Merkel cell polyomavirus small tumour antigen activates the p38 MAPK pathway to enhance cellular motility.

Merkel cell carcinoma (MCC) is an aggressive skin cancer with high rates of recurrence and metastasis. Merkel cell polyomavirus (MCPyV) is associated with the majority of MCC cases. MCPyV-induced tumourigenesis is largely dependent on the expression of the small tumour antigen (ST). Recent findings implicate MCPyV ST expression in the highly metastatic nature of MCC by promoting cell motility and migration, through differential expression of cellular proteins that lead to microtubule destabilisation, filopodium formation and breakdown of cell-cell junctions. However, the molecular mechanisms which dysregulate these cellular processes are yet to be fully elucidated. Here, we demonstrate that MCPyV ST expression activates p38 MAPK signalling to drive cell migration and motility. Notably, MCPyV ST-mediated p38 MAPK signalling occurs through MKK4, as opposed to the canonical MKK3/6 signalling pathway. In addition, our results indicate that an interaction between MCPyV ST and the cellular phospatase subunit PP4C is essential for its effect on p38 MAPK signalling. These results provide novel opportunities for the treatment of metastatic MCC given the intense interest in p38 MAPK inhibitors as therapeutic agents.

The pararectus approach for internal fixation of acetabular fractures involving the anterior column: evaluating the functional outcome.

INTRODUCTION: Aim of this retrospective analysis of prospectively collected data was to evaluate the functional mid-term outcome two years after open reduction and internal fixation of acetabular fractures involving the anterior column with affection of the quadrilateral plate using the pararectus approach on a large cohort. METHOD: Fifty-two patients (12 female, 40 male) with a median age of 55 (range 18-90) years and displaced acetabular fractures involving the anterior column were surgically treated in a single level I trauma centre between July 2012 and February 2016 using the pararectus approach. Thirty-four patients (8 female and 26 male) with a median age of 58 (range 20-85) years were available for complete clinical follow-up at regular intervals, finally 24 months post-operatively. Functional outcome was evaluated according to modified Merle d'Aubigné score, Lower Extremity Functional Scale, WOMAC, and SF-36. RESULTS: Range of time between trauma and surgical treatment was three (range 0-19) days. Operation time was 140 (range 60-240) minutes, and duration of hospital treatment was 19 (range 7-38) days. Functional results in 34 patients available for final follow-up demonstrated 68 points (median; range 39-80) according to the Lower Extremity Functional Scale, 6% according to the WOMAC (mean; SD ± 14.5%), and 69% (mean; SD ± 20.1%) according to the SF-36. The modified Merle d'Aubigné score was excellent in 22 patients, good in eight patients, and fair in four patients. DISCUSSION/CONCLUSION: Based on the good to excellent functional mid-term follow-up results of this study, the pararectus approach can be recommended as sufficient alternative single access to address displaced acetabular fractures involving the anterior column, independent of patients' age.

Merle allele variations in the Mudi dog breed and their effects on phenotypes.

A retrotransposon insertion in the SILV gene is associated with a peculiar phenotype of dog, known as a merle. It is characterised by various areas of their coat colour becoming diluted due to a malfunction in the eumelanin-producing pigment cells. Recent studies have shown that the exact size of the short interspersed element (SINE) insertion is in correlation with specific phenotypic attributes, but was not able to absolutely confine dogs to a certain colour pattern. Our study focused on the merle variations occurring in the Mudi breed. Altogether, 123 dog samples from 11 countries were tested and genotyped. The exact length of the merle alleles were determined by automated fluorescent capillary fragment analysis. The most frequent merle genotype in this Mudi sample collection was the 'classic' merle (m/M: 61.8%), whereas other variants, such as atypical (m/Ma and m/Ma+: 5.7%), harlequin (m/Mh: 13.8%), double merle (M/M: 0.8%) and mosaic profiles (17.9%) were also observed. The practical significance of testing this mutation is that, phenotypically, not only merle dogs are carriers of this insertion, but also the so-called hidden merle individuals (where the merle phenotype is fully covered by the pheomelanin-dominated colouration) are potentially capable of producing unintentionally homozygous 'double merle' progeny with ophthalmologic, viability and auditory impairments.

Synthesis and Biological Evaluation of Fluorescent Bryostatin Analogues.

