The aim was to evaluate the use of mixture of microencapsulated carvacrol and cinnamaldehyde as a replacement for growth-promoting antibiotics in broiler diets on performance, intestinal quality, ...organ development, carcass yields and cuts, and meat quality. In the trial were used 600 male chicks, allocated in a completely randomized design, with five treatments and eight replicates of 15 birds, reared up to 41 days of age. The treatments were: Negative Control (NC), Positive Control (PC) 30 mg/kg of virginiamycin, NC+100 mg/kg of essential oils, NC+200 mg/kg of essential oils and NC+400 mg/kg of essential oils. Essential oils were composed by a micro-encapsulated blend, with of 60% cinnamaldehyde, 30% carvacrol and 10% carrier. Birds received essential oils achieved performance equivalent to those birds received PC diets, having better development than NC broilers. No differences were found on relative organ weight, intestinal mucosa and meat quality parameters, however, higher villus:cript ratio was found in PC, NC+200 and NC+400 groups. Meat crude protein and yellowness were influenced by inclusion of carvacrol and cinnamaldehyde. It was concluded microencapsulated carvacrol and cinnamaldehyde can replace growth-promoting antibiotic in broiler diets, ensuring performance, intestinal integrity and broiler meat quality.
Patients with immunocompromised disorders have mainly been excluded from clinical trials of vaccination against COVID-19. Thus, the aim of this prospective clinical trial was to investigate safety ...and efficacy of BNT162b2 mRNA vaccination in five selected groups of immunocompromised patients and healthy controls.
539 study subjects (449 patients and 90 controls) were included. The patients had either primary (n=90), or secondary immunodeficiency disorders due to human immunodeficiency virus infection (n=90), allogeneic hematopoietic stem cell transplantation/CAR T cell therapy (n=90), solid organ transplantation (SOT) (n=89), or chronic lymphocytic leukemia (CLL) (n=90). The primary endpoint was seroconversion rate two weeks after the second dose. The secondary endpoints were safety and documented SARS-CoV-2 infection.
Adverse events were generally mild, but one case of fatal suspected unexpected serious adverse reaction occurred. 72.2% of the immunocompromised patients seroconverted compared to 100% of the controls (p=0.004). Lowest seroconversion rates were found in the SOT (43.4%) and CLL (63.3%) patient groups with observed negative impact of treatment with mycophenolate mofetil and ibrutinib, respectively.
The results showed that the mRNA BNT162b2 vaccine was safe in immunocompromised patients. Rate of seroconversion was substantially lower than in healthy controls, with a wide range of rates and antibody titres among predefined patient groups and subgroups. This clinical trial highlights the need for additional vaccine doses in certain immunocompromised patient groups to improve immunity.
Knut and Alice Wallenberg Foundation, the Swedish Research Council, Nordstjernan AB, Region Stockholm, Karolinska Institutet, and organizations for PID/CLL-patients in Sweden.
•Semi-empirical methods for pipelines failure pressure estimation were investigated.•Shell finite element models were employed to assess the results.•Guidelines for employing the semi-empirical ...methods studied were established.•Pit corrosion in pipelines was analyzed using finite element analysis.•An analytical procedure for failure pressure estimation of pit corrosion in pipelines has been derived from numerical results.
Corrosion defects which occur in oil and gas pipelines may compromise the safety of such structures. This paper makes an assessment of the accuracy of some of the analytical procedures commonly employed by industry to calculate the failure pressure of corroded pipelines via finite element analyses (FEA). Second, this paper studies the stress distribution on isolated pit corrosion defects also via FEA. Analytical procedures to calculate the failure pressure associated to isolated pits are not available yet. Thus, based on the stress analysis results, such a procedure is devised and proposed here.
Recipient-donor chimerism is routinely analyzed after allogeneic hematopoietic stem cell transplantation (HSCT) to monitor engraftment and graft rejection. For malignancies, chimerism can also be ...used to screen for disease relapse post-HSCT but methodology and interpretation of results are not standardized and likely depend on underlying diagnosis. We have implemented highly sensitive and accurate methodologies for chimerism analysis for the purpose of improving relapse prediction. Here, we report an exploratory retrospective analysis of clinical routine chimerism results from all 154 HSCTs for acute myeloid leukemia (AML) performed at our center during the years 2015-2020 with the aim of suggesting a clinically useful threshold at which risk of relapse is high. Relapse was not reliably predicted based on single elevated chimerism values obtained before time of overt relapse. However, early complete donor chimerism, here defined as recipient DNA < 0.2% in CD33
cells in any blood or bone marrow sample taken during the first 60 days after HSCT, correlated inversely with relapse during the observation time (log-rank test P = 0.033). We propose that achievement of complete chimerism determined early after HSCT using sensitive methods can be used for risk-stratification of AML patients.
