77 research outputs found
Is interpregnancy interval associated with cardiovascular risk factors in later life? A cohort study
No full textPublished 19 March 2014Objectives: Pregnancy represents a metabolic challenge to women; in a normal pregnancy, transient metabolic changes occur that support the needs of the growing fetus. It is possible that repeating this challenge within a relatively short amount of time may result in lasting damage to the woman's cardiovascular health. Conversely, it is also possible that a long interpregnancy interval (IPI) may reflect subfertility, which has been found to be associated with cardiovascular disease (CVD). We examine the associations of short and long IPI with measures of cardiovascular health. Design: Prospective cohort. Setting: Mothers of the Avon Longitudinal Study of Parents and Children (ALSPAC). Participants: Women with two live births in order to control for confounding by parity. Outcome measures: Arterial distensibility, common carotid intima, adiposity, blood pressure, lipids, glucose, insulin, proinsulin, triglycerides, C reactive protein. Results: 25% (n=3451) of ALSPAC mothers had provided sufficient data to determine full reproductive history—of these, 1477 had two live births, with 54% mothers having non-missing data on all variables required for our analyses. A total of 1268 mothers with IPI (interbirth interval minus 9 months’ gestation) had CVD risk factors measured/imputed at mean age 48 years. After adjusting for confounding, we found no association of either short (≤15 months) or long (>27 months) IPI and increased levels of cardiovascular risk factors. There was some suggestion that women with long and short IPIs had a more favourable lipid profile compared with women whose IPI was 16–27 months; however, the differences were small in magnitude and imprecisely estimated. Conclusions: This study does not support the hypothesis that either long or short IPI is a risk factor for later cardiovascular health.Duleeka W Knipe, Abigail Fraser, Debbie A Lawlor, Laura D How
Differential cargo mobilisation within Weibel-Palade bodies after transient fusion with the plasma membrane.
No full textInflammatory chemokines can be selectively released from Weibel-Palade bodies (WPBs) during kiss-and-run exocytosis. Such selectivity may arise from molecular size filtering by the fusion pore, however differential intra-WPB cargo re-mobilisation following fusion-induced structural changes within the WPB may also contribute to this process. To determine whether WPB cargo molecules are differentially re-mobilised, we applied FRAP to residual post-fusion WPB structures formed after transient exocytosis in which some or all of the fluorescent cargo was retained. Transient fusion resulted in WPB collapse from a rod to a spheroid shape accompanied by substantial swelling (>2 times by surface area) and membrane mixing between the WPB and plasma membranes. Post-fusion WPBs supported cumulative WPB exocytosis. To quantify diffusion inside rounded organelles we developed a method of FRAP analysis based on image moments. FRAP analysis showed that von Willebrand factor-EGFP (VWF-EGFP) and the VWF-propolypeptide-EGFP (Pro-EGFP) were immobile in post-fusion WPBs. Because Eotaxin-3-EGFP and ssEGFP (small soluble cargo proteins) were largely depleted from post-fusion WPBs, we studied these molecules in cells preincubated in the weak base NH4Cl which caused WPB alkalinisation and rounding similar to that produced by plasma membrane fusion. In these cells we found a dramatic increase in mobilities of Eotaxin-3-EGFP and ssEGFP that exceeded the resolution of our method (∼ 2.4 µm2/s mean). In contrast, the membrane mobilities of EGFP-CD63 and EGFP-Rab27A in post-fusion WPBs were unchanged, while P-selectin-EGFP acquired mobility. Our data suggest that selective re-mobilisation of chemokines during transient fusion contributes to selective chemokine secretion during transient WPB exocytosis. Selective secretion provides a mechanism to regulate intravascular inflammatory processes with reduced risk of thrombosis
The association between socioeconomic position and depression or suicidal ideation in low- and middle-income countries in Southeast Asia:a systematic review and meta-analysis
No full textBackgroundMental illnesses contribute to a significant burden of disease in low- and middle- income countries (LMICs). Understanding risk factors for poor mental health is essential to reducing the burden, and for preventative measures to be implemented. The role of socioeconomic position (SEP) in poorer mental health is well established in high income countries, but less is known in LMICs. This study aimed to identify and synthesise epidemiological evidence for the associations between SEP and depression and suicidal ideation in LMICs in Southeast Asia, and to describe the strength and direction of any associations identified. MethodsThis systematic review identified evidence by searching four databases in February 2023 (Medline, Embase, PsycInfo and Web of Science), grey literature and reference searching of included papers. Papers were included if they were based in a Southeast Asian LMIC general or hospital populations (≥16 years of age) and explored at least one measure of SEP in association with depression or suicidal ideation. Study quality was assessed using the Joanna Briggs Institute tool. A meta-analysis and narrative synthesis were performed. ResultsFifty-nine papers from six out of nine Southeast Asian LMICs were identified, with education the most commonly examined measure of SEP. Several papers explored more than one measure of SEP. Around half of the papers were rated as higher quality. Meta-analyses of education (OR: 1.87, 95% CI: 1.49-2.35) and working status (OR: 1.30, 95% CI: 0.99-1.71) provided evidence of lower levels of education and not being employed being associated with higher odds of depression. Consistent associations between lower SEP and higher odds of depression were also found for financial difficulty and subjective economic status. Three papers used suicidal ideation as their outcome, and there was some evidence of an association with lower SEP and higher ideation.ConclusionsEvidence indicates that lower SEP is associated with higher likelihood of depression, whereas for suicidal ideation, the evidence available is insufficient to reach a conclusion. The lack of longitudinal studies prevents the temporal nature of these associations being established. Systematic review registration: PROSPERO: CRD42023410444<br/
Temperature-Dependence of Weibel-Palade Body Exocytosis and Cell Surface Dispersal of von Willebrand Factor and Its Propolypeptide
No full textBackground: Weibel-Palade bodies (WPB) are endothelial cell (EC) specific secretory organelles containing Von Willebrand factor (VWF). The temperature-dependence of Ca2+-driven WPB exocytosis is not known, although indirect evidence suggests that WPB exocytosis may occur at very low temperatures. Here we quantitatively analyse the temperature-dependence of Ca2+-driven WPB exocytosis and release of secreted VWF from the cell surface of ECs using fluorescence microscopy of cultured human ECs containing fluorescent WPBs.
