Considerations beyond spine pain: do different co-occurring lower body joint pains differentially influence physical function and quality of life ratings?

BACKGROUND: Patients seeking medical care for back pain often have coexisting painful joints and the effects of different combinations and number of coexisting pain sites (hip, knee, foot/ankle) to back pain on physical function domains and quality of life rating are not yet established. The purpose of this study was to determine the differences in functional outcomes and QOL among individuals with back pain who have concurrent additional pain sites or no pain sites. METHODS: Data from the Osteoarthritis Initiative (OAI) cohort were used for this cross-sectional analysis. Men and women aged 45-79 years with back pain were binned into nine groups by presence or not of coexisting hip, knee, ankle/foot pain and combinations of these sites (N = 1,642). Healthy controls reported no joint pain. Main outcomes included Knee Injury and Osteoarthritis Outcome score (KOOS; quality of life and function-sports-and-recreation), Western Ontario McMaster Universities Osteoarthritis Index (WOMAC; Activities of Daily Living, Pain), Medical Outcomes Short Form-12 (SF-12) Physical Component score, and self-reported function in last 7-30 days (lifting 25-pound objects, housework). 20-m and 400-m walk times and gait speed and repeated chair rise test times were collected. RESULTS: Compared to back pain alone, pain at all five sites was associated with 39%-86% worse KOOS, WOMAC, and SF-12 scores (p < .0001). Back-Hip and Back-Knee did not produce worse scores than Back pain alone, but Back-Hip-Knee and Back-Knee-Ankle/Foot did. The 20-m, 400-m walk, and repeated chair times were worse among individuals with pain at all five sites. Additional hip and knee sites to back pain, but not ankle/foot, worsened performance-based walk times and chair rise scores. CONCLUSIONS: The number and type of coexistent lower body musculoskeletal pain among patients with back pain may be associated with perceived and performance-based assessments. Management plans that efficiently simultaneously address back and additional coexistent pain sites may maximize treatment functional benefits, address patient functional goals in life and mitigate disability.

Pilot Study on Therapeutic Horticulture for Chronic Low Back Pain: A Mixed Methods Study.

Background: Chronic low back pain (LBP) is common and associated with disability worldwide. Therapists trained in Therapeutic Horticulture (TH) use gardening activities and proximity to nature for therapy and rehabilitation. Patients seeking care for LBP would benefit physically and psychologically from participating in TH. Primary study objectives: The first aim of this study was to determine if and which patients who were receiving care for chronic LBP were interested in TH to help manage their pain. The second aim of the project was to quantify changes in LBP, functional tasks and anxiety upon completion of a TH session in patients with LBP. Methods/Design: This was a 2-part study with a mixed methods design: the cross-sectional survey Group and the pilot experimental Group. The Cross-sectional Survey component comprised a total of 170 patients; age 55.9±17.3 years; 58% women. The Pilot Experimental component comprised a total of 9 patients; age 48±14.7 years; 78% women. Participants Cross-sectional component: Patients receiving medical care for LBP with or without additional joint pain sites (n=170; age 55.9 ± 17.3 years; 58% women. Participants Pilot experimental component: A total of 9 patients (7 women); mean age 48 ± 14.7 years and mean duration of back pain 12.6 ± 8.1 years. Setting: Patients were receiving medical care at the University of Florida Health Comprehensive Spine Center in the United States, in the tertiary care health system. Intervention: 1-hour TH session that involved trained therapists using propagating and harvesting herbs planted at various heights in an outdoor setting for therapy and rehabilitation. Primary outcome measures: A therapeutic horticulture interest survey, PROMIS Pain Interference and Physical Function scores, functional tests (timed-get-up-and-go [TUG], spine range of motion), Roland Morris Disability Questionnaire (RMDQ), 11-point Numerical Pain Rating Scale (NRSpain), 10-item PROMIS Global Health Questionnaire, Tampa Scale of Kinesiophobia-11 and patient enjoyment. Results: Cross-sectional survey component: A total of 2% of patients had not previously heard of TH and 68% were interested in learning more about it. Patients who expressed interest in TH reported a higher level of agreement that TH could improve mood, improve muscle strength, lower stress level, increase movement and enable patients to perform self-care activities with less pain (all P < .001). PROMIS Pain Interference and Physical Function scores did not differ by interest in TH (P > .05). Pilot Experimental component: In the pilot session, 44% reported using pain medication to manage their low back pain and 66% believed gardening could provide pain relief. Improvements were observed in anxiety (55.3%; P =.017), spine flexion (31.4%; P =.003) and spine rotation to the left (26.7%; P =.005). All participants believed that gardening improved overall health and spine motion while reducing low back pain. All patients reported having gardening experience at home and none had TH experience. Conclusion: Patients presenting to an outpatient spine clinic may be receptive to trying TH in conjunction with or in place of conventional medicine to promote health and well-being. The pilot experimental group data suggested that acute TH is enjoyable and may confer the benefits of reducing anxiety and improving spine motion. Future larger studies could use different dose response approaches, explore different TH activity types and involve participants from different geographic locations while controlling for LBP history and psychological status.

