Investigation into the characteristics, triggers and mechanism of apnoea and bradycardia in the anaesthetized platypus (Ornithorhynchus anatinus)

Health and conservation research on platypuses (Ornithorhynchus anatinus) may require anaesthesia to reduce stress and the risk of injury to both the animal and the researcher, as well as to facilitate examination and sample collection. Platypus anaesthesia can be difficult to manage, with reports of periods of apnoea and bradycardia described. This study investigated the conditions around sudden-onset apnoea and bradycardia in 163 field-anaesthetized platypuses as part of a health study. Anaesthesia was induced and maintained using isoflurane delivered in oxygen by face mask. Sudden-onset apnoea and bradycardia was observed in 19% of platypuses, occurring either at induction of anaesthesia, during recovery, or both. At induction, occurrence was more often recorded for adults (P = 0.19) and was correlated with low body temperature (P < 0.001), season (P = 0.06; greater incidence in summer) and longer pre-anaesthetic holding time (P = 0.16). At recovery, sudden-onset apnoea and bradycardia occurred only in platypuses that had been placed in dorsal recumbency as part of their examination, and correlated with poor body condition (P = 0.002), time in dorsal recumbency (P = 0.005), adults (P = 0.06), number of fieldworkers (P = 0.06) and females (P = 0.11). The sudden-onset apnoea and bradycardia we observed is likely to result from the irritant nature of isoflurane (stimulating the trigeminal nerve via nasal chemoreceptors). We propose that this mechanism is analogous to that of submersion of the face/nasal cavity in cold water during a natural dive response, but that the term ‘nasopharyngeal response’ would more appropriately describe the changes observed under isoflurane anaesthesia. Although we did not record any long-term adverse effects on platypuses that had undergone this response, the nasopharyngeal response could complicate the diagnosis of anaesthetic dose-dependent apnoea and bradycardia. Therefore, we suggest that these responses during anaesthesia of platypuses might be avoided by minimizing the stress around capture and handling, as well as reducing the time in dorsal recumbency

Isotopic evidence of a wide spectrum of feeding strategies in Southern hemisphere humpback whale baleen records

Our current understanding of Southern hemisphere humpback whale (Megaptera novaeangliae) ecology assumes high-fidelity feeding on Antarctic krill in Antarctic waters during summer, followed by fasting during their annual migration to and from equatorial breeding grounds. An increase in the number of reported departures from this feeding/fasting model suggests that the current model may be oversimplified or, alternatively, undergoing contemporary change. Information about the feeding and fasting cycles of the two Australian breeding populations of humpback whales were obtained through stable isotope analysis of baleen plates from stranded adult individuals. Comparison of isotope profiles showed that individuals from the West Australian breeding population strongly adhered to the classical feeding model. By contrast, East Australian population individuals demonstrated greater heterogeneity in their feeding. On a spectrum from exclusive Antarctic feeding to exclusive feeding in temperate waters, three different strategies were assigned and discussed: classical feeders, supplemental feeders, and temperate zone feeders. Diversity in the interannual feeding strategies of humpback whales demonstrates the feeding plasticity of the species, but could also be indicative of changing dynamics within the Antarctic sea-ice ecosystem. This study presents the first investigation of trophodynamics in Southern hemisphere humpback whales derived from baleen plates, and further provides the first estimates of baleen plate elongation rates in the species

Knemidokoptinid (Epidermoptidae: Knemidokoptinae) mite infestation in wild red-crowned parakeets (cyanoramphus novaezelandiae): Correlations between macroscopic and microscopic findings

During a study on health and disease in Red-crowned Parakeets (Cyanoramphus novaezelandiae) on Tiritiri Matangi Island and Little Barrier Island (Hauturu-o-Toi) in New Zealand between 2011 and 2013, an outbreak of feather loss prompted the collection of skin biopsies (n5135) under anesthesia from the head of captured birds. A subset of samples (n57) was frozen to obtain whole specimens for identification of ectoparasites. Mites (range 1–11) were observed in 79/135 (58.5%) skin biopsies, whereas feather loss was only found in 47/142 (33.1%) birds captured during the sampling period. Compact orthokeratotic hyperkeratosis and acanthosis were found in association with mites. Procnemidocoptes janssensi (Acari: Epidermoptidae, Knemidokoptinae) was identified from whole mites obtained from skin biopsies. We describe the presence, pathology, and stages of infestation for knemidokoptinid mange in a wild parrot population in New Zealand. Given the clinical and pathologic changes observed and poor knowledge of the parasite’s New Zealand host and geographic distribution, further work is recommended for this and sympatric parrots, to understand relationships between the host, parasite, environment, and expression of disease. Results from this study reinforce the value of including biopsy samples for the investigation of skin disease in wild birds, particularly to link etiologic agents with pathologic changes

Targeting quiescent leukemic stem cells using second generation autophagy inhibitors

In chronic myeloid leukemia (CML), tyrosine kinase inhibitor (TKI) treatment induces autophagy that promotes survival and TKI-resistance in leukemic stem cells (LSCs). In clinical studies hydroxychloroquine (HCQ), the only clinically approved autophagy inhibitor, does not consistently inhibit autophagy in cancer patients, so more potent autophagy inhibitors are needed. We generated a murine model of CML in which autophagic flux can be measured in bone marrow-located LSCs. In parallel, we use cell division tracing, phenotyping of primary CML cells, and a robust xenotransplantation model of human CML, to investigate the effect of Lys05, a highly potent lysosomotropic agent, and PIK-III, a selective inhibitor of VPS34, on the survival and function of LSCs. We demonstrate that long-term haematopoietic stem cells (LT-HSCs: Lin−Sca-1+c-kit+CD48−CD150+) isolated from leukemic mice have higher basal autophagy levels compared with non-leukemic LT-HSCs and more mature leukemic cells. Additionally, we present that while HCQ is ineffective, Lys05-mediated autophagy inhibition reduces LSCs quiescence and drives myeloid cell expansion. Furthermore, Lys05 and PIK-III reduced the number of primary CML LSCs and target xenografted LSCs when used in combination with TKI treatment, providing a strong rationale for clinical use of second generation autophagy inhibitors as a novel treatment for CML patients with LSC persistence

