Framboesiform Facial Lesions and Chorioretinopathy as Presenting Signs of Syphilis in an Immunocompetent Patient.

ABSTRACT: Syphilis has long been considered the "great masquerader," notorious for its varying presentations and ability to affect most organ systems in the body. We report the case of a 41-year-old immunocompetent man who presented to ophthalmology with rapidly progressive visual complaints from bilateral panuveitis and concomitant verrucous facial lesions initially disregarded by the patient as acne. Serum testing for syphilis was positive, and he was admitted for 14 days of intravenous (IV) penicillin with multiservice care from dermatology, ophthalmology, and infectious disease. We present photographic documentation showing his stepwise resolution of his facial and retinal involvement with penicillin treatment course. This case is unusual in the concomitant presentation of ocular and facial syphilitic findings in an immunocompetent patient and highlights the need to include syphilis in the differential for unusual appearances.

The associations between dental disease and systemic health.

Understanding the relationship between a patient's systemic and oral health is key for clinicians. The aim of this study was to determine if there is an association between specific findings in a dental exam, such as class V carious lesions, and the American Society of Anesthesiologists (ASA) classification as a proxy for systemic health. A retrospective chart review was performed on all patient charts that met inclusion criteria including detailed, complete, and vetted charts obtained over a three-year period in the predoctoral clinic of a United States dental college. Findings recorded at the initial exam included the decayed, missing or filled teeth (DMFT) score, the location of carious lesions and restorations, the presence of periodontal disease, the number of endodontically treated teeth and the number of fractured teeth or restorations. We found no association found between DMFT score and ASA status but did find that ASA I patients had a higher degree of occlusal carious lesions and that ASA III patients were more likely to have interproximal restorations and fractured teeth. We found associations between a greater number of missing teeth and the presence of periodontal disease with worsening ASA status. Our data suggest that ASA classification cannot be used as a reliable predictor for the health of a patient's dentition or the number of cervical caries. However, the data does demonstrate a positive correlation between the number of missing teeth and ASA status, promoting the idea that the number of missing teeth is a crude prognosticator of systemic health. This information can be used by physicians and dentists to help understand the relationships between a patient's dental and systemic health.

Ethno-demographic disparities in humoral responses to the COVID-19 vaccine among healthcare workers.

The COVID-19 pandemic had a profound impact on global health, but rapid vaccine administration resulted in a significant decline in morbidity and mortality rates worldwide. In this study, we sought to explore the temporal changes in the humoral immune response against SARS-CoV-2 healthcare workers (HCWs) in Augusta, GA, USA, and investigate any potential associations with ethno-demographic features. Specifically, we aimed to compare the naturally infected individuals with naïve individuals to understand the immune response dynamics after SARS-CoV-2 vaccination. A total of 290 HCWs were included and assessed prospectively in this study. COVID status was determined using a saliva-based COVID assay. Neutralizing antibody (NAb) levels were quantified using a chemiluminescent immunoassay system, and IgG levels were measured using an enzyme-linked immunosorbent assay method. We examined the changes in antibody levels among participants using different statistical tests including logistic regression and multiple correspondence analysis. Our findings revealed a significant decline in NAb and IgG levels at 8-12 months postvaccination. Furthermore, a multivariable analysis indicated that this decline was more pronounced in White HCWs (odds ratio [OR] = 2.1, 95% confidence interval [CI] = 1.07-4.08, p = 0.02) and IgG (OR = 2.07, 95% CI = 1.04-4.11, p = 0.03) among the whole cohort. Booster doses significantly increased IgG and NAb levels, while a decline in antibody levels was observed in participants without booster doses at 12 months postvaccination. Our results highlight the importance of understanding the dynamics of immune response and the potential influence of demographic factors on waning immunity to SARS-CoV-2. In addition, our findings emphasize the value of booster doses to ensure durable immunity.

Pain Levels Did Not Differ Following Uncomplicated Third Molar Extractions Utilizing Liposomal Bupivacaine Versus Standard Bupivacaine.

