Healthy

The goal of this clinical trial is to learn if BLKR201 is safe in healthy adults. Researchers will also learn how the body absorbs and processes BLKR201 and how food may affect it. The main questions this study aims to answer are: * Is BLKR201 safe and well tolerated when taken as a single dose or for several days in a row? * How does BLKR201 move through and leave the body? * Does taking BLKR201 with food change how the body absorbs it? Researchers will compare BLKR201 to a placebo (a look-alike tablet that contains no drug) in most parts of the study to see how the drug affects participants. Participants will: * Take BLKR201 or a placebo by mouth * Stay at a clinical research unit for several days during dosing * Give blood and urine samples * Have heart tests, vital signs, and lab tests * Report any side effects In one part of the study, a small group of participants will receive BLKR201 only (no placebo). These participants will also have a sample of spinal fluid collected to measure how much BLKR201 reaches the fluid around the brain and spinal cord.

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....

This study aims to compare the effects of Dynamic Neuromuscular Stabilization (DNS) exercises delivered face-to-face (YDNS) and via tele-rehabilitation (TDNS) on respiratory function, balance, posture, core endurance, and deep stabilization system performance in healthy adults. A total of 34 participants will be randomly assigned to YDNS or TDNS groups and complete an identical 6-week DNS exercise program (3 sessions per week). Assessments will be conducted at baseline and post-intervention, including pulmonary function, Y-Balance Test, posture analysis, McGill's core stability tests, deep stabilization assessment, and patient satisfaction. All evaluations will be performed face-to-face by certified physiotherapists.

The purpose of this study is to quantify the added benefit of visual biofeedback from High Resolution Pharyngeal Manometry (HRPM) for swallowing rehabilitation. Primary aims including assessing changes in swallowing biomechanics (pressure generation, timing) during swallow maneuvers with and without HRPM visual biofeedback. Secondary aim includes participant attitudes related to visual biofeedback and the experience of HRPM.

BEATRIX (group B strEptococcus mATeRnal and Infant VaX study) The purpose of this study is to learn about the safety and how the group B streptococcus (GBS) vaccine works in pregnant women and their babies. This study is seeking healthy pregnant participants: * aged 49 or younger who can join. * between 24 and 36 weeks of gestation ("Gestational age" is a medical term used to describe how far along your pregnancy is) * had a fetal ultrasound examination performed with no major fetal abnormalities observed * documented negative for HIV, syphilis and Hepatitis B All participants in this study will receive only 1 shot in an arm. This could either be a group B streptococcus 6-valent polysaccharide conjugate vaccine (GBS6) or placebo. Placebo is an inactive substance used in the study for comparison purposes; in this study, the placebo injection will be saline (saltwater). The pregnant participants may take part in this study for a maximum of 14 months (6 months after delivery) , and their babies for about 12 months after they are born. The pregnant participants will need to visit the research site at least 3 to 4 times with some visits permitted to occur over the telephone. A subset of infants will be asked to take part in the study for up to 19 months. The subset will receive diphtheria toxoid-containing vaccine and/or pneumococcal vaccine following each country's standard immunization plan and have blood drawn 1 month after completion of the primary and/or toddler (booster) doses.

The present study in healthy participants will assess the safety, tolerability, immunogenicity, pharmacokinetics (PK) and pharmacodynamics (PD) of single ascending doses (SAD) of subcutaneously administered M5542.

The purpose of this study is to identify if two different tablets of LY4268989 (MORF 057) work similarly in healthy participants given different meals. Blood tests will be performed to investigate how the body processes the study drug and how the study drug affects the body. There will be 18 inpatient stays at the clinical research unit (CRU). The study will last about 9 weeks.

The main objectives of this trial are: To assess the mass balance (total recovery of \[14C\]-radioactivity) in urine, faeces, and expired air after a single subcutaneous dose of BI 3034701 (C-14) in healthy male trial participants.

Background: Researchers have developed a new radioactive tracer (11C-ARMI). A tracer is a drug that attaches itself to other chemicals in the body and lights up so that the chemicals can be seen in imaging scans. The new tracer may be able to help them with many diseases, such as Alzheimer s disease and Parkinson s disease. Researchers want to test the new tracer in healthy people. Objective: To test a new tracer (11C-ARMI) 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 01-M-0254 or 17M0181. Design: All participants will have a positron emission tomography (PET)/computed tomography (CT) scan. Before the scan, they will have blood and urine tests and a test of their heart function. The tracer will be given through a tube attached to a needle inserted into a vein in the arm. They will lie on a padded bed that fits inside a doughnut-shaped machine; the machine uses x-rays to create images of the inside of the body. Some participants will have a PET/CT scan of their whole body. They will need only 1 visit. Some participants will have a PET/CT scan of only their brain. They will have up to 2 visits. On the second visit, they will have a magnetic resonance imaging (MRI) scan of the brain. For the MRI, they will lie on a table that slides into a cylinder. The MRI uses magnetic fields to create images of the inside of the body. Participants will receive a follow-up call to check on their well-being after their PET/CT scans.

