During early lactation, both primiparous (PP) and multiparous (MP) cows are commonly fed diets rich in starch and low in forages to support their high energy requirements. Yet, the PP cows experience ...this dietary challenge for the first time, which might result in higher odds for them to develop rumen and systemic health disorders. The primary objective of this study was to evaluate the effect of decreasing the amount of forages in the diet on chewing and sorting behaviors and rumen and systemic health variables in PP and MP dairy cows. Twenty-four lactating Simmental cows 8 PP, average dry matter intake (DMI) of 19.1 ± 1.1 kg/d; 16 MP, average DMI of 22.5 ± 1.1 kg/d with a body weight of 737 ± 90 kg and 50 ± 22 days in milk were used in this study. Cows were first fed a total mixed ration with 60% forage and 40% concentrate on a dry matter (DM) basis considered marginal in forages for 2 wk. Then, cows were switched to a diet low in forages with 40% forage and 60% concentrate (on a DM basis) for 4 wk. Reticular pH was measured continuously with wireless pH-sensors inserted into the reticulum to calculate the subacute ruminal acidosis (SARA) index. Chewing activity was measured with noseband-sensor halters, and feed sorting was measured weekly. Blood samples were collected weekly and analyzed for metabolic and inflammation markers. Switching PP and MP cows from a marginal to low-forage diet decreased the time spent eating and ruminating per kilogram of DM. Primiparous cows chewed longer per kilogram of DMI than MP cows. Also, the PP cows sorted more pronounced for longer particles and against fine particles than MP cows did. Despite higher rumination activity per kilogram of DMI and the adaptive sorting behavior, the PP cows spent on average 4.6 h/d longer below a pH of 5.8 and had a higher SARA index (i.e., area pH <5.8/DMI) than MP cows, especially during the first week of the low-forage diet (9.5 vs. 4.8). The concentration of liver enzymes increased with the low-forage diet, which was especially pronounced in the PP cows. In conclusion, this study demonstrated greater susceptibility of PP cows to SARA and liver damage than MP cows fed the same diets. Although PP cows demonstrated greater chewing and ruminating activity per kilogram of DMI, as well as adapted sorting behavior in favor of large particles during the low-forage high-starch feeding, they developed more severe signs of SARA. This suggests higher forage fiber requirements for PP cows and the need for improved feeding strategies to mitigate rumen fermentation disorders during early lactation in these cows.
Subacute ruminal acidosis (SARA) causes ruminal dysbiosis, thereby increasing the risk of systemic metabolic disorders in cattle. We recently showed that supplementation with phytogenic compounds ...(PHY) or autolyzed yeast (AY) counteracted negative effects of SARA by improving ruminal pH and microbiome. This study investigated the effects of an intermittent SARA challenge on the ruminal concentration of biogenic amines (BA) and lipopolysaccharides (LPS), as well as on the blood metabolome. We also evaluated effects of PHY and AY on the latter variables. Eight rumen-cannulated nonlactating Holstein cows were arranged in an incomplete 4 × 3 Latin square design with 4 experimental runs and 3 treatment groups. During each run, cows were switched from an all-forage diet (baseline) to an intermittent concentrate-challenge diet with a forage:concentrate ratio of 35:65 (dry matter basis) to induce SARA for 1 (SARA1) or 2 (SARA2) wk, separated by 1 wk of forage-only feeding. The 3 treatment groups were no additive as control, PHY, or AY. During baseline, SARA1 and SARA2 rumen fluid samples were collected for analysis of BA and LPS. Blood samples were taken during baseline and SARA1 for a targeted metabolomics approach. High-concentrate feeding caused a 9-fold increase in ruminal LPS during SARA1 and an 11-fold increase in SARA2 compared with the baseline. Elevated concentrations of ruminal BA were found during both SARA periods, with histamine showing the strongest increase during SARA1. Moreover, a decrease in phosphatidylcholines, lysophosphatidylcholines, sphingomyelines, and several AA in the blood during SARA1 were detected. Supplementation of PHY decreased concentrations of LPS (−43%), histamine (−66%), pyrrolidine (−38%), and spermine (−54%) in SARA1 and cadaverine in SARA2 (−50%). Moreover, cows that received PHY had higher concentrations of cholesterol (+26%), several AA, and phosphatidylcholines in SARA1 compared with control cows. For AY, decreases in ruminal ethanolamine (−21%), methylamine (−52%), histamine (−54%), spermidine (−44%), and spermine (−80%) in SARA1 were observed, whereas in the blood an increase in tryptophan was noticed. In conclusion, the SARA was associated with markedly increased concentrations of LPS and BA in the rumen fluid and undesirable shifts in the plasma metabolome. Supplementation of PHY and AY counteracted some of these changes and therefore may help in attenuating negative effects of high-concentrate feeding in dairy cattle.
