Oral Probiotic Supplementation as an Adjunct to Non-surgical Therapy in Peri-implantitis Lesions: A Pilot Study

Introduction: During the last decade, the results of several clinical studies suggested that oral probiotics may potentially improve oral health. The first study examining the effects of probiotics on oral health demonstrated that almost every patient with gingivitis, periodontitis or pregnancy gingivitis, had significant improvements in measurable periodontal indices when they were treated with a locally administered culture supernatant of a Lactobacillus acidophilus strain. This finding sparked several other studies to further examine the potential for treating oral diseases, such as, combating halitosis, oral candidiasis, and dental caries with probiotics. Of our interest, Fernandez et al. and Hollstrom et al. published their clinical studies investigating the effects of probiotics on peri-implant mucositis lesions and had conflicting results. In a recent study investigating the effect of Lactobacillus reuteri on peri-implantitis lesions, it was concluded that the oral probiotics together with mechanical debridement gave additional improvement for all clinical parameters. However, more studies are needed to confirm this finding as the majority of published studies explored the effects of probiotics on periodontitis and peri-implant mucositis lesions, very few focused specifically on peri-implantitis lesions. Therefore, the goals of this study were to examine the clinical, inflammatory and microbiological effects of oral probiotics when used as an adjunct in addition to non-surgical debridement in treating peri-implantitis lesions. Methods: A double blind pilot study was conducted between the test group (probiotics) versus the control group (placebo) as an adjunct to non-surgical treatment of peri-implantitis sites. Peri-implantitis is defined when there is a probing depth of 6mm or more with bleeding on probing and 3mm or more radiographic bone loss compared to radiographs when implants were placed. A full mouth non-surgical treatment was performed and peri-implantitis sites were debrided using titanium curettes. Subsequently, oral probiotics containing strains of S. salivarius K12, S. salivarius M18, L. reuteri and L. paracasei were given to the test group while the control group received placebo tablets. Subgingival plaque, gingival crevicular fluid/peri-implant crevicular fluid volume and clinical parameters such as probing depth,clinical attachment level, bleeding on probing plaque index and gingival index were recorded for analysis. Moreover, these data were collected from not only peri-implantitis sites of each subject but also from healthy and periodontitis sites of all patients. Microbiological testing was done by 16sRNA analysis and GCF/PICF analysis were done by ELISA. Statistical analyses were done by using One-way Anova. Results: There were no statistically significant differences for all clinical parameters comparing baseline to 90 days for the test and control groups at all sites. However, biologically, only probiotic group in peri-implantitis sites demonstrated statistically significant reduction after 90 days. Moreover, there were no statistical differences for MMP-9 or interleukin-1β. There was a statistically significance increase for P. gingivalis for peri-implantitis sites (p=0.04) for the probiotic group. There was statistically significant increase in commensal bacteria of the green, purple and blue complexes specifically C.concisus (p=0.028), A. graevenitzii (p=0.023) and Actinomyces species (p=0.015) in probiotic group in peri-implantitis sites compared to placebo. . Conclusions: Our findings suggest that adjunctive use of oral probiotics appeared to have limited effects on clinical parameters, however, biologically, they significantly decreased PICF TNF-α levels, a pro-inflammatory cytokine which is associated with periodontal and peri-implant breakdown. Furthermore, oral probiotics may help to shift the microbial flora towards commensal bacteria as it was shown to be statistically increased. in peri-implantitis sites. This suggests that oral probiotics may play a role in affecting the overall microbiota of the oral cavity shift towards a healthier and more symbiotic environment

A Novel Gonadotropin-Releasing Hormone 1 (Gnrh1) Enhancer-Derived Noncoding RNA Regulates Gnrh1 Gene Expression in GnRH Neuronal Cell Models.