To investigate the cellular distribution of tumor-promoting vs. non-tumor-promoting bryostatin analogues, we synthesized fluorescently labeled variants of two bryostatin derivatives that have previously shown either phorbol ester-like or bryostatin-like biological activity in U937 leukemia cells. These new fluorescent analogues both displayed high affinity for protein kinase C (PKC) binding and retained the basic properties of the parent unlabeled compounds in U937 assays. The fluorescent compounds showed similar patterns of intracellular distribution in cells, however; this argues against an existing hypothesis that various patterns of intracellular distribution are responsible for differences in biological activity. Upon further characterization, the fluorescent compounds revealed a slow rate of cellular uptake; correspondingly, they showed reduced activity for cellular responses that were only transient upon treatment with phorbol ester or bryostatin 1.

The PMEL Gene and Merle in the Domestic Dog: A Continuum of Insertion Lengths Leads to a Spectrum of Coat Color Variations in Australian Shepherds and Related Breeds.

Merle is a distinct coat color and pattern found in numerous species, including the domestic dog, characterized by patches of diluted eumelanin (black pigment) interspersed among areas of normal pigmentation. In dogs, this variegated pattern is caused by an insertion of a SINE element into the canine PMEL gene. Although variation in the length of the SINE insertion - due to a variable-length poly(A) tail - has been observed to be associated with variation in merle coat color and patterning, no systematic evaluation of this correlation has been conducted and published in the scientific literature. We performed high-resolution analysis of the SINE insertion lengths in 175 dogs (99 Australian shepherds, 45 miniature Australian shepherds, and 31 miniature American shepherds) and compared the genotypes with the coat phenotypes (when available). SINE insertion lengths varied from 201 to 277 bp, indicating that merle insertion variants can occur in virtually any size along the entire continuum. Genotype-phenotype correlation of 126 dogs with only a single SINE insertion (m/M) identified at least 4 major phenotypic clusters designated as "cryptic," "atypical," "classic," and "harlequin" merle. However, we found several phenotypic outliers that did not cluster within these major groupings, suggesting that insertion size is not the only factor responsible for merle phenotypic variability. In addition, we detected 25 dogs with 2 SINE insertions (M/M) and 24 dogs with more than 2 PMEL (merle) alleles, indicating mosaicism. Genotype-phenotype correlation of M/M dogs suggests that cryptic merle alleles often act like non-merle (m) alleles when combined with atypical, classic, and harlequin-sized alleles. The finding of mosaicism has important implications for the dog's phenotype and the ability to potentially transmit various alleles to its offspring. Furthermore, we identified examples of the SINE insertion poly(A)-tail expansion and contraction between generations, which also has important implications for breeding practices and determining mating pairs to avoid producing double merle dogs. These data demonstrate that there is a continuum of merle insertion lengths associated with a spectrum of coat color and patterns and that genotype-phenotype exceptions and overlap make it difficult to strictly assign certain insertion sizes with an expected coat color, although some generalizations are possible.

Biological activity of the bryostatin analog Merle 23 on mouse epidermal cells and mouse skin.

Bryostatin 1, a complex macrocyclic lactone, is the subject of multiple clinical trials for cancer chemotherapy. Although bryostatin 1 biochemically functions like the classic mouse skin tumor promoter phorbol 12-myristate 13-acetate (PMA) to bind to and activate protein kinase C, paradoxically, it fails to induce many of the typical phorbol ester responses, including tumor promotion. Intense synthetic efforts are currently underway to develop simplified bryostatin analogs that preserve the critical functional features of bryostatin 1, including its lack of tumor promoting activity. The degree to which bryostatin analogs maintain the unique pattern of biological behavior of bryostatin 1 depends on the specific cellular system and the specific response. Merle 23 is a significantly simplified bryostatin analog that retains bryostatin like activity only to a limited extent. Here, we show that in mouse epidermal cells the activity of Merle 23 was either similar to bryostatin 1 or intermediate between bryostatin 1 and PMA, depending on the specific parameter examined. We then examined the hyperplastic and tumor promoting activity of Merle 23 on mouse skin. Merle 23 showed substantially reduced hyperplasia and was not tumor promoting at a dose comparable to that for PMA. These results suggest that there may be substantial flexibility in the design of bryostatin analogs that retain its lack of tumor promoting activity. © 2016 Wiley Periodicals, Inc.

