Blood profile and productive performance after partial substitution of maize grain with ancient wheat lines by-products in organic laying hens' diet

The aim of this research was to evaluate the effects of the partial substitution of maize grain with local ancient wheats by-products in an organic laying hens farm on animal performance and blood profile, as well as on eggs quality. A total of 80 Hy-Line W-36 Single Comb White Leghorn, 18 weeks old hens were homogenously divided into two groups. The two groups (40 laying hens each, 8 replicates, 5 hens/replicate) were fed two isoprotein and isoenergetic diets: the Control group (C) was fed a standard, organic maize-soybean meal diet whereas in the Ancient Grains group (AG) part of the maize grain was replaced by a mix of ancient grains middling, consisting in 50:50 of Triticum aestivum var. spelta (spelt) and Triticum durum dicoccum L. (emmer wheat). The birds fed the maize based-diet (C) showed a higher (P < 0.01) egg weight and feed intake than the Ancient Grains (AG) group. By contrary, the feed conversion ratio was more favourable (P < 0.05) in hens fed the Ancient Grains diet. The eggs produced by the hens fed the Control diet showed higher length and width than the other group (P < 0.01). The shell thickness and strength were also higher in the Control group (P < 0.01 and P < 0.05, respectively). The experimental dietary treatment positively affected some blood parameters. The Control group showed higher levels of cholesterol and triglycerides (P < 0.05) as well as of alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) (P < 0.01). In addition, butyrate, which may have great implications for the regulation of the immune response, resulted significantly higher in the caecal content of hens from the Ancient Grains group. Overall, the Ancient Grains diet seemed to be able to guarantee the production performances with positive effects on the animal health

Replacing maize grain with ancient wheat lines by‐products in organic laying hens’ diet affects intestinal morphology and enzymatic activity

The effects of replacement of maize grain with ancient wheat by‐products on intestinal morphometry and enzymatic activity in laying hens was studied. Eighty hens were divided into two groups (40 each, 8 replicates, 5 hens/replicate) fed two isoproteic and isoenergetic diets. In the treated group, part of the maize was replaced by a mix of ancient grains (AGs) middling, in a 50:50 ratio of Triticum aestivum L. var. spelta (spelt) and Triticum durum dicoccum L. (emmer wheat). The AG diet affected the weight of all the large intestine tracts, decreasing the weight of caeca (p < 0.01) and increasing those of colon (p < 0.01), rectum and cloaca (p < 0.05). Villus height in the AG group was higher (p < 0.01) than the control for the duodenum and jejunum, while for the ileum, the control group showed the highest values (p < 0.01). The submucosa thickness was higher (p < 0.01) in the control group for the duodenum and ileum, while the jejunum for the AG group showed the highest (p < 0.05) submucosa thickness. The crypts depth was higher (p < 0.01) in the control group for the duodenum and ileum. Enzyme activity was enhanced by AGs (p < 0.01) in the duodenum. Regarding the jejunum, sucrase‐isomaltase and alkaline phosphatase had higher activity (p < 0.05 and p < 0.01, respectively) in the AG group. In the ileum, sucrase‐isomaltase showed higher activity (p < 0.01) in the control group, while alkaline phosphatase showed the highest values (p < 0.05) in the AG group. Overall, results suggested that the dietary inclusion of AGs exerted positive effects in hens, showing an improved intestinal function

Antimicrobial activity of lipids extracted from Hermetia illucens reared on different substrates

Abstract: As the problem of antimicrobial resistance is constantly increasing, there is a renewed interest in antimicrobial products derived from natural sources, particularly obtained from innovative and eco-friendly materials. Insect lipids, due to their fatty acid composition, can be classified as natural antimicrobial compounds. In order to assess the antibacterial efficacy of Hermetia illucens lipids, we extracted this component from the larval stage, fed on different substrates and we characterized it. Moreover, we analyzed the fatty acid composition of the feeding substrate, to determine if and how it could affect the antimicrobial activity of the lipid component. The antimicrobial activity was evaluated against Gram-positive Micrococcus flavus and Gram-negative bacteria Escherichia coli. Analyzing the fatty acid profiles of larval lipids that showed activity against the two bacterial strains, we detected significant differences for C4:0, C10:0, C16:1, C18:3 n3 (ALA), and C20:1. The strongest antimicrobial activity was verified against Micrococcus flavus by lipids extracted from larvae reared on strawberry, tangerine, and fresh manure substrates, with growth inhibition zones ranged from 1.38 to 1.51&nbsp;mm, while only the rearing on manure showed the effect against Escherichia coli. Notably, the fatty acid profile of H. illucens seems to not be really influenced by the substrate fatty acid profile, except for C18:0 and C18:2 CIS n6 (LA). This implies that other factors, such as the rearing conditions, larval development stages, and other nutrients such as carbohydrates, affect the amount of fatty acids in insects. Key points: • Feeding substrates influence larval lipids and fatty acids (FA) • Generally, there is no direct correlation between substrate FAs and the same larvae FAs • Specific FAs influence more the antimicrobial effect of BSF lipids Graphical abstract: [Figure not available: see fulltext.

