Interrogation of transcriptomic changes associated with drug-induced hepatic sinusoidal dilatation in colorectal cancer

Drug-related sinusoidal dilatation (SD) is a common form of hepatotoxicity associated with oxaliplatin-based chemotherapy used prior to resection of colorectal liver metastases (CRLM). Recently, hepatic SD has also been associated with anti-delta like 4 (DLL4) cancer therapies targeting the NOTCH pathway. To investigate the hypothesis that NOTCH signaling plays an important role in drug-induced SD, gene expression changes were examined in livers from anti-DLL4 and oxaliplatin-induced SD in non-human primate (NHP) and patients, respectively. Putative mechanistic biomarkers of bevacizumab (bev)-mediated protection against oxaliplatin-induced SD were also investigated. RNA was extracted from whole liver sections or centrilobular regions by laser-capture microdissection (LCM) obtained from NHP administered anti-DLL4 fragment antigen-binding (F(ab’)2 or patients with CRLM receiving oxaliplatin-based chemotherapy with or without bev. mRNA expression was quantified using high-throughput real-time quantitative PCR. Significance analysis was used to identify genes with differential expression patterns (false discovery rate (FDR) < 0.05). Eleven (CCL2, CCND1, EFNB2, ERG, ICAM1, IL16, LFNG, NOTCH1, NOTCH4, PRDX1, and TGFB1) and six (CDH5, EFNB2, HES1, IL16, MIK67, HES1 and VWF) candidate genes were differentially expressed in the liver of anti-DLL4- and oxaliplatin-induced SD, respectively. Addition of bev to oxaliplatin-based chemotherapy resulted in differential changes in hepatic CDH5, HEY1, IL16, JAG1, MMP9, NOTCH4 and TIMP1 expression. This work implicates NOTCH and IL16 pathways in the pathogenesis of drug-induced SD and further explains the hepato-protective effect of bev in oxaliplatin-induced SD observed in CRLM patients

Evaluation of the Efficacy of Commercially Available Nano- Hydroxyapatite Paste as a Desensitizing Agent

Aim: To evaluate the efficacy of commercially available nano-hydroxyapaptite paste as a desensitizing agent. Materials & Methods: The study included 30 subjects complaining of dentinal hypersensitivity. After prophylactic scaling & root planing, patients were instructed to brush with the given commercially available nano-hydroxyapatite paste twice a day. A numeric rating scale was used to measure the parameter of pain related to the stimuli at the baseline and after the application of gel at the intervals of 24 hours, 1 month, 3 months and 6 months. Results: There was remarkable decrease in the dentinal hypersensitivity at the end of 6 months. Intragroup comparisons at various time intervals were significant (p<0.0001). The mean pain score at the end of 6 months was 3.00 +/- 0.468 from 7.93 +/- 0.248 at the baseline. Conclusion: Hence, commercially available nano-hydroxyapatite paste is effective in reducing dentinal hypersensitivity

Socket Preservation: A Foregoing Approach for Future Implant Placement

Background: Significant changes in bone volume and morphology following tooth extraction can make implant rehabilitation very difficult and these changes increase as the time from extraction to implant placement increases. The extraction socket preservation technique conserves the alveolar architecture and prevents hard and soft tissue collapse that minimizes the necessity for future augmentation procedures. Many techniques have been discovered for socket preservation which allows the dentist to place the implant in extraction sites that were thought to be compromised. Recently, to reinstate alveolar bone loss and to support efficient placement of dental implants many different bone substitute such as autografts, allografts, xenografts, synthetic biomaterials and osteoactive agents have been proposed. The aim of this case report was to evaluate the aptitude of bioactive glass with collagen membrane in the socket preservation for the development of ideal future implant site

Is pseudophakic astigmatism a desirable goal?

