Four Weeks of Minimalist Style Running Training Reduced Lumbar Paraspinal Muscle Activation during Shod Running

Background and Purpose: Research has shown that the risk of low back dysfunctions in runners is related to the increased mileage of distance running. Repetitive shock loading of the spinal structures during running has been indicated as one of the important biomechanical mechanisms underlying such injury. Acute changes in foot strike pattern, like those seen during minimalist style running, have been shown to lead to modifications in lumbar range of motion. Minimalist style running could lead to changes in lumbar biomechanics and muscle activation, potentially reducing the loading on the musculoskeletal structures of the lower back. However, the long term effects of minimalist style running on lumbar biomechanics have not been evaluated. The purpose of this study was to investigate the effects a 4-week training program aimed at transitioning recreational runners to minimalist style footwear would have on lower back kinematics and lumbar paraspinal muscle activation. Subjects: 17 volunteers between the ages of 18-45 years who were habitually shod runners and averaged running 10-50 km per week participated in the study. Data from 15 volunteers was used in the analysis of the biomechanics. Inclusion and exclusion criteria were used to determine the appropriateness of each volunteer for this study. Methods: Subjects participated in three data collection sessions at the beginning, during (2-week), and at the end of a 4-week training program. The training consists of progressively increasing the distance each runner ran in the minimalist shoes up to 30-50% of their regular running distance while maintaining the overall distance (minimalist + normal shoes) comparable to before training. Running trials were collected with the subject wearing their normal running shoes. Subjects were asked to run at a prescribed speed (11.2 km/h), and a blinded self-selected speed. During running, kinematics of the lower back in the sagittal plane was recorded using an electro-goniometer. Surface EMG was used to monitor the activation of the lower back (L3 level) paraspinal muscles. Data collected during 10 stance phases were averaged and used for analysis. One-way repeated measures ANOVA tests were used to analyze the effect of training on lumbar kinematics and lumbar paraspinal muscle activation. Results: For the 11.2 km/h running speed, statistically significant differences were found in mean lower back posture (PRE = 1.9 ± 15.3 degrees, MID = 0.4 ± 13.0 degrees, POST = -6.0 ± 13.3 degrees, p = 0.001) and contralateral lumbar paraspinal muscle activation (PRE = 47.0 ± 34.0%, MID = 24.9 ± 8.2%, POST = 29.4 ± 11.3%, p = 0.039) after training. For the self-selected running speed, statistically significant differences were found in mean lower back posture (PRE = 2.3 ± 15.5 degrees, MID = 0.9 ± 13.9 degrees, POST = -5.7 ± 14.2 degrees, p = 0.002) and contralateral lumbar paraspinal muscle activation (PRE = 41.6 ± 28.6%, MID = 23.4 ± 6.2%, POST = 30.3 ± 11.6%, p = 0.047) after training. During both speeds, lower back posture became more extended and contralateral lumbar paraspinal muscle activation decreased. No significant differences were noted in overall lower back range of motion or ipsilateral paraspinal muscle activation over the training period at either speed. Conclusions: Including minimalist running shoes and barefoot exercises into a runners’ training regime can alter the lumbar spinal kinematics and muscle activation. Specifically the runners adapted a more extended lumbar posture and reduced the lumbar paraspinal muscle activation after training. This effect carried over to shod running

Adaptations of Lumbar Biomechanics after Four Weeks of Running Training with Minimalist Footwear and Technique guidance: Implications for Running-Related Lower Back Pain

Objectives To investigate the changes in lumbar kinematic and paraspinal muscle activation before, during, and after a 4-week minimalist running training. Design Prospective cohort study. Setting University research laboratory. Participants Seventeen habitually shod recreational runners who run 10–50 km per week. Main outcome measures During stance phases of running, sagittal lumbar kinematics was recorded using an electrogoniometer, and activities of the lumbar paraspinal muscles were assessed by electromyography. Runners were asked to run at a prescribed speed (3.1 m/s) and a self-selected speed. Results For the 3.1 m/s running speed, significant differences were found in the calculated mean lumbar posture (p = 0.001) during the stance phase, including a more extended lumbar posture after minimalist running training. A significant reduction in the contralateral lumbar paraspinal muscle activation was also observed (p = 0.039). For the preferred running speed, similar findings of a more extended lumbar posture (p = 0.002) and a reduction in contralateral lumbar paraspinal muscle activation (p = 0.047) were observed. Conclusion A 4-week minimalist running training program produced significant changes in lumbar biomechanics during running. Specifically, runners adopted a more extended lumbar posture and reduced lumbar paraspinal muscle activation. These findings may have clinical implications for treating individuals with running-related lower back pain