The feeding of concentrate-rich diets may lead to microbial imbalances and dysfermentation in the rumen. The main objective of this study was to determine the effects of supplementing phytogenic ...compounds (PHY) or autolyzed yeast (AY) on rumen fermentation and microbial abundance in cows intermittently fed concentrate-rich diets. The experiment was carried out as an incomplete 3 × 4 Latin square design, with 8 nonlactating rumen-fistulated Holstein-Friesian cows. The cows were randomly assigned to a concentrate diet that was either not supplemented (CON), or supplemented with PHY or AY. Each of the 4 consecutive experimental periods was composed of a 1-wk roughage-only diet (RD), 6-d gradual concentrate increase, followed by 1 wk of 65% concentrate (dry matter basis; Conc I), and 1 wk of RD and a final 2-wk 65% concentrate (dry matter basis; Conc II) phase. Digesta samples were collected from the rumen mat for bacterial 16S rRNA gene Illumina MiSeq (Illumina, Balgach, Switzerland) sequencing, and samples of particle-associated rumen liquid were obtained for measuring short-chain fatty acids, lactate, ammonia, and pH during RD (d 6), Conc I (d 19), and Conc II (d 39). The concentrate feeding caused a decrease of overall bacterial diversity indices, especially during Conc I. The genera Ruminococcus, Butyrivibrio, and Coprococcus were decreased, whereas Prevotella, Megasphaera, Lachnospira, and Bacteroides were increased in abundance. Supplementation of both feed additives increased the abundance of gram-positive and decreased that of gram-negative bacteria. Supplementation of AY enhanced cellulolytic bacteria such as Ruminococcus spp., whereas PHY decreased starch and sugar fermenters including Bacteroides spp., Shuttleworthia spp., and Syntrophococcus spp. Moreover, PHY supplementation increased butyrate percentage in the rumen in both concentrate phases. In conclusion, intermittent high-concentrate feeding altered the digesta-associated rumen bacterial community and rumen fermentation with more significant alterations found in Conc I than in Conc II. The data also showed that both feed additives had the most significant modulatory effects on the bacterial community, and their subsequent fermentation, during periods of low pH.