Eradication of chronic myeloid leukemia stem cells: a novel mathematical model predicts no therapeutic benefit of adding G-CSF to imatinib

Imatinib mesylate induces complete cytogenetic responses in patients with chronic myeloid leukemia (CML), yet many patients have detectable BCR-ABL transcripts in peripheral blood even after prolonged therapy. Bone marrow studies have shown that this residual disease resides within the stem cell compartment. Quiescence of leukemic stem cells has been suggested as a mechanism conferring insensitivity to imatinib, and exposure to the Granulocyte-Colony Stimulating Factor (G-CSF), together with imatinib, has led to a significant reduction in leukemic stem cells in vitro. In this paper, we design a novel mathematical model of stem cell quiescence to investigate the treatment response to imatinib and G-CSF. We find that the addition of G-CSF to an imatinib treatment protocol leads to observable effects only if the majority of leukemic stem cells are quiescent; otherwise it does not modulate the leukemic cell burden. The latter scenario is in agreement with clinical findings in a pilot study administering imatinib continuously or intermittently, with or without G-CSF (GIMI trial). Furthermore, our model predicts that the addition of G-CSF leads to a higher risk of resistance since it increases the production of cycling leukemic stem cells. Although the pilot study did not include enough patients to draw any conclusion with statistical significance, there were more cases of progression in the experimental arms as compared to continuous imatinib. Our results suggest that the additional use of G-CSF may be detrimental to patients in the clinic

Presentation and prognostic indicators for free-living black cockatoos (Calyptorhynchus SPP.) admitted to an Australian Zoo Veterinary Hospital over 10 years

The veterinary records of three species of free-living, endangered black cockatoos (Calyptorhynchus spp.; n5565) admitted to the Perth Zoo Veterinary Hospital in Western Australia during a 10-yr period (2000–09) were analyzed to determine the effect of clinical presentation and treatment on survival to release. The most-common reason for admission was trauma (at least 76.7%of cases), and trauma was also the most-frequent finding on necropsy examination (80.1% of cases). Anemia and paralysis-paresis were significant factors determining the decreased likelihood of survival of cockatoos undergoing rehabilitation. Human activities, in particular vehicle strike, were significant causes of morbidity and mortality in free-living black cockatoo populations

MTSS1 is a critical epigenetically regulated tumor suppressor in CML

Chronic myeloid leukemia (CML) is driven by malignant stem cells that can persist despite therapy. We have identified Metastasis suppressor 1 (Mtss1/MIM) to be downregulated in hematopoietic stem and progenitor cells from leukemic transgenic SCLtTA/Bcr-Abl mice and in patients with CML at diagnosis, and Mtss1 was restored when patients achieved complete remission. Forced expression of Mtss1 decreased clonogenic capacity and motility of murine myeloid progenitor cells and reduced tumor growth. Viral transduction of Mtss1 into lineage depleted SCLtTA/Bcr-Abl bone marrow cells decreased leukemic cell burden in recipients, and leukemogenesis was reduced upon injection of Mtss1 overexpressing murine myeloid 32D cells. Tyrosine kinase inhibitor (TKI) therapy and reversion of Bcr-Abl expression increased Mtss1 expression but failed to restore it to control levels. CML patient samples revealed higher DNA methylation of specific Mtss1 promoter CpG sites that contain binding sites for Kaiso and Rest transcription factors. In summary, we identified a novel tumor suppressor in CML stem cells that is downregulated by both Bcr-Abl kinase-dependent and -independent mechanisms. Restored Mtss1 expression markedly inhibits primitive leukemic cell biology in vivo, providing a therapeutic rationale for the Bcr-Abl-Mtss1 axis to target TKI resistant CML stem cells in patients

Cancer: repositioned to kill stem cells

Chemotherapy-resistant cancer stem cells make it hard to cure many forms of the disease. Repositioning an existing drug to tackle this problem could significantly improve treatment for one form of leukaemia

‘Don’t just travel’: thinking poetically on the way to professional knowledge

This paper describes how the medium of ‘found poetry’ is incorporated into a doctoral programme for nurses, educators and allied health and social care professionals at the start of their various doctoral journeys. It advocates a narrative practice approach to issues of researcher identity and reflexivity. ‘Finding’ the poems begins with the creation of collages as representational anchors for students to talk about themselves, their professional practice, their hopes and expectations of the doctoral experience, and their research ideas. (Re)presenting their transcribed talk as poetry involves culling and playing with words, phrases and segments, making changes in spacing, lines and rhythm to arrive at an evocative distillation (Butler-Kisber, 2002). This process enables each person to bring stories and/or fragments of experience into critical engagement with others. Poetic thinking functions pedagogically, helping students find a critical voice to enliven and hone their reflexive writing in relation to their doctoral experience and their research positioning. Arts-based methods of inquiry are an ongoing topic of interest in research communities. Found poetry is a useful starting point to explore creative means by which research participants can recount their stories, and equally, by which researchers can witness and disseminate what they have to tell.self funde