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Purpose The purpose of this study is to describe and assess the impact of multi-domain biopsychosocial (BPS) recovery on outcomes following lumbar spine fusion. We hypothesized that discrete patterns of BPS recovery (e.g., clusters) would be identified, and then associated with postoperative outcomes and preoperative patient data. Methods Patient-reported outcomes for pain, disability, depression, anxiety, fatigue, and social roles were collected at multiple timepoints for patients undergoing lumbar fusion between baseline and one year. Multivariable latent class mixed models assessed composite recovery as a function of (1) pain, (2) pain and disability, and (3) pain, disability, and additional BPS factors. Patients were assigned to clusters based on their composite recovery trajectories over time. Results Using all BPS outcomes from 510 patients undergoing lumbar fusion, three multi-domain postoperative recovery clusters were identified: Gradual BPS Responders (11%), Rapid BPS Responders (36%), and Rebound Responders (53%). Modeling recovery from pain alone or pain and disability alone failed to generate meaningful or distinct recovery clusters. BPS recovery clusters were associated with number of levels fused and preoperative opioid use. Postoperative opioid use (p p Conclusion This study describes distinct clusters of recovery following lumbar spine fusion derived from multiple BPS factors, which are related to patient-specific preoperative factors and postoperative outcomes. Understanding postoperative recovery trajectories across multiple health domains will advance our understanding of how BPS factors interact with surgical outcomes and could inform personalized care plans.

Purpose This study explores the biomechanics underlying the sit-to-stand (STS) functional maneuver in chronic LBP patients to understand how different spinal disorders and levels of pain severity relate to unique compensatory biomechanical behaviors. This work stands to further our understanding of the relationship between spinal loading and symptoms in LBP patients. Methods We collected in-clinic motion data from 44 non-specific LBP (NS-LBP) and 42 spinal deformity LBP (SD-LBP) patients during routine clinical visits. An RGB-depth camera tracked 3D joint positions from the frontal view during unassisted, repeated STS maneuvers. Patient-reported outcomes (PROs) for back pain (VAS) and low back disability (ODI) were collected during the same clinical visit. Results Between patient groups, SD-LBP patients had 14.3% greater dynamic sagittal vertical alignment (dSVA) and 10.1% greater peak spine torque compared to NS-LBP patients (p p p = 0.04) compared to NS-LBP patients. There were no significant differences between patient groups in regard to anterior or vertical torso velocities, but anterior and vertical torso velocities correlated with both VAS (r = − 0.38, p r = − 0.29, p = 0.01). PROs did not correlate with other variables. Conclusion Patients with LBP differ in movement biomechanics during an STS transfer as severity of symptoms may relate to different compensatory strategies that affect spinal loading. Further research aims to establish relationships between movement and PROs and to inform targeted rehabilitation approaches.

Background Context For chronic low back pain, the causal mechanisms between pathological features from imaging and patient symptoms are unclear. For instance, disc herniations can often be present without symptoms. There remains a need for improved knowledge of the pathophysiological mechanisms that explore spinal tissue damage and clinical manifestations of pain and disability. Spaceflight and astronaut health provides a rare opportunity to study potential low back pain mechanisms longitudinally. Spaceflight disrupts diurnal loading on the spine and several lines of evidence indicate that astronauts are at a heightened risk for low back pain and disc herniation following spaceflight. Purpose To examine the relationship between prolonged exposure to microgravity and the elevated incidence of postflight disc herniation, we conducted a longitudinal study to track the spinal health of twelve NASA astronauts before and after approximately 6-months in space. We hypothesize that the incidence of postflight disc herniation and low back complaints associates with spaceflight-included muscle atrophy and pre-existing spinal pathology. Study Design This is a prospective longitudinal study. Patient Sample Our sample included a cohort of twelve astronaut crewmembers. Outcome Measures From 3T MRI, we quantified disc water content (ms), disc degeneration (Pfirrmann grade), vertebral end plate irregularities, facet arthropathy and/ fluid, high intensity zones, disc herniation, multifidus total cross-sectional area (cm2), multifidus lean muscle cross-sectional area (cm2), and muscle quality/composition (%). From quantitative fluoroscopy we quantified, maximum flexion-extension ROM (°), maximum lateral bending ROM (°), and maximum translation (%). Lastly, patient outcomes and clinical notes were used for identifying postflight symptoms associated with disc herniations from 3T MRI. Methods Advanced imaging data from 3T MRI were collected at three separate time points in relation to spending 6-months in space: (1) within a year before launch (“pre-flight”), (2) within a week after return to Earth (“post-flight”), and (3) between 1- and 2-months after return to Earth (“recovery”). Fluoroscopy of segmental kinematics was collected at preflight and postflight timepoints. We assessed the effect of spaceflight and postflight recovery on longitudinal changes in spinal structure and function, as well as differences between crew members who did and did not present a symptomatic disc herniation following spaceflight. Results Half of our astronauts (n=6) experienced new symptoms associated with a new or previously asymptomatic lumbar disc protrusion or extrusion following spaceflight. We observed decreased multifidus muscle quality following spaceflight in the lower lumbar spine, with a reduced percentage of lean muscle at L4L5(-6.2%, p=.009) and L5S1 (-7.0%, p=.006) associated with the incidence of new disc herniation. Additionally, we observed reduced lumbar segment flexion-extension ROM for L2L3 (-17.2%, p=.006) and L3L4 (-20.5%, p=.02) following spaceflight, and furthermore that reduced ROM among the upper three lumbar segments (-24.1%, p=.01) associated with the incidence of disc herniation. Existing end plate pathology was most prevalent in the upper lumbar spine and associated with reduced segmental ROM (-20.5%, p=.02). Conclusions In conclusion from a 10-year study investigating the effects of spaceflight on the lumbar spine and risk for disc herniation, we found the incidence of lumbar disc herniation following spaceflight associates with compromised multifidus muscle quality and spinal segment kinematics, as well as pre-existing spinal end plate irregularities. These findings suggest differential effects of spinal stiffness and muscle loss in the upper versus lower lumbar spine regions that may specifically provoke risk for symptomatic disc herniation in the lower lumbar spine following spaceflight. Results from this study provide a unique longitudinal assessment of mechanisms and possible risk factors for developing disc herniations and related low back pain. Furthermore, these findings will help inform physiologic countermeasures to maintain spinal health in astronauts during long-duration missions in space.

Background #OrthoTwitter has evolved to disseminate findings and engage the public. However, the academic impact of Twitter utilization in orthopaedic surgery is unknown. Questions/purposes The purpose of the study was to evaluate relationships between the author and manuscript Twitter activity and citations. Methods Manuscripts in 17 orthopaedic journals from 2018 were identified. Citations, online mentions, impact factors, and subspecialties were obtained. H-index and Twitter account details for authors were obtained for a subset of manuscripts. Relationships between Twitter activity and citations were evaluated. Results 2,473/4,224 (58.5%) manuscripts were mentioned on Twitter (n=29,958 mentions), with Twitter manuscripts cited more frequently (median 10 vs. 7, p

Paraspinal muscle imaging is of growing interest related to improved phenotyping, prognosis, and treatment of common spinal disorders. We reviewed issues related to paraspinal muscle imaging measurement that contribute to inconsistent findings between studies and impede understanding. Three key contributors to inconsistencies among studies of paraspinal muscle imaging measurements were reviewed: failure to consider possible mechanisms underlying changes in paraspinal muscles, lack of control of confounding factors, and variations in spinal muscle imaging modalities and measurement protocols. Recommendations are provided to address these issues to improve the quality and coherence of future research. Possible pathophysiological responses of paraspinal muscle to various common spinal disorders in acute or chronic phases are often overlooked, yet have important implications for the timing, distribution, and nature of changes in paraspinal muscle. These considerations, as well as adjustment for possible confounding factors, such as sex, age, and physical activity must be considered when planning and interpreting paraspinal muscle measurements in studies of spinal conditions. Adoption of standardised imaging measurement protocols for paraspinal muscle morphology and composition, considering the strengths and limitations of various imaging modalities, is critically important to interpretation and synthesis of research. Study designs that consider physiological and pathophysiological responses of muscle, adjust for possible confounding factors, and use common, standardised measures are needed to advance knowledge of the determinants of variations or changes in paraspinal muscle and their influence on spinal health.

