The effects of concurrent increases in supplementation of calcium and phytase on growth performance, balance of Ca and P, and bone mineralization in nursery pigs.

The objective of this study was to investigate the effects of concomitantly increasing supplementation of Ca and phytase on growth performance, balance of Ca and P, and bone mineralization in nursery pigs. There were eight experimental diets. The positive control (PC) one and two were formulated to contain 0.64% and 0.85% total Ca, respectively, whereas the dietary concentrations of other nutrients were identical and adequate. The negative control (NC) was deficient in total Ca (0.48%) and total P (0.41%). Five combinations of incremental levels of Ca and phytase (0.48% and 1,750 phytase units [FYT]/kg, 0.52% and 2,000 FYT/kg, 0.55% and 2,250 FYT/kg, 0.59% and 2,600 FYT/kg, and 0.63% and 3,000 FYT/kg) were added to the NC to establish the remaining five experimental diets. Each diet was fed to six pens of six pigs (three barrows and three gilts per pen). All diets contained 3 g/kg TiO2, and fecal samples were collected from each pen during the trial. In the end, one pig per pen was euthanized to collect the right tibia and urine in bladder. The results showed that the pigs of NC gained less weight, consumed less feed, and utilized feed less efficiently than their counterparts fed the PC and the treatments with phytase (P < 0.01). With increasing supplementation of Ca and phytase, there was a tendency for gain:feed to decrease (P < 0.10). There was a significant reduction in bone dry weight; and in percentages, as well as weights of bone ash, Ca, and P; in pigs of NC compared with pigs of PC1, PC2, or phytase treatments. In comparison to PC2, PC1 and phytase treatments resulted in a higher percentage of bone P and greater weights of bone ash, Ca, and P (P < 0.05). There was no significant effect of concurrent supplementation of Ca and phytase on bone mineralization. The NC had significantly lower apparent total tract digestibility (ATTD) of Ca and P, lower concentrations of digestible Ca and P, but a higher ATTD Ca/ATTD P ratio than PC1, PC2, or the phytase treatments. The averages of ATTD of Ca and P in treatments with phytase were significantly higher than PC1 or PC2 (P < 0.01). With increasing addition of Ca and phytase, the ATTD of P, digestible Ca and P, and the ATTD Ca/ATTD P ratio increased linearly (P < 0.05), which contrasted with a linear reduction in ATTD of Ca (P < 0.05). Meanwhile, there was a linear (P < 0.01) increase in the concentration of urinary Ca. In conclusion, increasing the dietary supplementation of phytase in conjunction with the increasing dietary Ca level increased the dietary ATTD Ca/ATTD P ratio without damaging the absorption of P in the current study. The higher ATTD Ca/ATTD P ratio did not improve the bone mineralization markedly and thus the extra Ca was voided through urine.

The effects of increasing dietary total Ca/total P ratios on growth performance, Ca and P balance, and bone mineralization in nursery pigs fed diets supplemented with phytase.

The objective of this study was to investigate the effects of increasing dietary total Ca/total P ratios on growth performance, digestibility of Ca and P, bone mineralization, and concentrations of Ca and P in urine and plasma in nursery pigs. There were six diets in a randomized complete block design, including one positive control and five diets corresponding to five total Ca/total P ratios: 0.55, 0.73, 0.90, 1.07, and 1.24 (analyzed as 0.58, 0.75, 0.93, 1.11, and 1.30). These five diets were deficient in P but supplemented with 1,000 phytase units/kg feed. Each diet was fed to six pens of eight pigs (four barrows and four gilts per pen). All diets contained 3 g/kg TiO2, and fecal samples were collected from each pen on days 5-7 of trial. At the end, one pig per pen was sacrificed to collect the right tibia and urine in the bladder. The results showed that increasing dietary Ca/P ratio to 0.93 increased gain:feed but then gain:feed decreased as the Ca/P ratio was increased to 1.30 (linear and quadratic, P < 0.05). Although average daily gain and final BW were unaffected by changing Ca/P ratio in diet, dry bone weight; weights of bone ash, Ca and P; and bone Ca/P ratio increased linearly (P < 0.001) with increasing dietary Ca/P ratio. The percent bone Ca showed a tendency to increase (P = 0.064). Increasing dietary Ca/P ratio decreased apparent total tract digestibility (ATTD) of Ca and P linearly (P < 0.05) and the concentration of digestible P linearly (P < 0.001), but increased the concentration of digestible Ca (linear and quadratic effects: P < 0.01) and the digestible Ca/P ratio (linear effect: P < 0.001). In plasma, the concentration of Ca increased both linearly (P < 0.01) and quadratically (P = 0.051), whereas the concentration of P tended (linear and quadratic, P < 0.10) to decrease with increasing dietary Ca/P ratio. Similarly, in urine, the concentration of Ca increased both linearly and quadratically (P < 0.05), whereas the concentration of P decreased linearly (P < 0.01). In conclusion, increasing the dietary Ca/P ratio reduced feed efficiency but increased bone mass and the amounts of Ca and P deposited in bone of nursery pigs fed diets supplemented with 1,000 FYT/kg phytase. The increases in bone growth led to a reduction of urinary P excretion that exceeded the decreased digestible P supplied in diet with the widening dietary Ca/P ratios.

Use of fixed calcium to phosphorus ratios in experimental diets may create bias in phytase efficacy responses in swine.

