Healthy Adults

The purpose of this study to understand how the study medicine atirmociclib behaves in the body and how safe it is for people with different levels of liver health. The study is seeking participants who are: * Aged 18 years or older * Have a BMI of 17.5 to 40 kg/m2, and body weight more than 50 kg. * Have normal liver function or have stable mild, moderate, or severe liver disease Participants will receive study medicine by mouth. Blood samples will be collected to see how much of the medicine is in the body over time. This will help understand whether liver disease changes how the medicine is handled. Participants will be in the study for about 9 weeks. Those with normal liver function will stay in the clinic for about 7 days. People with liver disease will stay for about 9 days. After leaving the clinic, people may be contacted for follow-up. This may be done by phone or through a clinic visit.

This study aimed to develop and validate an innovative proprioceptive assessment instrument for the upper extremities, the PropArm-PosiMoF (PropArm). This observational study was conducted in three stages. The first stage focused on the development and validation of PropArm, including test-retest reliability, concurrent validity, and convergent validity. The second stage established age norms and cut-off points in healthy adults. In the final stage, PropArm was applied to patients with proprioceptive impairments (stroke, shoulder impingement syndrome, and diabetes mellitus patients) to examine its diagnostic accuracy and clinical applicability.

The goal of this study is to see if gentle electrical stimulation can help children with cerebral palsy (CP) walk more easily. This stimulation, called neuromuscular electrical stimulation (NMES), sends small pulses to muscles to help them activate. Researchers will test different ways of using NMES to find out which method works best. Participants will walk on a treadmill at a comfortable speed while NMES is applied to leg muscles. The study will compare different stimulation settings to see which one helps the most.

Self-awareness, the capacity of becoming the object of one's own awareness, is a frontier of scientific knowledge. Over centuries, distinct philosophical and religious traditions have grappled with the subject, but only recently has the importance of self-awareness been established as a central concept for scientific investigation, to which scientific methods can be applied to explore and characterize this phenomenon. Self-awareness has important implications, notably from a clinical perspective. Psychedelics can affect the sense of self, with 'ego dissolution' being an essential feature of the experience of substances such as psilocybin and dimethyltryptamine. Recent evidence indicates that psychedelics can rearrange brain connectivity, with these changes being linked to alterations in self-awareness. Nevertheless, the extent to which specific components of self-awareness are modified by these substances has not been fully explored. It is possible that part of the clinical benefits of psychedelics, for conditions such as depression, OCD, and anxiety, is mediated by changes in self-awareness. Given this clinical potential, the current study aims to examine the effects of psilocybin on various components of self-awareness in healthy participants. 100 participants will be allocated to receive either 15mg of psilocybin (n=50) or an active placebo (100mg niacin; n=50). Participants will be assessed one week before, immediately after, and one week after the administration of the substances, performing tasks and completing questionnaires measuring self-awareness at these time points. The neural correlates of self-awareness, before and after substance effects, will be investigated using near-infrared spectroscopy. Participants allocated to the placebo group will be invited to an open-label extension with psilocybin upon availability of the substance. It is expected that the results of the study will elucidate the brain regions involved in self-awareness, as well as the alterations induced by psilocybin in this process, opening the possibility of new therapeutic interventions for different clinical groups.

The purpose of the study is to assess the effect of food (high-fat, high-calorie meal) on the total and peak drug exposure of the planned to be marketed tablet formulation of prifetrastat. This study is seeking participants who are: \- Healthy males and females of nonchildbearing potential ≥18 years of age at screening The participants will receive study medicine prifetrastat as a single tablet by mouth at study clinic under fed or fasted condition. After at least 14 days, they will receive another single tablet of prifetrastat by mouth under fasted or fed condition. The sequence of conditions (fed or fasted first) will be randomized. The results of this study will enable data-driven guidance regarding food intake for participants enrolled in clinical studies of prifetrastat as well as patients receiving prifetrastat post-marketing. Participants will remain in clinic for about 21 days and have one follow up contact.

The aim of this study is to investigate whether a smartphone-based Acceptance and Commitment Therapy (ACT) program can improve the mental health and quality of life of care workers in long-term care facilities. The research question of this study is as follows: Among caregivers working in long-term care facilities, are there differences in mental health, quality of life, and job burnout between the experimental group that participated in a smartphone-based ACT program and the control group that participated in a document-based ACT program? Participants in the experimental group will complete 70 daily sessions of a smartphone-based ACT program using Anzeilax-Plus, administered Monday through Friday over a 14-week period. Participants in the control group will complete 70 daily assignments from a document-based ACT program, administered Monday through Friday over the same 14-week period.

