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Aim: The purpose of this study is to evaluate the Antimicrobial effect of liquorice extracts and compare its action to commonly used root canal medicaments like calcium hydroxide and chlorhexidine against Enterococcus faecalis and Candida albicans. Materials and Methods: Ethanolic and aqueous extracts of liquorice root were prepared. Antimicrobial activity was tested by agar well diffusion method on E. faecalis and C. albicans using Mueller Hinton agar. Wells were prepared and filled with ethanolic extract, aqueous extract of liquorice, calcium hydroxide, and chlorhexidine. Samples were incubated at 37°C, zone of inhibition was examined after 24 h. Results and Statistical Analysis: Ethanolic extract was significantly better (P < 0.001) than calcium hydroxide and aqueous extract of liquorice and less effective than chlorhexidine against E.faecalis. In C. albicans, ethanolic extract was less significant (P < 0.001) when compared to calcium hydroxide and chlorhexidine. Conclusion and Clinical Relevance: Ethanolic extract of liquorice has potent bactericidal effect against E. faecalis and C. albicans over aqueous extract. Hence, it can be used as intracanal medicaments in routine endodontic therapy.

The Carabelli cusp (Cusp of Carabelli) is a tubercle or the extra fifth cusp found on the mesiopalatal cusp of the maxillary permanent and deciduous molars. It is nonfunctional but it can be used to distinguish populations and is also used in forensic and anthropological studies. This condition is uncommon on deciduous teeth. In this case report, we present a rare case of unilateral presence of cusp of Carabelli in deciduous dentition.

BackgroundBarrett's esophagus is strongly associated with esophageal adenocarcinoma. Considering costs and risks associated with invasive surveillance endoscopies better methods of risk stratification are required to assist decision-making and move toward more personalised tailoring of Barrett's surveillance.MethodsA Bayesian network was created by synthesizing data from published studies analysing risk factors for developing adenocarcinoma in Barrett's oesophagus through a two-stage weighting process.ResultsData was synthesized from 114 studies (n = 394,827) to create the Bayesian network, which was validated against a prospectively maintained institutional database (n = 571). Version 1 contained 10 variables (dysplasia, gender, age, Barrett's segment length, statin use, proton pump inhibitor use, BMI, smoking, aspirin and NSAID use) and achieved AUC of 0.61. Version 2 contained 4 variables with the strongest evidence of association with the development of adenocarcinoma in Barrett's (dysplasia, gender, age, Barrett's segment length) and achieved an AUC 0.90.ConclusionThis Bayesian network is unique in the way it utilizes published data to translate the existing empirical evidence surrounding the risk of developing adenocarcinoma in Barrett's esophagus to make personalized risk predictions. Further work is required but this tool marks a vital step towards delivering a more personalized approach to Barrett's surveillance.

Abstract Recycled manure solids (RMS) are dried cow dung processed using a manure dewatering machine and subsequently sun-dried to ~ 20% moisture. Benefits of RMS include abundant availability, low cost, and eco-friendliness, but its use as bedding material for cows is hindered by a moisture content that promotes microbial growth. This in vitro study evaluated impacts of calcium hydroxide (CH; 5 and 7.5%) and sodium hydrosulphate (SHS; 6 and 8%), independently and in combinations, at various depths of RMS, on physicochemical and microbial properties. The CH-treated groups had increased pH and reduced moisture on Day 0. Incorporating 7.5% CH + 6% SHS at 15–20 cm, and 7.5% CH + 8% SHS at all depths, effectively suppressed Escherichia coli and Klebsiella spp. Furthermore, a combination of 7.5% CH + 8% SHS at 20 cm inhibited coliform growth, whereas 7.5% CH with 6% SHS inhibited Streptococcus spp. In conclusion, a combination of 7.5% CH with either 6 or 8% SHS at a depth of 15 cm in RMS was particularly effective in controlling environmental mastitis-causing pathogens, specifically E. coli and Klebsiella spp. Graphical Abstract

Abstract Background Oil palm (Elaeis guineensis Jacq.) is a very important tropical woody oil plant with high commercial and ornamental value. The exocarp of the oil palm fruit is rich in anthocyanosides and proanthocyanidins, which not only give it a bright colour, but also mark the maturity of the fruit. The study of the dynamic change pattern of anthocyanoside content and important anthocyanoside metabolism-related regulatory genes during oil palm ripening is conducive to the improvement of the ornamental value of oil palm and the determination of the optimal harvesting period of the fruits. Methods We analyzed the virescens oil palm (AS) and nigrescens oil palm (AT) at 95 days (AS1, AT1), 125 days (AS2, AT2) and 185 days (AS3, AT3) after pollination were used as experimental materials for determining the changes in the total amount of anthocyanins as well as their metabolomics and transcriptomics studies by using the LC-MS/MS technique and RNA-Seq technique. Result The results showed that the total anthocyanin content decreased significantly from AS1 (119 µg/g) to AS3 (23 µg/g), and from AT1 (1302 µg/g) to AT3 (170 µg/g), indicating a clear decreasing trend during fruit development. Among them, the higher flavonoids in AS and AT included anthocyanins such as peonidin-3-O-rutinoside (H35), pelargonidin-3-O-rutinoside (H21), and cyanidin-3-O-glucoside (H7), as well as condensed tannins such as procyanidin B2 (H47), procyanidin C1 (H49), and procyanidin B3 (H48). Notably, nine genes involved in the anthocyanin biosynthetic pathway exhibited up-regulated expression during the pre-development stage of oil palm fruits, particularly during the AS1 and AT1 periods. These genes include: Chalcone synthase (CHS; LOC105036364); Flavanone 3-hydroxylase (F3H; LOC105054663); Dihydroflavonol 4-reductase (DFR; LOC105040724, LOC105048473); Anthocyanidin synthase (ANS; LOC105035842), UDP-glucose: flavonoid 3-O-glucosyltransferase (UFGT; LOC105039612); Flavonoid 3’,5’-hydroxylase (F3’5’H; LOC105036086, LOC105044124, LOC105045493). In contrast, five genes demonstrated up-regulated expression as the fruits developed, specifically during the AS3 and AT3 periods. These genes include: Chalcone synthase (CHS; LOC105036921, LOC105035716); Chalcone isomerase (CHI; LOC105045978); UDP-glucose: flavonoid 3-O-glucosyltransferase (UFGT; LOC105046326); Flavonoid 3’-hydroxylase (F3’H; LOC105036086). Conclusion Most of differentially expressed genes exhibited up-regulation during the early stages of fruit development, which may contribute to the elevated anthocyanin content observed in oil palm fruits of both types during the pre-developmental period. Furthermore, the expression levels of most genes were found to be higher in the AT fruit type compared to the AS fruit type, suggesting that the differential expression of these genes may be a key factor underlying the differences in anthocyanoside production in the exocarp of oil palm fruits from these two fruit types. The findings of this study provide a theoretical foundation for the identification and characterization of genes involved in anthocyanin synthesis in oil palm fruits, as well as the development of novel variations using molecular biology approaches.

