11319 research outputs found
Sort by
The proportion of plant-based foods in the diets of adolescent females in New Zealand
No full textAbstract
Background: There is a worldwide movement towards a plant-based diet, with the EAT-Lancet commission recommending consumption of largely plant-based foods to address both human and planetary health. Several plant-based dietary patterns are associated with a reduced risk of non-communicable diseases, including regular consumption of whole grains, fruits, vegetables, legumes, nuts and seeds. Adolescence is a critical stage of life as physical growth and development reach their peak during this time, and optimal nutrition is needed to ensure proper growth. Adopting a healthy dietary pattern, including more plant foods, in adolescence will have long-term health benefits. However, there are no data on the proportion of plant-based energy in the diets of adolescent females in NZ.
Objective: To determine the proportion of energy that comes from plant-based sources in female adolescents aged 15 to 19 years. A comparison of the diets of adolescent females with the EAT-Lancet recommendations was a secondary objective.
Design: A clustered, cross-sectional study of schoolgirls aged 15 to 19 years was carried out throughout New Zealand. A self-administered online questionnaire was used to collect sociodemographic and health information. Using the Multiple Source Method, adjusted dietary intakes were calculated from two non-consecutive 24-hour diet recalls obtaining participants’ usual intakes. Anthropometric measurements such as height and weight were measured to calculate the body mass index z-score. Based on the recipes provided by participants, all foods have been classified as either plant or animal. Foods that mixed animal and plant components were deconstructed.
Results: Of the 256 participants included in this study, 15.2% were vegetarians. The mean daily energy intake of schoolgirls was 7946 kJ/d. The mean proportion of plant-based energy in the adolescent female cohort was 70.8%; omnivores and vegetarians consumed 70.2%, and 80.2%, respectively, of their energy from plant-based foods. The range of energy intake from plant-based foods was 43 to 92% for omnivores, 51 to 97% for vegetarians, and 89 to 100% for vegans. For nutrients of interest related to vegetarianism, protein intake was 1.2 g/kg/d for omnivores and 1.0 g/kg/d for vegetarians. There was no difference in the dietary intake of calcium, zinc, and iron between omnivores and vegetarians. However, a difference in vitamin B12 was found. In comparison with EAT-Lancet recommendations, the diets of vegetarian female adolescents were, on average, better aligned than the diets of omnivores. Participants ate fewer whole grains and more tubers daily than recommended by EAT-Lancet.
Conclusion: This is the first study in which the energy intake from plant-based foods has been estimated in a sample of female adolescents in New Zealand. An important finding to emerge from this study is the considerable overlap in the energy that comes from plant sources of omnivores and vegetarians. This means that a person can be an omnivore and still have a predominantly plant-based diet, and, conversely, being a vegetarian does not necessarily equate to a high proportion of plant energy in the diet
Sixth Annual Report of the Perinatal and Maternal Mortality Review Committee
Get PDFThis is the sixth annual report of the Perinatal and Maternal Mortality Review Committee (PMMRC). The aim of this committee is to identify areas in maternity and newborn care where improvements could be made. The purpose of this report is to provide an accurate estimate of the numbers and rates of perinatal and maternal deaths in New Zealand, to describe the risk factors for perinatal and maternal deaths, and to attempt to identify where the attention of maternity and neonatal services might be focused to prevent perinatal and maternal deaths
Tenth Annual Report of the Perinatal and Maternal Mortality Review Committee
Get PDFThis report considers perinatal and maternal mortality and morbidity from 1 January to 31 December 2014; perinatal mortality from 2007 to 2014; maternal mortality from 2006 to 2014; and babies with neonatal encephalopathy from 2010 to 2014.
