A survey on bloat in southern Australian beef production systems.

Frothy bloat, associated predominantly with grazing legume-based pastures, is considered the second most costly disease in beef cattle in southern Australia, costing $84.4 M annually. It frequently results in the sudden death of cattle. In response to concerns from cattle producers, an online survey was conducted in southern Australia in late 2020 to determine the impact of bloat, identify risk factors and determine the efficacy of current preventive measures. For 217 responses, over two-thirds (70%) of producers reported bloat occurring in the previous 12 months, with estimated morbidity and mortality rates of 3.7% and 5.0% respectively. Bloat was associated with clover or clover-dominant paddocks (79%) and was not associated with grass or grass-dominant pastures or low clover pastures (92%) nor grazing crops (27%). For bloat that occurred in the past 12 months, cattle were very commonly grazing on clover or clover-dominant paddocks (90%) and occasionally lucerne-dominated paddocks (7%). Two-thirds of producers reported having preventive measures in place when losses occurred. Bayesian Network analysis confirmed that grazing clover-based pastures for more than 7 days, yearling cattle and the months of July-September were the main risk factors for bloat occurrence, with pasture type (clover) being the most important. Conversely, no clear relationship between weather conditions and bloat occurrence was evident. This survey highlights the known risk of clover-based pastures for causing bloat in cattle, and that losses occur in many cases despite preventive measures being used. This suggests that current methods for preventing bloat in cattle are suboptimal.

Serial neuropsychological testing in MOG antibody-associated disease to improve understanding of outcomes.

Neurocognitive outcomes data in patients with myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease are limited. Within MOG-positive cohorts, outcomes data typically utilize gross psychological, cognitive, or physical disability measures. Here, we report a pediatric patient who presented with two clinically heterogeneous events and was found to have MOG-associated encephalomyelitis. We administered detailed neuropsychological test batteries to obtain a robust understanding of the patient's neurocognitive profile over time. This case exemplifies the need to perform systematic and serial neuropsychological testing in patients with MOG-associated disease to better understand neurocognitive outcomes, facilitate multidisciplinary management, and improve recovery.

Echinococcus granulosus in the Northern Territory, Australia: hydatid disease reported in beef cattle from the region.

Hydatid disease in beef cattle has been reported to be widespread throughout Australia, but cattle bred and raised in the Northern Territory were previously believed to be free of the disease. Between 2010 and 2016, 1061 cattle from the Northern Territory were slaughtered at a New South Wales abattoir and inspected for hydatid disease. The proportion of cattle reported infected with hydatid disease was 3.5%. Individual cattle identification numbers indicated that the cattle included in the study had most likely remained within the Northern Territory from birth until immediately prior to slaughter, so were assumed to have become infected within the region. We suspect that the sylvatic cycle of Echinococcus granulosus transmission could be responsible for infection of cattle in this region.

Parkinson's disease: Evolution of the scientific literature from 1983 to 2017 by countries and journals.

This study charts the evolution of the scientific literature on Parkinson's disease (PD) from 1983 to 2017 to inform communities of scientists, physicians, patients, caregivers and politicians concerned with PD. Articles published in journals indexed in the Science Citation Index-Expanded database of the Web of Science were retrieved and analyzed in seven five-year periods: 1983-1987, 1988-1992, 1993-1997, 1998-2002, 2003-2007, 2008-2012 and 2013-2017. Over 35 years the number of research papers on PD increased 33-fold: 885 papers in 1983-1987 to 29,972 in 2013-2017. At the same time the number of countries contributing to PD research increased from 37 to 131. The USA was the most prolific country throughout, followed by several European (UK, Germany, Italy and France) and English-speaking (Canada and Australia) countries. By 2003, several Asian countries (China, South Korea, India and Turkey) emerged with rapid increases in publications related to PD. By 2013-2017, China surpassed all but the USA to rank 2nd globally in productivity. Despite an increase from 4 to 22 African countries publishing PD research from 1983 to 2017, most were either unproductive or contributed ≤5 papers in each five-year period. There has also been a 12-fold increase in the number of journals (232-2824) containing papers on PD. In 2013-2017 three PD-focused journals (Parkinsonism & Related Disorders, Movement Disorders and Journal of Parkinson's Disease) contained 6.8% of all PD papers while a large majority (82.5%) of journals published ≤ 10 papers. This quantitative study complements the numerous extant qualitative reviews to provide a global perspective on PD research.

