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.

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.

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.

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.

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.

Potential role of dietary Boswellia serrata resin against mancozeb fungicide-induced immune-antioxidant suppression, histopathological alterations, and genotoxicity in Nile tilapia, Oreochromis niloticus.

This study was established to look into the toxicological consequences of chronic exposure to a fungicide (mancozeb; MAZ) on the immune-antioxidant response, gene expressions, hepato-renal functions, and histological pictures of Nile tilapia (Oreochromis niloticus). Additionally, the effectiveness of Indian frankincense resin extract (IFRE) to mitigate their toxicity was taken into account. Fish (n =240; average body weight: 22.45 ± 2.21 g) were randomized into four groups for eight weeks in six replicates (control, IFRE, MAZ, and IFRE + MAZ), where ten fish were kept per replicate. The control and IFRE groups received basal diets that included 0.0 and 5 g/kg of IFRE without MAZ exposure. The MAZ and IFRE+MAZ groups received the same diets and were exposed to 1/10 of the 96-h of LC50 of MAZ (1.15 mg/L). The outcomes displayed that MAZ exposure resulted in a lower survival rate (56.67 %) and significantly decreased levels of immune-antioxidant variables (antiprotease, complement3, phagocytic activity, lysozyme, glutathione peroxidase, superoxide dismutase, and total antioxidant capacity) compared to the control group. The MAZ-exposed fish showed the greatest levels of lipid peroxide (malondialdehyde), alkaline phosphatase, alanine amino-transferase, and stress indicators (cortisol and glucose). Additionally, histopathological alterations, including vacuolation, severe necrosis, degeneration, and mononuclear cell infiltrations in the hepatic, renal, and splenic tissues resulted, besides a reduction in the melanomacrophage center in the spleen. A down-regulation of immune-antioxidant-associated genes [toll-like receptors (TLR-2 and TLR-7), nuclear factor kappa beta (NF-κß), transforming growth factor-beta (TGF-ß), phosphoinositide-3-kinase regulatory subunit 3 gamma b (pik3r3b), interleukins (IL-1ß and IL-8), glutathione synthetase (GSS), glutathione peroxidase (GPx), and superoxide dismutase (SOD)] were the consequences of the MAZ exposure. Remarkably, the dietary inclusion of IFRE in MAZ-exposed fish augmented the immune-antioxidant parameters, including their associated genes, decreased stress response, and increased survival rate (85 %) compared with the MAZ-exposed fish. Moreover, dietary IFRE improved hepato-renal function indices by preserving the histological architecture of the hepatic, renal, and splenic tissues. The insights of this study advocate the use of an IFRE-dietary addition to protect Nile tilapia from MAZ toxicity, which provides perspectives for future implementations in enhancing fish health for sustainable aquaculture.

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.

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.

Dietary Frankincense (Boswellia serrata) Oil Modulates the Growth, Intestinal Morphology, the Fatty Acid Composition of Breast Muscle, Immune Status, and Immunoexpression of CD3 and CD20 in Broiler Chickens.

This investigation explored the impact of dietary frankincense resin oil (FO) on growth performance parameters, intestinal histomorphology, fatty acid composition of the breast muscle, and the immune status of broilers. We allotted 400, three-day-old, male chicks (Ross 308 broiler) into four treatment groups (ten replicates/group; ten chicks/replicate). They were fed a basal diet with different concentrations of FO (0, 200, 400, and 600 mg kg-1). FO supplementation increased the overall body weight (BW) and body weight gain (BWG) by different amounts, linearly improving the feed conversion ratio with the in-supplementation level. Total feed intake (TFI) was not affected. Growth hormones and total serum protein levels also linearly increased with the FO level, while albumin was elevated in the FO600 group. Moreover, total globulins increased linearly in FO400 and FO600 treatment groups. Thyroxin hormone (T3 and T4) levels increased in all FO treatment groups without affecting glucose and leptin serum values. Different concentrations of FO supplementation in the diet increased the activities of Complement 3, lysozyme, and interleukin 10 levels in the serum. Dietary FO in broilers increased the total percentage of n-3 and n-6 fatty acids. It also increased the ratio of n-3 to n-6 linearly and quadratically. Additionally, FO supplementation led to the upregulation of immune clusters of differentiation 3 and 20 (CD3 and CD20) in the spleen, along with improving most of the morphometric measures of the small intestine. In conclusion, FO up to 600 mg kg-1 as a feed additive in broiler chicken production is valuable for promoting their growth, intestinal histomorphology, and immune status along with enriching breast muscle with polyunsaturated fatty acids (PUFA).