Principal Findings: Ca2+-driven WPB exocytosis occurred at all temperatures studied (7–37°C). The kinetics and extent of WPB exocytosis were strongly temperature-dependent: Delays in exocytosis increased from 0.92 s at 37°C to 134.2 s at 7°C, the maximum rate of WPB fusion decreased from 10.0±2.2 s−1 (37°C) to 0.80±0.14 s−1 (7°C) and the fractional extent of degranulation of WPBs in each cell from 67±3% (37°C) to 3.6±1.3% (7°C). A discrepancy was found between the reduction in Ca2+-driven VWF secretion and WPB exocytosis at reduced temperature; at 17°C VWF secretion was reduced by 95% but WPB exocytosis by 75–80%. This discrepancy arises because VWF dispersal from sites of WPB exocytosis is largely prevented at low temperature. In contrast VWF-propolypeptide (proregion) dispersal from WPBs, although slowed, was complete within 60–120 s. Novel antibodies to the cleaved and processed proregion were characterised and used to show that secreted proregion more accurately reports the secretion of WPBs at sub-physiological temperatures than assay of VWF itself.
Conclusions : We report the first quantitative analysis of the temperature-dependence of WPB exocytosis. We provide evidence; by comparison of biochemical data for VWF or proregion secretion with direct analysis of WPB exocytosis at reduced temperature, that proregion is a more reliable marker for WPB exocytosis at reduced temperature, where VWF-EC adhesion is increased
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Multi-responsive microencapsulated nanogels for the oral delivery of small interfering RNA
No full textMulti-responsive, anionic poly(methacrylic acid-co-N-vinyl-2-pyrrolidone) microscale hydrogels (microgels) encapsulating polycationic nanoscale hydrogels (nanogels) were synthesized with either degradable or nondegradable crosslinks. The pH-responsive volume phase transition of these formulations was consistent with the pH transition experienced during intestinal delivery, as the hydrogels swelled at pH values greater than pH 5. The physicochemical characteristics of the nondegradable formulations were evaluated by microscopy, potentiometric titration, Fourier transform infrared spectroscopy, and thermal gravimetric analysis. The nondegradable formulations successfully loaded and released a model protein in physiological buffers, but the ability of the microgels to release the nanogels upon exposure to intestinal conditions was inadequate. Therefore, microgels containing enzyme-degradable oligopeptide crosslinks were synthesized then characterized using Fourier transform infrared spectroscopy, electron microscopy, confocal microscopy, and ImageStream flow cytometry. Degradation of the microgels upon incubation in trypsin solutions, simulated gastric fluid, or simulated intestinal fluid was evaluated by measuring the change in relative turbidity over time. Microgels were degraded specifically by the enzyme trypsin, and the rate of degradation was dependent upon the microgel to trypsin concentration ratio; for all ratios tested, degradation was complete within 4 hours. The cytocompatibility of the enzyme-degraded microgels encapsulating nanogels was evaluated in both a human and a murine cell line; at microgel concentrations less than 0.4 mg/ml the cell viability was greater than 90%. Confocal microscopy was used to obtain Z-stack images of the cells following incubation with the microgels, confirming that nanogels were released from the degraded microgels and subsequently inteRNAlized by RAW 264.7 murine macrophage cells. The microencapsulated nanogels were able to load siRNA via electrostatic complexation with loading efficiencies ranging from 60-80%. Incubation of loaded microgels in simulated intestinal fluid with reduced trypsin concentrations or in rat intestinal fluid resulted in successful degradation of the microgel matrix and release of a detectable amount of viable siRNA. The degraded microgels with nanogels transfected the two different cell lines with up to 20% silencing efficiency. Though the knockdown efficiency is not as high as that of nanogels alone, the microgel results are consistent and reproducible across two cell lines.Chemical Engineerin
The Critical Need for Critical Consciousness: Exploring Challenges and Cultivating Effective Pedagogy
No full textThis banded dissertation examines the challenges and barriers inherent to the complex process of critical consciousness development in undergraduate social work students. The research explores teaching methods and other suggestions for overcoming these obstacles. The assumptions used to guide this research stem from the Critical Consciousness Conceptual Model created by Pitner and Sakamoto (2016, 2005), which is based on Paulo Freire’s concept of conscientização.
