Runx1 is sufficient but not required for cardiomyocyte cell cycle activation.

Factors responsible for cardiomyocyte proliferation could serve as potential therapeutics to stimulate endogenous myocardial regeneration following insult, such as ischemic injury. A previously published forward genetics approach on cardiomyocyte cell cycle and ploidy led us to the transcription factor, RUNX1. Here, we examine the effect of Runx1 on cardiomyocyte cell cycle during postnatal development and cardiac regeneration using cardiomyocyte-specific gain- and loss-of-function mouse models. RUNX1 is expressed in cardiomyocytes during early postnatal life, decreases to negligible levels by 3 weeks of age, and increases upon myocardial injury, all consistent with observed rates of cardiomyocyte cell cycle activity. Loss of Runx1 transiently stymied cardiomyocyte cell cycle activity during normal postnatal development, a result that corrected itself and did not extend to the context of neonatal heart regeneration. On the other hand, cardiomyocyte-specific Runx1 overexpression resulted in an expansion of diploid cardiomyocytes in uninjured hearts and expansion of 4N cardiomyocytes in the context of neonatal cardiac injury, suggesting Runx1 overexpression is sufficient to induce cardiomyocyte cell cycle responses. Persistent overexpression of Runx1 for >1 month continued to promote cardiomyocyte cell cycle activity resulting in substantial hyperpolyploidization (≥8N DNA content). This persistent cell cycle activation was accompanied by ventricular dilation and adverse remodeling, raising the concern that continued cardiomyocyte cell cycling can have detrimental effects.

Safe streets for some: A review of local active transportation responses across the U.S. during the COVID-19 pandemic.

Introduction & research objectives: The COVID-19 pandemic significantly disrupted daily travel. This paper contrasts 51 US cities' responses, namely street reallocation criteria and messaging related to physical activity (PA) and active transportation (AT) during the early months of the pandemic. This study can be utilized by cities for aiding in the creation of locally responsive policies that acknowledge and remedy a lack of safe active transportation. Methods: A content analysis review was conducted of city orders and documents related to PA or AT for the largest city by population in all 50 US states and the District of Columbia. Authoritative documents issued from each city's public health declaration (ca. March 2020) to September 2020 were reviewed. The study obtained documents from two crowdsourced datasets and municipal websites. Descriptive statistics were used to compare policies and strategies, with a focus on reallocation of street space. Results: A total of 631 documents were coded. Considerable variation existed in city responses to COVID-19 that impacted PA and AT. Most cities' stay-at-home orders explicitly permitted outdoor PA (63%) and many encouraged PA (47%). As the pandemic continued, 23 cities (45%) had pilot programs that reallocated street space for non-motorized road users to recreate and travel. Most cities explicitly mentioned a rationale for the programs (e.g., to provide space for exercise (96%) and to alleviate crowding or provide safe AT routes (57%)). Cities used public feedback to guide placement decisions (35%) and several welcomed public input to adjust initial actions. Geographic equity was a criterion in 35% of programs and 57% considered inadequately sized infrastructure in decision-making. Conclusions: If cities want to emphasize AT and the health of their citizens, safe access to dedicated infrastructure needs to be prioritized. More than half of study cities did not instate new programs within the first 6 months of the pandemic. Cities should study peer responses and innovations to inform and create locally responsive policies that can acknowledge and remedy a lack of safe AT.

Cardiomyocyte ploidy is dynamic during postnatal development and varies across genetic backgrounds.

Somatic polyploidization, an adaptation by which cells increase their DNA content to support growth, is observed in many cell types, including cardiomyocytes. Although polyploidization is believed to be beneficial, progression to a polyploid state is often accompanied by loss of proliferative capacity. Recent work suggests that genetics heavily influence cardiomyocyte ploidy. However, the developmental course by which cardiomyocytes reach their final ploidy state has only been investigated in select backgrounds. Here, we assessed cardiomyocyte number, cell cycle activity, and ploidy dynamics across two divergent mouse strains: C57BL/6J and A/J. Both strains are born and reach adulthood with comparable numbers of cardiomyocytes; however, the end composition of ploidy classes and developmental progression to reach the final state differ substantially. We expand on previous findings that identified Tnni3k as a mediator of cardiomyocyte ploidy and uncover a role for Runx1 in ploidy dynamics and cardiomyocyte cell division, in both developmental and injury contexts. These data provide novel insights into the developmental path to cardiomyocyte polyploidization and challenge the paradigm that hypertrophy is the sole mechanism for growth in the postnatal heart.