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Real‐world treatment escalation from metformin monotherapy in youth‐onset Type 2 diabetes mellitus: A retrospective cohort study

BackgroundDue to high rates of comorbidities and rapid progression, youth with Type 2 diabetes may benefit from early and aggressive treatment. However, until 2019, the only approved medications for this population were metformin and insulin.ObjectiveTo investigate patterns and predictors of treatment escalation within 5 years of metformin monotherapy initiation for youth with Type 2 diabetes in clinical practice.SubjectsCommercially‐insured patients with incident youth‐onset (10–18 years) Type 2 diabetes initially treated with metformin only.MethodsRetrospective cohort study using a patient‐level medical claims database with data from 2000 to 2020. Frequency and order of treatment escalation to insulin and non‐insulin antihyperglycemics were determined and categorized by age at diagnosis. Cox proportional hazards regression was used to evaluate potential predictors of treatment escalation, including age, sex, race/ethnicity, comorbidities, complications, and metformin adherence (medication possession ratio ≥ 0.8).ResultsThe cohort included 829 (66% female; median age at diagnosis 15 years; 19% Hispanic, 17% Black) patients, with median 2.9 year follow‐up after metformin initiation. One‐quarter underwent treatment escalation (n = 207; 88 to insulin, 164 to non‐insulin antihyperglycemic). Younger patients were more likely to have insulin prescribed prior to other antihyperglycemics. Age at diagnosis (HR 1.14, 95% CI 1.07–1.21), medication adherence (HR 4.10, 95% CI 2.96–5.67), Hispanic ethnicity (HR 1.83, 95% CI 1.28–2.61), and diabetes‐related complications (HR 1.78, 95% CI 1.15–2.74) were positively associated with treatment escalation.ConclusionsIn clinical practice, treatment escalation for pediatric Type 2 diabetes differs with age. Off‐label use of non‐insulin antihyperglycemics occurs, most commonly among older adolescents.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/169332/1/pedi13232_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/169332/2/pedi13232.pd

Hyperlipidemia affects multiscale structure and strength of murine femur

To improve bone strength prediction beyond limitations of assessment founded solely on the bone mineral component, we investigated the effect of hyperlipidemia, present in more than 40% of osteoporotic patients, on multiscale structure of murine bone. Our overarching purpose is to estimate bone strength accurately, to facilitate mitigating fracture morbidity and mortality in patients. Because (i) orientation of collagen type I affects, independently of degree of mineralization, cortical bone׳s micro-structural strength; and, (ii) hyperlipidemia affects collagen orientation and μCT volumetric tissue mineral density (vTMD) in murine cortical bone, we have constructed the first multiscale finite element (mFE), mouse-specific femoral model to study the effect of collagen orientation and vTMD on strength in Ldlr(-/-), a mouse model of hyperlipidemia, and its control wild type, on either high fat diet or normal diet. Each µCT scan-based mFE model included either element-specific elastic orthotropic properties calculated from collagen orientation and vTMD (collagen-density model) by experimentally validated formulation, or usual element-specific elastic isotropic material properties dependent on vTMD-only (density-only model). We found that collagen orientation, assessed by circularly polarized light and confocal microscopies, and vTMD, differed among groups and that microindentation results strongly correlate with elastic modulus of collagen-density models (r(2)=0.85, p=10(-5)). Collagen-density models yielded (1) larger strains, and therefore lower strength, in simulations of 3-point bending and physiological loading; and (2) higher correlation between mFE-predicted strength and 3-point bending experimental strength, than density-only models. This novel method supports ongoing translational research to achieve the as yet elusive goal of accurate bone strength prediction

Continuous fish muscle cell line with capacity for myogenic and adipogenic-like phenotypes

