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/ ).

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.

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.

Impact of liposomal hesperetin in broilers: prospects for improving performance, antioxidant potential, immunity, and resistance against Listeria monocytogenes.

Liposomal encapsulated phytogenics, such as liposomal hesperetin, are considered novel substitutes for antibiotics in the broiler industry owing to their improved nutritional and therapeutic properties. Therefore, our key goal was to investigate liposomal hesperetin impact on broiler growth performance, health, antioxidant status, tight junction proteins (TJP), and resistance against Listeria monocytogenes. Four broiler groups were fed 0, 150, 250, or 400 mg/kg of liposomal hesperetin-supplemented diets and experimentally infected with L. monocytogenes strain. Herein, liposomal hesperetin, especially at higher concentrations, augmented broilers FCR with upregulation of genes encoding TJP (occludin, JAM-2, MUC-2), and antioxidant attributes (GPX-1, SOD-1, CAT, HO-1, NQO1, COX2), which reflect enhancing health and welfare of broilers. Muscle antioxidant biomarkers were enhanced; meanwhile, muscle MDA, ROS, and H2O2 levels were reduced in response to 400 mg/kg of liposomal hesperetin. Liposomal hesperetin fortification reduced L. monocytogenes loads and expression levels of its virulence-related genes (flaA, hlyA, and ami). Remarkably, histopathological alterations in intestinal and brain tissues of L. monocytogenes-infected broilers were restored post-inclusion at higher levels of liposomal hesperetin, which reflects increase of the birds' resistance to L. monocytogenes infection. Transcription levels of genes encoding cytokines/chemokines (MyD88, AVBD6, CCL20, IL-1ß, IL-18), and autophagy (Bcl-2, LC3, AMPK, AKT, CHOP, Bip, p62, XBP1) were ameliorated following dietary liposomal hesperetin fortification, which suggests enhancement of the birds' immunity and health. Collectively, our research recommends liposomal hesperetin application in broiler diets owing to its promoting impact on growth performance, antioxidant status, immunity, health, and welfare besides its antibacterial, and antivirulence characteristics to fight against L. monocytogenes.

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.

Alleviating effects of Gracilaria verrucosa supplement on non-specific immunity, antioxidant capacity and immune-related genes of pacific white shrimp (Litopenaeus vannamei) provoked with white spot syndrome virus.

Our work evaluated the possible underlying roles of dietary dried seaweed (Gracilaria verrucosa; GV) on the inherent immune response, antioxidant capacity, immune-related gene expression, and protection of whiteleg shrimp (Litopenaeus vannamei) contra white spot syndrome virus (WSSV). Three hundred and sixty healthy L. vannamei (15.26 g ± 1.29 g) were graded into four supplemental groups ( Triplicate/group) and fed with diets including 0 (control), 2, 4, and 8 g GV (kg diet) -1 for 21 days. Following the feeding period, each group of shrimp received an intramuscular WSSV injection (1.4 × 106 copies/ml). Hemolymph and gills samples were collected before and after the challenge with WSSV. Notably, the administration of dietary GV significantly enhanced the innate immune parameters of pacific white shrimp including total hemocyte count (THC), phagocytosis, phenoloxidase activity, reactive oxygen species (ROS) production, and lysozyme activity before and after challenge with WSSV. Additionally, dietary supplementation of 4, and 8 g of GV (kg diet)-1 remarkably elevated ACP, AKP, SOD, GPx, and catalase activities along with a decrease in the MDA level in gills of shrimp before and post-WSSV challenge. In response to the GV supplement, significant upregulation of expression of ALF1, CRU1, PEN4, and CTL with downregulation of TRAF6, STAT, TLR1, and NOS genes was recorded in the gills tissue before and post-challenge with WSSV, especially at a dose of 8.0 GV g kg - 1. Dietary inoculated shrimp with GV revealed notably higher survival percentages after being challenged with WSSV. Conclusively, these data indicate that Gracilaria verrucosa can be recommended as a valuable supplemented seaweed to stimulate the innate immunity and enhance the health of Litopenaeus vannamei against viral infection.

Immune protective, stress indicators, antioxidant, histopathological status, and heat shock protein gene expression impacts of dietary Bacillus spp. against heat shock in Nile tilapia, Oreochromis niloticus.

