ABSTRACT Hemifacial spasm is an uncontrollable, recurrent facial muscular contraction that typically occurs on one side of the face, cannot be suppressed, and can last the entire day and during sleep. The most common underlying cause of facial nerve compression is an enlarged or abnormal tracking blood vessel at the brainstem level. Clinical diagnoses are frequently based on a patient's medical history and physical examination. Before deciding on a course of action, however, an electromyogram and MRI are performed to determine the underlying cause. Due to its high effectiveness (success rates of 85% to 95%) and low frequency of adverse reactions, botulinum toxin is the preferred therapy for hemifacial spasm and can provide transient symptomatic alleviation. Surgical microvascular decompression is a therapeutic approach that targets the underlying cause of this condition and has an average success rate of 85%.

Using 16 rRNA sequencing, a total of 233 subgingival sites from 8 smokers and 9 non-smokers over 6-12 months(804 subgingival samples total) were analyzed to study subgingival microbiome dysbiosis in smokers over time.

The subgingival microbiome is one of the most stable microbial ecosystems in the human body. Alterations in the subgingival microbiome have been associated with periodontal disease, but their variations over time and between different subgingival sites in periodontally healthy individuals have not been well described. We performed extensive, longitudinal sampling of the subgingival microbiome from five periodontally healthy individuals to define baseline spatial and temporal variations. A total of 251 subgingival samples from 5 subjects were collected over 6–12 months and deep sequenced. The overall microbial diversity and composition differed significantly between individuals. Within each individual, we observed considerable differences in microbiome composition between different subgingival sites. However, for a given site, the microbiome was remarkably stable over time, and this stability was associated with increased microbial diversity but was inversely correlated with the enrichment of putative periodontal pathogens. In contrast to microbiome composition, the predicted functional metagenome was similar across space and time, suggesting that periodontal health is associated with shared gene functions encoded by different microbiome consortia that are individualized. To our knowledge, this is one of the most detailed longitudinal analysis of the healthy subgingival microbiome to date that examined the longitudinal variability of different subgingival sites within individuals. These results suggest that a single measurement of the healthy subgingival microbiome at a given site can provide long term information of the microbial composition and functional potential, but sampling of each site is necessary to define the composition and community structure at individual subgingival sites.

With the increased incidence of traumatic injuries and the advanced understanding of the periodontal and alveolar healing process, teeth splinting has become a common practice for stabilizing traumatized teeth. Consequently, several splinting materials and techniques have been introduced in the past few years. Despite the detrimental role of bacterial biofilm on healing, the level of biofilm development on these material surfaces has not been well investigated. Bacterial biofilms are severely detrimental for periodontal healing of avulsed and luxated teeth. Thus, biofilm growth becomes a critical factor in selecting the material of choice for dental splints. In this study, we aim to assess the level of oral biofilm growth on four different splinting systems: Ribbond©, orthodontic NiTi wire, monofilament fishing line, and Titanium Trauma Splint. A total of 72 extracted anterior teeth were divided into four groups. We splinted six rows of three teeth each per group. The teeth selected were caries-free and periodontitis-free at the time of extraction. To assess biofilm growth, a supragingival dental plaque sample was cultured and directly inoculated into all groups. After 7 days, bacterial growth was quantified by live/dead fluorescent microscopy assay and colony forming unit counts (CFU). Using one-way ANOVA and Bonferroni’s post hoc tests, we demonstrated that all splint systems allowed for bacterial growth. However, the Titanium Trauma Splint (TTS) allowed for the least amount of biofilm growth compared to other splint systems.

Aims Assess the impact of nurse-led clinical review and the application of guidelines (European Society of Gastroenterology and National GI Endoscopy Quality Improvement Programme) to endoscopy lists to see if this will result in an increase in capacity within the system.

Aims This study aimed to characterize the value of Endoscopic Ultrasound (EUS)-guided drainage of Pancreatic Fluid collections (PFCs) with either plastic or Lumen Apposing Metal Stents (LAMS).

