Novel and deleterious nucleotide variations in the HAND1 gene probably affect miRNA target sites and protein function in pediatric patients with congenital heart disease.

BACKGROUND: Congenital heart disease (CHD) is the most prevalent developmental defect and principal cause of infant mortality and affects cardiac and large blood vessel structures in approximately 1% of live births worldwide. To date, numerous studies have related critical genetic dysfunctions to the pathogenesis of CHDs. However, the genetic basis underlying CHD remains largely unknown. In the present study, we investigated the association of nucleotide variations in coding and noncoding regions of the HAND1 gene with the risk of CHD. The HAND1 gene, encoding a helix-loop-helix transcription factor, is particularly relevant for mechanisms underlying CHD since it plays a significant role in heart development. METHODS AND RESULTS: The genomic DNA of 150 unrelated pediatric patients with CHD was screened by PCR-SSCP and direct sequencing. Four novel and heterozygous missense mutations were identified in the first exon, with three causing amino acid substitutions (p.Val149Met, p.Tyr142His, and p.Leu146Met). In-silico analysis also indicated their deleterious impact on protein structure and function. In addition, we identified five novel nucleotide variants in the 3'UTR region (c.*461, c.*342, c.*529, c.*448, c.*593), potentially altering the target sites of miRNAs. These changes include the loss of certain target sites and the acquisition of new ones. CONCLUSIONS: These findings confirm the phenotypic association between CHDs and HAND1 mutations and can pave the way for developing new preventive and therapeutic strategies.

A comparison between the efficacy of eccentric exercise and extracorporeal shock wave therapy on tendon thickness, vascularity, and elasticity in Achilles tendinopathy: A randomized controlled trial.

Objectives: This study aims to compare the efficacy of the eccentric exercise (EE) and extracorporeal shock wave therapy (ESWT) on chronic midportion Achilles tendinopathy and evaluate the efficacy of these treatment modalities on tendon thickness, vascularity, and elasticity. Patients and methods: In this randomized controlled trial, a total of 63 patients (40 females, 23 males; mean age: 37.3±12.2; range, 18 to 55 years) with chronic midportion Achilles tendinopathy were enrolled between April 2017 and December 2019. The patients were allocated randomly to two groups: the first group was treated with EE every day for three months with the Alfredson protocol, and the second group received four sessions of ESWT at weekly intervals. The study was terminated at the end of three months. Visual Analog Scales (VAS), Victorian Institute of Sports Assessment-Achilles (VISA-A) questionnaires, and ultrasonography measurements were assessed before and after treatment. Patient pain was evaluated at the two-year follow-up. Results: At the three-month follow up, VAS scores decreased, and VISA-A scores increased in both groups (p<0.001). At the two-year-follow-up, VAS scores significantly decreased in the EE group (p<0.001), but the difference was statistically insignificant in the ESWT group (p=0.095). Tendon thickness and stiffness increased in the EE group (p=0.003 and p=0.03, respectively) while the difference was statistically insignificant in the ESWT group after treatment (p=0.173 and p=0.702, respectively). Conclusion: Eccentric exercise and ESWT are efficient in the short term, whereas EE is efficient on tendon pain in the long term. While EE increases tendon thickness and stiffness, ESWT has no effect on these measures.

Hexagonal grafts in mosaicplasty: Biomechanical comparison of standard cylindrical and novel hexagonal grafts in calf cadaver model.

OBJECTIVE: Cylindrical grafts are currently used to cover defected area in mosaicplasty. However, there are some difficulties with cylindrical grafts, such as potential dead space between grafts and insufficient coverage. Hexagonal graft (honeycomb model) was created and evaluated in this biomechanical study. Hypothesis was that harvesting grafts with hexagonal shape, which has the best volume geometry characteristics in nature, would be biomechanically advantageous and provide superior pull-out strength. METHODS: Total of 24 fresh calf femurs were divided into 3 equal groups. In the first group, 1 cylindrical and 1 hexagonal graft were compared. Second group consisted of 3 cylindrical and 3 hexagonal grafts. Third group was designed to evaluate effect of graft depth; hexagonal graft implanted at 5 mm depth was compared with 20-mm-deep hexagonal graft. All specimens were subjected to pull-out test. Friction field and graft surface area were also evaluated. RESULTS: Pull-out strength comparison of 15-mm-deep triple cylindrical grafts and 15-mm-deep triple hexagonal grafts in second group revealed statistically significant difference in favor of hexagonal grafts (p < 0.05). Surface area of cylindrical graft with 9-mm diameter was calculated to be 50.27 mm2, while hexagonal graft surface area was 55.425 mm2. Volume ratio of cylindrical and hexagonal grafts was 753.98 mm3 and 831.375 mm3, respectively. CONCLUSION: This biomechanical study demonstrated that graft geometry, especially in multiple graft applications, is a factor that influences stability. Hexagonal grafts appear to be more stable than cylindrical grafts in multiple applications, and they may be used to cover a larger defected area.