Mindy Hong,1 Melanie Topete,1 Manshu Yang,2 Jeannie F Bailey3 1Hinge Health, Inc, San Francisco, CA, USA; 2Department of Psychology, University of Rhode Island, Kingston, RI, USA; 3Department of Orthopaedic Surgery, University of California San Francisco, San Francisco, CA, USACorrespondence: Mindy Hong, Hinge Health, Inc, 455 Market Street, Suite 700, San Francisco, CA, 94105, USA, Email mindy.hong@hingehealth.comBackground: There is limited research on whether digital interventions can prevent acute or subacute pain from developing into chronic pain. This observational study’s primary objective examined whether chronic pain was more likely to be prevented in digital acute MSK program participants than nonparticipants. An exploratory objective was time to pain relief for program participants versus nonparticipants.Patients and Methods: The intervention group participants conducted video visits with physical therapists and were recommended exercise therapies and educational articles delivered through an app dedicated to addressing musculoskeletal (MSK) needs. This study used a multidimensional approach incorporating pain, function, depression, and anxiety scores to determine whether chronic pain prevention was achieved at 12 weeks. Descriptive analyses, unadjusted, and adjusted logistic regression were conducted. Time-to-event analysis was performed to compare the time to pain relief between groups.Results: A total of 171 participants (intervention: 75, nonparticipants: 96) with baseline and 3, 6, and 12 week follow-up data were included in the sample. Baseline mean (SD) age was 44.2 (11.8) years and mean VAS pain was 43.3 (22.9), out of 100. Results showed significantly higher odds of achieving chronic pain prevention at 12 weeks in the intervention participants versus nonparticipants. After adjusting for age, pain region, registration month, number of weeks of pain experienced, and healthcare service use at 12 weeks, 20.5% of the intervention group and 5.5% of the nonparticipant group achieved chronic pain prevention. At 91 days, the probability of developing chronic pain was 77.7% for nonparticipants and 46.5% for intervention participants (p< 0.001; Log rank test).Conclusion: A digital acute MSK program may help to prevent chronic pain from developing among those with acute and subacute MSK needs. Study results also suggest that program participants achieve chronic pain relief sooner compared to nonparticipants.Keywords: acute, chronic, musculoskeletal, pain, prevention, telemedicine

Background Surgery can sometimes be the best solution for chronic musculoskeletal pain, but presurgical preparation and postsurgical rehabilitation are often required to achieve the maximum benefits. A digital musculoskeletal surgical care program was developed to support the population of patients undergoing total knee arthroplasty. Objective We aimed to demonstrate safety, engagement, and acceptability and explore clinical outcomes, health care use, and satisfaction among participants of a digital musculoskeletal surgical care program who were undergoing total knee arthroplasty. Methods A retrospective, observational feasibility study comparing digital musculoskeletal surgical care program participants to a comparison group was conducted. The intervention group registered for a digital musculoskeletal surgical care program, which included health coaches, physical therapists, and tailored exercises and educational articles to provide preoperative and postoperative support to patients who had recently undergone total knee arthroplasty. Comparison group members received standard-of-care treatment. Engagement (number of exercise therapy sessions and educational articles accessed per week) and acceptability (Net Promoter Score) were examined among intervention group participants. Descriptive statistics for postoperative outcomes, including safety (postoperative complications), clinical improvement (pain, function, anxiety, and depression), and health care use and experiences (length of hospital stay, surgery satisfaction, and physical therapy adherence), were reported for both groups. Differences among postoperative results were compared by using the independent samples 2-tailed t test or Mann-Whitney test for continuous outcomes and the Fisher exact test or chi-square test for categorical outcomes. Results Of the 53 participants (intervention group: n=22; comparison group: n=31) who were included in this study, 35 (66%) were female and 25 (47%) were aged from 45 to 60 years. On average, the intervention group completed 23 exercise sessions, read 2.7 educational articles, sent 45.5 texts to their health coaches, and were actively engaged for 6 weeks after their operation. Among 21 participants, 14 (67%) self-reported as promoters on the Net Promoter Score scale. Intervention group members reported fewer postoperative complications (6/22, 27%) than the comparison group (15/31, 48%), and they experienced better outcomes with regard to function (Knee Injury and Osteoarthritis Outcome Score–Physical Function Short Form—intervention group: mean 23.0; comparison group: mean 32.5), depression (Patient Health Questionnaire 2-Item—intervention group: mean 0.4; comparison group: mean 1.6), anxiety (General Anxiety Disorder 2-Item—intervention group: mean 0.6; comparison group: mean 1.5), and impressions of change (Patient Global Impression of Change—intervention group: median 7.0; comparison group: median 6.0). Intervention group participants also reported less health care use, better adherence to their physical therapy exercises, and higher surgery satisfaction. Conclusions Our digital musculoskeletal surgical care program shows promising levels of engagement and acceptability among those who recently underwent total knee arthroplasty. The surgical care program may also help with improving postsurgical complications and clinical outcomes and lowering health care use.

BACKGROUND Clinical guidelines typically recommend conservative interventions before invasive procedures in people with chronic musculoskeletal (MSK) pain. However, conservative treatment is not effective for everyone, and surgery can sometimes be the best solution. There is a lack of social support, care, and assistance in helping patients both prepare and recover from surgery. A digital MSK surgical care program was developed to address these care gaps and subsequent impacts on care quality and outcomes. OBJECTIVE To demonstrate safety, engagement, and acceptability and explore clinical outcomes, healthcare use, and satisfaction among participants of a digital MSK surgical care program METHODS The intervention group registered for a digital MSK surgical care program, which included health coaches, physical therapists (PTs), customized exercises, and tailored educational articles to provide pre and postoperative support to those who recently underwent total knee arthroplasty (TKA). Comparison group members received standard-of-care treatment. Engagement and acceptability were examined among those in the intervention group. Postoperative safety, clinical outcomes, healthcare use, and experience outcomes were compared against a comparison group. RESULTS 53 participants (intervention: 22, comparison: 31) were included in this study, of which 35 (66.0%) were female and 25 (47.2%) were ages 45-60 years. On average, the intervention group completed 23 exercise therapy sessions (ETs), read 2.7 educational articles, sent 45.5 text messages to their health coach, and were actively engaged for 6 weeks after their operation. 14 out of 21 participants (66.7%) self-reported as Promoters on the Net Promoter Score (NPS). Intervention group members reported fewer postoperative complications (intervention: 6 out of 22 participants [27.3%], comparison: 15 out of 31 participants [48.4%]) and experienced better outcomes in function (mean KOOS-PS; intervention: 23.0, comparison: 32.5), depression (mean PHQ-2; intervention: 0.4, comparison: 1.6), anxiety (mean GAD-2; intervention: 0.6, comparison: 1.5), and impression of change (median PGIC; intervention: 7.0, comparison: 6.0), than comparison group members. The intervention group also reported less healthcare use, better adherence to their PT exercises, and higher surgery satisfaction. CONCLUSIONS A digital surgical care MSK program shows promising levels of engagement and acceptability among those who recently underwent TKA. The surgical care program may also help with improving postsurgical complications and clinical outcomes, as well as lowering healthcare use.

