End Of Trial Research Articles

Potential role of dietary white poplar (Populus alba L.) in stimulating growth, digestion, and antioxidant/immune status of Nile tilapia (Oreochromis niloticus)

The potential use of feed supplements as immune-stimulant and growth-promoting agents in fish diets has drawn much attention. The current research investigated the effects of feeding Nile tilapia (Oreochromis niloticus) on white poplar (Populus alba L.) (WP) leaves powder as a dietary supplement on the growth, digestive functions, immune, and oxidant-antioxidant parameters. In addition, the fish resistance against the Aeromonas sobria (A. sobria) challenge was investigated. For 60 days, fish (n = 160; 34.61 ± 0.16 g) were divided equally into four groups, each had four replicates. Fish were fed on four isonitrogenous and isolipidic diets supplemented with varying levels of WP; 0 g/kg (WP0, crude protein (CP) = 37.18%; crude lipid (CL) = 9.98%), 2 g/kg (WP2, CP = 37.22%; CL = 9.56%), 4 g/kg (WP4, CP = 36.95%; CL = 9.47%), and 6 g/kg (WP6, CP = 36.88%; CL = 9.33%), where WP0 was the control diet. The results revealed that WP diets substantially boosted the growth (final body weight, weight gain, and specific growth rate) with an improvement of feed conversion ratio of Nile tilapia in a level-dependent manner with the WP6 group attaining the best outcomes. WP diets improved the amylase (4–6 g/kg level) and lipase (2–6 g/kg level) activity and the intestinal morphometric measures (2–6 g/kg level), where the WP6 group recorded the highest values. WP diets increased the growth hormone (2–6 g/kg level) and reduced leptin hormone and glucose levels (2–6 g/kg level). WP diets boosted the immune-antioxidant indices (total protein, albumin, globulin, complement 3, lysozyme, nitric oxide, total antioxidant capacity, glutathione peroxidase, and catalase) in a level-dependent manner and the WP6 group attained the highest values. All experimental groups exhibited 100% survival at the end of the feeding trial. During the A. sobria challenge, the survival of fish was improved in a level-dependent manner (2–6 g/kg) (80%, 85%, 95%, respectively) compared to the control (70%), where the WP6 group recorded the highest survival. Noteworthy, WP diets especially at a level of 6 g/kg can be used as a feed supplement for improving the health, growth, immune-antioxidant functions, and disease resistance of Nile tilapia.

Body Shape Variation in Atlantic Salmon (Salmo salar, L.) Fed Fishmeal and Fish Oil-Free Diets

Post-smolt Atlantic salmon were fed control (C), plant protein- (PP), and animal protein (AP)-based diets over a 90-day period. At trial start, the outline shape variation in the salmon body was recorded using two-dimensional Cartesian coordinates of a combination of 12 landmarks (LM) and three semi-landmarks from each of the 48 fish. The identical landmarks were then assessed at trial end for the differing dietary treatments. These datasets were used to determine whether diet exerted a measurable effect on body shape to enable authentication of fishmeal/fish oil-free status. Most differences in shape at trial end were visualized at the base of the dorsal and pelvic fins and caudal peduncle. The greatest shape variation between PP and AP groups was found at the base of the pectoral and pelvic fins. While PP and AP groups were more similar in shape than control fish, the recorded differences were not significant enough to verify dietary origins. The number of animals employed and the length of the trial period were likely insufficient to distinguish alterations in body shape with any certainty. Future trials should employ larger numbers of animals and be of longer length to verify whether PP-based feeds cause changes in body shape.

Dietary organic acid blend modulates hemato-immunological parameters, digestive and reproductive performances in red tilapia (Oreochromis niloticus × O. mossambicus) broodstock.

This study evaluated the effects of dietary organic acid (OA) blend on hemato-immunological responses, reproduction capacity, gene expression, and histological features of red tilapia (Oreochromis niloticus × O. mossambicus) broodstock. Four diets were formulated, containing 0 (control), 2, 3, and 4g OAs kg-1. The diets were fed to triplicate groups (n = 3) of red tilapia broodstock (75 ± 5.56g( (mean ± standard deviation (SD)) stocked in 10-m3 concrete tanks at a male to female ratio of 1:3, to satiation, twice a day, for 8weeks. At the end of the feeding trial, fish in each tank were collected, counted, and weighed. Blood samples were collected from five fish from each tank and used for the determination of hematological and biochemical parameters. The fish were then dissected to study the reproductive performance and reproduction-related genes. The red blood cells (RBCs), hemoglobin (Hb), packed cell volume (PCV%), mean corpuscular volume (MCV), and lysozyme activity were significantly increased (P < 0.05) with increasing dietary OAs to 4gkg-1. Mean corpuscular hemoglobin (MCH), white blood cells (WBCs), total protein, albumin, and globulin), and digestive enzyme activity values leveled off or slightly decreased (P > 0.05) at OA levels above 3gkg-1. Optimum liver enzyme activity was obtained at 2gkg-1 OA. The reproductive hormones: testosterone (T), follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and progesterone (Prog), organo-somatic index (GSI), reproductive performance, and the expression of reproductive genes (vasa, nanos1a, nanos2, dnd1, pum1, amh, and VTG) exhibited dose-dependent responses (P < 0.05), suggesting that 4g OA kg-1 boosted the optimum reproductive performance. In conclusion, about 2-3g OA kg-1 diet can improve the hemato-biochemical parameters, immune response, antioxidant status, and digestive enzyme activity in red tilapia broodstock, whereas 4gkg-1 could accelerate their reproductive performance through upregulation of reproductive genes.

