Dispase/collagenase cocktail allows for coisolation of satellite cells and fibroadipogenic progenitors from human skeletal muscle.

Satellite cells (SCs) and fibroadipogenic progenitors (FAPs) are progenitor populations found in muscle that form new myofibers postinjury. Muscle development, regeneration, and tissue-engineering experiments require robust progenitor populations, yet their isolation and expansion are difficult given their scarcity in muscle, limited muscle biopsy sizes in humans, and lack of methodological detail in the literature. Here, we investigated whether a dispase and collagenase type 1 and 2 cocktail could allow dual isolation of SCs and FAPs, enabling significantly increased yield from human skeletal muscle. Postdissociation, we found that single cells could be sorted into CD56 + CD31-CD45- (SC) and CD56-CD31-CD45- (FAP) cell populations, expanded in culture, and characterized for lineage-specific marker expression and differentiation capacity; we obtained ∼10% SCs and ∼40% FAPs, with yields twofold better than what is reported in current literature. SCs were PAX7+ and retained CD56 expression and myogenic fusion potential after multiple passages, expanding up to 1012 cells. Conversely, FAPs expressed CD140a and differentiated into either fibroblasts or adipocytes upon induction. This study demonstrates robust isolation of both SCs and FAPs from the same muscle sample with SC recovery more than two times higher than previously reported, which could enable translational studies for muscle injuries.NEW & NOTEWORTHY We demonstrated that a dispase/collagenase cocktail allows for simultaneous isolation of SCs and FAPs with 2× higher SC yield compared with other studies. We provide a thorough characterization of SC and FAP in vitro expansion that other studies have not reported. Following our dissociation, SCs and FAPs were able to expand by up to 1012 cells before reaching senescence and maintained differentiation capacity in vitro demonstrating their efficacy for clinical translation for muscle injury.

Network model of skeletal muscle cell signalling predicts differential responses to endurance and resistance exercise training.

Exercise-induced muscle adaptations vary based on exercise modality and intensity. We constructed a signalling network model from 87 published studies of human or rodent skeletal muscle cell responses to endurance or resistance exercise in vivo or simulated exercise in vitro. The network comprises 259 signalling interactions between 120 nodes, representing eight membrane receptors and eight canonical signalling pathways regulating 14 transcriptional regulators, 28 target genes and 12 exercise-induced phenotypes. Using this network, we formulated a logic-based ordinary differential equation model predicting time-dependent molecular and phenotypic alterations following acute endurance and resistance exercises. Compared with nine independent studies, the model accurately predicted 18/21 (85%) acute responses to resistance exercise and 12/16 (75%) acute responses to endurance exercise. Detailed sensitivity analysis of differential phenotypic responses to resistance and endurance training showed that, in the model, exercise regulates cell growth and protein synthesis primarily by signalling via mechanistic target of rapamycin, which is activated by Akt and inhibited in endurance exercise by AMP-activated protein kinase. Endurance exercise preferentially activates inflammation via reactive oxygen species and nuclear factor κB signalling. Furthermore, the expected preferential activation of mitochondrial biogenesis by endurance exercise was counterbalanced in the model by protein kinase C in response to resistance training. This model provides a new tool for investigating cross-talk between skeletal muscle signalling pathways activated by endurance and resistance exercise, and the mechanisms of interactions such as the interference effects of endurance training on resistance exercise outcomes.

Scaling relationships between human leg muscle architectural properties and body size.

A skeletal muscle's peak force production and excursion are based on its architectural properties that are, in turn, determined by its mass, muscle fiber length and physiological cross-sectional area (PCSA). In the classic interspecific study of mammalian muscle scaling, it was demonstrated that muscle mass scales positively allometrically with body mass whereas fiber length scales isometrically with body mass, indicating that larger mammals have stronger leg muscles than they would if they were geometrically similar to smaller ones. Although this relationship is highly significant across species, there has never been a detailed intraspecific architectural scaling study. We have thus created a large dataset of 896 muscles across 34 human lower extremities (18 females and 16 males) with a size range including approximately 90% and 70% of the United States population height and mass, respectively, across the range 36-103 years. Our purpose was to quantify the scaling relationships between human muscle architectural properties and body size. We found that human muscles depart greatly from isometric scaling because muscle mass scales with body mass1.3 (larger exponent than isometric scaling of 1.0) and muscle fiber length scales with negative allometry with body mass0.1 (smaller exponent than isometric scaling of 0.33). Based on the known relationship between architecture and function, these results suggest that human muscles place a premium on muscle force production (mass and PCSA) at the expense of muscle excursion (fiber length) with increasing body size, which has implications for understanding human muscle design as well as biomechanical modeling.

