handgrip and treadmill walking 4 days per week

6 weeks of exercise training (Pre-training)

6 weeks of exercise training (Post-training)

Jill Slade, PhD

Katharine Currie, PhD

All participants will undergo four experimental sessions in a randomized, counterbalanced order: 1) Resting with Placebo; 2) Resting with Nitrate Supplementation; 3) Aerobic Exercise with Placebo; and 4) Aerobic Exercise with Nitrate Supplementation. A washout period of at least 2 days will be respected between sessions.

Participants will ingest 2 capsules of a standardized beetroot extract (Berkeley Life Nitric Oxide Foundation). Each dose provides approximately 314 mg of dietary nitrate.

Beetroot Extract (Nitrate-rich)

Capsules identical in appearance, color, and size to the experimental supplement, but containing an inert substance (starch). This intervention is used to maintain the double-blind design of the study.

Placebo

Participants will perform a single aerobic exercise session on a treadmill. The protocol consists of a 7-minute warm-up followed by 30 minutes of continuous exercise at an intensity corresponding to 60-80% of maximum heart rate (HRmax), estimated using Tanaka's formula (208 - 0.7 \* age). Rate of Perceived Exertion (RPE) will be monitored periodically using the Borg scale (6-20).

Exercise

Participants will remain seated for 30 minutes (matching the exercise session duration). During this time, a researcher will administer a Food Frequency Questionnaire (FFQ) in an interview format. This activity serves to assess dietary habits and simulates a routine, low-exertion daily activity (similar to a conversation), acting as a time-matched control for the exercise session.

Rest (Control Condition)

Anderson S Zago, Professor

Nutritional intervention: Routine postoperative oral nutritional supplements (ONS) will be provided, and patients with metabolic diseases such as diabetes will undergo strict glycemic control. Psychological intervention: Patients with a Hospital Anxiety and Depression Scale (HADS) score ≥ 8 will receive cognitive behavioral therapy (CBT), and those with a HADS score ≥ 11 will be referred for psychological consultation. Exercise intervention: Postoperative rehabilitation training will be guided according to different postoperative periods.

Early structured postoperative intervention encompassing nutrition, psychology, and exercise

Healthy volunteers will undergo RHC while exercising and an optional muscle biopsy.

A procedure to measure how well or poorly your heart is pumping and to measure the pressures in the heart and lungs. A catheter will be inserted into a vein and artery in order to take the measurements and this will be conducted while exercising on a supine cycle ergometer. Various measurements will be taken during periods of rest and exercise.

Right Heart Catheterization (RHC) while exercising

A sample of muscle tissue will be collected and analyzed for the ability of the cells to utilize oxygen.

Optional Muscle Biopsy

Patients diagnosed with PAH-ILD will undergo RHC while exercising, receive inhaled treprostinil, and undergo an optional muscle biopsy.

30mcg (5 breaths) of inhaled treprostinil will be administered during the RHC procedure and patients will be initiated on outpatient inhaled treprostinil therapy for 3-months with gradual up titration to target dose as per standard clinical practice.

Treprostinil

Temporary target during an anaerobic training session

SmartGuard during an anaerobic training session

Maria M Manrique

Ana M Gómez, Endocrinologyst

Receive tele-exercise training and undergo pulmonary function testing and exercise testing

Tele-exercise

The intervention consists of a supervised, in-person, combined exercise program lasting 16 consecutive weeks, conducted at a specialized exercise unit. Participants attend two sessions per week, with at least 48 hours of recovery between sessions, and each session lasts between 55 and 85 minutes. The program follows a "combined" methodology, meaning every session integrates both resistance (strength) and aerobic training. To ensure safety and precision, sessions are led by a graduate in Physical Activity and Sport Sciences with specialized training in oncology, and participants work in small groups of 6 to 8 people.

