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.

Investigating the impact of nanoemulsion of curcumin-loaded olive oil on growth performance, feed utilization, immunological responses, and redox status of Litopenaeus vannamei shrimp with emphasis on economic efficiency of supplementation.

The trail aimed to explore the effect of dietary supplementation of curcumin loaded olive oil nanoemulsion (CUR-OLNE) on growth performance, feed utilization, blood biochemical, redox status, and immune response of Litopenaeus vannamei shrimp, considering the economic efficiency of supplementation. A total of 280 healthy shrimps (3.42 ± 0.02 g) were randomly distributed into five equal groups and were fed diets containing 0 (CUR-OLNE0), 5(CUR-OLNE5), 10(CUR-OLNE10), 15(CUR-OLNE15) and 20 (CUR-OLNE20) mg CUR-OLNE/kg diet, respectively for 16 weeks. Among CUR-OLNE treated groups, CUR-OLNE20 showed the highest growth performance and feed utilization traits, including final body weight, specific growth rate, feed conversion ratio, and protein efficiency ratio. Notably, the photomicrographs provided further compelling evidence regarding the potential effect of CUR-OLNE supplementation on muscle structure and integrity. Compared to the control, the levels of blood protein significantly induced in CUR-OLNE15 and CUR-OLNE20 treated groups (p < 0.05). All CUR-OLNE -supplemented groups possessed lower activities of liver enzymes as well as the levels of urea and creatinine compared to the control (p < 0.05). The addition of 20 mg CUR-OLNE/kg diet decreased the concentrations of cortisol, glucose and triglycerides. The dietary treatment significantly improved the secretion of digestive enzymes, including amylase, lipase, and protease. The lowest levels of Malondialdehyde and the highest levels of total antioxidant capacity, super oxide dismutase, catalase, lysozyme and immunoglobulin M were detected in both of CUR-OLNE15, and CUR-OLNE20 treated groups compared to the control (p < 0.05). There were considerable significant effects of dietary supplementation of CUR-OLNE on economic efficiency. In conclusion, the application of nanocarriers for the delivery of dietary immune stimulants such as CUR-OLNE to Litopenaeus vannamei shrimp is a promising strategy for improving shrimp nutrition. The addition of 20 mg CUR-OLNE/kg to the diets of can be recommended as an affective intervention to improve growth performance, feed utilization, and health status of shrimp. Implementing this intervention can maximize the economic efficiency of shrimp farming while promoting sustainable practices in the industry.

Hexaflumuron insecticide exposure induces behavior alterations, hemato-biochemical disorders, antioxidant-immune dysfunction, and histopathological alterations in Nile tilapia (Oreochromis niloticus).

Hexaflumuron (HEX) insecticide is widely used in agriculture practices to fight crop insects. The toxicological effect of HEX on Nile tilapia (Oreochromis niloticus) was investigated in this study. Two hundred and forty fish (35.50 ± 1.45 g) were divided into six groups in four replicates (40 fish/group; 10 fish/replicate) and were exposed to six distinct HEX concentrations (0, 2, 4, 6, 8, and 10 mg L-1) for 96-h. The 96-h lethal concentration 50 (96-h LC50) of HEX was calculated to be 7.19 mg L-1. The fish exhibited reduced surface and middle swimming, aggressiveness, and tail-spreading behaviors with increasing bottom swimming and resting patterns after HEX exposure. HEX exposure resulted in body bleeding and fin rot. The erythrogram (red blood cell count, hemoglobin, and packed cell volume %) was significantly reduced with increased mean corpuscular volume by HEX exposure. HEX exposure decreased the white blood cells (WBCs) and differential WBC counts. Acute HEX exposure raised 8-hydroxy-2-deoxyguanosine level while lowering brain acetylcholine esterase activity. HEX exposure caused hepato-renal dysfunction and increased stress-related parameters (glucose and cortisol). Exposure to HEX reduced the immune responses (lysozyme, nitric oxide, immunoglobulin M, and complement 3). A substantial decrease in the antioxidant variables (reduced glutathione content and catalase) with increasing the malondialdehyde was noted by HEX exposure. Moreover, histopathological changes resulted from HEX exposure in the gills, liver, kidney, and spleen. These results indicate that HEX exposure induced behavioral changes, hepato-renal dysfunction, and immune-antioxidant disruption, indicating a possible physiological disruption in O. niloticus.

