Axial Muscles Research Articles

Wing osteology, myology, and function of Rhea americana (Aves, Rheidae).

The Greater Rhea (Rhea americana, Rheidae) is a flightless paleognath with a wide geographical distribution in South America. The morphology of its shoulder girdle and wings are different from those of flying birds and some characteristics are similar to basal birds and paravian theropods. We present a detailed osteological, myological, and functional study of the shoulder and the wing of the Greater Rhea. Particular features of the anatomy of the pectoral girdle and wing of Rheainclude the lack of triosseal canal, reduced origin area of the mm. pectoralis p. thoracica and supracoracoideus and the lack of a propatagium. The wing muscle mass is markedly reduced, reaching only 0.89% of total body mass (BM). Forelimb muscles mass values are low compared to those of flying birds and are congruent with the non-use of wings for active locomotion movements. R. americanadoes not flap the wings dorso-ventral as typical for flying birds, but predominantly in cranio-caudal direction, following a craniolateral to caudomedial abduction-adduction arc. When the wings are fully abducted, they are inverted L-shaped, with the inner surface caudally faced, and when the wings are folded against the body, they do not perform the complete automatic wing folding nor the circumduction of the manus, a movement performed by extant volant birds. This study complements our knowledge of the axial musculature of the flightless paleognaths and highlights the use of the Greater Rhea as a model, which may help understand the evolution of Palaeognathae, as well as the origin of flapping flight among paravian theropods.

Towards defining muscular regions of interest from axial magnetic resonance imaging with anatomical cross-reference: a scoping review of lateral hip musculature

BackgroundMeasures of hip muscle morphology and composition (e.g., muscle size and fatty infiltration) are possible with magnetic resonance imaging (MRI). Standardised protocols or guidelines do not exist for evaluation of hip muscle characteristics, hindering reliable and valid inter-study analysis. This scoping review aimed to collate and synthesise MRI methods for measuring lateral hip muscle size and fatty infiltration to inform the future development of standardised protocols.MethodsFive electronic databases (Medline, CINAHL, Embase, SportsDISCUS and AMED) were searched. Healthy or musculoskeletal pain populations that used MRI to assess lateral hip muscle size and fatty infiltration were included. Lateral hip muscles of interest included tensor fascia late (TFL), gluteus maximus, gluteus medius, and gluteus minimus. Data on MRI parameters, axial slice location, muscle size and fatty infiltrate measures were collected and analysed. Cross referencing for anatomical locations were made between MRI axial slice and E-12 anatomical plastinate sections.ResultsFrom 2684 identified publications, 78 studies contributed data on volume (n = 31), cross sectional area (CSA) (n = 24), and fatty infiltration (n = 40). Heterogeneity was observed for MRI parameters and anatomical boundaries scrutinizing hip muscle size and fatty infiltration. Seven single level axial slices were identified that provided consistent CSA measurement, including three for both gluteus maximus and TFL, and four for both gluteus medius and minimus. For assessment of fatty infiltration, six axial slice locations were identified including two for TFL, and four for each of the gluteal muscles.ConclusionsSeveral consistent anatomical levels were identified for single axial MR slice to facilitate muscle size and fatty infiltration muscle measures at the hip, providing the basis for reliable and accurate data synthesis and improvements in the validity of future between studies analyses. This work establishes the platform for standardised methods for the MRI assessment of lateral hip musculature and will aid in the examination of musculoskeletal conditions around the hip joint. Further studies into whole muscle measures are required to further optimise methodological parameters for hip muscle assessment.

The Human Neck is Part of the Musculoskeletal Core: Cervical Muscles Help Stabilize the Pelvis During Running and Jumping.

