Toxicological insight of metiram: immuno-oxidative, neuro-behavioral, and hemato-biochemical changes during acute exposure of Nile tilapia (Oreochromis niloticus).

BACKGROUND: The inappropriate use of pesticides including fungicides creates severe biological hazards that can endanger fish health and impede sustainable aquaculture. OBJECTIVE: This study investigated the negative impacts of metiram (MET), a fungicide on the health status of Nile tilapia (Oreochromis niloticus) for a 96-hour duration as an acute exposure in a static renewal system. METHODS: Three hundred fish (average body weight: 37.50 ± 0.22 g) were assigned into six groups (50 fish/group) with five replicates (10 fish/replicate). Fish were exposed to various six concentrations (0, 1.5, 3, 4.5, 6, and 7.5 mg/L) of MET as a water exposure to for 96-hour without water exchange. The fish's behavior, clinical signs, and mortalities were documented every day of the exposure period. Additionally, MET's impact on blood profile, stress biomarkers, hepato-renal functions, immune-antioxidant status, and brain biomarker were closely monitored. RESULTS: The lethal concentration (LC50) of MET estimated using Finney's probit technique was 3.77 mg/L. The fish's behavior was severely impacted by acute MET exposure, as clear by an increase in surfacing, loss of equilibrium, unusual swimming, laterality, abnormal movement, and a decline in aggressive behaviors. The survivability and hematological indices (white and red blood cell count, differential white blood cell count, hematocrit value, and hemoglobin) were significantly reduced in a concentration-dependent manner following MET exposure. Acute exposure to MET (1.5-7.5 mg/L) incrementally increased stress biomarkers (nor-epinephrine, cortisol, and glucose), lipid peroxides (malondialdehyde), and brain oxidative DNA damage biomarker (8-hydroxy-2-deoxyguanosine). A hepato-renal dysfunction by MET exposure (4.5-7.5 mg/L) was evidenced by the significant increase in the alanine and aspartate aminotransferases and creatinine values. Moreover, a substantial decline in the immune parameters (lysozyme, complement 3, serum bactericidal activity, and antiprotease activity) and antioxidant variables (total antioxidant capacity, superoxide dismutase, and glutathione peroxidase) resulted from acute MET exposure. CONCLUSION: According to these findings, the 96-hour LC50 of MET in Nile tilapia was 3.77 mg/L. MET exposure triggered toxicity in Nile tilapia, as seen by alterations in fish neuro-behaviors, immune-antioxidant status, hepato-renal functioning, and signifying physiological disturbances. This study emphasizes the potential ecological dangers provoked by MET as an environmental contaminant to aquatic systems. However, the long-term MET exposure is still needed to be investigated.

Antifungal and antibiofilm effects of probiotic Lactobacillus salivarius, zinc nanoparticles, and zinc nanocomposites against Candida albicans from Nile tilapia (Oreochromis niloticus), water and humans.

Introduction: Candida albicans (C. albicans) can form biofilms; a critical virulence factor that provides effective protection from commercial antifungals and contributes to public health issues. The development of new antifungal therapies, particularly those targeting biofilms, is imperative. Thus, this study was conducted to investigate the antifungal and antibiofilm effects of Lactobacillus salivarius (L. salivarius), zinc nanoparticles (ZnNPs) and nanocomposites (ZnNCs) on C. albicans isolates from Nile tilapia, fish wash water and human fish sellers in Sharkia Governorate, Egypt. Methods: A cross-sectional study collected 300 samples from tilapia, fish wash water, and fish sellers (100 each). Probiotic L. salivarius was immobilized with ZnNPs to synthesize ZnNCs. The study assessed the antifungal and antibiofilm activities of ZnNPs, L. salivarius, and ZnNCs compared to amphotericin (AMB). Results: Candida spp. were detected in 38 samples, which included C. albicans (42.1%), C. glabrata (26.3%), C. krusei (21.1%), and C. parapsilosis (10.5%). A total of 62.5% of the isolates were resistant to at least one antifungal agent, with the highest resistance to nystatin (62.5%). However, 75% of the isolates were highly susceptible to AMB. All C. albicans isolates exhibited biofilm-forming capabilities, with 4 (25%) isolates showing strong biofilm formation. At least one virulence-associated gene (RAS1, HWP1, ALS3, or SAP4) was identified among the C. albicans isolates. Probiotics L. salivarius, ZnNPs, and ZnNCs displayed antibiofilm and antifungal effects against C. albicans, with ZnNCs showing significantly higher inhibitory activity. ZnNCs, with a minimum inhibitory concentration (MIC) of 10 µg/mL, completely reduced C. albicans biofilm gene expression. Additionally, scanning electron microscopy images of C. albicans biofilms treated with ZnNCs revealed asymmetric, wrinkled surfaces, cell deformations, and reduced cell numbers. Conclusion: This study identified virulent, resistant C. albicans isolates with strong biofilm-forming abilities in tilapia, water, and humans, that pose significant risks to public health and food safety.

