A Highly Effective Protocol for the Rapid and Consistent Induction of Digital Dermatitis in Holstein Calves

Bovine Digital Dermatitis (DD) is a leading cause of lameness in dairy cattle. DD is reportedly increasing in prevalence in beef cattle feedlots of the US. The exact etiologic agent(s) responsible for the disease have yet to be determined. Multiple studies have demonstrated the presence of a variety of Treponema spp. within lesions. Attempts to reproduce clinically relevant disease using pure cultures of these organisms has failed to result in lesions that mirror the morphology and severity of naturally occurring lesions. This manuscript details the systematic development of an experimental protocol that reliably induces digital dermatitis lesions on a large enough scale to allow experimental evaluation of treatment and prevention measures. In total, 21 protocols from five experiments were evaluated on their effectiveness in inducing DD lesions in 126 Holstein calves (504 feet). The protocols varied in the type and concentration of inoculum, frequency of inoculation, duration the feet were wrapped, and type of experimental controls need to validate a successful induction. Knowledge gained in the first four experiments resulted in a final protocol capable of inducing DD lesions in 42 of 44 (95%) feet over a 28 day period. All induced lesions were macroscopically and microscopically identified as clinical DD lesions by individuals blinded to protocols. Lesions were also located at the site of inoculation in the palmer aspect of the interdigital space, and induced clinically measurable lameness in a significant portion of the calves. Collectively these results validate the model and provide a rapid and reliable means of inducing DD in large groups of calves

Asymmetric band profile of the Soret band of deoxymyoglobin is caused by electronic and vibronic perturbations of the heme group rather than by a doming deformation

Journal of Chemical Physics, 127(13): pp. 135103We measured the Soret band of deoxymyoglobin deoxyMb , myoglobin cyanide MbCN , and aquo-metmyoglobin all from horse heart with absorption and circular dichroism CD spectroscopies. A clear non-coincidence was observed between the absorption and CD profiles of deoxyMb and MbCN, with the CD profiles red- and blueshifted with respect to the absorption band position, respectively. On the contrary, the CD and absorption profiles of aquametMb were nearly identical. The observed noncoincidence indicates a splitting of the excited B state due to heme-protein interactions. CD and absorption profiles of deoxyMb and MbCN were self-consistently analyzed by employing a perturbation approach for weak vibronic coupling as well as the relative intensities and depolarization ratios of seven bands in the respective resonance Raman spectra measured with B-band excitation. The respective By component was found to dominate the observed Cotton effect of both myoglobin derivatives. The different signs of the noncoincidences between CD and absorption bands observed for deoxyMb and MbCN are due to different signs of the respective matrix elements of A1g electronic interstate coupling, which reflects an imbalance of Gouterman’s 50:50 states. The splitting of the B band reflects contributions from electronic and vibronic perturbations of B1g symmetry. The results of our analysis suggest that the broad and asymmetric absorption band of deoxyMb results from this band splitting rather than from its dependence on heme doming. Thus, we are able to explain recent findings that the temperature dependences of CO rebinding to myoglobin and the Soret band profile are uncorrelated Ormos et al., Proc. Natl. Acad. Sci U.S.A. 95, 6762 1998

Molecular epidemiology of coagulase-negative Staphylococcus species isolated at different lactation stages from dairy cattle in the United States

