Intravenous calcium infusion in a calving protocol disrupts calcium homeostasis compared with an oral calcium supplement.

Hypocalcemia is a common postpartum condition in dairy cows, which negatively affects health and production. Intravenous Ca infusions are commonly included in calving protocols to prevent or mitigate the effect of hypocalcemia in multiparous cows. Thus, we sought to contrast the effect of intravenous Ca infusion against voluntary oral Ca intake on Ca metabolism. Serum total Ca (tCa) and whole-blood ionized Ca (iCa) were monitored in 24 multiparous Holstein cows after parturition. Precalving diets were formulated with a positive dietary cation-anion difference of 172 mEq/kg of DM and contained 4.1 g of Ca/kg of DM. At parturition, cows were blocked by calving sequence and calcemic status as either normocalcemic (cutoff threshold of iCa ≥1.10 mmol/L) or hypocalcemic (cutoff threshold of iCa <1.10 mmol/L). Cows in each block were randomly assigned to 1 of 2 treatments: either an oral source of Ca (Ca-Oral; n = 12) or an intravenous source of Ca (Ca-IV; n = 12). Cows in the Ca-Oral group were offered a 20-L commercial Ca suspension (48 g of Ca) for voluntary consumption. The supplement contained Ca carbonate, Ca formate, Ca propionate, and other minerals and vitamins (Farm-O-San Reviva, Trouw Nutrition, Amersfoort, the Netherlands). Cows in the Ca-IV group received a 450-mL intravenous Ca solution (13 g of Ca) that contained 298 mg/mL of Ca gluconate, 33 mg/mL of magnesium chloride, and 82 mg/mL of boric acid (AmosCAL, Kommer-Biopharm BV, Heiloo, the Netherlands). Both treatments were initiated within 25 ± 10 min after calving. The oral Ca suspension was offered to cows in a 25-L bucket and was available for 10 min. All cows in the Ca-Oral group voluntarily consumed the entire 20 L of the Ca suspension within 5 min. Blood samples for Ca analyses were collected at 0 (before treatment initiation), 1, 3, 10, and 18 h relative to treatment, and at 0700 and 1900 h for the next 2 consecutive days, to represent the 24-, 36-, 48-, and 60-h sampling time points. In Ca-IV cows, both iCa and tCa concentrations peaked at 1 h (1.54 mmol/L for iCa and 2.85 mmol/L for tCa) and declined to a nadir at 24 h following treatment initiation (0.94 mmol/L for iCa and 1.74 mmol/L for tCa). Although whole-blood iCa and serum tCa were higher at 1 and 3 h in Ca-IV cows, concentrations of iCa were greater for Ca-Oral cows at 18, 24, and 36 h and for tCa at 24 and 36 h. Our data indicate that intravenous Ca infusion immediately induced a state of hypercalcemia followed by lower whole-blood iCa and serum tCa concentrations 24 h later compared with oral Ca.

Design and Synthesis of a Novel Series of Orally Bioavailable, CNS-Penetrant, Isoform Selective Phosphoinositide 3-Kinase γ (PI3Kγ) Inhibitors with Potential for the Treatment of Multiple Sclerosis (MS).

The lipid kinase phosphoinositide 3-kinase γ (PI3Kγ) has attracted attention as a potential target to treat a variety of autoimmune disorders, including multiple sclerosis, due to its role in immune modulation and microglial activation. By minimizing the number of hydrogen bond donors while targeting a previously uncovered selectivity pocket adjacent to the ATP binding site of PI3Kγ, we discovered a series of azaisoindolinones as selective, brain penetrant inhibitors of PI3Kγ. This ultimately led to the discovery of 16, an orally bioavailable compound that showed efficacy in murine experimental autoimmune encephalomyelitis (EAE), a preclinical model of multiple sclerosis.

The effect of spiritual interventions addressing existential themes using a narrative approach on quality of life of cancer patients: a systematic review and meta-analysis.

OBJECTIVE: The aim of this study was to examine the effect of spiritual interventions on quality of life of cancer patients. METHODS: We conducted our search on June 6, 2014 in Medline, PsycINFO, Embase, and PubMed. All clinical trials were included that compared standard care with a spiritual intervention that addressed existential themes using a narrative approach. Study quality was evaluated by the Cochrane Risk of Bias Tool. RESULTS: A total of 4972 studies were identified, of which 14 clinical trials (2050 patients) met the inclusion criteria, and 12 trials (1878 patients) were included in the meta-analysis. The overall risk of bias was high. When combined, all studies showed a moderate effect (d) 0.50 (95% CI = 0.20-0.79) 0-2 weeks after the intervention on overall quality of life in favor of the spiritual interventions. Meta-analysis at 3-6 months after the intervention showed a small insignificant effect (0.14, 95% CI = -0.08 to 0.35). Subgroup analysis including only the western studies showed a small effect of 0.17 (95% CI = 0.05-0.29). Including only studies that met the allocation concealment criteria showed an insignificant effect of 0.14 (95% CI = -0.05 to 0.33). CONCLUSIONS: Directly after the intervention, spiritual interventions had a moderate beneficial effect in terms of improving quality of life of cancer patients compared with that of a control group. No evidence was found that the interventions maintained this effect up to 3-6 months after the intervention. Further research is needed to understand how spiritual interventions could contribute to a long-term effect of increasing or maintaining quality of life.