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Filter by:The investigators propose a behavioral experiment with SEEG recording and stimulation, to both confirm the role of a brain region known as the anterior insula in identifying surprise, and disambiguate between competing principles behind adaptation: optimizing and satisficing. Optimizers continue to learn and adapt if performance can be improved, while satisficers are satisfied with a good enough performance and will cease adapting once that is reached. To study surprise signals in the anterior insula, a brain structure where these signals have been very prominent, the investigators will employ an experiment with subjects who are under SEEG (stereoelectroencephalogram) recording, that is, recording from electrodes which have been surgically implanted in the brain. These recordings will be done as patients perform a task where they try to anticipate the movements of a target on a line in two different learning environments (conditions). The experimenters will then determine whether these signals reflect surprise relative to past engagement with the environment, or surprise that reveals that the agent no longer feels in control because uncertainty is not in line with the reference model. If evidence is consistent with the former, adaptation reflects traditional reinforcement and aims at optimizing behavior. If evidence instead is consistent with the latter, behavior is guided by a prior model (a reference model) and behavior is satisficing. An fMRI study by d'Acremont and Bossaerts provides initial evidence that activation in the anterior insula supports the satisficing hypothesis, however it lacks the temporal granularity to completely rule out optimizing. In the current project, the investigators propose to use the higher time resolution of SEEG recordings to confirm these findings and reject the optimizing hypothesis. Additionally, stimulations of the anterior insula during a subset of trials will be used to determine whether insular activation following surprise signals and preceding changes in behavior (learning) is merely correlational or in fact causal. Stimulation will allow us to determine to what extent the subjects' sense of control and subsequent behavior can be influenced in accordance with surprise-based modeling of behavior. The cohort for this study will be patients with drug-resistant, focal epilepsy and who are hospitalized at the Hôpitaux Universitaires de Genève (HUG) for pre-surgical evaluation of their epilepsy using SEEG. The protocol will run in parallel with the patients' clinical procedures.
The goal of this clinical trial is to evaluate the safety, tolerability, and pharmacokinetics (PK; drug metabolism) of DF-003 after oral administration of single and multiple ascending doses in healthy subjects. The choice of using healthy subjects is standard in establishing the preliminary safety and PK profile of a drug. DF-003 is a potent small molecule inhibitor of alpha-kinase 1 (ALPK1), which plays an important role in immunity and inflammation. DF-003 can inhibit the immune inflammatory response and has been shown to reduce renal fibrosis in preclinical models. Thus, this study aims to determine the role of DF-003 in the treatment of chronic kidney disease. This study will include 2 parts. Part 1 is a single ascending dose (SAD) phase with an optional food effect (FE) assessment, while Part 2 is a multiple ascending dose (MAD) phase. Part 1 - SAD Phase with optional FE assessment will include approximately 64 subjects (up to 8 cohorts of 8 subjects each) and Part 2 - MAD Phase will include approximately 32 subjects (up to 4 cohorts of 8 subjects each). Therefore, up to 96 subjects will be included in the study. Study participants will be screened approximately 42 days within the first scheduled administration of study medication. Screening data will be reviewed to determine subject eligibility. In Part 1, subjects will be randomly assigned to receive a single oral dose of DF-003 (3 x 1 milligram capsules) or matching placebo. The doses to be evaluated in Part 2 will be determined based on review of the available safety and PK data from Part 1. Subjects will be monitored for adverse events (AEs) and data will be collected for physical examination, eye examination, vital signs, 12-lead electrocardiogram (ECG), Holter monitoring, and clinical laboratory findings at various timepoints throughout the study.
This project aims to identify, through RNA-Seq technology, the genetic alterations underlying undiagnosed rare diseases in pediatric and adult patients with early onset and with negative WES. - Objective 1: Set up and validate techniques. Set-up and validation of the transcriptome analysis protocol in healthy subjects and in patients with known splicing alterations and/or altered RNA expression. - Objective 2: Diagnostic phase. Study of splicing alterations and RNA levels in cultured fibroblasts obtained from skin biopsies of patients with rare genetic diseases and negative exome. Exploratory goals - Compare the RNA expression profile obtained from skin biopsy-derived fibroblasts with the RNA expression profile from blood. The most relevant results will be validated in qRT-PCR. - To analyze the transcriptional and protein profile heterogeneity in skin-derived fibroblasts in enrolled subjects. To explore the effects of genetic (from WES) and transcriptional (from RNA-seq) alterations in participants' plasma and serum. Healthy controls Five healthy subjects will be recruited from the staff of the Mario Negri Institute for Pharmacological Research. The coded samples will be used to set up the method of isolation and culture of skin fibroblasts and RNA-Seq. Validation group For the set-up and validation of the skin fibroblast isolation and RNA-Seq procedure, ten adult patients with known diagnosis and with alterations in RNA levels and/or splicing will be recruited as positive controls. Patients who meet the requirements described above will be contacted by the doctors of the Daccò Center for an interview explaining the project. Those who agree to participate in the study will be asked to sign the informed consent before proceeding with the experimental part. "Discovery/Exploration" group The exploration cohort will be composed of 30 symptomatic undiagnosed patients with suspected genetic disease (children and adults with infantile onset) belonging to the Clinical Center of the Mario Negri Institute for Pharmacological Research and for whom WES investigations did not reveal causative genetic alterations.