Background Coagulase negative Staphylococcus (CNS) species are currently the most prevalent intra-mammary pathogens causing subclinical mastitis and occasional clinical mastitis or persistent infection in lactating dairy cattle. More than 10 CNS species have been identified, but they are generally managed as one group on most dairies in the United States. However, improved management decisions and treatment outcomes may be achieved with better understanding of the prevalent species, pathogenicity and strain diversity within and across dairies. Methodology A total of 604 CNS isolates were cultured from milk samples collected during a dry-cow treatment clinical trial conducted on 6 dairy herds in 4 states in the US. All the study cows were randomized to receive 1 of the 3 different intra-mammary antimicrobial infusions (Quatermaster, Spectramast DC or ToMorrow Dry Cow) at dry-off. Milk samples were collected at dry-off, calving (0–6 days in milk, DIM), post-calving (7–13 DIM) and at mastitis events within the first 100 DIM. The CNS isolates were identified to species level by partial sequencing of the rpoβ gene, and genetic relatedness within species was investigated by phylogenetic analysis of the pulse-field gel electrophoresis profiles of the isolates. Results The major CNS species identified were S. chromogenes (48.3%), S. haemolyticus (17.9%), S. simulans and S. epidermidis (each at 6.5%). Other CNS species identified at lower frequencies included S. hominis, S. auricularis, S. sciuri, S. spp KS-SP, S. capitis, S. cohnii, S. warneri, S. pasteuri, S. xylosus, S. hyicus, S. equorum, S. microti, S. rostri, S. gallinarum, S. saprophyticus and S. succinus. Phylogenetic analyses of the major species types demonstrated an association between genetic relatedness and epidemiological distributions of S. chromogenes, S. simulans, S. haemolyticus and S. auricularis. Additionally, identical strains of S. chromogenes and S. simulans were isolated from the same udder quarter of several cows at consecutive sample stages. The rest of the minor species had no deducible genetic-epidemiological link. Discussion The observed association between genetic and epidemiological distributions indicated animal-adapted nature of four CNS species, suggesting possible host-adapted and environmental transmission of these species. Multi-stage isolation of the same udder quarter strain was evidence for chronic intra-mammary infection. Conclusion The different CNS species and strains circulating on US dairy herds were genetically diverse. Four species identified were likely udder-adapted pathogens, 2 of which caused persistent infection. Our findings are important in guiding the design of effective mastitis control strategies

A Phase II Trial of Sorafenib in Metastatic Melanoma with Tissue Correlates

Sorafenib monotherapy in patients with metastatic melanoma was explored in this multi-institutional phase II study. In correlative studies the impact of sorafenib on cyclin D1 and Ki67 was assessed. mutational status and clinical activity. No significant changes in expression of cyclin D1 or Ki67 with sorafenib treatment were demonstrable in the 15 patients with pre-and post-treatment tumor samples. mutational status of the tumor was not associated with clinical activity and no significant effect of sorafenib on cyclin D1 or Ki67 was seen, suggesting that sorafenib is not an effective BRAF inhibitor or that additional signaling pathways are equally important in the patients who benefit from sorafenib

Patient-reported outcome measures of the impact of cancer on patient’s everyday lives: a systematic review

Purpose: Patients with advanced disease are living longer and commonly used patient-reported outcome measures (PROMs) may miss relevant elements of the quality of extended survival. This systematic review examines the measures used to capture aspects of the quality of survival including impact on patients’ everyday lives such as finances, work and family roles. Methods: Searches were conducted in MEDLINE, EMBASE, CINAHL and PsycINFO restricted to English language articles. Information on study characteristics, instruments and outcomes was systematically extracted and synthesised. A predefined set of criteria was used to rate the quality of studies. Results: From 2761 potentially relevant articles, 22 met all inclusion criteria, including 10 concerning financial distress, 3 on roles and responsibilities and 9 on multiple aspects of social well-being. Generally, studies were not of high quality; many lacked bias free participant selection, had confounding factors and had not accounted for all participants. High levels of financial distress were reported and were associated with multiple demographic factors such as age and income. There were few reports concerned with impacts on patients’ roles/responsibilities in everyday life although practical and emotional struggles with parenting were identified. Social difficulties were common and associated with multiple factors including being a caregiver. Many studies were single time-point surveys and used non-validated measures. Exceptions were employment of the COST and Social Difficulties Inventory (SDI), validated measures of financial and social distress respectively. Conclusions: Impact on some important parts of patients’ everyday lives is insufficiently and inconsistently captured. Further PROM development focussing on roles and responsibilities, including work and caring for dependents, is warranted. Implications for Cancer Survivors: Factors such as finances, employment and responsibility for caring for dependents (e.g. children and elderly relatives) can affect the well-being of cancer survivors. There is a need to ensure that any instruments used to assess patients’ social well-being are broad enough to include these areas so that any difficulties arising can be better understood and appropriately supported

A Highly Effective Protocol for the Rapid and Consistent Induction of Digital Dermatitis in Holstein Calves

