Reconstruction options in pediatric population with hemi or total mandibulectomy defects: A systematic review.

Purpose: Mandibular pathologies causing extensive defects in pediatrics is relatively rare, and sparse literature is available for the reconstructive options of the same. The main aim is to provide optimum esthetics and function. Materials and methods: PubMed, Cochrane CENTRAL, Embase, MEDLINE and Scopus databases were searched for articles published only in English language up to May 2021, involving reconstruction of hemi or total mandibulectomy defects in patients with the age of 8 years or less, associated with benign or malignant pathology. Primary outcome variable was the success of reconstruction. Qualitative analysis was performed using a microsoft excel-sheet. Results: Of the 2201 articles reviewed, only fourteen were selected for data extraction. 22 patients were included. Fifteen were benign, six were malignant pathologies, and one was not defined. Hemi-mandibulectomy was performed in twenty-one cases, while one underwent total mandibulectomy. Condyle was preserved in five cases, while was removed in nine. Single-stage reconstruction was done in nineteen cases, while second-stage reconstruction was done in the other three. Reconstruction was done with fibular graft in thirteen cases, while CCG was used in others with variable follow-up time. Though minor complications were observed, success was observed in all cases post reconstruction with either fibula or CCG graft, defined either by function, or growth. Conclusion: Irrespective of the age-group, nature of pathology and size of the defect, reconstruction should be considered with either fibula or CCG in single-stage, as they are equally efficacious, with minor complications. Well-defined reconstructive paradigm should be developed for pediatric mandibular reconstruction.

Apical extrusion of debris with root canal instrumentation in primary teeth: A systematic review.

Aim: This study aimed to systematically review available literature of in vitro studies on apical extrusion of debris through rotary instrumentation in comparison to manual instrumentation in pediatric endodontics, and also to perform a comparison between various rotary instrumentation systems for assessment of debris extrusion. Materials and Methods: A comprehensive search was conducted on PubMed, Medline, Cochrane Library, Embase, Scopus, and Google Scholar without any language restriction and year of publication. A planned search strategy was made for PubMed and applied to other databases. After full-text reading, 7 articles were selected for quantitative synthesis. Modified CONSORT checklist of items for reporting in vitro studies of dental materials was used for quality assessment of included studies. Results: Root canal preparation with rotary instrumentation led to lesser apical debris extrusion than manual instrumentation. Self-adjusting file system was associated with the least debris extrusion among all included studies, followed by ProTaper Next, Kedo-S, ProTaper, K3, Mtwo, Revo-S, and Wave One. Conclusion: More apical debris extrusion was seen with manual instrumentation than rotary instrumentation. Furtrhermore, variance in debris extrusion was seen with different rotary file systems.

Relapse and temporomandibular joint dysfunction (TMD) as postoperative complication in skeletal class III patients undergoing bimaxillary orthognathic surgery: A systematic review.

OBJECTIVES: The aim of this study was to determine Relapse and TMD as postoperative complication in skeletal class III patients undergoing bimaxillary orthognathic surgery. MATERIALS AND METHODS: Data was obtained by database searching using The Cochrane Central Register of Controlled Trials (central), PUBMED, SCOPUS, EMBASE, Google scholar, National Medical library, New Delhi. The titles and abstracts of the electronic search results were screened and evaluated by two observers for eligibility according to the inclusion and exclusion criteria. RESULTS: 5261 articles were retrieved for the review. Among these, 3474 duplicate articles were removed. 418 studies were selected based on the eligibility criteria. For the present review, 30 articles were included after elimination according to the inclusion criteria. The Prisma diagram flowchart demonstrates our selection scheme. Quality assessment criteria to evaluate the studies were decided by two review authors in accordance with CONSORT guidelines. Each study was assessed using the evaluation method described in the Cochrane Handbook for Systematic Reviews. Among the 30 studies included in the review, marked degree of relapse in the mandible was noted from 3 months - 1 year postoperatively in 8 studies, 5 studies reported both TMD prevalence and relapse, whereas only 4 studies reported TMD disorder alone. CONCLUSION: Complications of relapse and TMD are associated with bimaxillary orthognathic surgery procedures. More RCTs and CCTs are needed in this regard to get better quality evidence. This review was registered with PROSPERO: CRD42020211342.

