Background: People use virtual reality (VR) technology to play games, socialize, work, or receive medical care. Some people have "cybersickness" after using VR. Cybersickness is similar to motion sickness. Symptoms include eye strain, nausea, dizziness, or headache. The symptoms are usually mild and go away after the person stops using VR. New software called Motion Reset is being designed to reduce symptoms of cybersickness during VR use. Objective: To see if Motion Reset software can reduce cybersickness in people using VR. Eligibility: Healthy adults aged 18 to 60 years. Design: Participants will have 1 clinic visit that will last about 1 hour. They will answer questions about how they are feeling. They will learn how to use the VR headset and the handheld game controllers. The study will be broken into 2 parts. For the first part, participants will be assigned to 1 of 3 groups: Group 1 will participate in a VR experience designed to prevent cybersickness. They will view screens and move around while they press buttons on a controller. Group 2 will participate in a VR experience that is not designed to prevent cybersickness. They will view screens and move around while they press buttons on a controller. Group 3 will have no VR experience. Participants will complete 2 questionnaires about their experiences in the first part of the study. For the second part, all participants will spend up to 20 minutes playing a commercial VR game called Jurassic World Aftermath. Every few minutes, they will be asked if they are experiencing discomfort. After playing the game, participants will complete 12 questionnaires about their experience....

Type: Interventional

Start Date: Sep 2025

open study

Background: - Painful stimuli cause changes in a network of brain regions called the "Pain Matrix." But most of these regions respond to many other stimuli, not just pain. Researchers want to understand how different factors influence pain. They want to test what happens when people expect different levels of pain and receive treatments that can modify pain. They want to see if these factors influence decisions about pain and how the body responds to it. They also want to compare pain with responses like taste and vision. Objectives: - To better understand how pain and emotions are processed and influenced by psychological factors. Eligibility: - Healthy volunteers ages 18-50. Design: - This study requires 1 to 2 clinic visits that last 1 to 3 hours. - Participants will be screened with medical history and physical exam. - Some participants will have one or more magnetic resonance imaging (MRI) scans of their brain. For MRI, participants will lie on a table that slides in and out of a cylinder. The scanner makes loud knocking noises. They will get earplugs. - Participants' heart activity will be recorded with electrocardiogram. Their pulse, sweating, and breathing will be monitored. - Some participants will take a taste test. Others may perform simple tasks. Others may receive pain in their arm, leg, or hand. The pain will come from heat or electric shocks. Others may judge pain using a topical pain-relieving cream. Some of these tests may be given during MRI. - Participants will fill out questionnaires. - The study will last 3 years.

Type: Interventional

Start Date: Jun 2015

open study

The purpose of this study is to use brain imaging technology to measure changes in blood flow to areas in the brain as individuals perform intellectual tasks. This study will use functional magnetic resonance imaging (fMRI) to examine blood flow to areas of the brain as participants engage in tasks associated with visual perception, visual recognition, and memory....

Type: Observational

Start Date: Sep 1993

open study

Background: People with alcohol use disorder (AUD) have a higher rate of dental and gum disease. Poor oral health can increase the risk of other diseases, such as diabetes and stroke. Researchers want to learn more about how to identify developing inflammation in the mouth. They also want to know how improved oral health education and behaviors can affect inflammation in people with AUD. Objective: This study has 2 goals: (1) to test the usefulness of a new questionnaire about oral health and (2) to learn more about how oral health behaviors affect inflammation in people with AUD. Eligibility: People aged 18 years and older who are staying on an inpatient unit being treated for AUD. Healthy volunteers are also needed. Design: The study is divided into 2 parts: People will participate in either one part or the other. In part 1, participants will have 1 visit. They will have a physical exam. They will answer 18 questions for a survey about how they care for their teeth. In part 2, participants with AUD will have a physical exam. They will provide saliva and blood samples. They will have a dental exam with X-rays. They will fill out questionnaires about their health, mental health, social habits, diet, and sleep. They will keep a diary of their nicotine use for 4 weeks while inpatient. Healthy volunteers will have 1 visit. They will have a physical exam and provide blood and saliva samples. They will have a dental exam with X-rays. They will fill out questionnaires.

