Publications by authors named "Plummer N"

Background: Identifying women at highest or lowest risk of perinatal intensive care unit (ICU) admission may enable clinicians to risk stratify women antenatally so that enhanced care or elective admission to ICU may be considered or excluded in birthing plans. We aimed to develop a statistical model to predict the risk of maternal ICU admission.

Methods: We studied 762,918 pregnancies between 2005 and 2018.

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Article Synopsis
  • Researchers used genetically engineered mice and cell lines to study how the depletion of endoplasmic reticulum (ER) calcium stores activates specific calcium entry channels (SOCE) that primarily rely on Orai1 molecules.
  • They discovered that Orai1 is the dominant calcium entry pathway compared to Orai2 and Orai3, and this process does not require functional TRPC molecules, as shown by experiments using cells with inactive TRPC genes.
  • The study also found that even though the TRPC genes were disrupted, both store-depletion-activated calcium entry and receptor-operated calcium entry (ROCE) still relied on Orai1, leading to the establishment of a new strain of mice called TRPC heptaKO mice, which are
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CO exposure has been used to investigate the panicogenic response in patients with panic disorder. These patients are more sensitive to CO, and more likely to experience the "false suffocation alarm" which triggers panic attacks. Imbalances in locus coeruleus noradrenergic (LC-NA) neurotransmission are responsible for psychiatric disorders, including panic disorder.

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Purpose: Factors increasing the risk of maternal critical illness are rising in prevalence in maternity populations. Studies of general critical care populations highlight that severe illness is associated with longer-term physical and psychological morbidity. We aimed to compare short- and longer-term outcomes between women who required critical care admission during pregnancy/puerperium and those who did not.

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HAND2 is a basic helix-loop-helix transcription factor with diverse functions during development. To facilitate the investigation of genetic and functional diversity among Hand2-expressing cells in the mouse, we have generated Hand2, a knock-in allele expressing Dre recombinase. To avoid disrupting Hand2 function, the Dre cDNA is inserted at the 3' end of the Hand2 coding sequence following a viral 2A peptide.

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Background: Contextual fear learning is heavily dependent on the hippocampus. Despite evidence that catecholamines contribute to contextual encoding and memory retrieval, the precise temporal dynamics of their release in the hippocampus during behavior is unknown. In addition, new animal models are required to probe the effects of altered catecholamine synthesis on release dynamics and contextual learning.

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Jails and prisons in the United States house people with elevated rates of mental health and substance use disorders. The goal of this cross-sectional study was to evaluate the frequency of racial/ethnic differences in the self-report of mental illness and psychiatric medication use at jail entry. Our sample included individuals who had been incarcerated between 2016 and 2020 at the Middlesex Jail & House of Correction, located in Billerica, MA.

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Purpose: To compare the prediction accuracy of the Argos biometer using standard keratometry to the prediction accuracy of the IOLMaster 700 biometer using Total Keratometry.

Methods: This was a randomized, prospective, single surgeon study of 80 right eyes of 80 patients that had preoperative biometry with both the Argos and IOLMaster 700 devices, followed by cataract surgery and intraocular lens (IOL) implantation. Prediction errors (directional and absolute) for each device were determined from the 1 month postoperative manifest refraction.

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The brainstem nucleus locus coeruleus (LC) sends projections to the forebrain, brainstem, cerebellum and spinal cord and is a source of the neurotransmitter norepinephrine (NE) in these areas. For more than 50 years, LC was considered to be homogeneous in structure and function such that NE would be released uniformly and act simultaneously on the cells and circuits that receive LC projections. However, recent studies have provided evidence that LC is modular in design, with segregated output channels and the potential for differential release and action of NE in its projection fields.

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The COVID-19 pandemic had a major impact on UK deceased organ donation and transplantation activity. We used national audit data from NHS Blood and Transplant to explore in detail the effects of the pandemic in comparison with 12 months pre-pandemic, and to consider the impact of the mitigating strategies and challenges placed on ICU by 'waves' of patients with COVID-19. Between 11 March 2020 and 10 March 2021, referrals to NHS Blood and Transplant of potential organ donors were initially inversely related to the number of people with COVID-19 undergoing mechanical ventilation in intensive care (incident rate ratio (95%CI) per 1000 patients 0.

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Recent data demonstrate that noradrenergic neurons of the locus coeruleus (LC-NE) are required for fear-induced suppression of feeding, but the role of endogenous LC-NE activity in natural, homeostatic feeding remains unclear. Here, we found that LC-NE activity was suppressed during food consumption, and the magnitude of this neural response was attenuated as mice consumed more pellets throughout the session, suggesting that LC responses to food are modulated by satiety state. Visual-evoked LC-NE activity was also attenuated in sated mice, suggesting that satiety state modulates LC-NE encoding of multiple behavioral states.

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Background And Objectives: Adsorption of uremic solutes to activated carbon provides a potential means to limit dialysate volumes required for new dialysis systems. The ability of activated carbon to take up uremic solutes has, however, not been adequately assessed.