The purpose of this study is to learn how different preparations of sisunatovir are taken up into the blood when taken on an empty stomach or with a meal in healthy adults. This study has two Parts and is seeking participants who: - are healthy males or females of 18 years of age or older. Part 1: All participants will receive treatments: A, B, and C. The participants will be assigned to take medicines A, B or C by chance, like drawing names out of a hat. All treatments will be taken by mouth. - Participants assigned to treatment A will take four capsules of sisunatovir on empty stomach. - Participants assigned to treatment B will take two sisunatovir tablets on empty stomach. - Participants assigned to treatment C will take two sisunatovir tablets with a high-fat meal. Part 2: All participants will receive treatments: B and D. The participants will be assigned to take medicines B and D by chance, like drawing names out of a hat. All treatments will be taken by mouth. - Participants assigned to treatment B will take two sisunatovir tablets on empty stomach. - Participants assigned to treatment D will take two sisunatovir tablets with a low-fat meal. The participants will be in the study clinic for 10 days in Part 1 and 7 days in Part 2, for: - safety checks, - sample collection for lab tests, - understanding how different preparations of sisunatovir are taken up into the blood when taken on an empty stomach or with a meal. All participants selected in the study will be required to go through a screening period up to 28 days. A screening period is the time during which a few participants are tested to see whether they are fit for the study. The participants can join the study only if they are tested be fit and are interested to take part in the study. The participants will be allowed to go home on Day 10 during Part 1, and on Day 7 during Part 2. About 28 to 35 days after being sent home following the final treatment, the participant will be contacted for a follow up visit either in person or by telephone. This is to check up on how the participant is doing and to end the study.
This study aimed to assess if nitrate supplementation influence motor unit (MU) activity following a sustained ischemic contraction and whether this is affected by blood flow restriction (BFR) during the recovery period. Fourteen male participants (mean ± SD, 25 ± 6 years) completed two experimental trials following 5-days of supplementation with either nitrate-rich (NIT) or nitrate-depleted (PLA) beetroot juice in a randomized, double-blinded, cross-over design. Intramuscular electromyography was used to assess MU potential (MUP) size and firing rates (MUFR) during a submaximal (25% MVC) sustained isometric contraction with BFR. These variables were also assessed during a 90 s recovery period with the first half completed with, and the second half completed without, BFR. Nitrate supplementation can expedite the recovery of MUP duration following a sustained ischemic contraction in healthy adults. These novel observations improve understanding of the effects of nitrate on the recovery of neuromuscular function post-exercise and might have implications for recovery of muscle contractile function.
This is an open-label, 2-Part, phase 1 study to evaluate drug interactions when DA-8010 is co-administered with Paroxetine or Mirabegron in healthy adult subjects
The purpose of the study is to assess whether high or low arch foot types influence the overall performance of the athlete.
This project aims to collect peripheral blood samples from newly diagnosed gastric cancer patients and healthy individuals. Various techniques such as cfDNA sequencing, proteomics, and fragmentomics will be employed to analyze differences in the expression of ctDNA mutations, fragmentomics, and protein biomarkers between gastric cancer patients and healthy individuals. A new comprehensive diagnostic model will be established and its diagnostic value (sensitivity, specificity, accuracy, etc.) for gastric cancer will be validated. Specifically, the study will involve the following subjects and quantities: 700 participants from Zhejiang Cancer Hospital (350 gastric cancer patients and 350 healthy individuals), 200 participants from Sichuan Cancer Hospital (100 gastric cancer patients and 100 healthy individuals), and 200 participants from the Sixth Affiliated Hospital of Sun Yat-sen University (100 gastric cancer patients and 100 healthy individuals). Peripheral blood samples (a total of 15mL from each participant, collected in 3 tubes) will be collected from all subjects. The collected blood samples will undergo multi-omics sequencing including cfDNA methylation sequencing, proteomics, and genomics to establish a multi-omics-based early diagnostic model.
This is an open-label, fixed-sequence, phase 1 study to evaluate the effect of clarithromycin/rifampicin on the pharmacokinetics of DA-8010 in healthy adults.
To determine whether there is an ipsilateral transfer of motor skill from the lower to the upper limb in healthy adults.