11319 research outputs found
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Crisis management toolkit for food rescue organisations
Get PDFThis infographic was adapted from the dissertation “The impact of COVID19 on food rescue organisations in New Zealand/Aotearoa”. This is designed as a resource to be utilised by food rescue organisations, taking learnings from the COVID19 crisis to develop a framework for food rescue organisations to be better prepared for future disruptions
Consuming Church: The Impact of Consumerism on Ecclesiology Amongst 18-25 Year Old Churchgoers in Christchurch
Get PDFConsumerism is an ideology that greatly impacts our society. The Church is not immune to the logic and the practices of consumerism. In fact, one might suggest that our ecclesiology is often informed by consumerism. Consumerism presents the Church with a problem because the very logic of consumerism shapes the way that one thinks about Church. Church can become another commodity like everything else that exists to be consumed for its own sake. This research project focusses on young adult churchgoers in Christchurch (18-25 years old) from a variety of denominations to explore how their ecclesiology has been shaped by consumerism. This age group is one that has in many ways been discipled by consumerism. This project seeks also to articulate how the Church is to participate in the mission of the Triune God. A participative model grounded in Trinitarian theological reflection can give young adults an alternative ecclesiological vision – a participative ecclesiology that invites churchgoers to be participators rather than consumers, or in other words to be the Church rather than consume Church
Dental health needs and access to dental care in low-income groups (including refugees and migrants)
Get PDFAims This study sought to identify the dental care needs of people on low incomes in Christchurch (including refugees and migrants). An attempt was also made to identify the barriers to access to dental care services experienced by these groups.
Methods A literature search was conducted on health care needs and barriers to access to care for the target group. The review focussed particularly on dental care needs and the New Zealand context. An initial survey of organisations working with and for refugees, migrants and people on low incomes in Christchurch was conducted. This was followed by a survey of the clients of these organisations. Key informant interviews were also conducted with representatives of these groups and local dental care providers. Survey data was analysed using Epi-lnfo and interviews were transcribed and the transcripts analysed for emergent themes.
Results This study identified a need for the provision of more accessible dental care services for people on low income (including refugees and migrants) in Christchurch. Participants were concerned about high levels of need for dental health care in the target groups and the perceived inadequacy of available services. Cost of care was identified as the most significant barrier for most. However, non-cost barriers like lack of knowledge about services and English language skills were also identified as important by some groups.
Public Health Implications Dental health care for low income adults has been a low priority for health policy makers. While free access to basic dental health care is universally available for children in New Zealand, access to care for adults is mostly on a fee for service basis. This study suggests that many low income adults, including refugees and migrants, are missing out on needed dental care. The barriers to access to care they experience are predominantly but not entirely related to cost. The information derived from this study could be used as part of a needs assessment for public health intervention programmes to improve access to dental health care facilities. A number of improvements in the provision of dental services are suggested. These include: increased government funding for dental services for people on low incomes, provision of interpreter services for those who cannot speak and understand English, more widespread education for adults about the importance of dental health and better information on how to access available dental health services and dental benefits.
Key words: refugees, immigrants, lowincome, dental care and services
Exploration of exosomes as potential biomarkers for oral cancers
No full textExosomes are membrane-bound nanovesicles released by cells into their extracellular environment via fusion of the multivesicular endosome with the plasma membrane. These cell-derived vesicles are present in numerous body fluids, including blood, saliva, urine and lymph, under healthy and pathological conditions. They play a crucial role in cell-to-cell communication by virtue of the exchange of their contents which include proteins, lipids and nucleic acids. The contents can be transferred from one cell to another, including transfer from normal to cancer cells and between cancer cells that can lead to transcriptional and translational changes in the recipient cell. The contents of exosomes are influenced by various physiological and pathological stimuli received by the parent cell. Exosomal contents may thus provide a valuable source for screening and early detection of cancer, as well as monitoring cancer progression and interventions.
The management of patients with oral cancer is a tremendous worldwide liability. Despite significant efforts, the worldwide five-year relative survival rate from oral cancer is generally less than 50%. This low survival rate has remained unchanged for more than three decades. Early diagnosis of oral cancer is associated with improved survival; however, the invasive nature, technical requirements and skill required to perform intra-oral biopsies limits their usefulness as a part of community oral cancer screening. The use of saliva-based diagnostic testing to assess the presence of established salivary biomarkers would be advantageous if it could be shown to be a reliable method to detect early-stage tumours and identify high-risk patients. Saliva is a thick fluid that is 98% water, and the remaining 2% contains proteins, potentially including salivary biomarkers that have diagnostic potential. There have been various advances in saliva analysis, but to date, no saliva-based oral cancer diagnostic tests have made it to the market. The discovery of exosomes in saliva has provided a pathway to detect oncogenic biomarkers protected within salivary exosomes. If we can show that salivary exosomes are a reliable and effective method for detecting oral cancer biomarkers, potentially saliva can be used to develop a non-invasive oral cancer diagnostic test to run community screening programs.
