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PURPOSE: To assess the prevalence of caries experience and periodontal pathology on third molar teeth compared with first and second molars and teeth more anterior from subjects who had data collected over time in a longitudinal clinical study. PATIENTS AND METHODS: Healthy subjects with 4 asymptomatic third molars and data for at least 4 years after enrollment were included in these analyses. The presence or absence of caries experience on the occlusal surface of the third molars and any surface of the first or second molars was assessed using a visual-tactile caries examination. Full mouth periodontal probing, 6 sites per tooth, was conducted as a measure of clinical periodontal status. The primary outcome measures were at least 1 periodontal probing depth of at least 4 mm versus none, and caries experience versus no caries experience. The prevalence of caries experience and periodontal pathologic findings at follow-up and the relationship of the occurrence between the third molars and teeth more anterior in the mouth were examined using McNemar's statistics. RESULTS: The follow-up was a median of 6.9 years (interquartile range 4.6 to 7.7 years) for 179 subjects, with a mean age of 29 years. More subjects were female (54%) and white (80%). At follow-up, 85% of the subjects had caries experience detected on the first or second molars, and only 50% had a third molar affected. In contrast, at follow-up, the presence of at least 1 periodontal probing depth of at least 4 mm was marginally more prevalent on the third molars than on the first or second molars (56% and 50%, respectively). Fewer subjects had third molars free of caries experience and periodontal pathology at follow-up compared with at enrollment (28% versus 38%, respectively). CONCLUSIONS: The prevalence of both third molar caries experience and third molar periodontal pathology increased from baseline to the follow-up examination. At follow-up, the prevalence of caries experience was greater on the first or second molars than on the third molars, and periodontal pathology were greater on the third molars than on the more anterior teeth. [ABSTRACT FROM AUTHOR]

PURPOSE: We assessed the prevalence of caries experience and periodontal pathology on asymptomatic third molars in young adults. SUBJECTS AND METHODS: Healthy subjects with 4 asymptomatic third molars were enrolled in an institutional review board-approved study during a 5-year period. Full mouth periodontal probing, 6 sites per tooth, was the measure of clinical periodontal status. The presence or absence of occlusal caries experience (carious lesions or restorations, including sealants) on third molars and on any surface of the first and second molars were assessed using a visual-tactile examination and panoramic radiographs. The primary outcome measures were at least 1 periodontal probing depth of at least 4 mm versus none and caries experience versus no caries experience. RESULTS: The data were analyzed from 409 subjects, who averaged 25 years old. More subjects were female (53%) and white (76%). More subjects had at least 1 periodontal probing depth of 4 mm or deeper on a third molar (55%) than on the distal of a second molar (46%). These findings were more likely to be detected around a third molar in subjects with all third molars at the occlusal plane (72%) than in subjects with at least one third molar below (33%). Overall, fewer subjects were affected by third molar caries experience than first or second molars (24% vs 73%, respectively). Of the subset of subjects with all four third molars at the occlusal plane, 26% were affected by both third molar periodontal pathology and caries experience and 16% were caries and periodontal pathology free. CONCLUSIONS: In these cross-sectional analyses, periodontal pathology was detected more frequently on third molars than on first and second molars and caries experience was detected more frequently on first and second molars than on third molars. [ABSTRACT FROM AUTHOR]

Abstract Background To describe how frequently harm is reported in the abstract of high impact factor medical journals. Methods Design and population: We carried out a blinded structured review of a random sample of 363 Randomised Controlled Trials (RCTs) carried out on human beings, and published in high impact factor medical journals in 2003. Main endpoint: 1) Proportion of articles reporting harm in the abstract; and 2) Proportion of articles that reported harm in the abstract when harm was reported in the main body of the article. Analysis: Corrected Prevalence Ratio (cPR) and its exact confidence interval were calculated. Non-conditional logistic regression was used. Results 363 articles and 407 possible comparisons were studied. Overall, harm was reported in 135 abstracts [37.2% (CI95%:32.2 to 42.4)]. Harm was reported in the main text of 243 articles [66.9% (CI95%: 61.8 to 71.8)] and was statistically significant in 54 articles [14.9% (CI95%: 11.4 to 19.0)]. Among the 243 articles that mentioned harm in the text, 130 articles [53.5% (CI95% 47.0 to 59.9)] reported harm in the abstract; a figure that rose to 75.9% (CI95%: 62.4 to 86.5) when the harm reported in the text was statistically significant. Harm in the abstract was more likely to be reported when statistically significant harm was reported in the main body of the article [cPR = 1.70 (CI95% 1.47 to 1.92)] and when drug companies (not public institutions) funded the RCTs [cPR = 1.29 (CI95% 1.03 to 1.67)]. Conclusion Abstracts published in high impact factor medical journals underreport harm, even when harm is reported in the main body of the article.

Inborn errors of metabolism (IEMs) and immunity (IEIs) are Mendelian diseases in which complex phenotypes and patient rarity have limited clinical understanding. Whereas few genes have been annotated as contributing to both IEMs and IEIs, immunometabolic demands suggested greater functional overlap. Here, CRISPR screens tested IEM genes for immunologic roles and IEI genes for metabolic effects and found considerable previously unappreciated crossover. Analysis of IEMs showed that N-linked glycosylation and the hexosamine pathway enzyme Gfpt1 are critical for T cell expansion and function. Further, T helper (T H 1) cells synthesized uridine diphosphate N -acetylglucosamine more rapidly and were more impaired by Gfpt1 deficiency than T H 17 cells. Screening IEI genes found that Bcl11b promotes the CD4 T cell mitochondrial activity and Mcl1 expression necessary to prevent metabolic stress. Thus, a high degree of functional overlap exists between IEM and IEI genes, and immunometabolic mechanisms may underlie a previously underappreciated intersection of these disorders.

