Acute hypoalgesic, neurophysiological and perceptual responses to low-load blood flow restriction exercise and high-load resistance exercise.

This study compared the acute hypoalgesic and neurophysiological responses to low-load resistance exercise with and without blood flow restriction (BFR), and free-flow, high-load exercise. Participants performed four experimental conditions where they completed baseline measures of pain pressure threshold (PPT), maximum voluntary force (MVF) with peripheral nerve stimulation to determine central and peripheral fatigue. Corticospinal excitability (CSE), corticospinal inhibition and short interval intracortical inhibition (SICI) were estimated with transcranial magnetic stimulation. Participants then performed low-load leg press exercise at 30% of one-repetition maximum (LL); low-load leg press with BFR at 40% (BFR40) or 80% (BFR80) of limb occlusion pressure; or high-load leg press of four sets of 10 repetitions at 70% one-repetition maximum (HL). Measurements were repeated at 5, 45 min and 24 h post-exercise. There were no differences in CSE or SICI between conditions (all P > 0.05); however, corticospinal inhibition was reduced to a greater extent (11%-14%) in all low-load conditions compared to HL (P < 0.005). PPTs were 12%-16% greater at 5 min post-exercise in BFR40, BFR80 and HL compared to LL (P ≤ 0.016). Neuromuscular fatigue displayed no clear difference in the magnitude or time course between conditions (all P > 0.05). In summary, low-load BFR resistance exercise does not induce different acute neurophysiological responses to low-load, free-flow exercise but it does promote a greater degree of hypoalgesia and reduces corticospinal inhibition more than high-load exercise, making it a useful rehabilitation tool. The changes in neurophysiology following exercise were not related to changes in PPT.

Emergency Department Volumes After State-Wide Lockdown Orders Across the United States During the COVID-19 Pandemic: COVID-19 lockdown and emergency volume.

OBJECTIVE: The objective of this study was to describe changes in emergency department volumes after statewide lockdown in a network of hospitals across the United States during the COVID-19 global pandemic. METHODS: A retrospective study was performed utilizing data on daily volumes across multiple emergency departments from a centralized data warehouse from a private for-profit hospital system during the COVID-19 pandemic. The mean daily volumes of 148 emergency departments were evaluated across 16 states in relation to each state's governmental statewide lockdown orders. Comparisons of the same period in the prior year were evaluated for percent changes in volumes. We also compared pre-lockdown to post-lockdown volumes. A separate analysis was made for the pediatric ED volumes. RESULTS: The 2020 post-lockdown volumes compared to the same 2019 dates revealed a mean percent change of -43.09%. The overall post-lockdown volumes compared to the pre-lockdown volumes had a mean percent change of -45.00%. The pediatric data revealed a greater mean percentage change in volumes of -71.52% (post-lockdown compared to 2019) and -69.03% (post-lockdown compared to pre-lockdown). CONCLUSIONS: This study found an overall decrease in volumes among 148 emergency departments across 16 states when compared to the comparable period pre-global pandemic.

Optimising the Early-Stage Rehabilitation Process Post-ACL Reconstruction.

Outcomes following anterior cruciate ligament reconstruction (ACLR) need improving, with poor return-to-sport rates and a high risk of secondary re-injury. There is a need to improve rehabilitation strategies post-ACLR, if we can support enhanced patient outcomes. This paper discusses how to optimise the early-stage rehabilitation process post-ACLR. Early-stage rehabilitation is the vital foundation on which successful rehabilitation post-ACLR can occur. Without high-quality early-stage (and pre-operative) rehabilitation, patients often do not overcome major aspects of dysfunction, which limits knee function and the ability to transition through subsequent stages of rehabilitation optimally. We highlight six main dimensions during the early stage: (1) pain and swelling; (2) knee joint range of motion; (3) arthrogenic muscle inhibition and muscle strength; (4) movement quality/neuromuscular control during activities of daily living (5) psycho-social-cultural and environmental factors and (6) physical fitness preservation. The six do not share equal importance and the extent of time commitment devoted to each will depend on the individual patient. The paper provides recommendations on how to implement these into practice, discussing training planning and programming, and suggests specific screening to monitor work and when the athlete can progress to the next stage (e.g. mid-stage rehabilitation entry criteria).

Current Implementation and Barriers to Using Blood Flow Restriction Training: Insights From a Survey of Allied Health Practitioners.