Child and Caregiver Beliefs of Importance of Physical Function and Quality of Life in Juvenile Idiopathic Arthritis: A Survey Study.

PURPOSE: To evaluate patient-caregiver beliefs of relative importance across 4 domains while living with juvenile idiopathic arthritis (JIA). METHODS: This was a cross-sectional, anonymous survey study conducted in an academic medical center. Participants with JIA and caregivers (N = 151) completed a Likert-style survey to rate items by importance of knowledge about 4 domains: medications, physical activity, routine measures, and quality of life. RESULTS: Knowledge of medication issues ranked higher than the remaining 3 domains (4.2 ± 0.7 points vs 4.0 ± 0.7, 4.1 ± 0.8, and 4.0 ± 0.9 points, respectively; P = .026; P = .026). Compared with caregivers, participants rated importance lower for all 4 domains. CONCLUSIONS: Gait and physical activity and well-being are not uniformly measured as part of routine clinical care and disease tracking in JIA. Both participants and caregivers ranked knowledge of physical activity similarly to routine office measures and quality of life. Inclusion of these measures in routine care could improve people centeredness and inform treatment plans.

Development of a Moral Resilience Collaborative Program During a Pandemic.

Elevated psychological stress can lead to moral distress affecting health care workers and organizations affecting patient care, job satisfaction, and retention. A Moral Resilience Collaborative program was implemented through an academic partnership between a school of nursing and a rehabilitation facility to provide the health care workers in the facility the skills necessary for self-management of moral distress and move them toward moral resilience. Moral distress and resiliency were measured pre-implementation using the Measure of Moral Distress for Healthcare Professionals (MMD-HP) and Short Resiliency Survey (SRS), respectively. Unfortunately, postsurvey quantitative data collection failed due to COVID-19 surges though qualitative data obtained during debriefing sessions demonstrated effectiveness of the project. Based on debriefing comments and the preimplementation MMD-HP mean score and SRS decompression score, the staff in this facility experienced similar types of moral distress as those working in acute care or critical care settings. Even when resiliency programs are needed the most and readily available, patient care demands, a busy work environment, and external factors can hinder staff participation in such endeavors.

A Research and Clinical Framework for Understanding Achilles Injury in Female Collegiate Gymnasts.

ABSTRACT: Gymnastics is a popular sport with a high injury rate, particularly at the collegiate level. Achilles tendon rupture is a catastrophic injury with career-changing impact. Over the last decade, there has been a growing incidence of Achilles tendon ruptures, especially in female gymnasts. Currently, neither the effects of contributing risk factors on Achilles tendon rupture nor the research frameworks to guide future intervention strategies have been well described. This article reviews the functional anatomy and mechanical properties of the Achilles tendon, provides precollegiate and collegiate intrinsic and extrinsic risk factors for Achilles tendon rupture, and proposes a research framework to address this injury from a systemic perspective. Potential clinical interventions to mitigate Achilles tendon injury are proposed based on currently available peer-reviewed evidence.