Effects of graded levels Citri Reticulatae Pericarpium (Chenpi) on growth performance, serum biochemical indices, meat quality, and caecal microbiota and metabolite in yellow-feathered broilers.

The Citri Reticulatae Pericarpium (CRP), is the aged peel of Citrus fruit, which contains phenols, flavonoids, and polysaccharides. This study aims to investigate dietary CRP supplementation on the growth performance, serum biochemical indices, meat quality, intestinal morphology, microbiota, and metabolite of yellow-feathered broilers. A total of 240 yellow-feathered broilers (1.00 ± 0.22 kg, 9weeks old) were randomly allotted into 4 treatments feeding a basal diet (control), the basal diet containing antibiotics (positive control), and the control diet containing 1.5% and 3% CRP, respectively. At the end of a 56-day trial, one broiler from each replicate was selected, and samples of ileal tissue and cecal digesta were collected to analyze intestinal morphology, microbial composition, and metabolites. The results revealed that 3% CRP decreased average daily feed intake (ADFI), serum total cholesterol (TC), and low-density lipoprotein (LDL). The CRP supplementation could increase serum superoxide dismutase (SOD) and meat pH. Broilers fed CRP had elevated antioxidant and liquid-regulated metabolites. Together, the results suggested that incorporating a moderate level of CRP has a minor impact on growth performance and could benefit health to some extent by enhancing antioxidants, regulating serum liquid, and changing microbial composition and metabolites.

Feed intake, preferences, in vivo digestibility, and nutritional value of tedera (B. bituminosa var. bituminosa) and maralfalfa (Pennisetum purpureum) in Canary sheep

This study evaluated the nutritional value and energy content of tedera (B. bituminosa var. bituminosa) and maralfalfa (Pennisetum purpureum) through analyses of chemical composition, digestibility, intake, and preference trials. Tedera was compared with maralfalfa and alfalfa hay (Medicago sativa). Tedera showed higher crude protein (193 g CP/kg DM) and estimated energy (10.5 MJ DE/kg DM) but lower dry matter (286.3 g DM/kg) and neutral detergent fiber (373 g NDF/kg DM) than both maralfalfa and alfalfa hay. The in vitro organic matter digestibility (IVOMD) of tedera was 61.7%, compared to 51.0% for alfalfa hay and 66.3% for maralfalfa. Digestible organic matter (DOM) ranged from 467 g/kg DM in alfalfa hay to 566.4 g/kg DM in tedera. Four Canary sheep with a mean body weight (BW) of 42.2 ± 5.0 kg were used for digestibility and preference trials. The live weights of the sheep were recorded at the start and end of the 12-day trial. Feed offered and refusals were weighed and recorded daily for eight days, while feces were collected for four days to calculate apparent in vivo digestibility. For tedera, the apparent in vivo OM digestibility, estimated digestible energy, and digestible organic matter were 69.4%, 11.8 MJ/kg DM, and 637.7 g/kg DM, respectively. Preference and feed intake were compared between tedera, maralfalfa and alfalfa hay. Total DM consumption was 1091.3 g/day (tedera + maralfalfa + alfalfa hay), with alfalfa hay intake representing 40.8%, maralfalfa 37.3%, and tedera 21.9% of the total DM consumed. However, no significant differences were observed in the ratio of forages consumed/offered (44.8% for tedera and 51.8% for maralfalfa) or in the total grams of DM, CP, and MJ/kg of DE consumed by the sheep with both forages. The sheep adopted different feeding strategies in response to the chemical composition and nutritive value of the forages. Preferences and intake in this trial were associated with high NDF content in maralfalfa and alfalfa hay and with the high CP content in tedera rather than digestibility results. This may be due to the complementarity of the three forages and the higher CP content in tedera affecting intake. Nevertheless, tedera and marafalfa could be a good forage considering its nutritive value, digestibility, and proven growth performance in herbivores.

Efficacy and Safety of Proactive Therapy with 2% Crisaborole Ointment in Children with Mild-to-Moderate Atopic Dermatitis: A Randomized Controlled Study.

