Non-invasive quantification of exercise-induced changes in regional left ventricular function in normals and patients with one vessel coronary artery disease using radionuclide ventriculography

To quantitate changes in regional left ventricular function induced by ischemia or scar, rest and exercise equilibrium radionuclide studies of 26 patients with one vessel coronary artery disease and 12 normal individuals were analysed with a new method for regional ejection fraction determination. A computer algorithm provided observer-independent segmental analysis from a centre of gravity of the left ventricular activity at end-diastole (left anterior oblique projection). Special segments were assigned for anteroseptal, inferoapical and posterolateral areas corresponding to the three main coronary arteries. Reproducibility using an unchanged camera positioning was excellent even for 2 min acquisition studies (r=0.93) and still good after repositioning (r=0.80 to 0.87). In normal areas, regional ejection fraction increased or showed no change during exercise. In contrast, it decreased significantly in regions supplied by stenosed coronary arteries (ischemia) and remained depressed in scar zones. The method proved to be valid for regional changes induced by left anterior descending and left circumflex coronary obstructions, but less for right coronary artery lesions. Global ejection fraction reflected a sum of all regional changes implying that regional analysis should be more sensitive in detecting coronary artery diseas

Prognostic significance of right ventricular ejection fraction for persistent complex ventricular arrhythmias and/or sudden cardiac death after first myocardial infarction: Relation to infarct location, size and left ventricular function

To assess the prognostic significance of right ventricular dysfunction after a first myocardial infarction for complex ventricular arrhythmias and or sudden cardiac death in relation to infarct location, size and left ventricular function, a series of 127 consecutive patients was prospectively studied and followed up for one year. Prior to hospital discharge, a 24-hour electrocardiographic recording and radionuclide angiocardiography were performed. Right ventricular ejection fraction was related to inferior infarct location and size (r = 0.45, P 0.40 vs. ≤ 0.40 showed that presence of complex ventricular ectopic activity and/or sudden cardiac death after myocardial infarction was related not only to left, but also independently to right ventricular dysfunction. These results imply a significant prognostic contribution of right ventricular dysfunction to the occurrence of severe ventricular arrhythmias and/or sudden cardiac death after myocardial infarction independent of and additive to left ventricular dysfunctio

Continuous isotopic composition measurements of tropospheric CO₂ at Jungfraujoch (3580 m a.s.l.), Switzerland: real-time observation of regional pollution events

A quantum cascade laser based absorption spectrometer (QCLAS) is applied for the first time to perform in situ, continuous and high precision isotope ratio measurements of CO₂ in the free troposphere. Time series of the three main CO₂ isotopologue mixing ratios (¹²C¹⁶CO₂, ¹³C¹⁶CO₂ and ¹²C¹⁸O¹⁶O) have simultaneously been measured at one second time resolution over two years (from August 2008 to present) at the High Altitude Research Station Jungfraujoch (3580 m a.s.l., Switzerland). This work focuses on periods in February 2009 only, when sudden and pronounced enhancements in the tropospheric CO₂ were observed. These short-term changes were closely correlated with variations in CO mixing ratios measured at the same site, indicating combustion related emissions as potential source. The analytical precision of 0.046‰ (at 50 s integration time) for both δ¹³C and δ¹⁸O and the high temporal resolution allowed the application of the Keeling plot method for source signature identification. The spatial origin of these CO₂ emission sources was then determined by backward Lagrangian particle dispersion simulations

Stable Isotope Analysis of Greenhouse Gases Requires Analyte Preconcentration

Nitrous oxide (N2O) is an important trace gas contributing to global warming and depletion of ozone in the stratosphere. Its increasing abundance is caused mainly by anthropogenic sources, such as application of fertilizers in agriculture or emissions from industry. To understand the N2O global budget, its sources and sinks need to be well-described and quantified. In this project, a new method for N2O source appointment was developed that can help with this task. The method is based on analysis of the eight most abundant isotopic molecules of N2O, using quantum cascade laser absorption spectroscopy (QCLAS). The applicability of the method towards the N2O biogeochemical cycle was demonstrated on a prominent N2O source (bacterial denitrification) and the most important N2O sink (UV photolysis) on samples prepared in laboratory experiments. An extension of the QCLAS method to natural samples can be achieved by hyphenation with a preconcentration technique that increases concentration of the analyte and standardizes the sample matrix. This article provides an overview of currently applied preconcentration techniques in the field of greenhouse-gas analysis and a description of the preconcentration device TREX that will be employed in future projects with the developed QCLAS method