Feeding of concentrate-rich diets impairs chewing behavior and leads to rumen acidosis in cattle. Because of their modulatory effects on ruminal fermentation, phytogenic compounds (PHY) and autolyzed ...yeast derivatives (AY) may alleviate the negative consequences of high-concentrate diets. Therefore, this research investigated if chewing behavior and the reticular pH dynamics are modulated by AY and PHY supplementation during repeated concentrate-rich challenges used to simulate intermittent rumen acidotic insults. Eight rumen-cannulated, dry, and nonpregnant Holstein cows were assigned to an incomplete double 4 × 3 Latin square design with 3 treatments and 4 experimental runs (n = 8/treatment). Cows were fed concentrates either not supplemented (CON) or supplemented with PHY or AY. Initially, cows were fed a pure forage diet (FD) and switched to a 65% concentrate diet on DM basis for 1 (CONC 1) and 2 (CONC 2) wk. Between CONC 1 and CONC 2, the cows were fed the FD for 1 wk. Chewing activity was measured using noseband sensors and reticular pH by wireless pH sensors. Data showed that cows spent less time ruminating in CONC 1 than in CONC 2. In agreement, reticular pH drop was more pronounced during CONC 1 than during CONC 2. Cows fed with PHY spent 4 h less with reticular pH <6.0 during CONC 1 and 3 h less with pH <6.0 h in CONC 2 as compared with CON cows. Similarly, PHY supplementation extended rumination time with 88 min/d compared with CON cows during CONC 1. The AY supplementation increased DMI by 20% resulting in a longer eating time compared with CON diet during CONC 1. Enhancement of ruminating by PHY and eating time by AY supplementation resulted in longer total chewing time for PHY (474 min/d) and AY (466 min/d) as compared with CON (356 min/d) in CONC 1. In conclusion, cows experiencing 2 intermittent concentrate-rich challenges increased their ruminating behavior during the second challenge, and this effect was associated with higher reticular pH readings. The PHY supplementation enhanced rumination as well as reticular pH during CONC 1. However, the enhanced pH of cows fed with PHY during CONC 2 was not related to greater rumination, suggesting that influencing factors beyond rumination seemed to play a role in modulating reticular pH in PHY cows during CONC 2. The AY supplementation increased DMI without depressing rumination or reticular pH. Effects of both feed additives were more pronounced during CONC 1 challenge when reticular pH was lower.
Summary
Feeding of high‐concentrate diets to cattle increases the risk of subacute ruminal acidosis (SARA). Indwelling wireless pH sensors have become popular as an early diagnostic tool for SARA ...recently. However, the recommended pH thresholds of SARA derive from measurements taken from free‐rumen liquid (FRL) in the ventral rumen, and not from the reticulum, where the mentioned sensors are located. The aim of this study was to evaluate commercially available indwelling pH boli for the accuracy and precision in predicting ruminal pH of FRL and the particle‐associated rumen liquid (PARL) under varying dietary concentrate levels. An additional aim was to define SARA pH thresholds of indwelled pH boli, which can be used for SARA diagnostics. The experiment was conducted with eight nonlactating rumen cannulated Holstein cows fed 0% or 65% concentrate. Data showed that the mean pH of indwelled boli was consistently higher than in FRL and PARL (pH 6.62 ± 0.02, 6.43 ± 0.02 and 6.18 ±0.02, respectively) across feeding regimens. Interestingly, the diurnal differences in pH among indwelled boli, FRL and PARL became greater during concentrate feeding, especially at 8 h after the morning feeding, suggesting that with high‐concentrate diets a particular adjustment of reticular sensor pH vs. ruminal pH in FRL and PARL is needed. The concordance correlation coefficient analysis, representing the reproducibility of the bolus measurements, was high for bolus‐FRL (0.733) and moderate for bolus‐PARL (0.510) associations. Furthermore, the quantitative relationship of the pH in FRL and PARL to the pH of the boli was described by linear regression analysis. The study determined that the common SARA threshold of pH 5.8 in FRL corresponds to a bolus pH of 6.0.
Grain-rich diets often lead to subacute ruminal acidosis (SARA) impairing rumen and systemic cattle health. Recent data suggest beneficial effects of a clay mineral (CM)- based product on the rumen ...microbiome of cattle during SARA. This study sought to investigate whether the CM supplementation can counteract SARA-induced perturbations of the bovine systemic health. The study used an intermittent diet-induced SARA-model with eight dry Holstein cows receiving either no additive as control or CM via concentrates (n=8 per treatment). Cows received first a forage diet (Baseline) for 1 week, followed by a 1-week SARA-challenge (SARA 1), a 1-week recovery phase (Recovery) and finally a second SARA-challenge for 2 weeks (SARA 2). Cows were monitored for feed intake, reticular pH and chewing behavior. Blood samples were taken and analyzed for metabolites related to glucose and lipid metabolism as well as liver health biomarkers. In addition, a targeted electrospray ionization-liquid chromatography-MS-based metabolomics approach was carried out on the plasma samples obtained at the end of the Baseline and SARA 1 phase. Data showed that supplementing the cows’ diet with CM improved ruminating chews per regurgitated bolus by 16% in SARA 1 (P=0.01) and enhanced the dry matter intake during the Recovery phase (P=0.05). Moreover, the SARA-induced decreases in several amino acids and phosphatidylcholines were less pronounced in cows receiving CM (P≤0.10). The CM-supplemented cows also had lower concentrations of lactate (P=0.03) and biogenic amines such as histamine and spermine (P<0.01) in the blood. In contrast, the concentration of acylcarnitines with key metabolic functions was increased in the blood of treated cows (P≤0.05). In SARA 2, the CM-cows had lower concentrations of the liver enzymes aspartate aminotransferase and γ-glutamyltransferase (P<0.05). In conclusion, the data suggest that supplementation of CM holds the potential to alleviate the negative effects of high-grain feeding in cattle by counteracting multiple SARA-induced perturbations in the systemic metabolism and liver health.