Cost of Cancer in Adolescents and Young Adults in the United States: Results of the 2021 Report by Deloitte Access Economics, Commissioned by Teen Cancer America.

PURPOSE: The purpose of this report, commissioned by Teen Cancer America and performed by Deloitte Access Economics in 2021, was to estimate the total costs incurred by adolescent and young adults (AYAs) after cancer diagnosis in the United States (US) over their life course. METHODS: The incidence of cancer in 2019 among AYAs age 15-39 years was estimated from the US Cancer Statistics Public Use Database, and relative survival was projected from the Surveillance, Epidemiology, and End Results Program. Cost domains included health system, productivity, and well-being costs. Components were estimated with published literature and pooled data from the Medical Expenditure Panel Survey from 2008 to 2012 and inflated to 2019 dollars. RESULTS: The economic and human costs of cancer in AYAs are substantial-$23.5 billion overall, corresponding to $259,324 per person over the lifetime. The majority of costs are borne by AYA cancer survivors themselves in the form of lost productivity, loss of well-being, and loss of life. CONCLUSION: These findings underscore the need to address the burden of cancer in AYAs through targeted programs for AYAs, such as financial navigation and health insurance literacy interventions, as well as local and national policy initiatives to address access to and enhanced coverage for clinical trials participation, fertility services, and survivorship care.

Immune-antioxidant trait, growth, splenic cytokines expression, apoptosis, and histopathological alterations of Oreochromis niloticus exposed to sub-lethal copper toxicity and fed thyme and/or basil essential oils enriched diets.