PURPOSE: Operations in the oral cavity are often characterized by an acute period of postoperative pain historically mitigated via opioids and other analgesics. The purpose of the study was to determine if liposomal bupivacaine infiltration (LBI) following uncomplicated extraction of bilateral, mandibular third molars will significantly reduce postoperative pain when compared to standard bupivacaine. MATERIALS AND METHODS: The study was designed as a parallel-arm randomized clinical trial. The sample size was calculated for the primary outcome variable: postoperative pain levels measured at 48-hours. Using a power analysis, a sample size of n = 13 for each group was required. Patients meeting the inclusion/exclusion criteria requiring exodontia from November 4, 2018, to June 16, 2022, were recruited out of the oral and maxillofacial surgery clinic. The patients were randomized and divided into 2 groups. Group A was administered 0.50% bupivacaine (with 1:200,000 epinephrine) via infiltration while group B underwent LBI. The primary outcome of interest was postoperative pain levels followed by the secondary outcomes of postoperative narcotic analgesic use, return to oral function, and satisfaction. Patient demographics and characteristics were analyzed as potential covariates utilizing the Fisher exact test and t test for continuous outcomes, respectively. RESULTS: Thirty patients were recruited for the study. The average age of patients receiving the third molar operation was 24.1 ± 5.8 years. Of the 30, 62.5% were female, and 37.5% were male. Seventy-five percent of the patients were Caucasian, 20.8% were African American, and 4.2% were Asian. Forty-eight-hour postoperative interviews revealed mean pain levels of 2.5 ± 2.8 in the control group and 2.9 ± 2.3 in the LBI group (P = .730) as measured on a visual analog scale. The 48-hour postoperative interview identified a mean of 1.9 ± 2.1 narcotic pills used in the control group and 2.5 ± 5.0 pills used in the LBI group (P = .693). CONCLUSIONS: Mandibular LBIs following bilateral mandibular third molar extractions showed no statistically significant advantage over the standard bupivacaine at either time point analyzed. Furthermore, no statistically significant difference was found regarding narcotic use between the 2 groups.

Developmental plasticity of epithelial stem cells in tooth and taste bud renewal.

In Lake Malawi cichlids, each tooth is replaced in one-for-one fashion every ∼20 to 50 d, and taste buds (TBs) are continuously renewed as in mammals. These structures are colocalized in the fish mouth and throat, from the point of initiation through adulthood. Here, we found that replacement teeth (RT) share a continuous band of epithelium with adjacent TBs and that both organs coexpress stem cell factors in subsets of label-retaining cells. We used RNA-seq to characterize transcriptomes of RT germs and TB-bearing oral epithelium. Analysis revealed differential usage of developmental pathways in RT compared to TB oral epithelia, as well as a repertoire of genome paralogues expressed complimentarily in each organ. Notably, BMP ligands were expressed in RT but excluded from TBs. Morphant fishes bathed in a BMP chemical antagonist exhibited RT with abrogated shh expression in the inner dental epithelium (IDE) and ectopic expression of calb2 (a TB marker) in these very cells. In the mouse, teeth are located on the jaw margin while TBs and other oral papillae are located on the tongue. Previous study reported that tongue intermolar eminence (IE) oral papillae of Follistatin (a BMP antagonist) mouse mutants exhibited dysmorphic invagination. We used these mutants to demonstrate altered transcriptomes and ectopic expression of dental markers in tongue IE. Our results suggest that vertebrate oral epithelium retains inherent plasticity to form tooth and taste-like cell types, mediated by BMP specification of progenitor cells. These findings indicate underappreciated epithelial cell populations with promising potential in bioengineering and dental therapeutics.

The genomic substrate for adaptive radiation in African cichlid fish.

