Distinct Effects of Respiratory Viral Infection Models on miR-149-5p, IL-6 and p63 Expression in BEAS-2B and A549 Epithelial Cells.

Respiratory viruses cause airway inflammation, resulting in epithelial injury and repair. miRNAs, including miR-149-5p, regulate different pathological conditions. We aimed to determine how miR-149-5p functions in regulating pro-inflammatory IL-6 and p63, key regulators of airway epithelial wound repair, in response to viral proteins in bronchial (BEAS-2B) and alveolar (A549) epithelial cells. BEAS-2B or A549 cells were incubated with poly (I:C, 0.5 µg/mL) for 48 h or SARS-CoV-2 spike protein-1 or 2 subunit (S1 or S2, 1 µg/mL) for 24 h. miR-149-5p was suppressed in BEAS-2B challenged with poly (I:C), correlating with IL-6 and p63 upregulation. miR-149-5p was down-regulated in A549 stimulated with poly (I:C); IL-6 expression increased, but p63 protein levels were undetectable. miR-149-5p remained unchanged in cells exposed to S1 or S2, while S1 transfection increased IL-6 expression in BEAS-2B cells. Ectopic over-expression of miR-149-5p in BEAS-2B cells suppressed IL-6 and p63 mRNA levels and inhibited poly (I:C)-induced IL-6 and p63 mRNA expressions. miR-149-5p directly suppressed IL-6 mRNA in BEAS-2B cells. Hence, BEAS-2B cells respond differently to poly (I:C), S1 or S2 compared to A549 cells. Thus, miR-149-5p dysregulation may be involved in poly (I:C)-stimulated but not S1- or S2-stimulated increased IL-6 production and p63 expression in BEAS-2B cells.

Thymic en-bloc resection with veins: case demonstrations and review of the literature.

Locally invasive thymic neoplasms are challenging clinical scenarios and typically require a multidisciplinary approach. The involvement of major mediastinal veins such as the superior vena cava (SVC) used to be a contraindication to surgery, but with improved surgical technique and outcomes, this paradigm has shifted. In some situations, complex resections and reconstructions may be indicated and required to improve the long-term outcome of these patients. We report two of our cases along with a current review of literature. We also describe the preoperative workup, operative techniques, postoperative management, complications, and outcomes of patients with invasive thymic neoplasms that involve the mediastinal veins. Our first case describes a patient who was diagnosed with a thymoma extending from the diaphragm to the base of the neck that was also encasing major vascular structures including the SVC and left innominate vein. Our second case describes a patient who was also diagnosed with a large anterior mediastinal mass encasing the great veins and invading the chest wall. We describe the management of these patients and then delve deeper into operative techniques including SVC resection and reconstruction. We describe the types of conduits that can be used and complications to be mindful of when clamping the great veins, such as the SVC. Improvements in conduit materials and neoadjuvant and adjuvant therapies over the years have made it more feasible for patients with invasive thymic neoplasms to undergo surgery.

The effects of sleep deprivation, acute hypoxia, and exercise on cognitive performance: A multi-experiment combined stressors study.

INTRODUCTION: Both sleep deprivation and hypoxia have been shown to impair executive function. Conversely, moderate intensity exercise is known to improve executive function. In a multi-experiment study, we tested the hypotheses that moderate intensity exercise would ameliorate any decline in executive function after i) three consecutive nights of partial sleep deprivation (PSD) (Experiment 1) and ii) the isolated and combined effects of a single night of total sleep deprivation (TSD) and acute hypoxia (Experiment 2). METHODS: Using a rigorous randomised controlled crossover design, 12 healthy participants volunteered in each experiment (24 total, 5 females). In both experiments seven executive function tasks (2-choice reaction time, logical relations, manikin, mathematical processing, 1-back, 2-back, 3-back) were completed at rest and during 20 min semi-recumbent, moderate intensity cycling. Tasks were completed in the following conditions: before and after three consecutive nights of PSD and habitual sleep (Experiment 1) and in normoxia and acute hypoxia (FIO2 = 0.12) following one night of habitual sleep and one night of TSD (Experiment 2). RESULTS: Although the effects of three nights of PSD on executive functions were inconsistent, one night of TSD (regardless of hypoxic status) reduced executive functions. Significantly, regardless of sleep or hypoxic status, executive functions are improved during an acute bout of moderate intensity exercise. CONCLUSION: These novel data indicate that moderate intensity exercise improves executive function performance after both PSD and TSD, regardless of hypoxic status. The key determinants and/or mechanism(s) responsible for this improvement still need to be elucidated. Future work should seek to identify these mechanisms and translate these significant findings into occupational and skilled performance settings.