Photochemical and Single Electron Transfer Generation of 2'-Deoxycytidin-N4-yl Radical from Oxime Esters.

A 2'-deoxycytidin-N4-yl radical (dC·), a strong oxidant that also abstracts hydrogen atoms from carbon-hydrogen bonds, is produced in a variety of DNA damaging processes. We describe here the independent generation of dC· from oxime esters under UV-irradiation or single electron transfer conditions. Support for this σ-type iminyl radical generation is provided by product studies carried out under aerobic and anaerobic conditions, as well as electron spin resonance (ESR) characterization of dC· in a homogeneous glassy solution at low temperature. Density functional theory (DFT) calculations also support fragmentation of the corresponding radical anions of oxime esters 2d and 2e to dC· and subsequent hydrogen atom abstraction from organic solvents. The corresponding 2'-deoxynucleotide triphosphate (dNTP) of isopropyl oxime ester 2c (5) is incorporated opposite 2'-deoxyadenosine and 2'-deoxyguanosine by a DNA polymerase with approximately equal efficiency. Photolysis experiments of DNA containing 2c support dC· generation and indicate that the radical produces tandem lesions when flanked on the 5'-side by 5'-d(GGT). These experiments suggest that oxime esters are reliable sources of nitrogen radicals in nucleic acids that will be useful mechanistic tools and possibly radiosensitizing agents when incorporated in DNA.

Paraspinal muscle gene expression across different aetiologies in individuals undergoing surgery for lumbar spine pathology.

PURPOSE: The purpose of this study was to understand potential baseline transcriptional expression differences in paraspinal skeletal muscle from patients with different underlying lumbar pathologies by comparing multifidus gene expression profiles across individuals with either disc herniation, facet arthropathy, or degenerative spondylolisthesis. METHODS: Multifidus biopsies were obtained from patients (n = 44) undergoing lumbar surgery for either disc herniation, facet arthropathy, or degenerative spondylolisthesis. Diagnostic categories were based on magnetic resonance images, radiology reports, and intraoperative reports. Gene expression for 42 genes was analysed using qPCR. A one-way analysis of variance was performed for each gene to determine differences in expression across diagnostic groups. Corrections for multiple comparisons across genes (Benjamini-Hochberg) and for between-group post hoc comparisons (Sidak) were applied. RESULTS: Adipogenic gene (ADIPOQ) expression was higher in the disc herniation group when compared to the facet arthropathy group (p = 0.032). Adipogenic gene (PPARD) expression was higher in the degenerative spondylolisthesis group when compared to the disc herniation group (p = 0.013), although absolute gene expression levels for all groups was low. Fibrogenic gene (COL3A1) had significantly higher expression in the disc herniation group and facet arthropathy group when compared to the degenerative spondylolisthesis group (p < 0.001 and p = 0.038, respectively). When adjusted for multiple comparisons, only COL3A1 remained significant (p = 0.012). CONCLUSION: Individuals with disc herniation and facet arthropathy demonstrate higher COL3A1 gene expression compared to those with degenerative spondylolisthesis. Future research is required to further understand the biological relevance of these transcriptional differences.

Paraspinal Muscle Health is Related to Fibrogenic, Adipogenic, and Myogenic Gene Expression in Patients with Lumbar Spine Pathology.