Type: Observational

Start Date: Jan 2025

open study

Background: -A gene provides instructions to the body. Mutated genes can sometimes cause cancer. Germline mutations are those people are born with. These mutations in the BAP1 gene can cause mesothelioma and other cancers. Researchers want to study people with germline mutations of BAP1 and other genes known to cause cancer. Objective: -To learn how cancer might develop in people with BAP1 mutations. Eligibility: -People ages 2 and older with a germline mutation in BAP1 Design: - Participants will be screened with: - Medical and family history - Saliva test - Participants with mesothelioma will be in the NIH Group. Participants without mesothelioma can choose to be in either the NIH Group or the Remote Group. - Remote Group participants will have a medical and family history by phone. If they have tumor tissue from a previous surgery, it will be tested. They will be contacted once a year by phone. - NIH Group participants will have a baseline visit. This can take up to 4 days. They may have to stay in the area overnight. The visit will include: - Physical exam - Evaluation of tumor tissue if available - Optional tumor biopsy - Blood tests - Scans: A machine will take pictures of the body. - Photographs of skin lesions or other issues - Skin exam - Eye exam - NIH Group participants will have visits once or twice a year. These will include a physical exam, lab tests, scans, and other tests as needed. - Participants who have a confirmed mutation will be asked to contact any relatives who may be at risk and ask them about joining the study.

Type: Observational

Start Date: Mar 2019

open study

Background: Cell therapy is an experimental cancer therapy. It takes young tumor infiltrating lymphocytes (Young TIL) cells from a person s tumors and grows them in a lab. Then they are returned to the person. Researchers think adding the drug pembrolizumab might make the therapy more effective. Objective: To test if adding pembrolizumab to cell therapy is safe and effective to shrink melanoma tumors. Eligibility: People ages 18-72 years with metastatic melanoma OF THE SKIN Design: Participants will be screened with: Physical exam CT, MRI, or PET scans X-rays Heart and lung function tests if indicated Blood and urine tests Before treatment, participants will have: A piece of tumor taken from a biopsy or during surgery in order to grow TIL cells Leukapheresis: Blood flows through a needle in one arm and into a machine that removes white blood cells. The rest of the blood returns through a needle in the other arm. An IV catheter placed in the chest for getting TIL cells, aldesleukin, and pembrolizumab (if assigned) Participants will stay in the hospital for treatment. This includes: Daily chemotherapy for 1 week For some participants, pembrolizumab infusion 1 day after chemotherapy TIL cell infusion 2-4 days after chemotherapy, then aldesleukin infusion every 8 hours for up to 12 doses Filgrastim injections to help restore your blood counts Recovery for 1-3 weeks After treatment, participants will: Take an antibiotic and an antiviral for at least 6 months, as applicable If assigned, have pembrolizumab treatment every 3 weeks for 3 more doses. They may have another round. Have 2-day follow-up visits every 1-3 months for 1 year and then every 6 months

Type: Interventional

Start Date: Dec 2015

open study

Background: Research has identified some of the genes involved in inherited eye diseases. But for many of these diseases, the genes are not yet known. Researchers want to try to find these genes. They also hope to learn more about how symptoms differ in people with similar gene changes. Objective: To learn more about genes involved in eye diseases. Eligibility: People who have a known or suspected inherited eye disease, and their relatives. Design: - All participants will have a medical history, physical exam, and eye exam. They will have blood taken. - Participants with an eye disease may have eye cell samples taken using a swab or biopsy procedure. - Participants may have a skin biopsy. A 3mm piece of skin will be removed. - Participants may provide samples of tears, urine, saliva, stool, hair, or inner cheek cells. - Participants may have a retina test. They may also have a test that uses light to measure retina thickness. - Participants may have an eye movement test. Electrodes will be placed on the skin next to both eyes. - Participants may have a fluorescein angiography. A dye will be given through an intravenous line in the arm. A camera will take pictures of the dye as it flows through the eyes blood vessels. - Participants may have microperimetry. They will sit at a computer screen and press a button when they see a light. - Participants may have an eye movement test. They will wear contact lenses or goggles and watch a series of spots on a computer screen. - Participants may complete a color vision test. - Participants will provide a specimen for genetic testing. - Participants may have a MRI. - Participants may complete questionnaires.