Chronic low back pain (LBP) is a leading cause of disability and opioid prescriptions worldwide, representing a significant medical and socioeconomic problem. Clinical heterogeneity of LBP limits accurate diagnosis and precise treatment planning, culminating in poor patient outcomes. A current priority of LBP research is the development of objective, multidimensional assessment tools that subgroup LBP patients based on neurobiological pain mechanisms, to facilitate matching patients with the optimal therapies. Using unsupervised machine learning on full body biomechanics, including kinematics, dynamics, and muscle forces, captured with a marker-less depth camera, this study identified a forward-leaning sit-to-stand strategy (STS) as a discriminating movement biomarker for LBP subjects. A forward-leaning STS strategy, as opposed to a vertical rise strategy seen in the control participants, is less efficient and results in increased spinal loads. Inefficient STS with the subsequent higher spinal loading may be a biomarker of poor motor control in LBP patients as well as a potential source of the ongoing symptomology.

Mutant phenotype analysis of bacteria has been revolutionized by genome-scale screening procedures, but essential genes have been left out of such studies because mutants are missing from the libraries analyzed. Since essential genes control the most fundamental processes of bacterial life, this is a glaring deficiency. To address this limitation, we developed a procedure for transposon insertion mutant sequencing that includes essential genes. The method, called transformation transposon insertion mutant sequencing (TFNseq), employs saturation-level libraries of bacterial mutants generated by natural transformation with chromosomal DNA mutagenized heavily by in vitro transposition. The efficient mutagenesis makes it possible to detect large numbers of insertions in essential genes immediately after transformation and to follow their loss during subsequent growth. It was possible to order 45 essential processes based on how rapidly their inactivation inhibited growth. Inactivating ATP production, deoxyribonucleotide synthesis, or ribosome production blocked growth the fastest, whereas inactivating cell division or outer membrane protein synthesis blocked it the slowest. Individual mutants deleted of essential loci formed microcolonies of nongrowing cells whose sizes were generally consistent with the TFNseq ordering. The sensitivity of essential functions to genetic inactivation provides a metric for ranking their relative importance for bacterial replication and growth. Highly sensitive functions could represent attractive antibiotic targets since even partial inhibition should reduce growth.

Retrospective cohort study.Evaluate the effects of parity (number of births) on measures of sagittal posture in elderly women. The long-term objective of this study is to identify and mitigate factors contributing to age-related postural deformity in older adults.Adult spinal deformity is a prevalent condition that often requires costly surgical management. Females are disproportionately represented in spinal deformity surgical cases with up to 90% of patients being women. The potential contributions of pregnancy on postural degeneration have only begun to be acknowledged and require further study.Two hundred eight women with standing lateral radiographs were selected from the TwinsUK register. Parity information was extracted from questionnaires. Sagittal balance measurements (thoracic kyphosis, lumbar lordosis [LL], pelvic incidence [PI]) were collected and PI-LL mismatch was calculated. One-way analysis of variance tests were done between three separate age categories for measures of sagittal balance and parity and stepwise multivariate regression was done for PI-LL.Both age and PI-LL mismatch significantly differed between parity categories. PI-LL was on average 7.0° ± 2.5° greater in multiparous (3+ births) subjects than in nulliparous subjects (P 0.01). Parity did not have an independent relationship with lumbar disc degeneration, lumbar bone mineral density, or any of the individual sagittal balance parameters (P 0.05 for all), except for PI-LL. From a subanalysis of the effect of parity on sagittal alignment within twin pairs, we found that within pair differences in parity associate with within pair differences in thoracic kyphosis.This study established correlations between measures of spinal curvature in older women and parity for the first time. Longitudinal research is required to establish a causative relationship.4.

Purpose The paraspinal muscles (PSM) are a key feature potentially related to low back pain (LBP), and their structure and composition can be quantified using MRI. Most commonly, quantifying PSM measures across individual muscles and individual spinal levels renders numerous separate metrics that are analyzed in isolation. However, comprehensive multivariate approaches would be more appropriate for analyzing the PSM within an individual. To establish and test these methods, we hypothesized that multivariate summaries of PSM MRI measures would associate with the presence of LBP symptoms (i.e., pain intensity). Methods We applied hierarchical multiple factor analysis (hMFA), an unsupervised integrative method, to clinical PSM MRI data from unique cohort datasets including a longitudinal cohort of astronauts with pre- and post-spaceflight data and a cohort of chronic LBP subjects and asymptomatic controls. Three specific use cases were investigated: (1) predicting longitudinal changes in pain using combinations of baseline PSM measures; (2) integrating baseline and post-spaceflight MRI to assess longitudinal change in PSM and how it relates to pain; and (3) integrating PSM quality and adjacent spinal pathology between LBP patients and controls. Results Overall, we found distinct complex relationships with pain intensity between particular muscles and spinal levels. Subjects with high asymmetry between left and right lean muscle composition and differences between spinal segments PSM quality and structure are more likely to increase in pain reported outcome after prolonged time in microgravity. Moreover, changes in PSM quality and structure between pre and post-spaceflight relate to increase in pain after prolonged microgravity. Finally, we show how unsupervised hMFA recapitulates previous research on the association of CEP damage and LBP diagnostic. Conclusion Our analysis considers the spine as a multi-segmental unit as opposed to a series of discrete and isolated spine segments. Integrative and multivariate approaches can be used to distill large and complex imaging datasets thereby improving the clinical utility of MRI-based biomarkers, and providing metrics for further analytical goals, including phenotyping.

IntroductionMany studies have attempted to link multifidus (MF) fat infiltration with muscle quality and chronic low back pain (cLBP), but there is no consensus on these relationships.MethodsIn this cross-sectional cohort study, 39 cLBP patients and 18 asymptomatic controls were included. The MF muscle was manually segmented at each lumbar disc level and fat fraction (FF) measurements were taken from the corresponding advanced imaging water-fat images. We assessed the distribution patterns of MF fat from L1L2 to L5S1 and compared these patterns between groups. The sample was stratified by age, sex, body mass index (BMI), subject-reported pain intensity (VAS), and subject-reported low back pain disability (oswestry disability index, ODI).ResultsOlder patients had significantly different MF FF distribution patterns compared to older controls (p

Purpose Fat infiltration (FI) of the paraspinal muscles (PSMs) measured using MRI is an aspect of muscle quality and is considered to be worse in chronic low back pain (cLBP) patients. However, there is not a clear association between paraspinal muscle FI and cLBP, leaving the clinical importance of paraspinal muscle composition unestablished. The spatial distribution of FI in the PSMs may inform mechanistic understanding of non-specific cLBP as it relates to degenerative intervertebral disc (IVD) pathology. We hypothesized that paraspinal muscle fat-mapping would reveal distinct FI distribution patterns in relation to cLBP symptoms and proximity to symptomatic IVD degeneration. Methods From advanced-sequence water-fat MRI of 40 axial cLBP patients and 21 controls, we examined the spatial distribution of paraspinal muscle FI in relation to the center of rotation at the L4L5 disc. Using statistical parametric mapping, we compared FI patterns for multifidus (MF), erector spinae (ES), and psoas between patients and controls, and to the presence and severity of adjacent degenerative IVD pathology. Results The spatial distribution of PSMs FI differs between PSMs and according to symptoms and the adjacent degenerative IVD pathology. Furthermore, the region of MF closest to the disc center of rotation appears most susceptible to FI in the presence of symptomatic IVD degeneration. Conclusion Our study identified spatial distribution patterns of FI in the PSMs as a potential diagnostic biomarker that may also provide granular mechanistic insights into spine biomechanics related to cLBP, as well as advancing the use of prior summary measures limited to overall muscle FI.

