Longitudinal stability of JCV antibody index in Natalizumab treated people with multiple sclerosis.

OBJECTIVE: The aim of this study was to evaluate the evolution of JCV index over time in Natalizumab treated people with multiple sclerosis. MATERIALS AND METHODS: We retrospectively reviewed antibody index values from pwMS who were treated with Natalizumab for greater than six months and had at least two antibody results available between 2011 and 2019. Survival analysis was performed on those who were JCV index value negative at baseline to evaluate time to seroconversion. In pwMS who had index values available at 48 and/or 96 months post Natalizumab initiation, t-tests were performed to evaluate change in index over time. RESULTS: 1144 JCV antibody index results were available for 132 pwMS. Median time to seroconversion based on survival analysis was 103 months. Annualised seroconversion rate was 5.8%. Initial antibody index and rate of seroconversion did not differ with regards to age or gender. Antibody index increased significantly over time on treatment for the cohort as a whole, initial antibody index (0.27) to final antibody testing (0.86), t(131)=6.45, p<.0005. There was a significant increase in those with initial positive index value, between first (0.95) and final index (2.14), t(33) = 4.85, p<.0005 over a median of 77 months. CONCLUSIONS: In those who were seronegative at baseline there is a long median duration of treatment with Natalizumab prior to seroconversion. In individuals with positive JCV antibody index at treatment initiation, antibody index increases over time.

Evaluating the application of the dual path platform VetTB test for badgers (Meles meles) in the test and vaccinate or remove (TVR) wildlife research intervention project in Northern Ireland.

European badgers (Meles meles) are accepted as a wildlife reservoir host for Mycobacterium bovis, which causes bovine tuberculosis (bTB) in the British Isles. The objective of this study was to evaluate the use of Dual Path Platform (DPP) VetTB test (Chembio Diagnostic Systems Inc., Medford, NY, USA) within a Test and Vaccinate or Remove (TVR) wildlife research intervention project. Blood samples were collected from 456 individual badgers, trapped in 2015 and 2016, and tested in the field with DPP VetTB test using whole blood. Additionally, whole blood and serum samples were taken to the laboratory for further DPP VetTB testing and for gamma interferon (IFN-γ) testing. Swabs were taken from the oropharynx and trachea and submitted for bacteriological culture as were swabs from wounds, if present. Field DPP VetTB test positive badgers were euthanised and underwent post-mortem examination and bTB confirmatory testing. The results demonstrated that the test performed as well in the field using whole blood as DPP Vet TB tests in the laboratory using sera or whole blood, and as well as other established tests for M. bovis. Visual assessment of the DPP VetTB test using serum under laboratory conditions showed a high degree of consistency between raters. Using a relative gold standard (parallel interpretation of IFN-γ assay and oropharyngeal/tracheal sample/culture), sensitivity estimates for the DPP VetTB test using sera and whole blood were 0.5 (95%CI 0.34-0.66) and 0.42 (95%CI 0.24-0.66), respectively. Specificity estimates were 0.95 (95%CI 0.93-0.97) for sera and 0.89 (95%CI 0.86-0.92) for whole blood. Parallel interpretation of Band 1 (MPB83) and Band 2 (CFP-10/ESAT-6) of the DPP VetTB test was not superior to interpretation of Band 1 only. The results give confidence in the reliability and reproducibility of the DPP VetTB test for badgers under field conditions and therefore it is considered appropriate for use in a badger bTB control campaign.

Chicken astrovirus capsid proteins produced by recombinant baculoviruses: potential use for diagnosis and vaccination.

Chicken astroviruses (CAstVs) have been characterized recently. Due to their relatively poor growth in cell culture, virus-specific antigens are not readily available for the development of diagnostic reagents and vaccines. For this purpose two capsid protein antigens, specified by the 11672 isolate of CAstV, were produced in insect cells following infection with recombinant baculoviruses. The GST-11672 capsid protein, a fusion protein comprising the capsid protein and glutathione-S-transferase (GST) as an N-terminal affinity tag, and the 11672 capsid protein alone were detected by western blotting as proteins of ~100 and 70 kDa, respectively. Immunization with the affinity-purified GST-11672 capsid protein produced a polyclonal rabbit antiserum, which reacted by indirect immunofluorescence with Group B CAstVs but which showed no reactivity with the Group A CAstV isolate, 612. When used as part of an immunoperoxidase-based immunohistochemical procedure, this rabbit antiserum facilitated the detection of CAstV antigen in formalin-fixed, paraffin-embedded kidney tissue at the sites of histopathology characteristic of nephritis. Although further evaluation with sera from commercial chickens is required, a prototype indirect antibody-detecting enzyme-linked immunosorbent assay (ELISA) based on affinity-purified GST-11672 capsid protein as coating antigen demonstrated considerable potential with low ELISA absorbance values being generated with sera from specific pathogen free (SPF) chickens, and high absorbance values being generated with serum samples from experimentally infected chickens. Immunization experiments of SPF chickens showed that, when administered as mixtures with oil adjuvant, crude cell lysates containing the GST-11672 capsid protein or the 11672 capsid protein elicited virus-specific antibody responses that were detectable by indirect immunofluorescence and by virus neutralization assays.

