Search

The myotendinous junction (MTJ) is a weak link in the musculoskeletal system. Here, we isolated the tips of single myofibres from healthy human hamstring muscles for confocal microscopy (n=6) and RNAscope in situ hybridization (n=6) to gain insight into the profiles of cells and myonuclei in this region. A marked presence of mononuclear cells was observed coating the fibre tips, with a median of 29 (range 16-63) and 16 (9-23) cells per fibre for type I and II myofibres, respectively (p<0.05). The number and density of myonuclei gradually increased from the myofibre proper towards the tip (p<0.05), similarly for both fibre types, and a greater number of COL22A1-expressing nuclei was seen in type II vs type I myofibres (p<0.05). These divergent fibre type-specific characteristics of the MTJ reflect the respective demands for remodelling of the tendon and myofibre sides of the junction according to loading patterns. This insight refines our fundamental understanding of the human MTJ at the cell and structural levels.Competing Interest StatementThe authors have declared no competing interest.

Background: Plantar fasciitis is a painful tendinous condition (tendinopathy) with a high prevalence in athletes. While a healthy tendon has limited blood flow, ultrasound has indicated elevated blood flow in tendinopathy, but it is unknown if this is related to a de facto increase in the tendon vasculature. Likewise, an accumulation of glycosaminoglycans (GAGs) is observed in tendinopathy, but its relationship to clinical pain is unknown. Purpose: To explore to what extent vascularization, inflammation, and fat infiltration were present in patients with plantar fasciitis and if they were related to clinical symptoms. Study Design: Descriptive laboratory study. Methods: Biopsy specimens from tendinopathic plantar fascia tissue were obtained per-operatively from both the primary site of tendon pain and tissue swelling (“proximal”) and a region that appeared macroscopically healthy at 1 to 2 cm away from the primary site (“distal”) in 22 patients. Biopsy specimens were examined with immunofluorescence for markers of blood vessels, tissue cell density, fat infiltration, and macrophage level. In addition, pain during the first step in the morning (registered during an earlier study) was correlated with the content of collagen and GAGs in tissue. Results: High vascularization (and cellularity) was present in both the proximal (0.89%) and the distal (0.96%) plantar fascia samples, whereas inconsistent but not significantly different fat infiltration and macrophage levels were observed. The collagen content was similar in the 2 plantar fascia regions, whereas the GAG content was higher in the proximal region (3.2% in proximal and 2.8% in distal; P = .027). The GAG content in the proximal region was positively correlated with the subjective morning pain score in the patients with tendinopathy (n = 17). Conclusion: In patients with plantar fasciitis, marked tissue vascularization was present in both the painful focal region and a n