This research evaluated the efficacy of mixed Bacillus strains probiotic supplements in mitigating acute thermal-induced stress in Nile tilapia (Oreochromis niloticus). Three experimental fish groups involved 135 Nile tilapia (49 ± 2 g); one control (no added probiotics), 0.5, and 1% of selected Bacillus strains (B. subtilis, B. licheniformis, and B. pumilus) for 58 days. After the feeding period, growth parameters, immunological parameters, stress biochemical markers, and antioxidant parameters in addition to genes related to stress and histopathological changes in fish, were assessed; subsequently subjected to heat shock at 36 ± 0.5 ◦C for 2 h. Before the heat challenge, our results exhibited a marked increase in the growth efficacy (P < 0.05), lower marked serum levels of triglycerides and cholesterol, and tissue malondialdehyde (MDA) levels along with significantly increased superoxide dismutase (SOD) and catalase (CAT) enzymes activity in fish-fed Bacillus probiotic at 0.5% concerning the control group (P < 0.05). There were no significant changes in the serum levels of glucose, cortisol, lactate, phagocytic activity, respiratory burst (ROS), total immunoglobulin Ig, alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), total protein, albumin, globulin, uric acid, urea, creatinine, as well as HSP70, GST, and GPx mRNA expression in most of the probiotic groups compared to the control group (P > 0.05). When Nile tilapia was exposed to heat stress, supplementation with Bacillus probiotic in the diet significantly decreased most of the indices related to serum biochemical (ALT (P < 0.01; P < 0.001), AST (P < 0.01), LDH (P < 0.01), urea (P < 0.05), and creatinine (P < 0.01)), triglycerides (P < 0.001; (P < 0.01)), cholesterol (P < 0.01; (P < 0.05)), glucose (P < 0.001), and cortisol (P < 0.01; (P < 0.05)), with tissue oxidative stress MDA levels (P < 0.05), and HSP70 mRNA expression (P < 0.01; P < 0.001), aligned with the stressed control group. In addition, a notable upsurge in the total protein, albumin, globulin, phagocytic and ROS activities, and total Ig, as well as the enzymatic antioxidant ability (SOD, CAT) (P < 0.01), with GST and GPx mRNA expression (P < 0.05; P < 0.01), were shown in fish-fed Bacillus spp. post-exposure compared with the stressed control group. Besides, no histopathological alterations were revealed in the spleen and brain of fish pre- and post-heat exposure. According to our findings, diet supplementation of Bacillus species has the potential to combat the suppressive effects of heat shock in Nile tilapia.

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.

Enhancing impact of dietary nano formulated quercetin on laying performance: egg quality, oxidative stability of stored eggs, intestinal immune and antioxidants related genes expression.

BACKGROUND: Nutritional interventions with natural antioxidants can provide a pragmatic solution for modifying hens' performance and maintaining oxidative stability of eggs during storage. Quercetin is the most abundant flavonoids with potent antioxidant and immune stimulant activities. The concept of incorporating of quercetin, as potent antioxidant and immunostimulant, into effective nano-carriers (QNPs) has promoted their bioavailability and stability thus, their effectiveness for the first time were assessed on laying hens' performance and immunity, eggs quality during storage. Four hundred 12-weeks-old Hy-line brown laying hens were distributed to four experimental groups: control group fed basal diets, and other 3 groups fed basal diets fortified with 100, 200 and 300 mg/kg QNPs for 60 weeks. RESULTS: Laying performance and quality of laid eggs were improved as expressed by elevated laying rate, egg mass %, eggs weight and yolk weight in QNPs200 and 300. Fortification of QNPs300 remarkably decreased layers serum total cholesterol concurrently with decreased egg yolk saturated fatty acids and cholesterol while increased polyunsaturated fatty acids. Over- 45 days storage period, QNPs enhanced phospholipids, total phenolics and flavonoids, total antioxidant activity (T-AOC) simultaneous with decreased MDA content in eggs. Furthermore, enhanced immune response was detected in both in serum and intestine of QNPs fed hens as reflected by higher lysozymes activity, IgM, IgG and phagocytic index and demotion of NO together with AvBD 6-12, IL-10, IgM and ATg 5-7-12 upregulation and downregulation of IL-1ß and TNF-α especially at QNPs200 and 300. Intestinal redox balance was modified via decreasing H2O2 and MDA simultaneous with upregulation of catalase, SOD, GSH-Px, HO-1 and NQO1 in groups fed higher doses of QNPs. CONCLUSIONS: QNPs supplementation provides a new nutritional strategy towards increasing hen performance, fortification of eggs with natural antioxidants that prevents egg quality deterioration during storage.