Primitive neuroectodermal tumour in a striped dolphin (Stenella coeruleoalba) with features of ependymoma and neural tube differentiation (Medulloepithelioma).

Primary brain tumours in cetaceans are rare with only four reported cases of intracranial tumours in the scientific literature. A juvenile female, striped dolphin live-stranded at Whitepark Bay, Co Antrim, Northern Ireland, UK, and died after an unsuccessful attempt at refloatation. Necropsy examination revealed a large, soft, non-encapsulated friable mass, which expanded and replaced the frontal lobes, corpus callosum and caudate nucleus of the brain and extended into the lateral ventricles, displacing the thalamus caudally. Microscopically, this comprised moderately pleomorphic neoplastic cells arranged variably in dense monotonous sheets, irregular streams, ependymal rosettes, 'ependymoblastomatous rosettes' and multilayered to pseudostratified tubules. Liquefactive necrosis, palisading glial cells, haemorrhage and mineralization were also observed. Immunohistochemically, the neoplastic cells expressed vimentin but not S100, glial fibrillary acidic protein, cytokeratin, neuron-specific enolase or synaptophysin. Based on these findings a diagnosis of primitive neuroectodermal tumour was made. Monitoring and recording such cases is crucial as neoplasia may be related to viral, carcinogenic or immunosuppressive chemical exposure and can ultimately contribute to assessing the ocean health.

Proposal of Bisgaardia hudsonensis gen. nov., sp. nov. and an additional genomospecies, isolated from seals, as new members of the family Pasteurellaceae.

Phenotypic and phylogenetic studies were performed on eight Gram-negative-staining, rod-shaped bacteria isolated from seals. Biochemical and physiological studies showed identical profiles for all of the isolates and indicated that they were related to the family Pasteurellaceae. 16S rRNA gene sequencing demonstrated that the organism represented a distinct cluster with two sublines within the family Pasteurellaceae with <96% sequence similarity to any recognized species. Multilocus sequence analysis (MLSA) including rpoB, infB and recN genes further confirmed these findings with the eight isolates forming a genus-like cluster with two branches. Genome relatedness as deduced from recN gene sequences suggested that the isolates represented a new genus with two species. On the basis of the results of the phylogenetic analysis and phenotypic criteria, it is proposed that these bacteria from seals are classified as Bisgaardia hudsonensis gen. nov., sp. nov. (the type species) and Bisgaardia genomospecies 1. The G+C content of the DNA was 39.5 mol%. The type strain of Bisgaardia hudsonensis gen. nov., sp. nov. is M327/99/2(T) (=CCUG 43067(T)=NCTC 13475(T)=98-D-690B(T)) and the reference strain of Bisgaardia genomospecies 1 is M1765/96/5 (=CCUG 59551=NCTC 13474).

Acute and chronic gas bubble lesions in cetaceans stranded in the United Kingdom.

The first evidence suggestive of in vivo gas bubble formation in cetacea, including eight animals stranded in the UK, has recently been reported. This article presents the pathologic findings from these eight UK-stranded cetaceans and two additional UK-stranded cetacean cases in detail. Hepatic gas-filled cavitary lesions (0.2-6.0 cm diameter) involving approximately 5-90% of the liver volume were found in four (two juvenile, two adult) Risso's dolphins (Grampus griseus), three (two adult, one juvenile) common dolphins (Delphinus delphis), an adult Blainville's beaked whale (Mesoplodon densirostris), and an adult harbour porpoise (Phocoena phocoena). Histopathologic examination of the seven dolphin cases with gross liver cavities revealed variable degrees of pericavitary fibrosis, microscopic, intrahepatic, spherical, nonstaining cavities (typically 50-750 microm in diameter) consistent with gas emboli within distended portal vessels and sinusoids and associated with hepatic tissue compression, hemorrhages, fibrin/organizing thrombi, and foci of acute hepato-cellular necrosis. Two common dolphins also had multiple and bilateral gross renal cavities (2.0-9.0 mm diameter) that, microscopically, were consistent with acute (n = 2) and chronic (n = 1) arterial gas emboli-induced renal infarcts. Microscopic, bubblelike cavities were also found in mesenteric lymph node (n = 4), adrenal (n = 2), spleen (n = 2), pulmonary associated lymph node (n = 1), posterior cervical lymph node (n = 1), and thyroid (n = 1). No bacterial organisms were isolated from five of six cavitated livers and one of one cavitated kidneys. The etiology and pathogenesis of these lesions are not known, although a decompression-related mechanism involving embolism of intestinal gas or de novo gas bubble (emboli) development derived from tissues supersaturated with nitrogen is suspected.

A review of Brucella sp. infection of sea mammals with particular emphasis on isolates from Scotland.

