Different descending pathways mediate early and late portions of lower limb responses to transcranial magnetic stimulation.

Although recent studies in nonhuman primates have provided evidence that transcranial magnetic stimulation (TMS) activates cells within the reticular formation, it remains unclear whether descending brain stem projections contribute to the generation of TMS-induced motor evoked potentials (MEPs) in skeletal muscles. We compared MEPs in muscles with extensive direct corticomotoneuronal input (first dorsal interosseous) versus a prominent role in postural control (gastrocnemius) to determine whether the amplitudes of early and late MEPs were differentially modulated by cortical suppression. Suprathreshold TMS was applied with and without a preceding suprathreshold TMS pulse at two interstimulus intervals (50 and 80 ms). H reflexes in target muscles were also tested with and without TMS conditioning. Early and late gastrocnemius MEPs were differentially modulated by cortical inhibition, the amplitude of the early MEP being significantly reduced by cortical suppression and the late MEP facilitated. The amplitude of H reflexes in the gastrocnemius was reduced within the cortical silent period. Early MEPs in the first dorsal interosseous were also reduced during the silent period, but late MEPs were unaffected. Independent modulation of early and late MEPs in the gastrocnemius muscle supports the idea that the MEP is generated by multiple descending pathways. Suppression of the early MEP is consistent with transmission along the fast-conducting corticospinal tract, whereas facilitation of the late MEP suggests transmission along a corticofugal, potentially cortico-reticulospinal, pathway. Accordingly, differences in late MEP modulation between the first dorsal interosseous and gastrocnemius reflect an increased role of corticofugal pathways in the control of postural muscles.NEW & NOTEWORTHY Early and late portions of the response to transcranial magnetic stimulation (TMS) in a lower limb postural muscle are modulated independently by cortical suppression, late motor evoked potentials (MEPs) being facilitated during cortical inhibition. These results suggest a cortico-brain stem transmission pathway for late portions of the TMS-induced MEP.

Fatty infiltration of gastrocnemius-soleus muscle complex: Considerations for myosteatosis rehabilitation.

Although previous studies have reported fatty infiltration of the gastrocnemius-soleus complex, little is known about the volumetric distribution and patterns of fatty infiltration. The purpose of this anatomical study was to document and quantify the frequency, distribution, and pattern of fatty infiltration of the gastrocnemius-soleus complex. One hundred formalin-embalmed specimens (mean age 78.1 ± 12.3 years; 48F/52M) were serially dissected to document the frequency, distribution, and pattern of fatty infiltration in the medial and lateral heads of gastrocnemius and soleus muscles. Fatty infiltration was found in 23% of specimens, 13 unilaterally (8F/5M) and 10 (5M/5F) bilaterally. The fatty infiltration process was observed to begin medially from the medial aspect of the medial head of gastrocnemius and medial margin of soleus and then progressed laterally throughout the medial head of gastrocnemius and the marginal, anterior, and posterior soleus. The lateral head of gastrocnemius remained primarily muscular in all specimens. Microscopically, the pattern of infiltration was demonstrated as intramuscular with intact aponeuroses, and septa. The remaining endo-, peri-, and epimysium preserved the overall contour of the gastrocnemius-soleus complex, even in cases of significant fatty replacement. Since the external contour of the calf is preserved, the presence of fatty infiltration may be underdiagnosed in the clinic without imaging. Myosteatosis is associated with gait and balance challenges in the elderly, which can impact quality of life and result in increased risk of falling. The findings of the study have implications in the rehabilitation management of elderly patients with sarcopenia and myosteatosis.

The effects of residual dipolar coupling on carnosine in proton muscle spectra.