Design, Setting, Participants, & Measurements: Graded volumes of waste dialysate collected from clinical hemodialysis treatments were passed through activated carbon blocks.

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Background: We aimed to assess whether asymptomatic ("happy") hypoxia was an identifiable physiological phenotype of COVID-19 acute respiratory distress syndrome (ARDS), and associated with need for ICU admission.

Methods: We performed an observational cohort study of all adult patients admitted with hypoxaemic respiratory failure to a large acute hospital Trust serving the East Midlands, UK. Patients with confirmed COVID-19 were compared to those without.

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Neuroscience research is changing at an incredible pace due to technological innovation and recent national and global initiatives such as the BRAIN initiative. Given the wealth of data supporting the value of course-based undergraduate research experiences (CUREs) for students, we developed and assessed a neurotechnology CURE, . The goal of the course is to immerse undergraduate and graduate students in research and to explore technological advances in neuroscience.

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Background: The clearance of solutes removed by tubular secretion may be altered out of proportion to the GFR in CKD. Recent studies have described considerable variability in the secretory clearance of waste solutes relative to the GFR in patients with CKD.

Methods: To test the hypothesis that secretory clearance relative to GFR is reduced in patients approaching dialysis, we used metabolomic analysis to identify solutes in simultaneous urine and plasma samples from 16 patients with CKD and an eGFR of 7±2 ml/min per 1.

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Background And Objectives: Residual native kidney function confers health benefits in patients on dialysis. It can facilitate control of extracellular volume and inorganic ion concentrations. Residual kidney function can also limit the accumulation of uremic solutes.

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Background: Impairment of kidney function is routinely assessed by measuring the accumulation of creatinine, an organic solute cleared largely by glomerular filtration. We tested whether the clearance of solutes that undergo tubular secretion is reduced in proportion to the clearance of creatinine in humans with AKI.

Methods: Four endogenously produced organic solutes (phenylacetylglutamine [PAG], hippurate [HIPP], indoxyl sulfate [IS], and p-cresol sulfate [PCS]) were measured in spot urine and plasma samples from ten patients with AKI and 17 controls.

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Understanding the function of broadly projecting neurons depends on comprehensive knowledge of the distribution and targets of their axon collaterals. While retrograde tracers and, more recently, retrograde viral vectors have been used to identify efferent projections, they have limited ability to reveal the full pattern of axon collaterals from complex, heterogeneous neuronal populations. Here we describe TrAC (tracing axon collaterals), an intersectional recombinase-based viral-genetic strategy that allows simultaneous visualization of axons from a genetically defined neuronal population and a projection-based subpopulation.

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Accumulating evidence indicates that disruption of galanin signaling is associated with neuropsychiatric disease, but the precise functions of this neuropeptide remain largely unresolved due to lack of tools for experimentally disrupting its transmission in a cell type-specific manner. To examine the function of galanin in the noradrenergic system, we generated and crossed two novel knock-in mouse lines to create animals lacking galanin specifically in noradrenergic neurons (Gal). We observed reduced levels of galanin peptide in pons, hippocampus, and prefrontal cortex of Gal mice, indicating that noradrenergic neurons are a significant source of galanin to those brain regions, while midbrain and hypothalamic galanin levels were comparable to littermate controls.

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Background: Dialysis in children as well as adults is prescribed to achieve a target spKt/V, where V is the volume of distribution of urea. Waste solute production may however be more closely correlated with body surface area (BSA) than V which rises in proportion with body weight. Plasma levels of waste solutes may thus be higher in smaller patients when targeting spKt/V since they have higher BSA relative to body weight.

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The accumulation of uremic solutes in kidney failure may impair mental function. The present study profiled the accumulation of uremic solutes in the cerebrospinal fluid (CSF) in acute renal failure. CSF and plasma ultrafiltrate were obtained from rats at 48 h after sham operation (control; = 10) or bilateral nephrectomy ( = 10) and analyzed using an established metabolomic platform.

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Introduction: Elevated sound levels in critical care are associated with sleep deprivation and an increased incidence of delirium. We aimed to determine whether a sound-activated visual noise display meter could cause a sustained reduction in sound levels overnight in an adult critical care unit.

Method: Sound levels were recorded overnight for eight days before and after the introduction of a visual noise display meter, with a further eight days recorded four months later after continued use of the visual noise display meter.

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Background: Residual kidney function (RKF) is thought to exert beneficial effects through clearance of uremic toxins. However, the level of native kidney function where clearance becomes negligible is not known.

Methods: We aimed to assess whether levels of nonurea solutes differed among patients with 'clinically negligible' RKF compared with those with no RKF.

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Cholecystokinin-expressing GABAergic (CCK-GABA) neurons are perisomatic inhibitory cells that have been argued to regulate emotion and sculpt the network oscillations associated with cognition. However, no study has selectively manipulated CCK-GABA neuron activity during behavior in freely-moving animals. To explore the behavioral effects of activating CCK-GABA neurons on emotion and cognition, we utilized a novel intersectional genetic mouse model coupled with a chemogenetic approach.

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