List of Titles

Automated segmentation of mouse OCT volumes (ASiMOV): Validation & clinical study of a light damage model

- Antony, Bhavna, Kim, Byung-Jin, Lang, Andrew, Carass, Aaron, Prince, Jerry, Zack, Donald

Authors: Antony, Bhavna , Kim, Byung-Jin , Lang, Andrew , Carass, Aaron , Prince, Jerry , Zack, Donald
Date: 2017
Type: Text , Journal article
Relation: PLoS One Vol. 12, no. 8 (2017), p. e0181059-e0181059
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Description: The use of spectral-domain optical coherence tomography (SD-OCT) is becoming commonplace for the in vivo longitudinal study of murine models of ophthalmic disease. Longitudinal studies, however, generate large quantities of data, the manual analysis of which is very challenging due to the time-consuming nature of generating delineations. Thus, it is of importance that automated algorithms be developed to facilitate accurate and timely analysis of these large datasets. Furthermore, as the models target a variety of diseases, the associated structural changes can also be extremely disparate. For instance, in the light damage (LD) model, which is frequently used to study photoreceptor degeneration, the outer retina appears dramatically different from the normal retina. To address these concerns, we have developed a flexible graph-based algorithm for the automated segmentation of mouse OCT volumes (ASiMOV). This approach incorporates a machine-learning component that can be easily trained for different disease models. To validate ASiMOV, the automated results were compared to manual delineations obtained from three raters on healthy and BALB/cJ mice post LD. It was also used to study a longitudinal LD model, where five control and five LD mice were imaged at four timepoints post LD. The total retinal thickness and the outer retina (comprising the outer nuclear layer, and inner and outer segments of the photoreceptors) were unchanged the day after the LD, but subsequently thinned significantly (p < 0.01). The retinal nerve fiber-ganglion cell complex and the inner plexiform layers, however, remained unchanged for the duration of the study.

Testing the NKT cell hypothesis in lenalidomide-treated myelodysplastic syndrome patients

- Chan, Angela, Neeson, Paul, Leeansyah, Edwin, Tainton, K., Quach, Hang, Prince, Henry, Godfrey, Dale, Ritchie, David, Berzins, Stuart

Authors: Chan, Angela , Neeson, Paul , Leeansyah, Edwin , Tainton, K. , Quach, Hang , Prince, Henry , Godfrey, Dale , Ritchie, David , Berzins, Stuart
Date: 2010
Type: Text , Journal article
Relation: Leukemia Vol. 24, no. 3 (2010), p. 592-600
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Description: Myelodysplastic syndrome (MDS) comprises a group of clonal bone marrow disorders characterized by ineffective hematopoiesis and increased predisposition to acute myeloid leukemia. The causes of MDS remain poorly defined, but several studies have reported the NKT cell compartment of patients with MDS is deficient in number and functionally defective. In support of a central role for NKT cells, a pilot clinical study reported that lenalidomide (an approved treatment for MDS) increased NKT cell numbers in patients with MDS, and several in vitro studies showed lenalidomide specifically promoted NKT cell proliferation and cytokine production. We tested this in a much larger study and confirm a moderate in vitro augmentation of some NKT cell functions by lenalidomide, but find no impact on the NKT cell compartment of patients treated with lenalidomide, despite a consistently positive clinical response. We further show that the frequency and cytokine production of NKT cells is normal in patients with MDS before treatment and remains stable throughout 10 months of lenalidomide therapy. Collectively, our data challenge the concept that NKT cell defects contribute to the development of MDS, and show that a clinical response to lenalidomide is not dependent on modulation of NKT cell frequency or function. © 2010 Macmillan Publishers Limited All rights reserved.

Breastfeeding, antidepressants, and depression in the mercy pregnancy and emotional well-being study

- Galbally, Megan, Watson, Stuart, Ball, Helen, Lewis, Andrew

Authors: Galbally, Megan , Watson, Stuart , Ball, Helen , Lewis, Andrew
Date: 2019
Type: Text , Journal article
Relation: Journal of Human Lactation Vol. 35, no. 1 (2019), p. 127-136
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Description: Background: Depression is consistently shown to predict lower rates of breastfeeding. In a handful of studies, breastfeeding has predicted lower depression symptoms. However, studies demonstrating the latter are limited in their measurement of both depression and breastfeeding and have not followed participants from pregnancy across the postpartum period. Research Aim: The primary aim of this study was to describe breastfeeding intentions and behaviors for the first 12 months postpartum among nonmedicated depressed, antidepressant-exposed, and control participants. The secondary aim was to examine group differences in the association between depressive symptoms and breastfeeding duration up to 12 months postpartum. Methods: First-trimester women (N = 212) were recruited into a prospective longitudinal study. Depressive disorders at baseline were diagnosed using the Structured Clinical Interview for DSM-IV Axis I Disorders, and depressive symptoms were measured at the first and second trimesters and 6 and 12 months postpartum using the Edinburgh Postnatal Depression Scale. Breastfeeding duration, support from family and employers, and perceptions of participants’ experience were measured. Results: Depressed women and antidepressant-exposed women reported a trend toward lower rates of intention, initiation, and duration, but this did not reach statistical significance. There was a statistically significant difference on depressive symptoms for women taking antidepressants during pregnancy, compared with controls, when they continued to breastfeed for 12 months postpartum. Conclusions: This study did not find a strong association between depression or antidepressant use and intention to breastfeed, partner breastfeeding support, or initiation or duration of breastfeeding. However, for women who took antidepressants, there was evidence that breastfeeding for 12 months was associated with lower depressive symptoms.

Telomere therapy for chronic kidney disease

- Akinnibosun, Olutope, Maier, Michelle, Eales, James, Tomaszewski, Maciej, Charchar, Fadi

Authors: Akinnibosun, Olutope , Maier, Michelle , Eales, James , Tomaszewski, Maciej , Charchar, Fadi
Date: 2022
Type: Text , Journal article
Relation: Epigenomics Vol. 14, no. 17 (2022), p. 1039-1054
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Description: Chronic kidney disease (CKD) is estimated to affect almost 10% of individuals worldwide and is one of the leading causes of morbidity and mortality. Renal fibrosis, a central pathway in CKD progression (irrespective of etiology), is associated with shortened or dysfunctional telomeres in animal studies. Telomeres are specialized nucleoprotein structures located at the chromosome end that maintain genomic integrity. The mechanisms of associations between telomere length and CKD have not yet been fully elucidated, however, CKD patients with shorter telomere length may have decreased renal function and a higher mortality rate. A plethora of ongoing research has focused on possible therapeutic applications of telomeres with the overall goal to preserve telomere length as a therapy to treat CKD. Chronic kidney disease or CKD is one of the leading causes of illness and death worldwide. Scarring of the kidney tissue that occurs in CKD has been associated with shorter telomeres in studies using rats. Telomeres, said to act as the cellular ‘shoelace caps’, maintain the structure of chromosomes, allowing for genetic material inside cells to divide correctly. The length of telomeres (TL) is influenced by diverse factors such as genetics and lifestyle. The underlying processes for the associations between TL and CKD are still not understood, however, patients with CKD and shorter TL have reduced kidney function and an increased death rate. Therefore, research is focused on possible ways to preserve TL and treat CKD. Preserving telomere length may reduce rates of chronic kidney disease, thereby decreasing morbidity & mortality worldwide.

The role of glucocorticoid and mineralocorticoid receptor DNA methylation in antenatal depression and infant stress regulation

- Galbally, Megan, Watson, Stuart, van Ijzendoorn, Marinus, Saffery, Richard, Ryan, Joanne, de Kloet, Edo, Oberlander, Tim, Lappas, Martha, Lewis, Andrew

Authors: Galbally, Megan , Watson, Stuart , van Ijzendoorn, Marinus , Saffery, Richard , Ryan, Joanne , de Kloet, Edo , Oberlander, Tim , Lappas, Martha , Lewis, Andrew
Date: 2020
Type: Text , Journal article
Relation: Psychoneuroendocrinology Vol. 115, no. (2020), p. 104611
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Description: •Maternal depression is associated with lower infant cortisol reactivity.•Early pregnancy depression is associated with reduced placental NR3C2 DNA methylation.•No association of maternal depression and cortisol with placental or infant buccal NR3C1 DNA methylation.•No association of antidepressant use with cortisol and placental or infant buccal NR3C1 and NR3C2 DNA methylation.•Association between infant cortisol reactivity and maternal depression was suppressed by placental NR3C2 DNA methylation. Understanding fetal programming pathways that underpin the relationship between maternal and offspring mental health necessitates an exploration of potential role of epigenetic variation in early development. Two genes involved in stress response regulation, the glucocorticoid and mineralocorticoid receptors (NR3C1 and NR3C2) have been a focus in understanding stressful exposures and mental health outcomes. Data were obtained from 236 pregnant women from the Mercy Pregnancy Emotional Wellbeing Study (MPEWS), a selected pregnancy cohort, recruited in early pregnancy. Depression was measured using the Structured Clinical Interview for DSM-IV (SCID-IV) and repeated measures of the Edinburgh Postnatal Depression Scale (EPDS). Antidepressant use, stressful events and anxiety symptoms were measured. NR3C1 and NR3C2 DNA methylation was measured in placental and infant buccal samples. Infant cortisol was measured in repeat saliva samples across a task. This study found maternal early pregnancy depressive disorder and symptoms were associated with lower DNA methylation at NR3C2 CpG_24 in placental tissue. There were no significant differences for depression or antidepressant use for DNA methylation of NR3C1. Antenatal depression was associated with lower infant cortisol reactivity at 12 months. DNA methylation in CpG_24 site in NR3C2 in placental samples suppressed the relationship between early maternal depressive symptoms and infant cortisol reactivity. These findings show a relationship between antenatal depression, NR3C2 DNA methylation and infant cortisol response providing support for a specific fetal programming pathway. Further research is required to examine the stability of this epigenetic mark across childhood and long-term mental health outcomes.

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