The Influence of COVID-19 Disease on Pre-Analytical Blood Sample Haemolysis Rates in Three Acute Medical Units: An Interrupted Time Series Analysis.

The COVID-19 pandemic impacted delivery of health services. The aim of our study was to determine the impact of COVID-19 disease on pre-analytical blood sample haemolysis by modelling the daily haemolysis rates variations pre and post COVID-19 infections. Ethics approval was obtained prior to study commencing. Interrupted Time Series data analysis was conducted on UK National Health Service Acute Admissions Unit 25-month (1 February 2019 to 28 February 2021) biochemistry (total and haemolysed) blood sample dataset. Interruption was set on 23 March 2021, the start of the first UK lockdown. Daily haemolysis rate (% samples haemolysed) data were fitted with a spline curve to determine influence of haemolysis rates on short or medium-term temporal trends. Linear regression was performed so as to determine long-term temporal trends pre- and post-intervention. There were 32,316 biochemistry blood sample results: 19,058 pre and 13,258 (342 days) from the post-intervention period. Overall median daily haemolysis rate was 7.3% (range: 0-30.6%), 7.7% pre-intervention versus 6.5% post-intervention (p<0.0001). The proportion of haemolysis cases negatively correlated with the number of samples processed (rho=0.09; p=0.01). The pre-intervention slope was -1.70 %.y-1, y intercept 9.04%; post-intervention slope was -1.88%.y-1, y intercept was 10.2%; with no difference in either the slope (p=0.87) or intercept (p=0.16). There was no association between short-term variation in haemolysis rates with changes in practice due to COVID-19 disease and the disease itself. The negative correlation between haemolysis rate and the number of samples processed highlights the importance of continued venepuncture practice to facilitate haemolysis rate reduction.

Effect of different levels of acute hypoxia on subsequent oral glucose tolerance in males with overweight: A balanced cross-over pilot feasibility study.

Previous research has shown that ≤60 min hypoxic exposure improves subsequent glycaemic control, but the optimal level of hypoxia is unknown and data are lacking from individuals with overweight. We undertook a cross-over pilot feasibility study investigating the effect of 60-min prior resting exposure to different inspired oxygen fractions (CON FI O2  = 0.209; HIGH FI O2  = 0.155; VHIGH FI O2  = 0.125) on glycaemic control, insulin sensitivity, and oxidative stress during a subsequent oral glucose tolerance test (OGTT) in males with overweight (mean (SD) BMI = 27.6 (1.3) kg/m2 ; n = 12). Feasibility was defined by exceeding predefined withdrawal criteria for peripheral blood oxygen saturation (SpO2 ), partial pressure of end-tidal oxygen or carbon dioxide and acute mountain sickness (AMS), and dyspnoea symptomology. Hypoxia reduced SpO2 in a stepwise manner (CON = 97(1)%; HIGH = 91(1)%; VHIGH = 81(3)%, p < 0.001), but did not affect peak plasma glucose concentration (CON = 7.5(1.8) mmol∙L-1 ; HIGH = 7.7(1.1) mmol∙L-1 ; VHIGH = 7.7(1.1) mmol∙L-1 ; p = 0.777; η2  = 0.013), plasma glucose area under the curve, insulin sensitivity, or metabolic clearance rate of glucose (p > 0.05). We observed no between-conditions differences in oxidative stress (p > 0.05), but dyspnoea and AMS symptoms increased in VHIGH (p < 0.05), with one participant meeting the withdrawal criteria. Acute HIGH or VHIGH exposure prior to an OGTT does not influence glucose homeostasis in males with overweight, but VHIGH is associated with adverse symptomology and reduced feasibility.