Objectives
We aimed to evaluate the ability of feed-forward neural networks (fNNs) to predict the neurodevelopmental outcome (NDO) of very preterm neonates (VPIs) at 12 months corrected age by using ...biomarkers of cerebral MR proton spectroscopy (
1
H-MRS) and diffusion tensor imaging (DTI) at term-equivalent age (TEA).
Methods
In this prospective study, 300 VPIs born before 32 gestational weeks received an MRI scan at TEA between September 2013 and December 2017. Due to missing or poor-quality spectroscopy data and missing neurodevelopmental tests, 173 VPIs were excluded. Data sets consisting of 103 and 115 VPIs were considered for prediction of motor and cognitive developmental delay, respectively. Five metabolite ratios and two DTI characteristics in six different areas of the brain were evaluated. A feature selection algorithm was developed for receiving a subset of characteristics prevalent for the VPIs with a developmental delay. Finally, the predictors were constructed employing multiple fNNs and fourfold cross-validation.
Results
By employing the constructed fNN predictors, we were able to predict cognitive delays of VPIs with 85.7% sensitivity, 100% specificity, 100% positive predictive value (PPV) and 99.1% negative predictive value (NPV). For the prediction of motor delay, we achieved a sensitivity of 76.9%, a specificity of 98.9%, a PPV of 90.9% and an NPV of 96.7%.
Conclusion
FNNs might be able to predict motor and cognitive development of VPIs at 12 months corrected age when employing biomarkers of cerebral
1
H-MRS and DTI quantified at TEA.
Key Points
• A feed-forward neuronal network is a promising tool for outcome prediction in premature infants.
• Cerebral proton magnetic resonance spectroscopy and diffusion tensor imaging can be used for the construction of early prognostic biomarkers.
• Premature infants that would most benefit from early intervention services can be spotted at the time of optimal neuroplasticity.
Feeding high-grain diets leads to the release and accumulation of short-chain fatty acids in the rumen. The subsequent prolonged decline in ruminal pH can lead to subacute ruminal acidosis (SARA). ...Accumulation of short-chain fatty acids can cause proliferation of rumen papillae to increase absorption surface, subsequently leading to a thickening of the rumen mucosa. The aim of this study was to evaluate the appropriateness of continuous measurements of the rumen mucosa thickness (RMT) as a diagnostic tool for SARA in dairy cows compared with continuous measurements of ruminal pH. The study used 6 lactating Simmental cows switched from a moderate-grain (MG) diet with 40% concentrate (dry matter basis) for 1 wk to a high-grain (HG) diet with 60% concentrate (dry matter basis) for 4 wk. Reticuloruminal pH was recorded with indwelling sensors throughout the trial. Rumen mucosa thickness was measured by transabdominal ultrasound at 4 d during the MG diet and 23 d during the HG diet. Mean RMT increased from 4.7 ± 0.19 mm in the MG diet to 5.3 ± 0.17 mm in the HG diet, whereas daily mean reticular pH decreased from 6.8 ± 0.01 in the MG diet to 6.5 ± 0.01 in the HG diet. Older cows (>3 lactations) had increased RMT, associated with higher reticular pH throughout the experiment. The higher RMT and pH level in older cows underlines their lesser susceptibility to SARA during high-grain feeding. In conclusion, RMT can successfully be measured using linear ultrasound probes, commonly used by veterinary practitioners as rectal probes. By combining noninvasive RMT measurements with the lactation number of the individual cows in a herd, this study suggests that RMT is a viable option for diagnosing SARA. Further research, using a larger number of cows with different lactations numbers, is needed to establish a cut-off RMT indicating the risk of SARA.
