An integrated practical placement programme for students with disability: A pilot study.

Supported work internship programmes for young adults with disability are an evidence-based model, leading to greater employment outcomes. This mixed methods pilot study evaluated the experiences of students, supervisors and a project coordinator, who participated in an Integrated Practical Placement (IPP) programme for students with disability in Australia. Intervention students (n = 10) completed 3, 9-week rotations, and accessed personal placement support and employment coaches. Comparison students (n = 38) completed 3, 2-week placements without additional support. Intervention students perceived significantly greater initial changes in work skills (p < 0.01) and work readiness (p < 0.05). Intervention students reported development of communication and self-organisational skills and stressed the value of staff support. Post programme 70% of intervention students gained employment, compared with 15.4% of comparison students. The findings suggest an evidence-based supported employment programme emphasising personalised assessment and training, could provide individuals with disability the required skills to enable successful employment.

Recasting Human Vδ1 Lymphocytes in an Adaptive Role.

γδ T cells are unconventional lymphocytes commonly described as 'innate-like' in function, which can respond in both a T cell receptor (TCR)-independent and also major histocompatibility complex (MHC)-unrestricted TCR-dependent manner. While the relative importance of TCR recognition had remained unclear, recent studies revealed that human Vδ1 T cells display unexpected parallels with adaptive αß T cells. Vδ1 T cells undergo profound and highly focussed clonal expansion from an initially diverse and private TCR repertoire, most likely in response to specific immune challenges. Concomitantly, they differentiate from a Vδ1 T cell naïve (Tnaïve) to a Vδ1 T cell effector (Teffector) phenotype, marked by the downregulation of lymphoid homing receptors and upregulation of peripheral homing receptors and effector markers. This suggests that an adaptive paradigm applies to Vδ1 T cells, likely involving TCR-dependent but MHC-unrestricted responses to microbial and non-microbial challenges.

Papillomas and probable in situ carcinoma in association with a novel papillomavirus in a red-billed gull (Chroicocephalus novaehollandiae scopulinus).

Numerous raised plaques were observed on the feet of a red-billed gull (Chroicocephalus novaehollandiae scopulinus) that had been found dead. The plaques consisted of thickened epidermis with cell changes indicative of papillomavirus (PV) infection prominent within affected areas. Evidence suggesting progression to neoplasia was visible in one lesion. A DNA sequence that was most similar, but only 68.3% identical, to duck PV type 3 was amplified from the papillomas, suggesting a novel PV type. Lesions containing PV DNA have only previously been reported in three avian species. This is the first evidence that PVs could cause neoplasia in birds.

Bidirectional Cross-Talk between Biliary Epithelium and Th17 Cells Promotes Local Th17 Expansion and Bile Duct Proliferation in Biliary Liver Diseases.

There is no effective treatment for autoimmune biliary diseases. Therefore, understanding their immunopathology is crucial. The biliary epithelial cells (BEC), expressing TLR-4, are constantly exposed to gut microbes and bacterial wall LPS, and in settings of inflammation, the immune infiltrate is dense within the peribiliary region of human liver. By dual immunohistochemistry, we affirm human intrahepatic T cell infiltrate includes CCR6+CD4+ and AhR+CD4+ T cells with potential for plasticity to Th17 phenotype. Mechanistically, we demonstrate that Th1 and Th17 inflammatory cytokines and LPS enhance human primary BEC release of the CCR6 ligand CCL20 and BEC secretion of Th17-polarizing cytokines IL-6 and IL-1ß. Cell culture assays with human BEC secretome showed that secretome polarizes CD4 T cells toward a Th17 phenotype and supports the survival of Th17 cells. BEC secretome did not promote Th1 cell generation. Additionally, we give evidence for a mutually beneficial feedback of the type 17 cell infiltrate on BEC, showing that treatment with type 17 cytokines increases BEC proliferation, as monitored by Ki67 and activation of JAK2-STAT3 signaling. This study identifies human BEC as active players in determining the nature of the intrahepatic immune microenvironment. In settings of inflammation and/or infection, biliary epithelium establishes a prominent peribiliary type 17 infiltrate via recruitment and retention and enhances polarization of intrahepatic CD4 cells toward Th17 cells via type 17 cytokines, and, reciprocally, Th17 cells promote BEC proliferation for biliary regeneration. Altogether, we provide new insight into cross-talk between Th17 lymphocytes and human primary biliary epithelium in biliary regenerative pathologies.

