Aluminosilicates and yeast-based mycotoxin binders: Their ameliorated effects on growth, immunity and serum chemistry in broilers fed aflatoxin and ochratoxin

The aim of this study was to evaluate the effects of commercial toxin binders on growth performance, organ morphology, immunity and serum biochemistry in broilers. Dietary treatments consisted of the negative control (NC): experimental diet with aflatoxin B1 <20 parts per billion (ppb), ochratoxin A (OTA) <5 ppb; control (C) experimental diet without toxin binder; Z1: toxin binder 1 g/kg of zeta plus; Z2: toxin binder 2 g/kg of zeta plus; TX1: toxin binder 1 g/kg of Toxfin Dry; and TX2: toxin binder 2 g/kg of Toxfin Dry). Except for NC, all diets contained 57 ppb aflatoxin B1 and 23 ppb ochratoxin A. Feed intake was higher in the TX1, TX2, NC, Z2 and Z1 treatments than in the control. Weight gain was higher in Z2, TX2, Z1, TX1 and NC than in C. Feed conversion ratio (FCR) was poor in C. The control had the highest liver weight, though the weights of the spleen, kidneys and hearts of the birds were similar in all treatments. Gizzard weight, thymus weight, and bursa of Fabricius were lowest in C. The weight of the pancreas was similar among treatments. The antibody titres against new castle disease were higher in treatments Z2, Z1, TX2, TX1 and NC than in C. Urea and creatinine concentrations, and aspartate aminotransferase activity in serum were similar among treatments, whereas the serum alanine transaminase activity was higher in C than in Z1, TX1, TX2, Z2 and NC. It was concluded that growth rate, FCR and immunity indices were improved in broilers fed toxin binder. At lower levels of mycotoxin in feed, 1 g/kg of toxin binder (clay based or yeast based) was sufficient to ameliorate the adverse effects of aflatoxin B1 and OTA, whereas at higher levels of mycotoxins, supplementation of toxin binder should be increased.Keywords: alanine aminotransferase, aspartate aminotransferase, carcass characteristics, growth performance, toxin binders, urea, creatinin

Effect of Moringa oleifera (Lam.) pods as feed additive on egg antioxidants, chemical composition and performance of commercial layers

The present study was designed to investigate the influence of Moringa oleifera (Lam.) pod meal (MPM) on production, immunity, and functional food index of chicken eggs. Two hundred HyLine W36 layer birds aged 50 weeks, 1469 ± 46.63 g, were assigned to four treatments in a completely randomized design, with five replicates and ten birds each. Diets A, B, C, and D were formulated with the same caloric and protein levels, but with differing MPM dose levels of 0, 5, 10, and 15g MPM/kg finisher diet, respectively. Data for production performance, quality, and chemical composition of eggs were analysed by one-way ANOVA, and means were compared with Duncan’s multiple range test. As a result of this study, feed conversion ratio (FCR) and egg mass (EM) were significantly decreased and recorded lowest in Group B, which was offered 5 g/kg above the basal diet. Bioactives such as β-carotene, quercetin, and selenium levels were increased (540, 121, & 72.21μg/100g of yolk, respectively), whereas cholesterol levels in egg yolk and serum were decreased significantly, that is, 201.87 mg/100g and 8.47 mg/dl, respectively. Serum biochemical indicators, including serum glutamic-pyruvic transaminase (SGPT), glucose, creatinine and cholesterol levels, were lowered significantly. Proximate analysis of egg yolk showed that moisture and ether extract were decreased, whereas crude protein (CP), ash and minerals, sodium (Na), potassium (K), calcium (Ca), magnesium (Mg), and phosphorus (P) contents were increased. The outcomes of this study showed that MPM supplementation affects EM, serum biochemistry and bioactive compounds of the egg yolk positively. Keywords: Antibody titers, β-carotene, cholesterol, egg quality, quercetin, seleniu

Analysis and Optimisation of Best Practice for Proper Lookout at Night

A significant proportion of accidents appear to be caused by a lack of maintaining a ‘proper lookout’ on a ship’s bridge. The root cause for these accidents could be the result of watchkeeper’s lack of awareness of requirements to maintain a proper lookout. This paper utilises the authors’ proposed definition of this term and then discusses the outputs from a study on improving watchkeeper behaviour carried out in ship bridge simulators, using eye tracking devices. The study involves applying the proposed method of carrying out visual search scans together with underlining distractions caused by Multifunction Displays (MFDs) found on modern ship bridges. Based on the findings, the paper evaluates the impact of the proposed scan method for maintaining a proper lookout, reduction in distractions caused by MFDs and discusses how it is almost impossible to achieve a complete dark adaptation with the presence of MFDs and other lighting on modern ship bridges. This research offers a solution to control these risks through risk assessment, together with training and education for watchkeepers to overcome these issues. This study is expected to contribute significantly to improving watchkeeper’s behaviour in maintaining lookout and application of the proposed scan method

