Inhibition of Soluble Epoxide Hydrolase Reduces Inflammation and Myocardial Injury in Arrhythmogenic Cardiomyopathy.

Previous studies have implicated persistent innate immune signaling in the pathogenesis of arrhythmogenic cardiomyopathy (ACM), a familial non-ischemic heart muscle disease characterized by life-threatening arrhythmias and progressive myocardial injury. Here, we provide new evidence implicating inflammatory lipid autocoids in ACM. We show that specialized pro-resolving lipid mediators are reduced in hearts of Dsg2mut/mut mice, a well characterized mouse model of ACM. We also found that ACM disease features can be reversed in rat ventricular myocytes expressing mutant JUP by the pro-resolving epoxy fatty acid (EpFA) 14,15-eicosatrienoic acid (14-15-EET), whereas 14,15-EE-5(Z)E which antagonizes actions of the putative 14,15-EET receptor, intensified nuclear accumulation of the desmosomal protein plakoglobin. Soluble epoxide hydrolase (sEH), an enzyme that rapidly converts pro-resolving EpFAs into polar, far less active or even pro-inflammatory diols, is highly expressed in cardiac myocytes in Dsg2mut/mut mice. Inhibition of sEH prevented progression of myocardial injury in Dsg2mut/mut mice and led to recovery of contractile function. This was associated with reduced myocardial expression of genes involved in the innate immune response and fewer pro-inflammatory macrophages expressing CCR2, which mediate myocardial injury in Dsg2mut/mut mice. These results suggest that pro-inflammatory eicosanoids contribute to the pathogenesis of ACM and, further, that inhibition of sEH may be an effective, mechanism-based therapy for ACM patients.

The protein-only RNase Ps, endonucleases that cleave pre-tRNA: Biological relevance, molecular architectures, substrate recognition and specificity, and protein interactomes.

Protein-only RNase P (PRORP) is an essential enzyme responsible for the 5' maturation of precursor tRNAs (pre-tRNAs). PRORPs are classified into three categories with unique molecular architectures, although all three classes of PRORPs share a mechanism and have similar active sites. Single subunit PRORPs, like those found in plants, have multiple isoforms with different localizations, substrate specificities, and temperature sensitivities. Most recently, Arabidopsis thaliana PRORP2 was shown to interact with TRM1A and B, highlighting a new potential role between these enzymes. Work with At PRORPs led to the development of a ribonuclease that is being used to protect against plant viruses. The mitochondrial RNase P complex, found in metazoans, consists of PRORP, TRMT10C, and SDR5C1, and has also been shown to have substrate specificity, although the cause is unknown. Mutations in mitochondrial tRNA and mitochondrial RNase P have been linked to human disease, highlighting the need to continue understanding this complex. The last class of PRORPs, homologs of Aquifex RNase P (HARPs), is found in thermophilic archaea and bacteria. This most recently discovered type of PRORP forms a large homo-oligomer complex. Although numerous structures of HARPs have been published, it is still unclear how HARPs bind pre-tRNAs and in what ratio. There is also little investigation into the substrate specificity and ideal conditions for HARPs. Moving forward, further work is required to fully characterize each of the three classes of PRORP, the pre-tRNA binding recognition mechanism, the rules of substrate specificity, and how these three distinct classes of PRORP evolved. This article is categorized under: RNA Structure and Dynamics > RNA Structure, Dynamics and Chemistry RNA Structure and Dynamics > Influence of RNA Structure in Biological Systems.

Enhancing cancer immunotherapy via inhibition of soluble epoxide hydrolase.

Cancer therapy, including immunotherapy, is inherently limited by chronic inflammation-induced tumorigenesis and toxicity within the tumor microenvironment. Thus, stimulating the resolution of inflammation may enhance immunotherapy and improve the toxicity of immune checkpoint inhibition (ICI). As epoxy-fatty acids (EpFAs) are degraded by the enzyme soluble epoxide hydrolase (sEH), the inhibition of sEH increases endogenous EpFA levels to promote the resolution of cancer-associated inflammation. Here, we demonstrate that systemic treatment with ICI induces sEH expression in multiple murine cancer models. Dietary omega-3 polyunsaturated fatty acid supplementation and pharmacologic sEH inhibition, both alone and in combination, significantly enhance anti-tumor activity of ICI in these models. Notably, pharmacological abrogation of the sEH pathway alone or in combination with ICI counter-regulates an ICI-induced pro-inflammatory and pro-tumorigenic cytokine storm. Thus, modulating endogenous EpFA levels through dietary supplementation or sEH inhibition may represent a unique strategy to enhance the anti-tumor activity of paradigm cancer therapies.