"May the Force Be with You!" Force-Volume Mapping with Atomic Force Microscopy.

Information of the chemical, mechanical, and electrical properties of materials can be obtained using force volume mapping (FVM), a measurement mode of scanning probe microscopy (SPM). Protocols have been developed with FVM for a broad range of materials, including polymers, organic films, inorganic materials, and biological samples. Multiple force measurements are acquired with the FVM mode within a defined 3D volume of the sample to map interactions (i.e., chemical, electrical, or physical) between the probe and the sample. Forces of adhesion, elasticity, stiffness, deformation, chemical binding interactions, viscoelasticity, and electrical properties have all been mapped at the nanoscale with FVM. Subsequently, force maps can be correlated with features of topographic images for identifying certain chemical groups presented at a sample interface. The SPM tip can be coated to investigate-specific reactions; for example, biological interactions can be probed when the tip is coated with biomolecules such as for recognition of ligand-receptor pairs or antigen-antibody interactions. This review highlights the versatility and diverse measurement protocols that have emerged for studies applying FVM for the analysis of material properties at the nanoscale.

Widespread intracranial calcifications in the follow-up of a patient with cartilage-hair hypoplasia--anauxetic dysplasia spectrum disorder: a coincidental finding?

BACKGROUND/PURPOSE: Intracranial calcifications have been identified in many neurological disorders. To our knowledge, however, such findings have not been described in cartilage-hair hypoplasia - anauxetic dysplasia spectrum disorders (CHH-AD), a group of conditions characterized by a wide spectrum of clinical manifestations. METHODS/RESULTS: We report a 22-year old female patient, diagnosed with this disorder during her first year of life, and in whom bilateral intracranial calcifications (frontal lobes, basal ganglia, cerebellar dentate nuclei) were discovered by brain MRI at the age of 17 years. CONCLUSION: The etiology of this finding remains unclear. Some causes of such deposits can be of a reversible nature, thus prompting early recognition although their consequences on clinical outcome remain mostly unknown.

Early-onset or rapidly progressive scoliosis in children: check the eyes!

Horizontal gaze palsy with progressive scoliosis (HGPPS) is a rare autosomal recessive disorder characterized by the absence of conjugate horizontal eye movements, and progressive scoliosis developing in childhood and adolescence, caused by mutations in the ROBO3 gene which has an important role in axonal guidance and neuronal migration. We describe two female children aged 12 years and 18 months, with progressive scoliosis, in whom the neurological examination showed absent conjugate horizontal eye movements, but preserved vertical gaze and convergence. Cerebral Magnetic resonance imaging findings included pontine hypoplasia, absent facial colliculi, butterfly configuration of the medulla and a deep midline pontine cleft, while Diffusion tensor imaging (DTI) maps showed the absence of decussating ponto-cerebellar fibers and superior cerebellar peduncles. Somatosensory and motor evoked potential studies demonstrated ipsilateral sensory and motor responses. The diagnosis was confirmed by the identification of bi-allelic mutations in the ROBO3 gene.

Full body gait analysis may improve diagnostic discrimination between hereditary spastic paraplegia and spastic diplegia: a preliminary study.

