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Subclinical chronic inflammation (SCI) is associated with impaired animal growth. Previous work has demonstrated that olive-derived plant bioactives exhibit anti-inflammatory properties that could possibly counteract the growth-depressing effects of SCI. To test this hypothesis and define the underlying mechanism, we conducted a 30-day study in which piglets fed an olive-oil bioactive extract (OBE) and their control counterparts (C+) were injected repeatedly during the last 10 days of the study with increasing doses of Escherichia coli lipopolysaccharides (LPS) to induce SCI. A third group of piglets remained untreated throughout the study and served as a negative control (C-). In C+ pigs, SCI increased the circulating concentration of interleukin 1 beta (p < 0.001) and decreased feed ingestion (p < 0.05) and weight gain (p < 0.05). These responses were not observed in OBE animals. Although intestinal inflammation and colonic microbial ecology was not altered by treatments, OBE enhanced ileal mRNA abundance of tight and adherens junctional proteins (p < 0.05) and plasma recovery of mannitol (p < 0.05) compared with C+ and C-. In line with these findings, OBE improved transepithelial electrical resistance (p < 0.01) in TNF-α-challenged Caco-2/TC-7 cells, and repressed the production of inflammatory cytokines (p < 0.05) in LPS-stimulated macrophages. In summary, this work demonstrates that OBE attenuates the suppressing effect of SCI on animal growth through a mechanism that appears to involve improvements in intestinal integrity unrelated to alterations in gut microbial ecology and function.

Antiangiogenics promote immune activation by reducing myeloid-derived suppressor cells (MDSCs) and enhancing natural killer (NK) and T cell functions in metastatic RCC patients. However, these effects are transient, leading to compensatory immunosuppression. Platelets (PLT) and their extracellular vesicles (PLT-EVs) modulate immune and angiogenic pathways, suggesting a role in immune reprogramming during therapy. Circulating EVs were longitudinally profiled in metastatic RCC patients (n=8) undergoing Pazopanib therapy. EVs, isolated by differential ultracentrifugation from baseline, 3- and 6-month plasma samples, were characterized by bead-based multiplex assay and nanoparticle tracking analysis. Results were correlated with blood counts, RNA-seq and flow cytometry immune profiles. Pazopanib induced temporally structured EV compartment alterations. After three months, EVs were enriched in immune markers (CD8, CD56, CD19, CD1c, HLA-DR), consistent with immune activation, whereas PLT-derived markers (CD41b, CD42a, CD29) were diminished. By six months, PLT-EV markers recovered, with CD62P and CD29 EVs co-expressing immunoregulatory and angiogenic molecules (CD209, CD105). PLT-EV abundance correlated with the expansion of regulatory T cells (Tregs), PD-L1 monocytes and MDSCs, together with suppression of NK cells. PLT activation and PDGF signaling pathways decreased in PBMC from patients with clinical benefit. Despite the small sample size and absence of functional experiments, our results suggest that Pazopanib promotes cytotoxic immune programs but, by six months, reprograms PLT-EVs towards different adhesion characteristics contributing to Treg and MDSC expansion while suppressing NK activity. PLT-EVs may influence the balance between immune activation and suppression during anti-angiogenic therapy, suggesting PLT-EVs as biomarkers and therapeutic targets in mRCC.

ObjectiveThe objective was to compare the results of performance-based and self-assessed measures of health literacy (HL) and to evaluate the contribution of their joint use in assessing some HL antecedents.DesignThis was a cross-sectional study.SettingThe study was conducted on the general population in Florence (Italy).ParticipantsThis study is part of a larger one, where participants were randomly selected from the registries of 11 general practitioners working in the municipality of Florence. Inclusion criteria were the following: 18–69 years of age and Italian speaking. Exclusion criteria included cognitive impairment, severe psychiatric disease or end-stage disease. In this paper, 212 adults were included.Outcome measuresHL was measured using the European Health Literacy Survey Questionnaire (HLS-EU-Q16) and the Newest Vital Sign (NVS). The HL levels obtained by means of the two measurement tools were combined into a new variable that described three different levels of HL skills: low HL skills, partial HL skills and high HL skills. Multivariate ordinal logistic regression analysis was performed to assess the predictive roles of age class, educational level and financial resources with respect to HL skills.ResultsTwenty-two per cent of the sample had high HL skills, 28.3% had low HL skills and 49.5% had partial HL skills. Educational level, age class and financial resources were significantly associated with HL skills, with OR values being higher than those obtained using the NVS or the HLS-EU-Q16 individually.ConclusionThe combination of the results obtained using the NVS and the HLS-EU-Q16 improves the understanding of HL. The new variable generated by this combination could be considered as a different way to assess HL and its multidimensional contents.

