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OBJECTIVE: To describe the microvascular anatomy of the equine hind limb suspensory ligament. ANIMALS: 18 hind limbs harvested from 9 adult horses euthanized for reasons unrelated to lameness. METHODS: A catheter was placed in the transected cranial tibial artery at the level of the mid-distal tibia for each hind limb and used to inject 120 to 150 mL of contrast medium (2 limbs) to identify principal vasculature using contrast-enhanced CT or India ink (11 limbs) to identify microvasculature using the Spalteholz tissue-clearing technique. Routine histologic evaluation was performed on transverse sections from 4 hind limbs. RESULTS: The hind limb suspensory ligament is principally supplied by branches of the medial and lateral plantar metatarsal arteries and, to a lesser extent, the medial and lateral plantar arteries as well as the associated proximal and distal deep plantar arches. A uniformly distributed intraligamentous microvascular supply was observed without relative deficiencies in vascularity between the proximal, midbody, and distal regions. Histologic examination supported these findings, demonstrating a network of connective tissue surrounding and entering the suspensory ligament containing cross-sections of branches of the principal vasculature. CLINICAL RELEVANCE: The equine hind limb suspensory ligament has a uniformly distributed and abundant microvascular supply throughout its length, with no evidence of relative deficiency of vascular supply in any region. A region of hypovascularity does not appear to be a viable explanation for the high rate of injury to and commonality of lameness associated with the proximal hind suspensory ligament in horses. [ABSTRACT FROM AUTHOR]

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Simple Summary: Ischemia reperfusion injury in skeletal muscle is common, yet the underlying mechanisms are not well understood. Additionally, the role of brain-derived neurotrophic factor and its precursor in skeletal muscle have not been determined. To address this, the present study aimed to investigate the role of pro-brain-derived neurotrophic factor in ischemia reperfusion injury of the hind limb. It was shown that pro-brain-derived neurotrophic factor is significantly upregulated in skeletal muscle following injury, and that in the absence of skeletal muscle pro-brain-derived-neurotrophic factor signaling, the inflammatory response was significantly blunted. The overall conclusion is that pro-brain-derived neurotrophic factor is essential to the inflammatory response following ischemia reperfusion injury. Brain-derived neurotropic factor (BDNF) has been shown to be expressed in many nonneuronal tissues including skeletal muscle. Skeletal muscle BDNF has been studied regarding its function in metabolism and exercise; however, less is known about its role in skeletal muscle injury. The precursor to BDNF, proBDNF, has an unknown role in skeletal muscle. The levels of proBDNF, mature BDNF, and their receptors were compared in the skeletal muscle and brain tissues of C57BL/6J mice. Tourniquet-induced hind limb ischemia-reperfusion injury was used to assess the function of skeletal muscle-derived proBDNF in skeletal muscle injury. Skeletal muscle-specific knockout of BDNF and pharmacological inhibition of p75NTR, the proBDNF receptor, were used to determine the role of proBDNF–p75NTR signaling. We show for the first time that proBDNF is the predominantly expressed form of BDNF in skeletal muscle and that proBDNF is significantly upregulated in skeletal muscle following hind limb ischemia-reperfusion injury. Skeletal muscle-specific knockout of BDNF blunted the inflammatory response in the injured tissue and appears to be mediated by the proBDNF–p75NTR pathway, as shown by the pharmacological inhibition of p75NTR. These findings suggest that skeletal muscle proBDNF plays a critical role in driving the inflammatory response following skeletal muscle injury. [ABSTRACT FROM AUTHOR]

IntroductionDogs with medial patellar luxation can be affected by pelvic limb deformities whose corrective osteotomies and associated biomechanical rebalancing might provide higher success rates than standard surgical procedures limited to the stifle joint. In bilaterally affected canine patients, comparison with the contralateral normal limb is impossible. Reference values are useful for orthopedic decision-making. Inconsistency of published reference values might depend on methodology or canine breed. We hypothesized that canine pelvic limb alignment is breed-specific.MethodsCT scans of 42 pelvic limbs of dog breeds predisposed for medial patellar luxation, with an orthotopic patellar position and stability were studied. Several angleswere measured with an open-source 3D Slicer plugin using vector calculations. The breeds were compared with a general linear model with a Bonferonni adjustment using SPSS.ResultsChihuahuas, Pomeranians, Jack Russel Terriers, Pugs, French Bulldogs, Maltese were examined. In the order of the listed breeds, the angles were as follows: 28.3°±10.7°, 20.1°±2.9°, 35.4°±6.9°, 32.8°±3.0°, 19.0°±7.1°, 26.6°±5.3° for the antetorsion, 5.3°±1.8°, 2.8°±2.8°, 8°±4.4°, 3.8 °±3.1°, 4.7°±3.3°, 2.3°±3.3° for the femoral varus, of −5.5°±6.2°, 1.1°±4.1°, −5.2°±9.5°, 6.1°±8.0°, −0.1°±5.9°, −9.2°±4.7° for the tibial torsion, 2.0°±2.9°, 2.1°±2.7°, 6.4°±6.8°, 0.0°±5.7°, 3.0°±5.8°, 8.8°±8.6° for the tibial valgus, 1.2°±10.4°, 1.8°±3.4°, −1.7°±4.9°, −1.7°±9.4°, 5.1°±8.8°, −0.2°±8.6° for the femorotibial rotation and −3.4°±2.2°, 1.1°±4.1°, −2.8°±3.4°, −5.2°±4.0°, −2.1°±4.4°, −5.4°±3.7° for the tibiotalar rotation. There were significant differences between breeds in femoral torsion, femoral varus, and tibial torsion angles, but no significant differences in tibial valgus, femorotibial, and tibiotalar rotation angles.DiscussionOur hypothesis is therefore partially correct. Our results are limited to small dogs prone to medial patellar luxation and might not be generalized. To establish robust reference values larger case numbers and more breeds should be evaluated. In conclusion, canine pelvic limb alignment reference values for small dogs with a predisposition for medial patellar luxation should be considered breed-specific.

