Reproducibility of grading systems in oral epithelial dysplasia

Objective: To assess inter and intra observer variability in grading oral epithelial dysplasia (OED) using Smith and Pindborg grading system, WHO classification system and Brothwell DJ et al. classification system. Study design: In the study 45 histological tissues of dysplasia, 15 each of mild, moderate and severe dysplasia were coded and blindly graded by three observers in three grading systems. Further on the same observers graded 15 slides again of the previous 45 for analyzing the reproducibility in the three grading systems. The individual significance of various indicators of dysplasia among various grades of dysplasia was also assessed. Result: Inter observer agreement was significantly higher in Brothwell system as compared to WHO and Smith and Pindborg system. Intra observer agreement was significantly higher in Smith and Pindborg system, but the predictability and the probability index was distributed over a larger range in this system. Each indicator of dysplasia was also found to be statistically significant (P<0.05) for grading dysplasia. Conclusion: The present study puts forth the inherent intricacies in the grading of oral premalignant lesions

PROTECTIVE EFFECT OF KADUKKAI MAATHIRAI (TERMINALIA CHEBULA-BASED POLYHERBAL SIDDHA FORMULATION) IN ETHANOL-INDUCED LIVER DISEASE IN RATS

Objective: The objective of this study was to evaluate the prophylactic effect of Kadukkai maathirai (KM) against ethanol-induced hepatotoxicity in rats.Methods: Four groups (n=6) of adult female Sprague–Dawley rats were used. Ethanol was administered in the dose of 45% v/v 15 mL/kg/body weight twice a day for 8 weeks in the study. The four groups were treated orally for 8 weeks with 2% gum acacia (control), ethanol (toxic control), ethanol + KM 72 mg/kg, and ethanol + KM 400 mg/kg, respectively. At the end of 8 weeks, blood was collected by a retro-orbital puncture for the estimation of liver enzymes (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]). The liver was dissected out for histopathology. Using one-way ANOVA and post hoc Tukey's test, the data were analyzed.Results: There was a significant (p&lt;0.05) decrease in the serum AST and ALT level in rats treated with KM 72 mg/kg as compared to toxic control. Liver parenchyma showed near normal architecture in KM 72 mg/kg-treated group as compared to ethanol-treated group which showed extensive ballooning degeneration of hepatocytes and microvesicular steatosis.Conclusion: KM, in the dose of 72 mg/kg, which is the therapeutic dosage described in Siddha additional literature, exerted hepatoprotective effect against ethanol-induced liver damage in rats

Association of FADS2 rs174575 gene polymorphism and insulin resistance in type 2 diabetes mellitus

Background: Many risk factors contribute to the pathogenesis of diabetes. Gene and lifestyle factors are considered to be the major contributors. A dietary pattern is attributed to be one of the lifestyle risk factors favoring diabetes. The present study aims to find an association between fatty acid desaturase (FADS) gene polymorphism and glycemic profile in type 2 diabetes mellitus (T2DM). Methodology: A total of 429 subjects were included in the study on the basis of inclusion and exclusion criteria, of which 213 and 216 subjects were diabetic and control, respectively. Body mass index was calculated. Fasting plasma glucose, glycated hemoglobin (HbA1c) and insulin were measured using commercially available kits. rs174575 of FADS2 was selected based on previous publications and identified using the dbSNP database. To compare the biochemical parameters with the genotype, the following three models were used: additive model (CC vs CG vs GG), dominant model (CC + CG vs GG), and recessive model (CC vs CG + GG). Results and Discussion: FBS, HbA1c, insulin, HOMA-IR, and HOMA-B exhibited a high and statistically significant difference between subjects and controls. The three models exhibited a statistically significant difference between FBS, HOMA-IR, and HOMA- B (p&lt;0.05). Conclusion: The distribution of rs174575 genotype differed significantly between the subjects and controls in the present study. The study revealed that genetic variation in FADS2 is an additional facet to consider while studying the risk factors of T2DM

Relevance of tumor angiogenesis patterns as a diagnostic value and prognostic indicator in oral precancer and cancer

Tumor angiogenesis occurs by recruitment of endothelial cell precursors or by sprouting of existing capillaries, which differ from the normal vasculature by having an altered morphology that can be exploited for diagnosis and as a prognostic indicator. Improved technologies have propelled diagnosis into a new era. These technologies have to be used with great precision. The diagnosis of a dysplastic premalignant lesion of the oral mucosa cannot be based solely on clinical findings. Therefore histologic evaluation of a representative biopsy specimen is necessary. Accurate judgment of the proper site for biopsy is essential for reaching a correct diagnosis. The aim of this report is to analyze the vascular patterns with the help of direct oral microscopy and the technique of stereo-optical microscopy in the oral cavity to select biopsy sites, and compare the outcome of a directed biopsy with that of biopsy specimens obtained from sites selected solely on the basis of clinical criteria. The study sample comprised 50 oral mucosal lesions. A statistically significant difference was noted between samples judged to be microscopically representative sites. We conclude that this method would aid in early and better diagnosis and treatment planning of oral premalignant and malignant lesions by assessing the various vascular patterns in the mucosa