Clinical and functional outcomes and proprioception after a modified accelerated rehabilitation program following anterior cruciate ligament reconstruction with patellar tendon autograft.

OBJECTIVES: The aim of this study was to evaluate the clinical and functional outcomes and proprioceptive function in patients who received a modified accelerated rehabilitation program after anterior cruciate ligament (ACL) reconstruction with a patellar tendon (PT) graft. METHODS: The study included 38 patients (33 men, 5 women; mean age 27.6 ± 6.4 years; range 18 to 45 years) who underwent ACL reconstruction with a PT graft and participated in a modified accelerated rehabilitation program. Only six patients were athletes. Isokinetic strengths of concentric knee extension and flexion were measured with the Cybex isokinetic dynamometer, and static balance was tested with the Sport-KAT device. For proprioceptive assessment, active repositioning was measured at knee flexions of 40°, 20°, and 5° with an isokinetic dynamometer. Activity levels and subjective functional results were evaluated with the Tegner activity scale and Lysholm knee score, respectively. For objective functional testing, single leg hop, triple leg hop, and one-legged crossover hop tests were used. Knee stability was assessed with the Lachman test and anterior drawer test and knee range of motion was measured. The mean follow-up period was 16.2 ± 9.8 months. RESULTS: There was no graft failure during the follow-up. Twenty patients (52.6%) had hypoesthesia at the donor site and 15 patients (39.5%) had anterior knee pain. Before surgery, all the patients had positive results in the Lachman and anterior drawer tests. After surgery, the Lachman test was negative in 32 patients (84.2%), while six patients (15.8%) had grade 1 laxity. The mean Lysholm knee score showed a significant increase postoperatively (p<0.001). The mean preoperative and postoperative Tegner activity scores were not significantly different (p>0.05). There were no significant differences in the range of motion between operated and uninjured extremities (p>0.05). The two extremities were similar in proprioception and balance (p>0.05). Isokinetic quadriceps muscle strength was significantly decreased in the operated extremity only in extension at 60°/sec angular velocity (p<0.05). Other muscle strength measurements were similar in both extremities. The ratios of flexion/extension muscle strength were significantly greater in the involved extremity at all angular velocities (p<0.05). The mean performance scores of three functional tests were more than 85% of the uninvolved extremity. All the patients returned to preinjury daily activities or sports activities in 6 to 12 months postoperatively. CONCLUSION: We had satisfactory clinical, proprioceptive, and functional results in achieving dynamic and static stability of the knee with the modified accelerated rehabilitation program after ACL reconstruction with a PT graft.

Effects of human amniotic fluid and membrane in the treatment of Achilles tendon ruptures in locally corticosteroid-induced Achilles tendinosis: an experimental study on rats.

BACKGROUND: To determine the effects of human amniotic fluid and membrane in the treatment of Achilles tendon ruptures, 72 tendons of 36 Wistar rats were injected with betamethasone sodium phosphate. METHODS: By the end of fourth week, both tendons were tenotomized and repaired, then the samples were divided into three groups. The first group was left untreated after suturing. Human amniotic fluid was injected to the second and amniotic fluid and membrane were both administered to the third group. Twenty-four tendons were scored at the end of the first week, and 24 at the end of the second week histopathologically, and 24 biomechanically at the end of the third week. RESULTS: There was a significant statistical difference only between the histopathological results of Groups 2 and 3 at the first week. CONCLUSIONS: Human amniotic membrane and fluid do not add anything to the healing process of Achilles tendon ruptures in the early phase.

The stiffness characteristics of hybrid Ilizarov fixators.

