More smooth-spored species of Inocybe (): type studies and 12 new species from Europe.

Twelve new species of () are described from Europe on the basis of detailed morphological and molecular investigation. A portrait of the recently described is given. All species are smooth-spored and some pruinose only in the apical part of the stipe, and some on entire length.

Serum 4β-hydroxycholesterol increases during fluconazole treatment.

Purpose: The antifungal drugs ketoconazole and itraconazole reduce serum concentrations of 4β-hydroxycholesterol, which is a validated marker for hepatic cytochrome P450 (CYP) 3A4 activity. We tested the effect of another antifungal triazole agent, fluconazole, on serum concentrations of different sterols and oxysterols within the cholesterol metabolism to see if this inhibitory reaction is a general side effect of azole antifungal agents.

Methods: In a prospective, double-blind, placebo-controlled, two-way crossover design, we studied 17 healthy subjects (nine men, eight women) who received 400 mg fluconazole or placebo daily for 8 days.

Central encoding of the strength of intranasal chemosensory trigeminal stimuli in a human experimental pain setting.

An important measure in pain research is the intensity of nociceptive stimuli and their cortical representation. However, there is evidence of different cerebral representations of nociceptive stimuli, including the fact that cortical areas recruited during processing of intranasal nociceptive chemical stimuli included those outside the traditional trigeminal areas. Therefore, the aim of this study was to investigate the major cerebral representations of stimulus intensity associated with intranasal chemical trigeminal stimulation.

Machine-Learned Association of Next-Generation Sequencing-Derived Variants in Thermosensitive Ion Channels Genes with Human Thermal Pain Sensitivity Phenotypes.

Genetic association studies have shown their usefulness in assessing the role of ion channels in human thermal pain perception. We used machine learning to construct a complex phenotype from pain thresholds to thermal stimuli and associate it with the genetic information derived from the next-generation sequencing (NGS) of 15 ion channel genes which are involved in thermal perception, including , , , , , , , , , , , , , and . Phenotypic information was complete in 82 subjects and NGS genotypes were available in 67 subjects.

Delta-9-tetrahydrocannabinol reduces the performance in sensory delayed discrimination tasks. A pharmacological-fMRI study in healthy volunteers.

Background: Cannabis proofed to be effective in pain relief, but one major side effect is its influence on memory in humans. Therefore, the role of memory on central processing of nociceptive information was investigated in healthy volunteers.

Methods: In a placebo-controlled cross-over study including 22 healthy subjects, the effect of 20 mg oral Δ-tetrahydrocannabinol (THC) on memory involving nociceptive sensations was studied, using a delayed stimulus discrimination task (DSDT).

A data science approach to the selection of most informative readouts of the human intradermal capsaicin pain model to assess pregabalin effects.

Persistent and, in particular, neuropathic pain is a major healthcare problem with still insufficient pharmacological treatment options. This triggered research activities aimed at finding analgesics with a novel mechanism of action. Results of these efforts will need to pass through the phases of drug development, in which experimental human pain models are established components e.

A phylogenetic approach to a global supraspecific taxonomy of () with an emphasis on the southern mycota.

A section-based taxonomy of , covering large parts of the temperate North and South Hemispheres, is presented. Thirty-seven previously described sections are reviewed, while another forty-two sections are proposed as new or as new combinations. Twenty additional clades are recovered but not formally described.

Advances in the knowledge of the group (, ), through molecular and morphological studies.

constitutes a complex of species characterized by nodulose-angulose spores, absence of cortina and a more or less bulbous marginate stipe that is not darkening when desiccated. In order to elucidate species limits within the complex, an ITS-RPB2 phylogeny was performed and interpreted using morphological and ecological characters. Six supported clades were obtained in our analyses that correspond to , , and four new species to science: , , and .

Machine-learned analysis of the association of next-generation sequencing-based human TRPV1 and TRPA1 genotypes with the sensitivity to heat stimuli and topically applied capsaicin.

Heat pain and its modulation by capsaicin varies among subjects in experimental and clinical settings. A plausible cause is a genetic component, of which TRPV1 ion channels, by their response to both heat and capsaicin, are primary candidates. However, TRPA1 channels can heterodimerize with TRPV1 channels and carry genetic variants reported to modulate heat pain sensitivity.