Bovine Digital Dermatitis (DD) is a leading cause of lameness in dairy cattle. DD is reportedly increasing in prevalence in beef cattle feedlots of the US. The exact etiologic agent(s) responsible for the disease have yet to be determined. Multiple studies have demonstrated the presence of a variety of Treponema spp. within lesions. Attempts to reproduce clinically relevant disease using pure cultures of these organisms has failed to result in lesions that mirror the morphology and severity of naturally occurring lesions. This manuscript details the systematic development of an experimental protocol that reliably induces digital dermatitis lesions on a large enough scale to allow experimental evaluation of treatment and prevention measures. In total, 21 protocols from five experiments were evaluated on their effectiveness in inducing DD lesions in 126 Holstein calves (504 feet). The protocols varied in the type and concentration of inoculum, frequency of inoculation, duration the feet were wrapped, and type of experimental controls need to validate a successful induction. Knowledge gained in the first four experiments resulted in a final protocol capable of inducing DD lesions in 42 of 44 (95%) feet over a 28 day period. All induced lesions were macroscopically and microscopically identified as clinical DD lesions by individuals blinded to protocols. Lesions were also located at the site of inoculation in the palmer aspect of the interdigital space, and induced clinically measurable lameness in a significant portion of the calves. Collectively these results validate the model and provide a rapid and reliable means of inducing DD in large groups of calves.This article is published as Krull, Adam C., Vickie L. Cooper, John W. Coatney, Jan K. Shearer, Patrick J. Gorden, and Paul J. Plummer. "A highly effective protocol for the rapid and consistent induction of digital dermatitis in Holstein calves." PloS one 11, no. 4 (2016): e0154481. doi: 10.1371/journal.pone.0154481. Posted with permission.</p

Molecular epidemiology of coagulase-negative Staphylococcus species isolated at different lactation stages from dairy cattle in the United States.

BackgroundCoagulase negative Staphylococcus (CNS) species are currently the most prevalent intra-mammary pathogens causing subclinical mastitis and occasional clinical mastitis or persistent infection in lactating dairy cattle. More than 10 CNS species have been identified, but they are generally managed as one group on most dairies in the United States. However, improved management decisions and treatment outcomes may be achieved with better understanding of the prevalent species, pathogenicity and strain diversity within and across dairies.MethodologyA total of 604 CNS isolates were cultured from milk samples collected during a dry-cow treatment clinical trial conducted on 6 dairy herds in 4 states in the US. All the study cows were randomized to receive 1 of the 3 different intra-mammary antimicrobial infusions (Quatermaster, Spectramast DC or ToMorrow Dry Cow) at dry-off. Milk samples were collected at dry-off, calving (0-6 days in milk, DIM), post-calving (7-13 DIM) and at mastitis events within the first 100 DIM. The CNS isolates were identified to species level by partial sequencing of the rpoβ gene, and genetic relatedness within species was investigated by phylogenetic analysis of the pulse-field gel electrophoresis profiles of the isolates.ResultsThe major CNS species identified were S. chromogenes (48.3%), S. haemolyticus (17.9%), S. simulans and S. epidermidis (each at 6.5%). Other CNS species identified at lower frequencies included S. hominis, S. auricularis, S. sciuri, S. spp KS-SP, S. capitis, S. cohnii, S. warneri, S. pasteuri, S. xylosus, S. hyicus, S. equorum, S. microti, S. rostri, S. gallinarum, S. saprophyticus and S. succinus. Phylogenetic analyses of the major species types demonstrated an association between genetic relatedness and epidemiological distributions of S. chromogenes, S. simulans, S. haemolyticus and S. auricularis. Additionally, identical strains of S. chromogenes and S. simulans were isolated from the same udder quarter of several cows at consecutive sample stages. The rest of the minor species had no deducible genetic-epidemiological link.DiscussionThe observed association between genetic and epidemiological distributions indicated animal-adapted nature of four CNS species, suggesting possible host-adapted and environmental transmission of these species. Multi-stage isolation of the same udder quarter strain was evidence for chronic intra-mammary infection.ConclusionThe different CNS species and strains circulating on US dairy herds were genetically diverse. Four species identified were likely udder-adapted pathogens, 2 of which caused persistent infection. Our findings are important in guiding the design of effective mastitis control strategies

A summary of each protocol evaluated during the five experiments.

<p>A summary of each protocol evaluated during the five experiments.</p