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ABSTRACT: In a previously established animal model, 38 multiparous Holstein cows were assigned to 2 groups fed different diets to achieve either a normal (NBCS) or high (HBCS) body condition score (BCS) and backfat thickness (BFT) until dry-off at −49 d before calving (NBCS: BCS 3.75 [3.82 ± 0.33] and BFT >1.4 cm [2.36 ± 0.35], mean ± SD). The groups were also stratified for comparable milk yields (NBCS: 10,361 ± 302 kg; HBCS: 10,315 ± 437 kg; mean ± SD). The cows were then fed the same diet during the dry period and subsequent lactation, maintaining the differences in BFT and BCS throughout the study. Using the serum metabolomics data, we created a classification model that identified different metabotypes. Machine learning classifiers revealed a distinct cluster labeled HBCS-PN (HBCS predicted normal BCS) among over-conditioned cows. These cows showed higher feed intake and better energy balance than the HBCS-PH (high BCS predicted high BCS) group, while milk yield was similar. The aim of this study was to investigate the changes in the hepatic transcriptome of cows differing in serum-metabotype postpartum. We performed hepatic transcriptome analysis in cows from 3 metabolic clusters: HBCS-PH (n = 8), HBCS-PN (n = 6), and normal BCS predicted normal BCS (NBCS-PN, n = 8) on d 21 (±2) postpartum. Liver tissue from cows expressed a total of 13,118 genes aligned with the bovine genome. A total of 48 differentially expressed genes (DEG; false discovery rate ≤0.1 and fold-change >1.5) were found between NBCS-PN and HBCS-PH cows, whereas 24 DEG (14 downregulated and 10 upregulated) were found between HBCS-PN and HBCS-PH cows. The downregulated DEG (n = 31) in NBCS-PN cows compared with HBCS-PH cows are involved in biosynthetic processes such as lipid, lipoprotein, and cholesterol synthesis (e.g., APOA1, MKX, RPL3L, CANT1, CHPF, FUT1, ZNF696), cell organization, biogenesis, and localization (e.g., SLC12A8, APOA1, BRME1, RPL3L, STAG3, FBXW5, TMEM120A, SLC16A5, FGF21), catabolic processes (e.g., BREH1, MIOX, APOBEC2, FBXW5, NUDT16), and response to external stimuli (e.g., APOA1, FGF21, TMEM120A, FNDC4), whereas upregulated DEG (n = 17) are related to signal transduction and cell motility (e.g., RASSF2, ASPN, SGK1, KIF7, ZEB2, MAOA, ACKR4, TCAF1), suggesting altered metabolic adaptations during lactation. Our results showed 24 DEG between HBCS-PN and HBCS-PH in the liver. The expression of SLC12A8, SLC16A5, FBXW5, OSGIN1, LAMA3, KDELR3, OR4X17, and INHBE, which are responsible for regulating cellular processes was downregulated in HBCS-PN cows compared with HBCS-PH cows. In particular, the downregulation of SLC12A8 and SLC16A5 expression in HBCS-PN cows indicates lower metabolic load and reduced need for NAD+ biosynthesis to support mitochondrial respiratory processes. The upregulation of MAOA, ACKR4, KIF27, SFRP1, and CAV2 in the liver of HBCS-PN cows may indicate adaptive mechanisms to maintain normal liver function in response to increased metabolic demands from over-conditioning. These molecular differences underscore the existence of distinct metabolic types in cows and provide evidence for the role of the liver in shaping different metabolic patterns.

ABSTRACT: Heat stress (HS) impairs productivity, health, and welfare in dairy cows, and additionally causes metabolic changes. Hence, specific metabolites could be used as HS biomarkers. Consequently, the aim of the present study was to compare blood metabolite concentrations of German Holstein dairy cows and of their female calves suffering from high temperature-humidity index (THI) during late gestation (cows) or during their first week of life (calves) or not. According to the mean daily THI (mTHI) at the day before blood sampling, animals were classified into 2 groups: high mTHI ≥60 (hmTHI) and low mTHI