The use of hybrid Ilizarov models around femoral area is gaining clinical popularity lately. Hybrid systems show different mechanical properties. The purpose of this report is to examine the stiffness characteristics of the C-arch and half-pins on the hybrid Ilizarov fixators. Eight models that included standard Ilizarov and hybrid models were applied to six femoral sawbones. The distal part of fixation was composed of a two-ring frame applied identically to all bones. The difference of the configuration was at the proximal part, where half-pins with or without C-arches were either added to the proximal two-ring frame or replaced the proximal one- or two-ring frame. Osteotomy was performed in the femoral diaphysis and the bone was distracted 2cm. The stability of the system was tested with the axial compression testing machine. Displacements between the adjacent fracture sides were measured with the video extensometer in three dimensions. We found that proximal half-pin applications alone had less stiffness, but half-pins with C-arch had more stiffness than the model including only half-pins. Additional half-pins onto one- or two-ring frames had more longitudinal stiffness, but this system showed weak resistance against transverse displacement.

A new device to produce a standardized experimental fracture in the rat tibia.

OBJECTIVE: To develop and introduce a new device to produce a standardized closed experimental fracture in the rat tibia. METHODS: This study took place in the Research Laboratory, Medical Faculty, Dokuz Eylul University, in the year 2003. We include 20 healthy male white Wistar rats. After pinning both tibia of the rat intramedullary with the needle of a sterile injector without any incision, we tried to produce a fracture with the pendulum of the device, which was dropped in different angles in 9 rats. The tibial diaphysis of 14 rats in the main study were fractured at 60 degrees. After the fractures were confirmed radiologically, 4 tibia underwent pathological analysis to determine the degree of soft tissue damage and 24 tibia were examined in terms of histological fracture healing. RESULTS: Radiologically, this technique resulted in a transverse or short oblique bicortical fracture in the middle of the tibial diaphysis. The healing process was well adjusted with the classification of Allen. No noticeable soft tissue damage in the fracture region was demonstrated. CONCLUSION: This method of producing an easy and reproducible fracture in a standard fashion without displacement and minimal soft tissue trauma in laboratory animals with this simple apparatus make it a useful technique for bone healing studies.

[The structure, physiology, and biomechanics of articular cartilage: injury and repair]. / Eklem kikirdaginin yapisi, fizyolojisi ve biyomekanigi: Yaralanma ve onarim.

Hyaline cartilage which surrounds the articular surfaces and allows for painless movement of synovial joints by reducing friction is composed of chondrocytes embedded within an extracellular matrix made up of a macromolecular framework and water. Due to its avascular, aneural, and hypocellular structure, its response to trauma is very restricted. The main components of the extracellular matrix are water, proteoglycans, collagen, and other proteins and glycoproteins. Homeostasis of the hyaline cartilage is maintained mainly by chondrocytes. Collagen provides the tensile and shearing properties of the cartilage and immobilizes the proteoglycans within the matrix. The mechanical behavior of the cartilage depends on the interactions between collagen, proteoglycans, and interstitial fluid components. The mechanical strength of the hyaline cartilage is determined by the permeability of the solid matrix, flow of the interstitial fluid in the tissue, and the balance between the solid and fluid phases. Injuries that only disrupt the hyaline cartilage do not have a healing potential; but those involving the subchondral bone as well as articular cartilage cause fibrin clot formation, release of growth factors, and increase in cell activities like migration, proliferation, differentiation, and matrix synthesis.

Report of experience in 190 patients with the use of closed suction drainage in arthroscopic knee procedures.

The goal of this study is to report our experience with the use of suction drainage for various arthroscopic knee procedures. One hundred and ninety patients who underwent arthroscopic knee procedures participated in the study, and were divided into two groups (Group 1: Suction drainage, Group 2: No suction drainage). For every patient, the following parameters were recorded: age, gender, operative time, tourniquet or pump use, the amount of fluid collected in the hemovac drain, presence of meniscal tear, type of the operative procedure, date of the operation, and presence of effusion at the follow-up. Statistical analysis was performed to detect any significant statistical difference between the amount of fluid collected in the hemovac drain and the other mentioned parameters in Group 1; and these patients were divided into four subgroups to facilitate the statistical evaluation between the procedures and the amount of fluid collected in the hemovac drain. The partial meniscectomy subgroup had significantly lower amounts of collected fluid when compared to the subtotal meniscectomy subgroup. Drilling of the osteochondral faces led to significantly higher amounts of fluid when compared to non-drilling cases. Use of an infusion pump during surgery and shorter operation time led to lower amounts of fluid to be collected. No case in either main group suffered from effusion at the follow-up. Our investigation demonstrated that in different arthroscopic interventions, variable amounts of fluid can be collected in the hemovac drains. Subtotal meniscal resection, drilling of the osteochondral faces and longer duration of the operation increase the amount of fluid. In cases of partial meniscal resection and/or chondral debridement, limited synovial and plica resection, suction drainage is unnecessary.