Pilot study to explore girls' lacrosse players' attitudes toward headgear.

Headgear adoption is a controversial issue in girls' lacrosse due to concerns that headgear use will facilitate greater risk-taking by players and contribute to more aggressive game play behaviours. The purpose of this pilot study was to evaluate high school girls' lacrosse players' attitudes towards headgear before and after a season of use. Twenty-five high school girls' lacrosse athletes wore headgear for one competitive season and completed a pre- and post-season survey. The survey evaluated players' attitudes towards headgear use, with Aggressiveness, and Anger scales. Wilcoxon ranked tests were conducted to compare scores pre- and post-season. Players' attitude towards headgear largely remained unchanged and "neutral" after a season of wearing headgear. Players endorsed slightly greater agreement for three Headgear survey items post-season compared to pre-season: " … headgear allows me to be more aggressive … " (p = .01), " … players should wear more protective equipment " (p = .04) and " … wearing headgear increases how often I am hit in the head … " (p = .04). However, Aggressiveness and Anger scale scores were not changed following headgear use. Our findings suggest the perception of headgear use in high school girls' lacrosse is complex and could be associated with minor perceived changes in game play behaviours.

Comparable outcomes with intramedullary nail and plate constructs for Schatzker VI tibial plateau fractures.

BACKGROUND: Outcomes data of intramedullary nail fixation (IMN) constructs for complex Schatzker VI tibial plateau fractures are scant in the literature. This study compares the clinical and radiographic outcomes of IMN, dual plate, and single plate constructs for Schatzker IV tibial plateau fractures. METHODS: Retrospective cohort study of sixty-two patients at a University-based Level 1 trauma center who underwent open reduction internal fixation for Schatzker VI tibial plateau fracture. Constructs evaluated were IMN (with or without raft screws), dual plating, and single plating. Demographic, clinical, and radiographic outcomes were recorded. All fractures were additionally classified based on the OTA classification for sub analyses. Mean follow-up was 13.2 (SD 13.3) months. Predictors of construct selection and outcomes were evaluated with bivariate logistic regression. Outcomes were compared between groups with independent samples t-tests and Chi Square tests. RESULTS: No significant demographic differences were found between IMN, dual plate or single plate construct cohorts. There was a higher proportion of open fractures within the IMN construct group versus the dual plate cohort (21.1% vs 3.6%). No statistically significant differences in radiographic outcomes were observed between cohort groups except for small but statistically significant differences in condylar width (CW) ratio change and tibial slope; when fracture cohorts were sub analyzed by specific OTA classification, there were no significant differences in any radiographic outcomes. There was a significant difference between the ratio of OTA 41C1, C2 and C3 fractures regarding treatment allocation (p = 0.004), favoring dual plate fixation for OTA 41C3 fractures. There were no significant differences found between treatment cohorts in terms of all cause complications (p > 0.05). IMN and single plate constructs were utilized when posteromedial condyle fractures were nondisplaced or minimally displaced. CONCLUSION: Intramedullary nail fixation with or without supplemental raft screws produced similar short-term clinical and radiographic results compared to dual and single plate constructs among patients with Schatzker VI fracture types, regardless of OTA classification. Level of Evidence Level III retrospective cohort.

Association of headgear mandate and concussion injury rates in girls' high school lacrosse.