This report also includes special topics on two causes of maternal mortality: suicide and amniotic fluid embolism
Investigating the Molecular Pharmacology of Novel Allosteric Modulators at the Type 2 Cannabinoid Receptor
Get PDFThe endocannabinoid system plays essential roles in normal physiology and a variety of disease states. A component of this system is the type-2 cannabinoid receptor (CB2); a G protein-coupled receptor predominantly expressed in peripheral tissues, primarily in the immune system. Thus, CB2 is a promising candidate therapeutic target for treating inflammation, diabetes, cancer, pain, and other diseases. However, CB2-selective drug candidates thus far have failed in clinical trials. A contributor to this problem is difficulties in developing CB2-selective compounds. As a result, novel therapeutic strategies for modulating CB2 are currently under study, with allosteric modulation being proposed as a potentially important approach for targeting CB2 receptors. A positive allosteric modulator would potentiate the functional response to an orthosteric agonist, allowing affinity modulation and/or efficacy modulation. However, proper spaciotemporal regulation of signalling would theoretically remain under physiological control due to the allosteric compound being dependent on an endogenous orthosteric ligand. The compounds C2 and A5 are among the first small synthetic CB2 positive allosteric modulators (PAMs) reported. This project aimed to characterise the molecular pharmacology of these allosteric modulators together with a series of proposed novel allosteric modulators (which comprise analogues of C2 and A5, and novel compounds from a in silico virtual screen) at CB2 using G protein dissociation (TRUPATH) and β- arrestin-2 translocation assays; both real-time bioluminescence resonance energy transfer (BRET) assays. Assays were conducted in human embryonic kidney (HEK) cells, where compounds were tested alone, and in the presence of the orthosteric agonist CP55,940. Results showed that neither C2 or A5 could modulate CP55,940-dependent G protein dissociation or CP55,940-dependent β- arrestin-2 translocation at CB2, contradicting the published evidence describing these compounds as PAMs. However, C2 was active as an agonist alone. Surprisingly, C2 alone also induced G protein dissociation at the CB1 receptor, and increased CP55,940-dependent G protein dissociation through CB1, suggesting that this compound is both an agonist and a positive allosteric modulator at CB1 (i.e., an ago-PAM). The remaining set of proposed novel allosteric modulators (C2 and A5 analogues and “hits” from the in silico virtual screen) did not able appear to modulate CP55,940- dependent G protein dissociation or CP55,940-dependent β-arrestin-2 translocation at CB2. The findings from this study add to the body of work on allosteric modulators of CB2 and highlight discrepancies from published literature, which present C2 and A5 as PAMs. Therefore further investigation requires more rigour to address these differences
ADSC-EVs Effect on Fibroblast Phenotyping in vitro
Get PDFBackground: Breast Cancer is the most common cancer amongst wāhine in Aotearoa, with approximately 3,300 diagnoses every year. Breast reconstruction after breast cancer treatment (e.g. mastectomy) is an important part of the overall treatment process. Autologous Fat Grafting (AFG) is an increasingly popular breast reconstruction option with minimal risks. However, a major caveat of AFG is only 30% of the original fat graft retained in the recipient site. Fat graft retention is regulated by the tissue microenvironment involving complex cross-talk between Adipose derived stem cells (ADSCs) in the donor site and fibroblasts cells in the breast cavity. The release of extracellular vesicles (EVs) from ADSCs is one signalling pathway between these two sites and investigating this dynamic further could help to improve fat graft retention.
Aim: The aim of this study was to investigate the role of ADSC-EVs on human dermal fibroblast wound healing activity in vitro.
Methods: Adipose tissue samples were collected from three patients undergoing an AFG procedure at Wellington Regional Hospital and digested using collagenase. EVs were isolated from ADSCs using size exclusion chromatography (SEC) on a qEV10/35nm column with an automated fraction collector. ADSC-EVs were added to fibroblast cells (CCD-1128Sk) for 48 hrs. Following incubation fibroblast proliferation was measured using Cell counting kit-8, wound migration using a scratch-wound assay and mRNA expression levels using RT-qPCR at 0, 24 and 48 hr time points in ADSC-EVs co-cultures. Dummy EVs which were collected from ADSC media with no cells were used as a negative control against ASDC-EVs. Statistical Analysis of results were compared using a paired t-test and deemed significant if (p <0.05).
Results: ADSC-EVs show trends towards promoting a pro-inflammatory environment with IL-6 trending towards an increased expression in ADSC-EV co-cultures (6.556 +/- 6.512; p= 0.2775) and a decrease in ACTA2 expression (0.5328 +/- 0.3200, p= 0.1272). Based on standard deviation assessment, ADSC-EV co-cultures exhibited numerically larger levels of variation in gene expression compared to DEVs. Cell proliferation was not significantly different between ADSC-EV (0.8319 +/- 0.340) and DEV (0.8067 +/- 0.2757) co-cultures (p= 0.6290). EVs had no significant effect on cell migration compared to DEVs at 24 and 48 hr time points (p= 0.8976, 0.4931 respectively).
Conclusion: ADSC-EVs show a trend towards promoting a pro-inflammatory environment in human dermal fibroblast cells, potentially influencing fibroblast function. ADSC-EVs also showed large levels of variation in gene expression compared to DEVs. This suggests that primary ADSC-EVs from patients have diverse effects and further investigation is warranted
Transitioning from analysing methylation profiles in bulk populations of Colorectal cancer cells to methylation profiles of single cells
Get PDFColorectal cancer (CRC) is one of the leading causes of death by cancer in New Zealand, largely due to metastasis of the primary tumour to secondary sites around the body. The initiation, progression and eventual metastasis has been shown to be largely influenced by epimutations. DNA methylation is a stable, heritable epigenetic mark which has been heavily implicated in disease. In cancer contexts, global hypomethylation and focal hypermethylation act to grossly dysregulate the genome, while simultaneously acting as potential biomarkers for initial detection and therapeutic response.