Effect of hylan G-F 20 in Achilles' tendonitis: an experimental study in rats.

OBJECTIVE: To investigate the local effects of hylan G-F 20 on locally administered corticosteroid-induced experimental Achilles' tendonitis. DESIGN: Before-after trial. SETTING: Institutional practice. ANIMALS: Convenience sample of 18 male Wistar white rats (weight range, 322-375 g). INTERVENTIONS: After performing Achilles' degeneration with local corticosteroid injections, the rats were divided into 4 groups. The right Achilles' tendon of the rats served as the hylan injection group and the left tendon as the control group, which was injected with saline at 5-day intervals. The tendons and paratenons were excised at the end of 60 or 75 days and evaluated histopathologically and statistically. MAIN OUTCOME MEASURE: Histopathologic changes, including staining affinity, nuclear appearance, fibrillar appearance for tendon and thickness, occurrence of fibrosis and edema, capillary changes, and inflammation for paratenon, were assessed according to a semiquantitative scoring system. The Mann-Whitney U test was used for statistical analysis, with a P value of.05 or less considered statistically significant. RESULTS: Semiquantitative scoring of histopathologic changes showed that histologic appearances differed between the hylan and saline groups and between 2 hylan groups. Hylan-injected tendons and paratenons demonstrated significantly lower scores, especially after 75 days. CONCLUSIONS: Hylan G-F 20 has a promising curative effect on the tendon and paratenon and can be used in Achilles' tendonitis. This finding should be supported by biomechanical and biochemical studies.

Extraarticular pigmented villonodular synovitis of the hip.

Pigmented villonodular synovitis of any joint in the extraarticular region is very rare. Its clinical and radiological differential diagnosis is difficult due to exhibiting findings of any soft tissue tumor. Here we report an extrarticular pigmented villonodular synovitis case of the hip of a five-year-old boy, with its radiological and histopathological aspects. The mass was completely extraarticular and was identified histologically and radiologically as pigmented villonodular synovitis. Six months after marginal excision, the lesion recurred. The physicians can face such cases of pigmented villonodular synovitis presenting with unusual extraarticular location, and the preferred excision should be wide to avoid possible recurrences.

Calcium pyrophosphate dihydrate crystal deposition disease mimicking malignant soft tissue tumor.

Calcium pyrophosphate dihydrate (CPPD) crystal deposition disease has multiple clinical features with variable courses creating several pitfalls in clinical diagnosis. There are number of reported cases mimicking malignant skeletal tumors such as chondrosarcoma. However, no case of CPPD disease with radiographic noncalcified soft tissue mass has been reported in the literature. Here we report a case of CPPD disease clinically mimicking soft tissue tumor with its magnetic resonance imaging appearance and histopathology.

Bone mineral density reference values in the normal female and male population of Izmir, Turkey.

In this study we aimed to establish the dual-energy X-ray absorptiometry (DXA) bone mineral density (BMD) reference values of healthy Turkish women and men residing in Izmir, western Turkey. We examined 347 women and 119 men (age range 20-80 years) who did not have any known risk factor that might affect bone mass. The BMD measurements were performed by Hologic QDR 4500 W Elite DXA instrument from the lumbar spine (L1-L4) and non-dominant hip. In women the mean BMD (g/cm(2))+/-standard deviation (SD) of the normal reference group between 20 and 39 years of age was 0.963+/-0.121 g/cm(2) in the lumbar spine and 0.891+/-0.119 g/cm(2) in total femoral region. The percentages of annual and total BMD losses in women between 30 and 80 years of age were 0.74 and 29% at spinal level and 0.65 and 26% in femoral region, respectively. The average BMD of the normal men's group between 20 and 39 years of age was 0.996+/-0.111 g/cm(2) in the lumbar spine and 1.025+/-0.110 g/cm(2) in femoral region. The percentages of annual and total BMD losses were 0.33 and 13% at spinal level and 0.50 and 20% in femoral region, respectively. In conclusion, like the values reported from mid-Anatolian region of Turkey, the BMD values of Turkish women and men residing in Izmir, western Anatolia, are also lower than in most European countries with regard to US and preinstalled Hologic values.