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Our basic knowledge of downward positive lightning leaders is incomplete due to their rarity and limited ability of VHF mapping systems to image positive streamers. Here, using high‐speed optical records and wideband electric field and magnetic field derivative signatures, we examine in detail the development of a descending positive leader, which extended intermittently via alternating branching at altitudes of 4.2 to 1.9 km and involved luminosity transients separated by millisecond‐scale quiet intervals. We show that the transients (a) are mostly initiated in previously created but already decayed branches, at a distance of the order of 100 m above the branch lower extremity, (b) extend bidirectionally with negative charge moving up, (c) establish a temporary (1 ms or so) steady‐current connection to the negative part of the overall bidirectional leader tree, and (d) exhibit brightening accompanied by new breakdowns at the positive leader end. One of the transients unexpectedly resulted in a negative cloud‐to‐ground discharge. Both positive and negative ends of the transients extended at speeds of 106–107 m/s, while the overall positive leader extension speed was as low as 103–104 m/s. Wideband electric field signatures of the transients were similar to K‐changes, with their millisecond‐ and microsecond‐scale features being associated with the steady current and new breakdowns, respectively. For transients with both ends visible in our optical records, charge transfers and average currents were estimated to be typically a few hundreds of millicoulombs and some hundreds of amperes, respectively. Plain Language Summary: Our knowledge of downward positive lightning is very limited. Positive lightning constitutes only about 5% of the global lightning activity, but it causes the most severe damage to various objects and systems, as well as most transient luminous events in the mesosphere. The leader processes in positive lightning remain a mystery and are widely debated in the atmospheric electricity community. In this paper, we present two new findings on propagation mechanisms of branched downward positive leader: (a) its ability to produce an opposite‐polarity (negative) lightning discharge to ground and (b) its unusual mode of propagation involving bidirectional transients, which temporarily reactivate individual leader branches and facilitate their alternating extension. Key Points: Branched positive leader extending at an average speed of 103–104 m/s resulted in a three‐stroke negative cloud‐to‐ground flashPositive leader extension involved bidirectional transients, moving negative charge up, separated by millisecond‐scale quiet intervalsElectric field signatures of the transients are similar to K‐changes and are associated with steady currents and new breakdowns at far end [ABSTRACT FROM AUTHOR]

Objectives: Estimation of body mass from skeletal metrics can reveal important insights into the paleobiology of archeological or fossil remains. The standard approach constructs predictive equations from postcrania, but studies have questioned the reliability of traditional measures. Here, we examine several skeletal features to assess their accuracy in predicting body mass. Materials and Methods: Antemortem mass measurements were compared with common skeletal dimensions from the same animals postmortem, using 115 rhesus macaques (male: n = 43; female: n = 72). Individuals were divided into training (n = 58) and test samples (n = 57) to build and assess Ordinary Least Squares or multivariate regressions by residual sum of squares (RSS) and AIC weights. A leave‐one‐out approach was implemented to formulate the best fit multivariate models, which were compared against a univariate and a previously published catarrhine body‐mass estimation model. Results: Femur circumference represented the best univariate model. The best model overall was composed of four variables (femur, tibia and fibula circumference and humerus length). By RSS and AICw, models built from rhesus macaque data (RSS = 26.91, AIC = −20.66) better predicted body mass than did the catarrhine model (RSS = 65.47, AIC = 20.24). Conclusion: Body mass in rhesus macaques is best predicted by a 4‐variable equation composed of humerus length and hind limb midshaft circumferences. Comparison of models built from the macaque versus the catarrhine data highlight the importance of taxonomic specificity in predicting body mass. This paper provides a valuable dataset of combined somatic and skeletal data in a primate, which can be used to build body mass equations for fragmentary fossil evidence. [ABSTRACT FROM AUTHOR]

Although modern antibiotics and surgical technology have made great progress, when using carbon nanomaterials to treat bone marrow-induced inflammation after martial arts fractures, how to simultaneously repair bone defects and control wound infections is the current focus of orthopedics research. This paper uses electrospinning technology to develop a carbon nanomaterial based on PLA, HA-g-PLA, and vancomycin. The surface morphology, biocompatibility, drug release, and osteogenesis of carbon nanomaterials are studied, selecting animal models to verify its effect in the treatment of osteomyelitis with bone defects and provide new ideas and new methods for the treatment of bone defects complicated by osteomyelitis infection. In this paper, carbon nanofibers containing doxycycline, a small molecule protease inhibitor, were prepared by simple blending. Encapsulation of carbon nanofibers can control the slow release of doxycycline and improve the effect of doxycycline in treating chronic wounds. This article uses two methods to prepare different types of osteomyelitis models and compare them. After injecting saline or bacterial solution, the two groups were sealed with bone wax and the incision was closed; the blank group did not do any treatment. Within 30 days after surgery, the appearance of the left hind limb wound and general signs of infection were closely monitored, body temperature was measured, and blood was collected from the ear veins of experimental animals to analyze the changes in C-reactive protein (CRP) and procalcitonin levels (PCT); X-ray, CT imaging, and histological observation were performed on 14 and 28 days. Studies have shown that when the drug loading of doxycycline increases from 10% to 15%, this is related to the change in properties of the polylactic acid fiber membrane from hydrophobic to hydrophilic caused by the increase in doxycycline drug loading. [ABSTRACT FROM AUTHOR]

This paper proposes the mechanical design and wheel–leg–body cooperation control of a robot capable of climbing stairs for the RoboMaster competition. The robot is comprised of a robot body and four legs with wheels on each end. The front and hind legs composed of the linkages and sliders complete the climbing stairs motion under the coordination of the motors and the cylinders. The dynamic stair‐climbing motion is realized by control the wheel speed and leg motion corresponding to the body motion of the robot relative to the stair environment. Compared with the common split stair climbing designed, the robot can dynamically climb the stairs without losing the forward speed, which makes climbing stairs more smoothly while retaining the ability to move on the flat. Experimental results demonstrate that the robot can climb stairs with a riser height up to 20 cm and a tread depth more than 80 cm. And the process of climbing each stair is reduced to 1–2 s. [ABSTRACT FROM AUTHOR]

In order to shorten the research and development cycle of quadruped robot, it is significant to solve the problem of single leg weight-bearing and obtain a smooth gait switching. Firstly, a leg structure with an antiparallelogram is proposed, which greatly enhances the strength and stiffness of the leg in this paper. Secondly, the Simulink-ADAMS cosimulation platform is built and the improved Hopf oscillator is used in the control of robot. This control mode based on CPG realizes the walk and trot gait of quadruped robot. Thirdly, in order to solve the problems of breakpoints, phase-locked, and stopping of gait curve in the process of gait switching by directly replacing the gait matrix, the functional relationship between the right hind leg and duty cycle is introduced to realize the smooth transition of gait curve. The simulation results show that the proposed algorithm can achieve a smooth gait transformation within 4–6 second, which preliminarily proves the feasibility of the algorithm. Finally, the experimental platform is built and the control algorithm is written into the controller to realize the specific gait of the robot, which proves the effectiveness of the proposed method. [ABSTRACT FROM AUTHOR]

Presents an abstract of the study `An allometric analysis of lemurid, anthropoid and notharctine hindlimbs,' by E. Strasser and M. Dagosto. Hindlimb morphology among lemurid, anthropoid and notharctine primates.

Aim: To investigate the regulation of ginsenoside Rg1 on the PI3K/AKT pathway through the lncRNA‐Malat1/miR‐124‐3p/ Laminin gamma1 (Lamc1) axis, activating astrocytes (As) to promote the repair of spinal cord injury (SCI). Methods: Bioinformatics analysis was used to predict miRNA targeting Lamc1 and lncRNA targeting miR‐124‐3p, which were then validated through a dual‐luciferase assay. Following transfection, the relationships between Malat1, miR‐124‐3p, and Lamc1 expression levels were assessed by qRT‐PCR and Western blot (WB). Immunofluorescence staining and immunohistochemistry were utilized to measure Lamc1 expression, while changes in cavity area were observed through hematoxylin–eosin (HE) staining. Basso‐Beattie‐Bresnahan (BBB) scale and footprint analysis were used to evaluate functional recovery. WB was performed to assess the expression of PI3K/AKT pathway‐related protein. Results: Rg1 was found to upregulate Malat1 expression, which in turn modulated the Malat1/miR‐124‐3p/Lamc1 axis. Furthermore, Rg1 activated the PI3K/Akt signaling pathway, significantly reducing the SCI cavity area and improving hind limb motor function. However, knockout of Malat1 hindered these effects, and inhibition of miR‐124‐3p reversed the silencing effects of Malat1. Conclusions: Rg1 can induce Malat1 expression to activate the Lamc1/PI3K/AKT signaling pathway by sponging with miR‐124‐3p, thereby regulating As activity to repair SCI. [ABSTRACT FROM AUTHOR]