Differentially expressed full-length, fusion and novel isoforms transcripts-based signature of well-differentiated keratinized oral squamous cell carcinoma.

Highly keratinized oral squamous cell carcinoma (OSCC) exhibits an improved response to treatment and prognosis compared with weakly keratinized OSCC. Therefore, we aimed to develop gene transcript signature and to identify novel full-length isoforms, fusion transcript and non-coding RNA to differentiate well-differentiated (WD) with Moderately Differentiated (MD)/Poorly Differentiated (PD)/WD-lymphadenopathy OSCC through, HTA, Isoform sequencing, and NanoString. Additionally, specific copy number gain and loss were also identify in WD keratinized OSCC through Oncoscan array and validated through Real-time PCR in histopathologically characterized FFPE-WD keratinized OSCC. Three-hundred-thirty-eight (338) differentially expressed full-length (FL) transcript isoforms (317 upregulated and 21 down-regulated in OSCC) were identified through Isoform Sequencing using the PacBio platform. Thirty-four (34) highly upregulated differentially expressed transcripts from IsoSeq data were also correlated with HTA2.0 and validated in 42 OSCC samples. We were able to identify 18 differentially expressed transcripts, 12 fusion transcripts, and two long noncoding RNAs. These transcripts were involved in increased cell proliferation, dysregulated metabolic reprogramming, oxidative stress, and immune system markers with enhanced immune rearrangements, suggesting a cancerous nature. However, an increase in proteasomal activity and hemidesmosome proteins suggested an improved prognosis and tumor cell stability in keratinized OSCC and helped to characterize WD with MD/PD/WD with lymphadenopathy OSCC. Additionally, novel isoforms of IL37, NAA10, UCHL3, SPAG7, and RAB24 were identified while in silico functionally validated SPAG7 represented the premalignant phenotype of keratinized (K4) OSCC. Most importantly we found copy number gain and overexpression of EGFR suggest that TKIs may also be used as therapeutics in WD-OSCCs.

Dysbiosis and Variation in Predicted Functions of the Granulation Tissue Microbiome in HPV Positive and Negative Severe Chronic Periodontitis.

Retrospective analysis has already shown correlation between severe Chronic Periodontitis (CP) cases with human papiloma virus (HPV). Hence, we aimed to explore deep-seated infected granulation tissue removed during periodontal flap surgery procedures for residential bacterial species between HPV+ and HVP- CP cases, which may serve as good predisposition marker for oral cancer. All CP-granulation samples showed the prominence of Firmicutes, Proteobacteria, and Bacteroidetes phyla with an abundance of gram negative anaerobes, except Streptococcus. In Beta diversity nonmetric multidimensional scaling plot, the random distribution of species was observed between HPV+ and HPV- CP granulation-samples. However, an abundance of Capnocytophaga ochracea was observed in HPV+ CP samples (p<0.05), while Porphyromonas endodontalis, Macellibacteroides fermentas, Treponema phagedenis, and Campylobacter rectus species were highly abundant in HPV- CP samples (p<0.05). The differential species richness leads altered functions related to mismatch-repair and nucleotide excision-repair and cytoskeleton-proteins. Hence, differential abundance of gram negative bacterial species between HPV+ and HPV- granulation-samples under anaerobic conditions may release virulence factors which may alter pathways favouring carcinogenesis. Hence, these species may serve as good predisposition marker for oral-cancer.

16S rRNA Long-Read Sequencing of the Granulation Tissue from Nonsmokers and Smokers-Severe Chronic Periodontitis Patients.

Smoking has been associated with increased risk of periodontitis. The aim of the present study was to compare the periodontal disease severity among smokers and nonsmokers which may help in better understanding of predisposition to this chronic inflammation mediated diseases. We selected deep-seated infected granulation tissue removed during periodontal flap surgery procedures for identification and differential abundance of residential bacterial species among smokers and nonsmokers through long-read sequencing technology targeting full-length 16S rRNA gene. A total of 8 phyla were identified among which Firmicutes and Bacteroidetes were most dominating. Differential abundance analysis of OTUs through PICRUST showed significant (p>0.05) abundance of Phyla-Fusobacteria (Streptobacillus moniliformis); Phyla-Firmicutes (Streptococcus equi), and Phyla Proteobacteria (Enhydrobacter aerosaccus) in nonsmokers compared to smokers. The differential abundance of oral metagenomes in smokers showed significant enrichment of host genes modulating pathways involving primary immunodeficiency, citrate cycle, streptomycin biosynthesis, vitamin B6 metabolism, butanoate metabolism, glycine, serine, and threonine metabolism pathways. While thiamine metabolism, amino acid metabolism, homologous recombination, epithelial cell signaling, aminoacyl-tRNA biosynthesis, phosphonate/phosphinate metabolism, polycyclic aromatic hydrocarbon degradation, synthesis and degradation of ketone bodies, translation factors, Ascorbate and aldarate metabolism, and DNA replication pathways were significantly enriched in nonsmokers, modulation of these pathways in oral cavities due to differential enrichment of metagenomes in smokers may lead to an increased susceptibility to infections and/or higher formation of DNA adducts, which may increase the risk of carcinogenesis.