BACKGROUND: Lumbar spine pathology is a common feature of lower back and/or lower extremity pain and is associated with observable degenerative changes in the lumbar paraspinal muscles that are associated with poor clinical prognosis. Despite the commonly observed phenotype of muscle degeneration in this patient population, its underlying molecular mechanisms are not well understood. The aim of this study was to investigate the relationships between groups of genes within the atrophic, myogenic, fibrogenic, adipogenic, and inflammatory pathways and multifidus muscle health in individuals undergoing surgery for lumbar spine pathology. METHODS: Multifidus muscle biopsies were obtained from patients (n = 59) undergoing surgery for lumbar spine pathology to analyze 42 genes from relevant adipogenic/metabolic, atrophic, fibrogenic, inflammatory, and myogenic gene pathways using quantitative polymerase chain reaction. Multifidus muscle morphology was examined preoperatively in these patients at the level and side of biopsy using T2-weighted magnetic resonance imaging to determine whole muscle compartment area, lean muscle area, fat cross-sectional areas, and proportion of fat within the muscle compartment. These measures were used to investigate the relationships between gene expression patterns and muscle size and quality. RESULTS: Relationships between gene expression and imaging revealed significant associations between decreased expression of adipogenic/metabolic gene (PPARD), increased expression of fibrogenic gene (COL3A1), and lower fat fraction on MRI (r = -0.346, p = 0.018, and r = 0.386, p = 0.047 respectively). Decreased expression of myogenic gene (mTOR) was related to greater lean muscle cross-sectional area (r = 0.388, p = 0.045). CONCLUSION: Fibrogenic and adipogenic/metabolic genes were related to pre-operative muscle quality, and myogenic genes were related to pre-operative muscle size. These findings provide insight into molecular pathways associated with muscle health in the presence of lumbar spine pathology, establishing a foundation for future research that addresses how these changes impact outcomes in this patient population.

Varying diffusion time to discriminate between simulated skeletal muscle injury models using stimulated echo diffusion tensor imaging.

PURPOSE: Evaluate the relationship between muscle microstructure, diffusion time (Δ), and the diffusion tensor (DT) to identify the optimal Δ where changes in muscle fiber size may be detected. METHODS: The DT was simulated in models with histology informed geometry over a range of Δ with a stimulated echo DT imaging (DTI) sequence using the numerical simulation application DifSim. The difference in the DT at each Δ between healthy and injured skeletal muscle models was calculated, to identify the optimal Δ at which changes in muscle fiber size may be detected. The random permeable barrier model (RPBM) was used to estimate muscle microstructure from the simulated DT measurements, which were compared to the ground truth. RESULTS: Across all models, fractional anisotropy provided greater contrast between injured and control models than diffusivity measurements. Compared to control models, in atrophic injury models, the greatest difference in the DT was found between 90 ms and 250 ms. In models with acute edema, the contrast between injured and control muscle increased with increasing diffusion time, although these models had smaller mean fiber areas. RPBM systematically underestimated fiber size but accurately estimated surface area-to-volume ratio of simulated models. CONCLUSION: These findings may better inform pulse sequence parameter selection when performing DTI experiments in vivo. If only a single diffusion experiment can be performed, the selected Δ should be ~170 ms to maximize the ability to discriminate between different injury models. Ideally several diffusion times between 90 ms and 500 ms should be sampled in order to maximize diffusion contrast, particularly when the disease process is unknown.

Practical ultrasonographic technique to precisely identify and differentiate tendons and ligaments of the elbow at the level of the humeral epicondyles: anatomical study.

OBJECTIVES: To develop a practical step-by-step technique to precisely identify and differentiate tendons and ligaments attaching to the humeral epicondyles, to confirm through gross anatomical study the accurate structure identification provided by this technique and to determine the frequency at which each structure can be identified in healthy volunteers. MATERIALS AND METHODS: First, ten fresh frozen cadavers (6 men, age at death = 58-92 years) were examined by two musculoskeletal radiologists and a step-by-step technique for the identification of tendons and ligaments at the level of humeral epicondyles was developed. Second, the accurate identification of structures was confirmed through gross anatomical study including anatomical sections on five specimens and layer-by-layer dissection technique on five others. Finally, 12 healthy volunteers (6 men, average age = 36, range = 28-52) were scanned by two radiologists following the same technique. RESULTS: An ultrasonographic technique based on the recognition of bony landmarks and the use of ultrasonographic signs to differentiate overlapping structures was developed and validated through gross anatomical study. In healthy volunteers, most tendons and ligaments were identified and well-defined in ≥ 80% of cases, except for the extensor carpi radialis brevis and extensor digiti minimi tendons on the lateral epicondyle (having common attachments with the extensor digitorum communis) and the palmaris longus tendon on the medial epicondyle (absent, or common attachment with the flexor carpi radialis). CONCLUSION: A step-by-step approach to the ultrasonographic assessment of tendons and ligaments at the humeral epicondyles allowed accurate identification of and differentiation among these structures, in particular those relevant to pathological conditions.

