Thymoquinone decreases oxidative DNA damage (8-OHdG) in DMBA treated female Sprague Dawley rats

Tamoxifen (TAM) is used widely for treatment and prevention of breast cancer. However, TAM has been reported to have a negative effect on glutathione (GSH) levels and 8-hydroxydeoxyguanosine (8-OHdG). Thymoquinone (TQ), the main active ingredient of Nigella sativa, or Black seeds, is used in the Middle East for treatment of several diseases, especially cancer. The aim of my research was to investigate the role of thymoquinone in improving 8-OHdG and GSH compared with tamoxifen in female Sprague Dawley rats treated with 7,12 dimethylbenz (a)anthracene (DMBA, a drug that induces mammary cancer). 8-OHdG is the most commonly assayed fingerprint of free radical attack on DNA and is involved in tumor progression. Five groups of 10 rats (Controls, DMBA, TAM, TQ, and TAM+TQ) were treated for 10 weeks after injection of DMBA. Tumors were found in only two DMBA treated rats. However, there was a coloration observed in the mammary glands in another four of the DMBA treated rats. There were no mammary gland changes in the other four groups. 8-OHdG in blood samples was significantly higher in the TAM group compared with the TQ (P \u3c0.001), the controls (P= 0.008) and the DMBA (P=0.041) treated groups. TQ significantly decreased 8-OHdG by itself compared with DMBA (P= 0.039) and TAM, but did not significantly reduce the effect of TAM in the TAM+TQ group. On the other hand, GSH did not differ among treatments. The data for body weight gain over 12 weeks showed a significant difference among the groups (P\u3c0.001). The TAM and TAM+TQ groups had the lowest weight gain compared with the TQ, the control and the DMBA (P\u3c0.01) treated groups. I conclude that TQ could be a better anticancer drug than TAM because it decreased 8-OHdG and protected growth --Document

Association of mutation and expression of the brother of the regulator of imprinted sites (BORIS) gene with breast cancer progression

INTRODUCTION: The BORIS, 11 zinc-finger transcription factors, is a member of the cancer-testis antigen (CTA) family. It is mapped to chromosome number 20q13.2 and this region is genetically linked to the early onset of breast cancer. The current study analyzed the correlation between BORIS mutations and the expression of the protein in breast cancer cases. MATERIALS AND METHODS: A population-based study including a total of 155 breast cancer tissue samples and an equal number of normal adjacent tissues from Indian female breast cancer patients was carried out. Mutations of the BORIS gene were detected by polymerase chain reaction-single standard confirmation polymorphisms (PCR-SSCP) and automated DNA sequencing and by immunohistochemistry for BORIS protein expression were performed. The observed findings were correlated with several clinicopathological parameters to find out the clinical relevance of associations. RESULTS: Of all the cases 16.12% (25/155) showed mutations in the BORIS gene. The observed mutations present on codon 329 are missense, leading to Val\u3e Ile (G\u3eA) change on exon 5 of the BORIS gene. A significant association was observed between mutations of the BORIS gene and some clinicopathological features like nodal status (p = 0.013), estrogen receptor (ER) expression (p = 0.008), progesterone receptor (PR) expression (p = 0.039), clinical stage (p = 0.010) and menopausal status (p = 0.023). The protein expression analysis showed 20.64% (32/155) samples showing low or no expression (+), 34.19% (53/155) with moderate expression (++), and 45.17% (70/155) showing high expression (+++) of BORIS protein. A significant association was observed between the expression of BORIS protein and clinicopathological features like clinical stage (p = 0.013), nodal status (p = 0.049), ER expression (p = 0.039), and PR expression (p = 0.027). When mutation and protein expression were correlated in combination with clinicopathological parameters a significant association was observed in the category of high (+++) level of BORIS protein expression (p = 0.017). CONCLUSION: The BORIS mutations and high protein expression occur frequently in carcinoma of the breast suggesting their association with the onset and progression of breast carcinoma. Further, the BORIS has the potential to be used as a biomarker

CONCOMITANT USE OF NON-STEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDS) WITH WARFARIN

Introduction: Oral anticoagulation with warfarin is the accepted technique for treatment and prophylaxis of thromboembolic diseases. Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most broadly administered medications to control musculoskeletal pain or inflammation. besides to their antiplatelet work, NSAIDs can influence the pharmacologic activity of warfarin through their immediate interaction. High protein binding and the cytochrome P450 (CYP)- dependent clearance systems of NSAIDs can influence the serum levels of warfarin. Aim of work: In this review, we will discuss whether using warfarin with NSAID has any effect on the pharmacokinetics and pharmacodynamics of both drugs. Methodology: We conducted this review using a comprehensive search of MEDLINE, PubMed, and EMBASE, January 1985, through February 2017. The following search terms were used: Non-steroidal anti-inflammatory drug mechanism, warfarin mechanism, adverse effects of NSAID, adverse effect of warfarin, NSAID-warfarin interaction Conclusions: Co-administration of NSAIDs and Warfarin is a topic of debate. However, there are reasons for concern. Some NSAIDs alter hemostasis and, when combined with warfarin, may lead to an increase in bleeding time. There is also a risk of increased hepatic and renal toxicity which complicates things further. Balancing the pros and cons of this drug combination should be carefully done on a case to case basis to avoid any negative consequences. Key words: NSAID, warfarin, Aspirin, drug-drug interaction, bleedin

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Artisanal Kefir: Antimicrobial Activity and Bacterial Populations