Background: Achilles tendon ruptures often result in long-term functional deficits despite accelerated (standard) rehabilitation. Purpose/Hypothesis: The purpose of this study was to investigate if delayed loading would influence functional, clinical, and structural outcomes of the muscles and tendon 1 year after a surgical repair. It was hypothesized that delaying the loading would reduce the heel-rise height deficit 1 year after Achilles tendon rupture. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: In total, 48 patients with a surgically repaired Achilles tendon rupture were randomized to 2 groups: the standard group received the currently accepted rehabilitation, and the delayed group received the same rehabilitation except that initial loading was delayed by 6 weeks. The primary outcome was the heel-rise height difference between the injured and uninjured sides at 1 year. The secondary outcomes were (1) tendon length measured with magnetic resonance imaging, (2) muscle fascicle length and pennation angle of the gastrocnemius medialis muscle, (3) Doppler activity measured with ultrasonography, (4) Achilles tendon Total Rupture Score (ATRS), and (5) isometric muscle strength. Results: The mean heel-rise height deficits for the standard and delayed groups were −2.2 cm and −2.1 cm, respectively (P = .719). The soleus part of the tendon was already elongated 1 week after surgery in both groups without a between-group difference (side-to-side difference: standard, 16.3 mm; delayed, 17.5 mm; P = .997) and did not change over 52 weeks. The gastrocnemius tendon length was unchanged at 1 week but elongated over time without a between-group difference (side-to-side difference at 52 weeks: standard, 10.5 mm; delayed, 13.0 mm; P = .899). The delayed group had less Doppler activity at 12 weeks (P = .006) and a better ATRS (standard, 60 points; delayed, 72 points; P = .032) at 52 weeks. Conclusion: Delayed, Background: Achilles tendon ruptures often result in long-term functional deficits despite accelerated (standard) rehabilitation. Purpose/Hypothesis: The purpose of this study was to investigate if delayed loading would influence functional, clinical, and structural outcomes of the muscles and tendon 1 year after a surgical repair. It was hypothesized that delaying the loading would reduce the heel-rise height deficit 1 year after Achilles tendon rupture. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: In total, 48 patients with a surgically repaired Achilles tendon rupture were randomized to 2 groups: the standard group received the currently accepted rehabilitation, and the delayed group received the same rehabilitation except that initial loading was delayed by 6 weeks. The primary outcome was the heel-rise height difference between the injured and uninjured sides at 1 year. The secondary outcomes were (1) tendon length measured with magnetic resonance imaging, (2) muscle fascicle length and pennation angle of the gastrocnemius medialis muscle, (3) Doppler activity measured with ultrasonography, (4) Achilles tendon Total Rupture Score (ATRS), and (5) isometric muscle strength. Results: The mean heel-rise height deficits for the standard and delayed groups were −2.2 cm and −2.1 cm, respectively (P =.719). The soleus part of the tendon was already elongated 1 week after surgery in both groups without a between-group difference (side-to-side difference: standard, 16.3 mm; delayed, 17.5 mm; P =.997) and did not change over 52 weeks. The gastrocnemius tendon length was unchanged at 1 week but elongated over time without a between-group difference (side-to-side difference at 52 weeks: standard, 10.5 mm; delayed, 13.0 mm; P =.899). The delayed group had less Doppler activity at 12 weeks (P =.006) and a better ATRS (standard, 60 points; delayed, 72 points; P =.032) at 52 weeks. Conclusion: Delayed loading was not superior to standard loading

INTRODUCTION: The population-based Inter99 cohort has contributed extensively to our understanding of effects of a systematic screening and lifestyle intervention, as well as the multifactorial aetiology of type 2 diabetes (T2D) and cardiovascular disease. To understand causes, trajectories and patterns of early and overt cardiometabolic disease manifestations, we will perform a combined clinical deep phenotyping and registry follow-up study of the now 50-80 years old Inter99 participants.METHODS AND ANALYSIS: The Inter99 cohort comprises individuals aged 30-60 years, who lived in a representative geographical area of greater Copenhagen, Denmark, in 1999. Age-stratified and sex-stratified random subgroups were invited to participate in either a lifestyle intervention (N=13 016) or questionnaires (N=5264), while the rest served as a reference population (N=43 021). Of the 13 016 individuals assigned to the lifestyle intervention group, 6784 (52%) accepted participation in a baseline health examination in 1999, including screening for cardiovascular risk factors and prediabetic conditions. In total, 6004 eligible participants, who participated in the baseline examination, will be invited to participate in the deep phenotyping 20-year follow-up clinical examination including measurements of anthropometry, blood pressure, arterial stiffness, cardiometabolic biomarkers, coronary artery calcification, heart rate variability, heart rhythm, liver stiffness, fundus characteristics, muscle strength and mass, as well as health and lifestyle questionnaires. In a subsample, 10-day monitoring of diet, physical activity and continuous glucose measurements will be performed. Fasting blood, urine and faecal samples to be stored in a biobank. The established database will form the basis of multiple analyses. A main purpose is to investigate whether low birth weight independent of genetics, lifestyle and glucose tolerance predicts later common T2D cardiometabolic comorbiditi

