Stroke-induced excess in capillarization relative to oxidative capacity in rats is muscle specific.

Stroke is not only associated with muscle weakness, but also associated with reduced muscle fatigue resistance and reduced desaturation during exercise that may be caused by a reduced oxidative capacity and/or microvasculature. Therefore, the objective of the present study was to determine the effects of stroke on muscle mass, fiber size and shape, capillarization and oxidative capacity of the rat m. extensor carpi radialis (ECR) and m. flexor carpi ulnaris (FCU) after a photothrombotic stroke in the forelimb region of the primary sensorimotor cortex. The main observation of the present study was that 4 weeks after induction of stroke there were no significant changes in muscle fiber size and shape. Although there was no significant capillary rarefaction, there was some evidence for remodeling of the capillary bed as reflected by a reduced heterogeneity of capillary spacing (p = 0.006) that may result in improved muscle oxygenation. In the ECR, but not in the FCU, this was accompanied by reduction in muscle fiber oxidative capacity as reflected by reduced optical density of sections stained for succinate dehydrogenase (p = 0.013). The reduced oxidative capacity and absence of significant capillary rarefaction resulted in a capillary to fiber ratio per unit of oxidative capacity that was higher after stroke in the ECR (p = 0.01), but not in the FCU. This suggests that at least during the early stages, stroke is not necessarily accompanied by muscle fiber atrophy, and that stroke-induced reductions in oxidative capacity resulting in relative excess of capillarization are muscle specific.

Knee movements cause changes in the firing behaviour of muscle spindles located within the mono-articular ankle extensor soleus in the rat.

We recently showed that within an intact muscle compartment, changing the length of one muscle affects the firing behaviour of muscle spindles located within a neighbouring muscle. The conditions tested, however, involved muscle lengths and relative positions that were beyond physiological ranges. The aim of the present study was to investigate the effects of simulated knee movements on the firing behaviour of muscle spindles located within rat soleus (SO) muscle. Firing from single muscle spindle afferents in SO was measured intra-axonally for different lengths (static) and during lengthening (dynamic) of the lateral gastrocnemius and plantaris muscles. Also, the location of the spindle within the muscle was assessed. Changing the length of synergistic ankle plantar flexors (simulating different static knee positions, between 45 and 130°) affected the force threshold, but not the length threshold, of SO muscle spindles. The effects on type II afferents were substantially (four times) higher than those on type IA afferents. Triangular stretch-shortening of synergistic muscles (simulating dynamic knee joint rotations of 15°) caused sudden changes in the firing rate of SO type IA and II afferents. Lengthening decreased and shortening increased the firing rate, independent of spindle location. This supports our prediction that the major point of application of forces exerted by connections between adjacent muscles is at the distal end of SO. We conclude that muscle spindles provide the CNS with information about the condition of adjacent joints that the muscle does not span.

Stab lesion of the L4/L5 intervertebral disc in the rat causes acute changes in disc bending mechanics.

Low-back pain often coincides with altered neuromuscular control, possibly due to changes in spine stability resulting from injury or degeneration, or due to effects of nociception. The relative importance of these mechanisms, and their possible interaction, are unknown. In spine bending, the bulk of the load is borne by the IVD, yet the acute effects of intervertebral disc (IVD) injury on bending mechanics have not been investigated. In the present study, we aimed to quantify the acute effects of a stab lesion of the disc on its mechanical properties, because such changes can be expected to elicit compensatory changes in neuromuscular control. L4/L5 spinal segments were collected from 27 Wistar rats within two hours after sacrifice and stored at -20℃. Following thawing, bending tests were performed to assess the intersegmental angle-moment characteristics. Specimens were loaded in right bending, left bending and flexion, before and after a stab lesion of the IVD fully penetrating the nucleus pulposus. In the angle-moment curves, we found reduced moments at equal bending angles after IVD lesion in left bending, right bending and flexion. Peak stiffness, peak moment, and hysteresis were significantly decreased (by 7.8-27.7 %) after IVD lesion in all directions. In conclusion, L4/L5 IVD lesion in the rat caused small to moderate acute changes in IVD mechanical properties. Our next steps will be to evaluate the longer term effects of IVD lesion on spine mechanics and the neural control of trunk muscles.