Objective: Severe limb amputation trauma often results in bone and soft tissue defects after debridement. Traditional replantation aims to save the limb by shortening the ischemic period and using autologous transplantation for repair, but it can lead to surgical trauma, donor site damage, and prolonged operation time. Due to contusion, pollution, and complex injury, there is no unified standard for replantation and fixation. Improper operation can easily lead to complications such as bone infection, nonunion, bone defect, and joint stiffness. This study introduces the Ilizarov technique into microsurgery to improve limb lengthening after reconstruction and standardizes the steps of replantation fixation for complex limb avulsion injuries, with a focus on clinical efficacy. Methods: A retrospective analysis was performed on 51 patients with complex limb amputation who were treated in Zhengzhou Renji Hospital from June 2009 to March 2021. On the basis of microsurgical limb replantation, Ilizarov technology was introduced to innovate the internal and external combined stepwise fixation method for replantation. Patients' gender, age, height, weight, BMI, and other general information were collected. X‐ray films were reviewed regularly to observe the surgical healing of fracture, that is, the degree of limb shortening. The lengthening time, carrying time after lengthening, follow‐up time, Dahl classification, Paley fracture healing classification, and Chen Zhongwei's replantation function score were used to evaluate the recovery of the affected limb. Results: A total of 51 patients were included in this group, including 36 male patients and 15 female patients. All the amputated wounds were single limb amputation. In this group of patients, the hind limbs were shortened by 2–12.5 cm (5.32 ± 2.24) after replantation. A total of 44 patients whose hind limbs were shortened by more than 2.5 cm were treated with two‐stage Ilizarov lengthening for 1.5–5.5 months (3.19 ± 1.03). The carrying time was 3–7.5 months (4.25 ± 0.94), and the follow‐up time was 1–7.8 years (3.76 ± 1.69). Among the 49 survived patients, the Dahl grade of external fixation was less than Grade 2 in 89.8%. The excellent and good rate of Paley fracture healing classification was 89.8%. The excellent and good rate of Chen Zhongwei's limb replantation function classification was 79.6%. Conclusion: Microsurgery combined with Ilizarov technique in the treatment of limb amputation injury, limb salvage reconstruction with internal and external combined step‐by‐step combined fixation, and one‐stage shortening and two‐stage limb lengthening can reduce the occurrence of osteomyelitis, bone defect and nonunion, expand the indications of limb replantation, improve the success rate of limb replantation, with satisfactory results, and facilitate the promotion of clinical techniques. [ABSTRACT FROM AUTHOR]

The axolotl A mbystoma mexicanum is one of the most used model organisms in evolutionary, developmental and regenerative studies, particularly because it can reconstitute a fully functional and complete forelimb/hindlimb. Surprisingly, there is no publication that describes all the pectoral and forelimb muscles of this species or provides a comparative framework between these muscles and those of other model organisms and of modern humans. In the present paper we describe and illustrate all these muscles in A . mexicanum and provide the first report about the myology of adults of a model organism that is based on analyses and dissections of both wildtype animals and transgenic animals that express green fluorescent protein ( GFP) in muscle fibers. On the one hand, the inclusion of GFP-transgenic animals allows us to show the muscles as more commonly seen, and thus easier to understand, by current developmental and regenerative biologists. On the other hand, by including wildtype and GFP-transgenic animals and by visualizing these latter animals with and without a simultaneous transmission laser light, we were able to obtain a more complete and clearer understanding of the exact limit of the fleshy and tendinous parts of the muscles and their specific connections with the skeletal elements. This in turn allowed us to settle some controversies in previous anatomical and comparative studies. As most developmental, regenerative and evolutionary biologists are interested in comparing their observations of A . mexicanum with observations in other model organisms, and ultimately in using this information to increase the understanding of human evolution and medicine, we also provide tables showing the homologies between the pectoral and forelimb muscles of axolotls, of model organisms such as mice, frogs and chicken, and of H omo sapiens. An example illustrating the outcomes of using our methodology and of our observations is that they revealed that, contrary to what is often stated in the literature, A . mexicanum has a muscle coracoradialis that has both a well developed proximal fleshy belly and a distal long and thin tendon, supporting the idea that this muscle very likely corresponds to at least part of the amniote biceps brachii. Our observations also: (i) confirmed that the flexores digitorum minimi, interphalangeus digiti 3, pronator quadratus and palmaris profundus 1 are present as distinct muscles in A . mexicanum, supporting the idea that the latter muscle does not correspond to the pronator accessorius of reptiles; (ii) confirmed that the so-called extensor antebrachii radialis is present as a distinct muscle in this species and, importantly, indicated that this muscle corresponds to the supinator of other tetrapods; (iii) showed that, contrary to some other urodeles, including some other A mbystoma species, there is no distinct muscle epitrochleoanconeus in A . mexicanum and; (iv) showed that the ulnar and radial bundles of the abductor et extensor digiti 1 correspond to the abductor pollicis longus and extensor pollicis longus of other tetrapods, respectively. [ABSTRACT FROM AUTHOR]

Several groups of birds have convergently evolved the ability to swim using their feet despite facing trade-offs with walking. However, swimming relative to terrestrial performance varies across these groups. Highly specialized divers, such as loons and grebes, excel at swimming underwater but struggle to stand on land, whereas species that primarily swim on the water surface, such as Mallards, retain the ability to move terrestrially. The identification of skeletal features associated with a swimming style and conserved across independent groups suggests that the hindlimb of foot-propelled swimming birds has adapted to suit the physical challenges of producing propulsive forces underwater. But in addition to skeletal features, how do hindlimb muscles reflect swimming ability and mode? This paper presents the first comparative myology analysis associated with foot-based swimming. Our detailed dissections of 35 specimens representing eight species reveal trends in hindlimb muscle size and attachment location across four independent lineages of extant swimming birds. We expand upon our dissections by compiling data from historical texts and provide a key to any outdated muscle nomenclature used in these sources. Our results show that highly diving birds tuck the femur and proximal tibiotarsus next to the ribcage and under the skin covering the abdomen, streamlining the body. Several hindlimb muscles exhibit dramatic anatomical variation in diving birds, including the flexor cruris lateralis ( FCL) and iliofibularis ( IF), which reduce in size and shift distally along the tibiotarsus. The femorotibialis medius ( FTM) extends along an expanded cnemial crest. The resulting increased moment arms of these muscles likely help stabilize the hip and knee while paddling. Additionally, distal ankle plantarflexors, including the gastrocnemius and digital flexors, are exceptionally large in diving birds in order to power foot propulsion. These patterns exist within distantly related lineages of diving birds and, to a lesser extent, in surface swimmers. Together, our findings verify conserved muscular adaptations to a foot-propelled swimming lifestyle. The association of muscle anatomy with skeletal features and biomechanical movement demands can inform functional interpretation of fossil birds and reveal selective pressures underlying avian diversification. [ABSTRACT FROM AUTHOR]

Specialized organisms are useful for exploring the combined effects of selection of functional traits and developmental constraints on patterns of phenotypic integration. Sabretooth predators are one of the most interesting examples of specialization among mammals. Their hypertrophied, sabre-shaped upper canines and their powerfully built forelimbs have been interpreted as adaptations to a highly specialized predatory behaviour. Given that the elongated and laterally compressed canines of sabretooths were more vulnerable to fracture than the shorter canines of conical-tooth cats, it has been long hypothesized that the heavily muscled forelimbs of sabretooths were used for immobilizing prey before developing a quick and precise killing bite. However, the effect of this unique adaptation on the covariation between the fore- and the hindlimb has not been explored in a quantitative fashion. In this paper, we investigate if the specialization of sabretooth predators decoupled the morphological variation of their forelimb with respect to their hindlimb or, in contrast, both limbs vary in the same fashion as in conical-tooth cats, which do not show such extreme adaptations in their forelimb. We use 3D geometric morphometrics and different morphological indices to compare the fore- and hindlimb of conical- and sabretooth predators. Our results indicate that the limb bones of sabretooth predators covary following the same trend of conical-tooth cats. Therefore, we show that the predatory specialization of sabretooth predators did not result in a decoupling of the morphological evolution of their fore- and hindlimbs. The role of developmental constraints and natural selection on this coordinate variation between the fore- and the hindlimb is discussed in the light of this new evidence. [ABSTRACT FROM AUTHOR]