BACKGROUND: Age-related loss of strength is disproportionally greater than the loss of mass, suggesting maladaptations in the neuro-myo-tendinous system. Myofibers are often misshaped in aged and diseased muscle, but systematic analyses of large sample sets are lacking. Our aim was to investigate myofiber shape in relation to age, exercise, myofiber type, species and sex.METHODS: Vastus lateralis muscle biopsies (n = 265) from 197 males and females, covering an age span of 20-97 years, were examined. The gastrocnemius and soleus muscles of 11 + 22-month-old male C57BL/6 mice were also examined. Immunofluorescence and ATPase stainings of muscle cross-sections were used to measure myofiber cross-sectional area (CSA) and perimeter. From these, a shape factor index (SFI) was calculated in a fibre-type-specific manner (type I/II in humans; type I/IIa/IIx/IIb in mice), with higher values indicating increased deformity. Heavy resistance training (RT) was performed three times per week for 3-4 months by a subgroup (n = 59). Correlation analyses were performed comparing SFI and CSA with age, muscle mass, maximal voluntary contraction (MVC), rate of force development and specific force (MVC/muscle mass).RESULTS: In human muscle, SFI was positively correlated with age for both type I (R2 = 0.20) and II (R2 = 0.38) myofibers. When subjects were separated into age cohorts, SFI was lower for type I (4%, P < 0.001) and II (6%, P < 0.001) myofibers in young (20-36) compared with old (60-80) and higher for type I (5%, P < 0.05) and II (14%, P < 0.001) myofibers in the oldest old (>80) compared with old. The increased SFI in old muscle was observed in myofibers of all sizes. Within all three age cohorts, type II myofiber SFI was higher than that for type I myofiber (4-13%, P < 0.001), which was also the case in mice muscles (8-9%, P < 0.001). Across age cohorts, there was no difference between males and females in SFI for either type I (P = 0.496

This chapter explores the establishing, and subsequent reproduction, of modern western cartographic visuality. Such visuality has been a contributing factor in the transformation of the planet during the Anthropocene, the magnitude of which we have only begun to understand in recent years. My main thesis is that, over the seventeenth century, Western Enlightenment cartography developed in correlation with a dark, imaginary space, set apart from perception of the circumambient world, a space unfolded in the chiaroscuro of the Baroque. Together, they formed a complex cartographic and visual motor which contributed to making the modern, Western subject at least partially incapable of comprehending, imagining, and imaging the actual pulsating world it both found itself in and affected. The characterization of this cartographic visual complex as a motor is a term coined by the author of this chapter. The chapter is uncovering the ways in which this complex was and still is epistemically possible, how it functions, and which worlds it allows and disallows Western man to perceive.

The myotendinous junction (MTJ) is a specialized domain of the multinucleated myofibre that is faced with the challenge of maintaining robust cell–matrix contact with the tendon under high mechanical stress and strain. Here, we profiled 24,124 nuclei in semitendinosus muscle–tendon samples from three healthy males by using single-nucleus RNA sequencing (snRNA-seq), alongside spatial transcriptomics, to gain insight into the genes characterizing this specialization in humans. We identified a cluster of MTJ myonuclei represented by 47 enriched transcripts, of which the presence of ABI3BP, ABLIM1, ADAMTSL1, BICD1, CPM, FHOD3, FRAS1 and FREM2 was confirmed at the MTJ at the protein level in immunofluorescence assays. Four distinct subclusters of MTJ myonuclei were apparent, comprising two COL22A1-expressing subclusters and two subclusters lacking COL22A1 expression but with differing fibre type profiles characterized by expression of either MYH7 or MYH1 and/or MYH2. Our findings reveal distinct myonuclei profiles of the human MTJ, which represents a weak link in the musculoskeletal system that is selectively affected in pathological conditions ranging from muscle strains to muscular dystrophies.

Understanding individual variability in response to physical activity is key to developing more effective and personalised interventions for healthy ageing. Here, we aimed to unpack individual differences by using longitudinal data from a randomised-controlled trial of a 12-month muscle strengthening intervention in older adults. Physical function of the lower extremities was collected from 247 participants (66.3 ± 2.5 years) at four time-points. At baseline and at year 4, participants underwent 3 T MRI brain scans. K-means longitudinal clustering was used to identify patterns of change in chair stand performance over 4 years, and voxel-based morphometry was applied to map structural grey matter volume at baseline and year 4. Results identified three groups showing trajectories of poor (33.6%), mid (40.1%), and high (26.3%) performance. Baseline physical function, sex, and depressive symptoms significantly differed between trajectory groups. High performers showed greater grey matter volume in the motor cerebellum compared to the poor performers. After accounting for baseline chair stand performance, participants were re-assigned to one of four trajectory-based groups: moderate improvers (38.9%), maintainers (38.5%), improvers (13%), and decliners (9.7%). Clusters of significant grey matter differences were observed between improvers and decliners in the right supplementary motor area. Trajectory-based group assignments were unrelated to the intervention arms of the study. In conclusion, patterns of change in chair stand performance were associated with greater grey matter volumes in cerebellar and cortical motor regions. Our findings emphasise that how you start matters, as baseline chair stand performance was associated with cerebellar volume 4 years later.