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.

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.

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.

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 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.

Comparison of Differences in Cohort (Forward) and Case Control (Backward) Methodologic Approaches for Validation of the Hypotension Prediction Index.

BACKGROUND: The Hypotension Prediction Index (the index) software is a machine learning algorithm that detects physiologic changes that may lead to hypotension. The original validation used a case control (backward) analysis that has been suggested to be biased. This study therefore conducted a cohort (forward) analysis and compared this to the original validation technique. METHODS: A retrospective analysis of data from previously reported studies was conducted. All data were analyzed identically with two different methodologies, and receiver operating characteristic curves were constructed. Both backward and forward analyses were performed to examine differences in area under the receiver operating characteristic curves for the Hypotension Prediction Index and other hemodynamic variables to predict a mean arterial pressure (MAP) less than 65 mmHg for at least 1 min 5, 10, and 15 min in advance. RESULTS: The analysis included 2,022 patients, yielding 4,152,124 measurements taken at 20-s intervals. The area under the curve for the index predicting hypotension analyzed by backward and forward methodologies respectively was 0.957 (95% CI, 0.947 to 0.964) versus 0.923 (95% CI, 0.912 to 0.933) 5 min in advance, 0.933 (95% CI, 0.924 to 0.942) versus 0.923 (95% CI, 0.911 to 0.933) 10 min in advance, and 0.929 (95% CI, 0.918 to 0.938) versus 0.926 (95% CI, 0.914 to 0.937) 15 min in advance. No variable other than MAP had an area under the curve greater than 0.7. The areas under the curve using forward analysis for MAP predicting hypotension 5, 10, and 15 min in advance were 0.932 (95% CI, 0.920 to 0.940), 0.929 (95% CI, 0.918 to 0.938), and 0.932 (95% CI, 0.921 to 0.940), respectively. The R2 for the variation in the index due to MAP was 0.77. CONCLUSIONS: Using an updated methodology, the study found that the utility of the Hypotension Prediction 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.

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.

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.].

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.

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 definition of treatment resistance in anxiety disorders: a Delphi method-based consensus guideline.

Anxiety disorders are very prevalent and often persistent mental disorders, with a considerable rate of treatment resistance which requires regulatory clinical trials of innovative therapeutic interventions. However, an explicit definition of treatment-resistant anxiety disorders (TR-AD) informing such trials is currently lacking. We used a Delphi method-based consensus approach to provide internationally agreed, consistent and clinically useful operational criteria for TR-AD in adults. Following a summary of the current state of knowledge based on international guidelines and an available systematic review, a survey of free-text responses to a 29-item questionnaire on relevant aspects of TR-AD, and an online consensus meeting, a panel of 36 multidisciplinary international experts and stakeholders voted anonymously on written statements in three survey rounds. Consensus was defined as ≥75% of the panel agreeing with a statement. The panel agreed on a set of 14 recommendations for the definition of TR-AD, providing detailed operational criteria for resistance to pharmacological and/or psychotherapeutic treatment, as well as a potential staging model. The panel also evaluated further aspects regarding epidemiological subgroups, comorbidities and biographical factors, the terminology of TR-AD vs. "difficult-to-treat" anxiety disorders, preferences and attitudes of persons with these disorders, and future research directions. This Delphi method-based consensus on operational criteria for TR-AD is expected to serve as a systematic, consistent and practical clinical guideline to aid in designing future mechanistic studies and facilitate clinical trials for regulatory purposes. This effort could ultimately lead to the development of more effective evidence-based stepped-care treatment algorithms for patients with anxiety disorders.

The immunosuppressive, growth-hindering, hepatotoxic, and oxidative stress and immune related-gene expressions-altering effects of gibberellic acid in Oreochromis niloticus: A mitigation trial using alpha-lipoic acid.