Background: Angiogenesis is critical for forming new blood vessels from antedating vascular vessels. The endothelium is essential for angiogenesis, vascular remodelling and minimisation of functional deficits following ischaemia. The insulin‐like growth factor (IGF) family is crucial for angiogenesis. Insulin‐like growth factor‐binding protein 5 (IGFBP5), a binding protein of the IGF family, may have places in angiogenesis, but the mechanisms are not yet completely understood. We sought to probe whether IGFBP5 is involved in pathological angiogenesis and uncover the molecular mechanisms behind it. Methods and results: IGFBP5 expression was elevated in the vascular endothelium of gastrocnemius muscle from critical limb ischaemia patients and hindlimb ischaemic (HLI) mice and hypoxic human umbilical vein endothelial cells (HUVECs). In vivo, loss of endothelial IGFBP5 (IGFBP5EKO) facilitated the recovery of blood vessel function and limb necrosis in HLI mice. Moreover, skin damage healing and aortic ring sprouting were faster in IGFBP5EKO mice than in control mice. In vitro, the genetic inhibition of IGFBP5 in HUVECs significantly promoted tube formation, cell proliferation and migration by mediating the phosphorylation of IGF1R, Erk1/2 and Akt. Intriguingly, pharmacological treatment of HUVECs with recombinant human IGFBP5 ensued a contrasting effect on angiogenesis by inhibiting the IGF1 or IGF2 function. Genetic inhibition of IGFBP5 promoted cellular oxygen consumption and extracellular acidification rates via IGF1R‐mediated glycolytic adenosine triphosphate (ATP) metabolism. Mechanistically, IGFBP5 exerted its role via E3 ubiquitin ligase Von Hippel‐Lindau (VHL)‐regulated HIF1α stability. Furthermore, the knockdown of the endothelial IGF1R partially abolished the reformative effect of IGFBP5EKO mice post‐HLI. Conclusion: Our findings demonstrate that IGFBP5 ablation enhances angiogenesis by promoting ATP metabolism and stabilising HIF1α, implying IGFBP5 is a novel therapeutic target for treating abnormal angiogenesis‐related conditions. [ABSTRACT FROM AUTHOR]

In posterior spine surgery, retractors exert pressure on paraspinal muscles, elevating intramuscular pressure and compromising blood flow, potentially causing muscle injury during ischemia–reperfusion. Ginkgo biloba extract (EGb 761), known for its antioxidant and free radical scavenging properties and its role in treating cerebrovascular diseases, is investigated for its protective effects against muscle ischemia–reperfusion injury in vitro and in vivo. Animals were randomly divided into the control group, receiving normal saline, and experimental groups, receiving varying doses of EGb761 (25/50/100/200 mg/kg). A 2‐h hind limb tourniquet‐induced ischemia was followed by reperfusion. Blood samples collected pre‐ischemia and 24 h post‐reperfusion, along with muscle tissue samples after 24 h, demonstrated that EGb761 at 1000 μg/mL effectively inhibited IL‐6 and TNF‐α secretion in RAW 264.7 cells without cytotoxicity. EGb761 significantly reduced nitric oxide (NO) and malondialdehyde (MDA) levels, myeloperoxidase (MPO) activity, and increased glutathione (GSH) levels compared to the control after 24 h. Muscle tissue sections revealed more severe damage in the control group, indicating EGb761's potential in mitigating inflammatory responses and oxidative stress during ischemia–reperfusion injury, effectively protecting against muscle damage. [ABSTRACT FROM AUTHOR]

Sepsis induces a myopathy characterized by loss of muscle mass and weakness. Septic patients undergo prolonged periods of limb muscle disuse due to bed rest. The contribution of limb muscle disuse to the myopathy phenotype remains poorly described. To characterize sepsis‐induced myopathy with hindlimb disuse, we combined the classic sepsis model via cecal ligation and puncture (CLP) with the disuse model of hindlimb suspension (HLS) in mice. Male C57bl/6j mice underwent CLP or SHAM surgeries. Four days after surgeries, mice underwent HLS or normal ambulation (NA) for 7 days. Soleus (SOL) and extensor digitorum longus (EDL) were dissected for in vitro muscle mechanics, morphological, and histological assessments. In SOL muscles, both CLP+NA and SHAM+HLS conditions elicited ~20% reduction in specific force (p < 0.05). When combined, CLP+HLS elicited ~35% decrease in specific force (p < 0.05). Loss of maximal specific force (~8%) was evident in EDL muscles only in CLP+HLS mice (p < 0.05). CLP+HLS reduced muscle fiber cross‐sectional area (CSA) and mass in SOL (p < 0.05). In EDL muscles, CLP+HLS decreased absolute mass to a smaller extent (p < 0.05) with no changes in CSA. Immunohistochemistry revealed substantial myeloid cell infiltration (CD68+) in SOL, but not in EDL muscles, of CLP+HLS mice (p < 0.05). Combining CLP with HLS is a feasible model to study sepsis‐induced myopathy in mice. Hindlimb disuse combined with sepsis induced muscle dysfunction and immune cell infiltration in a muscle dependent manner. These findings highlight the importance of rehabilitative interventions in septic hosts to prevent muscle disuse and help attenuate the myopathy. [ABSTRACT FROM AUTHOR]

Lameness is one of the greatest constraints on the productivity, health, and welfare of dairy cattle. A cross-sectional study was carried out from March 2021 to September 2021 in Hawassa town with the aim of assessing the prevalence and identifying the associated risk factors of lameness in dairy farms. The study was conducted on 440 animals belonging to 19 randomly selected intensive dairy farms. Data regarding lameness and its possible risk factors were collected both at animal and farm level using a questionnaire. The results showed that the overall prevalence of lameness was 10.2% (n = 45/440). The association of lameness prevalence with various risk factors including milking status, exercise, age, parity, milk yield, and lactation stage was statistically tested using logistic regression model. There was a significant variation in the prevalence of lameness (P < 0.05) between cattle with different milking status, age, parity, milk yield, and stage of lactation by the univariable analysis result. According to the multivariable analysis, only milk yield and lactation stage were statistically associated with the occurrence of lameness. Milking animals (8%) had higher prevalence of lameness than nonmilking (2.2%). The occurrence of lameness increased with milk yield. The highest prevalence of lameness was recorded in the early stage of lactation. Lameness was more frequent in hind limbs (6.6%) than in forelimbs (3.6%). The main causes of lameness observed in this study were both claw overgrowth 10 (2.3%), unequal claw size 10 (2.3%), solar ulcer 8 (1.8%), interdigital necrobacillosis 2 (0.5%), interdigital hyperplasia 2 (0.5%), and digital dermatitis 1 (0.2%). There was no means of early lameness diagnosis in 94.7% of farms. Lameness was found to be an important disease in dairy cows at Hawassa town. Prevention and early diagnosis leading to prompt treatment of lameness in cows should be part of dairy farm management practice. [ABSTRACT FROM AUTHOR]

The cheetah is capable of a top speed of 29 ms compared to the maximum speed of 17 ms achieved by the racing greyhound. In this study of the hindlimb and in the accompanying paper on the forelimb we have quantified the musculoskeletal anatomy of the cheetah and greyhound and compared them to identify any differences that may account for this variation in their locomotor abilities. Specifically, bone length, mass and mid-shaft diameter were measured, along with muscle mass, fascicle lengths, pennation angles and moment arms to enable estimates of maximal isometric force, joint torques and joint rotational velocities to be calculated. Surprisingly the cheetahs had a smaller volume of hip extensor musculature than the greyhounds, and we therefore propose that the cheetah powers acceleration using its extensive back musculature. The cheetahs also had an extremely powerful psoas muscle which could help to resist the pitching moments around the hip associated with fast accelerations. The hindlimb bones were proportionally longer and heavier, enabling the cheetah to take longer strides and potentially resist higher peak limb forces. The cheetah therefore possesses several unique adaptations for high-speed locomotion and fast accelerations, when compared to the racing greyhound. [ABSTRACT FROM AUTHOR]

Aging results in the progressive decline of muscle strength. Interventions to maintain muscle strength may mitigate the age‐related loss of physical function, thus maximizing health span. The work on environmental enrichment (EE), an experimental paradigm recapitulating aspects of an active lifestyle, has revealed EE‐induced metabolic benefits mediated by a brain‐fat axis across the lifespan of mice. EE initiated at 18‐month of age shows a trend toward an increased mean lifespan. While previous work described EE's influences on the aging dynamics of several central‐peripheral processes, its influence on muscle remained understudied. Here, the impact of EE is investigated on motor function, neuromuscular physiology, and the skeletal muscle transcriptome. EE is initiated in 20‐month‐old mice for a five‐month period. EE mice exhibit greater relative lean mass that is associated with improved mobility and hindlimb grip strength. Transcriptomic profiling of muscle tissue reveals an EE‐associated enrichment of gene expression within several metabolic pathways related to oxidative phosphorylation and the TCA cycle. Many mitochondrial‐related genes—several of which participate in the electron transport chain—are upregulated. Stress‐responsive signaling pathways are downregulated because of EE. The results suggest that EE improves motor function—possibly through preservation of mitochondrial function—even late in life. [ABSTRACT FROM AUTHOR]

