Longitudinal Treatment Outcomes of Microsurgical Treatment of Neurosensory Deficit after Lower Third Molar Surgery: A Prospective Case Series

Objective

To prospectively evaluate the longitudinal subjective and objective outcomes of the microsurgical treatment of lingual nerve (LN) and inferior alveolar nerve (IAN) injury after third molar surgery.

Materials and Methods

A 1-year longitudinal observational study was conducted on patients who received LN or IAN repair after third molar surgery-induced nerve injury. Subjective assessments (“numbness”, “hyperaesthesia”, “pain”, “taste disturbance”, “speech” and “social life impact”) and objective assessments (light touch threshold, two-point discrimination, pain threshold, and taste discrimination) were recorded.

Results

12 patients (10 females) with 10 LN and 2 IAN repairs were recruited. The subjective outcomes at post-operative 12 months for LN and IAN repair were improved. “Pain” and “hyperaesthesia” were most drastically improved. Light touch threshold improved from 44.7g to 1.2g for LN repair and 2g to 0.5g for IAN repair.

Conclusion

Microsurgical treatment of moderate to severe LN injury after lower third molar surgery offered significant subjective and objective sensory improvements. 100% FSR was achieved at post-operative 6 months.     

New Candidate Biomarkers in the Female Genital Tract to Evaluate Microbicide Toxicity

Vaginal microbicides hold great promise for the prevention of viral diseases like HIV, but the failure of several microbicide candidates in clinical trials has raised important questions regarding the parameters to be evaluated to determine in vivo efficacy in humans. Clinical trials of the candidate microbicides nonoxynol-9 (N9) and cellulose sulfate revealed an increase in HIV infection, vaginal inflammation, and recruitment of HIV susceptible lymphocytes, highlighting the need to identify biomarkers that can accurately predict microbicide toxicity early in preclinical development and in human trials. We used quantitative proteomics and RT-PCR approaches in mice and rabbits to identify protein changes in vaginal fluid and tissue in response to treatment with N9 or benzalkonium chloride (BZK). We compared changes generated with N9 and BZK treatment to the changes generated in response to tenofovir gel, a candidate microbicide that holds promise as a safe and effective microbicide. Both compounds down regulated mucin 5 subtype B, and peptidoglycan recognition protein 1 in vaginal tissue; however, mucosal brush samples also showed upregulation of plasma proteins fibrinogen, plasminogen, apolipoprotein A-1, and apolipoprotein C-1, which may be a response to the erosive nature of N9 and BZK. Additional proteins down-regulated in vaginal tissue by N9 or BZK treatment include CD166 antigen, olfactomedin-4, and anterior gradient protein 2 homolog. We also observed increases in the expression of C-C chemokines CCL3, CCL5, and CCL7 in response to treatment. There was concordance in expression level changes for several of these proteins using both the mouse and rabbit models. Using a human vaginal epithelial cell line, the expression of mucin 5 subtype B and olfactomedin-4 were down-regulated in response to N9, suggesting these markers could apply to humans. These data identifies new proteins that after further validation could become part of a panel of biomarkers to effectively evaluate microbicide toxicity.     

PERGA: A Paired-End Read Guided De Novo Assembler for Extending Contigs Using SVM and Look Ahead Approach

Since the read lengths of high throughput sequencing (HTS) technologies are short, de novo assembly which plays significant roles in many applications remains a great challenge. Most of the state-of-the-art approaches base on de Bruijn graph strategy and overlap-layout strategy. However, these approaches which depend on k-mers or read overlaps do not fully utilize information of paired-end and single-end reads when resolving branches. Since they treat all single-end reads with overlapped length larger than a fix threshold equally, they fail to use the more confident long overlapped reads for assembling and mix up with the relative short overlapped reads. Moreover, these approaches have not been special designed for handling tandem repeats (repeats occur adjacently in the genome) and they usually break down the contigs near the tandem repeats. We present PERGA (Paired-End Reads Guided Assembler), a novel sequence-reads-guided de novo assembly approach, which adopts greedy-like prediction strategy for assembling reads to contigs and scaffolds using paired-end reads and different read overlap size ranging from O _max to O _min to resolve the gaps and branches. By constructing a decision model using machine learning approach based on branch features, PERGA can determine the correct extension in 99.7% of cases. When the correct extension cannot be determined, PERGA will try to extend the contig by all feasible extensions and determine the correct extension by using look-ahead approach. Many difficult-resolved branches are due to tandem repeats which are close in the genome. PERGA detects such different copies of the repeats to resolve the branches to make the extension much longer and more accurate. We evaluated PERGA on both Illumina real and simulated datasets ranging from small bacterial genomes to large human chromosome, and it constructed longer and more accurate contigs and scaffolds than other state-of-the-art assemblers. PERGA can be freely downloaded at https://github.com/hitbio/PERGA.     