Simple Summary: Wounds of the extremities in cats accompanied by considerable loss of substance are frequently encountered in current practice and their therapeutic management and choice of closing method is a challenge for the veterinarian while also exerting an influence on the evolution of healing. In this case report, a new complementary technique is proposed, which involved supporting a skin graft using ozone therapy both before and after applying the graft. This approach accelerated the recovery of the patient and no complications were observed. This case report describes a new therapeutic approach for a domestic shorthaired female cat, who has an extensive posttraumatic wound in the right hind limb. After patient stabilization, general anesthesia was started and the wound was cleaned and debrided of devitalized tissues, followed by the application of ozone therapy and bandage. Eight sessions of ozone therapy were performed for 17 days until the application of the skin graft. Three more sessions of ozone therapy were performed every 3 days postoperatively. The bagging method and the perilesional infiltration method were used. The ozone therapy ensured an accelerated recovery of the patient without any complications. According to our knowledge, this is the first case report with the use of ozone therapy to support a free skin graft in a cat. The new therapeutic approach could be used to accelerate healing of the wounds with a significant lack of substance, by supporting pre- and post-operative skin grafts. [ABSTRACT FROM AUTHOR]

Reperfusion of ischemic skeletal muscle triggers oxidative stress and an immediate inflammatory reaction, leading to damage of distant organs such as the lungs. The inflammatory process implicates numerous mediators, including cytokines, chemokines, and arachidonic acid metabolites. In the orchestration of the inflammatory cascade, a critical role is played by the cluster of differentiation-36 receptor (CD36), a scavenger receptor class B protein (SR-B2) which is expressed on macrophages and functions as a Toll-like receptor coreceptor. A mouse model of hind limb ischemia-reperfusion has been used to investigate the interplay between CD36 signaling and remote inflammation: leukocyte recruitment, regulation of the nucleotide-binding domain leucin-rich repeat and pyrin-containing receptor 3 (NLRP3) inflammasome, and release of nuclear factor-kappa B (NF-ĸB) and arachidonic acid metabolites. Levels of reactive oxygen species, inflammatory mediators, and gene expression were measured in blood and lung tissue samples collected from anesthetized mice on which unilateral hind limb ischemia was induced by rubber band constriction for 30 min followed by reperfusion for 3 h. The CD36 modulator EP 80317, a member of the growth hormone releasing peptide 6 family, was employed as a pharmacological agent to mitigate distant lung injury following skeletal limb ischemia-reperfusion. Targeting CD36 on monocytes/macrophages, EP 80317 abated pro-inflammatory signaling and transcriptional activity encompassing lipid and cytokine mediators. Targeting CD36 was shown to offer promise for curtailing tissue injury following hind limb ischemia-reperfusion., (© 2024 The Author(s). Journal of Biochemical and Molecular Toxicology published by Wiley Periodicals LLC.)

This study was performed to provide a description of the normal anatomy of the canine hindlimb veins using helical CT images. The studies of 30 dogs that underwent CT venography with a 64‐slice helical CT scanner were retrospectively reviewed. The dogs were positioned in a head‐first prone or head‐first supine body position. A topogram CT scan was performed from the pelvic limbs cranial to the iliac wings to the tips of the paws. Bolus‐tracking software was used for the dual‐phase angiogram, and contrast medium was administered in a cephalic vein. The venous phase was scanned after a delay time of a few seconds after the arterial phase in a caudocranial direction. Three‐dimensional images were generated using maximum intensity projections and volume rendering technique. Representative images of three of the 30 dogs were selected and anatomic structures labelled. [ABSTRACT FROM AUTHOR]