Goodwin's brush‐tailed mouse (Calomyscus elburzensis Goodwin, 1939) is a poorly known small rodent that occupies rocky habitats in Iran, Turkmenistan, Afghanistan, Pakistan, Azerbaijan, and Syria. Herein, a detailed description of the shape, size, and function of the postcranial skeleton of this species is presented for the first time. Trapping was carried out in eastern Iran between the years 2013 and 2015. Skeletal parts of 24 adult male specimens were removed using the papain digestion protocol, and several postcranial morphological characteristics and measurements were examined. We attempted to achieve a morpho‐functional characterization of Goodwin's brush‐tailed mouse and to match morphological specializations with previous information on the ecology, behavior, and phylogenetic inferences of this rodent. Goodwin's brush‐tailed mouse has extended transverse processes and long zygapophyses in the first five caudal vertebrae along with a good innervation of the caudal vertebrae, which has resulted in a well‐developed basal musculature of the tail. It has extended forelimb, long ilium, and short post‐acetabular part of the innominate bone, loose hip joint with high degree of lateral movement of the hindlimb, and long distal elements of the hindlimb. These features have resulted in fast terrestrial movements in open microhabitats, including climbing and jumping. Although superficial scratching of the ground is observed, the species is incapable of digging burrows. Evaluation of postcranial morphological characteristics and character states further indicated the basal radiation of the genus Calomyscus among other Muroidea. Findings constitute a source of information for morpho‐functional and phylogenetic comparisons between Calomyscidae and other mouse‐like muroids. Research Highlights: Postcranial morphological specializations of Calomyscus elburzensis were matched with information on its ecology and phylogeny.Findings constitute a data set for morpho‐functional and phylogenetic comparisons between Calomyscidae and other rodents. [ABSTRACT FROM AUTHOR]

The traditional focus on morphological rather than mechanical units has obscured some significant functional differences in the hindlimbs of primates. This paper examines the allometric and biomechanical basis for some distinctive proportional differences among pairs of morphological units in the hindlimb, and especially the foot, of cercopithecid primates. Five major conclusions are reached. First, many hindlimb dimensions scale allometrically with body mass to maintain mechanical similarity within taxonomic and locomotor groups. Therefore, the majority of traditional indices which describe the shape of the foot within cercopithecids reveal differences which are primarily a function of size. Second, the hindlimb segments in colobines, and especially in Presbytis, are relatively long, probably to enhance leaping. Third, the major distinction of terrestrial cercopithecines among the features analysed is reduction in the length of the phalanges, due to the reduced importance of grasping during locomotion and the assumption of digitigrady. Fourth, Theropithecus and male Erythrocebus have high crural indices, relative to their body masses, which can facilitate curosoriality. Female E. patas already has a high crural index as a function of its body mass. Fifth, macaques form a distinctive group among cercopithecines, characterized by relatively short hindlimbs. Relatively very short hindlimbs in Macaca fuscata and M. thibetana suggest that climatic conditions can have an added effect on the lengths of the hindlimb segments. In summary, this analysis of the lengths of the hindlimb segments relative to body size reveals taxonomic differences which are due in part to phylogeny, to differences in locomotor behavior, and to substrate use.

Aims: Neuropathic pain after spinal cord injury (SCI) remains a common and thorny problem, influencing the life quality severely. This study aimed to elucidate the reorganization of the primary sensory cortex (S1) and the regulatory mechanism of the lateral parabrachial nucleus (lPBN) in the presence of allodynia or hyperalgesia after left spinal cord hemisection injury (LHS). Methods: Through behavioral tests, we first identified mechanical allodynia and thermal hyperalgesia following LHS. We then applied two‐photon microscopy to observe calcium activity in S1 during mechanical or thermal stimulation and long‐term spontaneous calcium activity after LHS. By slice patch clamp recording, the electrophysiological characteristics of neurons in lPBN were explored. Finally, exploiting chemogenetic activation or inhibition of the neurons in lPBN, allodynia or hyperalgesia was regulated. Results: The calcium activity in left S1 was increased during mechanical stimulation of right hind limb and thermal stimulation of tail, whereas in right S1 it was increased only with thermal stimulation of tail. The spontaneous calcium activity in right S1 changed more dramatically than that in left S1 after LHS. The lPBN was also activated after LHS, and exploiting chemogenetic activation or inhibition of the neurons in lPBN could induce or alleviate allodynia and hyperalgesia in central neuropathic pain. Conclusion: The neuronal activity changes in S1 are closely related to limb pain, which has accurate anatomical correspondence. After LHS, the spontaneously increased functional connectivity of calcium transient in left S1 is likely causing the mechanical allodynia in right hind limb and increased neuronal activity in bilateral S1 may induce thermal hyperalgesia in tail. This state of allodynia and hyperalgesia can be regulated by lPBN. [ABSTRACT FROM AUTHOR]

An 8‐month‐old, entire, male, 32‐kg golden retriever dog was presented with a grade 4/5 right hindlimb lameness. No history of trauma or injury was noted and the clinical symptoms had appeared suddenly. A computed tomography examination of the hindlimbs was performed, and changes in the right stifle joint included moderate joint effusion, synovial thickening, a detached fragment from the medial aspect of the lateral femoral condyle and concurrent changes of the condylar bone. The cortical bone of that area appeared damaged and had lost its smooth margins A cranial cruciate ligament avulsion was later confirmed by arthroscopy. Osteochondrosis dissecans was confirmed histopathologically, based on chondral necrosis and a clear fissure evident in the fragment. Osteochondrosis dissecans is associated with cartilage and bone changes in growing animals. There are known anatomical predilection sites for development of osteochondrosis, one of which is the lateral condyle of the femur. This is the first reported case where the dislodged bone fragment is also the point of origin for the cranial crucial ligament. [ABSTRACT FROM AUTHOR]

As frogs undergo metamorphosis from tadpole to adult, they may be susceptible to decreases in locomotor performance and survival during stages in which the tail and limbs are both present. Because these alternative axial and appendicular propulsive systems might interfere with each other, performance might be better when only one or the other system predominates. This framework, termed the 'adaptive peak hypothesis' emerged from studies of generalist anuran taxa with biphasic life histories in which aquatic larvae transition to terrestrial adults. However, it is not clear that such patterns apply to taxa with different patterns of ontogenetic environmental transitions.We evaluated the relationship between morphology, locomotor performance and survival versus predators across metamorphic stages of a fully aquatic frog, the pipid Xenopus laevis. We measured escape performance from individuals of four developmental stages spanning possession of just a tail, the presence of both tail and legs and resorption of the tail, and then conducted selection trials in which equal numbers of individuals of all stages were exposed to an aquatic predator (cichlid fish). After collecting survivors from these trials, we calculated linear and nonlinear selection gradients for a suite of morphological traits.Unlike generalist frogs, we found that both locomotor performance and survival increased across metamorphic stages of X. laevis. Linear selection gradients favoured tadpoles with longer hindlimbs, longer and narrower bodies, and shorter tails—patterns that generally parallel trends during metamorphic growth. Nonlinear selection showed that longer hindlimbs were favoured as body length increased and the positive effect of forelimb length was reduced as tail length increased.The relationship between hindlimb and body length aligns with expected changes in growth postmetamorphosis where postmetamorphic individuals are expected to have greater survival. However, longer forelimbs are generally associated with decreased locomotor performance, suggesting that alternative mechanisms of selection may be acting on the forelimbs of Xenopus through development.Overall, our results indicate that the generality of the adaptive peak framework, as applied to amphibian metamorphosis, can be impacted by specifics of life history patterns across species. Read the free Plain Language Summary for this article on the Journal blog. [ABSTRACT FROM AUTHOR]

Aims: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with complex aetiology. Despite evidence of neuromuscular junction (NMJ) denervation and 'dying‐back' pathology in models of SOD1‐dependent ALS, evidence in other genetic forms of ALS is limited by a lack of suitable animal models. TDP‐43, a key mediator protein in ALS, is overexpressed in neurons in Thy1‐hTDP‐43WT mice. We therefore aimed to comprehensively analyse NMJ pathology in this model of ALS. Methods: Expression of TDP‐43 was assessed via western blotting. Immunohistochemistry techniques, alongside NMJ‐morph quantification, were used to analyse motor neuron number, NMJ denervation status and terminal Schwann cell morphology. Results: We present a time course of progressive, region‐specific motor neuron pathology in Thy1‐hTDP‐43WT mice. Thy1‐driven hTDP‐43 expression increased steadily, correlating with developing hindlimb motor weakness and associated motor neuron loss in the spinal cord with a median survival of 21 days. Pronounced NMJ denervation was observed in hindlimb muscles, mild denervation in cranial muscles but no evidence of denervation in either forelimb or trunk muscles. NMJ pathology was restricted to motor nerve terminals, with denervation following the same time course as motor neuron loss. Terminal Schwann cells were lost from NMJs in hindlimb muscles, directly correlating with denervation status. Conclusions: Thy1‐hTDP‐43WT mice represent a severe model of ALS, with NMJ pathology/denervation of distal muscles and motor neuron loss, as observed in ALS patients. This model therefore provides an ideal platform to investigate mechanisms of dying‐back pathology, as well as NMJ‐targeting disease‐modifying therapies in ALS. [ABSTRACT FROM AUTHOR]