Utilizing Functional Genomics Screening to Identify Potentially Novel Drug Targets in Cancer Cell Spheroid Cultures

The identification of functional driver events in cancer is central to furthering our understanding of cancer biology and indispensable for the discovery of the next generation of novel drug targets. It is becoming apparent that more complex models of cancer are required to fully appreciate the contributing factors that drive tumorigenesis in vivo and increase the efficacy of novel therapies that make the transition from preclinical models to clinical trials. Here we present a methodology for generating uniform and reproducible tumor spheroids that can be subjected to siRNA functional screening. These spheroids display many characteristics that are found in solid tumors that are not present in traditional two-dimension culture. We show that several commonly used breast cancer cell lines are amenable to this protocol. Furthermore, we provide proof-of-principle data utilizing the breast cancer cell line BT474, confirming their dependency on amplification of the epidermal growth factor receptor HER2 and mutation of phosphatidylinositol-4,5-biphosphate 3-kinase (PIK3CA) when grown as tumor spheroids. Finally, we are able to further investigate and confirm the spatial impact of these dependencies using immunohistochemistry.Open Access fees were supported by Nexcelom Bioscience, LLCThis work was funded by Breast Cancer Now. RN is the recipient of a Breast Cancer Now Career Development Fellowship (2011MaySF01

Identification of RAD51 foci in cancer-associated circulating cells of patients with high-grade serous ovarian cancer: Association with treatment outcomes

Data availability statement: Data are available upon reasonable request. Datasets will be made available on reasonable request from the corresponding author.Supplementary Data are available online at https://ijgc.bmj.com/content/33/9/1427#supplementary-materials .Objective Fifty percent of patients with high-grade serous ovarian cancer harbor defects in the homologous recombination repair pathway. RAD51 foci form where DNA is damaged, indicating its involvement in repairing double-stranded breaks. High levels of RAD51 in ovarian cancer tissue have been associated with a poorer prognosis. Objective To demonstrate RAD51 foci in circulating cancer-associated cells of patients with ovarian cancer and their association with clinical outcomes. Methods One hundred and twenty-four patients with high-grade serous ovarian cancer had blood samples taken at strategic points during treatment and follow-up. Cells were stained using WT1 and RAD51 antibodies with immunofluorescence and reviewed under Leica camera microscopy; RAD51 foci were counted. Correlations were made between numbers of RAD51 foci and treatment response, BRCA status, and progression-free survival. Results RAD51 foci were identified in all patients (n=42) with wild-type BRCA. BRCA mutant/homologous recombination deficiency-positive patients (n=8) had significantly lower numbers of RAD51 foci (p=0.009). Responders to treatment (n=32) had a reduction in circulating cells (p=0.02) and RAD51 foci (p=0.0007). Numbers of RAD51 foci were significantly higher in the platinum-resistant population throughout treatment: At the start of treatment, in 56 platinum-sensitive patients there was a mean of 3.6 RAD51 foci versus 6.2 in 15 platinum-resistant patients (p=0.02). Patients with a high number of RAD51 foci had worse median progression-free survival: in 39 patients with a mean of 3 RAD51 foci whose progression-free survival was 13 months (p=0.04). Conclusions Levels of RAD51 foci in circulating cancer-associated cells of patients with high-grade serous ovarian cancer are associated with clinical outcomes and may be a more pragmatic method of determining a homologous repair-deficient population.John Bush Academic Fund, Mount Vernon Cancer Centre, and the Cancer Treatment Research Trust

The addition of genetic testing and cardiovascular magnetic resonance to routine clinical data for stratification of aetiology in dilated cardiomyopathy

Background: Guidelines recommend genetic testing and cardiovascular magnetic resonance (CMR) for the investigation of dilated cardiomyopathy (DCM). However, the incremental value is unclear. We assessed the impact of these investigations in determining etiology. Methods: Sixty consecutive patients referred with DCM and recruited to our hospital biobank were selected. Six independent experts determined the etiology of each phenotype in a step-wise manner based on (1) routine clinical data, (2) clinical and genetic data and (3) clinical, genetic and CMR data. They indicated their confidence (1-3) in the classification and any changes to management at each step. Results: Six physicians adjudicated 60 cases. The addition of genetics and CMR resulted in 57 (15.8%) and 26 (7.2%) changes in the classification of etiology, including an increased number of genetic diagnoses and a reduction in idiopathic diagnoses. Diagnostic confidence improved at each step (p < 0.0005). The number of diagnoses made with low confidence reduced from 105 (29.2%) with routine clinical data to 71 (19.7%) following the addition of genetics and 37 (10.3%) with the addition of CMR. The addition of genetics and CMR led to 101 (28.1%) and 112 (31.1%) proposed changes to management, respectively. Interobserver variability showed moderate agreement with clinical data (κ = 0.44) which improved following the addition of genetics (κ = 0.65) and CMR (κ = 0.68). Conclusion: We demonstrate that genetics and CMR, frequently changed the classification of etiology in DCM, improved confidence and interobserver variability in determining the diagnosis and had an impact on proposed management