Carnosine, an MR-visible dipeptide in human muscle, is well characterized by two peaks at ~8 and ~7 ppm from C2 and C4 imidazole protons. Like creatine and other metabolites, carnosine is subject to residual dipolar coupling in the anisotropic environment of muscle fibers, but the effects have not been studied extensively. Single-voxel TE 30-32 PRESS spectra from three different 3T studies were acquired from gastrocnemius medialis and soleus muscles in the human lower leg. In these studies, carnosine T2 values were measured, and spectra were obtained at three different foot angles. LCModel was used to fit the carnosine peaks with a basis set that was generated using shaped RF pulses and included a range of dipolar couplings affecting the C4 peak. A seven-parameter analytic expression was used to fit the CH2 doublets of creatine. It incorporated an optimized "effective TE" value to model the effect of shaped RF pulses. The fits confirm that the triplet C4 peak of carnosine is dipolar coupled to a pair of CH2 protons, with no need to include a contribution from a separate pool of freely rotating uncoupled carnosine. Moreover, the couplings experienced by carnosine C4 protons and creatine CH2 protons are strongly correlated (R2 = 0.88, P<0.001), exhibiting a similar 3cos2 θ - 1 dependence on the angle θ between fiber orientation and B0. T2 values for the singlet C2 peak of gastrocnemius carnosine are inversely proportional to the C4 dipolar coupling strength (R2 = 0.97, P < 0.001), which in turn is a function of foot orientation. This dependence indicates that careful positioning of the foot while acquiring lower leg muscle spectra is important to obtain reproducible carnosine concentrations. As proton magnetic resonance spectroscopy of carnosine is currently used to non-invasively estimate the muscle fiber typology, these results have important implications in sport science.

Ameliorative effect of nano-pregabalin in gastrocnemius muscle of gamma irradiated rats with an experimental model of fibromyalgia: Crosstalk of Sirt3, IL-1ß and PARP1 pathways.

BACKGROUND: Fibromyalgia (FM) is a complex syndrome with somatic symptoms connected to the operational state of muscles. Although radiotherapy is a cornerstone in cancer treatment, it is implicated in the aggravation of FM. Lately, formulation of medicines in nano-forms become of great prominence due to their prospective applications in medicine. So, this study aimed to assess possible therapeutic benefits of formulating pregabalin in a nono-form (N-PG) for managing FM during exposure to gamma radiation. METHODS: Gamma rays administered in fractionated doses (2 Gy/day) to male rats after one hour of s.c. injection of reserpine (1 mL/kg per day) to induce FM, then treated with single daily dose of (30 mg/kg, p.o.) PG or N-PG for ten successive days. Rats were subjected to behavioral tests, then sacrificed to obtain serum and gastrocnemius muscles. RESULTS: N-PG significantly antagonized reserpine-induced FM as proved by; the immobility and performance times in forced swim and rotarod performance tests, respectively were restored near to the normal time, serum IL-8 and MCP-1 chemokines were nearby the normal levels, mitigated oxidative stress through increasing total thiol, Sirt3, CAT enzyme and decreasing COX-1, inhibition of inflammation via IL-1ß and MIF significant reduction, it possessed anti-apoptotic effect verified by decreasing PARP-1 and increasing Bcl-XL, gastrocnemius muscles had minimal fibrosis levels as seen after Masson trichrome staining. Histopathological results were coincidence with biochemical inspection. CONCLUSION: This study identifies N-PG as a novel drug that could be of a value in the management of FM particularly in cancer patients undergoing radiotherapy.

The interaction of in vivo muscle operating lengths and passive stiffness in rat hindlimbs.

The operating length of a muscle is a key determinant of its ability to produce force in vivo. Muscles that operate near the peak of their force-length relationship will generate higher forces whereas muscle operating at relatively short length may be safe from sudden lengthening perturbations and subsequent damage. At longer lengths, passive mechanical properties have the potential to contribute to force or constrain operating length with stiffer muscle-tendon units theoretically being restricted to shorter lengths. Connective tissues typically increase in density during aging, thus increasing passive muscle stiffness and potentially limiting the operating lengths of muscle during locomotion. Here, we compare in vivo and in situ muscle strain from the medial gastrocnemius in young (7 months old) and aged (30-32 months old) rats presumed to have varying passive tissue stiffness to test the hypothesis that stiffer muscles operate at shorter lengths relative to their force-length relationship. We measured in vivo muscle operating length during voluntary locomotion on inclines and flat trackways and characterized the muscle force-length relationship of the medial gastrocnemius using fluoromicrometry. Although no age-related results were evident, rats of both age groups demonstrated a clear relationship between passive stiffness and in vivo operating length, such that shorter operating lengths were significantly correlated with greater passive stiffness. Our results suggest that increased passive stiffness may restrict muscles to operating lengths shorter than optimal lengths, potentially limiting force capacity during locomotion.

iMS-Bmal1-/- mice show evident signs of sarcopenia that are counteracted by exercise and melatonin therapies.