Traveling wave solution and qualitative behavior of fractional stochastic Kraenkel-Manna-Merle equation in ferromagnetic materials.

The main purpose of this article is to investigate the qualitative behavior and traveling wave solutions of the fractional stochastic Kraenkel-Manna-Merle equations, which is commonly used to simulate the zero conductivity nonlinear propagation behavior of short waves in saturated ferromagnetic materials. Firstly, fractional stochastic Kraenkel-Manna-Merle equations are transformed into ordinary differential equations by using the traveling wave transformation. Secondly, the phase portraits, sensitivity analysis, and Poincaré sections of the two-dimensional dynamic system and its perturbation system of ordinary differential equations are drawn. Finally, the traveling wave solutions of fractional stochastic Kraenkel-Manna-Merle equations are obtained based on the analysis theory of planar dynamical system. Moreover, the obtained three-dimensional graphs of random solutions, two-dimensional graphs of random solutions, and three-dimensional graphs of deterministic solutions are drawn.

Can hip function be assessed with self-report questionnaires? Feasibility study of a French self-report version of the Harris Hip and Merle d'Aubigné scores.

INTRODUCTION: The Harris Hip Score (HHS) and the Merle D'Aubigné Postel (MDP) score both provide an objective and subjective evaluation of hip function. These scores are collected during the follow-up of patients who have a hip disease. The objectives of this prospective study were (1) to analyze the differences between the two new French self-report versions of the HHS and MDP, and the traditional surgeon-assessed HHS and MDP; (2) to analyze the correlation between the self-report HHS and MDP and the surgeon-assessed HHS and MDP; (3) to analyze the floor and ceiling effects of the two self-report scores and the reliability of these self-report scores in operated and non-operated patients. HYPOTHESIS: The French self-report HHS and MDP are sufficiently reliable to accurately estimate the patient's objective and subjective outcomes compared to the clinical examination done by a surgeon. METHODS: A prospective multicenter study was done with patients who had a hip disease. Two self-report questionnaires were completed by the patient, independently of the clinical examination done by the surgeon. The questionnaires were in French and consisted solely of checkboxes, with sample photos that corresponded to the various range of motion items in the HHS and MDP. The agreement between the self-report scores and the surgeon-assessed scores were evaluated using the intraclass correlation coefficient (ICC). Differences in the mean values were evaluated with a paired t test. RESULTS: The analysis involved 89 patients. The self-report HHS was 2.7±3.7 points (/100) lower than the surgeon-assessed HHS, but this difference was not statistically significant (p=0.34). The self-report MDP was significantly less by 1.2±2.9 points (/18) than the surgeon-assessed MDP (p=0.01). The agreement between the self-report HSS and the surgeon-assessed HSS was excellent (ICC=0.86) as was the one between the self-report MDP and the surgeon-assessed MDP (ICC=0.75). There was a strong positive correlation between the surgeon-assessed and self-report HHS in operated patients (ICC= 0.84; R=0.75; p<0.001) and in non-operated patients (ICC=0.96; R=0.89; p<0.001). This positive correlation was also found between the surgeon-assessed and self-report MDP for operated patients (ICC=0.73; R=0.62; p<0.001) and non-operated patients (ICC=0.79; R=0.64; p<0.001). A ceiling effect (maximum of 100 points) was found in 22% of patients (20/89) for the self-report HHS and in 34% of patients (30/89) for the self-report MDP (maximum of 18 points). No floor effect was observed for either questionnaire. CONCLUSION: The French version of the HHS self-report questionnaire is an excellent overall estimator of the HHS score for patients with hip osteoarthritis or fracture, whether operated or not. The addition of the MDP, whose self-report version is less accurate, is also a reliable tool. These self-report questionnaires, when validated on a larger scale, will be useful for the long-term follow-up of patients undergoing hip arthroplasty. LEVEL OF EVIDENCE: III; prospective diagnostic study.

Radiological and Functional Assessment of Treatment Outcomes in Patients after Open Reduction with Internal Fixation (ORIF) of Acetabular Fractures.