Creation of a decellularized vaginal matrix from healthy human vaginal tissue for potential vagina reconstruction: experimental studies.

BACKGROUND: When a disorder causes the absence of a healthy, full-size vagina, various neovaginal creation methods are available. Sometimes dilation or stretching of the vaginal cavity is sufficient, but intestinal or dermal flap tissue is generally required. However, different inherent tissue properties cause complications. Therefore, a lost body part should be replaced with a similar material. The use of organ-specific acellular vaginal tissue carries great potential, as its similar architecture and matrix composition make it suitable for vaginal regeneration. METHODS: The authors developed an optimized protocol for decellularization of healthy human vaginal tissue. Resected colpectomy tissue from 12 healthy transgender patients was used. Successful decellularization was confirmed by applying acellular criteria from in-vivo remodeling reports. Suitability as a tissue-mimicking scaffold for vaginal reconstruction was determined by visible structural features, biocompatibility during stretching, and the presence of visible collagen, elastin, laminin, and fibronectin. RESULTS: Histological examination confirmed the preservation of structural features, and minimal cellular residue was seen during fluorescence microscopy, DNA and RNA quantification, and fragment length examination. Biomechanical testing showed decreased peak load (55%, P <0.05), strain at rupture (23%, P <0.01), and ultimate tensile stress (55%, P <0.05) after decellularization, while the elastic modulus (68%) did not decrease significantly. Fluorescence microscopy revealed preserved Fibronectin-I/II/III and Laminin-I/II, while Collagen-I and Ficolin-2B were decreased but mostly retained. CONCLUSIONS: The absence of cellular residue, moderately altered biomechanical extracellular matrix properties, and mostly preserved structural proteins appear to make our decellularized human vaginal matrix a suitable tissue-mimicking scaffold for vagina transplantation when tissue survival through vascularization and innervation are accomplished in the future.

The Effect of the Nordic Hamstring Exercise on Muscle Activity: A Multichannel Electromyography Randomized Controlled Trial.

The aim of this study was to evaluate the effect of a Nordic hamstring exercise intervention on biceps femoris long head, semitendinosus, and semimembranosus muscle's activity and relative contributions through multichannel electromyography. Twenty-four injury-free male basketball players (mean age 20 [3] y) were randomly assigned to a 12-week intervention (n = 13) or control group (n = 11). The primary outcome measures were normalized muscle activity (percentage of maximal voluntary isometric contraction, %MVIC) and relative contribution of hamstring muscles over 12 weeks. No effects were found on any of the primary outcome measures. Between-group differences over 12 weeks were 2.7%MVIC (95% confidence interval 95% CI, -0.7 to 6.1) for the biceps femoris long head, 3.4%MVIC (95% CI, -1.4 to 8.2) for the semitendinosus, and 0.8%MVIC (95% CI, -3.0 to 4.6) for the semimembranosus, P = .366. Between-group differences over 12 weeks were 1.0% relative contribution (%con; 95% CI, -3.0 to 5.1) for the biceps femoris long head, 2.2% relative contribution (95% CI, -2.8 to 7.2) for the semitendinosus, and -3.3% relative contribution (95% CI, -6.4 to -0.1) for the semimembranosus P = .258. A positive value implies a higher value for the Nordic group. A Nordic hamstring exercise intervention did not affect the level of muscle activity and relative contribution of hamstring muscles in performance of the Nordic hamstring exercise.

Morphology of proximal and distal human semitendinosus compartments and the effects of distal tendon harvesting for anterior cruciate ligament reconstruction.

