities, providing an ab initio mechanism for altering the RNA 5'-end. In Escherichia coli cells, RNAs with a 5'-end hydroxyl are generated by use of dinucleotide RNAs as primers for transcription initiation, "primer-dependent initiation." Here, we use massively systematic transcript end readout (MASTER) to detect and quantify RNA 5'-ends generated by primer-dependent initiation for ∼4 10 (∼1,000,000) promoter sequences in E. coli The results show primer-dependent initiation in E. coli involves any of the 16 possible dinucleotide primers and depends on promoter sequences in, upstream, and downstream of the primer binding site. The results yield a consensus sequence for primer-dependent initiation, Y TSS-2 N TSS-1 N TSS W TSS+1 , where TSS is the transcription start site, N TSS-1 N TSS is the primer binding site, Y is pyrimidine, and W is A or T. Biochemical and structure-determination studies show that the base pair (nontemplate-strand base:template-strand base) immediately upstream of the primer binding site (Y:R TSS-2 , where R is purine) exerts its effect through the base on the DNA template strand (R TSS-2 ) through interchain base stacking with the RNA primer. Results from analysis of a large set of natural, chromosomally encoded E coli promoters support the conclusions from MASTER. Our findings provide a mechanistic and structural description of how TSS-region sequence hard-codes not only the TSS position but also the potential for epitranscriptomic regulation through primer-dependent transcription initiation., Competing Interests: The authors declare no competing interest.

Background: Mass spectrometry-based proteomics can identify and quantify thousands of proteins from individual microbial species, but a significant percentage of these proteins are unannotated and hence classified as proteins of unknown function (PUFs). Due to the difficulty in extracting meaningful metabolic information, PUFs are often overlooked or discarded during data analysis, even though they might be critically important in functional activities, in particular for metabolic engineering research., Results: We optimized and employed a pipeline integrating various "guilt-by-association" (GBA) metrics, including differential expression and co-expression analyses of high-throughput mass spectrometry proteome data and phylogenetic coevolution analysis, and sequence homology-based approaches to determine putative functions for PUFs in Clostridium thermocellum. Our various analyses provided putative functional information for over 95% of the PUFs detected by mass spectrometry in a wild-type and/or an engineered strain of C. thermocellum. In particular, we validated a predicted acyltransferase PUF (WP&#95;003519433.1) with functional activity towards 2-phenylethyl alcohol, consistent with our GBA and sequence homology-based predictions., Conclusions: This work demonstrates the value of leveraging sequence homology-based annotations with empirical evidence based on the concept of GBA to broadly predict putative functions for PUFs, opening avenues to further interrogation via targeted experiments.

Background: Researchers often measure changes in gene expression across conditions to better understand the shared functional roles and regulatory mechanisms of different genes. Analogous to this is comparing gene expression across species, which can improve our understanding of the evolutionary processes shaping the evolution of both individual genes and functional pathways. One area of interest is determining genes showing signals of coevolution, which can also indicate potential functional similarity, analogous to co-expression analysis often performed across conditions for a single species. However, as with any trait, comparing gene expression across species can be confounded by the non-independence of species due to shared ancestry, making standard hypothesis testing inappropriate., Results: We compared RNA-Seq data across 18 fungal species using a multivariate Brownian Motion phylogenetic comparative method (PCM), which allowed us to quantify coevolution between protein pairs while directly accounting for the shared ancestry of the species. Our work indicates proteins which physically-interact show stronger signals of coevolution than randomly-generated pairs. Interactions with stronger empirical and computational evidence also showing stronger signals of coevolution. We examined the effects of number of protein interactions and gene expression levels on coevolution, finding both factors are overall poor predictors of the strength of coevolution between a protein pair. Simulations further demonstrate the potential issues of analyzing gene expression coevolution without accounting for shared ancestry in a standard hypothesis testing framework. Furthermore, our simulations indicate the use of a randomly-generated null distribution as a means of determining statistical significance for detecting coevolving genes with phylogenetically-uncorrected correlations, as has previously been done, is less accurate than PCMs, although is a significant improvement over standard hypothesis testing. These methods are further improved by using a phylogenetically-corrected correlation metric., Conclusions: Our work highlights potential benefits of using PCMs to detect gene expression coevolution from high-throughput omics scale data. This framework can be built upon to investigate other evolutionary hypotheses, such as changes in transcription regulatory mechanisms across species.