We determined whether sheep discriminate among different mineral supplements containing P and Mg and if they modify their selection as a function of the basal diet received. Forty lambs were offered four-way choices among inorganic sources of P and Mg: magnesium oxide in its coarse 1) C-MgO and granular 2) MgO forms and magnesium phosphate: 3) Mag33 (33% Mg and 2.7% P), and 4) MGP (25% Mg and 15% P), and two-way choices between MGP and each of the other minerals, and between MgO and C-MgO (baseline). Subsequently, lambs were randomly assigned to four groups (10 lambs/group) and fed rations such that the levels of Mg and P were low (LMg_LP), adequate (NMg_NP), low in Mg and adequate in P (LMg_NP), or adequate in Mg and low in P (NMg_LP). After 29 d, choice tests (post-deficiency) were repeated. During baseline, lambs ate and preferred Mag33 > C-MgO = MGP > MgO (P < 0.05). This pattern remained during post-deficiency tests, but lambs in LMg_LP and LMg_NP increased their preference for MGP and C-MgO, respectively, whereas lambs in NMg_LP increased their preference for C-MgO and MGP relative to baseline (P < 0.05). The serum concentrations of P and Mg increased after preference tests, and preference for MgO and MGP in low-Mg groups increased as the serum concentration of Mg declined (P < 0.05). Thus, lambs discriminated among different minerals and some groups modified their preferences based on the basal diets received, which rectified mineral imbalances.

Health literacy(HL) has recently been proposed as a potential mediator in the pathway through which socio-economic status(SES) affects health. However, empirical research investigating the contribution of HL in this relationship remains scarce. This study investigated whether functional HL mediates the association between SES and self-reported health(SRH) in an adult population-based sample. The study adopted a cross-sectional design. Education level and financial status were used as measures of SES, while functional HL was assessed with the Newest Vital Sign. Moderated mediation analyses were conducted using SES variables as independent variables, SRH as dependent variable and functional HL as mediator variable. Furthermore, age, sex and chronic diseases were tested as moderators of the effect mediated by functional HL. 452 subjects completed the study (58,8% female; mean age 53,25±11,7). Results showed that functional HL mediates on average 18.5% of the association between education and SRH (p = 0.02) and 12.9% (p = 0.01) of the association between financial status and SRH. Furthermore, the proportion of effect mediated by functional HL was found to be higher in lower socio-economic classes for both SES variables considered. No significant moderation effects of age, sex or chronic diseases were observed for both SES variables. Findings suggest that functional HL may serve as a pathway by which SES affects health status, especially in lower SES groups. HL may be a valuable and actionable intermediate target for addressing health inequalities. However, further studies are needed to better define the mediating role of HL across socio-economic classes.

Abstract We determined whether sheep discriminate among mineral supplements containing P and Mg and if they modify their selection as a function of need. During 3 consecutive days, 40 lambs under a basal diet of alfalfa pellets and barley grain were offered 4-way choices among= (1) MgO-powder form (MgO-82% Mg), (2)MgO-coarse form (C-MgO-82% Mg), (3) Magnesium Phosphate (Bolifor® Mag33-33% Mg, 2.7% P), and (4)Magnesium Phosphate (Bolifor® MGP-25% Mg, 15% P), and 2-way choices between MGP and each of the other minerals, and between MgO and C-MgO (Baseline). Subsequently, lambs were randomly assigned to 4 groups (10 lambs/group) and fed rations such that the levels of Mg and P were low (LMg-LP), adequate (NMg-NP), low in Mg and adequate in P (LMg-NP), or adequate in Mg and low in P (NMg-LP). After 29 d, groups received again the described choices (post-deficiency). Intake and preference indexes during choice tests were analyzed as a split-plot design with lambs nested within group and day as the repeated measure. During Baseline, lambs ate and preferred Mag33 > C-MgO = MGP > MgO (P < 0.05). This pattern remained during post-deficiency, but lambs in LMg showed the greatest preference for Mag33 (P < 0.05). All lambs preferred C-MgO over MgO or MGP (P < 0.05), but lambs in LMg-NP showed the greatest preference for C-MgO (P < 0.05) and the lowest preference for MGP (P < 0.05). Serum concentrations of P (7.1 to 8.4±0.2 mg/dL) and Mg (3.0 to 3.9±0.1 mg/dL) increased after post-deficiency tests relative to Baseline (P < 0.05). Lambs discriminated among different mineral sources and the physical form of MgO influenced preference. Groups in low Mg diets favored sources of Mg with no or low concentration of P, and when P was adequate (LMg-NP), they reduced their preference for the source with the greatest concentration of P (MGP).

