Systematic analysis of nonprogrammed frameshift suppression in E. coli via translational tiling proteomics.

The synthesis of proteins as encoded in the genome depends critically on translational fidelity. Nevertheless, errors inevitably occur, and those that result in reading frame shifts are particularly consequential because the resulting polypeptides are typically nonfunctional. Despite the generally maladaptive impact of such errors, the proper decoding of certain mRNAs, including many viral mRNAs, depends on a process known as programmed ribosomal frameshifting. The fact that these programmed events, commonly involving a shift to the -1 frame, occur at specific evolutionarily optimized "slippery" sites has facilitated mechanistic investigation. By contrast, less is known about the scope and nature of error (i.e., nonprogrammed) frameshifting. Here, we examine error frameshifting by monitoring spontaneous frameshift events that suppress the effects of single base pair deletions affecting two unrelated test proteins. To map the precise sites of frameshifting, we developed a targeted mass spectrometry-based method called "translational tiling proteomics" for interrogating the full set of possible -1 slippage events that could produce the observed frameshift suppression. Surprisingly, such events occur at many sites along the transcripts, involving up to one half of the available codons. Only a subset of these resembled canonical "slippery" sites, implicating alternative mechanisms potentially involving noncognate mispairing events. Additionally, the aggregate frequency of these events (ranging from 1 to 10% in our test cases) was higher than we might have anticipated. Our findings point to an unexpected degree of mechanistic diversity among ribosomal frameshifting events and suggest that frameshifted products may contribute more significantly to the proteome than generally assumed.

Measuring prion propagation in single bacteria elucidates a mechanism of loss.

Prions are self-propagating protein aggregates formed by specific proteins that can adopt alternative folds. Prions were discovered as the cause of the fatal transmissible spongiform encephalopathies in mammals, but prions can also constitute nontoxic protein-based elements of inheritance in fungi and other species. Prion propagation has recently been shown to occur in bacteria for more than a hundred cell divisions, yet a fraction of cells in these lineages lost the prion through an unknown mechanism. Here, we investigate prion propagation in single bacterial cells as they divide using microfluidics and fluorescence microscopy. We show that the propagation occurs in two distinct modes. In a fraction of the population, cells had multiple small visible aggregates and lost the prion through random partitioning of aggregates to one of the two daughter cells at division. In the other subpopulation, cells had a stable large aggregate localized to the pole; upon division the mother cell retained this polar aggregate and a daughter cell was generated that contained small aggregates. Extending our findings to prion domains from two orthologous proteins, we observe similar propagation and loss properties. Our findings also provide support for the suggestion that bacterial prions can form more than one self-propagating state. We implement a stochastic version of the molecular model of prion propagation from yeast and mammals that recapitulates all the observed single-cell properties. This model highlights challenges for prion propagation that are unique to prokaryotes and illustrates the conservation of fundamental characteristics of prion propagation.

Systemic racism and racial inequities in periodontal health: The long journey from upstream determinants to downstream treatment.

Racial disparities in the prevalence of periodontal disease are consistent and persistent. The epidemiology of periodontal disease demonstrates racial inequities: non-Hispanic Black (14.7%), Mexican American (13.4%), and other Hispanic adults (7.8%) experience a higher prevalence of severe periodontal disease than non-Hispanic White adults (5.9%). Epidemiologic and clinical research on periodontal health suffers from the same problem that has plagued the health equity movement, an over emphasis on describing racial inequities coupled with few interventions that reduce racial health inequity. Over the decades that racial inequities in periodontal disease have been observed, many have argued that systemic racism is the fundamental driver of racial health inequity. This paper interrogates the roles of systemic racism, dental education, clinical treatment, and patient behavior in periodontal disease. We describe how, together, these mechanisms contribute to racial disparities in periodontal outcomes. However, it is insufficient for oral health equity scientists to only describe and discuss the negative effects of systemic racism. The imperative is to create antiracist strategies designed to eliminate systemic racism. Health equity scientists must also specify how dental systems operate in a racist manner and create effective clinical strategies designed to reduce racial disparities in periodontal disease.