Objectives To profile and compare the subgingival microbiome of RA patients with OA controls. Methods RA (n = 260) and OA (n = 296) patients underwent full-mouth examination and subgingival samples were collected. Bacterial DNA was profiled using 16 S rRNA Illumina sequencing. Following data filtering and normalization, hierarchical clustering analysis was used to group samples. Multivariable regression was used to examine associations of patient factors with membership in the two largest clusters. Differential abundance between RA and OA was examined using voom method and linear modelling with empirical Bayes moderation (Linear Models for Microarray Analysis, limma), accounting for the effects of periodontitis, race, marital status and smoking. Results Alpha diversity indices were similar in RA and OA after accounting for periodontitis. After filtering, 286 taxa were available for analysis. Samples grouped into one of seven clusters with membership sizes of 324, 223, 3, 2, 2, 1 and 1 patients, respectively. RA-OA status was not associated with cluster membership. Factors associated with cluster 1 (vs 2) membership included periodontitis, smoking, marital status and Caucasian race. Accounting for periodontitis, 10 taxa (3.5% of those examined) were in lower abundance in RA than OA. There were no associations between lower abundance taxa or other select taxa examined with RA autoantibody concentrations. Conclusion Leveraging data from a large case-control study and accounting for multiple factors known to influence oral health status, results from this study failed to identify a subgingival microbial fingerprint that could reliably discriminate RA from OA patients.

In Part 1 of this three-part article series, antibiotic exposure, prescribing patterns, and clinical sequelae of antibiotic consumption were discussed. The information gleaned from available literature and from the perspectives of professionals with knowledge and strong interest in this area will hopefully guide clinicians in using antibiotics more judiciously and responsibly. In this second part of the series, potential effects of antibiotic use on the human microbiome are discussed along with data on oral isotretinoin, subantimicrobial (subantibiotic) dose doxycycline, and other therapeutic agents commonly used in dermatology.

Traditionally, the dental profession has primarily treated periodontitis using a mechanical/surgical, rather than a pharmaceutical, approach. However, based on experiments several decades ago which demonstrated that tetracyclines, unexpectedly, inhibit collagen- and bone-destructive mammalian-derived enzymes (e.g. the collagenases), and through non-antibiotic mechanisms, the concept of host-modulation therapy (HMT) was developed. Accordingly, two drug-development strategies evolved: (i) the development of non-antimicrobial formulations of doxycycline; and (ii) the chemical modification of tetracyclines to eliminate their antibiotic activity but retain (or even enhance) their anti-collagenase properties. Regarding the latter, these chemically modified tetracyclines (CMTs) showed efficacy in vitro, in animal models of periodontal (and relevant systemic) disease, and in preliminary clinical trials on patients with Kaposi's sarcoma (however, at the high doses used, photosensitivity was a significant side-effect). In the first strategy, subantimicrobial-dose doxycycline (SDD) demonstrated safety and efficacy in human clinical trials and was approved by the U S Food and Drug Administration (U S FDA) and in other countries for the treatment of periodontitis (20 mg, twice daily, i.e. once every 12 hours) adjunctive to scaling and root planing, and for chronic inflammatory skin diseases (40-mg sustained-release 'beads'). SDD also showed efficacy in patients with systemic diseases relevant to periodontitis, including diabetes mellitus and arthritis, and in postmenopausal women with local and systemic bone loss. Importantly, long-term administration of SDD, of up to 2 years, in clinical trials did not produce antibiotic side-effects. SDD (and in the future, new HMTs, such as low-dose CMT-3, resolvins and chemically modified curcumins) may shift the paradigm of periodontal therapy from a predominantly surgical approach to the greater use of medicinal/pharmacologic strategies, ultimately to benefit larger numbers of patients.

Oral and topical antibiotics are commonly prescribed in dermatologie practice, often for noninfectious disorders, such as acne vulgaris and rosacea. Concerns related to antibiotic exposure from both medical and nonmedical sources require that clinicians consider in each case why and how antibiotics are being used and to make appropriate adjustments to limit antibiotic exposure whenever possible. This first article of a three-part series discusses prescribing patterns in dermatology, provides an overview of sources of antibiotic exposure, reviews the relative correlations between the magnitude of antibiotic consumption and emergence of antibiotic resistance patterns, evaluates the impact of alterations in antibiotic prescribing, and discusses the potential relevance and clinical sequelae of antibiotic use, with emphasis on how antibiotics are used in dermatology.