Hepatoprotective effect of Cichorium Intybus linn (Kasni) Extracts against Carbon Tetrachloride induced Liver Damage

Abstract Background: To assess the effect of aqueous an

Phenotype, outcomes and natural history of early-stage non-ischaemic cardiomyopathy

Aims To characterize the phenotype, clinical outcomes and rate of disease progression in patients with early-stage non-ischaemic cardiomyopathy (early-NICM). Methods and results We conducted a prospective observational cohort study of patients with early-NICM assessed by late gadolinium enhancement cardiovascular magnetic resonance (CMR). Cases were classified into the following subgroups: isolated left ventricular dilatation (early-NICM H−/D+), non-dilated left ventricular cardiomyopathy (early-NICM H+/D−), or early dilated cardiomyopathy (early-NICM H+/D+). Clinical follow-up for major adverse cardiovascular events (MACE) included non-fatal life-threatening arrhythmia, unplanned cardiovascular hospitalization or cardiovascular death. A subset of patients (n = 119) underwent a second CMR to assess changes in cardiac structure and function. Of 254 patients with early-NICM (median age 46 years [interquartile range 36–58], 94 [37%] women, median left ventricular ejection fraction [LVEF] 55% [52–59]), myocardial fibrosis was present in 65 (26%). There was no difference in the prevalence of fibrosis between subgroups (p = 0.90), however fibrosis mass was lowest in early-NICM H−/D+, higher in early-NICM H+/D− and highest in early-NICM H+/D+ (p = 0.03). Over a median follow-up of 7.9 (5.5–10.0) years, 28 patients (11%) experienced MACE. Non-sustained ventricular tachycardia (hazard ratio [HR] 5.1, 95% confidence interval [CI] 2.36–11.00, p < 0.001), myocardial fibrosis (HR 3.77, 95% CI 1.73–8.20, p < 0.001) and diabetes mellitus (HR 5.12, 95% CI 1.73–15.18, p = 0.003) were associated with MACE in a multivariable model. Only 8% of patients progressed from early-NICM to dilated cardiomyopathy with LVEF <50% over a median of 16 (11–34) months. Conclusion Early-NICM is not benign. Fibrosis develops early in the phenotypic course. In-depth characterization enhances risk stratification and might aid clinical management

Description of a Retrospective Cohort of Epithelial Ovarian Cancer Patients with Brain Metastases: Evaluation of the Role of PARP Inhibitors in this Setting

Data Availability Statement: Data will be available upon reasonable request.Copyright © 2023 by the authors. Background: The incidence of brain metastases (BM) in patients with epithelial ovarian cancer (EOC) is low: 0.3–11%. The onset of BM has been regarded as a late event with limited treatment options and poor prognosis. This retrospective case series aims to explore the current management strategies with particular emphasis on the use of PARP inhibitors and outcomes, as well as identification of other prognostic indicators. Methods: A total of 39 ovarian cancer patients with brain metastases were identified from eight cancer centres in the UK. Clinical characteristics, details of management, and survival data were collected. Results: A total of 14/39 had BM as their first site of relapse. The majority (29 patients) received systemic treatments in addition to local radiotherapy (RT)/surgery. Nineteen patients had BRCA mutations (one somatic), one had a RAD51C mutation, and eighteen were BRCA wild type; one was unknown. A total of 14/39 patients received maintenance PARP inhibitors. As is well known, patients who received PARPi had consistently better outcomes. This was no different for those who received PARPi as part of the management of their BM. Platinum sensitivity and receiving more than one modality of therapy (e.g., radiation +/− chemotherapy and PARPi) for BM were also good prognostic indicators. Median PFS/OS for those treated with chemotherapy and either RT or surgery, then PARP inhibitor maintenance, have not been reached after a median of 33 months follow up. Conclusions: As with abdominal relapse, maintenance treatment with PARP inhibitors also has a valuable role in managing BMs in EOC patients.This research received no extra funding