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.

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.

Aerosol and spatter mitigation in dentistry: Analysis of the effectiveness of 13 setups.

OBJECTIVES: The current study aims to investigate the aerosol and spatter mitigation quality of 13 dry-field isolation methods in a simulated setup that replicates real-life work scenarios encountered in dental practices. METHODS: A crown preparation on a manikin was performed on tooth number 30 and repeated five times for each setup to simulate a patient under care. Aerosol, environmental, and operator face shield spatter, and sound intensity was measured. Generalized linear mixed models were used, and posthoc pairwise comparisons were performed to compare least-squares means when appropriate using a Tukey adjustment. RESULTS: All tested setups showed some environmental spatter formation; however, these were able to control most (and in some cases all) spatter on the operator face shield. All methods resulted in excellent aerosol mitigation when a second line of high-volume evacuation (HVE) was added to the device setup. However, in most setups, total sound levels exceeded 85 dB, posing a concern for prolonged noise exposure. CONCLUSIONS: The Prototype device and four other tested setups with secondary HVE addition completely eliminated aerosol creation as tested. Spatter of the Face Shield was best eliminated using the Prototype device. CLINICAL SIGNIFICANCE: Within the limitations of this study, it can be concluded that the dental community has at its disposal equipment that can effectively mitigate aerosol and spatter.

The effect different substrates have on the trueness and precision of eight different intraoral scanners.

OBJECTIVE: This in vitro study compares the newest generation of intraoral scanners to their older counterparts, and tests whether material substrates affect the trueness and precision of intraoral scanners (IOS). MATERIAL AND METHODS: A custom model, used as the reference standard, was fabricated with teeth composed of different dental materials. The reference standard scan was obtained using a three-dimensional (3D) optical scanner, the ATOS III. Experimental scans were obtained using eight different IOS, operated by experienced clinicians, using the manufacturer's recommended scanning strategy. A comprehensive metrology program, Geomagic Control X, was used to compare the reference standard scan with the experimental scans. RESULTS: For all scanners tested, except Trios3, the substrate does influence the trueness and precision of the scan. Furthermore, differences exist when comparing the same substrate across different scanners with some of the latest generation scanners clearly leaping ahead of the older generation regarding both trueness and precision. CONCLUSIONS: Substrate type affects the trueness and precision of a scan. Active Triangulation scanners are more sensitive to substrate differences than their parallel confocal counterparts. Some scanners scan certain substrates better, but in general the new generation of scanners outperforms the old, across all substrates. CLINICAL SIGNIFICANCE: The substrates being scanned play an import role in the trueness and precision of the 3D model. The new generation of scanners is remarkably accurate across all substrates and for complete-arch scanning.

Effect of scan pattern on complete-arch scans with 4 digital scanners.

STATEMENT OF PROBLEM: Complete-arch digital scans are becoming popular as digital dentistry is adopted for expanded clinical situations such as complete-arch prostheses, removable prostheses, extensive implant-supported treatment, and orthodontic aligners. Whether the scan pattern technique affects the trueness and precision of complete-arch scans and whether differences in accuracy exist among different scanners remain unclear. Furthermore, each manufacturer recommends a different scan pattern, but evidence of the superiority of the manufacturer's recommended pattern is lacking. PURPOSE: The purpose of this in vitro study was to determine whether the scan pattern affects the trueness, precision, and speed of complete-arch digital scans performed by using 4 different digital scanning systems. MATERIAL AND METHODS: A custom model used as the reference standard was fabricated with teeth having the same refractive index as dentin and enamel to simulate the natural dentition. The scan of the custom typodont was obtained by using an ATOS III Triple Scan 3D optical scanner. This study evaluated the CEREC Omnicam, Planmeca Emerald, Align iTero Element, and 3Shape TRIOS 3. Experimental scans were obtained from each of the 4 different digital scanning systems by using 4 unique scan patterns by experienced clinicians. Four experimental scans were acquired from each of the scanners by using 4 distinct scan patterns for a total of 16 scans for each scanner. Scan patterns 1 to 4 were based on the operator manuals for each different scanner. The scan time was recorded for each scan. All experimental scans were converted to standard tessellation language (STL) format, and a comprehensive metrology program, Geomagic Control X, was used to compare the reference standard scan with the experimental scans. RESULTS: For trueness, the scanner (P<.001), scan pattern (P=.001), and their interaction (P<.001) were found to be significant. Overall, scan pattern 2 showed the highest average trueness and precision. Likewise, for overall scan pattern precision, the scanner, scan pattern, and their interaction were found to be significant (P<.001). CONCLUSIONS: Scan pattern affected trueness and precision for some scanners, but not for others. Differences exist in the complete-arch scan speed, trueness, and precision of individual scanners. Scan pattern can play an important role in the success of digital scanning.