Hereditary spastic paraplegia (HSP) and spastic diplegia (SD) patients share a strong clinical resemblance. Thus, HSP patients are frequently misdiagnosed with a mild form of SD. Clinical gait analysis (CGA) has been highlighted as a possible tool to support the differential diagnosis of HSP and SD. Previous analysis has focused on the lower-body but not the upper-body, where numerous compensations during walking occur. The aim of this study was to compare the full-body movements of HSP and SD groups and, in particular, the movement of the upper limbs. Ten HSP and 12 SD patients were evaluated through a CGA (VICON 460 and Mx3+; ViconPeak(®), Oxford, UK) between 2008 and 2012. The kinematic parameters were computed using the ViconPeak(®) software (Plug-In-Gait). In addition, the mean amplitude of normalised (by the patient's height) arm swing was calculated. All patients were asked to walk at a self-selected speed along a 10-m walkway. The mean kinematic parameters for the two populations were analysed with Mann-Whitney comparison tests, with a significant P-value set at 0.05. The results demonstrated that HSP patients used more spine movement to compensate for lower limb movement alterations, whereas SD patients used their arms for compensation. SD patients had increased shoulder movements in the sagittal plane (Flexion/extension angle) and frontal plane (elevation angle) compared to HSP patients. These arm postures are similar to the description of the guard position that toddlers exhibit during the first weeks of walking. To increase speed, SD patients have larger arm swings in the sagittal, frontal and transversal planes. Upper-body kinematics, and more specifically arm movements and spine movements, may support the differential diagnosis of HSP and SD.

Benign fibrous histiocytoma of bone in a paediatric population: a report of 6 cases.

Case records and radiological investigations of six children with benign fibrous histiocytoma were studied retrospectively. BFH occurred in the femur (n = 2), tibia (n = 2) and fibula (n = 2). Clinically, patients reported pain from the lesion lasting several months (mean 6 months). The pain was not associated with pathological fracture in any patient. On X-rays, the lesions appeared as lytic and sharply demarcated with a sclerotic rim and fine trabeculations. The reported cases were located in the metaphysis and the diaphysis of the long bones. The tumour was restricted to bone, without periosteal or soft tissue reaction. Treatment consisted of careful intralesional curettage of the lesion; the defect was thereafter filled with bone bank graft or injectable phosphocalcic cement. The length of follow-up ranged from 24 months to 4.75 years (mean 35.2 months). One case presented with recurrence of the disease and required successful repeat intralesional curettage. Benign fibrous histiocytoma is probably underestimated among patients less than 20 years of age. This diagnosis should be considered in any child or teenager who presents with a non-ossifying fibroma accompanied by unexplainable pain or a rapid growing. Surgery restricted to the osteolytic lesion seems sufficient to achieve bone healing.

Synovial sarcomas usually metastasize after >5 years: a multicenter retrospective analysis with minimum follow-up of 10 years for survivors.

BACKGROUND: Synovial sarcoma (SS) is a malignant soft tissue sarcoma with a poor prognosis because of late local recurrence and distant metastases. To our knowledge, no studies have minimum follow-up of 10 years that evaluate long-term outcomes for survivors. PATIENTS AND METHODS: Data on 62 patients who had been treated for SS from 1968 to 1999 were studied retrospectively in a multicenter study. Mean follow-up of living patients was 17.2 years and of dead patients 7.7 years. RESULTS: Mean age at diagnosis was 35.4 years (range 6-82 years). Overall survival was 38.7%. The 5-year survival was 74.2%; 10-year survival was 61.2%; and 15-year survival was 46.5%. Fifteen patients (24%) died of disease after 10 years of follow-up. Local recurrence occurred after a mean of 3.6 years (range 0.5-14.9 years) and metastases at a mean of 5.7 years (range 0.5-16.3 years). Only four patients were treated technically correctly with a planned biopsy followed by a wide resection or amputation. Factors associated with significantly worse prognosis included larger tumor size, metastases at the time of diagnosis, high-grade histology, trunk-related disease, and lack of wide resection as primary surgical treatment. CONCLUSIONS: In SS, metastases develop late with high mortality. Patients with SS should be followed for >10 years.

Pediatric leukemia revealed by a limping episode: a report of four cases.

Acute limping in children is a common reason for consultation in pediatric emergency units. Acute leukemia is a rarely encountered disease in the orthopedic surgeon's activity. In addition, its clinical presentation is not typical and therefore is a source of possible diagnostic delay. For such reasons, there is a definite risk of undiagnosing the actual etiology of the limping episode. We report our experience with four cases of children initially seen in the pediatric emergency department for limping, as their revealing presentation of acute leukemia. The limb pain was highly variable. The radiographic work-up was always normal. Peripheral blood abnormalities were initially absent in one case and blastic cells were absent in two cases. The physician in charge should remember that paraclinical work-up normal results do not exclude a diagnosis of acute leukemia, that any drop in hematopoietic cell counts should call for a myelogram and that paraclinical exams, including the hemogram, should be repeated until a diagnosis and improvement or confirmed cure is achieved over time.