SynopsisDuring locomotion, cervical muscles must be active to stabilize the head as the body accelerates and decelerates. We hypothesized that cervical muscles are also part of the linked chain of axial muscles that provide core stabilization against torques applied to the hip joint by the extrinsic muscles of the legs. To test whether specific cervical muscles play a role in postural stabilization of the head and/or core stabilization of the pelvic girdle, we used surface electromyography to measure changes in muscle activity in response to force manipulations during constant speed running and maximum effort counter-movement jumps. We found that doubling the mass of the head during both running and maximum effort jumping had little or no effect on (1) acceleration of the body and (2) cervical muscle activity. Application of horizontal forward and rearward directed forces at the pelvis during running tripled mean fore and aft accelerations, thereby increasing both the pitching moments on the head and flexion and extension torques applied to the hip. These manipulations primarily resulted in increases in cervical muscle activity that is appropriate for core stabilization of the pelvis. Additionally, when subjects jumped maximally with an applied downward directed force that reduced acceleration and therefore need for cervical muscles to stabilize the head, cervical muscle activity did not decrease. These results suggest that during locomotion, rather than acting to stabilize the head against the effects of inertia, the superficial muscles of the neck monitored in this study help to stabilize the pelvis against torques imposed by the extrinsic muscles of the legs at the hip joint. We suggest that a division of labor may exist between deep cervical muscles that presumably provide postural stabilization of the head versus superficial cervical muscles that provide core stabilization against torques applied to the pelvic and pectoral girdles by the extrinsic appendicular muscles.

Royal knifefish generate powerful suction feeding through large neurocranial elevation and high epaxial muscle power.

Suction feeding in ray-finned fishes involves powerful buccal cavity expansion to accelerate water and food into the mouth. Previous XROMM studies in largemouth bass (Micropterus salmoides), bluegill sunfish (Lepomis macrochirus) and channel catfish (Ictalurus punctatus) have shown that more than 90% of suction power in high performance strikes comes from the axial musculature. Thus, the shape of the axial muscles and skeleton may affect suction feeding mechanics. Royal knifefish (Chitala blanci) have an unusual postcranial morphology, with a ventrally flexed vertebral column and relatively large mass of epaxial muscle. Based on their body shape, we hypothesized that royal knifefish would generate high power strikes by utilizing large neurocranial elevation, vertebral column extension and epaxial shortening. As predicted, C. blanci generated high suction expansion power compared with the other three species studied to date (up to 160 W), which was achieved by increasing both the rate of volume change and the intraoral subambient pressure. The large epaxial muscle (25% of body mass) shortened at high velocities to produce large neurocranial elevation and vertebral extension (up to 41deg, combined), as well as high muscle mass-specific power (up to 800 W kg-1). For the highest power strikes, axial muscles generated 95% of the power, and 64% of the axial muscle mass consisted of the epaxial muscles. The epaxial-dominated suction expansion of royal knifefish supports our hypothesis that postcranial morphology may be a strong predictor of suction feeding biomechanics.

Effect of gluteal muscle strengthening exercise on sagittal balance and muscle volume in adult spinal deformity following long-segment fixation surgery

This study aimed to investigate the changes in gluteal muscle volume and the effects of such changes in spinal alignment as a result of postoperative gluteal muscle strengthening exercise (GMSE) in patients following long-segment fixation for adult spinal deformity (ASD). Eighty-three consecutive patients (average age, 70.1 years) were analyzed. Three-dimensional CT scans were conducted to obtain serial axial gluteus muscle image slices. The size of each muscle area in every image slice was measured by Computer Aided Design and the sum of each muscle area was calculated. At the last follow-up, the sagittal vertical axis was significantly greater in the basic postoperative exercise group (1.49 mm vs. 17.94 mm), and the percentage of optimal sagittal alignment was significantly higher in the GMSE group (97.8% vs. 84.2%). At the last follow-up, the gluteus maximus volume was significantly higher in the GMSE group (900,107.1 cm3 vs. 825,714.2 cm3, p = 0.036). For the increase in muscle volume after 1 year, gluteus maximus and medius volumes showed a significant intergroup difference (+ 6.8% vs. + 2.4% and + 6.9% vs. + 3.6%). The GMSE protocol developed in this study could effectively increase gluteal muscle volume and maintain the optimal sagittal balance in patients with ASD.

Association of Paraspinal Muscle CSA and PDFF Measurements With Lumbar Intervertebral Disk Degeneration in Patients With Chronic Low Back Pain.