ABSTRACT: Scott, BR, Marston, KJ, Owens, J, Rolnick, N, and Patterson, SD. Current implementation and barriers to using blood flow restriction training: Insights from a survey of allied health practitioners. J Strength Cond Res 38(3): 481-490, 2024-This study investigated the use of blood flow restriction (BFR) exercise by practitioners working specifically with clinical or older populations, and the barriers preventing some practitioners from prescribing BFR. An online survey was disseminated globally to allied health practitioners, with data from 397 responders included in analyses. Responders who had prescribed BFR exercise ( n = 308) completed questions about how they implement this technique. Those who had not prescribed BFR exercise ( n = 89) provided information on barriers to using this technique, and a subset of these responders ( n = 22) completed a follow-up survey to investigate how these barriers could be alleviated. Most practitioners prescribe BFR exercise for musculoskeletal rehabilitation clients (91.6%), with the BFR cuff pressure typically relative to arterial occlusion pressure (81.1%) and implemented with resistance (96.8%) or aerobic exercise (42.9%). Most practitioners screen for contraindications (68.2%), although minor side effects, including muscle soreness (65.8%), are common. The main barriers preventing some practitioners from using BFR are lack of equipment (60.2%), insufficient education (55.7%), and safety concerns (31.8%). Suggestions to alleviate these barriers included developing educational resources about the safe application and benefits of BFR exercise ( n = 20) that are affordable ( n = 3) and convenient ( n = 4). These results indicate that BFR prescription for clinical and older cohorts mainly conforms with current guidelines, which is important considering the potentially increased risk for adverse events in these cohorts. However, barriers still prevent broader utility of BFR training, although some may be alleviated through well-developed educational offerings to train practitioners in using BFR exercise.

Remote ischaemic preconditioning increase tolerance to experimentally induced cold pain.

Ischaemic preconditioning (IPC) applied locally and remotely has been shown to reduce pain which may underpin its ergogenic effect on exercise performance, however, it is unclear how many IPC cycles are needed to induce hypoalgesia. Therefore the purpose of this study was to examine the number of cycles of IPC on experimental pain perception. Sixteen healthy participants underwent four, randomised, experimental sessions where they either underwent a sham protocol (1 × 5 min at 20 mmHg), and 1, 2 or 3 cycles × 5 min of remote IPC at 105% of limb occlusion pressure. Ten minutes post-intervention, participants underwent a cold-pressor test where pain threshold, pain tolerance and pain intensity were examined and compared between conditions with a one-way repeated measure analysis of variance. Pain threshold was not different between conditions (P = 0.065); but pain tolerance was increased by ∼30% in the 1 × 5 condition, 2 × 5 condition, and 3 × 5 condition compared to the sham condition. No differences in pain tolerance were seen between the different numbers of cycles (all P > 0.05). There was also no difference in the perception of pain 30 s into the cold pressor test (P = 0.279). Remote IPC appears to significantly improve tolerance to pain which may have significant implications for endurance performance and exercise rehabilitation, but this warrants further investigation.

We found that one, two or three cycles of ischaemic preconditioning improved cold pain tolerance by 30% compared to a sham protocol, but there was no clear effect of IPC on pain threshold or pain intensity.The pain reported during IPC decreased from cycle one to cycle three in the three cycle condition, suggesting a potential conditioned pain modulation effect.An increase in pain tolerance may explain why IPC can improve exercise performance and IPC itself could be used as a tool to improve tolerance to pain.

Femoroacetabular Impingement in Ice Hockey Athletes.

ABSTRACT: Femoroacetabular impingement (FAI) in ice hockey is a concern for many athletes. The biomechanics of skating and the injury mechanism, prevalence, identification, and treatment protocols currently available for FAI in ice hockey athletes are important for all coaches and practitioners to understand. This article discusses the underlying anatomical issues and biomechanical considerations surrounding FAI. Furthermore, this article describes the interventions that can be used when encountering FAI and well-established protocols to aid in the return to play. Finally, prevention strategies that can aid in injury prevention are discussed.

Development of a 2,4-Diaminothiazole Series for the Treatment of Human African Trypanosomiasis Highlights the Importance of Static-Cidal Screening of Analogues.