Adverse Outcomes Associated With Atrial Arrhythmias After Veno-Venous Extracorporeal Membrane Oxygenation.

Veno-venous extracorporeal membrane oxygenation (VV ECMO) is used as a treatment modality in those who fail to respond to conventional care. Hypoxia and medications used in the intensive care unit may increase risk for atrial arrhythmias (AA). This study aims to evaluate the impact of AA on post-VV ECMO outcome. A retrospective review of patients who were placed on VV ECMO between October 2016 and October 2021. One hundred forty-five patients were divided into two groups, AA and no AA. Baseline characteristic and potential risk factors were assessed. Uni- and multivariate analysis using logistic regression models were constructed to evaluate the predictors of mortality between groups. Survival between groups was estimated by the Kaplan-Meier method using the log-rank test. Advanced age with history of coronary artery disease and hypertension were associated with increased risk to develop AA post-VV ECMO placement ( p value < 0.05). Length on ECMO, time intubated, hospital length of stay, and sepsis were significantly increased in patients in the AA group ( p value < 0.05). There was no difference in the overall mortality between the two groups. AAs were associated with worse hospital course and complications but no difference in overall mortality rate. Age and cardiovascular disease seem to be predisposing risk factors for this. Further studies are needed to investigate potential strategies to prevent AAs development in this population.

Plasma biomarkers of endothelial function, inflammation and oxidative stress in individuals with non-freezing cold injury.

NEW FINDINGS: What is the central question of this study? Are biomarkers of endothelial function, oxidative stress and inflammation altered by non-freezing cold injury (NFCI)? What is the main finding and its importance? Baseline plasma [interleukin-10] and [syndecan-1] were elevated in individuals with NFCI and cold-exposed control participants. Increased [endothelin-1] following thermal challenges might explain, in part, the increased pain/discomfort experienced with NFCI. Mild to moderate chronic NFCI does not appear to be associated with either oxidative stress or a pro-inflammatory state. Baseline [interleukin-10] and [syndecan-1] and post-heating [endothelin-1] are the most promising candidates for diagnosis of NFCI. ABSTRACT: Plasma biomarkers of inflammation, oxidative stress, endothelial function and damage were examined in 16 individuals with chronic NFCI (NFCI) and matched control participants with (COLD, n = 17) or without (CON, n = 14) previous cold exposure. Venous blood samples were collected at baseline to assess plasma biomarkers of endothelial function (nitrate, nitrite and endothelin-1), inflammation [interleukin-6 (IL-6), interleukin-10 (IL-10), tumour necrosis factor alpha and E-selectin], oxidative stress [protein carbonyl, 4-hydroxy-2-nonenal (4-HNE), superoxide dismutase and nitrotyrosine) and endothelial damage [von Willebrand factor, syndecan-1 and tissue type plasminogen activator (TTPA)]. Immediately after whole-body heating and separately, foot cooling, blood samples were taken for measurement of plasma [nitrate], [nitrite], [endothelin-1], [IL-6], [4-HNE] and [TTPA]. At baseline, [IL-10] and [syndecan-1] were increased in NFCI (P < 0.001 and P = 0.015, respectively) and COLD (P = 0.033 and P = 0.030, respectively) compared with CON participants. The [4-HNE] was elevated in CON compared with both NFCI (P = 0.002) and COLD (P < 0.001). [Endothelin-1] was elevated in NFCI compared with COLD (P < 0.001) post-heating. The [4-HNE] was lower in NFCI compared with CON post-heating (P = 0.032) and lower than both COLD (P = 0.02) and CON (P = 0.015) post-cooling. No between-group differences were seen for the other biomarkers. Mild to moderate chronic NFCI does not appear to be associated with a pro-inflammatory state or oxidative stress. Baseline [IL-10] and [syndecan-1] and post-heating [endothelin-1] are the most promising candidates for diagnosing NFCI, but it is likely that a combination of tests will be required.

