Executive function deficits, common in psychiatric disorders, hinder daily activities and may be linked to diminished neural plasticity, affecting treatment and training responsiveness. In this pioneering study, we evaluated the feasibility and preliminary efficacy of psilocybin-assisted frontal-midline theta neurofeedback (NF), a neuromodulation technique leveraging neuroplasticity, to improve executive functions (EFs). Thirty-seven eligible participants were randomized into an experimental group (n = 18) and a passive control group (n = 19). The experimental group underwent three microdose sessions and then three psilocybin-assisted NF sessions, without requiring psychological support, demonstrating the approach's feasibility. NF learning showed a statistical trend for increases in frontal-midline theta from session to session with a large effect size and non-significant but medium effect size dynamical changes within sessions. Placebo effects were consistent across groups, with no tasks-based EF improvements, but significant self-reported gains in daily EFs-working memory, shifting, monitoring and inhibition-showing medium and high effect sizes. The experimental group's significant gains in their key training goals underscored the approach's external relevance. A thorough study with regular sessions and an active control group is crucial to evaluate EFs improvement and their specificity in future. Psilocybin-enhanced NF could offer significant, lasting benefits across diagnoses, improving daily functioning. This article is part of the theme issue 'Neurofeedback: new territories and neurocognitive mechanisms of endogenous neuromodulation'.

• MeSH
• Adult MeSH
• Executive Function * drug effects   MeSH
• Humans MeSH
• Young Adult MeSH
• Neurofeedback * methods   MeSH
• Psilocybin * pharmacology   MeSH
• Feasibility Studies * MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Randomized Controlled Trial MeSH

Alergie na roztoče patří mezi jednu z nejčastějších příčin alergické rýmy. Mezi hlavní druhy roztočů bytového prachu patří Dermatophagoides pteronyssinus a Dermatophagoides farinae. Alergická rýma způsobená roztoči bytového prachu je vysoce rozšířené, ale často poddiagnostikované a nedostatečně léčené chronické onemocnění. Má negativní dopad na spánek, práci, volnočasové aktivity a kvalitu života. Pacienti alergičtí na roztoče mají výrazně vyšší riziko vývoje do astmatu ve srovnání s pylovými alergiky. Alergenová imunoterapie má chorobu modifikující účinek, potenciál zabránit další progresi alergických projevů a navozuje vznik alergen specifické imunologické tolerance, přetrvávající několik let po jejím ukončení. K novým možnostem alergenové imunoterapie řadíme sublingvální alergenovou imunoterapii v podobě 300 IR HDM SLIT tablety, která je nyní dostupná i v České republice. Je prokázáno, že je tato léčba efektivní a dobře tolerovaná. Článek prezentuje výsledky klinických studií před uvedením léku na trh.

Allergy to dust mites is one of the most common causes of allergic rhinitis. The two main species od house dust mites are Dermatophagoides pteronyssinus and Dermatophagoides farinae. Allergic rhinitis induced by dust mites is a highly prevalent but often underdiagnosed and undertreated chronic disease. It has a negative impact on sleep, work, leisure activities and quality of life. Patients allergic to dust mites have a significantly higher risk of developing into asthma than those allergic to pollens. Allergen immunotherapy has a disease-modifying effect, the potential to prevent further progression of allergic symptoms and induces allergen-specific immunological tolerance persisting for several years after its cessation. New options for allergen immunotherapy include sublingual allergen immunotherapy by 300 IR HDM SLIT tablet, which is now available in the Czech Republic. This treatment is proven to be effective and well tolerated. The article presents the results of clinical trials before the drug was marketed.

• Keywords
• 300 IR HDM Slit tableta /Actair/, Evropská klinická studie, Globální studie,
• MeSH
• Rhinitis, Allergic * diagnosis   prevention & control   therapy   MeSH
• Dust Mite Allergy * complications   MeSH
• Allergoids administration & dosage   therapeutic use   MeSH
• Antigens, Dermatophagoides MeSH
• Asthma MeSH
• Clinical Trials, Phase I as Topic MeSH
• Clinical Trials, Phase II as Topic MeSH
• Clinical Trials, Phase III as Topic MeSH
• Humans MeSH
• Risk Factors MeSH
• Sublingual Immunotherapy * MeSH
• Check Tag
• Humans MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH

Animal testing has made a significant and unequalled contribution to important discoveries and advancements in the fields of research, medicine, vaccine development, and drug discovery. Each year, millions of animals are sacrificed for various experiments, and this is an ongoing process. However, the debate on the ethical and sensible usage of animals in in vivo experimentation is equally important. The need to explore and adopt newer alternatives to animals so as to comply with the goal of reduce, refine, and replace needs attention. Besides the ever-increasing debate on ethical issues, animal research has additional drawbacks (need of trained labour, requirement of breeding area, lengthy protocols, high expenses, transport barriers, difficulty to extrapolate data from animals to humans, etc.). With this scenario, the present review has been framed to give a comprehensive insight into the possible alternative options worth exploring in this direction especially targeting replacements for animal models of bacterial infections. There have been some excellent reviews discussing on the alternate methods for replacing and reducing animals in drug research. However, reviews that discuss the replacements in the field of medical bacteriology with emphasis on animal bacterial infection models are purely limited. The present review discusses on the use of (a) non-mammalian models and (b) alternative systems such as microfluidic chip-based models and microdosing aiming to give a detailed insight into the prospects of these alternative platforms to reduce the number of animals being used in infection studies. This would enlighten the scientific community working in this direction to be well acquainted with the available new approaches and alternatives so that the 3R strategy can be successfully implemented in the field of antibacterial drug research and testing.