The goal is to look for qualitative differences in visual search behavior when one search is performed many times in a row compared to when multiple search tasks are intermixed. Four search tasks are tested. The target is the same in every task but the types of distractors change from task to task. In this version, observers get some degree of choice in what they are searching.

The goal is to look for qualitative differences in visual search behavior when one search is performed many times in a row compared to when multiple search tasks are intermixed. Four search tasks are tested. In the Mixed condition, the four tasks are randomly changed from trial to trial. In the Blocked condition, each task is run as a block of 100 trials.

This clinical trial evaluates a community health education intervention (I CAN) for increasing community-driven actions to reduce the cancer burden in Western New York. Engaging community members is a critical component of designing impactful programs to reduce the cancer burden. Leaders at the national, state, and local levels have all called for more community partnerships and engagement in design of health intervention and policies. The I CAN intervention is a workshop that includes a presentation outlining key concepts related to social network processes and the cancer burden in Western New York, a structured skill-building activity, and then empowering and motivating activities meant to cultivate momentum and excitement for action. This community health education intervention may be able to provide a formalized process for empowering and facilitating community members to take steps to reduce the community cancer burden.

The goal of this trial is to learn what happens to different formulations (types) of enlicitide in a healthy person's body over time. Researchers will compare the amount of enlicitide in a healthy person's body over time when different formulations are given on an empty stomach and after a high-fat meal.

The main objective of this trial is to investigate the effects of multiple doses of Itraconazole and multiple doses of Ciclosporin on the pharmacokinetics of BI 3000202 in plasma following a single oral dose in healthy male trial participants.

The main objective of this trial is to establish the bioequivalence of survodutide in a pre-filled syringe (reference product \[formulation A\]) and in a vial (test product \[formulation B2\]) in male and female trial participants who are healthy or otherwise healthy with overweight/obesity, following subcutaneous administration.

The goal of this study is to find out whether pramipexole tablets made at two different production sites are handled in the same way by the body.

The purpose of this trial is to learn about a trial medicine called MK-1403. Researchers designed MK-1403 to treat a type of heart and blood vessel disease called atherosclerotic cardiovascular disease (ASCVD). Before giving a trial medicine to people with a health condition, researchers first do clinical trials in healthy people. This trial will help researchers learn about the safety of MK-1403 and if participants tolerate it. Tolerate means participants receive the trial medicine and they do not need to stop taking it due to health problems. The trial will also measure what happens to MK 1403 in a healthy person's body over time.

A generic screening study to establish structural and/or functional baselines of specific organs.

Background: PDE4D is a protein in the body that plays a role in thinking and depression. This protein may play a major role in disorders such as Alzheimer disease or major depressive disorder. To learn more about these disorders, researchers want to be able to detect levels of PDE4D in the brain. 11C-JMJ-129 is a new radiotracer (a radioactive substance that highlights parts of the body during imaging scans) that was developed to attach only to PDE4D. However, early human studies showed that the tracer may break down in the body and create byproducts that interfere with the brain signal, making the results harder to interpret. This study will test whether a medication called disulfiram can improve PET imaging with 11C-JMJ-129. Disulfiram blocks an enzyme in the body that may be responsible for breaking down the tracer. By reducing this breakdown, the study aims to improve the quality and accuracy of brain images. The results may help researchers better measure PDE4D in the brain and support future studies of brain disorders. Objective: To test the new radiotracer 11C-JMJ-129, with and/or without disulfiram pretreatment during imaging scans in healthy volunteers. Eligibility: Healthy people aged 18 years and older who had a screening assessment under protocol 01-M-0254. Design: Participants will have 1 to 4 clinic visits. Participants will be screened. They will have a physical exam. They will have blood tests and a test of their heart function. Participants will undergo 1 or more of these scans: A positron emission tomography (PET) scan of the whole body. The radiotracer will be injected through a tube placed in a vein in the arm. Participants will lie on a table while a donut-shaped machine passes over them. Blood will be drawn from the arm during this scan. In Phase 5, disulfiram (500 mg orally) will be administered approximately 20 hours before the post-disulfiram PET scan A magnetic resonance imaging (MRI) scan of the brain. Participants will lie on a table that slides into a tube. A PET scan of the brain. These participants will be injected with the radiotracer. They will lie on a table with their head in the scanner. Participants will be called within 3 days after each PET scan for a check on their health.