Background The evidence base for the impact of digital health on musculoskeletal (MSK) outcomes is growing, but it is unclear how much digital MSK programs address pain and function in the intermediate and long term. Methods This observational study of digital MSK program participants versus nonparticipants (n = 2570) examined pain, function, depression, and anxiety at 3, 6, and 12 months, and health care use at 12 months. The intervention group engaged in a digital MSK program that included exercise, education, and coaching for at least 3 months. The nonparticipant group registered, but never started the program. We collected data in app or by emailed survey at 3, 6, and 12 months after registering for the program. We conducted descriptive analyses and unadjusted and adjusted regression modeling. Results The odds ratio of achieving a minimally clinically important difference (MCID) in pain improvement for the intervention versus the nonparticipant group was 1.97 (95% CI: 1.28, 3.02; p = .002) at 3 months, 1.44 (95% CI: 0.91, 2.25; p = .11) at 6 months, and 2.06 (95% CI: 1.38, 3.08; p = .004) at 12 months in adjusted models. The odds ratio of achieving a MCID in functional improvement for the intervention versus the nonparticipant group was 1.56 (95% CI: 1.03, 2.38; p = .01) at 3 months, 1.55 (95% CI: 1.02, 2.37; p = .04) at 6 months, and 1.35 (95% CI: 0.89, 2.06, p = 0.16) at 12 months in adjusted models. For those with moderate to severe depression or anxiety at baseline, we observed statistically significant lower odds of moderate to severe depression or anxiety at 3 months, 6 months, and 12 months for the intervention versus the nonparticipant group in adjusted models (p p Conclusions A digital MSK program may offer participants sustained improvement in pain, depression, and anxiety with concomitant decreases in health care use.

Summary Teredinibacter turnerae is an intracellular bacterial symbiont in the gills of wood-eating shipworms, where it is proposed to use antibiotics to defend itself and its animal host. Several biosynthetic gene clusters are conserved in T. turnerae and their host shipworms around the world, implying that they encode defensive compounds. Here, we describe turnercyclamycins, lipopeptide antibiotics encoded in the genomes of all sequenced T. turnerae strains. Turnercyclamycins are bactericidal against challenging Gram-negative pathogens, including colistin-resistant Acinetobacter baumannii. Phenotypic screening identified the outer membrane as the likely target. Turnercyclamycins and colistin operate by similar cellular, although not necessarily molecular, mechanisms, but turnercyclamycins kill colistin-resistant A. baumannii, potentially filling an urgent clinical need. Thus, by exploring environments that select for the properties we require, we harvested the fruits of evolution to discover compounds with potential to target unmet health needs. Investigating the symbionts of shipworms is a powerful example of this principle.

Background Context The association between low back pain and lumbar disc degeneration is not fully characterized. One potentially overlooked factor of this process is the lumbar multifidus, which plays a role in segmental stabilization and locomotion. Previous reports have shown multifidus degeneration to be associated with disc degeneration. The goal of this study was to develop a mouse model of advanced lumbar disc degeneration to recapitulate the pathology of the human multifidus in patients with lumbar disc degeneration and low back pain. Methods C57BL/6 mice underwent a left anterolateral approach to the lumbar spine and disc puncture with a micro scalpel at L5/6 and L6/S1. Mice underwent behavioral analysis and functional gait testing. A subset of mice underwent 14T T2-weighted MRI to assess disc degeneration and paraspinal muscle quality. At 6 and 15 weeks, mice were sacrificed, and the multifidus muscles were harvested and divided into proximal and distal segments relative to disc injury. Histological analysis was performed to assess muscle degeneration, fiber type, and macrophage density. Fibroadipogenic progenitors (FAPs) were isolated for gene expression analysis with qPCR. Results MRI demonstrated decreased intervertebral disc signal and paraspinal muscle atrophy at 6 weeks, with progressive degeneration and atrophy at 15 weeks. Disc injury resulted in delayed functional recovery and impaired gait. Histology demonstrated progressive multifidus fibrofatty degeneration between 6 and 15 weeks. CD68+ macrophage density was increased at 6 weeks but not 15 weeks. FAPs exhibited increased fibrotic and adipogenic gene expression at 6 weeks compared to sham with less of a difference in gene expression by 15 weeks. Conclusions We have developed a mouse model of disc injury-mediated paraspinal muscle degeneration that recapitulates features of degenerative muscle pathology observed in patients with lumbar disc degeneration, and highlights the role of FAPs in mediating fibrofatty muscle degeneration after disc injury.

STUDY DESIGN: Cross-sectional cohort study of chronic low back pain (CLBP) patients and matched controls. OBJECTIVE: To explore the interplay between vertebral endplate damage and adjacent paraspinal muscle (PSM) quality, and to test their association in a cohort of patients with chronic low back pain (CLBP) and matched controls. SUMMARY OF BACKGROUND DATA: Non-specific CLBP is challenging to diagnose, in part, due to uncertainty regarding the source of pain. Delineating interactions among potential CLBP mechanisms may enhance diagnosis and treatment customization. METHODS: We collected advanced MRI imaging on 52 adult subjects, including 38 CLBP patients and 14 age- and sex-matched asymptomatic control subjects. Mean multifidus and erector spinae fat fraction (FF) was measured throughout the spine using an IDEAL MRI sequence. Presence of cartilage endplate (CEP) defects was determined at each disc level using UTE MRI. Logistic regression was used to test association of PSM FF, CEP defects, modic changes (MC), disc degeneration, and their interplay. RESULTS: We observed that CEP defects were the strongest predictor of non-specific CLBP (OR: 14.1, p

Low back pain (LBP) is the leading cause of disability throughout the world and is economically burdensome. The recommended first line treatment for non-specific LBP is non-invasive care. A digital care program (DCP) delivering evidence-based non-invasive treatment for LBP can aid self-management by engaging patients and scales personalized therapy for patient-specific needs. We assessed the efficacy of a 12-week DCP for LBP in a two-armed, pre-registered, randomized, controlled trial (RCT). Participants were included based on self-reported duration of LBP, but those with surgery or injury to the lower back in the previous three months were excluded. The treatment group (DCP) received the 12-week DCP, consisting of sensor-guided exercise therapy, education, cognitive behavioral therapy, team and individual behavioral coaching, activity tracking, and symptom tracking – all administered remotely via an app. The control group received three digital education articles only. All participants maintained access to treatment-as-usual. At 12 weeks, an intention-to-treat analysis showed each primary outcome—Oswestry Disability Index (p p p p p

Efficient, cost-effective methods for quantifying patient biomechanics at the point of care can facilitate faster and more accurate diagnoses. This work presents a new method to diagnose pre-surgical back, hip, and knee patients by analysing their sit-to-stand motion captured by a Kinect camera. Kinematic and dynamic time-series features were extracted from patient movements collected in clinic. These features were used to test a variety of machine learning methods for patient classification. The performance of models trained on time-series features were compared against models trained on domain-knowledge features, highlighting the importance of using time-series data for the classification of human movement. Additionally, the effectiveness of using semi-supervised learning is tested on partially labelled datasets, providing insight on how to boost classification performance in situations where labelled patient data is difficult to obtain. The best semi-supervised model achieves ∼73% accuracy in distinguishing individuals with low-back pain, and hip and knee degeneration from control subjects.