Surgical Mobilization of Skeletal Muscles Changes Functional Properties-Implications for Tendon Transfers.

PURPOSE: Tendon transfer surgery restores function by rerouting working muscle-tendon units to replace the function of injured or paralyzed muscles. This procedure requires mobilizing a donor muscle relative to its surrounding myofascial connections, which improves the muscle's new line of action and increases excursion. However, the biomechanical effect of mobilization on a donor muscle's force-generating function has not been previously studied under in vivo conditions. The purpose of this study was to quantify the effect of surgical mobilization on active and passive biomechanical properties of 3 large rabbit hind limb muscles. METHODS: Myofascial connections were mobilized stepwise from the distal end to the proximal end of muscles (0%, 25%, 50%, and 75% of muscle length) and their active and passive length-tension curves were measured after each degree of mobilization. RESULTS: Second toe extensor, a short-fibered muscle, exhibited a 30% decline in peak stress and 70% decline in passive stress, whereas extensor digitorum longus, a short-fibered muscle, and tibialis anterior, a long-fibered muscle, both exhibited similar smaller declines in active (about 18%) and passive stress (about 65%). CONCLUSIONS: The results highlight 3 important points: (1) a trade-off exists between increasing muscle mobility and decreasing force-generating capacity; (2) intermuscular force transmission is important, especially in second toe extensor, because it was able to generate 70% of its premobilization active force although most fibers were freed from their native origin; and (3) muscle architecture is not the major influence on mobilization-induced force impairment. CLINICAL RELEVANCE: These data demonstrate that surgical mobilization itself alters the passive and active force-generating capacity of skeletal muscles. Thus, surgical mobilization should not be viewed simply as a method to redirect the line of action of a donor muscle because this procedure has an impact on the functional properties of the donor muscle itself.

One Way Traffic: Base-to-Backbone Hole Transfer in Nucleoside Phosphorodithioate.

The directionality of the hole-transfer processes between DNA backbone and base was investigated by using phosphorodithioate [P(S- )=S] components. ESR spectroscopy in homogeneous frozen aqueous solutions and pulse radiolysis in aqueous solution at ambient temperature confirmed initial formation of G.+ -P(S- )=S. The ionization potential of G-P(S- )=S was calculated to be slightly lower than that of guanine in 5'-dGMP. Subsequent thermally activated hole transfer from G.+ to P(S- )=S led to dithiyl radical (P-2S. ) formation on the µs timescale. In parallel, ESR spectroscopy, pulse radiolysis, and density functional theory (DFT) calculations confirmed P-2S. formation in an abasic phosphorodithioate model compound. ESR investigations at low temperatures and higher G-P(S- )=S concentrations showed a bimolecular conversion of P-2S. to the σ2 -σ*1 -bonded dimer anion radical [-P-2S - . 2S-P-]- [ΔG (150 K, DFT)=-7.2 kcal mol-1 ]. However, [-P-2S - . 2S-P-]- formation was not observed by pulse radiolysis [ΔG° (298 K, DFT)=-1.4 kcal mol-1 ]. Neither P-2S. nor [-P-2S - . 2S-P-]- oxidized guanine base; only base-to-backbone hole transfer occurs in phosphorodithioate.

One Way Traffic: Base-to-Backbone Hole Transfer in Nucleoside Phosphorodithioate.

Invited for the cover of this issue are the groups of Roman Dembinski, Mehran Mostafavi, and Amitava Adhikary at the Polish Academy of Sciences, Université Paris-Saclay, and Oakland University. The image depicts a doughnut as a way of illustrating the hole transfer process. Read the full text of the article at 10.1002/chem.202000247.

Examination of the human motor endplate after brachial plexus injury with two-photon microscopy.