Evolution of the scientific literature on drug delivery: A 1974-2015 bibliometric study.

This study charts the growth of the drug delivery literature published during 1974-2015 from journals indexed in the Science Citation Index Expanded database. The growth of publications on drug delivery paralleled the total scientific publications for three decades (1974-2003); however, from 2004 to 2015 it exploded fourfold, while the total increased only 1.75 fold. Industrialized countries (USA, UK, Germany, Japan, Italy, France and Canada) were the most prolific during the first decades, but in 2014-2015 China, India and South Korea ranked 1st, 3rd and 4th respectively among the productive countries. The number of participating countries increased fivefold (from 19 to 96). During the last 15years, the journals targeted by drug delivery research increased nearly 2.4 fold (416 to 1001) and three journals (Journal of Controlled Release, Advanced Drug Delivery Reviews, and International Journal of Pharmaceutics) published nearly one-fifth of the drug delivery research in 2014-2015.

Myc enhances B-cell receptor signaling in precancerous B cells and confers resistance to Btk inhibition.

Dysregulation of the oncogenic transcription factor MYC induces B-cell transformation and is a driver for B-cell non-Hodgkin lymphoma (B-NHL). MYC overexpression in B-NHL is associated with more aggressive phenotypes and poor prognosis. Although genomic studies suggest a link between MYC overexpression and B-cell receptor (BCR) signaling molecules in B-NHL, signaling pathways essential to Myc-mediated B-cell transformation have not been fully elucidated. We utilized intracellular phospho-flow cytometry to investigate the relationship between Myc and BCR signaling in pre-malignant B cells. Utilizing the Eµ-myc mouse model, where Myc is overexpressed specifically in B cells, both basal and stimulated BCR signaling were increased in precancerous B lymphocytes from Eµ-myc mice compared with wild-type littermates. B cells overexpressing Myc displayed constitutively higher levels of activated CD79α, Btk, Plcγ2 and Erk1/2. Notably, Myc-overexpressing B cells maintained elevated BCR signaling despite treatment with ibrutinib, a Bruton's tyrosine kinase inhibitor. Furthermore, PI3K/Akt pathway signaling was also increased in Eµ-myc B cells, and this increase was partially suppressed with ibrutinib. In addition, experiments with Btk-null B cells revealed off-target effects of ibrutinib on BCR signaling. Our data show that in pre-malignant B cells, Myc overexpression is sufficient to activate BCR and PI3K/Akt signaling pathways and further enhances signaling following BCR ligation. Therefore, our results indicate that precancerous B cells have already acquired enhanced survival and growth capabilities before transformation, and that elevated MYC levels confer resistance to pharmacologic inhibitors of BCR signaling, which has significant implications for B-NHL treatment.

Oesophageal lumen pH in yearling horses and effects of management and administration of omeprazole.