Peptidoglycan degradation machinery in Clostridium difficile forespore engulfment.

Clostridium difficile remains the leading cause of antibiotic-associated diarrhoea in hospitals worldwide, linked to significant morbidity and mortality. As a strict anaerobe, it produces dormant cell forms - spores - which allow it to survive in the aerobic environment. Importantly, spores are the transmission agent of C. difficile infections. A key aspect of sporulation is the engulfment of the future spore by the mother cell and several proteins have been proposed to be involved. Here, we investigated the role of the SpoIID, SpoIIM and SpoIIP (DMP) machinery and its interplay with the SpoIIQ:SpoIIIAH (Q:AH) complex in C. difficile. We show that, surprisingly, SpoIIM, the proposed machinery anchor, is not required for efficient engulfment and sporulation. We demonstrate the requirement of DP for engulfment due to their sequential peptidoglycan degradation activity, both in vitro and in vivo. Finally, new interactions within DMP and between DMP and Q:AH suggest that both systems form a single engulfment machinery to keep the mother cell and forespore membranes together throughout engulfment. This work sheds new light upon the engulfment process and on how different sporeformers might use the same components in different ways to drive spore formation.

Effect of scan substrates on accuracy of 7 intraoral digital impression systems using human maxilla model.

OBJECTIVE: This study aimed to determine how the accuracy of digital impressions was affected by four common dental substrates using seven prevalent IOS systems to scan the complete arch of a human maxilla. SETTING AND SAMPLE POPULATION: The Department of Oral Rehabilitation at the Medical University of South Carolina. A single cadaver maxilla. MATERIALS AND METHODS: Seven digital intraoral impression systems were used to scan a freshly harvested human maxilla. The maxilla contained several teeth restored with amalgam and composite, as well as unrestored teeth characterized by enamel. Also, three teeth were prepared for full coverage restorations to expose natural dentin. An industrial grade metrology software program that allowed 3D overlay and dimensional computation compared deviations of the complete arch and its substrates on the test model from the reference model. RESULTS: Substrates were significantly different from each other when considering scan data as a whole, as well as when comparing IOS devices individually. Only PlanScan failed to reveal trueness differences between the different substrates, while only Emerald revealed precision differences between the substrates. CONCLUSIONS: Substrate type does impact the overall accuracy of intraoral scans with dentin being the most accurate and enamel being the least accurate. The four substrates scanned impacted the trueness of all IOS devices.

The engulfasome in C. difficile: Variations on protein machineries.

Clostridioides difficile infection (CDI) continues to be a substantial healthcare burden, and the changing disease profile raises new challenges in CDI management, both in clinical settings and in the community. CDI is transmitted by spores, which are formed by a subset of the cell population where an asymmetric septum is formed. A full copy of the chromosome is transported into the smaller compartment which is then engulfed by the mother cell. After engulfment, multiple metabolic and morphological changes occur, eventually resulting in the release of the mature spore. Whilst studies in the model organism Bacillus subtilis have demonstrated the importance of the DMP and Q:AH machineries in engulfment, it is becoming clear that there are fundamental differences in the way the two organisms organise these machineries. As spores are the infectious agent in CDI, it is crucial to understand how these dormant cells are formed, and how sporulation can be prevented or disrupted with the view of reducing CDI. Here, we review the current literature on the DMP and Q:AH machineries in C. difficile, and how they compare and contrast to those of B. subtilis.

Evaluation of the trueness and precision of complete arch digital impressions on a human maxilla using seven different intraoral digital impression systems and a laboratory scanner.