The effectiveness of crisaborole for proactive treatment of atopic dermatitis (AD) is not well established. This study aims to investigate the efficacy and safety of a proactive treatment strategy with 2% crisaborole ointment for managing mild-to-moderate AD in children. In this 16-week randomized-controlled trial, children aged 2-17 years with mild-to-moderate AD were enrolled. All participants received treatment with 0.1% mometasone furoate cream for 2 weeks. Those with an IGA score of ≤ 1 were randomly assigned in a 1:1 ratio to either the proactive treatment group, which received crisaborole combined with emollient twice daily, or the reactive treatment group, which received emollients alone, and in the event of disease relapse, both groups received 0.1% mometasone furoate cream as rescue treatment. Of the 153 patients screened, 142 were randomized; 73 to the proactive treatment group and 69 to the reactive treatment group. At the end of the 16-week trial, the proactive treatment group had a relapse rate of 43.84%, significantly lower than the 71.01% relapse rate in the reactive group (P = 0.001). Additionally, the proactive treatment group demonstrated a significant reduction in the need for mometasone furoate prescriptions at weeks 4, 8, 12, and 16 (P < 0.05). Improvements were also observed in IGA, EASI, PP-NRS, and POEM scores at 12 weeks (P < 0.05). No significant differences in adverse events were found between the groups (χ2 = 2.237, P = 0.135). Proactive treatment with crisaborole ointment for children older than 2 years with mild-to-moderate AD effectively reduces flare-ups and reliance on topical corticosteroids, demonstrating good tolerability and safety. ChiCTR2100054340 (Date of Trial Registration: 14 December 2021).

P0169 Relapse of ulcerative colitis on dose reduction of tofacitinib is associated with markers of T-cell activation but not clinical features: a prospective, multicentre observational study

Abstract Background Tofacitinib (TOF) is an effective treatment for ulcerative colitis (UC). A relationship between dose and both response and side-effect profile is recognised for JAK inhibitors. Dose reduction from 10mg bd to 5mg bd is therefore associated with improved safety but also with a risk of relapse. The BRITE study aimed to identify clinical predictors and biomarkers of relapse in a cohort of patients with stable UC undergoing TOF dose reduction. Methods Steroid-free patients with stable UC responding to TOF 10mg bd for at least 8 weeks were followed from dose reduction to time of relapse or for one year. Relapse was defined by worsening modified Mayo score, including an increase in the rectal bleeding and endoscopic subscores of ≥ 1 point. Clinical and endoscopic assessment with biopsy was performed prior to dose reduction (baseline) and at end of trial. PBMCs were isolated at baseline and were cryopreserved. Flow cytometry analysis of phospho-STAT levels of STAT1, STAT3, STAT4 and STAT5 was performed in T cells from unstimulated and cytokine-stimulated baseline PBMC. In addition, CD4 T cells were isolated from PBMC and were stimulated with plate-bound anti-CD3 and anti-CD28 (TCR activation) for 5 days; cell supernatants were analysed for 17 CD4 T-helper (Th) cell effector cytokines using a 17-cytokine Luminex assay. Results 50 patients were enrolled across 3 centres; baseline characteristics are displayed in table 1. 23 (46%) patients relapsed after a median duration of 23 weeks (IQR 9-45). Demographics, disease duration, prior advanced therapy exposure (including duration on TOF), and baseline clinical, biochemical (calprotectin/CRP), and histo-endoscopic disease severity were not associated with risk of relapse. In contrast, molecular differences in CD4 T-cell function were identified in relapsers and non-relapsers. pSTAT5 levels were significantly induced by IFNa in relapse patients (p&amp;lt;0.05), but not in remission patients (Fig 1a), while canonical pSTAT5 activation by IL2 showed no significant differences between the two cohorts of patients. Furthermore, TCR activation of baseline CD4 T cells showed significantly higher expression of IL10 (p=0.01) in remission patients compared to relapse (Fig 1b). Higher levels of resting pSTAT1High expression that was refractory to IFNa stimulation in relapse patients but inducible in remission patients was also identified (p=&amp;lt;0.01). Conclusion In this large prospective study of TOF dose reduction, in contrast to previous studies, no baseline clinical or endoscopic predictors of relapse were found. However, potentially clinically useful association with markers of T cell activation were identified and should be investigated further.

P0636 Impact of obefazimod treatment on histologic and combined histologic and endoscopic outcomes in patients with moderately to severely active ulcerative colitis: results from the Phase 2b open-label maintenance study