The human semitendinosus muscle is characterized by a tendinous inscription separating proximal and distal neuromuscular compartments. As each compartment is innervated by separate nerve branches, potential exists for independent operation and control of compartments. However, the morphology and function of each compartment have not been thoroughly examined in an adult human population. Further, the distal semitendinosus tendon is typically harvested for use in anterior cruciate ligament reconstruction surgery, which induces long-term morphological changes to the semitendinosus muscle-tendon unit. It remains unknown if muscle morphological alterations following anterior cruciate ligament reconstruction are uniform between proximal and distal semitendinosus compartments. Here, we performed magnetic resonance imaging on 10 individuals who had undergone anterior cruciate ligament reconstruction involving an ipsilateral distal semitendinosus tendon graft 14 ± 4 months prior, extracting morphological parameters of the whole semitendinosus muscle and each individual compartment from both the (non-injured) contralateral and surgical legs. In the contralateral leg, volume and length of the proximal compartment were smaller than the distal compartment. No between-compartment differences in volume or length were found for anterior cruciate ligament reconstructed legs, likely due to greater shortening of the distal compared to the proximal compartment after anterior cruciate ligament reconstruction. The maximal anatomical cross-sectional area of both compartments was substantially smaller on the anterior cruciate ligament reconstructed leg but did not differ between compartments on either leg. The absolute and relative between-leg differences in proximal compartment morphology on the anterior cruciate ligament reconstructed leg were strongly correlated with the corresponding between-leg differences in distal compartment morphological parameters. Specifically, greater between-leg morphological differences in one compartment were highly correlated with large between-leg differences in the other compartment, and vice versa for smaller differences. These relationships indicate that despite the heterogeneity in compartment length and volume, compartment atrophy is not independent or random. Further, the tendinous inscription endpoints were generally positioned at the same proximodistal level as the compartment maximal anatomical cross-sectional areas, providing a wide area over which the tendinous inscription could mechanically interact with compartments. Overall, results suggest the two human semitendinosus compartments are not mechanically independent.

Force transmission and interactions between synergistic muscles.

The classical view of muscles as independent motors has been challenged over the past decades. An alternative view has emerged in which muscles are not isolated but embedded in a three-dimensional connective tissue network that links them to adjacent muscles and other non-muscular structures in the body. Animal studies showing that the forces measured at the distal and proximal ends of a muscle are not equal have provided undisputable evidence that these connective tissue linkages are strong enough to serve as an extra pathway for muscular force transmission. In this historical review, we first introduce the terminology and anatomy related to these pathways of muscle force transmission and provide a definition for the term epimuscular force transmission. We then focus on important experimental evidence indicating mechanical interactions between synergistic muscles that may affect force transmission and/or influence the muscles' force generating capacity. We illustrate that there may exist different expressions of the highly relevant force-length properties depending on whether the force is measured at the proximal or distal tendon and depending on the dynamics of surrounding structures. Changes in length, activation level or disruption of the connective tissue of neighboring muscles, can affect how muscles interact and produce force on the skeleton. While most direct evidence is from animal experiments, studies on humans also suggest functional implications of the connective tissues surrounding muscles. These implications may explain how distant segments, which are not part of the same joint system, affect force generation at a given joint, and, in clinical conditions, explain observations from tendon transfer surgeries, where a muscle transferred to act as an antagonist continues to produce agonistic moments.

Activity distribution among the hamstring muscles during high-speed running: A descriptive multichannel surface EMG study.

PURPOSE: This study assessed activity distribution among the hamstring muscles during high-speed running. The objective was to compare within and between muscle activity, relative contribution and hip and knee joint angles at peak muscle activity during high-speed running. METHODS: Through multichannel electromyography, we measured muscle activity in male basketball players during high-speed running on a treadmill at 15 locations: five for biceps femoris long head, four for semitendinosus, and six for semimembranosus. Muscle activity was calculated for each location within each hamstring muscle individually for each percent of a stride cycle. RESULTS: Twenty-nine non-injured basketball players were included (mean age: 17 ± 1 years; mass, 85 ± 9 kg; height, 193 ± 9 cm). Heterogeneous activity was found for all individual hamstring muscles across multiple events of the stride cycle. In the late-swing phase, muscle activity and relative contribution of the semimembranosus was significantly higher than of the semitendinosus. There was no significant difference in hip and knee joint angles at instant of peak muscle activity, assessed locally within individual hamstring muscles, as well as in general over the whole hamstring muscle. CONCLUSION: Hamstring muscles were most active in the late-swing phase during high-speed running. In this phase, the semimembranosus was most active and the semitendinosus was least active. Within the biceps femoris long head, the most proximal region was significantly more active in the late-swing phase, compared to other muscle regions. For each muscle and location, peak muscle activity occurred at similar hip and knee joint angles.