Sarcopenia is an age-related disease characterized by a reduction in muscle mass, strength, and function and, therefore, a deterioration in skeletal muscle health and frailty. Although the cause of sarcopenia is still unknown and, thus, there is no treatment, increasing evidence suggests that chronodisruption, particularly alterations in Bmal1 clock gene, can lead to those deficits culminating in sarcopenia. To gain insight into the cause and mechanism of sarcopenia and the protective effect of a therapeutic intervention with exercise and/or melatonin, the gastrocnemius muscles of male and female skeletal muscle-specific and inducible Bmal1 knockout mice (iMS-Bmal1-/- ) were examined by phenotypic tests and light and electron microscopy. Our results revealed a disruption of the normal activity/rest rhythm, a drop in skeletal muscle function and mass, and increased frailty in male and female iMS-Bmal1-/- animals compared to controls. A reduction in muscle fiber size and increased collagenous tissue were also detected, accompanied by reduced mitochondrial oxidative capacity and a compensatory shift towards a more oxidative fiber type. Electron microscopy further supports mitochondrial impairment in mutant mice. Melatonin and exercise ameliorated the damage caused by loss of Bmal1 in mutant mice, except for mitochondrial damage, which was worsened by the latter. Thus, iMS-Bmal1-/- mice let us to identify Bmal1 deficiency as the responsible for the appearance of sarcopenia in the gastrocnemius muscle. Moreover, the results support the exercise and melatonin as therapeutic tools to counteract sarcopenia, by a mechanism that does not require the presence of Bmal1.

Resveratrol relieves HFD-induced insulin resistance in skeletal muscle tissue through antioxidant capacity enhancement and the Nrf2-Keap1 signaling pathway.

BACKGROUND: Resveratrol has received much attention due to its beneficial effects including antioxidant activity. The purpose of this study was to investigate the therapeutic effects of resveratrol treatment on oxidative stress and insulin resistance in the skeletal muscle of high-fat diet (HFD)-fed animals. METHODS AND RESULTS: A total of 30 six-week-old C57BL/6J mice were randomly allocated to three groups (10 animals in each group): The control group in which mice were fed a normal chow diet (NCD); the HFD group in which mice were fed an HFD for 26 weeks; and the HFD-resveratrol group in which HFD was replaced by a resveratrol supplemented-HFD (400 mg/kg diet) after 10 weeks of HFD feeding. At the end of this period, gastrocnemius muscle samples were examined to determine insulin resistance and the oxidative status in the presence of HFD and resveratrol. Resveratrol supplementation in HFD-fed mice reduced body and adipose tissue weight, improved insulin sensitivity, and decreased oxidative stress as indicated by lower malonaldehyde (MDA) levels and higher total antioxidant capacity. The supplement also increased the expression and activity of antioxidative enzymes in gastrocnemius muscle and modulated Nrf2 and Keap1 expression levels. CONCLUSIONS: These results suggest that resveratrol is effective in improving the antioxidant defense system of the skeletal muscle in HFD-fed mice, indicating its therapeutic potential to combat diseases associated with insulin resistance and oxidative stress.

Azilsartan prevents muscle loss and fast- to slow-twitch muscle fiber shift in natural ageing sarcopenic rats.