The aim of this study was to isolate exosomes and assess the expression of genes of interest (GOI) FOXM1, HOXA7, CCNB1, DNMT1 and HSPA1A genes and FOXM1, DNMT1 and HSP70 proteins of interest (POI) in exosomes, both in vitro, using oral squamous cell carcinoma (OSCC) and normal primary gingival keratinocyte (PKG) cell lines and ex vivo, in exosomes derived from plasma and saliva samples from OSCC patients and healthy controls. The oncogenes and oncoproteins selected for this study had been documented previously to be overexpressed in oral cancers. The hypothesis tested was that FOXM1, HOXA7, CCNB1, DNMT1 and HSPA1 genes and FOXM1, DNMT1 and HSP70 proteins would be highly expressed in exosomes derived from OSCC patients in comparison with healthy controls.
A major hurdle in studying exosomes is their isolation. Their small size and the fact that they do not have any specific surface protein markers make them difficult to isolate. Thus, this research initially looked into determining and optimising a method to isolate exosomes, which was both cost-effective and yielded enough exosomes for downstream analysis. An Exoquick-TC plus exosome isolation kit (kit) was compared with the classic ultracentrifugation (UC) method for exosome isolation from the concentrated cell-conditioned medium of a representative OSCC cell line (SCC-4). Cryo-Electron Microscopy (Cryo-EM) showed vesicles were delimited by a bilayered membrane and had either a round or slightly elongated shape with diameters ranging between 50 and 150nm in samples obtained using both methods. Dynamic light scattering resulted in multiple peaks for kit exosomes, whereas a single peak was observed for UC exosomes. The multiple peaks most likely came from proteins co-precipitating with exosomes. A significantly higher total RNA was observed in UC exosomes in contrast to kit exosomes (P < 0.0001). This was reflected in subsequent mRNA analysis using quantitative polymerase chain reaction (qPCR), where UC exosomes had lower cycle threshold (Ct) values compared to kit exosomes. UC proved a better option and was used for exosome isolation for all subsequent experiments.
The presence of the GOI and POI were evaluated using the concentrated cell-conditioned medium of normal oral keratinocyte (PGK) and SCC-4 and SCC-25 cell lines. The results showed a significantly higher expression level of all the GOI in exosomes derived from SCC-4 and SCC-25 exosomes than PGK exosomes. The POI results suggested a higher expression of all POI in SCC-4, and DNMT1 and HSP70 in SCC-25 exosomes when compared with cells. Even though their expression was lower in SCC-4 and SCC-25 cells compared to PGK cells, DNMT1 and HSP70 were highly expressed in SCC-4 and SCC-25 exosomes compared to PGK exosomes implying that the cells preferentially package certain proteins for transport via exosomes to recipient cells.
The selected GOI and POI were then further evaluated in exosomes derived from blood plasma and saliva of OSCC patients compared with healthy controls. Due to the low quantity of total RNA, only HSPA1A and housekeeping genes were detected in plasma and saliva exosome samples despite adding a preamplification step. The mean expression level of HSPA1A was higher in both OSCC plasma and saliva exosomes compared to controls. Enzyme linked immunosorbent assay (ELISA) results showed a higher expression of FOXM1, DNMT1 and CCNB1 in OSCC plasma exosomes than controls. There was a marginally lower expression of HSP70 in OSCC plasma exosomes. A similar trend was observed in OSCC saliva exosomes for FOXM1, DNMT1 and HSP70, whereas a lower expression level of CCNB1 was observed in OSCC saliva exosomes compared to controls. Even though a majority of the GOI and POI were overexpressed in OSCC samples, due to the small sample size and a high variation in expression levels between samples, the differences of the means were not statistically significant except for FOXM1 protein, which was significantly higher in OSCC plasma.