Three-dimensional technologies in chest wall resection and reconstruction.

Resection and reconstruction of the chest wall can pose unique challenges given its vital role in the protection of the thoracic viscera and the dynamic part it plays in respiration. A number of new three-dimensional (3D) technologies may be invaluable in tackling these challenges. Herein we review the use of 3D technologies in preoperative imaging with virtual 3D models, printing of 3D models for preoperative planning, and printing of 3D prostheses when approaching complex chest wall reconstruction.

Urinary Trace Elements Are Biomarkers for Early Detection of Acute Kidney Injury.

Introduction: Acute kidney injury (AKI) is common in hospitalized patients and associated with poor outcomes. Current methods for identifying AKI (rise in serum creatinine [sCr] or fall in urine output [UO]) are inadequate and delay detection. Early detection of AKI with easily measurable biomarkers might improve outcomes by facilitating early implementation of AKI care pathways. Methods: From a porcine model of AKI, we identified trace elements (TEs) in urine that were associated with subsequent development of AKI. We tested these putative biomarkers in 2 observational cohort studies of patients at high risk of AKI: 151 patients undergoing cardiac surgery and 150 patients admitted to a general adult intensive care unit (ICU). Results: In adults admitted to the ICU, urinary cadmium (Cd) (adjusted for urinary creatinine) had area under the receiver operating characteristic curve (AUROC) 0.70 and negative predictive value (NPV) 89%; copper (Cu) had AUROC 0.76 and NPV 91%. In humans (but not pigs), urinary zinc (Zn) was also associated with AKI and, in the ICU study, had AUROC 0.67 and NPV 80%. In patients undergoing cardiac surgery, Zn had AUROC 0.77 and NPV 91%; urinary Cd and Cu had poor AUROC but NPV of 93% and 95%, respectively. In control studies, we found that the urinary biomarkers are stable at room temperature for at least 14 days and are not affected by other confounding factors, such as chronic kidney disease (CKD). Conclusion: Urinary Cd, Cu, and Zn are novel biomarkers for early detection of AKI. Urinary trace metals have advantages over proteins as AKI biomarkers because they are stable at room temperature and have potential for cheap point-of-care testing using electrochemistry.

Pleurabrade: A Spiral Brush for Mechanical Pleurodesis and a Review of the Literature.

Background While the optimal treatment for primary spontaneous pneumothorax remains unclear, mechanical pleurodesis is a well-established treatment. The Pleurabrade is a spiral brush designed for mechanical pleurodesis during thoracoscopy. We present two patients who underwent mechanical pleurodesis with the Pleurabrade. Case Description Two patients with spontaneous pneumothorax underwent operative intervention including mechanical pleurodesis with the Pleurabrade. Chest tubes were removed within 48 hours postoperatively and they were discharged home. Both patients remain recurrence free at 11 and 22 months, respectively. Conclusion While further testing is needed, these case reports and operative video highlight the Pleurabrade as an efficient device for thoracoscopic mechanical pleurodesis.

Esophageal disease in lung transplant patients.

There is a very well-established and complex interplay between gastroesophageal reflux and lung disease. This is particularly true in end-stage lung disease and post-lung transplant patients. Numerous studies have shown that in patients who are undergoing pre-lung transplant evaluations for diseases such as idiopathic pulmonary fibrosis (IPF), emphysema, connective tissue disease, there is a high prevalence of gastroesophageal reflux and esophageal dysmotility. Post-lung transplant, many of the reflux issues persist or worsen, and there is some evidence to suggest that this leads to worsened long-term allograft function and bronchiolitis obliterans. Anti-reflux operations in patients with lung disease have been shown to be safe in both the pre and post-lung transplant setting and lead to improved reflux symptoms, as well as protecting against reflux induced allograft dysfunction in the post-lung transplant patients. Barrett's esophagus and esophageal malignancy are also not unheard of in these patients, and select patients may benefit from operative intervention. This review discusses the links between gastroesophageal reflux and lung transplant patients in both the pre and post-transplant setting. We also review the approach to the workup of esophageal disease in the pre-lung transplant setting as well as the surgical management of this unique group of patients.