Atypical presentation of COVID-19 in older patients is associated with frailty but not with adverse outcomes.

PURPOSE: Older patients with COVID-19 can present with atypical complaints, such as falls or delirium. In other diseases, such an atypical presentation is associated with worse clinical outcomes. However, it is not known whether this extends to COVID-19. We aimed to study the association between atypical presentation of COVID-19, frailty and adverse outcomes, as well as the incidence of atypical presentation. METHODS: We conducted a retrospective observational multi-center cohort study in eight hospitals in the Netherlands. We included patients aged ≥ 70 years hospitalized with COVID-19 between February 2020 until May 2020. Atypical presentation of COVID-19 was defined as presentation without fever, cough and/or dyspnea. We collected data concerning symptoms on admission, demographics and frailty parameters [e.g., Charlson Comorbidity Index (CCI) and Clinical Frailty Scale (CFS)]. Outcome data included Intensive Care Unit (ICU) admission, discharge destination and 30-day mortality. RESULTS: We included 780 patients, 9.5% (n = 74) of those patients had an atypical presentation. Patients with an atypical presentation were older (80 years, IQR 76-86 years; versus 79 years, IQR 74-84, p = 0.044) and were more often classified as severely frail (CFS 6-9) compared to patients with a typical presentation (47.6% vs 28.7%, p = 0.004). Overall, there was no significant difference in 30-day mortality between the two groups in univariate analysis (32.4% vs 41.5%; p = 0.173) or in multivariate analysis [OR 0.59 (95% CI 0.34-1.0); p = 0.058]. CONCLUSIONS: In this study, patients with an atypical presentation of COVID-19 were more frail compared to patients with a typical presentation. Contrary to our expectations, an atypical presentation was not associated with worse outcomes.

Activity Distribution Among the Hamstring Muscles During the Nordic Hamstring Exercise: A Multichannel Surface Electromyography Study.

This study assessed activity distribution among the hamstring muscles during the Nordic hamstring exercise (NHE). The objective was to compare muscle activity between and within muscles during the NHE to add insights in its underlying protective mechanism. Through multichannel electromyography, we measured muscle activity in male basketball players during the NHE. Electromyography was assessed at 15 locations: 5 for biceps femoris long head, 4 for semitendinosus, and 6 for semimembranosus. For each percent of the eccentric phase of the NHE, muscle activity was calculated for each electrode location within each hamstring muscle individually. To quantify whole muscle head activity, means and variances across electrodes within each muscle were calculated. Thirty-five noninjured participants were included (mean age, 18 [2] y; mass, 87 [12] kg; height, 192 [9] cm). Heterogeneous muscle activity was found between 38% and 62% and over the whole eccentric contraction phase within the semitendinosus and the semimembranosus, respectively. Muscle activity of the semitendinosus was significantly higher than that of the biceps femoris long head. During the NHE, the relative contribution of the semitendinosus is the highest among hamstring muscles. Its strong contribution may compensate for the biceps femoris long head, the most commonly injured hamstring muscle head.

Three-Dimensional Interactive Graphical Model of the Hindlimb Muscles of the Rat.

Many questions in human movement sciences are addressed by exploiting the advantages of animal models. However, a 3D graphical model of the musculoskeletal system of the frequently used rat model that includes a sufficient level of detail does not exist. Therefore, the aim of the present work was to develop an freely accessible 3D graphical model of the rat hindlimb. Using the anatomical data of the Wistar rat (Mus norvegicus albinus) published by Greene [1935], a 3D representation of 34 muscles of the hindlimb was drawn. Two models were created, one using muscle-like appearances and one using different colors. Each muscle can be viewed separately or within the context of its synergistic and antagonistic muscles. This model can serve to train new students before starting their experiments but also for producing illustrations of experimental conditions or results. Further development of the model will be needed to equip it with the same advanced functionalities of some of the human anatomy atlases.

Detection of intermuscular coordination based on the causality of empirical mode decomposition.