In this third article of the three-part series, management of skin and soft tissue infections is reviewed with emphasis on new information on methicillin-resistant Staphylococcus aureus. Due to changes in the evolution of methicillin-resistant Staphylococcus aureus clones, previous distinctions between healthcare-acquired methicillin-resistant Staphylococcus aureus and community-acquired methicillin-resistant Staphylococcus aureus are currently much less clinically relevant. Many nosocomial cases of methicillin-resistant Staphylococcus aureus infection are now caused by community-acquired methicillin-resistant Staphylococcus aureus, with changing patterns of antibiotic susceptibility and resistance. Also reviewed are clinical scenarios where antibiotics may not be needed and suggestions for optimal use of antibiotic therapy for dermatologie conditions, including recommendations on perioperative antibiotic use.

BACKGROUND AND OBJECTIVE:Periodontitis results from interplay between genetic and environmental factors. Single nucleotide polymorphisms (SNPs) in the coding region of the toll-like receptor 4 gene (TLR4) may be associated with periodontitis, although previous studies have been inconclusive. Moreover, the interaction between environmental factors, such as cigarette smoking (a major risk factor for periodontitis), and Porphyromonas gingivalis (a major periodontal pathogen) with the TLR4 coding region Asp299Gly SNP (rs4986790; a SNP associated with lipopolysaccharide-mediated inflammatory responses in periodontitis), have been largely ignored in previous reports. Therefore, the objective of this study was to examine the association between TLR4 Asp299Gly (rs4986790) with alveolar bone height loss (ABHL) and periodontitis, accounting for interactions between this SNP with smoking and P. gingivalis prevalence. The CD14/-260 SNP (rs2569190) served as a control, as a recent meta-analysis suggested no relationship between this SNP and periodontitis. MATERIAL AND METHODS:This multicenter study included 617 participants who had rheumatoid arthritis or osteoarthritis. This report presents a secondary outcome from the primary case-control study examining the relationship of periodontitis with established rheumatoid arthritis. The Centers for Disease Control/American Academy of Periodontology case definitions of periodontitis were used for this analysis. Participants received a full-mouth clinical periodontal examination and panoramic radiograph. Percentage ABHL was measured on posterior teeth. The TLR4 Asp299Gly and CD14/-260 SNPs were selected a priori and genotypes were determined using the ImmunoChip array (Illumina(®) ). Minor allele frequencies and associations with periodontitis and ABHL did not differ according to rheumatoid arthritis vs. osteoarthritis status; therefore, data from these two groups were pooled. The presence of P. gingivalis was detected in subgingival plaque by PCR. Multivariate ordinal logistic regression examined associations between the SNPs and periodontitis or ABHL. SNP interactions with smoking and P. gingivalis were analyzed. RESULTS:A significant, negative interaction was observed between the TLR4 SNP and the presence of P. gingivalis (p = 0.045) with respect to periodontitis. The TLR4 minor variant was also associated with less ABHL: 16.8% of individuals with low ABHL, 9.0% with moderate ABHL and 11.2% with high ABHL had the minor allele [p = 0.029; odds ratio = 0.58 (95% confidence interval: 0.36-0.95)]. The interaction between the TLR4 SNP and smoking was not significant with respect to periodontitis or ABHL. The CD14 SNP was not associated with periodontitis or ABHL. CONCLUSION:The TLR4 Asp299Gly SNP significantly interacted with P. gingivalis in conferring a decreased risk of periodontitis and may be protective against ABHL, a feature of periodontitis. Agents blocking TLR4 signaling, a strategy currently under investigation for the treatment of other inflammatory conditions, may warrant investigation in the context of periodontitis related to the presence of P. gingivalis.

Chronic periodontitis is an inflammatory disease of the periodontium affecting nearly 65 million adults in the United States. Changes in subgingival microbiota have long been associated with chronic periodontitis. Recent culture-independent molecular studies have revealed the immense richness and complexity of oral microbial communities. However, data sets across studies have not been directly compared, and whether the observed microbial variations are consistent across different studies is not known. Here, we used 16S rRNA sequencing to survey the subgingival microbiota in 25 subjects with chronic periodontal disease and 25 healthy controls and compared our data sets with those of three previously reported microbiome studies. Consistent with data from previous studies, our results demonstrate a significantly altered microbial community structure with decreased heterogeneity in periodontal disease. Comparison with data from three previously reported studies revealed that subgingival microbiota clustered by study. However, differences between periodontal health and disease were larger than the technical variations across studies. Using a prediction score and applying five different distance metrics, we observed two predominant clusters. One cluster was driven by Fusobacterium and Porphyromonas and was associated with clinically apparent periodontitis, and the second cluster was dominated by Rothia and Streptococcus in the majority of healthy sites. The predicted functional capabilities of the periodontitis microbiome were significantly altered. Genes involved in bacterial motility, energy metabolism, and lipopolysaccharide biosynthesis were overrepresented in periodontal disease, whereas genes associated with transporters, the phosphotransferase system, transcription factors, amino acid biosynthesis, and glycolysis/gluconeogenesis were enriched in healthy controls. These results demonstrate significant alterations in microbial composition and function in periodontitis and suggest genes and metabolic pathways associated with periodontal disease.

