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This experiment was motivated by the need to understand the impacts of delaying the first colostrum collection on immunoglobulin G (IgG) concentrations in goat colostrum, addressing a gap in caprine-specific research, despite its significance in dairy farming. Concurrently, we examined the relationship between colostral IgG, total protein (TP) and Brix values. Two colostrum samples were collected from 56 Saanen goats, one from each udder half. The first sample was collected from the right teat immediately postbirth, and the second sample was collected from the left teat at one of the predetermined postpartum intervals: 0, 4–6, 8–10, or 12–14 h postpartum, each time interval comprising 14 goats. Colostral IgG was determined by ELISA, Brix was determined by digital refractometry, and TP was determined by the Bradford protein method. Sperman’s correlations and Lin’s concordance correlation coefficient were used to determine the direction and strength of the association and to assess agreement (prediction accuracy) between methods, respectively. Receiver operator characteristic analysis was used to determine Brix and TP thresholds for predicting good-quality colostrum using several cut-offs (20, 30, 40, and 50 g/L IgG). Mean (± SD) for colostral IgG, Brix, and TP were 54 ± 22.6 g/L, 22 ± 5.0%, and 12 ± 2.8 g/dL, respectively. The statistical analysis did not provide evidence of a significant impact of time of first collection (up to 14 h postpartum), on IgG, Brix, and TP. Brix and IgG values exhibited both a high degree of correlation (r = 0.89–90) and concordance (ρc = 0.89–90), indicating a strong and reliable relationship between the two measurements. The prevalence of samples ≥ 20, 30, 40, and 50 g of IgG/L were 96, 88, 71, and 54%, respectively. Optimal Brix and TP thresholds predicting IgG ≥ 20, 30, 40, and 50 g/L IgG were 13.8, 17.5, 20.1, and 22.5%, and 6.8, 9.3, 10.8, and 11.1 g/dL, respectively. Increasing the IgG threshold resulted in lower sensitivity but higher specificity for estimating colostral IgG using Brix or TP values. The present findings indicate that delaying the first colostrum collection up to 14 h postpartum did not result in conclusive changes in colostral IgG concentration, Brix values, or total protein levels. Our results also confirm the reliability of Brix refractometry as an on-farm tool for estimating IgG concentrations in goat colostrum. These results are particularly relevant to intensive dairy systems, offering insights to enhance colostrum management and task prioritisation, especially during the bustling kidding periods.

This experiment was motivated by the need to understand the impacts of delaying the first colostrum feeding on the prevalence of failed transfer of passive immunity (FTPI). A cohort of 216 kids was stratified into groups based on the colostrum feeding delay postbirth: 0–4 h, 4–8 h, 8–12 h, and 12–16 h. All kids received a single colostrum meal of 300 mL, and blood samples were collected approximately 36 h after feeding. Serum immunoglobulin G (SIgG) was measured using ELISA, and serum total protein (STP) was assessed using the Bradford method and refractometry (STPb and STPr). Statistical methods like Pearson correlations, Bland-Altman plots, and Lin’s concordance coefficient were employed to assess associations and agreements between SIgG, STPb and STPr. Receiver operator characteristic analysis was employed to determine optimal STPb and STPr thresholds for predicting FTPI (SIgG < 12 g/L). Subsequently, areas under the curve, sensitivity, and specificity were examined to assess the accuracy of these thresholds. Our results showed that for each hour’s delay from birth to colostrum intake (up to 16 h), IgG apparent efficiency of absorption (AEA) decreases at an approximate rate of 2.0% per hour, and SIgG decreases at an approximate rate of 1.0 g/L per hour. However, this decline is not constant over time but intensifies progressively with increased feeding delay. Specifically, reductions in IgG AEA were 1.3, 2.9, and 5.9% per hour, and decreases in SIgG were 0.2, 0.3, and 0.7 g per hour for SIgG across the time intervals of 0–4 to 4–8 h, 4–8 to 8–12 h, and 8–12 to 12–16 h, respectively. Additionally, there was an increase in SIgG of 1.2 g/dL but a decrease in IgG AEA of 1.9% for each gram per kg of BW increase in IgG intake. The correlations between SIgG and STPr and STPb were 0.62, and 0.36, respectively. Optimal STPr and STPb thresholds predicting FTPI were determined to be 4.6 and 6.2 g/dL. The prevalence of FTPI, according to SIgG, STPr, and STPb thresholds were 63, 62, and 45%. Overall, STPr showed higher values for key performance metrics (i.e., sensitivity, likelihood ratio of positive tests, overall accuracy, and Youden’s index), indicating better prediction ability than STPb. Our findings corroborate the critical importance of swift colostrum administration, ideally occurring no later than 12 h postbirth. Moreover, our research validates the effectiveness of Brix refractometry as a practical, on-farm method for assessing FTPI in goat kids.