This study aims to evaluate whether personalized gamma-frequency auditory stimulation enhances cognitive function and brain synchronization. While 40 Hz auditory stimulation has been widely studied, recent evidence suggests optimal frequencies vary by individual. Using a cross-over design with 20 healthy adults, the research compares "optimal" versus "non-optimal" frequencies over one-month intervention periods. Effectiveness is measured through EEG recordings and executive function tasks. The goal is to determine if personalized sensory intervention provides a more effective, non-invasive strategy for enhancing cognitive performance.

Knee osteoarthritis (OA) is a common degenerative joint disease in middle-aged and older adults and is frequently associated with pain, quadriceps weakness, reduced mobility, impaired proprioception, balance deficits, and limitations in daily functional activities. Exercise therapy is recommended as a first-line conservative treatment for early to moderate knee OA; however, conventional rehabilitation programs often rely on therapist supervision and lack objective, quantitative movement monitoring, real-time feedback, and personalized adjustment for home-based training. These limitations may reduce exercise adherence and make it difficult to ensure correct movement execution outside the clinical setting. The overall aim of this study is to develop and evaluate a digital rehabilitation exercise program and user interface for individuals with arthritis, using a smart elastic knee brace integrated with wearable sensing technology, surface electromyography biofeedback, joint-angle monitoring, multisensory stimulation, and artificial intelligence-based musculoskeletal monitoring. The proposed system is designed to provide personalized digital rehabilitation courses, real-time visual and auditory feedback, and objective assessment of movement performance to support knee joint motor control, gait retraining, and individualized rehabilitation planning for patients with knee OA. The investigators hypothesize that digital rehabilitation courses combined with multisensory stimulation, including neuromuscular electrical stimulation and vibration, will improve functional performance, movement quality, muscle activation, proprioception, and knee-related symptoms in patients with knee OA compared with conventional home exercise or gait retraining alone. The expected outcome of this study is to establish the feasibility, reliability, and clinical utility of a smart knee brace-based digital rehabilitation system for personalized knee OA management. This study will achieve the following four specific aims: Aim 1: To determine the feasibility of home-based exercise combined with electrical stimulation and the reliability of digital assessment for tracking exercise performance. Patients with knee OA and healthy adults will be recruited to complete selected quadriceps strengthening exercises based on exercise difficulty levels. Participants will perform a two-week home-based training program using exercise combined with electrical stimulation. Feasibility will be assessed using questionnaires, and movement performance will be tracked using inertial sensors during functional tasks. This aim will provide evidence regarding the practicality of integrating electrical stimulation into home-based rehabilitation and the reliability of digital monitoring for exercise performance. Aim 2: To evaluate the effects of digital rehabilitation exercise courses combined with multisensory stimulation in patients with knee OA and healthy adults. Participants will be randomly assigned to an experimental group or a control group. Both groups will complete a twelve-week home exercise program, three times per week for 40 minutes per session. The experimental group will follow the digital rehabilitation exercise course combined with electrical stimulation or vibration, whereas the control group will perform home exercises based on therapist education. Outcomes will be assessed at four time points: before training, after eight weeks of training, after twelve weeks of training, and six weeks after the intervention. Assessments will include pain, WOMAC scores, hemodynamic responses, muscle strength, electromyographic activity, proprioception, functional performance, body composition, knee structure, and biomechanical parameters. Aim 3: To determine the immediate effects of gait retraining combined with neuromuscular electrical stimulation in patients with knee OA. Patients with knee OA will be randomly assigned to either a gait retraining group or a gait retraining combined with neuromuscular electrical stimulation group. Both groups will receive a single 15-minute gait retraining intervention focused on modifying the foot progression angle. The experimental group will receive synchronized quadriceps electrical stimulation during gait training, while the control group will receive gait retraining alone. Pre- and post-intervention assessments will be performed to examine the immediate effects on gait parameters and functional movement performance. Aim 4: To develop and validate a personalized knee joint digital twin model using artificial intelligence, multisensory stimulation, and wearable sensing technology. This aim will develop an AI-based musculoskeletal monitoring system that integrates wearable sensor data, functional movement analysis, and personalized knee joint modeling. Patients with knee OA and healthy adults will perform functional tasks such as squatting, stair stepping, and walking under different stimulation conditions, including conti

The aim of this research is to develop protocols that selectively target and improve speech-motor learning processes. Participants will be asked to name pictures, read words/sentences, and listen to sounds while their speech signals will be collected during the study.