ABSTRACT: The objective of the current study was to develop a predictive model for calf disease detection in the preweaning period using data from automated milk feeders (AMF). A deep convolutional neural network (CNN) architecture for the detection of respiratory disease and diarrhea in dairy calves was developed. German Holstein calves were fed milk replacer either ad libitum (up to 25 L/d; n = 32) or restrictively (6 L/d; n = 32) via AMF from 10 ± 3 d of life on. Concentrate, hay, and water were freely available. Calf health parameters were scored daily. The AMF measured milk replacer (MR) intake, number of rewarded visits, number of unrewarded visits, and drinking speed. A calf was considered sick if its fecal score was 3 or 4 and its respiratory score was 2 or 3. Only data from AMF up to 47 d of age were included in the analysis. This cut in the data was made to avoid data from the weaning period. Data were split in 80:20 ratios for training and testing data sets according to the Pareto principle. A minimum sensitivity of 80% was considered an appropriate requirement for the prediction models. Considering all calves in group housing, cross-validation of the test data set showed a sensitivity of 83% and a specificity of 79%, with a positive predictive value and a negative predictive value of 37 and 97%, respectively. The area under the curve of the receiver operating characteristic for the deep CNN model was 0.81 for all group-housed calves. The CNN model yielded sensitivity and specificity of 83 and 71%, respectively (for ad libitum-fed calves), and 82 and 87%, respectively (for restricted-fed calves), with good area under the curve-receiver operating characteristic (0.77 to 0.87), indicating that the CNN models can predict calf disease in both groups with different MR allowances. The permutation feature importance was measured by the decrease in model accuracy, and features (behaviors) were summarized in descending order of their relative importance to the CNN model. Drinking speed and MR intake were the main factors to predict calf disease in calves fed ad libitum. The number of unrewarded visits to the milk feeder and MR intake were the main factors to predict calf disease in restricted-fed calves. Despite the relatively small sample size, the results provide strong evidence that daily feeding behavior data from AMF can be used to identify calves at risk for disease. In conclusion, despite a very good testing performance of the CNN model, the relatively low daily prevalence of calf disease in the present study resulted in a high proportion of false-positive alarms.

ABSTRACT: Telomeres cap the ends of eukaryotic chromosomes, and the telomere length (TL) is related to cellular age. The mitochondrial DNA copy number (mtDNAcn) reflects the abundance of mitochondria in a cell. In addition to generating energy, mitochondria are also the main producers of reactive oxygen species, which in turn can accelerate TL attrition and impair mitochondrial function. Nutrition in early life could influence mtDNAcn and TL in later life. In the present study, we investigated the effects of feeding different levels of milk replacer (MR) on TL shortening and energetic status by examining mtDNAcn of heifers during their first year of life. In this study, whole blood samples were obtained from German Holstein heifer calves 36 to 48 h after birth (wk 1) and at wk 12 and wk 16 of life (n = 37), as well as from 31 calves when reaching 1 yr of age. Calves were fed either a high level of MR (14% solids) at 10 L/d (1.4 kg of MR/d; n = 18) or a restrictive low level at 5.7 L/d (0.8 kg of MR/d; n = 19) until linear weaning in wk 13 to 14 of life. Additional whole blood samples were taken from their respective dams 36 to 48 h after calving. Relative TL (qT) and mtDNAcn in cells from whole blood were measured by multiplex quantitative PCR. The greatest qT values were observed in neonates (36–48 h after birth), with decreasing qT values thereafter. Delta qT values were calculated as ΔqT = qT (first year of life) − initial qT (36–48 h after birth). We found no effect of the feeding regimen on qT values, but qT decreased with age. The mtDNAcn was lowest in neonates, increased until wk 12 of life, and then remained at a constant level until after weaning (wk 16). After the first year of life, mtDNAcn was decreased and returned to levels comparable to those of the neonatal stage. No differences in mtDNAcn were detectable between feeding groups within each time point. When comparing the values of qT and mtDNAcn between the calves and their dams after calving (36–48 h after birth and after calving), greater values were observed in calves than in dams. Delta qT values were negative in all but 2 calves (on the restricted diet), indicating that the change in TL with age was not uniform among individual animals, whereas no difference in mean ΔqT values occurred between the feeding groups. Additional analyses of the correlation between qT, mtDNAcn, and various indicators of oxidative status from birth until wk 16 of life did not indicate major interactions between oxidative status, qT and mtDNAcn. The results of this study support an age-dependent decrease of TL in calves independent of the MR feeding level and show the dynamic changes of mtDNAcn in early life.