INTRODUCTION: After traumatic nerve injury, neuromuscular junction remodeling plays a key role in determining functional outcomes. Immunohistochemical analyses of denervated muscle biopsies may provide valuable prognostic data regarding clinical outcomes to supplement electrodiagnostic studies. METHODS: We performed biopsies on nonfunctioning deltoid muscles in two patients after gunshot wounds and visualized the neuromuscular junctions using two-photon microscopy with immunohistochemistry. RESULTS: Although the nerves in both patients showed evidence of acute Wallerian degeneration, some of the motor endplates were intact but exhibited significantly decreased surface area and volume. Both patients exhibited substantial recovery of motor function over several weeks postinjury. DISCUSSION: Two-photon microscopic assessment of neuromuscular junction integrity and motor endplate morphometry in muscle biopsies provided evidence of partial sparing of muscle innervation. This finding supported the clinical judgment that eventual recovery would occur. With further study, this technique may help to guide operative decisionmaking after traumatic nerve injuries.

Regional differences between superficial and deep lumbar multifidus in patients with chronic lumbar spine pathology.

BACKGROUND: Due to its unique arrangement, the deep and superficial fibers of the multifidus may have differential roles for maintaining spine stabilization and lumbar posture; the superficial multifidus is responsible for lumbar extension and the deep multifidus for intersegmental stability. In patients with chronic lumbar spine pathology, muscle activation patterns have been shown to be attenuated or delayed in the deep, but not superficial, multifidus. This has been interpreted as pain differentially influencing the deep region. However, it is unclear if degenerative changes affecting the composition and function of the multifidus differs between the superficial and deep regions, an alternative explanation for these electrophysiological changes. Therefore, the goal of this study was to investigate macrostructural and microstructural differences between the superficial and deep regions of the multifidus muscle in patients with lumbar spine pathology. METHODS: In 16 patients undergoing lumbar spinal surgery for degenerative conditions, multifidus biopsies were acquired at two distinct locations: 1) the most superficial portion of muscle adjacent to the spinous process and 2) approximately 1 cm lateral to the spinous process and deeper at the spinolaminar border of the affected vertebral level. Structural features related to muscle function were histologically compared between these superficial and deep regions, including tissue composition, fat fraction, fiber cross sectional area, fiber type, regeneration, degeneration, vascularity and inflammation. RESULTS: No significant differences in fat signal fraction, muscle area, fiber cross sectional area, muscle regeneration, muscle degeneration, or vascularization were found between the superficial and deep regions of the multifidus. Total collagen content between the two regions was the same. However, the superficial region of the multifidus was found to have less loose and more dense collagen than the deep region. CONCLUSIONS: The results of our study did not support that the deep region of the multifidus is more degenerated in patients with lumbar spine pathology, as gross degenerative changes in muscle microstructure and macrostructure were the same in the superficial and deep regions of the multifidus. In these patients, the multifidus is not protected in order to maintain mobility and structural stability of the spine.

Correction to: Distal insertional anatomy of the triceps brachii muscle: MRI assessment in cadaveric specimens employing histologic correlation and Play-doh® models of the anatomic findings.

Figures 9, 10, 11, 12 and 15 corrected.

Distal insertional anatomy of the triceps brachii muscle: MRI assessment in cadaveric specimens employing histologic correlation and Play-doh® models of the anatomic findings.

OBJECTIVES: Assess the insertional anatomy of the distal aspect of the triceps brachii muscle using magnetic resonance imaging (MRI) in cadavers with histologic correlation and Play-doh® models of the anatomic findings. MATERIALS: Elbows were obtained from twelve cadaveric arm specimens by transverse sectioning through the proximal portion of the humerus and the midportion of the radius and ulna. MRI was performed in all elbows. Two of the elbow specimens were then dissected while ten were studied histologically. Subsequently, Play-doh® models of the anatomic findings of the distal attachment sites of the triceps brachii muscle were prepared. RESULTS: MRI showed a dual partitioned appearance of the distal attachment sites into the olecranon in all specimens. In the deeper tissue planes, the medial head muscle insertion was clearly identified while superficially, the terminal portion of the long and lateral heads appeared as a conjoined tendon. Histologic analysis, however, showed continuous tissue rather than separate structures attaching to the olecranon. CONCLUSION: Although MRI appeared to reveal separate and distinct attachments of the triceps brachii muscle into the olecranon, histologic analysis delineated complex but continuous tissue related to the attachments of the three heads of this muscle. The Play-doh® models were helpful for the comprehension of this complex anatomy and might serve as a valuable educational tool when applied to the analysis of other musculoskeletal regions.