Two experiments were conducted in this study, using 250 Oreochromis niloticus (O. niloticus) (average weight 30.28 ± 0.27 g). The first experiment was conducted to investigate the 96-h lethal concentration 50 (LC50) of copper chloride (CuCl2) using the probit analysis, seventy fish was divided into seven different concentration of CuCl2 (0, 22, 23, 24, 25, 26, and 27 mg/L), the accurate Cu concentrations were (1.23, 5.36, 6.02, 6.98, 7.05, 7.93, 8.12 mg/L Cu). The second experiment was conducted for investigating the effect of dietary supplementation with thyme (Thymus vulgaris, T. vulgaris) and sweet basil (Ocimum basilicum, O. basilicum) essential oils (TEO and BEO respectively) against sub-lethal Cu exposure (1/10 96-h LC50 of CuCl2). About 180 fish was divided into six groups in triplicate (10 fish/replicate, 30 fish/group). Group 1 (C) was kept as a control group with no Cu exposure and was fed the control basal diet. Group 2 (C-Cu) was fed the control basal diet and simultaneously exposed to 1/10 of the 96 h LC50 of CuCl2 (2.574 mg/L) as a sub-lethal concentration of Cu, where the realistic Cu concentration was 3.976 mg/L. Group 3 (TEO) and group 4 (BEO) were fed the diets fortified with 1%TEO and BEO, respectively without exposure to Cu. Group 5 (TEO-Cu) and group 6 (BEO-Cu) were fed the diets fortified with 1%TEO and 1%BEO, respectively, and simultaneously exposed to 1/10 of the 96 h LC50 of CuCl2 (2.574 mg/L). The growth and behavioral performance, immunological response and its related gene expression, antioxidant status, stress biomarker indicators, apoptosis biomarkers, and histopathological alteration were investigated. The results of the first experiment showed that the 96-h LC50 of CuCl2 in O. niloticus was 25.740 mg/L with lower and upper confidence limits of 25.152 and 26.356 mg/L, respectively. The results of the second experiment showed that sub-lethal Cu exposure induced growth retardation (lowered final body weight, total weight gain, and specific growth rate %), behavioral abnormalities (slower swimming activity and feeding performance), immunosuppression (lowered nitric oxide, complement-3, lysozyme, total proteins, albumin, and globulin), and lowering the hepatic antioxidant functions (higher MDA, and lower SOD, CAT, and GPx) in the exposed fish. Furthermore, alteration in the immune-related genes expression (down-regulation of IL-10 and TGF-ß and up-regulation of IL-1ß, IL-6, IL-8, and TRL-4), hepato-renal dysfunction (elevated ALT, AST, urea, and creatinine), and high levels of serum stress indicators (cortisol and glucose) were markedly evident. sub-lethal Cu toxicity induced significant up-regulation of apoptosis biomarkers involving, nuclear factor-κß (NF-κß), Bcl-2 Associated X-protein (BAX), meanwhile, the expression of B-cell lymphoma 2 (BCL2) and Proliferating cell nuclear antigen (PCNA) was remarkably down-regulated. In addition, apoptosis was also evident by histopathological investigation of branchial, hepatic, and renal sections. TEO and/or BEO dietary supplementation mitigate the destructive impacts of sub-lethal Cu exposure in O. niloticus, depending on the results of our study, it could be concluded that TEO and BEO with a 1% dietary level could be a promising antioxidant, immunostimulant, anti-stress factors, and anti-apoptosis mediators against heavy metal contaminants (Cu) in O. niloticus, providing a solution to the problem of aquatic bodies pollution, consequently aiding in the development of aquaculture industry.

Impact of standardizing care for agitation in dementia using an integrated care pathway on an inpatient geriatric psychiatry unit.

OBJECTIVES: This study examined the effectiveness of an integrated care pathway (ICP), including a medication algorithm, to treat agitation associated with dementia. DESIGN: Analyses of data (both prospective and retrospective) collected during routine clinical care. SETTING: Geriatric Psychiatry Inpatient Unit. PARTICIPANTS: Patients with agitation associated with dementia (n = 28) who were treated as part of the implementation of the ICP and those who received treatment-as-usual (TAU) (n = 28) on the same inpatient unit before the implementation of the ICP. Two control groups of patients without dementia treated on the same unit contemporaneously to the TAU (n = 17) and ICP groups (n = 36) were included to account for any secular trends. INTERVENTION: ICP. MEASUREMENTS: Cohen Mansfield Agitation Inventory (CMAI), Neuropsychiatric Inventory Questionnaire (NPIQ), and assessment of motor symptoms were completed during the ICP implementation. Chart review was used to obtain length of inpatient stay and rates of psychotropic polypharmacy. RESULTS: Patients in the ICP group experienced a reduction in their scores on the CMAI and NPIQ and no changes in motor symptoms. Compared to the TAU group, the ICP group had a higher chance of an earlier discharge from hospital, a lower rate of psychotropic polypharmacy, and a lower chance of having a fall during hospital stay. In contrast, these outcomes did not differ between the two control groups. CONCLUSIONS: These preliminary results suggest that an ICP can be used effectively to treat agitation associated with dementia in inpatients. A larger randomized study is needed to confirm these results.

International Anemia Prevalence and Management in Peritoneal Dialysis Patients.