CRC is a molecularly heterogeneous disease, including between patients, tumours and even within the tumours. As well as this, tumours are comprised of immune cells, healthy tissue cells and blood cells in tandem with the neoplastic cells. Traditionally, these populations are sequenced as a whole. Consequently, the methylomes of each cell are coalesced, giving rise to averaged methylation profiles. The emergence of single cell technologies allows us deconvolute heterogeneous populations of cells and identify different cell states and types.
Obtaining high quality data from a single cell is difficult due to the minimal amount of starting DNA, particularly in single-cell bisulfite sequencing as the bisulfite conversion is harsh on the DNA. Hence, the main aim of this project was to optimise and implement single-cell bisulfite sequencing on a sorted human colorectal cancer cell line. Following this, my second aim was to compare the methylation profiles of the single-cell methylation libraries to uncover heterogeneity in the population. In this project, I use a post-bisulfite adaptor tagging (PBAT) method to perform single cell bisulfite sequencing on the CRC human cell line HT29. Following this, I use a publicly available data set to investigate intra- and inter- tumour heterogeneity.
With a few optimization steps the PBAT method was able to successfully amplify very small numbers of cells, including 100, 10, 5 and two single cell samples. Following this, publicly available data showed even in a small population of single cells, there was evident heterogeneity regarding global, chromosomal and focal promoter methylation.
These results highlighted the heterogeneity which can be unmasked using single cell technologies, even on a small scale. While also confirming renowned biological models such as the global hypomethylation undertaken by cancer cells
Māori Instagram: The Social Media Lifeworlds and Decolonising Practices of Rangatahi Māori
Get PDFIn a growing corner of the internet, rangatahi (young) Māori are finding and creating a place to gather, to discuss, and to explore their indigeneity. As a member of this community, the following thesis explores my own personal and research journey, alongside the rangatahi of Māori Instagram, by way of digital ethnography and supplemented by semi-structured interviews with three influential ‘leaders’ within this community. Kaupapa Māori methodologies were considered thoroughly throughout this process, and in relation to my positionality, which led to a strong autoethnographic component. This became particularly appropriate as Ihumātao occupation coincided unexpectedly with the beginning of my data gathering in late July, 2019. What emerged from this month of digital fieldwork and interviews, was an ethnography that explores what it means to be Māori for the diverse, dispersed, yet digitally connected rangatahi of Aotearoa, New Zealand and abroad. This includes considering the contexts and histories of colonisation, historical trauma, and urbanisation alongside the transformative possibilities of digital practices of decolonisation through Instagram. These practices incorporated relationships with the land and technologically-facilitated activism which I have termed e-kaitiakitanga. They further included the utilisation of Instagram’s dialogical affordances which enabled rangatahi to discuss personal and collective identity in relation to tradition, authenticity, and modernity, resulting in new adaptations of tradition through fashion and personal expression. Lastly, the transformative potential of Instagram as a socially constituted ‘place’, which I theorise as a ‘digital marae’, was seen in practices of connection and vulnerability, that in turn supported decolonisation and healing. The thesis then concludes by highlighting the agency of these community leaders in continuing the intergenerational struggle of dismantling colonial ideology, and in doing so, healing the disconnection lived and experienced by those I spoke with, by myself, and by so many other contemporary Māori
Mitochondria function in differentiating Megakaryocytes
Get PDFMegakaryocytes (MKs) are specialised cells which function to produce platelets and release them into the blood stream. MKs descend from hematopoietic stem cells (HSCs), via a stepwise differentiation model. A reduction in platelet number or function is described as thrombocytopenia and is typically accompanied by bleeding abnormalities. Surprisingly, a mutation in CYCS, the gene encoding cytochrome c, was identified in patients who had thrombocytopenia but no other deficiencies. This prompted the need for investigation into the energy demands of MKs as there is currently no understood role for cytochrome c in thrombopoiesis. To do so, a MK cell model was developed using K562 cells and phorbol 12- myristate 13-acetate (PMA). To elucidate a megakaryocytic specific function for cytochrome c, the mitochondrial respiratory capacity of the cell models was explored. Cytochrome c shuttles electrons via redox reactions in the electron transport chain (ETC); therefore, it was hypothesised that MKs may have specific energy demands that lead to thrombocytopenia in patients with CYCS mutations. Furthermore, this study aimed to test whether inhibition of mitochondrial ROS impacted on the megakaryocytic differentiation capability of K562 cells.