The purpose of this study is to longitudinally characterize and evaluate changes in synaptic density in the brain using novel positron-emission tomography (PET) scans; magnetic resonance imaging (MRI), and clinical laboratory markers associated with HIV-related injury in the central nervous system. This study will test hypotheses relating to the presence and mechanisms of aberrant brain structure at the synaptic level in living humans with virologically controlled HIV on antiretroviral therapy. To evaluate associations between PET imaging radiotracers \[11C\]UCB-J, a ligand for presynaptic vesicle protein 2A (SV2A), a vesicle membrane protein expressed in synapses, and PET \[11C\]PBR28 a measure of microglia function in the brain, the Yale PET center has developed an advanced approach of combining multiple distinct ligands in coordinated same-day PET imaging. Additionally, the study will evaluate the associations of this novel synaptic density marker with well-established clinical measures of neurocognitive performance and laboratory measures of blood and cerebrospinal fluid (CSF).

Background: PDE4B is a protein in cells that helps turn off certain chemical signals after they ve done their job. It controls inflammation, immune responses, and some brain signaling. Measuring PDE4B levels in the body can help doctors manage a disease or know if a treatment is working. Researchers want to find out if a new tracer (a radioactive substance injected during imaging scans) can help them measure PDE4B in people more effectively. Objective: To test a new tracer (\[11C\]ZTP-1) during imaging scans of the brain and body in healthy people. Eligibility: Healthy people aged 18 and older. They must have been screened under protocols 01M-0254 or 17M0181. Design: Participants will have either 1 or 2 clinic visits. During their first visit, all participants will have a positron emission tomography (PET)/computed tomography (CT) scan. Prior to the scan, they will have blood and urine tests and a test of their heart function. The study tracer will be given through a tube attached to a needle inserted into a vein in the arm. They will lie on a padded bed that fits inside a doughnut-shaped machine; the machine uses x-rays to create images of the inside of the body. Some participants will have a PET/CT scan of their whole body. They will need only 1 visit. The visit will last up to about 8 hours. Some participants will have a PET/CT scan of only their brain. They will also have a magnetic resonance imaging (MRI) scan of the brain. They may need to return for a second visit for the MRI scan. Participants will receive a follow-up call to check on their well-being after their PET/CT scans.

The purpose of this study is to demonstrate that V181 is safe and well tolerated, elicits an immune response, and reduces the frequency of virologically confirmed dengue (VCD) of any severity, due to any of the 4 dengue serotypes, regardless of dengue serostatus at baseline in children 2 to 17 years of age.

In the present study, 120 healthy volunteers (HV) will be randomized to one of three ketamine-induced pharmacoBOLD (phBOLD) arms: low, medium, and high. Within each ketamine arm, participants will be randomized to 4 days of "study drug" \[TS-134 (1st 20 participants) or XT (remaining 100 participants)\] or placebo in a 5:3 ratio (25 study drug:15 placebo per arm). During the study, each participant will undergo a Screening Period (up to 31 days), a 4-day Treatment Period, and a total of two phBOLD sessions: a first session at Baseline and a second session on Day 4 of the Treatment Period, conducted at least 7 days apart, and a follow up visit.

MEND-HD is a longitudinal study evaluating the feasibility of passive monitoring of gait and chorea in patients with HD and the meaningfulness of these outcomes for patients with HD and their care partners/support persons. Participants will take part in four virtual visits with study investigators to answer survey questions on movement and cognition, perform in-home movement assessments, and take part in an interview regarding the meaningfulness of gait and chorea in their daily lives. Participant and care partner interviews will be used for symptom mapping and qualitative data analysis to assess the relevance and impact of the targeted symptoms on the participant's daily life. The study may be extended to 3 years to include yearly visits.

The main purpose of this study is to assess how well LY4226695 is tolerated and what side effects may occur in healthy participants. Blood tests will be performed to investigate how the body processes the study drug and how the study drug affects the body. For each participant in Parts A \& D, the study will last about 64 days and will include a stay in the Clinical Research Unit (CRU) lasting at most 7 days. For each participant in Parts B \& C, the study will last about 92 days and will include 5 stays in the CRU with each visit lasting at most 7 days.