Desflurane Selectively Suppresses Long-latency Cortical Neuronal Response to Flash in the Rat

Background—The effect of inhalational anesthetics on sensory-evoked unit activity in the cerebral cortex has been controversial. Desflurane has desirable properties for in vivo neurophysiologic studies but its effect on cortical neuronal activity and neuronal responsiveness is not known. We studied the effect of desflurane on resting and visual evoked unit activity in rat visual cortex in vivo. Methods—Desflurane was administered to adult albino rats at steady-state concentrations at 2%, 4%, 6% and 8%. Flashes from a light emitting diode were delivered to the left eye at 5-second intervals. Extracellular unit activity within the right visual cortex was recorded using a 49-electrode array. Individual units were identified using principal components analysis. Results—At 2% desflurane 578 active units were found. Of these, 75% increased their firing rate in response to flash. Most responses contained early (0–100ms) and late (150–1000ms) components. With increasing desflurane concentration, the number of units active at baseline decreased (−13%), the number of early responding units increased (+31%), and number of late responding units decreased (−15%). Simultaneously, baseline firing rate decreased (−77%), the early response was unchanged, and the late response decreased (−60%). Conclusions—The results indicate that visual cortex neurons remain responsive to flash stimulation under desflurane anesthesia but the long-latency component of their response is attenuated in a concentration-dependent manner. Suppression of the long-latency response may be related to a loss of cortico-cortical feedback and loss of consciousness

Antimalarial Therapy Selection for Quinolone Resistance among Escherichia coli in the Absence of Quinolone Exposure, in Tropical South America

BACKGROUND: Bacterial resistance to antibiotics is thought to develop only in the presence of antibiotic pressure. Here we show evidence to suggest that fluoroquinolone resistance in Escherichia coli has developed in the absence of fluoroquinolone use. METHODS: Over 4 years, outreach clinic attendees in one moderately remote and five very remote villages in rural Guyana were surveyed for the presence of rectal carriage of ciprofloxacin-resistant gram-negative bacilli (GNB). Drinking water was tested for the presence of resistant GNB by culture, and the presence of antibacterial agents and chloroquine by HPLC. The development of ciprofloxacin resistance in E. coli was examined after serial exposure to chloroquine. Patient and laboratory isolates of E. coli resistant to ciprofloxacin were assessed by PCR-sequencing for quinolone-resistance-determining-region (QRDR) mutations. RESULTS: In the very remote villages, 4.8% of patients carried ciprofloxacin-resistant E. coli with QRDR mutations despite no local availability of quinolones. However, there had been extensive local use of chloroquine, with higher prevalence of resistance seen in the villages shortly after a Plasmodium vivax epidemic (p<0.01). Antibacterial agents were not found in the drinking water, but chloroquine was demonstrated to be present. Chloroquine was found to inhibit the growth of E. coli in vitro. Replica plating demonstrated that 2-step QRDR mutations could be induced in E. coli in response to chloroquine. CONCLUSIONS: In these remote communities, the heavy use of chloroquine to treat malaria likely selected for ciprofloxacin resistance in E. coli. This may be an important public health problem in malarious areas

Non-Parametric Time-Series Analysis of Cortical Gamma Functional Connectivity Under General Anesthesia

The overall goal of my research is to better understand the mechanism of general anesthesia on the central nervous system with a special reference to the loss of consciousness. Studying the effects of anesthesia on sensory perception and consciousness necessitates the examination of the spatio-temporal distribution of neural events in the primary sensory and association cortical brain regions. In this study, I applied non-parametric spectral and information-theoretic time-series analyses to quantify concentration-dependent effect of general anesthetics on spontaneous and visually evoked local field potentials in rat primary visual (Vl), parietal association (PTA), and frontal (FR) cortices. I focused on gamma (20-60 Hz) frequency components of the local field potentials as these oscillations have been suggested to play a role in the mechanism underlying consciousness [l]. The importance of the selected cortical regions in visual awareness, selective attention and working memory has been previously demonstrated [2]. The loss of righting reflex, a generally accepted behavioral index of loss of consciousness in rat [3], was assessed simultaneously with the electrophysiological recordings in rat in awake and steady state graded levels of anesthesia bracketing the point of loss of consciousness. In an attempt to reveal a unitary component of the anesthetic action producing unconsciousness, I used three general anesthetic agents halothane, isoflurane, and desflurane. These anesthetic agents belong to the family of inhalational anesthetics but have slightly different chemical structures and potencies