Mechanical impact of parturition-related strains on rat pelvic striated sphincters.

AIMS: To define the operational resting sarcomere length (Ls ) of the female rat external urethral sphincter (EUS) and external anal sphincter (EAS) and to determine the mechanism of parturition-related injury of EUS and EAS using a simulated birth injury (SBI) vaginal distention model. METHODS: EUS and EAS of 3-month-old Sprague-Dawley control and injured rats were fixed in situ, harvested, and microdissected for Ls measurements and assessment of ultrastructure. EUS and EAS function was determined at baseline, and immediately and 4 weeks after SBI, using leak point pressure (LPP) and anorectal manometry (ARM), respectively. Operational L s was compared to species-specific optimal L s using one sample Student's t test. Data (mean ± SD) were compared between groups and time points using repeated measures one-way analysis of variance, followed by Tukey's post hoc pairwise comparisons, with significance set to 0.05. RESULTS: The operational resting Ls of both sphincters (EUS: 2.09 ± 0.07 µm, EAS: 2.02 ± 0.03 µm) was significantly shorter than optimal rat Ls of 2.4 µm. Strains imposed on EUS and EAS during SBI resulted in significant sarcomere elongation and disruption, compared with the controls (EUS: 3.09 ± 0.11 µm, EAS: 3.37 ± 0.09 µm). Paralleling structural changes, LPP and ARM measures were significantly lower immediately (LPP: 21.5 ± 1.0 cmH2 O, ARM: 5.1 ± 2.31 cmH2 O) and 4 weeks (LPP: 27.7 ± 1.3cmH2 O, ARM: 2.5 ± 1.0 cmH2 O) after SBI relative to the baseline (LPP: 43.4 ± 8.5 cmH2 O, ARM: 8.2 ± 2.0 cmH2 O); P < 0.05. CONCLUSIONS: Analogous to humans, the short resting Ls of rat EUS and EAS favors their sphincteric function. The insult experienced by these muscles during parturition leads to sarcomere hyperelongation, myofibrillar disruption, and dysfunction of the sphincters long-term.

Implications of seasonal and annual heat accumulation for population dynamics of an invasive defoliator.

Increasing temperatures can drive changes in the distribution and abundance of insects. The time of year when warming occurs (e.g., spring vs. autumn) may disparately influence the phenology of herbivorous insects and their host plants. We investigated the role of changing phenology in recent outbreaks of larch casebearer, an invasive defoliator of eastern larch in North America. We quantified degree-days required for eastern larch to break bud and larch casebearer to develop through each life stage from the onset of development in spring to autumnal dormancy. We developed degree-day models to reconstruct (1) spring phenological synchrony and (2) cumulative proportion of larvae reaching the overwintering stage based on historical climate data. The consequences of warmer autumns and winters (i.e., pre-spring warming) for the incidence and timing of spring activation of larvae were also investigated. Our results suggested that no significant changes have occurred in spring phenological synchrony, but the estimated proportions of larvae reaching the overwintering stage have significantly increased through time. Autumnal warming resulted in delayed spring activation, suggesting that warmer temperatures may act antagonistically on casebearer development, depending on time of year and intensity of warming. Our results provide evidence that increases in annual degree-day accumulation may have helped facilitate recent outbreaks of this invasive defoliator in North America.

Determinants and consequences of plant-insect phenological synchrony for a non-native herbivore on a deciduous conifer: implications for invasion success.