Type: Observational

Start Date: Jun 2015

open study

Background: - Sometimes people with HIV, the virus that causes AIDS, can have new or worsening symptoms soon after starting HIV medications. Often these symptoms are caused by immune reconstitution inflammatory syndrome (IRIS). Researchers want to study why and how people develop IRIS and how best to prevent and treat it. Objectives: - To learn the causes and effects of IRIS, and how to best manage it. Eligibility: - Adults 18 and older with HIV and low CD4 counts,, about to start HIV medicines; or those already taking HIV medicines with symptoms thought to be related to IRIS. Design: - Participants not on ART will have screening blood tests for CD4 count, HIV viral load and genetic testing. - After the screening blood tests and before starting HIV medicines., participants will return for more than 1 visit for the following: - review of medical history<TAB> - physical and eye exams - blood, urine, and tuberculosis (TB) tests - electrocardiogram (EKG) - chest x-ray - apheresis: a blood drawing procedure where blood is removed from a vein, white blood cells are separated and collected, and the rest of the blood is returned to the person using another vein - - PET scan - a procedure where a small amount of radioactive material is injected in a vein. The participant then lies on a table that slides into a scanner which takes images of the body. - lymph node biopsy - stool collection by swab - After completion of the above, HIV medicines will be started. - Follow-up visits will be at 2, 4, 8, and 12 weeks after starting ART, then every 12 weeks. Some of the tests above may be repeated. - Participants already on HIV medicines who may have IRIS will be screened over a 4 week time period to see if they really are experiencing IRIS. The screening process will include all of the items listed above. Follow-up visits will be at Weeks, 4, 8, 12 and then every 12 weeks. - The study will last 1 year for both groups but may be extended to 2 years (3 additional appointments) for some participants....

Type: Observational

Start Date: May 2014

open study

Background: - Uveal coloboma is a condition where the eye does not form normally. It occurs early in the fetus s development during pregnancy. It can lead to different kinds of eye problems, including blindness. Uveal coloboma is part of a spectrum of developmental eye conditions that include anophthalmia and microphthalmia, typically referred to as "MAC". Several genes have been linked to MAC, but the cause of most causes are hard to find. Researchers want to study the genes of people who have MAC and genes from their close, unaffected relatives (such as parents and siblings). Objectives: - To study the genes associated with MAC. Eligibility: - Individuals at least 1 years of age who either have MAC or are an unaffected relative (such as a parent or sibling). Design: - Participants will have a physical exam and medical history. They will also have a full eye exam. - Participants with MAC may have other exams, such as imaging studies and hearing assessments. - All participants will also provide blood, cheek swab or saliva or DNA samples for genetic testing.

Type: Observational

Start Date: Jan 2013

open study

Background: People with systemic lupus erythematosus (SLE) are at risk of developing complications in their blood vessels. This can increase the risk of heart attacks or stroke. No medications have been effective at reducing this risk in people with lupus. Objective: To test whether a drug (anifrolumab) can improve blood vessel function and reduce blood vessel inflammation in people with SLE. Eligibility: People aged 18 to 80 years with SLE. Design: Participants will undergo screening. They will have a physical exam. They will have blood and urine tests. They will have a test of their heart function and a chest X-ray. They will answer questions about their SLE symptoms. Participants will visit the clinic 9 times in 8 months. After screening, visits will be 4 weeks apart. Each visit may take up to 4 hours. Participants will receive infusions from a tube attached to a needle inserted into a vein in the arm (IV). Some will receive anifrolumab. Others will receive a placebo treatment. They will not know which one they are getting. At some visits they will have additional tests: CAVI (cardio-ankle vascular index) tests blood vessel function. Participants will lie still for 20 minutes. Small electrodes will be placed on both wrists with stickers. A microphone will be placed on their chest. Blood pressure cuffs will be wrapped around their ankles and arms. FDG-PET/CT is an imaging procedure. Participants will receive a substance through an IV line. They will lie on a table for 110 minutes while a machine captures images of their body.