BACKGROUND: In human subjects, arytenoid chondritis can be caused by chemical trauma of mucosa attributable to gastro-oesophageal reflux. Although a similar process may be involved in the aetiopathogenesis of arytenoid chondritis in horses, the oesophageal lumen pH in this species is poorly understood. OBJECTIVES: To determine if gastro-oesophageal reflux occurs in horses by characterising oesophageal lumen pH. STUDY DESIGN: Blinded, randomised, placebo-controlled, crossover, experimental study. METHODS: Luminal oesophageal pH in six yearling horses was recorded over four 24 h periods using an ambulatory pH recorder attached to a catheter with two electrodes (proximal and distal) inserted into the oesophagus. Recordings of pH were made during three management protocols. Initially, horses grazed in a paddock (Protocol A). Horses were then moved to stables to simulate sale preparation of Thoroughbred yearlings, and were given either omeprazole (Protocol B) or placebo paste (Protocol C) orally once per day. Protocol A was repeated for each horse (after a 13 day washout period) between Protocols B and C. Summary statistics described pH range and frequency of pH changes. Associations with predictor variables were investigated using linear mixed-effects models. Data are presented as the mean ± s.d. RESULTS: Oesophageal lumen pH ranged from 4.90 to 9.70 (7.36 ± 0.27 and 7.18 ± 0.24 for the proximal and distal electrodes, respectively) and varied frequently (1.2 ± 0.9 changes/min and 0.8 ± 0.8 changes/min for the proximal and distal electrodes, respectively). Oesophageal lumen pH was associated with time since concentrate feeding, activity and time of day, but not with treatment of omeprazole. MAIN LIMITATIONS: A small number of horses were used and measurement periods were limited. CONCLUSIONS: Gastro-oesophageal reflux occurs in clinically normal yearling horses. Although omeprazole had no detectable effect, oesophageal lumen pH recorded during this study did not fall within the therapeutic range of omeprazole.

Lupus-Prone Mice Resist Immune Regulation and Transplant Tolerance Induction.

The strongly immunogenic environment in autoimmune diseases such as lupus may pose a stringent barrier to transplantation. Despite available murine models of lupus, transplant tolerance in this setting has yet to be fully investigated in highly penetrant genetic models of disease. Such studies are of clear clinical importance because lupus is a transplant indication in which transplanted kidneys have a substantially increased risk of rejection including a role for recurrent nephritis. In the fully penetrant B6.SLE123 mouse, we determined that CD4 T follicular helper and germinal center B cells were significantly expanded compared with healthy controls. We traced this expansion to resistance of effector CD4 T and B cells in B6.SLE123 mice to regulation by either CD4 T regulatory cells (CD4Tregs) or CD8 T regulatory cells (CD8Tregs), despite demonstrating normal function by Tregs in this strain. Finally, we determined that B6.SLE123 mice resist anti-CD45RB-mediated tolerance induction to foreign islet allografts, even in the absence of islet autoimmunity. Overall, B6.SLE123 lupus-prone mice are highly resistant to transplant tolerance induction, which provides a new model of failed tolerance in autoimmunity that may elucidate barriers to clinical transplantation in lupus through further cellular and genetic dissection.

Biobanking genetic resources: challenges and implementation at the USDA National Animal Germplasm Program.

There is adequate infrastructure in the US to identify and acquire germplasm from the major beef and dairy cattle and swine breeds. However, when we venture outside these species, the same tasks become more difficult because of a lack of breed associations, databases that include genotypic and phenotypic data and low numbers of animals. Furthermore, acquisition of germplasm from non-cattle and non-swine species can be difficult because these animals are often not located near the National Animal Germplasm Program, which makes collection and preservation of the samples in a timely manner that much more complicated. This problem is compounded because not all preservation protocols are optimised for field collection conditions or for all types of germplasm. Since 1999, the USDA National Animal Germplasm Program has worked to overcome these obstacles by developing policies, procedures and techniques in order to create a germplasm repository for all agricultural species (wild and domesticated) in the US. Herein, we describe these activities and illustrate them via a case study on how our efforts collecting Navajo-Churro sheep have created a secure backup of germplasm and how we specifically overcome these issues as they relate to rare and minor breeds of agricultural species.

Mantle cell lymphoma lacking the t(11;14) translocation: a case report and brief review of the literature.