Associations between vascular risk factors and brain MRI indices in UK Biobank.

AIMS: Several factors are known to increase risk for cerebrovascular disease and dementia, but there is limited evidence on associations between multiple vascular risk factors (VRFs) and detailed aspects of brain macrostructure and microstructure in large community-dwelling populations across middle and older age. METHODS AND RESULTS: Associations between VRFs (smoking, hypertension, pulse pressure, diabetes, hypercholesterolaemia, body mass index, and waist-hip ratio) and brain structural and diffusion MRI markers were examined in UK Biobank (N = 9722, age range 44-79 years). A larger number of VRFs was associated with greater brain atrophy, lower grey matter volume, and poorer white matter health. Effect sizes were small (brain structural R2 ≤1.8%). Higher aggregate vascular risk was related to multiple regional MRI hallmarks associated with dementia risk: lower frontal and temporal cortical volumes, lower subcortical volumes, higher white matter hyperintensity volumes, and poorer white matter microstructure in association and thalamic pathways. Smoking pack years, hypertension and diabetes showed the most consistent associations across all brain measures. Hypercholesterolaemia was not uniquely associated with any MRI marker. CONCLUSION: Higher levels of VRFs were associated with poorer brain health across grey and white matter macrostructure and microstructure. Effects are mainly additive, converging upon frontal and temporal cortex, subcortical structures, and specific classes of white matter fibres. Though effect sizes were small, these results emphasize the vulnerability of brain health to vascular factors even in relatively healthy middle and older age, and the potential to partly ameliorate cognitive decline by addressing these malleable risk factors.

Sex Differences in the Adult Human Brain: Evidence from 5216 UK Biobank Participants.

Sex differences in the human brain are of interest for many reasons: for example, there are sex differences in the observed prevalence of psychiatric disorders and in some psychological traits that brain differences might help to explain. We report the largest single-sample study of structural and functional sex differences in the human brain (2750 female, 2466 male participants; mean age 61.7 years, range 44-77 years). Males had higher raw volumes, raw surface areas, and white matter fractional anisotropy; females had higher raw cortical thickness and higher white matter tract complexity. There was considerable distributional overlap between the sexes. Subregional differences were not fully attributable to differences in total volume, total surface area, mean cortical thickness, or height. There was generally greater male variance across the raw structural measures. Functional connectome organization showed stronger connectivity for males in unimodal sensorimotor cortices, and stronger connectivity for females in the default mode network. This large-scale study provides a foundation for attempts to understand the causes and consequences of sex differences in adult brain structure and function.

Human liver infiltrating γδ T cells are composed of clonally expanded circulating and tissue-resident populations.