Brucellae recovered from sea mammals were first reported in 1994. In the years since both culture and serological analysis have demonstrated that the infection occurs in a wide range of species of marine mammals inhabiting a vast amount of the world's oceans. Molecular studies have demonstrated that the isolates differ from those found amongst terrestrial animals and also distinguish between strains which have seals and cetaceans as their preferred hosts. At the phenotypic level seal and cetacean strains can also be differed with respect to their CO(2) requirement, primary growth on Farrells medium and metabolic activity on galactose. Two new species B. cetaceae and B. pinnipediae have been proposed as a result. This paper provides a review of Brucella in sea mammals and updates findings from the study of sea mammals from around the coast of Scotland.

Chronic meningoencephalitis associated with Brucella sp. infection in live-stranded striped dolphins (Stenella coeruleoalba).

A chronic, non-suppurative meningoencephalitis was found in three young striped dolphins (Stenella coeruleoalba) during routine neuropathological examination of marine mammals live-stranded on the Scottish coast. In all three dolphins the lesions were associated with the isolation of a Brucella sp. from the brain and with the immunohistochemical detection of brucella antigen. Moreover, antibodies to Brucella spp. were detected in the two dolphins that were subjected to serological examination. Immunohistochemical and serological examinations for morbillivirus antigen and antibodies, respectively, were negative in all cases. Although brucella infection of marine mammals has been extensively documented in recent years, its association with lesions and disease is less well recognized. The present report provides the first description of an association between Brucella sp. infection and neuropathological changes in a cetacean species.

Contextual influences on learning application in practice. An extended role for process evaluation.

Although process evaluation usually ends with the program, process itself does not end. This study analyzed process or contextual influences health professionals face when returning from continuing professional education (CPE) and attempting to apply learning. Follow-up survey data were analyzed for a sample (N = 549) of physicians, nurses, counselors, and rehabilitation specialists. Contextual influences studied include resources, encouragement, support, opportunity, and authority. Logistic regression analysis found support for changes to apply training ideas was a predictor of application for the sample as a whole and for all professional groups except one. Encouragement from others was a predictor of application for rehabilitation specialists, and opportunity to apply learning was a second predictor for nurses. Sufficient resources was not a predictor in any models tested. Results indicate that the practice context can affect educational outcomes and an extended vision of process evaluation is needed to incorporate such variables in the evaluation of CPE.

Supporting staff in employment: the emotional wellbeing of staff in an NHS psychiatric hospital.

OBJECTIVE: The objective of this study was to assess the emotional wellbeing of a broad sample of NHS employees in a psychiatric setting; to seek their views on sources of distress; and to identify preferred ways of dealing with it. DESIGN: A cross-sectional postal survey, employing two questionnaires: GHQ-28, and a semi-structured questionnaire. These were sent to a nominal 50% sample (n = 599). SETTING: The population was the staff of a large Scottish psychiatric service. RESULTS: A 47.9% response rate was achieved; 32.9% of respondents exceeded a cut-off score of four on the GHQ-28. Neither occupational, group nor gender effects were significant on this measure. The reporting of emotionally-distressing problems affecting their performance was found to be more common amongst doctors; males, overall, showed a non-significant trend towards having been affected more than females by such problems; and older staff (above 45) were affected significantly more often than younger staff. Almost a third of staff were unaware of the availability of an internal organisational resource (the Occupational Health service). CONCLUSION: NHS Trusts should ensure the culture at work is appropriate from a preventative point of view and be aware that factors outwith the workplace can affect employees emotional wellbeing and performance. Preventative and supportive measures to minimise psychological distress in the workforce should be considered; the Scottish Needs Assessment Programme: Mental Health in the Workplace offers useful guidance.

Monophasic group B Salmonella species infecting harbour porpoises (Phocoena phocoena) inhabiting Scottish coastal waters.

A monophasic strain of Salmonella group B having the antigenic structure 4, 12: a: - was isolated in culture from various tissues of 39 harbour porpoises (Phocoena phocoena). The tissue from which the organism was recovered most frequently was lung in 33 animals and intestine in 16 animals, but it was also isolated from heart valve, liver, kidney, spleen, mesenteric lymph node, pulmonary lymph node, hepatic lymph node, urethra, sheath and epididymis. As far as we are aware this is the first record of this strain from an animal source, raising the possibility that it may be host-adapted to harbour porpoises. The possible modes of transmission of monophasic group B Salmonella between porpoises are discussed.

Actinobacillus scotiae sp. nov., a new member of the family Pasteurellaceae Pohl (1979) 1981 isolated from porpoises (Phocoena phocoena).

Phenotypic and phylogenetic studies were performed on a Gram-negative, rod-shaped bacterium isolated from three porpoises. Biochemical and physiological studies indicated that the bacterium was related to the family Pasteurellaceae. Comparative 16S rRNA gene sequencing studies confirmed these findings and demonstrated that the bacterium represents a hitherto unknown subline. The nearest phylogenetic relative of the unknown bacterium was Actinobacillus delphinicola, an organism also originating from sea mammals, although a sequence divergence of 3% demonstrated that the newly isolated bacterium is a distinct species. On the basis of the results of the phylogenetic analysis and phenotypic criteria, it is proposed that the bacterium should be classified as a new species, Actinobacillus scotiae sp. nov. The type strain of Actinobacillus scotiae sp. nov. is NCTC 12922T (= M2000/95/1T).