Responses to incremental nutrient supply on energy and protein metabolism in pre-weaning dairy calves.

Recently reviewed development objectives and feeding practices in young dairy calves require an adaptation of nutrient recommendations set for milk replacer (MR) composition. Nutrient requirements of calves younger than 21 d of age, and those of calves fed with high levels of milk replacer are insufficiently quantified. The efficiency at which macronutrients are utilized, particularly protein, substantially diminishes with age, and there is little data for the first weeks of life. In addition, in older (pre-)ruminants, protein and energy can be simultaneously limiting for protein gain. Whether this also applies to calves in the first weeks of life is unknown. Therefore, this study aimed to quantify the responses in protein and fat gain to incremental supply of protein, fat, or lactose to MR in very young calves. Thirty-two groups of 3 mixed-sex Holstein-Frisian newborn calves (3.4 ± 1.6 d of age), were randomly assigned to one of 4 dietary treatments applied for 19 d: a basal MR (23.3% CP, 21.2% CF and 48.8% lactose of DM), provided at 550 kJ/kg BW0.85 per day (CON; n = 24), or the basal MR incrementally supplied with 126 kJ of DE/BW0.85 per day as milk fat (+FAT; n = 23), lactose (+LAC; n = 24) or milk protein (+PRO; n = 23). Calves were fed MR in 2 daily meals and had ad libitum access to water, but did not have access to calf starter nor any other solid feed. After 2 weeks of adaptation to their respective diets, groups of calves were placed for one week in an open-circuit respiration chamber for nitrogen and energy balance measurements (5 d). The incremental nutrient efficiencies indicate what percentage of extra intake of nutrients is retained. In this study, we observed that with every 100 g increase in protein intake, 52% was converted into protein deposition, while 44% contributed to heat production. Similarly, a 100 g increase in fat intake resulted in 67% being stored as fat, 22% being released as heat, and only 5% being retained as protein. Likewise, a 100 g increment in lactose intake led to 49% being stored as fat, with 38% being released as heat. Additional protein intake was not deposited as fat, extra energy intake (fat, and additional lactose) increased post absorptive N efficiency in young calves.

Fat composition of milk replacer influences growth performance, feeding behavior, and plasma fatty acid profile in ad libitum-fed calves.

Fat composition in milk replacers (MR) for calves differs from bovine milk fat in multiple ways. The aim of the study was to investigate the impact of different approaches of formulating fat in MR on growth, ad libitum intakes of MR and solid feeds, as well as blood metabolites in dairy calves. Upon 24 to 96 h after birth, 63 calves were acquired from dairy farms and incorporated into the study. Calves were blocked based on arrival day and randomly assigned within each block to one of 3 treatments differing in MR fat composition (n = 21 per group): VG was based on vegetable fats including 80% rapeseed and 20% coconut fats; AN was formulated with animal fats including 65% lard and 35% dairy cream; and MX with a mixture of 80% lard and 20% coconut fats. All 3 MR contained 30% fat, 24% crude protein, and 36% lactose and were formulated to have a fatty acid profile resembling that of milk fat. From arrival onward (3.1 ± 0.84 d of age; means ± standard deviation), calves were group housed and were offered an ad libitum supply of MR at 135 g/L (13.5% solids). Weaning was gradual and induced between wk 7 and 10, after which calves were fed only solid feeds. Starter feed, chopped straw, and water were offered ad libitum throughout the study. Calves were weighed, and blood was collected weekly until d 84 after arrival. Preweaning average daily gain was greater in calves fed AN (915 g/d) than other treatments (783 g/d), whereas no differences were detected in the weaning and postweaning phases. Preweaning MR intake was greater in calves fed AN than MX from wk 2 to 6 and was also higher in calves fed AN than VG in wk 5 and 6. Consistently, the number of rewarded visits during the ad libitum phase was greater in calves fed AN than MX, whereas VG showed no differences. This led to a higher preweaning total metabolizable energy intake in calves fed AN than in calves fed VG and MX. Serum cholesterol was higher, and serum albumin was lower in calves fed VG than other treatments. The proportion of high-density lipoprotein cholesterol in total plasma cholesterol was lower and that of low-density lipoprotein (LDL) cholesterol was higher in calves fed VG compared with other treatments. Overall, the fatty acid profile of plasma largely mirrored the MR fat composition during the preweaning period. Feeding AN enhanced MR intake and improved preweaning growth compared with other treatments. Feeding VG resulted in a marked increase in plasma cholesterol, particularly in the form of LDL cholesterol, which could be linked to an excessive intake of polyunsaturated fatty acids. These findings underscore the importance of formulating the fat content of MR to be similar to bovine milk fat.

Water, mineral, and blood acid-base balance in calves with naturally occurring diarrhea receiving two alternative oral rehydration solutions or a placebo.