In dairy operations, antibiotics have traditionally been used to treat, prevent, and control diseases. However, given the mounting global crisis of antimicrobial resistance (AMR), farmers are urged to re-assess and reduce their reliance on antibiotics. Thus, this randomized, double-blinded cohort study aimed to estimate the prevalence of failed and successful transfer of passive immunity (FTPI and STPI) in dairy goat kids reared under commercial conditions, and the effects of antibiotic metaphylaxis on the pre-weaning (≤42 d old) mortality in FTPI and STPI kids. Plasma concentration of immunoglobulin G at 1d old (pIgG-24 h) was measured in 747 male Saanen kids for the determination of FTPI and STPI (pIgG-24 h

The high preweaning mortality rate is a concerning issue for the commercial dairy industry. In this context, early identification of at-risk individuals can be instrumental. To address this, we conducted a prospective cohort study with the objective of evaluating plasma immunoglobulin G concentration (pIgG-24 h) and initial BW (IBW) measured at 1d old in 363 male dairy kids (Saanen) for predicting preweaning mortality under commercial conditions. Receiver operator characteristic (ROC) analysis was used to determine critical thresholds for pIgG-24 h and IBW. Subsequently, areas under the curve (AUC), sensitivity (Se), and specificity (Sp) were examined to assess the accuracy of these thresholds. Multivariable regressions were used to model odds ratios (OR) for mortality, controlling for confounding effects between IBW and pIgG-24 h. The mean (±SD) pIgG-24 h and IBW were 16.4 ± 9.37 g/L and 4.0 ± 0.61 kg. Overall mortality ≤ 14d and ≤42d old was 12% and 21%, respectively. Critical pIgG-24 h thresholds predicting mortality ≤ 14 d and ≤42 d old were

Goat kid rearing is a key profit driver and the cornerstone of future herd productivity in dairy systems. As goat kids get older, and progress from liquid (i.e., colostrum, milk) to solid feed (i.e., concentrate, hay, pasture), there is a reduction not only in feed cost but also in labour cost, disease susceptibility and mortality rates. Hence, research on rearing dairy goats has traditionally focused on improving early neonatal performance. However, recent research reveals that early-life nutrition may have long-term effects, and consequently, impact the lifetime productive performance and health of dairy goats. Therefore, this literature review has collected research on the various aspects of rearing replacement dairy goat kids in different production systems. It summarises research on areas such as colostrum management (i.e., colostrum quality, time, volume and frequency of colostrum feeding), liquid feeding in preweaned kids (i.e., maternal suckling vs artificial, restricted vs unrestricted), weaning strategies (i.e., abrupt vs step-down), and postweaning to postpubertal nutrition in replacement dairy goats, whilst highlighting gaps in the existing literature, and areas where it would be beneficial to refine and validate current recommendations. Such information can be used in the development of management plans to maximise the benefits of early-life nutrition on the long-term productivity of dairy goats.

This experiment aimed to investigate the correlations between surrogate indices of insulin resistance (IR)—namely, the homeostasis model of IR, the quantitative insulin sensitivity check index, and the revised quantitative insulin sensitivity check index—and measures of IR obtained from an intravenous glucose tolerance test (IVGTT) performed in early-lactation dairy goats. Saanen goats (n = 26) with varying levels of milk production (1.7–4.8 kg/d) were selected and underwent an IVGTT on 43 ± 0.7 d postpartum (mean ± standard deviation). Data from the IVGTT were fitted in the minimal model to calculate parameters of glucose–insulin dynamics such as insulin sensitivity index and acute insulin response to glucose. Surrogate indices were computed using the average of the IVGTT basal samples. Correlation analysis revealed no relationship between surrogate indices of IR and measures of IR derived from the IVGTT (e.g., insulin sensitivity index, glucose clearance rate, glucose area under the curve). Therefore, our results suggest that surrogate indices of IR are not suitable for assessing the insulin sensitivity of peripheral tissue in early-lactation goats.