Non-parametric time-series analysis of cortical gamma functional connectivity under general anesthesia

I seek to understand the mechanism of anesthetic ablation of consciousness. Gamma (20-60 Hz) oscillations in cortical neuronal activity have been associated with neural processes supporting conscious perception and action (Engel et al. 2001. Trends Cogn Sci ). In my dissertation, I examined the effect of volatile anesthetics halothane, isoflurane, and desflurane on spontaneous and visually evoked gamma activity in rat primary visual cortex. I also investigated the question whether these anesthetics at doses that produce unconsciousness may interfere with the exchange of information encoded in gamma oscillations between frontal and posterior regions. Spontaneous and event-related local field potentials to sixty light flashes presented every five seconds, were recorded with chronically implanted bipolar intracortical electrodes from rat primary visual, parietal association, and frontal cortical regions in the waking state and at increasing concentrations of halothane (0-2%), isoflurane (0-2%), and desflurane (0-10%). Also, the loss of righting reflex--a generally accepted behavioral index of the loss of consciousness in rat--was assessed as a function of steady-state graded anesthetic concentrations. The local field potentials were band-pass filtered at gamma frequencies. Thomson\u27s Multitaper power spectral analysis and wavelet decomposition were used to estimate gamma power and capture its temporal and spectral variations at the time scale of neuronal communication. Transfer entropy was calculated from wavelet-transformed flash-induced gamma oscillations to quantify feedforward and feedback information exchange among primary visual, parietal association, and frontal cortices. I showed that the three anesthetic agents studied augmented gamma power at the anesthetic concentrations producing unconsciousness. Since gamma power was not reduced even at surgical anesthetic levels, this finding suggested that gamma power alone is not a correlate of volatile anesthetic-induced loss of consciousness. On the other hand, I showed that halothane, isoflurane, and desflurane selectively decreased information transfer of the feedback projection at 50 Hz more than that of the feedforward projection between frontal and posterior cortical regions at similar anesthetic concentrations. This finding supports the role of cortical feedback projection in consciousness, and suggests that the disruption of information transfer at 50 Hz along the feedback projection is a likely neurophysiological correlate of the anesthetic-induced unconsciousness

EVS Trend File 1981-2017 – Sensitive Dataset

The European Values Study is a large-scale, cross-national and longitudinal survey research program on how Europeans think about family, work, religion, politics, and society. Repeated every nine years in an increasing number of countries, the survey provides insights into the ideas, beliefs, preferences, attitudes, values, and opinions of citizens all over Europe. The EVS Trend File 1981-2017 is constructed from the five EVS waves and covers almost 40 years. In altogether 160 surveys, more than 224.000 respondents from 48 countries/regions were interviewed. It is based on the updated data of the EVS Longitudinal Data File 1981-2008 (v.3.1.0) and the current EVS 2017 Integrated Dataset (v.5.0.0). For the EVS Trend File, a Restricted-Use File (ZA7504) is available in addition to the (factually anonymised) Scientific-Use File (ZA7503). The EVS Trend File – Sensitive Dataset (ZA7504) is provided as an add-on file. In addition to a small set of admin and protocol variables needed to merge with the SUF data, the Sensitive Dataset contains the following variables that could not be included in the scientific-use file due to their sensitive nature: W005_3 Job profession/industry (3-digit ISCO88) - spouse/partner EVS 2008W005_3_01 Job profession/industry (3-digit ISCO08) - spouse/partner EVS 2017W005_4 Job profession/industry (4-digit ISCO88) - spouse/partner EVS 2008X035_3 Job profession/industry (3-digit ISCO88) – respondent EVS 1999, EVS 2008 X035_3_01 Job profession/industry (3-digit ISCO08) - respondent EVS 2017X035_4 Job profession/industry (4-digit ISCO88) – respondent EVS 1999, EVS 2008 x048c_n3 Region where the interview was conducted (NUTS-3): NUTS version 2006 EVS 2008X048J_N3 Region where the interview was conducted (NUTS-3): NUTS version 2016 EVS 2017X049 Size of town (8 categories) EVS 2008, EVS 2017 Detailed information on the anonymization process in the EVS Trend File is provided in the EVS Trend File Variable Report