Background:The optimal treatment for managing anemia in peritoneal dialysis (PD) patients and best clinical practices are not completely understood. We sought to characterize international variations in anemia measures and management among PD patients.Methods:The Peritoneal Dialysis Outcomes and Practice Patterns Study (PDOPPS) enrolled adult PD patients from 6 countries from 2014 to 2017. Hemoglobin (Hb), ferritin levels, and transferrin saturation (TSAT), as well as erythropoiesis stimulating agents (ESAs) and iron use were compared cross-sectionally at study enrollment in Australia and New Zealand (A/NZ), Canada, Japan, the United Kingdom (UK), and the United States (US).Results:Among 3,603 PD patients from 193 facilities, mean Hb ranged from 11.0 - 11.3 g/dL across countries. The majority of patients (range 53% - 59%) had Hb 10 - 11.9 g/dL, with 4% - 12% patients ≥ 13 g/dL and 16% - 23% < 10 g/dL. Use of ESAs was higher in Japan (94% of patients) than elsewhere (66% - 79% of patients). In the US, 63% of patients had a ferritin level > 500 ng/mL, compared with 5% - 38% in other countries. In the US and Japan, 87% - 89% of PD patients had TSAT ≥ 20%, compared with 73% - 76% in other countries. Intravenous (IV) iron use within 4 months of enrollment was higher in the US (55% of patients) than elsewhere (6% - 17% patients).Conclusions:In this largest international observational study of anemia and anemia management in patients receiving PD, comparable Hb levels across countries were observed but with notable differences in ESA and iron use. Peritoneal dialysis patients in the US have higher ferritin levels and higher IV iron use than other countries.

Ventilatory inefficiency adversely affects outcomes and longer-term survival after planned colorectal cancer surgery.

BACKGROUND: Impaired cardiorespiratory reserve is an accepted risk factor for patients having major surgery. Ventilatory inefficiency, defined by an elevated ratio of minute ventilation to carbon dioxide excretion (VE/VCO2), and measured by cardiopulmonary exercise testing (CPET), is a pathophysiological characteristic of patients with cardiorespiratory disease. We set out to evaluate the prevalence of ventilatory inefficiency in a colorectal cancer surgical population, and its influence on surgical outcomes and long-term cancer survival. METHODS: In this retrospective study of 1375 patients who had undergone preoperative CPET followed by colorectal cancer surgery, we used receiver operating characteristic curve analysis to identify an optimal value of VE/VCO2 associated with 90-day mortality. Binary logistic regression was used to evaluate whether this degree of ventilatory inefficiency was independently associated with decreased survival, both after surgery and in the longer term. RESULTS: We identified an optimal VE/VCO2 >39 cut-off for predicting 90-day mortality; 245 patients (17.8%) had VE/VCO2 >39, of which 138 (10% of total cohort) had no known cardiorespiratory risk factors. Ventilatory inefficiency was independently associated with death at 90-days (8.2% mortality vs 1.9%; adjusted odds ratio [OR], 4.04; 95% confidence interval [CI], 2.09-7.84), with death after unplanned critical care admission (OR=4.45; 95% CI, 1.37-14.46) and with decreased survival at 2 yr (OR=2.21; 95%, 1.49-3.28) and 5 yr (OR=2.87; 95% CI, 1.54-5.37) after surgery. CONCLUSIONS: A significant proportion of patients having colorectal cancer surgery have ventilatory inefficiency observed on CPET, the majority of whom have no history of cardiorespiratory risk factors. This group of patients has significantly decreased survival both after surgery and in the long-term, irrespective of cancer stage. Survival might be improved by formal medical evaluation and intervention in this group.

Rationale and design of BISTRO: a randomized controlled trial to determine whether bioimpedance spectroscopy-guided fluid management maintains residual kidney function in incident haemodialysis patients.