There is an interaction between the lumbar spine and paraspinal muscles, which may play a role in the development of intervertebral disc (IVD) degeneration and may affect CLBP. The study aims to assess the relationship between IVD degeneration and paraspinal muscle fat infiltration in CLBP patients by quantitative MR imaging, and to evaluate the influence of sex and age on CLBP muscle fat infiltration. Sixty CLBP patients (46.3 years ±17.0) and thirty-two healthy subjects (44.9 years ±17.6) were recruited for this study. 3.0 T MRI was used to perform the sagittal and axial T1, T2 of the lumbar spine, and axial paraspinal muscle IDEAL imaging at the L4/5 and L5/S1 levels. Proton density fat fraction (PDFF) of the multifidus and erector spinae at two IVD levels were measured. The Pfirrmann grades of IVD degeneration, Oswestry Disability Index (ODI), and Visual Analog Scale (VAS) were also evaluated. Compare the cross-sectional area (CSA) and PDFF of the paraspinal muscles between CLBP patients and healthy subjects, and analyze the relationship between the muscle PDFF and Pfirrmann grades, gender, and age of CLBP patients. Compared with healthy subjects, the CSA of the multifidus muscle in CLBP patients decreased (1320.2±188.1mm2 vs. 1228.7±191.0 mm2, p<0.05) at the L4/5 level, the average PDFF increased, (7.7±2.6% vs. 14.79±5.3%, 8.8±4.2% vs. 16.03±5.3%, all p<0.05) at both L4/5 and L5/S1 levels. The PDFF of paraspinal muscles were correlated with adjacent IVD degeneration, ODI and VSA in CLBP patients (all p<0.05). After using age and body mass index (BMI) as control variables, significance was retained (all p<0.05). Multiple regression analysis revealed sex and age also were significantly associated with multifidus PDFF (all p < 0.05). This study confirmed that the CSA decreased and the PDFF increased of the paraspinal muscles in CLBP patients. It reveals a significant correlation between the PDFF of CLBP paraspinal muscles and the grade of IVD degeneration. Sex and age are also important factors influencing CLBP paraspinal muscle infiltration.

Les parakinésies. Phénoménologie des mouvements anormaux intrinsèques aux psychoses endogènes

Abnormal movements are long known to be intrinsic to some forms of endogenous psychoses. Spontaneous dyskinesia are the ones observed by naïve first episode patients and at-risk subjects. Yet, these are only the rediscovery of more complex phenomena denoted as “parakinesias”, which had been described and documented by extensive kinetographic recordings and long-term observations decades before the introduction of neuroleptics. Unfortunately, they were largely neglected by mainstream psychiatry to the point of privation in the French and English literature. Renewed interest in psychomotor phenomena deems it timely to remind the neuropsychiatric community about that concept. Parakinesias consist of various deformations of psychomotor sequences which, for descriptive purpose, can be separated into parakinesias, i.e. abnormal, dyskinetic-like movements, and parakinetic psychomotricity (PPM). Parakinesias are a form of hyperkinetic movement disorder that is quite specific to endogenous psychoses. Parakinesias can be described as pseudo-reactive and pseudo-expressive motions, i.e. they resemble psychomotor gestures that are not only occurring inappropriately, but that are also somewhat distorted. These deformities do not only affect parakinesias but also the individual style of psychomotor outputs resulting in PPM. Gestures and mimics lose their naturalness and become awkward, disharmonious, stiff, mannered, and bizarre. Parakinetic distortions increase over time, so that parakinesias lose their expressiveness and have a more choreiform appearance. They also become more uniform and stereotyped. PK are prevailing in the upper face and the axial and proximal musculature of the upper body. They are not experienced as self-dystonic or alien by the patients, who are not aware of them, even when their attention is drawn to them. Finally, PK are more frequent and manifest as the level of psychomotor excitement is increased whereas they are attenuated up to disappear under high affinity antipsychotics. In non-naive patients, parakinesias might be mistaken for tardive dyskinesia. When they resemble distorted facial expressions, they fit with the concept of “grimacing” whereas PPM is partly captured by the concept of “mannerism”. The goal of this paper is to enhance recognition of parakinesias beyond grimacing and spontaneous dyskinesias. They deserve to be known by clinicians, especially for their prognostic value. From a general perspective, parakinesias and PPM allow to formulate new hypotheses of psychomotor phenomena that ought to be debated, investigated, and tested.