This study aimed to examine the effects of gibberellic acid (GBA) on growth, hemato-biochemical parameters related to liver functions, digestive enzymes, and immunological response in Oreochromis niloticus. Besides, the probable underlying mechanisms were explored by assessing antioxidant, apoptotic, and immune-related gene expression. Furthermore, the likelihood of restoration following alpha-lipoic acid (LIP) dietary supplementation was explored. The fish (average initial weight 30.75 ± 0.46) were equally classified into four groups: the control group, the LIP group (fed on a basal diet plus 600 mg/kg of LIP), the GBA group (exposed to 150 mg GBA/L), and the GBA + LIP group (exposed to 150 mg GBA/L and fed a diet containing LIP and GBA) for 60 days. The study findings showed that LIP supplementation significantly reduced GBA's harmful effects on survival rate, growth, feed intake, digestive enzymes, and antioxidant balance. Moreover, the GBA exposure significantly increased liver enzymes, stress markers, cholesterol, and triglyceride levels, all of which were effectively mitigated by the supplementation of LIP. Additionally, LIP addition to fish diets significantly minimized the histopathological alterations in the livers of GBA-treated fish, including fatty change, sharply clear cytoplasm with nuclear displacement to the cell periphery, single-cell necrosis, vascular congestion, and intralobular hemorrhages. The GBA-induced reduction in lysozyme activity, complement C3, and nitric oxide levels, together with the downregulation of antioxidant genes (cat and sod), was significantly restored by dietary LIP. Meanwhile, adding LIP to the GBA-exposed fish diets significantly corrected the aberrant expression of hsp70, caspase- 3, P53, pcna, tnf-a, and il-1ß in O. niloticus liver. Conclusively, dietary LIP supplementation could mitigate the harmful effects of GBA exposure on fish growth and performance, physiological conditions, innate immunity, antioxidant capability, inflammatory response, and cell apoptosis.

Effect of dietary intervention with Capsicum annuum extract on growth performance, physiological status, innate immune response, and related gene expression in Nile tilapia.

The red pepper (Capsicum annuum) has gained great attention recently because of its biological and pharmacological characteristics. The present approach aimed to evaluate the effects of C. annuum alcoholic extract (CAE) supplementation on Nile tilapia (Oreochromis niloticus) growth performance, physiological status, some metabolic, immune, and regulatory genes expression, and resistance against Streptococcus agalactiae infection. Fish (22.26 ± 0.19 g) were assigned to four treatments (five replicates, each with 10 fish replicate-1) and fed tested diets for 60 days. The experimental diets were supplemented with CAE at 0, 0.4, 0.8, and 1.6 g kg-1, expressed as CAE0, CAE0.4, CAE0.8, and CAE1.6, respectively. The findings exhibited that CAE dietary supplementation improved growth performance, feed utilization, elevated growth hormone level, and digestive enzyme activities (amylase and protease), and lowered leptin hormone in a level-dependent manner. Boosting the mRNA expression of the transporter proteins (solute carrier family 15 member 2 and solute carrier family 26 member 6) and insulin-like growth factor-1 genes with a decrease in the myostatin gene expression was noticed in the CAE-fed groups. The innate immune (serum bactericidal activity %, complement 3, and phagocytic activity %) and antioxidant (glutathione peroxidase and total antioxidant capacity) parameters were significantly (p < 0.05) improved, and the serum malondialdehyde level was significantly decreased by CAE dietary inclusion. A marked upregulation in the mRNA expression of interleukins (il-1ß, il-6, il-8, and il-10), transforming growth factor-ß, glutathione peroxidase, and glutathione synthetase genes were observed in CAE-fed groups. Dietary CAE decreased the cumulative mortalities after the challenge with S. agalactiae by 20, 13.33, and 10% in CAE0.4, CAE0.8, and CAE1.6, respectively, compared to the control (40%). Overall, dietary supplementation with CAE could improve growth performance and physiological status, and modulate the expression of several regulatory genes in Nile tilapia. The recommended level of CAE is 1.6 g kg-1 to augment growth and health status.

Nelumbo nucifera synthesized selenium nanoparticles modulate the immune-antioxidants, biochemical indices, and pro/anti-inflammatory cytokines pathways in Oreochromis niloticus infected with Aeromonas veronii.