Gonadotropin-releasing hormone (GnRH), a neuropeptide released from a small population of neurons in the hypothalamus, is the central mediator of the hypothalamic-pituitary-gonadal axis, and is required for normal reproductive development and function. Evolutionarily conserved regulatory elements in the mouse, rat, and human Gnrh1 gene include three enhancers and the proximal promoter, which confer Gnrh1 gene expression specifically in GnRH neurons. In immortalized mouse hypothalamic GnRH (GT1-7) neurons, which show pulsatile GnRH release in culture, RNA sequencing and RT-qPCR revealed that expression of a novel long noncoding RNA at Gnrh1 enhancer 1 correlates with high levels of GnRH mRNA expression. In GT1-7 neurons, which contain a transgene carrying 3 kb of the rat Gnrh1 regulatory region, both the mouse and rat Gnrh1 enhancer-derived noncoding RNAs (GnRH-E1 RNAs) are expressed. We investigated the characteristics and function of the endogenous mouse GnRH-E1 RNA. Strand-specific RT-PCR analysis of GnRH-E1 RNA in GT1-7 cells revealed GnRH-E1 RNAs that are transcribed in the sense and antisense directions from distinct 5' start sites, are 3' polyadenylated, and are over 2 kb in length. These RNAs are localized in the nucleus and have a half-life of over 8 hours. In GT1-7 neurons, siRNA knockdown of mouse GnRH-E1 RNA resulted in a significant decrease in the expression of the Gnrh1 primary transcript and Gnrh1 mRNA. Over-expression of either the sense or antisense mouse GnRH-E1 RNA in immature, migratory GnRH (GN11) neurons, which do not express either GnRH-E1 RNA or GnRH mRNA, induced the transcriptional activity of co-transfected rat Gnrh1 gene regulatory elements, where the induction requires the presence of the rat Gnrh1 promoter. Together, these data indicate that GnRH-E1 RNA is an inducer of Gnrh1 gene expression. GnRH-E1 RNA may play an important role in the development and maturation of GnRH neurons

Measurement of the Negative Muon Anomalous Magnetic Moment to 0.7 ppm

The anomalous magnetic moment of the negative muon has been measured to a precision of 0.7 parts per million (ppm) at the Brookhaven Alternating Gradient Synchrotron. This result is based on data collected in 2001, and is over an order of magnitude more precise than the previous measurement of the negative muon. The result a_mu= 11 659 214(8)(3) \times 10^{-10} (0.7 ppm), where the first uncertainty is statistical and the second is sytematic, is consistend with previous measurements of the anomaly for the positive and negative muon. The average for the muon anomaly a_{mu}(exp) = 11 659 208(6) \times 10^{-10} (0.5ppm).Comment: 4 pages, 4 figures, submitted to Physical Review Letters, revised to reflect referee comments. Text further revised to reflect additional referee comments and a corrected Fig. 3 replaces the older versio

News from the Muon (g-2) Experiment at BNL

The magnetic moment anomaly a_mu = (g_mu - 2) / 2 of the positive muon has been measured at the Brookhaven Alternating Gradient Synchrotron with an uncertainty of 0.7 ppm. The new result, based on data taken in 2000, agrees well with previous measurements. Standard Model evaluations currently differ from the experimental result by 1.6 to 3.0 standard deviations.Comment: Talk presented at RADCOR - Loops and Legs 2002, Kloster Banz, Germany, September 8-13 2002, to be published in Nuclear Physics B (Proc. Suppl.); 5 pages, 3 figure

The Muon Anomalous Magnetic Moment and the Standard Model

The muon anomalous magnetic moment measurement, when compared with theory, can be used to test many extensions to the standard model. The most recent measurement made by the Brookhaven E821 Collaboration reduces the uncertainty on the world average of a_mu to 0.7 ppm, comparable in precision to theory. This paper describes the experiment and the current theoretical efforts to establish a correct standard model reference value for the muon anomaly.Comment: Plenary Talk; PANIC'02 XVI Particles and Nuclear International Conference, Osaka, Japan; Sept. 30 - Oct. 4, 2002; Report describes the published 0.7 ppm result and updates the theory statu