OBJECTIVES: Headgear use is a controversial issue in girls' lacrosse. We compared concussion rates among high school lacrosse players in an American state with a headgear mandate (HM) to states without an HM. METHODS: Participants included high schools with girls' lacrosse programmes in the USA. Certified athletic trainers reported athlete exposure (AE) and injury data via the National Athletic Treatment, Injury and Outcomes Network during the 2019-2021 seasons. The HM cohort was inclusive of high schools from the state of Florida, which mandates the use of ASTM standard F3137 headgear, while the non-HM (NHM) cohort was inclusive of high schools in 31 states without a state-wide HM. Incidence rate ratios (IRRs) and 95% CIs were calculated. RESULTS: 141 concussions (HM: 25; NHM: 116) and 357 225 AEs were reported (HM: 91 074 AEs; NHM: 266 151 AEs) across all games and practices for 289 total school seasons (HM: 96; NHM: 193). Overall, the concussion injury rate per 1000 AEs was higher in the NHM cohort (0.44) than the HM cohort (0.27) (IRR=1.59, 95% CI: 1.03 to 2.45). The IRR was higher for the NHM cohort during games (1.74, 95% CI: 1.00 to 3.02) but not for practices (1.42, 95% CI: 0.71 to 2.83). CONCLUSIONS: These findings suggest a statewide HM for high school girls' lacrosse is associated with a lower concussion rate than playing in a state without an HM. Statewide mandates requiring ASTM standard F3137 headgear should be considered to reduce the risk of concussion.

Impact of COVID on Sports Injury Patterns, Changes in Mental Well-Being, and Strategies to Prepare for Future Pandemics in Sport.

ABSTRACT: This review describes the available evidence of the acute respiratory syndrome coronavirus 2 (SARS-CoV-2, referred to COVID-19) pandemic on musculoskeletal injury patterns and prevalence in athletes. A brief overview of the epidemiology of COVID-19 and prevalence in active populations from youth through professional are provided. Responses to COVID-19 regarding sport participation at regional, national, and international organizations are summarized. Downstream effects of complete or partial training shutdown on injury risk and mental health are discussed. Strategies to maintain athletic potential and overall well-being include maintaining safe access to training facilities and resources, implementation of injury prevention programs, organization of athlete support networks, and incorporation of resilience and coping training.

Healthy Running Habits for the Distance Runner: Clinical Utility of the American College of Sports Medicine Infographic.

ABSTRACT: Healthy running form is characterized by motion that minimizes mechanical musculoskeletal injury risks and improves coactivation of muscles that can buffer impact loading and reduce stresses related to chronic musculoskeletal pain. The American College of Sports Medicine Consumer Outreach Committee recently launched an infographic that describes several healthy habits for the general distance runner. This review provides the supporting evidence, expected acute motion changes with use, and practical considerations for clinical use in patient cases. Healthy habits include: taking short, quick, and soft steps; abdominal bracing; elevating cadence; linearizing arm swing; controlling forward trunk lean, and; avoiding running through fatigue. Introduction of these habits can be done sequentially one at a time to build on form, or more than one over time. Adoption can be supported by various feedback forms and cueing. These habits are most successful against injury when coupled with regular dynamic strengthening of the kinetic chain, adequate recovery with training, and appropriate shoe wear.

The Golgi Calcium ATPase Pump Plays an Essential Role in Adeno-associated Virus Trafficking and Transduction.

Adeno-associated viruses (AAVs) are dependoparvoviruses that have proven useful for therapeutic gene transfer; however, our understanding of host factors that influence AAV trafficking and transduction is still evolving. Here, we investigated the role of cellular calcium in the AAV infectious pathway. First, we demonstrated a critical role for the host Golgi compartment-resident ATP-powered calcium pump (secretory pathway calcium ATPase 1 [SPCA1]) encoded by the ATP2C1 gene in AAV infection. CRISPR-based knockout (KO) of ATP2C1 decreases transduction by different AAV serotypes. ATP2C1 KO does not appear to inhibit AAV binding, cellular uptake, or nuclear entry; however, capsids within ATP2C1 KO cells demonstrate dispersed and punctate trafficking distinct from the perinuclear, trans-Golgi pattern observed in normal cells. In addition, we observed a defect in the ability of AAV capsids to undergo conformational changes and support efficient vector genome transcription in ATP2C1 KO cells. The calcium chelator BAPTA-AM, which reduces cytosolic calcium, rescues the defective ATP2C1 KO phenotype and AAV transduction in vitro Conversely, the calcium ionophore ionomycin, which disrupts calcium gradients, blocks AAV transduction. Further, we demonstrated that modulating calcium in the murine brain using BAPTA-AM augments AAV gene expression in vivo Taking these data together, we postulate that the maintenance of an intracellular calcium gradient by the calcium ATPase and processing within the Golgi compartment are essential for priming the capsid to support efficient AAV genome transcription.IMPORTANCE Adeno-associated viruses (AAVs) have proven to be effective gene transfer vectors. However, our understanding of how the host cell environment influences AAV transduction is still evolving. In the present study, we investigated the role of ATP2C1, which encodes a membrane calcium transport pump, SPCA1, essential for maintaining cellular calcium homeostasis on AAV transduction. Our results indicate that cellular calcium is essential for efficient intracellular trafficking and conformational changes in the AAV capsid that support efficient genome transcription. Further, we show that pharmacological modulation of cellular calcium levels can potentially be applied to improve the AAV gene transfer efficiency.