OBJECTIVE:To examine the degree to which shared risk factors explain the relationship of periodontitis (PD) to rheumatoid arthritis (RA) and to determine the associations of PD and Porphyromonas gingivalis with pathologic and clinical features of RA.METHODS:Patients with RA (n = 287) and patients with osteoarthritis as disease controls (n = 330) underwent a standardized periodontal examination. The HLA-DRB1 status of all participants was imputed using single-nucleotide polymorphisms from the extended major histocompatibility complex. Circulating anti-P gingivalis antibodies were measured using an enzyme-linked immunosorbent assay, and subgingival plaque was assessed for the presence of P gingivalis using polymerase chain reaction (PCR). Associations of PD with RA were examined using multivariable regression.RESULTS:Presence of PD was more common in patients with RA and patients with anti-citrullinated protein antibody (ACPA)-positive RA (n = 240; determined using the anti-cyclic citrullinated peptide 2 [anti-CCP-2] test) than in controls (35% and 37%, respectively, versus 26%; P = 0.022 and P = 0.006, respectively). There were no differences between RA patients and controls in the levels of anti-P gingivalis or the frequency of P gingivalis positivity by PCR. The anti-P gingivalis findings showed a weak, but statistically significant, association with the findings for both anti-CCP-2 (r = 0.14, P = 0.022) and rheumatoid factor (RF) (r = 0.19, P = 0.001). Presence of PD was associated with increased swollen joint counts (P = 0.004), greater disease activity according to the 28-joint Disease Activity Score using C-reactive protein level (P = 0.045), and higher total Sharp scores of radiographic damage (P = 0.015), as well as with the presence and levels of anti-CCP-2 (P = 0.011) and RF (P < 0.001). The expression levels of select ACPAs (including antibodies to citrullinated filaggrin) were higher in patients with subgingival P gingivalis and in those with higher levels of anti-P gingivalis antibodies, irrespective of smoking status. Associations of PD with established seropositive RA were independent of all covariates examined, including evidence of P gingivalis infection.CONCLUSION:Both PD and P gingivalis appear to shape the autoreactivity of RA. In addition, these results demonstrate an independent relationship between PD and established seropositive RA.

BACKGROUND:Matrix metalloproteinases (MMPs) are a family of host-derived proteinases reported to mediate multiple functions associated with periodontal breakdown and inflammation. High MMP levels in African-American children with localized aggressive periodontitis (LAgP) have been reported previously by the present authors. However, little is known about MMP reductions in gingival crevicular fluid (GCF) after therapy. This study aims to evaluate MMP levels in the GCF after treatment of LAgP and to correlate these levels with clinical response. METHODS:GCF samples were collected from 29 African-American individuals diagnosed with LAgP. GCF was collected from one diseased site (probing depth [PD] >4 mm, bleeding on probing [BOP], and clinical attachment level ≥ 2 mm) and one healthy site (PD ≤ 3 mm, no BOP) from each individual at baseline and 3 and 6 months after periodontal treatment, which consisted of full-mouth scaling and root planing (SRP) and systemic antibiotics. The volume of GCF was controlled using a calibrated gingival fluid meter, and levels of MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, MMP-12, and MMP-13 were assessed using fluorometric kits. RESULTS:MMP-1, MMP-8, MMP-9, MMP-12, and MMP-13 levels were reduced significantly up to 6 months, comparable to healthy sites at the same point. Significant correlations were noted between MMP-2, MMP-3, MMP-8, MMP-9, MMP-12, and MMP-13 levels and percentage of sites with PD >4 mm. MMP-3, MMP-12, and MMP-13 levels also correlated with mean PD of affected sites. CONCLUSION:Treatment of LAgP with SRP and systemic antibiotics was effective in reducing local levels of specific MMPs in African-American individuals, which correlated positively with some clinical parameters.