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.

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.

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.

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.

Home dialysis: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference.

Home dialysis modalities (home hemodialysis [HD] and peritoneal dialysis [PD]) are associated with greater patient autonomy and treatment satisfaction compared with in-center modalities, yet the level of home-dialysis use worldwide is low. Reasons for limited utilization are context-dependent, informed by local resources, dialysis costs, access to healthcare, health system policies, provider bias or preferences, cultural beliefs, individual lifestyle concerns, potential care-partner time, and financial burdens. In May 2021, KDIGO (Kidney Disease: Improving Global Outcomes) convened a controversies conference on home dialysis, focusing on how modality choice and distribution are determined and strategies to expand home-dialysis use. Participants recognized that expanding use of home dialysis within a given health system requires alignment of policy, fiscal resources, organizational structure, provider incentives, and accountability. Clinical outcomes across all dialysis modalities are largely similar, but for specific clinical measures, one modality may have advantages over another. Therefore, choice among available modalities is preference-sensitive, with consideration of quality of life, life goals, clinical characteristics, family or care-partner support, and living environment. Ideally, individuals, their care-partners, and their healthcare teams will employ shared decision-making in assessing initial and subsequent kidney failure treatment options. To meet this goal, iterative, high-quality education and support for healthcare professionals, patients, and care-partners are priorities. Everyone who faces dialysis should have access to home therapy. Facilitating universal access to home dialysis and expanding utilization requires alignment of policy considerations and resources at the dialysis-center level, with clear leadership from informed and motivated clinical teams.

Bio-impedance spectroscopy added to a fluid management protocol does not improve preservation of residual kidney function in incident hemodialysis patients in a randomized controlled trial.

Avoiding excessive dialysis-associated volume depletion may help preserve residual kidney function (RKF). To establish whether knowledge of the estimated normally hydrated weight from bioimpedance measurements (BI-NHW) when setting the post-hemodialysis target weight (TW) might mitigate rate of loss of RKF, we undertook an open label, randomized controlled trial in incident patients receiving HD, with clinicians and patients blinded to bioimpedance readings in controls. A total of 439 patients with over 500 ml urine/day or residual GFR exceeding 3 ml/min/1.73m2 were recruited from 34 United Kingdom centers and randomized 1:1, stratified by center. Fluid assessments were made for up to 24 months using a standardized proforma in both groups, supplemented by availability of BI-NHW in the intervention group. Primary outcome was time to anuria, analyzed using competing-risk survival models adjusted for baseline characteristics, by intention to treat. Secondary outcomes included rate of RKF decline (mean urea and creatinine clearance), blood pressure and patient-reported outcomes. There were no group differences in cause-specific hazard rates of anuria (0.751; 95% confidence interval (0.459, 1.229)) or sub-distribution hazard rates (0.742 (0.453, 1.215)). RKF decline was markedly slower than anticipated, pooled linear rates in year 1: -0.178 (-0.196, -0.159)), year 2: -0.061 (-0.086, -0.036)) ml/min/1.73m2/month. Blood pressure and patient-reported outcomes did not differ by group. The mean difference agreement between TW and BI-NHW was similar for both groups, Bioimpedance: -0.04 kg; Control: -0.25 kg. Thus, use of a standardized clinical protocol for fluid assessment when setting TW is associated with excellent preservation of RKF. Hence, bioimpedance measurements are not necessary to achieve this.

Interleukin-6 signaling drives fibrosis in unresolved inflammation.

Fibrosis in response to tissue damage or persistent inflammation is a pathological hallmark of many chronic degenerative diseases. By using a model of acute peritoneal inflammation, we have examined how repeated inflammatory activation promotes fibrotic tissue injury. In this context, fibrosis was strictly dependent on interleukin-6 (IL-6). Repeat inflammation induced IL-6-mediated T helper 1 (Th1) cell effector commitment and the emergence of STAT1 (signal transducer and activator of transcription-1) activity within the peritoneal membrane. Fibrosis was not observed in mice lacking interferon-γ (IFN-γ), STAT1, or RAG-1. Here, IFN-γ and STAT1 signaling disrupted the turnover of extracellular matrix by metalloproteases. Whereas IL-6-deficient mice resisted fibrosis, transfer of polarized Th1 cells or inhibition of MMP activity reversed this outcome. Thus, IL-6 causes compromised tissue repair by shifting acute inflammation into a more chronic profibrotic state through induction of Th1 cell responses as a consequence of recurrent inflammation.

