Progressive resistance exercise training

Cerebral blood pulsatility will be measured using the same techniques and conditions described for cerebral mean blood velocity, above for the MCA (primary outcome) and ACA (secondary outcome). Cerebral pulsatility will be quantified using the pulsatility index, calculated as (systolic - diastolic velocity)/mean velocity.

The RET-specific self-efficacy scale is a 2-item scale to assess RET-specific self-efficacy. Responses are reported using a 5-point Likert scale ranging from "Not at all confident" to "Very confident." Responses are summed, with higher scores indicating greater levels of RET-specific self-efficacy.

This is used to assess current suicidal ideation and behavior. The severity of ideation subscale is rated on a 5-point ordinal scale: 1 = no wish to be dead, 2 = nonspecific active suicidal thoughts, 3 = suicidal thoughts with methods, 4 = suicidal intent, and 5 = suicidal intent with plan. Suicide behavior is rated on a nominal scale that includes actual, aborted, and interrupted attempts; preparatory behavior; and non-suicidal, self-injurious behavior. The C-SSRS is recommended because it is used in clinical trials, is low burden to participants and researchers, and has extensive training materials available.

An estimated 1-RM testing method will be used to calculate each participants' actual 1-RM, in which participants will lift the maximum amount of weight that can be lifted 2-5 times with correct form, timing, and breathing. Maximum strength will be assessed on two upper body (chest press and lat. pulldown) and one lower body (leg press) major muscle group lift, completed using resistance machines.

Hand grip strength will be assessed with a hand-held dynamometer. A research assistant will ask the participant to sit in a chair and rest his/her arm on the table with the elbow on top of a mouse pad and arm held at a right angle to adjust the dynamometer to the participant's hand size. The participant will then squeeze the dynamometer twice to practice. To begin the assessment, the participant will use his/her right hand and squeeze as hard as possible. Three trials will be attempted with each hand. When the right hand is complete, the left hand will be assessed (i.e., 3 trials). A sum of the greatest effort (number) for each hand is totaled (rounded to the nearest 2 kilograms) and will be recorded.

Global cerebral blood flow will be assessed as the sum of bilateral internal carotid artery (ICA) and vertebral artery blood flow via ultrasound. Mean blood velocity will be assessed via Doppler ultrasound over a 20-sec epoch at each artery and combined with diameter measurements (averaged across 5-10 beats) to calculate volumetric blood flow (60 x mean blood velocity x π∙radius2) for each artery and summed for global volumetric cerebral blood flow. Artery diameter will be assessed using semi-automated calipers, and blood velocity metrics (e.g., mean blood velocity) computed via standard onboard algorithms.

Blood pressure will be measured at the brachial artery (i.e. upper arm) using a standard automated, oscillometric blood pressure cuff (similar to those used clinically at the physician's office). Brachial blood pressure will be taken in duplicate and averaged. If pressures differ by >5 millimeters of mercury (mmHg) it will be re-assessed until 2 values are obtained within 5 mmHg.

Carotid blood pressure waveforms will be measured using applanation tonometry over a 20-sec epoch. Pressure waves are then ensemble averaged and aligned and calibrated to brachial blood pressure waveforms (also assessed via tonometry and subsequently calibrated to brachial blood pressure derived via oscillometric cuff, described above). Carotid blood pressure will be used in the derivation of carotid stiffness metrics.

Aortic stiffness will be assessed via carotid-femoral pulse wave velocity (CfPWV) assessed via tonometry. Carotid and femoral pressure waveforms will be captured over a 20-sec epoch with simultaneous R-wave gating. CfPWV will be calculated as the distance between carotid and femoral sites divided by the difference in time lag (∆t) between the peak R-wave and foot of the respective carotid and femoral waves.

Carotid stiffness will be determined via ultrasound measurement of changes in carotid diameter (e.g., distension and the movement of the artery walls throughout the cardiac cycle) relative to carotid pressures obtained from carotid tonometry. Carotid distension will be assessed over 5-8 beats and used to derive carotid Beta stiffness index (ln(PMax/PMin)/[(maximum diameter-minimum diameter)/minimum diameter] ), where Pmax and Pmin are carotid systolic and diastolic pressure derived from 20-sec of carotid blood pressure waveforms calibrated to brachial blood pressure waveforms obtained via oscillometry and tonometry.

End-tidal CO2 will be assessed using a small mouthpiece with sampling lines the participant breathes normally through for ~2 minutes while wearing a nose clip to ensure all air moves through their mouth during respiration. The participant will also wear this device during the breath-hold protocol required to assess cerebrovascular reactivity.

Changes in MCA and ACA cerebral blood velocity during breath hold-induced changes in CO2. MCA and ACA blood velocity will be measured across 8, 20-sec breath holds with each hold separated by 30 seconds of breathing at a paced 16 breaths per minute. This breath-hold protocol is a validated test to manipulate CO2 levels and assess cerebrovascular function. The first 2 breath holds will be used as familiarization. Changes in MCA/ACA mean blood velocity will be calculated as the change in mean velocity from the 7 sec after exhalation minus the mean velocity for the 7 sec before the breath hold initiation across the remaining 6 breath holds. Changes in mean blood velocity will be expressed relative to average changes in end-tidal CO2. ICA diameter and blood flow (as described above) will also be assessed during 2 of the 8 breath holds and averaged for analysis.