The alleviative effect of Bacillus subtilis-supplemented diet against Vibrio cholerae infection in Nile tilapia (Oreochromis niloticus).

Bacterial illness causes detrimental impacts on fish health and survival and finally economic losses for the aquaculture industry. Antibiotic medication causes microbial resistance, so alternative control strategies should be applied. In this work, we investigated the probiotic-medicated diet as an alternative control approach for antibiotics in treating Vibrio cholerae infection in Nile tilapia (Oreochromis niloticus). One hundred eighty fish (50 ± 2.5 g Mean ± SD) were allocated into six groups in glass aquariums (96 L) in triplicate for 10 days. Groups 1 (G1), G2, and G 3 were intraperitoneally (IP) injected with 0.5 mL sterilized tryptic soy broth and fed on a basal diet, basal diet contained B. subtilis (BS) (1 × 10 5 CFU/ kg-1 diet), and basal diet contained trimethoprim-sulfamethoxazole (TMP-SMX) (1.5 g/kg-1 diet), respectively. Additionally, G4, G5, and G6 were IP challenged with 0.5 mL of V. cholerae (1.5 × 107 CFU) and received the same feeding regime as G 1 to 3, respectively. The results exhibited that the V. cholera-infected fish exhibited skin hemorrhage, fin rot, and the lowest survival (63.33%). Additionally, lowered immune-antioxidant biomarkers (white blood cells count, serum bactericidal activity, phagocytic activity, phagocytic index, and lysozymes) with higher lipid peroxidation marker (malondialdehyde) were consequences of V. cholerae infection. Noteworthy, fish-fed therapeutic diets fortified with BS and TMP-SMX showed a substantial amelioration in the clinical signs and survival. The BS diet significantly improved (P < 0.05) the immune-antioxidant indices of the infected fish compared to the TMP-SMX diet. The current findings supported the use of a BS-enriched diet as an eco-friendly approach for the control of V. cholerae in O. niloticus.

Effects of dietary supplementation with benthic diatom Amphora coffeaeformis on blood biochemistry, steroid hormone levels and seed production efficiency of Nile tilapia Oreochromis niloticus broodstock.

Aquafeed additive quality and quantity remain pivotal factors that constrain the sustainability and progress of aquaculture feed development. This study investigates the impact of incorporating the benthic diatom Amphora coffeaeformis into the diet of Nile tilapia (Oreochromis niloticus) broodstock, on the blood biochemistry, steroid hormone (SH) levels and seed production efficiency. Broodstock females displaying mature ovary indications were initially combined with males at a ratio of three females to one male. A total of 384 adult Nile tilapia (288 females and 96 males) were used, with 32 fish (24 females and eight males) assigned to each of 12 concrete tanks (8 m³; 2 m × 4 m × 1 m), with three replicate tanks for each dietary treatment, throughout a 14-day spawning cycle until egg harvest. Fish were fed one of four different dietary treatments: AM0% (control diet), and AM2%, AM4% and AM6% enriched with the diatom A. coffeaeformis at levels of 20, 40 and 60 g/kg of diet respectively. At the trial's conclusion, total protein, albumin, triglyceride and creatinine), SHs (follicle-stimulating hormone, luteinizing hormone, free testosterone, total testosterone, progesterone and prolactin) and seeds production efficiency of Nile tilapia improved significantly (p < 0.05) in alignment with the increment of A. coffeaeformis supplementation. The findings propose that including A. coffeaeformis at levels ranging from 4% to 6% could be effectively employed as a feed additive during the Nile tilapia broodstock's spawning season.