(1) Fracture of the pelvis usually happens in young men and results from high-energy trauma. It generates high social and economic costs and results in further health problems. It is therefore important to assess long-term treatment results. (2) The study (NCT04902209) involved 31 patients (mean age 43.6 ± 14.8 years). We conducted fixation assessment on the basis of radiographs and CT scans and functional assessment based on functional scales. (3) We observed more degenerative changes in the less precise reconstruction of the acetabulum (p = 0.075). We did not find statistically significant relationships between the area of surgical approach, the gravity of fracture, and the development of degenerative changes. We did not find statistically significant relationships between patients' functional states and the type of surgical approach or the complexity of the fracture. We found a positive correlation between the time of surgical treatment and patients' functional state (p = 0.04). Patients whose joint surfaces were reconstructed anatomically had significantly higher scores in functional scales (HHS p = 0.05, Merle p = 0.03). (4) Patients after surgical fixation of the acetabulum have low functional abilities. The quality of reconstruction of the loaded surface as well as the length of time post-surgery seems to be essential for the patients' functional state.

Being Merle: The Molecular Genetic Background of the Canine Merle Mutation.

The intensity of the merle pattern is determined by the length of the poly(A) tail of a repeat element which has been inserted into the boundary of intron 10 and exon 11 of the PMEL17 locus in reverse orientation. This poly(A) tail behaves as a microsatellite, and due to replication slippage, longer and shorter alleles of it might be generated during cell divisions. The length of the poly(A) tail regulates the splicing mechanism. In the case of shorter tails, the removal of intron 10 takes place at the original splicing, resulting in a normal premelanosome protein (PMEL). Longer tails generate larger insertions, forcing splicing to a cryptic splice site, thereby coding for an abnormal PMEL protein, which is unable to form the normal fibrillar matrix of the eumelanosomes. Thus, eumelanin deposition ensuring the dark color formation is reduced. In summary, the longer the poly(A) tail, the lighter the coat color intensity of the melanocytes. These mutations can occur in the somatic cells and the resulting cell clones will shape the merle pattern of the coat. When they take place in the germ line, they occasionally produce offspring with unexpected color variations which are different from those of their parents.

Comparison and agreement of outcome scores through nine months after acetabular fracture fixation.

INTRODUCTION: The Modified Merle d'Aubigne-Postel Score and the Harris Hip Score are commonly used to assess the functional outcomes after acetabular fractures. A previous report showed that correlation between scores is good, that there is poor concordance among functional classes, and that the distribution of the scores is highly asymmetrical. Several issues were not addressed in this report, mainly that the data set was treated as transversal data without comparison of scores through time; therefore the objective of this article is to assess the degree of correlation and concordance between the Modified Merle d'Aubigne-Postel Score and the Harris Hip Score during the first 9 months after acetabular fracture treatment. METHODS: Both scores were recorded in a cohort of 23 previously healthy patients after 3, 6 and 9 months after fixation of acetabular fractures. Through a mixed-effects repeated measures model, we assessed differences between standardized scores. Pearson's interclass correlation coefficients for full scores and each of their domains, as well as agreement for clinical graduation classification was calculated. RESULTS: Between score correlation was 89%. We found no differences between scores at 3, 6 and 9 month follow-ups. Agreement between scores was 0.95, while agreement for clinical graduation classification was 0.67. DISCUSSION: Very short term correlation and concordance between scores is excellent, while concordance for clinical graduation classification is modest. We suggest the widespread use of the simpler score.

The Genetics of Deafness in Domestic Animals.

Although deafness can be acquired throughout an animal's life from a variety of causes, hereditary deafness, especially congenital hereditary deafness, is a significant problem in several species. Extensive reviews exist of the genetics of deafness in humans and mice, but not for deafness in domestic animals. Hereditary deafness in many species and breeds is associated with loci for white pigmentation, where the cochlear pathology is cochleo-saccular. In other cases, there is no pigmentation association and the cochlear pathology is neuroepithelial. Late onset hereditary deafness has recently been identified in dogs and may be present but not yet recognized in other species. Few genes responsible for deafness have been identified in animals, but progress has been made for identifying genes responsible for the associated pigmentation phenotypes. Across species, the genes identified with deafness or white pigmentation patterns include MITF, PMEL, KIT, EDNRB, CDH23, TYR, and TRPM1 in dog, cat, horse, cow, pig, sheep, ferret, mink, camelid, and rabbit. Multiple causative genes are present in some species. Significant work remains in many cases to identify specific chromosomal deafness genes so that DNA testing can be used to identify carriers of the mutated genes and thereby reduce deafness prevalence.