Pathophysiological mechanisms of neuropathic pain: comparison of sensory phenotypes in patients and human surrogate pain models.

As an indirect approach to relate previously identified sensory phenotypes of patients suffering from peripheral neuropathic pain to underlying mechanisms, we used a published sorting algorithm to estimate the prevalence of denervation, peripheral and central sensitization in 657 healthy subjects undergoing experimental models of nerve block (NB) (compression block and topical lidocaine), primary hyperalgesia (PH) (sunburn and topical capsaicin), or secondary hyperalgesia (intradermal capsaicin and electrical high-frequency stimulation), and in 902 patients suffering from neuropathic pain. Some of the data have been previously published. Randomized split-half analysis verified a good concordance with a priori mechanistic sensory profile assignment in the training (79%, Cohen κ = 0.

Effects of oral Δ-tetrahydrocannabinol on the cerebral processing of olfactory input in healthy non-addicted subjects.

Background: Considering the increasing acknowledgment of the human sense of smell as a significant component of the quality of life, olfactory drug effects gain potential clinical importance. A recent observation in a human experimental context indicated that Δ-tetrahydrocannabinol (THC) impaired the subject's performance in olfactory tests. To further analyze the role of THC in human olfaction, the present report addresses its effects on the central processing of olfactory stimuli.

Quantitative sensory testing response patterns to capsaicin- and ultraviolet-B-induced local skin hypersensitization in healthy subjects: a machine-learned analysis.

The comprehensive assessment of pain-related human phenotypes requires combinations of nociceptive measures that produce complex high-dimensional data, posing challenges to bioinformatic analysis. In this study, we assessed established experimental models of heat hyperalgesia of the skin, consisting of local ultraviolet-B (UV-B) irradiation or capsaicin application, in 82 healthy subjects using a variety of noxious stimuli. We extended the original heat stimulation by applying cold and mechanical stimuli and assessing the hypersensitization effects with a clinically established quantitative sensory testing (QST) battery (German Research Network on Neuropathic Pain).

Pharmacoepigenetics of the role of DNA methylation in μ-opioid receptor expression in different human brain regions.

Aim: Exposure to opioids has been associated with epigenetic effects. Studies in rodents suggested a role of varying degrees of DNA methylation in the differential regulation of μ-opioid receptor expression across the brain.

Methods: In a translational investigation, using tissue acquired postmortem from 21 brain regions of former opiate addicts, representing a human cohort with chronic opioid exposure, μ-opioid receptor expression was analyzed at the level of DNA methylation, mRNA and protein.

Using a Standardized Clinical Quantitative Sensory Testing Battery to Judge the Clinical Relevance of Sensory Differences Between Adjacent Body Areas.

Background: Skin sensitivity to sensory stimuli varies among different body areas. A standardized clinical quantitative sensory testing (QST) battery, established for the diagnosis of neuropathic pain, was used to assess whether the magnitude of differences between test sites reaches clinical significance.

Methods: Ten different sensory QST measures derived from thermal and mechanical stimuli were obtained from 21 healthy volunteers (10 men) and used to create somatosensory profiles bilateral from the dorsum of the hands (the standard area for the assessment of normative values for the upper extremities as proposed by the German Research Network on Neuropathic Pain) and bilateral at volar forearms as a neighboring nonstandard area.

Determining threshold values for barcoding fungi: lessons from Cortinarius (Basidiomycota), a highly diverse and widespread ectomycorrhizal genus.

Different distance-based threshold selection approaches were used to assess and compare use of the internal transcribed spacer (ITS) region to distinguish among 901 Cortinarius species represented by >3000 collections. Sources of error associated with genetic markers and selection approaches were explored and evaluated using MOTUs from genus and lineage based-alignments. Our study indicates that 1%-2% more species can be distinguished by using the full-length ITS barcode as compared to either the ITS1 or ITS2 regions alone.

Brain Mapping-Based Model of Δ(9)-Tetrahydrocannabinol Effects on Connectivity in the Pain Matrix.