Considering the stochastic nature of electromyographic (EMG) signals, nonlinear methods may be a more accurate approach to study intermuscular coordination than the linear approach. The aims of this study were to assess the coordination between two ankle plantar flexors using EMG by applying the causal decomposition approach and assessing whether the intermuscular coordination is affected by the slope of the treadmill. The medial gastrocnemius (MG) and soleus muscles (SOL) were analyzed during the treadmill walking at inclinations of 0°, 5°, and 10°. The coordination was evaluated using ensemble empirical mode decomposition, and the causal interaction was encoded by the instantaneous phase dependence of time series bi-directional causality. To estimate the mutual predictability between MG and SOL, the cross-approximate entropy (XApEn) was assessed. The maximal causal interaction was observed between 40 and 75 Hz independent of inclination. XApEn showed a significant decrease between 0° and 5° (p = 0.028), between 5° and 10° (p = 0.038), and between 0° and 10° (p = 0.014), indicating an increase in coordination. Thus, causal decomposition is an appropriate methodology to study intermuscular coordination. These results indicate that the variation of loading through the change in treadmill inclination increases the interaction of the shared input between MG and SOL, suggesting increased intermuscular coordination.

Improved Postoperative Outcomes after Prehabilitation for Colorectal Cancer Surgery in Older Patients: An Emulated Target Trial.

BACKGROUND: The aim of this study was to assess the effect of a multimodal prehabilitation program on perioperative outcomes in colorectal cancer patients with a higher postoperative complication risk, using an emulated target trial (ETT) design. PATIENTS AND METHODS: An ETT design including overlap weighting based on propensity score was performed. The study consisted of all patients with newly diagnosed colorectal cancer (2016-2021), in a large nonacademic training hospital, who were candidate to elective colorectal cancer surgery and had a higher risk for postoperative complications defined by: age ≥ 65 years and or American Society of Anesthesiologists score III/IV. Intention-to-treat (ITT) and per-protocol analyses were performed to evaluate the effect of prehabilitation compared with usual care on perioperative complications and length of stay (LOS). RESULTS: Two hundred fifty-one patients were included: 128 in the usual care group and 123 patients in the prehabilitation group. In the ITT analysis, the number needed to treat to reduce one or more complications in one person was 4.2 (95% CI 2.6-10). Compared with patients in the usual care group, patients undergoing prehabilitation had a 55% lower comprehensive complication score (95% CI -71 to -32%). There was a 33% reduction (95% CI -44 to -18%) in LOS from 7 to 5 days. CONCLUSIONS: This study showed a clinically relevant reduction of complications and LOS after multimodal prehabilitation in patients undergoing colorectal cancer surgery with a higher postoperative complication risk. The study methodology used may serve as an example for further larger multicenter comparative effectiveness research on prehabilitation.

[Prehabilitation before surgery: in all cases?] / Prehabilitatie voorafgaand aan iedere operatie?

While the concept of prehabilitation sounds logical and study results are promising, so far there is no unequivocal answer to the question whether prehabilitation is (cost-)effective. Therefore, positioning prehabilitation as standard care is not yet on the agenda. To achieve this multicenter research should be stimulated through national coordination and research funding in order to clarify the (cost-)effectiveness of prehabilitation.

Trajectories and prognostic factors for recovery after hip fracture: a longitudinal cohort study.

PURPOSE: The aim of this study was to determine recovery trajectories and prognostic factors for poor recovery in frail and non-frail patients after hip fracture. METHODS: Patients with a hip fracture aged 65 years and older admitted to a hospital in the Netherlands from August 2015 to November 2016 were asked to complete questionnaires at one week and one, three, six, 12, and 24 months after injury. The questionnaires included the ICEpop CAPability measure for older people, Health Utility Index, and the Hospital Anxiety Depression Scale. Latent class trajectory analysis was used to determine trajectories of recovery. Patient and injury characteristics for favourable and unfavourable outcome were compared with logistic regression. RESULTS: In total, 696 patients were included of which 367 (53%) patients were frail. Overall, recovery trajectories in frail patients were worse compared to trajectories in non-frail patients. In frail patients, poor recovery was significantly associated with dementia. Lower age was a prognostic factor for good recovery. Immobility, loneliness and weight loss were prognostic for respectively poor capability and symptoms of anxiety and depression. In non-frail patients, recovery after hip fracture was associated with loneliness and the type of hip fracture. CONCLUSION: Although frailty is associated with poor recovery in older patients with hip fracture, a large proportion of frail patients show good recovery. Loneliness determines poor recovery with anxiety and depressive symptoms. TRAIL REGISTRATION: ClinicalTrials.gov identifier: NCT02508675 (July 27, 2015).