Scoliosis in Spinal Muscular Atrophy Type 1 in the Nusinersen Era.

The introduction of spinal muscular dystrophy (SMA)-modifying therapies, such as antisense oligonucleotide therapy, has changed the natural history of SMA. Most reports on treatment outcomes have focused on motor scores and respiratory function. The objective of this study is to document the development and progression of scoliosis in patients with SMA1 treated with nusinersen. A descriptive single-center study was conducted in patients with SMA1 who were treated with nusinersen before 6 months of age. Data were collected on patients who met criteria, including age at the first nusinersen dose, number of nusinersen doses, degree of scoliosis, respiratory parameters, feeding route, and motor scores at baseline and follow-up. The Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) was subanalyzed using axial (AxS) and appendicular motor (ApS) scores to evaluate a possible correlation between scoliosis and axial muscle strength. From our cohort, 31 percent (11/35) of patients had a diagnosis of SMA1. Sixty-three percent (7/11) met the inclusion criteria. All patients (7/7) showed initial improvement in their CHOP-INTEND scores in correlation with improvement on the ApS. Despite this, most patients did not show improvement in the AxS. Subsequently, all patients developed scoliosis in the first year of life with Cobb angles that ranged between 18° and 60°. Furthermore, total CHOP-INTEND scores had dropped in 2 patients alongside the development of a Cobb angle of >40°. Despite the significant improvement in functional motor assessment in patients with SMA1, there is a progression of significant scoliosis despite treatment. Subsequently, lack or minimal improvement on the axial CHOP-INTEND scores may predict worsening on the total motor scores.

Wnt11 acts on dermomyotome cells to guide epaxial myotome morphogenesis.

The dorsal axial muscles, or epaxial muscles, are a fundamental structure covering the spinal cord and vertebrae, as well as mobilizing the vertebrate trunk. To date, mechanisms underlying the morphogenetic process shaping the epaxial myotome are largely unknown. To address this, we used the medaka zic1/zic4-enhancer mutant Double anal fin (Da), which exhibits ventralized dorsal trunk structures resulting in impaired epaxial myotome morphology and incomplete coverage over the neural tube. In wild type, dorsal dermomyotome (DM) cells reduce their proliferative activity after somitogenesis. Subsequently, a subset of DM cells, which does not differentiate into the myotome population, begins to form unique large protrusions extending dorsally to guide the epaxial myotome dorsally. In Da, by contrast, DM cells maintain the high proliferative activity and mainly form small protrusions. By combining RNA- and ChIP-sequencing analyses, we revealed direct targets of Zic1, which are specifically expressed in dorsal somites and involved in various aspects of development, such as cell migration, extracellular matrix organization, and cell-cell communication. Among these, we identified wnt11 as a crucial factor regulating both cell proliferation and protrusive activity of DM cells. We propose that dorsal extension of the epaxial myotome is guided by a non-myogenic subpopulation of DM cells and that wnt11 empowers the DM cells to drive the coverage of the neural tube by the epaxial myotome.

Complex forelimb movements and cortical topography evoked by intracortical microstimulation in male and female mice.

The motor cortex is crucial for the voluntary control of skilled movement in mammals and is topographically organized into representations of the body (motor maps). Intracortical microstimulation of the motor cortex with long-duration pulse trains (LD-ICMS; ~500ms) evokes complex movements, occurring in multiple joints or axial muscles, with characteristic movement postures and cortical topography across a variety of mammalian species. Although the laboratory mouse is extensively used in basic and pre-clinical research, high-resolution motor maps elicited with electrical LD-ICMS in both sexes of the adult mouse has yet to be reported. To address this knowledge gap, we performed LD-ICMS of the forelimb motor cortex in both male (n = 10) and naturally cycling female (n = 8) C57/BL6J mice under light ketamine-xylazine anesthesia. Complex and simple movements were evoked from historically defined caudal (CFA) and rostral (RFA) forelimb areas. Four complex forelimb movements were identified consisting of Elevate, Advance, Dig, and Retract postures with characteristic movement sequences and endpoints. Furthermore, evoked complex forelimb movements and cortical topography in mice were organized within the CFA in a unique manner relative to a qualitative comparison with the rat.