Vascular Endothelial Growth Factor-C Treatment Enhances Cerebrospinal Fluid Outflow during Toxoplasma gondii Brain Infection but Does Not Improve Cerebral Edema.

Cerebral edema frequently develops in the setting of brain infection and can contribute to elevated intracranial pressure, a medical emergency. How excess fluid is cleared from the brain is not well understood. Previous studies have shown that interstitial fluid is transported out of the brain along perivascular channels that collect into the cerebrospinal fluid (CSF)-filled subarachnoid space. CSF is then removed from the central nervous system through venous and lymphatic routes. The current study tested the hypothesis that increasing lymphatic drainage of CSF would promote clearance of cerebral edema fluid during infection with the neurotropic parasite Toxoplasma gondii. Fluorescent microscopy and magnetic resonance imaging was used to show that C57BL/6 mice develop vasogenic edema 4 to 5 weeks after infection with T. gondii. Tracer experiments were used to evaluate how brain infection affects meningeal lymphatic function, which demonstrated a decreased rate in CSF outflow in T. gondii-infected mice. Next, mice were treated with a vascular endothelial growth factor (VEGF)-C-expressing viral vector, which induced meningeal lymphangiogenesis and improved CSF outflow in chronically infected mice. No difference in cerebral edema was observed between mice that received VEGF-C and those that rececived sham treatment. Therefore, although VEGF-C treatment can improve lymphatic outflow in mice infected with T. gondii, this effect does not lead to increased clearance of edema fluid from the brains of these mice.

Bacterial RNA-free RNase P: Structural and functional characterization of multiple oligomeric forms of a minimal protein-only ribonuclease P.

tRNAs are typically transcribed with extended 5' and 3' ends that must be removed before they attain their active form. One of the first steps of tRNA processing in nearly every organism is the removal of the 5' leader sequence by ribonuclease P (RNase P). Here, we investigate a recently discovered class of RNase P enzymes, Homologs of Aquifex RNase P (HARPs). In contrast to other RNase Ps, HARPs consist only of a metallonuclease domain and lack the canonical substrate recognition domain essential in other classes of proteinaceous RNase P. We determined the cryo-EM structure of Aquifex aeolicus HARP (Aq880) and two crystal structures of Hydrogenobacter thermophilus HARP (Hth1307) to reveal that both enzymes form large ring-like assemblies: a dodecamer in Aq880 and a tetradecamer in Hth1307. In both oligomers, the enzyme active site is 42 Å away from a positively charged helical region, as seen in other protein-only RNase P enzymes, which likely serves to recognize and bind the elbow region of the pre-tRNA substrate. In addition, we use native mass spectrometry to confirm and characterize the previously unreported tetradecamer state. Notably, we find that multiple oligomeric states of Hth1307 are able to cleave pre-tRNAs. Furthermore, our single-turnover kinetic studies indicate that Hth1307 cleaves pre-tRNAs from multiple species with a preference for native substrates. These data provide a closer look at the nuanced similarities and differences in tRNA processing across disparate classes of RNase P.

Diverse Durham collection phages demonstrate complex BREX defense responses.

