Objective

Overall aim of this prospective, randomized, positive controlled, double-blind in vivo study was to identify the effects of a test dental gel containing 2.6% edathamil with an added carrier and permeability enhancer vs. a positive control dentifrice on periodontal health measures in patients with Stage II and III periodontitis.

Methods

In this prospective double-blinded, randomized study, 33 subjects were randomly assigned in a 1:1 ratio to brushing their teeth with either the test gel (LivFresh^®, Livionex Dental Gel, Los Gatos, CA 95030) or the positive control toothpaste (Crest ProHealth^®, P&G, Cincinnati, OH 45202).Full-mouth gingival index, modified sulcus bleeding index, and periodontal pocket probing depths were recorded for all teeth at baseline, and on days 90 and 180.Subjects brushed with the study material twice a day.

Results

The test dental gel reduced gingival inflammation and bleeding, as well as periodontal pocket probing depths significantly more than a control dentifrice.

Conclusions

In this pilot study in subjects with Stage II and III periodontitis, a test dental gel was found to improve gingival inflammation and bleeding, as well as periodontal pocket depths significantly better than a control dentifrice.

Background

Interferon-gamma (IFNγ) exerts potent growth inhibitory effects on a wide range of cancer cells through unknown signaling pathways. We pursued complementary screening approaches to characterize the growth inhibition pathway.

Methods

We performed chemical genomics and whole genome targeting CRISPR/Cas9 screens using patient-derived melanoma lines to uncover essential nodes in the IFNγ-mediated growth inhibition pathway. We used transcriptomic profiling to identify cell death pathways activated upon IFNγ exposure. Live imaging experiments coupled with apoptosis assays confirmed the involvement of these pathways in IFNγ-mediated cell death.

Results

We show that IFNγ signaling activated ERK. Blocking ERK activation rescued IFNγ-mediated apoptosis in 17 of 23 (~ 74%) cell lines representing BRAF, NRAS, NF1 mutant, and triple wild type subtypes of cutaneous melanoma. ERK signaling induced a stress response, ultimately leading to apoptosis through the activity of DR5 and NOXA proteins.

Conclusions

Our results provide a new understanding of the IFNγ growth inhibition pathway, which will be crucial in defining mechanisms of immunotherapy response and resistance.

Background

Compliance to periodontal maintenance therapy (PMT) is essential for long-term periodontal health. Between PMT visits, patients must maintain good oral hygiene. A dentifrice with demonstrable clinical benefits for use between PMT visits would be highly desirable. The aim of this clinical study was to investigate the effect of a novel dental gel on probing depths (PD) and inflammation when used as a home care dentifrice in Stage I and II periodontitis patients.

Methods

This double-blind clinical study randomized 65 subjects with Stage I and II periodontitis to the novel dental gel containing 2.6% EDTA, and a commercially available anti-gingivitis dentifrice with 0.454% stannous fluoride. Primary endpoint was PD at 6 months for those sites with baseline PD ≥ 4 mm and secondary endpoints included whole mouth mean scores of modified gingival index (MGI), modified sulcus bleeding index (mSBI) and plaque index (PI). No SRP was performed at baseline.

Results

Subjects using the novel dentifrice showed significant PD reductions of 1.18 mm (from 4.27 mm at baseline to 3.09 mm at 6 months) compared to 0.93 mm (from 4.23 mm at baseline to 3.30 mm at 6 months) shown for those using the positive control dentifrice. Difference between treatments at 6 months was 0.21 mm with P-value = 0.0126. Significant improvements in MGI (P = 0.0000), mSBI (P = 0.0000), and PI (P = 0.0102) were also observed in 6 months.

Conclusion

The novel dentifrice showed significant reductions in PD and gingival inflammation over 6 months solely as a home care dentifrice without baseline SRP in Stage I and II periodontitis maintenance patients.

We describe the landscape of somatic genomic alterations of 66 chromophobe renal cell carcinomas (ChRCCs) on the basis of multidimensional and comprehensive characterization, including mtDNA and whole-genome sequencing. The result is consistent that ChRCC originates from the distal nephron compared with other kidney cancers with more proximal origins. Combined mtDNA and gene expression analysis implicates changes in mitochondrial function as a component of the disease biology, while suggesting alternative roles for mtDNA mutations in cancers relying on oxidative phosphorylation. Genomic rearrangements lead to recurrent structural breakpoints within TERT promoter region, which correlates with highly elevated TERT expression and manifestation of kataegis, representing a mechanism of TERT upregulation in cancer distinct from previously observed amplifications and point mutations.