WHOQOL-BREF Hindi questionnaire: Quality of life assessment in acetabular fracture patients.

BACKGROUND: The incidence of acetabular fractures in India has increased over the past years but so has the operating skills of pelvi-acetabular trauma surgeons. The outcomes of surgical management need to be assessed so as to be able to devise proper treatment plan and execute the same during and after surgery, which in turn requires assessment of quality of life indices as well as functional scores. While there are studies assessing Harris Hip scores (HHS) and world health organization quality of life BREF (WHOQOL BREF) in the western population there is no study which assesses the same in Indian population. We designed this study to evaluate and define reference values for use of WHOQOL BREF Hindi scores in QOL Assessment in patients with acetabular fractures and to assess the relationship between it and HHS. MATERIALS AND METHODS: 118 patients with acetabular fractures who were treated surgically were included in this retrospective study. Assessment of reduction quality (Matta's radiological criteria), clinical outcome (HHS) and functional outcome (WHOQOL-BREF score) were done. The affect of age, gender, fracture displacement, hip dislocation, delay in surgery and associated injury on the clinical and functional outcome was evaluated. RESULTS: The mean HHS was 90.65 (42-100) which showed an overall good to excellent outcome in 78.8% cases. WHOQOL-BREF Hindi score of domain-one was 63.06 ± 20.31 (13-94), of domain-two was 58.22 ± 19.57 (13-100), of domain-three was 70.49 ± 17.92 (13-100) and of domain-four was 64.48 ± 18.46 (13-100), which showed significant functional deficit in domain-one (P = 0.0001) and domain-two (P = 0.0001) but not in domain-three (P = 0.458) and domain-four (P = 0.722) when compared to score of general healthy population. The domain scores of general population norms were achieved in 59.3%, 61.9%, 69.5% and 66.1% cases in domain one, two, three and four respectively. CONCLUSIONS: Based on these results one can conclude that WHOQOL-Hindi questionnaire is good enough for assessment of QOL in addition to clinical measures in acetabular fracture patients.

Treatment of trochanteric fractures with the gamma3 nail - methodology and early results of a prospective consecutive monitored clinical case series.

OBJECTIVES: There is only sparse data on clinical results and complications of the third-generation Gamma nailing system (Gamma3, Stryker). Therefore, we started a large multi-centre case series in 2008. The aim of this paper is to present the study design and early results of a single arm of a prospective, consecutive, monitored, post-market follow-up evaluation of Gamma3 nails. METHODS: From September 2009 to January 2012, 154 consecutive patients with an average age of 80 ± 1.43 years (50-99 years) and a trochanteric femoral fracture were included in the local arm of the trial. All patients that fulfilled the inclusion criteria were treated with a Gamma3 nail. Preoperative variables included age, gender, fracture classification, walking ability (Merle d'Aubigné score), daily activity level (retrospective Zuckerman score), ASA rating of operative risk, waiting time for operation, use of walker or crutches and body mass index (BMI). Skin-to-skin time, fluoroscopy time, blood loss, intraoperative complications and device information were recorded for each patient. Follow-up postoperative assessment was undertaken at 4, 12 and 24 months. Hip range of motion, pain around the hip and the tight, walking ability (Merle d'Aubigné score, Sahlgrenska mobility score) and management of daily life (Zuckerman score) were used to evaluate the outcome. RESULTS: The descriptive data of age, gender, BMI, ASA classification, fracture type and skin-to-skin time is similar to other studies. Median fluoroscopy time was 62 seconds (range: 4-225 seconds) and significantly shorter in closed reductions. No intraoperative implant-related complication was recorded. A cut-out of the leg-screw during assessment period occurred in 2.6% patients (n = 4). At the 12-month assessment two (1.8%) non-unions were identified and two patients (1.8%) had broken the femoral shaft below the 180 mm nail after a fall. Analysis of the scores showed significantly declined mobility and activity in daily life four months after operation which increased significantly from four to 12 months and increased slightly between 12 and 24 months after fracture. CONCLUSION: A low implant-associated complication rate was achieved in geriatric patients with trochanteric femoral fractures using the Gamma3 nail. A better outcome concerning mobility, activity in daily life and complications compared to the Gamma2 nail could not be found in comparison to historic data.