Impact of dietary administration of Arthrospira platensis free-lipid biomass on growth performance, body composition, redox status, immune responses, and some related genes of pacific whiteleg shrimp, Litopenaeus vannamei.

The current study aimed to assess the influence of dietary inclusion of cyanobacterium Arthrospira platensis NIOF17/003 as a dry material and as a free-lipid biomass (FL) on the growth performance, body composition, redox status, immune responses, and gene expression of whiteleg shrimp, Litopenaeus vannamei postlarvae. L. vannamei were fed five different supplemented diets; the first group was fed on an un-supplemented diet as a negative control group (C-N), the second group was fed on a commercial diet supplemented with 2% of A. platensis complete biomass as a positive control group (C-P20), whereas, the three remaining groups were fed on a commercial diet supplemented with graded amounts of FL at 1%, 2%, and 3% (FL10, FL20, and FL30, respectively). The obtained results indicated that the diet containing 1% FL significantly increased the growth performance, efficiency of consumed feed, and survival percentage of L. vannamei compared to both C-N and C-P20 groups. As for the carcass analysis, diets containing A. platensis or its FL at higher levels significantly increased the protein, lipid, and ash content compared to the C-N group. Moreover, the shrimp group fed on C-P20 and FL10 gave significantly stimulated higher digestive enzyme activities compared with C-N. The shrimp fed C-P20 or FL exhibited higher innate immune responses and promoted their redox status profile. Also, the shrimp fed a low FL levels significantly upregulated the expression of both the peroxiredoxin (Prx) and prophenoloxidase (PPO1) genes than those receiving C-N. The current results recommended that dietary supplementation with 1% FL is the most effective treatment in promoting the performance and immunity of whiteleg shrimp.

Arthrospira platensis nanoparticles dietary supplementation improves growth performance, steroid hormone balance, and reproductive productivity of Nile tilapia (Oreochromis niloticus) broodstock.

This study evaluates the impact of dietary supplementation of the blue-green alga Arthrospira platensis NIOF17/003 nanoparticles (AN) on the growth performance, whole-body biochemical compositions, blood biochemistry, steroid hormonal, and fry production efficiency of Nile tilapia (Oreochromis niloticus) broodstock, during the spawning season. After a 21-day preparation period to equip the females and ensure that their ovaries were filled with eggs, mating between the mature females and males took place in a 3:1 ratio during a 14-day spawning cycle. A total of 384 tilapia broodstock 288 females and 96 males with an initial body weight of 450.53±0.75, were divided into four groups; AN0: a basal diet as a control group with no supplementation of Arthrospira platensis, and the other three groups (AN2, AN4, and AN6) were diets supplemented with nanoparticles of A. platensis at levels of 2, 4, and 6 g kg─1 diet, respectively. The results found that fish-fed group AN6 showed the highest significant differences in weight gain (WG), final weight (FW), feed conversion ratio (FCR), protein efficiency ratio (PER), and feed efficiency ratio (FER). Females fed the AN6 diet showed the highest significant fat content. Compared to the AN0 group, fish fed on the supplemented diets showed significant improvement (p < 0.05) in triglyceride, glucose, and aspartate aminotransferase (AST). A gradual increase in AN inclusion level resulted in a gradual increase in the concentrations of luteinizing hormone (LH), and follicle-stimulating hormone (FSH), testosterone, progesterone, and prolactin. The rates (%) of increase in fry production for females fed supplemented diets were 10.5, 18.6, and 32.2% for AN2, AN4, and AN6, respectively, compared to the control group. This work concluded that the inclusion levels of 6 g kg─1 of A. platensis nanoparticles in the diet of Nile tilapia broodstock significantly improved the growth performances, steroid hormone concentrations, and increased the fry production efficiency by 32.2%, respectively. These findings revealed that A. platensis nanoparticles resulted in a significantly enhanced female' reproductive productivity of Nile tilapia broodstock.

Accelerated Stability Assessment of Extemporaneously Compounded Amiloride Nasal Spray.