Each session is structured into four distinct parts: a 10-minute warm-up involving low-to-moderate intensity activity and joint mobility; a resistance training block; an aerobic training block; and a cool-down featuring static stretching for 30-40 seconds per muscle group. The resistance training portion utilizes a "full body" approach.

Participants assigned to the control group receive standard care typically provided to patients in this phase of recovery. Instead of a supervised exercise program, these individuals are sent educational materials via email. This material consists of a video and official documents containing basic guidelines and recommendations for a healthy lifestyle, based on standards from the World Health Organization (WHO) and the American College of Sports Medicine (ACSM) for cancer survivors. The documents provide general instructions on physical activity, reducing sedentary behavior, and maintaining overall health habits. Like the intervention group, participants in the control group undergo all clinical and functional evaluations at the start of the study, after 16 weeks, and during a 3-month follow-up.

Control

Susana Aznar Laín

This group will receive basic body awareness training

Basic body awareness training will be applied to preschool children in terms of motor development and body perception

body awareness therapy

An obstacle course will be set up for this group and play-based exercise methods will be implemented.

Play-based exercise training will be implemented for preschool children by designing games that they enjoy playing, in order to support motor development and body perception.

play-based exercise

harran lecturer

Patients in the conventional rehabilitation group will participate in a rehabilitation program at least 3 days a week, with each session lasting 1.5 hours. The program will include neurophysiological exercises, strengthening exercises, and balance and coordination exercises, performed in three sets of 10 repetitions. There will be warm-up and cool-down periods before and after each session.

: Patients in the conventional rehabilitation group will participate in a rehabilitation program 3 days a week, with each session lasting 1.5 hours. The program will include neurophysiological exercises, strengthening exercises, and balance and coordination exercises, performed in three sets of 10 repetitions. There will be warm-up and cool-down periods before and after each session.

Conventional rehabilitation therapy

This group will take 3 times a week Qi gong therapy with classical conventional therapy.

The protocol includes eight traditional movements, such as:

* Raising Hands to the Sky,
* Drawing the Bow to Hit the Hawk,
* Separating Heaven and Earth,
* The Wise Owl Looking Back,
* Shaking the Head and Tail,
* Bending to Touch the Feet,
* Clenching Fists and Gathering Energy with a Fierce Look,
* Shaking the Body by Hitting the Heels. Each exercise sequence will be performed with warm-up (deep breathing) and cool-down (focusing on energy flow). The Qigong group will participate in a 45-minute additional Qigong session (three times a week), led by a physiotherapist, after their conventional rehabilitation program.

The protocol includes eight traditional movements, such as:

* Raising Hands to the Sky (9 repeats)
* Drawing the Bow to Hit the Hawk (9 left, 9 right repeats)
* Separating Heaven and Earth (9 repeats)
* The Wise Owl Looking Back. (9 left, 9 right repeats)
* Shaking the Head and Tail (9 left, 9 right repeats)
* Bending to Touch the Feet (9 repeats)
* Clenching Fists and Gathering Energy with a Fierce Look (9 left, 9 right repeats)
* Shaking the Body by Hitting the Heels (9 repeats) Each exercise sequence will be performed with warm-up (deep breathing) and cool-down (focusing on energy flow). The Qigong group will participate in a Qigong session 3 days a week,30-45 minutes, led by a physiotherapist, after their conventional rehabilitation program (3 days a week, with each session lasting 1,5 hours).Breathing in and out will be performed in coordination with qigong movements.

Qi gong Baduanjin Exercises

Intervention group that receive 30 min exercise training twice weekly in 20 weeks

Exercise training with aerobic and strength training, 30 min per session

Exercise training

Stig Molsted, PhD

Stig Moelsted, PhD

Participants complete a 20-minute aerobic cycling session at individually prescribed intensity to achieve lactate threshold, based on VO2 max and blood lactate data. This condition is designed to induce metabolic stress and engage neuromodulatory pathways related to cortical plasticity. Participants complete TMS and motor learning tasks before and after the intervention.