Increased Dephospho-uncarboxylated Matrix Gla-Protein Is Associated With Lower Axial Skeletal Muscle Mass in Patients With Hypertension.

Matrix Gla-protein (MGP) is a well-established inhibitor of vascular calcification that is activated by vitamin K-dependent carboxylation. In the setting of vitamin K2 deficiency, dephospho-uncarboxylated MGP (dpucMGP) levels increase, and have been associated with large artery stiffening. Vitamin K2 is also a mitochondrial electron carrier in muscle, but the relationship of vitamin K2 deficiency and dpucMGP with muscle mass is not well understood. We therefore aimed to examine the association of vitamin K2 deficiency and dpucMGP with skeletal muscle mass in patients with hypertension. We studied 155 hypertensive adults without heart failure. Axial skeletal muscle mass was measured using magnetic resonance imaging from axial steady-state free precession images. DpucMGP was measured with ELISA. Carotid-femoral pulse wave velocity (CF-PWV) was measured from high-fidelity arterial tonometry recordings. We found an inverse relationship between dpucMGP levels and axial muscle mass, with progressively rising dpucMGP levels correlating with decreasing axial muscle mass. In an unadjusted linear regression model, correlates of dpucMGP included axial skeletal muscle area factor (β = -0.32; P < 0.0001) and CF-PWV (β = 0.31; P = 0.0008). In adjusted analyses, independent correlates of dpucMGP included axial skeletal muscle area factor (β = -0.30; P = 0.0003) and CF-PWV (β = 0.20; P = 0.019). In hypertensive adults, dpucMGP is independently associated with lower axial muscle mass, in addition to increased large artery stiffness. Further studies are required to investigate the role of vitamin K supplementation in this population.

Randomised clinical trial: effect of adding branched chain amino acids to exercise and standard-of-care on muscle mass in cirrhotic patients with sarcopenia.

BackgroundThe role of branched-chain amino acids (BCAA) in improving muscle mass in cirrhosis is presently debatable.AimsTo evaluate the role of BCAA in improving muscle mass in a double-blind randomized placebo-controlled trial in patients with cirrhosis having sarcopenia.MethodsConsecutive patients with cirrhosis with Child–Pugh score < 10 and sarcopenia were randomized to receive either 12 g/day of BCAA orally or a placebo (1:1) for 6 months in addition to a home-based exercise program (30 min/day), dietary counselling and standard medical therapy. Sarcopenia was defined according to gender-specific axial skeletal muscle index (SMI) cut-offs. The primary endpoint was a change in muscle mass based on CT scan (SMI) after 6 months of supplementation.ResultsSixty patients [mean age 41.6 ± 9.9 years; males (66.6%) of predominantly viral (40%) and alcohol-related (31.7%) cirrhosis] were randomized. Baseline clinical and demographic characters were similar except MELD score (10.2 ± 2.8 vs. 12.2 ± 3.5, p = 0.02) and calorie intake (1838.1 kcal ± 631.5 vs. 2217.5 kcal ± 707.3, p = 0.03), both being higher in the placebo arm. After adjusting for both baseline confounders, baseline SMI and protein intake, the change in SMI at 6 months was similar in both groups [mean adjusted difference (MAD) + 0.84, CI − 2.9; + 1.2, p = 0.42] by intention-to-treat analysis. The secondary outcomes including change in handgrip strength (p = 0.65), 6-m gait speed (p = 0.20), 6-min walk distance (p = 0.39) were similar in both arms. Four patients had minor adverse events in each arm.ConclusionAddition of BCAA to exercise, dietary counselling and standard medical therapy did not improve muscle mass in patients with cirrhosis having sarcopenia. (CTRI/2019/05/019269).Trial registration numberCTRI/2019/05/019269 (Clinical Trials Registry of India).Supplementary InformationThe online version contains supplementary material available at 10.1007/s12072-022-10334-7.