Abstract Background Obefazimod is an investigational, oral, once-daily (QD), small molecule which enhances expression of microRNA-124 and demonstrated efficacy and safety in patients with moderately to severely active ulcerative colitis (UC) in a placebo-controlled, Phase 2b induction trial and the subsequent 96-week open-label maintenance (OLM) study [1, 2]. Here, we report proportions of patients that met endoscopic, histologic and combined histologic-endoscopic outcomes at the end of the induction trial (baseline of OLM), Weeks 48 (W48) and 96 (W96) of the OLM study. Methods Patients received obefazimod 25mg, 50mg or 100mg once daily (QD) or placebo during induction and could enter the optional 96-week OLM study irrespective of their clinical response to receive obefazimod 50mg QD. Rectal or sigmoidal biopsies were collected during endoscopy at OLM baseline, W48 and W96 to evaluate treatment effect on histopathology scores using the Geboes score. Endoscopic improvement (endoscopic sub-score ≤1), endoscopic remission (endoscopic sub-score = 0), histologic improvement (Geboes histologic score ≤3.1), histologic remission (Geboes histologic score &amp;lt;2.0), histo-endoscopic mucosal improvement (HEMI, Geboes histologic score ≤ 3.1 and endoscopic improvement) and histo-endoscopic mucosal remission (HEMR, Geboes histologic score &amp;lt;2.0 and endoscopic remission) were evaluated using as observed analysis (i.e. only patients with both endoscopic and histologic outcome for each endpoint) and non-responder imputation (NRI) for patients missing either endoscopy data and/or histology data. Results There were 217 patients that completed the induction trial and entered OLM. In a data-as-observed analysis, the proportions of patients achieving endoscopic improvement increased from 49% at OLM baseline to 73% at W48, and 78% at W96. The proportion of patients achieving histologic improvement rose from 59% at OLM baseline to 85% at W48, and 89% at W96; 39% achieved HEMI at OLM baseline, and increased to 69% at W48, and 74% at W96 (Table 1). Similar trends were observed for remission endpoints as well as in the NRI analysis. Conclusion In this Phase 2b OLM study, patients with moderately to severely active UC treated with obefazimod experienced clinically meaningful improvements in endoscopic, histologic, and combined histologic-endoscopic outcomes with proportions of patients meeting these endpoints consistently increasing from OLM baseline through W96. These data suggest sustained and progressive therapeutic benefits over time.

P0858 Rate of participation in a second randomized clinical trial and factors associated with the likelihood of participation among inflammatory bowel disease patients who already experienced a randomized clinical trial

Abstract Background The development of new therapies in inflammatory bowel disease (IBD) has become increasingly difficult, partly due to challenges in recruiting patients for clinical trials. In the last 20 years, the average recruitment for IBD-trials has decreased to approximately 0.1 patients per site per month. The aim of our study is to assess the rate of participation in a second trial in IBD patients who already experienced a clinical trial and to investigate factors that are associated with a patient’s likelihood of participating in a second clinical trial. Methods This is a single-center, retrospective study. We included IBD patients who participated in at least one for-profit randomised clinical trial at the IBD centre of IRCCS Humanitas Research Hospital (Milan, Italy) between 2015 and 2024. Results 293 patients were included. Baseline demographic and clinical characteristics are shown in Table 1. After the end of the 1° trial, patients were followed for a median of 30 months (range 1-169). During the follow-up, 85 (29.0%) participated in a second trial. In the multivariate analysis, a distance from home to the IBD clinic &amp;gt; 100 km (OR 0.556, 95% CI 0.326-0.983, p=0.043) and being in clinical remission at the end of the first trial (OR 0.567, 95% CI 0.324-0.991, p=0.046) were significantly associated with a lower likelihood of participating in the second trial. Conclusion Approximately one third of patients participated again in a second clinical trial. Long distance from the IBD clinic and remission at the end of the first trail reduce the probability of participation in the second trial. Understanding the factors that hinder or promote participation in IBD clinical trials is crucial for enhancing patient involvement in research.

Cost Benefits and Growth Promoting Ability of Dietary Bambara Nut (Vigna subterranean) Powder on the Rearing of Catfish (Clarias gariepinus)

The efficacy of dietary Bambara nut (Vigna subterranean) in the growth performance and cost benefit of Clarias gariepinus culture was evaluated. To this end 35% CP diet was formulated using locally available ingredients. Five different diets were prepared from the 35% CP diet, replacing Soybean with Bambara nuts at different percentage as follows: T1 (0% BN: 100 SB), T2 (25% BN: 75% SB) T3 (50% BN: 50% SB), T4 (75% BN: 25% SB) and T5 (100% BN: 0% SB), and organoleptic assessment was conducted on the diets to determine texture, aroma and color, while chemical assessment was conducted to determine the nutritional qualities of the diets. One hundred and fifty (150) sub-adult Clarias gariepinus were distributed into five (5) groups in triplicates of ten (10) using fifteen aquaria, and were fed T1 – T5, for eight (8) weeks. Length and weight of fish were evaluated fortnightly to determine: weight gain, percentage weight gain, specific growth rate, performance index and condition factor. And the cost of feed and fish were determined to evaluate the cost benefits of the various diets. At the end of the feeding trials, data were collected and analysed using ANOVA followed by a Turkey multi-companism test with SPSS 170 package software and the following results were obtained: (1) the experimental diets T1-T5 had no effects on the physico-chemical properties of the experimental waters (2) the aroma of the experimental diets were less fishy, their texture ranges from fibrous to less fibrous and the colour from dark brown to light brown as the quantity of the Bambara nut in the diets increases (T1-T5). (3) The % lipid, % proteins and % fibre decreased as the quantity of Bambara nut increased in the experimental diets (T1-T5). (4) All the growth parameters and performance index increased significantly (P&lt;0.05) as the quantity of Bambara nuts increased in the various diets (T1-T5):- Weight gain (WG): T1 (54.61+2.11), T2 (70.96+8.47), T3 (67.82+0.63), T4 (70.90+5.90) and T5 (77.35+3.81), Percentage weight gain (PWG): T1 (30.76+0.77), T2 (40.66+1.46), T3 (35.64+1.64), T4 (37.46+1.13) and T5 (44.84+10.30); Condition factor (CF): T1 (0.55+0.13), T2 (0.62+1.02), T3 (0.70+0.41), T4 (0.64+11.4) and T5 (0.64+4.30); Specific growth rate (SGR): T1 (0.34+0.02), T2 (0.43+0.05), T3 (0.42+0.01), T4 (0.43+0.02) and T5 (0.49+0.02); Performance index (PI): T1 (158.99+2.76), T2 (208.99+25.84), T3 (210.98+2.28), T4 (203.85+11.87) and T5 (213.13+4.30). The fish fed the Bambara nut diets (T2-T5) had enhanced net profit, profit index and benefit cost ratio, but lower economic weight gain. Bambara nut is unarguably a better feed ingredient than Soybean in the culture of Clarias gariepinus.