Introduction: Most patients with HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) have an excellent response to chemoradiation, and trials are now investigating de-escalated treatment. However, up to 25% of patients with HPV-positive OPSCC will experience recurrence, and up to 5% will even progress through primary treatment. Currently, there are no molecular markers to identify patients with poor prognosis who would be harmed by de-escalation. Herein we report the clinical and genomic characteristics of persistent HPV-positive OPSCC after definitive platinum-based chemoradiation therapy., Methods: Patients with HPV-positive OPSCC treated with curative intent platinum-based chemoradiation between 2007 and 2017 at two institutions and with a persistent locoregional disease were included. We evaluated clinical characteristics, including smoking status, age, stage, treatment, and overall survival. A subset of five patients had tissue available for targeted exome DNA sequencing and RNA sequencing. Genomic analysis was compared to a previously published cohort of 47 treatment-responsive HPV+ OPSCC tumors after batch correction. Mutational landscape, pathway activation, and OncoGPS tumor states were employed to characterize these tumors., Results: Ten patients met the inclusion criteria. The tumor and nodal stages ranged from T1 to T4 and N1 to N2 by AJCC 8th edition staging. All patients were p16-positive by immunohistochemistry, and eight with available in situ hybridization were confirmed to be HPV-positive. The 1-year overall survival from the time of diagnosis was 57%, and the 2-year overall survival was 17%. TP53 mutations were present in three of five (60%) persistent tumors compared to 2% (one of 47) of treatment-responsive HPV-positive tumors ( p = 0.008). Other genes with recurrent mutations in persistent HPV-positive OPSCC tumors were NF1 , KMT2D , PIK3C2B , and TFGBR2 . Compared to treatment-responsive HPV-positive tumors, persistent tumors demonstrated activation of DNA Repair and p53, EMT, MYC, SRC, and TGF-beta signaling pathways, with post-treatment samples demonstrating significant activation of the PI3K-EMT-Stem pathways compared to pretreatment samples., Conclusion: Chemoradiation-resistant HPV-positive OPSCC occurs infrequently but portends a poor prognosis. These tumors demonstrate higher rates of p53 mutation and activation of MYC, SRC, and TGF-beta pathways. A comparison of tumors before and after treatment demonstrates PI3K-EMT-Stem pathways post-treatment in HPV-positive tumors with persistent disease after platinum-based chemoradiation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Guo, Zamuner, Ting, Chen, Rooper, Tamayo, Fakhry, Gaykalova and Mehra.)

Evidence suggests that camel milk (CM) can have insulin-like actions, although the mode of action is not understood. Using the pig as a monogastric model, this pilot experiment examined the effects of CM consumption on metabolic responses to an in vitro glucose tolerance test (IVGTT). Twenty female Large White × Landrace pigs were individually housed for 6 wks and randomly allocated to one of the following four diets (fed ad libitum; n = 5): control (Con); high fat (HF; ~16% fat); raw CM (the HF diet plus 500 mL CM/ day); or pasteurized CM (PCM). Blood samples were collected on two occasions (weeks 2 and 5). At week 6, the pigs were fitted with an ear vein cannula and the following day an in vitro glucose tolerance test (IVGTT) was conducted (0.3 g/kg BW glucose). Plasma fatty acids and cholesterol concentrations were greater in the pigs fed the HF diet and greatest in those fed CM, while there was no effect of diet on insulin concentrations. The pigs fed CM tended to have a reduced peak insulin ( p = 0.058) and an increased glucose nadir ( p = 0.009) in response to the IVGTT. These preliminary results tend to support the hypothesis that feeding CM can improve glycemic control in pigs.