Quantifying the water and mineral losses in feces is essential to determine the optimal composition of oral rehydration solutions (ORS) for diarrheic animals. In a randomized complete block design, this study evaluated water, mineral, and blood acid-base balance of calves with naturally occurring diarrhea receiving ORS or a placebo. On d 0, 45 calves (age: 18 ± 3.2 d; mean ± SD) were selected based on the presence of visual signs of diarrhea, such as dirty tail or wet feces, along with clinical symptoms evaluated by measuring the skin turgor and the degree of enophthalmos. On d 1, calves were divided into blocks of 3 animals based on blood base excess (BE) measured at 0900 h, and within each block, calves were randomly assigned to 1 of 3 treatments (15 calves per treatment) including (1) a hypertonic ORS (HYPER; Na+ = 110 mmol/L; 370 mOsm/kg; strong ion difference [SID] = 60 mEq/L), (2) a hypotonic ORS with low Na+ (HYPO; Na+ = 77 mmol/L; 278 mOsm/kg; SID = 71 mEq/L), and (3) a placebo consisting of lukewarm water with 5 g/L of whey powder (CON). Milk replacer (MR) was fed through teat buckets twice daily at 0630 h and 1700 h in 2 equally sized meals of 2.5 L from d 1 to 3 and of 3.0 L on d 4 and 5. Treatments consisting of 2.0 L lukewarm solutions were administered between milk meals from d 1 to 3 at 1200 h and 2030 h through teat buckets. Refusals of MR and treatments were recorded daily, and blood samples were collected from the jugular vein once daily at arrival in the afternoon of d 0 and at 0900 h from d 1 to 5 after arrival. Urine and feces were collected quantitatively over a 48-h period from 1200 h on d 1 to 1200 h on d 3, and a representative sample of each 24-h period was stored. In addition, the volume of extracellular fluid was evaluated on d 2 by postprandial sampling over a 4-h period relative to the injection of sodium thiosulfate at 1300 h. Total daily fluid intake (MR, treatment, and water) from d 1 to 3 was greater in HYPER (LSM ± SEM; 8.9 ± 0.36 L/d) and HYPO (7.8 ± 0.34 L/d) than in CON (6.6 ± 0.34 L/d). This resulted in a greater water balance (water intake - fluid output in urine and feces) in calves receiving ORS (59.6 ± 6.28 g/kg BW per 24 h vs. 39.6 ± 6.08 g/kg BW per 24 h). Fecal Na+ losses were greater in HYPER than in the other treatments (81 ± 12.0 mg/kg BW per 24 h vs. 24 ± 11.8 mg/kg BW per 24 h). Blood pH was higher in HYPO (7.41 ± 0.016) than CON (7.35 ± 0.016) over the 5 monitoring days, whereas HYPER (7.37 ± 0.017) did not differ with other treatments. In this experimental model, diarrheic calves were likely unable to absorb the high Na+ load from HYPER, resulting in greater Na+ losses in feces, which might have impaired the alkalinizing capacity of HYPER. In contrast, HYPO significantly sustained blood acid-base balance compared with CON, whereas HYPER did not. This suggests that low tonicity ORS with a high SID are more suitable for diarrheic calves.

Postprandial metabolism and gut permeability in calves fed milk replacer with different macronutrient profiles or a whole milk powder.

Significant differences exist in the composition of current milk replacers (MR) and bovine whole milk. This study investigated how the macronutrient profile of 3 different MR formulations containing varying amounts of fat, lactose, and protein, and a whole milk powder (WP), affect postprandial metabolism and gut permeability in male Holstein calves. Sixty-four calves (45.4 ± 4.19 kg [mean ± SD] and 1.8 ± 0.62 d of age) were blocked in order of arrival to the facility and within each block, calves were randomly assigned to 1 of 4 treatments. Treatments included a high-fat MR (HF: 25.0% dry matter [DM] fat, 22.5% protein, 38.6% lactose; n = 14), a high-lactose MR (HL: 44.6% lactose, 22.5% protein, 18.0% fat; n = 17), a high-protein MR (HP: 26.0% protein, 18.0% fat, 41.5% lactose; n = 17), and WP (26.0% fat, 24.5% protein, 38.0% lactose; n = 16). Calves were fed 3.0 L (135 g/L) 3 times daily at 0600, 1200, and 1800 h with a teat bucket. Milk intake was recorded daily for the first 28 d after arrival, and blood sampling and body weight measurements were performed at arrival and on d 7, 14, 21, and 27. Gut permeability was estimated from fractional urinary excretion of indigestible markers (Cr-EDTA, lactulose, and d-mannitol) administered as a single dose on d 21 instead of the morning milk meal. Digestibility was determined simultaneously from a total collection of feces over 24 h. Postprandial dynamics were measured on d 28 by sequential blood sampling over 7.5 h. Dry matter intake of MR over 28 d was slightly greater in calves fed HL and HP than in WP. Recovery of Cr-EDTA and d-mannitol over a 24-h urine collection was greater in calves fed WP and HP than HL calves. Apparent total-tract digestibility of crude ash, protein, and fat did not differ among treatments; however, DM digestibility was lower in calves fed WP than in other treatment groups. In addition, abomasal emptying, as indicated by the area under the curve (AUC) for acetaminophen, was slower in calves fed WP than in calves fed HF and HL. The AUC for postprandial plasma glucose was lower in calves fed HL than WP and HF and lower in calves fed HP than WP. The AUC for postprandial serum insulin was greater in calves fed HP than WP and HF, whereas calves fed HL did not differ from the other treatments. Postprandial triglycerides were greater in calves fed WP, and postprandial adiponectin was higher in calves fed HL than other treatments. The high content of lactose and protein in MR had a major effect on postprandial metabolism. This raises the possibility of optimizing MR formulations to maintain metabolic homeostasis and influence development.