Bull-fattening diets in Europe and most developed countries around the world have traditionally been based on corn silage, starch-rich, and high-energy/ high-protein supplemental feeds. The impact of climate change on crop yields feed availability, and price volatility, requires new and adapted feeding strategies, including for fattening bulls. Therefore, the objective of this study was to compare the growth performance and economic impact of a representative, conventional corn silage-based (CONVL) total mixed ration, and a dry (DRY) total mixed ration (TMR) fed to Simmental bulls. For nine months (272 days), 24 bulls (215 ± 10 kg BW) were randomly assigned to one of two TMR feeding groups (n = 12 per group). The DRY–TMR was primarily characterised by the nutrient fibre source, exclusively based on straw and other by-products. The diets were formulated and balanced based on the Cornell Net Carbohydrate and Protein System. After 272 days of fattening, bulls were slaughtered. Feed intake, average daily gain (ADG)/DM intake (DMI) ratio, and nutrient intake were affected by treatment, time, and their interaction (P

Abstract In high-yielding dairy cows, the rapidly increasing milk production after parturition can result in a negative nutrient balance, since feed intake is insufficient to cover the needs for lactation. Mobilizing body reserves, mainly adipose tissue (AT), might affect steroid metabolism. We hypothesized, that cows differing in the extent of periparturient lipomobilization, will have divergent steroid profiles measured in serum and subcutaneous (sc)AT by a targeted metabolomics approach and steroidogenic enzyme profiles in scAT and liver. Fifteen weeks antepartum, 38 multiparous Holstein cows were allocated to a high (HBCS) or normal body condition (NBCS) group fed differently until week 7 antepartum to either increase (HBCS BCS: 3.8 ± 0.1 and BFT: 2.0 ± 0.1 cm; mean ± SEM) or maintain BCS (NBCS BCS: 3.0 ± 0.1 and BFT: 0.9 ± 0.1 cm). Blood samples, liver, and scAT biopsies were collected at week −7, 1, 3, and 12 relative to parturition. Greater serum concentrations of progesterone, androsterone, and aldosterone in HBCS compared to NBCS cows after parturition, might be attributed to the increased mobilization of AT. Greater glucocorticoid concentrations in scAT after parturition in NBCS cows might either influence local lipogenesis by differentiation of preadipocytes into mature adipocytes and/or inflammatory response.

Abstract Ultrasound-(US) emitting sources are highly present in modern human environments (e.g., movement sensors, electric transformers). US affecting humans or even posing a health hazard remains understudied. Hence, ultrasonic (22.4 kHz) vs. sham devices were installed in participants’ bedrooms, and active for 28 nights. Somatic and psychiatric symptoms, sound-sensitivity, sleep quality, executive function, and structural MRI were assessed pre-post. Somatization (possible nocebo) and phasic alertness increased significantly in sham, accuracy in a flexibility task decreased significantly in the verum condition (indicating hastier responses). Effects were not sustained after p-level adjustment. Exploratory voxel-based morphometry (VBM) revealed regional grey matter (rGMV) but no regional white matter volume changes in verum (relative to placebo). rGMV increased in bilateral cerebellum VIIb/Crus II and anterior cingulate (BA24). There were rGMV decreases in two bilateral frontal clusters: in the middle frontal gyri/opercular part of inferior frontal gyrus (BA46, 44), and the superior frontal gyri (BA4 ,6, 8). No brain-behavior-links were identified. Given the overall pattern of results, it is suggested that ultrasound may particularly induce regional gray matter decline in frontal areas, however with yet unclear behavioral consequences. Given the localization of clusters, candidate behavioral variables for follow-up investigation are complex motor control/coordination, stress regulation, speech processing, and inhibition tasks. Trial registration: The trial was registered at NIH www.clinicaltrials.gov , trial identifier: NCT03459183, trial name: SonicBrain01, full trial protocol available here: https://clinicaltrials.gov/ct2/show/NCT03459183 .