Differential genomics and transcriptomics between tyrosine kinase inhibitor-sensitive and -resistant BCR-ABL-dependent chronic myeloid leukemia.

Previously, it has been stated that the BCR-ABL fusion-protein is sufficient to induce Chronic Myeloid Leukemia (CML), but additional genomic-changes are required for disease progression. Hence, we profiled control and tyrosine kinase inhibitors (TKI) alone or in combination with other drug-treated CML-samples in different phases, categorized as drug-sensitive and drug-resistant on the basis of BCR-ABL transcripts, the marker of major molecular-response. Molecular-profiling was done using the molecular-inversion probe-based-array, Human Transcriptomics-Array2.0, and Axiom-Biobank genotyping-arrays. At the transcript-level, clusters of control, TKI-resistant and TKI-sensitive cases were correlated with BCR-ABL transcript-levels. Both at the gene- and exon-levels, up-regulation of MPO, TPX2, and TYMS and down-regulation of STAT6, FOS, TGFBR2, and ITK lead up-regulation of the cell-cycle, DNA-replication, DNA-repair pathways and down-regulation of the immune-system, chemokine- and interleukin-signaling, TCR, TGF beta and MAPK signaling pathways. A comparison between TKI-sensitive and TKI-resistant cases revealed up-regulation of LAPTM4B, HLTF, PIEZO2, CFH, CD109, ANGPT1 in CML-resistant cases, leading to up-regulation of autophagy-, protein-ubiquitination-, stem-cell-, complement-, TGFß- and homeostasis-pathways with specific involvement of the Tie2 and Basigin signaling-pathway. Dysregulated pathways were accompanied with low CNVs in CP-new and CP-UT-TKI-sensitive-cases with undetectable BCR-ABL-copies. High CNVs (previously reported gain of 9q34) were observed in BCR-ABL-independent and -dependent TKI, non-sensitive-CP-UT/AP-UT/B-UT and B-new samples. Further, genotyping CML-CP-UT cases with BCR-ABL 0-to-77.02%-copies, the identified, rsID239798 and rsID9475077, were associated with FAM83B, a candidate for therapeutic resistance. The presence of BCR-ABL, additional genetic-events, dysregulated-signaling-pathways and rsIDs associated with FAM83B in TKI-resistant-cases can be used to develop a signature-profile that may help in monitoring therapy.

IsoSeq analysis and functional annotation of the infratentorial ependymoma tumor tissue on PacBio RSII platform.

Here, we sequenced and functionally annotated the long reads (1-2 kb) cDNAs library of an infratentorial ependymoma tumor tissue on PacBio RSII by Iso-Seq protocol using SMRT technology. 577 MB, data was generated from the brain tissues of ependymoma tumor patient, producing 1,19,313 high-quality reads assembled into 19,878 contigs using Celera assembler followed by Quiver pipelines, which produced 2952 unique protein accessions in the nr protein database and 307 KEGG pathways. Additionally, when we compared GO terms of second and third level with alternative splicing data obtained through HTA Array2.0. We identified four and twelve transcript cluster IDs in Level-2 and Level-3 scores respectively with alternative splicing index predicting mainly the major pathways of hallmarks of cancer. Out of these transcript cluster IDs only transcript cluster IDs of gene PNMT, SNN and LAMB1 showed Reads Per Kilobase of exon model per Million mapped reads (RPKM) values at gene-level expression (GE) and transcript-level (TE) track. Most importantly, brain-specific genes--PNMT, SNN and LAMB1 show their involvement in Ependymoma.