Participants cycle on a stationary ergometer at an intensity prescribed to reach their lactate threshold, guided by VO2 max results and lactate sampling. The session lasts approximately 20 minutes and is preceded and followed by TMS assessments and a structured motor learning task. This condition is designed to evaluate the effect of exercise-induced metabolic stress on cortical inhibition and motor learning.

High intensity cycling

Participants complete a 20-minute cycling session at a light workload, below lactate threshold. This condition controls for movement and engagement without significant metabolic challenge. TMS and motor learning outcomes are assessed pre- and post-intervention.

Participants perform 20 minutes of cycling at a light workload below their lactate threshold. Exercise intensity is individualized using heart rate and perceived exertion (Borg RPE scale), avoiding significant metabolic activation. TMS and motor learning are assessed pre- and post-exercise. This condition serves as an active comparator to assess the impact of exercise intensity.

Low-intensity cycling

Participants engage in a 20-minute health education session instead of exercise. This arm serves as a non-exercise control to isolate the effects of physical exertion on neuroplasticity. All outcome measures are collected similarly to the exercise groups.

Participants receive a 20-minute session of health education content (e.g., wellness, healthy aging). No exercise is performed. Participants undergo TMS and motor learning testing before and after the session. This condition is used to control for attention and cognitive engagement without physical activity.

Health education session

Arm Description: Participants complete a 20-minute cycling session at a moderate workload, surrounding lactate threshold. This condition controls for movement and engagement without advanced metabolic challenge. TMS and motor learning outcomes are assessed pre- and post-intervention.

Participants cycle on a stationary ergometer at an intensity prescribed to surround, but not exceed their lactate threshold, guided by VO2 max results and lactate sampling. The session lasts approximately 20 minutes and is preceded and followed by TMS assessments and a structured motor learning task. This condition is designed to evaluate the effect of moderate exercise-induced metabolic stress on cortical inhibition and motor learning.

Moderate Intensity Aerobic Exercise

Keith M McGregor, PhD

Ayat Najmi, BS

The protocol will be comprised of up to 15 exercise sessions over the course of participants' 5-6 weeks radiation treatment period with each session lasting up to 60 minutes. Exercise sessions are a combination of resistance, aerobic, and flexibility training using bodyweight and/or elastic bands for resistance.

Study participants will engage in 7-10 exercises per session targeting major muscle groups (e.g. quadriceps, hamstrings, glutes, back, chest, arms, abdominal muscles). Movements will alternate between the lower and upper body thus allowing ample time for muscle-group recovery between exercises.

Kathrin Milbury, MA,PHD

Patients receive fisetin PO on days 1-3 of each cycle. Treatment repeats every 14 days for 8 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive handout on the importance of physical activity during baseline. Patients undergo collection of blood samples on study.

Biospecimen Collection

Educational Intervention

Fisetin

Physical Performance Testing

Quality-of-Life Assessment

Questionnaire Administration

Patients receive fisetin PO on days 1-3 of each cycle. Treatment repeats every 14 days for 8 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive individually tailored supervised exercise training consisting of 30-45 minutes of aerobic training and 20-30 minutes of resistance training three times a week over 16 weeks. Patients undergo collection of blood samples on study.

Receive individually tailored exercise intervention

Exercise Intervention

Patients receive placebo PO on days 1-3 of each cycle. Treatment repeats every 14 days for 8 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive individually tailored supervised exercise training consisting of 30-45 minutes of aerobic training and 20-30 minutes of resistance training three times a week over 16 weeks. Patients undergo collection of blood samples on study.

Placebo Administration

Patients receive placebo PO on days 1-3 of each cycle. Treatment repeats every 14 days for 8 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive handout on the importance of physical activity during baseline. Patients undergo collection of blood samples on study.

Mina S. Sedrak, MD

Mina S. Sedrak

Mina S. sedrak, MD

All participants will complete one, 60-minute bout of stationary cycling

Exercise Mode

All participants will complete one, 60-minute bout of treadmill walking

Exercise training will be performed in the fasted state (i.e., before breakfast).