Brain-derived neurotropic factor (BDNF) has been shown to be expressed in many nonneuronal tissues including skeletal muscle. Skeletal muscle BDNF has been studied regarding its function in metabolism and exercise; however, less is known about its role in skeletal muscle injury. The precursor to BDNF, proBDNF, has an unknown role in skeletal muscle. The levels of proBDNF, mature BDNF, and their receptors were compared in the skeletal muscle and brain tissues of C57BL/6J mice. Tourniquet-induced hind limb ischemia-reperfusion injury was used to assess the function of skeletal muscle-derived proBDNF in skeletal muscle injury. Skeletal muscle-specific knockout of BDNF and pharmacological inhibition of p75NTR, the proBDNF receptor, were used to determine the role of proBDNF–p75NTR signaling. We show for the first time that proBDNF is the predominantly expressed form of BDNF in skeletal muscle and that proBDNF is significantly upregulated in skeletal muscle following hind limb ischemia-reperfusion injury. Skeletal muscle-specific knockout of BDNF blunted the inflammatory response in the injured tissue and appears to be mediated by the proBDNF–p75NTR pathway, as shown by the pharmacological inhibition of p75NTR. These findings suggest that skeletal muscle proBDNF plays a critical role in driving the inflammatory response following skeletal muscle injury.

The exploration of underwater narrow space is of great significance to study the phenomena, process and laws of life in the ocean. The existing underwater robots are not suitable for the underwater narrow area exploration. Beavers use the hind limbs with webfeet to provide power for flexible movement and possess certain underwater operation ability. In this study, based on the bionic prototype of beaver hind limb, the system structure of beaver-like hind limb is designed, and the paddling motion of beaver-like hind limb is realized by combining servos with rope drive. On this basis, the concept of swimming gait is proposed, and swimming process of beavers with one leg and two legs is analyzed, and the movement sequence of various joints and parts in the swimming is studied. Then, the joint angle data of beavers from the video are obtained and a nonlinear oscillation swimming controller based on Fourier technology is proposed to plan the bionic swimming trajectory of the beaver. Further, the swimming efficiency of the beaver-like hind limb is analyzed, and a model of the swimming efficiency is proposed, which can provide a basis for evaluating its swimming effect. Finally, an experimental platform for the swimming of the beaver-like hind limb is set up, and bionic and reconstruction of the swimming gaits are generated by the nonlinear oscillation swimming controller, and the swimming experiment is carried out. The results show that the propulsion efficiencies of the alternate and synchronous bionic gait are 0.5 × 10−3 and 0.6 × 10−3, higher than those of the generated gaits which are 0.2 × 10−3 and 0.3 × 10−3. This verifies the rationality of the beaver swimming, and lays a theoretical foundation for the swimming realization of the beaver-like hind limb, which provides theoretical support for us to further understand the swimming mechanism of the beaver. [ABSTRACT FROM AUTHOR]

Vertebrate musculoskeletal locomotion is realized through lever-arm systems. The instantaneous muscle moment arm (IMMA), which is expected to be under selective pressure and thus of interest for ecomorphological studies, is a key aspect of these systems. The IMMA changes with joint motion. It’s length change is technically difficult to acquire and has not been compared in a larger phylogenetic ecomorphological framework, yet. Usually, proxies such as osteological in-levers are used instead. We used 18 species of the ecologically diverse clade of caviomorph rodents to test whether its diversity is reflected in the IMMA of the hip extensor M. gluteus medius. A large IMMA is beneficial for torque generation; a small IMMA facilitates fast joint excursion. We expected large IMMAs in scansorial species, small IMMAs in fossorial species, and somewhat intermediate IMMAs in cursorial species, depending on the relative importance of acceleration and joint angular velocity. We modeled the IMMA over the entire range of possible hip extensions and applied macroevolutionary model comparison to selected joint poses. We also obtained the osteological in-lever of the M. gluteus medius to compare it to the IMMA. At little hip extension, the IMMA was largest on average in scansorial species, while the other two lifestyles were similar. We interpret this as an emphasized need for increased hip joint torque when climbing on inclines, especially in a crouched posture. Cursorial species might benefit from fast joint excursion, but their similarity with the fossorial species is difficult to interpret and could hint at ecological similarities. At larger extension angles, cursorial species displayed the second-largest IMMAs after scansorial species. The larger IMMA optimum results in powerful hip extension which coincides with forward acceleration at late stance beneficial for climbing, jumping, and escaping predators. This might be less relevant for a fossorial lifestyle. The results of the in-lever only matched the IMMA results of larger hip extension angles, suggesting that the modeling of the IMMA provides more nuanced insights into adaptations of musculoskeletal lever-arm systems than this osteological proxy.