Amiloride is a U.S. Food and Drug Administration-approved diuretic agent used to treat hypertension and congestive heart failure. Recent human and animal studies have suggested that amiloride may also have a role in treating anxiety through its acid-sensing ion channel antagonism. Intranasal administration of amiloride nasal spray via an extemporaneously compounded preparation has the potential for rapid delivery to the site of action to achieve therapeutic outcomes in individual patients with anxiety disorders. However, these patient-specific preparations do not have the pre-formulation characterization, including chemical stability, that conventional manufactured dosage forms have. The objective of this study was to assess the estimated chemical stability of compounded amiloride nasal spray over 6 months and 12 months utilizing accelerated degradation with high heat and the Arrhenius equation. A stability-indicating highperformance liquid chromatography analytical method was employed at appropriate intervals over a 12-month period to reveal that amiloride remained chemically stable over the period tested and by extrapolation. Physical stability and compatibility with the preservative benzyl alcohol were also confirmed via visual inspection, pH monitoring, and measurement of turbidity.

The therapeutic role of Azadirachta indica leaves ethanolic extract against detrimental effects of Aeromonas veronii infection in Nile tilapia, Oreochromis niloticus.

Bacterial pathogens cause high fish mortalities and in turn economic losses in fish farms. Innovative strategies should be applied to control bacterial infections instead of antibiotics to avoid the resistance problem. Consequently, the present investigation studied the curative potential of Azadirachta indica leave ethanolic extract (AILEE) on Aeromonas veronii infection in Oreochromis niloticus. A preliminary trial was assessed to evaluate the curative dose of AILEE which was found to be 2.5 mg/L. One hundred and sixty fish were divided into equal four groups in four replications, where group 1 and group 2 were non-challenged and treated with 0- and 2.5-mg/L AILEE, respectively. Group 3 and group 4 were challenged with A. veronii and treated with 0- and 2.5-mg/L AILEE, respectively for 10 days. A. veronii infection produced severe clinical manifestations and a high mortality rate in the infected fish. Furthermore, the infected fish exhibited a significant rise in the hepatorenal indices (aspartate aminotransferase, alanine aminotransferase, and creatinine), the oxidant biomarker (malondialdehyde), and the stress indicators (glucose and cortisol). A significant reduction in the protein profile and antioxidant/immune parameters (catalase, immunoglobulin M, lysozyme, nitric oxide, and phagocytic activity) was observed in the infected fish. Water application of the infected group to 2.5-mg/L AILEE notably ameliorated the hepatorenal indices, the oxidant biomarker, and the stress indicators. Furthermore, AILEE improved the antioxidant/immune indices. Water application of 2.5-mg/L AILEE could be useful against A. veronii infection in O. niloticus culture.

Mixed Methods EvAluation of the high-volume low-complexity Surgical hUb pRogrammE (MEASURE): a mixed methods study protocol.

INTRODUCTION: The waiting list for elective surgery in England recently reached over 7.8 million people and waiting time targets have been missed since 2010. The high-volume low complexity (HVLC) surgical hubs programme aims to tackle the backlog of patients awaiting elective surgery treatment in England. This study will evaluate the impact of HVLC surgical hubs on productivity, patient care and the workforce. METHODS AND ANALYSIS: This 4-year project consists of six interlinked work packages (WPs) and is informed by the Consolidated Framework for Implementation Research. WP1: Mapping current and future HVLC provision in England through document analysis, quantitative data sets (eg, Hospital Episodes Statistics) and interviews with national service leaders. WP2: Exploring the effects of HVLC hubs on key performance outcomes, primarily the volume of low-complexity patients treated, using quasi-experimental methods. WP3: Exploring the impact and implementation of HVLC hubs on patients, health professionals and the local NHS through approximately nine longitudinal, multimethod qualitative case studies. WP4: Assessing the productivity of HVLC surgical hubs using the Centre for Health Economics NHS productivity measure and Lord Carter's operational productivity measure. WP5: Conducting a mixed-methods appraisal will assess the influence of HVLC surgical hubs on the workforce using: qualitative data (WP3) and quantitative data (eg, National Health Service (NHS) England's workforce statistics and intelligence from WP2). WP6: Analysing the costs and consequences of HVLC surgical hubs will assess their achievements in relation to their resource use to establish value for money. A patient and public involvement group will contribute to the study design and materials. ETHICS AND DISSEMINATION: The study has been approved by the East Midlands-Nottingham Research Ethics Committee 23/EM/0231. Participants will provide informed consent for qualitative study components. Dissemination plans include multiple academic and non-academic outputs (eg, Peer-reviewed journals, conferences, social media) and a continuous, feedback-loop of findings to key stakeholders (eg, NHS England) to influence policy development. TRIAL REGISTRATION: Research registry: Researchregistry9364 (https://www.researchregistry.com/browse-the-registry%23home/registrationdetails/64cb6c795cbef8002a46f115/).