Histone deacetylase 3 (Hdac3) is an epigenetic regulator of gene expression and interacts with skeletal transcription factors such as Runx2. We previously reported that conditional deletion of Hdac3 in Osterix-Cre recombinase-expressing osteoprogenitor cells (Hdac3 CKOOsx) caused osteopenia and increased marrow adiposity, both hallmarks of skeletal aging. We also showed that Runx2+ cells within osteogenic cultures of Hdac3-depleted bone marrow stromal cells (BMSCs) contain lipid droplets (LDs). Cellular senescence, a nonproliferative metabolically active state, is associated with increased marrow adiposity, bone loss, and aging. In this study, we sought to determine if Hdac3 depleted Runx2+ pre-osteoblasts from young mice exhibit chromatin changes associated with early cellular senescence and how these events correlate with the appearance of LDs. We first confirmed that BMSCs from Hdac3 CKOOsx mice have more Runx2 + LD+ cells compared with controls under osteogenic conditions. We then measured senescence-associated distention of satellite (SADS) DNA and telomere-associated foci (TAFs) in Hdac3 CKOOsx and control BMSCs. In situ, Runx2+ cells contained more SADS per nuclei in Hdac3 CKOOsx femora than in controls. Runx2+ BMSCs from Hdac3 CKOOsx mice also contained more SADS and TAFs per nuclei than Runx2+ cells from age-matched control mice in vitro. SADs and TAFs were present at similar levels in Runx2 + LD+ cells and Runx2 + LD- cells from Hdac3 CKOOsx mice. Hdac inhibitors also increased the number of SADS in Runx2 + LD+ and Runx2 + LD- WT BMSCs. Senolytics reduced viable cell numbers in Hdac3 CKOOsx BMSC cultures. These data demonstrate that the depletion of Hdac3 in osteochondral progenitor cells triggers LD formation and early events in cellular senescence in Runx2+ BMSCs through mutually exclusive mechanisms., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Karl Friston's free-energy principle casts agents as self-evidencing through active inference. This implies that decision-making, planning and information-seeking are, in a generic sense, 'wishful'. We take an interdisciplinary perspective on this perplexing aspect of the free-energy principle and unpack the epistemological implications of wishful thinking under the free-energy principle. We use this epistemic framing to discuss the emergence of biases for self-evidencing agents. In particular, we argue that this elucidates an optimism bias as a foundational tenet of self-evidencing. We allude to a historical precursor to some of these themes, interestingly found in Machiavelli's oeuvre, to contextualise the universal optimism of the free-energy principle.

While causal reasoning is a core facet of our cognitive abilities, its time-course has not received proper attention. As the duration of reasoning might prove crucial in understanding the underlying cognitive processes, we asked participants in two experiments to make probabilistic causal inferences while manipulating time pressure. We found that participants are less accurate under time pressure, a speed-accuracy-tradeoff, and that they respond more conservatively. Surprisingly, two other persistent reasoning errors-Markov violations and failures to explain away-appeared insensitive to time pressure. These observations seem related to confidence: Conservative inferences were associated with low confidence, whereas Markov violations and failures to explain were not. These findings challenge existing theories that predict an association between time pressure and all causal reasoning errors including conservatism. Our findings suggest that these errors should not be attributed to a single cognitive mechanism and emphasize that causal judgements are the result of multiple processes., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Kolvoort et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

A method to assemble (hetero)aryl sulfonamides via the reductive coupling of aryl sulfinates and nitroarenes is reported. Various reducing conditions with sodium bisulfite and with or without tin(II) chloride in DMSO were developed using an ultrasound bath to improve reaction homogeneity and mixing. A range of (hetero)aryl sulfonamides bearing a selection of functional groups were prepared, and the mechanism of the transformation was investigated. These investigations have led us to propose the formation of nitrosoarene intermediates, which were established via an independent molecular coupling strategy.

Mononuclear phagocytes (MPs) play a crucial role in tissue homeostasis; however, MPs also contribute to tumor progression and resistance to immune checkpoint blockade (ICB). Targeting MPs could be an effective strategy to enhance ICB efficacy. We report that protein kinase C delta (PKCδ), a serine/threonine kinase, is abundantly expressed by MPs in human and mouse tumors. PKCδ -/- mice displayed reduced tumor progression compared to wild types, with increased response to anti-PD-1. Tumors from PKCδ -/- mice demonstrated T H 1-skewed immune response including increased antigen presentation and T cell activation. Depletion of MPs in vivo altered tumor growth in control but not PKCδ -/- mice. Coinjection of PKCδ -/- M2-like macrophages with cancer cells into wild-type mice markedly delayed tumor growth and significantly increased intratumoral T cell activation compared to PKCδ +/+ controls. PKCδ deficiency reprogrammed MPs by activating type I and type II interferon signaling. Thus, PKCδ might be targeted to reprogram MPs to augment ICB efficacy.

GPR61 is an orphan GPCR related to biogenic amine receptors. Its association with phenotypes relating to appetite makes it of interest as a druggable target to treat disorders of metabolism and body weight, such as obesity and cachexia. To date, the lack of structural information or a known biological ligand or tool compound has hindered comprehensive efforts to study GPR61 structure and function. Here, we report a structural characterization of GPR61, in both its active-like complex with heterotrimeric G protein and in its inactive state. Moreover, we report the discovery of a potent and selective small-molecule inverse agonist against GPR61 and structural elucidation of its allosteric binding site and mode of action. These findings offer mechanistic insights into an orphan GPCR while providing both a structural framework and tool compound to support further studies of GPR61 function and modulation., (© 2023. Springer Nature Limited.)

Activated T cells undergo metabolic reprogramming to meet anabolic, differentiation, and functional demands. Glutamine supports many processes in activated T cells, and inhibition of glutamine metabolism alters T cell function in autoimmune disease and cancer. Multiple glutamine-targeting molecules are under investigation, yet the precise mechanisms of glutamine-dependent CD8 T cell differentiation remain unclear. We show that distinct strategies of glutamine inhibition by glutaminase-specific inhibition with small molecule CB-839, pan-glutamine inhibition with 6-diazo-5-oxo-l-norleucine (DON), or by glutamine-depleted conditions (No Q) produce distinct metabolic differentiation trajectories in murine CD8 T cells. T cell activation with CB-839 treatment had a milder effect than did DON or No Q treatment. A key difference was that CB-839-treated cells compensated with increased glycolytic metabolism, whereas DON and No Q-treated cells increased oxidative metabolism. However, all glutamine treatment strategies elevated CD8 T cell dependence on glucose metabolism, and No Q treatment caused adaptation toward reduced glutamine dependence. DON treatment reduced histone modifications and numbers of persisting cells in adoptive transfer studies, but those T cells that remained could expand normally upon secondary Ag encounter. In contrast, No Q-treated cells persisted well yet demonstrated decreased secondary expansion. Consistent with reduced persistence, CD8 T cells activated in the presence of DON had reduced ability to control tumor growth and reduced tumor infiltration in adoptive cell therapy. Overall, each approach to inhibit glutamine metabolism confers distinct effects on CD8 T cells and highlights that targeting the same pathway in different ways can elicit opposing metabolic and functional outcomes., (Copyright © 2023 by The American Association of Immunologists, Inc.)