This is the first study, to the best of my knowledge, which has shown a similar trend of expression of biomarkers in exosomes in both saliva and plasma. It was also observed that despite having less total RNA and total proteins, a higher expression of the GOI and POI was observed in salivary exosomes compared to plasma exosomes. It is thus proposed that saliva may be a suitable alternative to blood in the future for the detection of disease biomarkers. The results also provide the first evidence that the selected proteins were detected and quantified in exosomes using ELISA. This suggests a change of focus from mRNAs to proteins since they are more stable and easier to detect and quantify. While more precise exosome isolation methods are still underway, it was shown that saliva exosomes are very important for future research and potential clinical application as they carry genes and proteins in greater quantities when compared with plasma exosomes
Prescriptive and Holistic Contextualism: Emerging Variants of Modern Contract Interpretation
Get PDFDebate over the proper approach to modern contract interpretation continues even in this era of modern contract interpretation where context is always considered. This paper identifies and contrasts two rival approaches to contract interpretation: “prescriptive contextualism” which demands that contract interpretation start with plain meaning, and only then go on to consider textual context, extra-textual context and finally commercial sense; and “holistic contextualism” which involves consideration of those same factors but is not fussy about the order. In setting out the two approaches, I provide an exposition of the present law of contract interpretation. Then, I consider the main arguments that can be advanced by proponents of the two approaches, and conclude by offering my own arguments that, I suggest, tip the scales in favour of holistic contextualism: the prescriptive process inhibits identification of viable interpretation, and is overly dependant on which words are used to start the interpretive process.Peer Reviewe
Refugee State and Community Sponsorship in Aotearoa New Zealand
No full textThere are over 79.5 million people globally who have been forcibly displaced, comprising refugees, asylum seekers, and internally displaced people. In 2019, 26 million of these were registered as refugees. People may be forced to flee to safety for a plethora of reasons. Aotearoa New Zealand accepts refugees for resettlement under various pathway programmes. This thesis investigates two refugee resettlement pathways in Aotearoa New Zealand: the state-led Refugee Quota Programme, and the community sponsor-led Community Organisation Refugee Sponsorship (CORS) category. Dunedin is used as a case study for the state-led programme, with Timaru and Nelson as the CORS-led case studies. The research examines what both programmes consist of and seeks to uncover and understand the everyday lived experiences of support organisations, volunteers, and former refugees who have entered the country through these two pathways. Refugees’ backgrounds are precarious, and the negotiation often carries into the resettlement period since refugees must adapt to a new country and way of life. To aid in resettlement, frameworks must be both pragmatic in meeting the needs of former refugees, and must also encompass a network of genuine care to ensure the successful integration of former refugees into the host community. It is, however, not a simple process to foster both a top-down approach and a caring strategy, and this thesis considers the barriers to effective refugee resettlement such as structural injustices and the depoliticisation of the ‘refugee’. Support agencies, volunteers, and the overall host community hold important roles to easing former refugees’ transition to life in Aotearoa New Zealand
Application of pharmaceutical drug delivery for biological control of the common brushtail possum in New Zealand: a review
Get PDFThe common brushtail possum (Trichosurus vulpecula) is the most significant vertebrate pest in New Zealand, being a major ecological threat to the indigenous biodiversity and an economic threat as a vector for bovine tuberculosis. Novel and effective strategies to reduce the population of T. vulpecula are needed urgently. A number of biocontrol agents are currently being assessed and from research to date it is likely that the biocontrol agents will be peptide or protein molecules. It is not possible to administer such biocontrol agents alone because they would be degraded rapidly in the animal, especially if delivered via the oral route. Technologies used in the pharmaceutical industry to design efficacious drug delivery systems for humans and animals can be applied to the design of delivery systems for biocontrol agents used in wildlife management, although there are some unique challenges that must be overcome.Peer Reviewe
A cyclodextrin formulation to improve use of the anaesthetic tribromoethanol (Avertin)
No full textObjective: Efficacy and safety concerns have been raised in the literature with the use of tribromoethanol (Avertin) for anaesthesia in rats and mice when administered by intraperitoneal injection. Despite the controversy, it remains in common usage as an anaesthetic agent in laboratory rodents for short-term surgical procedures. Cyclodextrins have been shown to improve drug solubility and were investigated here as an improved anaesthetic formulation for mice.
Materials and Methods: The phase solubility of TBE with HP-β-CD was estimated. The efficacy of two anaesthetic regimens were compared in this study; the conventional tribromoethanol (TBE) formulation solubilized in tertiary amyl alcohol and a HP-β-CD cyclodextrin formulation containing TBE. Mice (n=6) were administered the formulations by IP injection and the pharmacodynamic parameters of time to induction of anaesthesia, duration of anaesthesia and recovery time were measured using a combined reflex score.