The first product of this banded dissertation is a conceptual article that presents problemposing education as a prime teaching method to facilitate consciousness raising. Problem-posing education is a liberatory method that counters the standard banking model of education that sees students as “empty vessels” and professors as experts. The author argues that educators can maximize engagement of undergraduate students in consciousness raising by utilizing the Critical Consciousness Conceptual Model to guide implementation of problem-posing education.
The second scholarly product is a qualitative phenomenological inquiry that explores how undergraduate social work instructors experience obstacles in facilitating consciousness raising in students, as well as methods to overcome these obstacles. Key discoveries include affective challenges, challenges and barriers due to socialization, challenges of perception, educational barriers, and group identity. Identified methods of promoting consciousness raising include use of self-reflection, encouraging students to “do their own work”, modeling, and vulnerability.
The final product in the banded dissertation is a personal narrative reflection. In this reflection, the author describes the process of critical consciousness development and its importance for educators, highlighting particular points of emphasis in her own journey of consciousness raising. The author also reflects on how this journey has influenced her evolving teaching pedagogy.
This research provides practical support for instructors facilitating consciousness raising in their students. Results are unique and important for three reasons. First, weighing educator perception of obstacles to consciousness raising addresses a large gap in the literature, as most existing literature focuses on student perception. Second, it provides practical classroom approaches for success in facilitating this complex process. Third, it provides a model for the kind of critical reflection and vulnerability that consciousness raising requires
Artist in the making
No full textThis thesis was scanned from the print manuscript for digital preservation and is copyright the author.
Researchers can access this thesis by asking their local university, institution or public library to
make a request on their behalf. Monash staff and postgraduate students can use the link in the References field
"different sentiments & different connections supports them" : sensibility, community, and diversity in British women's Romantic-period poetry
No full textWith diversity
as an overarching theme, women writers' responses to the
cultural
feminisation and developing social climate of
late eighteenth- and early
nineteenth-century Britain
are explored through analyses of their poems on
sensibility, community, and abolition.
To determine a
focus for
expressive criticism
and recover Romantic women writers
from the social and historical
contexts that have
previously succeeded in highlighting
male literary
achievements, women's poetry is
considered a distinct
contribution to Romanticism. This dissertation analyses poems
written
by Joanna Baillie, Anna Barbauld, Harriet
and Maria Falconar, Frances
Greensted, Frances Greville, Elizabeth Hands, Eliza Knipe, Isabella Lickbarrow,
Hannah More, Amelia Opie, Priscilla Pointon, Mary Robinson, Mary Scott, Helen
Maria Williams, Ann Yearsley, and Mary Julia Young.
Although literature brought together the public and private spheres, sensibility
mediated
between the two and served as a social currency
for
women.
The
various
applications of sensibility are apparent
in its dual-gendered nature,
its link
with
reason, and the significance of economic
language. A
new genre of the "Address to
Sensibility" was prominent
in the period and
followed
a
loose formula
which
defined
sensibility,
traced its
personal
impact,
and
determined
a
link between the Romantic
culture and
heightened
emotion.
Through
explorations of poems on
intellectual
coteries, patronage, creative
influence, Reviews, and
literary
critique,
it is
evident that women poets' affiliations
with the literary
community were marked
by
a
discomfort based on their literary
associations,
the anxiety about their public reception, and the social
differences in the
literary
community.
However, the development
of social,
intellectual, literary,
and
critical communities alleviated this discomfort
and contributed
to women's
participation
in literary
culture.
In
addition, women poets expressed sensibility and used images of community
in diverse ways in their works against slavery and the trade.
Abolitionist
poetry acts
as a case study of the particular motifs,
highlighted throughout, such as the
amalgamation of masculine and
feminine, the political and economic applications of
sensibility, the association of
feeling
with reason and community, and the assertion of
individuality
amidst commonality.
Women
poets' petitions
to alleviate the sufferings
of slaves paralleled arguments
for the improvement
of
British
society to benefit
women.
The poems discussed signify the complexity of the issues of sensibility,
community, and diversity
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