The purpose of this study is to learn about the safety of a new study medicine called PF-08103402 in healthy adults (do not have disease) and or in adults with mild-to-moderate asthma. This is the first time the study medicine is being given to people. For Parts A, B, C, D and F, the study is seeking participants who: * Are healthy (do not have disease) males or females who can no longer have children, * Are 18 to 65 years old, * Have a body mass index (BMI) of 16 to 32 kilograms per meter squared and a body weight of more than 50 kilograms (110 pounds). Body mass index is a way to measure body fat by using a person's height and weight For Part A (optional group or cohort 3: Japanese participants only): * A body weight of more than 45 kilograms (100 pounds). * Have 4 biological Japanese grandparents who were born in Japan. For Part E only: * Adults with a documented history of asthma (confirmed by a doctor) for at least 12 months before entering the study. * Have a body mass index (BMI) of 16 to 35 kilograms per meter squared and a total body weight of more than 50 kilograms (110 pounds). The study has six parts: Part A, Part B, Part C, Part D, Part E and Part F. The study medicine will be taken as a suspension or tablet by mouth 1 time a day (except in Parts B and E where it will be taken 1 time a day for 14 days) at the study clinic. The study will help understand: * how the body processes the study medicine in healthy participants (Parts A and B), * how much of the study medicine gets into the bloodstream and if food affects the amount of study medicine in the blood in healthy participants (Part C), * how the study medicine is broken down and leaves the body in healthy participants (Optional Part D), * how the study medicine is processed in adults with mild-to-moderate asthma (Optional Part E), * if taking the study medicine together with another medicine affects how each medicine is processed by the body in healthy participants (Optional Part F). Participants will take part in the study for about 10 weeks (Parts A and F), 12 weeks (Part B), 9 weeks (Parts C and D), and 16 weeks (Part E). During this time, they will have 2 study visits at the study clinic and up to 28 overnight stays (Part A), 18 overnight stays (Parts B and E), 10 overnight stays (Part C), 11 overnight stays (Part D), and 16 overnight stays (Part F). The study team will also call participants 1 time over the phone at the end of the study to assess how they are doing. Study measurements will be taken by body examination, monitoring side effects, blood and urine tests, heart tests (ECG), vital signs (blood pressure and pulse), questionnaires (Parts C and E), stool samples (Part D only), and breathing tests (Part E only).

The purpose of this study is to learn how different forms of the study medicine called PF-08049820 are absorbed and eliminated in healthy adults. The study will assess whether the study medicine is absorbed differently when taken with or without food. It will also assess absorption when the study medicine is taken with another medicine called rabeprazole. Rabeprazole is an FDA approved medicine that reduces stomach acid. The study has two parts. In Part A, participants will take three forms of study medicine, one after the other. They will take each form either with or without food for a total of five doses. Each dose will be separated by a few days. Participants will stay in the clinic for about two weeks. They will receive a telephone follow-up call about a month after the last dose. In Part B, participants will take three forms of study medicine. They will take each one with or without food, and with or without another medicine called rabeprazole. This means they will take a total of six doses of study medicine. Each dose will be separated by a few days. Participants will stay at the clinic for about three weeks, and about a month after their last dose. They will get a follow-up phone call. Part B may or may not be conducted depending on the results from Part A. The study is seeking participants who: 1. Are males or females, 2. Are at least 18 years of age, 3. Have a body mass index (BMI) 16 to 32 kilograms per meter squared (kg/m2). Have a total body weight of more than 50 kilograms (kg) (110 pounds).

The purpose of this study is to determine nicotinamide adenine dinucleotide (NAD) levels in healthy adult subjects before and after supplementing with over-the counter nicotinamide riboside (NR) using magnetic resonance spectroscopy (MRS).

The SOLVE-01 trial is a study evaluating four SARS-CoV-2 vaccines as booster injections: two experimental vaccines (CD40.RBDv and CD40.Pan.CoV, both combined with the Hiltonol® adjuvant) and two authorised vaccines (Comirnaty® and NuvaxovidTM). This trial is designed for healthy adults aged 18 to 65 at the time of signing the informed consent form. The main objectives of this trial are: * to evaluate the safety of the two experimental vaccines, * to determine the antibody response induced by the vaccines and its durability. Participants will: * Receive one injection of vaccine and two intradermal skin tests * Come to the hospital 10 visits for medical exams and blood and saliva sample collection * Keep a diary of their symptoms and the treatments taken