Bacterial infection is considered one of the major issues in fish culturing that results in economic losses. Metal nanoparticles are a cutting-edge and effective disease management and preventive strategy because of their antibacterial ability. In this investigation, the selenium nanoparticles were prepared by a biological method using Nelumbo nucifera leaves extract. The in-vitro antibacterial activity of N. nucifera synthesized selenium nanoparticles (NN-SeNPs) was tested against Aeromonas veronii. A treatment assay was conducted on 210 Oreochromis niloticus (average body weight: 27 ± 2.00 g). A preliminary approach was conducted on 90 fish for determination of the therapeutic concentration of NN-SeNPs which was found to be 4 mg/L. Fish (n = 120) were categorized into four groups for 10 days; G1 (control) and G2 (NN-SeNPs) were non-challenged and treated with 0 and 4 mg/L NN-SeNPs, respectively. While, G3 and G4 were infected with 2 × 106 CFU/mL of A. veronii and treated with 0 and 4 mg/L NN-SeNPs, respectively. NN-SeNPs exhibited an inhibition zone against A. veronii with a diameter of 16 ± 1.25 mm. The A. veronii infection increased the hepato-renal biomarkers (alanine and aspartate aminotransferases and creatinine) than the control group. An oxidative stress was the consequence of A. veronii infection (higher malondialdehyde and hydrogen peroxide levels with lower glutathione peroxidase superoxide, dismutase, and catalase activity). A. veronii infection resulted in lower immunological biomarker values (immunoglobulin M, lysozyme, and complement 3) with higher expression of the inflammatory cytokines (interleukin-1ß and tumor necrosis factor-ɑ) as well as lower expression of the anti-inflammatory cytokines (interleukin-10 and transforming growth factor-ß). Therapeutic application with 4 mg/L NN-SeNPs prevented the disease progression; and modulated the hepato-renal function disruptions, oxidant-immune dysfunction, as well as the pro/anti-inflammatory cytokines pathway in the A. veronii-infected fish. These findings suggest that NN-SeNPs, employed as a water therapy, can safeguard fish from the harmful effects of A. veronii and serve as a promising antibacterial agent for sustainable aquaculture.

Antipsychotic Medication and Risk of Metabolic Disorders in People With Schizophrenia: A Longitudinal Study Using the UK Clinical Practice Research Datalink.

BACKGROUND AND HYPOTHESIS: Antipsychotics are first-line drug treatments for schizophrenia. When antipsychotic monotherapy is ineffective, combining two antipsychotic drugs is common although treatment guidelines warn of possible increases in side effects. Risks of metabolic side effects with antipsychotic polypharmacy have not been fully investigated. This study examined associations between antipsychotic polypharmacy and risk of developing diabetes, hypertension, or hyperlipidemia in adults with schizophrenia, and impact of co-prescription of first- and second-generation antipsychotics. STUDY DESIGN: A population-based prospective cohort study was conducted in the United Kingdom using linked primary care, secondary care, mental health, and social deprivation datasets. Cox proportional hazards models with stabilizing weights were used to estimate risk of metabolic disorders among adults with schizophrenia, comparing patients on antipsychotic monotherapy vs polypharmacy, adjusting for demographic and clinical characteristics, and antipsychotic dose. STUDY RESULTS: Median follow-up time across the three cohorts was approximately 14 months. 6.6% developed hypertension in the cohort assembled for this outcome, with polypharmacy conferring an increased risk compared to monotherapy, (adjusted Hazard Ratio = 3.16; P = .021). Patients exposed to exclusive first-generation antipsychotic polypharmacy had greater risk of hypertension compared to those exposed to combined first- and second-generation polypharmacy (adjusted HR 0.29, P = .039). No associations between polypharmacy and risk of diabetes or hyperlipidemia were found. CONCLUSIONS: Antipsychotic polypharmacy, particularly polypharmacy solely comprised of first-generation antipsychotics, increased the risk of hypertension. Future research employing larger samples, follow-up longer than the current median of 14 months, and more complex methodologies may further elucidate the association reported in this study.

Effects of Empagliflozin on Fluid Overload, Weight, and Blood Pressure in CKD.