Abstract Airborne infrasound (IS; emitted by e.g., large machinery, wind farms) is ubiquitous in technologized environments. Health hazards are controversially discussed at present. This study investigated long-term effects of IS on brain (regional grey matter volume; rGMV) and behavior in humans. Specifically engineered infrasonic (6 Hz, 80–90 dB) vs. sham devices were installed in participants’ (N = 38) bedrooms and active for 28 nights. Somatic and psychiatric symptoms, sound-sensitivity, sleep quality, cognitive performance, and structural MRI were assessed pre-post. Null findings emerged for all behavioral variables. Exploratory analyses revealed a trend (p = .083) with individuals exposed to IS reporting more physical weakness at post-test (d = 0.38). Voxel-based morphometry (VBM) revealed no rGMV increases, but there were decreases within clusters in the cerebellum VIIIa (bilateral) and left angular gyrus (BA39) in verum. In conclusion, IS does not affect healthy individuals on a global scale. However, future trials should consider more fine-grained specific effects, combining self-report with physiological assessments, particularly directed at bodily sensations and perception. As no brain-behavior-links could be established, the identified grey matter decline cannot be interpreted in terms of potential harmfulness vs. improvement through IS-exposure. Parameters that may best reflect brain changes as established in the present study include motor function, sensory processing/ bodily- and motor-perceptions, working memory, and higher auditory processing (i.e., language-related tasks), which are hence potential target variables for further research.

Abstract Background Computed tomography in standing horses has revolutionized diagnostic imaging. The O-arm®, a cone beam computed tomography (CBCT) scanner with a gantry opening of 96.5 cm is routinely used for image-guided spine and neurosurgery in humans. The aim of this study is to describe the set-up and first experiences using the O-arm® to achieve CBCT imaging of the head in standing horses. CT imaging of the predefined region of interest (ROI) was tested on 2 cadaveric heads, concentrating on centering issues within the gantry, as well as determining the number of scans needed per ROI. All horses presented with head-related diseases and subjected to a CBCT examination between February 2015 and November 2016 for CBCT were included. Per scan, a limited field of view, i.e. a cylindrical volume of 21 cm in diameter and 16 cm in height was acquired within 13 s. Depending on the dimensions of the ROI, the minimum number of scans could range from one to six, if the entire equine head is to be examined in an adult horse. Results Sixty-eight horses were included, five of which had a follow-up CBCT exam, and two of which were presented twice for two different indications (75 clinical cases). A total number of 449 acquired three-dimensional (3D) scans were recorded for these 75 cases. Two-hundred and forty-two 3D scans (54%) were considered as diagnostic quality. The imaging procedure was generally well tolerated by the sedated, standing equid, and diagnostic studies were performed in 73 out of 75 cases (97.3%). Motion artefacts and inadequate centering of the ROI were the most common reasons for non-diagnostic quality images and repeat scans of the same ROI. Conclusions CBCT is a valuable imaging modality for the equine head. Advantages of the O-arm® compared to a conventional multi-slice helical CT for imaging of the head in standing equids include the rapid image acquisition, the gantry’s mobility in all dimensions, and the free movability of the entire imaging unit. Disadvantages include the considerable sensitivity to motion artefact, increased scatter, low soft tissue contrast and the limited dimensions of the field of view.

Excessive mobilization of body reserves during the transition from pregnancy to lactation imposes a risk for metabolic diseases on dairy cows. We aimed to establish an experimental model for high v. normal mobilization and herein characterized performance, metabolic and endocrine changes from 7 weeks antepartum (a.p.) to 12 weeks postpartum (p.p.). Fifteen weeks a.p., 38 pregnant multiparous Holstein cows were allocated to two groups that were fed differently to reach either high or normal body condition scores (HBCS: 7.2 NEL MJ/kg dry matter (DM); NBCS: 6.8 NEL MJ/kg DM) at dry-off. Allocation was also based on differences in body condition score (BCS) in the previous and the ongoing lactation that was further promoted by feeding to reach the targeted BCS and back fat thickness (BFT) at dry-off (HBCS: >3.75 and >1.4 cm; NBCS:

Feeding management of the postnatal and preweaning calf has an important impact on calf growth and development during this critical period and affects the health and well-being of the calves. After birth, an immediate and sufficient colostrum supply is a prerequisite for successful calf rearing. Colostrum provides high amounts of nutrient as well as non-nutrient factors that promote the immune system and intestinal maturation of the calf. The maturation and function of the neonatal intestine enable the calf to digest and absorb the nutrients provided by colostrum and milk. Therefore, colostrum intake supports the start of anabolic processes in several tissues, stimulating postnatal body growth and organ development. After the colostrum feeding period, an intensive milk feeding protocol, that is, at least 20% of BW milk intake/day, is required to realise the calf potential for growth and organ development during the preweaning period. Insufficient milk intake delays postnatal growth and may have detrimental effects on organ development, for example, the intestine and the mammary gland. The somatotropic axis as the main postnatal endocrine regulatory system for body growth is stimulated by the intake of high amounts of colostrum and milk and indicates the promotion of anabolic metabolism in calves. The development of the forestomach is an important issue during the preweaning period in calves, and forestomach maturation is best achieved by solid feed intake. Unfortunately, intensive milk-feeding programmes compromise solid feed intake during the first weeks of life. In the more natural situation for beef calves, when milk and solid feed intake occurs at the same time, calves benefit from the high milk intake as evidenced by enhanced body growth and organ maturation without impaired forestomach development during weaning. To realise an intensive milk-feeding programme, it is recommended that the weaning process should not start too early and that solid feed intake should be at a high extent despite intensive milk feeding. A feeding concept based on intensive milk feeding prevents hunger and abnormal behaviour of the calves and fits the principles of animal welfare during preweaning calf rearing. Studies on milk performance in dairy cows indicate that feeding management during early calf rearing influences lifetime performance. Therefore, an intensive milk-feeding programme affects immediate as well as long-term performance, probably by programming metabolic pathways during the preweaning period.

Abstract Background Ischemia of intestinal organs is a main cause of complications in surgical intensive care patients. Changes in the tonus of arteries contributing to vascular resistance play an important role in the determination of blood flow and thus oxygen supply of various abdominal organs. It is generally acknowledged that hypoxia itself is able to alter arterial tonus and thus blood flow. Methods The present study compared the effects of various degrees of hypoxia on second-order mesenteric arteries from male C57BL/6J mice. After vessel isolation and preparation, we assessed vessel diameter using an arteriograph perfusion chamber. Investigating mechanisms promoting hypoxia-induced vasodilatation, we performed experiments in Ca2+-containing and Ca2+-free solutions, and furthermore, Ca2+-influx was inhibited by NiCl2, eNOS−/−-, and TASK1−/−-mice were investigated too. Results Mild hypoxia 14.4% O2 induced, in 50% of mesenteric artery segments from wild-type (wt) mice, a vasodilatation; severe hypoxia recruited further segments responding with vasodilatation reaching 80% under anoxia. However, the extension of dilatation of luminal arterial diameter reduced from 1.96% ± 0.55 at 14.4% O2 to 0.68% ± 0.13 under anoxia. Arteries exposed to hypoxia in Ca2+-free solution responded to lower oxygen levels with increasing degree of vasodilatation (0.85% ± 0.19 at 14.4% O2 vs. 1.53% ± 0.42 at 2.7% O2). Inhibition of voltage-gated Ca2+-influx using NiCl2 completely diminished hypoxia-induced vasodilatation. Instead, all arterial segments investigated constricted. Furthermore, we did not observe altered hypoxia-induced vasomotion in eNOS−/−- or TASK1−/− mice compared to wt animals. Conclusions The present study demonstrated that hypoxic vasodilatation in mice mesenteric arteries is mediated by a NO-independent mechanism. In this experimental setting, we found evidence for Ca2+-mediated activation of ion channels causing hypoxic vasodilatation.

The aim of this study was to determine whether feed intake amount and feed intake behaviour could be related to oestrus in dairy cows. Furthermore, we investigated whether oestrus had an effect on daily milk yield. A total of 138 oestrus cycles, leading to conception of 100 cows, were analysed. The parameters "daily fresh matter intake amount (kg)", "daily number of visits to the feeding trough" and "time spent feeding per day (min)" were electronically measured and recorded. For a sub-quantity of all animals, daily milk yield (kg) was recorded continuously and stored in the herd management software. Special attention was given to the day of oestrus, which was defined as the day of successful insemination. All remaining days of the oestrus cycle were considered as the reference period. Among all animals and cycles, fresh matter intake amount per day, number of visits per day, and time spent feeding per day were reduced by 10.3, 9.1 and 20.8 %, respectively, on the day of oestrus. Fresh matter intake was significantly lower in primiparous cows than in multiparous cows. However, number of visits to the trough and time spent feeding per day were significantly higher in primiparous cows compared to multiparous cows. Day of oestrus did not have a significant effect on daily milk yield, as this parameter was characterized by high variation among all days of the oestrus cycle. In conclusion, if an RIC system is used, monitoring of feeding behaviour appears to be a potential auxiliary aid in oestrus detection.