BACKGROUND & AIMS: γδ T cells comprise a substantial proportion of tissue-associated lymphocytes. However, our current understanding of human γδ T cells is primarily based on peripheral blood subsets, while the immunobiology of tissue-associated subsets remains largely unclear. Therefore, we aimed to elucidate the T cell receptor (TCR) diversity, immunophenotype and function of γδ T cells in the human liver. METHODS: We characterised the TCR repertoire, immunophenotype and function of human liver infiltrating γδ T cells, by TCR sequencing analysis, flow cytometry, in situ hybridisation and immunohistochemistry. We focussed on the predominant tissue-associated Vδ2- γδ subset, which is implicated in liver immunopathology. RESULTS: Intrahepatic Vδ2- γδ T cells were highly clonally focussed, with single expanded clonotypes featuring complex, private TCR rearrangements frequently dominating the compartment. Such T cells were predominantly CD27lo/- effector lymphocytes, whereas naïve CD27hi, TCR-diverse populations present in matched blood were generally absent in the liver. Furthermore, while a CD45RAhi Vδ2- γδ effector subset present in both liver and peripheral blood contained overlapping TCR clonotypes, the liver Vδ2- γδ T cell pool also included a phenotypically distinct CD45RAlo effector compartment that was enriched for expression of the tissue tropism marker CD69, the hepatic homing chemokine receptors CXCR3 and CXCR6, and liver-restricted TCR clonotypes, suggestive of intrahepatic tissue residency. Liver infiltrating Vδ2- γδ cells were capable of polyfunctional cytokine secretion, and unlike peripheral blood subsets, were responsive to both TCR and innate stimuli. CONCLUSION: These findings suggest that the ability of Vδ2- γδ T cells to undergo clonotypic expansion and differentiation is crucial in permitting access to solid tissues, such as the liver, which results in functionally distinct peripheral and liver-resident memory γδ T cell subsets. They also highlight the inherent functional plasticity within the Vδ2- γδ T cell compartment and provide information that could be used for the design of cellular therapies that suppress liver inflammation or combat liver cancer. LAY SUMMARY: γδ T cells are frequently enriched in many solid tissues, however the immunobiology of such tissue-associated subsets in humans has remained unclear. We show that intrahepatic γδ T cells are enriched for clonally expanded effector T cells, whereas naïve γδ T cells are largely excluded. Moreover, whereas a distinct proportion of circulating T cell clonotypes was present in both the liver tissue and peripheral blood, a functionally and clonotypically distinct population of liver-resident γδ T cells was also evident. Our findings suggest that factors triggering γδ T cell clonal selection and differentiation, such as infection, can drive enrichment of γδ T cells into liver tissue, allowing the development of functionally distinct tissue-restricted memory populations specialised in local hepatic immunosurveillance.

Human intrahepatic regulatory T cells are functional, require IL-2 from effector cells for survival, and are susceptible to Fas ligand-mediated apoptosis.

UNLABELLED: Regulatory T cells (Treg ) suppress T effector cell proliferation and maintain immune homeostasis. Autoimmune liver diseases persist despite high frequencies of Treg in the liver, suggesting that the local hepatic microenvironment might affect Treg stability, survival, and function. We hypothesized that interactions between Treg and endothelial cells during recruitment and then with epithelial cells within the liver affect Treg stability, survival, and function. To model this, we explored the function of Treg after migration through human hepatic sinusoidal-endothelium (postendothelial migrated Treg [PEM Treg ]) and the effect of subsequent interactions with cholangiocytes and local proinflammatory cytokines on survival and stability of Treg . Our findings suggest that the intrahepatic microenvironment is highly enriched with proinflammatory cytokines but deficient in the Treg survival cytokine interleukin (IL)-2. Migration through endothelium into a model mimicking the inflamed liver microenvironment did not affect Treg stability; however, functional capacity was reduced. Furthermore, the addition of exogenous IL-2 enhanced PEM Treg phosphorylated STAT5 signaling compared with PEMCD8. CD4 and CD8 T cells are the main source of IL-2 in the inflamed liver. Liver-infiltrating Treg reside close to bile ducts and coculture with cholangiocytes or their supernatants induced preferential apoptosis of Treg compared with CD8 effector cells. Treg from diseased livers expressed high levels of CD95, and their apoptosis was inhibited by IL-2 or blockade of CD95. CONCLUSION: Recruitment through endothelium does not impair Treg stability, but a proinflammatory microenvironment deficient in IL-2 leads to impaired function and increased susceptibility of Treg to epithelial cell-induced Fas-mediated apoptosis. These results provide a mechanism to explain Treg dysfunction in inflamed tissues and suggest that IL-2 supplementation, particularly if used in conjunction with Treg therapy, could restore immune homeostasis in inflammatory and autoimmune liver disease. (Hepatology 2016;64:138-150).

Investigation of a mortality cluster in wild adult yellow-eyed penguins (Megadyptes antipodes) at Otago Peninsula, New Zealand.

