Healthy

Background: PDE4D is a protein found in the brain. It helps control chemical signals that affect mood, memory, and thinking. Problems with PDE4D may play a role in depression and Alzheimer's disease. Being able to measure PDE4D levels in the body would help doctors identify and manage these diseases. Researchers want to find out if a new tracer (a radioactive substance injected during imaging scans) can help them see PDE4D in people more effectively. Objective: To test a new tracer (\[11C\]JMJ-129-d2) during imaging scans of the brain and body in healthy people. Eligibility: Healthy people aged 18 years and older. They must have been screened under protocols 01M0254 or 17M0181. Design: All participants will give samples of blood and urine. They will have a test of their heart function. A plastic tube will be inserted into a vein in their arm; the new tracer will be given through this tube. Some participants will have 1 positron emission tomography (PET)/computed tomography (CT) scan of their whole body. They will lie on a padded bed that slides into a doughnut-shaped machine; the machine uses x-rays to create images of the inside of the body. Some participants will have 1 or 2 PET/CT scans of their brain only. Their head will be supported to keep it still during the scan. They will also have a magnetic resonance imaging (MRI) scan of the brain. MRI uses magnetic fields to capture images of the inside of the body. The MRI scan may require a second visit. All participants will receive a follow-up call to check on their well-being 1 to 3 business days after their scans.

Background: About 5 million adults in the United States have age-related brain disorders. These include Alzheimer disease (AD), mild cognitive impairment (MCI), and other dementias. The number of people with these disorders will likely increase as the population ages and life span increases. Inflammation is thought to play a role in AD and MCI. Researchers want to know if an enzyme called PDE4B increases inflammation in people with AD or MCI. Objective: To test whether medical imaging using a new radiotracer (\[18F\]PF-06445974) can measure PDE4B in the brains of people with AD or MCI. Eligibility: People aged 50 years and older with AD or MCI. Healthy volunteers are also needed. Design: Participants will have up to 5 clinic visits with 3 imaging scans of the brain. They will have be screened. They will have a physical exam with blood tests. This will include tests of their heart and nerve function, including memory. Participants will have 2 positron emission tomography (PET) scans. One will use a standard radiotracer. The other will use the study radiotracer. They will receive each tracer through a tube attached to a needle inserted into a vein. During the scan with the study tracer, participants will have a second tube inserted into a vein in the wrist; this tube will be used to draw blood during the scan. Participants will lie on a bed that slides into a doughnut-shaped machine. These visits will take about 6 hours each. Participants will have 1 magnetic resonance imaging (MRI) scan. They will lie on a bed that slides into a cylinder. This visit will take up to 2 hours....

Background: Infections in the lower respiratory tract (lungs) are the leading cause of death from infectious disease worldwide. This was true even before the COVID-19 pandemic. Respiratory viruses are still a major health threat. Many of these viruses infect people by penetrating the thin skin that lines the nose. These viruses can also spread easily to other people when they multiply in the tissues that line the nose. Researchers want to learn more about what these viruses do inside the nose, how they get from the nose to the lungs, and how they spread from person to person. Objective: To collect cell samples from inside the noses of healthy people. These cells will be stored for use in future research on respiratory diseases. Eligibility: Healthy volunteers aged 18 years and older. Design: Most participants will have 1 visit on 1 day. They will be asked questions. Those who have a runny nose, coughing, congestion, or fever will be asked to wait up to 21 days before participating. Participants will be given a slender swab with small bristles at the end. They will rub the inside of their nose with the swab. A clinic staff member will be present to help, if needed. Participants will provide their name, age, and sex. This information will be encoded so that only certain researchers will know the participants identities. Participants will not be contacted again....

The purpose of the study is to assess how LY4355756 is absorbed by the body and how safe it is to healthy participants. There will be four inpatient stays at the clinical research unit (CRU). For Part A there will be 5 continuous days, Part B 22 continuous days, Part C 5 continuous days in each of the 3 periods, and Part D 18 continuous days in the CRU.

The purpose of this study is to investigate the safety and tolerability of LY4298445 in healthy participants and in participants with systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA). Participation in the study will last up to approximately 52 weeks.