A bacteria-based genetic assay detects prion formation.

Prions are infectious, self-propagating protein aggregates that are notorious for causing devastating neurodegenerative diseases in mammals. Recent evidence supports the existence of prions in bacteria. However, the evaluation of candidate bacterial prion-forming proteins has been hampered by the lack of genetic assays for detecting their conversion to an aggregated prion conformation. Here we describe a bacteria-based genetic assay that distinguishes cells carrying a model yeast prion protein in its nonprion and prion forms. We then use this assay to investigate the prion-forming potential of single-stranded DNA-binding protein (SSB) of Campylobacter hominis Our findings indicate that SSB possesses a prion-forming domain that can transition between nonprion and prion conformations. Furthermore, we show that bacterial cells can propagate the prion form over 100 generations in a manner that depends on the disaggregase ClpB. The bacteria-based genetic tool we present may facilitate the investigation of prion-like phenomena in all domains of life.

Chronic Disease Counseling and Screening by Dental Professionals: Results From NHANES, 2011-2016.

INTRODUCTION: Dental visits may provide an opportunity to counsel and screen for chronic disease prevention. However, few studies have used nationally representative data to assess the potential role of dental professionals in chronic disease prevention. We examined the percentage of US adults who reported chronic disease counseling and screening by dental professionals. METHODS: We analyzed data from the National Health and Nutrition Examination Survey 2011-2016 for 5,541 participants aged 30 or older who reported seeing a dental professional in the past year and estimated the percentage who reported receiving counseling about selected chronic disease prevention during the visit. We used logistic regressions to examine associations between risk factors and counseling. RESULTS: Overall, 4.0% (standard error [SE], 0.3) of adults were told by a dental professional about the benefits of checking blood glucose, 42.4% (SE, 2.9) giving up tobacco (among tobacco users), 26.6% (SE, 1.2) about checking for oral cancer, and 43.0% (SE, 1.8) had an oral cancer examination. Groups with risk factors were more likely to receive health behavior counseling than those without (eg, those previously told they had diabetes risk factors were more likely to receive blood glucose counseling than those without [8.1% vs 3.3%, P < .05]). The pattern for oral cancer counseling and receiving an oral cancer examination was different: adults without oral cancer risk factors (no tobacco use, normal/underweight, and/or excellent/very good health) were more likely to receive oral cancer counseling or screening. Adjusted analyses did not change these associations. CONCLUSION: Most adults were not counseled about chronic disease prevention during a visit with a dental professional. Current tobacco users and those with overweight or obesity were more likely to report receiving counseling.

ManLMN is a glucose transporter and central metabolic regulator in Streptococcus pneumoniae.

Streptococcus pneumoniae is a common colonizer of the human nasopharynx and a leading cause of bacterial pneumonia and otitis media, among other invasive diseases. During both colonization and invasive disease S. pneumoniae ferments host-derived carbohydrates as its primary means of generating energy. This pathogen is adept at transporting and metabolizing a wide variety of carbohydrates. We found the highly conserved PTS ManLMN contributes to growth on glucose and is also essential for growth on a variety of nonpreferred carbohydrates, suggesting it is a multisubstrate transporter. Exploration of this phenotype revealed ManLMN is required for inducing expression of downstream metabolic genes in response to carbohydrate stimuli. We further demonstrate that ManLMN's role as a constitutively expressed transporter is likely unique and integral to pneumococcus's strategy of carbon catabolite repression (CCR). Using a selection for suppressors, we explored how ManLMN is integrated into the CCR regulatory framework in S. pneumoniae. We identified two hypothetical small proteins and the virulence regulator SmrC as potential mediators of CCR in connection with ManLMN. Characterization of these two hypothetical proteins revealed they influence transcriptional regulation of carbohydrate transporters. We propose a model unifying these observations in which ManLMN is a versatile surveyor of available carbohydrates in S. pneumoniae.