Bacteriophages (phages) outnumber bacteria ten-to-one and cause infections at a rate of 1025 per second. The ability of phages to reduce bacterial populations makes them attractive alternative antibacterials for use in combating the rise in antimicrobial resistance. This effort may be hindered due to bacterial defenses such as Bacteriophage Exclusion (BREX) that have arisen from the constant evolutionary battle between bacteria and phages. For phages to be widely accepted as therapeutics in Western medicine, more must be understood about bacteria-phage interactions and the outcomes of bacterial phage defense. Here, we present the annotated genomes of 12 novel bacteriophage species isolated from water sources in Durham, UK, during undergraduate practical classes. The collection includes diverse species from across known phylogenetic groups. Comparative analyses of two novel phages from the collection suggest they may be founding members of a new genus. Using this Durham phage collection, we determined that particular BREX defense systems were likely to confer a varied degree of resistance against an invading phage. We concluded that the number of BREX target motifs encoded in the phage genome was not proportional to the degree of susceptibility. IMPORTANCE Bacteriophages have long been the source of tools for biotechnology that are in everyday use in molecular biology research laboratories worldwide. Phages make attractive new targets for the development of novel antimicrobials. While the number of phage genome depositions has increased in recent years, the expected bacteriophage diversity remains underrepresented. Here we demonstrate how undergraduates can contribute to the identification of novel phages and that a single City in England can provide ample phage diversity and the opportunity to find novel technologies. Moreover, we demonstrate that the interactions and intricacies of the interplay between bacterial phage defense systems such as Bacteriophage Exclusion (BREX) and phages are more complex than originally thought. Further work will be required in the field before the dynamic interactions between phages and bacterial defense systems are fully understood and integrated with novel phage therapies.

Regulation of inflammation in cancer by dietary eicosanoids.

BACKGROUND: Cancer is a major burden of disease worldwide and increasing evidence shows that inflammation contributes to cancer development and progression. Eicosanoids are derived from dietary polyunsaturated fatty acids, such as arachidonic acid (AA), and are mainly produced by a series of enzymatic pathways that include cyclooxygenase (COX), lipoxygenase (LOX), and cytochrome P-450 epoxygenase (CYP). Eicosanoids consist of at least several hundred individual molecules and play important roles in the inflammatory response and inflammation-related cancers. SCOPE AND APPROACH: Dietary sources of AA and biosynthesis of eicosanoids from AA through different metabolic pathways are summarized. The bioactivities of eicosanoids and their potential molecular mechanisms on inflammation and cancer are revealed. Additionally, current challenges and limitations in eicosanoid research on inflammation-related cancer are discussed. KEY FINDINGS AND CONCLUSIONS: Dietary AA generates a large variety of eicosanoids, including prostaglandins, thromboxane A2, leukotrienes, cysteinyl leukotrienes, lipoxins, hydroxyeicosatetraenoic acids (HETEs), and epoxyeicosatrienoic acids (EETs). Eicosanoids exert different bioactivities and mechanisms involved in the inflammation and related cancer developments. A deeper understanding of eicosanoid biology may be advantageous in cancer treatment and help to define cellular targets for further therapeutic development.

Toxin-antitoxin systems as mediators of phage defence and the implications for abortive infection.

Bacteria have evolved a broad range of defence mechanisms to protect against infection by their viral parasites, bacteriophages (phages). Toxin-antitoxin (TA) systems are small loci found throughout bacteria and archaea that in some cases provide phage defence. The recent explosion in phage defence system discovery has identified multiple novel TA systems with antiphage activity. Due to inherent toxicity, TA systems are thought to mediate abortive infection (Abi), wherein the host cell dies in response to phage infection, removing the phage, and protecting clonal siblings. Recent studies, however, have uncovered molecular mechanisms by which TA systems are activated by phages, how they mediate toxicity, and how phages escape the defences. These new models reveal dazzling complexity in phage-host interactions and provide further evidence that TA systems do not in all cases inherently perform classic Abi, suggesting an evolved conceptual definition is required.

Perceptions about human papillomavirus vaccine and oropharyngeal cancers, and the role of dental care providers in human papillomavirus prevention among US adults.