Nitrous oxide net exchange in a beech dominated mixed forest in Switzerland measured with a quantum cascade laser spectrometer

International audienceNitrous oxide fluxes were measured at the Lägeren CarboEurope IP flux site over the multi-species mixed forest dominated by European beech and Norway spruce. Measurements were carried out during a four-week period in October?November 2005 during leaf senescence. Fluxes were measured with a standard ultrasonic anemometer in combination with a quantum cascade laser absorption spectrometer that measured N2O, CO2, and H2O mixing ratios simultaneously at 5 Hz time resolution. To distinguish insignificant fluxes from significant ones it is proposed to use a new approach based on the significance of the correlation coefficient between vertical wind speed and mixing ratio fluctuations. This procedure eliminated roughly 56% of our half-hourly fluxes. Based on the remaining, quality checked N2O fluxes we quantified the mean efflux at 0.8 ± 0.4 ?mol m?2 h?1 (mean ± standard error). Most of the contribution to the N2O flux occurred during a 6.5-h period starting 4.5 h before each precipitation event. No relation with precipitation amount could be found. Visibility data representing fog density and duration at the site indicate that wetting of the canopy may have as strong an effect on N2O effluxes as does below-ground microbial activity. It is speculated that above-ground N2O production from the senescing leaves at high moisture (fog, drizzle, onset of precipitation event) may be responsible for part of the measured flux. In comparison with the annual CO2 budget of ?342 g C m?2 yr?1 it is estimated that concurrent N2O fluxes offset at least 5% of the greenhouse forcing reduction via net CO2 uptake

Longitudinal microbiome investigation throughout prion disease course reveals pre- and symptomatic compositional perturbations linked to short-chain fatty acid metabolism and cognitive impairment in mice

Commensal intestinal bacteria shape our microbiome and have decisive roles in preserving host metabolic and immune homeostasis. They conspicuously impact disease development and progression, including amyloid-beta (Aβ) and alpha (α)-synuclein pathology in neurodegenerative diseases, conveying the importance of the brain–gut–microbiome axis in such conditions. However, little is known about the longitudinal microbiome landscape and its potential clinical implications in other protein misfolding disorders, such as prion disease. We investigated the microbiome architecture throughout prion disease course in mice. Fecal specimens were assessed by 16S ribosomal RNA sequencing. We report a temporal microbiome signature in prion disease and uncovered alterations in Lachnospiraceae, Ruminococcaceae, Desulfovibrionaceae, and Muribaculaceae family members in this disease. Moreover, we determined the enrichment of Bilophila, a microorganism connected to cognitive impairment, long before the clinical manifestation of disease symptoms. Based on temporal microbial abundances, several associated metabolic pathways and resulting metabolites, including short-chain fatty acids, were linked to the disease. We propose that neuroinflammatory processes relate to perturbations of the intestinal microbiome and metabolic state by an interorgan brain–gut crosstalk. Furthermore, we describe biomarkers possibly suitable for early disease diagnostics and anti-prion therapy monitoring. While our study is confined to prion disease, our discoveries might be of equivalent relevance in other proteinopathies and central nervous system pathologies

Seasonal and diurnal characteristics of water soluble inorganic compounds in the gas and aerosol phase in the Zurich area

Gas and aerosol samples were taken using a wet effluent diffusion denuder/aerosol collector (WEDD/AC) coupled to ion chromatography (IC) in the city of Zurich, Switzerland from August to September 2002 and in March 2003. Major water soluble inorganic ions; nitrate, sulfate, and nitrite were analyzed online with a time resolution of two hours for the gas and aerosol phase. The fraction of water soluble inorganic anions in PM10 varied from 15% in August to about 38% in March. Seasonal and diurnal variations of nitrate in the gas and aerosol phase were observed with more than 50% of the total nitrate in the gas phase during August and more than 80% of nitrate in the aerosol phase during March exceeding the concentration of sulfate by a factor of 2. Aerosol sulfate, on the other hand, did not show significant variability with season. However, in the gas phase, the SO₂ concentration was 6.5 times higher in winter than in summer. Nitrous acid (HONO) also showed a diurnal variation in both the gas and aerosol phase with the lowest concentration (0.2–0.6 µg/m³) in the afternoon. The primary pollutants, NO, CO and SO₂ mixing ratios were often at their highest between 04:00–10:00 local time due to the build up of fresh vehicle emission under a nocturnal inversion