Type: Interventional

Start Date: Dec 2023

open study

Background: Aldesleukin is used to treat metastatic or advanced melanoma and renal cell carcinoma. Pembrolizumab is used to treat many cancers including melanoma. Researchers want to see if these drugs can be used together to produce better results in people with these types of cancer. Objective: To learn if the combination of pembrolizumab and aldesleukin can be used to treat metastatic or advanced melanoma and renal cell cancer. Eligibility: Adults aged 18 years or older who have metastatic or advanced melanoma or renal cell carcinoma. Design: Participants will be screened with: - Medical history - Physical exam - Electrocardiogram - Blood and urine tests - Ability to perform tasks of daily living - Imaging scans (CT, MRI, PET, and/or X-rays). They may get a contrast agent to enhance the images. - Photographs, if needed Some of these tests will be repeated during the study. Participants will receive the study drugs by IV (a plastic tube that is put into a vein) for 4 days. A second cycle of treatment will be given 21 days later. They will stay in the hospital for each of the cycles in the first course of treatment. After 2 months, their cancer will be evaluated. They may receive a second course of pembrolizumab alone on Days 1 and 21. They will not have to stay in the hospital for this course. About 30 days after treatment ends, participants will have a safety follow-up visit. Then they will have visits every 3 months for up to 1 year, and then every 6 months for up to 4 years. Follow-up can also be done by phone, email, and mail. If their cancer gets worse, they will stop having visits. Participation will last for 5 years.

Type: Interventional

Start Date: Aug 2022

open study

Background: People with rare cancers often have limited treatment options. The biology of rare cancers is not well understood. Researchers want to find better treatments for these cancers. They want to test 2 drugs that, taken separately, have helped people with non-rare cancers. They want to see if these drugs together can make rare cancers shrink or stop growing. Objective: To learn if nilotinib and paclitaxel will benefit people with rare cancers. Eligibility: People age 18 and older who have a rare, advanced cancer that has progressed after receiving standard treatment, or for which no effective therapy exists. Design: Participants will be screened with medical history and physical exam. They will have blood and urine tests. They will have a pregnancy test if needed. They will have an electrocardiogram to check their heart. They will have imaging scans to measure their tumors. Participants will repeat the screening tests during the study. Participants will receive nilotinib and paclitaxel. The drugs are given in 28-day cycles. Nilotinib is a capsule taken by mouth twice a day. Paclitaxel will be given intravenously by peripheral line or central line once a week for the first 3 weeks of each cycle. Participants will keep a medicine diary. They will track when they take the study drugs and any side effects they may have. Participants may have optional tumor biopsies. Participants can stay on the study until their disease gets worse or they have intolerable side effects. Participants will have a follow-up phone call about 30 days after taking the last dose of study drugs.

Type: Interventional

Start Date: Aug 2020

open study

Background: Bladder cancer is the sixth most common cancer in the United States. The way that doctors remove tumors in bladder surgeries may leave some cancer . Also, many people have their tumors return or progress after surgery. Researchers want to test a modified device. It might tell doctors more about bladder tumors. Objective: To see if using a modified standard device with bladder surgery can provide better information about tumors in bladder specimens. Eligibility: People ages 18 and older who need to have their bladder removed at the NIH. Design: Participants will be screened with: Medical and prior surgical history Review of existing MRI, x-ray, or CT scans Review of existing specimens and reports Pregnancy test for women of childbearing age CT or MRI: Participants will lie in a machine. The machine will take pictures of their body. Participants will have bladder surgery. This will occur in the same way as if they did not take part in this study. A member of the research team will cut the removed bladder using the modified device. This will most likely be done on a separate back table in the operating room. The bladder and samples after cutting will be sent out for review. The will occur just as it would if the participants were not in this study. The only difference is the way that the specimen is prepared for review. Participants follow-up care will occur per standard of care. Or it will occur as part of any other study in which they might also be enrolled.

Type: Observational

Start Date: Sep 2020

open study

Background: There are two basic types of movement disorders. Some cause excessive movement, some cause slowness or lack of movement. Some of these are caused by mutations in genes. On the other hand, dementia is a condition of declining mental abilities, especially memory. Dementia can occur at any age but becomes more frequent with age. Researchers want to study the genes of families with a history of movement disorders or dementia. They hope to find a genetic cause of these disorders. This can help them better understand and treat the diseases. This study will not be limited to a particular disorder, but will study all movement disorders or dementias in general. This study will perform genetic testing to identify the genetic causes of movement disorders and dementia. Today, genetic testing can be done to analyze multiple genes at the same time. This increases the chances of finding the genetic cause of movement disorders and dementias. Objectives: To learn more about movement disorders and dementia, their causes, and treatments. Eligibility: Adults and children with a movement disorder or dementia, and their family members. Healthy volunteers. Design: Participants will be screened with medical history and blood tests. Some will have physical exam. Participants will give a blood sample by a needle in the arm. This can be done at the clinic, by their own doctor, or at home. Alternatively, a saliva sample may be provided if a blood sample cannot be obtained. Participants can opt to send an extra blood sample to a repository for future study. Genetic test will be done on these samples. The samples will be coded. The key to the code will remain at NIA. Only NIA investigators will have access to the code key. Participants can request to receive results of the tests. Participation is generally a single visit. Participants may be called back for extra

Type: Observational

Start Date: Jul 2003

open study

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.