Heart rate variability (HRV) will be assessed following a 10-minute supine rest by collecting 5 minutes of continuous beat-to-beat heart rate and blood pressure. Heart rate (HR) will be measured noninvasively via a standard limb electrocardiogram by placing 3 electrodes on the torso of the subject. Beat-to-beat blood pressure (BP) will be measured using a non-invasive finger photoplethysmographic technique.

Blood pressure variability (BPV) will be assessed following a 10-minute supine rest by collecting 5 minutes of continuous beat-to-beat heart rate and blood pressure. Heart rate (HR) will be measured noninvasively via a standard limb electrocardiogram by placing 3 electrodes on the torso of the subject. Beat-to-beat blood pressure (BP) will be measured using a non-invasive finger photoplethysmographic technique.

The SF-36 assesses health-related qualify of life. It consists of eight scaled scores (including vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, social role functioning, mental health), which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The higher the score the less disability (i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability).

The Penn State Worry Questionnaire (PSWQ) is a 16-item questionnaire that assesses the trait of worry, using Likert rating from 1 (not at all typical of me) to 5 (very typical of me). The total scores range from 16 to 80 with higher scores indicating greater levels of worry.

This is a 10-item questionnaire to measure an individual's level of perceived stress in the past month. The response options for each feeling or thought indicate the frequency with which it occurred: 0 = Never; 1 = Almost Never; 2 = Sometimes; 3 = Fairly Often; 4 = Very Often.

This is a brief, self-administered questionnaire that captures the respondent's perception of his or her current insomnia. The ISI includes seven items that assess severity of sleep onset, sleep maintenance, and early morning awakening problems; sleep dissatisfaction; interference of sleep difficulties with daytime functioning; noticeability of sleep problems by others; and distress caused by the sleep difficulties. Each item is rated on a 4-point Likert scale, and the total score ranges from 0 to 28. A higher score suggests more severe insomnia.

This is a six-item sub-set scale of the PROMIS Cognitive Function item bank that assesses patient-perceived cognitive deficits. Participants will be instructed to respond to 6 statements about their cognitive functioning over the past 7 days on a scale from 1 [Very often - several times a day] to 5 [Never], with lower scores indicating greater impairment in cognitive functioning.

This is a 10-item scale designed to measure respondents' tendency to regulate their emotions in two ways: (1) Cognitive Reappraisal and (2) Expressive Suppression. Respondents answer each item on a 7-point Likert-type scale ranging from 1 (strongly disagree) to 7 (strongly agree). From responses, scores is calculated for both level of Cognitive Reappraisal and Expressive Suppression.

The Patient Global Impression of Change scale is a single, self-administered question asking respondents to rate how their condition has changed since a certain point in time. Participants respond to the prompt "Since the start of the study, my overall status is: [1] 'Very Much Improved', [2] 'Much Improved', [3] 'Minimally Improved', [4] 'No Change', [5] 'Minimally Worse', [6] 'Much Worse', or [7] 'Very Much Worse'.

A modified questionnaire will be used to assess change in exercise habits, adapted from the Self-Reported Habit Index (SRHI) and the Self-Report Behavioural Automaticity Index (SRBAI). The modified version includes six questions related to habit strength, instigation habit strength, intrinsic motivation, and identity and consists of 12 items scored on a Likert scale with anchors ranging from strongly agree (1) to strongly disagree (7), with total scores ranging from 12 (strong habits) to 14 (weak habits).

A modified questionnaire will be used to assess exercise identity and intrinsic motivation, adapted from the Exercise Identity Scale (a 9-item questionnaire used to assess the salience of identifying with exercise as an integral portion of the self-concept) and the Behavioral Regulation Exercise Questionnaire (BREQ; a questionnaire that is used to assess intrinsic motivation regarding exercise). The modified version includes 10 statements related to exercise identity and intrinsic motivation, with responses on a Likert scale anchored by (1) Not at all true and (5) Very true of me. Higher scores reflect greater feelings of exercise as an integral part of their self-identity.

The IPAQ is a physical activity questionnaire that inquiries about physical activity in different domains, including occupation, transportation, housework/maintenance, and recreational physical activity, as well as total sedentary time. This is designed to be performed in an interview format which will be how this is administered in this project.

Participants will place an accelerometer on the midline of the thigh on either leg and wear the monitor during all waking hours, removing it only for water-based activities (e.g., swimming). For data to be valid, the monitor must have been worn for 20 hours on at least 4 days, including a minimum of 3 weekdays and 1 weekend day. Sleep time will be parsed out from each day's sitting/lying time. From these data, average minutes of sitting per day will be used to assess total sedentary time, minutes of stepping time with a cadence #75 and <100 will be used to assess minutes of light intensity physical activity and minutes of stepping time with a cadence #100 will be used to assess minutes of moderate to vigorous physical activity (MVPA).