Brain responses to hypnotic verbal suggestions predict pain modulation

Background: The effectiveness of hypnosis in reducing pain is well supported by the scientific literature. Hypnosis typically involves verbal suggestions but the mechanisms by which verbal contents are transformed into predictive signals to modulate perceptual processes remain unclear. We hypothesized that brain activity during verbal suggestions would predict the modulation of responses to acute nociceptive stimuli. Methods: Brain activity was measured using BOLD-fMRI in healthy participants while they listened to verbal suggestions of HYPERALGESIA, HYPOALGESIA, or NORMAL sensation (control) following a standardized hypnosis induction. Immediately after the suggestions, series of noxious electrical stimuli were administered to assess pain-related responses. Brain responses measured during the suggestions were then used to predict changes in pain-related responses using delayed regression analyses. Results: Listening to suggestions of HYPERALGESIA and HYPOALGESIA produced BOLD decreases (vs. control) in the parietal operculum (PO) and in the anterior midcingulate cortex (aMCC), and increases in the left parahippocampal gyrus (lPHG). Changes in activity in PO, aMCC and PHG during the suggestions predicted larger pain-evoked responses following the HYPERALGESIA suggestions in the anterior cingulate cortex (ACC) and the anterior insula (aINS), and smaller pain-evoked responses following the HYPOALGESIA suggestions in the ACC, aMCC, posterior insula (pINS) and thalamus. These changes in pain-evoked brain responses are consistent with the changes in pain perception reported by the participants in HYPERALGESIA and HYPOALGESIA, respectively. Conclusions: The fronto-parietal network (supracallosal ACC and PO) has been associated with self-regulation and perceived self-agency. Deactivation of these regions during suggestions is predictive of the modulation of brain responses to noxious stimuli in areas previously associated with pain perception and pain modulation. The response of the hippocampal complex may reflect its role in contextual learning, memory and pain anticipation/expectations induced by verbal suggestions of pain modulation. This study provides a basis to further explore the transformation of verbal suggestions into perceptual modulatory processes fundamental to hypnosis neurophenomenology. These findings are discussed in relation to predictive coding models

Polymorphisms in Plasmodium falciparum chloroquine resistance transporter and multidrug resistance 1 genes: parasite risk factors that affect treatment outcomes for P. falciparum malaria after artemether-lumefantrine and artesunate-amodiaquine.

Adequate clinical and parasitologic cure by artemisinin combination therapies relies on the artemisinin component and the partner drug. Polymorphisms in the Plasmodium falciparum chloroquine resistance transporter (pfcrt) and P. falciparum multidrug resistance 1 (pfmdr1) genes are associated with decreased sensitivity to amodiaquine and lumefantrine, but effects of these polymorphisms on therapeutic responses to artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL) have not been clearly defined. Individual patient data from 31 clinical trials were harmonized and pooled by using standardized methods from the WorldWide Antimalarial Resistance Network. Data for more than 7,000 patients were analyzed to assess relationships between parasite polymorphisms in pfcrt and pfmdr1 and clinically relevant outcomes after treatment with AL or ASAQ. Presence of the pfmdr1 gene N86 (adjusted hazards ratio = 4.74, 95% confidence interval = 2.29 - 9.78, P < 0.001) and increased pfmdr1 copy number (adjusted hazards ratio = 6.52, 95% confidence interval = 2.36-17.97, P < 0.001 : were significant independent risk factors for recrudescence in patients treated with AL. AL and ASAQ exerted opposing selective effects on single-nucleotide polymorphisms in pfcrt and pfmdr1. Monitoring selection and responding to emerging signs of drug resistance are critical tools for preserving efficacy of artemisinin combination therapies; determination of the prevalence of at least pfcrt K76T and pfmdr1 N86Y should now be routine

Sentinel network for monitoring in vitro susceptibility of Plasmodium falciparum to antimalarial drugs in Colombia: a proof of concept

Drug resistance is one of the principal obstacles blocking worldwide malaria control. In Colombia, malaria remains a major public health concern and drug-resistant parasites have been reported. In vitro drug susceptibility assays are a useful tool for monitoring the emergence and spread of drug-resistant Plasmodium falciparum. The present study was conducted as a proof of concept for an antimalarial drug resistance surveillance network based on in vitro susceptibility testing in Colombia. Sentinel laboratories were set up in three malaria endemic areas. The enzyme linked immunosorbent assay-histidine rich protein 2 and schizont maturation methods were used to assess the susceptibility of fresh P. falciparum isolates to six antimalarial drugs. This study demonstrates that an antimalarial drug resistance surveillance network based on in vitro methods is feasible in the field with the participation of a research institute, local health institutions and universities. It could also serve as a model for a regional surveillance network. Preliminary susceptibility results showed widespread chloroquine resistance, which was consistent with previous reports for the Pacific region. However, high susceptibility to dihydroartemisinin and lumefantrine compounds, currently used for treatment in the country, was also reported. The implementation process identified critical points and opportunities for the improvement of network sustainability strategies.PAHO [057-1-3144141]; COLCIENCIAS [ID 2229-405-20319]info:eu-repo/semantics/publishedVersio

Efficacy of artesunate-amodiaquine and artemether-lumefantrine fixed-dose combinations for the treatment of uncomplicated Plasmodium falciparum malaria among children aged six to 59 months in Nimba County, Liberia: an open-label randomized non-inferiority trial.