Sarcopenia is a musculoskeletal disease that reduces muscle mass and strength in older individuals. The study investigates the effects of azilsartan (AZL) on skeletal muscle loss in natural sarcopenic rats. Male Sprague-Dawley rats aged 4-6 months and 18-21 months were selected as young-matched control and natural-aged (sarcopenic) rats, respectively. Rats were allocated into young and old control (YC and OC) and young and old AZL treatment (YT and OT) groups, which received vehicles and AZL (8 mg/kg, orally) for 6 weeks. Rats were then sacrificed after muscle function analysis. Serum and gastrocnemius (GN) muscles were isolated for further endpoints. AZL significantly improved muscle grip strength and antioxidant levels in sarcopenic rats. AZL also restored the levels of insulin, testosterone, and muscle biomarkers such as myostatin and creatinine kinase in sarcopenic rats. Furthermore, AZL treatment improved the cellular and ultrastructure of GN muscle and prevented the shift of type II (glycolytic) myofibers to type I (oxidative) myofibers. The results showed that AZL intervention restored protein synthesis in natural sarcopenic rats by increasing p-Akt-1 and decreasing muscle RING-finger protein-1 and tumor necrosis factor alpha immunoexpressions. In conclusion, the present findings showed that AZL could be an effective intervention in treating age-related muscle impairments.

Effects of gait retraining using minimalist shoes on the medial gastrocnemius muscle-tendon unit behavior and dynamics during running.

The effects of a 12-week gait retraining program on the adaptation of the medial gastrocnemius (MG) and muscle-tendon unit (MTU) were investigated. 26 runners with a rearfoot strike pattern (RFS) were randomly assigned to one of two groups: gait retraining (GR) or control group (CON). MG ultrasound images, marker positions, and ground reaction forces (GRF) were collected twice during 9 km/h of treadmill running before and after the intervention. Ankle kinetics and the MG and MTU behavior and dynamics were quantified. Runners in the GR performed gradual 12-week gait retraining transitioning to a forefoot strike pattern. After 12-week, (1) ten participants in each group completed the training; eight participants in GR transitioned to non-RFS with reduced foot strike angles; (2) MG fascicle contraction length and velocity significantly decreased after the intervention for both groups, whereas MG forces increased after intervention for both groups; (3) significant increases in MTU stretching length for GR and peak MTU recoiling velocity for both groups were observed after the intervention, respectively; (4) no significant difference was found for all parameters of the series elastic element. Gait retraining might potentially influence the MG to operate at lower fascicle contraction lengths and velocities and produce greater peak forces. The gait retraining had no effect on SEE behavior and dynamics but did impact MTU, suggesting that the training was insufficient to induce mechanical loading changes on SEE behavior and dynamics.

Association of the rate of torque development and joint angle with passive muscle stiffness.

PURPOSE: The purpose of this study was to statistically compare the rate of torque development normalized by maximal strength (relative RTD) across ankle angles. Additionally, this study was aimed at exploring the correlation coefficients between relative RTD and passive stiffness of the medial gastrocnemius (MG) at different ankle angles. METHODS: Twenty-two healthy men and women (age: 31 ± 4 years) performed randomly-ordered explosive isometric plantar flexions at plantarflexed (15°), neutral (0°), and dorsiflexed (- 15°) angles; relative RTD comprised the slope of the time-torque curve normalized to maximal torque. The shear wave velocity (SWV; index of stiffness) of the MG at rest was measured at each angle using ultrasound shear wave elastography. RESULTS: The relative RTD was greater at 15° than - 15° for 0-50, 0-100, and 0-150 ms time-windows and at 15° than 0° for the 0-150 ms time-window (P < 0.05), although peak torque was lower at 15° than 0° and - 15° (P < 0.05). The relative RTD for the 0-50 ms time-window correlated with SWV at - 15° (rs = 0.475, P < 0.05), but not at 15º and 0º. Furthermore, the correlation coefficient of RTD for the 0-100 ms time-window with SWV was significantly greater at - 15° (rs = 0.420) than 0 ° (rs = - 0.109). CONCLUSIONS: A greater relative RTD occurs at plantarflexed angles (i.e., the ascending limb of the force-length curve) in the triceps surae, and relative RTD is strongly related to passive MG stiffness at dorsiflexed angles (i.e., longer muscle lengths).