Immunostimulatory effect of mannan-oligosaccharides supplementation diet in milkfish (Chanos chanos).

The current study was designed to examine the impacts of dietary mannan-oligosaccharides (MOS) on growth, hemato-biochemical changes, digestive-antioxidant enzyme activity, immune response, and disease resistance of milkfish (Chanos chanos) fed diets contained MOS i.e. 1g, 2g, and 3g MOS. The growth parameters were significantly influence in milkfish fed all MOS diets, whereas the feed conversion ratio (FCR) and protein efficiency ratio (PER) were significantly influence with 2g or 3g MOS diets. The total protein (TP), globulin (GB), and glucose (GLU) levels, amylase, protease, liver enzymes were found significantly high in fish fed 2g or 3g MOS diets; but, lipase, trypsin, and alkaline phosphatase (ALP) enzymes were increased significantly at 3g MOS diet. All MOS inclusion levels were significantly increased total and Lactobacillus intestinal microflora population. The oxidative enzymes activity as superoxide desmutase (SOD) and catalyze (CAT) were progressively increased with all MOS supplementation diet, but the glutathione peroxidase (GPx) and lactate dehydrogenase (LDH) content were found significantly high in fish fed 2g or 3g MOS diets. Similarly, the reduced glutathione (GSH) and glutathione reductase (GR) contents were observed significantly high level in fish fed 3g MOS diet. The phagocytic (PC) and lysozyme (LYZ) activities were found gradually increase in fish fed increasing level of MOS diets, while the respiratory burst (RB) and malondialdehyde (MDA) activities were seen significant in fish fed 2g and 3g MOS diets. The current research work confirmed that C. chanos fed diets contained 3g kg-1 MOS recorded better growth performance, digestive-antioxidant, immune response, and disease resistance.

Estimating the association between systemic Interleukin-6 and mortality in the dialysis population. Re-analysis of the global fluid study, systematic review and meta-analysis.

BACKGROUND: Systemic inflammation, measured as circulating Interleukin-6 (IL-6) levels, is associated with cardiovascular and all-cause mortality in chronic kidney disease. However, this has not been convincingly demonstrated in a systematic review or a meta-analysis in the dialysis population. We provide such evidence, including a re-analysis of the GLOBAL Fluid Study. METHODS: Mortality in the GLOBAL fluid study was re-analysed using Cox proportional hazards regression with IL-6 levels as a covariate using a continuous non-logarithmic scale. Literature searches of the association of IL-6 levels with mortality were conducted on MEDLINE, EMBASE, PyschINFO and CENTRAL. All studies were assessed for risk of bias using the QUIPS tool. To calculate a pooled effect size, studies were grouped by use of IL-6 scale and included in the meta-analysis if IL-6 was analysed as a continuous linear covariate, either per unit or per 10 pg/ml, in both unadjusted or adjusted for other patient characteristics (e.g. age, comorbidity) models. Funnel plot was used to identify potential publication bias. RESULTS: Of 1886 citations identified from the electronic search, 60 were included in the qualitative analyses, and 12 had sufficient information to proceed to meta-analysis after full paper screening. Random effects meta-analysis of 11 articles yielded a pooled hazard ratio (HR) per pg/ml of 1.03, (95% CI 1.01, 1.03), [Formula: see text]= 81%. When the analysis was confined to seven articles reporting a non-adjusted HR the result was similar: 1.03, per pg/ml (95% CI: 1.03, 1.06), [Formula: see text]=92%. Most of the heterogeneity could be attributed to three of the included studies. Publication bias could not be determined due to the limited number of studies. CONCLUSION: This systematic review confirms the adverse association between systemic IL-6 levels and survival in people treated with dialysis. The heterogeneity that we observed may reflect differences in study case mix. SYSTEMATIC REVIEW REGISTRATION: PROSPERO - CRD42020214198.

Alpha-lipoic acid suppresses gibberellic acid nephrotoxicity in Nile tilapia (Oreochromis niloticus) via modulating oxidative stress, inflammation, cytokine production, and apoptosis.