This article describes a project that assessed whether routinely collected antibiotic prescribing and NHS dental treatment data could be linked to produce personalised prescribing profiles for general dental practitioners working in Wales, UK. Dental public health competencies required for this work included: Multi-agency working to develop a sustainable system of monitoring antibiotic prescribing in primary dental care in Wales, Dental public health intelligence, Development of dental service quality indicators., (Copyright© 2019 Dennis Barber Ltd.)

The Sec secretion pathway is found across all domains of life. A critical feature of Sec secreted proteins is the signal peptide, a short peptide with distinct physicochemical properties located at the N-terminus of the protein. Previous work indicates signal peptides are biased towards translationally inefficient codons, which is hypothesized to be an adaptation driven by selection to improve the efficacy and efficiency of the protein secretion mechanisms. We investigate codon usage in the signal peptides of E. coli using the Codon Adaptation Index (CAI), the tRNA Adaptation Index (tAI), and the ribosomal overhead cost formulation of the stochastic evolutionary model of protein production rates (ROC-SEMPPR). Comparisons between signal peptides and 5'-end of cytoplasmic proteins using CAI and tAI are consistent with a preference for inefficient codons in signal peptides. Simulations reveal these differences are due to amino acid usage and gene expression - we find these differences disappear when accounting for both factors. In contrast, ROC-SEMPPR, a mechanistic population genetics model capable of separating the effects of selection and mutation bias, shows codon usage bias (CUB) of the signal peptides is indistinguishable from the 5'-ends of cytoplasmic proteins. Additionally, we find CUB at the 5'-ends is weaker than later segments of the gene. Results illustrate the value in using models grounded in population genetics to interpret genetic data. We show failure to account for mutation bias and the effects of gene expression on the efficacy of selection against translation inefficiency can lead to a misinterpretation of codon usage patterns., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: There are approximately 380 000 dental consultations in UK general practice every year., Aim: To explore the reasons why patients may consult a GP rather than a dentist when experiencing problems with their teeth or gums., Design and Setting: A qualitative semi-structured interview study with adults who had consulted a UK GP with a dental problem in the previous 12 months., Method: Participants were recruited via print and social media; internet adverts; HealthWise Wales, the Welsh national population research cohort; and word of mouth. In total, 39 telephone interviews were conducted, and transcripts thematically analysed., Results: Participants' consultation behaviour was influenced by their interpretation of their symptoms; their perceptions of the scope of practice of primary care practitioners; the comparative ease of navigating medical and dental care systems; previous experiences of dental care, including dental anxiety and dissatisfaction with prior treatment; and willingness and ability to pay for dental care., Conclusion: There are several reasons why patients may consult a GP with a dental problem. Effective interventions will need to break down the barriers preventing access to dental care. Accessible public-facing information on where to seek care for dental problems is required, and general practice teams should be able to signpost patients who present with dental problems, if appropriate. Dental providers should also be encouraged to maintain timely access to urgent care for their patients., (© British Journal of General Practice 2018.)

Objective: to systematically appraise and synthesise the existing evidence regarding the reasons why patients in the UK may consult a general medical practitioner (GMP) when experiencing a dental problem., Basic Research Design: a systematic review of the scientific and grey literature published between 1996 and 2017., Participants: dental service users (adults or children) from the UK and/or their carers who were seeking, or had sought, care for a dental problem from a GMP., Main Outcomes: patients' perspectives on reasons for consulting a GMP were qualitatively synthesised according to Levesque et al.'s conceptual framework of access to health care., Results: Out of 1,232 references screened, 2 studies met the inclusion criteria for the review. They identified the following factors that can influence care-seeking for dental problems: patients' interpretation of their symptoms; their understanding of practitioners' scope of practice; the availability of timely dental care; and the affordability of care. Both studies had weaknesses with regard to either their conduct and/or reporting., Conclusions: Choice of practitioner for dental problems is likely to be influenced by both the beliefs and attitudes of the individual patient and the organisation and attributes of the providers of dental and medical care. However, in light of the quality of the existing evidence base, there is a need for high-quality studies exploring the reasons why patients in the UK may seek care from a GMP when experiencing dental problems., (Copyright© 2018 Dennis Barber Ltd.)