BACKGROUND: Preserved residual kidney function (RKF) and normal fluid status are associated with better patient outcomes in incident haemodialysis patients. The objective of this trial is to determine whether using bioimpedance technology in prescribing the optimal post-dialysis weight can reduce the rate of decline of RKF and potentially improve patient outcomes. METHODS/DESIGN: 516 pateints commencing haemodialysis, aged >18 with RKF of > 3 ml/min/1.73 m2 or a urine volume >500 ml per day or per the shorter inter-dialytic period will be consented and enrolled into a pragmatic, open-label, randomized controlled trial. The intervention is incorporation of bioimpedance spectroscopy (BI) determination of normally hydrated weight to set a post-dialysis target weight that limits volume depletion, compared to current standard practice. Clinicians and participants will be blinded to BI measures in the control group and a standardized record capturing management of fluid status will be used in all participants. Primary outcome is preservation of residual kidney function assessed as time to anuria (≤100 ml/day or ≤200 ml urine volume in the short inter-dialytic period). A sample size of 516 was based upon a cumulative incidence of 30% anuria in the control group and 20% in the treatment group and 11% competing risks (death, transplantation) over 10 months, with up to 2 years follow-up. Secondary outcomes include rate of decline in small solute clearance, significant adverse events, hospitalization, loss of vascular access, cardiovascular events and interventions, dialysis efficacy and safety, dialysis-related symptoms and quality of life. Economic evaluation will be carried out to determine the cost-effectiveness of the intervention. Analyses will be adjusted for patient characteristics and dialysis unit practice patterns relevant to fluid management. DISCUSSION: This trial will establish the added value of undertaking BI measures to support clinical management of fluid status and establish the relationship between fluid status and preservation of residual kidney function in incident haemodialysis patients. TRIAL REGISTRATION: ISCCTN Number: 11342007 , completed 26/04/2016; NIHR Portfolio number: CPMS31766; Sponsor: Keele University.

Comparison of esophageal Doppler and plethysmographic variability index to guide intraoperative fluid therapy for low-risk patients undergoing colorectal surgery.

STUDY OBJECTIVE: This study aims to investigate if there is equivalence in volumes of fluid administered when intravenous fluid therapy is guided by Pleth Variability Index (PVI) compared to the established technology of esophageal Doppler in low-risk patients undergoing major colorectal surgery. DESIGN: Randomized controlled trial. SETTING: Operating room. PATIENTS: Forty low-risk patients undergoing elective colorectal surgery. INTERVENTION: Patients were monitored by esophageal Doppler and PVI probes and were randomized to have fluid therapy directed by using one of these technologies, with 250 mL boluses of colloid to maintain a maximal stroke volume, or a PVI of less than 14%. MEASUREMENTS: Absolute volumes of fluid volumes given intraoperatively were measured as were 24 hours fluid volumes. Perioperative measurements of lactate and base excess were recorded as were postoperative complications. MAIN RESULT: There was no significant difference between PVI and esophageal Doppler groups in mean total fluid administered (1286 vs 1520 mL, P=.300) or mean intraoperative fluid balance (+839 v+1145 mL, P=.150). CONCLUSIONS: PVI offers an entirely non-invasive alternative for goal-directed fluid therapy in this group of patients.

Peritoneal inflammation precedes encapsulating peritoneal sclerosis: results from the GLOBAL Fluid Study.

BACKGROUND: Encapsulating peritoneal sclerosis (EPS) is an uncommon condition, strongly associated with a long duration of peritoneal dialysis (PD), which is itself associated with increased fibrosis in the peritoneal membrane. The peritoneal membrane is inflamed during PD and inflammation is often associated with fibrosis. We hypothesized that patients who subsequently develop EPS might have a more inflamed peritoneal membrane during PD. METHODS: We performed a nested, case-control study identifying all EPS cases in the UK arm of the GLOBAL Fluid Study and matching them by centre and duration of PD with two to three controls. Dialysate and plasma samples were taken during repeated peritoneal equilibration tests prior to cessation of PD from cases and controls. Samples were assayed by electrochemiluminescence immunoassay for interleukin-1ß (IL-1ß), tumour necrosis factor α (TNF-α), interferon-γ (IFN-γ) and IL-6. Results were analysed by linear mixed models adjusted for age and time on PD. RESULTS: Eleven EPS cases were matched with 26 controls. Dialysate TNF-α {0.64 [95% confidence interval (CI) 0.23, 1.05]} and IL-6 [0.79 (95% CI 0.03, 1.56)] were significantly higher in EPS cases, while IL-1ß [1.06 (95% CI -0.11, 2.23)] and IFN-γ [0.62 (95% CI -0.06, 1.29)] showed a similar trend. Only IL-6 was significantly higher in the plasma [0.42 (95% CI 0.07, 0.78)]. Solute transport was not significantly different between cases and controls but did increase in both groups with the duration of PD. CONCLUSIONS: The peritoneal cavity has higher levels of inflammatory cytokines during PD in patients who subsequently develop EPS, but neither inflammatory cytokines nor peritoneal solute transport clearly discriminates EPS cases. Increased systemic inflammation is also evident and is probably driven by increased peritoneal inflammation.