High Erk-1 activation and Gadd45a expression as prognostic markers in high risk pediatric haemolymphoproliferative diseases

Studies on activated cell-signaling pathways responsible for neoplastic transformation are numerous in solid tumors and in adult leukemias. Despite of positive results in the evolution of pediatric hematopoietic neoplasias, there are some high-risk subtypes at worse prognosis. The aim of this study was to asses the expression and activation status of crucial proteins involved in cell-signaling pathways in order to identify molecular alterations responsible for the proliferation and/or escape from apoptosis of leukemic blasts. The quantitative and qualitative expression and activation of Erk-1, c-Jun, Caspase8, and Gadd45a was analyzed, by immunocytochemical (ICC) and western blotting methods, in bone marrow blasts of 72 patients affected by acute myeloid leukemia (AML), T-cell acute lymphoblastic leukemia (ALL) and stage IV non-Hodgkin Lymphoma (NHL). We found an upregulation of Erk-1, Caspase8, c-Jun, and Gadd45a proteins with a constitutive activation in 95.8%, 91.7%, 86.2%, 83.4% of analyzed specimens, respectively. It is worth noting that all AML patients showed an upregulation of all proteins studied and the high expression of GADD45a was associated to the lowest DFS median (p = 0.04). On univariate analysis, only Erk-1 phosphorylation status was found to be correlated with a significantly shorter 5-years DFS in all disease subgroups (p = 0.033) and the lowest DFS median in ALL/NHL subgroup (p = 0.04). Moreover, the simultaneous activation of multiple kinases, as we found for c-Jun and Erk-1 (r = 0.26; p = 0.025), might synergistically enhance survival and proliferation potential of leukemic cells. These results demonstrate an involvement of these proteins in survival of blast cells and, consequently, on relapse percentages of the different subgroups of patients

Zoledronic acid in metastatic chondrosarcoma and advanced sacrum chordoma: two case reports

<p>Abstract</p> <p>Introduction</p> <p>Chondrosarcomas and chordomas are usually chemoresistant bone tumors and may have a poor prognosis when advanced. They are usually associated with worsening pain difficult to control.</p> <p>Patients and Methods</p> <p>Zoledronic acid was used in a 63-year-old man with metastatic chondrosarcoma and in a 66-year-old woman with a diagnosis of sacrum chordoma both reporting severe pain related to tumor.</p> <p>Results</p> <p>In the first case, zoledronic acid was able to maintain pain control despite disease progression following chemotherapy, in the other case, zoledronic acid only produced significant clinical benefit.</p> <p>Conclusion</p> <p>Control of pain associated with bone tumors such as chondrosarcoma and chondroma may significantly improve from use of zoledronic acid, independently from tumor response to other treatments. Evaluation on larger series are needed to confirm the clinical effect of this bisphosphonate on such tumors.</p

Testing a Model of Care for Patients on Immune Checkpoint Inhibitors Based on Electronic Patient-Reported Outcomes: Protocol for a Randomized Phase II Controlled Trial.

Management of severe symptomatic immune-related adverse events (IrAEs) related to immune checkpoint inhibitors (ICIs) can be facilitated by timely detection. As patients face a heterogeneous set of symptoms outside the clinical setting, remotely monitoring and assessing symptoms by using patient-reported outcomes (PROs) may result in shorter delays between symptom onset and clinician detection. We assess the effect of a model of care for remote patient monitoring and symptom management based on PRO data on the time to detection of symptomatic IrAEs from symptom onset. The secondary objectives are to assess its effects on the time between symptomatic IrAE detection and intervention, IrAE grade (severity), health-related quality of life, self-efficacy, and overall survival at 6 months. For this study, 198 patients with cancer receiving systemic treatment comprising ICIs exclusively will be recruited from 2 Swiss university hospitals. Patients are randomized (1:1) to a digital model of care (intervention) or usual care (control group). Patients are enrolled for 6 months, and they use an electronic app to complete weekly Functional Assessment of Cancer Therapy-General questionnaire and PROMIS (PROs Measurement Information System) Self-Efficacy to Manage Symptoms questionnaires. The intervention patient group completes a standard set of 37 items in a weekly PROs version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) questionnaire, and active symptoms are reassessed daily for the first 3 months by using a modified 24-hour recall period. Patients can add items from the full PRO-CTCAE item library to their questionnaire. Nurses call patients in the event of new or worsening symptoms and manage them by using a standardized triage algorithm based on the United Kingdom Oncology Nursing Society 24-hour triage tool. This algorithm provides guidance on deciding if patients should receive in-person care, if monitoring should be increased, or if self-management education should be reinforced. The Institut Suisse de Recherche Expérimentale sur le Cancer Foundation and Kaiku Health Ltd funded this study. Active recruitment began since November 2021 and is projected to conclude in November 2023. Trial results are expected to be published in the first quarter of 2024 and will be disseminated through publications submitted at international scientific conferences. This trial is among the first trials to use PRO data to directly influence routine care of patients treated with ICIs and addresses some limitations in previous studies. This trial collects a wider spectrum of self-reported symptom data daily. There are some methodological limitations brought by changes in evolving treatment standards for patients with cancer. This trial's results could entail further academic discussions on the challenges of diagnosing and managing symptoms associated with treatment remotely by providing further insights into the burden symptoms represent to patients and highlight the complexity of care procedures involved in managing symptomatic IrAEs. ClinicalTrials.gov NCT05530187; https://www.clinicaltrials.gov/study/NCT05530187. DERR1-10.2196/48386