Cichlid fishes are famous for large, diverse and replicated adaptive radiations in the Great Lakes of East Africa. To understand the molecular mechanisms underlying cichlid phenotypic diversity, we sequenced the genomes and transcriptomes of five lineages of African cichlids: the Nile tilapia (Oreochromis niloticus), an ancestral lineage with low diversity; and four members of the East African lineage: Neolamprologus brichardi/pulcher (older radiation, Lake Tanganyika), Metriaclima zebra (recent radiation, Lake Malawi), Pundamilia nyererei (very recent radiation, Lake Victoria), and Astatotilapia burtoni (riverine species around Lake Tanganyika). We found an excess of gene duplications in the East African lineage compared to tilapia and other teleosts, an abundance of non-coding element divergence, accelerated coding sequence evolution, expression divergence associated with transposable element insertions, and regulation by novel microRNAs. In addition, we analysed sequence data from sixty individuals representing six closely related species from Lake Victoria, and show genome-wide diversifying selection on coding and regulatory variants, some of which were recruited from ancient polymorphisms. We conclude that a number of molecular mechanisms shaped East African cichlid genomes, and that amassing of standing variation during periods of relaxed purifying selection may have been important in facilitating subsequent evolutionary diversification.

Coevolutionary patterning of teeth and taste buds.

Teeth and taste buds are iteratively patterned structures that line the oro-pharynx of vertebrates. Biologists do not fully understand how teeth and taste buds develop from undifferentiated epithelium or how variation in organ density is regulated. These organs are typically studied independently because of their separate anatomical location in mammals: teeth on the jaw margin and taste buds on the tongue. However, in many aquatic animals like bony fishes, teeth and taste buds are colocalized one next to the other. Using genetic mapping in cichlid fishes, we identified shared loci controlling a positive correlation between tooth and taste bud densities. Genome intervals contained candidate genes expressed in tooth and taste bud fields. sfrp5 and bmper, notable for roles in Wingless (Wnt) and bone morphogenetic protein (BMP) signaling, were differentially expressed across cichlid species with divergent tooth and taste bud density, and were expressed in the development of both organs in mice. Synexpression analysis and chemical manipulation of Wnt, BMP, and Hedgehog (Hh) pathways suggest that a common cichlid oral lamina is competent to form teeth or taste buds. Wnt signaling couples tooth and taste bud density and BMP and Hh mediate distinct organ identity. Synthesizing data from fish and mouse, we suggest that the Wnt-BMP-Hh regulatory hierarchy that configures teeth and taste buds on mammalian jaws and tongues may be an evolutionary remnant inherited from ancestors wherein these organs were copatterned from common epithelium.

Common developmental pathways link tooth shape to regeneration.

In many non-mammalian vertebrates, adult dentitions result from cyclical rounds of tooth regeneration wherein simple unicuspid teeth are replaced by more complex forms. Therefore and by contrast to mammalian models, the numerical majority of vertebrate teeth develop shape during the process of replacement. Here, we exploit the dental diversity of Lake Malawi cichlid fishes to ask how vertebrates generally replace their dentition and in turn how this process acts to influence resulting tooth morphologies. First, we used immunohistochemistry to chart organogenesis of continually replacing cichlid teeth and discovered an epithelial down-growth that initiates the replacement cycle via a labial proliferation bias. Next, we identified sets of co-expressed genes from common pathways active during de novo, lifelong tooth replacement and tooth morphogenesis. Of note, we found two distinct epithelial cell populations, expressing markers of dental competence and cell potency, which may be responsible for tooth regeneration. Related gene sets were simultaneously active in putative signaling centers associated with the differentiation of replacement teeth with complex shapes. Finally, we manipulated targeted pathways (BMP, FGF, Hh, Notch, Wnt/ß-catenin) in vivo with small molecules and demonstrated dose-dependent effects on both tooth replacement and tooth shape. Our data suggest that the processes of tooth regeneration and tooth shape morphogenesis are integrated via a common set of molecular signals. This linkage has subsequently been lost or decoupled in mammalian dentitions where complex tooth shapes develop in first generation dentitions that lack the capacity for lifelong replacement. Our dissection of the molecular mechanics of vertebrate tooth replacement coupled to complex shape pinpoints aspects of odontogenesis that might be re-evolved in the lab to solve problems in regenerative dentistry.

How can physicians improve medication adherence and outcomes in dermatological conditions?