<i>In Vitro</i> Activity of Two Cefepime-Based Novel Combinations, Cefepime/Taniborbactam and Cefepime/Zidebactam, against Carbapenemase-Expressing <i>Enterobacterales </i>Collected in India

In recent times, discovery efforts for novel antibiotics have mostly targeted carbapenemase-producing Gram-negative organisms. Two different combination approaches are pertinent: b-lactam-b-lactamase inhibitor (BL/BLI) or b-lactam-b-lactam enhancer (BL/ BLE). Cefepime combined with a BLI, taniborbactam, or with a BLE, zidebactam, has been shown to be promising. In this study, we determined the in vitro activity of both these agents along with comparators against multicentric carbapenemase-producing Enterobacterales (CPE). Nonduplicate CPE isolates of Escherichia coli (n = 270) and Klebsiella pneumoniae (n = 300), collected from nine different tertiary-care hospitals across India during 2019 to 2021, were included in the study. Carbapenemases in these isolates were detected by PCR. E. coli isolates were also screened for the presence of the 4-Amino-Acid insert in penicillin binding protein 3 (PBP3). MICs were determined by reference broth microdilution. Higher MICs of cefepime/taniborbactam (.8 mg/L) were linked to NDM, both in K. pneumoniae and in E. coli. In particular, such higher MICs were observed in 88 to 90% of E. coli isolates producing NDM and OXA-48-like or NDM alone. On the other hand, OXA-48-like-producing E. coli or K. pneumoniae isolates were nearly 100% susceptible to cefepime/taniborbactam. Regardless of the carbapenemase types and the pathogens, cefepime/ zidebactam showed potent activity (.99% inhibited at#8mg/L). It seems that the 4-amino-Acid insert in PBP3 (present universally in the study E. coli isolates) along with NDM adversely impact the activity of cefepime/taniborbactam. Thus, the limitations of the BL/BLI approach in tackling the complex interplay of enzymatic and nonenzymatic resistance mechanisms were better revealed in whole-cell studies where the activity observed was a net effect of b-lactamase inhibition, cellular uptake, and target affinity of the combination. IMPORTANCE The study revealed the differential ability of cefepime/taniborbactam and cefepime/zidebactam in tackling carbapenemase-producing Indian clinical isolates that also harbored additional mechanisms of resistance. NDM-expressing E. coli with 4-Amino-Acid insert in PBP3 are predominately resistant to cefepime/taniborbactam, while the b-lactam enhancer mechanism-based cefepime/zidebactam showed consistent activity against single-or dual-carbapenemase-producing isolates including E. coli with PBP3 inserts.</p

Kadukkai maathirai (a polyherbal traditional siddha formulation) prevents D-galactosamine induced hepatic necrosis in rats

708-713This study evaluated the prophylactic effect of Kadukkai maathirai in D-galactosamine (D-gal) induced hepatotoxicity in rats. D-galactosamine (D-gal) 400 mg/kg intraperitoneally was used to induce liver damage in rats. To assess the hepatoprotective effect of KM, three different doses of KM (36, 72 and 144 mg/kg body weight) were used. The hepatoprotective effect of KM was compared with standard drug silymarin (50 mg/kg). The biochemical parameters such as AST, ALT, ALP and total bilirubin were estimated. The livers were dissected out to look for histological changes. KM 144 mg/kg and silymarin showed a significant decrease in AST, ALP and total bilirubin. Both KM and silymarin significantly prevented decrease in liver weight. In KM treated groups, the liver did not show necrosis of hepatocytes, and apoptotic bodies with mild to moderate inflammatory infiltrate in the lobules and portal tracts. Hence, the results of this study confirms the hepatoprotective effect KM in rats

Kadukkai maathirai (a polyherbal traditional siddha formulation) prevents D-galactosamine induced hepatic necrosis in rats

This study evaluated the prophylactic effect of Kadukkai maathirai in D-galactosamine (D-gal) induced hepatotoxicity in rats. D-galactosamine (D-gal) 400 mg/kg intraperitoneally was used to induce liver damage in rats. To assess the hepatoprotective effect of KM, three different doses of KM (36, 72 and 144 mg/kg body weight) were used. The hepatoprotective effect of KM was compared with standard drug silymarin (50 mg/kg). The biochemical parameters such as AST, ALT, ALP and total bilirubin were estimated. The livers were dissected out to look for histological changes. KM 144 mg/kg and silymarin showed a significant decrease in AST, ALP and total bilirubin. Both KM and silymarin significantly prevented decrease in liver weight. In KM treated groups, the liver did not show necrosis of hepatocytes, and apoptotic bodies with mild to moderate inflammatory infiltrate in the lobules and portal tracts. Hence, the results of this study confirms the hepatoprotective effect KM in rats