Assessing Different Partner Notification Methods for Assuring Partner Treatment for Gonorrhea: Looking for the Best Mix of Options.

CONTEXT: Partner notification for gonorrhea is intended to interrupt transmission and to bring people exposed to infection to care. Partner notification may be initiated through public health professionals (disease intervention specialist: DIS referral) or patients (patient referral). In some cases, patients may carry medications or prescriptions for partners (patient-delivered partner therapy: PDPT). OBJECTIVE: To examine how patterns of notifying and treating partners of persons with gonorrhea differ by partner notification approach. DESIGN: From published literature (2005-2012), we extracted 10 estimates of patient referral data from 7 studies (3853 patients, 7490 partners) and 5 estimates of PDPT data from 5 studies (1781 patients, 3125 partners). For DIS referral estimates, we obtained 2010-2012 data from 14 program settings (4581 patients interviewed, 8301 partners). For each approach, we calculated treatment cascades based on the proportion of partners who were notified and treated. We also calculated cascades based on partners notified and treated per patient diagnosed. RESULTS: Proportions of partners notified and treated were, for patient referral, 56% and 34%; for PDPT, 57% and 46%; for DIS referral, 25% and 22%. Notification and treatment estimates for patient referral and PDPT were significantly higher than for DIS referral, but DIS referral was more efficacious than the other methods in assuring treatment among those notified (all Ps < .001). The notification and treatment ratios per patient seen were, for patient referral, 0.96 and 0.61; for PDPT, 0.90 and 0.73; for DIS referral, 0.45 and 0.40. CONCLUSION: Patient-based methods had higher proportions of partners treated overall, but provider referral had the highest proportion treated among those notified. These data may assist programs to align the most efficacious strategies with the most epidemiologically or clinically important cases while assuring the best scalable standard of care for others.

A Self-Report to 2-Domain Questions May Accurately Screen for Periodontitis.

ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: A two-domain self-report measure of periodontal disease has good accuracy for periodontitis screening in dental school outpatients. Chatzopoulos GS, Tsalikis L, Konstantinidis A, Kotsakis GA. J Periodontol 2016;87:1165-73. SOURCE OF FUNDING: Information not available TYPE OF STUDY/DESIGN: Cohort study.

Carbon catabolite repression by seryl phosphorylated HPr is essential to Streptococcus pneumoniae in carbohydrate-rich environments.

Carbon catabolite repression (CCR) is a regulatory phenomenon implemented by bacteria to hierarchically organize carbohydrate utilization in order to achieve maximal growth. CCR is likely of great importance to Streptococcus pneumoniae because the human host sites inhabited by this pathogen represent complex carbohydrate environments. In this species, inactivation of the prototypical Gram-positive CCR master regulator, ccpA, attenuates virulence in mice but does not relieve CCR of most metabolic enzymes, suggesting CcpA-independent CCR mechanisms predominate. Here we show the activities of three transcriptional regulators constitute the majority of transcriptional CCR of galactose metabolism operons. We determined seryl-phosphorylated histidine phosphocarrier protein (HPr-Ser∼P)-mediated regulation is a major CCR mechanism and an essential activity in the pneumococcus, as an HPr point mutation abolishing HPrK/P-dependent phosphorylation was not tolerated nor was deletion of hprk/p. The HPr-Ser∼P phosphomimetic mutant HPr S46D had reduced phosphotransferase system transport rates and limited induction of CCR-repressed genes. These results support a model of pneumococcal CCR in which HPr-Ser∼P directly affects the activity of CcpA while indirectly affecting the activity of pathway-specific transactional regulators. This report describes the first CcpA-independent CCR mechanism identified in the pneumococcus and the first example of lethality from loss of HPr-Ser∼P-mediated CCR in any species.

North Carolina's Operation Medicine Drop: Results From One of the Nation's Largest Drug Disposal Programs.