Food products can be contaminated by a range of pathogenic and spoilage bacteria. Contamination of foods results in food spoilage and foodborne illnesses and leads to economic losses in the food industry. Similar to chemical antimicrobials, natural preservatives (biopreservatives) can be used to improve food quality and safety. Biologically-based preservation (biopreservation) uses lactic acid bacteria (LAB), their bacteriocins, bacteriophages and bacteriophage-encoded enzymes to ensure food safety and quality for foods that are not fermented. Among biopreservatives, bacteriocins are ribosomally synthesized small antimicrobial proteins, secreted by bacteria to inhibit the growth of other, usually closely related bacteria. Bacteriocins inhibit select pathogenic and/or spoilage bacteria without changing the chemical and physical characteristics of food. Kefir is a fermented dairy product made using kefir grains, which are composed of LAB and yeast in a protein-polysaccharide matrix called kefiran. Kefir has antimicrobial activity due to many metabolic products, including bacteriocins produced by LAB. For this study, it was hypothesized that international artisanal kefirs have diverse microflora, generating distinctive bacteriocin content, resulting in varied levels of antimicrobial activities. The objectives of this work were: 1) compare the antimicrobial activity of artisanal kefirs from Fusion Tea, Britain, the Caucuses region, Ireland, Lithuania, and South Korea against select foodborne pathogens, 2) examine whether the antimicrobial effect is due to bacteriocin production or other antimicrobials present in kefir, and 3) reveal bacterial populations and elucidate the diversity and abundance of LAB species in artisanal kefirs. This dissertation is comprised of two interconnected studies. In the first study, the antimicrobial activities of artisanal kefir products from Fusion Tea (A), Britain (B), Ireland (I), Lithuania (L), the Caucuses region (C), and South Korea (K) were investigated against select foodborne pathogens. Listeria monocytogenes CWD 1198, Salmonella enterica serovar Enteritidis ATCC 13076, Staphylococcus aureus ATCC 25923, and Bacillus cereus ATCC 14579 were inhibited by artisanal kefirs made with kefir grains from diverse origins. Kefirs A, B, and I inhibited all bacterial indicator strains examined at varying levels, except Escherichia coli ATCC 12435 (non-pathogenic, negative control). Kefirs K, L, and C inhibited all indicator strains, except S. aureus ATCC 25923 and E. coli ATCC 12435. Bacteriocins present in artisanal kefirs were determined to be the main antimicrobials in all kefirs examined. Kefir-based antimicrobials are being proposed as promising natural biopreservatives as per the results of the study. A typical kefir microbial community includes LAB, acetic acid bacteria, and yeast among other species in a symbiotic matrix. In the second study, the 16S rRNA gene sequencing was used to reveal bacterial populations and elucidate the diversity and abundance of LAB species in international artisanal kefirs from Fusion Tea, Britain, the Caucuses region, Ireland, Lithuania, and South Korea. Bacterial species found in high abundance in most artisanal kefirs included Lactobacillus kefiranofaciens, Lentilactobacillus kefiri, Lactobacillus ultunensis, Lactobacillus apis, Lactobacillus gigeriorum, Gluconobacter morbifer, Acetobacter orleanensis, Acetobacter pasteurianus, Acidocella aluminiidurans, and Lactobacillus helveticus. Some of these bacterial species are LAB that have been reported for their bacteriocin production capabilities and/or health promoting properties.doctoral, Ph.D., Food Science -- University of Idaho - College of Graduate Studies, 2020-1

Bacterial Populations in International Artisanal Kefirs

Artisanal kefir is a traditional fermented dairy product made using kefir grains. Kefir has documented natural antimicrobial activity and health benefits. A typical kefir microbial community includes lactic acid bacteria (LAB), acetic acid bacteria, and yeast among other species in a symbiotic matrix. In the presented work, the 16S rRNA gene sequencing was used to reveal bacterial populations and elucidate the diversity and abundance of LAB species in international artisanal kefirs from Fusion Tea, Britain, the Caucuses region, Ireland, Lithuania, and South Korea. Bacterial species found in high abundance in most artisanal kefirs included Lactobacillus kefiranofaciens, Lentilactobacillus kefiri,Lactobacillus ultunensis, Lactobacillus apis, Lactobacillus gigeriorum, Gluconobacter morbifer, Acetobacter orleanensis, Acetobacter pasteurianus, Acidocella aluminiidurans, and Lactobacillus helveticus. Some of these bacterial species are LAB that have been reported for their bacteriocin production capabilities and/or health promoting properties

Antimicrobial Activity of Six International Artisanal Kefirs against Bacillus cereus, Listeria monocytogenes, Salmonella enterica Serovar Enteritidis, and Staphylococcus aureus

Kefir, a fermented dairy beverage, exhibits antimicrobial activity due to many metabolic products, including bacteriocins, generated by lactic acid bacteria. In this study, the antimicrobial activities of artisanal kefir products from Fusion Tea (A), Britain (B), Ireland (I), Lithuania (L), the Caucuses region (C), and South Korea (K) were investigated against select foodborne pathogens. Listeria monocytogenes CWD 1198, Salmonella enterica serovar Enteritidis ATCC 13076, Staphylococcus aureus ATCC 25923, and Bacillus cereus ATCC 14579 were inhibited by artisanal kefirs made with kefir grains from diverse origins. Kefirs A, B, and I inhibited all bacterial indicator strains examined at varying levels, except Escherichia coli ATCC 12435 (non-pathogenic, negative control). Kefirs K, L, and C inhibited all indicator strains, except S. aureus ATCC 25923 and E. coli ATCC 12435. Bacteriocins present in artisanal kefirs were determined to be the main antimicrobials in all kefirs examined. Kefir-based antimicrobials are being proposed as promising natural biopreservatives as per the results of the study