Mercury, selenium, and fatty acids in the axial muscle of largemouth bass: evaluating the influence of seasonal and sexual changes in fish condition and reproductive status.

Largemouth bass (LMB, 265-475 mm) were collected to document whether changes in fish condition and reproductive status influenced the concentration of total mercury (Hg) and selenium (Se) in axial muscle by season and sex. The fatty acid (FA) composition of fish was also examined to describe seasonal and sexual differences and identify whether arachidonic acid (ARA) could be used as a biomarker of Hg toxicity. There was a trend for females to have lower (p < 0.062) Se concentrations than males. The concentration of Se for females during spring (mean ± SD, 686 ± 51 ng/g dw) was 15% lower than males (806 ± 67 ng/g dw). Lower Se concentrations in females than males continued through summer and fall. Concentration of Hg for females during spring (152 ± 39 ng/g ww) was also 59% lower than males (373 ± 303 ng/g ww), but the difference was not significant (p > 0.2). The percent of lipids was greatest in fall and winter (3%) and comprised primarily of omega-3 fatty acids (35 g/100 g lipid). Fish condition as measured by percent lipids and relative weight was negatively (p < 0.02) related to Hg concentration for females and males. Lipid content for both sexes was also positively (p < 0.05) related to the Se:Hg ratio. Relative weight was positively related to the Se:Hg ratio for females during all seasons (p = 0.014), but only during spring and summer for males (p < 0.007). A low Se:Hg value was associated with an elevation in ARA for both sexes and a reduced hepatosomatic index in males. Data suggested that females transferred muscle stores of Se and Hg to developing oocytes during spring. This study generates hypotheses regarding the physiological drivers of seasonal and sexual variability in Hg, Se, and FA in LMB that may be applicable to other species and have implications for fisheries health and management.

Monitoring and Management of Fibrodysplasia Ossificans Progressiva: Current Perspectives.

Fibrodysplasia ossificans progressiva (FOP), sometimes known as myositis ossificans progressiva, is an ultra-rare disease in which bone is formed in muscular tissue, tendons and ligaments. This is known as heterotopic ossification (HO). FOP is caused by a heterozygous mutation in the highly conserved ACVR1/ALK2 gene which affects about 1 in 1.5–2 million individuals. At birth, patients with the predominant R206H mutation only exhibit a bilateral hallux valgus. During childhood, heterotopic bone formation develops in a typical pattern, affecting the axial muscles first before appendicular body parts are involved. HO can start spontaneously but is often elicited by soft tissue trauma or medical procedures. After soft tissue injury, an inflammatory process called a flare-up can start, followed by the formation of HO. HO leads to a limited range of motion, culminating in complete ankylosis of nearly all joints. As a result of HO surrounding the thorax, patients often suffer from thoracic insufficiency syndrome (TIS). TIS is the most common cause of a limited life expectancy for FOP patients, with a median life expectancy of 56 years. Management is focused on preventing soft-tissue injury that can provoke flare-ups. This includes prevention of iatrogenic damage by biopsies, intramuscular injections and surgery. Anti-inflammatory medication is often started when a flare-up occurs but has a poor basis of evidence. Several forms of potential treatment for FOP are being researched in clinical trials. Progression of the disease is monitored using CT and 18F-NaF PET/CT combined with functional assessments. Patients are regularly evaluated for frequently occurring complications such as restrictive lung disease. Here, we review the current management, monitoring and treatment of FOP.