Type: Interventional

Start Date: Apr 2025

open study

Background: A neuroendocrine tumor is a rare type of tumor. It comes from body cells called neuroendocrine cells. Sometimes, these tumors develop in the gastrointestinal tract and pancreas. Researchers want to find out if a combination of drugs can shrink these tumors. Objective: To learn if people with certain neuroendocrine tumors can take a combination of 2 drugs, Lutathera and Olaparib, without having severe side effects, and if this treatment makes the tumors shrink. Eligibility: Adults 18 and older who have a neuroendocrine tumor in the pancreas or intestine that cannot be cured by surgery and has somatostatin receptors on the cells. Design: Eligible participants will get Lutathera through an intravenous (IV) infusion every 8 weeks for 4 cycles. One cycle is 8 weeks. Each cycle includes a follow-up visit at week 4. For the IV, a small plastic tube is put into an arm vein. Participants will also take Olaparib by mouth twice a day for 4 weeks of each cycle. They will use a medicine diary to track the doses. During the study, participants will have physical exams. They will have blood and urine tests. They will fill out questionnaires about their general well-being and function. Their heart function will be tested. They will have scans of their chest, abdomen, and pelvis. One type of scan will use an IV infusion of a radioactive tracer. Participants will have a follow-up visit about 4 weeks after treatment ends. Then they will have follow-up visits every 12 weeks for 3 years. Then they will have yearly phone calls.

Type: Interventional

Start Date: Oct 2022

open study

Background: Magnetic resonance imaging (MRI) is an important non-invasive tool to study and diagnose cardiovascular disease. MRI scanners use strong magnetic fields and radio waves to create pictures of body organs. Researchers want to find better MRI methods and new ways of imaging cardiovascular disease and better understand normal and abnormal cardiovascular and brain function. Researchers are also interested in seeing if gadolinium, the commonly used MRI contrast agent, stays in the body long after the MRI was performed. Objectives: To develop new methods for imaging the heart and other organs of the body. To describe cardiovascular diseases using newer MRI methods To look at the relationship between cardiovascular disease and cardiovascular risk factors and other organ systems To look for gadolinium deposits in the brain from prior exams. Eligibility: Healthy people and people with known or suspected cardiovascular disease ages 7 and older may be eligible for this study. Researchers may be particularly interested in those who: - Have suspected or known cardiovascular disease - Were previously exposed to a gadolinium-based contrast agent, - Need to have a heart MRI scheduled - Need a test of the heart or other body part or will be undergoing a future cardiac catheterization Design: There are multiple arms to the study with optional components; therefore, there are multiple variations as to what an individual participant s experience may involve. Participants will have an MRI scan lasting up to 2 hours. The scanner is a large hollow tube. During the scan, there may be loud knocking and buzzing sounds caused by the scanner. Participants will lie on a table that slides in and out of the tube. Their vital signs may be monitored. Participants may have a test of heart electrical activity using wires connected to pads on the skin. Participants may have blood drawn. Participants may be injected with an MRI contrast agent through a plastic tube inserted in the arm.