BACKGROUND: The authors examined adults' perceptions about the importance of the human papillomavirus (HPV) vaccine in preventing oropharyngeal cancers and dental care providers' role in HPV prevention and identified associated factors. METHODS: Adults (≥ 18 years) completed a national survey of consumer and patient attitudes, experiences, and behaviors on oral health. Descriptive and multivariable logistic regression models determined associations between perceptions regarding HPV and attitudes toward dental care providers' role and HPV knowledge, HPV vaccine recommendation, and sociodemographic characteristics. RESULTS: One in 3 adults (32.8%; n = 5,320) said the HPV vaccine was very important, 1 in 2 said it was somewhat important (48.1%), and 1 in 5 said it was not important (19.1%) in preventing mouth and throat cancers. More than one-half (56.7%) of adults had positive perceptions about dental care providers' role in HPV education and were comfortable discussing the HPV vaccine with a dental care provider (59.4%). Adults with knowledge about HPV and oral health linkage and those who received HPV vaccine recommendation from a dental care provider had 2.0 to 2.5 times higher odds of reporting positively for all 3 outcomes (P < .001). CONCLUSIONS: Most adults are comfortable discussing HPV and the HPV vaccine with their oral health care provider. Perceptions about the HPV vaccine's importance in preventing oropharyngeal cancers and the role of dental care providers in HPV prevention can be improved by means of increasing adults' knowledge about the relationship between HPV and oral health. PRACTICAL IMPLICATIONS: Dental care providers' engagement in HPV conversations with patients may increase their knowledge about the HPV and oral health linkage and their understanding of the role of the HPV vaccine in preventing oropharyngeal cancers.

Periodontal treatment associated with decreased diabetes mellitus-related treatment costs: An analysis of dental and medical claims data.

BACKGROUND: Diabetes mellitus (DM) and periodontal disease have a suggested bidirectional relationship. Researchers have reported decreases in DM-related health care costs after periodontal treatment. The authors examined the relationship between periodontal disease treatment and DM health care costs in commercial insurance and Medicaid claims data. METHODS: This study of IBM MarketScan commercial insurance and Medicaid databases included overall outpatient, inpatient, and drug costs for patients with DM. The authors examined associations between overall health care costs per patient in 2019 according to use of periodontal services from 2017 through 2018 using generalized linear modeling. The average treatment effect on treated was calculated by means of propensity score matching using a logistic model for periodontal treatment on covariates. RESULTS: For commercial insurance enrollees, periodontal treatment was associated with reduced overall health care costs of 12% compared with no treatment ($13,915 vs $15,739; average treatment effect on treated, -$2,498.20; 95% CI, -$3,057.21 to -$1,939.19; P < .001). In the Medicaid cohort, periodontal treatment was associated with a 14% decrease in costs compared with patients with DM without treatment ($14,796 vs $17,181; average treatment effect on treated, -$2,917.84; 95% CI, -$3,354.48 to -$2,480.76; P < .001). There were no significant differences in inpatient costs (commercial insurance) or drug costs (Medicaid). CONCLUSIONS: Undergoing periodontal treatment is associated with reduced overall and outpatient health care costs for patients with DM in Medicaid and commercial insurance claims data. There were no significant differences in inpatient costs for commercial insurance enrollees or in drug costs for Medicaid beneficiaries. PRACTICAL IMPLICATIONS: A healthy mouth can play a key role in DM management. Expanding Medicaid benefits to include comprehensive periodontal treatment has the potential to reduce health care costs for patients with DM.

Targeting Angiogenesis via Resolution of Inflammation.

Angiogenesis, the growth of new blood vessels, plays a critical role in tissue repair and regeneration, as well as in cancer. A paradigm shift is emerging in our understanding of the resolution of inflammation as an active biochemical process with the discovery of novel endogenous specialized pro-resolving mediators (SPMs), including resolvins. Angiogenesis and the resolution of inflammation are critical interdependent processes. Disrupted inflammation resolution can accelerate tumor growth, which is angiogenesis-dependent. SPMs, including resolvins and lipoxins, inhibit physiologic and pathological angiogenesis at nanogram concentrations. The failure of resolution of inflammation is an emerging hallmark of angiogenesis-dependent diseases including arthritis, psoriasis, diabetic retinopathy, age-related macular degeneration, inflammatory bowel disease, atherosclerosis, endometriosis, Alzheimer's disease, and cancer. Whereas therapeutic angiogenesis repairs tissue damage (e.g., limb ischemia), inhibition of pathological angiogenesis suppresses tumor growth and other non-neoplastic diseases such as retinopathies. Stimulation of resolution of inflammation via pro-resolving lipid mediators promotes the repair of tissue damage and wound healing, accelerates tissue regeneration, and inhibits cancer. Here we provide an overview of the mechanisms of cross talk between angiogenesis and inflammation resolution in chronic inflammation-driven diseases. Stimulating the resolution of inflammation via pro-resolving lipid mediators has emerged as a promising new field to treat angiogenic diseases.