Timing of acute passive heating on glucose tolerance and blood pressure in people with type 2 diabetes: a randomized, balanced crossover, control trial.

Type 2 diabetes mellitus (T2DM) is characterized by chronic hyperglycemia and progressive insulin resistance, leading to macro and microvascular dysfunction. Passive heating has potential to improve glucose homeostasis and act as an exercise mimetic. We assessed the effect of acute passive heating before or during an oral glucose tolerance test (OGTT) in people with T2DM. Twelve people with T2DM were randomly assigned to the following three conditions: 1) 3-h OGTT (control), 2) 1-h passive heating (40°C water) 30 min before an OGTT (HOT-OGTT), and 3) 1-h passive heating (40°C water) 30 min after commencing an OGTT (OGTT-HOT). Blood glucose concentration, insulin sensitivity, extracellular heat shock protein 70 (eHSP70), total energy expenditure (TEE), heart rate (HR), systolic blood pressure (SBP), and diastolic blood pressure (DBP) were recorded. Passive heating did not alter blood glucose concentration [control: 1,677 (386) arbitrary units (AU), HOT-OGTT: 1,797 (340) AU, and OGTT-HOT: 1,662 (364) AU, P = 0.28], insulin sensitivity (P = 0.15), or SBP (P = 0.18) but did increase eHSP70 concentration in both heating conditions [control: 203.48 (110.81) pg·mL-1; HOT-OGTT: 402.47 (79.02) pg·mL-1; and OGTT-HOT: 310.00 (60.53) pg·mL-1, P < 0.001], increased TEE (via fat oxidation) in the OGTT-HOT condition [control: 263 (33) kcal, HOT-OGTT: 278 (40) kcal, and OGTT-HOT: 304 (38) kcal, P = 0.001], increased HR in both heating conditions (P < 0.001), and reduced DBP in the OGTT-HOT condition (P < 0.01). Passive heating in close proximity to a glucose challenge does not alter glucose tolerance but does increase eHSP70 concentration and TEE and reduce blood pressure in people with T2DM.NEW & NOTEWORTHY This is the first study to investigate the timing of acute passive heating on glucose tolerance and extracellular heat shock protein 70 concentration ([eHSP70]) in people with type 2 diabetes. The principal novel findings from this study were that both passive heating conditions: 1) did not reduce the area under the curve or peak blood glucose concentration, 2) elevated heart rate, and 3) increased [eHSP70], which was blunted by glucose ingestion, while passive heating following glucose ingestion, 4) increased total energy expenditure, and 5) reduced diastolic blood pressure.

A pilot study to investigate the associations of urinary concentrations of NO, ATP and derivatives with overactive bladder symptom severity.

NEW FINDINGS: What is the central question of this study? Are the urinary concentrations of NO and ATP, and their metabolites, associated with the severity of symptoms of overactive bladder? What is the main finding and its importance? The urinary ratios of [ATP/NO], [ADP/NO] and a combination of these, [ATP/Cr*ADP/Cr]/[NO/Cr], were correlated with overall OAB symptom severity, with the latter combination also being correlated with the severity of urinary frequency and urgency symptoms individually. Together, these data reveal changes in urothelial signalling that accompany the transition from physiology to pathology. ABSTRACT: Overactive bladder (OAB) is a highly prevalent symptom complex characterized by symptoms of urinary urgency and increased frequency and waking to void (nocturia), with or without urge incontinence and in the absence of proven infection or other obvious pathology. The underlying pathophysiology of idiopathic OAB is not clearly known, and the existence of several phenotypes has been proposed. Current diagnostic approaches are based on discordant measures, suffer from subjectivity and are incapable of detecting the proposed OAB phenotypes. Nitric oxide, ATP and their metabolites have previously been shown to underlie the perception of bladder fullness, with their release modifying the pathological perception of urgency. Therefore, in this study we assessed the concentrations of NO, ATP and associated metabolites in the urine of 113 consenting participants recruited from the general population. Recruited participants completed a questionnaire to measure the severity of OAB-associated urinary symptoms and provided a mid-stream urine sample. After identification of infection and haematuria using microbiology and microscopy, 95 samples were subjected to assays to measure NO, NO2- , NO3- , ATP, ADP and creatinine (Cr). There was no correlation between [NO/Cr], [NO2- /Cr] or [NO3- /Cr] and overall OAB symptom severity. In contrast, [ATP/NO], [ADP/NO] and a combination of these, [ATP/Cr*ADP/Cr]/[NO/Cr], were correlated with OAB symptom severity, and [ATP/Cr*ADP/Cr]/[NO/Cr] was also correlated with the severity of urinary frequency and urgency. This study adds to a growing literature that demonstrates the potential of urinary biomarkers and provides a foundation for a larger, longitudinal study.