We investigated an epidemic mortality cluster of yellow-eyed penguins (Megadyptes antipodes) that involved 67 moribund or dead birds found on various beaches of the Otago Peninsula, New Zealand, between 21 January and 20 March 2013. Twenty-four carcases were examined post-mortem. Histological lesions of pulmonary, hepatic and splenic erythrophagocytosis and haemosiderosis were found in 23 of 24 birds. Fifteen birds also had haemoglobin-like protein droplets within renal tubular epithelial cells. Despite consistent histological lesions, a cause of death could not be established. Virology, bacteriology and molecular tests for avian influenza, avian paramyxovirus-1, avipoxvirus, Chlamydia psittaci, Plasmodium spp., Babesia spp., Leucocytozoon spp. and Toxoplasma gondii were negative. Tissue concentrations of a range of heavy metals (n = 4 birds) were consistent with low level exposure, while examination of proventricular contents and mucus failed to detect any marine biotoxins or Clostridium botulinum toxin. Hepatic concentrations of total polycyclic aromatic hydrocarbons (PAHs) (n = 5 birds) were similar to background concentrations of polycyclic aromatic hydrocarbons previously found in yellow-eyed penguins from the South Island of New Zealand, but there were significantly higher concentrations of 1-methylnapthelene and 2-methylnapthelene in the birds found dead in this mortality cluster. The biological significance of this finding is unclear. A temporal investigation of the epidemic did not indicate either a common source or propagative epidemic pattern. Although our investigation did not definitively implicate a toxic or infectious agent, we could not rule out causes such as toxic marine organisms or mycoplasmosis. Further investigations should therefore by carried out in the event of future mortality clusters.

Biliary epithelium and liver B cells exposed to bacteria activate intrahepatic MAIT cells through MR1.

BACKGROUND & AIMS: Mucosal-Associated Invariant T (MAIT) cells are innate-like T cells characterised by the invariant TCR-chain, Vα7.2-Jα33, and are restricted by MR1, which presents bacterial vitamin B metabolites. They are important for antibacterial immunity at mucosal sites; however, detailed characteristics of liver-infiltrating MAIT (LI-MAIT) and their role in biliary immune surveillance remain unexplored. METHODS: The phenotype and intrahepatic localisation of human LI-MAIT cells was examined in diseased and normal livers. MAIT cell activation in response to E. coli-exposed macrophages, biliary epithelial cells (BEC) and liver B cells was assessed with/without anti-MR1. RESULTS: Intrahepatic MAIT cells predominantly localised to bile ducts in the portal tracts. Consistent with this distribution, they expressed biliary tropic chemokine receptors CCR6, CXCR6, and integrin αEß7. LI-MAIT cells were also present in the hepatic sinusoids and possessed tissue-homing chemokine receptor CXCR3 and integrins LFA-1 and VLA-4, suggesting their recruitment via hepatic sinusoids. LI-MAIT cells were enriched in the parenchyma of acute liver failure livers compared to chronic diseased livers. LI-MAIT cells had an activated, effector memory phenotype, expressed α4ß7 and receptors for IL-12, IL-18, and IL-23. Importantly, in response to E. coli-exposed macrophages, liver B cells and BEC, MAIT cells upregulated IFN-γ and CD40 Ligand and degranulated in an MR1-dependent, cytokine-independent manner. In addition, diseased liver MAIT cells expressed T-bet and RORγt and the cytokines IFN-γ, TNF-α, and IL-17. CONCLUSIONS: Our findings provide the first evidence of an immune surveillance effector response for MAIT cells towards BEC in human liver; thus they could be manipulated for treatment of biliary disease in the future.

IMAGING DIAGNOSIS--USE OF RADIOGRAPHY AND COMPUTED TOMOGRAPHY IN THE DIAGNOSIS OF A MINERALIZED YOLK SAC IN A BROWN KIWI (APTERYX MANTELLI).

A 12-day-old Brown Kiwi (Apteryx mantelli) was presented with anorexia, torticollis, head-tilt, and coelomic distension. Radiographs showed an ill-defined, fat-opaque, coelomic mass displacing viscera craniodorsally. Curvilinear mineral opacities were superimposed over the ventral aspect of the mass. Computed tomography demonstrated the presence of mineral within the periphery of a fat attenuating mass consistent with a retained yolk sac. A deutectomy (yolk sac excision) was performed. Histopathology of the excised tissue confirmed the diagnosis of a retained yolk sac with multifocal mineralization.

Four cases of fatal toxoplasmosis in three species of endemic New Zealand birds.