Immobilization leads to muscle wasting and insulin resistance, particularly during ageing. It has been suggested that undercarboxylated osteocalcin (ucOC) improves muscle mass and glucose metabolism. Bisphosphonates, an anti‐osteoporosis treatment, might protect muscle wasting independent of ucOC. We hypothesize that the combination of ucOC and ibandronate (IBN) treatments has superior protective effects against immobilization‐induced muscle wasting and insulin resistance than either treatment alone. C57BL/6J mice were hindlimb‐immobilized for two weeks, with injections of vehicle, ucOC (90 ng/g daily) and/or IBN (2 μg/g weekly). Insulin/oral glucose tolerance tests (ITT/OGTT) were performed. Immediately after immobilization, muscles (extensor digitorum longus (EDL), soleus, tibialis anterior, gastrocnemius and quadriceps) were isolated and measured for muscle mass. Insulin‐stimulated glucose uptake (EDL and soleus) was examined. Phosphorylation/expression of proteins in anabolic/catabolic pathways were examined in quadriceps. Primary human myotubes derived from older adult muscle biopsies were treated with ucOC and/or IBN, then signalling proteins were analysed. Combined treatment, but not individual treatments, significantly increased the muscle weight/body weight ratio in immobilized soleus (31.7%; P = 0.013) and quadriceps (20.0%; P = 0.0008) muscles, concomitant with elevated p‐Akt (S473)/Akt ratio (P = 0.0047). Combined treatment also enhanced whole‐body glucose tolerance (16.6%; P = 0.0011). In human myotubes, combined treatment stimulated greater activation of ERK1/2 (P = 0.0067 and 0.0072) and mTOR (P = 0.036), and led to a lesser expression of Fbx32 (P = 0.049) and MuRF1 (P = 0.048) than individual treatments. These findings suggest a potential therapeutic role for the ucOC and bisphosphonates combination in protecting against muscle wasting induced by immobilization and ageing. Key points: It has been suggested that undercarboxylated osteocalcin (ucOC) improves muscle mass and glucose metabolism.Bisphosphonates, an anti‐osteoporosis treatment, might protect against muscle wasting independent of ucOC.The combination treatment of ucOC and ibandronate was shown to exert a greater therapeutic effect against immobilization‐induced muscle wasting, and led to greater activation of anabolic pathway and less expression of catabolic signalling proteins in myotubes derived from older adults, compared with individual treatments.The combination treatment was found to improve whole‐body glucose tolerance.Our findings suggest a potential therapeutic role for the ucOC and bisphosphonates combination in protecting against muscle wasting induced by immobilization and ageing. [ABSTRACT FROM AUTHOR]

Background: In non‐lame horses, the tubera sacrale (TS) are usually lower than or, less commonly, equal in height to the withers. Thoracolumbosacral, pelvic and hindlimb posture/conformation may be influenced by musculoskeletal pain, and development and function of epaxial, pelvic and abdominal muscles. Objectives: To investigate relationships between (1) conformation of the withers and pelvis and orthopaedic injuries; (2) tarsal angles and relative heights of the withers and TS. Study design: Retrospective cross‐sectional clinical study. Methods: Horses (n = 193) presented for lameness or poor performance with a conclusive diagnosis based on abolition of clinical signs by diagnostic anaesthesia and imaging were included. Polystyrene hemispheres were adhered to the withers, TS and tubera ischiadica (TI). Lateral photographs were acquired with each horse standing squarely, with the head and neck in a neutral position, the metatarsal regions vertical, aligned with the TI. Relative heights of the withers and TS were determined using ImageJ. A line from the TS to the TI relative to the horizontal defined the pelvic angle. A line from the TS tangential to the lumbar region relative to the horizontal defined the lumbar angle. Measurements were compared across four injury groups consisting of hindlimb proximal suspensory desmopathy, primary sacroiliac joint region pain, a combination of both, and other causes of lameness. Results: The withers height was ≥TS in 138/193 (71.5%) horses; the withers were lower than the TS in 55/193 (28.5%) horses. Pelvic and lumbar angles ranged from 20.0–42.7° (mean 28.9°, SD 3.4°) and 6.3–18.7° (mean 12.2°, SD 2.3°), respectively. No association between measurements and injury groups was determined. Main limitations: There was a lack of non‐lame control horses. It was not possible to differentiate between innate conformation versus acquired posture. Conclusions: Withers height was

Key Clinical Message: Case report summary: A 9–year‐old male castrated domestic shorthair feline was presented to the emergency department with a chief complaint of constipation of 3‐day duration, decreased urination of 1‐day duration, vomiting, and hind limb weakness. Physical examination abnormalities included hypothermia, dehydration, and generalized paresis with inability to stand for a prolonged period of time. Abdominal ultrasonography showed pinpoint hyperechoic foci throughout the hepatic parenchyma, small gas foci circulating within the portal vasculature consistent with emphysematous hepatitis, and mild volume of ascites. Cytology of the ascites was consistent with inflammatory effusion. Hepatic cytology was consistent with mixed inflammation/hepatitis with no apparent cause for inflammation noted. Urine culture yielded a negative result. Surgical liver biopsy and culture were declined by the patient's family. Ultrasound changes were presumed to be most likely secondary to an ascending infection. [ABSTRACT FROM AUTHOR]

Major transformations in the locomotor system of archosaurs (a major clade of reptiles including birds, crocodiles, dinosaurs, and pterosaurs) were accompanied by significant modifications to ankle anatomy. How the evolution of such a complex multi‐joint structure is related to shifts in ankle function and locomotor diversity across this clade remains unclear and weakly grounded in extant experimental data. Here, we used X‐ray Reconstruction of Moving Morphology to reconstruct skeletal motion and quantify the sources of three‐dimensional ankle mobility in the American alligator, a species that retains the ancestral archosaur ankle structure. We then applied the observed relationships between joint excursion and locomotor behaviors to predict ankle function in extinct archosaurs. High‐resolution reconstructions of Alligator skeletal movement revealed previously unseen regionalized coordination among joints responsible for overall ankle rotation. Differences in joint contributions between maneuvers and steady walking parallel transitions in mobility inferred from the ankle structure of fossil taxa in lineages with more erect hind limb postures. Key ankle structures related to ankle mobility were identified in the alligator, which permitted the characterization of ancestral archosaur ankle function. Modifications of these structures provide morphological evidence for functional convergence among sublineages of bird‐line and crocodylian‐line archosaurs. Using the dynamic insight into the internal sources of Alligator ankle mobility and trends among locomotor modes, we trace anatomical shifts and propose a mechanistic hypothesis for the evolution of ankle structure and function across Archosauria. [ABSTRACT FROM AUTHOR]

Lymphangiogenesis is the mechanism by which the lymphatic system develops and expands new vessels facilitating fluid drainage and immune cell trafficking. Models to study lymphangiogenesis are necessary for a better understanding of the underlying mechanisms and to identify or test new therapeutic agents that target lymphangiogenesis. Across the lymphatic literature, multiple models have been developed to study lymphangiogenesis in vitro and in vivo. In vitro, lymphangiogenesis can be modeled with varying complexity, from monolayers to hydrogels to explants, with common metrics for characterizing proliferation, migration, and sprouting of lymphatic endothelial cells (LECs) and vessels. In comparison, in vivo models of lymphangiogenesis often use genetically modified zebrafish and mice, with in situ mouse models in the ear, cornea, hind leg, and tail. In vivo metrics, such as activation of LECs, number of new lymphatic vessels, and sprouting, mirror those most used in vitro, with the addition of lymphatic vessel hyperplasia and drainage. The impacts of lymphangiogenesis vary by context of tissue and pathology. Therapeutic targeting of lymphangiogenesis can have paradoxical effects depending on the pathology including lymphedema, cancer, organ transplant, and inflammation. In this review, we describe and compare lymphangiogenic outcomes and metrics between in vitro and in vivo studies, specifically reviewing only those publications in which both testing formats are used. We find that in vitro studies correlate well with in vivo in wound healing and development, but not in the reproductive tract or the complex tumor microenvironment. Considerations for improving in vitro models are to increase complexity with perfusable microfluidic devices, co‐cultures with tissue‐specific support cells, the inclusion of fluid flow, and pairing in vitro models of differing complexities. We believe that these changes would strengthen the correlation between in vitro and in vivo outcomes, giving more insight into lymphangiogenesis in healthy and pathological states. [ABSTRACT FROM AUTHOR]

