Effects of Bacillus subtilis PB6 supplementation on production, metabolism, inflammatory biomarkers, and gastrointestinal tract permeability in transition dairy cows.

Objectives were to evaluate the effects of Bacillus subtilis PB6 (BSP) on gastrointestinal tract permeability, metabolism, inflammation, and production parameters in periparturient Holstein cows. Multiparous cows (n = 48) were stratified by previous 305-d mature equivalent milk yield and parity and assigned to 1 of 2 top-dressed dietary treatments 21 d before expected calving through 63 DIM: (1) control (CON; 13 g/d calcium carbonate; n = 24) or (2) BSP (13 g/d BSP; CLOSTAT, Kemin Industries, Des Moines, IA; n = 24). Gastrointestinal tract permeability was evaluated in vivo using the oral paracellular marker chromium (Cr)-EDTA. Effects of treatment, time, and treatment × time were assessed using PROC MIXED of SAS version 9.4 (SAS Institute Inc.). Prepartum dry matter intake (DMI) was unaffected by treatment; however, BSP supplementation decreased postpartum DMI relative to CON (0.7 kg). Milk yield, energy-corrected milk (ECM), fat-corrected milk (FCM), and solids-corrected milk (SCM) increased in BSP cows compared with CON (1.6, 1.8, 1.6, and 1.5 kg, respectively). Decreased DMI and increased production collectively improved feed efficiency of milk yield, ECM, FCM, and SCM for BSP cows (6, 5, 5, and 5%, respectively). No treatment differences were observed for concentrations of milk fat, protein, total solids, somatic cell count, somatic cell score, body weight, or body condition score. Milk urea nitrogen concentrations decreased (5%), whereas milk protein and lactose yield increased (5 and 2%, respectively) with BSP supplementation. Prepartum fecal pH did not differ among treatments; conversely, postpartum fecal pH was increased with BSP supplementation (0.09 pH units). Prepartum fecal dry matter percentage, starch, acetic acid, propionic acid, butyric acid, and ethanol did not differ among treatments. Postpartum concentrations of the aforementioned fecal parameters were also unaffected by treatment, but fecal propionic acid concentration was decreased (24%) in BSP cows relative to CON. Circulating glucose, nonesterified fatty acids, l-lactate, and insulin were similar between treatments both pre- and postpartum. Prepartum ß-hydroxybutyrate (BHB) did not differ between treatments, but postpartum BSP supplementation decreased (21%) circulating BHB relative to CON. Regardless of treatment, inflammatory markers (serum amyloid A and haptoglobin) peaked immediately following parturition and progressively decreased with time, but this pattern was not influenced by treatment. Postpartum lipopolysaccharide binding protein tended to be decreased on d 3 in BSP relative to CON cows (19%). Neither treatment nor time affected Cr-EDTA area under the curve. In summary, supplementing BSP had no detectable effects prepartum, but increased key postpartum production parameters. Bacillus subtilis PB6 consistently increased postpartum fecal pH and decreased fecal propionate concentrations but did not appear to have an effect on gastrointestinal tract permeability.

Effect of chromium on bioenergetics and leukocyte dynamics following immunoactivation in lactating Holstein cows.

