Bioinformatics Analysis and Experimental Verification Identify Downregulation of COL27A1 in Poor Segmental Congenital Scoliosis.

BACKGROUND: Congenital scoliosis (CS) represents the congenital defect disease, and poor segmental congenital scoliosis (PSCS) represents one of its types. Delayed intervention can result in disability and paralysis. In this study, we would identify the core biomarkers for PSCS progression through bioinformatics analysis combined with experimental verification. METHODS: This work obtained the GSE11854 expression dataset associated with somite formation in the GEO database, which covers data of 13 samples. Thereafter, we utilized the edgeR of the R package to obtain DEGs in this dataset. Then, GO annotation, KEGG analyses, and DO annotation of DEGs were performed by "clusterProfiler" of the R package. This study performed LASSO regression for screening the optimal predicting factors for somite formation. Through RNA sequencing based on peripheral blood samples from healthy donors and PSCS cases, we obtained the RNA expression patterns and screen out DEGs using the R package DESeq2. The present work analyzed COL27A1 expression in PSCS patients by the RT-PCR assay. RESULTS: A total of 443 genes from the GSE11854 dataset were identified as DEGs, which were involved in BP associated with DNA replication, CC associated with chromosomal region, and MF associated with ATPase activity. These DEGs were primarily enriched in the TGF-ß signaling pathway and spinal deformity. Further, LASSO regression suggested that 9 DEGs acted as the signature markers for somite formation. We discovered altogether 162 DEGs in PSCS patients, which were involved in BP associated with cardiac myofibril assembly and MF associated with structural constituent of muscle. However, these 162 DEGs were not significantly correlated with any pathways. Finally, COL27A1 was identified as the only intersected gene between the best predictors for somite formation and PSCS-related DEGs, which was significantly downregulated in PSCS patients. CONCLUSION: This work sheds novel lights on DEGs related to the PSCS pathogenic mechanism, and COL27A1 is the possible therapeutic target for PSCS. Findings in this work may contribute to developing therapeutic strategies for PSCS.

[Homeostasis and Disorder of Musculoskeletal System.Diagnosis and Treatment of Congenital Musculoskeletal Diseases.]

Congenital skeletal dysplasias have been considered to be fundamentally untreatable diseases. However, molecular diagnosis by genetic testing has become more prevalent, and efforts are being made to develop novel therapies based on the pathogenesis. As treatments for osteogenesis imperfecta, in addition to anti-resorptive agents, neutralizing antibodies against sclerostin and transforming growth factor(TGF)-ß and chemical chaperones can be beneficial. Enzyme replacement therapy using bone-targeting recombinant alkaline phosphatase has been recently developed to treat hypophosphatasia and has much improved the prognosis of the patients affected with severe forms of the disease. To treat the severe short stature in achondroplasia, drugs targeting the fibroblast growth factor receptor 3(FGFR3)-mediated signal are in development for clinical use.

Pediatric musculoskeletal ultrasound.

The expanding applications of musculoskeletal ultrasound include many examinations that are new to pediatric radiologists but are well known to our adult colleagues. In this review we present an introduction and guide to some of these entities for pediatric radiologists making inroads into the world of musculoskeletal ultrasound.

Orthopedic Conditions of the Premature and Dysmature Foal.

Incomplete ossification of the cuboidal bones is a common finding in premature and dysmature foals, and possibly in foals with hypothyroidism. Radiographs of the carpus and tarsus should be performed in any high-risk foal to obtain a diagnosis. Goals of treatment include limiting weight bearing and exercise. The prognosis is guarded depending on the degree of incomplete ossification.

Medial malleolar screw versus tension-band plate hemiepiphysiodesis for ankle valgus in the skeletally immature.