Articular nodular fasciitis in the glenohumeral joint.

We describe a case of multiple intra-articular masses in the glenohumeral joint of a 15-year-old patient. The patient was treated with arthroscopic excision of the masses and synovectomy. Histological and immunohistochemical studies were consistent with those of a nodular fasciitis. Follow-up examination did not reveal recurrence at 6 months. In this article we report the first case of articular nodular fasciitis in the glenohumeral joint with unusual imaging findings.

Electrical conductivity measurement: a new technique to detect iatrogenic initial pedicle perforation.

Pedicle screw fixation has achieved significant popularity amongst spinal surgeons for both single and multi-level spinal fusion. Misplacement and pedicle cortical violation occurs in over 20% of screw placement and can result in potential complications such as dysthesia, paraparesis or paraplegia. There have been many advances in techniques available for navigating through the pedicle; however, these techniques are not without drawbacks. A new electrical conductivity-measuring device, previously evaluated on the porcine model to detect the pedicle violation, was evaluated amongst nine European Hospitals to be used in conjunction with the methods currently used in that centre. This new device is based on two original principles; the device is integrated in the drilling or screwing tool. The technology allows real-time detection of perforation through two independent parameters, impedance variation and evoked muscle contractions. Data was collected twofold. Initially, the surgeon was given the device and a comparison was made between the devices ability to detect a breech and the surgeon's ability to detect one using his traditional methods of pedicle preparation. In the second module of the study, the surgeon was limited to using the electrical conductivity detection device as their sole guide to detect pedicle breaches. A comparison was made between the detection ability of the device and the other detection possibilities. Post-operative fine cut CT scanning was used to detect the pedicle breaches. Overall, the 11 trial surgeons performed a total of 521 pedicle drillings on 97 patients. Initially there were 147 drillings with 23 breaches detected. The detection rate of these breaches were 22/23 for the device compared to 10/23 by the surgeon. Over both parts of the study 64 breaches (12.3%) were confirmed on post-operative CT imaging. The electrical conductivity detection device detected 63 of the 64 breaches (98.4%). There was one false negative and four false positives. This gives the device an overall sensitivity of 98% and specificity of 99% for detecting a pedicle breach. The negative predictive value was 99.8%, with a positive predictive value of 94%. No adverse event was noted with the use of the electrical conductivity device. Electrical conductivity monitoring may provide a simple, safe and sensitive method of detecting pedicle breech during routine perforation of the pedicle, in the course of pedicle screw placement.

[The Legg-Calvé-Perthes disease: which assessment? Which therapeutic approach?]. / L'ostéochondrite primitive de to hanche ou maladie de Legg- Calvé-Perthes: quel bitan ? quelle prise en charge?

Legg-Calvé-Perthes disease remains indefinite from an etiologic point of view and unforeseable in its evolution. The evolution depends on the extent of epiphyseal involvement and the age of the child. It may safely be stated that the more extensive the epiphyseal involvement, the more compromised is the prognosis. Also the older the child, the more the femoral head remoulding will be limited. Preserving articular mobility and containing the head within the depth of acetabulum constitute the mainstay of treatment aiming for a femoral head as spherical as possible upon completion of growth. At the end of growth spherical or ovoid heads will cause no or few problems, however strongly deformed femoral heads will evolve into early hip arthritis. The early recognition of which hip will profit from which treatment, constitutes the major difficulty of the therapeutic process.

Gorham-Stout disease of costo-vertebral localization: radiographic, scintigraphic, computed tomography, and magnetic resonance imaging findings.

Gorham-Stout disease is a clinical, radiographic, and histological entity characterized by progressive osteolysis as a result of a histologically benign vascular proliferation involving bone. We present a case involving the cervical and thoracic spine and the osseous thorax, with attention to the clinical, radiographic, scintigraphic, computed tomography, and magnetic resonance imaging findings. These subjects are discussed in the light of the literature.

