The Potential of Light Microscopic Features of the Oral Mucosa in Predicting Post-mortem Interval

Objectives: The post-mortem interval (PMI) refers to the amount of time elapsed between death and discovery of the body. This study aimed to evaluate light microscopic cellular changes in the oral mucosa and identify the potential of this method for predicting PMI. Methods: This prospective study was conducted between July 2016 and January 2018 at the Institute of Dental Sciences, Siksha ‘O’ Anusandhan University, Bhubaneswar, India. A total of 150 post-mortem (including 75 gingival and 75 buccal mucosa samples) and 40 ante-mortem (including 20 gingival and 20 buccal mucosa samples) tissue samples were compared using haematoxylin and eosin, periodic acid-Schiff (PAS) and van Gieson stains. Microscopic changes in the epithelium and connective tissue were categorised according to PMI stage as early (<12.5 hours since death), intermediate (12.5–20.5 hours since death) or late (>20.5 hours since death). Results: Most epithelial cellular changes occurred early, except for arc-shaped nuclei and epithelial shredding which were intermediate and late changes, respectively. However, microscopic changes in the connective tissue were only observable at ≥12.5 hours. There was a progressive decrease in intensity in van Gieson stains and an increase in intensity in PAS stains as PMI increased. Several microscopic features were found to be significant predictors of PMI including epithelial homogenisation, cytoplasmic vacuolation, nuclear degeneration, arc-shaped nuclei, chromatin clumping, red blood cell clumping and lysis, melanin incontinency, myofibril degeneration, salivary gland acini degeneration and epithelial connective tissue separation (P <0.050 each). Conclusion: These findings indicate that microscopic evaluation of the oral mucosa may be helpful for PMI prediction.   KEYWORDS Post-mortem Changes; Light Microscopy; Oral Mucosa; Epithelial Cells; Lamina Propria; Salivary Glands; Histocytochemistry; Periodic Acid-Schiff Reaction; India

Electron microscopy of the K2 killer effect of Saccharomyces cerevisiae T206 on a mesophilic wine yeast

A mesophilic wine yeast, Saccharomyces cerevisiae CSIR Y217 K-R- was subjected to the K2 killer effect of Saccharomyces cerevisiae T206 K+R+ in a liquid grape medium. The lethal effect of the K2 mycoviral toxin was confirmed by methylene blue staining. Scanning electron microscopy of cells from challenge experiments revealed rippled cell surfaces, accompanied by cracks and pores, while those unaffected by the toxin, as in the control experiments, showed a smooth surface. Transmission electron microscopy revealed that the toxin damaged the cell wall structure and perturbed cytoplasmic membranes to a limited extent.6 page(s

Properties of a wine yeast antagonist, saccharomyces cerevisiae T206. a review

CITATION: Vadasz, A. S., et. al. 2002. Properties of a wine yeast antagonist, saccharomyces cerevisiae T206. a review. South African Journal of Enology & Viticulture, 23(2):39-47, doi:10.21548/23-2-2154.The original publication is available at http://www.journals.ac.za/index.php/sajevRegardless of the type of killer yeast, winemaking may be adversely affected by a single type of killer yeast. In this review we present the properties of a single K2 strain, Saccharomyces cerevisiae T206, which was isolated from a stuck fermentation in a South African winery. This zymotidal strain has demonstrated its potential as a wine yeast antagonist and may be differentiated from other NCYC killer strains of S. cerevisiae on the basis of CHEF karyotyping and mycoviral RNA separations. Resolution of its genomic DNA into 13 chromosome bands, ranging from 0.2 to 2.2 Mb, has been reported. The resident viral-like particle in strain T206 yields pancreatic RNase-sensitive L and M double-stranded RNA species of 5.1 and 2.0 kb, respectively. The latter can be cured using cycloheximide to produce a K-R- derivative. In microscale vinifications the K2 toxin of strain T206 demonstrates a lethal effect on sensitive mesophilic wine yeasts over a narrow pH range of 3.2 to 3.5, disrupting the cell wall structure and perturbing cytoplasmic membranes. Contrary to known fermentation trends, the challenged fermentations are neither stuck nor protracted as strain T206 competes for substrates and induces over 65 % cell death in enriched Hanepoot grape juice media. Mucoid secretions of mesophilic wine yeasts, induced by nutrient limitation, appear to restrict the K2 killer effect. However, the supplementation of 1 to 100 ppm bovine submaxillary gland mucin in nutrientenriched grape juice media also depresses the K2 killer effect of strain T206 in mesophilic wine yeast starter culture strain, S. cerevisiae VIN7. Preliminary results suggest that mucoid secretions either affect the level of toxin production by strain T206 or block the cognate K2 receptor on the cell wall of challanged yeasts.http://www.journals.ac.za/index.php/sajev/article/view/2154Publisher's versio