Four cases of fatal toxoplasmosis in three endemic New Zealand avian species are reported. Between 2009 and 2012, two kereru (Hemiphaga novaeseelandiae), one North Island brown kiwi (Apteryx mantelli), and one North Island kaka (Nestor meridionalis) were submitted for necropsy examination. On gross postmortem, the kiwi had marked hepatosplenomegaly while the kaka and two kereru had swollen, slightly firm, deep-red lungs. Histologically there was extensive hepatocellular necrosis in the liver of the kiwi while the kaka and kereru showed severe fibrinous bronchointerstitial pneumonia. In the kiwi, protozoal organisms were present within both hepatocytes and Kupffer cells of the liver and within the epithelial cells and macrophages of the interstitium of the lungs in the kaka and two kereru. The diagnosis of toxoplasmosis was confirmed with immunohistochemistry and PCR of paraffin-embedded formalin-fixed tissue of the liver, lungs, or both. Genotyping of up to seven markers revealed that an atypical Type II isolate of Toxoplasma gondii was present in at least three of the cases. This study provides evidence that T. gondii can cause mortality in these endemic species and suggests further research is needed to determine the full extent of morbidity and mortality caused by this parasite in New Zealand's unique avifauna.

A novel gyrovirus is abundant in yellow-eyed penguin (Megadyptes antipodes) chicks with a fatal respiratory disease.

Yellow-eyed penguins (Megadyptes antipodes), or hoiho in te reo Maori, are predicted to become extinct on mainland Aotearoa New Zealand in the next few decades, with infectious disease a significant contributor to their decline. A recent disease phenomenon termed respiratory distress syndrome (RDS) causing lung pathology has been identified in very young chicks. To date, no causative pathogens for RDS have been identified. In 2020 and 2021, the number of chick deaths from suspected RDS increased four- and five-fold, respectively, causing mass mortality with an estimated mortality rate of >90%. We aimed to identify possible pathogens responsible for RDS disease impacting these critically endangered yellow-eyed penguins. Total RNA was extracted from tissue samples collected during post-mortem of 43 dead chicks and subject to metatranscriptomic sequencing and histological examination. From these data we identified a novel and highly abundant gyrovirus (Anelloviridae) in 80% of tissue samples. This virus was most closely related to Gyrovirus 8 discovered in a diseased seabird, while other members of the genus Gyrovirus include Chicken anaemia virus, which causes severe disease in juvenile chickens. No other exogenous viral transcripts were identified in these tissues. Due to the high relative abundance of viral reads and its high prevalence in diseased animals, it is likely that this novel gyrovirus is associated with RDS in yellow-eyed penguin chicks.

Computer-Aided Imaging Analysis of Probe-Based Confocal Laser Endomicroscopy With Molecular Labeling and Gene Expression Identifies Markers of Response to Biological Therapy in IBD Patients: The Endo-Omics Study.

BACKGROUND: We aimed to predict response to biologics in inflammatory bowel disease (IBD) using computerized image analysis of probe confocal laser endomicroscopy (pCLE) in vivo and assess the binding of fluorescent-labeled biologics ex vivo. Additionally, we investigated genes predictive of anti-tumor necrosis factor (TNF) response. METHODS: Twenty-nine patients (15 with Crohn's disease [CD], 14 with ulcerative colitis [UC]) underwent colonoscopy with pCLE before and 12 to 14 weeks after starting anti-TNF or anti-integrin α4ß7 therapy. Biopsies were taken for fluorescein isothiocyanate-labeled infliximab and vedolizumab staining and gene expression analysis. Computer-aided quantitative image analysis of pCLE was performed. Differentially expressed genes predictive of response were determined and validated in a public cohort. RESULTS: In vivo, vessel tortuosity, crypt morphology, and fluorescein leakage predicted response in UC (area under the receiver-operating characteristic curve [AUROC], 0.93; accuracy 85%, positive predictive value [PPV] 89%; negative predictive value [NPV] 75%) and CD (AUROC, 0.79; accuracy 80%; PPV 75%; NPV 83%) patients. Ex vivo, increased binding of labeled biologic at baseline predicted response in UC (UC) (AUROC, 83%; accuracy 77%; PPV 89%; NPV 50%) but not in Crohn's disease (AUROC 58%). A total of 325 differentially expressed genes distinguished responders from nonresponders, 86 of which fell within the most enriched pathways. A panel including ACTN1, CXCL6, LAMA4, EMILIN1, CRIP2, CXCL13, and MAPKAPK2 showed good prediction of anti-TNF response (AUROC >0.7). CONCLUSIONS: Higher mucosal binding of the drug target is associated with response to therapy in UC. In vivo, mucosal and microvascular changes detected by pCLE are associated with response to biologics in inflammatory bowel disease. Anti-TNF-responsive UC patients have a less inflamed and fibrotic state pretreatment. Chemotactic pathways involving CXCL6 or CXCL13 may be novel targets for therapy in nonresponders.