Background: Dental pain can have a detrimental effect on quality of life. Symptomatic apical periodontitis and acute apical abscess are common causes of dental pain and arise from an inflamed or necrotic dental pulp, or infection of the pulpless root canal system. Clinical guidelines recommend that the first-line treatment for teeth with these conditions should be removal of the source of inflammation or infection by local, operative measures, and that systemic antibiotics are currently only recommended for situations where there is evidence of spreading infection (cellulitis, lymph node involvement, diffuse swelling) or systemic involvement (fever, malaise). Despite this, there is evidence that dentists frequently prescribe antibiotics in the absence of these signs. There is concern that this could contribute to the development of antibiotic-resistant bacterial colonies within both the individual and the community. This review is an update of the original version that was published in 2014., Objectives: To evaluate the effects of systemic antibiotics provided with or without surgical intervention (such as extraction, incision and drainage of a swelling, or endodontic treatment), with or without analgesics, for symptomatic apical periodontitis and acute apical abscess in adults., Search Methods: Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 26 February 2018), the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 1) in the Cochrane Library (searched 26 February 2018), MEDLINE Ovid (1946 to 26 February 2018), Embase Ovid (1980 to 26 February 2018), and CINAHL EBSCO (1937 to 26 February 2018). The US National Institutes of Health Ongoing Trials Register (ClinicalTrials.gov) and the World Health Organization International Clinical Trials Registry Platform were searched for ongoing trials. A grey literature search was conducted using OpenGrey (to 26 February 2018) and ZETOC Conference Proceedings (1993 to 26 February 2018). No restrictions were placed on the language or date of publication when searching the electronic databases., Selection Criteria: Randomised controlled trials of systemic antibiotics in adults with a clinical diagnosis of symptomatic apical periodontitis or acute apical abscess, with or without surgical intervention (considered in this situation to be extraction, incision and drainage or endodontic treatment) and with or without analgesics., Data Collection and Analysis: Two authors screened the results of the searches against inclusion criteria, extracted data and assessed risk of bias independently and in duplicate. We calculated mean differences (MD) (standardised mean difference (SMD) when different scales were reported) and 95% confidence intervals (CI) for continuous data. A fixed-effect model was used in the meta-analysis as there were fewer than four studies. We contacted study authors to obtain missing information., Main Results: We included two trials in this review, with 62 participants included in the analyses. Both trials were conducted in university dental schools in the USA and compared the effects of oral penicillin V potassium (penicillin VK) versus a matched placebo when provided in conjunction with a surgical intervention (total or partial pulpectomy) and analgesics to adults with acute apical abscess or symptomatic necrotic tooth. The patients included in these trials had no signs of spreading infection or systemic involvement (fever, malaise). We assessed one study as having a high risk of bias and the other study as having unclear risk of bias.The primary outcome variables reported in both studies were participant-reported pain and swelling (one trial also reported participant-reported percussion pain). One study reported the type and number of analgesics taken by participants. One study recorded the incidence of postoperative endodontic flare-ups (people who returned with symptoms that necessitated further treatment). Adverse effects, as reported in one study, were diarrhoea (one participant, placebo group) and fatigue and reduced energy postoperatively (one participant, antibiotic group). Neither study reported quality of life measurements.Objective 1: systemic antibiotics versus placebo with surgical intervention and analgesics for symptomatic apical periodontitis or acute apical abscessTwo studies provided data for the comparison between systemic antibiotics (penicillin VK) and a matched placebo for adults with acute apical abscess or a symptomatic necrotic tooth when provided in conjunction with a surgical intervention. Participants in one study all underwent a total pulpectomy of the affected tooth, while participants in the other study had their tooth treated by either partial or total pulpectomy. Participants in both trials received oral analgesics. There were no statistically significant differences in participant-reported measures of pain or swelling at any of the time points assessed within the review. The MD for pain (short ordinal numerical scale 0 to 3) was -0.03 (95% CI -0.53 to 0.47) at 24 hours; 0.32 (95% CI -0.22 to 0.86) at 48 hours; and 0.08 (95% CI -0.38 to 0.54) at 72 hours. The SMD for swelling was 0.27 (95% CI -0.23 to 0.78) at 24 hours; 0.04 (95% CI -0.47 to 0.55) at 48 hours; and 0.02 (95% CI -0.49 to 0.52) at 72 hours. The body of evidence was assessed as at very low quality.Objective 2: systemic antibiotics without surgical intervention for adults with symptomatic apical periodontitis or acute apical abscessWe found no studies that compared the effects of systemic antibiotics with a matched placebo delivered without a surgical intervention for symptomatic apical periodontitis or acute apical abscess in adults., Authors' Conclusions: There is very low-quality evidence that is insufficient to determine the effects of systemic antibiotics on adults with symptomatic apical periodontitis or acute apical abscess.