Phenological synchrony between herbivorous insects and host plants is an important determinant of insect distribution and abundance. Non-native insects often experience novel climates, photoperiods, and host plants. How critical time periods of insect life cycles coincide with-or diverge from-phenological windows of host plant suitability could affect invasion success and the dynamics of outbreaks. Larch casebearer is an invasive defoliator that has recently undergone anomalous outbreaks on eastern larch in North America. We conducted growth chamber, greenhouse, and field studies to quantify the spring phenological window for larch casebearer on eastern larch and importance of phenological synchrony for casebearer development and survival. We constructed degree-day models of spring activity for both species and investigated responses of casebearers to early and delayed activation relative to bud break. Both species had lower developmental thresholds of ~ 5 °C, but mean activation of casebearers occurred 245 degree-days after bud break by eastern larch. In addition to forcing temperatures, phenologies of eastern larch and casebearer larvae were significantly influenced by chilling and photoperiod, respectively. Larvae were robust to both starvation and delayed activation; days between larval activation and bud break (range: 0-58 days) had no influence on larval development and survival to adulthood. Disparate plant-insect responses to environmental cues and robustness of casebearers to changes in phenology result in a wide phenological window that likely has contributed to the insect's broad distribution in eastern North America. Changes in phenological synchrony, however, do not appear to have facilitated recent outbreaks of larch casebearer on eastern larch.

The effect of high-intensity resistance exercise on lumbar musculature in patients with low back pain: a preliminary study.

BACKGROUND: Muscle atrophy and fatty infiltration of the lumbar extensors is associated with LBP. Exercise-based rehabilitation targets strengthening these muscles, but few studies show consistent changes in muscle quality with standard-of-care rehabilitation. The goal of this study was to assess the effect of high-intensity resistance exercise on lumbar extensor muscle size (cross sectional area) and quality (fat fraction) in individuals with low back pain (LBP). METHODS: Fourteen patients with LBP were recruited from a local rehabilitation clinic. Patients underwent MRI scanning before and after a standardized 10-week high-intensity machine-based, resistance exercise program. Patient pain, disability, anxiety/depression, satisfaction, strength, and range of motion was compared pre- and post-rehabilitation using analysis of covariance (covariates: age, gender). Exercise-induced changes in MRI, and patient functional outcome measures were correlated using Pearson's correlation test. RESULTS: No significant differences were found in muscle size or fatty infiltration of the lumbar extensors over the course of rehabilitation (p > 0.31). However, patients reported reduced pain (p = 0.002) and were stronger (p = 0.03) at the conclusion of the program. Improvements in muscle size and quality for both multifidus and erector spinae correlated with improvements in disability, anxiety/depression, and strength. CONCLUSION: While average muscle size and fatty infiltration levels did not change with high-intensity exercise, the results suggest that a subgroup of patients who demonstrate improvements in muscle health demonstrate the largest functional improvements. Future research is needed to identify which patients are most likely to respond to this type of treatment.

Architecture of the Short External Rotator Muscles of the Hip.

BACKGROUND: Muscle architecture, or the arrangement of sarcomeres and fibers within muscles, defines functional capacity. There are limited data that provide an understanding of hip short external rotator muscle architecture. The purpose of this study was thus to characterize the architecture of these small hip muscles. METHODS: Eight muscles from 10 independent human cadaver hips were used in this study (n = 80 muscles). Architectural measurements were made on pectineus, piriformis, gemelli, obturators, quadratus femoris, and gluteus minimus. Muscle mass, fiber length, sarcomere length, and pennation angle were used to calculate the normalized muscle fiber length, which defines excursion, and physiological cross-sectional area (PCSA), which defines force-producing capacity. RESULTS: Gluteus minimus had the largest PCSA (8.29 cm2) followed by obturator externus (4.54 cm2), whereas superior gemellus had the smallest PCSA (0.68 cm2). Fiber lengths clustered into long (pectineus - 10.38 cm and gluteus minimus - 10.30 cm), moderate (obturator internus - 8.77 cm and externus - 8.04 cm), or short (inferior gemellus - 5.64 and superior gemellus - 4.85). There were no significant differences among muscles in pennation angle which were all nearly zero. When the gemelli and obturators were considered as a single functional unit, their collective PCSA (10.00 cm2) exceeded that of gluteus minimus as a substantial force-producing group. CONCLUSIONS: The key findings are that these muscles have relatively small individual PCSAs, short fiber lengths, and low pennation angles. The large collective PCSA and short fiber lengths of the gemelli and obturators suggest that they primarily play a stabilizing role rather than a joint rotating role.