In vertebrates, active movement is driven by muscle forces acting on bones, either directly or through tendinous insertions. There has been much debate over how muscle size and force are reflected by the muscular attachment areas (AAs). Here we investigate the relationship between the physiological cross‐sectional area (PCSA), a proxy for the force production of the muscle, and the AA of hindlimb muscles in Nile crocodiles and five bird species. The limbs were held in a fixed position whilst blunt dissection was carried out to isolate the individual muscles. AAs were digitised using a point digitiser, before the muscle was removed from the bone. Muscles were then further dissected and fibre architecture was measured, and PCSA calculated. The raw measures, as well as the ratio of PCSA to AA, were studied and compared for intra‐observer error as well as intra‐ and interspecies differences. We found large variations in the ratio between AAs and PCSA both within and across species, but muscle fascicle lengths are conserved within individual species, whether this was Nile crocodiles or tinamou. Whilst a discriminant analysis was able to separate crocodylian and avian muscle data, the ratios for AA to cross‐sectional area for all species and most muscles can be represented by a single equation. The remaining muscles have specific equations to represent their scaling, but equations often have a relatively high success at predicting the ratio of muscle AA to PCSA. We then digitised the muscle AAs of Coelophysis bauri, a dinosaur, to estimate the PCSAs and therefore maximal isometric muscle forces. The results are somewhat consistent with other methods for estimating force production, and suggest that, at least for some archosaurian muscles, that it is possible to use muscle AA to estimate muscle sizes. This method is complementary to other methods such as digital volumetric modelling. [ABSTRACT FROM AUTHOR]

Background and Purpose: Capillary arterialization, characterized by the coverage of pre‐existing or nascent capillary vessels with vascular smooth muscle cells (VSMCs), is critical for the development of collateral arterioles to improve post‐ischaemic blood flow. We previously demonstrated that the inhibition of transient receptor potential 6 subfamily C, member 6 (TRPC6) channels facilitate contractile differentiation of VSMCs under ischaemic stress. We here investigated whether TRPC6 inhibition promotes post‐ischaemic blood flow recovery through capillary arterialization in vivo. Experimental Approach: Mice were subjected to hindlimb ischaemia by ligating left femoral artery. The recovery rate of peripheral blood flow was calculated by the ratio of ischaemic left leg to non‐ischaemic right one. The number and diameter of blood vessels were analysed by immunohistochemistry. Expression and phosphorylation levels of TRPC6 proteins were determined by western blotting and immunohistochemistry. Key Results: Although the post‐ischaemic blood flow recovery is reportedly dependent on endothelium‐dependent relaxing factors, systemic TRPC6 deletion significantly promoted blood flow recovery under the condition that nitric oxide or prostacyclin production were inhibited, accompanying capillary arterialization. Cilostazol, a clinically approved drug for peripheral arterial disease, facilitates blood flow recovery by inactivating TRPC6 via phosphorylation at Thr69 in VSMCs. Furthermore, inhibition of TRPC6 channel activity by pyrazole‐2 (Pyr2; BTP2; YM‐58483) promoted post‐ischaemic blood flow recovery in Apolipoprotein E‐knockout mice. Conclusion and Implications: Suppression of TRPC6 channel activity in VSMCs could be a new strategy for the improvement of post‐ischaemic peripheral blood circulation. [ABSTRACT FROM AUTHOR]

Background. Knowledge of the musculoskeletal loading conditions during strength training is essential for performance monitoring, injury prevention, rehabilitation, and training design. However, measuring muscle forces during exercise performance as a primary determinant of training efficacy and safety has remained challenging. Methods. In this paper we review existing computational techniques to determine muscle forces in the lower limbs during strength exercises in vivo and discuss their potential for uptake into sports training and rehabilitation. Results. Muscle forces during exercise performance have almost exclusively been analysed using so-called forward dynamics simulations, inverse dynamics techniques, or alternative methods. Musculoskeletal models based on forward dynamics analyses have led to considerable new insights into muscular coordination, strength, and power during dynamic ballistic movement activities, resulting in, for example, improved techniques for optimal performance of the squat jump, while quasi-static inverse dynamics optimisation and EMG-driven modelling have helped to provide an understanding of low-speed exercises. Conclusion. The present review introduces the different computational techniques and outlines their advantages and disadvantages for the informed usage by nonexperts. With sufficient validation and widespread application, muscle force calculations during strength exercises in vivo are expected to provide biomechanically based evidence for clinicians and therapists to evaluate and improve training guidelines. [ABSTRACT FROM AUTHOR]

Background: The clinical examination of lame horses in real world settings often requires the use of sloped surfaces. Objectives: This pilot study aimed to evaluate the effects of uphill and downhill locomotion on asymmetry in horses with naturally occurring lameness affecting forelimbs and hindlimbs. Methods: Ten horses (8–19 years) with forelimb lameness and eight horses (7–16 years) with hindlimb lameness were fitted with inertial sensors at the poll, withers, sacrum and both tuber coxae. Data were collected whilst the horses were trotted in hand on a level surface (<0.7%), as well as up and down a minor slope of 2.4%. Data were collected for a minimum of 25 strides at each incline type. Effect of incline was compared using a repeated measures ANOVA and, where significant, a subsequent Bonferroni's multiple comparisons. Results: Of the horses with hindlimb lameness, there were reductions in asymmetry seen during downhill locomotion when compared with trotting on the flat (flat: 6.6 ± 4.4 mm to downhill: 1.9 ± 2.9 mm; p = 0.015) and when compared with uphill locomotion (8.4 ± 4.3 mm; p = 0.007). Horses with forelimb lameness showed no significant difference in asymmetry. However, there were considerable changes in poll asymmetry (>20 mm) among conditions in individual horses. Two horses with hindlimb lameness and two horses with forelimb lameness switched asymmetry between left and right by changing incline. Conclusions: These results confirm that incline can be an influential factor in the assessment of lame horses. Further work is justified to elucidate the types of pathology associated with the most relevant changes in asymmetry which would allow the use of an incline to prioritise a list of differential diagnoses. [ABSTRACT FROM AUTHOR]

Continuous, real‐time monitoring of biomarkers associated with local regions of the body can enhance both temporal and dimensional accuracy of proactive treatment to acute syndromes for critical illnesses, especially peripheral artery diseases. Conventional health monitors often face grand challenges in leveraging deep‐tissue sensing capability with a safe and compatible biointerface. Optical‐based noninvasive monitors may lack the ability to detect oximetry under subcutaneous fatty tissue due to the light scattering and absorption; implantables offer targeted sensing at depth, but may induce infection and inflammation. This report puts forward a wireless, wearable deep‐tissue sensing patch by incorporating biocompatible microneedle waveguides at the sensing interface, to bypass the light extinction in epidermic and dermic tissue and enable the tracking of oximetry at muscular tissue. The sensing patch provides multiple physiological measurements at the sensing area, including tissue oximetry, pulse oximetry, heart pulsation, and respiratory activities with a wireless platform for uninterrupted data advertising and processing to enable real‐time diagnostic analysis. The mechanical and thermal characterizations of the sensing patch with the microneedle waveguides validate the durable and safe operation at the skin interface. In vivo study with animal models of hindlimb ischemia demonstrates the high sensitivity and timely response of the sensing patch as muscle tissue hypoxia emerges. [ABSTRACT FROM AUTHOR]

The Mechanostat Theory states that osteocytes sense both the intensity and directionality of the strains induced by mechanical usage and modulate the bone design accordingly. In long bones, this process may adapt anterior‐posterior and lateral‐medial strength to their mechanical environment showing regional specificity. Anuran species are ideal for analyzing the muscle‐bone relationships related to the different mechanical stresses induced by their many locomotor modes and habitat uses. This work aimed to explore the relationships between indicators of the force of the most relevant muscles to locomotion and the mechanical properties of femur and tibia fibula in preserved samples of three anuran species with different habitat use (aquatic, arboreal) and locomotion modes (swimmer, jumper, walker/climber). For that purpose, we measured the anatomical cross‐sectional area of each dissected muscle and correlated it with the moments of inertia and bone strength indices. Significant, species‐specific covariations between muscle and bone parameters were observed. Pseudis platensis, the aquatic swimmer, showed the largest muscles, followed by Boana faber, the jumper and Phyllomedusa sauvagii, the walker/climber. As we expected, bigger muscles correlate with bone parameters in all the species. Nevertheless, smaller muscles also play an important role in bone design. In aquatic species, muscle interaction enhances mostly lateral bending strength throughout the femur and lateral and antero‐posterior bending strength in the tibia fibula. In the jumper species, muscles affected the femur and tibia fibula mostly in anterior‐posterior bending. In the walker/climber species, responses involving both antero‐posterior and lateral bending strengths were observed in the femur and tibia fibula. These results show that bones will be more or less resistant to lateral and antero‐posterior bending according to the different mechanical challenges of locomotion in aquatic vs. arboreal habitats. This study provides new evidence of the muscle‐bone relationships in three frog species associated with their different locomotion and habitat uses, highlighting the crucial role of muscle in determining the architectural properties of bones. [ABSTRACT FROM AUTHOR]