Transcriptome sequencing and bioinformatics analysis of gastrocnemius muscle in type 2 diabetes mellitus rats.

OBJECTIVE: Type 2 diabetes mellitus (T2DM) is one of the high risk factors for sarcopenia. However, the pathogenesis of diabetic sarcopenia has not been fully elucidated. This study obtained transcriptome profiles of gastrocnemius muscle in normal and T2DM rats based on high-throughput sequencing technology, which may provide new ideas for exploring the pathogenesis of diabetic sarcopenia. METHODS: Twelve adult male Sprague-Dawley rats were randomly divided into Control group and T2DM group, and gastrocnemius muscle tissue was retained for transcriptome sequencing and real-time quantitative polymerase chain reaction (qRT-PCR) 6 months later. Screening differentially expressed genes (DEGs), Cluster analysis, gene ontology (GO) functional annotation analysis and Kyoto Encyclopedia of Genes and Gnomes (KEGG) functional annotation and enrichment analysis were performed for DEGs. Six DEGs related to apoptosis were selected for qTR-PCR verification. RESULTS: Transcriptomic analysis showed that there were 1016 DEGs between the gastrocnemius muscle of T2DM and normal rats, among which 665 DEGs were up-regulated and 351 DEGs were down-regulated. GO analysis showed that the extracellular matrix organization was the most enriched in biological processes, with 26 DEGs. The extracellular matrix with 35 DEGs was the most abundant cellular component. The extracellular matrix structural constituent, with 26 DEGs, was the most enriched in molecular functions. The highest number of DEGs enriched in biological processes, cellular components and molecular functions were positive regulation of transcription by RNA polymerase II, nucleus and metal ion binding, respectively. There were 78, 230 and 89 DEGs respectively. KEGG pathway enrichment analysis showed that ECM-receptor interaction, PI3K-Akt signaling pathway and TGF-ß signaling pathway(p < 0.001) had higher enrichment degree and number of DEGs. qRT-PCR results showed that the fold change of Map3k14, Atf4, Pik3r1, Il3ra, Gadd45b and Bid were 1.95, 3.25, 2.97, 2.38, 0.43 and 3.6, respectively. The fold change of transcriptome sequencing were 3.45, 2.21, 2.59, 5.39, 0.49 and 2.78, respectively. The transcriptional trends obtained by qRT-PCR were consistent with those obtained by transcriptome sequencing. CONCLUSIONS: Transcriptomic analysis was used to obtain the "gene profiles" of gastrocnemius muscle of T2DM and normal rats. qRT-PCR verification showed that the genes related to apoptosis were differentially expressed. These DEGs and enrichment pathways may provide new ideas for exploring the pathogenesis of diabetic sarcopenia.

Reliability of muscle stiffness measures in popliteus, medial and lateral gastrocnemius muscles by ultrasound shear wave elastography in participants with knee osteoarthritis accompanied by myofascial trigger points.

BACKGROUND: The objective of this investigation is to evaluate the consistency of intra-rater and inter-rater assessments utilizing ultrasound elastography to examine the muscle stiffness of the popliteus and gastrocnemius (medial and lateral heads) in patients with knee osteoarthritis accompanied by myofascial trigger points. METHODS: Thirty individuals with knee osteoarthritis accompanied by myofascial trigger points were assessed. Two examiners independently measured the muscle stiffness levels of the popliteus and gastrocnemius (medial and lateral heads) three times using ultrasound elastography in the first session. The second session was conducted one week later. RESULTS: In the initial test session, the mean shear modulus values for the popliteus and gastrocnemius (medial and lateral heads) muscles were measured as follows for tester 1 (12.75, 13.72, 14.13 kPa) and tester 2 (11.66, 12.81, 13.17 kPa). During the retest session, the previously measured variables by tester 1 and tester 2 yielded the following values: (12.61, 13.43, 14.26 kPa) and (11.62, 12.87, 13.30 kPa) respectively." Good to excellent intra-rater reliability (ICC = 0.912-0.986) and inter-rater reliability (ICC = 0.766-0.956) were reported for the shear moduli of the popliteus, medial and lateral gastrocnemius muscles. CONCLUSIONS: The assessment of muscle stiffness in the popliteus and gastrocnemius (medial and lateral heads) using ultrasound elastography is a reliable method in patients with knee osteoarthritis accompanied by myofascial trigger points.