Search for Lorentz and CPT Violation Effects in Muon Spin Precession

The spin precession frequency of muons stored in the $(g-2)$ storage ring has been analyzed for evidence of Lorentz and CPT violation. Two Lorentz and CPT violation signatures were searched for: a nonzero $\Delta\omega_{a}$ (=$\omega_{a}^{\mu^{+}}-\omega_{a}^{\mu^{-}}$); and a sidereal variation of $\omega_{a}^{\mu^{\pm}}$. No significant effect is found, and the following limits on the standard-model extension parameters are obtained: $b_{Z} =-(1.0 \pm 1.1)\times 10^{-23}$ GeV; $(m_{\mu}d_{Z0}+H_{XY}) = (1.8 \pm 6.0 \times 10^{-23})$ GeV; and the 95% confidence level limits $\check{b}_{\perp}^{\mu^{+}}< 1.4 \times 10^{-24}$ GeV and $\check{b}_{\perp}^{\mu^{-}} < 2.6 \times 10^{-24}$ GeV.Comment: 5 pages, 3 figures, submitted to Physical Review Letters, Modified to answer the referees suggestion

An Improved Limit on the Muon Electric Dipole Moment

Three independent searches for an electric dipole moment (EDM) of the positive and negative muons have been performed, using spin precession data from the muon g-2 storage ring at Brookhaven National Laboratory. Details on the experimental apparatus and the three analyses are presented. Since the individual results on the positive and negative muon, as well as the combined result, d=-0.1(0.9)E-19 e-cm, are all consistent with zero, we set a new muon EDM limit, |d| < 1.9E-19 e-cm (95% C.L.). This represents a factor of 5 improvement over the previous best limit on the muon EDM.Comment: 19 pages, 15 figures, 7 table

Search for Lorentz and CPT Violation Effects in Muon Spin Precession

The spin precession frequency of muons stored in the $(g-2)$ storage ring has been analyzed for evidence of Lorentz and CPT violation. Two Lorentz and CPT violation signatures were searched for: a nonzero $\Delta\omega_{a}$ (=$\omega_{a}^{\mu^{+}}-\omega_{a}^{\mu^{-}}$); and a sidereal variation of $\omega_{a}^{\mu^{\pm}}$. No significant effect is found, and the following limits on the standard-model extension parameters are obtained: $b_{Z} =-(1.0 \pm 1.1)\times 10^{-23}$ GeV; $(m_{\mu}d_{Z0}+H_{XY}) = (1.8 \pm 6.0 \times 10^{-23})$ GeV; and the 95% confidence level limits $\check{b}_{\perp}^{\mu^{+}}< 1.4 \times 10^{-24}$ GeV and $\check{b}_{\perp}^{\mu^{-}} < 2.6 \times 10^{-24}$ GeV.Comment: 5 pages, 3 figures, submitted to Physical Review Letters, Modified to answer the referees suggestion

Final Report of the Muon E821 Anomalous Magnetic Moment Measurement at BNL

We present the final report from a series of precision measurements of the muon anomalous magnetic moment, a_mu = (g-2)/2. The details of the experimental method, apparatus, data taking, and analysis are summarized. Data obtained at Brookhaven National Laboratory, using nearly equal samples of positive and negative muons, were used to deduce a_mu(Expt) = 11 659 208.0(5.4)(3.3) x 10^-10, where the statistical and systematic uncertainties are given, respectively. The combined uncertainty of 0.54 ppm represents a 14-fold improvement compared to previous measurements at CERN. The standard model value for a_mu includes contributions from virtual QED, weak, and hadronic processes. While the QED processes account for most of the anomaly, the largest theoretical uncertainty, ~0.55 ppm, is associated with first-order hadronic vacuum polarization. Present standard model evaluations, based on e+e- hadronic cross sections, lie 2.2 - 2.7 standard deviations below the experimental result.Comment: Summary paper of E821 Collaboration measurements of the muon anomalous magnetic moment, each reported earlier in Letters or Brief Reports; 96 pages, 41 figures, 16 tables. Revised version submitted to PR