Cerebral Hemodynamic Responses to Disease-Modifying and Curative Sickle Cell Disease Therapies.

Sickle cell disease (SCD) is a hemoglobinopathy resulting in hemoglobin-S production, hemolytic anemia, and elevated stroke risk. Treatments include oral hydroxyurea, blood transfusions, and hematopoietic stem cell transplantation (HSCT). Our objective was to evaluate the neurologic relevance of these therapies by characterizing how treatment-induced changes in hemoglobin (Hb) affect brain health biomarkers. In this interventional study, adults with and without SCD underwent a 3T-MRI at Vanderbilt University Medical Center at 2 time points before and after clinically indicated transfusion or HSCT or at 2 time points without the introduction of a new Hb-altering therapy (adult controls and patients with SCD on hydroxyurea). Cerebral blood flow (CBF; mL/100 g/min) and cerebral venous blood relaxation rate (s-1; a marker of Hb and blood oxygen content) responses were assessed to understand how these markers of brain health vary with Hb modulation. CBF was assessed with arterial spin labeling MRI, and blood relaxation rate was assessed using T2 relaxation under spin tagging MRI. Measures were pairwise compared within each cohort using a 2-tailed Wilcoxon signed-rank test, and regression was applied to evaluate the parameter and Hb change relationships. The significance criterion was 2-sided p < 0.05. Adults with (n = 43; age 28.7 ± 7.7 years; 42% male) and without (n = 13; age 33.5 ± 12.2 years; 46% male) SCD were evaluated. In adults receiving hydroxyurea (n = 10), neither Hb, CBF, nor venous relaxation rate changed between time 1 (Hb = 8.6 ± 1.2 g/dL) and time 2 (Hb = 9.0 ± 1.8 g/dL) (all p > 0.05). In transfusion patients (n = 19), Hb increased from 8.2 ± 1.4 g/dL to 9.3 ± 1.3 g/dL before vs after transfusion (p < 0.001), paralleling a CBF decrease of 14.2 mL/100 g/min (p < 0.001) toward control levels. The venous relaxation rate did not change after transfusion (p = 0.71). In HSCT patients (n = 14), Hb increased from 8.9 ± 1.9 g/dL to 12.9 ± 2.7 g/dL (p < 0.001) before vs after transplant, paralleling CBF decreases from 68.16 ± 20.24 to 47.43 ± 12.59 mL/100 g/min (p < 0.001) and increase in venous relaxation rate (p = 0.004). Across the Hb spectrum, a CBF decrease of 5.02 mL/100 g/min per g/dL increase in Hb was observed. Findings demonstrate improvement in cerebral hemodynamics after transfusion and transplant therapies compared with hydroxyurea therapy; quantitative relationships should provide a framework for using these measures as trial end points to assess how new SCD therapies affect brain health.

Effects of Feed Supplementation With Fulvic Acid on the Systemic and Mucosal Protective Mechanisms of Juvenile Rainbow Trout (Oncorhynchus mykiss).

Rainbow trout (Oncorhynchus mykiss) is an important fish species raised in aquaculture, but it is susceptible to stress, infections diseases. The present study aimed to determine the effects of fulvic acid feed addition on the systemic and mucosal protective mechanisms of juvenile rainbow trout and to elucidate the underlying molecular mechanisms of changes in the gut. Rainbow trout (4.30 ± 0.6 g) diet was supplemented with different levels of fulvic acid: 0% (Control), 0.5%, 1% and 2%. At the end of 8-week feeding trial, growth parameters such as final weight gained weight (%), SGR (F1%) increased, and FCR (all levels) decreased significantly compared to the control group. We found that the activity of lysozyme, glutathione peroxidase, and catalase in the serum were significantly improved, especially after the addition of 0.5% and 1% of fulvic acid. At the same time, the immunoglobulin concentration in the skin mucus was increased with 0.5% supplementation. However, the expression of tnf-α, il-6 and gpx in the intestine was strongly upregulated after supplementation with 2%, indicating oxidative stress and inflammation with this level of fulvic acid inclusion. Furthermore, the mucus lysozyme activity was reduced at this concentration, which can increase the susceptibility to pathogen invasion. The results suggest that adding 0.5%-1% of fulvic acid to the feed of juvenile rainbow trout can help to improve their immune and antioxidative defenses and thereby support the wellbeing of fish.