Abstract Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterized by loss of tolerance to nuclear antigens. The formation of autoantibodies and the deposition of immune complexes trigger inflammatory tissue damage that can affect any part of the body. In most cases, SLE is a complex disease involving multiple genetic and environmental factors. Despite advances in the treatment of SLE, there is currently no cure for SLE and patients are treated with immunosuppressive drugs with significant side effects. The elucidation of rare monogenic forms of SLE has provided invaluable insights into the molecular mechanisms underlying systemic autoimmunity. Harnessing this knowledge will facilitate the development of more refined and reliable biomarker profiles for diagnosis, therapeutic monitoring, and outcome prediction, and guide the development of novel targeted therapies not only for monogenic lupus, but also for complex SLE.

PURPOSE: Magrolimab is a first-in-class humanized monoclonal antibody against cluster of differentiation 47, an antiphagocytic signal used by cancer cells to evade phagocytosis. Azacitidine upregulates prophagocytic signals on AML cells, further increasing phagocytosis when combined with magrolimab. We report final phase Ib data for magrolimab with azacitidine in patients with untreated AML ineligible for intensive chemotherapy (ClinicalTrials.gov identifier: NCT03248479). PATIENTS AND METHODS: Patients with previously untreated AML, including TP53-mutant AML, received magrolimab intravenously as an initial dose (1 mg/kg, days 1 and 4), followed by 15 mg/kg once on day 8 and 30 mg/kg once weekly or every 2 weeks as maintenance. Azacitidine 75 mg/m2 was administered intravenously/subcutaneously once daily on days 1-7 of each 28-day cycle. Primary end points were safety/tolerability and proportion with complete remission (CR). RESULTS: Eighty-seven patients were enrolled and treated; 72 (82.8%) had TP53 mutations with a median variant allele frequency of 61% (range, 9.8-98.7). Fifty-seven (79.2%) of TP53-mutant patients had European LeukemiaNet 2017 adverse-risk cytogenetics. Patients received a median of 4 (range, 1-39) cycles of treatment. The most common treatment-emergent adverse events included constipation (49.4%), nausea (49.4%), and diarrhea (48.3%). Thirty (34.5%) experienced anemia, and the median hemoglobin change from baseline to first postdose assessment was -0.9 g/dL (range, -3.6 to 2.5 g/dL). Twenty-eight (32.2%) patients achieved CR, including 23 (31.9%) patients with TP53 mutations. The median overall survival in TP53-mutant and wild-type patients were 9.8 months and 18.9 months, respectively. CONCLUSION: Magrolimab with azacitidine was relatively well tolerated with promising efficacy in patients with AML ineligible for intensive induction chemotherapy, including those with TP53 mutations, warranting further evaluation of magrolimab with azacitidine in AML. The phase III randomized ENHANCE-2 (ClinicalTrials.gov identifier: NCT04778397) and ENHANCE-3 (ClinicalTrials.gov identifier: NCT05079230) studies are recruiting frontline patients with AML.

This is the primary report of the randomized, placebo-controlled phase 3 BRIGHT AML 1019 clinical trial of glasdegib in combination with intensive chemotherapy (cytarabine and daunorubicin) or non-intensive chemotherapy (azacitidine) in patients with untreated acute myeloid leukemia. Overall survival (primary endpoint) was similar between the glasdegib and placebo arms in the intensive (n = 404; hazard ratio [HR] 1.05; 95% confidence interval [CI]: 0.782-1.408; two-sided p = 0.749) and non-intensive (n = 325; HR 0.99; 95% CI: 0.768-1.289; two-sided p = 0.969) studies. The proportion of patients who experienced treatment-emergent adverse events was similar for glasdegib versus placebo (intensive: 99.0% vs. 98.5%; non-intensive: 99.4% vs. 98.8%). The most common treatment-emergent adverse events were nausea, febrile neutropenia, and anemia in the intensive study and anemia, constipation, and nausea in the non-intensive study. The addition of glasdegib to either cytarabine and daunorubicin or azacitidine did not significantly improve overall survival and the primary efficacy endpoint for the BRIGHT AML 1019 phase 3 trial was not met. Clinical trial registration: ClinicalTrials.gov: NCT03416179.