The aim of this crossover intervention study is to evaluate the volatile organic compounds (VOCs) present in participants at baseline and how these levels change after consuming either a low- or high-dietary fiber diet for three days. This study will involve adults, 18-65 years old, without any gastrointestinal diseases. The primary objectives are to characterize baseline VOC profiles, assess changes in these profiles after a short-term dietary fiber intervention, determine if specific VOC patterns correlate with dietary fiber intake, and identify the time points at which VOC levels peak. This information will help establish the optimal timing for breath sampling and potentially provide insight into how VOC patterns relate to dietary fiber consumption and degradation. The expected outcome is that a high-dietary fiber diet will produce a VOC profile enriched in metabolites associated with fiber fermentation compared to a low-dietary fiber diet, and that these VOCs will be consistent with those identified in vitro during fecal fermentation. Each participant will serve as an internal control, enabling within-subject comparisons of VOC levels at baseline and following the dietary fiber intervention. Participants will receive a whole-food product that is rich in dietary fiber and will consume either a low-fiber diet (10 g/day) or a high-fiber diet (40 g/day) for three days. On the first day of each intervention, participants will also ingest a pH capsule to monitor gastrointestinal pH continuously throughout the three days. After a three-week washout period, participants will cross over to the other intervention arm and undergo another round of gastrointestinal pH monitoring. In addition to the dietary intervention, participants will complete food and health questionnaires to assess habitual fiber intake and dietary habits. Fecal samples will be collected for in vitro fermentation to functionally profile the gut microbiota by assessing fecal VOCs, short-chain fatty acids (SCFA), and the microbial enzymatic activity and its pH-dependent modulation.

Respiratory muscle training (RMT) strengthens breathing muscles and may improve exercise performance and reduce breathlessness. However, different training methods and devices create controversy in the field. Two main types of RMT exist: inspiratory muscle training (IMT) and respiratory endurance training, like voluntary isocapnic hyperpnea (VIH). While IMT is well-studied, the impact of VIH on breathlessness remains unclear. This study will use the Canadian-developed BreathWayBetter device to examine how 5 weeks of VIH affects breathing discomfort and muscle function. Findings may help personalize RMT for athletes and clinical patients, improving respiratory care and exercise tolerance.

Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease of the central nervous system that frequently leads to walking impairment, balance deficits, fatigue, cognitive difficulties, and an increased risk of falls. Importantly, these problems can already be present in the early stages of the disease and may not be adequately captured by standard clinical walking tests, which primarily assess speed or distance. Such tests are often insufficient to reflect the complexity of real-life walking, which requires continuous adaptation to environmental challenges, and attention to internal and external stimuli. Gait adaptability, the ability to modify walking patterns in response to changing and unpredictable demands such as obstacles or sudden perturbations, is critical for safe mobility and fall prevention. Both proactive (anticipatory) and reactive (feedback-driven) gait adaptations are essential for maintaining balance and functional independence. However, gait adaptability and its underlying neural mechanisms remain insufficiently understood in people with MS. This study aims to provide a comprehensive assessment of gait adaptability in people with MS by evaluating both proactive and reactive gait adaptations using objective gait measurements and cortical activity recordings. The findings may contribute to the development of more sensitive outcome measures and inform targeted rehabilitation strategies that better reflect real-life mobility demands. Primary aims: • To investigate the behavioral measures and neural correlates of reactive and proactive gait adaptability in pwMS compared to HC Secondary aims: * To investigate factors related to gait adaptability * To investigate changes in gait adaptability during prolonged walking conditions

The purpose of this study is to learn about safety in participants taking the study vaccine (mRNA-based vaccine) and the ability of the study vaccine to trigger the body's immune response, targeting the flu virus (influenza virus). This study is seeking healthy participants 18 years of age or older. All participants in this study will receive only 1 dose in their arm, to deliver one of the experimental flu vaccines or one of the approved flu vaccines used for comparison. Participants will take part in this study for about 6 months, and participants will need to visit the study site at least 3 times. A blood sample will be taken at each of the 3 planned study visits and a swab from inside the nose will be taken at the first study visit.

The goal of this clinical trial is to learn if a combined treatment using repetitive transcranial magnetic stimulation (rTMS) and expressive writing works to reduce symptoms of post-traumatic stress in adults. It will also study how safe this treatment is and whether the timing of rTMS changes how well it works. The main questions it aims to answer are: * Does this combined treatment lower symptoms of post-traumatic stress? * Does it work better when rTMS is given before or after expressive writing? Researchers will compare three groups to see which approach works best: * rTMS given before expressive writing * rTMS given after expressive writing * Sham stimulation (a look-alike procedure that does not provide real stimulation) Participants will: * Take part in sessions that include expressive writing about emotional experiences * Receive either real rTMS or sham stimulation * Complete questionnaires about post-traumatic stress, anxiety, depression, and mood * Have their heart rate and skin responses measured during the sessions * Be assessed before the study, after the sessions, and one month later This study includes adults aged 18 to 65 who have experienced at least one traumatic or highly stressful event and report symptoms of post-traumatic stress.