Ex vivo adult stem cell characterization from multiple muscles in ambulatory children with cerebral palsy during early development of contractures.

Cerebral palsy (CP) is one of the most common conditions leading to lifelong childhood physical disability. Literature reported previously altered muscle properties such as lower number of satellite cells (SCs), with altered fusion capacity. However, these observations highly vary among studies, possibly due to heterogeneity in patient population, lack of appropriate control data, methodology and different assessed muscle. In this study we aimed to strengthen previous observations and to understand the heterogeneity of CP muscle pathology. Myogenic differentiation of SCs from the Medial Gastrocnemius (MG) muscle of patients with CP (n = 16, 3-9 years old) showed higher fusion capacity compared to age-matched typically developing children (TD, n = 13). Furthermore, we uniquely assessed cells of two different lower limb muscles and showed a decreased myogenic potency in cells from the Semitendinosus (ST) compared to the MG (TD: n = 3, CP: n = 6). Longitudinal assessments, one year after the first botulinum toxin treatment, showed slightly reduced SC representations and lower fusion capacity (n = 4). Finally, we proved the robustness of our data, by assessing in parallel the myogenic capacity of two samples from the same TD muscle. In conclusion, these data confirmed previous findings of increased SC fusion capacity from MG muscle of young patients with CP compared to age-matched TD. Further elaboration is reported on potential factors contributing to heterogeneity, such as assessed muscle, CP progression and reliability of primary outcome parameters.

Both acute glyphosate and the aminomethylphosphonic acid intoxication decreased the acetylcholinesterase activity in rat hippocampus, prefrontal cortex and gastrocnemius muscle.

It has been reported that glyphosate, one of the most common herbicides used in agriculture, impairs locomotion and cognition. Glyphosate has a variable half-life in soil up to biotic and/or abiotic factors transform the molecule in metabolites such as the aminomethylphosphonic acid (AMPA) that has a longer half-life. In this study, female Sprague Dawley rats were acutely exposed to different doses of glyphosate or AMPA (i.e. 10, 56 or 100 mg/kg) and, subsequently, the acetylcholinesterase (AChE) activity was measured in the hippocampus, prefrontal cortex (PFC) and the gastrocnemius muscle. Both glyphosate and AMPA produced a similar decrease in the AChE activity in all the tissues tested. These results suggest that interference with normal cholinergic neurotransmission may be one of the mechanisms involved in glyphosate-induced motor alterations in rats. Moreover, our results highlight the biological importance of AMPA as a molecule with anticholinesterase action in brain and skeletal muscle. To our knowledge, this is the first report showing in vivo that AMPA, the major metabolite of glyphosate, behaves as an organophosphate.

Antagonist Activation Measurement in Triceps Surae Using High-Density and Bipolar Surface EMG in Chronic Hemiparesis.

After a stroke, antagonist muscle activation during agonist command impedes movement. This study compared measurements of antagonist muscle activation using surface bipolar EMG in the gastrocnemius medialis (GM) and high-density (HD) EMG in the GM and soleus (SO) during isometric submaximal and maximal dorsiflexion efforts, with knee flexed and extended, in 12 subjects with chronic hemiparesis. The coefficients of antagonist activation (CAN) of GM and SO were calculated according to the ratio of the RMS amplitude during dorsiflexion effort to the maximal agonist effort for the same muscle. Bipolar CAN (BipCAN) was compared to CAN from channel-specific (CsCAN) and overall (OvCAN) normalizations of HD-EMG. The location of the CAN centroid was explored in GM, and CAN was compared between the medial and lateral portions of SO. Between-EMG system differences in GM were observed in maximal efforts only, between BipCAN and CsCAN with lower values in BipCAN (p < 0.001), and between BipCAN and OvCAN with lower values in OvCAN (p < 0.05). The CAN centroid is located mid-height and medially in GM, while the CAN was similar in medial and lateral SO. In chronic hemiparesis, the estimates of GM hyperactivity differ between bipolar and HD-EMGs, with channel-specific and overall normalizations yielding, respectively, higher and lower CAN values than bipolar EMG. HD-EMG would be the way to develop personalized rehabilitation programs based on individual antagonist activations.