Adolescents with idiopathic scoliosis show decreased intermuscular coherence in lumbar paraspinal muscles: A new pathophysiological perspective

ObjectiveAlthough adolescent idiopathic scoliosis is thought to be an orthopedic disorder, sensorimotor deficits resulting in asymmetric neural drive to the axial musculature have been proposed as contributing factors. Asymmetry in the vestibular control of spinal motoneurons can cause spine deformation reminiscent of idiopathic scoliosis in animal models. MethodsTo examine the neural control of axial muscles, we compared common oscillatory drive to bilateral lumbar muscles between 19 participants with adolescent idiopathic scoliosis and 19 healthy adolescents. We measured right and left paraspinal muscle activity during steady isometric back extensions at 15% or 30% of their maximum voluntary contraction. ResultsThe variance in exerted force and symmetry in bilateral muscle activation were similar between groups. We estimated the strength of common oscillations between muscle motoneuron pools using intermuscular coherence. Compared to controls, participants with adolescent idiopathic scoliosis exhibited smaller intermuscular coherence between paraspinal muscles in the alpha and beta bands. To identify the cause of the observed decreased in intermuscular coherence, we quantified variability of electromyography power ratio and relative activation timing between the paraspinal muscle. Intermuscular phase between muscle oscillations across the alpha band demonstrated larger variability in adolescent with idiopathic scoliosis. The variability of the ratio of lumbar muscles power was similar between groups in the alpha and beta bands. ConclusionOur results suggest that altered bilateral control of axial muscles characterized by increased variability in the timing of alpha oscillations may be linked to spine deformation in adolescents. SignificanceOur findings provide a new perspective on neural factors associated with a common spine deformation, adolescent idiopathic scoliosis.

Reemployment of Kupffer's vesicle cells into axial and paraxial mesoderm via transdifferentiation.

Kupffer's vesicle (KV) in the teleost embryo is a fluid-filled vesicle surrounded by a layer of epithelial cells with rotating primary cilia. KV transiently acts as the left-right organizer and degenerates after the establishment of left-right asymmetric gene expression. Previous labelling experiments in zebrafish embryos indicated that descendants of KV-epithelial cells are incorporated into mesodermal tissues after the collapse of KV. However, the overall picture of their differentiation potency had been unclear due to the lack of suitable genetic tools and molecular analyses. In the present study, we established a novel zebrafish transgenic line with a promoter of dand5, in which all KV-epithelial cells and their descendants are specifically labelled until the larval stage. We found that KV-epithelial cells undergo epithelial-mesenchymal transition upon KV collapse and infiltrate into adjacent mesodermal progenitors, the presomitic mesoderm and chordoneural hinge. Once incorporated, the descendants of KV-epithelial cells expressed distinct mesodermal differentiation markers and contributed to the mature populations such as the axial muscles and notochordal sheath through normal developmental process. These results indicate that differentiated KV-epithelial cells possess unique plasticity in that they are reemployed into mesodermal lineages through transdifferentiation after they complete their initial role in KV.

A new conceptual framework for the musculoskeletal biomechanics and physiology of ray-finned fishes.

ABSTRACTSuction feeding in ray-finned fishes requires substantial muscle power for fast and forceful prey capture. The axial musculature located immediately behind the head has been long known to contribute some power for suction feeding, but recent XROMM and fluoromicrometry studies found nearly all the axial musculature (over 80%) provides effectively all (90–99%) of the power for high-performance suction feeding. The dominance of axial power suggests a new framework for studying the musculoskeletal biomechanics of fishes: the form and function of axial muscles and bones should be analysed for power production in feeding (or at least as a compromise between swimming and feeding), and cranial muscles and bones should be analysed for their role in transmitting axial power and coordinating buccal expansion. This new framework is already yielding novel insights, as demonstrated in four species for which suction power has now been measured. Interspecific comparisons suggest high suction power can be achieved in different ways: increasing the magnitude of suction pressure or the rate of buccal volume change, or both (as observed in the most powerful of these species). Our framework suggests that mechanical and evolutionary interactions between the head and the body, and between the swimming and feeding roles of axial structures, may be fruitful areas for continued study.

Bioimpedance Phase Angle as a Prognostic Tool in Late-Onset Pompe Disease: A Single-Centre Prospective Study With a 15-year Follow-Up.