The goal of this clinical study is to evaluate how adults aged 18 to 65 move their bodies and eyes when they use screens, with various eyeglasses. The main questions it aims to answer are : * How the behaviour between young and presbyopes is different while performing visual tasks on digital devices ? * How the behaviour while performing visual tasks changes according to different types of eyeglasses ? Participants will be asked to take part in an eye exam and do simple visual tasks on digital devices.

The goal of this observational study is to evaluate whether optimized high-resolution MRI can better visualize very fine nerves in the cervical spine and neck region compared to standard MRI. The main question it aims to answer is: Can high-resolution MRI reliably show small nerves and potentially detect their injuries or diseases that are often invisible on conventional MRI scans? Participants will come once to Balgrist University Hospital for a one-hour visit. They will fill out a questionnaire and have a single 30-minute MRI scan of the cervical spine without contrast.

This study consists of two parts: the first part is a single-dose escalating（SAD） and food effect （FE）study, and the second part is a multiple-dose (14-day) escalating(MAD) study. Both phases are designed as randomized, double-blind, dose-escalation, placebo-controlled clinical studies.

The goal of this clinical trial is to test whether statins can protect the heart and brain from the biological stress and inflammatory responses caused by breathing bushfire smoke in healthy adult volunteers aged 18-64 years. The main questions it aims to answer are: 1. Does short-term statin use (2 days) reduce bushfire smoke-induced changes in heart rate variability, blood pressure, arterial stiffness, inflammation and oxidative stress markers, and cognitive function? 2. Does long-term statin use (≥12 months) reduce bushfire smoke-induced changes in heart rate variability, blood pressure, arterial stiffness, inflammation and oxidative stress markers, and cognitive function? The study includes two streams: Stream 1:short-term statin use (2 days) where participants receive either statin tablets (80mg atorvastatin) or placebo; Stream 2: long-term statin use (≥12 months) where participants include those already taking statins (≥12 months) with statin-naïve individuals. Participants will: * Attend two 3½-hour visits to a Climate Hut, which are approximately 4 weeks apart, where they will spend 2 hours exposed to either filtered air or simulated dilute bushfire smoke (average particulate matter (PM2.5) concentration of 300μg/m\^3) in randomised order; * Have continuous heart monitoring with ECG leads and blood pressure checks every 15 minutes during each visit * Provide urine, saliva, and nose swab samples before and after each exposure, plus follow-up samples the next morning * Complete cognitive tests (reaction time, memory tasks) and postural balance measurements during exposure * Complete questionnaires about anxiety levels, symptoms, diet, and health status * Have blood samples collected and pulse wave velocity measurements (assessing arterial stiffness) immediately after each exposure session. Potential risks include time commitment, muscle pain from statins, eye irritation or throat discomfort from smoke exposure, and minor discomfort from blood collection.

The main goal of this clinical study is to see if consuming pecan nuts will result in improvements in overall body metabolism such as in blood lipids, markers of inflammation, blood pressure, cognitive performance and changes in bacteria living in the gut in adults 45 to 75 years of age. Participants will take part in two 3-month intervention periods, separated by 4-6 weeks, in random order ( a total of approximately 7 months). During one intervention period, they will include pecan nuts in their diet each day, while during the other intervention period they will avoid pecans in their diet. There will be an initial screening visit to evaluate eligibility and four study visits to the clinic. Participants will be asked to complete some questionnaires about their diet, physical and cognitive health, and provide blood and stool samples, and have their blood pressure measured.

This is a single center, open label (i.e. participants and study staff will not be masked to the intervention) single ascending dose study to evaluate the safety, tolerability, pharmaokinetics and pharmacodynamics of MIB-725 in community dwelling, healthy adults. Up to 4 successive groups (cohorts) of 8 subjects each will be enrolled in this trial. This study will determine the safety and tolerability of orally administered single ascending (increasing) doses (100, 200, 400, and 800 mg) of MIB-725 in healthy adults. The safety will be assessed by evaluating physical examination that includes an external eye examination, vital signs, adverse events, and changes in blood counts, EKG, urinalysis, coagulation measures, and blood chemistries, including but not limited to blood glucose, electrolytes, creatinine, liver function tests, uric acid, and creatine kinase.

The purpose of this study is to investigate the safety and efficacy of a gene therapy for Klotho, delivered via a nonviral plasmid in healthy adult volunteers. Additionally, this study seeks to understand the cognitive and health benefits of the Klotho gene therapy.