•Valproic acid (VPA) and suberoylanilide hydroxamic acid (SAHA) are histone deacetylase inhibitors with excellent repurposing value.•VPA, compared to SAHA showed superior activity against ...extracellular and intracellular Mycobacterium tuberculosis (M.tb).•Isoniazid (INH)/rifampicin (RIF) and VPA/SAHA co-treatment inhibited intracellular M.tb survival in a shorter time span than monotherapy.•Clinical evaluation of VPA and SAHA as adjuncts to standard therapy to reduce treatment duration and improve outcomes in TB is warranted
New tuberculosis (TB) drug treatment regimens are urgently needed. This study evaluated the potential of the histone deacetylase inhibitors (HDIs) valproic acid (VPA) and suberoylanilide hydroxamic acid (SAHA) to enhance the effects of first-line anti-TB drugs against intracellular Mycobacterium tuberculosis.
M. tuberculosis H37Rv cultures were exposed to VPA or SAHA over 6 days, in the presence or absence of isoniazid (INH) and rifampicin (RIF). The efficacy of VPA and SAHA against intracellular M. tuberculosis with and without INH or RIF was tested by treating infected macrophages. Bactericidal activity was assessed by counting mycobacterial colony-forming units (CFU).
VPA treatment exhibited superior bactericidal activity to SAHA (2-log CFU reduction), while both HDIs moderately improved the activity of RIF against extracellular M. tuberculosis. The bactericidal effect of VPA against intracellular M. tuberculosis was greater than that of SAHA (1-log CFU reduction) and equalled that of INH (1.5-log CFU reduction). INH/RIF and VPA/SAHA combination treatment inhibited intracellular M. tuberculosis survival in a shorter time span than monotherapy (3days vs. 6 days).
VPA and SAHA have adjunctive potential to World Health Organization-recommended TB treatment regimens. Clinical evaluation of the two drugs with regard to reducing the treatment duration and improving treatment outcomes in TB is warranted.
The protective role of B cells and humoral immune responses in tuberculosis infection has been regarded as inferior to cellular immunity directed to the intracellular pathogen Mycobacterium ...tuberculosis. However, B-cell–mediated immune responses in tuberculosis have recently been revisited in the context of B-cell physiology and antigen presentation. We discuss in this review the diverse functions of B cells in tuberculosis, with a focus on their biological and clinical relevance to progression of active disease. We also present the peptide microarray platform as a promising strategy to discover unknown antigenic targets of M. tuberculosis that could contribute to the better understanding of epitope focus of the humoral immune system against M. tuberculosis.
Memory B cells (MBCs) epitomize the adaptation of the immune system to the environment. We identify two MBC subsets in peripheral blood, CD27(dull) and CD27(bright) MBCs, whose frequency changes with ...age. Heavy chain variable region (VH) usage, somatic mutation frequency replacement-to-silent ratio, and CDR3 property changes, reflecting consecutive selection of highly antigen-specific, low cross-reactive antibody variants, all demonstrate that CD27(du)(ll) and CD27(bright) MBCs represent sequential MBC developmental stages, and stringent antigen-driven pressure selects CD27(du)(ll) into the CD27(bright) MBC pool. Dynamics of human MBCs are exploited in pregnancy, when 50% of maternal MBCs are lost and CD27(du)(ll) MBCs transit to the more differentiated CD27 bright stage. In the postpartum period, the maternal MBC pool is replenished by the expansion of persistent CD27(du)(ll) clones. Thus, the stability and flexibility of human B cell memory is ensured by CD27(du)(ll) MBCs that expand and differentiate in response to change.
Targeted antiviral immune responses to the widespread human pathogens cytomegalovirus (CMV) and Epstein-Barr virus (EBV) play a pivotal role in determining immune fitness. We show here for the first ...time that tumor-infiltrating B cell (TIB)- derived immunoglobulin G (IgG) from patients with pancreatic cancer or glioblastoma have unique anti-CMV/EBV immune recognition patterns compared to serum IgG. There is also great heterogeneity between patients, as well as between serum and TIB-IgG, while some viral targets elicited strongly both T-cell and IgG reactivity in tumor infiltrating T- and B-cells. These observations suggest that the anti-CMV/EBV humoral immune response in situ is highly unique and can be instrumental in developing next-generation immuno-biomarkers in addition to supplementing cellular therapy strategies for personalized cancer therapy targeting CMV or EBV in the tumor microenvironment.
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