Coincidence between the distribution of myofascial trigger points and the presence of blood vessels in the gastrocnemius muscle: Implications for invasive procedures.

PURPOSE: The gastrocnemius venous system presents different anatomical variants. There have been described four locations of myofascial trigger points (MTrPs) in this muscle. However, no studies have analyzed the coincidence between vessels and MTrPs present in the gastrocnemius. Therefore, the main objective was to study the anatomical variability of the venous system by ultrasound and its coincidence with the location of the MTrPs. METHODS: A total of 100 lower limbs were studied. The gastrocnemius vessels were analyzed one by one by sector (medial, central, and lateral), quantifying the number of vessels, their distribution, and the coincidence with MTrPs. RESULTS: All muscle heads showed at least one vessel per section. A large variability was observed, from one to eight vessels per muscle head, with the most frequent number being three in the gastrocnemius medialis and two in the gastrocnemius lateralis. In all cases, the location of the vessels coincided with the MTrPs. CONCLUSIONS: The proximal gastrocnemius venous pattern is very variable between subjects in number of vessels and distribution, which has made it impossible to define a "safe" approach window for invasive procedures without ultrasound guidance. The coincidence between the clinical location of MTrPs of the gastrocnemius and the presence of vessels is total.

Do the fasciae of the soleus have a role in plantar fasciitis?

Plantar fasciitis is a chronic, self-limiting, and painful disabling condition affecting the inferomedial aspect of the heel, usually extending toward the metatarsophalangeal joints. There is compelling evidence for a strong correlation between Achilles tendon (AT) loading and plantar aponeurosis (PA) tension. In line with this, tightness of the AT is found in almost 80% of patients affected by plantar fasciitis. A positive correlation has also been reported between gastrocnemius-soleus tightness and heel pain severity in this condition. Despite its high prevalence, the exact etiology and pathological mechanisms underlying plantar heel pain remain unclear. Therefore, the aim of the present paper is to discuss the anatomical and biomechanical substrates of plantar fasciitis with special emphasis on the emerging, though largely neglected, fascial system. In particular, the relationship between the fascia, triceps surae muscle, AT, and PA will be analyzed. We then proceed to discuss how structural and biomechanical alterations of the muscle-tendon-fascia complex due to muscle overuse or injury can create the conditions for the onset of PA pathology. A deeper knowledge of the possible molecular mechanisms underpinning changes in the mechanical properties of the fascial system in response to altered loading and/or muscle contraction could help healthcare professionals and clinicians refine nonoperative treatment strategies and rehabilitation protocols for plantar fasciitis.

Mitigating the Functional Deficit after Neurotoxic Motoneuronal Loss by an Inhibitor of Mitochondrial Fission.

Amyotrophic lateral sclerosis (ALS) is an extremely complex neurodegenerative disease involving different cell types, but motoneuronal loss represents its main pathological feature. Moreover, compensatory plastic changes taking place in parallel to neurodegeneration are likely to affect the timing of ALS onset and progression and, interestingly, they might represent a promising target for disease-modifying treatments. Therefore, a simplified animal model mimicking motoneuronal loss without the other pathological aspects of ALS has been established by means of intramuscular injection of cholera toxin-B saporin (CTB-Sap), which is a targeted neurotoxin able to kill motoneurons by retrograde suicide transport. Previous studies employing the mouse CTB-Sap model have proven that spontaneous motor recovery is possible after a subtotal removal of a spinal motoneuronal pool. Although these kinds of plastic changes are not enough to counteract the functional effects of the progressive motoneuron degeneration, it would nevertheless represent a promising target for treatments aiming to postpone ALS onset and/or delay disease progression. Herein, the mouse CTB-Sap model has been used to test the efficacy of mitochondrial division inhibitor 1 (Mdivi-1) as a tool to counteract the CTB-Sap toxicity and/or to promote neuroplasticity. The homeostasis of mitochondrial fission/fusion dynamics is indeed important for cell integrity, and it could be affected during neurodegeneration. Lesioned mice were treated with Mdivi-1 and then examined by a series of behavioral test and histological analyses. The results have shown that the drug may be capable of reducing functional deficits after the lesion and promoting synaptic plasticity and neuroprotection, thus representing a putative translational approach for motoneuron disorders.