Incertidumbre ante la enfermedad. Aplicación de la teoría para el cuidado enfermero / Uncertainty in illness. Application nurse care theory

La teoría de rango medio, propuesta por la Dra. Mishel, evalúa cuáles son las reacciones que las personas tienen ante la enfermedad, ya sea la propia o la de un ser querido, para lo cual conceptualiza el nivel de incertidumbre ante la enfermedad; por ejemplo, la incapacidad de la persona de determinar el significado de los hechos relacionados con la enfermedad, siendo incapaz de dar valores definidos a los objetos o hechos y por lo tanto no puede predecir los resultados; este fenómeno es motivado por la falta de información y/o conocimiento. Si el evento es evaluado de forma efectiva, entonces ocurrirá la adaptación. La dificultad de la adaptación dependerá de la habilidad de las estrategias recopiladas para manipular la incertidumbre en la dirección deseada, ya sea para mantenerla, si se valora como oportunidad, o para reproducirla, si se valora como un peligro. Así mismo, la teoría puede ser utilizada en una amplia gama de posibilidades, ya que tanto la persona enferma, como sus familiares, se enfrentan a situaciones estresantes generadoras de incertidumbre. Es por esto que el profesional de enfermería, al conocer la teoría, puede guiar u orientar a la persona para que enfoque su evaluación como una oportunidad, y dirija sus estrategias a lograr la adaptación.

The middle-range theory proposed by Dr. Mishel, which are evaluated reactions taking people to the disease, either their own or a loved one, for which conceptualizes the level of uncertainty in illness as: the inability of the person to determine the significance of the facts related to the disease, being unable to give definite values to objects or events and therefore can not predict the outcome, a phenomenon caused by a lack of information and / or knowledge. So that if the event is effectively evaluated, then the adjustment will occur. The difficulty of adaptation depends on the ability of strategies compiled to handle uncertainty in the desired direction, either to keep it, if we evaluate it as an opportunity, or to play, if we evaluate as a danger. Also the theory can be used in a wide range of possibilities, since both the sick person, and their families face stressful situations that generate uncertainty, which is why the nurse, knowing the theory can guide the person to focus their evaluation as an opportunity, and direct their strategies to achieve adaptation.

Ectopia ureteral unilateral congênita em uma cadela Teckel Dachshund com pelagem arlequim: relato de caso / Single congenital ureteral ectopy in a female dog Teckel Dachshund with merle colour pattern: case report

O presente relato apresenta a primeira descrição de ectopia ureteral congênita na raça Teckel Dachshund, diagnosticada em uma cadela com pelagem arlequim. O animal, aos dois meses de idade, apresentava sinais de incontinência urinária e cistite bacteriana, sendo submetido a um plano diagnóstico para confirmação de ureter ectópico. A urografia excretora revelou hidroureter direito com desembocadura caudal ao trígono da bexiga. O exame físico do animal evidenciou ainda hérnia inguinal bilateral, o que reforçou a caracterização da origem congênita das alterações. Aspectos de bem-estar animal são também discutidos.

The present work reports the first description of congenital ureteral ectopy in the canine breed Teckel Dachshund, diagnosed in a female dog with merle colour pattern. The two month old animal, presented with continuous dribbling of urine and bacterial cystitis, was subjected to a diagnostic plan for ectopic ureter. The excretory urography showed a right hidroureter, which had an orifice located caudally to the trigone of the bladder. The animal also presented a bilateral inguinal hernia, which confirmed the case description as a multiple congenital anomaly condition. Animal welfare aspects are also discussed.

Prognostic evaluation of posterior wall fractures of the acetabulum by two scoring systems / 中国矫形外科杂志

[Objective]To evaluate the outcome inforation provided by two scoring systems after operative treatment of elementary posterior wall fractures of the acetabulum.[Method]Thirty-two patients with elementary posterior wall fracture of the acetabulum were included in the study.Functional outcomes were assessed with use of the eight health dimensions of the short form(SF)-36,and clinical outcomes were evaluated with use of the modified Merle d' Aubign? score.The SF-36 scores were compared with previously reported normal values and the correlation was analyzed between the modified Merle d' Aubign? score and score of each SF-36 health dimension.[Result]The mean modified Merle d' Aubign? score was 16.28 (range 13-18,SD 1.3),indicating overall good-to-excellent clinical results.However,all SF-36 health dimensions were significatly lower than the expected forms,with a significant statistical difference(P