BACKGROUND: Ankle valgus is frequently encountered in skeletally immature patients in association with a variety of musculoskeletal disorders. Guided growth with temporary medial malleolar transphyseal screw (MMS) hemiepiphysiodesis is an established surgical treatment capable of correcting the angular deformity, but is often complicated by symptomatic screw head prominence and difficult hardware removal. Tension-band plate (TBP) hemiepiphysiodesis has recently been advocated as an alternative; however, the relative efficacy of these 2 techniques has not been directly investigated. Thus, the purpose of this study was to compare MMS and TBP in treatment of pediatric ankle valgus deformity. METHODS: Medical records and radiographs of all patients undergoing distal tibial medial hemiepiphysiodesis for ankle valgus between January 1, 2005 and November 1, 2010 at a pediatric orthopaedic specialty hospital were retrospectively reviewed. Radiographs obtained preoperatively and at 6-month intervals postoperatively were reviewed and the tibiotalar angle was measured. Patient age, sex, underlying diagnosis, concurrent surgical procedures, surgical and postoperative complications, and the presence or absence of symptomatic hardware complaints were documented. RESULTS: Sixty ankles in 42 patients met the inclusion criteria, with adequate radiographs and minimum postoperative follow-up of 12 months (mean: 34 mo). Thirty-five ankles were treated with MMS, and 25 with TBP. Good mean correction of the tibiotalar angle was achieved in both groups (MMS: pre-77.1 degrees to post-87.8 degrees over 25.2 mo; TBP: pre-81.3 to post-87.6 over 20.0 mo). The mean rate of correction was faster in ankles treated with MMS than TBP, but differences did not reach statistical significance (0.55 vs. 0.36 degrees/mo, respectively; P=0.057). Complications included 6 hardware-related surgical complications in MMS ankles (17.1%) and 1 in TBP ankles (4.0%). The incidence of symptomatic hardware complaints was low in both groups (MMS, 5.7%; TBP, 0%). CONCLUSIONS: Both MMS and TBP techniques can result in successful correction of ankle valgus in the growing child. Although the rate of deformity correction may be faster with MMS, TBP seems to be associated with fewer hardware-related complications. This information may aid the clinician in selecting the surgical option most appropriate for each individual patient. LEVEL OF EVIDENCE: Level II-retrospective study.

Perosomus elumbis in a Holstein calf infected with bovine viral diarrhea virus.

The detection of bovine viral diarrhea virus (BVDV) in a female Holstein calf presented with perosomus elumbis, a congenital anomaly, is reported here. A cow with dystocia was evaluated and an abnormal dead calf was detected during vaginal examination. The calf was retrieved via caesarean section and exhibited abnormalities characteristic of PE, such as vertebral and pelvic malformations. These abnormalities were further confirmed using radiographic and necropsy examinations. At necropsy cerebellar hypoplasia was an additional finding, which is a typical lesion associated with bovine virus diarrhea (BVD). Several tissue samples from the calf were tested for the presence of antigens of BVDV and bovine herpesvirus-1 (BHV-1) by ELISA. In addition, sera samples from the dam and calf were tested for the presence of antibodies against BVDV, BHV-1, and bluetongue disease virus (BTV) using a virus neutralization assay. Results indicated that the calf was congenitally infected with BVDV, whereas there was no evidence for the presence of BHV-1 and BTV. In the dam's serum no antibodies against BVDV, BHV-1, and BTV were detected. Even though the etiology of perosomus elumbis is unknown, BVDV, which causes fetal anomalies at early gestation in cows, may have been a contributing factor in this case.

MR imaging of the neonatal musculoskeletal system.

Experience in magnetic resonance (MR) imaging of the neonatal musculoskeletal system is rapidly increasing. The exquisite ability of MR to image the soft tissues, especially cartilage, without radiation is its key strength. Although it is not practical or sensible to undertake MR imaging in conditions in which radiography and ultrasound provide adequate information, MR is proving to be a useful adjunct and problem-solving tool in many neonatal musculoskeletal conditions.

Ultrasound of pediatric musculoskeletal disease: from head to toe.

Ultrasound (US) can be used to evaluate a variety of musculoskeletal pathologies related to developmental anomalies, most commonly developmental dysplasia of the hip (DDH), infection, inflammation, and trauma. US has unique advantages in evaluation of the immature bone in children. It is possible to directly visualize the cartilaginous epiphyses that are not demonstrated on radiographs, joints, and soft tissues. US is safe and does not involve ionizing radiation or the need for sedation. US also has the advantage of real-time imaging, which can be useful in evaluation of subluxation or clicking syndromes.

What has happened to people affected by thalidomide 50 years on?