INTRODUCTION: Medication non-adherence is a major contributor to suboptimal disease treatment across medical specialties and is a particular hurdle with topicals. While adherence is a patient behavior affected by many socioeconomic and health system factors, physicians can play an important role in encouraging good adherence. AREAS COVERED: We discuss methods for measuring adherence, including ethics of such research, provide select examples of dermatology-specific adherence studies, and conclude with physician-focused practices to improve patients' adherence. Articles were selected from a PubMed search spanning 2003 to 10 December 2023, using the following terms: 'dermatology,' 'medication,' 'treatment,' 'adherence,' 'compliance,' and 'intervention.' EXPERT OPINION: Poor adherence to treatment is a major cause of poor treatment outcomes. As the goal of medical care is to achieve successful treatment outcomes, encouraging good adherence may be as much a foundation of care as making the right diagnosis and prescribing the right treatment. Taking a doctor-centric perspective on reasons for non-adherence may be more productive than simply finding fault with the patient. Establishing trust and accountability is a foundation for good adherence; after establishing the provider-patient relationship, physicians can improve adherence by incorporating behavioral and counseling strategies, communicating through technology, and advocating for distribution of validated educational information.

Gene Regulatory Network Analysis of Post-Mortem Lungs Unveils Novel Insights into COVID-19 Pathogenesis.

The novel coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has emerged as one of the most significant global health crises in recent history. The clinical characteristics of COVID-19 patients have revealed the possibility of immune activity changes contributing to disease severity. Nevertheless, limited information is available regarding the immune response in human lung tissue, which is the primary site of infection. In this study, we conducted an extensive analysis of lung tissue to screen for differentially expressed miRNAs and mRNAs in five individuals who died due to COVID-19 and underwent a rapid autopsy, as well as seven control individuals who died of other causes unrelated to COVID-19. To analyze the host response gene expression, miRNA microarray and Nanostring's nCounter XT gene expression assay were performed. Our study identified 37 downregulated and 77 upregulated miRNAs in COVID-19 lung biopsy samples compared to the controls. A total of 653 mRNA transcripts were differentially expressed between the two sample types, with most transcripts (472) being downregulated in COVID-19-positive specimens. Hierarchical and PCA K-means clustering analysis showed distinct clustering between COVID-19 and control samples. Enrichment and network analyses revealed differentially expressed genes important for innate immunity and inflammatory response in COVID-19 lung biopsies. The interferon-signaling pathway was highly upregulated in COVID-19 specimens while genes involved in interleukin-17 signaling were downregulated. These findings shed light on the mechanisms of host cellular responses to COVID-19 infection in lung tissues and could help identify new targets for the prevention and treatment of COVID-19 infection.

Bilateral zonular dehiscence during cataract surgery in a patient with systemic sclerosis.

Purpose: Systemic sclerosis, also known as scleroderma, is a rare and chronic autoimmune connective disorder that affects most organs. While clinical findings of scleroderma patients in the context of the eye have been described to include lid fibrosis and glaucoma, almost nothing has been reported regarding ophthalmologic surgical complications in scleroderma patients. Observations: Here, we report bilateral zonular dehiscence and iris prolapse during two independent cataract extractions performed by separate experienced anterior segment surgeons in a patient with known systemic sclerosis. The patient did not have any other known risk factors for these complications to occur. Conclusions and Importance: In our patient, bilateral zonular dehiscence raised the possibility of poor connective tissue support secondary to scleroderma. We recommend that clinicians are aware of potential complications in performing anterior segment surgery in patients with known or suspected scleroderma.

Resveratrol Attenuates 2,3,7,8-Tetrachlorodibenzo-p-dioxin-Mediated Induction of Myeloid-Derived Suppressor Cells (MDSC) and Their Functions.