Off–label long acting injectable antipsychotics in real–world clinical practice: a cross-sectional analysis of prescriptive patterns from the STAR Network DEPOT study

Introduction: Information on the off–label use of Long–Acting Injectable (LAI) antipsychotics in the real world is lacking. In this study, we aimed to identify the sociodemographic and clinical features of patients treated with on– vs off–label LAIs and predictors of off–label First– or Second–Generation Antipsychotic (FGA vs. SGA) LAI choice in everyday clinical practice. Method: In a naturalistic national cohort of 449 patients who initiated LAI treatment in the STAR Network Depot Study, two groups were identified based on off– or on–label prescriptions. A multivariate logistic regression analysis was used to test several clinically relevant variables and identify those associated with the choice of FGA vs SGA prescription in the off–label group. Results: SGA LAIs were more commonly prescribed in everyday practice, without significant differences in their on– and off–label use. Approximately 1 in 4 patients received an off–label prescription. In the off–label group, the most frequent diagnoses were bipolar disorder (67.5%) or any personality disorder (23.7%). FGA vs SGA LAI choice was significantly associated with BPRS thought disorder (OR = 1.22, CI95% 1.04 to 1.43, p&nbsp;= 0.015) and hostility/suspiciousness (OR = 0.83, CI95% 0.71 to 0.97, p&nbsp;= 0.017) dimensions. The likelihood of receiving an SGA LAI grew steadily with the increase of the BPRS thought disturbance score. Conversely, a preference towards prescribing an FGA was observed with higher scores at the BPRS hostility/suspiciousness subscale. Conclusion: Our study is the first to identify predictors of FGA vs SGA choice in patients treated with off–label LAI antipsychotics. Demographic characteristics, i.e. age, sex, and substance/alcohol use co–morbidities did not appear to influence the choice towards FGAs or SGAs. Despite a lack of evidence, clinicians tend to favour FGA over SGA LAIs in bipolar or personality disorder patients with relevant hostility. Further research is needed to evaluate treatment adherence and clinical effectiveness of these prescriptive patterns

Comparing Long-Acting Antipsychotic Discontinuation Rates Under Ordinary Clinical Circumstances: A Survival Analysis from an Observational, Pragmatic Study

Background: Recent guidelines suggested a wider use of long-acting injectable antipsychotics (LAI) than previously, but naturalistic data on the consequences of LAI use in terms of discontinuation rates and associated factors are still sparse, making it hard for clinicians to be informed on plausible treatment courses. Objective: Our objective was to assess, under real-world clinical circumstances, LAI discontinuation rates over a period of 12 months after a first prescription, reasons for discontinuation, and associated factors. Methods: The STAR Network ‘Depot Study’ was a naturalistic, multicentre, observational prospective study that enrolled subjects initiating a LAI without restrictions on diagnosis, clinical severity or setting. Participants from 32 Italian centres were assessed at baseline and at 6 and 12 months of follow-up. Psychopathology, drug attitude and treatment adherence were measured using the Brief Psychiatric Rating Scale, the Drug Attitude Inventory and the Kemp scale, respectively. Results: The study followed 394 participants for 12 months. The overall discontinuation rate at 12 months was 39.3% (95% confidence interval [CI] 34.4–44.3), with paliperidone LAI being the least discontinued LAI (33.9%; 95% CI 25.3–43.5) and olanzapine LAI the most discontinued (62.5%; 95% CI 35.4–84.8). The most frequent reason for discontinuation was onset of adverse events (32.9%; 95% CI 25.6–40.9) followed by participant refusal of the medication (20.6%; 95% CI 14.6–27.9). Medication adherence at baseline was negatively associated with discontinuation risk (hazard ratio [HR] 0.853; 95% CI 0.742–0.981; p&nbsp;=&nbsp;0.026), whereas being prescribed olanzapine LAI was associated with increased discontinuation risk compared with being prescribed paliperidone LAI (HR 2.156; 95% CI 1.003–4.634; p&nbsp;=&nbsp;0.049). Conclusions: Clinicians should be aware that LAI discontinuation is a frequent occurrence. LAI choice should be carefully discussed with the patient, taking into account individual characteristics and possible obstacles related to the practicalities of each formulation