Fat composition of milk replacer influences postprandial and oxidative metabolisms in dairy calves fed twice daily.

Milk replacers (MR) for calves contain alternative fat sources as substitute for milk fat. This substitution leads to differences in fat properties, such as the fatty acid profile and the triglyceride structure. This study evaluated how fat composition in MR affects gastrointestinal health, blood redox parameters, and postprandial metabolism in calves fed twice daily. Forty-five individually housed male Holstein-Friesian calves (2.3 ± 0.85 d of age) were assigned to 1 of 15 blocks based on the age and the day of arrival. Within each block, calves were randomly assigned to 1 of 3 experimental diets and received their respective diet from arrival until 35 d after arrival. The 3 experimental diets (n = 15 per treatment group) consisted of an MR with a blend of vegetable fats containing rapeseed and coconut (VG), an MR with only animal fats from lard and dairy cream (AN), and an MR containing a mixture of animal and vegetable fats including lard and coconut (MX). The fatty acid profile of each MR was formulated to resemble that of bovine milk fat while using only 2 fat sources. All MR were isoenergetic, with 30% fat (% DM), 24% crude protein, and 36% lactose. Chopped straw and water were available ad libitum from arrival onward but no starter feed was provided. Daily milk allowances were 6.0 L from d 1 to 5, 7.0 L from d 6 to 9, and 8.0 L from d 10 to 35, divided into 2 equal meals and prepared at 135 g/L (13.5% solids). Fecal appearance was scored daily; calves were weighed and blood was drawn on arrival and weekly thereafter. Urine and feces were collected over a 24-h period at wk 3 and 5 to determine apparent total-tract digestibility and assess gastrointestinal permeability using indigestible markers. Postprandial metabolism was evaluated at wk 4 by sequential blood sampling over 7.5 h, and the abomasal emptying rate was determined by acetaminophen appearance in blood. Fat composition in MR did not affect growth, MR intake, gastrointestinal permeability, nor nutrient digestibility. The percentage of calves with abnormal fecal scores was lower at wk 2 after arrival in calves fed VG than MX, whereas AN did not differ from the other treatments. Calves fed AN and MX had higher thiobarbituric acid reactive substances measured in serum than VG, whereas plasma ferric-reducing ability was greater in calves fed MX than VG. Postprandial acetaminophen concentrations did not differ across treatment groups, but the area under the curve was smaller in calves fed VG than in the other 2 treatments, which is indicative of a slower abomasal emptying. Postprandial serum triglyceride concentration was greater in calves fed AN than VG, whereas MX did not differ from the other treatments. Based on these outcomes, all 3 fat blends can be considered suitable for inclusion in MR for calves.

Gastrointestinal structure and function of preweaning dairy calves fed a whole milk powder or a milk replacer high in fat.

The composition of milk replacer (MR) for calves greatly differs from that of bovine whole milk, which may affect gastrointestinal development of young calves. In this light, the objective of the current study was to compare gastrointestinal tract structure and function in response to feeding liquid diets having a same macronutrient profile (e.g., fat, lactose, protein) in calves in the first month of life. Eighteen male Holstein calves (46.6 ± 5.12 kg; 1.4 ± 0.50 d of age at arrival; mean ± standard deviation) were housed individually. Upon arrival, calves were blocked based on age and arrival day, and, within a block, calves were randomly assigned to either a whole milk powder (WP; 26% fat, DM basis, n = 9) or a MR high in fat (25% fat, n = 9) fed 3.0 L 3 times daily (9 L total per day) at 135 g/L through teat buckets. On d 21, gut permeability was assessed with indigestible permeability markers [chromium (Cr)-EDTA, lactulose, and d-mannitol]. On d 32 after arrival, calves were slaughtered. The weight of the total forestomach without contents was greater in WP-fed calves. Furthermore, duodenum and ileum weights were similar between treatment groups, but jejunum and total small intestine weights were greater in WP-fed calves. The surface area of the duodenum and ileum did not differ between treatment groups, but the surface area of the proximal jejunum was greater in calves fed WP. Urinary lactulose and Cr-EDTA recoveries were greater in calves fed WP in the first 6 h post marker administration. Tight junction protein gene expression in the proximal jejunum or ileum did not differ between treatments. The free fatty acid and phospholipid fatty acid profiles in the proximal jejunum and ileum differed between treatments and generally reflected the fatty acid profile of each liquid diet. Feeding WP or MR altered gut permeability and fatty acid composition of the gastrointestinal tract and further investigation are needed to understand the biological relevance of the observed differences.