PURPOSE: To determine whether pseudophakic astigmatism is a desirable goal, and if so, which one is better: against-the-rule (ATR) or with-the-rule (WTR). METHOD: Eyes were included only if they had an uncorrected vision &#x0026;gt; or = 6/18 and N/18. Three groups, of 40 patients each were evaluated: group 1, pseudophakes with neutral astigmatism; group 2, with ATR and group 3, with WTR astigmatism Unaided distance and near visual acuity was recorded. Statistical analysis was performed using the chi-square test for independence. RESULTS: Unaided distance vision of &#x0026;gt; or = 6/7.5 was achieved in 19 eyes (47.5&#x0025;) of group 1 (neutral), 12 eyes (30&#x0025;) in group 2 (ATR), and 5 eyes (12.5&#x0025;) in group 3 (WTR) (p = 0.0133, significant). Unaided near vision of &#x0026;gt; or = N/9 was achieved in 17 eyes (42.5&#x0025;) in group 1 (neutral), 34 eyes (85&#x0025;) in group 2 (ATR), and 10 eyes (25&#x0025;) in group 3 (WTR) (P &#x0026;lt; 0.001, significant). Group 1 (neutral) fared the best for unaided distance visual acuity. Group 2 (ATR) was better than in group 3 (WTR) for distant vision. Group 2 (ATR) fared the best for unaided near vision. CONCLUSION: ATR astigmatism could be a desirable goal after cataract extraction in selected populations because the largest proportion of these cases achieved good unaided near vision with acceptable distant vision

Evaluation of a Commercially Available Herbal Gel Containing Acacia Arabica in Chronic Generalized Gingivitis Patients

Background : The use of herbal drugs for the prevention and treatment of various health ailments has been in practice from the time immemorial. Acacia arabica is considered as an astringent, demulcent, aphrodisiac, antihelminthic, antimicrobial, antidiarrhoeal with good nutritional value in Indian traditional medicine system. This study was done to evaluate the efficacy of a commercially available gel containing Acacia Arabica in reducing the gingival inflammation in chronic generalized gingivitis patients. Materials and Method: The study included 15 subjects diagnosed with chronic generalized gingivitis. They were asked to apply the Acacia Arabica gel for 1 week before undergoing mechanical therapy. The clinical parameters such as the Gingival Index (GI) and the Plaque Index were taken at baseline and one week after application of the gel. Results: The clinical parameters were compared using the Paired sample t- test and the commercially available gel containing Acacia Arabica was found to be effective in reducing inflammation in patients with chronic generalized gingivitis. The gingival index score reduced from 1.94 ± 0.234 at baseline to 1.22 ± 0.196 after one week whereas the plaque score reduced from 3.82 ± 0.524 at baseline to 2.86 ± 0.520 after one week. Conclusion: Herbal gel containing Acacia Arabica has proven to be useful in reducing the inflammation as well as an anti-plaque agent

Clinical Evaluation of 0.10% Sodium Hypochlorite as an Oral Rinse in Chronic Generalized Periodontitis Patients

Aim: This study was done with an aim to evaluate the effect of 0.10% sodium hypochlorite in chronic periodontitis patients. Materials and Method: The study included 30 patients diagnosed with chronic generalized periodontitis who reported to the Department of Periodontology at Karnavati School of Dentistry. The duration of the study was 3 months with 30 patients are randomly divided into 2 groups. The test group consisted of 15 patients who were advised to rinse with 15 mL of a fresh solution of 0.10% sodium hypochlorite (test) for 30 seconds whereas the control group patients were advised to rinse with 15 mL of water (control) twice weekly. The test group patients received professional subgingival irrigation for 5 minutes with 0.10% sodium hypochlorite at baseline, 1st month, 2nd month and 3rd month and the control group patients received professional subgingival irrigation for 5 minutes with water, but no subgingival or supragingival scaling was undertaken. The cl inical parameters recorded were: Turesky et al modification of Quigley hein index (1970), Gingival index (1963) and Papillary Marginal Attachment index by Schour and Massler (1947). All the parameters were recorded at the baseline, 1 st month, 2nd month and 3rd month. Adverse events were evaluated by questionnaire and visual examination. Result: All 30 patients in the study completed the 3-month study. The differences in clinical parameters between the sodium hypochlorite rinse group and the water rinse group were statistically significant. No adverse events were reported by any of the study patients. Conclusion: The results from the study showed that rinsing with 0.10% sodium hypochlorite led to decrease in dental plaque level and bleeding on probing and may prove to be a promising new approach for the management of periodontal disease

Advances in Gingival Augmentation Techniques - A Literature Review

Background: In the current practice of periodontics, clinicians are faced with the challenge of not only addressing biological and functional problems present in the periodontium but also providing therapy that results in acceptable aesthetics. The presence of mucogingival problems and gingival recession around anterior, highly visible teeth exemplifies a situation in which a treatment modality that addresses both biological and aesthetic demands is required from the therapist. A variety of soft tissue augmentation procedures directed at root coverage have been documented in the literature utilizing autogenous or allogenic soft tissue grafting or guided tissue regeneration (GTR). The purpose of this review was to assess the effectiveness of newer materials in gingival augmentation procedures

Mutation scanning using MUT-MAP, a high-throughput, microfluidic chip-based, multi-analyte panel.