Abstract Cell-cultivated fish offers the potential for a more ethical, sustainable, and safe seafood system. However, fish cell culture is relatively understudied in comparison to mammalian cells. Here, we established and characterized a continuous Atlantic mackerel (Scomber scombrus) skeletal muscle cell line (“Mack” cells). The cells were isolated from muscle biopsies of fresh-caught fish, with separate isolations performed from two distinct fish. Mack1 cells (cells from the first isolation) were cultured for over a year and subcultured over 130 times. The cells proliferated at initial doubling times of 63.9 h (± 19.1 SD). After a spontaneous immortalization crisis from passages 37–43, the cells proliferated at doubling times of 24.3 h (± 4.91 SD). A muscle phenotype was confirmed through characterization of muscle stemness and differentiation via paired-box protein 7 and myosin heavy chain immunostaining, respectively. An adipocyte-like phenotype was also demonstrated for the cells through lipid accumulation, confirmed via Oil Red O staining and quantification of neutral lipids. New qPCR primers (HPRT, PAX3B, MYOD1, MYOG, TNNT3A, and PPARG) were tailored to the mackerel genome and used to characterize mackerel cell genotypes. This work provides the first spontaneously immortalized fish muscle cell line for research, ideally serving as a reference for subsequent investigation

Glioblastoma Spheroid Invasion through Soft, Brain-Like Matrices Depends on Hyaluronic Acid-CD44 Interactions.

Increased secretion of hyaluronic acid (HA), a glycosaminoglycan abundant in the brain extracellular matrix (ECM), correlates with worse clinical outcomes for glioblastoma (GBM) patients. GBM cells aggressively invade the brain parenchyma while encountering spatiotemporal changes in their local ECM, including HA concentration. To investigate how varying HA concentrations affect GBM invasion, patient-derived GBM cells are cultured within a soft, 3D matrix in which HA concentration is precisely varied and cell migration observed. Data demonstrate that HA concentration can determine the invasive activity of patient-derived GBM cells in a biphasic and highly sensitive manner, where the absolute concentration of HA at which cell migration peaked is specific to each patient-derived line. Furthermore, evidence that this response relies on phosphorylated ezrin, which interacts with the intracellular domain of HA-engaged CD44 to effectively link the actin cytoskeleton to the local ECM is provided. Overall, this study highlights CD44-HA binding as a major mediator of GBM cell migration that acts independently of integrins and focal adhesion complexes and suggests that targeting HA-CD44-ezrin interactions represents a promising therapeutic strategy to prevent tumor cell invasion in the brain

Hyperlipidemia affects multiscale structure and strength of murine femur

To improve bone strength prediction beyond limitations of assessment founded solely on the bone mineral component, we investigated the effect of hyperlipidemia, present in more than 40% of osteoporotic patients, on multiscale structure of murine bone. Our overarching purpose is to estimate bone strength accurately, to facilitate mitigating fracture morbidity and mortality in patients. Because i) orientation of collagen type I affects, independently of degree of mineralization, cortical bone’s micro-structural strength; and, ii) hyperlipidemia affects collagen orientation and µCT volumetric tissue mineral density (vTMD) in murine cortical bone, we have constructed the first multiscale finite element (mFE), mouse-specific femoral model to study the effect of collagen orientation and vTMD on strength in Ldlr(−/−), a mouse model of hyperlipidemia, and its control wild type, on either high fat diet or normal diet. Each µCT scan-based mFE model included either element-specific elastic orthotropic properties calculated from collagen orientation and vTMD (collagen-density model) by experimentally validated formulation, or usual element-specific elastic isotropic material properties dependent on vTMD-only (density-only model). We found that collagen orientation, assessed by circularly polarized light and confocal microscopies, and vTMD, differed among groups; and that microindentation results strongly correlate with elastic modulus of collagen-density models (r(2)=0.85, p=10(−5)). Collagen-density models yielded 1) larger strains, and therefore lower strength, in simulations of 3-point bending and physiological loading; and 2) higher correlation between mFE-predicted strength and 3-point bending experimental strength, than density-only models. This novel method supports ongoing translational research to achieve the as yet elusive goal of accurate bone strength prediction