A critical evaluation of psilocybin-assisted therapy protocol components from clinical trial patients, facilitators, and caregivers.

Psilocybin-assisted therapy (PAT) is an experimental treatment with transformative promise. Developing standards for PAT psychotherapy protocols is a priority, but psychotherapeutic protocol components of PAT have been subjected to little rigorous research. This study was designed to assess protocol components in a trial of PAT. The Enhanced Critical Incident Technique (E-CIT) was used to identify critical incidents in the treatment, wish list items comprising components or modifications that would have improved the treatment experience, and contributing factors that influenced the treatment. Participants included patients (n = 10), facilitators (n = 7 licensed mental health clinicians and certified spiritual health clinicians), and caregivers (n = 7) in an open-label trial investigating PAT for cancer-related demoralization and chronic pain. Patients and caregivers were interviewed after their last treatment session in the trial; facilitators were interviewed at the end of the entire trial. Rapid qualitative analysis identified specific domains for improvement in the treatment protocol based on the E-CIT. Critical incidents, wish list items, and contributing factors pertained to aspects of the therapy (e.g., importance of intention-setting) and the overall protocol (e.g., navigating transitions in the treatment). Findings indicate the importance of tailoring PAT to accommodate the medical history and needs of this population, support common factors, and ensure collaborative care. Recommendations across nine topic areas were derived from the data and presented in the Discussion. The E-CIT shows promise for advancing early stage research on PAT components. (PsycInfo Database Record (c) 2025 APA, all rights reserved).

Interactions Between Trace Elements and Macro Minerals in Pregnant Heifers

There is a lack of information on mineral interactions that take place during a heifer’s pregnancy when nutrient demand is high. The objective of the present study was to evaluate the interactions between the macro minerals calcium (Ca), phosphorus (P), magnesium (Mg), sulphur (S), sodium (Na) and potassium (K) and the trace elements copper (Cu), iron (Fe), manganese (Mn), molybdenum (Mo), selenium (Se), zinc (Zn) and cobalt (Co) in pregnant heifers. Twenty-four pregnant heifers (age 18.2 ± 0.14 months; 87.5 ± 4.74 days in gestation; 497 ± 8.5 kg of body weight) were used in a 7 d digestibility trial (indirect method using lignin as a marker) during which they were fed a diet that provided minerals in accordance with NASEM requirements for gestating beef cattle. At the end of the digestibility trial, blood (jugular venipuncture) and liver (biopsy) samples were collected from each heifer. Multiple linear regression models were developed based on the main correlations and by considering collinearity effects between variables. Iron intake positively affected Mo concentration in serum, which was &gt;10 µg/dL for most of the animals. Apparent absorption of Fe was negatively affected by Mo intake and Ca to P ratio in feed, whereas Se absorption was negatively affected by Fe intake and positively by Mo intake. The absorption coefficients of Mo and Fe were inversely related, emphasizing the interactions between these elements. Serum Fe and Cu in the liver were positively correlated, while liver Fe was inversely related to liver Mn. Fewer interactions were observed between the macro minerals. In conclusion, within the interactions observed, those between Fe and Mo deserve special attention, as high dietary Fe is commonly found in typical ruminant diets, and high serum Mo may indicate molybdenosis. Furthermore, high Fe intake appears to impact Se and Mn utilization.

Integrating Metabolomics and Genomics to Uncover the Impact of Fermented Total Mixed Ration on Heifer Growth Performance Through Host-Dependent Metabolic Pathways.

With the increasing demand for enhancing livestock production performance and optimizing feed efficiency, this study aimed to investigate the effects of fermented total mixed ration (FTMR) containing different proportions of rice straw and sheath and leaves of Zizania latifolia on systemic nutrient metabolism and oxidative metabolism under host genetic regulation and on growth performance of heifers. A total of 157 heifers aged 7-8 months were selected, and their hair was collected for whole-genome sequencing. They were randomly assigned into four groups of 18 to 21 cattle each and fed FTMR containing varying levels of rice straw (21% in LSF, 28% in MSF, 35% in HSF) or 31% sheath and leaves of Zizania latifolia (ZF) for a two-month period. At the end of trial, blood and urine samples were collected to measure biochemical indexes and metabolomics. The results showed that high rice straw content and ZF diets could increase blood glucose and non-protein nitrogen in heifers, that is, blood glucose and urea nitrogen levels in HSF and ZF groups were higher than those in LSF and MSF groups (p < 0.05). Meanwhile, the two diets could improve the antioxidant level of heifers. Urine metabolomics analysis between the groups identified three differential metabolic pathways, including 11 metabolites. Among them, l-homoserine and o-acetylserine had significant SNPs associated with them, which promoted glutathione metabolism. Although there was no significant effect of diet on heifers' average daily gain (ADG) in body weight (p > 0.05), there was substantial inter-individual variation in metabolites among all animals, as further correlation analyses illustrated. Twenty-eight metabolites were significantly associated with ADG (R > 0.3, p < 0.05). Four of them were identified as biomarkers, primarily regulating energy metabolism and oxidative balance. In conclusion, feeding HSF and ZF FTMR enhances glutathione metabolism and antioxidant capacity in heifers, positioning key metabolites as candidates for ADG markers. This integrative omics approach underscores the potential for enhancing livestock productivity and promoting sustainable agricultural practices.