The objective of this study was to investigate the effects of two dietary total Ca/P ratios on available P release by phytase, measured using growth performance and bone mineralization with 528 barrows and gilts according to a randomized complete block design. Three were 11 diets in a factorial of 2 by 4 plus 3, including 3 reference diets consisting of 0.25% (control), 0.70%, or 1.15% monocalcium phosphate (MCP) and 8 diets from combining 4 phytase doses (500, 1,000, 2,000, and 3,000 FYT/kg) with 0.25% MCP and 2 dietary Ca/P ratios (1.05 and 1.20). Each diet was fed to 6 pens of 8 pigs. All diets contained 3 g/kg TiO2, and fecal samples were collected from each pen on d 13-15 of trial. At the end of trial, one pig per pen was sacrificed to collect a tibia and urine in the bladder. The results showed that MCP improved growth performance linearly (P < 0.01), whereas both a linear and quadratic response was observed with the addition of phytase. The MCP increased the percent bone ash and weights of bone ash, Ca, and P linearly (P < 0.01). At both Ca/P ratios, increasing supplementation of phytase increased the percent bone ash and weights of bone ash, Ca, and P both linearly and quadratically (P < 0.05). Both MCP and phytase significantly increased digestibility of Ca and P as well as digestible Ca and P in diets and reduced the digestible Ca/P ratio. The dietary Ca/P ratio of 1.20 resulted in poorer feed utilization efficiency, more digestible Ca, greater percent bone ash, Ca, and P and heavier weights of bone Ca and P than the ratio of 1.05 (P < 0.05). The ratio of 1.20 elicited numerically higher available P release values from phytase, with percent bone ash and bone P weight as the response variables, but significantly lower values with gain:feed. The urinary concentration of Ca increased linearly (P < 0.01) with increasing digestible Ca/P ratios whilst urinary concentration of P decreased quadratically (P < 0.01). In conclusion, fixing the same total Ca/total P ratio in diets supplemented with increasing phytase dosing created an imbalance of digestible Ca and P, which could have an adverse effect on bone mineralization and thus compromise the phytase efficacy relative to mineral P.

The Calcitriol/Vitamin D Receptor System Regulates Key Immune Signaling Pathways in Chronic Lymphocytic Leukemia.

It has been proposed that vitamin D may play a role in prevention and treatment of cancer while epidemiological studies have linked vitamin D insufficiency to adverse disease outcomes in various B cell malignancies, including chronic lymphocytic leukemia (CLL). In this study, we sought to obtain deeper biological insight into the role of vitamin D and its receptor (VDR) in the pathophysiology of CLL. To this end, we performed expression analysis of the vitamin D pathway molecules; complemented by RNA-Sequencing analysis in primary CLL cells that were treated in vitro with calcitriol, the biologically active form of vitamin D. In addition, we examined calcitriol effects ex vivo in CLL cells cultured in the presence of microenvironmental signals, namely anti-IgM/CD40L, or co-cultured with the supportive HS-5 cells; and, CLL cells from patients under ibrutinib treatment. Our study reports that the calcitriol/VDR system is functional in CLL regulating signaling pathways critical for cell survival and proliferation, including the TLR and PI3K/AKT pathways. Moreover, calcitriol action is likely independent of the microenvironmental signals in CLL, since it was not significantly affected when combined with anti-IgM/CD40L or in the context of the co-culture system. This finding was also supported by our finding of preserved calcitriol signaling capacity in CLL patients under ibrutinib treatment. Overall, our results indicate a relevant biological role for vitamin D in CLL pathophysiology and allude to the potential clinical utility of vitamin D supplementation in patients with CLL.

Implementation of HPV-based Cervical Cancer Screening Combined with Self-sampling Using a Midwifery Network Across Rural Greece: The GRECOSELF Study.

Self-sampling for human papillomavirus (HPV) testing is an alternative to physician sampling particularly for cervical cancer screening nonattenders. The GRECOSELF study is a nationwide observational cross-sectional study aiming to suggest a way to implement HPV-DNA testing in conjunction with self-sampling for cervical cancer screening in Greece, utilizing a midwifery network. Women residing in remote areas of Greece were approached by midwives, of a nationwide network, and were provided with a self-collection kit (dry swab) for cervicovaginal sampling and asked to answer a questionnaire about their cervical cancer screening history. Each sample was tested for high-risk (hr) HPV with the Cobas HPV test. HrHPV-Positive women were referred to undergo colposcopy and, if needed, treatment according to colposcopy/biopsy results. Between May 2016 and November 2018, 13,111 women were recruited. Of these, 12,787 women gave valid answers in the study questionnaire and had valid HPV-DNA results; hrHPV prevalence was 8.3%; high-grade cervical/vaginal disease or cancer prevalence was 0.6%. HrHPV positivity rate decreased with age from 20.7% for women aged 25-29 years to 5.1% for women aged 50-60 years. Positive predictive value for hrHPV testing and for HPV16/18 genotyping ranged from 5.0% to 11.6% and from 11.8% to 27.0%, respectively, in different age groups. Compliance to colposcopy referral rate ranged from 68.6% (for women 25-29) to 76.3% (for women 40-49). For women residing in remote areas of Greece, the detection of hrHPV DNA with the Cobas HPV test, on self-collected cervicovaginal samples using dry cotton swabs, which are provided by visiting midwives, is a promising method for cervical cancer secondary prevention.