While treatment options for human African trypanosomiasis (HAT) have improved significantly, there is still a need for new drugs with eradication now a realistic possibility. Here, we report the development of 2,4-diaminothiazoles that demonstrate significant potency against Trypanosoma brucei, the causative agent of HAT. Using phenotypic screening to guide structure-activity relationships, potent drug-like inhibitors were developed. Proof of concept was established in an animal model of the hemolymphatic stage of HAT. To treat the meningoencephalitic stage of infection, compounds were optimized for pharmacokinetic properties, including blood-brain barrier penetration. However, in vivo efficacy was not achieved, in part due to compounds evolving from a cytocidal to a cytostatic mechanism of action. Subsequent studies identified a nonessential kinase involved in the inositol biosynthesis pathway as the molecular target of these cytostatic compounds. These studies highlight the need for cytocidal drugs for the treatment of HAT and the importance of static-cidal screening of analogues.

Chemical pulldown combined with mass spectrometry to identify the molecular targets of antimalarials in cell-free lysates.

Here, we provide a protocol using chemical pulldown combined with mass spectrometry (LC-MS/MS) to identify drug targets in Plasmodium falciparum. This approach works upon the principle that a resin-bound inhibitor selectively binds its molecular target(s) in cell-free lysates. We describe the preparation of drug beads and P. falciparum lysate, followed by chemical pulldown, sample fractionation, and LC-MS/MS analysis. We then detail how to identify specifically bound proteins by comparing protein enrichment in DMSO-treated relative to drug-treated lysates via quantitative proteomics. For complete details on the use and execution of this protocol, please refer to Milne et al. (2022).1.

The relationship between physical characteristics and match collision performance among elite international female rugby union players.

This study investigated whether anthropometric and physical abilities explained variance in match collision performance among international female rugby union players. Physical performance and anthropometric data for fifty-one international female rugby union players, and collision actions categorised as "effort" or "performance" variables, from 20 international matches, were analysed using partial least squares regression. Among forwards, variance in carries/min was explained (R2 = .22) by a combination of; body mass, skinfolds, acceleration momentum and negative associations with mean aerobic speed and single-leg isometric squat relative force (SLISO/kgBM). Variance in collision dominance among forwards was explained (R2 = .21) by lower skinfolds and higher acceleration momentum, while tackles/min (R2 = .19) were explained by greater jumping power and single-leg isometric squat (SLISO). Among backs, variance in tackles/min (R2 = .54) was explained by greater bench press, SLISO and SLISO/kgBM. Variance in collision dominance among backs was explained (R2 = .23) by negative and positive associations with body mass and SLISO/kgBM, respectively. These findings suggest the development of physical characteristics, such as body mass and composition, strength and power contribute towards successful collision actions among international female rugby union players. The contribution of different physical characteristics towards collision events is dependent on position, and whether the collision event is categorised by "performance" or "effort". It is suggested that physical training programmes should reflect this level of specificity.HighlightsAmong elite female rugby union forwards, acceleration momentum, body mass and skinfolds are positively associated with winning collisions and carrying the ball into contact more frequently, whilst tackle frequency is positively associated with relative leg strength and power output.Among elite female backs, the ability to win collisions is positively associated with relative leg power output, and negatively associated with body mass. Tackle frequency is associated with maximum upper- and lower-body strength in this group.Physical characteristics account for some of the variability in collision performance, but interpretation of these findings should consider that factors such as technique during collision events may account for a larger proportion of total variance.Sports science practitioners can improve collision performance, to varying degrees, by enhancing specific gross physical characteristics, according to a player's position and the tactical role they are expected to fulfil.

Repetitions in Reserve Is a Reliable Tool for Prescribing Resistance Training Load.

ABSTRACT: Lovegrove, S, Hughes, L, Mansfield, S, Read, P, Price, P, and Patterson, SD. Repetitions in reserve is a reliable tool for prescribing resistance training load. J Strength Cond Res 36(10): 2696-2700, 2022-This study investigated the reliability of repetitions in reserve (RIR) as a method for prescribing resistance training load for the deadlift and bench press exercises. Fifteen novice trained men (age: 17.3 ± 0.9 years, height: 176.0 ± 8.8 cm, body mass: 71.3 ± 10.7 kg) were assessed for 1 repetition maximum (1RM) for deadlift (118.1 ± 27.3 kg) and bench press (58.2 ± 18.6 kg). Subsequently, they completed 3 identical sessions (one familiarization session and 2 testing sessions) comprising sets of 3, 5, and 8 repetitions. For each repetition scheme, the load was progressively increased in successive sets until subjects felt they reached 1-RIR at the end of the set. Test-retest reliability of load prescription between the 2 testing sessions was determined using intraclass correlation coefficient (ICC) and coefficient of variation (CV). A 2-way analysis of variance with repeated measures was used for each exercise to assess differences in the load corresponding to 1-RIR within each repetition scheme. All test-retest comparisons demonstrated a high level of reliability (deadlift: ICC = 0.95-0.99, CV = 2.7-5.7% and bench press: ICC = 0.97-0.99, CV = 3.8-6.2%). Although there were no differences between time points, there was a difference for load corresponding to 1-RIR across the 3 repetition schemes (deadlift: 88.2, 84.3, and 79.2% 1RM; bench press: 93.0, 87.3, and 79.6% 1RM for the 3-, 5-, and 8-repetition sets, respectively). These results suggest that RIR is a reliable tool for load prescription in a young novice population. Furthermore, the between-repetition scheme differences highlight that practitioners can effectively manipulate load and volume (repetitions in a set) throughout a training program to target specific resistance training adaptations.