INTRODUCTION: There have been reports of thalidomide-affected people suffering a deterioration in their disability over time [1, 2]. This study assessed changes in disabilities among thalidomide-affected people in the Irish population. METHODS: A questionnaire, assessing musculo-skeletal health, quality-of-life, general health and illness intrusiveness was sent to 26 people affected by thalidomide in the Republic of Ireland. RESULTS: Seventeen (65%) responded. Six (35%) respondents were not working as a result of their disability. Eleven (65%) reported a worsening of their disability over time, with nine of them reporting the deterioration as moderate to severe. The impact of this decline was measured by respondents in terms of ability to perform daily tasks, emotional health and finances (due to extra costs related to clothing, transport, housing alterations and heating). CONCLUSION: There is a need to continually review the physical, psychological and social needs of thalidomide survivors in order to ensure optimum care is made available.

The diagnosis and management of common childhood orthopedic disorders.

Musculoskeletal illness represents a significant portion of office visits to primary care physicians. Despite this, little emphasis is placed on learning pediatric orthopedics during medical school or residency. Many articles have been written on selected disorders, or approaches to common conditions, such as the limping child. Sometimes determining where to start and how to move toward a diagnosis prevents prompt evaluation, referral, and treatment. Based on the author's experience as a general pediatrician trained in, and exclusively practicing, nonoperative pediatric orthopedics, approaches to selected complaints related to the musculoskeletal system are presented. Emphasis is placed on conditions resulting in frequent consultation with pediatric orthopedists from pediatricians and other primary care practitioners, either in the office or over the phone. Important features that may not be familiar to the primary care physician are highlighted, including the identification of aspects that require further evaluation and indications for consultation. Guidance regarding in-office management is also provided.

The orthopaedic needs of children in Rwanda: results from a national survey and orthopaedic service implications.

BACKGROUND: When faced with developing orthopaedic services for children in Sub-Saharan Africa, there is little objective evidence-based data on the magnitude and type of services needed. Rwanda is a small country that is in the process of developing orthopaedic and rehabilitation services, and its Ministry of Health supported a survey that would provide information necessary for planning such services. METHODS: A national survey of musculoskeletal impairment (MSI) prevalence was undertaken. Of a population of 8.4 million, 8368 people were enumerated. Four thousand one hundred thirty-four were aged 16 years or less. Cases who failed a screening test for MSI were examined, allocated a diagnostic category, and assessed as to treatment needed. RESULTS: Of 4134 people aged 16 years or less who were enumerated, 3526 (85%) were screened and 91 had MSI, giving a prevalence of MSI among children of 2.58% (95% confidence interval; 2.06-3.10). Twenty-three percent of MSIs were a result of congenital deformity, 14% neurologic conditions, 12% trauma, 3% infection, and 46% other acquired pathology. Of the MSIs, 56.7% were mild, 37.8% moderate, and 5.6% severe. Extrapolated treatment needs suggest that 2% of Rwandan children (approximately 80,000) need orthopaedic physical therapy, 1.2% (50,000) need orthopaedic surgery, and approximately 10,000 need orthopaedic appliances. CONCLUSIONS: These results will be of use in planning future paediatric orthopaedic services in Rwanda, and for comparative studies in other low-income countries.

Role of MRI in paediatric musculoskeletal conditions.

The aim of this review is to discuss the indications and use of MR imaging (MRI) in the paediatric musculoskeletal system. After briefly reviewing basic technical considerations the MRI appearance of the most relevant congenital, inflammatory, infectious, ischemic, and posttraumatic skeletal conditions, as well as benign and malignant bone and soft tissue tumours that are typical for the paediatric age group will be presented.

Whole-body MRI in children: current status and future applications.

Whole-body MRI (WBMRI) is a novel technique that makes imaging of the whole patient in a manner similar to scintigraphy or positron emission tomography (PET) possible. Unlike the latter two methods, it is without exposure to radiation and thus gaining increasing importance and application in pediatrics. With the introduction of a moving tabletop, sequential movement of the patient through the magnet has become possible with automatic direct realignment of the images after acquisition. The common scan plane is coronal with additional planes being added depending on the indication. WBMRI is targeted for maximum coverage of the body within the shortest possible time using the minimum number of sequences. The evaluation of the bone marrow has been the primary indication thus inversion recovery sequences like STIR or TIRM are mostly used with the T1-weighted sequence being added variably. For correct evaluation of the bone marrow in the pediatric age group understanding normal pattern of marrow transformation is essential. The primary role of WBMRI has been in oncology for the detection of tumor spread and also for the follow-up and evaluation of complications. The initial comparative studies of WBMRI with scintigraphy and PET in children have shown the high diagnostic potential of WBMRI. Emerging potential applications of WBMRI include the evaluation for osteonecrosis, chronic multifocal recurrent osteomyelitis, myopathies, and generalized vascular malformations. Future use of WBMRI may incorporate non-accidental trauma, virtual autopsy, body fat mapping and diffusion-weighted imaging.