Globally, gibberellic acid (GA) is one of the extensively used plant growth regulators in agriculture. Yet, there is limited information about their toxicity to fish. Recently, alpha lipoic acid (ALA) has drawn much interest due to its antioxidant properties. This study was planned to determine whether ALA might protect Nile tilapia's kidneys from the toxic effects of GA and the probable underlying mechanisms. Thus, 240 Oreochromis niloticus fish (average initial weight 30.67 ± 0.57) were allocated into four groups received a basal diet or a basal diet supplemented with 600 mg/kg ALA or a basal diet but exposed to a GA (150 mg/L), or ALA-fortified diet and concurrently exposed to GA as previously described. After 60 days, hematological, oxidative stress, lipid peroxidation, stress indices, selected kidney toxic byproducts, histological investigations, and associated gene expression were assessed. Anemia, leukopenia, hypoproteinemia, and elevated kidney function indicators were noticed in the GA-treated group. Additionally, there were detectable cortisol, glucose, 8-OHdG, and MDA increases. However, there was a considerable drop in Cat, Sod, Gpx, GSH, and AChE levels. Structural damage to the kidneys was also identified. In the kidney of fish treated with GA, pro-inflammatory cytokines (tnfα, il-1ß), stress, and apoptotic genes (hsp70, pcna, caspase-3, and p53) genes were markedly up-regulated, while anti-oxidative (cat, sod) gene expression was downregulated. Conversely, adding ALA to the diet abolished the GA-induced changes in most of the markers mentioned above. Conclusively, ALA protects against GA-induced hematotoxicity, oxidative damage, and nephrotoxic effects in Nile tilapia fish.

Using Azadirachta indica protein hydrolysate as a plant protein in Nile tilapia (Oreochromis niloticus) diet: Effects on the growth, economic efficiency, antioxidant-immune response and resistance to Streptococcus agalactiae.

A feeding trial for 90 days was conducted on Nile tilapia (Oreochromis niloticus) (average weight: 25.50 ± 0.05 g) to evaluate the effect of dietary inclusion of Azadirachta indica seed protein hydrolysate (AIPH). The evaluation included the impact on the growth metrics, economic efficiency, antioxidant potential, hemato-biochemical indices, immune response, and histological architectures. A total of 250 fish were randomly distributed in five treatments (n = 50) and received diets included with five levels of AIPH (%): 0 (control diet, AIPH0), 2 (AIPH2), 4 (AIPH4), 6 (AIPH6) or 8 (AIPH8), where AIPH partially replace fish meal by 0, 8.7%, 17.4%, 26.1%, and 34.8%, respectively. After the feeding trial, a pathogenic bacterium (Streptococcus agalactiae, 1.5 × 108 CFU/mL) was intraperitoneally injected into the fish and the survival rate was recorded. The results elucidated that AIPH-included diets significantly (p < 0.05) enhanced the growth indices (final body weight, total feed intake, total body weight gain, and specific growth rate) and intestinal morpho-metrics (villous width, length, muscular coat thickness, and goblet cells count) in comparison to the control diet, with the AIPH8 diet recording the highest values. Dietary AIPH inclusion significantly improved (p < 0.05) the economic efficacy indicated by reduced feed cost/kg gain and increased performance index. The fish fed on the AIPH diets had noticeably significantly higher (p < 0.05) protein profile variables (total proteins and globulin) and antioxidant capabilities (superoxide dismutase and total antioxidant capacity) than the AIPH0 group. The dietary inclusion of AIPH significantly (p < 0.05) boosted the haematological parameters (haemoglobin, packed cell volume %, and counts of red blood cells and white blood cells) and immune indices (serum bactericidal activity %, antiprotease activity, and immunoglobulin M level) in a concentration-dependent manner. The blood glucose and malondialdehyde levels were significantly (p < 0.05) lowered by dietary AIPH (2%-8%). The albumin level and hepatorenal functioning parameters (aspartate aminotransferase, alanine aminotransferase, and creatinine) were not significantly (p > 0.05) altered by AIPH diets. Additionally, AIPH diets did not adversely alter the histology of the hepatic, renal or splenic tissues with moderately activated melano-macrophage centres. The mortality rate among S. agalactiae-infected fish declined as dietary AIPH levels rose, where the highest survival rate (86.67%) was found in the AIPH8 group (p < 0.05). Based on the broken line regression model, our study suggests using dietary AIPH at the optimal level of 6%. Overall, dietary AIPH inclusion enhanced the growth rate, economic efficiency, health status, and resistance of Nile tilapia to the S. agalactiae challenge. These beneficial impacts can help the aquaculture sector to be more sustainable.