Utilization of the Rat Tibial Nerve Transection Model to Evaluate Cellular and Molecular Mechanisms Underpinning Denervation-Mediated Muscle Injury.

Peripheral nerve injury denervates muscle, resulting in muscle paralysis and atrophy. This is reversible if timely muscle reinnervation occurs. With delayed reinnervation, the muscle's reparative ability declines, and muscle-resident fibro-adipogenic progenitor cells (FAPs) proliferate and differentiate, inducing fibro-fatty muscle degradation and thereby physical disability. The mechanisms by which the peripheral nerve regulates FAPs expansion and differentiation are incompletely understood. Using the rat tibial neve transection model, we demonstrated an increased FAPs content and a changing FAPs phenotype, with an increased capacity for adipocyte and fibroblast differentiation, in gastrocnemius muscle post-denervation. The FAPs response was inhibited by immediate tibial nerve repair with muscle reinnervation via neuromuscular junctions (NMJs) and sensory organs (e.g., muscle spindles) or the sensory protection of muscle (where a pure sensory nerve is sutured to the distal tibial nerve stump) with reinnervation by muscle spindles alone. We found that both procedures reduced denervation-mediated increases in glial-cell-line-derived neurotrophic factor (GDNF) in muscle and that GDNF promoted FAPs adipogenic and fibrogenic differentiation in vitro. These results suggest that the peripheral nerve controls FAPs recruitment and differentiation via the modulation of muscle GDNF expression through NMJs and muscle spindles. GDNF can serve as a therapeutic target in the management of denervation-induced muscle injury.

Complex periprosthetic wound coverage in patients undergoing revision total knee arthroplasty: a single plastic surgeon study.

INTRODUCTION: Options for soft tissue coverage in revision total knee arthroplasty (rTKA) range from primary wound closure to complex muscle flap reconstructions. The purpose of this study was to investigate the institutional experience of wound coverage options for complex soft tissue defects in rTKA. MATERIALS AND METHODS: 77 patients undergoing rTKA with complex wound closure by a single plastic surgeon were retrospectively reviewed. The average follow-up was 30.1 months. In 18 (23.4%) patients, an intraoperative decision for primary closure was made. Fifty-nine patients (76.6%) received either a local fasciocutaneous (N = 18), a medial gastrocnemius (N = 37), a free latissimus dorsi (N = 3) or a lateral gastrocnemius flap (N = 1). Revision-free survival and complication rates were assessed and risk factors were analyzed with Cox-regression analysis. RESULTS: Medial gastrocnemius flaps had significant lower cumulative revision-free survival rates than local fasciocutaneous flaps (P = 0.021) and primary closures (P < 0.001) (42.5% vs. 71.5% vs. 100%,respectively). Comparing the most common complex closure procedures medial gastrocnemius flaps had the highest rate of prolonged wound healing (29.7%) and infection/reinfection (40.5%). Infection-associated flap procedures had significant lower cumulative revision-free survival rates (30.5%) than non-infection associated flap procedures (62.8%,P = 0.047). A history of more than two prior surgeries (HR = 6.11,P < 0.001) and an age ≥ 65 years (HR = 0.30,P = 0.018) significantly increased the risk of revision. CONCLUSIONS: The results of this study indicate that primary closure -if possible- should be preferred to early proactive muscle flap coverage. Even in the hands of an experienced plastic surgeon muscle flaps have high revision and complication rates. The study highlights the need to clarify flap indications and to investigate alternative approaches.