Comparison of differences in cohort (forwards) and case control (backwards) methodological approaches for validation of the Hypotension Prediction Index.

BACKGROUND: The Hypotension Prediction Index (the index) software is a machine learning algorithm that detects physiological changes that may lead to hypotension. The original validation used a case control (backwards) analysis that has been suggested to be biased. We therefore conducted a cohort (forwards) analysis and compared this to the original validation technique. METHODS: We conducted a retrospective analysis of data from previously reported studies. All data were analysed identically with 2 different methodologies and receiver operating characteristic curves (ROC) constructed. Both backwards and forwards analyses were performed to examine differences in area under the ROC for HPI and other haemodynamic variables to predict a MAP < 65mmHg for at least 1 minute 5, 10 and 15 minutes in advance. RESULTS: Two thousand and twenty-two patients were included in the analysis, yielding 4,152,124 measurements taken at 20 second intervals. The area-under-the-curve for the index predicting hypotension analysed by backward and forward methodologies respectively was 0.957 (95% CI, 0.947-0.964) vs 0.923 (95% CI, 0.912-0.933) 5 minutes in advance, 0.933 (95% CI, 0.924-0.942) vs 0.923 (95% CI, 0.911-0.933) 10 minutes in advance , and 0.929 (95% CI, 0.918-0.938) vs. 0.926 (95% CI, 0.914-0.937) 15 minutes in advance. No other variable had an area-under-the-curve > 0.7 except for MAP. Area-under-the-curve using forward analysis for MAP predicting hypotension 5, 10, and 15 minutes in advance was 0.932 (95% CI, 0.920-0.940), 0.929 (95% CI, 0.918-0.938), and 0.932 (95% CI, 0.921-0.940). The R 2 for the variation in the index due to MAP was 0.77. CONCLUSION: Using an updated methodology, we found the utility of the HPI index to predict future hypotensive events is high, with an area under the receiver-operating-characteristics curve similar to that of the original validation method.

Novel Colorimetric and Light Scatter Methods to Identify and Manage Peritoneal Dialysis-Associated Peritonitis at the Point-of-Care.

Introduction: Peritoneal dialysis (PD)-related peritonitis (PDRP) is a common cause of transfer to hemodialysis, patient morbidity, and is a risk factor for mortality. Associated patient anxiety can deter selection of PD for renal replacement therapy. Diagnosis relies on hospital laboratory tests; however, this might be achieved earlier if such information was available at the point-of-care (POC), thereby significantly improving outcomes. The presence of culturable microbes and the concentration of leukocytes in effluent both aid peritonitis diagnosis, as specified in the International Society for Peritoneal Dialysis (ISPD) diagnostic guidelines. Here, we report the development of 2 new methods providing such information in simple POC tests. Methods: One approach uses a tetrazolium-based chemical reporting system, primarily focused on detecting bacterial contamination and associated vancomycin-sensitivity. The second approach uses a novel forward light-scatter device (QuickCheck) to provide an instant quantitative cell count directly from PD patient effluent. Results: The tetrazolium approach detected and correctly distinguished laboratory isolates, taking 10 hours to provide non-quantitative results. We compared the technical performance of the light scatter leukocyte counting approach with spectrophotometry, hemocytometer counting and flow cytometry (Sysmex) using patient effluent samples. QuickCheck had high accuracy (94%) and was the most precise (coefficient of variation <4%), showing minimal bias, overall performing similarly to flow cytometry. Conclusion: These complementary new approaches provide a simple means to obtain information to assist diagnosis at the POC. The first provides antibiotic sensitivity following 10 hours incubation, whereas the second optical approach (QuickCheck), provides instant accurate total leukocyte count.