OBJECTIVES: An impression accuracy study using a cadaver maxilla was performed using both prepared and intact teeth as well as palatal tissue. MATERIALS AND METHODS: Three crown preparations were performed on a cadaver maxilla. Seven different digital impression systems along with polyvinylsiloxane impressions were used to create digital models of the maxilla. Three-dimensional (3D) files of the experimental models were compared to a master model. The 3D files were overlaid and analyzed using a comparison software to create color coded figures that were measured for deviations between the master and experimental models. RESULTS: For scanning tooth structure, only the Planscan was significantly less accurate than the rest of impression techniques. No significant differences in accuracy were found between models created using digital impressions and those created from traditional vinyl polysiloxane impressions with cross arch deviations ranging from 18 to 39 µm for each. CONCLUSIONS: Impressions taken using all digital impression systems, save for the Planscan, were able to accurately replicate the tissues of a complete arch human maxilla. CLINICAL SIGNIFICANCE: Studies examining accuracy of digital impression systems have generally been performed on materials other than dental tissues. Optically, materials such as plastic and metal have properties different from enamel and dentin. This study evaluates accuracy of digital impression systems on human dentin, enamel, and soft tissues.

Evaluation of removable partial denture frameworks fabricated using 3 different techniques.

STATEMENT OF PROBLEM: Rapid advancements in computer-aided design and computer-aided manufacturing (CAD-CAM) have opened new pathways in the fabrication of removable partial dentures (RPDs) through additive and subtractive processes. Questions remain whether the digital pathway is an acceptable one compared with conventional analog or combined analog and digital pathways. PURPOSE: The purpose of this clinical study was to determine the quality of RPD frameworks fabricated using 3 different fabrication methods: analog, combined analog-digital, and digital. MATERIAL AND METHODS: Three RPD frameworks were fabricated for each of the 9 participants using each of the 3 techniques. Of the 9 participants enrolled, 4 were of Kennedy class I, 3 were of Kennedy class II, and 2 were of Kennedy class III. The first technique was completely analog: a physical impression was made using polyvinyl siloxane, stone casts were made, a survey was performed, and a laboratory technician waxed and cast the RPD framework. The combined analog-digital workflow had the analog steps, but the stone cast was scanned with a laboratory scanner to generate a digital cast. The 3Shape CAD software was then used to design a digital RPD, which was fabricated from a cobalt-chroumum alloy by selective laser melting. The third technique was completely digital: an intraoral digital scanner was used to make a definitive scan, which was sent to the 3Shape software for digitally designing the RPD framework and subsequent selective laser melting for fabrication. For all frameworks in the same participant, the same design was used for consistency. The evaluation consisted of a yes/no survey with 7 framework-related parameters and was completed by 5 clinicians. For statistics, an overall P value was calculated using a chi-squared test to determine any difference among the groups (α=.05). RESULTS: Seven of the 9 participants received the framework fabricated using the digital pathway as their definitive prosthesis. The completely digital method was significantly better than the traditional method of analog fabrication (P<.001). Intraoral scanning was also significantly better than the combined method of fabrication (P<.001). The completely analog method was better than the combined method of framework fabrication (P=.008). CONCLUSIONS: Within the limitations of this clinical study, it was concluded that the combined analog-digital pathway of RPD fabrication was the least clinically acceptable one as determined by 5 calibrated clinicians using a yes/no questionnaire, whereas the completely digital method of fabrication was found to be the best.

Capturing Upper Limb Gross Motor Categories Using the Kinect® Sensor.

IMPORTANCE: Along with growth in telerehabilitation, a concurrent need has arisen for standardized methods of tele-evaluation. OBJECTIVE: To examine the feasibility of using the Kinect sensor in an objective, computerized clinical assessment of upper limb motor categories. DESIGN: We developed a computerized Mallet classification using the Kinect sensor. Accuracy of computer scoring was assessed on the basis of reference scores determined collaboratively by multiple evaluators from reviewing video recording of movements. In addition, using the reference score, we assessed the accuracy of the typical clinical procedure in which scores were determined immediately on the basis of visual observation. The accuracy of the computer scores was compared with that of the typical clinical procedure. SETTING: Research laboratory. PARTICIPANTS: Seven patients with stroke and 10 healthy adult participants. Healthy participants intentionally achieved predetermined scores. OUTCOMES AND MEASURES: Accuracy of the computer scores in comparison with accuracy of the typical clinical procedure (immediate visual assessment). RESULTS: The computerized assessment placed participants' upper limb movements in motor categories as accurately as did typical clinical procedures. CONCLUSIONS AND RELEVANCE: Computerized clinical assessment using the Kinect sensor promises to facilitate tele-evaluation and complement telehealth applications. WHAT THIS ARTICLE ADDS: Computerized clinical assessment can enable patients to conduct evaluations remotely in their homes without therapists present.

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.

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.

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.

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.

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.