Several species of African mole‐rats use seismic signalling by means of hind foot drumming for communication. The present study aimed to create three‐dimensional reconstructions and compare volumetric measurements of 27 muscles of the hind limb of two drumming (Georychus capensis and Bathyergus suillus) and one non‐drumming (Cryptomys hottentotus natalensis) species of African mole‐rats. Diffusible iodine contrast‐enhanced micro‐computed tomography (diceCT) scans were performed on six specimens per species. Manual segmentation of the scans using VGMAX Studio imaging software allowed for individual muscles to be separated while automatically determining the volume of each muscle. The volume of the individual muscles was expressed as a percentage of the total hind limb volume and statistically compared between species. Subsequently, three‐dimensional reconstructions of these muscles were created. Musculus gracilis anticus had a significantly larger percentage of the total hind limb muscle volume in both drumming species compared to the non‐drumming C. h. natalensis. Furthermore, several hip and knee extensors, namely mm. gluteus superficialis, semimembranosus, gluteofemoralis, rectus femoris and vastus lateralis, had significantly larger muscle volume percentages in the two drumming species (G. capensis and B. suillus) compared to the non‐drumming species. While not statistically significant, G. capensis had larger muscle volume percentages in several key hip and knee extensors compared to B. suillus. Additionally, G capensis had the largest summed percentage of the total hind limb volume in the hip flexor, hip extensor, knee extensor and ankle plantar flexor muscle groups in all the three species. This could be indicative of whole muscle hypertrophy in these muscles due to fast eccentric contractions that occur during hind foot drumming. However, significantly larger muscle volume percentages were observed in the scratch digging B. suillus compared to the other two chisel tooth digging species. Moreover, while not statistically significant, B. suillus had larger muscle volume percentages in several hip extensor and knee flexor muscles compared to G. capensis (except for m. vastus lateralis). These differences could be due to the large relative size of this species but could also be influenced by the scratch digging strategy employed by B. suillus. Therefore, while the action of hind foot drumming seems to influence certain key muscle volumes, digging strategy and body size may also play a role. [ABSTRACT FROM AUTHOR]

The present study was conducted on the pelvic limb bones of a five year old male umbrella cockatoo. The femur was light in weight and presented a straight shaft, two extremities and four surfaces. The proximal extremity had a head with distinct fovea capitis, neck and indistinct trochanter major, while the distal extremity had a trochlea, two condyles and a wide intercondyloid groove. Patella was a small pea-sized sesamoid bone. The tibiotarsus was the largest of the leg bones and was one third longer than femur. It presented a long shaft with distinct fibular crest and two extremities. Both extremities showed medial and lateral condyles. From proximal extremity, the straight cnemial crest extended ventrally. The condyles of distal extremity were separated by intercondyloid fossa and continued caudally to wide grooved trochlea. Instead of extensor canal in other birds, a deep groove was observed. The fibula was with small head and rudimentary shaft and terminated near the middle of the shaft of tibiotarsus. The tarsometatarsus was extremely short. Its shaft presented convex dorsal surface whereas the plantar surface was concave without ridges. The distal extremity presented three articular trochleae. Between the trochlea for third and fourth digits, a bony canal was noticed. The spur core seen in cockerel was not observed in the present study. Four digits from one to four showed zygodactyl type of arrangement and contained two, three, four and five phalanges, respectively. Distal phalanx in each digit was a claw. The light femur and highly reduced fibula in umbrella cockatoo showed adaptations for flight whereas the positioning of the digits showed adaptation for climbing and grasping

Introduction: As the space field has developed and our population ages, people engaged in space travel and those on prolonged bed rest are at increasing risk for bone loss and fractures. Disuse osteoporosis occurs frequently in these instances, for which the currently available anti-osteoporosis agents are far from satisfactory and have undesirable side effects. CEFFE is a cell-free fraction isolated from nanofat that is enriched with a variety of growth factors, and we aim to investigate its potential therapeutic effects on disuse osteoporosis.Methods: A tail suspension–induced osteoporosis model was applied in this study. Three weeks after tail suspension, CEFFE was intraperitoneally injected, and PBS was used as a control. The trabecular and cortical bone microstructures of the tibia in each group were assessed by μCT after 4 weeks of administration. Osteocyte lacunar-canalicularity was observed by HE and silver staining. In vitro, MLO-Y4 cell apoptosis was induced by reactive oxygen species (ROSUP). TUNEL staining and flow cytometry were used to detect apoptosis. CCK-8 was used to detect cell proliferation, and Western blotting was used to detect MAPK signaling pathway changes.Results: CEFFE increased the bone volume (BV/TV) and trabecular number (Tb.N) of the trabecular bone and increased the thickness of the cortical bone. HE and silver staining results showed that CEFFE reduced the number of empty lacunae and improved the lacuna-canalicular structure. CEFFE promoted osteocyte proliferative capacity in a dose-dependent manner. CEFFE protected MLO-Y4 from apoptosis by activating the serine/threonine-selective protein kinase (ERK) signaling pathways.Conclusion: CEFFE attenuated immobilization-induced bone loss by decreasing osteocyte apoptosis. CEFFE increased the survival of osteocytes and inhibited osteocyte apoptosis by activating the ERK signaling pathway in vitro.