Centre variation in home dialysis uptake: A survey of kidney centre practice in relation to home dialysis organisation and delivery in England.

BACKGROUND: Disparities in home dialysis uptake across England suggest inequity and unexplained variation in access. We surveyed staff at all English kidney centres to identify patterns in service organisation/delivery and explore correlations with home therapy uptake, as part of a larger study ('Inter-CEPt'), which aims to identify potentially modifiable factors to address observed variations. METHODS: Between June and September 2022, staff working at English kidney centres were surveyed and individual responses combined into one centre-level response per question using predetermined data aggregation rules. Descriptive analysis described centre practices and their correlation with home dialysis uptake (proportion of new home dialysis starters) using 2019 UK Renal Registry 12-month home dialysis incidence data. RESULTS: In total, 180 responses were received (50/51 centres, 98.0%). Despite varied organisation of home dialysis services, most components of service delivery and practice had minimal or weak correlations with home dialysis uptake apart from offering assisted peritoneal dialysis and 'promoting flexible decision-making about dialysis modality'. Moderate to strong correlations were identified between home dialysis uptake and centres reporting supportive clinical leadership (correlation 0.32, 95% Confidence Interval (CI): 0.05-0.55), an organisational culture that values trying new initiatives (0.57, 95% CI: 0.34-0.73); support for reflective practice (0.38, 95% CI: 0.11-0.60), facilitating research engagement (0.39, 95% CI: 0.13-0.61) and promoting continuous quality improvement (0.29, 95% CI: 0.01-0.53). CONCLUSIONS: Uptake of home dialysis is likely to be driven by organisational culture, leadership and staff attitudes, which provide a supportive clinical environment within which specific components of service organisation and delivery can be effective.

Feasibility of replacing fish oil with sunflower oil on the growth, body composition, fatty acid profile, antioxidant activity, stress response, and blood biomarkers of Labeo rohita.

A 90-day study was conducted to investigate the effects of substituting sunflower oil (SFO) for fish oil (FO) on various parameters in Labeo rohita (initial weight 18.21 ± 0.22 g). Five experimental diets with different levels of SFO (up to 7%) substitution for FO (0%, 25%, 50%, 75%, and 100%) were formulated, ensuring equal levels of nitrogen and lipids. The results indicated that even with 100% substitution of SFO with FO, there were no significant differences (P>0.05) were observed in growth performance. The survival rate (SR), hepato-somatic index (HSI), and viscero-somatic index (VSI) as well as whole-body composition were also nonsignificant by SFO substitution. However, the fatty acid profiles in both muscle and liver were influenced (P<0.05) by dietary substitution. Saturated fats (SFA) decreased, while monounsaturated fats (MUFA), and linoleic acid (LA) increased (P<0.05). On the other hand, the contribution of linolenic acid (ALA), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA) decreased (P<0.05) as the amount of SFO in the diet increased. Hematology parameters, including red blood cells (RBCs), hemoglobin (Hb), and hematocrit (Hct), were not affected. Globulin (GLO) levels decreased significantly (P<0.05), while alanine transaminase (ALT) and aspartate transaminase (AST) activity showed nonsignificant increases (P>0.05). Total protein (TP) increased (P<0.05) at 100% SFO inclusion in the diet, and albumin (ALB) levels increased (P<0.05) at 75% and 100% SFO inclusion in the diet. Cholesterol (CHOL), triacylglycerol (TG), and high-density lipids (HDL) were not significantly affected (P>0.05), while low-density lipids (LDL) were significantly increased (P<0.05) compared to the control group. Cortisol (CORT) and glucose (GLU) levels showed nonsignificant (P>0.05) changes. Superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) activities in the liver and serum were not significantly (P>0.05) affected, while malondialdehyde (MDA) status was significantly (P<0.05) reduced. In conclusion, the fatty acid profile of the muscle and liver of fish was modified by the diets, and FO can be substituted with SFO up to 100% for L. rohita, which is beneficial for growth and immunity while marinating the lipid contents in fish. Our study revealed that fully replacing fish oil with SFO shows promise in fully replacing FO without compromising the growth and overall health status of the fish.