Previously, we showed that 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), an aryl hydrocarbon receptor (AhR) ligand and a potent and persistent toxicant and carcinogenic agent, induces high levels of murine myeloid-derived suppressor cell (MDSC) when injected into mice. In the current study, we demonstrate that Resveratrol (3,4,5-trihydroxy-trans-stilbene; RSV), an AhR antagonist, reduces TCDD-mediated MDSC induction. RSV decreased the number of MDSCs induced by TCDD in mice but also mitigated the immunosuppressive function of TCDD-induced MDSCs. TCDD caused a decrease in F4/80+ macrophages and an increase in CD11C+ dendritic cells, while RSV reversed these effects. TCDD caused upregulation in CXCR2, a critical molecule involved in TCDD-mediated induction of MDSCs, and Arginase-1 (ARG-1), involved in the immunosuppressive functions of MDSCs, while RSV reversed this effect. Transcriptome analysis of Gr1+ MDSCs showed an increased gene expression profile involved in the metabolic pathways in mice exposed to TCDD while RSV-treated mice showed a decrease in such pathways. The bio-energetic profile of these cells showed that RSV treatment decreased the energetic demands induced by TCDD. Overall, the data demonstrated that RSV decreased TCDD-induced MDSC induction and function by altering the dynamics of various myeloid cell populations involving their numbers, phenotype, and immunosuppressive potency. Because MDSCs play a critical role in tumor growth and metastasis, our studies also support the potential use of RSV to attenuate the immunosuppressive properties of MDSC.

Estrobolome dysregulation is associated with altered immunometabolism in a mouse model of endometriosis.

Introduction: Endometriosis is a painful disease that affects around 5% of women of reproductive age. In endometriosis, ectopic endometrial cells or seeded endometrial debris grow in abnormal locations including the peritoneal cavity. Common manifestations of endometriosis include dyspareunia, dysmenorrhea, chronic pelvic pain and often infertility and symptomatic relief or surgical removal are mainstays of treatment. Endometriosis both promotes and responds to estrogen imbalance, leading to intestinal bacterial estrobolome dysregulation and a subsequent induction of inflammation. Methods: In the current study, we investigated the linkage between gut dysbiosis and immune metabolic response in endometriotic mice. Ovariectomized BALB/c mice received intraperitoneal transplantation of endometrial tissue from OVX donors (OVX+END). Control groups included naïve mice (Naïve), naïve mice that received endometrial transplants (Naive+END) and OVX mice that received the vehicle (OVX+VEH). Colonic content was collected 2 weeks post-transplantation for 16s rRNA pyrosequencing and peritoneal fluid was collected to determine the phenotype of inflammatory cells by flow cytometry. Results: We noted a significant increase in the number of peritoneal fluid cells, specifically, T cells, natural killer (NK) cells, and NKT cells in OVX+END mice. Phylogenetic taxonomy analysis showed significant dysbiosis in OVX+END mice, with an increase in abundance of Phylum Tenericutes, Class Mollicutes, Order Aneroplasmatales, and Genus Aneroplasma, and a decrease in Order Clostridiales, and Genus Dehalobacterium, when compared to OVX+VEH controls. The metabolomic profile showed an increase in some tricarboxylic acid cycle (TCA)-related metabolites accompanied by a reduction in short-chain fatty acids (SCFA) such as butyric acid in OVX+END mice. Additionally, the mitochondrial and ATP production of immune cells was enforced to a maximal rate in OVX+END mice when compared to OVX+VEH mice. Conclusion: The current study demonstrates that endometriosis alters the gut microbiota and associated immune metabolism.

Reduction of SARS-CoV-2 salivary viral load with pre-procedural mouth rinses: a randomised, controlled, clinical trial.

Introduction The purpose of this study was to test the short-term efficacy of four commercial mouthwashes versus water in reducing SARS-CoV-2 viral load in the oral cavity over clinically relevant time points.Methods In total, 32 subjects that were proven SARS-CoV-2-positive via polymerase chain reaction (PCR)-based diagnostic test were recruited and randomised into five parallel arms. Cycle threshold (Ct) values were compared in saliva samples between the groups, as well as within the groups at baseline (pre-rinse), zero hours, one hour and two hours post-rinse, using SARS-CoV-2 reverse transcription-PCR analysis.Results We observed a significant increase in Ct values in saliva samples collected immediately after rinsing with all the four mouthwashes - 0.12% chlorhexidine gluconate, 1.5% hydrogen peroxide, 1% povidone iodine, or Listerine - compared to water. A sustained increase in Ct values for up to two hours was only observed in the Listerine and chlorohexidine gluconate groups. We were not able to sufficiently power this clinical trial, so the results remain notional but encouraging and supportive of findings in other emerging mouthwash studies on COVID-19, warranting additional investigations.Conclusions Our evidence suggests that in a clinical setting, prophylactic rinses with Listerine or chlorhexidine gluconate can potentially reduce SARS-CoV-2 viral load in the oral cavity for up to two hours. While limited in statistical power due to the difficulty in obtaining this data, we advocate for pre-procedural mouthwashing, like handwashing, as an economical and safe additional precaution to help mitigate the transmission of SARS-CoV-2 from a potentially infected patient to providers.