This case report describes a new therapeutic approach for a domestic shorthaired female cat, who has an extensive posttraumatic wound in the right hind limb. After patient stabilization, general anesthesia was started and the wound was cleaned and debrided of devitalized tissues, followed by the application of ozone therapy and bandage. Eight sessions of ozone therapy were performed for 17 days until the application of the skin graft. Three more sessions of ozone therapy were performed every 3 days postoperatively. The bagging method and the perilesional infiltration method were used. The ozone therapy ensured an accelerated recovery of the patient without any complications. According to our knowledge, this is the first case report with the use of ozone therapy to support a free skin graft in a cat. The new therapeutic approach could be used to accelerate healing of the wounds with a significant lack of substance, by supporting pre- and post-operative skin grafts.

The complement system has long been recognized as a potential druggable target for a variety of inflammatory conditions. Very few complement inhibitors have been approved for clinical use, but a great number are in clinical development, nearly all of which systemically inhibit complement. There are benefits of targeting complement inhibition to sites of activation/disease in terms of efficacy and safety, and here we describe P-selectin targeted complement inhibitors, with and without a dual function of directly blocking P-selectin-mediated cell-adhesion. The constructs are characterized in vitro and in murine models of hindlimb ischemia/reperfusion injury and hindlimb transplantation. Both constructs specifically targeted to reperfused hindlimb and provided protection in the hindlimb ischemia/reperfusion injury model. The P-selectin blocking construct was the more efficacious, which correlated with less myeloid cell infiltration, but with similarly reduced levels of complement deposition. The blocking construct also improved tissue perfusion and, unlike the nonblocking construct, inhibited coagulation, raising the possibility of differential application of each construct, such as in thrombotic vs. hemorrhagic conditions. Similar outcomes were obtained with the blocking construct following vascularized composite graft transplantation, and treatment also significantly increased graft survival. This is outcome may be particularly pertinent in the context of vascularized composite allograft transplantation, since reduced ischemia reperfusion injury is linked to a less rigorous alloimmune response that may translate to the requirement of a less aggressive immunosuppressive regime for this normally nonlife-threatening procedure. In summary, we describe a new generation of targeted complement inhibitor with multi-functionality that includes targeting to vascular injury, P-selectin blockade, complement inhibition and anti-thrombotic activity. The constructs described also bound to both mouse and human P-selectin which may facilitate potential translation. [ABSTRACT FROM AUTHOR]

The complement system has long been recognized as a potential druggable target for a variety of inflammatory conditions. Very few complement inhibitors have been approved for clinical use, but a great number are in clinical development, nearly all of which systemically inhibit complement. There are benefits of targeting complement inhibition to sites of activation/disease in terms of efficacy and safety, and here we describe P-selectin targeted complement inhibitors, with and without a dual function of directly blocking P-selectin-mediated cell-adhesion. The constructs are characterized in vitro and in murine models of hindlimb ischemia/reperfusion injury and hindlimb transplantation. Both constructs specifically targeted to reperfused hindlimb and provided protection in the hindlimb ischemia/reperfusion injury model. The P-selectin blocking construct was the more efficacious, which correlated with less myeloid cell infiltration, but with similarly reduced levels of complement deposition. The blocking construct also improved tissue perfusion and, unlike the nonblocking construct, inhibited coagulation, raising the possibility of differential application of each construct, such as in thrombotic vs. hemorrhagic conditions. Similar outcomes were obtained with the blocking construct following vascularized composite graft transplantation, and treatment also significantly increased graft survival. This is outcome may be particularly pertinent in the context of vascularized composite allograft transplantation, since reduced ischemia reperfusion injury is linked to a less rigorous alloimmune response that may translate to the requirement of a less aggressive immunosuppressive regime for this normally nonlife-threatening procedure. In summary, we describe a new generation of targeted complement inhibitor with multi-functionality that includes targeting to vascular injury, P-selectin blockade, complement inhibition and anti-thrombotic activity. The constructs described also bound to both mouse and human P-selectin which may facilitate potential translation.

The kinkajou (Potos flavus) is a South and Central American procyonid that can plantarflex and invert its hindfoot around multiple joints in order to fully reverse the hindfoot 180°. However, the myological and osteological adaptions that facilitate this behavior have not been quantified metrically. Osteological correlates of hindfoot reversal have been described in the past, but recent advances in data collection allow for a more comprehensive evaluation of shape differences. Osteological features of the astragalus (talus), calcaneus, and distal tibia of P. flavus were collected and compared to other carnivoran species, including species that are full, partial, and non-reversers of the hindfoot. Hindfoot reversing procyonids were found to possess a relatively smaller medial malleousl, a wider sustentaculum tali, narrower calcaneal tuberosity, and a relatively longer astragalus. In general, the dimensions of the astragalus tend to discriminate hindfoot reversing taxa from other locomotor categories more reliably than the dimensions of the calcaneus or distal tibia. A detailed dissection, description, and documentation of the hind limb muscles in P. flavus was undertaken, and we present the first comprehensive review of its muscular anatomy utilizing muscle maps of the pelvis, femur, tibia, and fibula. Potos flavus has well-developed plantarflexor and invertor muscles, traits which have been hypothesized to characterize species that perform hindfoot reversal. This finding contrasts with other procyonid hindfoot reversing species, such as Bassariscus astutus, which appear to lack muscular adaptations to hindfoot reversal. Muscle semimembranosus, a muscle that facilitates hind limb suspension, was also enlarged. Overall, the hind limb musculature and hindfoot osteology of the kinkajou are consistent with proposed adaptations to hindfoot reversal. [ABSTRACT FROM AUTHOR]

