Physiology - Journal Articles

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    Swallow-breathing coordination during incremental ascent to altitude
    (Elsevier B.V., 2019) Huff, Alyssa; Day, Trevor A.; English, Mason; Reed, Mitchell D.; Zouboules, Shaelynn; Saran, Gurkarn; Leacy, Jack K.; Mann, Carli; Peltonen, Joel D. B.; O'Halloran, Ken D.; Sherpa, Mingma T.; Pitts, Teresa; National Institutes of Health; Kentucky Spinal Cord and Head Injury Trust; University of Louisville; Natural Sciences and Engineering Research Council of Canada
    Swallow and breathing are highly coordinated behaviors reliant on shared anatomical space and neural pathways. Incremental ascent to high altitudes results in hypoxia/hypocapnic conditions altering respiratory drive, however it is not known whether these changes also alter swallow. We examined the effect of incremental ascent (1045 m, 3440 m and 4371 m) on swallow motor pattern and swallow-breathing coordination in seven healthy adults. Submental surface electromyograms (sEMG) and spirometry were used to evaluate swallow triggered by saliva and water infusion. Swallow-breathing phase preference was different between swallows initiated by saliva versus water. With ascent, saliva swallows changed to a dominate pattern of occurrence during the transition from inspiration to expiration. Additionally, water swallows demonstrated a significant decrease in submental sEMG duration and a shift in submental activity to earlier in the apnea period, especially at 4371 m. Our results suggest that there are changes in swallow-breathing coordination and swallow production that likely increase airway protection with incremental ascent to high altitude. The adaptive changes in swallow were likely due to the exposure to hypoxia and hypocapnia, along with airway irritation. © 2018 Elsevier B.V.
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    Physiological bioactivity of a postbiotic consisting of heat-treated lactobacilli on mouse small intestine
    (Elsevier, 2023-08-16) Uhlig, Friederike; Warda, Alicja K.; Hueston, Cara M.; Draper, Lorraine A.; Chauvière, Gilles; Eckhardt, Erik; Hill, Colin; Hyland, Niall P.
    Lactobacillus LB is a postbiotic generated following fermentation by Limosilactobacillus fermentum and Lactobacillus delbrueckii. Lactobacillus LB alleviates acute diarrhoea and ameliorates the symptoms of irritable bowel syndrome. Here, we investigated whether modulation of intestinal ion transport and motility contributes to these beneficial effects and whether the postbiotic produced with both strains contributes to a unique biophysiological profile. In Ussing chamber studies, low lactose-Lactobacillus LB (LL-LB) significantly increased baseline short-circuit current, and this was partially mediated by sodium-D-glucose transporter 1. In organ baths, LL-LB significantly decreased ileal tone and increased carbachol-induced contractility. Relative to LL-LB, preparations produced using a single strain fermentate generated from L. fermentum significantly increased baseline short-circuit current and inhibited carbachol-induced contractility. Our data demonstrate a unique biophysiological profile for the dual strain postbiotic and support a direct and immediate effect of LL-LB on host physiology ex vivo which could contribute to the clinical efficacy of Lactobacillus LB.
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    Machine learning detects intraventricular haemorrhage in extremely preterm infants
    (MDPI, 2023-05-23) Ashoori, Minoo; O’Toole, John M.; O’Halloran, Ken D.; Naulaers, Gunnar; Thewissen, Liesbeth; Miletin, Jan; Cheung, Po-Yin; EL-Khuffash, Afif; Van Laere, David; Straňák, Zbyněk; Dempsey, Eugene M.; McDonald, Fiona B.; Science Foundation Ireland; Seventh Framework Programme; University College Cork
    Objective: To test the potential utility of applying machine learning methods to regional cerebral (rcSO2) and peripheral oxygen saturation (SpO2) signals to detect brain injury in extremely preterm infants. Study design: A subset of infants enrolled in the Management of Hypotension in Preterm infants (HIP) trial were analysed (n = 46). All eligible infants were <28 weeks’ gestational age and had continuous rcSO2 measurements performed over the first 72 h and cranial ultrasounds performed during the first week after birth. SpO2 data were available for 32 infants. The rcSO2 and SpO2 signals were preprocessed, and prolonged relative desaturations (PRDs; data-driven desaturation in the 2-to-15-min range) were extracted. Numerous quantitative features were extracted from the biosignals before and after the exclusion of the PRDs within the signals. PRDs were also evaluated as a stand-alone feature. A machine learning model was used to detect brain injury (intraventricular haemorrhage-IVH grade II–IV) using a leave-one-out cross-validation approach. Results: The area under the receiver operating characteristic curve (AUC) for the PRD rcSO2 was 0.846 (95% CI: 0.720–0.948), outperforming the rcSO2 threshold approach (AUC 0.593 95% CI 0.399–0.775). Neither the clinical model nor any of the SpO2 models were significantly associated with brain injury. Conclusion: There was a significant association between the data-driven definition of PRDs in rcSO2 and brain injury. Automated analysis of PRDs of the cerebral NIRS signal in extremely preterm infants may aid in better prediction of IVH compared with a threshold-based approach. Further investigation of the definition of the extracted PRDs and an understanding of the physiology underlying these events are required.