Participants will complete three sessions of combined resistance-aerobic exercise per week. Sessions will always start with resistance training followed by aerobic training, and will increase in duration throughout the intervention period, so that by the final three weeks of the intervention, all participants accumulate 150 minutes per week of moderate intensity aerobic exercise and 75 minutes of resistance exercise per week. Participants will complete three distinct resistance exercise sessions per week, which will increase in load, but decrease in repetition range throughout the trial. The aerobic component of the exercise sessions will increase in duration from 35 to 50 minutes per session. Participants will walk on a treadmill at a speed and incline that corresponds to 70-80% of ventilatory threshold.

Fasted Exercise

Exercise will be performed in the postprandial period (i.e., after breakfast)

Postprandial Exercise

Normand Boule, PhD

Reid McClure, MSc

Physicians will use Prioritizes Personalizes Prescribes Exercise (P3-EX), hosted by a web-based platform, to deliver P3-EX, an evidence-based personalized exercise prescription to improve cardiovascular disease (CVD) risk factors.

P3-EX will determine whether the patient needs medical clearance. P3-EX will score the patient's CVD risk factors using an adapted American Heart Association Life's Essential 8 cardiovascular health scoring system to determine the CVD risk factor posing the greatest risk. If ≥2 CVD risk factors are tied for the greatest risk, P3-EX will prompt the physician to choose an American College of Sports Medicine strategy to prioritize one CVD risk factor to personalize the Frequency, Intensity, Time, and Type (FITT) exercise prescription. P3-EX will also produce special exercise considerations for the prioritized CVD risk factor. The physician will print the exercise prescription and give it to the patient to perform for 12 weeks.

UConn Graduate Research Assistants will provide patients with virtual weekly oversight to follow their P3-EX unsupervised exercise program for 12 weeks. Patients will choose the location and the FITT of exercise they prefer. UConn Graduate Research Assistants will provide all patients with a 12-week exercise program information packet containing progressive FITT exercise recommendations for their exercise program. Patients will use an exercise diary called the Timeline Followback for Exercise to record the FITT of exercise daily. Patients will attend two virtual study visits led by UConn Graduate Research Assistants during the first week and midway through the intervention to receive standardized guidance on how they are doing following their exercise program. UConn Graduate Research Assistants will email all patients weekly to provide their progressive FITT exercise recommendations and summary reports of their Timeline Followback for Exercise recordings.

Experimental - 12 Week P3-EX Unsupervised Exercise Program with Virtual Weekly Oversight from Graduate Research Assistants

Physicians will use a hard copy instruction manual adapted from the Exercise is Medicine HealthCare Providers' Action Guide to deliver the American College of Sports Medicine Physical Activity Vital Sign (ACSM-PAVS), a generic exercise program to improve general health.

The physician will ask the patient exercise preparticipation health screening questions to determine whether medical clearance is needed. The physician will assess their patient's physical activity levels as a vital sign (i.e., minutes per week of moderate to vigorous intensity exercise and days per week of resistance exercise). The physician will give the patient the ACSM-PAVS exercise program as a handout, which recommends the Physical Activity Guidelines for Americans of 150 minutes per week of moderate and/or 75 minutes per week of vigorous intensity aerobic exercise (or a combination) and 2 days per week of muscular strengthening exercise.

University of Connecticut (UConn) Graduate Research Assistants will provide patients with virtual weekly oversight to follow their ACSM-PAVS unsupervised exercise program for 12 weeks. Patients will choose the location and the FITT of exercise they prefer. UConn Graduate Research Assistants will provide all patients with a 12-week exercise program information packet containing progressive FITT exercise recommendations for their exercise program. Patients will use an exercise diary called the Timeline Followback for Exercise to record the FITT of exercise daily. Patients will attend two virtual study visits led by UConn Graduate Research Assistants during the first week and midway through the intervention to receive standardized guidance. UConn Graduate Research Assistants will email all patients weekly to provide their progressive FITT exercise recommendations and summary reports of their Timeline Followback for Exercise recordings.