Targeted anticancer therapies rely on the identification of patient subgroups most likely to respond to treatment. Predictive biomarkers play a key role in patient selection, while diagnostic and prognostic biomarkers expand our understanding of tumor biology, suggest treatment combinations, and facilitate discovery of novel drug targets. We have developed a high-throughput microfluidics method for mutation detection (MUT-MAP, mutation multi-analyte panel) based on TaqMan or allele-specific PCR (AS-PCR) assays. We analyzed a set of 71 mutations across six genes of therapeutic interest. The six-gene mutation panel was designed to detect the most common mutations in the EGFR, KRAS, PIK3CA, NRAS, BRAF, and AKT1 oncogenes. The DNA was preamplified using custom-designed primer sets before the TaqMan/AS-PCR assays were carried out using the Biomark microfluidics system (Fluidigm; South San Francisco, CA). A cross-reactivity analysis enabled the generation of a robust automated mutation-calling algorithm which was then validated in a series of 51 cell lines and 33 FFPE clinical samples. All detected mutations were confirmed by other means. Sample input titrations confirmed the assay sensitivity with as little as 2 ng gDNA, and demonstrated excellent inter- and intra-chip reproducibility. Parallel analysis of 92 clinical trial samples was carried out using 2-100 ng genomic DNA (gDNA), allowing the simultaneous detection of multiple mutations. DNA prepared from both fresh frozen and formalin-fixed, paraffin-embedded (FFPE) samples were used, and the analysis was routinely completed in 2-3 days: traditional assays require 0.5-1 µg high-quality DNA, and take significantly longer to analyze. This assay can detect a wide range of mutations in therapeutically relevant genes from very small amounts of sample DNA. As such, the mutation assay developed is a valuable tool for high-throughput biomarker discovery and validation in personalized medicine and cancer drug development

Next generation MUT-MAP, a high-sensitivity high-throughput microfluidics chip-based mutation analysis panel.

Molecular profiling of tumor tissue to detect alterations, such as oncogenic mutations, plays a vital role in determining treatment options in oncology. Hence, there is an increasing need for a robust and high-throughput technology to detect oncogenic hotspot mutations. Although commercial assays are available to detect genetic alterations in single genes, only a limited amount of tissue is often available from patients, requiring multiplexing to allow for simultaneous detection of mutations in many genes using low DNA input. Even though next-generation sequencing (NGS) platforms provide powerful tools for this purpose, they face challenges such as high cost, large DNA input requirement, complex data analysis, and long turnaround times, limiting their use in clinical settings. We report the development of the next generation mutation multi-analyte panel (MUT-MAP), a high-throughput microfluidic, panel for detecting 120 somatic mutations across eleven genes of therapeutic interest (AKT1, BRAF, EGFR, FGFR3, FLT3, HRAS, KIT, KRAS, MET, NRAS, and PIK3CA) using allele-specific PCR (AS-PCR) and Taqman technology. This mutation panel requires as little as 2 ng of high quality DNA from fresh frozen or 100 ng of DNA from formalin-fixed paraffin-embedded (FFPE) tissues. Mutation calls, including an automated data analysis process, have been implemented to run 88 samples per day. Validation of this platform using plasmids showed robust signal and low cross-reactivity in all of the newly added assays and mutation calls in cell line samples were found to be consistent with the Catalogue of Somatic Mutations in Cancer (COSMIC) database allowing for direct comparison of our platform to Sanger sequencing. High correlation with NGS when compared to the SuraSeq500 panel run on the Ion Torrent platform in a FFPE dilution experiment showed assay sensitivity down to 0.45%. This multiplexed mutation panel is a valuable tool for high-throughput biomarker discovery in personalized medicine and cancer drug development