Summary: Vascularized composite allotransplants (VCAs) seem to have several unique features of clinical and experimental importance, including uniquely definable lymphatic drainage that can be easily accessed at the level of ipsilateral regional node beds. Thus, VCA offers a unique opportunity to assess the relative contribution of peripheral and secondary lymphoid tissue to the process of rejection. We transplanted hind limb grafts from C3H donors to six different groups of C57BL/6 recipients: Spleen+Map3k14−/−; Spleen−Map3k14−/−; Spleen+Node−Map3k14−/−; and Spleen−Node−Map3k14−/−. As positive controls, we used Map3k14+/− with or without spleen. Map3k14+/− mice demonstrated an average graft survival of 9.6 and 9.2 days for Spleen− and Spleen+Map3k14+/−, respectively. Rejection in the Map3k14−/− group was considerably delayed (28.4 days, P = 0.002) in all recipients. The Spleen−Map3k14−/− mice rejected their hind limb allografts in an even more delayed fashion compared to Spleen+Map3k14−/− (54.4 days, P = 0.02). Histological analysis of skin showed that acute rejection in both Map3k14+/− mice groups was graded as Banff III or Banff IV. In the Map3k14−/− groups, rejection was graded as Banff III. We demonstrated that in the absence of lymph nodes, grafts reject in a delayed fashion. Also, splenectomy in alymphoplastic mice further extends graft survival, but does not eliminate rejection all together. [ABSTRACT FROM AUTHOR]

Osteological correlates preserve more readily than their soft tissue counterparts in the fossil record; therefore, they can more often provide insight into the soft tissue anatomy of the organism. These insights can in turn elucidate the biology of these extinct organisms. In this study, we reconstruct the pelvic girdle and hind limb musculature of the giant titanosaurian sauropod Dreadnoughtus schrani based on observations of osteological correlates and Extant Phylogenetic Bracket comparisons. Recovered fossils of Dreadnoughtus exhibit remarkably well‐preserved, well‐developed, and extensive muscle scars. Furthermore, this taxon is significantly larger bodied than any titanosaurian for which a myological reconstruction has previously been performed, rendering this contribution highly informative for the group. All 20 of the muscles investigated in this study are sufficiently well supported to enable reconstruction of at least one division, including reconstruction of the M. ischiocaudalis for the first time in a sauropod dinosaur. In total, 34 osteological correlates were identified on the pelvic girdle and hind limb remains of Dreadnoughtus, allowing the reconstruction of 14 muscles on the basis of Level I or Level II inferences (i.e., not Level I' or Level II' inferences). Comparisons among titanosaurians suggest widespread myological variation, yet potential phylogenetic and other paleobiologic patterns are often obscured by fragmentary preservation, infrequent myological studies, and lack of consensus on the phylogenetic placement of many taxa. However, a ventrolateral accessory process is present on the preacetabular lobe of the ilium in all of the largest titanosauriforms that preserve this skeletal element, suggesting that the presence of this process (representing the origin of the M. puboischiofemoralis internus part II) may be associated with extreme body size. By identifying such myological patterns among titanosauriforms, we can begin to address specific evolutionary and biomechanical questions related to their skeletal anatomy, how they were capable of leaving wide‐gauge trackways, and resulting locomotor attributes unique to this clade. [ABSTRACT FROM AUTHOR]

Abstract Background Laboratory rats play a critical role in research because they provide a biological model that can be used for evaluating the affectation of diseases and injuries, and for the evaluation of the effectiveness of new drugs and treatments. The analysis of locomotion in laboratory rats facilitates the understanding of motor defects in many diseases, as well as the damage and recovery after peripheral and central nervous system injuries. However, locomotion analysis of rats remains a great challenge due to the necessity of labor intensive manual annotations of video data required to obtain quantitative measurements of the kinematics of the rodent extremities. In this work, we present a method that is based on the use of a bio-inspired algorithm that fits a kinematic model of the hind limbs of rats to binary images corresponding to the segmented marker of images corresponding to the rat’s gait. The bio-inspired algorithm combines a genetic algorithm for a group of the optimization variables with a local search for a second group of the optimization variables. Results Our results indicate the feasibility of employing the proposed approach for the automatic annotation and analysis of the locomotion patterns of the posterior extremities of laboratory rats. Conclusions The adjustment of the hind limb kinematic model to markers of the video frames corresponding to rat’s gait sequences could then be used to analyze the motion patterns during the steps, which, in turn, can be useful for performing quantitative evaluations of the effect of lesions and treatments on rats models.

