Mechanical nociceptive threshold testing in Bos indicus bull calves

The aim of this prospective, controlled, randomised trial was to develop a technique for mechanical nociceptive threshold testing (NTT) to assess pain in Bos indicus bull calves undergoing surgical castration. Analgesia was provided by 0.5 mg/kg subcutaneous (SC) meloxicam (M) and/or 2 mg/kg of intra-testicular and SC (at the surgery sites) lidocaine (L). Forty-eight Brahman bull calves at 6–8 months of age were divided into six study groups, each with eight animals: no surgery control; surgical castration (C) without analgesia; C and Mpre-op; C and Mpost-op; C, L and Mpost-op; C and L. Mechanical NTT was performed the day before surgery (Day –1) and on Days 1, 2, 6, 10 and 13 after surgery. A handheld manual pneumatic device with a 1-mm (diameter) blunt pin was used to deliver a mechanical stimulus to a maximum of 27 Newtons either side of the most dorsal aspect of the sacrum. The most frequent responses to the mechanical stimulus were lifting or kicking of the leg on the same side as the stimulus (31%) and stepping away from the stimulus (24.9%). Data were analysed with a mixed effect linear model with the nociceptive threshold (NT) as the response variable and day and analgesic treatment as predictors (P < 0.05 was considered significant). For all groups, there was a trend towards decreasing NT over the study period but there were no significant differences between groups. Step down model selection with day, batch and treatment terms revealed a significant effect of day (P < 0.001) and batch (P = 0.007). Mechanical NTT for assessment of pain in Bos indicus bull calves requires further refinement to determine if this is a useful method of pain assessment

Pregnant Sheep in a Farm Environment Did Not Develop Anaemia

The aim of this study was to document the haematological profile of pregnant ewes throughout gestation. Sheep were divided into three groups (n = 8 per group): non-pregnant, singleton, or twin pregnancy. Blood samples were collected every 14 days from day 55 of gestation for haemoglobin concentration; packed cell volume; total protein; and albumin concentration. On days 55 and 125 of gestation blood was collected for trace element estimation: soluble copper and zinc; glutathione peroxidase (GSHPx); and methylmalonic acid (MMA). Pooled faecal samples were collected on days 55, 97, and 139 of gestation. Pasture cuts were collected on days 97 and 153 of gestation. The haematology and protein concentrations were not different between groups throughout the study. Copper concentration increased in all animals during the study (p < 0.0001). Zinc concentration was lowest in the singleton and twin pregnant sheep on day 55 of gestation (p = 0.04). GSHPx was not different between groups during the study. MMA decreased in all animals during the study (p < 0.0001), but was not different between groups. Faecal samples were consistently negative for strongyle and nematode eggs, and coccidian oocysts. The pasture was good quality. Pregnant sheep in a farm environment with normal trace element status, no parasites, and an adequate diet, did not develop anaemia (PCV < 0.27)

Qualitative Behavioural Assessment of Bos indicus cattle after surgical castration

There are various methods to perform castration of cattle, but surgical castration is the most common. Although it is well documented that surgical procedures inflict pain, analgesic use is usually omitted for surgical castration of production animals in Australia. This study compares the behavioural responses of castrated cattle (C) with non-castrated (NC) controls, and C with those castrated and given lignocaine and meloxicam (CLM) for analgesia. Brahman bull calves (n = 8 for each treatment) were filmed in the morning pre- (day -1) and post- (day +1) castration in the paddock and feed yard (‘context’ of observation). Over four sessions, volunteer observers viewed the video footage for Qualitative Behaviour Analysis (QBA) using the Free Choice Profiling methodology comparing C and NC cattle, and C and CLM cattle under both contexts. The QBA consensus profiles explained 37.4% (C vs. NC) and 40.6% (C vs. CLM) of variation among observers for paddock sessions and 34.7% (C vs. NC) and 38.7% (C vs. CLM) for feed yard sessions. Significant treatment x day interaction effects were recorded in the paddock (P = 0.007 and P < 0.001) and yard (P =  0.004 and P =  0.025) contexts for comparisons between NC vs C, and C vs CLM respectively. Compared to NC, post-castration C cattle were described as more ‘bored’/’lethargic’ and ‘alone’ (paddock) and were more ‘calm’/’relaxed’ and ‘relaxed’/’lonely’ (yard). Similarly, compared to CLM, post-castration C cattle were described as more ‘docile’/’chilled’ and ‘curious’/’aware’ (paddock) and were less ‘hungry’/’alert’ (yard). There was only one correlation between qualitative and quantitative behaviour scoring; ruminating showed significant correlation with one dimension in each context, that reflected a positive emotion (‘calm, relaxed’). The comparison between C vs. NC suggest that C were less active and less engaged with their environment compared to the NC group following castration. The C vs. CLM comparison suggests a more subtle response whereby analgesia was associated with more positive valence (higher scores on ‘calm/comfortable’, and ‘hungry/alert’ dimensions) following castration. The interpretation of findings requires careful consideration of the emotional responses given these calves were unhabituated and reactive to their surroundings. These results suggest the body language of Bos indicus cattle may reveal indicators of pain, and that the administration of analgesia may be beneficial at the time of castration. The study highlights the complexities and challenges of identifying pain responses in Brahman cattle

Mitigation of electroencephalographic and cardiovascular responses to castration in Bos indicus bulls following the administration of either lidocaine or meloxicam

