Endodontic management of an unidentified foreign body in a maxillary central incisor of a HIV-positive patient

The Human Immunodeficiency Virus (HIV) has been a focal point of investigation over the last few years. Consideration of endodontic treatment in an HIV-positive patient needs a calculated approach as the choice of materials and chemicals may influence the final result. A recent investigation showed that cases presenting with pre-operative pathology during examinations have a significantly lower prognosis after treatment. This clinical case report discusses the treatment approach of an upper left central incisor of an HIV-positive patient. The treatment approach and the outcome after a fifteen-month follow-up period are outlined.https://www.sada.co.za/the-sadjam2020Odontolog

Mandibular first and second premolars with challenging root canal anatomy - Part 1 : Review of the literature

Mandibular premolars can be one of the most difficult teeth to treat endodontically because of the variations in root canal anatomy. According to England, Hartwell and Lance,3 variation in root canal anatomy is one of the main reasons why mandibular premolars have a high frequency of failures and flare-ups. The literature indicates that the incidence of the number of roots and the number of canals varies greatly in human teeth.https://www.sada.co.za/the-sadjam2021Odontolog

The effect of dosing Megasphaera elsdenii NCIMB 41125 (Me) on lactation performance of multiparous Holstein cows

The objective of the study was to determine whether early post-partum dosing of Megasphaera elsdenii NCIMB 41125 (Me) will be beneficial to performance of high producing TMR-fed cows. Sixty multiparous Holstein cows were randomly allocated to four treatments (60% or 70% concentrate diet and placebo or Me [single oral dose of 10 cfu in 250 mL suspension on day of calving and Days 10 and 20 post-partum, respectively]). Observations were recorded between calving and 80 days post-partum. Performance data were analysed for all 60 cows combined and for the 40 highest producing cows only, since they were considered more susceptible to ruminal acidosis. For all 60 cows, body weight, condition score and milk yield tended to increase with Me, but data for the 40 highest producing cows suggested that this response could be ascribed primarily to higher producing cows on the higher concentrate diet. Dry matter intake and milk protein were not affected by Me, whereas milk fat percentage increased with Me but only in cows on the 60% concentrate diet. Results support the hypothesis that dosing with Megasphaera elsdenii is most likely to benefit higher producing cows with greater risk of acidosis.http://www.sasas.co.za

Mandibular first and second premolars with challenging root canal anatomy - Part 2 : Endodontic management

In Part 1 of this article the authors give a literature review focussed on the complexity and variation in the anatomy of mandibular premolars. In Part 2 of this series the authors, by means of clinical case studies, will illustrate, discuss and give recommendations on diagnostic as well as endodontic clinical management of these, often complexed cases.https://www.sada.co.za/the-sadjam2021Odontolog

Cytotoxicity of diplodiatoxin, dipmatol and diplonine, metabolites synthesized by Stenocarpella maydis

The cytotoxicity of three Stenocarpella maydis metabolites (diplodiatoxin, dipmatol and diplonine) was investigated on Neuro-2a, CHO-K1 and MDBK cell lines. Diplodiatoxin was the most cytotoxic followed by dipmatol. Conversely, diplonine was not cytotoxic. Diplodiatoxin and dipmatol affected mitochondrial succinate dehydrogenase (MTT assay) and the overall viability of cells as assessed in real-time (xCELLigence assay). The results obtained so far indicate that diplodiatoxin and dipmatol exert their toxicity possibly via the necrotic cell death pathway.National Research Foundation (NRF), International Foundation for Science (IFS) and the Joy Liebenberg Trust Fund.http://www.elsevier.com/locate/toxiconhb201

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Driver Fusions and Their Implications in the Development and Treatment of Human Cancers.