Genotyping performance assessment of whole genome amplified DNA with respect to multiplexing level of assay and its period of storage

Whole genome amplification can faithfully amplify genomic DNA (gDNA) with minimal bias and substantial genome coverage. Whole genome amplified DNA (wgaDNA) has been tested to be workable for high-throughput genotyping arrays. However, issues about whether wgaDNA would decrease genotyping performance at increasing multiplexing levels and whether the storage period of wgaDNA would reduce genotyping performance have not been examined. Using the Sequenom MassARRAY iPLEX Gold assays, we investigated 174 single nucleotide polymorphisms for 3 groups of matched samples: group 1 of 20 gDNA samples, group 2 of 20 freshly prepared wgaDNA samples, and group 3 of 20 stored wgaDNA samples that had been kept frozen at -70°C for 18 months. MassARRAY is a medium-throughput genotyping platform with reaction chemistry different from those of high-throughput genotyping arrays. The results showed that genotyping performance (efficiency and accuracy) of freshly prepared wgaDNA was similar to that of gDNA at various multiplexing levels (17-plex, 21-plex, 28-plex and 36-plex) of the MassARRAY assays. However, compared with gDNA or freshly prepared wgaDNA, stored wgaDNA was found to give diminished genotyping performance (efficiency and accuracy) due to potentially inferior quality. Consequently, no matter whether gDNA or wgaDNA was used, better genotyping efficiency would tend to have better genotyping accuracy.     

An ORMOSIL-Containing Orthodontic Acrylic Resin with Concomitant Improvements in Antimicrobial and Fracture Toughness Properties

Global increase in patients seeking orthodontic treatment creates a demand for the use of acrylic resins in removable appliances and retainers. Orthodontic removable appliance wearers have a higher risk of oral infections that are caused by the formation of bacterial and fungal biofilms on the appliance surface. Here, we present the synthetic route for an antibacterial and antifungal organically-modified silicate (ORMOSIL) that has multiple methacryloloxy functionalities attached to a siloxane backbone (quaternary ammonium methacryloxy silicate, or QAMS). By dissolving the water-insoluble, rubbery ORMOSIL in methyl methacrylate, QAMS may be copolymerized with polymethyl methacrylate, and covalently incorporated in the pressure-processed acrylic resin. The latter demonstrated a predominantly contact-killing effect on Streptococcus mutans ATCC 36558 and Actinomyces naselundii ATCC 12104 biofilms, while inhibiting adhesion of Candida albicans ATCC 90028 on the acrylic surface. Apart from its favorable antimicrobial activities, QAMS-containing acrylic resins exhibited decreased water wettability and improved toughness, without adversely affecting the flexural strength and modulus, water sorption and solubility, when compared with QAMS-free acrylic resin. The covalently bound, antimicrobial orthodontic acrylic resin with improved toughness represents advancement over other experimental antimicrobial acrylic resin formulations, in its potential to simultaneously prevent oral infections during appliance wear, and improve the fracture resistance of those appliances.     

MetaCluster 4.0: a novel binning algorithm for NGS reads and huge number of species

Next-generation sequencing (NGS) technologies allow the sequencing of microbial communities directly from the environment without prior culturing. The output of environmental DNA sequencing consists of many reads from genomes of different unknown species, making the clustering together reads from the same (or similar) species (also known as binning) a crucial step. The difficulties of the binning problem are due to the following four factors: (1) the lack of reference genomes; (2) uneven abundance ratio of species; (3) short NGS reads; and (4) a large number of species (can be more than a hundred). None of the existing binning tools can handle all four factors. No tools, including both AbundanceBin and MetaCluster 3.0, have demonstrated reasonable performance on a sample with more than 20 species. In this article, we introduce MetaCluster 4.0, an unsupervised binning algorithm that can accurately (with about 80% precision and sensitivity in all cases and at least 90% in some cases) and efficiently bin short reads with varying abundance ratios and is able to handle datasets with 100 species. The novelty of MetaCluster 4.0 stems from solving a few important problems: how to divide reads into groups by a probabilistic approach, how to estimate the 4-mer distribution of each group, how to estimate the number of species, and how to modify MetaCluster 3.0 to handle a large number of species. We show that Meta Cluster 4.0 is effective for both simulated and real datasets. Supplementary Material is available at www.liebertonline.com/cmb.