New participant stratification and combination of urinary biomarkers and confounders could improve diagnostic accuracy for overactive bladder.

Overactive bladder (OAB) is a highly prevalent symptom complex characterised by symptoms of urinary urgency, increased frequency, nocturia, with or without urge incontinence; in the absence of proven infection or other obvious pathology. The underlying pathophysiology of idiopathic OAB is not clearly known and the existence of several phenotypes has been proposed. Current diagnostic approaches are based on discordant measures, suffer from subjectivity and are incapable of detecting the proposed OAB phenotypes. In this study, cluster analysis was used as an objective approach for phenotyping participants based on their OAB characteristic symptoms and led to the identification of a low OAB symptomatic score group (cluster 1) and a high OAB symptomatic score group (cluster 2). Furthermore, the ability of several potential OAB urinary biomarkers including ATP, ACh, nitrite, MCP-1 and IL-5 and participants' confounders, age and gender, in predicting the identified high OAB symptomatic score group was assessed. A combination of urinary ATP and IL-5 plus age and gender was shown to have clinically acceptable and improved diagnostic accuracy compared to urodynamically-observed detrusor overactivity. Therefore, this study provides the foundation for the development of novel non-invasive diagnostic tools for OAB phenotypes that may lead to personalised treatment.

Investigating the associations of mucosal P2Y6 receptor expression and urinary ATP and ADP concentrations, with symptoms of overactive bladder.

AIM: To characterize purinergic signaling in overactive bladder (OAB). METHODS: Mucosal biopsies were taken by flexible cystoscopy from patients with storage symptoms referred to Urology Departments of collaborating hospitals. Immunohistochemistry (n = 12) and Western blot analysis (n = 28) were used to establish the qualitative and quantitative expression profile of P2Y6 in human mucosa. Participants from the general population provided a mid-stream urine sample. Bioluminescent assays were used to quantify adenosine triphosphate (ATP; n = 66) and adenosine diphosphate (ADP; n = 60) concentrations, which were normalized to creatinine (Cr) concentration. All participants completed a questionnaire (International Consultation on Incontinence Questionnaire - Overactive Bladder) to score urinary symptoms of OAB. RESULTS: P2Y6 immunoreactivity, more prominent in the urothelium (colocalized with the uroepithelial marker pan-cytokeratin), was more greatly expressed in OAB compared to age- and sex-matched controls (benign prostatic hyperplasia) without OAB symptoms. Mucosal P2Y6 was positively correlated only with incontinence (P = .009). Both urinary ATP and its hydrolysis product, ADP, an agonist to P2Y6, were positively correlated with total OAB symptom score (P = .010 and P = .042, respectively). CONCLUSIONS: The positive correlation of P2Y6 only with incontinence may indicate a different phenotype in OAB wet and warrants further investigation. Positive correlations of ATP and ADP with total OAB symptom score demonstrate upregulation in purinergic signaling in OAB; shown previously only in animal models. Further research is required to validate whether purinoceptors are indeed new therapeutic targets for this highly prevalent symptom complex.