Growth, Oxygen Consumption, and Behavioral Responses of Danio rerio to Variation in Dietary Protein and Lipid Levels.

In recent years, there has been increasing interest in the welfare of ornamental fish. Diet can significantly impact the welfare of fish, which can manifest as changes in the fish's physical health and behavior. The zebrafish, Danio rerio, is a popular ornamental species; however, little is known about their nutritional requirements with possible implications for their welfare. Here, we investigated the effect of diets with increasing crude protein (iso-caloric diets) and lipid (iso-nitrogenous diets) on the growth performance, oxygen consumption, and behavior of zebrafish. We found no significant effects of crude protein (32%-75%) or lipid (8%-16%) on the specific growth rate or oxygen consumption of fish fed 5% of their body mass (BM)/day, although the highest crude protein and lipid diet resulted in an increase in condition factor. Furthermore, the crude protein diets did not affect zebrafish behavior when fed a 2% BM ration, once a day. This study has shown that a diet with 32% crude protein and a diet with 8% crude lipid, when fed at a 5% BM ration, were sufficient to meet the growth requirements of our zebrafish. These diets supported the fish's physical health and thus benefited their welfare.

The Impact of Sertraline Co-Administration on the Pharmacokinetics of Olanzapine: A Population Pharmacokinetic Analysis of the STOP-PD.

BACKGROUND AND OBJECTIVE: Clinical evidence and expert opinion support using a combination of an antipsychotic and an antidepressant when treating major depression with psychotic features. We characterized the impact of sertraline co-administration on olanzapine clearance in psychotic depression using population pharmacokinetic methods. METHODS: The Study of Pharmacotherapy for Psychotic Depression (STOP-PD) randomized 259 participants to olanzapine plus placebo or olanzapine plus sertraline. Olanzapine was started at 2.5-5 mg/day and sertraline at 25-50 mg/day. Doses were increased to a maximum of 20 mg/day for olanzapine and 200 mg/day for sertraline. Up to four olanzapine concentration samples were collected during the 12-week trial and 12-week continuation phase. We used NONMEM (Version VII) for population pharmacokinetic analysis, assessing effects of the covariates sex, African American origin, smoking, age, and sertraline co-administration. RESULTS: Population pharmacokinetic analysis comprised 336 samples from 175 individuals. The structural model published by Bigos et al. was sufficient to describe the olanzapine data adequately: a one-compartment model with first-order absorption and elimination, using an additive residual error structure with the absorption rate constant fixed to 0.5. Sertraline co-administration significantly increased olanzapine apparent clearance (p < 0.005) by 25-35 % depending on the patient characteristics included. Male sex was associated with a significantly increased clearance. Age and race did not have a significant impact on clearance. CONCLUSIONS: Contrary to expectations from the knowledge of cytochrome P450 interactions, sertraline increased olanzapine apparent clearance. Plausible explanations include patients treated with sertraline having poorer adherence to olanzapine, or the impact of sertraline inhibition of transporters resulting in increased intracellular concentrations and thus access to metabolizing enzymes.