CD193 (CCR3) expression by B cells correlates with reduced IgE production in paediatric schistosomiasis.

We demonstrate that CD193, the eotaxin receptor, is highly expressed on circulating B cells in paediatric schistosomiasis mansoni. CD193 plays a role in directing granulocytes into sites of allergic-like inflammation in the mucosa, but little is known about its functional significance on human B cells. We sought to characterize CD193 expression and its relationship with S. mansoni infection. We found that CD193+ B cells increased with the intensity of schistosome infection. In addition, a significant negative association was observed between CD193 expression by B cells and IgE production. Decreased IgE levels are generally associated with susceptibility to re-infection. B cell stimulation with eotaxin-1 increased CD193 levels whereas IL-4 led to a reduction. This was supported by plasma levels of eotaxin-1 correlating with CD193 levels on B cells and other cells. In contrast, CD193 expression was induced on naive B cells with a combination of IL-10 and schistosome antigens. Whereas T cells had a modest increase in CD193 expression, only B cell CD193 appeared functionally chemotactic to eotaxin-1. Thus, CD193+ B cells, which co-express CXCR5, may be enroute to sites with allergic-like inflammation, such as gastrointestinal follicles, or even to Th2 granulomas, which develop around parasite eggs. Overall, our results suggest that schistosome infection may promote CD193 expression and suppress IgE via IL-10 and other undefined mechanisms related to B cell trafficking. This study adds to our understanding of why young children may have poor immunity. Nonetheless, praziquantel treatment was shown to reduce percentages of circulating CD193+ B cells lending hope for future vaccine efforts.

Gastrointestinal permeability and inflammatory status of preweaning dairy calves in response to decreasing the ratio of n-6 to n-3 fatty acid in milk replacer.

The ratio of n-6 to n-3 fatty acid (FA) is between 2 and 10 times higher in milk replacer (MR) than in whole milk, which may promote inflammation and compromise the integrity of the intestinal epithelium. To evaluate how decreasing the n-6:n-3 FA ratio of MR affects gastrointestinal (GIT) permeability and inflammatory status, 30 dairy calves (2.8 ± 1.06 d of age; mean ± standard deviation) were randomly assigned to be fed an MR with an n-6:n-3 FA ratio of 40:1 (CON; 29.3% crude fat of DM; n = 15) or 6.5:1 (n-3; 29.1% crude fat of DM; n = 15). Calves were fed 7.0 L/d in 2 meals. Calves were weighed and fecal consistency was analyzed weekly. On d 22, calves were administered Cr-EDTA, lactulose, and d-mannitol to assess GIT permeability. Blood and total urine were sequentially collected for 6 and 24 h, respectively, and analyzed for marker content. Whole blood collected 4 h after the meal was subjected to an ex vivo lipopolysaccharide (LPS) challenge to evaluate cytokine secretion from blood cells. Calves were euthanized on d 25 for collection of intestinal tissue samples. Tissue samples were processed to assess FA composition by gas chromatography, histomorphology by bright-field microscopy, and gene expression of tight junction proteins, lipid metabolism enzymes, and immune molecules by real-time quantitative PCR. Data were analyzed using PROC GLIMMIX in SAS (version 9.4, SAS Institute Inc.). Growth performance and fecal consistency were unaffected. Calves fed MR with a lower ratio of n-6 to n-3 FA had 2-fold higher n-3 FA contents and 2-fold lower ratios of n-6 to n-3 FA in proximal jejunum and ileum tissues. Total urinary recovery (0-24 h relative to marker administration) and plasma concentrations of the markers were unaffected. Expression of TJP1 tended to be higher in proximal jejunum tissue and lower in ileum tissue of n-3 calves. The expression of TLR4 and TNFA tended to be higher and CD14 was higher in ileum tissue of n-3 calves. Plasma concentrations of interleukin-4 were decreased in response to the ex vivo LPS challenge in n-3 calves. Histomorphology and GIT permeability were largely unaffected by treatment. Furthermore, the inclusion of linseed and algae oil may promote inflammation, as suggested by greater concentrations of the acute-phase proteins haptoglobin and serum amyloid A postprandially, demonstrating that fat sources should be evaluated for their suitability for MR formulations. Understanding how MR composition affects dairy calf health may improve nutritional strategies on farm.

Effects of mixing a high-fat extruded pellet with a dairy calf starter on performance, feed intake, and digestibility.