Total infectome investigation of diphtheritic stomatitis in yellow-eyed penguins (Megadyptes antipodes) reveals a novel and abundant megrivirus.

First identified in 2002, diphtheritic stomatitis (DS) is a devastating disease affecting yellow-eyed penguins (Megadyptes antipodes, or hoiho in te reo Maori). The disease is associated with oral lesions in chicks and has caused significant morbidity and mortality. DS is widespread among yellow-eyed penguin chicks on mainland New Zealand yet appears to be absent from the subantarctic population. Corynebacterium spp. have previously been suspected as causative agents yet, due to inconsistent cultures and inconclusive pathogenicity, their role in DS is unclear. Herein, we used a metatranscriptomic approach to identify potential causative agents of DS by revealing the presence and abundance of all viruses, bacteria, fungi and protozoa - together, the infectome. Oral and cloacal swab samples were collected from presymptomatic, symptomatic and recovered chicks along with a control group of healthy adults. Two novel viruses from the Picornaviridae were identified, one of which - yellow-eyed penguin megrivirus - was highly abundant in chicks irrespective of health status but not detected in healthy adults. Tissue from biopsied oral lesions also tested positive for the novel megrivirus upon PCR. We found no overall clustering among bacteria, protozoa and fungi communities at the genus level across samples, although Paraclostridium bifermentans was significantly more abundant in oral microbiota of symptomatic chicks compared to other groups. The detection of a novel and highly abundant megrivirus has sparked a new line of inquiry to investigate its potential association with DS.

Malaria parasites (Plasmodium spp.) infecting introduced, native and endemic New Zealand birds.

Avian malaria is caused by intracellular mosquito-transmitted protist parasites in the order Haemosporida, genus Plasmodium. Although Plasmodium species have been diagnosed as causing death in several threatened species in New Zealand, little is known about their ecology and epidemiology. In this study, we examined the presence, microscopic characterization and sequence homology of Plasmodium spp. isolates collected from a small number of New Zealand introduced, native and endemic bird species. We identified 14 Plasmodium spp. isolates from 90 blood or tissue samples. The host range included four species of passerines (two endemic, one native, one introduced), one species of endemic pigeon and two species of endemic kiwi. The isolates were associated into at least four distinct clusters including Plasmodium (Huffia) elongatum, a subgroup of Plasmodium elongatum, Plasmodium relictum and Plasmodium (Noyvella) spp. The infected birds presented a low level of peripheral parasitemia consistent with chronic infection (11/15 blood smears examined). In addition, we report death due to overwhelming parasitemia in a blackbird, a great spotted kiwi and a hihi. These deaths were attributed to infections with either Plasmodium spp. lineage LINN1 or P. relictum lineage GRW4. To the authors' knowledge, this is the first published report of Plasmodium spp. infection in great spotted and brown kiwi, kereru and kokako. Currently, we are only able to speculate on the origin of these 14 isolates but consideration must be made as to the impact they may have on threatened endemic species, particularly due to the examples of mortality.

The Pathology of Fatal Avian Malaria Due to Plasmodium elongatum (GRW6) and Plasmodium matutinum (LINN1) Infection in New Zealand Kiwi (Apteryx spp.).