We describe the most complete postcranial remains of a pathological, large‐bodied sabretooth from the Lower Pliocene site of Langebaanweg 'E' Quarry (South Africa). The skeleton consists of hind limb and vertebral elements that exhibit distinctive exostoses, osteophytes and eburnation. We performed a quantitative morphological comparison of the new postcranial remains found in Langebaanweg, with other Neogene and Quaternary sabretooth and non‐sabretooth felids, consisting of the genera Amphimachairodus, Machairodus, Lokotunjailurus, Dinofelis, Panthera, Homotherium and Smilodon from several sites in Africa, Europe and North America, using principal component analysis and Mosimann transformations. Although the pathological deformation of the remains distorted some of the linear measurements, most of the analysed variables do not contain pathological features, and strongly indicate that the Langebaanweg sabretooth is morphologically closer to Machairodus aphanistus and Lokotunjailurus emageritus than it is to Amphimachairodus giganteus. This indicates that the remains could belong to an undetermined sabretooth species from the Langebaanweg locality. The observed pathologies in the foot and lumbar spine are consistent with diagnostic criteria for severe osteoarthritis (due to maturity), which would have limited limb mobility with severe consequences for hunting success. [ABSTRACT FROM AUTHOR]

Chloramphenicol is a broad spectrum antibiotic that has been increasingly utilised since the emergence of methicillin-resistant staphylococcal infections. Due to toxicities in humans, use of the drug has been limited. In dogs, gastrointestinal signs are common adverse events described, and bone marrow suppression is possible. The aim of this study was to evaluate the adverse events associated with chloramphenicol in dogs seen by one specialty practice from January 2007 through June 2013. The database was searched for all dogs prescribed chloramphenicol during the time period. Dosage, length of treatment, age and body weight of the dogs were recorded as well as any adverse events that occurred during treatment. A total of 105 cases were evaluated. Thirty-nine dogs experienced at least one adverse event while on the medication. The most commonly noted were gastrointestinal signs and hindlimb weakness. The mean body weight for dogs with hindlimb weakness was 35.3 kg, which was significant. Resolution was documented in 54 per cent of cases when the drug was discontinued. Methicillin-resistant Staphylococcus pseudintermedius on bacterial culture was listed as the reason for chloramphenicol use in 76 per cent of the cases. Based on this information, further prospective studies are recommended to evaluate the reproducibility of this report. [ABSTRACT FROM AUTHOR]

The knowledge of anatomy and imaging exams emerges as an important tool in the study of evolutionary processes of a species, in the elaboration of diagnosis, and the successful choice of the appropriate clinical and surgical procedures. Therefore, this study aims to describe the osteology of the hind limb of Sapajus libidinosus by means of gross, radiographic, and tomographic images. Four cadavers were used in the macroscopic analysis and five animals for the imaging exams, of which four were eventually euthanized and added to the macroscopic study. For imaging exams, they were kept anesthetized. All bones of the hind limb were documented, their structures were described, and compared with data in the literature from human and nonhuman primates. We have performed Student's t test for independent samples. There was no statistical difference between the sexes regarding the length of the hind limb bones. The coxal bone was largely well described using imaging methods. A small penile bone was present at the tip of the penis and it could be identified by all analysis methods. The femur, as well as the tibia and fibula, were not well portrayed in their proximal and distal epiphyses by radiography (Rx). However, they were well identified on tomography. No third trochanter was observed in the femur and the patella had a triangular shape. All the structures described by gross anatomy of the tarsus and metatarsus could be identified by Rx and tomography. More subtle structures, such as the popliteal notch on the tibia, and the gluteal tuberosity pectineal line and facies aspera on the coxal bone, were not identified by medical imaging. S. libidinosus presented anatomical characteristics that were similar to those of larger New World and Old World monkeys, including man. This suggests it's value as an experimental model for studies in recent primates. Research Highlights: A small penile bone is present at the end of the penis. It showed morphological differences between young and adult animals, and could be identified macroscopically, through radiography and by different tomographic methods.Sapajus libidinosus showed anatomical characteristics more similar to larger New World primates, as well as to man and Old World primates, being an excellent indicator of an experimental model for studies in recent primates. [ABSTRACT FROM AUTHOR]

Sauropodomorph dinosaurs include the largest terrestrial animals that ever lived on Earth. The early representatives of this clade were, however, relatively small and partially to totally bipedal, conversely to the gigantic and quadrupedal sauropods. Although the sauropod bauplan is well defined, notably by the acquisition of columnar limbs, the evolutionary sequence leading to its emergence remains debated. Here, we aim to tackle this evolutionary episode by investigating shape variation in the six limb long bones for the first time using three‐dimensional geometric morphometrics. The morphological features of the forelimb zeugopod bones related to the sauropod bauplan tend to appear abruptly, whereas the pattern is more gradual for the hindlimb zeugopod bones. The stylopod bones tend to show the same pattern as their respective zeugopods. The abrupt emergence of the sauropod forelimb questions the locomotor abilities of non‐sauropodan sauropodomorphs inferred as quadrupeds. Features characterizing sauropods tend to corroborate a view of their locomotion mainly based on stylopod retraction. An allometric investigation of the shape variation in accordance with size highlight differences in hindlimb bone allometries between the sauropods and the non‐sauropodan sauropodomorphs. These differences notably correspond to an unexpected robustness decrease trend in the sauropod hindlimb zeugopod. In addition to forelimb bones that appear to be proportionally more gracile than in non‐sauropodan sauropodomorphs, sauropods may have relied on limb architecture and features related to the size increase, rather than general robustness, to deal with the role of weight‐bearing. [ABSTRACT FROM AUTHOR]

Ostriches and emus are among the largest extant birds and are frequently used as modern analogs for the growth dynamics of non‐avian theropod dinosaurs. These ratites quickly reach adult size in under 1 year, and as such do not typically exhibit annually deposited growth marks. Growth marks, commonly classified as annuli or lines of arrested growth (LAGs), represent reduced or halted osteogenesis, respectively, and their presence demonstrates varying degrees of developmental plasticity. Growth marks have not yet been reported from ostriches and emus, prompting authors to suggest that they have lost the plasticity required to deposit them. Here we observe the hind limb bone histology of three captive juvenile emus and one captive adult ostrich. Two of the three juvenile emus exhibit typical bone histology but the third emu, a 4.5‐month‐old juvenile, exhibits a regional arc of avascular tissue, which we interpret as a growth mark. As this mark is not present in the other two emus from the same cohort and it co‐occurs with a contralateral broken fibula, we suggest variable biomechanical load as a potential cause. The ostrich exhibits a complete ring of avascular, hypermineralized bone with sparse, flattened osteocyte lacunae. We identify this as an annulus and interpret it as slowing of growth. In the absence of other growth marks and lacking the animal's life history, the timing and cause of this ostrich's reduced growth are unclear. Even so, these findings demonstrate that both taxa retain the ancestral developmental plasticity required to temporarily slow growth. We also discuss the potential challenges of identifying growth marks using incomplete population data sets and partial cortical sampling. [ABSTRACT FROM AUTHOR]

Limb ischemia occurs due to obstruction of blood perfusion to lower limbs, a manifestation that is associated with peripheral artery disease (PAD). Angiogenesis is important for adequate oxygen delivery. The present study investigated a potential role for chrysin, a naturally occurring flavonoid, in promoting angiogenesis in hindlimb ischemia (HLI) rat model. Rats were allocated into four groups: (1) sham‐operated control, (2) HLI: subjected to unilateral femoral artery ligation, (3) HLI + chrysin: received 100 mg/kg, i.p. chrysin immediately after HLI, and (4) HLI + chrysin + rapamycin: received 6 mg/kg/day rapamycin i.p. for 5 days then subjected to HLI and dosed with 100 mg/kg chrysin, i.p. Rats were killed 18 h later and gastrocnemius muscles were collected and divided into parts for (1) immunohistochemistry detection of CD31 and CD105, (2) qRT‐PCR analysis of eNOS and VEGFR2, (3) colorimetric analysis of NO, (4) ELISA estimation of TGF‐β, VEGF, ATG5 and Beclin‐1, and (5) Western blot analysis of p‐PI3K, PI3K, p‐Akt, Akt, p‐mTOR, mTOR, and HIF‐1α. Chrysin significantly enhanced microvessels growth in HLI muscles as indicated by increased CD31 and CD105 levels and decreased TGF‐β. Chrysin's proangiogenic effect is potentially mediated by increased VEGF, VEGFR2 and activation of PI3K/AKT/mTOR pathway, which promoted eNOS and NO levels as it was reversed by the mTOR inhibitor, rapamycin. Chrysin also inhibited autophagy as it decreased ATG5 and Beclin‐1. The current study shows that chrysin possesses a proangiogenic effect in HLI rats and might be useful in patients with PAD. [ABSTRACT FROM AUTHOR]