INTRODUCTION: In 2013, a total of 1,085 North Carolina residents died due to unintentional poisoning; 91% of these deaths were attributed to medications or drugs (over-the-counter, prescription, or illicit). Proper disposal of unused, unneeded, and/or expired medications is an essential part of preventing these unintentional deaths, as well as averting the other adverse consequences of these drugs on the environment and population health. METHODS: Operation Medicine Drop is a medication take-back program coordinated by Safe Kids North Carolina, a county-level, coalition-based injury prevention organization. The Operation Medicine Drop program and event registration system were used to review and validate the number of events, the counties where the events were held, and the number of unit doses (pills) collected from March 2010 to June 2014. SAS version 9.4 was used to generate basic counts and frequencies of events and doses, and ArcGIS version 10.0 was used to create the map. RESULTS: From March 2010 to June 2014, Operation Medicine Drop held 1,395 events with 245 different participating law enforcement agencies in 91 counties in North Carolina, and it collected 69.6 million unit doses of medication. More than 60 local Safe Kids North Carolina community coalitions had participated as of June 2014. Every year, Operation Medicine Drop has witnessed increases in events, participating agencies, participating counties, and the number of doses collected. CONCLUSION: Operation Medicine Drop is an excellent example of a successful and ongoing collaboration to improve public health. Medication take-back programs may play an important role in preventing future overdose deaths in North Carolina.

There is a Positive Long-term Effect of the Nexo-method on Caries Prevention.

ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Outcomes 18 years after implementation of a nonoperative caries preventive program-the Nexo-method-on children in Moscow, Russia. Kuzmina I, Ekstrand KR. Community Dent Oral Epidemiol 2015;43(4):308-16. SOURCE OF FUNDING: Information not available TYPE OF STUDY/DESIGN: Randomized controlled trial.

Aspirin Use for the Primary Prevention of Myocardial Infarction Among Men in North Carolina, 2013.

INTRODUCTION: The US Preventive Services Task Force recommends aspirin use for men aged 45 to 79, when the potential benefit of preventing myocardial infarctions outweighs the potential harm of gastrointestinal hemorrhage. We determined prevalence and predictors of aspirin use for primary prevention of myocardial infarction vis-à-vis risk among men aged 45 to 79 in North Carolina. METHODS: The study used data for men aged 45 to 79 without contraindications to aspirin use or a history of cardiovascular disease from the 2013 North Carolina Behavioral Risk Factor Surveillance System survey. Stratification by risk of myocardial infarction was based on history of diabetes, high cholesterol, high blood pressure, and smoking. Analyses were performed in Stata version 13.0 (StataCorp LP); survey commands were used to account for complex sampling design. RESULTS: Most respondents, 74.2% (95% confidence interval [CI], 71.2%-77.0%), had at least one risk factor for myocardial infarction. Prevalence of aspirin use among respondents with risk factors was 44.8% (95% CI, 41.0-48.5) and was significantly higher than the prevalence among respondents without risk factors (prevalence ratio: 1.44 [95% CI, 1.17-1.78]). No significant linear dose (number of risk factors)-response (taking aspirin) relationship was found (P for trend = .25). Older age predicted (P = .03) aspirin use among respondents with at least one myocardial infarction risk factor. CONCLUSION: Most men aged 45 to 79 in North Carolina have at least one risk factor for myocardial infarction, but less than half use aspirin. Interventions aimed at boosting aspirin use are needed among at-risk men in North Carolina.

Using community health needs assessments to improve population health.

This commentary describes the community health assessment process that is required of local health departments, and it explains how action plans targeting identified priorities can improve population health. It also highlights the use of evidence-based strategies to increase the overall impact of health improvement efforts.

Building a workforce of diverse women leaders: Understanding intersectional identities.