Evolution of surrogate light chain in tetrapods and the relationship between lengths of CDR H3 and VpreB tails.

In the mammalian immune system, the surrogate light chain (SLC) shapes the antibody repertoire during B cell development by serving as a checkpoint for production of functional heavy chains (HC). Structural studies indicate that tail regions of VpreB contact and cover the third complementarity-determining region of the HC (CDR H3). However, some species, particularly bovines, have CDR H3 regions that may not be compatible with this HC-SLC interaction model. With immense structural and genetic diversity in antibody repertoires across species, we evaluated the genetic origins and sequence features of surrogate light chain components. We examined tetrapod genomes for evidence of conserved gene synteny to determine the evolutionary origin of VpreB1, VpreB2, and IGLL1, as well as VpreB3 and pre-T cell receptor alpha (PTCRA) genes. We found the genes for the SLC components (VpreB1, VpreB2, and IGLL1) only in eutherian mammals. However, genes for PTCRA occurred in all amniote groups and genes for VpreB3 occurred in all tetrapod groups, and these genes were highly conserved. Additionally, we found evidence of a new VpreB gene in non-mammalian tetrapods that is similar to the VpreB2 gene of eutherian mammals, suggesting VpreB2 may have appeared earlier in tetrapod evolution and may be a precursor to traditional VpreB2 genes in higher vertebrates. Among eutherian mammals, sequence conservation between VpreB1 and VpreB2 was low for all groups except rabbits and rodents, where VpreB2 was nearly identical to VpreB1 and did not share conserved synteny with VpreB2 of other species. VpreB2 of rabbits and rodents likely represents a duplicated variant of VpreB1 and is distinct from the VpreB2 of other mammals. Thus, rabbits and rodents have two variants of VpreB1 (VpreB1-1 and VpreB1-2) but no VpreB2. Sequence analysis of VpreB tail regions indicated differences in sequence content, charge, and length; where repertoire data was available, we observed a significant relationship between VpreB2 tail length and maximum DH length. We posit that SLC components co-evolved with immunoglobulin HC to accommodate the repertoire - particularly CDR H3 length and structure, and perhaps highly unusual HC (like ultralong HC of cattle) may bypass this developmental checkpoint altogether.

Assessing the Antimicrobial Properties of Copper-Iodide Doped Adhesives in an In vitro Caries Model: A Pilot Study.

Context: Recurrent caries are the leading cause of composite resin failure. Aims: The purpose of this pilot study was to test the efficacy of a novel copper iodide (CuI) containing dental adhesive in an in vitro caries model. Subjects and Methods: Streptococcus mutans and Lactobacillus acidophilus were grown individually on the complex medium for 48 h at 37°C. The pH of the mixed medium was 7.0 initially and tested every 24 h. 40 extracted teeth were prepared with standardized cavity preparations and coated with control or experimental CuI adhesives and imaged using a micro-computed tomography (microCT). Four study groups were evaluated: (1) control (2) 0.5 µg/ml CuI (3) 1.0 µg/ml CuI, 4) 5.0 µg/ml CuI. After incubation, the teeth were re-imaged using the microCT. Utilizing AnalyzePro software the three-dimensional data sets were overlaid and demineralization was measured and statistics were run. Statistics: Stratified ANOVA models were run to determine if there were differences between the control and experimental adhesive groups. Similarly, pH and bacterial concentrations were evaluated to ensure the viability of polymicrobial specimen. Results and Conclusions: Significant differences were found between the control group and the 1.0 and 5.0 CuI adhesive groups. No differences in pH were noted between the groups. Overlaid changes in demineralization were recorded as volume loss. CuI adhesives with 5 mg/ml or higher have the potential to limit tooth demineralization after bacterial penetration of a dental restoration in an in vitro caries model. Further testing is needed.

Oral Cancer Prevalence, Mortality, and Costs in Medicaid and Commercial Insurance Claims Data.