Chronic non-specific low back pain and ankle proprioceptive acuity in community-dwelling older adults.

BACKGROUND: For people above 65 years old, low-back pain (LBP) is associated with balance problems and falls. Down-weighting of proprioception due to ageing and LBP may cause such balance problems. While lumbar proprioceptive deficits have been shown in LBP and indications for more generalized deficits have been found, ankle proprioception, which is crucial for balance control, has not been studied in people with LBP. RESEARCH QUESTION: Is there any difference in ankle proprioceptive acuity between community-dwelling older adults with and without LBP? We hypothesized that ankle proprioception was impaired in community-dwelling older adults with LBP compared to those without LBP. METHODS: Thirty participants over 65 years old volunteered. Fifteen had LBP (M/F = 2/13, age = 72.0 (4.6) years), fifteen were healthy controls without back pain (control group) (M/F = 2/13, age = 72.1 (4.8) years). Ankle proprioception was measured in normal weight-bearing conditions, using the Active Movement Extent Discrimination Apparatus (AMEDA). Accuracy on the ankle proprioceptive test was expressed as absolute error (AE), constant error (CE) and variable error (VE). RESULTS: AE was significantly larger (P = 0.029, 95 % CI = [0.00, 0.90]) in the LBP group, CE was also significantly larger (P = 0.046, 95 % CI = [-0.91, -0.01]), indicating an underestimation of ankle inversion in participants with LBP compared to controls. VE was not different between the two groups (P = 0.520, 95 % CI = [-0.20, 0.59]). No significant correlation was found between pain intensity and AE, CE or VE (P > 0.05). CONCLUSION: Ankle proprioception decreased in older people with LBP compared to healthy peers, suggesting impaired central proprioceptive processing. Older people with LBP underestimate the extent of ankle inversion, which may increase fall risk. Thus, evaluation and training of ankle proprioception may be useful in older people with LBP.

Implementation of prehabilitation in colorectal cancer surgery: qualitative research on how to strengthen facilitators and overcome barriers.

PURPOSE: Prehabilitation is increasingly offered to patients with colorectal cancer (CRC) undergoing surgery as it could prevent complications and facilitate recovery. However, implementation of such a complex multidisciplinary intervention is challenging. This study aims to explore perspectives of professionals involved in prehabilitation to gain understanding of barriers or facilitators to its implementation and to identify strategies to successful operationalization of prehabilitation. METHODS: In this qualitative study, semi-structured interviews were performed with healthcare professionals involved in prehabilitation for patients with CRC. Prehabilitation was defined as a preoperative program with the aim of improving physical fitness and nutritional status. Parallel with data collection, open coding was applied to the transcribed interviews. The Ottawa Model of Research Use (OMRU) framework, a comprehensive interdisciplinary model guide to promote implementation of research findings into healthcare practice, was used to categorize obtained codes and structure the barriers and facilitators into relevant themes for change. RESULTS: Thirteen interviews were conducted. Important barriers were the conflicting scientific evidence on (cost-)effectiveness of prehabilitation, the current inability to offer a personalized prehabilitation program, the complex logistic organization of the program, and the unawareness of (the importance of) a prehabilitation program among healthcare professionals and patients. Relevant facilitators were availability of program coordinators, availability of physician leadership, and involving skeptical colleagues in the implementation process from the start. CONCLUSIONS: Important barriers to prehabilitation implementation are mainly related to the intervention being complex, relatively unknown and only evaluated in a research setting. Therefore, physicians' leadership is needed to transform care towards more integration of personalized prehabilitation programs. IMPLICATIONS FOR CANCER SURVIVORS: By strengthening prehabilitation programs and evidence of their efficacy using these recommendations, it should be possible to enhance both the pre- and postoperative quality of life for colorectal cancer patients during survivorship.