We determined whether lambs discriminate among mineral supplements containing P and Ca and if they modify their choices as a function of need. During 3 consecutive days, 40 lambs under a basal diet of alfalfa pellets and barley were offered 4-way choices among= (1) Bolifor® Monosodium phosphate (MSP-24% P), (2) Bolifor® Magnesium phosphate (MGP-15% P, 25% Mg), (3) Bolifor® Monocalcium phosphate (MCP-22.7% P, 16.5% Ca) and (4) Dicalcium phosphate (DCP-18.5%P, 23% Ca), and 2-way choices between DCP and each of the remaining minerals (Baseline). Subsequently, lambs were randomly assigned to four groups (10 lambs/group) and fed beet pulp-based basal rations such that the levels of Ca and P were low (LCa-LP), adequate (NCa-NP), low in Ca and adequate in P (LCa-NP), or adequate in Ca and low in P (NCa-LP). After 60 d, groups had the described 4- and 2-way choices (Post-deficiency). Intake and preference indexes during choice tests were analyzed as a split-plot design with lambs nested within group and day as the repeated measure. During Baseline, lambs ate and preferred MSP > MGP > DCP = MCP (P < 0.0001). This pattern remained during post-deficiency, but in contrast to Baseline, lambs in NCa-LP, LCa-NP, and LCa-LP showed the greatest preferences for MSP (42%), MGP (42%) and MCP (22%), respectively (SEM = 4%; P < 0.05). Groups under LCa in 2-way choices showed greater preference for MCP (56%) than groups under NCa (39%; SEM = 5%; P < 0.05), and lambs in LCa-NP revealed the greatest preference for MGP (64%; SEM = 6%; P < 0.05). Serum P concentration after post-deficiency choice tests (9.7 ± 0.7 mg/dL) returned to Baseline values, but Ca concentration was 0.9 mg/dL lower (9.3 ± 0.3 mg/dL; P < 0.05) than in Baseline. Thus, lambs discriminated among mineral sources and displayed preferences reflecting their needs.

We determined whether sheep discriminate among different mineral supplements containing P and Mg and if they modify their selection as a function of the basal diet received. Forty lambs were offered four-way choices among inorganic sources of P and Mg: magnesium oxide in its coarse 1) C-MgO and granular 2) MgO forms and magnesium phosphate: 3) Mag33 (33% Mg and 2.7% P), and 4) MGP (25% Mg and 15% P), and two-way choices between MGP and each of the other minerals, and between MgO and C-MgO (baseline). Subsequently, lambs were randomly assigned to four groups (10 lambs/group) and fed rations such that the levels of Mg and P were low (LMg_LP), adequate (NMg_NP), low in Mg and adequate in P (LMg_NP), or adequate in Mg and low in P (NMg_LP). After 29 d, choice tests (post-deficiency) were repeated. During baseline, lambs ate and preferred Mag33 > C-MgO = MGP > MgO (P < 0.05). This pattern remained during post-deficiency tests, but lambs in LMg_LP and LMg_NP increased their preference for MGP and C-MgO, respectively, whereas lambs in NMg_LP increased their preference for C-MgO and MGP relative to baseline (P < 0.05). The serum concentrations of P and Mg increased after preference tests, and preference for MgO and MGP in low-Mg groups increased as the serum concentration of Mg declined (P < 0.05). Thus, lambs discriminated among different minerals and some groups modified their preferences based on the basal diets received, which rectified mineral imbalances.

The spread of bacterial resistance to antimicrobials (AMA) have intensified efforts to discontinue the non-therapeutic use of AMA in animal production. Finding alternatives to AMA, however, is currently encumbered by the obscure mechanism that underlies their growth-promoting action. In this report, we demonstrate that combinations of antibiotics and zinc oxide at doses commonly used for stimulating growth or preventing post-weaning enteritis in pigs converge in promoting microbial production of bile acids (BA) in the intestine. This leads to tissue-specific modifications in the proportion of BA, thereby amplifying BA signaling in intestine, liver, and white adipose tissue (WAT). Activation of BA-regulated pathways ultimately reinforces the intestinal protection against bacterial infection and pathological secretion of fluids and electrolytes, attenuates inflammation in colon and WAT, alters protein and lipid metabolism in liver, and increases the circulating levels of the hormone FGF19. Conceivably, these alterations could spare nutrients for growth and improve the metabolic efficiency of AMA-treated animals. This work provides evidence that BA act as signaling molecules that mediate host physiological, metabolic, and immune responses to the AMA-induced alterations in gut microbial metabolism, eventually permitting the growth-promoting action of AMA. Consequently, BA emerge as a promising target for developing efficacious alternatives to AMA.

The spread of bacterial resistance to antimicrobials (AMA) have intensified efforts to discontinue the non-therapeutic use of AMA in animal production. Finding alternatives to AMA, however, is currently encumbered by the obscure mechanism that underlies their growth-promoting action. In this report, we demonstrate that combinations of antibiotics and zinc oxide at doses commonly used for stimulating growth or preventing post-weaning enteritis in pigs converge in promoting microbial production of bile acids (BA) in the intestine. This leads to tissue-specific modifications in the proportion of BA, thereby amplifying BA signaling in intestine, liver, and white adipose tissue (WAT). Activation of BA-regulated pathways ultimately reinforces the intestinal protection against bacterial infection and pathological secretion of fluids and electrolytes, attenuates inflammation in colon and WAT, alters protein and lipid metabolism in liver, and increases the circulating levels of the hormone FGF19. Conceivably, these alterations could spare nutrients for growth and improve the metabolic efficiency of AMA-treated animals. This work provides evidence that BA act as signaling molecules that mediate host physiological, metabolic, and immune responses to the AMA-induced alterations in gut microbial metabolism, eventually permitting the growth-promoting action of AMA. Consequently, BA emerge as a promising target for developing efficacious alternatives to AMA.