Prospective efficacy monitoring of anti-malarial treatments is imperative for timely detection of resistance development. The in vivo efficacy of artesunate-amodiaquine (ASAQ) fixed-dose combination (FDC) was compared to that of artemether-lumefantrine (AL) among children aged six to 59 months in Nimba County, Liberia, where Plasmodium falciparum malaria is endemic and efficacy data are scarce

Enhancement of the Electron Spin Resonance of Single-Walled Carbon Nanotubes by Oxygen Removal

We have observed a nearly fourfold increase in the electron spin resonance (ESR) signal from an ensemble of single-walled carbon nanotubes (SWCNTs) due to oxygen desorption. By performing temperature-dependent ESR spectroscopy both before and after thermal annealing, we found that the ESR in SWCNTs can be reversibly altered via the molecular oxygen content in the samples. Independent of the presence of adsorbed oxygen, a Curie-law (spin susceptibility $\propto 1/T$) is seen from $\sim$4 K to 300 K, indicating that the probed spins are finite-level species. For both the pre-annealed and post-annealed sample conditions, the ESR linewidth decreased as the temperature was increased, a phenomenon we identify as motional narrowing. From the temperature dependence of the linewidth, we extracted an estimate of the intertube hopping frequency; for both sample conditions, we found this hopping frequency to be $\sim$100 GHz. Since the spin hopping frequency changes only slightly when oxygen is desorbed, we conclude that only the spin susceptibility, not spin transport, is affected by the presence of physisorbed molecular oxygen in SWCNT ensembles. Surprisingly, no linewidth change is observed when the amount of oxygen in the SWCNT sample is altered, contrary to other carbonaceous systems and certain 1D conducting polymers. We hypothesize that physisorbed molecular oxygen acts as an acceptor ($p$-type), compensating the donor-like ($n$-type) defects that are responsible for the ESR signal in bulk SWCNTs.Comment: 14 pages, 7 figure

Absence of association between Plasmodium falciparum small sub-unit ribosomal RNA gene mutations and in vitro decreased susceptibility to doxycycline

BACKGROUND: Doxycycline is an antibiotic used in combination with quinine or artesunate for malaria treatment or alone for malaria chemoprophylaxis. Recently, one prophylactic failure has been reported, and several studies have highlighted in vitro doxycycline decreased susceptibility in Plasmodium falciparum isolates from different areas. The genetic markers that contribute to detecting and monitoring the susceptibility of P. falciparum to doxycycline, the pfmdt and pftetQ genes, have recently been identified. However, these markers are not sufficient to explain in vitro decreased susceptibility of P. falciparum to doxycycline. In this paper, the association between polymorphism of the small sub-unit ribosomal RNA apicoplastic gene pfssrRNA (PFC10_API0057) and in vitro susceptibilities of P. falciparum isolates to doxycycline were investigated. METHODS: Doxycycline IC50 determinations using the hypoxanthine uptake inhibition assay were performed on 178 African and Thai P. falciparum isolates. The polymorphism of pfssrRNA was investigated in these samples by standard PCR followed by sequencing. RESULTS: No point mutations were found in pfssrRNA in the Thai or African isolates, regardless of the determined IC50 values. CONCLUSIONS: The pfssrRNA gene is not associated with in vitro decreased susceptibility of P. falciparum to doxycycline. Identifying new in vitro molecular markers associated with reduced susceptibility is needed, to survey the emergence of doxycycline resistance

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Viscoelastic properties of acid milk gel as affected by fat nature at low level

International audienceThe viscoelastic properties of acid milk gels containing small amounts of different fats were investigated. Skim milk was reconstituted from ultra low-heat skim milk powder and emulsions made with 2% (v/v) sunflower oil, olive oil, groundnut oil, or anhydrous milk fat using a pressure homogenizer. Acidification at 20 °C for 14 h to pH ∼4.6 was achieved by adding glucono-δ-lactone to the emulsion. Stress relaxation testing enabled determination of the firmness and the solid-like properties, i.e., elasticity. Regardless of the physical state of the fat, emulsion gels exhibited higher firmness than fat-free gels, despite the low fat level used. The firmness of the gels containing this small quantity of fat was more sensitive to temperature than was the firmness of fat-free gels. The relaxation time was higher in the presence of fat crystals. Modifications in the rheological properties of gels containing fat were attributed to fat droplets acting as active filler particles