• MeSH
• Bacterial Infections * prevention & control   veterinary   MeSH
• Animal Experimentation * MeSH
• Humans MeSH
• Models, Animal MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

• Keywords
• dostarlimab, studie GARNET,
• MeSH
• Antibodies, Monoclonal, Humanized * adverse effects   therapeutic use   MeSH
• Clinical Trials, Phase I as Topic MeSH
• Middle Aged MeSH
• Humans MeSH
• Neoplasm Metastasis therapy   MeSH
• Multicenter Studies as Topic MeSH
• Endometrial Neoplasms * surgery   drug therapy   classification   MeSH
• Recurrence MeSH
• Insurance, Health, Reimbursement MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Female MeSH
• Publication type
• Case Reports MeSH

• Keywords
• Koselugo, selumetinib,
• MeSH
• Child MeSH
• Clinical Trials, Phase I as Topic MeSH
• Clinical Trials, Phase II as Topic MeSH
• Humans MeSH
• Mitogen-Activated Protein Kinase Kinases * drug effects   MeSH
• Neurofibromatosis 1 * drug therapy   MeSH
• Antineoplastic Agents pharmacokinetics   pharmacology   therapeutic use   MeSH
• Drug Labeling MeSH
• Check Tag
• Child MeSH
• Humans MeSH

Hodgkinův lymfom lze v 80 až 90 % případů vyléčit první linií léčby. Brentuximab vedotin je konjugát chimérické monoklonální protilátky IgG1 anti-CD30 a monomethylauristatinu E. Nový mechanismus účinku brentuximab vedotinu, jeho účinnost v monoterapii a v kombinaci s chemoterapií nebo s inhibitory proteinu programované buněčné smrti 1 (programmed cell death protein 1, PD-1) v první linii léčby a v relapsu u Hodgkinova lymfomu a profil toxicity zlepšily prognózu těchto pacientů. V přehledovém článku jsou uvedeny výsledky klinických studií s brentuximab vedotinem u Hodgkinova lymfomu.

Hodgkin's lymphoma can be cured by the first-line treatment in 80% 90% of cases. Brentuximab vedotin is a chimeric IgG1 anti-CD30 antibody-drug conjugate with monomethylauristatin E. Novel mechanism of action of brentuximab vedotin, its activity in monotherapy and in combination with chemotherapy or with programmed cell death protein 1 inhibitors (anti-PD-1) in the front-line setting and in relapsed Hodgkin's lymphoma and toxicity profile improved prognosis of these patients. This review summarizes results of clinical trials including brentuximab vedotin for patients with Hodgkin's lymphoma.

• MeSH
• Ki-1 Antigen MeSH
• Brentuximab Vedotin * therapeutic use   MeSH
• Hodgkin Disease * drug therapy   MeSH
• Immunotoxins therapeutic use   MeSH
• Clinical Trials, Phase I as Topic MeSH
• Clinical Trials, Phase II as Topic MeSH
• Humans MeSH
• Recurrence MeSH
• Check Tag
• Humans MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH

BACKGROUND: Microdoses of psychedelics (i.e. a sub-hallucinogenic dose taken every third day) can reduce symptoms of depression, anxiety and stress according to anecdotal reports and observational studies. Research with medium to high doses of psilocybin points towards potential underlying mechanisms, including the modulation of emotion and interoceptive processing. AIMS: In this preregistered study, we investigated whether psilocybin microdoses alter self-reported interoceptive awareness and whether repeated microdosing over 3 weeks modulates emotion processing and reduces symptoms of anxiety and depression. METHODS: We used a double-blind, placebo-controlled, within-subject crossover design. Participants completed the Multidimensional Assessment of Interoceptive Awareness Questionnaire 11⁄2 h after self-administering their second dose (or placebo), and the emotional go/no-go task and the shortened Depression Anxiety Stress Scale 11⁄2 h after self-administering their seventh dose. RESULTS: Our confirmatory analyses revealed that psilocybin microdosing did not affect emotion processing or symptoms of anxiety and depression compared with placebo. Our exploratory analyses revealed that psilocybin microdosing did not affect self-reported interoceptive awareness, that symptoms of depression and stress were significantly reduced in the first block compared with baseline, that participants broke blind in the second block and that there was no effect of expectations. Further research in a substance-naïve population with clinical range anxiety and depressive symptoms is needed to substantiate the potential beneficial effects of microdosing.