It was determined that treatment with 0.5 nM PMA for three and six days represented a partially and fully differentiated megakaryocyte respectively. This cell model was used in further experiments looking at the energy demands of megakaryocytes. Using the Seahorse Cell Mito Stress test, the mitochondrial respiratory capacity was compared between wild type (WT) K562 cells and the differentiating MK cell models. Although no significant differences in the energy demands of MKs throughout differentiation were noted, this study suggests that partially differentiated MKs had increased maximal and spare respiratory capacity. K562 cells treated with mitochondrial inhibitors and PMA did not show any significant results when comparing their differentiation capability to cells with PMA alone. There did appear to
ii
be a positive correlation between CD61 mean fluorescent intensity (MFI) and oxygen consumption rate (OCR).
These results suggest that there is variation in the energy demands of MKs as they differentiate, however, the findings are inconclusive. Further study should be done to confirm the observations made of the increased maximal and spare capacity of partially differentiated megakaryocytes. It would be beneficial to re-define a partially and fully differentiated MK cell model using different cell markers
Epithelial Sodium Channel (ENaC) and the endothelial glycocalyx act synergistically to increase endothelial cell stiffness and downregulate nitric oxide production
No full textBackground:
Endothelial cells are the main source for nitric oxide (NO) production in the vasculature that regulates blood pressure and vascular tone. Studies suggest that the mechanical properties of endothelial cells, characterized by increased stiffness, predicts future cardiovascular events, and is linked with impaired endothelial cell derived NO production. Recent evidence suggests that Epithelial Sodium Channel (ENaC) and the endothelial glycocalyx (eGC) are potential players influencing endothelial cell stiffness (ECS). ENaC consists of four subunits (α, β, γ, and δ). Emerging evidence suggests that ENaC in the vasculature mediates vascular tone and regulates blood pressure. On the other side, the eGC is a carbohydrate rich layer on the luminal surface of endothelial cells. eGC comprises of glycoproteins with carbohydrate side chains and membrane bound proteoglycans with glycosaminoglycans (GAGs) side chains. GAGs like heparan sulfate (HS) and hyaluronic acid (HA) play a major role in NO production. Decreased NO production is linked with increased ECS and this is an important determinant of hypertension and endothelial dysfunction. However, how ENaC and the eGC mediate ECS and this impairs NO production are still poorly understood.
Hypotheses:
1) ENaC and the eGC act synergistically to contribute to increased ECS. 2) Increased F-actin cell cytoskeleton associates with increased ECS. 3) ECS is characterized by decreased NO production.
Methods:
To challenge the hypothesis, protocols were developed to increase and decrease ENaC expression and change the eGC. ENaC expression was increased in response to aldosterone and laminar shear stress (LSS) in human umbilical vein endothelial cells (HUVECs) and mouse myocardial endothelial (MyEnd) cells. Further, ENaC expressions were increased following overexpression of ENaC subunits and decreased following knockdown of ENaC subunits in HUVECs. The increase and decrease in ENaC expressions were detected through Western blot semi-quantitative analysis. On the other hand, the eGC was decreased in response to heparinase III (Hep III) and following knockdown of Hyaluronan synthase 2 (HAS2) and increased following overexpression of HAS2 in HUVECs. The increase and decrease in eGC were confirmed by confocal microscopy. These protocols were then utilized to measure Young’s modulus changes through the Atomic Force Microscopy (AFM). Here, Young’s modulus is an indicator of the mechanical properties of cells and was used to assess ECS. Furthermore, changes in F-actin cytoskeleton were detected through confocal microscopy. Finally, changes in intracellular NO production were detected through fluorescence microscopy.
Results:
Aldosterone (10 nM, 24 hrs) increased α and δ-ENaC (human specific) protein expression in HUVECs, and α-ENaC protein expression in MyEnd cells under static conditions. The result showed that LSS (10 dyn/cm², 24 hrs) alone increases δ-ENaC protein expression in HUVECs, and γ-ENaC protein expression in MyEnd cells. It was also evident that aldosterone increased β-ENaC protein expression in HUVECs, while α and β-ENaC in MyEnd cells in response to aldosterone under LSS. Further, the results indicated that Hep III and knockdown of HAS2 decreased eGC, and overexpression of HAS2 increased eGC. The results also showed that the increased ENaC expression and the degraded eGC were associated with an increased Young's modulus that is an indicator of elevated ECS. The upregulated ENaC expression, degraded eGC, and increased stiffness coincided with increased F-actin in response to aldosterone and Hep III. On the other hand, HAS2 siRNA transfection did not increase F-actin while HAS2 plasmid transfection decreased F-actin expression. Furthermore, the current study demonstrated that increased ECS associates with reduced NO level in response to aldosterone and Hep III, indicating that the cell’s ability to produce NO was decreased in response to aldosterone and Hep III treatment.