Corrigendum: Future impact of thymoquinone-loaded nanoemulsion in rabbits: prospects for enhancing growth, immunity, antioxidant potential and resistance against Pasteurella multocida.

[This corrects the article DOI: 10.3389/fvets.2023.1340964.].

Enhancing farmed striped catfish (Pangasianodon hypophthalmus) robustness through dietary ß-glucan.

ß-glucan is a well-documented feed additive for its potent immunostimulatory properties in many farmed fish species. This study examined how it can also be a promising growth promoter, modulate antioxidant enzyme activities, and act as an anti-stress agent in striped catfish (Pangasianodon hypophthalmus). A 12-week feeding experiment was untaken to determine the effects of dietary ß-glucan supplementation at graded levels (0, 0.5, 1.0, and 1.5 g kg-1). Measured indicators suggest that a dietary inclusion level of 1.5 g kg-1 ß-glucan gave the highest positive responses: weight gain (120.10 g fish-1), survival (98.30%), and lower FCR (1.70) (P<0.05). Whole body proximate analysis had only revealed that crude protein was significantly affected by the dietary inclusion of ß-glucan (P<0.05), with the highest protein content (19.70%) being in fish that were fed with 1.5 g kg-1 ß-glucan. Although other inclusion levels (i.e., 0.5 and 1 g kg-1) of ß-glucan did not enhance body protein content (P>0.05). The assessment of fatty acid composition in muscle, liver, and adipose tissues showed modifications with the inclusion of ß-glucan. Antioxidative-related enzyme activities (inc. catalase, glutathione peroxidase, and superoxide dismutase) that were measured in the liver had higher levels when fed with ß-glucan inclusion diets (P<0.05). Following the feed trial, fish were subjected to crowding stress treatment. It was subsequently found that catfish fed with ß-glucan-based diet groups had lower levels of blood stress-related indicators compared to the control group with no dietary ß-glucan. The use of 1.5 g kg-1 of dietary ß-glucan resulted in the lowest measured levels of cortisol (43.13 ng mL-1) and glucose (50.16 mg dL-1). This study has demonstrated that the dietary inclusion of ß-glucan can have functional benefits beyond the immunological enhancements in striped catfish. Furthermore, its use can increase production levels and mitigate the stress associated with intensive farming practices.

Antagonistic Effect of Zinc Oxide Nanoparticles Dietary Supplementation Against Chronic Copper Waterborne Exposure on Growth, Behavioral, Biochemical, and Gene Expression Alterations of African Catfish, Clarias gariepinus (Burchell, 1822).

The harmful impact of waterborne copper (Cu) as a common abiotic stressor in aquatic environments has gained much more interest. The present study aimed to investigate the utilization of zinc oxide nanoparticles (ZnONPs) dietary supplementation to mitigate the chronic toxicity of Cu in African catfish (Clarias gariepinus). Two hundred and forty fish (92.94 ± 0.13 g) were assigned into six groups for 60 days. Control (C), ZnONPs20, and ZnONPs30 groups were fed on basal diets fortified with 0, 20, and 30 mg kg-1 ZnONPs without Cu exposure. Cu, Cu + ZnONPs20, and Cu + ZnONPs30 groups were exposed to Cu at a dose of 10 mg L-1 and fed on basal diets fortified with 0, 20, and 30 mg kg-1 ZnONPs, respectively. The results revealed that the Cu-exposed fish experienced abnormal clinical signs and behavioral changes. The growth indices and acetylcholine esterase activity were significantly decreased (P < 0.05) in the Cu group. Meanwhile, hepatorenal and serum stress indices (P < 0.05) were significantly elevated with chronic Cu exposure. In addition, a higher expression of stress (P < 0.05) (heat shock protein 60 and hypoxia-inducible factor-1 alpha) and apoptotic-related genes (C/EBP homologous protein, caspase-3, and Bcl-2 Associated X-protein) with down-regulation (P < 0.05) of the anti-apoptotic-related genes (B-cell lymphoma 2 and proliferating cell nuclear antigen) was noticed in the Cu-exposed fish. Histopathological alterations in the gills, liver, kidney, and spleen were markedly reported in the Cu-exposed group. The dietary supplementation with ZnONPs significantly alleviated the negative impacts of chronic waterborne-Cu exposure on growth performance, physiological changes, gene expression, and tissue architecture, especially at 30 mg kg-1 diet level. In particular, the inclusion of ZnONPs at the 30 mg kg-1 diet level produced better outcomes than the 20 mg kg-1 diet. Overall, ZnONPs could be added as a feed supplement in the C. gariepinus diet to boost the fish's health and productivity and alleviate the stress condition brought on by Cu exposure.