Context Matters: Intertextuality and Voice in the Early Modern English Controversy about Women

This dissertation examines three clusters of works from the early modern English controversy about women--the debate about the merits and flaws of womankind--in order to argue that authors in the controversy took advantage of the malleability of women's voices to address issues beyond the worth of women. I depart from standard treatments of the controversy by giving priority to the intertextual contexts among works that engage with one another. Attending to the intertextual elements of this genre reveals the metapoetic concerns of the authors and the way such authors fashion their feminine apologists as discursive agents in order to express those concerns. Chapter 1 examines Edward Gosynhyll's sixteenth-century works in tandem with Geoffrey Chaucer's The Legend of Good Women and "The Wife of Bath's Prologue and Tale," arguing that Gosynhyll's revisions of Chaucer--revisions embodied by the feminine apologists in the texts--are integral to his project of establishing the controversy genre as multivalent and dialectical. The resulting metacommentary examines in a new light the age-old rhetorical tradition of exemplarity, a persuasive tool used in diverse literary genres. Chapter 2 considers the way the anonymous play Swetnam the Woman-Hater uses cross-voicing and cross-dressing to establish the performative nature of controversy conventions. In doing so, the play argues for the social benefits of abandoning essentialist logic in favor of gender performance, as such performance makes the role of apologist available to men and women alike. This cluster reconsiders the very processes by which a person--male or female--can be known to others. Finally, I trace John Taylor's use of the marginal woman in his controversy works in order to demonstrate the extent to which Taylor makes these women instrumental in establishing his own poetic and social identity. This project contributes to studies on the English controversy as well as to the field of early modern women and women's writing by arguing that authors found the genre generally and the woman's voice specifically to be fit vehicles for articulating poetic agendas beyond the immediate task of debating the nature of womankind

Global unmet needs in cardiac surgery

More than 6 billion people live outside industrialized countries and have insufficient access to cardiac surgery. Given the recently confirmed high prevailing mortality for rheumatic heart disease in many of these countries together with increasing numbers of patients needing interventions for lifestyle diseases due to an accelerating epidemiological transition, a significant need for cardiac surgery could be assumed. Yet, need estimates were largely based on extrapolated screening studies while true service levels remained unknown. A multi-author effort representing 16 high-, middle-, and low-income countries was undertaken to narrow the need assessment for cardiac surgery including rheumatic and lifestyle cardiac diseases as well as congenital heart disease on the basis of existing data deduction. Actual levels of cardiac surgery were determined in each of these countries on the basis of questionnaires, national databases, or annual reports of national societies. Need estimates range from 200 operations per million in low-income countries that are nonendemic for rheumatic heart disease to >1,000 operations per million in high-income countries representing the end of the epidemiological transition. Actually provided levels of cardiac surgery range from 0.5 per million in the assessed low- and lower-middle income countries (average 107 ± 113 per million; representing a population of 1.6 billion) to 500 in the upper-middle-income countries (average 270 ± 163 per million representing a population of 1.9 billion). By combining need estimates with the assessment of de facto provided levels of cardiac surgery, it emerged that a significant degree of underdelivery of often lifesaving open heart surgery does not only prevail in low-income countries but is also disturbingly high in middle-income countries

Biodegradation of ochratoxin A for food and feed decontamination

Ochratoxin A (OTA) is one of the most important mycotoxins that is found in food and feed products. It has proven toxic properties, being primarily known for its nephrotoxicity and carcinogenicity to certain animal species. OTA is produced by several species of Aspergillus and Penicillium that can be found in a wide variety of agricultural products, which makes the presence of OTA in these products common. Many countries have statutory limits for OTA, and concentrations need to be reduced to as low as technologically possible in food and feed. The most important measures to be taken to control OTA are preventive in order to avoid fungal growth and OTA production. However, these measures are difficult to implement in all cases with the consequence of OTA remaining in agricultural commodities. Remediation processes are often used to eliminate, reduce or avoid the toxic effects of OTA. Biological methods have been considered increasingly as an alternative to physical and chemical treatments. However, examples of practical applications are infrequent. This review will focus on the (i) known microorganisms and enzymes that are able to biodegrade OTA; (ii) mode of action of biodegradation and (iii) current applications. A critical discussion about the technical applicability of these strategies is presented.Luis Abrunhosa was supported by the grant SFRH/BPD/43922/2008 from Fundacao para a Ciencia e Tecnologia-FCT, Portugal. Russell Paterson is grateful for the research position in the FCT framework, Commitment to Science ref. C2008-UMINHO-CEB-2