Background: Late-onset Pompe disease (LOPD) is an autosomal-recessive metabolic myopathy caused by deficiency of the lysosomal enzyme Acid Alpha—Glucosidase (GAA), leading to glycogen accumulation in proximal and axial muscles, and in the diaphragm. Enzyme Replacement Therapy (ERT) with recombinant GAA became available in 2006. Since then, several outcome measures have been investigated for the adequate follow-up of disease progression and treatment response, usually focusing on respiratory and motor function. Prognostic factors predicting outcome have not been identified till now. Methods: In this single Centre, prospective study, we evaluate the response to enzyme replacement therapy in 15 patients (7 males) with LOPD in different stages of disease, aged 49.4 ± 16.1, followed-up for 15 years. Treatment response was measured by the 6-min walking test, vital capacity in supine and upright position, respiratory muscle strength, muscle MRI, manual muscle testing. We investigated the usefulness of Body Impedance Vectorial Analysis for serial body composition assessment. Results: Although most patients with LOPD benefit from long-term treatment, some secondary decline may occur after the first 3–5 years. Some nutritional (lower body mass index, higher fat free mass, higher phase angle) and disease parameters (higher creatinine and shorter disease duration at the beginning of treatment) seem to predict a better motor outcome. Lower Phase Angle, possibly reflecting loss of integrity of skeletal muscle membranes and thus treatment mis-targeting, seems to correlate with worse treatment response on long-term follow-up. Conclusion: Body Impedance Vectorial Analysis is a fast, easily performed and cheap tool that may be able to predict long-term treatment response in patients with LOPD. Low Phase angle may serve as a marker of muscle quality and may be used to predict the response to a muscle-targeted intervention such as ERT, thus improving the identification of patients needing a closer follow-up due to higher fragility and risk of deterioration.

Long-term follow-up of respiratory function in facioscapulohumeral muscular dystrophy

ObjectiveTo evaluate the 5-year change in respiratory function in patients with facioscapulohumeral muscular dystrophy (FSHD).MethodsGenetically confirmed patients with FSHD aged ≥ 18 years were examined twice over five years. Forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) were measured using hand-held spirometry with a face mask. Several clinical outcome measures were correlated to respiratory function.ResultsNinety-two patients were included (57% male, age 18–75 years). At baseline, the spirometry outcomes of 41 patients showed a restrictive ventilatory pattern (FVC < 80% and FEV1/FVC ≥ 70% of predicted) and of 48 patients at follow-up. The mean FVC decreased from baseline to follow-up from 79.0 to 76.7% predicted (p = 0.021). This decrease was driven by a subgroup of 15 patients who had a deterioration of FVC of > 10% predicted. The subgroup of 15 patients was more severely affected at baseline (p = 0.002 for FSHD clinical score and 0.007 for Ricci score). They developed more frequently spinal and thorax deformities (p < 0.001 for kyphoscoliosis and 0.012 for pectus excavatum) and had a larger decline in axial muscle function (p = 0.020). Only weak correlations were found between the change in FVC% predicted and the change in clinical scores between baseline and follow-up.InterpretationRespiratory function remained stable in most patients with FSHD, but a subgroup of patients showed a pronounced deterioration. They showed more severe muscle weakness including the leg muscles at baseline (Ricci score ≥ 6), had spinal and thorax deformities and a relatively fast decline in axial muscle function at follow-up.

Recessive variants in COL25A1 gene as novel cause of arthrogryposis multiplex congenita with ocular congenital cranial dysinnervation disorder.

A proper interaction between muscle-derived collagen XXV and its motor neuron-derived receptors protein tyrosine phosphatases σ and δ (PTP σ/δ) is indispensable for intramuscular motor innervation. Despite this, thus far, pathogenic recessive variants in the COL25A1 gene had only been detected in a few patients with isolated ocular congenital cranial dysinnervation disorders. Here we describe five patients from three unrelated families with recessive missense and splice site COL25A1 variants presenting with a recognizable phenotype characterized by arthrogryposis multiplex congenita with or without an ocular congenital cranial dysinnervation disorder phenotype. The clinical features of the older patients remained stable over time, without central nervous system involvement. This study extends the phenotypic and genotypic spectrum of COL25A1 related conditions, and further adds to our knowledge of the complex process of intramuscular motor innervation. Our observations indicate a role for collagen XXV in regulating the appropriate innervation not only of extraocular muscles, but also of bulbar, axial, and limb muscles in the human.