During weaning, withdrawal of milk replacer is not directly compensated for by an increase in solid feed intake. Therefore, greater fat inclusion in the starter might mitigate this temporary dietary energy decline. However, fat inclusion in solid feeds may generally limit rumen fermentability and development. To address these potentially conflicting outcomes, we conducted 2 experiments to evaluate the effect of supplementing a high-fat extruded pellet mixed with a calf starter on feed intake, performance, and nutrient digestibility in calves. In experiment 1, 60 Holstein bull calves were blocked by serum IgG (2,449 ± 176 mg/dL) and date of arrival (2.5 ± 0.5 d of age). Within each block, calves were randomly assigned to 1 of 3 treatments: a standard control calf starter (CON; 3.1% fat) and mixtures of CON with 10% inclusion of 1 of 2 different high-fat extruded pellets containing 85% of either hydrogenated free palm fatty acids (PFA, 7.1% fat) or hydrogenated rapeseed triglycerides (RFT, 6.7% fat). Calves were offered milk replacer up to 920 g/d until 42 d of age, followed by a gradual weaning period of 7 d. Calves had ad libitum access to the starter diets, straw, and water. No differences were observed between CON, PFA, and RFT calves on body weight (BW) or average daily gain (ADG) until 49 d of age. From weaning (50 d) until 112 d, PFA calves had a greater BW and ADG than RFT and CON animals. Moreover, PFA calves had the highest intakes of starter, straw, calculated metabolizable energy, and crude protein after weaning. Overall, no differences were present in blood ß-hydroxybutyrate and glucose concentrations between treatments; however, calves in the RFT treatment had a higher concentration of insulin-like growth factor-1. In experiment 2, 24 Holstein bull calves at 3 mo of age were assigned to 1 of 8 blocks based on arrival BW and age. Within each block, calves were randomly assigned to 1 of the 3 treatments previously described for experiment 1. Calves on the RFT treatment had the lowest total-tract apparent dry matter and fat digestibility, potentially explaining the differences in performance observed between PFA and RFT calves. Inclusion of the PFA pellet at 10% with a calf starter improved BW, solid feed, and energy intake after weaning. However, these benefits were conditioned by fat source and its digestibility.

Macronutrient profile in milk replacer or a whole milk powder modulates growth performance, feeding behavior, and blood metabolites in ad libitum-fed calves.

Milk replacers (MR) for calves usually contain more lactose and less fat than bovine whole milk (WM). There are insufficient data to determine whether these MR formulations are optimal for calves fed at high planes of nutrition. Thus, the effect of 3 MR formulations and a WM powder were evaluated on growth, feeding behavior, and blood metabolites in 96 male Holstein calves fed ad libitum and with 45.5 ± 4.30 kg (mean ± standard deviation) BW at arrival. Calves were blocked based on arrival sequence, and randomly assigned within block to one of the 4 treatments (n = 24 calves/group): a high-fat MR (25.0% fat, dry matter basis; 22.5% protein, 38.6% lactose; 21.3 MJ/kg; HF), a high lactose MR (44.6% lactose, 22.5% protein, 18.0% fat; 19.7 MJ/kg; HL), a high protein MR (26.0% protein, 18.0% fat, 41.5% lactose; 20.0 MJ/kg; HP), and a WM powder (26.0% fat; 24.5% protein, 38.0% lactose; 21.6 MJ/kg; WP). In the first 2 wk after arrival, calves were individually housed and were fed 3.0 L of their respective liquid feed 3 times daily at 135 g/L. They were then moved to group housing and fed ad libitum until d 42 after arrival. Weaning was gradual and took place between d 43 and 70 after arrival; thereafter, calves were fed solids only. Concentrates, chopped straw, and water were available ad libitum throughout the study. Body weight was measured, and blood was collected at arrival and then weekly thereafter from wk 1 to 12. Weight gain and height were greater in HL than WP calves. In the preweaning phase, HL and HP-fed calves consumed more milk than WP, and HL-fed calves consumed more milk than HF calves. In wk 10, starter feed intakes were lower in HF calves than in the other groups. In the preweaning phase, ME intakes were the same for all treatments. This suggests that milk intakes were regulated by the energy density of the milk supplied. The percentage of calves requiring therapeutic interventions related to diarrhea was greater in WP-fed calves (29%) than HF and HL calves (4%), whereas HP (13%) did not differ with other groups. This was coupled with lower blood acid-base, blood gas, and blood sodium in WP than in MR-fed calves. Calves fed HF had greater serum nonesterified fatty acids compared with other groups, and greater serum amyloid A compared with WP and HL calves. Among the serum parameters, insulin-like growth factor-1 and lactate dehydrogenase correlated positively with ME intake and average daily gain. The high lactose and protein intakes in HL and HP calves led to greater insulin-like growth factor-1 concentrations than in WP-fed calves. Although growth differences were limited among MR groups, the metabolic profile largely differed and these differences require further investigation.

Fatty acid profile characterization in colostrum, transition milk, and mature milk of primi- and multiparous cows during the first week of lactation.

