ORCID Profile
0000-0002-9585-4951
Current Organisations
University of South Australia
,
Max Planck Institute for Molecular Genetics
,
Gulf College
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Publisher: Springer Science and Business Media LLC
Date: 16-03-2022
DOI: 10.1007/S00421-022-04931-5
Abstract: Exercise improves measures of cardiovascular (CV) health and function. But as traditional measures improve gradually, it can be difficult to identify the effectiveness of an exercise intervention in the short-term. Left ventricular global longitudinal strain (LVGLS) is a highly sensitive CV imaging measure that detects signs of myocardial dysfunction prior to more traditional measures, with reductions in LVGLS a strong prognostic indicator of future CV dysfunction and mortality. Due to its sensitivity, LVGLS may offer useful method of tracking the effectiveness of an exercise intervention on CV function in the short-term, providing practitioners useful information to improve patient care in exercise settings. However, the effect of exercise on LVGLS is unclear. This systematic review and meta-analysis aimed to determine the effect exercise has on LVGLS across a range of populations. Included studies assessed LVGLS pre–post an exercise intervention (minimum 2 weeks) in adults 18 years and over, and were published in English from 2000 onwards. Study-level random-effects meta-analyses were performed using Stata (v16.1) to calculate summary standardized mean differences (SMD) and 95% confidence intervals (CI). 39 studies met selection criteria, with 35 included in meta-analyses (1765 participants). In primary analyses, a significant improvement in LVGLS was observed in populations with CV disease (SMD = 0.59 95% CI 0.16–1.02 p = 0.01), however, no significant effect of exercise was observed in CV risk factor and healthy populations. In populations with CV disease, LVGLS could be used as an early biomarker to determine the effectiveness of an exercise regime before changes in other clinical measures are observed.
Publisher: Elsevier BV
Date: 10-2023
Publisher: Elsevier BV
Date: 07-2022
Publisher: ACM
Date: 30-10-2023
Publisher: Springer Science and Business Media LLC
Date: 16-04-2021
DOI: 10.1186/S13059-021-02321-2
Abstract: X-chromosomal genes contribute to sex differences, in particular during early development, when both X chromosomes are active in females. Double X-dosage shifts female pluripotent cells towards the naive stem cell state by increasing pluripotency factor expression, inhibiting the differentiation-promoting MAP kinase (MAPK) signaling pathway, and delaying differentiation. To identify the genetic basis of these sex differences, we use a two-step CRISPR screening approach to comprehensively identify X-linked genes that cause the female pluripotency phenotype in murine embryonic stem cells. A primary chromosome-wide CRISPR knockout screen and three secondary screens assaying for different aspects of the female pluripotency phenotype allow us to uncover multiple genes that act in concert and to disentangle their relative roles. Among them, we identify Dusp9 and Klhl13 as two central players. While Dusp9 mainly affects MAPK pathway intermediates, Klhl13 promotes pluripotency factor expression and delays differentiation, with both factors jointly repressing MAPK target gene expression. Here, we elucidate the mechanisms that drive sex-induced differences in pluripotent cells and our approach serves as a blueprint to discover the genetic basis of the phenotypic consequences of other chromosomal effects.
Publisher: Informa UK Limited
Date: 11-2021
Publisher: Oxford University Press (OUP)
Date: 09-03-2022
Abstract: Breast cancer (BC) patients undergoing chemotherapy are at risk of developing cancer therapy-related cardiac dysfunction (CTRCD). Exercise has been proposed to prevent CTRCD however, its effectiveness remains unclear. The aim of this systematic review was to establish the effect of exercise on global longitudinal strain (GLS) and left ventricular ejection fraction (LVEF) in BC patients undergoing chemotherapy, to determine if exercise can prevent the development of CTRCD. Four databases (Medline, Scopus, eMbase, SPORTDiscus) were searched. Studies were eligible for inclusion if they measured GLS or LVEF prior to and following an exercise intervention of any length in BC patients undergoing chemotherapy and were published in English from 2000 onwards. Risk of bias was evaluated using the QUADAS-2 tool. Of the 398 studies screened, eight were eligible. Changes were similar in exercising (EX) and non-exercising (CON) groups for GLS (EX: pre: −19.6 ± 0.4, post: −20.1 ± 1.0, CON: pre: −20.0 ± 0.4, post: −20.1 ± 1) and LVEF (EX: pre: 58.5 ± 4.1%, post: 58.6 ± 2%, CON: pre: 56.6 ± 4.2%, post: 55.6 ± 4.6%). Exercise maintained or improved peak oxygen uptake (VO2peak) during chemotherapy, while declines were observed in non-exercising groups. The included studies were limited by methodological deficiencies. The ability of exercise to prevent CTRCD is unclear. However, exercise positively impacts cardiorespiratory fitness in BC patients undergoing chemotherapy. Future research must address the methodological limitations of current research to understand the true effect of exercise in the prevention of CTRCD.
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for James Murray.