Xenopus laevis tadpoles possess regenerative capacity in their hindlimb buds at early developmental stages (stages ~52–54); they can regenerate complete hindlimbs with digits after limb bud amputation. However, they gradually lose their regenerative capacity as metamorphosis proceeds. Tadpoles in late developmental stages regenerate fewer digits (stage ~56), or only form cartilaginous spike without digits or joints (stage ~58 or later) after amputation. Previous studies have shown that administration of fibroblast growth factor 10 (FGF10) in late‐stage (stage 56) tadpole hindlimb buds after amputation can improve their regenerative capacity, which means that the cells responding to FGF10 signaling play an important role in limb bud regeneration. In this study, we performed single‐cell RNA sequencing (scRNA‐seq) of hindlimb buds that were amputated and administered FGF10 by implanting FGF10‐soaked beads at a late stage (stage 56), and explored cell clusters exhibiting a differential gene expression pattern compared with that in controls treated with phosphate‐buffered saline. The scRNA‐seq data showed expansion of fgf8‐expressing cells in the cluster of the apical epidermal cap of FGF10‐treated hindlimb buds, which was reported previously, indicating that the administration of FGF10 was successful. On analysis, in addition to the epidermal cluster, a subset of myeloid cells and a newly identified cluster of steap4‐expressing cells showed remarkable differences in their gene expression profiles between the FGF10‐ or phosphate‐buffered saline‐treatment conditions, suggesting a possible role of these clusters in improving the regenerative capacity of hindlimbs via FGF10 administration. [ABSTRACT FROM AUTHOR]

Prolonged tourniquet use can lead to tissue ischemia and can cause progressive muscle and nerve injuries. Such injuries are accompanied by calpain activation and subsequent Wallerian‐like degeneration. Several known inhibitors, including leupeptin, are known to impede the activity of calpain and associated tissue damage. We hypothesize that employment of leupeptin in a rat model of prolonged hind limb ischemia can mitigate muscle and nerve injuries. Sprague–Dawley rats (n = 10) weighing between 300–400 g were employed in this study. Their left hind limbs were subjected to blood flow occlusion for a period of 2‐h using a neonatal blood pressure cuff. Five rats were given twice weekly intramuscular leupeptin injections, while the other five received saline. After 2 weeks, the animals were euthanized, their sciatic nerves and gastrocnemius muscles were harvested, fixed, stained, and analyzed using NIH Image J software. The administration of leupeptin resulted in larger gastrocnemius muscle fiber cross‐sectional areas for the right (non‐tourniquet applied) hindlimb as compared to that treated with the saline (p = 0.0110). However, no statistically significant differences were found between these two groups for the injured left hindlimb (p = 0.1440). With regards to the sciatic nerve cross‐sectional areas and sciatic functional index, no differences were detected between the leupeptin and control treated groups for both the healthy and injured hindlimbs. This research provides new insights on how to employ leupeptin to inhibit the degenerative effects of calpain and preserve tissues following ischemia resulting from orthopedic or plastic surgery procedures. [ABSTRACT FROM AUTHOR]

The last common ancestor of birds and crocodylians plus all of its descendants (clade Archosauria) dominated terrestrial Mesozoic ecosystems, giving rise to disparate body plans, sizes, and modes of locomotion. As in the fields of vertebrate morphology and paleontology more generally, studies of archosaur skeletal structure have come to depend on tools for acquiring, measuring, and exploring three‐dimensional (3‐D) digital models. Such models, in turn, form the basis for many analyses of musculoskeletal function. A set of shared conventions for describing 3‐D pose (joint or limb configuration) and 3‐D kinematics (change in pose through time) is essential for fostering comparison of posture/movement among such varied species, as well as for maximizing communication among scientists. Following researchers in human biomechanics, we propose a standard methodological approach for measuring the relative position and orientation of the major segments of the archosaur pelvis and hindlimb in 3‐D. We describe the construction of anatomical and joint coordinate systems using the extant guineafowl and alligator as examples. Our new standards are then applied to three extinct taxa sampled from the wider range of morphological, postural, and kinematic variation that has arisen across >250 million years of archosaur evolution. These proposed conventions, and the founding principles upon which they are based, can also serve as starting points for measuring poses between elements within a hindlimb segment, for establishing coordinate systems in the forelimb and axial skeleton, or for applying our archosaurian system more broadly to different vertebrate clades. [ABSTRACT FROM AUTHOR]

Background: Cranial cruciate ligament (CCL) disease remains one of the most common hindlimb orthopaedic conditions seen in dogs, and although surgical management provides good outcomes, prevention remains the holy grail. Aim of the article: This article presents a review of the current evidence and what has changed in the past 10 years to aid practitioners in decision‐making on the management of dogs with CCL disease. [ABSTRACT FROM AUTHOR]

Nine ferrets (Mustela putorius furo) were diagnosed with systemic granulomatous inflammatory syndrome between 2005 and 2006. Common signs included diarrhoea, lethargy, weight loss, and weakness in the hindlimbs. Pathological findings consisted of mesenteric lymphadenopathy, splenomegaly, hypergammaglobulinaemia and non-regenerative anaemia. The condition was progressive and fatal in all the cases. [ABSTRACT FROM AUTHOR]

The clinical signs and diagnostic imaging of two adult llamas with severe metatarsophalangeal valgus angular limb deformity causing metatarsophalangeal instability, severe osteoarthritis and marked bilateral hindlimb lameness are described. The metatarsophalangeal axis was corrected and arthrodesis of the metatarsophalangeal joint was achieved by distal medial metatarsal condylectomy and the medial application of a custom-made angled 4·5 mm dynamic compression plate. A secure construct with normal limb angulation and a good biomechanical outcome was achieved in each of the hindlimbs of both llamas. The development and final dimensions of the implants are described to assist decision making during the evaluation of the surgical management of such cases. [ABSTRACT FROM AUTHOR]

Experimental analyses of posttraumatic knee arthrofibrosis utilize a rabbit model as a gold standard. However, a rodent model of arthrofibrosis offers many advantages including reduced cost and comparison with other models of organ fibrosis. This study aimed to characterize the biomechanical, histological, and molecular features of a novel posttraumatic model of arthrofibrosis in rats. Forty eight rats were divided into two equal groups. An immobilization procedure was performed on the right hind limbs of experimental rats. One group was immobilized for 4 weeks and the other for 8 weeks. Both groups were remobilized for 4 weeks. Limbs were studied biomechanically via assessment of torque versus degree of extension, histologically via whole knee specimen, and molecularly via gene expression of posterior capsular tissues. Significant differences were observed between experimental and control limbs at 4 N‐cm of torque in the 4‐week (knee extension: 115° ± 8° vs. 169° ± 17°, respectively; p = 0.007) and 8‐week immobilization groups (knee extension: 99° ± 12° vs. 174° ± 9°, respectively; p = 0.008). Histologically, in each group experimental limbs demonstrated increased posterior capsular thickness and total area of tissue when compared to control limbs (p < 0.05). Gene expression values evaluated in each group were comparable. This study presents a novel rat model of arthrofibrosis with severe and persistent knee contractures demonstrated biomechanically and histologically. Statement of clinical significance: Arthrofibrosis is a common complication following contemporary total knee arthroplasties. The proposed model is reproducible, cost‐effective, and can be employed for translational investigations studying the pathogenesis of arthrofibrosis and efficacy of neoadjuvant pharmacologic agents. [ABSTRACT FROM AUTHOR]

This study investigated the eating quality of dry aged lamb using four cooking methods. A total of 28 lamb hind legs were selected and assigned randomly into wet aging, dry aging at 80% relative humidity (RH80 dry aging), and dry aging at 60% relative humidity (RH60 dry aging). The samples were aged for 0, 7, 14 days at 4°C and cooked using four cooking methods of hot pot, stir fry, grill, boiling to analyze cooking loss, texture profile, volatile compounds, taste compounds, and sensory characteristics. The tenderness of dry aged lamb was improved from 0 to 14 d except RH80 dry aged lamb for 7 d using stir fry. The lamb in RH80 dry aging for 7 and 14 d had rich aromatic compounds than wet aged lamb. The results of sensory evaluation showed that samples in RH80 dry aging for 7 d was fit for stir fry, boiling, and grill and it was fit for hot pot and grill after aging for 14 d. It can be concluded that the eating quality of RH80 dry aged lamb for 7 and 14 d using four cooking methods was better than RH60 dry aged lamb and wet aged lamb. Practical applications: The manuscript describes the eating quality of dry aged lamb using hot pot, stir fry, grill, and boiling cooking methods. The results from this study showed that RH80 dry aged lamb get better meat quality than RH60 dry aged lamb and wet aged lamb in sensory evaluation using four cooking methods, which indicates the potentiality for application of dry aging in Chinese lamb industry. [ABSTRACT FROM AUTHOR]