The specific fatty acid (FA) profile of colostrum may indicate a biological requirement for neonatal calves. The objective of this study was to characterize the FA profile and yields in colostrum, transition milk, and mature milk in primiparous (PP) and multiparous (MP) cows. Colostrum was milked from 10 PP and 10 MP Holstein cows fed the same pre- and postpartum rations. Milkings (M) 2 to 5 and 12 were respectively termed transition and mature milk. Overall, short-chain FA (C4:0 and C6:0) were 61 and 50% lower in colostrum than mature milk, respectively. A parity by milking interaction was also present, with higher C4:0 for PP cows at M2 and for MP cows at M12. Additionally, higher concentrations of C6:0 were present for PP cows at M2 through M4 and for MP cows at M12. Palmitic (C16:0) and myristic (C14:0) acids were 38% and 19% higher in colostrum than mature milk, respectively. However, total saturated FA remained relatively stable. Branched-chain FA were 13% lower in colostrum than mature milk and higher in PP than MP cows throughout the milking period. The proportion of trans-monounsaturated FA (MUFA) was 72% higher in PP cows throughout the milking period, as well as 13% lower in colostrum than mature milk. In contrast, cis-MUFA and total MUFA were not affected by milking nor parity. Linoleic acid (LA) was 25% higher in colostrum than transition and mature milks, but α-linolenic acid (ALA) did not differ. Consequently, the ratio of LA to ALA was 29% higher in colostrum than mature milk and 33% higher in MP cows. Linoleic acid was also 15% higher in MP cows, whereas ALA was 15% higher in PP cows. Conjugated linoleic acid (CLA, cis-9,trans-11) was 2.7-fold higher in PP cows, and no differences between colostrum and mature milk were detected. Overall, polyunsaturated FA (PUFA) from the n-6 and n-3 series were over 40% higher in colostrum compared with transition and mature milk. Milking by parity interactions were present for arachidonic acid (ARA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), docosahexaenoic acid (DHA), and total n-3 PUFA, translating to higher proportions in PP cows in M1 to M3, whereas proportions remained relatively stable throughout the milking period in MP cows. Despite increasing milk yields throughout the subsequent milkings, higher yields of EPA, ARA, DPA, and DHA were present in colostrum than in mature milk. Greater proportions and yields of n-3 and n-6 FA in colostrum may translate to specific requirements for newborn calves. Differences were also observed between PP and MP cows and may reflect different nutrient requirements and partitioning.

Fatty acid profile characterization in colostrum, transition milk, and mature milk of primi- and multiparous cows during the first week of lactation.

The specific fatty acid (FA) profile of colostrum may indicate a biological requirement for neonatal calves. The objective of this study was to characterize the FA profile and yields in colostrum, transition milk, and mature milk in primiparous (PP) and multiparous (MP) cows. Colostrum was milked from 10 PP and 10 MP Holstein cows fed the same pre- and postpartum rations. Milkings (M) 2 to 5 and 12 were respectively termed transition and mature milk. Overall, short-chain FA (C4:0 and C6:0) were 61 and 50% lower in colostrum than mature milk, respectively. A parity by milking interaction was also present, with higher C4:0 for PP cows at M2 and for MP cows at M12. Additionally, higher concentrations of C6:0 were present for PP cows at M2 through M4 and for MP cows at M12. Palmitic (C16:0) and myristic (C14:0) acids were 16% and 27% higher in colostrum than mature milk, respectively. However, total saturated FA remained relatively stable. Branched-chain FA were 13% lower in colostrum than mature milk and higher in PP than MP cows throughout the milking period. The proportion of trans-monounsaturated FA (MUFA) was 42% higher in PP cows throughout the milking period, as well as 15% lower in colostrum than mature milk. In contrast, cis-MUFA and total MUFA were not affected by milking nor parity. Linoleic acid (LA) was 13% higher in colostrum than transition and mature milks, but α-linolenic acid (ALA) did not differ. Consequently, the ratio of LA to ALA was 23% higher in colostrum than mature milk and 25% higher in MP cows. Linoleic acid was also 13% higher in MP cows, whereas ALA was 15% higher in PP cows. Conjugated linoleic acid (CLA, cis-9,trans-11) was 63% higher in PP cows, and no differences between colostrum and mature milk were detected. Overall, polyunsaturated FA (PUFA) from the n-6 and n-3 series were over 25% higher in colostrum compared with transition and mature milk. Milking by parity interactions were present for arachidonic acid (ARA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), docosahexaenoic acid (DHA), and total n-3 PUFA, translating to higher proportions in PP cows in M1 to M3, whereas proportions remained relatively stable throughout the milking period in MP cows. Despite increasing milk yields throughout the subsequent milkings, higher yields of EPA, ARA, DPA, and DHA were present in colostrum than in mature milk. Greater proportions and yields of n-3 and n-6 FA in colostrum may translate to specific requirements for newborn calves. Differences were also observed between PP and MP cows and may reflect different nutrient requirements and partitioning.

Intestinal adaptations to energy source of milk replacer in neonatal dairy calves.

Most milk replacers (MR) contain more lactose compared with whole milk, which, when fed at a large meal size, could influence gut barrier function in calves. This study evaluated how replacing lactose in MR with fat (on a wt/wt basis) affects intestinal histomorphology and permeability in neonatal dairy calves. Thirty-four Holstein-Friesian bull calves were blocked by dam parity and randomly assigned to 1 of 2 treatments (n = 17): a high-lactose (46.1% lactose, 18.0% crude fat, and 23.9% crude protein of dry matter) or a high-fat MR (HF; 39.9% lactose, 24.6% crude fat, and 24.0% crude protein of dry matter). Calves were individually housed and fed pooled colostrum at 1.5 h and 12 h postnatally, at 18 and 9% of metabolic body weight (BW0.75), respectively. From 24 h postnatally until the end of the study (d 7), calves were transitioned to be fed MR (prepared at 15% solids) at 18% of BW0.75 twice daily at 0700 and 1900 h. During postprandial sampling on d 6, intestinal permeability was assessed by mixing lactulose (1.03 g/kg of BW0.75) and d-mannitol (0.31 g/kg of BW0.75) into the morning meal without altering total meal volume. Sequential blood samples were collected via jugular catheter, and total urine was collected for 12 h to measure the marker content. Calves were euthanized 3 h after the morning meal on d 7, and gastrointestinal tract tissues and digesta were collected for analysis of histomorphology, digesta osmolality, and gene expression. The empty gastrointestinal tracts of HF calves were heavier, although length did not differ and differences in histomorphology were minor. Digesta osmolality changed along the tract without differences between treatments. Plasma lactulose was greater in HF, although plasma d-mannitol and the recovery of both markers in urine were unaffected. No significant differences were detected in gene expression, although HF calves tended to have lower expression of TJP1 and CLDN2 and higher expression of proinflammatory cytokine IL1B in ileum tissue. In conclusion, partially replacing lactose in MR with fat resulted in a heavier and more permeable gut, with minor histomorphological differences.

Impact of switching to raltegravir and/or adding losartan in lymphoid tissue fibrosis and inflammation in people living with HIV. A randomized clinical trial.

BACKGROUND: Persistent inflammation and immune activation are associated with lymph node fibrosis and end-organ diseases in treatment-suppressed people living with HIV (PLWH). We investigated the effect of switching to raltegravir and/or adding losartan on lymphoid tissue fibrosis and on the inflammatory/immune-activation mediators in treated HIV patients. METHODS: Chronic HIV-infected patients treated with two nucleoside reverse transcriptase inhibitors (2NRTI) and one non-NRTI (NNRTI) or protease inhibitor (PI) during at least 48 weeks were randomized to four groups (n = 48): 2NRTI + efavirenz (EFV), 2NRTI + EFV + losartan, 2NRTI + raltegravir and 2NRTI + raltegravir + losartan for 48 weeks. Tonsillar biopsy and peripheral blood markers of CD4 and CD8 T-lymphocyte activation and senescence, monocyte activation and soluble markers of inflammation were determined at baseline and at week 48 and compared between groups. RESULTS: No changes in lymphoid tissue architecture were observed. Adding losartan had no impact on lymphocyte subsets. Conversely, patients who switched to raltegravir showed a higher decrease in all activated [CD4+CD38+HLA-DR+, -0.3 vs. 0.48 (P = 0.033); CD8+CD38+ HLA-DR+, -1.6 vs. 1.3 (P = 0.02)] and senescent [CD4+CD28-CD57+, -0.3 vs. 0.26 (P = 0.04); CD8+CD28-CD57+, -6.1 vs. 3.8 (P = 0.002)] T lymphocytes. In addition, the median CD4/CD8 ratio increased by 0.35 in patients in the raltegravir group vs. 0.03 in the other arms (P = 0.002). Differences between groups in monocyte subpopulations or soluble inflammation markers were not observed. CONCLUSIONS: Losartan had no effect on lymphoid fibrosis or immune activation/inflammation. Conversely, switching to a regimen with raltegravir significantly decreased activated and senescent T-lymphocyte subpopulations and increased CD4/CD8 ratio in successfully treated PLWH.

Flow-Induced Concentration Nonuniformity and Shear Banding in Entangled Polymer Solutions.

Recent models have predicted entangled polymer solutions could shear band due to unstable flow-induced demixing. This work provides the first experimental probe of the in situ concentration profile of entangled polymer solutions under shear. At shear rates above a critical value, we show that the concentration and velocity profiles can develop bands, in quantitative agreement with steady-state model predictions. These findings highlight the critical importance of flow-concentration coupling in entangled polymer solutions.

Experience with the use of siltuximab in patients with SARS-CoV-2 infection.