Main conclusion:
This dissertation provided evidence that ENaC and the eGC have synergistic effects on ECS. The increased ECS coincides with increased F-actin, and lower NO contents, a hallmark of endothelial dysfunction and hypertension. This study help understands the physiology and pathophysiology of vascular function with new clinical implications for cardiovascular preventive strategies and treatment against increased blood pressure
Type II diabetes mellitus and other chronic conditions impact on self-identity and diabetes self-management practices
No full textGlobally, Type II Diabetes Mellitus (T2DM) is a common chronic disease, which, in recent years, has reached epidemic proportions and shows no sign of slowing. The disease, which is increasingly affecting adolescents, children, and indigenous and ethnic minority groups, is commonly associated with a wide range of serious acute and chronic physiological and psychological health conditions.
T2DM is treatable, but most people fail to maintain glycaemic control as it is highly reliant on their ability to adhere to a daily self-management regimen that is complex and often challenging to maintain. These challenges are usually increased by the influence of other factors, including the effects of other comorbidity and multimorbidity, and needing to simultaneously self-manage conditions. In recent years, a growing body of research has found people’s ability to self-manage T2DM, and other chronic conditions, can also be influenced by the effect the condition has on their self-identity. The aim of this thesis was to gain a greater understanding of how having T2DM and one or more other chronic conditions affect an individual’s self-identity and, in turn, their diabetic self-management practices.
A qualitative narrative research design was chosen. Forty individuals aged 25–65 years, who were diagnosed with poorly controlled T2DM and one or more other chronic health conditions, were recruited from a larger T2DM randomised controlled trial. Single, audio-taped telephone interviews were conducted and transcribed verbatim. Narratives within each transcript were identified, coded and analysed according to Riessman’s (1993, 2008a) thematic narrative analytical framework. The findings were also ‘mapped’ against Kralik, van Loon and Telford’s (2005) four phased conceptual transitional framework to gain a greater understanding of participants’ experiences and the study findings as a whole, and ascertain its clinical applicability for people diagnosed with T2DM and comorbidity or multimorbidity who struggled to maintain glycaemic control.
A collective story emerged, which found that the effect T2DM and comorbidity or multimorbidity had on participants’ self-identity was often profound, lasting and hindered their ability to self-manage T2DM and, at times, other conditions. The collective story plot followed a trajectory that encompassed three key stages that reflected participants’ experiences: a beginning: Life is different: the middle: Implementing prescribed self-management practices; and an end; Looking to the future Within the collective story three main stories were embedded. The first story, ‘The Visibility Level of T2DM,’ described the ways the visibility level of the disease significantly influenced the extent the disease affected participants’ self-identity and, consequently, their ability to self-manage the disease. When the disease was invisible, the threat to self-identity was usually minimal, but made it harder to self-manage the disease. Cultural and societal influences shaped the meanings participants assigned to the condition, which also influenced how they experienced the disease. Their personal coping strategies, the formal and informal support they received, and current or historical unresolved events, also influenced the meanings participants assigned to their condition.
The second story, ‘The Impact of Comorbidity and Multimorbidity,’ described the adverse effects other conditions frequently had on participants’ self-identity and the impact in further impeding their diabetic self-management efforts and, at times, other conditions, often for the same aforementioned reasons. The third story, ‘The Acceptance and Integration of T2DM and The Future,’ described the ways factors enabled or hindered participants to accept the condition. Most participants believed it was important that they accepted it, as it would enable them to self-manage the disease. However, participants who believed they had partially or fully accepted the disease, still struggled to self-manage the disease and maintain glycaemic control. How participants envisaged their future was highly dependent on the extent conditions affected their self-identity and life roles. Lastly, participants’ experiences matched many of the elements found within Kralik et al.’s (2005) framework, namely, health—illness transitions played an important, central role in participants’ lives, and were at the very core of who they were as individuals, and often influenced how they self-managed their diabetic and other condition(s).
This study found evidence that people diagnosed with T2DM may find it to be an intrusive, disruptive event in their lives, which could threaten their self-identity and make it more difficult to adjust to and self-manage the disease. The effect and reasons vary for complex multifactorial reasons. Key reasons include the effect of comorbidity or multimorbidity, the visibility level of conditions, the meanings people assign to each condition, and the support they receive