Teredinibacter turnerae is an intracellular bacterial symbiont that lives in the gills of wood-eating shipworms, where it is proposed to use antibiotics to defend itself and its animal host. Several biosynthetic gene clusters are conserved in T. turnerae and in their host shipworms around the world, implying that they encode the important defensive antibiotics. Here, we describe the turnercyclamycins, lipopeptide antibiotics encoded in the genomes of all sequenced T. turnerae strains. Turnercyclamycins A and B are bactericidal against challenging Gram-negative pathogens, Escherichia coli, Klebsiella pneumoniae, and Acinetobacter baumannii, at 1, 2, and 8 µg/mL, respectively, while lacking toxicity to mammalian cells. Phenotypic screening identified the outer membrane as the likely target. By exploring the inhabitants of environments that select for the properties we require, we can harvest the fruits of evolution to discover compounds with potential to target unmet health needs. Investigating the symbionts of animals, and shipworms in particular, is a powerful example of this principle.

Purpose Vertebral endplate bone marrow lesions (“Modic changes”, MC) are associated with chronic low back pain (CLBP). Bone marrow composition in MC is poorly understood. The goals of this study were to: (1) measure bone marrow fat fraction (BMF) in CLBP patients with MC using water–fat MRI and (2) assess the relationship between BMF measurements and patient-reported clinical characteristics. Methods In this cross-sectional study, 42 CLBP patients (men, n = 21; age, 48 ± 12.4 years) and 18 asymptomatic controls (men, n = 10; 42.7 ± 12.8 years) underwent 3 T MRI between January 2016 and July 2018. Imaging consisted of T1- and T2-weighted sequences to evaluate MC and spoiled gradient-recalled echo sequence with asymmetric echoes and least-squares fitting to measure BMF. BMF was compared between vertebrae with and without MC using mixed effects models. The relationship between the BMF measurements and patient-reported disability scores was examined using regression. Results Twenty-seven subjects (26 CLBP, 1 control) had MC, and MC presence coincided with significantly altered BMF. In MC 1, BMF was lower than endplates without MC (absolute difference −22.3%; p p p = 0.029–0.032) and were not associated with pain (p = 0.49–0.83). Conclusion BMF is significantly altered in MC. Water–fat MRI enables BMF measurements that may eventually form the basis for quantitative assessments of MC severity and progression.

Absract Background Paraspinal muscles are crucial for vertebral stabilization and movement. These muscles are prone to develop fatty infiltration (FI), fibrosis, and atrophy in many spine conditions. Fibro‐adipogenic progenitors (FAPs), a resident muscle stem cell population, are the main contributors of muscle fibrosis and FI. FAPs are involved in a complex interplay with satellite cells (SCs), the primary myogenic progenitor cells within muscle. Little is known about the stem cell composition of the multifidus. The aim of this study is to examine FAPs and SCs in the multifidus in disc herniation patients. Multifidus muscle samples were collected from 10 patients undergoing decompressive spine surgery for lumbar disc herniation. Hamstring muscle was collected from four patients undergoing hamstring autograft ACL reconstruction as an appendicular control. Multifidus tissue was analyzed for FI and fibrosis using Oil‐Red‐O and Masson's trichrome staining. FAPs and SCs were visualized using immunostaining and quantified with fluorescence‐activated cell sorting (FACS) sorting. Gene expression of these cells from the multifidus were analyzed with reverse transcription‐polymerase chain reaction and compared to those from hamstring muscle. FI and fibrosis accounted for 14.2%± 7.4% and 14.8%±4.2% of multifidus muscle, respectively. The multifidus contained more FAPs (11.7%±1.9% vs 1.4%±0.2%; P, Paraspinal muscles are known to develop muscle fatty infiltration (FI), fibrosis, and atrophy in a number of spine conditions, including intervertebral disc herniation. In this study, we histologically examined multifidus muscle specimens harvested from patients undergoing spine surgery for the degree of degenerative muscle pathology and characterized fibro‐adipogenic progenitors (FAPs) and Satellite cells (SCs) within the muscle in terms of quantity and gene expression profiles. We discovered a high degree of FI and fibrosis in the multifidus as well as large quantities of FAPs and SCs that displayed different gene expression profiles than those taken from healthy hamstring muscle controls.

Background Chronic musculoskeletal pain has a vast global prevalence and economic burden. Conservative therapies are universally recommended but require patient engagement and self-management to be effective. Objective This study aimed to evaluate the efficacy of a 12-week digital care program (DCP) in a large population of patients with chronic knee and back pain. Methods A longitudinal observational study was conducted using a remote DCP available through a mobile app. Subjects participated in a 12-week multimodal DCP incorporating education, sensor-guided exercise therapy (ET), and behavioral health support with 1-on-1 remote health coaching. The primary outcome was pain measured by the visual analog scale (VAS). Secondary measures included engagement levels, program completion, program satisfaction, condition-specific pain measures, depression, anxiety, and work productivity. Results A total of 10,264 adults with either knee (n=3796) or low back (n=6468) pain for at least three months were included in the study. Participants experienced a 68.45% average improvement in VAS pain between baseline intake and 12 weeks. In all, 73.04% (7497/10,264) participants completed the DCP into the final month. In total, 78.60% (5893/7497) of program completers (7144/10,264, 69.60% of all participants) achieved minimally important change in pain. Furthermore, the number of ET sessions and coaching interactions were both positively associated with improvement in pain, suggesting that the amount of engagement influenced outcomes. Secondary outcomes included a 57.9% and 58.3% decrease in depression and anxiety scores, respectively, and 61.5% improvement in work productivity. Finally, 3 distinct clusters of pain response trajectories were identified, which could be predicted with a mean 76% accuracy using baseline measures. Conclusions These results support the efficacy and scalability of a DCP for chronic low back and knee pain in a large, diverse, real-world population. Participants demonstrated high completion and engagement rates and a significant positive relationship between engagement and pain reduction was identified, a finding that has not been previously demonstrated in a DCP. Furthermore, the large sample size allowed for the identification of distinct pain response subgroups, which may prove beneficial in predicting recovery and tailoring future interventions. This is the first longitudinal digital health study to analyze pain outcomes in a sample of this magnitude, and it supports the prospect for DCPs to serve the overwhelming number of musculoskeletal pain sufferers worldwide.