This experiment aimed to examine endocrine and metabolic responses to glucose, insulin, and adrenocorticotropin (ACTH) infusions in early-lactation dairy goats of different levels of milk production (LMP). Goats were grouped as either high (HY; 4.0 L/d, n = 13) or low milk yield (LY; 2.4 L/d, n = 13). Individual milk yield (L/d) and dry matter intake (DMI; kg/d) were measured daily. Concentration (mM) of glucose, fatty acids, and β-hydroxybutyrate, percent of milk fat and protein, body weight (BW; kg), and body condition score (BCS) were assessed weekly (from 2-6 wk postpartum). An intravenous glucose tolerance test (IVGTT), an insulin tolerance test (ITT), and an ACTH stimulation test were carried out at 43, 44, and 45 ± 0.7 d in milk, respectively. The HY goats had greater milk yield (+67%), energy-corrected milk (ECM; +70%), DMI (+28%), ratio of ECM output to metabolic BW (+67%), and feed efficiency (+25%), but lesser BCS than LY goats (2.4 vs. 2.6). The DMI (% of BW) was moderately correlated with ECM (r = 0.70) and negatively correlated with BCS (r = -0.57). At the time of the IVGTT, HY goats had lesser basal insulin and glucose than LY goats. However, results from IVGTT and ITT indicate that the sensitivity of peripheral tissues to insulin was unaffected by LMP. Compared with LY, HY goats had lesser insulin secretion (-52%) and greater insulin clearance rate (+47%) after glucose infusion. The ITT and ACTH stimulation test results show that both the growth hormone response to insulin and the cortisol response to ACTH were unaffected by LMP. Also, basal plasma concentrations of GH and cortisol were not correlated with glucose and fatty acids concentrations or any performance traits. Collectively, our results suggest that differences between HY and LY goats, concerning milk yield and feed efficiency, were probably more closely related to differences in insulin secretion and clearance than to differences in peripheral tissue responsiveness to the effects of catabolic and anabolic hormones., (Copyright © 2020 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Background: Identifying potential resistance mechanisms while tumour cells still respond to therapy is critical to delay acquired resistance., Methods: We generated the first comprehensive multi-omics, bulk and single-cell data in sensitive head and neck squamous cell carcinoma (HNSCC) cells to identify immediate responses to cetuximab. Two pathways potentially associated with resistance were focus of the study: regulation of receptor tyrosine kinases by TFAP2A transcription factor, and epithelial-to-mesenchymal transition (EMT)., Results: Single-cell RNA-seq demonstrates heterogeneity, with cell-specific TFAP2A and VIM expression profiles in response to treatment and also with global changes to various signalling pathways. RNA-seq and ATAC-seq reveal global changes within 5 days of therapy, suggesting early onset of mechanisms of resistance; and corroborates cell line heterogeneity, with different TFAP2A targets or EMT markers affected by therapy. Lack of TFAP2A expression is associated with HNSCC decreased growth, with cetuximab and JQ1 increasing the inhibitory effect. Regarding the EMT process, short-term cetuximab therapy has the strongest effect on inhibiting migration. TFAP2A silencing does not affect cell migration, supporting an independent role for both mechanisms in resistance., Conclusion: Overall, we show that immediate adaptive transcriptional and epigenetic changes induced by cetuximab are heterogeneous and cell type dependent; and independent mechanisms of resistance arise while tumour cells are still sensitive to therapy.

Objectives: Notch signaling is frequently altered in head and neck squamous cell carcinoma (HNSCC). However, the nature and clinical implications of this dysregulation are not well understood. We previously described an association of transcriptionally active NOTCH1 Intracellular Domain (NICD1) immunohistochemical (IHC) expression pattern with high-risk pathologic characteristics. Here we further characterize Notch signaling in HNSCC., Materials and Methods: IHC expression patterns and clinicopathologic associations of Notch pathway molecules were evaluated among 78 tumors with known NOTCH1 mutation status. IHC was performed for JAG1, a NOTCH1 activating ligand, and HEY1, an NICD1 transcriptional target and Notch pathway activation marker. IHC pattern and H-score (% staining × intensity) were recorded and compared to clinicopathologic characteristics and survival. Survival was analyzed using Kaplan Meier method and Cox proportional hazards models (HR)., Results: JAG1 and NICD1 expression patterns were highly concordant among tumors without truncating NOTCH1 mutations (p < 0.001), but were dissimilar among tumors with truncating NOTCH1 mutations (p = 0.24). There was evidence for JAG1-independent NOTCH1 activation among seven tumors, all with wild-type NOTCH1. HEY1 expression was associated with neither JAG1 nor NICD1 expression, but was associated with NOTCH1 mutation status (p = 0.03). Twelve (16%) tumors expressed HEY1 but not NICD1. Higher HEY1 H-score was significantly associated with worse overall (adjusted hazard ratio [aHR] 2.0, 95% CI = 1.0-4.2) and disease-specific (aHR = 3.3, 95% CI = 1.4-7.9) survival, whereas JAG1 and NICD1 expression were not associated with survival., Conclusions: These findings suggest both NOTCH1-dependent and -independent HEY1 regulation, and imply a previously unrecognized prognostic role for HEY1 in HNSCC., (Copyright © 2018 Elsevier Ltd. All rights reserved.)