Cognitive performance is associated with cerebral oxygenation and peripheral oxygen saturation, but not plasma catecholamines, during graded normobaric hypoxia.

NEW FINDINGS: What is the central question of this study? What are the mechanisms responsible for the decline in cognitive performance following exposure to acute normobaric hypoxia? What are the main findings and their importance? We found that (1) performance of a complex central executive task (n-back) was reduced at FIO2 0.12; (2) there was a strong correlation between performance of the n-back task and reductions in SpO2 and cerebral oxygenation; and (3) plasma adrenaline, noradrenaline, cortisol and copeptin were not correlated with cognitive performance. ABSTRACT: It is well established that hypoxia impairs cognitive function; however, the physiological mechanisms responsible for these effects have received relatively little attention. This study examined the effects of graded reductions in fraction of inspired oxygen ( FIO2 ) on oxygen saturation ( SpO2 ), cerebral oxygenation, cardiorespiratory variables, activity of the sympathoadrenal system (adrenaline, noradrenaline) and hypothalamic-pituitary-adrenal axis (cortisol, copeptin), and cognitive performance. Twelve healthy males [mean (SD), age: 22 (4) years, height: 178 (5) cm, mass: 75 (9) kg, FEV1 /FVC ratio: 85 (5)%] completed a four-task battery of cognitive tests to examine inhibition, selective attention (Eriksen flanker), executive function (n-back) and simple and choice reaction time (Deary-Liewald). Tests were completed before and following 60 min of exposure to FIO2 0.2093, 0.17, 0.145 and 0.12. Following 60 min of exposure, response accuracy in the n-back task was significantly reduced in FIO2 0.12 compared to baseline [82 (9) vs. 93 (5)%; P < 0.001] and compared to all other conditions at the same time point [ FIO2 0.2093: 92 (3)%; FIO2 0.17: 91 (6)%; FIO2 0.145: 85 (10)%; FIO2 12: 82 (9)%; all P < 0.05]. The performance of the other tasks was maintained. Δaccuracy and Δreaction time of the n-back task was correlated with both Δ SpO2 [r(9) = 0.66, P < 0.001 and r(9) = -0.36, P = 0.037, respectively] and Δcerebral oxygenation [r(7) = 0.55, P < 0.001 and r(7) = -0.38, P = 0.045, respectively]. Plasma adrenaline, noradrenaline, cortisol and copeptin were not significantly elevated in any condition or correlated with any of the tests of cognitive performance. These findings suggest that reductions in peripheral oxygen saturation and cerebral oxygenation, and not increased activity of the sympathoadrenal system and hypothalamic-pituitary-adrenal axis, as previously speculated, are responsible for a decrease in cognitive performance during normobaric hypoxia.

Prosthetic Valve Legionella Endocarditis.

This report describes the case of an 80-year-old man with culture-negative prosthetic valve endocarditis who ultimately was given a diagnosis of Legionella pneumophila endocarditis.

Investigation of the Syncytial Nature of Detrusor Smooth Muscle as a Determinant of Action Potential Shape.

Unlike most excitable cells, certain syncytial smooth muscle cells are known to exhibit spontaneous action potentials of varying shapes and sizes. These differences in shape are observed even in electrophysiological recordings obtained from a single cell. The origin and physiological relevance of this phenomenon are currently unclear. The study presented here aims to test the hypothesis that the syncytial nature of the detrusor smooth muscle tissue contributes to the variations in the action potential profile by influencing the superposition of the passive and active signals. Data extracted from experimental recordings have been compared with those obtained through simulations. The feature correlation studies on action potentials obtained from the experimental recordings suggest the underlying presence of passive signals, called spontaneous excitatory junction potentials (sEJPs). Through simulations, we are able to demonstrate that the syncytial organization of the cells, and the variable superposition of the sEJPs with the "native action potential", contribute to the diversity in the action potential profiles exhibited. It could also be inferred that the fraction of the propagated action potentials is very low in the detrusor. It is proposed that objective measurements of spontaneous action potential profiles can lead to a better understanding of bladder physiology and pathology.