Type: Observational

Start Date: Jul 2018

open study

Background: - Radiation is a common treatment for prostate cancer. It helps damage tumor cells and causes them to die. Radiation can be effective, but some tumors may be harder to treat with radiation or even with surgery. This happens to a small number of men who have either radiation or surgery for prostate cancer. Most men who have these hard-to-treat tumors do not know if the tumor has recurred only in the prostate or has spread to another area. Also, men whose prostate cancer has recurred only after radiation may have different treatment options. This study will use improved imaging studies to better understand why some men do not respond as well to initial radiation treatments. Objectives: - To use detailed imaging studies to look at the results of local radiation therapy for prostate cancer. Eligibility: - Men at least 18 years of age who are scheduled to have radiation for prostate cancer. - Men at least 18 years of age whose prostate cancer has returned after earlier treatments. Design: - All participants will have a medical history and physical exam. Blood and urine samples will be collected. Imaging studies will be used to evaluate the cancer at the start of the study. - All participants will have an initial full magnetic resonance imaging (MRI) scan of the prostate. Tumor and healthy tissue samples will be collected. - Those whose cancer has recurred after treatment will discuss possible treatment options with the study doctors. - Participants who are scheduled to have radiation will have radiation therapy. This will be given according to the current standard of treatment. - After radiation, participants will have regular follow-up tests and imaging studies. They will have another full MRI scan 6 months after the end of radiation treatment.

Type: Observational

Start Date: Nov 2013

open study

Background The development of new technologies now allow scientists to investigate the molecular basis and clinical manifestations of monoclonal B cell lymphocytosis (MBL), chronic lymphocytic leukemia(CLL)/small lymphocytic lymphoma (SLL), lymphoplasmacytic lymphoma (LPL)/Waldenstrom macroglobulinemia (WM), and splenic marginal zone lymphoma (SMZL). Applying these methods in a natural history study can help identify processes involved in disease progression, and possibly lead to the discovery or validation of treatment targets. Objectives Study the history of MBL/CLL/SLL/LPL/WM/SMZL in patients prior to and after treatment. Characterize clinical, biologic and molecular events of disease stability and progression of patients enrolled on this protocol. Eligibility: - Diagnosis of CLL/SLL and on treatment/previously treated/nearing treatment - Diagnosis of LPL/WM - As of February 5, 2025, patients with MBL and SMZL will no longer be enrolled. - Age greater than or equal to 18 years. - ECOG performance status of 0-2. Design Patients are typically followed every 6 to 24 months in the clinic and have blood drawn. Patients may be asked to undergo additional testing, including bone marrow biopsy and aspiration, lymph node biopsy, positron emission tomography, and CT and MRI scans. Some of these tests (e.g., blood draw) may be required to monitor CLL/SLL and LPL/WM. Other tests (e.g., lymph node biopsy) may not be clinically indicated, but patients may be asked to undergo these procedures for research purposes. No treatment will be administered on this study. If a patients requires treatment for their cancer, available NIH clinical trials and alternative treatment options will be discussed with the patient.

Type: Observational

Start Date: May 2008

open study

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.

Type: Interventional

Start Date: Jul 2026

open study

Background: Memory consolidation is the process by which memories become stable, long-term representations in the brain. Consolidation of a motor skill is dependent upon sleep. Some research shows that daytime naps improve people s motor performance and memory retention. Researchers want to find out how daytime naps may contribute to learning and support consolidation of motor skill memories. Objective: To learn the role of memory replay during wakeful rest and sleep (naps) in retaining a newly learned skill. Eligibility: English-speaking adults ages 18 and older with chronic stroke, or healthy, right-handed, English-speaking adults ages 18-35 and 50-80 Design: Participants will be screened with: - medical history - neurological history - medicine review - medical exam - neurological exam. Participants will have a magnetic resonance imaging (MRI) scan of the brain. For this, they will lie down in a scanner. The scanner makes loud noises, so they will wear earplugs. They will fill out an MRI screening form before each MRI. Participants will also have magnetoencephalography (MEG). MEG maps brain activity. It does this by recording the magnetic fields produced by naturally occurring electrical currents in the brain. For MEG, participants will lie down in the MEG room. Their eye movements may be recorded by a video camera. Participants will have behavior testing. They will practice typing random keys. Then they will repeatedly type a custom sequence that they see on a computer screen. Then they will take a 2-hour nap. Then they will type the same sequence again. Participants will have no more than 4 visits at the NIH over 3 months. Visits will last 2-4 hours each.