Pediatric seatbelt injuries: unusual Chance's fracture associated with intra-abdominal lesions in a child.

The authors report the case of a 7-year-old child involved in a motor vehicle accident. She sustained an unusual flexion-distraction vertebral injury. This spinal injury was related to seatbelt use and was associated with intra-abdominal lesions. The spinal lesion consisted of a posterior ligamentous disruption with widening of the posterior intervertebral space at two adjacent lumbar levels. The purpose of this case report is to describe an atypical and perhaps often unrecognized spinal lesion and to explain our approach to diagnosis and treatment.

[Acute bone and joint infections in children: how much attention should be paid to persistent fever during intravenous antibiotic therapy?]. / Infections ostéo-articulaires aiguës de l'enfant et fièvre persistante: la temérature est-elle un critère d'efficacité de l'antibiothérapie.

PURPOSE OF THE STUDY: Bone and joint infections are challenging therapeutic situations requiring rapid antibiotic therapy as soon as bacteriology specimens have been obtained. Laboratory tests (C reactive protein, erythrocyte sedimentation rate, white cell count) and clinical findings are used to assess therapeutic efficacy. Most of the clinical signs however, particularly in children or after a surgical procedure, are not explicit enough to allow proper assessment of the clinical course under antibiotic therapy. Body temperature is the only parameter currently used in routine practice. But the measurement of body temperature is not always reliable and variations observed during treatment should not always be attributed to treatment failure. The purpose of this work was to assess the significance of changes in body temperature observed in children given effective intravenous antibiotic treatment for bone and joint infections. MATERIAL AND METHODS: We reviewed retrospectively the files of 60 children treated in our unit for acute bone and joint infections. The patients had acute hematogeneous osteomyelitis (n=27), septic arthritis (n=25), and infectious osteoarthritis (n=8). A bacterial strain was identified on cultures of blood, joint fluid, or metaphysis puncture samples in all cases. Blood test results (C-reactive protein, erythrocyte sedimentation rate, white cell count) were recorded during treatment. Body temperature was recorded three times a day until normalization then daily until discharge. We searched for correlations between variations in the temperature curve observed during treatment and blood test results. RESULTS: Ninety percent of the children had fever at admission (mean 39.1 degrees C). Among the six children without fever, the temperature rose in 5 during the first 48 hours of hospitalization. Even when the treatment was effective, apyrexia was achieved slowly, on the average after 8 days of antibiotic treatment. We also observed that the peak temperature occurred during the first 5 days of antibiotic treatment considered effective. C-reactive protein level normalized within a satisfactory time (10.5 days), reflecting the efficacy of the antibiotics. DISCUSSION: The efficacy of antibiotic treatment must always be verified in patients with acute bone and joint infections. Generally, biological parameters are used to monitor efficacy. Currently, C-reactive protein appears to be the most reliable parameter to assess efficacy, its rapid decline reflecting clinical cure. Erythrocyte sedimentation rate and white cell counts are poor surveillance parameters. Finally, body temperature is not a specific surveillance parameter and persistent fever during treatment does not necessarily signify ineffective antibiotic treatment. In light of this fact, body temperature should always be compared with C-reactive protein level to draw any conclusion concerning therapeutic failure.

An unusual Monteggia type-I equivalent fracture in a child.

A six-year-old girl sustained a Monteggia type-I equivalent fracture of the right forearm. We describe the method of treatment of this rare fracture and its outcome.

Corrective surgery for idiopathic scoliosis after heart transplantation.

Cardiac transplant surgery is being performed with increasing frequency as a treatment for end-stage heart disease. In addition to the well-known post-surgical problems of rejection and infection, these patients may present at a future date with other medical problems which require surgical treatment, including orthopaedic pathology. Severe idiopathic scoliosis has been described in association with congenital heart disease, and its surgical treatment poses considerable risks because of heart disease. Spinal fusion in heart transplant recipients involves similar risks due to the particular physiology and pharmacological reactions of the denervated heart. Several cases of cholecystectomy performed in heart transplant recipients have been described, but to our knowledge no orthopaedic procedures have been reported in such patients. We report on a 15-year-old patient who underwent successful corrective surgery for idiopathic scoliosis 14 months after heart transplant.