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    Role of Ca2+ stores in metabotropic L-glutamate receptor-mediated supralinear Ca2+ signaling in rat hippocampal neurons
    (Society for Neuroscience, 2000-12-01) Rae, Mark G.; Martin, Duncan J.; Collingridge, Graham L.; Irving, Andrew J.; Wellcome Trust
    The role of metabotropic l-glutamate (mGlu) receptors in supralinear Ca2+ signaling was investigated in cultured hippocampal cells using Ca2+ imaging techniques and whole-cell voltage-clamp recording. In neurons, but not glia, global supralinear Ca2+ release from intracellular stores was observed when the mGlu receptor agonist (RS)-3,5-dihydroxyphenylglycine (DHPG) was combined with elevated extracellular K+ levels (10.8 mm), moderate depolarization (15–30 mV), or NMDA (3 μm). There was a delay (2–8 min) before the stores were fully charged, and the enhancement persisted for a short period (up to 10 min) after removal of the store-loading stimulus. Studies with the mGlu receptor antagonist 2-methyl-6-(phenylethynyl)-pyridine demonstrated that these effects were mediated by activation of the mGlu5 receptor subtype. The L-type voltage-gated Ca2+ channel antagonist nifedipine (10 μm) substantially reduced responses to DHPG obtained in the presence of elevated extracellular K+ but not NMDA. This suggests that the Ca2+ that is required to load the stores can enter either through L-type voltage-gated Ca2+ channels or directly through NMDA receptors. The findings that both depolarization and NMDA receptor activation can facilitate mGlu receptor Ca2+ signaling adds considerable flexibility to the processes that underlie activity-dependent changes in synaptic strength. In particular, a temporal separation between the store-loading stimulus and the activation of mGlu receptors could be used as a recency detector in neurons.
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    Cannabinoids on the brain
    (Hindawi, 2002-03-09) Irving, Andrew J.; Rae, Mark G.; Coutts, Angela A.
    Cannabis has a long history of consumption both for recreational and medicinal uses. Recently there have been significant advances in our understanding of how cannabis and related compounds (cannabinoids) affect the brain and this review addresses the current state of knowledge of these effects. Cannabinoids act primarily via two types of receptor, CB1 and CB2, with CB1 receptors mediating most of the central actions of cannabinoids. The presence of a new type of brain cannabinoid receptor is also indicated. Important advances have been made in our understanding of cannabinoid receptor signaling pathways, their modulation of synaptic transmission and plasticity, the cellular targets of cannabinoids in different central nervous system (CNS) regions and, in particular, the role of the endogenous brain cannabinoid (endocannabinoid) system. Cannabinoids have widespread actions in the brain: in the hippocampus they influence learning and memory; in the basal ganglia they modulate locomotor activity and reward pathways; in the hypothalamus they have a role in the control of appetite. Cannabinoids may also be protective against neurodegeneration and brain damage and exhibit anticonvulsant activity. Some of the analgesic effects of cannabinoids also appear to involve sites within the brain. These advances in our understanding of the actions of cannabinoids and the brain endocannabinoid system have led to important new insights into neuronal function which are likely to result in the development of new therapeutic strategies for the treatment of a number of key CNS disorders.