Proteomic changes upon treatment with semaglutide in individuals with obesity

Obesity and type 2 diabetes are prevalent chronic diseases effectively managed by semaglutide. Here we studied the effects of semaglutide on the circulating proteome using baseline and end-of-treatment serum samples from two phase 3 trials in participants with overweight or obesity, with or without diabetes: STEP 1 (n = 1,311) and STEP 2 (n = 645). We identified evidence supporting broad effects of semaglutide, implicating processes related to body weight regulation, glycemic control, lipid metabolism and inflammatory pathways. Several proteins were regulated with semaglutide, after accounting for changes in body weight and HbA1c at end of trial, suggesting effects of semaglutide on the proteome beyond weight loss and glucose lowering. A comparison of semaglutide with real-world proteomic profiles revealed potential benefits on disease-specific proteomic signatures including the downregulation of specific proteins associated with cardiovascular disease risk, supporting its reported effects of lowering cardiovascular disease risk and potential drug repurposing opportunities. This study showcases the potential of proteomics data gathered from randomized trials for providing insights into disease mechanisms and drug repurposing opportunities. These data also highlight the unmet need for, and importance of, examining proteomic changes in response to weight loss pharmacotherapy in future trials.

Best clinical model predicting extubation failure: a diagnostic accuracy post hoc analysis

PurposePredicting extubation failure remains a clinical challenge. This study aimed to determine diagnostic accuracy of models used at the bed side.MethodsPost hoc analysis of 2341 patients at all risk included in five multicenter randomized trials. Diagnostic accuracy of three clinical prediction models was compared: 3-factors model including age > 65y, chronic heart or pulmonary disease; 4-factors model adding prolonged mechanical ventilation; and 11-factors model including age > 65 years, ≥ 2 comorbidities, prolonged mechanical ventilation, acute heart failure as the primary indication for mechanical ventilation, moderate-to-severe chronic obstructive pulmonary disease, APACHE II score > 12 on extubation day, airway patency problems, inability to deal with respiratory secretions, not simple weaning, obesity, or hypercapnia at the end of the spontaneous breathing trial. Crude and adjusted for spontaneous breathing trial (SBT) models were compared for all-cause reintubation at 7 days using Youden and Kappa indexes.ResultsThe 3-factors model had a very low global prediction capability (Youden index 0.08 and Kappa index 0.04); the 4-factors and 11-factors models had low global prediction capability (Youden index 0.12 and 0.16, and Kappa index 0.06 and 0.07, respectively). Aggressive SBT strategies (pressure support ≥ 7 cm H2O with or without positive end-expiratory pressure) were associated with extubation failure risk (p < 0.001). All adjusted models had low diagnostic capability (0.08/0.03, 0.07/0.03, and 0.06/0.02 respectively).ConclusionBased on these results, the 3-factors model reported a very low diagnostic accuracy, and the 4 or 11-factors models showed similar low accuracy. No improvement was observed after adjusting for other aspects of weaning.

Ziziphus nummularia and Acacia nilotica leaves based polyphenols rich diet modulates fatty acid profile and keeping quality of lamb meat

The polyphenols, due to their chemical characteristics, are known to alter microbial populations, impart antioxidant properties, and bind proteins. Accordingly, the present study was carried out to study the potential of plant polyphenol-rich diets in modulating the fatty acids (FAs) profiles and keeping quality of lamb meat. For this, thirty Avishan lambs (10 weeks old, 14.0 ± 0.2kg) were randomly distributed into three groups: control (T1) on a complete feed block containing Vigna sinensis hay, T2 on CFB containing Acacia nilotica, and T3 on CFB containing Ziziphus nummularia leaves. The CFB in T1 had a negligible quantity of polyphenols, whereas T2 was rich in hydrolysable tannins, and T3 was rich in condensed tannins. The feeding trial was carried out for 12 weeks. A lower intake of nutrients (per kg BW0.75) was recorded in T2 compared to T1 and T3, while feed efficiency was similar across all treatments. Five lambs from each group were slaughtered at the end of the feeding trial for studying carcass attributes. T1 and T3 recorded higher (P = 0.003) weight gain, whereas T2 and T3 had higher dressing percentages and loin-eye areas. The FAs profile of Longissimus thoracis muscle in T2 and T3 showed a positive shift (decreased saturated and trans-FAs and increased ω-3, ω-6, and polyunsaturated FAs) with healthier atherogenicity and thrombogenicity indices. The carcasses of T2 and T3 showed improved keeping quality following 14 days of refrigerated (4°C) storage, as evidenced by lower malondialdehyde values. Between the two sources, the condensed tannin-rich Z. nummularia showed superiority over the hydrolysable tannin-rich A. nilotica in modulating FA biohydrogenation and preserving keeping quality.