BACKGROUND: This study compared prevalence, incidence, mortality rates, treatment costs, and risk factors for oral and oropharyngeal cancer (OC/OPC) between two large United States adult cohorts in 2012-2019. METHODS: Medicaid and commercial claims data came from the IBM Watson Health MarketScan Database. Logistic regression analyses estimated incidence and risk factors for OC/OPC. Mortality was calculated by merging deceased individuals' files with those of the existing cancer cohort. Summing costs of outpatient and inpatient services determined costs. RESULTS: Prevalence of OC/OPC in Medicaid enrollees decreased each year (129.8 cases per 100,000 enrollees in 2012 to 88.5 in 2019); commercial enrollees showed a lower, more stable prevalence (64.7 per 100,000 in 2012 and 2019). Incidence trended downward in both cohorts, with higher incidence in the Medicaid (51.4-37.6 cases per 100,000) than the commercial cohort (31.9-31.0 per 100,000). Mortality rates decreased for Medicaid enrollees during 2012-2014 but increased in the commercial cohort. OC/OPC treatment costs were higher for commercial enrollees by $8.6 million during 2016-2019. OC/OPC incidence was higher among adults who were older, male, and white; used tobacco or alcohol; or had prior human immunodeficiency virus/acquired immune deficiency syndrome diagnosis and lower among those who had seen a dentist the prior year. CONCLUSIONS: Medicaid enrollees experienced higher OC/OPC incidence, prevalence, and mortality compared with commercially insured adults. Having seen a dentist within the prior year was associated with a lower risk of OC/OPC diagnosis. IMPACT: Expanding Medicaid dental benefits may allow OC/OPC to be diagnosed at earlier stages through regular dental visits.

The impact of underutilization of preventive dental care by adult Medicaid participants.

OBJECTIVE: To ascertain the financial impact associated with the underutilization of preventive dental care for adults enrolled in Medicaid. METHODS: We used adult claims data for patients aged 21-64 in the IBM Watson Marketscan Medicaid database. Enrollees were included if they had at least one dental claim in 2019 and were continuously enrolled between 2014 and 2019. We then evaluated the costs of their dental care in 2019, based on the number of years of preventive dental care they received between 2014 and 2018. We also assessed Emergency Department (ED) utilization for dental conditions, oral surgeries, and dental-related opioid prescriptions. RESULTS: The average Medicaid enrollee with five continuous years of preventive care prior to 2019 experienced 43% lower costs than an individual who received no preventive dental care at all. Most of the savings were a result of fewer oral surgeries. A Medicaid enrollee with no preventive dental visits was eight times more likely to have an ED visit for a nontraumatic dental condition (NTDC), seven times more likely to have oral surgery and six times more likely to receive a dental-related opioid prescription compared to those who had a dental prevention visit every year in the 5-year lookback period. CONCLUSIONS: Regular preventive dental care in the lookback period was associated with significant savings in overall dental care costs when compared to dental care costs for those individuals who received no or few preventive visits. Prior preventive dental care was also associated with lower rates of ED-NTDC utilization, oral surgery, and dental-related opioid prescriptions.

Comparison of two diphenyl polyenes as acid-sensitive additives during the biodegradation of a thermoset polyester polyurethane coating.

AIMS: Biochemical hydrolysis and chemical catalysis are involved in the successful biodegradation of polymers. In order to evaluate the potential separation between biochemical and chemical catalysis during the biodegradation process, we report the use of two diphenylpolyenes (DPPs), all trans-1,4-diphenylbutadiene (DPB) and all trans-1,6-diphenylhexatriene (DPH), as potential acid-sensitive indicators in polymers. METHODS AND RESULTS: 1,4-Diphenylbutadiene and DPH (0.1% w/w) were melt-cast successfully with poly(ethylene succinate) hexamethylene (PES-HM) polyurethane (thermoset polyester polyurethane) coatings above 80℃. When these two DPP/PES-HM coatings were exposed to a concentrated supernatant with significant esterase activity resulting from the growth of a recently isolated and identified strain of Tremellomycetes yeast (Naganishia albida 5307AI), the DPB coatings exhibited a measurable and reproducible localized decrease in the blue fluorescence emission in regions below where hydrolytic biodegradation was initiated in contrast with DPH blended coatings. The fluorescence changes observed in the biodegraded DPB coating were similar to exposing them to concentrated acids and not bases. CONCLUSIONS: Our experiments resulted in (1) a method to blend DPP additives into thermoset coatings, (2) the first report of the biodegradation of polyester polyurethane coating by N. albida, and (3) demonstration that hydrolytic supernatants from this strain generate acidic region within degrading polyester coatings using DPB as the indicator. SIGNIFICANCE AND IMPACT OF THE STUDY: Our experiments confirm that N. albida is an active polyester degrader and that DPB is a promising acid sensitive polymer coating additive.