Objective- The aim of this study was to determine the age of physical maturity and evaluation of radiology and histology of hind limb ossification centers in pigeon. Design- Fundamental study. Animals- 14 pigeons. Procedures- These pigeons were cultivated in identical and standard conditions and radiological and histological tests performed every 7 days to 91 days. Results- Based on the results of radiology and histology, the hind limb skeletal differentiation in pigeons with the appearance of centers of immature cartilages in diaphyses of the femur, tibiotarsus and tarsometatarsus at the end of the first week and the fibula bone at the end of the third week began. Growth sequences in the femur, tibiotarsus, fibula, tarsometatarsus and digits were observed during different stages. The maximum growth of these bones was related to the periods of maximum cartilage activity and their bone formation, and the femur holds steady its growth relation to the length of the skeletal body of the hind limb, although at the end of the fifth week its growth slowed down. The histological findings were based on the examination of the proximal extremity of the femur. The tissue samples at one day were lack of bone marrow and the bone marrow begins to form at the end of the first week. The presence of epiphyseal growth plate in samples and its bone formation was confirmed on the basis of radiology early in the fifth week. Conclusion and Clinical Relevance- According to this study, the best time to complete the development of bone formation and the formation of all parts of the hind limb skeleton of the pigeon is probably 35 days after the hatch.

The high prevalence of claw lesions in dairy cows necessitates the investigation and hopefully elimination of factors involved in the etiology and pathogenesis of these disorders. Indirect genetic selection for specific conformation traits in feet and legs has been evaluated as a means of improving claw health but to date has not been successful. Claw disorders are commonly discussed in context with unequal claw load, and thus this study was designed to investigate the relationship between hind limb conformation and the load exerted on the respective claws. A total of 36 cows were divided into 3 groups of 12 based on the presence of parallel, straight, and cow-hocked hind limb conformation. The vertical ground reaction forces, claw prints, and mean and maximum pressures under the claws were measured in these cows before and after claw trimming. The principal characteristic of all 3 conformation traits was a significantly higher load on the lateral claws compared with the medial claws, which was least severe in cow-hocked cows. After functional foot trimming, the claws of the cows with straight conformation tended to have the most pronounced disproportion between the loads of the paired claws. Considering that a significantly higher load on the lateral claws occurred with all 3 conformations, the potential for improvement of claw health by means of indirect genetic selection for specific hind limb traits appears limited. [ABSTRACT FROM AUTHOR]

Abstract Background Intravenous regional anaesthesia (IVRA) and hindfoot four-point nerve block anaesthesia (NBA) are recommended for local anaesthesia (LA) in the distal limb of dairy cows. Two studies were conducted to compare the efficacy, time until onset and stress responses to IVRA and NBA in dairy cows. In the first cross-over designed study, eight healthy unsedated German Holstein cows, restrained in lateral recumbency (LR) on a surgical tipping table, were treated with IVRA and NBA using procaine 2% as a local anaesthetic. Distal limb desensitization was tested by electrical (e-), mechanical (m-) and thermal (t-) nociceptive stimulation 10 min before and 15 and 30 min after LA. Hormonal-metabolic (blood concentrations of cortisol, lactate, non-esterified fatty acids, and glucose) and cardio-respiratory (heart and respiratory rate, mean arterial blood pressure) stress responses to treatment were assessed at predetermined intervals. In the second study, six healthy, unsedated German Holstein cows in LR were treated (crossover design) with IVRA and NBA. Short-interval e-stimulation was measured by the time until complete distal limb desensitization. Results In the first study, four of eight cows responded to e-stimulation 15 min after IVRA, while none of the cows treated with NBA responded until the safety cut-off level was reached. E-stimulation revealed complete desensitization of the distal limb 30 min after LA in all cows. Half of the cows did not respond to m- and t-stimulation before LA, so no further evaluation was performed. Stress reactions to IVRA and NBA treatment were similar, but differences may have been masked by stress response to LR restraint. In the second study, complete desensitization was achieved 12.5 min after NBA, while one of the six cows still responded to e-stimulation 20 min after IVRA. Conclusion Hindfoot nerve block anaesthesia and intravenous regional anaesthesia induced complete desensitization of the distal hind limb in dairy cows. However, the anaesthesia onset after NBA was significantly faster than that of IVRA, which may be clinically relevant in the field, particularly when distal limb anaesthesia is required for major claw surgeries under time constraints.