Since Tversky argued that similarity judgments violate the three metric axioms, asymmetrical similarity judgments have been particularly challenging for standard, geometric models of similarity, such as multidimensional scaling. According to Tversky, asymmetrical similarity judgments are driven by differences in salience or extent of knowledge. However, the notion of salience has been difficult to operationalize, especially for perceptual stimuli for which there are no apparent differences in extent of knowledge. To investigate similarity judgments between perceptual stimuli, across three experiments, we collected data where individuals would rate the similarity of a pair of temporally separated color patches. We identified several violations of symmetry in the empirical results, which the conventional multidimensional scaling model cannot readily capture. Pothos et al. proposed a quantum geometric model of similarity to account for Tversky's findings. In the present work, we extended this model to a more general framework that can be fit to similarity judgments. We fitted several variants of quantum and multidimensional scaling models to the behavioral data and concluded in favor of the quantum approach. Without further modifications of the model, the best-fit quantum model additionally predicted violations of the triangle inequality that we observed in the same data. Overall, by offering a different form of geometric representation, the quantum geometric framework of similarity provides a viable alternative to multidimensional scaling for modeling similarity judgments, while still allowing a convenient, spatial illustration of similarity., (© 2023 Cognitive Science Society LLC.)

People historically excluded from receiving medical care in the United States, in addition to being at greater risk for SARS-CoV-2 infection, have had slower vaccine uptake due to structural barriers to availability. We present one student-run free clinic's SARS-CoV-2 vaccination program from January 15 to August 1, 2021, in Nashville, Tennessee. We tracked SARS-CoV-2 vaccine primary series completion among 273 free clinic patients with the help of medical student volunteers, who scheduled appointments and answered vaccine-related questions. We worked with our academic medical center partner to host a single-dose vaccination event at our clinic. We compared vaccine series completion in our clinic to adult vaccine completion in Davidson County, Tennessee on August 1, 2021. Of the 273 free clinic participants, 144 identified as Spanish-speaking (52.7%) and 172 (63%) had at least one qualifying comorbidity per the December 30, 2020, Tennessee COVID-19 Vaccination Plan. As such, 183 (67%) were characterized as vaccine eligible in Phase 1a2, 1b, or 1c. On August 1, 2021, 63.1% of free clinic patients had completed their primary SARS-CoV-2 vaccination series compared with 58.9% of adults in Davidson County, Tennessee (RD 4.2%, 95% CI: -1.5% to 9.9%). Spanish-speaking free clinic patients were most likely to have completed their vaccination series. We describe a framework for a patient-centered vaccination effort to reach individuals traditionally missed by large vaccination campaigns. We highlight structural hurdles experienced by vulnerable populations, including language barriers, lack of technology or reliable internet access, inflexible working schedules, lack of transportation, and vaccine misinformation., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 Published by Elsevier Inc.)

Purpose: Literature on children who are deaf or hard of hearing (DHH) suggests overall increased rates of difficulties in emotional/behavioral and adaptive functioning. However, limitations of this literature include the failure to integrate issues unique to the experience of children who are DHH, such as home and school communication modalities and the consistency of modalities across settings., Method: This study examined de-identified data from a clinical database. Data included caregiver ratings of emotional/behavioral and adaptive functioning in a diverse sample of clinically referred children who are DHH ( N  = 177). Caregivers also reported home and school communication modalities (e.g., match, partial match, different modalities). We examined mean score differences between our sample and normative samples and compared functioning across subgroups of children with various home-school communication modality combinations., Results: Consistent with the literature, we found overall increased rates of emotional/behavioral and adaptive functioning concerns on parent rating scales. Emotional/behavioral concerns did not differ among children with spoken language match, sign language match, or partial match communication modalities combinations. Within adaptive functioning, communication and functional academics were significantly lower among children with partial match home-school communication modalities. Adaptive functioning did not differ between spoken language match and sign language match groups., Conclusions: Our findings suggest possible benefits to adaptive functioning among children who are DHH when home and school communication modalities match, regardless of which modality is used.

Objective: The primary aim of this project was to apply systematic review methods to synthesize the literature on outcomes of pediatric neuropsychological services. The secondary aim was to use the results of the systematic review to identify gaps in the extant literature and describe priorities for future research. Method: We identified the relevant studies using a rigorous search strategy, collected data on methodological variables, assessed the risk of bias in the studies, summarized findings by topic and subtopic areas, identified strengths and weaknesses of the literature, and provided recommendations for future research. The outcomes measured were satisfaction, changes in resource or strategy utilization, and changes in symptoms or functioning (i.e. changes in child emotional, behavioral, cognitive, or academic problems, parent stress, or family functioning). Results: The final sources of data were 26 records, pertaining to a total of 974 children who received neuropsychological services. Parents were generally satisfied with services and reported high clinician empathy and increased level of knowledge, based on the evaluation. However, they reported less often that the neuropsychologist provided actual help. Informal home and school-based strategies were implemented more often than other types of recommendations. The research on changes in child symptoms and functioning was limited, but suggests improvements. Conclusions: This is the first systematic review of outcomes of pediatric neuropsychological services. Larger studies involving data collection at multiple time points are needed in order to further clarify mechanisms leading to outcomes and potential targets for improving them.

In recent years, cardiovascular immuno-imaging by positron emission tomography (PET) has undergone tremendous progress in preclinical settings. Clinically, two approved PET tracers hold great potential for inflammation imaging in cardiovascular patients, namely FDG and DOTATATE. While the former is a widely applied metabolic tracer, DOTATATE is a relatively new PET tracer targeting the somatostatin receptor 2 (SST2). In the current study, we performed a detailed, head-to-head comparison of DOTATATE-based radiotracers and [ 18 F]F-FDG in mouse and rabbit models of cardiovascular inflammation. For mouse experiments, we labeled DOTATATE with the long-lived isotope [ 64 Cu]Cu to enable studying the tracer's mode of action by complementing in vivo PET/CT experiments with thorough ex vivo immunological analyses. For translational PET/MRI rabbit studies, we employed the more widely clinically used [ 68 Ga]Ga-labeled DOTATATE, which was approved by the FDA in 2016. DOTATATE's pharmacokinetics and timed biodistribution were determined in control and atherosclerotic mice and rabbits by ex vivo gamma counting of blood and organs. Additionally, we performed in vivo PET/CT experiments in mice with atherosclerosis, mice subjected to myocardial infarction and control animals, using both [ 64 Cu]Cu-DOTATATE and [ 18 F]F-FDG. To evaluate differences in the tracers' cellular specificity, we performed ensuing ex vivo flow cytometry and gamma counting. In mice subjected to myocardial infarction, in vivo [ 64 Cu]Cu-DOTATATE PET showed higher differential uptake between infarcted (SUV max 1.3, IQR, 1.2-1.4, N = 4) and remote myocardium (SUV max 0.7, IQR, 0.5-0.8, N = 4, p = 0.0286), and with respect to controls (SUV max 0.6, IQR, 0.5-0.7, N = 4, p = 0.0286), than [ 18 F]F-FDG PET. In atherosclerotic mice, [ 64 Cu]Cu-DOTATATE PET aortic signal, but not [ 18 F]F-FDG PET, was higher compared to controls (SUV max 1.1, IQR, 0.9-1.3 and 0.5, IQR, 0.5-0.6, respectively, N = 4, p = 0.0286). In both models, [ 64 Cu]Cu-DOTATATE demonstrated preferential accumulation in macrophages with respect to other myeloid cells, while [ 18 F]F-FDG was taken up by macrophages and other leukocytes. In a translational PET/MRI study in atherosclerotic rabbits, we then compared [ 68 Ga]Ga-DOTATATE and [ 18 F]F-FDG for the assessment of aortic inflammation, combined with ex vivo radiometric assays and near-infrared imaging of macrophage burden. Rabbit experiments showed significantly higher aortic accumulation of both [ 68 Ga]Ga-DOTATATE and [ 18 F]F-FDG in atherosclerotic (SUV max 0.415, IQR, 0.338-0.499, N = 32 and 0.446, IQR, 0.387-0.536, N = 27, respectively) compared to control animals (SUV max 0.253, IQR, 0.197-0.285, p = 0.0002, N = 10 and 0.349, IQR, 0.299-0.423, p = 0.0159, N = 11, respectively). In conclusion, we present a detailed, head-to-head comparison of the novel SST2-specific tracer DOTATATE and the validated metabolic tracer [ 18 F]F-FDG for the evaluation of inflammation in small animal models of cardiovascular disease. Our results support further investigations on the use of DOTATATE to assess cardiovascular inflammation as a complementary readout to the widely used [ 18 F]F-FDG., (© 2022. The Author(s).)