An ancient gene network is co-opted for teeth on old and new jaws.

Vertebrate dentitions originated in the posterior pharynx of jawless fishes more than half a billion years ago. As gnathostomes (jawed vertebrates) evolved, teeth developed on oral jaws and helped to establish the dominance of this lineage on land and in the sea. The advent of oral jaws was facilitated, in part, by absence of hox gene expression in the first, most anterior, pharyngeal arch. Much later in evolutionary time, teleost fishes evolved a novel toothed jaw in the pharynx, the location of the first vertebrate teeth. To examine the evolutionary modularity of dentitions, we asked whether oral and pharyngeal teeth develop using common or independent gene regulatory pathways. First, we showed that tooth number is correlated on oral and pharyngeal jaws across species of cichlid fishes from Lake Malawi (East Africa), suggestive of common regulatory mechanisms for tooth initiation. Surprisingly, we found that cichlid pharyngeal dentitions develop in a region of dense hox gene expression. Thus, regulation of tooth number is conserved, despite distinct developmental environments of oral and pharyngeal jaws; pharyngeal jaws occupy hox-positive, endodermal sites, and oral jaws develop in hox-negative regions with ectodermal cell contributions. Next, we studied the expression of a dental gene network for tooth initiation, most genes of which are similarly deployed across the two disparate jaw sites. This collection of genes includes members of the ectodysplasin pathway, eda and edar, expressed identically during the patterning of oral and pharyngeal teeth. Taken together, these data suggest that pharyngeal teeth of jawless vertebrates utilized an ancient gene network before the origin of oral jaws, oral teeth, and ectodermal appendages. The first vertebrate dentition likely appeared in a hox-positive, endodermal environment and expressed a genetic program including ectodysplasin pathway genes. This ancient regulatory circuit was co-opted and modified for teeth in oral jaws of the first jawed vertebrate, and subsequently deployed as jaws enveloped teeth on novel pharyngeal jaws. Our data highlight an amazing modularity of jaws and teeth as they coevolved during the history of vertebrates. We exploit this diversity to infer a core dental gene network, common to the first tooth and all of its descendants.

PARIS and SPARTA: Finding the Achilles' Heel of SARS-CoV-2.

To understand reinfection rates and correlates of protection for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), we established eight different longitudinal cohorts in 2020 under the umbrella of the PARIS (Protection Associated with Rapid Immunity to SARS-CoV-2)/SPARTA (SARS SeroPrevalence And Respiratory Tract Assessment) studies. Here, we describe the PARIS/SPARTA cohorts, the harmonized assays and analysis that are performed across the cohorts, as well as case definitions for SARS-CoV-2 infection and reinfection that have been established by the team of PARIS/SPARTA investigators. IMPORTANCE Determining reinfection rates and correlates of protection against SARS-CoV-2 infection induced by both natural infection and vaccination is of high significance for the prevention and control of coronavirus disease 2019 (COVID-19). Furthermore, understanding reinfections or infection after vaccination and the role immune escape plays in these scenarios will inform the need for updates of the current SARS-CoV-2 vaccines and help update guidelines suitable for the postpandemic world.

Pyroptosis at the forefront of anticancer immunity.