Gene fusions represent an important class of somatic alterations in cancer. We systematically investigated fusions in 9,624 tumors across 33 cancer types using multiple fusion calling tools. We identified a total of 25,664 fusions, with a 63% validation rate. Integration of gene expression, copy number, and fusion annotation data revealed that fusions involving oncogenes tend to exhibit increased expression, whereas fusions involving tumor suppressors have the opposite effect. For fusions involving kinases, we found 1,275 with an intact kinase domain, the proportion of which varied significantly across cancer types. Our study suggests that fusions drive the development of 16.5% of cancer cases and function as the sole driver in more than 1% of them. Finally, we identified druggable fusions involving genes such as TMPRSS2, RET, FGFR3, ALK, and ESR1 in 6.0% of cases, and we predicted immunogenic peptides, suggesting that fusions may provide leads for targeted drug and immune therapy

Somatic Mutational Landscape of Splicing Factor Genes and Their Functional Consequences across 33 Cancer Types

Hotspot mutations in splicing factor genes have been recently reported at high frequency in hematological malignancies, suggesting the importance of RNA splicing in cancer. We analyzed whole-exome sequencing data across 33 tumor types in The Cancer Genome Atlas (TCGA), and we identified 119 splicing factor genes with significant non-silent mutation patterns, including mutation over-representation, recurrent loss of function (tumor suppressor-like), or hotspot mutation profile (oncogene-like). Furthermore, RNA sequencing analysis revealed altered splicing events associated with selected splicing factor mutations. In addition, we were able to identify common gene pathway profiles associated with the presence of these mutations. Our analysis suggests that somatic alteration of genes involved in the RNA-splicing process is common in cancer and may represent an underappreciated hallmark of tumorigenesis

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although the MYC oncogene has been implicated in cancer, a systematic assessment of alterations of MYC, related transcription factors, and co-regulatory proteins, forming the proximal MYC network (PMN), across human cancers is lacking. Using computational approaches, we define genomic and proteomic features associated with MYC and the PMN across the 33 cancers of The Cancer Genome Atlas. Pan-cancer, 28% of all samples had at least one of the MYC paralogs amplified. In contrast, the MYC antagonists MGA and MNT were the most frequently mutated or deleted members, proposing a role as tumor suppressors. MYC alterations were mutually exclusive with PIK3CA, PTEN, APC, or BRAF alterations, suggesting that MYC is a distinct oncogenic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such as immune response and growth factor signaling; chromatin, translation, and DNA replication/repair were conserved pan-cancer. This analysis reveals insights into MYC biology and is a reference for biomarkers and therapeutics for cancers with alterations of MYC or the PMN. We present a computational study determining the frequency and extent of alterations of the MYC network across the 33 human cancers of TCGA. These data, together with MYC, positively correlated pathways as well as mutually exclusive cancer genes, will be a resource for understanding MYC-driven cancers and designing of therapeutics

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dysregulated in tumors, but only a handful are known to play pathophysiological roles in cancer. We inferred lncRNAs that dysregulate cancer pathways, oncogenes, and tumor suppressors (cancer genes) by modeling their effects on the activity of transcription factors, RNA-binding proteins, and microRNAs in 5,185 TCGA tumors and 1,019 ENCODE assays. Our predictions included hundreds of candidate onco- and tumor-suppressor lncRNAs (cancer lncRNAs) whose somatic alterations account for the dysregulation of dozens of cancer genes and pathways in each of 14 tumor contexts. To demonstrate proof of concept, we showed that perturbations targeting OIP5-AS1 (an inferred tumor suppressor) and TUG1 and WT1-AS (inferred onco-lncRNAs) dysregulated cancer genes and altered proliferation of breast and gynecologic cancer cells. Our analysis indicates that, although most lncRNAs are dysregulated in a tumor-specific manner, some, including OIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergistically dysregulate cancer pathways in multiple tumor contexts. Chiu et al. present a pan-cancer analysis of lncRNA regulatory interactions. They suggest that the dysregulation of hundreds of lncRNAs target and alter the expression of cancer genes and pathways in each tumor context. This implies that hundreds of lncRNAs can alter tumor phenotypes in each tumor context