Using SHAPE-MaP To Model RNA Secondary Structure and Identify 3'UTR Variation in Chikungunya Virus.

Chikungunya virus (CHIKV) is a mosquito-borne alphavirus associated with debilitating arthralgia in humans. RNA secondary structure in the viral genome plays an important role in the lifecycle of alphaviruses; however, the specific role of RNA structure in regulating CHIKV replication is poorly understood. Our previous studies found little conservation in RNA secondary structure between alphaviruses, and this structural divergence creates unique functional structures in specific alphavirus genomes. Therefore, to understand the impact of RNA structure on CHIKV biology, we used SHAPE-MaP to inform the modeling of RNA secondary structure throughout the genome of a CHIKV isolate from the 2013 Caribbean outbreak. We then analyzed regions of the genome with high levels of structural specificity to identify potentially functional RNA secondary structures and identified 23 regions within the CHIKV genome with higher than average structural stability, including four previously identified, functionally important CHIKV RNA structures. We also analyzed the RNA flexibility and secondary structures of multiple 3'UTR variants of CHIKV that are known to affect virus replication in mosquito cells. This analysis found several novel RNA structures within these 3'UTR variants. A duplication in the 3'UTR that enhances viral replication in mosquito cells led to an overall increase in the amount of unstructured RNA in the 3'UTR. This analysis demonstrates that the CHIKV genome contains a number of unique, specific RNA secondary structures and provides a strategy for testing these secondary structures for functional importance in CHIKV replication and pathogenesis.IMPORTANCE Chikungunya virus (CHIKV) is a mosquito-borne RNA virus that causes febrile illness and debilitating arthralgia in humans. CHIKV causes explosive outbreaks but there are no approved therapies to treat or prevent CHIKV infection. The CHIKV genome contains functional RNA secondary structures that are essential for proper virus replication. Since RNA secondary structures have only been defined for a small portion of the CHIKV genome, we used a chemical probing method to define the RNA secondary structures of CHIKV genomic RNA. We identified 23 highly specific structured regions of the genome, and confirmed the functional importance of one structure using mutagenesis. Furthermore, we defined the RNA secondary structure of three CHIKV 3'UTR variants that differ in their ability to replicate in mosquito cells. Our study highlights the complexity of the CHIKV genome and describes new systems for designing compensatory mutations to test the functional relevance of viral RNA secondary structures.

Community socioeconomic disadvantage drives type of 30-day medical-surgical revisits among patients with serious mental illness.

BACKGROUND: Patients with serious mental illness (SMI) are vulnerable to medical-surgical readmissions and emergency department visits. METHODS: We studied 1,914,619 patients with SMI discharged after medical-surgical admissions in Florida and New York between 2012 and 2015 and their revisits to the hospital within 30 days of discharge. RESULTS: Patients with SMI from the most disadvantaged communities had greater adjusted 30-day revisit rates than patients from less disadvantaged communities. Among those that experienced a revisit, patients from the most disadvantaged communities had 7.3 % greater 30-day observation stay revisits. CONCLUSIONS: These results suggest that additional investments are needed to ensure that patients with SMI from the most disadvantaged communities are receiving appropriate post-discharge care.