The increasing emergence of antibiotic resistance is a major international public health problem. As a consequence, it is essential that steps are taken to conserve the effectiveness of existing antimicrobial agents. Consumption of antibiotics is the prime contributor to the development of resistance. General dental practitioners write almost 1 out of 10 prescriptions for antibiotics in primary care within the UK and therefore the prudent prescribing of antibiotics in dentistry has never been more vital. This paper outlines the impact of antimicrobial resistance on modern healthcare, describes the current use of antibiotics in general dental practice, and recommends pragmatic ways in which dental practitioners can evaluate and optimize their prescribing. Clinical relevance: Dental professionals have a responsibility to both their patients and the wider community to prescribe antibiotics appropriately.

Objective To describe the findings of the first cycle of a clinical audit of antimicrobial use by general dental practitioners (GDPs).Setting General dental practices in Wales, UK.Subjects and methods Between April 2012 and March 2015, 279 GDPs completed the audit. Anonymous information about patients prescribed antimicrobials was recorded. Clinical information about the presentation and management of patients was compared to clinical guidelines published by the Scottish Dental Clinical Effectiveness Programme (SDCEP).Results During the data collection period, 5,782 antimicrobials were prescribed in clinical encounters with 5,460 patients. Of these 95.3% were antibiotic preparations, 2.7% were antifungal agents, and 0.6% were antivirals. Of all patients prescribed antibiotics, only 37.2% had signs of spreading infection or systemic involvement recorded, and 31.2% received no dental treatment. In total, 79.2% of antibiotic, 69.4% of antifungal, and 57.6% of antiviral preparations met audit standards for dose, frequency, and duration. GDPs identified that failure of previous local measures, patient unwillingness or inability to receive treatment, patient demand, time pressures, and patients' medical history may influence their prescribing behaviours.Conclusions The findings of the audit indicate a need for interventions to support GDPs so that they may make sustainable improvements to their antimicrobial prescribing practices.

Background: The frequency of consulting for dental problems in general medical practice, and antibiotic prescribing associated with these consultations, is poorly described., Aim: To describe consultation rates and antibiotic use for dental problems in UK general medical practice, and explore factors associated with antibiotic prescribing for dental conditions., Design and Setting: A retrospective cohort study using Clinical Practice Research Datalink, a database of general practice patient records in the UK., Method: All dental consultations between 2004 and 2013 were identified. The main outcome was the prescription of an antibiotic during a dental consultation. Multilevel logistic regression was conducted to examine factors associated with antibiotic prescription., Results: In all, 288 169 dental consultations were included in the cohort. The average rate of dental consultations was 6.06 consultations per 1000 patient-years. Rates of dental consultation decreased from 6.84 consultations per 1000 patient-years in 2008, to 4.23 consultations per 1000 patient-years in 2013. Consultation rates were higher among females than males and highest in patients aged 20-29 years. An antibiotic was prescribed in 57.1% of consultations. Significant predictors (P<0.001) of antibiotic prescribing included: patient middle age, male sex, and previous consultations for tooth-related problems. Antibiotics were more likely to be prescribed during consultations in December (odds ratio [OR] 1.18, 95% confidence interval [CI] = 1.13 to 1.24, P<0.001, reference month: June) and on a Monday (OR 1.10, 95% CI = 1.07 to 1.13, P<0.001) or a Friday (OR 1.15, 95% CI = 1.12 to 1.18, P<0.001, reference day: Wednesday)., Conclusion: Consultation rates for dental problems in UK general practice are relatively low but more than half result in the prescription of an antibiotic. This raises concerns about patient morbidity and contributions to antimicrobial resistance., (© British Journal of General Practice 2016.)