Identifying the Utility of Dental Providers in Human Papillomavirus Prevention Efforts: Results From the National Health and Nutrition Examination Survey 2015-2018.

PURPOSE: The aim of this study is to (1) examine the prevalence of human papillomavirus (HPV) vaccination in adolescents and young adults in the U.S., including those who had a dental visit in the last year but not a medical visit and (2) to determine an association between last visit to the dentist and HPV vaccination status. METHODS: We conducted a cross-sectional study using data from the National Health and Nutrition Examination Survey from 2015 to 2018, including participants 9-26 years. Descriptive statistical analyses were conducted to characterize the study population and calculate the prevalence of HPV vaccination in adolescents and young adults, including those who had a dental visit in the last year but not a medical visit. Logistic regression analyses were performed to examine the association between last visit to the dentist and HPV vaccination status. RESULTS: In total, 38.6% of participants were vaccinated for HPV, with higher prevalence of vaccination in those with the following characteristics: female, older age, higher income, higher education level, and having medical insurance. Participants who had a dental visit in the last year had an HPV vaccination rate of 40.8%. Of those who had a dental visit and were not vaccinated for HPV, 12.5% did not have a medical visit. Having a dental visit in the last year increased the odds of being vaccinated for HPV (odds ratio 1.69, confidence interval 1.26-2.28). CONCLUSIONS: Dentists see a significant number of adolescents and young adults who are unvaccinated for HPV in a given year and could serve as an access point for HPV vaccine delivery in the future.

Evaluation of the accuracy of multiple digital impression systems on a fully edentulous maxilla.

OBJECTIVE: This study aimed to compare the accuracy performance of five different intraoral scanning systems for a full-arch scan on an edentulous cadaver maxilla. METHOD AND MATERIALS: Five digital intraoral impression systems were used to scan a fully edentulous cadaver maxilla. A master scan obtained with an ATOS Capsule industrial grade scanner provided the point of comparison. Experimental scans were compared to the master scan using a metrology software that allows images to be overlayed on one another and deviations interpreted. Once aligned, three comparisons were made between the experimental scans and the reference: the entire maxilla, the ridge area only, and the palate area only. RESULTS: Trueness deviations between the experimental scans and the master digital model were up to 0.1 mm in the 75th percentile. For the whole maxilla, only the Medit scanner had statistically significantly inferior trueness compared to other scanners. When only the palate was considered, Medit was significantly different from Element (P = .0025) and Trios 4 (P = .0040), with no differences found between other scanners. For the ridge region the results replicate the trend observed for the whole maxilla. In regard to precision, differences were found only in the whole maxilla and the ridge area. In both areas, only Medit's precision was significantly different compared to other scanners, with the exception of Element. However, Element performance was similar to all other scanners. CONCLUSION: Most intraoral scanners exhibited similar performance. Although several statistically significant differences were identified, the clinical impact of these variances is probably not meaningful. (Quintessence Int 2021;52:488-495; doi: 10.3290/j.qi.b1244373).

Brain capillary pericytes exert a substantial but slow influence on blood flow.

The majority of the brain's vasculature is composed of intricate capillary networks lined by capillary pericytes. However, it remains unclear whether capillary pericytes influence blood flow. Using two-photon microscopy to observe and manipulate brain capillary pericytes in vivo, we find that their optogenetic stimulation decreases lumen diameter and blood flow, but with slower kinetics than similar stimulation of mural cells on upstream pial and precapillary arterioles. This slow vasoconstriction was inhibited by the clinically used vasodilator fasudil, a Rho-kinase inhibitor that blocks contractile machinery. Capillary pericytes were also slower to constrict back to baseline following hypercapnia-induced dilation, and slower to dilate towards baseline following optogenetically induced vasoconstriction. Optical ablation of single capillary pericytes led to sustained local dilation and a doubling of blood cell flux selectively in capillaries lacking pericyte contact. These data indicate that capillary pericytes contribute to basal blood flow resistance and slow modulation of blood flow throughout the brain.