Association that Neuroimaging and Clinical Measures Have with Change in Arm Impairment in a Phase 3 Stroke Recovery Trial.

Vagus nerve stimulation (VNS) paired with rehabilitation therapy improved motor status compared to rehabilitation alone in the phase III VNS-REHAB stroke trial, but treatment response was variable and not associated with any clinical measures acquired at baseline, such as age or side of paresis. We hypothesized that neuroimaging measures would be associated with treatment-related gains, examining performance of regional injury measures versus global brain health measures in parallel with clinical measures. Baseline magnetic resonance imaging (MRI) scans in the VNS-REHAB trial were used to derive regional injury measures (extent of injury to corticospinal tract, the primary regional measure; plus extent of injury to precentral gyrus and postcentral gyrus; lesion volume; and lesion topography) and global brain health measures (degree of white matter hyperintensities, the primary global brain measure; plus volumes of cerebrospinal fluid, cortical gray matter, white matter, each thalamus, and total brain). Eight clinical measures assessed at baseline were also evaluated (treatment group, age, race, gender, paretic side, pre-stroke dominant hand, time since stroke, and baseline Fugl-Meyer upper extremity score). Bivariate analyses compared each measure with the primary trial end point (change in Fugl-Meyer upper extremity score from baseline to end of 6 weeks of treatment) across all subjects, with secondary analyses examining trial groups separately. MRIs were available from 80 patients (age = 59.8 ± 9.5 years, 29 women). Across all patients, less white matter hyperintensities (r = -0.25, p = 0.028) at baseline was associated with larger Fugl-Meyer score change. In the VNS group, less white matter hyperintensities (r = -0.37, p = 0.018) and larger ipsilesional thalamus volume (r = 0.33, p = 0.046) were each associated with larger Fugl-Meyer score change. Analysis of covariance (ANCOVA) analyses tested the interaction that each baseline measure had with treatment group and found that the model examining white matter hyperintensities had a significant interaction term, indicating 2.3 less change in Fugl-Meyer Upper Extremity (FM-UE) points in the VNS group relative to the control group for each point increase in modified Fazekas scale. Neuroimaging measures are associated with extent of gains on the primary endpoint of a phase III stroke recovery trial. Among the neuroimaging measures examined, a measure of global brain health (extent of white matter hyperintensities) was better at explaining the change in arm impairment as compared with measures of regional injury; this was true when examining all study subjects as well as only those in the VNS group and is consistent with the global mechanism of action that VNS has throughout the cerebrum. Future studies can evaluate additional measures that further predict response to VNS therapy. The current findings suggest that individual patient neuroimaging results may be useful for a personalized medicine approach to stroke recovery therapeutics. ANN NEUROL 2024.

Tryptophan-supplemented diet modulates the metabolic response of European seabass (Dicentrarchus labrax) juveniles reared under space-confined conditions and submitted to acute inflammation

The energetic costs of being in stressful conditions require the involvement of hormones associated with metabolic support, which may also influence immune function. The present work aimed to explore the links between tryptophan nutrition and metabolic responses in European seabass (Dicentrarchus labrax) held under space-confined conditions, and subsequently submitted to an immune challenge. To study that, two dietary treatments were evaluated, i.e. control diet (CTRL) and CTRL-based diet supplemented with tryptophan (0.3%; TRP) to fish under space-confinement conditions (10 kg/m3) or not (5 kg/m3). Dietary treatments were offered for 15 days after which fish were intraperitoneally injected (i.p.) with Photobacterium damselae piscicida. Liver was sampled before the immune challenge (at end of the nutritional trial, 0 h) and at 4, 24, 48 and 72 h post-injection. Fish-fed TRP exhibited distinct metabolic profiles compared to those fed CTRL diets, particularly in energy metabolism and stress response. CTRL-fed fish in space-confined conditions showed a gradual reduction of lipid oxidative enzyme activity post-injection, pointing to acute stress-induced lipid catabolism feedback. In contrast, stressed fish fed TRP under same rearing conditions presented reduced glucose levels and cortisol production but unchanged 3-hydroxiacil-CoA dehydrogenase (EC 1.1.1.35, HOAD) activity patterns, suggesting an inhibitory and modulatory role of tryptophan in stress response. Discriminant analysis revealed that fish fed TRP under space-confined conditions resembled fish CTRL-fed under non-stressful conditions. These findings suggest that tryptophan dietary supplementation for stressed fish modulates their metabolic responses and potentially mitigates the negative effects of rearing stressful conditions after subsequent acute stress induced by an immune challenge.