Toolkit of Approaches To Support Target-Focused Drug Discovery for Plasmodium falciparum Lysyl tRNA Synthetase.

There is a pressing need for new medicines to prevent and treat malaria. Most antimalarial drug discovery is reliant upon phenotypic screening. However, with the development of improved target validation strategies, target-focused approaches are now being utilized. Here, we describe the development of a toolkit to support the therapeutic exploitation of a promising target, lysyl tRNA synthetase (PfKRS). The toolkit includes resistant mutants to probe resistance mechanisms and on-target engagement for specific chemotypes; a hybrid KRS protein capable of producing crystals suitable for ligand soaking, thus providing high-resolution structural information to guide compound optimization; chemical probes to facilitate pulldown studies aimed at revealing the full range of specifically interacting proteins and thermal proteome profiling (TPP); as well as streamlined isothermal TPP methods to provide unbiased confirmation of on-target engagement within a biologically relevant milieu. This combination of tools and methodologies acts as a template for the development of future target-enabling packages.

Safety and Feasibility Assessment of Repetitive Vascular Occlusion Stimulus (RVOS) Application to Multi-Organ Failure Critically Ill Patients: A Pilot Randomised Controlled Trial.

Muscle wasting is implicated in the pathogenesis of intensive care unit acquired weakness (ICU-AW), affecting 40% of patients and causing long-term physical disability. A repetitive vascular occlusion stimulus (RVOS) limits muscle atrophy in healthy and orthopaedic subjects, thus, we explored its application to ICU patients. Adult multi-organ failure patients received standard care +/- twice daily RVOS {4 cycles of 5 min tourniquet inflation to 50 mmHg supra-systolic blood pressure, and 5 min complete deflation} for 10 days. Serious adverse events (SAEs), tolerability, feasibility, acceptability, and exploratory outcomes of the rectus femoris cross-sectional area (RFCSA), echogenicity, clinical outcomes, and blood biomarkers were assessed. Only 12 of the intended 32 participants were recruited. RVOS sessions (76.1%) were delivered to five participants and two could not tolerate it. No SAEs occurred; 75% of participants and 82% of clinical staff strongly agreed or agreed that RVOS is an acceptable treatment. RFCSA fell significantly and echogenicity increased in controls (n = 5) and intervention subjects (n = 4). The intervention group was associated with less frequent acute kidney injury (AKI), a greater decrease in the total sequential organ failure assessment score (SOFA) score, and increased insulin-like growth factor-1 (IGF-1), and reduced syndecan-1, interleukin-4 (IL-4) and Tumor necrosis factor receptor type II (TNF-RII) levels. RVOS application appears safe and acceptable, but protocol modifications are required to improve tolerability and recruitment. There were signals of possible clinical benefit relating to RVOS application.

Slow-Speed Compared With Fast-Speed Eccentric Muscle Actions Are Detrimental to Jump Performance in Elite Soccer Players In-Season.

PURPOSE: To examine the effect of fast- versus slow-speed eccentric-muscle-action resistance training on lower-body strength, vertical jump height, sprint speed, and change-of-direction performance in elite soccer players during a competitive season. METHODS: Twenty-two elite soccer players, from a single team, were randomly assigned to groups that undertook either 1- (fast speed) or 4-second (slow speed) eccentric resistance training during the in-season period. A 5-week program was conducted during an elite top-division European League soccer season. Performance measures including predicted 1-repetition-maximum back squat, countermovement jump, 20-m sprint, and change of direction were tested before and after the intervention period. Total match and training running distance and muscle soreness were also recorded during each week of the intervention. RESULTS: An analysis of covariance showed significant group effects (P = .01) for countermovement jump with a greater jump height in the 1-second fast-speed group postintervention (95% CI, 1.1-6.9 cm). Despite an overall increase in 1-repetition maximum pretraining to posttraining (95% CI, 10.0-15.3 kg, effect size 0.69), there were no significant differences (P > .05) between groups after the intervention. Similarly, there were no differences between groups for change of direction, 20-m sprint, or muscle soreness. CONCLUSION: Faster eccentric muscle actions may be superior for increasing movements in elite soccer players in-season.