BACKGROUND Chronic musculoskeletal pain has a vast global prevalence and economic burden. Conservative therapies are universally recommended but require patient engagement and self-management to be effective. OBJECTIVE This study aimed to evaluate the efficacy of a 12-week digital care program (DCP) in a large population of patients with chronic knee and back pain. METHODS A longitudinal observational study was conducted using a remote DCP available through a mobile app. Subjects participated in a 12-week multimodal DCP incorporating education, sensor-guided exercise therapy (ET), and behavioral health support with 1-on-1 remote health coaching. The primary outcome was pain measured by the visual analog scale (VAS). Secondary measures included engagement levels, program completion, program satisfaction, condition-specific pain measures, depression, anxiety, and work productivity. RESULTS A total of 10,264 adults with either knee (n=3796) or low back (n=6468) pain for at least three months were included in the study. Participants experienced a 68.45% average improvement in VAS pain between baseline intake and 12 weeks. In all, 73.04% (7497/10,264) participants completed the DCP into the final month. In total, 78.60% (5893/7497) of program completers (7144/10,264, 69.60% of all participants) achieved minimally important change in pain. Furthermore, the number of ET sessions and coaching interactions were both positively associated with improvement in pain, suggesting that the amount of engagement influenced outcomes. Secondary outcomes included a 57.9% and 58.3% decrease in depression and anxiety scores, respectively, and 61.5% improvement in work productivity. Finally, 3 distinct clusters of pain response trajectories were identified, which could be predicted with a mean 76% accuracy using baseline measures. CONCLUSIONS These results support the efficacy and scalability of a DCP for chronic low back and knee pain in a large, diverse, real-world population. Participants demonstrated high completion and engagement rates and a significant positive relationship between engagement and pain reduction was identified, a finding that has not been previously demonstrated in a DCP. Furthermore, the large sample size allowed for the identification of distinct pain response subgroups, which may prove beneficial in predicting recovery and tailoring future interventions. This is the first longitudinal digital health study to analyze pain outcomes in a sample of this magnitude, and it supports the prospect for DCPs to serve the overwhelming number of musculoskeletal pain sufferers worldwide.

Background: Chronic musculoskeletal pain has a vast global prevalence and economic burden. Conservative therapies are universally recommended but require patient engagement and self-management to be effective. In this study, we assessed engagement behaviors and subject-reported outcomes in subjects with chronic low back or knee pain who participated in a 12-week digital care pathway (DCP). Methods: Subjects participated in a 12-week multi-modal DCP administered via a mobile app incorporating education, sensor-guided exercise therapy, and behavioral health support with 1-on-1 remote health coaching. Primary outcome was VAS pain. Secondary measures included engagement levels, program completion, program satisfaction, condition-specific pain measures, depression, anxiety, and work productivity. Findings: Of 10,264 participants with chronic back or knee pain, 73% completed the DCP into the final month. 79% of these participants (70% of all participants) achieved minimally important change in pain. Mean improvement in VAS pain was 68% and the number of exercise therapy sessions and coaching interactions were both positively associated with improvement in pain, supporting that the amount of engagement influenced VAS pain outcomes. Secondary outcomes included 58% decrease in both depression and anxiety scores, and 62% improvement in work productivity. Lastly, three groups with distinct longitudinal pain response behaviors were identified and could be predicted from baseline measures with 76% accuracy. Interpretation: This is the first longitudinal digital health study to analyze musculoskeletal pain outcomes in a sample of this magnitude, supporting the efficacy and safety of using a digital care approach in a large, real-world population. Participants demonstrated high completion and engagement rates, and a significant positive relationship between engagement and pain reduction was identified, a finding not previously demonstrated in a DCP. Furthermore, the large sample size allowed for identification of distinct pain response subgroups which may prove beneficial in predicting recovery and tailoring future interventions. Funding Statement: Hinge Health, Inc. Declaration of Interests: Authors Bailey and Agarwal were academic collaborators on this study and were paid as consultants for their expertise for conducting this study. Bailey and Agarwal had unrestricted access to the data and lead the analysis and interpretation of the results. Author Krauss works at Hinge Health, Inc., and receives salary and equity compensation. Subsequent to paper completion, author Agarwal became employed at Hinge Health, Inc., and receives salary and equity compensation. Ethics Approval Statement: The trial was approved by the Western Institutional Review Board and complied with all ethical regulations.

Spinal muscle cross‐sectional area has been highly associated with spinal pathology. Despite the medium‐high prevalence of spinal pathology in children, there is very limited knowledge regarding muscle size and growth pattern in individuals younger than 20 years of age. The aim of this study is to analyze the change in size and symmetry of spinal muscles (erector spinae, multifidus, psoas and quadratus lumborum) in children 2–20 years of age. We studied reformatted images from 91 abdominal computed tomographic scans of children aged 2–20 years, from an existing imaging dataset. The cross‐sectional area of the muscles was bilaterally measured parallel to the upper endplate of the lumbar vertebrae L3–L5 and at true horizontal for S1. The cross‐sectional area of the upper vertebral endplate was measured at spinal levels L3–L5. Results were analyzed according to six groups based on children's age: 2–4 years (group 1), 5–7 years (group 2), 8–10 years (group 3), 11–13 years (group 4), 14–16 years (group 5) and 17–20 years (group 6). Vertebral endplate and spinal muscles cross‐sectional area increased with age. Two patterns were observed: Endplate, psoas and quadratus lumborum increased up to our 6th oldest age group (17–20), and multifidus and erector spinae reached their largest size in the 5th age group (14–16). The epaxial muscles (erector spinae and multifidus) reached their maximal cross‐sectional area before skeletal maturity (18–21 years of age). The hypaxial muscles (psoas and quadratus lumborum) continued to increase in size at least until spinal maturity. Contributing factors for the differences in developmental pattern between the epaxial and hypaxial muscles might include functional, embryological and innervation factors. In conclusion, this research is the first to describe the cross‐sectional area of spinal muscles in children. Future longitudinal studies are needed for further understanding of muscle development during childhood and adolescence. Level of evidence: level 2b, Retrospective cohort study.

STUDY DESIGN Prospective case series. OBJECTIVE Evaluate lumbar paraspinal muscle (PSM) cross-sectional area and intervertebral disc (IVD) height changes induced by a 6-month space mission on the International Space Station. The long-term objective of this project is to promote spine health and prevent spinal injury during space missions and here on Earth. SUMMARY OF BACKGROUND DATA National Aeronautics and Space Administration (NASA) crewmembers have a 4.3 times higher risk of herniated IVDs, compared with the general and military aviator populations. The highest risk occurs during the first year after a mission. Microgravity exposure during long-duration spaceflights results in approximately 5 cm lengthening of body height, spinal pain, and skeletal deconditioning. How the PSMs and IVDs respond during spaceflight is not well described. METHODS Six NASA crewmembers were imaged supine with a 3 Tesla magnetic resonance imaging. Imaging was conducted preflight, immediately postflight, and then 33 to 67 days after landing. Functional cross-sectional area (FCSA) measurements of the PSMs were performed at the L3-4 level. FCSA was measured by grayscale thresholding within the posterior lumbar extensors to isolate lean muscle on T2-weighted scans. IVD heights were measured at the anterior, middle, and posterior sections of all lumbar levels. Repeated measures analysis of variance was used to determine significance at P

Standing from a seated position is an activity of daily living and a common clinical test of strength and balance. While this action is well-studied biomechanically, there remains a need for a clear modelling method for appropriately capturing performance and discriminating between standing strategies. This paper presents a simple framework for representing the rise from a chair as a set of splines. This formulation is inherently differentiable, defines a clear start and end point of the motion, and allows for secondary analysis of dynamic and energetic effects. This method is tested on two healthy subjects performing four different standing strategies. The spline method was found to accurately capture the standing action, with mean absolute errors of 1-2 cm for joint position, and 2-3 degrees angular error across the different standing strategies. Analysis of the spline trajectories revealed strategy-specific differences in kinematic, kinetic, and dynamic bio-markers. This suggests that low order splines can be used to accurately capture variations in sit-to-stand actions.