Type: Observational

Start Date: Mar 2021

open study

Background: Genes tell the body and its cells how to work. Familial platelet disease (FPD) or FPD with associated malignancies (FPDMM) is caused by a variant in the gene RUNX1. People with this disease may have problems with their blood and bleed for a long time when they are injured. Researchers want to learn more about RUNX1 variants and FPD. Objective: To learn more about FPD in people with RUNX1 variants to lead to better diagnosis, monitoring, and treatment. Eligibility: People any age with a suspected or confirmed RUNX1 variant People who have a family member with the variant Design: All participants will be screened with a phone call and a blood, saliva, or cheek cell sample. Participants with a suspected or confirmed variant will have 1 visit. It will last about 2 days. They will then have visits at least once a year. Visits will include: - Medical history and physical exam - Blood tests or saliva sample - Possible skin biopsy: A small piece of the participant s skin will be removed. - Bone marrow aspiration or biopsy: The participant s bone marrow will be removed by needle from a large bone such as the hip bone. - Possible apheresis: Blood will be removed from the body and certain blood cells will be taken out. The rest of the blood is returned to the body. Between visits, participants with a suspected or confirmed variant will keep a diary of disease symptoms and signs. Samples from all participants may be used for genetic testing ...

Type: Observational

Start Date: Mar 2019

open study

This study is not a treatment protocol and no experimental treatments are involved. Study participants may be seen as needed for clinical, translational and basic research studies, or as medically indicated. Subjects will receive their general medical care outside the NIH and will be seen at our clinic or at CNHS with varying frequency. Subjects may be seen for multiple visits. Subjects may be asked to return for additional testing as needed. Clinical care for patients with sickle cell disease will be provided as appropriate through the Sickle Cell Clinic and the inpatient clinical center.

Type: Observational

Start Date: Apr 2004

open study

There is a variety of tumors affecting the pituitary gland in childhood; some of these tumors (eg craniopharyngioma) are included among the most common central nervous system tumors in childhood. The gene(s) involved in the pathogenesis of these tumors are largely not known; their possible association with other developmental defects or inheritance pattern(s) has not been investigated. The present study serves as a (i) screening/training, and, (ii) a research protocol. As a screening and training study, this protocol allows our Institute to admit children with tumors of the hypothalamic-pituitary unit to the pediatric endocrine clinics and wards of the NIH Clinical Center for the purposes of (i) training our fellows and students in the identification of genetic defects associated with pituitary tumor formation, and (ii) teaching our fellows and students the recognition, management and complications of pituitary tumors As a research study, this protocol aims at (i) developing new clinical studies for the recognition and therapy of pituitary tumors; as an example, two new studies have emerged within the context of this protocol: (a) investigation of a new research magnetic resonance imaging (MRI) tool and its usefulness in the identification of pituitary tumors, and (b) investigation of the psychological effects of cortisol secretion in pediatric patients with Cushing disease. Continuation of this protocol will eventually lead to new, separate protocols that will address all aspects of diagnosis of pituitary tumors and their therapy in childhood. (ii) Identifying the genetic components of pituitary oncogenesis; those will be investigated by (a) studying the inheritance pattern of pituitary tumors in childhood and their possible association with other conditions in the families of the patients, and (ii) collecting tumor tissues and examining their molecular genetics. As with the clinical studies, the present protocol may help generate ideas for future studies on the treatment and clinical follow up of pediatric patients with tumors of the pituitary gland and, thus, lead to the development of better therapeutic regimens for these neoplasms.

Type: Observational

Start Date: Apr 1997

open study

Background: Diffuse gliomas are tumors that affect the brain and spinal cord. Gliomas that develop in people with certain gene mutations (IDH1 or IDH2) are especially aggressive. Better treatments are needed. Objective: To see if a study drug (zotiraciclib) is effective in people with recurrent diffuse gliomas who have IDH1 or IDH2 mutations. Eligibility: People aged 15 years and older with diffuse gliomas that returned after treatment. They must also have mutations in the IDH1 or IDH2 genes. Design: Participants will be screened. They will have a physical exam with blood and urine tests. They will have tests of their heart function. They will have an MRI of their brain. A new biopsy may be needed if previous results are not available. Zotiraciclib is a capsule taken by mouth with a glass of water. Participants will take the drug at home on days 1, 4, 8, 11, 15, and 18 of a 28-day cycle. They may also be given medications to prevent side effects of the study drug. The schedule for taking the study drug may vary for participants who will undergo surgery. Participants will be given a medication diary for each cycle. They will write down the date and time of each dose of the study drug. Participants will visit the clinic about once a month. They will have a physical exam, blood tests, and tests to evaluate their heart function. An MRI of the brain will be repeated every 8 weeks. Participants may remain in the study for up to 18 cycles (1.5 years).

Type: Interventional

Start Date: May 2023

open study