Corticospinal and peripheral responses to heat-induced hypo-hydration: potential physiological mechanisms and implications for neuromuscular function.

Heat-induced hypo-hydration (hyperosmotic hypovolemia) can reduce prolonged skeletal muscle performance; however, the mechanisms are less well understood and the reported effects on all aspects of neuromuscular function and brief maximal contractions are inconsistent. Historically, a 4-6% reduction of body mass has not been considered to impair muscle function in humans, as determined by muscle torque, membrane excitability and peak power production. With the development of magnetic resonance imaging and neurophysiological techniques, such as electromyography, peripheral nerve, and transcranial magnetic stimulation (TMS), the integrity of the brain-to-muscle pathway can be further investigated. The findings of this review demonstrate that heat-induced hypo-hydration impairs neuromuscular function, particularly during repeated and sustained contractions. Additionally, the mechanisms are separate to those of hyperthermia-induced fatigue and are likely a result of modulations to corticospinal inhibition, increased fibre conduction velocity, pain perception and impaired contractile function. This review also sheds light on the view that hypo-hydration has 'no effect' on neuromuscular function during brief maximal voluntary contractions. It is hypothesised that irrespective of unchanged force, compensatory reductions in cortical inhibition are likely to occur, in the attempt of achieving adequate force production. Studies using single-pulse TMS have shown that hypo-hydration can reduce maximal isometric and eccentric force, despite a reduction in cortical inhibition, but the cause of this is currently unclear. Future work should investigate the intracortical inhibitory and excitatory pathways within the brain, to elucidate the role of the central nervous system in force output, following heat-induced hypo-hydration.

A Survey of Combat Athletes' Rapid Weight Loss Practices and Evaluation of the Relationship With Concussion Symptom Recall.

OBJECTIVE: There is a high incidence of concussion and frequent utilization of rapid weight loss (RWL) methods among combat sport athletes, yet the apparent similarity in symptoms experienced as a result of a concussion or RWL has not been investigated. This study surveyed combat sports athletes to investigate the differences in symptom onset and recovery between combat sports and evaluated the relationships between concussion and RWL symptoms. DESIGN: Cross-sectional study. SETTING: Data were collected through an online survey. PARTICIPANTS: One hundred thirty-two (115 male athletes and 17 female athletes) combat sport athletes. INTERVENTIONS: Modified Sport Concussion Assessment Tool (SCAT) symptom checklist and weight-cutting questionnaire. MAIN OUTCOME MEASURES: Survey items included combat sport discipline, weight loss, medical history, weight-cutting questionnaire, and concussion and weight-cutting symptom checklists. RESULTS: Strong associations ( rs = 0.6-0.7, P < 0.05) were observed between concussion and RWL symptoms. The most frequently reported symptom resolution times were 24 to 48 hours for a weight cut (WC; 59%) and 3 to 5 days for a concussion (43%), with 60% to 70% of athletes reporting a deterioration and lengthening of concussion symptoms when undergoing a WC. Most of the athletes (65%) also reported at least one WC in their career to " not go according to plan ," resulting in a lack of energy (83%) and strength/power (70%). CONCLUSIONS: Rapid weight loss and concussion symptoms are strongly associated, with most of the athletes reporting a deterioration of concussion symptoms during a WC. The results indicate that concussion symptoms should be monitored alongside hydration status to avoid any compound effects of prior RWL on the interpretation of concussion assessments and to avoid potential misdiagnoses among combat athletes.

Repositioning of a Diaminothiazole Series Confirmed to Target the Cyclin-Dependent Kinase CRK12 for Use in the Treatment of African Animal Trypanosomiasis.

African animal trypanosomiasis or nagana, caused principally by infection of the protozoan parasites Trypanosoma congolense and Trypanosoma vivax, is a major problem in cattle and other livestocks in sub-Saharan Africa. Current treatments are threatened by the emergence of drug resistance and there is an urgent need for new, effective drugs. Here, we report the repositioning of a compound series initially developed for the treatment of human African trypanosomiasis. A medicinal chemistry program, focused on deriving more soluble analogues, led to development of a lead compound capable of curing cattle infected with both T. congolense and T. vivax via intravenous dosing. Further optimization has the potential to yield a single-dose intramuscular treatment for this disease. Comprehensive mode of action studies revealed that the molecular target of this promising compound and related analogues is the cyclin-dependent kinase CRK12.