Study design A longitudinal cohort study. Objective To define a set of objective biomechanical metrics that are representative of adult spinal deformity (ASD) post-surgical outcomes and that may forecast post-surgical mechanical complications. Summary of background data Current outcomes for ASD surgical planning and post-surgical assessment are limited to static radiographic alignment and patient-reported questionnaires. Little is known about the compensatory biomechanical strategies for stabilizing sagittal balance during functional movements in ASD patients. Methods We collected in-clinic motion data from 15 ASD patients and 10 controls during an unassisted sit-to-stand (STS) functional maneuver. Joint motions were measured using noninvasive 3D depth mapping sensor technology. Mathematical methods were used to attain high-fidelity joint-position tracking for biomechanical modeling. This approach provided reliable measurements for biomechanical behaviors at the spine, hip, and knee. These included peak sagittal vertical axis (SVA) over the course of the STS, as well as forces and muscular moments at various joints. We compared changes in dynamic sagittal balance (DSB) metrics between pre- and post-surgery and then separately compared pre- and post-surgical data to controls. Results Standard radiographic and patient-reported outcomes significantly improved following realignment surgery. From the DSB biomechanical metrics, peak SVA and biomechanical loads and muscular forces on the lower lumbar spine significantly reduced following surgery (− 19 to − 30%, all p

Kinetic and dynamic motion analysis provides quantitative, functional assessments of human ability that are unobtainable through static imaging methods or subjective surveys. While biomechanics facilities are equipped to perform this measurement and analysis, the clinical translation of these methods is limited by the specialized skills and equipment needed. This paper presents and validates a method for estimating dynamic effects such as joint torques and body momenta using a single depth camera. An allometrically scaled, sagittal plane dynamic model is used to estimate the joint torques at the ankles, knees, hips, and low back, as well as the torso momenta, and shear and normal loads at the L5-S1 disk. These dynamic metrics are applied to the sit-to-stand motion and validated against a gold-standard biomechanical system consisting of full-body active motion-capture and force-sensing systems. The metrics obtained from the proposed method were found to have excellent concordance with peak metrics that are consistent with prior biomechanical studies. This suggests the feasibility of using this system for rapid clinical assessment, with applications in diagnostics, longitudinal tracking, and quantifying patient recovery.

The vertebral column is the fundamental body part that determines locomotion and function in vertebrates. Understanding spinal posture, kinetics and kinematics is of great importance to the study of the paleobiology of extinct species. When discussing the biomechanics of the spine of extinct hominins, arguments are based solely on osseous material, as soft tissues are basically absent from the fossil record and because there is no living representative of these species to track and measure movement and function. In this article, we tried to determine the interactions between spinal posture and biomechanics within modern humans and translate the results to extinct hominins. Our main findings indicate that each group/lineage of hominins had special biomechanical characteristics. Early Homo sapiens and Homo erectus with moderate to high spinal curvatures, similar to the posture of modern humans, probably had similar spinal biomechanical characteristics as modern humans. Neanderthal lineage hominins (NLH) with small spinal curvatures might have had somewhat different biomechanics characterized by more stable spine, with reduced shock attenuation abilities compared to modern humans. NLH probably also preferred to squat rather than stoop and had better overhead throwing kinematics compared to modern humans. Australopithecus probably had lumbar biomechanical characteristics within the range of modern humans together with stable cervical spine and a small cervical range of motion (ROM).

Pelvic incidence (PI) is a measure of the sagittal orientation of the sacrum relative to the acetabula and is not dependent on posture. In asymptomatic adults, PI correlates with lumbar lordosis. Lumbar lordosis is shown to increase with age following the onset of unassisted bipedal locomotion in children, but to what extent PI changes in relation to lumbar lordosis during skeletal maturation is unclear. The purpose of this study is to understand how PI, lumbar lordosis, and age are related in children and adolescents. PI, supine lumbar lordosis (SLL), and individual wedging angles of the lumbar vertebral bodies were measured on mid-sagittal reformatted images from 144 abdominal computed tomographic scans of individuals aged 2-20 years old, divided into three separate age categories representing pre-growth spurt (ages 2-9), growth spurt (10-15), and post-growth spurt (16-20). Our results showed that, while SLL significantly increased with age during development, PI did not. Despite the fact that PI hardly changed with age, the difference between PI and SLL decreased nonlinearly with age. SLL did not correlate with PI in the youngest age category, but positively correlated with PI in the middle and oldest age categories. The relationship between lumbar lordosis and PI, which is correlated in adults, was significant in our older age categories and not in our youngest age category. Our results indicate that PI in children and adolescents may have some predictive value for adult lumbar lordosis. Anat Rec, 302:2132-2139, 2019. © 2019 American Association for Anatomy.

Age related spinal deformity is becoming an increasingly prevalent problem, resulting in decreased quality of life. While spinal deformity can be corrected via surgical intervention, a large number of people with spinal fusions require follow-up surgery due to further degeneration. The identification of changes to a subjects kinematics and kinetics post-surgery are limited by a lack of methods to collect patient specific motion data over the course of surgical recovery. This paper introduces an Instrumented Spine Orthosis (ISO) that can capture the motions of the subjects torso without requiring the use of a control computer or other dedicated motion capture equipment. This system is used to collect the peak torso angles and velocities for a single subject performing sit-to-stand actions. The accuracy of the ISO is evaluated using motion capture, during different sit-to-stand protocols designed to highlight motion changes that have been seen in subjects with reduced mobility. This system was found to provide reliable measurements of these kinematic and kinetic torso measures across all tested motions, demonstrating the potential for the use of Instrumented Spine Orthotics to provide quantitative measures during the surgical recovery process.

PurposeTo characterize the distribution of nerves within a single S1 vertebral body, with particular emphasis on the superior endplate that interfaces with the L5/S1 disc.MethodsMusculature and connective tissue surrounding the sacrum was carefully dissected away for close visual inspection of penetrating nerve fibers. The S1 vertebral body was then isolated for histology and serial coronal sections were cut and stained with a ubiquitous neural antibody marker (PGP 9.5). Slides were analyzed and nerves were manually marked on high resolution, composite captured images, rendering 3D depictions of internal nerve distribution.ResultsThe vast majority of nerves were closely associated with blood vessels within the marrow space with a uniform distribution in both the superior and inferior endplates of the S1 vertebral body. The highest nerve density was seen at the centrum (anatomic center) of the S1 vertebral body with smaller peaks seen at the lateral borders. Nerve fibers were observed branching from anterior sacral nerves and penetrating the lateral border of the S1 (during dissection), corresponding with peaks on nerve density maps.ConclusionsOur results demonstrate that the S1 body and endplate are densely innervated and the peak in nerve density at the vertebral center coincides with vasculature patterns previously described in lumbar vertebral bodies. In the sacrum, however, there is no posterior nutrient foramen that facilitates nerve penetration through the vertebral cortex. Rather, our data indicate that nerves penetrate the S1 via the lateral aspects, consistent with being branches of the anterior sacral nerve. Since PGP 9.5 is a ubiquitous neural marker these identified nerves are likely composed of a mixed population of nociceptive and autonomic fibers.