[The prevalance of orthopedic disabilities in the district of Cay, Afyon, Turkey]. / Afyon'un Cay ilçesinde ortopedik özürlerin sikligi.

OBJECTIVES: Data were collected on disabilities from a sample population in order to estimate the prevalence of orthopedic disabilities in the general population. METHODS: A two-stage field study was conducted in Cay, a district of Afyon, Turkey. In the first stage, a list of all individuals with orthopedic disabilities was derived. Then, medical histories were elicited and examinations were made by a team of specialists of orthopedics and traumatology. Radiographic studies were made when necessary. Orthopedic disabilities were defined as any muscle or skeletal abnormality that was associated with a permanent functional loss and were classified as congenital, traumatic, cerebral palsy, poliomyelitis, and other causes. RESULTS: The overall population was 35,571, of whom 189 had orthopedic disabilities (53/10,000). The male-to-female ratio was 1.8. The most common cause was congenital diseases (25.9%; 13.7/10,000), followed by trauma (23.8%; 12.6/10,000), cerebral palsy (21.7%; 11.5/10,000), poliomyelitis (10.1%; 5.3/10,000), and others (18.5%; 9.8/10,000). The lowest mean age (19+/-5 years) was found in those with cerebral palsy, which was associated with the highest degree of functional loss. The mean age in patients with poliomyelitis was 29+/-7 years. It was found that 37% of the disabled could benefit from either a limited or extensive surgical intervention, and 9% could have significant improvement both in functional ability and life quality through physical therapy or the use of a prosthesis/orthosis. Only 18% were under the coverage of a health insurance, though. CONCLUSION: The data of this study may throw some new light on the prevalence and implications of orthopedic disabilities in Turkey.

[Dental enamel hypoplasia in children with combined congenital and hereditary defects in the development of the CNS and the locomotor system (infantile cerebral palsy, spinal cord hernias and myopathies)]. / Gipoplazia émali zubov u detei s sochetannymi vrozhdennymi i nasledstvennymi porokami razvitiia TsNS i oporno-dvigatel'nogo apparata (detskii tserebral'nyi paralich, spinnomozgovye gryzhi, miopatii).

The incidence of hypoplasia in children with congenital and hereditary developmental defects of the central nervous system and the locomotor system is high (44.5 +/- 3.5%), much higher than the incidence of hypoplasia in children without neurological disorders (2.0 +/- 2.0%). This is explained by exposure of the fetus and newborn to numerous intensive factors complicating the biological anamnesis because of profound disturbances of the metabolic processes and largely responsible for the underlying neurological disease and defects of hard dental tissues presenting as hypoplasia of the enamel.

Prophylactic laser photocoagulation in Stickler syndrome.

The ocular manifestations in a family with Stickler syndrome and the results of laser photocoagulation as preventive treatment for retinal detachment are described. Forty-two family members with Stickler syndrome were retrospectively reviewed; 22 had ocular abnormalities, 22 had myopia and 16 had high myopia. Ten patients had developed retinal detachment and 9 of them were blind in one or both eyes because of irreparable detachment. Only 2 eyes had been operated on successfully. Ten eyes were lasered prophylactically. In eyes with extensive vitreoretinopathy laser burns were applied 360 degrees around the peripheral retina at the border between the pathological and normal retina. Eyes with isolated lesions received focal treatment around the pathological areas. Four eyes received 360 degrees laser photocoagulation and 6 eyes received focal treatment. Of the treated cases, 9 retinas remained attached for a follow-up period ranging from 1 to 15 years. One patient was lost to follow-up, and 5 years later developed retinal detachment in one eye from a new non-lasered lesion. In conclusion, in this particular family the incidence of retinal detachment was significantly higher in non-lasered eyes than in lasered eyes (p < 0.025).