Pomalidomide, bortezomib, and dexamethasone for patients with relapsed or refractory multiple myeloma previously treated with lenalidomide (OPTIMISMM): a randomised, open-label, phase 3 trial

Background As lenalidomide becomes increasingly established for upfront treatment of multiple myeloma, patients refractory to this drug represent a population with an unmet need. The combination of pomalidomide, bortezomib, and dexamethasone has shown promising results in phase 1/2 trials of patients with relapsed or refractory multiple myeloma. We aimed to assess the efficacy and safety of this triplet regimen in patients with relapsed or refractory multiple myeloma who previously received lenalidomide.Methods We did a randomised, open-label, phase 3 trial at 133 hospitals and research centres in 21 countries. We enrolled patients (aged >= 18 years) with a diagnosis of multiple myeloma and measurable disease, an Eastern Cooperative Oncology Group performance status of 0-2, who received one to three previous regimens, including a lenalidomide-containing regimen for at least two consecutive cycles. We randomly assigned patients (1:1) to bortezomib and dexamethasone with or without pomalidomide using a permutated blocked design in blocks of four, stratified according to age, number of previous regimens, and concentration of beta(2) microglobulin at screening. Bortezomib (1.3 mg/m(2)) was administered intravenously until protocol amendment 1 then either intravenously or subcutaneously on days 1,4, 8, and 11 for the first eight cycles and subsequently on days 1 and 8. Dexamethasone (20 mg [10 mg if age >75 years]) was administered orally on the same days as bortezomib and the day after. Patients allocated pomalidomide received 4 mg orally on days 1-14. Treatment cycles were every 21 days. The primary endpoint was progression-free survival in the intention-to-treat population, as assessed by an independent review committee. Safety was assessed in all patients who received at least one dose of study medication. This trial is registered at ClinicalTrials.gov, number NCT01734928; patients are no longer being enrolled.Findings Between Jan 7, 2013, and May 15,2017,559 patients were enrolled. 281 patients were assigned pomalidomide, bortezomib, and dexamethasone and 278 were allocated bortezomib and dexamethasone. Median follow-up was 15.9 months (IQR 9.9-21.7). Pomalidomide, bortezomib, and dexamethasone significantly improved progression-free survival compared with bortezomib and dexamethasone (median 11.20 months [95% CI 9.66-13-73] vs 7.10 months [5.88-8-48]; hazard ratio 0.61, 95% CI 0.49-0-77; p<0-0001). 278 patients received at least one dose of pomalidomide, bortezomib, and dexamethasone and 270 patients received at least one dose of bortezomib and dexamethasone, and these patients were included in safety assessments. The most common grade 3 or 4 treatment-emergent adverse events were neutropenia (116 [42%] of 278 patients vs 23 [9%1 of 270 patients; nine p.m vs no patients had febrile neutropenia), infections (86 [31%] vs 48 118%1), and thrombocytopenia (76 [27%1 vs 79 [29%]). Serious adverse events were reported in 159 (57%) of 278 patients versus 114 (42%) of 270 patients. Eight deaths were related to treatment; six (2%) were recorded in patients who received pomalidomide, bortezomib, and dexamethasone (pneumonia [n=2], unknown cause [n=2], cardiac arrest [n=1], cardiorespiratory arrest [n=11) and two (1%) were reported in patients who received bortezomib and dexamethasone (pneumonia In=11, hepatic encephalopathy [n=1.]).Interpretation Patients with relapsed or refractory multiple myeloma who previously received lenalidomide had significantly improved progression-free survival when treated with pomalidomide, bortezomib, and dexamethasone compared with bortezomib and dexamethasone. Adverse events accorded with the individual profiles of pomalidomide, bortezomib, and dexamethasone. This study supports use of pomalidomide, bortezomib, and dexamethasone as a treatment option in patients with relapsed or refractory multiple myeloma who previously received lenalidomide. Copyright (C) 2019 Elsevier Ltd. All rights reserved