Avian malaria caused by Plasmodium species is a known cause of mortality in avifauna worldwide, however reports within New Zealand kiwi (Apteryx spp.) are scant. Postmortem reports from kiwi were obtained from the Massey University/Te Kunenga ki Purehuroa School of Veterinary Science Pathology Register from August 2010-August 2020. Gross lesions were described from postmortem reports, and archived H.E.-stained slides used for histological assessment. Nested PCR testing was performed on formalin-fixed paraffin-embedded tissue samples to assess the presence of Plasmodium spp. and Toxoplasma gondii DNA and cases with a PCR-positive result were sequenced to determine the lineage involved. Of 1005 postmortem reports, 23 cases of confirmed or suspected avian malaria were included in this study. The most consistent gross lesions included splenomegaly, hepatomegaly, and interstitial pneumonia with oedema. Histological lesions were characterised by severe interstitial pneumonia, pulmonary oedema, interstitial myocarditis, hepatic sinusoidal congestion and hypercellularity, and splenic macrophage hyperplasia and hyperaemia/congestion with numerous haemosiderophages. Cytoplasmic meronts were consistently found within endothelial cells of a variety of tissues, and within tissue macrophages of the liver, lung and spleen. A diagnosis of avian malaria was confirmed via PCR testing in 13 cases, with sequencing revealing P. matutinum (LINN1) and P. elongatum (GRW6) as the species involved. This is the largest case series describing the pathology of avian malaria as a cause of mortality in endemic New Zealand avifauna.

Telangiectatic Osteosarcoma of the Tibiotarsus in a North Island Brown Kiwi (Apteryx mantelli).

A North Island brown kiwi (Apteryx mantelli) with lameness and weight loss had a telangiectatic osteosarcoma. The left proximal tibiotarsus had bony lysis with multiple blood-filled spaces separated by thick fibrous septa and neoplastic mesenchymal cells producing osteoid (5-bromo-4-chloro-3'-indolyl phosphate/nitro blue tetrazolium positive on cytology). No metastases were noted on necropsy.

MUCOPOLYSACCHARIDOSIS II (MPS II) IN A FREE-LIVING KAKA (NESTOR MERIDIONALIS) IN NEW ZEALAND.

A lysosomal storage disease, identified as a mucopolysaccharidosis (MPS), was diagnosed in a free-living Kaka (Nestor meridionalis), an endemic New Zealand parrot, which exhibited weakness, incoordination, and seizures. Histopathology showed typical colloid-like cytoplasmic inclusions in Purkinje cells and many other neurons throughout the brain. Electron microscopy revealed that storage bodies contained a variety of linear, curved, or circular membranous profiles and electron-dense bodies. Because the bird came from a small isolated population of Kaka in the northern South Island, a genetic cause was deemed likely. Tandem mass spectrometry revealed increased levels of heparan sulfate-derived disaccharides in the brain and liver compared with tissues from controls. Enzymatic assays documented low levels of iduronate-2-sulfatase activity, which causes a lysosomal storage disorder called MPS type II or Hunter syndrome. A captive breeding program is currently in progress, and the possibility of detecting carriers of this disorder warrants further investigation.

Assessment of reproductive tract disease in cats at risk for Tritrichomonas foetus infection.

OBJECTIVE: To determine whether Tritrichomonas foetus infection resides in reproductive tract tissues from cats housed for breeding and for which a high prevalence of colonic T foetus infection has been reported. ANIMALS: 61 purebred cats in 36 catteries undergoing elective ovariohysterectomy or castration and for which reproductive tract tissues, feces, and a reproductive history were obtained. PROCEDURES: Reproductive tract tissues were examined for T foetus via light microscopy, immunohistochemical analysis, and PCR assay. History of reproductive tract disease was examined to detect statistical associations with identified or reported exposure to colonic T foetus infection. RESULTS: 15 of 61 (25%) cats and 22 of 33 (67%) catteries were identified with active or reported T foetus infection. Light microscopic, immunohistochemical, or molecular evidence of T foetus infection of the reproductive tract was not detected in any cats, including 15 cats with colonic T foetus infection, 29 cats residing in a cattery in which T foetus-infected cats were identified, and 8 cats for which gross or light microscopic evidence of reproductive tract disease was identified. There were no differences in total number of litters, number of litters per breeding, kitten mortality rate, or birth defects between cats or catteries infected with T foetus and those for which T foetus infection was not identified. CONCLUSIONS AND CLINICAL RELEVANCE: No evidence of reproductive tract colonization by T foetus was detected in this study. Accordingly, it is unlikely that reproductive tract infection with T foetus plays an important role in overall disease transmission.