BACKGROUND: Women have made significant advancements in the dentist workforce, growing from 20% of dentists in 2005 to 34.5% in 2020. Women have also made inroads in academic dentistry. While much scholarship has documented a growing feminization in dentistry and efforts to promote gender equity in the profession, there has been less exploration of the intersectional identities of these women. This manuscript explores how academic dentistry can support diverse women's leadership focusing on intersectional identities. METHODS: Applying the theoretical framework of intersectionality, we assess publicly available data to explore the percentages of faculty and deans who are women of color. Drawing upon best practices in higher education and our personal experiences, we explore opportunities to increase participation and support the advancement of women of color in academia. RESULTS: In the academic year 2018-2019, of the 5066 full-time faculty members, 40.5% were women. Minoritized women comprised 13.4% of full-time faculty members, compared to White women who were 20.6% of full-time faculty. Minoritized women comprised 7.3% of dental school deans, compared to White women who were 17.6% of deans. CONCLUSION: Intersectionality allows for a deeper examination of women in academic dentistry. Women of color are often erased in discussions about women in academic dentistry, even as the profession celebrates the progress made by women. Embracing the intersectional identities of women and by extension, people who identify as gender non-confirming may help dental schools to become humanistic environments where faculty and leadership represent the growing diversity in the profession and in the world.

Black and Hispanic predoctoral dental students' perceptions and considerations of careers in academic dentistry.

BACKGROUND: Dental schools aim to train and support a diverse dentist workforce. Among all faculty, full-time and part-time faculty who identify as members of historically underrepresented groups are 13.9% and 8.4%, respectively. The recruitment and retention of faculty is a known challenge, with growing faculty vacancies at dental schools. This study explored dental student perceptions of academic careers, specifically focusing on Black and Hispanic predoctoral students. METHODS: From August to November 2022, we conducted focus group with second-, third-, and fourth-year predoctoral dental students who identified as Black or Hispanic using a semi-structured interview guide that was developed for this study. Data were analyzed using inductive thematic analysis. RESULTS: Four themes emerged: (1) students perceived academic dental dentistry as inclusive but not diverse spaces for Black and Hispanic people; (2) academic dental careers were perceived as secondary careers; (3) academic dental careers were perceived as a career option with a lack of autonomy and less income, compared to clinical practice in other settings; (4) students expressed a lack of knowledge about pathways to academic dental careers. Despite these challenges, students expressed interest in academic dental careers and noted being inspired by younger faculty members. CONCLUSION: Dental schools must do more to encourage dental students to consider careers in academic dentistry. Pathway programs, mentoring, and the presentation of academic careers as a viable career option for students by faculty should be further emphasized practices. Increasing the diversity of faculty members is also key. Students cannot be who they cannot see.

Centring anti-oppressive justice: Re-envisioning dentistry's social contract.

OBJECTIVES: We re-envision dentistry's social contract and elaborate on the idea that it is not neutral and free from such things as racism and white supremacy and can act as a tool of oppression. METHODS: We critique social contract theory through examination of classical and contemporary contract theorists. More specifically, our analysis draws from the work of Charles W. Mills, a philosopher of race and liberalism, as well as the theoretical and praxis framework of intersectionality. RESULTS: Social contract theory supports hierarchies and inequities that may be used to sustain unfair and unjust differences in oral health between social groups. When dentistry's social contract becomes a tool of oppression, its practice does not promote health equity but reinforces damaging social norms. CONCLUSION: Dentistry must embrace an anti-oppression framing of equity and elevate the principle of justice to one of liberation and not just fairness. In doing so, the profession can better understand itself, act more equitably and empower practitioners to advocate for justice in health and healthcare in its fullest sense. Anti-oppressive justice supports health not as merely an obligation but as a human duty.

Are there more women in the dentist workforce? Using an intersectionality lens to explore the feminization of the dentist workforce in the UK and US.