Previously either regarded as insignificant or feared as potential sources of infection, the bacteria living on our skin are increasingly recognized for their role in benefitting human health. Skin commensals modulate mucosal immune defenses and directly interfere with pathogens; however, their contribution to the skin's physical integrity is less understood. Here, we show that the abundant skin commensal Staphylococcus epidermidis contributes to skin barrier integrity. S. epidermidis secretes a sphingomyelinase that acquires essential nutrients for the bacteria and assists the host in producing ceramides, the main constituent of the epithelial barrier that averts skin dehydration and aging. In mouse models, S. epidermidis significantly increases skin ceramide levels and prevents water loss of damaged skin in a fashion entirely dependent on its sphingomyelinase. Our findings reveal a symbiotic mechanism that demonstrates an important role of the skin microbiota in the maintenance of the skin's protective barrier., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022. Published by Elsevier Inc.)

Purpose: Language comprehension, or the ability to understand spoken language, is critical to a variety of child outcomes. Effective early intervention relies on valid, reliable language comprehension assessment. The purpose of this study was to explore language comprehension in a sample of toddlers with significant developmental delays associated with varied medical conditions., Method: We investigated language comprehension in a sample of 112 toddlers by applying Item Response Theory (IRT) methods to two measures; one standardized and one flexible., Results: Data from a standardized measure fit the unidimensional model, whereas the flexible measure did not. The overall pattern of results suggested that items related to early social/contextual comprehension are distinct from linguistic comprehension items., Conclusion: Our findings inform clinical practice by underscoring the importance of comprehensive assessment of language comprehension and considering strengths and weaknesses across social/contextual and linguistic comprehension among toddlers with developmental delays., (Copyright © 2022 Elsevier Inc. All rights reserved.)

T cell metabolism is dynamic and highly regulated. While the intrinsic metabolic programs of T cell subsets are integral to their distinct differentiation and functional patterns, the ability of cells to acquire nutrients and cope with hostile microenvironments can limit these pathways. T cells must function in a wide variety of tissue settings, and how T cells interpret these signals to maintain an appropriate metabolic program for their demands or if metabolic mechanisms of immune suppression restrain immunity is an area of growing importance. Both in inflamed and cancer tissues, a wide range of changes in physical conditions and nutrient availability are now acknowledged to shape immunity. These include fever and increased temperatures, depletion of critical micro and macro-nutrients, and accumulation of inhibitory waste products. Here we review several of these factors and how the tissue microenvironment both shapes and constrains immunity., (© 2022. The Author(s), under exclusive licence to CSI and USTC.)

Swift recruitment of phagocytic leucocytes is critical in preventing infection when bacteria breach through the protective layers of the skin. According to canonical models, this occurs via an indirect process that is initiated by contact of bacteria with resident skin cells and which is independent of the pathogenic potential of the invader. Here we describe a more rapid mechanism of leucocyte recruitment to the site of intrusion of the important skin pathogen Staphylococcus aureus that is based on direct recognition of specific bacterial toxins, the phenol-soluble modulins (PSMs), by circulating leucocytes. We used a combination of intravital imaging, ear infection and skin abscess models, and in vitro gene expression studies to demonstrate that this early recruitment was dependent on the transcription factor EGR1 and contributed to the prevention of infection. Our findings refine the classical notion of the non-specific and resident cell-dependent character of the innate immune response to bacterial infection by demonstrating a pathogen-specific high-alert mechanism involving direct recruitment of immune effector cells by secreted bacterial products., (© 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

Vulnerable populations such as the uninsured, unemployed, and unhoused face significant morbidity and mortality from influenza but are less likely to receive the annual vaccine and have limited access to medical care. We describe an interprofessional, student-run vaccine outreach program (VOP) in Davidson County, Tennessee that lowers barriers to vaccination through free vaccination events in nontraditional community locations. We provide this framework as a model to expand novel, seasonal, or outbreak-oriented vaccine outreach to resource-poor populations. Demographic data were collected from the patients who received an influenza vaccine between 2015 and 2019 through an optional survey to determine whether these events were reaching unhoused, uninsured, and/or unemployed individuals. Of 1,803 patients, 1,733 (96.1%) completed at least one field of the demographic form. Overall, 481 (27.8%) were individuals without homes or living in temporary housing and 673 (38.8%) were unemployed. Most patients, 1,109 (64.0%), did not have health insurance at any point during the prior two years. With the addition of a nurse practitioner student to VOP leadership, the 2018-2019 VOP reached the most unhoused or temporarily-housed (228, 32.3%), unemployed (313, 18.5%), and disabled (60, 8.5%) patients. The VOP can be adapted to meet community needs, funding, and volunteer interest. The VOP model may be applicable to a SARS-CoV-2 vaccine, especially since the economic impact of COVID-19 has increased unemployment rates and housing instability. Healthcare students serve as an eager, underutilized resource who can be leveraged to disseminate vaccines to individuals with limited access to care., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Staphylococcal enterotoxin B (SEB), which is produced by the major human pathogen, Staphylococcus aureus, represents a powerful superantigenic toxin and is considered a bioweapon. However, the contribution of SEB to S. aureus pathogenesis has never been directly demonstrated with genetically defined mutants in clinically relevant strains. Many isolates of the predominant Asian community-associated methicillin-resistant S. aureus lineage sequence type (ST) 59 harbor seb, implying a significant role of SEB in the observed hypervirulence of this lineage. We created an isogenic seb mutant in a representative ST59 isolate and assessed its virulence potential in mouse infection models. We detected a significant contribution of seb to systemic ST59 infection that was associated with a cytokine storm. Our results directly demonstrate that seb contributes to S. aureus pathogenesis, suggesting the value of including SEB as a target in multipronged antistaphylococcal drug development strategies. Furthermore, they indicate that seb contributes to fatal exacerbation of community-associated methicillin-resistant S. aureus infection., (Published by Oxford University Press for the Infectious Diseases Society of America 2020.)