Researchers are looking for new ways to prevent cancers related to human papillomavirus (HPV). HPV is a common virus that can cause an infection. There are many different types of HPV. Most people's immune system can fight HPV infection and it goes away without treatment. For some people, HPV infections can last longer and may cause cancer years later. A standard vaccine to prevent HPV-related cancers is GARDASIL®9 (G9). G9 protects against 9 types of HPV but it does not protect against other types of HPV. The study vaccine (called V540B) is designed to protect against the same HPV types that G9 protects against plus other HPV types. The main goal of this study is to learn about the safety of V540B in healthy adults and if people tolerate it.

Background: \- Magnetic resonance imaging (MRI) scans must be performed according to specified sets of parameters that provide optimal images of each organ and each area of the body. These scanning parameters are often specific to the institution or organization at which they are employed, and may also depend on the manufacturer of the MRI scanning equipment. Because MRI scanning equipment is always being updated and upgraded, researchers are interested in developing new and optimized scanning parameters for MRI scans. Objectives: \- To improve current methods and develop new techniques for magnetic resonance imaging. Eligibility: * Individuals 18 years of age and older who are either volunteers or current NIH protocol participants. * Participants must not have any medical history factors (e.g., extreme claustrophobia, history of metal implants) that would prevent them from receiving MRI scans. Design: * Participants will have at least one MRI scan that will last from 20 minutes to 2 hours (most scans will last between 45 and 90 minutes). The total time commitment for most visits will be approximately 4 hours from start to finish. * Some MRI techniques require standard monitoring equipment or specific procedures during the scanning, such as an electrocardiogram. * Participants will have blood samples taken at the time of the scan. Some MRI studies will require the use of a contrast agent that will be administered during the scan. * Volunteers may be asked to return for additional MRI scans over the course of a few years. Follow-up scans may be done on the same part of the body or on different parts of the body. No more than one MRI scan will be performed in any 4-week period for this protocol....

The purpose of this investigation is to develop improved magnetic resonance imaging (MRI) techniques and hardware for studying brain function. MRI is a diagnostic tool that provides information about brain chemistry and physiology. This study will evaluate new MRI methods for monitoring blood flow to regions of the brain in response to simple tasks. The MRI machine used in this study is more powerful than those in most hospitals, permitting a higher visual resolution. Normal healthy volunteers over 18 years old may be eligible for this study. Candidates will be screened with a medical history and questionnaire, and a neurological examination. Study participants will have a yearly MRI scan. For this procedure, the subject lies on a stretcher that is moved into a donut-shaped machine with a strong magnetic field. A lightweight circular or rectangular coil-a device that improves the quality of the images-may be placed on the head. The scan time varies from 20 minutes to 3 hours; most scans last between 45 and 90 minutes. During the scan, the subject may perform simple tasks, such as listening to tapes, tapping a finger, moving a hand, watching a screen, or smelling a fragrance. More complex tasks may require thinking about tones or pictures and responding to them by pressing buttons. Information from this study will be used to develop better imaging methods that will, in turn, permit a greater understanding of normal and abnormal brain behaviors. ...

This study evaluates the collection of dermal interstitial fluid using a vacuum-assisted microneedle device in healthy adult volunteers. The study will assess the device-based collection procedure and characterize the collected dermal interstitial fluid. Healthy adult volunteers will undergo dermal interstitial fluid collection using a vacuum-assisted microneedle device at the Stanford study site. Participants will complete the study procedures described in the protocol, which may include device application, vacuum-assisted microneedle sampling, collection and analysis of dermal interstitial fluid, assessment of procedure-related effects, and follow-up as specified by the study protocol.

This is a single-centre, open-label, fixed-sequence, 2-period study in healthy participants. The total study duration for each participant will be up to approximately 56 days, including a 28-day screening period, a 19-day assessment period (including Period 1 and Period 2), and a follow-up (FU) visit approximately 7 days after clinical research unit (CRU) discharge.

The purpose of this study is to evaluate how well LY4088044 is tolerated and what side effects may occur in healthy participants. The study drug will be administered either subcutaneously (SC) (under the skin) or intravenously (IV) (into a vein in the arm). Blood tests will be performed to check how much LY4088044 gets into the bloodstream and how long it takes the body to eliminate it. The study will last up to approximately 92 weeks for Parts A, B, and C, excluding screening.