Summary
Controlling rumen disorders is critical to ensure successful dairy herd health management. Lactation diets of dairy cows are commonly rich in concentrates and low in physically effective ...fibre. Feeding of these diets increases the risk of rumen disorders with far‐reaching consequences for cattle health, welfare and sustainability of dairy production. The term subacute ruminal acidosis or SARA is often used as a synonym for poor rumen health. Being subclinical, SARA lacks of clear symptoms and is therefore difficult to diagnose and to control in the practice. This review article summarises common and identifies new direct and indirect cow signals related to SARA. We have performed a scientific evaluation and interpretation of each of these cow signals by highlighting their advantages and disadvantages from the practitioner's point of view. The gold standard of SARA cow signals still remains direct measurement of ruminal pH. However, continuous pH monitoring is cost‐intensive and often biased by sensor drift. Single‐point ruminal pH measurements by oral stomach tubing or rumenocentesis have strong limitations. Therefore, there is a need for reliable and robust markers of SARA that are easily accessible and inexpensive. Such indirect parameters are the observation of chewing and feeding activities, as well as the monitoring of milk, faecal, urine and blood variables. Also, novel technologies that allow rapid and non‐invasive measurement of the rumen mucosa thickness and ruminal motility patterns might provide advantages in SARA diagnosis. Due to several constraints of these indirect diagnostic tools, such as limited specificity and sensitivity, we strongly recommend using a combination of the signals to reliably identify cows at risk of SARA in a dairy herd.
Excessive glutamate release followed by N-methyl-d-aspartate receptor (NMDAR) activation plays a crucial role in perinatal brain injury. We have previously shown that dextromethorphan, a low‐affinity ...NMDAR antagonist with anti-inflammatory properties, is neuroprotective against neonatal excitotoxic brain injury. Of interest, dextromethorphan is also a sigma-1 receptor (σ1R) agonist. The pharmacologic class of σ1R agonists has yielded propitious results in various animal models of adult central nervous system pathology. In an established neonatal mouse model of excitotoxic brain injury, we evaluated the effect of the selective σ1R agonist 2-(4-morpholinethyl) 1-phenylcyclohexanecarboxylate (PRE-084). A single intraperitoneal injection of 0.1μg/g (low dose) or 10μg/g (high dose) bodyweight (bw) PRE-084, given 1h after the excitotoxic insult, significantly reduced lesion size in cortical gray matter 24h and 120h after the insult. Repetitive injections of 0.1μg/g PRE-084 proved to be equally effective. PRE-084 treatment resulted in a decrease in cell death indicated by reduced TUNEL positivity and caspase-3 activation. Furthermore, it lowered the number of isolectin B4-positive, activated microglial cells. PRE‐084 had no effect on developmental apoptosis in the undamaged brain. In vitro findings in primary hippocampal neurons suggest that PRE-084 treatment provides partial protection against glutamate induced morphological and functional changes. For excitotoxicity as playing a crucial role in the pathogenesis of perinatal brain injury, we demonstrate for the first time that systemic treatment with the highly selective σ1R agonist PRE-084 protects against NMDAR-mediated excitotoxic brain damage.
► We evaluate neuroprotective effects of a highly selective sigma receptor agonist. ► We use an established mouse model of neonatal excitotoxic brain injury. ► Administration of PRE-084 reduces cell death and microglial cell activation. ► PRE-084 has a beneficial effect in vitro after glutamate exposure. ► Sigma receptor agonists are a potential strategy in perinatal brain injury.
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