Results and Discussion: Phase solubility studies showed a linear increase in the solubility of TBE with increasing HP-β-CD concentration and suggested > 1:1 binding of the drug in the cyclodextrin complex. At a dose of 260 mg/kg the standard TBE formulation appeared to produce deeper anaesthesia than the cyclodextrin formulation, with a minimum average CRS of 1.8 compared to 5.2. No post-mortem pathology was observed in mice that received either the conventional or cyclodextrin formulation.
Conclusion: The cyclodextrin TBE formulation did not conclusively provide an improved anaesthetic response at a dose of 260 mg/kg compared to the conventional formulation. The improved solubility of TBE with HP-β-CD and the reduced variability in anaesthetic response warrants the further investigation of this formulation. This study has also identified the value of using the anticholinergic atropine in association with TBE for anaesthesia.Peer Reviewe
Cytostatic and anti-angiogenic roles of novel histone deacetylase inhibitors in androgen receptor negative prostate cancer
No full textAndrogen receptor-negative (AR-) prostate tumours are observed in 11-24% of prostate cancer patients. To date, no treatments have been clinically approved for AR- prostate cancers. Histone deacetylases (HDACs) are overexpressed in late-stage prostate cancers and in AR- prostate cancer cell lines (PC3 and DU145). However, HDAC inhibitors, including suberanlihohydroxamic acid (SAHA), showed toxicity and lack of efficacy in clinical trials for prostate cancer. Novel HDAC inhibitors, N1-hydroxy-N8-(4-(pyridine-2-carbothioamido)phenyl)octanediamide) (Jazz90) and [chlorido(η5-pentamethylcyclopentadienyl)(N1-hydroxy-N8-(4-(pyridine-2-carbothioamido-κ2N,S)phenyl)octanediamide)rhodium(III)] chloride (Jazz167), were synthesised based on SAHA with the objective of making more efficacious and safer drugs. Jazz90 and rhodium-containing Jazz167 exhibited lesser toxicity towards non-cancerous (PNT1A and NIH 3T3) cells as compared to SAHA and were also non-toxic in BALB/c mice at the highest dose of 75 mg/kg. On comparing the selectivity of these compounds towards cancerous cells, Jazz90 was 2.9- and 2.5-fold more potent against PC3 and DU145 cells as compared to PNT1A cells, respectively, whereas Jazz167 was 3.5- and 1.3-fold more potent against PC3 and DU145 cells in contrast to PNT1A cells, respectively. As these drugs were effective at inhibiting the growth of PC3 and DU145 cells, they were also tested against PC3 and DU145 spheroids. Growth was inhibited by 78-89% in PC3 and DU145 spheroids, whereas branching was reduced in PC3 spheroids by ~95% following treatment. These compounds also reduced HDAC activity by 60% at 50 nM in PC3 nuclear lysates, whereas these drugs increased acetylation of histone-3 by 6- to 8-fold in PC3 cells. Although these compounds exhibited equipotent HDAC inhibition to SAHA, they were not as potent at inducing acetylation of histone-3 as compared to SAHA, which induced 14- and 3-fold acetylation in PC3 and DU145 cells in comparison to the control, respectively. Furthermore, the Jazz compounds exhibited a G0/G1 arrest and minimal apoptosis was recorded in AR- cells. Therefore, the drugs were concluded to be cytostatic and induced quiescence on their withdrawal. The mechanism of action by which these drugs induce cytostaticity remains unclear as different responses following drug treatment were observed on phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) and Ras/mitogen-activated protein kinase (Ras/MAPK) pathway in PC3 and DU145 cells. Although Jazz90 and Jazz167 did not induce cell death, they had anti-angiogenic effects, as they reduced vascular endothelial growth factor-A (VEGF-A) and vascular endothelial growth factor receptor-2 (VEGFR-2) levels by 67-72% and 71-93%, respectively, in PC3 cells and decreased human umbilical vein endothelial (HUVEC) cells from assembling into tubes. In conclusion, Jazz90 and Jazz167 function via cytostatic and anti-angiogenic mechanisms and are well-tolerated in BALB/c mice. However, as these compounds are not as potent at inducing acetylation of histone-3 in comparison to SAHA, they may have off-target cytostatic effects. Future studies should address their off-target effects on ribonucleotide reductase inhibition and outer dense fibre protein-2, as past studies suggest that the pyridine carbothioamide (PCA) and rhodium cyclopentadienyl complex PCA in these compounds have selectivity for these molecules. Furthermore, as these compounds contain an additional aromatic ring, their effects on pharmacokinetic profile need to be investigated