Activated immune cells are insulin sensitive and utilize copious amounts of glucose. Because chromium (Cr) increases insulin sensitivity and may be immunomodulatory, our objective was to evaluate the effect of supplemental Cr (KemTrace Cr propionate, 20 g/d; Kemin Industries Inc., Des Moines, IA) on immune system glucose utilization and immune system dynamics following an intravenous endotoxin challenge in lactating Holstein cows. Twenty cows (320 ± 18 d in milk) were randomly assigned to 1 of 4 treatments: (1) pair-fed (PF) control (PF-CON; 5 mL of saline; n = 5), (2) PF and Cr supplemented (PF-Cr; 5 mL of saline; n = 5), (3) lipopolysaccharide (LPS)-euglycemic clamp and control supplemented (LPS-CON; 0.375 µg/kg of body weight LPS; n = 5), and (4) LPS-euglycemic clamp and Cr supplemented (LPS-Cr; 0.375 µg/kg of body weight LPS; n = 5). The experiment was conducted serially in 3 periods (P). During P1 (3 d), cows received their respective dietary treatments and baseline values were obtained. At the initiation of P2 (2 d), either a 12-h LPS-euglycemic clamp was conducted or cows were PF to their respective dietary counterparts. During P3 (3 d), cows consumed feed ad libitum and continued to receive their respective dietary treatment. During P2, LPS administration decreased dry matter intake (DMI; 40%) similarly among diets, and by experimental design the pattern and magnitude of reduced DMI were similar in the PF cohorts. During P3, LPS-Cr cows tended to have decreased DMI (6%) relative to LPS-CON cows. Relative to controls, milk yield from LPS-challenged cows decreased (58%) during P2 and LPS-Cr cows produced less (16%) milk than LPS-CON cows. During P3, milk yield progressively increased similarly in LPS-administered cows, but overall milk yield remained decreased (24%) compared with PF controls. There were no dietary treatment differences in milk yield during P3. Circulating insulin increased 9- and 15-fold in LPS-administered cows at 6 and 12 h postbolus, respectively, compared with PF controls. Compared with LPS-CON cows, circulating insulin in LPS-Cr cows was decreased (48%) at 6 h postbolus. Relative to PF cows, circulating LPS binding protein and serum amyloid A from LPS-administered cows increased 2- and 5-fold, respectively. Compared with PF cows, blood neutrophil counts in LPS-infused cows initially decreased, then gradually increased 163%. Between 18 and 48 h postbolus, the number of neutrophils was increased (12%) in LPS-Cr versus LPS-CON cows. The 12-h total glucose deficit was 220 and 1,777 g for the PF and LPS treatments, respectively, but glucose utilization following immune activation was not influenced by Cr. In summary, supplemental Cr reduced the insulin response and increased circulating neutrophils following an LPS challenge but did not appear to alter the immune system's glucose requirement following acute and intense activation.

Real-world data in the molecular era-finding the reality in the real world.

Real-world data (RWD) promises to provide a pivotal element to the understanding of personalized medicine. However, without true representation (or the reality) of the patient-disease biosystem and its molecular contributors, RWD may hamper rather than help this advancement. In this review article, we discuss RWD vs. clinical reality and the disconnects that exist currently (emphasizing molecular medicine), and methods of closing the gaps between RWD and reality.

Angiogenesis in acute and chronic leukemias.

Angiogenesis plays a key role in the growth of solid tumors. More recently, accumulating evidence has linked angiogenesis to the pathophysiology of leukemias. Different investigators have shown evidence of increased angiogenesis in the bone marrows of patients with acute and chronic leukemias. Elevated levels of angiogenic factors have also been reported in leukemic patients. A potential role for VEGF as an autocrine growth factor in AML has been suggested. Studies on the role of angiogenesis and VEGF as prognostic factors in leukemia require confirmation. The role of angiogenesis inhibitors in the treatment of leukemia is currently under investigation.

A compliance study in general practice of patients switched from phenylbutazone and oxyphenbutazone to naproxen and other non-steroidal anti-inflammatory drugs.

Fifty-nine patients on long-term treatment with phenylbutazone or oxyphenbutazone for chronic rheumatic conditions were switched to treatment with naproxen and followed-up for 6 months in a compliance study. All patients were started on 500 mg naproxen twice daily but adjustment of the dosage was permitted. During the 6 months of the study only 3 patients returned to treatment with phenylbutazone. Of the remaining 56 patients, 45 were still taking naproxen after 6 months, 9 were changed to other non-steroidal, anti-inflammatory drugs and 2 were lost to follow-up. The study demonstrates that in routine general practice, phenylbutazone and oxyphenbutazone can be successfully replaced by less toxic drugs.