Helping Children with Obesity "Move Well" To Move More: An Applied Clinical Review.

ABSTRACT: Children with obesity experience musculoskeletal pain and reduced physical function and well-being, which collectively impact their fitness, strength, motor skills, and even their ability to undertake simple tasks, like walking and climbing stairs. Disrupting obesity-related disability may be critical to increasing children's physical activity. Thus, barriers to movement should be considered by health practitioners to improve the efficacy of prescribed physical activity. This applied clinical review highlights key subjective and objective findings from a hypothetical case scenario, linking those findings to the research evidence, before exploring strategies to enhance movement and increase physical activity.

Musculoskeletal pain in lacrosse officials impacts function on the field.

This study determined the prevalence of joint pain among lacrosse officials and described the impact of pain thereof on current officiating duties on the field. Members of the US Lacrosse Officials Development Programme were provided with an electronic survey (a 15.7% response rate resulted in N = 1,441 of completed surveys). Pain sites and severity, previous injuries and current impact of musculoskeletal pain on officiating duties were captured. Pain was present in 18.1-40.1% of respondents at the foot, shoulder, back and knee. A total of 437 officials reported diagnoses of osteoarthritis ([OA]; knee 48.7%, hip 10.5%, spine 10.1%, shoulder 8.0%) and 247 reported OA in more than one joint (p < .05). Officials with OA or previous lacrosse-related injuries reported frequent difficulty with running the entire field distance (p < 0.0001), starting and stopping on the field (p < 0.0001), keeping pace (p < 0.0001), focusing on multiple actions of players at once (p < 0.0001), and enjoyment (all p < 0.0001). Musculoskeletal pain is a common, unrecognized issue in this population that interferes with sport officiating functions. Additional study is needed to objectively determine the impact of OA pain and musculoskeletal injuries on measurable performance outcomes on the field and subjective measures of focus, attention and enjoyment.

mTORC2 Activity Disrupts Lysosome Acidification in Systemic Lupus Erythematosus by Impairing Caspase-1 Cleavage of Rab39a.

Lysosomes maintain immune homeostasis through the degradation of phagocytosed apoptotic debris; however, the signaling events regulating lysosomal maturation remain undefined. In this study, we show that lysosome acidification, key to the maturation process, relies on mTOR complex 2 (mTORC2), activation of caspase-1, and cleavage of Rab39a. Mechanistically, the localization of cofilin to the phagosome recruits caspase-11, which results in the localized activation of caspase-1. Caspase-1 subsequently cleaves Rab39a on the phagosomal membrane, promoting lysosome acidification. Although caspase-1 is critical for lysosome acidification, its activation is independent of inflammasomes and cell death mediated by apoptosis-associated speck-like protein containing a caspase recruitment domain, revealing a role beyond pyroptosis. In lupus-prone murine macrophages, chronic mTORC2 activity decouples the signaling pathway, leaving Rab39a intact. As a result, the lysosome does not acidify, and degradation is impaired, thereby heightening the burden of immune complexes that activate FcγRI and sustain mTORC2 activity. This feedforward loop promotes chronic immune activation, leading to multiple lupus-associated pathologies. In summary, these findings identify the key molecules in a previously unappreciated signaling pathway that promote lysosome acidification. It also shows that this pathway is disrupted in systemic lupus erythematosus.

Structural divergence creates new functional features in alphavirus genomes.