Active Control - 12 Week ACSM-PAVS Unsupervised Exercise Program with Virtual Weekly Oversight from Graduate Research Assistants

Peter F Robinson, MD

Antonio B Fernandez, MD

Linda S Pescatello, PhD

Subsequently, the intervention group underwent an eight-week exercise program using an incentive spirometer (Triflow) provided by the researchers. Patients were each given the same brand and model of Triflow device (manufactured in Turkey). Practical training on the use of the Triflow was provided, and visual materials prepared by the researcher were given to the patients. Exercise training was administered to the patients in the Chest Diseases Outpatient Clinic by the second author. Patients were instructed to perform the exercise hourly, 10 times per repetition, after waking up at home. The breathing exercise program was evaluated weekly via telephone calls with the patients. No changes were made to the patients' inhaler treatments during the study period.

Initially, pre-test data were collected from both the intervention and control groups using the measurement instruments prior to the commencement of the exercise program. Subsequently, the intervention group underwent an eight-week exercise program using an incentive spirometer (Triflow) provided by the researchers. Patients were each given the same brand and model of Triflow device (manufactured in Turkey). Practical training on the use of the Triflow was provided, and visual materials prepared by the researcher were given to the patients. Exercise training was administered to the patients in the Chest Diseases Outpatient Clinic by the second author. Patients were instructed to perform the exercise hourly, 10 times per repetition, after waking up at home \[14\]. The breathing exercise program was evaluated weekly via telephone calls with the patients. No changes were made to the patients' inhaler treatments during the study period.

breathing exercises

No exercise regimen was applied to the control group; however, they were contacted regularly each week to inquire about any changes in their health status.

4 mg qd titrated to 8 mg qd perindopril + aerobic exercise

Twice weekly centered based aerobic exercise + 3/week home-based walking

Aerobic exercise

Perindopril

50 mg qd titrated to 100 mg qd losartan + aerobic exercise

Losartan

12.5 mg qd titrated to 25 mg qd HCTZ + aerobic exercise

HCTZ

Home-based relaxation therapy using a Virtual Reality system with a via guided breathing exercise application.

Home-based guided breathing exercise using a virtual reality system application.

Virtual Reality Guided Breathing Exercise

Persons with ALS will be monitored with the same outcome measures as the intervention group, but no intervention will be provided.

6주간의 운동 훈련(Pre-training), 6주간의 운동 훈련(Post-training)

비트루트 추출물(질산염 함유), 위약, 운동, 휴식(대조군)

영양, 심리 및 운동을 포함하는 조기 구조화된 수술 후 중재

트레프로스티닐, 운동 중 우심장 카테터 도관술(RHC), 선택적 근육 생검

무산소 운동 훈련 세션 중 임시 목표, 무산소 운동 훈련 세션 중 SmartGuard

원격 운동

통제, 운동

신체 인식 치료, 놀이 기반 운동

전통 재활 치료, 기공 팔단금 운동

운동 훈련

운동

고강도 사이클링, 저강도 사이클링, 건강 교육, 중강도 유산소 운동

운동

생체 시료 채취, 교육적 중재, 운동 중재, 피세틴, 신체 성능 검사, 위약 투여, 삶의 질 평가, 설문지 투여

운동 모드

공복 운동, 식후 운동

실험군 - 12주간 P3-EX 자율 운동 프로그램 (대학원 연구 조교의 주간 온라인 지도 포함), 대조군 - 12주간 ACSM-PAVS 자율 운동 프로그램 (대학원 연구 조교의 주간 온라인 지도 포함)

호흡 운동

유산소 운동, 페린도프릴, 로사르탄, HCTZ

가상현실을 활용한 호흡 운동