• MeSH
• Depression drug therapy   MeSH
• Adult MeSH
• Double-Blind Method MeSH
• Emotions drug effects   MeSH
• Hallucinogens administration & dosage   pharmacology   MeSH
• Cross-Over Studies MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Surveys and Questionnaires MeSH
• Psilocybin administration & dosage   pharmacology   MeSH
• Anxiety drug therapy   MeSH
• Dose-Response Relationship, Drug MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Randomized Controlled Trial MeSH

The use of low sub-perceptual doses of psychedelics ("microdosing") has gained popularity in recent years. Although anecdotal reports claim multiple benefits associated with this practice, the lack of placebo-controlled studies severely limits our knowledge of microdosing and its effects. Moreover, research conducted in standard laboratory settings could fail to capture the motivation of individuals engaged or planning to engage in microdosing protocols, thus underestimating the likelihood of positive effects on creativity and cognitive function. We recruited 34 individuals starting to microdose with psilocybin mushrooms (Psilocybe cubensis), one of the materials most frequently used for this purpose. Following a double-blind placebo-controlled experimental design, we investigated the acute and short-term effects of 0.5 g of dried mushrooms on subjective experience, behavior, creativity (divergent and convergent thinking), perception, cognition, and brain activity. The reported acute effects were significantly more intense for the active dose compared to the placebo, but only for participants who correctly identified their experimental condition. These changes were accompanied by reduced EEG power in the theta band, together with preserved levels of Lempel-Ziv broadband signal complexity. For all other measurements there was no effect of microdosing except for few small changes towards cognitive impairment. According to our findings, low doses of psilocybin mushrooms can result in noticeable subjective effects and altered EEG rhythms, but without evidence to support enhanced well-being, creativity and cognitive function. We conclude that expectation underlies at least some of the anecdotal benefits attributed to microdosing with psilocybin mushrooms.

• MeSH
• Agaricales * MeSH
• Double-Blind Method MeSH
• Hallucinogens * pharmacology   MeSH
• Humans MeSH
• Motivation MeSH
• Psilocybin pharmacology   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Randomized Controlled Trial MeSH

RATIONALE: Serotonergic psychedelics are being studied as novel treatments for mental health disorders and as facilitators of improved well-being, mental function, and creativity. Recent studies have found mixed results concerning the effects of low doses of psychedelics ("microdosing") on these domains. However, microdosing is generally investigated using instruments designed to assess larger doses of psychedelics, which might lack sensitivity and specificity for this purpose. OBJECTIVES: Determine whether unconstrained speech contains signatures capable of identifying the acute effects of psilocybin microdoses. METHODS: Natural speech under psilocybin microdoses (0.5 g of psilocybin mushrooms) was acquired from thirty-four healthy adult volunteers (11 females: 32.09 ± 3.53 years; 23 males: 30.87 ± 4.64 years) following a double-blind and placebo-controlled experimental design with two measurement weeks per participant. On Wednesdays and Fridays of each week, participants consumed either the active dose (psilocybin) or the placebo (edible mushrooms). Features of interest were defined based on variables known to be affected by higher doses: verbosity, semantic variability, and sentiment scores. Machine learning models were used to discriminate between conditions. Classifiers were trained and tested using stratified cross-validation to compute the AUC and p-values. RESULTS: Except for semantic variability, these metrics presented significant differences between a typical active microdose and the inactive placebo condition. Machine learning classifiers were capable of distinguishing between conditions with high accuracy (AUC [Formula: see text] 0.8). CONCLUSIONS: These results constitute first evidence that low doses of serotonergic psychedelics can be identified from unconstrained natural speech, with potential for widely applicable, affordable, and ecologically valid monitoring of microdosing schedules.

• MeSH
• Adult MeSH
• Mental Disorders * MeSH
• Double-Blind Method MeSH
• Hallucinogens * pharmacology   MeSH
• Language MeSH
• Creativity MeSH
• Humans MeSH
• Psilocybin pharmacology   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

There is an increased societal trend to engage in microdosing, in which small sub-hallucinogenic amounts of psychedelics are consumed on a regular basis. Following subjective reports that microdosing enhances the experience of nature and art, in the present study we set out to study the effects of psilocybin microdosing on feelings of awe and art perception. In this preregistered combined field- and lab-based study, participants took part in a microdosing workshop after which they volunteered to self-administer a psilocybin microdose or a placebo for three consecutive weeks, while the condition was kept blind to the participants and researchers. Following a 2-week break, the condition assignment was reversed. During each block, participants visited the lab twice to measure the effects of psilocybin microdosing vs. placebo. We used standardized measures of awe, in which participants reported their experiences in response to short videos or when viewing abstract artworks from different painters. Our confirmatory analyses showed that participants felt more awe in response to videos representing funny animals and moving objects in the microdosing compared to the placebo condition. However, about two-third of our participants were breaking blind to their experimental condition. Our exploratory findings suggest that expectancy-effects may be a driving factor underlying the subjective benefits of microdosing.

• MeSH
• Esthetics MeSH
• Hallucinogens * pharmacology   MeSH
• Humans MeSH
• Surveys and Questionnaires MeSH
• Psilocybin * pharmacology   MeSH
• Dose-Response Relationship, Drug MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH