Publications by authors named "Roger Young"

Multichannel uterine electromyography (uEMG) during pregnancy is traditionally performed with electrocardiography (ECG) sensors. Similar signals are often observed in two or more channels, suggesting the ECG sensors report activities originating from the same location on the uterus. To improve signal source localization, we designed a directional sensor or "Area Sensor".

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Organ-level models are used to describe how cellular and tissue-level contractions coalesce into clinically observable uterine contractions. More importantly, these models provide a framework for evaluating the many different contraction patterns observed in laboring patients, ideally offering insight into the pitfalls of currently available recording modalities and suggesting new directions for improving recording and interpretation of uterine contractions. Early models proposed wave-like propagation of bioelectrical activity as the sole mechanism for recruiting the myometrium to participate in the contraction and increase contraction strength.

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The intracellular signaling pathways that regulate myometrial contractions can be targeted by drugs for tocolysis. The agents, 2-APB, glycyl-H-1152, and HC-067047, have been identified as inhibitors of uterine contractility and may have tocolytic potential. However, the contraction-blocking potency of these novel tocolytics was yet to be comprehensively assessed and compared to agents that have seen greater scrutiny, such as the phosphodiesterase inhibitors, aminophylline and rolipram, or the clinically used tocolytics, nifedipine and indomethacin.

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Background: Preterm birth is the largest single cause of infant death in the United States. A cervical length of <2.5 cm, measured in the mid-trimester, has been shown to identify individuals at increased risk.

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Progesterone (P4) and cyclic adenosine monophosphate (cAMP) are regarded as pro-quiescent factors that suppress uterine contractions during pregnancy. We previously used human primary cells in vitro and mice in vivo to demonstrate that simultaneously enhancing myometrial P4 and cAMP levels may reduce inflammation-associated preterm labor. Here, we assessed whether aminophylline (Ami; phosphodiesterase inhibitor) and P4 can reduce myometrial contractility and contraction-associated proteins (CAPs) better together than individually; both agents are clinically used drugs.

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Despite several decades of encouraging land management actions to improve water quality on rural land, we are still struggling to accurately quantify what management actions have been implemented, where these actions have been used and the intensity of implementation. This is largely because standardised approaches to recording and reporting of land management actions have not been established, resulting in a lack of robust information that can be used to determine the effectiveness and longevity of these actions at a catchment or larger scale. Better information on the effectiveness of different land management actions will provide land managers with more certainty that their investments in land management actions will make a difference.

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The uterine pacemaker of labor.

Best Pract Res Clin Obstet Gynaecol

October 2018

The laboring uterus is generally thought to initiate contractions much similar to the heart, with a single, dedicated pacemaker. Research on human and animal models over decades has failed to identify such pacemaker. On the contrary, data indicate that instead of being fixed at a site similar to the sinoatrial node of the heart, the initiation site for each uterine contraction changes during time, often with each contraction.

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Effective ecosystem management requires a robust methodology to analyse, remedy and avoid ecosystem damage. Here we propose that the overall conceptual framework and approaches developed over millennia in medical science and practice to diagnose, cure and prevent disease can provide an excellent template. Key principles to adopt include combining well-established assessment methods with new analytical techniques and restricting both diagnosis and treatment to qualified personnel at various levels of specialization, in addition to striving for a better mechanistic understanding of ecosystem structure and functioning, as well as identifying the proximate and ultimate causes of ecosystem impairment.

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The setting of numeric instream objectives (effects-based criteria) and catchment limits for major agricultural stressors, such as nutrients and fine sediment, is a promising policy instrument to prevent or reduce degradation of stream ecosystem health. We explored the suitability of assemblage thresholds, defined as a point at which a small increase in a stressor will result in a disproportionally large change in assemblage structure relative to other points across the stressor gradient, to inform instream nutrient and sediment objectives. Identification and comparison of thresholds for macroinvertebrate, periphyton, and bacterial assemblages aimed at making the setting of objectives more robust and may further provide a better understanding of the underlying mechanisms of nutrient and fine sediment effects.

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Research insights into uterine function and the mechanisms of labour have been hindered by the lack of suitable animal and cellular models. The use of traditional culturing methods limits the exploration of complex uterine functions, such as cell interactions, connectivity and contractile behaviour, as it fails to mimic the three-dimensional (3D) nature of uterine cell interactions in vivo. Animal models are an option, however, use of these models is constrained by ethical considerations as well as translational limitations to humans.

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This review presents evolving concepts of how the human uterus contracts in pregnancy, with emphasis on the mechanisms of long-distance signaling. Action potential propagation has historically been assumed to be the sole mechanism for signaling and tissue recruitment over both short and long distances. However, data in animals and humans indicate that a single action potential does not travel distances greater than a few centimeters.

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Benthic proliferations of the cyanobacteria Phormidium can cover many kilometres of riverbed. Phormidium can produce neurotoxic anatoxins and ingestion of benthic mats has resulted in numerous animal poisonings in the last decade. Despite this, there is a poor understanding of the environmental factors regulating growth and anatoxin production.

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Objective: Uterine overdistention is thought to induce preterm labor in women with twin and multiple pregnancies, but the pathophysiology remains unclear. We investigated for the first time the pathogenesis of preterm birth associated with rapid uterine distention in a pregnant nonhuman primate model.

Study Design: A nonhuman primate model of uterine overdistention was created using preterm chronically catheterized pregnant pigtail macaques (Macaca nemestrina) by inflation of intraamniotic balloons (N = 6), which were compared to saline controls (N = 5).

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The human uterus has no pacemaker or motor innervation, yet develops rhythmic, powerful contractions that increase intrauterine pressure to dilate the cervix and force the fetus through the pelvis. To achieve the synchronous contractions required for labor, the muscle cells of the uterus act as independent oscillators that become increasingly coupled by gap junctions toward the end of pregnancy. The oscillations are facilitated by changes in resting membrane potential that occur as pregnancy progresses.

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The mechanisms used to coordinate organ-level contractions of human labor are not universally accepted. We previously proposed a dual mechanism, where electrical activity coordinates cellular contractions into tissue-level regional contractions, and mechanotransduction synchronizes the regional contractions into organ-level contractions. The simulation of this model successfully recapitulates the phasic pressure rises typical of human labor.

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Anatoxins are powerful neuromuscular blocking agents produced by some cyanobacteria. Consumption of anatoxin-producing cyanobacterial mats or the water containing them has been linked to numerous animal poisonings and fatalities worldwide. Despite this health risk, there is a poor understanding of the environmental factors regulating anatoxin production.

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The mechanisms used to coordinate uterine contractions are not known. We develop a new model based on the proposal that there is a maximum distance to which action potentials can propagate in the uterine wall. This establishes "regions", where one action potential burst can rapidly recruit all the tissue.

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K-sensitive microelectrodes were used to measure K(+) within the extracellular space (K(o)) of pregnant rat myometrium. Contractile activity was monitored by measuring either force or bioelectrical signals. Single and double-barreled electrodes were used.

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Neo-myometrium was created by culturing isolated myocytes into decellularized rat and human myometrial scaffolds. The dual purpose of the uterus is to accommodate the growing fetus, and then expel the fetus at term by phasically contracting it. The first function requires physical robustness as well as the ability to expand and remodel.

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Synechocystis sp. strain PCC 6803 grows photoautotrophically across a broad pH range, but wild-type cultures reach a higher density at elevated pH; however, photoheterotrophic growth is similar at high and neutral pH. A number of PSII mutants each lacking at least one lumenal extrinsic protein, and carrying a second PSII lumenal mutation, are able to grow photoautotrophically in BG-11 medium at pH 10.

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