Alphaviruses are mosquito-borne pathogens that cause human diseases ranging from debilitating arthritis to lethal encephalitis. Studies with Sindbis virus (SINV), which causes fever, rash, and arthralgia in humans, and Venezuelan equine encephalitis virus (VEEV), which causes encephalitis, have identified RNA structural elements that play key roles in replication and pathogenesis. However, a complete genomic structural profile has not been established for these viruses. We used the structural probing technique SHAPE-MaP to identify structured elements within the SINV and VEEV genomes. Our SHAPE-directed structural models recapitulate known RNA structures, while also identifying novel structural elements, including a new functional element in the nsP1 region of SINV whose disruption causes a defect in infectivity. Although RNA structural elements are important for multiple aspects of alphavirus biology, we found the majority of RNA structures were not conserved between SINV and VEEV. Our data suggest that alphavirus RNA genomes are highly divergent structurally despite similar genomic architecture and sequence conservation; still, RNA structural elements are critical to the viral life cycle. These findings reframe traditional assumptions about RNA structure and evolution: rather than structures being conserved, alphaviruses frequently evolve new structures that may shape interactions with host immune systems or co-evolve with viral proteins.

Can an Integrative Care Approach Improve Physical Function Trajectories after Orthopaedic Trauma? A Randomized Controlled Trial.

BACKGROUND: Orthopaedic trauma patients frequently experience mobility impairment, fear-related issues, self-care difficulties, and work-related disability []. Recovery from trauma-related injuries is dependent upon injury severity as well as psychosocial factors []. However, traditional treatments do not integrate psychosocial and early mobilization to promote improved function, and they fail to provide a satisfying patient experience. QUESTIONS/PURPOSES: We sought to determine (1) whether an early psychosocial intervention (integrative care with movement) among patients with orthopaedic trauma improved objective physical function outcomes during recovery compared with usual care, and (2) whether an integrative care approach with orthopaedic trauma patients improved patient-reported physical function outcomes during recovery compared with usual care. METHODS: Between November 2015 and February 2017, 1133 patients were admitted to one hospital as orthopaedic trauma alerts to the care of the three orthopaedic trauma surgeons involved in the study. Patients with severe or multiple orthopaedic trauma requiring one or more surgical procedures were identified by our orthopaedic trauma surgeons and approached by study staff for enrollment in the study. Patients were between 18 years and 85 years of age. We excluded individuals outside of the age range; those with diagnosis of a traumatic brain injury []; those who were unable to communicate effectively (for example, at a level where self-report measures could not be answered completely); patients currently using psychotropic medications; or those who had psychotic, suicidal, or homicidal ideations at time of study enrollment. A total of 112 orthopaedic trauma patients were randomized to treatment groups (integrative and usual care), with 13 withdrawn (n = 99; 58% men; mean age 44 years ± 17 years). Data was collected at the following time points: baseline (acute hospitalization), 6 weeks, 3 months, 6 months, and at 1 year. By 1-year follow-up, we had a 75% loss to follow-up. Because our data showed no difference in the trajectories of these outcomes during the first few months of recovery, it is highly unlikely that any differences would appear months after 6 months. Therefore, analyses are presented for the 6-month follow-up time window. Integrative care consisted of usual trauma care plus additional resources, connections to services, as well as psychosocial and movement strategies to help patients recover. Physical function was measured objectively (handgrip strength, active joint ROM, and Lower Extremity Gain Scale) and subjectively (Patient-Reported Outcomes Measurement Information System-Physical Function [PROMIS®-PF] and Tampa Scale of Kinesiophobia). Higher values for hand grip, Lower Extremity Gain Scale (score range 0-27), and PROMIS®-PF (population norm = 50) are indicative of higher functional ability. Lower Tampa Scale of Kinesiophobia (score range 11-44) scores indicate less fear of movement. Trajectories of these measures were determined across time points. RESULTS: We found no differences at 6 months follow-up between usual care and integrative care in terms of handgrip strength (right handgrip strength ß = -0.0792 [95% confidence interval -0.292 to 0.133]; p = 0.46; left handgrip strength ß = -0.133 [95% CI -0.384 to 0.119]; p = 0.30), or Lower Extremity Gain Scale score (ß = -0.0303 [95% CI -0.191 to 0.131]; p = 0.71). The only differences between usual care and integrative care in active ROM achieved by final follow-up within the involved extremity was noted in elbow flexion, with usual care group 20° ± 10° less than integrative care (t [27] = -2.06; p = 0.05). Patients treated with usual care and integrative care showed the same Tampa Scale of Kinesiophobia score trajectories (ß = 0.0155 [95% CI -0.123 to 0.154]; p = 0.83). CONCLUSION: Our early psychosocial intervention did not change the trajectory of physical function recovery compared with usual care. Although this specific intervention did not alter recovery trajectories, these interventions should not be abandoned because the greatest gains in function occur early in recovery after trauma, which is the key time in transition to home. More work is needed to identify ways to capitalize on improvements earlier within the recovery process to facilitate functional gains and combat psychosocial barriers to recovery. LEVEL OF EVIDENCE: Level II, therapeutic study.