Kiwi (Aves; genus Apteryx) are famous for laying an enormous egg in comparison with their relatively small body size. Considering the peculiar gait of this flightless bird, we suspected the existence of morpho‐functional trade‐offs between reproduction and locomotion. To understand how structural constraints, imposed by a large egg size, might influence the terrestrial locomotion of Apteryx, we analysed the anatomy of the limb osteomuscular system in two species of kiwi (Apteryx mantelli and Apteryx owenii). We performed detailed dissections and brought to light specific anatomical features of kiwi, in comparison with other ratites and neognathous birds. Our osteological study revealed a strongly curved pelvis, a rigid tail, and enlarged ribs. Our myology study showed an unusual location of the caudofemoralis muscle origin and insertion. The insertion of the pars pelvica along the entire caudal face of the femur, contrasts with the proximal insertion usually seen in other birds. Additionally, the pars caudalis originates along the entire tail, whereas it only inserts on the uropygium in the other birds. To interpret these specificities from a functional point of view, we built three‐dimensional osteomuscular models based on computed tomography scans, radiographies and our dissections. We chose three postures associated with reproductive constraints: the standing position of a gravid compared with a non‐gravid bird, as well as the brooding position. The 3D model of the brooding position suggested that the enlarged ribs could support the bodyweight when leaning on the huge egg in both males and females. Moreover, we found that in gravid females, the unusual shape of the pelvis and tail allowed the huge egg to sit ventrally below the pelvis, whereas it is held closer to the rachis in other birds. The specific conformation of the limb and the insertions of the two parses of the caudofemoralis help to maintain the tail flexed, and to keep the legs adducted when carrying the egg. The caudal location of the hip and its flexed position explains the long stance phase during the strange gait of kiwi, revealing the functional trade‐off between reproduction and locomotion in this emblematic New Zealand bird. [ABSTRACT FROM AUTHOR]

The modern dairy industry is plagued by a high prevalence of claw horn lesions in cows, which cause lameness, affect well-being, limit milk production, and are responsible for premature removal of cows from the herd. The lateral hind claws are primarily affected, and this has been linked to a relatively higher load being exerted on the lateral claws when cows shift weight from one hind limb to the other. The vertical ground reaction forces and mean and maximum pressures under the claws were measured in 40 nonlame dairy cows before and during a shift in weight from one hind limb to the other, which was accomplished by applying pressure manually to one side of the pelvis. During square standing on firm ground, about two-thirds of the entire hind limb load was exerted on the 2 lateral claws, and the remaining one-third was exerted on the medial claws combined. At the moment of maximum weight shift, the lateral claw of the loaded limb bore almost two-thirds of the entire load of both hind limbs, with the heel zone bearing almost half of the load of both hind limbs. Subsequently, the load of the lateral claw of the contralateral hind limb decreased, as did the load of both medial claws. Thus, the weight redistribution had occurred predominantly between the lateral hind claws. The high load exerted on a lateral hind claw during weight shift and at maximum weight shift is assumed to play a role in the pathogenesis of claw horn lesions, particularly when accentuated by a softened claw horn and hard flooring. [ABSTRACT FROM AUTHOR]

Humans are unique among terrestrial mammals in our manner of walking and running, reflecting 7 to 8 Ma of musculoskeletal evolution since diverging with the genus Pan. One component of this is a shift in our skeletal muscle biology towards a predominance of myosin heavy chain (MyHC) I isoforms (i.e. slow fibers) across our pelvis and lower limbs, which distinguishes us from chimpanzees. Here, new MyHC data from 35 pelvis and hind limb muscles of a Western gorilla (Gorilla gorilla) are presented. These data are combined with a similar chimpanzee dataset to assess the MyHC I content of humans in comparison to African apes (chimpanzees and gorillas) and other terrestrial mammals. The responsiveness of human skeletal muscle to behavioral interventions is also compared to the human-African ape differential. Humans are distinct from African apes and among a small group of terrestrial mammals whose pelvis and lower limb muscle is slow fiber dominant, on average. Behavioral interventions, including immobilization, bed rest, spaceflight and exercise, can induce modest decreases and increases in human MyHC I content (i.e. -9.3% to 2.3%, n = 2033 subjects), but these shifts are much smaller than the mean human-African ape differential (i.e. 31%). Taken together, these results indicate muscle fiber content is likely an evolvable trait under selection in the hominin lineage. As such, we highlight potential targets of selection in the genome (e.g. regions that regulate MyHC content) that may play an important role in hominin skeletal muscle evolution. [Display omitted] • Gorilla muscle MyHC content is similar to chimpanzees and distinct from humans. • Human slow fiber content is distinct from African apes and most mammals. • Behavioral interventions (e.g. exercise) induce modest shifts in slow fiber content. • MyHC I content is an evolvable trait under selection within the hominin lineage. • MyHC genes are conserved in mammals so selection likely operates on enhancers. [ABSTRACT FROM AUTHOR]