In 1983, it was first reported that tetracyclines (TCs) can modulate the host response, including (but not limited to) inhibition of pathologic matrix metalloproteinase (MMP) activity, and by mechanisms unrelated to the antibacterial properties of these drugs. Soon thereafter, strategies were developed to generate non-antibacterial formulations (subantimicrobial-dose doxycycline; SDD) and compositions (chemically modified tetracyclines; CMTs) of TCs as host-modulating drugs to treat periodontal and other inflammatory diseases. This review focuses on the history and rationale for the development of: (a) SDD which led to two government-approved medications, one for periodontitis and the other for acne/rosacea and (b) CMTs, which led to the identification of the active site of the drugs responsible for MMP inhibition and to studies demonstrating evidence of efficacy of the most potent of these, CMT-3, as an anti-angiogenesis agent in patients with the cancer, Kaposi's sarcoma, and as a potential treatment for a fatal lung disease (acute respiratory distress syndrome; ARDS). In addition, this review discusses a number of clinical studies, some up to 2 years' duration, demonstrating evidence of safety and efficacy of SDD formulations in humans with oral inflammatory diseases (periodontitis, pemphigoid) as well as medical diseases, including rheumatoid arthritis, post-menopausal osteopenia, type II diabetes, cardiovascular diseases, and a rare and fatal lung disease, lymphangioleiomyomatosis.

Aim To demonstrate a capacity for producing exopolysaccharides (EPSs) and an ability to form biofilm on abiotic materials of Actinomyces oris strain K20. Methodology The productivity of EPSs and the ability to form biofilm of strain K20 were evaluated by measuring viscosity of spent culture media and by scanning electron microscopy (SEM) and the biofilm assay on microtitre plates, respectively. High-performance liquid chromatography was used to determine the chemical composition of the viscous materials. To examine the role of the viscous materials attributable to the pathogenicity in this organism, the ability of strain K20 to induce abscess formation was compared in mice to that of ATCC 27044. Results The viscosity of the spent culture media of K20 was significantly higher than that of ATCC 27044. Strain K20 showed dense meshwork structures around the cells and formed biofilms on microtitre plates, whereas ATCC 27044 did not. Chemical analysis of the viscous materials revealed that they were mainly composed of neutral sugars with mannose constituting 77.5% of the polysaccharides. Strain K20 induced persistent abscesses in mice lasting at least 5 days at a concentration of 108 cells mL−1, whereas abscesses induced by ATCC 27044 healed and disappeared or decreased in size at day 5. Conclusions Strain K20 produced EPSs, mainly consisting of mannose, and formed biofilms. This phenotype might play an important role for A. oris to express virulence through the progression of apical periodontitis.

The objective of this study was to characterize the subgingival microbiota of African-American children with Localized Aggressive Periodontitis (LAP). Fifty-one children were included. Subgingival plaque samples were taken from diseased (DD) and healthy sites (DH) in LAP and from healthy sites in HS and HC and analyzed by 16S rRNA-based microarrays. Aggregatibacter actinomycetemcomitans (Aa) was the only species found to be both more prevalent (OR = 8.3, p = 0.0025) and abundant (p < 0.01) in DD. Filifactor alocis (Fa) was also found to be more prevalent in DD (OR 2.31, CI 1.06-5.01, p = 0.03). Most prevalent species in healthy sites were Selenomonas spp, Veillonella spp, Streptococcus spp, Bergeyella sp, and Kingella oralis. Overall, Streptococcus spp, Campylobacter gracilis, Capnocytophaga granulosa, Haemophilus parainfluenzae, and Lautropia mirabilis were most abundant in healthy children, while Aa, Fa, Tannerella sp, Solobacterium moorei, Parvimonas micra, and Capnocytophaga sp were most abundant in LAP. Based on a comprehensive analysis with 16S rRNA-based microarrays, Aa was strongly associated and site-specific in LAP. In contrast, other species were found to be associated with healthy sites and individuals (ClinicalTrials.gov number CT01330719). Abbreviations: healthy site in healthy sibling (HS); healthy site in healthy control child (HC).