Tumor resistance to apoptosis and the immunosuppressive tumor microenvironment are two major contributors to poor therapeutic responses during cancer intervention. Pyroptosis, a lytic and inflammatory programmed cell death pathway distinct from apoptosis, has subsequently sparked notable interest among cancer researchers for its potential to be clinically harnessed and to address these problems. Recent evidence indicates that pyroptosis induction in tumor cells leads to a robust inflammatory response and marked tumor regression. Underlying its antitumor effect, pyroptosis is mediated by pore-forming gasdermin proteins that facilitate immune cell activation and infiltration through their release of pro-inflammatory cytokines and immunogenic material following cell rupture. Considering its inflammatory nature, however, aberrant pyroptosis may also be implicated in the formation of a tumor supportive microenvironment, as evidenced by the upregulation of gasdermin proteins in certain cancers. In this review, the molecular pathways leading to pyroptosis are introduced, followed by an overview of the seemingly entangled links between pyroptosis and cancer. We describe what is known regarding the impact of pyroptosis on anticancer immunity and give insight into the potential of harnessing pyroptosis as a tool and applying it to novel or existing anticancer strategies.

Bleaching: the initial treatment consideration for tetracycline-stained teeth.

Tray tooth bleaching involves the use of carbamide peroxide in a custom-fitted tray to bleach teeth. One of the most difficult stains to bleach is tetracycline. This paper will present several different patient situations of tetracycline-stained teeth being bleached and will discuss the benefits and limitations of bleaching tetracycline-stained teeth. By providing the patient with realistic potential outcomes of bleaching, as well as the preservation of tooth structure and cost-benefit ratio of bleaching compared to veneers or crowns, the chance for a successful acceptance of the outcome is better, even if the outcome is less than ideal. Bleaching before prosthodontic treatment can also provide a better outcome for subsequent veneers or crowns if that is possible, but sensitivity may preclude bleaching.

Matrix-Bound Zolzoledronate Enhances the Biofilm Colonization of Hydroxyapatite: Effects on Osteonecrosis.

(1) Background: The aim of this study was to test whether matrix-bound zoledronate (zol) molecules enhanced the oral biofilm colonization of a mineralized matrix, rendering the alveolar bone more susceptible to medication-related osteonecrosis of the jaw (MRONJ) following invasive dental procedures. (2) Methods: We tested the effect of matrix-bound zol on the growth and attachment of Porphyromonas gingivalis (Pg), Fusobacterium nucleatum (Fn) and Actinomyces israelii (Ai), and whether the nitrogen-containing component of zol contributed to such effect. The role of oral bacteria in the induction of osteonecrosis was then tested using an extra-oral bone defect model. (3) Results: The attachment of biofilm to hydroxyapatite discs increased when the discs were pre-treated with zol. Bacterial proliferation was not affected. Matrix-bound zol was more potent than non-nitrogen-containing etidronate in enhancing the colonization. Stimulation was dampened by pre-treating the bacteria with histidine. The delivery of oral biofilm to a tibial defect caused osteonecrosis in zol-treated rats. (4) Conclusions: We conclude that matrix-bound zol enhances the oral biofilm colonization of hydroxyapatite. This enhancement depended on the presence of the nitrogen-containing group. The oral biofilm rendered the extra-oral bone susceptible to medication-related osteonecrosis, suggesting that it has an important role in the induction of MRONJ.

Genome-enabled discovery of evolutionary divergence in brains and behavior.

Lake Malawi cichlid fishes exhibit extensive divergence in form and function built from a relatively small number of genetic changes. We compared the genomes of rock- and sand-dwelling species and asked which genetic variants differed among the groups. We found that 96% of differentiated variants reside in non-coding sequence but these non-coding diverged variants are evolutionarily conserved. Genome regions near differentiated variants are enriched for craniofacial, neural and behavioral categories. Following leads from genome sequence, we used rock- vs. sand-species and their hybrids to (i) delineate the push-pull roles of BMP signaling and irx1b in the specification of forebrain territories during gastrulation and (ii) reveal striking context-dependent brain gene expression during adult social behavior. Our results demonstrate how divergent genome sequences can predict differences in key evolutionary traits. We highlight the promise of evolutionary reverse genetics-the inference of phenotypic divergence from unbiased genome sequencing and then empirical validation in natural populations.