OBJECTIVE: The study aims to describe characteristics and clinical outcome of patients with SARS-CoV-2 infection that received siltuximab according to a protocol that aimed to early block the activity of IL-6 to avoid the progression of the inflammatory flare. METHODS: Retrospective review of the first 31 patients with SARS-CoV-2 treated with siltuximab, in Hospital Clinic of Barcelona or Hospital Universitario Salamanca, from March to April 2020 with positive polymerase-chain reaction (PCR) from a nasopharyngeal swab. RESULTS: The cohort included 31 cases that received siltuximab with a median (IQR) age of 62 (56-71) and 71% were males. The most frequent comorbidity was hypertension (48%). The median dose of siltuximab was 800 mg ranging between 785 and 900 mg. 7 patients received siltuximab as a salvage therapy after one dose of tocilizumab. At the end of the study, a total of 26 (83.9) patients had been discharged alive and the mortality rate was 16.1% but only 1 out of 24 that received siltuximab as a first line option (4%). CONCLUSIONS: Siltuximab is a well-tolerated alternative to tocilizumab when administered as a first line option in patients with COVID-19 pneumonia within the first 10 days from symptoms onset and high C-reactive protein.

ADSA Foundation Scholar Award: New frontiers in calf and heifer nutrition-From conception to puberty.

Dairy calf nutrition is traditionally one of the most overlooked aspects of dairy management, despite its large effect on the efficiency and profitability of dairy operations. Unfortunately, among all animals on the dairy farm, calves suffer from the highest rates of morbidity and mortality. These challenges have catalyzed calf nutrition research over the past decade to mitigate high incidences of disease and death, and improve animal health, growth, welfare, and industry sustainability. However, major knowledge gaps remain in several crucial stages of development. The purpose of this review is to summarize the key concepts of nutritional physiology and programming from conception to puberty and their subsequent effects on development of the calf, and ultimately, future performance. During fetal development, developmental plasticity is highest. At this time, maternal energy and protein consumption can influence fetal development, likely playing a critical role in calf and heifer development and, importantly, future production. After birth, the calf's first meal of colostrum is crucial for the transfer of immunoglobulin to support calf health and survival. However, colostrum also contains numerous bioactive proteins, lipids, and carbohydrates that may play key roles in calf growth and health. Extending the delivery of these bioactive compounds to the calf through a gradual transition from colostrum to milk (i.e., extended colostrum or transition milk feeding) may confer benefits in the first days and weeks of life to prepare the calf for the preweaning period. Similarly, optimal nutrition during the preweaning period is vital. Preweaning calves are highly susceptible to health challenges, and improved calf growth and health can positively influence future milk production. Throughout the world, the majority of dairy calves rely on milk replacer to supply adequate nutrition. Recent research has started to re-evaluate traditional formulations of milk replacers, which can differ significantly in composition compared with whole milk. Transitioning from a milk-based diet to solid feed is critical in the development of mature ruminants. Delaying weaning age and providing long and gradual step-down protocols have become common to avoid production and health challenges. Yet, determining how to appropriately balance the amount of energy and protein supplied in both liquid and solid feeds based on preweaning milk allowances, and further acknowledging their interactions, shows great promise in improving growth and health during weaning. After weaning and during the onset of puberty, heifers are traditionally offered high-forage diets. However, recent work suggests that an early switch to a high-forage diet will depress intake and development during the time when solid feed efficiency is greatest. It has become increasingly clear that there are great opportunities to advance our knowledge of calf nutrition; yet, a more concentrated and rigorous approach to research that encompasses the long-term consequences of nutritional regimens at each stage of life is required to ensure the sustainability and efficiency of the global dairy industry.

Tocilizumab reduces the risk of ICU admission and mortality in patients with SARS-CoV-2 infection.

OBJECTIVE: In some patients the immune response triggered by SARS-CoV-2 is unbalanced, presenting an acute respiratory distress syndrome which in many cases requires intensive care unit (ICU) admission. The limitation of ICU beds has been one of the major burdens in the management around the world; therefore, clinical strategies to avoid ICU admission are needed. We aimed to describe the influence of tocilizumab on the need of transfer to ICU or death in non-critically ill patients. METHODS: A retrospective study of 171 patients with SARS-CoV-2 infection that did not qualify as requiring transfer to ICU during the first 24h after admission to a conventional ward, were included. The criteria to receive tocilizumab was radiological impairment, oxygen demand or an increasing of inflammatory parameters, however, the ultimate decision was left to the attending physician judgement. The primary outcome was the need of ICU admission or death whichever came first. RESULTS: A total of 77 patients received tocilizumab and 94 did not. The tocilizumab group had less ICU admissions (10.3% vs. 27.6%, P=0.005) and need of invasive ventilation (0 vs 13.8%, P=0.001). In the multivariable analysis, tocilizumab remained as a protective variable (OR: 0.03, CI 95%: 0.007-0.1, P=0.0001) of ICU admission or death. CONCLUSIONS: Tocilizumab in early stages of the inflammatory flare could reduce an important number of ICU admissions and mechanical ventilation. The mortality rate of 10.3% among patients receiving tocilizumab appears to be lower than other reports. This is a non-randomized study and the results should be interpreted with caution.