Optimization of Exercise Countermeasures to Spaceflight Using Blood Flow Restriction.

INTRODUCTION: During spaceflight missions, astronauts work in an extreme environment with several hazards to physical health and performance. Exposure to microgravity results in remarkable deconditioning of several physiological systems, leading to impaired physical condition and human performance, posing a major risk to overall mission success and crew safety. Physical exercise is the cornerstone of strategies to mitigate physical deconditioning during spaceflight. Decades of research have enabled development of more optimal exercise strategies and equipment onboard the International Space Station. However, the effects of microgravity cannot be completely ameliorated with current exercise countermeasures. Moreover, future spaceflight missions deeper into space require a new generation of spacecraft, which will place yet more constraints on the use of exercise by limiting the amount, size, and weight of exercise equipment and the time available for exercise. Space agencies are exploring ways to optimize exercise countermeasures for spaceflight, specifically exercise strategies that are more efficient, require less equipment, and are less time-consuming. Blood flow restriction exercise is a low intensity exercise strategy that requires minimal equipment and can elicit positive training benefits across multiple physiological systems. This method of exercise training has potential as a strategy to optimize exercise countermeasures during spaceflight and reconditioning in terrestrial and partial gravity environments. The possible applications of blood flow restriction exercise during spaceflight are discussed herein.Hughes L, Hackney KJ, Patterson SD. Optimization of exercise countermeasures to spaceflight using blood flow restriction. Aerosp Med Hum Perform. 2021; 93(1):32-45.

International female rugby union players' anthropometric and physical performance characteristics: A five-year longitudinal analysis by individual positional groups.

Longitudinal changes in anthropometric and physical performance characteristics of International female rugby union players were evaluated across 5-seasons, according to field position. Sixty-eight international female rugby union players from a top 2 ranked international team, undertook anthropometric and physical performance measurements across five seasons. Anthropometric and physical performance changes occurred, with skinfolds decreasing between 2015 and 2017 and body mass increasing between 2017 and 2019. Single-leg isometric squat (SL ISO), 0-10 m momentum (0-10 Mom) and 20-30 m momentum (20-30Mom) were higher in 2018 and 2019 than all years. Front-row players were characterised by greater SL ISO and 1-RM bench press than inside and outside backs, with higher skinfolds and lower endurance levels than all positions. Between 2017 and 2019, front-row players had larger decreases and increases in endurance and one repetition maximum (1-RM) bench press, respectively, compared to all other positions. Forwards had the highest 0-10Mom and 20-30Mom, and scrum-half the lowest, while outside backs had faster 0-10, 30-40, and 40 m (TT40 m) times, and greater peak velocity (Vmax) compared to forward positions. These longitudinal findings show that physical performance has increased, with anthropometric and performance characteristics becoming more distinctive between positions, among elite female rugby union players.

The iTHRIV Commons: a cross-institution information and health research data sharing architecture and web application.

OBJECTIVE: The integrated Translational Health Research Institute of Virginia (iTHRIV) aims to develop an information architecture to support data workflows throughout the research lifecycle for cross-state teams of translational researchers. MATERIALS AND METHODS: The iTHRIV Commons is a cross-state harmonized infrastructure supporting resource discovery, targeted consultations, and research data workflows. As the front end to the iTHRIV Commons, the iTHRIV Research Concierge Portal supports federated login, personalized views, and secure interactions with objects in the ITHRIV Commons federation. The canonical use-case for the iTHRIV Commons involves an authenticated user connected to their respective high-security institutional network, accessing the iTHRIV Research Concierge Portal web application on their browser, and interfacing with multi-component iTHRIV Commons Landing Services installed behind the firewall at each participating institution. RESULTS: The iTHRIV Commons provides a technical framework, including both hardware and software resources located in the cloud and across partner institutions, that establishes standard representation of research objects, and applies local data governance rules to enable access to resources from a variety of stakeholders, both contributing and consuming. DISCUSSION: The launch of the Commons API service at partner sites and the addition of a public view of nonrestricted objects will remove barriers to data access for cross-state research teams while supporting compliance and the secure use of data. CONCLUSIONS: The secure architecture, distributed APIs, and harmonized metadata of the iTHRIV Commons provide a methodology for compliant information and data sharing that can advance research productivity at Hub sites across the CTSA network.