The approach of a competition can be associated to a decrease in sleep duration and quality which can negatively impact athlete's performance and health (injury risk, fall, accident). Ultra-endurance competitions even involve partial and/or total sleep deprivation over one or several nights. Studied investigating this question suggest that endurance performance under sleep deprivation is altered, mainly because of an effect on the rate of perceived exertion (RPE), which regulates effort intensity. One of the methods used by athletes to limit the impact of sleep deprivation in competition is to implement sleep extension in the days prior to a competition. However, few studies have investigated the impact of sleep deprivation et its reproducibility on performance and fatigue during a prolonged running exercise, as well as the efficiency of prior sleep extension. The importance of such a preventive measure might also depend on individual resistance to sleep deprivation, which is variable between persons and could have genetic determinants. This aspect remains under-studied, particularly regarding the impact of sleep deprivation on physical performance. Therefore, this study aims at investigating the effects of sleep deprivation and prior sleep extension on prolonged duration performance.

Objective: To use clinical, genetic and genome analysis to better understand and define the genetic and environmental factors that contribute to IBD within affected populations.

The purpose of this study is to determine the effect of obesity on cardiovascular responses during various breathing maneuvers.

Background: \- Imaging tests, such as magnetic resonance imaging (MRI), can provide information about heart and blood vessels. The tests let doctors can see the amount of blood vessel narrowing and vessel wall thickness. This information may help diagnose and treat heart disease and other conditions that lead to heart attacks. Better MRI methods are needed to improve heart disease diagnosis, especially by avoiding the use of radiation. Researchers are testing new techniques to improve the quality of heart MRI, compared with more complex studies like catheterization or angiography. Objectives: \- To compare heart MRI techniques with other tests used to diagnose heart disease. Eligibility: \- People at least 18 years of age who either have or may have heart disease, or are healthy volunteers. Design: * Participants will be screened with a physical exam, medical history, and blood tests. * They will have an angiography to study the inside of blood vessels. This test is an x-ray study of the blood vessels. It will be done either separately or as part of a set of tests to diagnose possible heart disease. * Participants will have at least one and up to five MRI scans. The scans will involve different methods of studying the heart and blood vessels. Participants may also have a computed tomography scan to confirm the findings of an MRI scan. * No treatment will be provided as part of this protocol.

The main purpose of this study is to evaluate how the body handles \[¹⁴C\]-LY4515100. The study will investigate how much \[¹⁴C\]-LY4515100 enters the bloodstream from the stomach or intestines and is available to have an effect on the body, how the body changes \[¹⁴C\]-LY4515100 so that it can be used or removed, and how the body gets rid of \[¹⁴C\]-LY4515100. For each participant, the study will last about 9 weeks and will include a Clinical Research Unit (CRU) stay lasting between 10 and 30 days.

Researchers are looking for new treatments for pain. The goal of this trial is to learn if MK-6916 changes what happens to the midazolam and rosuvastatin in healthy participants' bodies. Researchers will compare the amount of midazolam and rosuvastatin in a participant's body over time when they are given with and without MK-6916.

Researchers are looking for new treatments for people living with HIV-1 (Human Immunodeficiency Virus Type 1). HIV-1 is the most common type of HIV, which is a virus that attacks cells of the immune system. MK-4646 is a trial medicine designed to treat HIV-1. Before giving a trial medicine to people with a health condition, researchers first do studies in healthy participants. The goals of this trial are to learn: * What happens to rosuvastatin in a participant's body over time when it is taken with MK-4646 * About the safety of MK-4646 when taken with rosuvastatin and if people tolerate it. Tolerate means participants will receive trial medicine in the trial unless they need to stop it due to health problems.

The purpose of this trial is to compare what happens to MK-1406 in the body of healthy participants when it is given as 2-injections and 3-injections. Researchers also want to learn about the safety of MK-1406 and if people tolerate it.

The goal of this study is to learn about the safety and immune response to the V132 vaccine in healthy older adults.

This study investigates the causal effects of low-intensity transcranial focused ultrasound (tFUS) on odor valence perception and odor-elicited avoidance behaviors in healthy adults. Participants undergo sham and active tFUS targeting the amygdala (AMYG) and ventral striatal olfactory tubercle (VSOT) in a within-subject, randomized, sham-controlled crossover design. Outcomes include subjective odor ratings and objective neurophysiological and behavioral indices of odor valence processing. This research is exploratory and mechanistic in nature and is not intended to evaluate clinical safety or therapeutic efficacy.