The diagnosis of mantle cell lymphoma (MCL) requires a multifaceted approach with integration of morphology and immunophenotype, supported by cyclin D1 positivity or identification of t(11;14)(q13;q32). Interphase fluorescence in situ hybridisation (FISH) using a dual colour, dual fusion probe strategy for t(11;14) is a rapid test with high sensitivity and specificity for MCL, and is easily performed on routine bone marrow aspirate or peripheral blood specimens. This test has become the method of choice for many pathologists to confirm a diagnosis of MCL. This report describes a case of MCL with a normal (negative) FISH signal pattern for t(11;14) that was found to be cyclin D1 positive by immunohistochemistry in tissue sections. This case illustrates the need for additional testing when the t(11;14) abnormality is not identified but the morphology and immunophenotype are otherwise suggestive of MCL.

Utilisation of the c-fos immunohistochemical method: a 2004 quantitative study.

The aim of this study was to provide a quantitative view of the utilisation of the c-fos immunohistochemical method. Articles including the term "c-fos" in their title, abstract or keywords and published in 2004 were retrieved from the Current Content/Life Sciences or Current Content/Clinical Medicine collection of the SCI database. The 933 article-type documents retained were distributed in almost all the sub-disciplines of the Life Sciences and Clinical Medicine, but were principally published in the field of neuroscience. They were authored by researchers from 44 countries - the most prolific were the USA (435 articles), Japan (135) and the UK (55). The 933 articles were published in 283 different journals; all but one of the top-20 most prolific journals are in the Life Sciences discipline, and their Impact Factors ranged from 2.0 to 7.9. A comparison of the USA and the European Union scientific profiles is also made.

Malignant pleural effusion of multiple myeloma: prognostic factors and outcome.

Malignant pleural effusion (MPE) in multiple myeloma (MM) is rare. Approximately 80 cases have been reported. To delineate optimal treatment and prognostic variables in these patients, we reviewed 11 MM patients with MPE. MPE developed at median of 12 months from diagnosis of MM. All the patients had high-risk disease based on complex karyotypic abnormalities including deletions of chromosome-13 (n=9), elevated beta-2 microglobulin (B2M) (n=9), high C-reactive protein (CRP) (n=8), high plasma cell labeling index (n=5) or high LDH (n=5). A significant increase in B2M, LDH, and CRP was observed at the onset of MPE. The initial diagnosis of MPE was based on positive cytology (n=9), pleural fluid cIg/DNA (n=9) or pleural fluid cytogenetics (n=4). Pleural tissue infiltration was found on pleural biopsy and autopsy in one patient each. Systemic chemotherapy comprising dexamethasone, cyclophosphamide, etoposide and cisplatin (DCEP) (n=7) and pleurodesis (n=7) were effective in resolving MPE but survival was short. High dose chemotherapy with peripheral blood stem cell support for MPE in six patients conferred no clear survival advantage. These patients died at median of four months from onset of MPE. Patients with bone marrow complex karyotypic abnormalities including deletion-13 (n=9) had a shorter (median--18 months) overall survival compared to patients with normal cytogenetics (median--38 months). MPE in patients with MM is often associated with high-risk disease including deletion 13 chromosomal abnormality and heralds a poor prognosis despite aggressive local and systemic treatment.

Syndecan-1 (CD138) immunoreactivity in bone marrow biopsies of multiple myeloma: shed syndecan-1 accumulates in fibrotic regions.

Syndecan-1 (CD138) mediates myeloma cell adhesion, and loss of syndecan-1 from the cell surface may contribute to myeloma proliferation and dissemination. Flow cytometry analysis of myeloma cells in bone marrow specimens shows heterogeneity in cell surface syndecan-1 expression. It is not known whether weaker expression correlates with more aggressive disease. However, recent reports suggest that variations in syndecan-1 staining intensity on myeloma cells may be an artifact of specimen handling. In this study, we evaluate syndecan-1 expression in bone marrow biopsy sections from 28 multiple myeloma patients, to elucidate the heterogeneity of syndecan-1 expression in situ. Immunoreactivity for syndecan-1, using the antibody B-B4 (CD138), was found in more than 95% of multiple myeloma cells in 27 of 28 biopsies. However, one biopsy had more than 50% CD138-negative cells and cells with weak CD138 expression were identified in the majority of cases. Loss of syndecan-1 did not appear to relate to myeloma cell differentiation. In addition, syndecan-1 was detected on intravascular and intrasinusoidal myeloma cells suggesting that loss of syndecan-1 may not be required for extramedullary dissemination. Bone marrow biopsies from nine additional patients, with variable CD138 staining intensity on myeloma cells as determined by flow cytometry, were studied by immunohistochemistry. The heterogeneous CD138 expression was confirmed in situ, with weakly positive cells concentrated in areas of reticulin fibrosis. These cells had a disrupted pattern of membrane staining in contrast to the strong linear membrane staining seen in the other multiple myeloma cells. In addition, the fibrotic stroma stained intensely for syndecan-1. Accumulation of syndecan-1 within the extracellular matrix of the marrow likely is derived by shedding of the molecule from the surface of myeloma cells. Because syndecan-1 can act to regulate the activity of heparan-binding growth factors, these reservoirs of syndecan-1 may play a critical role in promoting myeloma pathogenesis, or in regeneration of the tumor after chemotherapy.

DNA topoisomerase IIalpha in multiple myeloma: a marker of cell proliferation and not drug resistance.

DNA topoisomerase IIalpha (topo IIalpha) is the target for a number of antineoplastic agents. Down-regulation of this enzyme is one form of drug resistance. Topo IIalpha is also involved in DNA replication and transcription and serves as an indicator of proliferation rate in many human malignancies. This study examines whether topo IIalpha is one of the mechanisms of chemoresistance commonly observed in multiple myeloma (MM) or alternatively, whether topo IIalpha is associated with tumor cell proliferation. Bone marrow (BM) biopsy sections from 72 cases of MM, stratified according to proliferative activity (bromodeoxyuridine uptake), were immunostained for topo IIalpha. Immunoreactivity with an additional marker of drug resistance, glutathione-S-transferase pi, and the proliferation marker Ki-67 were also examined. Topo IIalpha was expressed in 26 (36%) cases and correlated strongly with proliferative activity (P <.001). A role for drug resistance could not be supported, given this strong relationship with proliferation and the finding that glutathione-S-transferase pi expression in 57 (78%) cases was independent of topo IIalpha immunoreactivity. Topo IIalpha was identified in 91 to 100% of highly proliferative tumors, as evaluated by bromodeoxyuridine uptake or Ki-67 reactivity, respectively. Proliferation also correlated with the histologic grade of the MM. Therefore, topo IIalpha immunoreactivity is primarily a marker of cell proliferation in MM and as such is likely to have prognostic significance. Highly proliferative tumors are most likely to be sensitive to chemotherapeutic protocols using anti-topo IIalpha agents.

Soft tissue masses in patients with multiple myeloma: a fine-needle aspiration study of 30 cases with flow cytometry and clinical correlation.

BACKGROUND: To the authors' knowledge, the prognostic significance of plasma cell cytology in soft tissue (ST) masses from patients with multiple myeloma (MM) is unknown. Myeloma patients usually are monitored by bone marrow (BM) aspirates and biopsies to assess plasma cell differentiation, tumor burden, and response to treatment. Monitoring of ST lesions by fine-needle aspiration (FNA) is not performed routinely. The objective of the current study was to examine ST masses in MM patients using FNA and to classify and determine the prognostic significance of MM in these lesions based on cytologic features. METHODS: FNAs of 30 ST masses from 27 patients with a history of MM were examined for disease involvement. In the patients with MM, the cytologic features were evaluated and the lesions were graded as low grade, intermediate grade, or high grade based on the classification of Bartl et al. for MM in BM specimens. Concurrent BM samples as well as cytogenetic and flow cytometric results also were reviewed. RESULTS: Twenty-seven of the FNA specimens (90%) were positive for MM, and three specimens (10%) were negative (one case each of lipoma, keratinous cyst, and aspergillosis). Among the MM cases, 5 (18.5%) were low grade, 15 (55.6%) were intermediate grade, and 7 (25.9%) were high grade (blastic MM). Simultaneous BM involvement was present in 23.5% of low-grade MM (4 of 17 cases), 35.3% of intermediate-grade MM (6 of 17 cases), and 71% of high-grade MM (5 of 7 cases). Clinically, 10 of 24 patients (42%) died within 9 months (median, 2 months). Patients with high-grade myeloma (blastic MM) in ST masses appeared to have worse survival; 43% (3 of 7 patients) died by a median time of 2 months, compared with 12% of patients with low-grade and intermediate-grade MM (2 of 17 patients). CONCLUSIONS: FNA of ST masses appears to improve the management of MM patients by providing diagnostic material, samples for ancillary studies, and prognostic information. ST MM can be classified reliably into grades of prognostic significance utilizing the classification of Bartl et al. Intermediate-grade MM was the most frequent subtype present in ST masses.