An RNA structure-mediated, posttranscriptional model of human α-1-antitrypsin expression.

Chronic obstructive pulmonary disease (COPD) affects over 65 million individuals worldwide, where α-1-antitrypsin deficiency is a major genetic cause of the disease. The α-1-antitrypsin gene, SERPINA1, expresses an exceptional number of mRNA isoforms generated entirely by alternative splicing in the 5'-untranslated region (5'-UTR). Although all SERPINA1 mRNAs encode exactly the same protein, expression levels of the individual mRNAs vary substantially in different human tissues. We hypothesize that these transcripts behave unequally due to a posttranscriptional regulatory program governed by their distinct 5'-UTRs and that this regulation ultimately determines α-1-antitrypsin expression. Using whole-transcript selective 2'-hydroxyl acylation by primer extension (SHAPE) chemical probing, we show that splicing yields distinct local 5'-UTR secondary structures in SERPINA1 transcripts. Splicing in the 5'-UTR also changes the inclusion of long upstream ORFs (uORFs). We demonstrate that disrupting the uORFs results in markedly increased translation efficiencies in luciferase reporter assays. These uORF-dependent changes suggest that α-1-antitrypsin protein expression levels are controlled at the posttranscriptional level. A leaky-scanning model of translation based on Kozak translation initiation sequences alone does not adequately explain our quantitative expression data. However, when we incorporate the experimentally derived RNA structure data, the model accurately predicts translation efficiencies in reporter assays and improves α-1-antitrypsin expression prediction in primary human tissues. Our results reveal that RNA structure governs a complex posttranscriptional regulatory program of α-1-antitrypsin expression. Crucially, these findings describe a mechanism by which genetic alterations in noncoding gene regions may result in α-1-antitrypsin deficiency.

Comparison of wet bulb globe temperature measured on-site vs estimated and the impact on activity modification in high school football.

Exertional heat stroke is one of the top three causes of death in young athletes, particularly high school football players. Despite evidence that these deaths are completely avoidable with appropriate prevention and treatment, deaths still occur at an alarming rate. Wet bulb globe temperature (WBGT) is the preferred method of both the National Athletic Trainers' Association and American College of Sports Medicine to measure heat intensity. Based on the WBGT, activity modification guidelines (AMG) dictate work-to-rest ratios, activity levels and duration, protective equipment worn, and length and frequency of hydration breaks. Due to the cost of handheld WBGT monitors, smartphone apps that estimate WBGT have been considered an alternative. However, it is unclear how WBGT values estimated by these smartphone apps compare to those measured on-site using handheld WBGT monitors. We compared WBGT values estimated by a commercial smartphone app to those taken on-site at the same time and place. Thirteen athletic trainers measured WBGT in the field during high school football practices over a three-month season in North Central Florida. A paired sample t-test indicated the smartphone app significantly overestimated WBGT (29.0°C ± 4.1°C) compared to on-site measures (26.4°C ± 3.2°C) ( r =0.580; t(943)=-23.38, p <0.0001). The smartphone app-estimated values were consistently greater than on-site measures, resulting in potentially unnecessary activity modifications and cancellations if the app was used in place of on-site handheld WBGT monitors. Despite being significantly cheaper than handheld WBGT monitors, at this time, smartphone apps are not ready for widespread use to guide activity modification decisions.