Objectives: To assess the extent to which antibiotic prescribing in general dental practice conforms to clinical guidelines and to describe factors associated with antibiotic prescription in the absence of spreading infection or systemic involvement., Methods: A cross-sectional study of the management of adult patients with acute dental conditions by General Dental Practitioners (GDPs) in Wales, UK. Clinical information on the management of patients was compared to clinical and prescribing guidelines published by the Scottish Dental Clinical Effectiveness Programme and the Faculty of General Dental Practice (UK). Multilevel logistic regression was used to identify patient, practitioner and consultation characteristics predictive of antibiotic prescribing in the absence of infection., Results: Antibiotics were prescribed to 57.4% of 568 patients. Over half of antibiotics (65.6%) were prescribed in situations where there was no evidence of spreading infection, and 70.6% were used without the provision of an operative intervention. Only 19.0% of antibiotics were prescribed in situations where their use was indicated by clinical guidelines. Factors associated (P < 0.05) with antibiotic prescription in the absence of infection were failure of previous operative treatment (Odds Ratio (OR) 13.57), shortage of clinical time to undertake treatment (OR 10.21), patients who were unable or unwilling to accept operative treatment (OR 4.89), patient requests for antibiotics (OR 3.69) and acute periodontal conditions (OR 3.37)., Conclusions: A high level of inappropriate antibiotic prescribing was observed amongst the GDPs studied. Features of the healthcare environment, such as clinical time pressures, and patient-related characteristics, such as expectations for antibiotics and refusal of operative treatment, are associated with antibiotic prescribing in the absence of infection. Individuals responsible for the commissioning and delivery of dental services should seek to develop targeted interventions addressing these issues in order to ensure optimal antimicrobial stewardship within dentistry., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: This study aimed to produce an account of the attitudes of general practitioners (GPs) towards the management of dental conditions in general practice, and sought to explore how GPs use antibiotics in the treatment of dental problems., Design: Qualitative study employing semistructured telephone interviews and thematic analysis., Participants: 17 purposively sampled GPs working in Wales, of which 9 were male. The median number of years since graduation was 21. Maximum variation sampling techniques were used to ensure participants represented different Rural-Urban localities, worked in communities with varying levels of deprivation, and had differing lengths of practising career., Results: Most GPs reported regularly managing dental problems, with more socioeconomically deprived patients being particularly prone to consult. Participants recognised that dental problems are not optimally managed in general practice, but had sympathy with patients experiencing dental pain who reported difficulty obtaining an emergency dental consultation. Many GPs considered antibiotics an acceptable first-line treatment for acute dental problems and reported that patients often attended expecting to receive antibiotics. GPs who reported that their usual practice was to prescribe antibiotics were more likely to prioritise patients' immediate needs, whereas clinicians who reported rarely prescribing often did so to encourage patients to consult a dental professional., Conclusions: The presentation of patients with dental problems presents challenges to GPs who report concerns about their ability to manage such conditions. Despite this, many reported frequently prescribing antibiotics for patients with dental conditions. This may contribute to both patient morbidity and the emergence of antimicrobial resistance. This research has identified the need for quantitative data on general practice consultations for dental problems and qualitative research exploring patient perspectives on reasons for consulting. The findings of these studies will inform the design of an intervention to support patients in accessing appropriate care when experiencing dental problems., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

The injudicious use of antibiotics is one of the key contributors to the emergence of antibiotic-resistant bacterial strains. It is therefore imperative that antibiotics are prescribed only when they are likely to result in clinical benefit for a patient. Clinical guidelines have been produced to assist dental practitioners in the appropriate use of antimicrobials. Despite these guidelines, there is evidence that antibiotics are still widely used and misused in the management of acute dental conditions. This article explores the barriers that exist with regard to the implementation of antibiotic prescribing guidelines and discusses some of the interventions that aim to optimise antibiotic prescribing in primary dental care.

Background: Dentists are responsible for 9-10% of all antibiotics dispensed in primary care in the UK, many of which may be provided contrary to clinical guidelines. Since antibiotic consumption has been identified as a major cause of antibiotic resistance, dental prescribing may be a significant contributor to this important public health problem.Objective This study aims to explore general dental practitioners' (GDPs) perceptions and attitudes towards antibiotic use and resistance., Method: Qualitative interview study with 19 purposively sampled GDPs working in Wales. A set of open-ended questions were developed and amended during semi-structured telephone interviews. Interviews were recorded, transcribed verbatim and codes were developed using thematic analysis., Results: Perceptions of antibiotic use and resistance varied widely between practitioners, particularly with respect to the prevalence and impact of resistant strains on the management of dentoalveolar infection, and the impact of dental prescribing on the emergence of resistance. GDPs reported that their antibiotic prescribing decisions were driven by both clinical pressures and wider public health considerations., Conclusions: Interventions to enhance the quality of antibiotic prescribing in primary care dentistry should address issues associated with inappropriate prescribing as well as providing education about the causes, prevalence and impact of antibiotic resistance.