SIGNIFICANCE STATEMENT: SGLT2 inhibitors reduce risk of kidney progression, AKI, and cardiovascular disease, but the mechanisms of benefit are incompletely understood. Bioimpedance spectroscopy can estimate body water and fat mass. One quarter of the EMPA-KIDNEY bioimpedance substudy CKD population had clinically significant levels of bioimpedance-derived "Fluid Overload" at recruitment. Empagliflozin induced a prompt and sustained reduction in "Fluid Overload," irrespective of sex, diabetes, and baseline N-terminal pro B-type natriuretic peptide or eGFR. No significant effect on bioimpedance-derived fat mass was observed. The effects of SGLT2 inhibitors on body water may be one of the contributing mechanisms by which they mediate effects on cardiovascular risk. BACKGROUND: CKD is associated with fluid excess that can be estimated by bioimpedance spectroscopy. We aimed to assess effects of sodium glucose co-transporter 2 inhibition on bioimpedance-derived "Fluid Overload" and adiposity in a CKD population. METHODS: EMPA-KIDNEY was a double-blind placebo-controlled trial of empagliflozin 10 mg once daily in patients with CKD at risk of progression. In a substudy, bioimpedance measurements were added to the main trial procedures at randomization and at 2- and 18-month follow-up visits. The substudy's primary outcome was the study-average difference in absolute "Fluid Overload" (an estimate of excess extracellular water) analyzed using a mixed model repeated measures approach. RESULTS: The 660 substudy participants were broadly representative of the 6609-participant trial population. Substudy mean baseline absolute "Fluid Overload" was 0.4±1.7 L. Compared with placebo, the overall mean absolute "Fluid Overload" difference among those allocated empagliflozin was -0.24 L (95% confidence interval [CI], -0.38 to -0.11), with similar sized differences at 2 and 18 months, and in prespecified subgroups. Total body water differences comprised between-group differences in extracellular water of -0.49 L (95% CI, -0.69 to -0.30, including the -0.24 L "Fluid Overload" difference) and a -0.30 L (95% CI, -0.57 to -0.03) difference in intracellular water. There was no significant effect of empagliflozin on bioimpedance-derived adipose tissue mass (-0.28 kg [95% CI, -1.41 to 0.85]). The between-group difference in weight was -0.7 kg (95% CI, -1.3 to -0.1). CONCLUSIONS: In a broad range of patients with CKD, empagliflozin resulted in a sustained reduction in a bioimpedance-derived estimate of fluid overload, with no statistically significant effect on fat mass. TRIAL REGISTRATION: Clinicaltrials.gov: NCT03594110 ; EuDRACT: 2017-002971-24 ( https://eudract.ema.europa.eu/ ).

Impact of clinicians' behavior, an educational intervention with mandated blood pressure and the hypotension prediction index software on intraoperative hypotension: a mixed methods study.

PURPOSE: Intraoperative hypotension (IOH) is associated with adverse outcomes. We therefore explored beliefs regarding IOH and barriers to its treatment. Secondarily, we assessed if an educational intervention and mandated mean arterial pressure (MAP), or the implementation of the Hypotension Prediction Index-software (HPI) were associated with a reduction in IOH. METHODS: Structured interviews (n = 27) and questionnaires (n = 84) were conducted to explore clinicians' beliefs and barriers to IOH treatment, in addition to usefulness of HPI questionnaires (n = 14). 150 elective major surgical patients who required invasive blood pressure monitoring were included in three cohorts to assess incidence and time-weighted average (TWA) of hypotension (MAP < 65 mmHg). Cohort one received standard care (baseline), the clinicians of cohort two had a training on hypotension and a mandated MAP > 65 mmHg, and patients of the third cohort received protocolized care using the HPI. RESULTS: Clinicians felt challenged to manage IOH in some patients, yet they reported sufficient knowledge and skills. HPI-software was considered useful and beneficial. No difference was found in incidence of IOH between cohorts. TWA was comparable between baseline and education cohort (0.15 mmHg [0.05-0.41] vs. 0.11 mmHg [0.02-0.37]), but was significantly lower in the HPI cohort (0.04 mmHg [0.00 to 0.11], p < 0.05 compared to both). CONCLUSIONS: Clinicians believed they had sufficient knowledge and skills, which could explain why no difference was found after the educational intervention. In the HPI cohort, IOH was significantly reduced compared to baseline, therefore HPI-software may help prevent IOH. TRIAL REGISTRATION: ISRCTN 17,085,700 on May 9th, 2019.