The clinical significance of sub-total surgical resection in childhood medulloblastoma: a multi-cohort analysis of 1100 patients.

Background: Medulloblastoma patients with a sub-total surgical resection (STR; >1.5 cm2 primary tumour residuum post-surgery) typically receive intensified treatment. However, the association of STR with poor outcomes has not been observed consistently, questioning the validity of STR as a high-risk disease feature. Methods: We collected extent of resection (EOR) data from 1110 patients (from UK CCLG centres (n = 416, collected between September 1990 and July 2014) and published (n = 694) cohorts), the largest cohort of molecularly and clinically annotated tumours assembled to specifically assess the significance of EOR. We performed association and univariable/multivariable survival analyses, assessing overall survival (OS) cohort-wide and with reference to the four consensus medulloblastoma molecular groups and clinical features. Findings: STR was reported in 20% (226/1110) of patients. Non-WNT (p = 0.047), children <5 years at diagnosis (p = 0.021) and metastatic patients (p < 0.0001) were significantly more likely to have a STR. In cohort-wide analysis, STR was associated with worse survival in univariable analysis (p < 0.0001). Examination of specific disease contexts showed that STR was prognostic in univariate analysis for patients receiving cranio-spinal irradiation (CSI) and chemotherapy (p = 0.016) and for patients with Group 3 tumours receiving CSI (p = 0.039). STR was not independently prognostic in multivariable analyses; outcomes for patients who have STR as their only risk-feature are as per standard-risk disease. Specifically, STR was not prognostic in non-metastatic patients that received upfront CSI. Interpretation: In a cohort of 1100 molecularly characterised medulloblastoma patients, STR (n = 226) predicted significantly lower OS in univariable analysis, but was not an independent prognostic factor. Our data suggest that maximal safe resection can continue to be carried out for patients with medulloblastoma and suggest STR should not inform patient management when observed as a sole, isolated risk-feature. Funding: Cancer Research UK, Newcastle Hospitals Charity, Children's Cancer North, British Division of the International Academy of Pathology.

BIPOC experiences of (anti-)racist patient engagement in adolescent and young adult oncology research: an electronic Delphi study.

Aims: To characterize Black, Indigenous and People of Color (BIPOC) adolescent and young adult (AYA) cancer patients' experiences of patient engagement in AYA oncology and derive best practices that are co-developed by BIPOC AYAs and oncology professionals. Materials & methods: Following a previous call to action from AYA oncology professionals, a panel of experts composed exclusively of BIPOC AYA cancer patients (n = 32) participated in an electronic Delphi study. Results: Emergent themes described BIPOC AYA cancer patients' direct experiences and consensus opinion on recommendations to advance antiracist patient engagement from BIPOC AYA cancer patients and oncology professionals. Conclusion: The findings reveal high-priority practices across all phases of research and are instructional for advancing health equity.

The Point-of-Care Peritoneal Dialysis System Early Evaluation Study (POC-PDEE): A pilot proof-of-principal study of the Ellen Medical Devices Point-of-Care affordable peritoneal dialysis system.

The global unmet need for kidney replacement therapy means that millions of people die every year as they cannot afford treatment. Peritoneal dialysis (PD) offers comparable survival to haemodialysis and is often more affordable, but one barrier to increasing access is that conventional manufacturing and distribution of PD fluid is costly. Here we report the results from a pilot proof-of-principal study demonstrating for the first time that the Ellen Medical Devices Point-of-Care system can be used by patients to produce sterile PD fluid at the point-of-care. With further development, this low-cost system could offer a solution to the many millions of people around the world who currently cannot afford treatment for kidney failure.