Background Context Prolonged microgravity exposure is associated with localized low back pain and an elevated risk of post-flight disc herniation. Although the mechanisms by which microgravity impairs the spine are unclear, they should be foundational for developing in-flight countermeasures for maintaining astronaut spine health. Because human spine anatomy has adapted to upright posture on Earth, observations of how spaceflight affects the spine should also provide new and potentially important information on spine biomechanics that benefit the general population. Purpose This study compares quantitative measures of lumbar spine anatomy, health, and biomechanics in astronauts before and after 6 months of microgravity exposure on board the International Space Station (ISS). Study Design This is a prospective longitudinal study. Sample Six astronaut crewmember volunteers from the National Aeronautics and Space Administration (NASA) with 6-month missions aboard the ISS comprised our study sample. Outcome Measures For multifidus and erector spinae at L3–L4, measures include cross-sectional area (CSA), functional cross-sectional area (FCSA), and FCSA/CSA. Other measures include supine lumbar lordosis (L1–S1), active (standing) and passive (lying) flexion-extension range of motion (FE ROM) for each lumbar disc segment, disc water content from T2-weighted intensity, Pfirrmann grade, vertebral end plate pathology, and subject-reported incidence of chronic low back pain or disc injuries at 1-year follow-up. Methods 3T magnetic resonance imaging and dynamic fluoroscopy of the lumbar spine were collected for each subject at two time points: approximately 30 days before launch (pre-flight) and 1 day following 6 months spaceflight on the ISS (post-flight). Outcome measures were compared between time points using paired t tests and regression analyses. Results Supine lumbar lordosis decreased (flattened) by an average of 11% (p=.019). Active FE ROM decreased for the middle three lumbar discs (L2–L3: −22.1%, p=.049; L3–L4: −17.3%, p=.016; L4–L5: −30.3%, p=.004). By contrast, no significant passive FE ROM changes in these discs were observed (p>.05). Disc water content did not differ systematically from pre- to post-flight. Multifidus and erector spinae changed variably between subjects, with five of six subjects experiencing an average decrease 20% for FCSA and 8%–9% for CSA in both muscles. For all subjects, changes in multifidus FCSA strongly correlated with changes in lordosis (r2=0.86, p=.008) and active FE ROM at L4–L5 (r2=0.94, p=.007). Additionally, changes in multifidus FCSA/CSA correlated with changes in lordosis (r2=0.69, p=.03). Although multifidus-associated changes in lordosis and ROM were present among all subjects, only those with severe, pre-flight end plate irregularities (two of six subjects) had post-flight lumbar symptoms (including chronic low back pain or disc herniation). Conclusions We observed that multifidus atrophy, rather than intervertebral disc swelling, associated strongly with lumbar flattening and increased stiffness. Because these changes have been previously linked with detrimental spine biomechanics and pain in terrestrial populations, when combined with evidence of pre-flight vertebral end plate insufficiency, they may elevate injury risk for astronauts upon return to gravity loading. Our results also have implications for deconditioned spines on Earth. We anticipate that our results will inform new astronaut countermeasures that target the multifidus muscles, and research on the role of muscular stability in relation to chronic low back pain and disc injury.

Summary Objective To compare gross and histologic patterns of age-related degeneration within the intervertebral disc and adjacent vertebra between rhesus monkeys and humans. Materials and methods We examined age-related patterns of disc degeneration from mid-sagittal sections of the intervertebral disc and adjacent vertebral bodies (VB) among six rhesus monkey thoracolumbar and seven human lumbar spines. Gross morphology and histopathology were assessed via the Thompson grading scheme and other degenerative features of the disc and adjacent bone. Results Thompson grades ranged from 3 through 5 for rhesus monkey discs (T9–L1) and 2 through 5 for the human discs (T12–S1). In both rhesus monkey and human discs, presence of distinct lesions was positively associated with Thompson grade of the overall segment. Degenerative patterns differed for radial tears, which were more prevalent with advanced disc degeneration in humans only. Additionally, compared to the more uniform anteroposterior disc degeneration patterns of humans, rhesus monkeys showed more severe osteophytosis and degeneration on the anterior border of the vertebral column. Conclusions Rhesus monkey spines evaluated in the present study appear to develop age-related patterns of disc degeneration similar to humans. One exception is the absence of an association between radial tears and disc degeneration, which could reflect species-specific differences in posture and spinal curvature. Considering rhesus monkeys demonstrate similar patterns of disc degeneration, and age at a faster rate than humans, these findings suggest longitudinal studies of rhesus monkeys may be a valuable model for better understanding the progression of human age-related spinal osteoarthritis (OA) and disc degeneration.

To characterize the consequences of eliminating essential functions needed for peptidoglycan synthesis, we generated deletion mutations of Acinetobacter baylyi by natural transformation and visualized the resulting microcolonies of dead cells. We found that loss of genes required for peptidoglycan precursor synthesis or polymerization led to the formation of polymorphic giant cells with diameters that could exceed ten times normal. Treatment with antibiotics targeting early or late steps of peptidoglycan synthesis also produced giant cells. The giant cells eventually lysed, although they were partially stabilized by osmotic protection. Genome-scale transposon mutant screening (Tn-seq) identified mutations that blocked or accelerated giant cell formation. Among the mutations that blocked the process were those inactivating a function predicted to cleave murein glycan chains (the MltD murein lytic transglycosylase), suggesting that giant cell formation requires MltD hydrolysis of existing peptidoglycan. Among the mutations that accelerated giant cell formation after ß-lactam treatment were those inactivating an enzyme that produces unusual 3->3 peptide cross-links in peptidoglycan (the LdtG L,D-transpeptidase). The mutations may weaken the sacculus and make it more vulnerable to further disruption. Although the study focused on A. baylyi, we found that a pathogenic relative (A. baumannii) also produced giant cells with genetic dependencies overlapping those of A. baylyi. Overall, the analysis defines a genetic pathway for giant cell formation conserved in Acinetobacter species in which independent initiating branches converge to create the unusual cells., Author summary Although essential genes control the most basic functions of bacterial life, they are difficult to study genetically because mutants lacking the functions die. We have developed a simple procedure for creating bacteria in which different essential genes have been completely deleted, making it possible to analyze the roles of the missing functions based on the features of the dead cells that result. When genes needed for the production of the cell wall were inactivated, the bacteria formed bizarre giant cells. It was possible to identify the functions responsible for forming the giant cells, and to formulate a model for how they form. Since cell wall synthesis is one of the most important antibiotic targets, understanding how bacteria respond to its disruption may ultimately help in developing procedures to overcome antibiotic resistant bacterial infections.

Previous work suggests females are evolutionarily adapted to have greater lumbar lordosis than males to aid in pregnancy load-bearing, but no consensus exists. To explore further sex-differences in the lumbar spine, and to understand contradictions in the literature, we conducted a cross-sectional retrospective study of sex-differences in lumbar spine morphology and sacral orientation. In addition, our sample includes data for separate standing and supine samples of males and females to examine potential sex-differences in postural loading on lumbosacral morphology. We measured sagittal lumbosacral morphology on 200 radiographs. Measurements include: lumbar angle (L1-S1), lumbar vertebral body and disc wedging angles, sacral slope and pelvic incidence. Lumbar angle, representative of lordotic curvature between L1 and S1, was 7.3° greater in females than males, when standing. There were no significant sex-differences in lumbar angle when supine. This difference in standing lumbar angle can be explained by greater lordotic wedging of the lumbar vertebrae (L1-L5) in females. Additionally, sacral slope was greater in females than males, when standing. There were no significant sex-differences in pelvic incidence. Our results support that females have greater lumbar lordosis than males when standing, but not when supine - suggesting a potentially greater range of motion in the female spine. Furthermore, sex-differences in the lumbar spine appear to be supported by postural differences in sacral-orientation and morphological differences in the vertebral body wedging. A better understanding of sex-differences in lumbosacral morphology may explain sex-differences in spinal conditions, as well as promote necessary sex-specific treatments.