Cannabinoids receive increasing interest as analgesic treatments. However, the clinical use of Δ(9)-tetrahydrocannabinol (Δ(9)-THC) has progressed with justified caution, which also owes to the incomplete mechanistic understanding of its analgesic effects, in particular its interference with the processing of sensory or affective components of pain. The present placebo-controlled crossover study therefore focused on the effects of 20 mg oral THC on the connectivity between brain areas of the pain matrix following experimental stimulation of trigeminal nocisensors in 15 non-addicted healthy volunteers.

A small yet comprehensive subset of human experimental pain models emerging from correlation analysis with a clinical quantitative sensory testing protocol in healthy subjects.

Background: Picturing the complexity of pain in human experimental settings has increased the predictivity for clinical pain but requires increasingly complex test batteries. This raises problems in studies in which time is objectively limited, for example by the course of action of an analgesic drug. We addressed the selection of a small yet comprehensive set of pain tests for the use in such a situation.

Inverted Perceptual Judgment of Nociceptive Stimuli at Threshold Level following Inconsistent Cues.

Objective: The perception of pain is susceptible to modulation by psychological and contextual factors. It has been shown that subjects judge noxious stimuli as more painful in a respective suggestive context, which disappears when the modifying context is resolved. However, a context in which subjects judge the painfulness of a nociceptive stimulus in exactly the opposite direction to that of the cues has never been shown so far.

[Drug interactions in pain therapy].

Background: Pain is one of the most common reasons for consulting a physician. Chronic pain patients often suffer from a variety of comorbidities, such as depression and anxiety and they are therefore often simultaneously treated with more than one drug. The probability of drug interactions increases with every additional drug.

A more pessimistic life orientation is associated with experimental inducibility of a neuropathy-like pain pattern in healthy individuals.

Unlabelled: The clinical pattern of neuropathic pain, diagnosed using the quantitative sensory testing (QST) battery (German Research Network on Neuropathic Pain), could be partly mimicked in healthy volunteers after topical capsaicin application. However, similar to clinical neuropathic pain that develops in only a subgroup of patients who have a neurologic lesion, this attempt to mimick a neuropathic pain pattern succeeded only in a small fraction (18%) of healthy individuals. In the present assessment, we pursued the hypothesis that the inducible subgroup differed from the other healthy participants with respect to their psychological phenotype.

Multimodal distribution of human cold pain thresholds.

Background: It is assumed that different pain phenotypes are based on varying molecular pathomechanisms. Distinct ion channels seem to be associated with the perception of cold pain, in particular TRPM8 and TRPA1 have been highlighted previously. The present study analyzed the distribution of cold pain thresholds with focus at describing the multimodality based on the hypothesis that it reflects a contribution of distinct ion channels.

Pattern of neuropathic pain induced by topical capsaicin application in healthy subjects.

Human experimental pain models are widely used to study drug effects under controlled conditions, but they require further optimization to better reflect clinical pain conditions. To this end, we measured experimentally induced pain in 110 (46 men) healthy volunteers. The quantitative sensory testing (QST) battery (German Research Network on Neuropathic Pain) was applied on untreated ("control") and topical capsaicin-hypersensitized ("test") skin.

Lack of fluconazole effects on human chemosensation.

Objective: Drug effects on the function of smell and taste are occasionally mentioned in prescription information however, most originate from anecdotal reports without even distinguishing between gustatory or olfactory deteriorations. This includes the antifungal fluconazole.

Material And Methods: In a randomized, placebo-controlled, double-blind, two-way crossover study, 12 healthy men and 9 healthy women (age 26.

Cytochrome P450 epoxygenase dependence of opioid analgesia: fluconazole does not interfere with remifentanil-mediated analgesia in human subjects.

Cytochrome P450 (CYP) inhibitors may reduce opioid analgesia by inhibiting CYP activity-dependent post-opioid receptor signaling pathways in the brain. This suggestion was predicated on observations of highly attenuated morphine antinociception in rodents after intracerebroventricular injection of fluconazole or carrying a neuron-specific deletion of the cytochrome P450 reductase. However, based on assessments of thermal and electrical pain tolerance, respiratory function, and side effects in 21 healthy volunteers, before and during steady-state concentrations of 1.