Cyclin D1 and E2F-1 immunoreactivity in bone marrow biopsy specimens of multiple myeloma: relationship to proliferative activity, cytogenetic abnormalities and DNA ploidy.

Cyclin D1, encoded by the CCND1 gene, is immunohistochemically detectable in up to one-third of cases of multiple myeloma (MM). To examine the mechanism of cyclin D1 overexpression, we compared cyclin D1 immunoreactivity with the results of conventional cytogenetics to determine if the t(11;14)(q13;q32) or other abnormalities of 11q11-14 explained cyclin D1 overexpression. Karyotypic abnormalities were found in 45 out of 67 (67%) MM cases; the t(11;14) was present in seven cases (10%). Additional 11q11-14 abnormalities were not identified. The t(11;14) correlated with cyclin D1 upregulation in low to intermediately proliferative MM, but was not present in highly proliferative tumours (assessed using bromodeoxyuridine labelling index). Cyclin D1 indirectly activates the transcription factor E2F-1. In the bone marrow biopsy specimens of MM cases, E2F-1 was concurrently expressed with cyclin D1 (P = 0.001), indicating that cyclin D1 is functional. However, as neither E2F-1 nor cyclin D1 expression correlated with proliferative activity, the speculation that t(11;14) upregulates the CCND1 gene to induce higher proliferation and possibly more aggressive disease is not supported. We conclude that in low to intermediately proliferative MM cases, cyclin D1 is probably upregulated by t(11;14), but an alternative mechanism is more probable in highly proliferative MM.

Cytology and flow cytometry of malignant effusions of multiple myeloma.

Identifying malignant plasma cells in body fluids from multiple myeloma patients is important for therapeutic and prognostic considerations. This can be difficult when plasma cells are mature in appearance or low in number. We examined the cytological and flow cytometric findings of myelomatous pleural and pericardial effusions from 8 patients with advanced multiple myeloma. Cytoplasmic immunoglobulin light chain excess vs. DNA ploidy in the plasma-cell population was evaluated by flow cytometry (FCM). The cytology smears of one pericardial and 14 pleural effusions from the 8 patients were reviewed. Screening Papanicolaou-stained smears facilitated the detection of malignant nuclear features; however, morphology of plasma cells was best seen in Diff-Quik-stained smears. Low cellularity and inadequate air-drying of smears accounted for the false-negative cytology seen in two fluids from a single patient. A malignant plasma cell population was identified in 9 of 10 fluids submitted for FCM, including the two fluids with negative cytology. The false-negative FCM was from a suboptimal specimen with high background staining. Six fluids had an aneuploid DNA content, and four were diploid. A combination of Papanicolaou- and Diff-Quik-stained smears is recommended for the evaluation of plasma cells in effusions from patients with multiple myeloma. Cytology and flow cytometry confirmed malignancy in 87% and 90% of fluids evaluated, respectively; all cases were diagnosed by either one or both methods. Our results suggest that FCM and cytology of serous effusions in multiple myeloma patients are complementary and should be used in difficult cases. Diagn. Cytopathol. 2000;22:147-151.