In this paper, we seek to understand feminization of the dentist workforce moving beyond previous research that has looked at gender in isolation. We contend that little consideration has been given to how gender interacts with other important social identities such as race/ethnicity to influence the opportunities and barriers that female dentists encounter during their dental career. We argue that the scholarly debate about the feminization of the dentistry has not acknowledged the intersectionality of women's lives. Intersectionality describes how multiple social identities (such as race/ethnicity, gender, and class) overlap and interact to inform outcomes, creating disadvantages and/or privileges. Our thesis is that the increasing feminization of the dentist workforce is complicated and paradoxical, creating both opportunities for women and gender imbalances and blockages within the profession. To support our thesis, we critically reviewed the literature on feminization and analysed UK and US workforce data. While the female dentist workforce in both the UK and the US has increased significantly over the past decade, the growth in the number of female dentists was not equal across all racial/ethnic groups. The largest increase in the number of female dentists was among White and Asian women. Viewing the feminization of the dentist workforce through an intersectionality lens exposes the multiple and complex experiences of women, as well as the power dynamics in dentistry. Feminization in dentistry demonstrates the importance of presence, privilege, and power. Based on our assessment of the dentist workforce, dentistry may be less inclusive, despite being perceived as more diverse. Further research should explore how power and privilege may operate in dentistry. Dentistry should embrace intersectionality to provide an inclusive evaluation of equity in the workforce.

Access to dental insurance and oral health inequities in the United States.

While the oral health status of the United States (U.S.) population has improved over the years, racial/ethnic inequities are pervasive with Black Americans carrying a greater burden of oral diseases in most measured outcomes. Access to dental care is a major structural and societal determinant of oral health inequities rooted in structural racism. From post-Civil War-era to present day, this essay presents a series of examples of racist policies that have shaped access to dental insurance for Black Americans both directly and indirectly. Additionally, this essay explains the unique challenges of Medicare and Medicaid highlighting the specific disparities that these public insurance programs face, and proposes policy recommendations aimed to reduce racial/ethnic inequities in dental coverage and access to advance the nation's oral health with comprehensive dental benefits in public insurance programs.

Discrimination and Dignity Experiences in Prior Oral Care Visits Predict Racialized Oral Health Inequities Among Nationally Representative US Adults.

Racism, an oppressive and fallacious sociopolitical hierarchy, is a fundamental cause of oral health inequities worldwide. Everyday discrimination is associated with worse self-rated oral health, toothache and adult tooth loss, and lower oral care utilization. Few studies examine discrimination or microaggressions within oral care settings or their effects on oral health outcomes. We adapted the seven-item Everyday Discrimination Scale to the oral care setting (EDSOC); developed a four-item Dignity in Oral Care Scale (DOCS); fielded them to a probability-based nationally representative sample of US households as part of the 2022 State of Oral Health Equity in America survey (SOHEA, n = 5682); and examined associations between EDSOC and DOCS scores and three outcomes: self-rated oral health, duration since last oral care visit, and planning for future preventive/routine oral care. Nearly, all EDSCOC and DOCS measures were significantly associated with oral health outcomes. Discrimination experience in dental settings had an additive effect on reporting fair/poor oral health and a suppressive effect on planning a future dental visit. Indignity experience doubled-to-quadrupled the likelihood of reporting fair/poor oral health, not having visited a dentist in 2 years, and not planning a future oral care visit. Racio-ethnically minoritized patients may experience the unjust double bind of resolving urgent dental or completing preventive services needs amidst being treated in a discriminatory manner or without dignity. Oral health stakeholders should invest more effort to understand relationships between racism and oral health outcomes and introduce evidence-based interventions to ultimately abolish this societal harm.

Conceptualizing inequities and oppression in oral health research.

Major sociohistorical processes have profound effects on oral health, with impacts experienced through structural oppression manifested in policies and practices across the lifespan. Structural oppression drives oral health inequities and impacts population-level oral health. In this global perspective paper, we challenge old assumptions about oral health inequities, address misleading conceptualizations in their description and operation and reframe oral health through the lens of intersecting systems of oppression. Furthermore, we emphasize the need for oral health researchers to explore causal pathways through which oppression harms oral health and engage in social science concepts to understand the root causes of oral health inequities fully. Finally, we call on policymakers, dental scholars and decision makers to consider health equity in all policies and to take a systems-oriented approach to effectively address oral health inequities.