Aquatic germplasm repositories can play a pivotal role in securing the genetic diversity of natural populations and agriculturally important aquatic species. However, existing technologies for repository development and operation face challenges in terms of accuracy, precision, efficiency, and cost-effectiveness, especially for microdevices used in gamete quality evaluation. Quality management is critical throughout genetic resource protection processes from sample collection to final usage. In this study, we examined the potential of using three-dimensional (3-D) stereolithography resin printing to address these challenges and evaluated the overall capabilities and limitations of a representative industrial 3-D resin printer with a price of US$18,000, a consumer-level printer with a price

L’étude avait pour objectif de compléter les données sur l’épidémiologie des strongyloses gastrointestinales dans l’espèce caprine et de préciser l’influence relative de divers facteurs sur ce parasitisme et ses conséquences sur la production laitière. Plusieurs paramètres parasitologiques et physiopathologiques ont été mesurés dans un troupeau de 120 chèvres laitières au pâturage pendant deux ans. Les pics de parasitisme ont été observés en début d’automne et les genres dominants identifiés étaient "Teladorsagia" et Trichostrongylus. La conduite du troupeau selon un système de pâturage tournant ou continu n’a eu que peu d’influence sur les infestations par les nématodes. En revanche plusieurs facteurs de réceptivité de l’hôte ont été identifiés. Au cours des deux années, une excrétion d’œufs de parasites plus forte, entraînant une contamination accrue du pâturage, a été relevée dans deux groupes d’animaux au sein du troupeau : d’une part, chez les chèvres en première saison de pâturage et notamment les primipares ; d’autre part, chez les chèvres présentant le meilleur niveau de production de lait. Chez ces dernières, des répercussions physiopathologiques plus marquées du parasitisme ont aussi été notées, en particulier lors des pics d’excrétion d’œufs de strongles. Les implications de cette identification d’individus à risque parasitaire élevé dans le troupeau sur la possibilité d’application ciblée des traitements anthelminthiques sont discutées.

In esperienze eseguite su conigli di ambo i sessi e delpeso medio di kg 2, sottoposti ad accelerazioni trasversali comprese tra3 e 9-10 g, prima e dopo la deafferentazione delle zone vasosensibili pertaglio dei glossi-faringei, del nervo di Cyon e dei vaghi bilateralmente alcollo, è stato studiato il comportamento del nistagmo orizzontale prima,d u r a n t e e dopo le accelerazioni.

CRTC1::TRIM11 cutaneous tumor (CTCT) is a rare skin tumor of uncertain differentiation. In the 49 reported cases, only four cases showed regional or distant metastasis, but follow‐up remains limited. Herein, we present a case of metastatic CTCT with ulceration, a histological feature that has not been previously described. A 75‐year‐old male with a 2‐month history of toe ulceration underwent a shave biopsy, which showed a dermal nodular neoplasm that was immunoreactive for SOX10 and S100, negative for Melan‐A, and was initially diagnosed as melanoma. Upon pathology review at our institution, the tumor was composed of intersecting fascicles and nests of epithelioid and spindle cells. Additional immunohistochemistry revealed immunoreactivity of the tumor for MiTF and NTRK and negativity for HMB‐45 and PRAME. Next‐generation sequencing identified CRTC1::TRIM11 fusion, leading to a revised diagnosis of CTCT. The patient proceeded to a toe amputation and sentinel lymph node (SLN) biopsy 5 months after the shave biopsy. The amputation showed residual CTCT and a focus on lymphovascular invasion. The SLN revealed multifocal subcapsular metastases. The patient was started on adjuvant nivolumab and showed biopsy‐proven recurrence in the right inguinal lymph nodes and imaging findings suspicious for pulmonary metastases 8 months after the excision. In summary, we present a case of CTCT with ulceration and lymphovascular invasion. We also provide additional evidence that a subset of CTCT behaves aggressively. The optimal surgical and medical treatments are unknown. [ABSTRACT FROM AUTHOR]