This study is open to adults aged between 18 and 80 years of age with a body mass index (BMI) of 18.5 to 42 kg/m². People with or without liver problems can take part in the study. The purpose of this study is to find out how much of a medicine called BI 1291583 gets into the blood of people with and without liver problems. BI 1291583 is being developed to treat people with bronchiectasis, a chronic disease of the lungs. People living with this condition often also have liver problems. Therefore, it is important to find out whether liver problems influence the amount of BI 1291583 that gets into the blood. Study participants receive a single dose of BI 1291583 as a tablet taken by mouth. Participants are divided into 4 groups based on how well their liver works: 1 group without liver problems, and 3 groups with mild, moderate, and severe liver problems. Each participant without liver problems is matched with participants from the other groups based on factors such as age, sex, smoking habits, and body weight to ensure accurate comparisons. Participants are in the study for about 3 months. They stay for 3 days at the study site and also visit the study site up to 9 times. During these visits, the doctors collect information about participants' health. To assess the study endpoints, the doctors regularly take blood samples from the participants. The doctors regularly check participants' health and take note of any unwanted effects.

Background: When people have a stroke, they often have difficulty moving their arms and hands. Transcranial magnetic stimulation (TMS) can improve how well people with and without stroke can move their arms and hands. But the effects of TMS are minor, and it doesn t work for everyone. Researchers want to study how to time brain stimulation so that the effects are more consistent. Objective: To understand how the brain responds to transcranial magnetic stimulation so that treatments for people with stroke can be improved. Eligibility: Adults ages 18 and older who had a stroke at least 6 months ago Healthy volunteers ages 50 and older Design: Participants will have up to 5 visits. At visit 1, participants will be screened with medical history and physical exam. Participants with stroke will also have TMS and surface electromyography (sEMG). For TMS, a brief electrical current will pass through a wire coil on the scalp. Participants may hear a click and feel a pull. Muscles may twitch. Participants may be asked to do simple movements during TMS. For sEMG, small electrodes will be attached to the skin and muscle activity will be recorded. At visit 2, participants will have magnetic resonance imaging (MRI). They will lie on a table that slides into a metal cylinder in a strong magnetic field. They will get earplugs for the loud noise. At visit 3, participants will have TMS, sEMG, and electroencephalography (EEG). For EEG, small electrodes on the scalp will record brainwaves. Participants will sit still, watch a movie, or do TMS. Participants may be asked to have 2 extra visits to redo procedures.

This is a double-blind, placebo-controlled, parallel-group, study evaluating the effect of a Qualia Vitamin C+ formulation on Whole Blood Vitamin C levels in the blood of healthy adults aged 25 years or older that have suboptimal vitamin C blood levels (i.e., 0.4 - 0.9 mg/dL) and those with adequate vitamin C blood levels (≥0.9 mg/dL). Approximately 152 (76 in the suboptimal stratum and 76 in the adequate stratum) participants will be assigned to one of two study arms: Qualia Vitamin C+ or placebo. Each participant will take two capsules of their assigned product once daily in the morning, with or without food, over a 28-day period. The primary outcome is the change in blood vitamin C levels in the suboptimal stratum, assessed via lab blood collection at baseline and study completion. Secondary endpoints include the change in blood vitamin C levels, assessed via lab blood collection at baseline and study completion in the entire group, questionnaires measuring health-related Quality of Life and fatigue (RAND-36 and the FACIT-Fatigue Scale), the Single-item Assessment of Immune Fitness, evaluation of safety and tolerability, and an Overall Experience Questionnaire. Further, a sub-group analysis of fatigued participants meeting at least mild to moderate fatigue as measured by the FACIT-Fatigue will be a secondary objective. The NCI Fruits and Vegetable Screener - All-Day Screener will also be used to assess intake at baseline and study completion. All assessments, including electronic questionnaires, are completed remotely without in-person visits.

Twenty healthy adults (≥21 years old) will be enrolled to evaluate the efficacy of a single oral dose of psilocybin (25 mg) administered with or without pretreatment using oral pimavanserin (34 mg) or placebo. Outcome assessments will occur at 1 week and 1 month following psilocybin administration. The purpose of this study is to clarify the receptor-level mechanisms underlying psilocybin's effects on mood and well-being, along with the associated neurophysiologic signatures. These mechanisms will be examined using psychometric scales, autonomic and fMRI-based neurophysiologic markers, and integrated pharmacokinetic/pharmacodynamic modeling.