Herein, we report a general and simplified synthesis of fluorophosphonates directly from p-nitrophenylphosphonates. This FP on-demand reaction is mediated by a commercially available polymer-supported fluoride reagent that produces a variety (25 examples) of fluorophosphonates in high yields while only requiring reagent filtration for pure fluorophosphonate isolation. This reaction protocol facilitates the rapid profiling of serine hydrolases with diverse and novel sets of activated phosphonates with differential proteome reactivity. Moreover, slight modification of the procedure into a reaction-to-assay format has enabled additional screening efficiency., (© 2021 Wiley-VCH GmbH.)

Utilizing a phenotypic screen, we identified chemical matter that increased astrocytic apoE secretion in vitro. We designed a clickable photoaffinity probe based on a pyrrolidine lead compound and carried out probe-based quantitative chemical proteomics in human astrocytoma CCF-STTG1 cells to identify liver x receptor β (LXRβ) as the target. Binding of the small molecule ligand stabilized LXRβ, as shown by cellular thermal shift assay (CETSA). In addition, we identified a probe-modified peptide by mass spectrometry and proposed a model where the photoaffinity probe is bound in the ligand-binding pocket of LXRβ. Taken together, our findings demonstrated that the lead chemical matter bound directly to LXRβ, and our results highlight the power of chemical proteomic approaches to identify the target of a phenotypic screening hit. Additionally, the LXR photoaffinity probe and lead compound described herein may serve as valuable tools to further evaluate the LXR pathway., Competing Interests: Declaration of Interests All authors of this manuscript are (or were at the time of their involvement with the apoE project) employees of Pfizer., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Trained immunity, a functional state of myeloid cells, has been proposed as a compelling immune-oncological target. Its efficient induction requires direct engagement of myeloid progenitors in the bone marrow. For this purpose, we developed a bone marrow-avid nanobiologic platform designed specifically to induce trained immunity. We established the potent anti-tumor capabilities of our lead candidate MTP 10 -HDL in a B16F10 mouse melanoma model. These anti-tumor effects result from trained immunity-induced myelopoiesis caused by epigenetic rewiring of multipotent progenitors in the bone marrow, which overcomes the immunosuppressive tumor microenvironment. Furthermore, MTP 10 -HDL nanotherapy potentiates checkpoint inhibition in this melanoma model refractory to anti-PD-1 and anti-CTLA-4 therapy. Finally, we determined MTP 10 -HDL's favorable biodistribution and safety profile in non-human primates. In conclusion, we show that rationally designed nanobiologics can promote trained immunity and elicit a durable anti-tumor response either as a monotherapy or in combination with checkpoint inhibitor drugs., Competing Interests: Declaration of Interests W.J.M.M., L.A.B.J., J.O., Z.A.F., and M.G.N. are scientific co-founders of and have equity in Trained Therapeutix Discovery. W.J.M.M. and Z.A.F. have consulting agreements with Trained Therapeutix Discovery., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Although the first nanomedicine was clinically approved more than two decades ago, nanoparticles' (NP) in vivo behavior is complex and the immune system's role in their application remains elusive. At present, only passive-targeting nanoformulations have been clinically approved, while more complicated active-targeting strategies typically fail to advance from the early clinical phase stage. This absence of clinical translation is, among others, due to the very limited understanding for in vivo targeting mechanisms. Dynamic in vivo phenomena such as NPs' real-time targeting kinetics and phagocytes' contribution to active NP targeting remain largely unexplored. To better understand in vivo targeting, monitoring NP accumulation and distribution at complementary levels of spatial and temporal resolution is imperative. Here, we integrate in vivo positron emission tomography/computed tomography imaging with intravital microscopy and flow cytometric analyses to study α v β 3 -integrin-targeted cyclic arginine-glycine-aspartate decorated liposomes and oil-in-water nanoemulsions in tumor mouse models. We observed that ligand-mediated accumulation in cancerous lesions is multifaceted and identified "NP hitchhiking" with phagocytes to contribute considerably to this intricate process. We anticipate that this understanding can facilitate rational improvement of nanomedicine applications and that immune cell-NP interactions can be harnessed to develop clinically viable nanomedicine-based immunotherapies.

Purpose Children with dyslexia often struggle with nonphonological aspects of language and executive functioning. The purpose of this study was to investigate the impact of executive functioning on language abilities at both structural (e.g., grammar in sentences) and functional (e.g., narrative) levels in 92 third- and 4th-grade students with dyslexia. Additionally, we asked if working memory updating contributed a significant amount of variance in narrative language ability beyond what would be expected by students' structural language skills alone. Method Students' language and executive functioning skills were evaluated using a range of language and cognitive measures including the Clinical Evaluation of Language Fundamentals-Fourth Edition (Semel, Wiig, & Secord, 2003), the Peabody Picture Vocabulary Test-Fourth Edition (Dunn & Dunn, 2007), the Test of Narrative Language (Gillam & Pearson, 2004), the Delis-Kaplan Executive Function Scale (Kaplan, Kramer, & Delis, 2001), and the Corsi Block-Tapping Test (WISC-IV Integrated; Kaplan, Fein, Kramer, Delis, & Morris, 2004). Results Low correlations between the language measures suggested that each of these assessments captures a unique element of language ability for children with dyslexia. Hierarchical regression analysis indicated that working memory updating accounted for a significant amount of unique variance in oral narrative production beyond what would be expected by structural language ability. Conclusions The range of performance found across language measures suggests that it may be important to include a variety of language measures assessing both structural and functional language skills when evaluating children with dyslexia. Including cognitive measures of executive functioning may also be key to determine if deficits in working memory updating are contributing to functional expressive language difficulties.

Phenol-soluble modulins (PSMs) are amphipathic, alpha-helical peptides that are secreted by staphylococci in high amounts in a quorum-sensing-controlled fashion. Studies performed predominantly in Staphylococcus aureus showed that PSMs structure biofilms, which results in reduced biofilm mass, while it has also been reported that S. aureus PSMs stabilize biofilms due to amyloid formation. We here analyzed the roles of PSMs in in vitro and in vivo biofilms of Staphylococcus epidermidis, the leading cause of indwelling device-associated biofilm infection. We produced isogenic deletion mutants for every S. epidermidis psm locus and a sequential deletion mutant in which production of all PSMs was abolished. In vitro analysis substantiated the role of all PSMs in biofilm structuring. PSM-dependent biofilm expansion was not observed, in accordance with our finding that no S. epidermidis PSM produced amyloids. In a mouse model of indwelling device-associated infection, the total psm deletion mutant had a significant defect in dissemination. Notably, the total psm mutant produced a significantly more substantial biofilm on the implanted catheter than the wild-type strain. Our study, which for the first time directly quantified the impact of PSMs on biofilm expansion on an implanted device, shows that the in vivo biofilm infection phenotype in S. epidermidis is in accordance with the PSM biofilm structuring and detachment model, which has important implications for the potential therapeutic application of quorum-sensing blockers., (Published by Elsevier Ltd.)

Herein we describe the 2,2,2-trifluoroethoxy group as an alternative leaving group for hydrolytically unstable heteroaryl chlorides. This group provides improved shelf stability by years while maintaining reactivity toward nucleophiles in S N Ar reactions. A highlighted trifluoroethyl ether was shown to be tolerant to aqueous Suzuki conditions, permitting sequential Suzuki/S N Ar processes inaccessible to the heterocyclic chlorides. The strategic use of trifluoroethyl ethers enables storage of otherwise unstable heterocyclic chlorides and limits costly decomposition.

Probiotic nutrition is frequently claimed to improve human health. In particular, live probiotic bacteria obtained with food are thought to reduce intestinal colonization by pathogens, and thus to reduce susceptibility to infection. However, the mechanisms that underlie these effects remain poorly understood. Here we report that the consumption of probiotic Bacillus bacteria comprehensively abolished colonization by the dangerous pathogen Staphylococcus aureus in a rural Thai population. We show that a widespread class of Bacillus lipopeptides, the fengycins, eliminates S. aureus by inhibiting S. aureus quorum sensing-a process through which bacteria respond to their population density by altering gene regulation. Our study presents a detailed molecular mechanism that underlines the importance of probiotic nutrition in reducing infectious disease. We also provide evidence that supports the biological significance of probiotic bacterial interference in humans, and show that such interference can be achieved by blocking a pathogen's signalling system. Furthermore, our findings suggest a probiotic-based method for S. aureus decolonization and new ways to fight S. aureus infections.

The hetisine-type natural products exhibit one of the most complex carbon skeletons within the diterpenoid alkaloid family. The use of network analysis has enabled a synthesis strategy to access alkaloids in this class with hydroxylation on the A-ring. Key transformations include a benzyne acyl-alkylation to construct a key fused 6-7-6 tricycle, a chemoselective nitrile reduction, and sequential C-N bond formations using a reductive cyclization and a photochemical hydroamination to construct an embedded azabicycle. Our strategy should enable access to myriad natural and unnatural products within the hetisine-type.

The Staphylococcus aureus enterotoxins are a superfamily of secreted virulence factors that share structural and functional similarities and possess potent superantigenic activity causing disruptions in adaptive immunity. The enterotoxins can be separated into two groups; the classical (SEA-SEE) and the newer (SEG-SE l Y and counting) enterotoxin groups. Many members from both these groups contribute to the pathogenesis of several serious human diseases, including toxic shock syndrome, pneumonia, and sepsis-related infections. Additionally, many members demonstrate emetic activity and are frequently responsible for food poisoning outbreaks. Due to their robust tolerance to denaturing, the enterotoxins retain activity in food contaminated previously with S. aureus . The genes encoding the enterotoxins are found mostly on a variety of different mobile genetic elements. Therefore, the presence of enterotoxins can vary widely among different S. aureus isolates. Additionally, the enterotoxins are regulated by multiple, and often overlapping, regulatory pathways, which are influenced by environmental factors. In this review, we also will focus on the newer enterotoxins (SEG-SE l Y), which matter for the role of S. aureus as an enteropathogen, and summarize our current knowledge on their prevalence in recent food poisoning outbreaks. Finally, we will review the current literature regarding the key elements that govern the complex regulation of enterotoxins, the molecular mechanisms underlying their enterotoxigenic, superantigenic, and immunomodulatory functions, and discuss how these activities may collectively contribute to the overall manifestation of staphylococcal food poisoning.

Antimicrobial peptides (AMPs) constitute an important part of innate host defense. Possibly limiting the therapeutic potential of AMPs is the fact that bacteria have developed AMP resistance mechanisms during their co-evolution with humans. However, there is no direct evidence that AMP resistance per se is important during an infection. Here we show that the Staphylococcus aureus Pmt ABC transporter defends the bacteria from killing by important human AMPs and elimination by human neutrophils. By showing that Pmt contributes to virulence during skin infection in an AMP-dependent manner, we provide evidence that AMP resistance plays a key role in bacterial infection.

Late-stage oxidation using liver microsomes was applied to phosphodiesterase 2 inhibitor 1 to reduce its clearance by cytochrome P450 enzymes, introduce renal clearance, and minimize the risk for victim drug-drug interactions. This approach yielded PF-06815189 ( 2 ) with improved physicochemical properties and a mixed metabolic profile. This example highlights the importance of C-H diversification methods to drug discovery., Competing Interests: The authors declare no competing financial interest.

Hoarseness is a common presentation in primary care practices. Combined with other voice-related changes, it falls under the umbrella diagnosis of dysphonia. Hoarseness has a number of causes, ranging from simple inflammatory processes to less common psychiatric disorders to more serious systemic, neurologic, or cancerous conditions. Medication-induced hoarseness is common and should be considered. The initial evaluation begins with a targeted history and physical examination, while also looking for signs of potential systemic etiologies. Treatment should begin with voice rest, especially avoidance of whispering, and conservative management directed toward a presumptive cause. For example, proton pump inhibitors are appropriate for hoarseness due to reflux, and proper vocal hygiene is recommended for vocal abuse-related indications. In the absence of a clear indication, antibiotics, oral corticosteroids, and proton pump inhibitors should not be used for the empiric treatment of hoarseness. Direct visualization of the larynx and vocal folds, commonly mislabeled as vocal cords, should be performed within three months if an etiology has not been determined or if conservative management has been ineffective. Patients who experience symptoms lasting longer than two weeks and who have risk factors for dysplasia (e.g., tobacco use, heavy alcohol use, hemoptysis) may require earlier laryngoscopic evaluation. Voice therapy is effective for improving voice quality in patients with dysphonia if conservative measures are unsuccessful, and it can also be helpful for prophylaxis in high-risk individuals (e.g., vocalists, public speakers). Surgical management is indicated for laryngeal or vocal fold dysplasia or malignancy, airway obstruction, or benign pathology resistant to conservative treatment.

Purpose: The purpose of this study was to explore the literature on predictors of outcomes among late talkers using systematic review and meta-analysis methods. We sought to answer the question: What factors predict preschool-age expressive-language outcomes among late-talking toddlers?, Method: We entered carefully selected search terms into the following electronic databases: Communication & Mass Media Complete, ERIC, Medline, PsycEXTRA, Psychological and Behavioral Sciences, and PsycINFO. We conducted a separate, random-effects model meta-analysis for each individual predictor that was used in a minimum of 5 studies. We also tested potential moderators of the relationship between predictors and outcomes using metaregression and subgroup analysis. Last, we conducted publication-bias and sensitivity analyses., Results: We identified 20 samples, comprising 2,134 children, in a systematic review. According to the results of the meta-analyses, significant predictors of expressive-language outcomes included toddlerhood expressive-vocabulary size, receptive language, and socioeconomic status. Nonsignificant predictors included phrase speech, gender, and family history., Conclusions: To our knowledge this is the first synthesis of the literature on predictors of outcomes among late talkers using meta-analysis. Our findings clarify the contributions of several constructs to outcomes and highlight the importance of early receptive language to expressive-language development., Supplemental Materials: https://doi.org/10.23641/asha.5313454.

A mechanistic study of a new heterocycloisomerization reaction that forms annulated aminopyrroles is presented. Density functional theory calculations and kinetic studies suggest the reaction is catalyzed by trace copper salts and that a Z- to E-hydrazone isomerization occurs through an enehydrazine intermediate before the rate-determining cyclization of the hydrazone onto the alkyne group. The aminopyrrole products are obtained in 36-93% isolated yield depending on the nature of the alkynyl substituent. A new automated sampling technique was developed to obtain robust mechanistic data.

Purpose: The purpose of this study was to compare the prevalence of third molars from the US National Health and Nutrition Examination Survey (NHANES) and the Swedish survey., Materials and Methods: This cross-sectional study involved the comparison of the only published data on third molar prevalence. The number of visible third molars in the NHANES of 2011 through 2012 were assessed in nonclinical settings by trained, calibrated dental hygienists and reported by age decade (approximately 5,000 patients). Similar data were reported for the Swedish population with data collected in clinical settings (approximately 700 patients). The primary outcome variable was the number of third molars (0 to 4); the predictor variables were age cohorts (20 to 29 through 70 to 79 yr). Outcome data were reported with descriptive statistics., Results: In the youngest cohort (20 to 29 yr), having no visible third molars was more likely in the US population than in the Swedish population (47 vs 2%, respectively). By 50 to 59 years, outcomes for no third molars were similar in the United States and Sweden (53 and 57%, respectively)., Conclusion: The presence or absence of third molars reported from the US and Swedish populations presented contrasting patterns, particularly in the younger cohorts. More comprehensive and detailed data are required in future surveys as population studies on third molars become more important for clinicians and other stakeholders., (Copyright © 2017 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Bacterial sepsis is a major killer in hospitalized patients. Coagulase-negative staphylococci (CNS) with the leading species Staphylococcus epidermidis are the most frequent causes of nosocomial sepsis, with most infectious isolates being methicillin-resistant. However, which bacterial factors underlie the pathogenesis of CNS sepsis is unknown. While it has been commonly believed that invariant structures on the surface of CNS trigger sepsis by causing an over-reaction of the immune system, we show here that sepsis caused by methicillin-resistant S. epidermidis is to a large extent mediated by the methicillin resistance island-encoded peptide toxin, PSM-mec. PSM-mec contributed to bacterial survival in whole human blood and resistance to neutrophil-mediated killing, and caused significantly increased mortality and cytokine expression in a mouse sepsis model. Furthermore, we show that the PSM-mec peptide itself, rather than the regulatory RNA in which its gene is embedded, is responsible for the observed virulence phenotype. This finding is of particular importance given the contrasting roles of the psm-mec locus that have been reported in S. aureus strains, inasmuch as our findings suggest that the psm-mec locus may exert effects in the background of S. aureus strains that differ from its original role in the CNS environment due to originally "unintended" interferences. Notably, while toxins have never been clearly implied in CNS infections, our tissue culture and mouse infection model data indicate that an important type of infection caused by the predominant CNS species is mediated to a large extent by a toxin. These findings suggest that CNS infections may be amenable to virulence-targeted drug development approaches., Competing Interests: The authors have declared that no competing interests exist.

Mucolipidosis Type IV (ML IV) is an autosomal recessive genetic disorder characterized by severe psychomotor impairments and ophthalmologic abnormalities. Reports on the cognitive development of people with ML IV are limited, but suggest that achievement of language and cognitive milestones varies between a 3- and 18-month level. There is also variability in reports of whether people with ML IV make developmental progress, regress, or remain static after infancy. This study examines the longitudinal development of a young child with ML IV who participated in an augmentative and alternative communication (AAC) intervention.At 26 months, the child displayed significant developmental delays on direct assessment, with the exception of a possible relative strength in receptive language. An examination of adaptive behavior over time indicated improvements in raw scores but declines in standard scores across all domains. She learned to use 13 new words with a speech generating device (SGD) by the end of intervention.These results add to literature on the clinical manifestations of ML IV and indicate that although children with this disorder have deficits in many domains, they may be most severely affected in gross motor or oral motor development and have a relative strength in receptive language. Moreover, this child made progress in all domains of adaptive functioning, but at a slower pace than typically developing children. She also gained expressive vocabulary in the AAC intervention, and this may have supported her development in other areas.

Purpose: To determine the prevalence of third molars in the US population and to report the differences in prevalence of visible third molars in the most recent National Health and Nutrition Examination Survey (NHANES) population of 2011 through 2012 by participant, jaw, and demographics., Materials and Methods: The number of visible third molars in the NHANES data was assessed in nonclinical settings by trained, calibrated dental hygienists by decade of age beginning in the 20- to 29-year-old cohort through the 70- to 79-year-old cohort. Cross-sectional analyses of third molar data were conducted by the authors from the NHANES databases of 2001 through 2002, 2009 through 2010, and 2011 through 2012 to compare data for similarity of outcomes on third molar prevalence in the US population. Outcomes on third molar prevalence also were assessed from the NHANES of 2011 through 2012 by participant, jaw, and demographics: gender, race or ethnicity (Caucasian, African American, other), and education (less than high school, high school graduate, some college, college graduate)., Results: Data on the mean number of third molars from NHANES of 2001 through 2002, 2009 through 2010, and 2011 through 2012 were similar. The number of visible third molars in the NHANES of 2011 through 2012 decreased progressively from a mean of 1.48 in the 20- to 29-year-old cohort to 0.81 in the 60- to 69-year-old cohort, No visible third molars were observed in 47% of the 20- to 29-year-old cohort compared with 53% in the 50- to 59-year-old cohort. Participants who were male, non-Caucasian, and had less than a high school education were more likely to have a visible third molar in all age cohorts. No data were collected by NHANES examiners to determine why third molars were absent., Conclusion: Third molar prevalence did not appear to differ in the US population during the first decade of the 21st century. Numbers of visible third molars, prevalent in young adults, decreased progressively through each successive age cohort. Demographic differences exist for prevalence of third molars in the US population., (Copyright © 2016 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

The objective of the study was to compare executive functioning (EF) profiles across several pediatric medical conditions and explore the influence of age of diagnosis and evaluation. A retrospective, cross-sectional study of 734 children aged 5 to 18 years was conducted across five medical groups (brain tumor, leukemia [ALL], epilepsy [EPI], neurofibromatosis type 1 [NF1], and ornithine transcarbamylase deficiency [OTC-D]), attention deficit hyperactivity disorder (ADHD) controls, and matched healthy controls. We compared groups across the scales of a parent-completed Behavior Rating Inventory of Executive Functioning (BRIEF) using a repeated measures analysis of variance (ANOVA). Separate ANOVAs were conducted to look at age factors. The results showed that the ADHD group differed from all other groups and had the highest level of reported EF problems. The NF1 and OTC-D groups differed significantly from the healthy comparison group for overall EF problems, while the EPI and cancer groups did not. Working memory was the most elevated scale across medical groups, followed by plan/organize. Children with medical disorders were two to four times more likely than healthy controls to have clinically significant problems in several EF domains. There was a main effect for age at diagnosis and age at evaluation. A subset of children with medical disorders were found to have parent-reported EF difficulties, with particular vulnerability noted in working memory and organizational/planning skills. This has relevance for the development of interventions that may be helpful across disorders. Children with particular diagnoses and earlier age of diagnosis and evaluation had greater reported EF problems., Competing Interests: Lauren Krivitzky is a consultant with Hyperion Therapeutics. There are no other conflicts of interest.

Purpose: To assess the impact of mechanical debridement of subgingival biofilm on periodontal outcomes in adolescents and young adults with asymptomatic third molars., Methods: Healthy participants with 4 asymptomatic third molars were enrolled in an institutional review board-approved longitudinal study. Clinical data were collected at enrollment and at follow-up visits. Full-mouth periodontal probing, 6 sites per tooth, was assessed as a measure of clinical periodontal status. At enrollment, all participants had dental prophylaxis after data collection, which included removal of subgingival biofilm; this was repeated annually. The primary outcome measures were the comparison from baseline to follow-up 2 years after enrollment of participants' periodontal probing depths for third molars and first/second molars. In addition, a comparison of extent scores at baseline to follow-up 2 years after enrollment for periodontal probing sites of at least 4 mm was performed for the same molar regions of the mouth. Changes over time in clinical periodontal status from enrollment to the follow-up at least 2 years later were analyzed with Mantel-Haenszel row mean score statistics. The level of significance was set at P < .05., Results: The median follow-up from entry to the study was 2.2 years (interquartile range, 2.0-2.8 years) for 262 participants who averaged 27.7 years of age (SD, 1.2 years); 53% were female participants, and 81% were white. Most participants (90%) were educated beyond high school. On the basis of periodontal probing depths, participants' clinical periodontal status did not differ from enrollment to follow-up., Conclusions: Dental prophylaxis at yearly intervals in participants with asymptomatic third molars, which included mechanical removal of subgingival biofilm, had minimal or no impact on reducing deeper probing depths, clinical indicators of periodontal pathology in young adults., (Copyright © 2013 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Research on the psychological bases of political attitudes tends to dwell on the attitudes of conservatives, rarely placing a conscious thematic emphasis on what motivates liberals to adopt the attitudes they do. This research begins to address this imbalance by examining whether the need for cognitive closure is equally associated with conservatism in policy attitudes among those who broadly identify with the liberal and conservative labels. Counterintuitively, we predict and find that the need for closure is most strongly associated with policy conservatism among those who symbolically identify as liberals or for whom liberal considerations are made salient. In turn, we also find that the need for closure is associated with reduced ideological consistency in issue attitudes among liberal identifiers but not conservative identifiers. Although supportive of our predictions, these results run counter to a simple "rigidity of the right" hypothesis, which would predict a positive link between need for closure and policy conservatism regardless of ideological self-description, and the "ideologue" hypothesis, which would predict a positive link between these variables among conservative identifiers and a negative one among liberal identifiers. We discuss the implications these findings for understanding the motivations underlying liberals' and conservatives' attitudes and suggest that future research attend to the important distinction between ideology in the sense of symbolic identification with conservatism versus liberalism and ideology in the sense of an average tilt to the right or left in one's policy attitudes.

Purpose: To study the third molar occlusal caries incidence and identify related patient-level sociodemographic, dental behavior, and clinical risk factors., Patients and Methods: A prospective cohort study was used to study caries risk (crude increment and incidence rate) on retained and erupted to the occlusal plane third molars among a moderate-size (n = 215) group of healthy (American Society of Anesthesiologists class I and II) young adults (median age, 26 years) followed up for a mean of 4.6 years. Clinical data were gathered by calibrated examiners using visual-tactile and radiographic diagnostic methods on all molar teeth. The covariates included age at enrollment, gender, race, income, education, frequency of dental visits, oral hygiene behaviors, and smoking. Summary statistics and visual methods were used for data description. The analyses relied on bivariate and multivariate methods using generalized estimating equations, extensions of Poisson modeling., Results: Of the 215 patients, 33% developed occlusal caries on 1 or more retained third molars. The incidence rate was 0.11 (95% confidence interval 0.09 to 0.13) third molar "increments"/person-year. Those with any molar caries at baseline were 80% more likely to have a new third molar caries lesion at the end of follow-up compared with those with caries-free molars (prevalence ratio, 1.80; 95% confidence interval, 1.08 to 3.00). The third molar caries rate was halved for every approximately 9 years of the subjects' baseline age. Favorable oral hygiene behaviors and better socioeconomic status were associated with decreased caries risk. However, independent of other covariates, smoking increased the third molar caries risk twofold., Conclusions: Younger patients from lower socioeconomic strata, smokers, and those with poor oral hygiene behavior are at an increased risk of occlusal caries development on their retained third molars., (Copyright © 2012 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)