Objective To investigate the mitigating effects of administration of local or systemic meloxicam on the electroencephalographic (EEG) and cardiovascular responses during surgical castration of Bos indicus bull calves. Study design Prospective, randomized, experimental study. Animals Thirty-six 6–8 month-old Bos indicus bull calves, with a mean ± standard deviation weight of 237 ± 19 kg. Methods Animals were randomly allocated to three groups of 12 (group L, 260 mg of 2% lidocaine subcutaneously and intratesticularly 5 minutes prior to castration; group M, 0.5 mg kg−1 of meloxicam subcutaneously 30 minutes prior to castration; group C, no pre-operative analgesia administered). Anaesthesia was induced and maintained with halothane (0.9–1.1%) in oxygen. Electroencephalogram, heart rate (HR) and mean blood pressure (MAP) were recorded for 300 seconds prior to (baseline, B) and from the start of surgery (first testicle incision, T1). HR and MAP were compared at 10 second intervals for 90 seconds from the start of T1. Median frequency (F50), spectral edge frequency (F95) and total power of the EEG (Ptot) were analysed using area under the curve comparing T1 to B. Results All EEG variables were significantly different between B and T1 (p ≤ 0.0001). No differences in F50 were found between groups during T1 (p = 0.6491). F95 and Ptot were significantly different between group L and groups C and M during T1 (p = 0.0005 and 0.0163, respectively). There were transient significant changes in HR and MAP in groups L and M compared to group C during the 20–50 second periods. Conclusions The EEG changes indicate nociceptive responses in all three groups during surgical castration, greater in group L compared to groups C and M. Both analgesics attenuated the peracute cardiovascular response. Lidocaine and meloxicam administered prior to castration attenuated these responses in Bos indicus bull calves. Clinical relevance These findings provide support for the pre-operative administration of lidocaine and potentially meloxicam for castration in Bos indicus bull calves

Phylogenomic analysis of a 55.1 kb 19-gene dataset resolves a monophyletic Fusarium that includes the Fusarium solani Species Complex

Scientific communication is facilitated by a data-driven, scientifically sound taxonomy that considers the end-user¿s needs and established successful practice. In 2013, the Fusarium community voiced near unanimous support for a concept of Fusarium that represented a clade comprising all agriculturally and clinically important Fusarium species, including the F. solani species complex (FSSC). Subsequently, this concept was challenged in 2015 by one research group who proposed dividing the genus Fusarium into seven genera, including the FSSC described as members of the genus Neocosmospora, with subsequent justification in 2018 based on claims that the 2013 concept of Fusarium is polyphyletic. Here, we test this claim and provide a phylogeny based on exonic nucleotide sequences of 19 orthologous protein-coding genes that strongly support the monophyly of Fusarium including the FSSC. We reassert the practical and scientific argument in support of a genus Fusarium that includes the FSSC and several other basal lineages, consistent with the longstanding use of this name among plant pathologists, medical mycologists, quarantine officials, regulatory agencies, students, and researchers with a stake in its taxonomy. In recognition of this monophyly, 40 species described as genus Neocosmospora were recombined in genus Fusarium, and nine others were renamed Fusarium. Here the global Fusarium community voices strong support for the inclusion of the FSSC in Fusarium, as it remains the best scientific, nomenclatural, and practical taxonomic option availabl

Associations of common breast cancer susceptibility alleles with risk of breast cancer subtypes in BRCA1 and BRCA2 mutation carriers

Introduction: More than 70 common alleles are known to be involved in breast cancer (BC) susceptibility, and several exhibit significant heterogeneity in their associations with different BC subtypes. Although there are differences in the association patterns between BRCA1 and BRCA2 mutation carriers and the general population for several loci, no study has comprehensively evaluated the associations of all known BC susceptibility alleles with risk of BC subtypes in BRCA1 and BRCA2 carriers. Methods: We used data from 15,252 BRCA1 and 8,211 BRCA2 carriers to analyze the associations between approximately 200,000 genetic variants on the iCOGS array and risk of BC subtypes defined by estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and triple-negative- (TN) status; morphologic subtypes; histological grade; and nodal involvement. Results: The estimated BC hazard ratios (HRs) for the 74 known BC alleles in BRCA1 carriers exhibited moderate correlations with the corresponding odds ratios from the general population. However, their associations with ER-positive BC in BRCA1 carriers were more consistent with the ER-positive as

Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk

Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk

BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7×10-8, HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4×10-8, HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4×10-8, HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific associat

Classification of current anticancer immunotherapies

During the past decades, anticancer immunotherapy has evolved from a promising therapeutic option to a robust clinical reality. Many immunotherapeutic regimens are now approved by the US Food and Drug Administration and the European Medicines Agency for use in cancer patients, and many others are being investigated as standalone therapeutic interventions or combined with conventional treatments in clinical studies. Immunotherapies may be subdivided into “passive” and “active” based on their ability to engage the host immune system against cancer. Since the anticancer activity of most passive immunotherapeutics (including tumor-targeting monoclonal antibodies) also relies on the host immune system, this classification does not properly reflect the complexity of the drug-host-tumor interaction. Alternatively, anticancer immunotherapeutics can be classified according to their antigen specificity. While some immunotherapies specifically target one (or a few) defined tumor-associated antigen(s), others operate in a relatively non-specific manner and boost natural or therapy-elicited anticancer immune responses of unknown and often broad specificity. Here, we propose a critical, integrated classification of anticancer immunotherapies and discuss the clinical relevance of these approaches