Electroencephalogram paroxysmal theta characterizes cataplexy in mice and children

Astute control of brain activity states is critical for adaptive behaviours and survival. In mammals and birds, electroencephalographic recordings reveal alternating states of wakefulness, slow wave sleep and paradoxical sleep (or rapid eye movement sleep). This control is profoundly impaired in narcolepsy with cataplexy, a disease resulting from the loss of orexin/hypocretin neurotransmitter signalling in the brain. Narcolepsy with cataplexy is characterized by irresistible bouts of sleep during the day, sleep fragmentation during the night and episodes of cataplexy, a sudden loss of muscle tone while awake and experiencing emotions. The neural mechanisms underlying cataplexy are unknown, but commonly thought to involve those of rapid eye movement-sleep atonia, and cataplexy typically is considered as a rapid eye movement sleep disorder. Here we reassess cataplexy in hypocretin (Hcrt, also known as orexin) gene knockout mice. Using a novel video/electroencephalogram double-blind scoring method, we show that cataplexy is not a state per se, as believed previously, but a dynamic, multi-phased process involving a reproducible progression of states. A knockout-specific state and a stereotypical paroxysmal event were introduced to account for signals and electroencephalogram spectral characteristics not seen in wild-type littermates. Cataplexy almost invariably started with a brief phase of wake-like electroencephalogram, followed by a phase featuring high-amplitude irregular theta oscillations, defining an activity profile distinct from paradoxical sleep, referred to as cataplexy-associated state and in the course of which 1.5-2 s high-amplitude, highly regular, hypersynchronous paroxysmal theta bursts (∼7 Hz) occurred. In contrast to cataplexy onset, exit from cataplexy did not show a predictable sequence of activities. Altogether, these data contradict the hypothesis that cataplexy is a state similar to paradoxical sleep, even if long cataplexies may evolve into paradoxical sleep. Although not exclusive to overt cataplexy, cataplexy-associated state and hypersynchronous paroxysmal theta activities are highly enriched during cataplexy in hypocretin/orexin knockout mice. Their occurrence in an independent narcolepsy mouse model, the orexin/ataxin 3 transgenic mouse, undergoing loss of orexin neurons, was confirmed. Importantly, we document for the first time similar paroxysmal theta hypersynchronies (∼4 Hz) during cataplexy in narcoleptic children. Lastly, we show by deep recordings in mice that the cataplexy-associated state and hypersynchronous paroxysmal theta activities are independent of hippocampal theta and involve the frontal cortex. Cataplexy hypersynchronous paroxysmal theta bursts may represent medial prefrontal activity, associated in humans and rodents with reward-driven motor impulse, planning and conflict monitorin

Altered sleep homeostasis in rev-erbα knockout mice

Study Objectives: The nuclear receptor REV-ERBα is a potent, constitutive transcriptional repressor critical for the regulation of key circadian and metabolic genes. Recently, REV-ERBα's involvement in learning, neurogenesis, mood, and dopamine turnover was demonstrated suggesting a specific role in central nervous system functioning. We have previously shown that the brain expression of several core clock genes, including Rev-erbα, is modulated by sleep loss. We here test the consequences of a loss of REV-ERBα on the homeostatic regulation of sleep.Methods: EEG/EMG signals were recorded in Rev-erbα knockout (KO) mice and their wild type (WT) littermates during baseline, sleep deprivation, and recovery. Cortical gene expression measurements after sleep deprivation were contrasted to baseline.Results: Although baseline sleep/wake duration was remarkably similar, KO mice showed an advance of the sleep/wake distribution relative to the light-dark cycle. After sleep onset in baseline and after sleep deprivation, both EEG delta power (1–4 Hz) and sleep consolidation were reduced in KO mice indicating a slower increase of homeostatic sleep need during wakefulness. This slower increase might relate to the smaller increase in theta and gamma power observed in the waking EEG prior to sleep onset under both conditions. Indeed, the increased theta activity during wakefulness predicted delta power in subsequent NREM sleep. Lack of Rev-erbα increased Bmal1, Npas2, Clock, and Fabp7 expression, confirming the direct regulation of these genes by REV-ERBα also in the brain.Conclusions: Our results add further proof to the notion that clock genes are involved in sleep homeostasis. Because accumulating evidence directly links REV-ERBα to dopamine signaling the altered homeostatic regulation of sleep reported here are discussed in that context