A novel surgical strategy of three column osteotomy at non-lesioned area for correcting severe angular kyphosis due to Pott's disease: a retrospectively study.

Severe sharp angular kyphosis resulting from Pott's disease typically necessitates surgical intervention. The deployment of three-column osteotomy within the lesion and apical regions has been validated as an effective modality for the amelioration of angular kyphosis. Nonetheless, a propensity for residual kyphosis persists, accompanied by a significant perioperative risk profile. In pursuit of optimizing correctional outcomes and diminishing complication rates, we proposed an innovative surgical approach, utilizing osteotomy in the non-lesioned zones for the rectification of severe angular kyphosis associated with Pott's disease. This retrospective investigation encompasses 16 subjects who underwent this novel surgical tactic, involving osteotomies in non-lesioned vertebral segments, at our institution from 2016 to 2018. Radiographic measures, encompassing kyphotic angle and sagittal vertical axis (SVA), were documented at baseline and during terminal follow-up. Neurological status was evaluated via the American Spinal Injury Association (ASIA) grading system. Operative duration, volume of hemorrhage, and perioperative complications were systematically recorded. The cohort included 6 males and 10 females with an average age of 30.7 ± 11.41 years. Follow-up intervals spanned 24 to 42 months. Mean operative time and blood loss were 492 ± 127.3 min and 1791 ± 788.8 ml, respectively. The kyphotic angle improved from 97.6 ± 14.6° to 28.8 ± 18.70°. In cases with lumbar afflictions, vertebral restoration was achieved (L1-L5 and L2-S1). Initial mean SVA of 6.7 ± 3.58 cm was reduced to 3.3 ± 1.57 cm at follow-up. Neurological function enhancement was observed in six patients, while ten maintained baseline status. Complication rates, including wound infection and rod fracture at 12 months, were observed in approximately 11.8% of cases. Our findings suggest that the surgical strategy is both effective and safe for addressing severe angular kyphosis due to Pott's disease, contingent upon the expertise of the surgical unit.

Pulmonary and clinical outcomes of patients with severe rigid scoliosis and type I respiratory failure treated with halo-pelvic distraction.

BACKGROUND: The severe rigid scoliosis patients with type I respiratory failure could not tolerate complicated corrective surgery. Preoperative halo-pelvic distraction (HPD) is used to reduce the curve magnitude and improve the pulmonary function before surgery. The present study aimed to retrospectively analyze the pulmonary and clinical outcomes of preoperative HPD in severe rigid spinal deformity with type I respiratory failure. METHODS: Eighteen cases of severe rigid scoliosis and type I respiratory failure treated with preoperative HPD and corrective surgery for spinal deformity between 2016 and 2018 were retrospectively reviewed. Patient demographics, major coronal curve and kyphosis, correction rates, heights, pulmonary function, distraction time, and postoperative neurological complications were recorded for all cases. RESULTS: The averaged duration of distraction was 9.1 ± 2.3 months. The coronal curve was corrected from 168° ± 14° to 58° ± 11° at the end of HPD. The kyphosis curve reduced from 151° ± 29° to 65° ± 10°. Meanwhile, the mean stand body height increased by 23.9 ± 5.3 cm. Significantly increased mean FVC (1.52 ± 0.43 L vs. 0.95 ± 0.44 L) and improved percent-predicted values for FVC (37 ± 10% vs. 23 ± 9%) were observed after HPD. The pressure of oxygen (PaO2) increased from 54.5 ± 2.0 to 84.8 ± 4.7 mmHg. Scoliosis and kyphosis curve, respectively, averaged 48 ± 8°and 30 ± 14° after final fusion and instrumentation, with a mean correction of 71% and 80%, respectively. No severe complication occurred during the distraction. CONCLUSIONS: HPD may be useful for severe rigid scoliosis patients with type I respiratory failure. Pulmonary functions in patients with severe rigid scoliosis can be significantly improved by HPD. They are then better able to tolerate complicated corrective surgery.

Effectiveness of Halo-Pelvic Traction and Thoracoplasty for Pulmonary Artery Pressure and Cardiopulmonary Function in Patients With Severe Spinal Deformity.

STUDY DESIGN: Retrospective review. OBJECTIVE: To evaluate the effectiveness of halo-pelvic traction and thoracoplasty for pulmonary artery pressure (PAP) and cardiopulmonary function in patients with severe spinal deformity. SUMMARY OF BACKGROUND DATA: The effect of severe spinal deformity on pulmonary arterial hypertension, cardiac structure, and function has received little attention before. PATIENTS AND METHODS: A total of 21 patients with severe spinal deformity were included in our study; all patients were examined by echocardiography and pulmonary function test before and after treatment. The correlations between PAP and pulmonary function were examined using Pearson correlation analysis. RESULTS: The PAP decreased from 58.67 ± 20.24 to 39.00 ± 12.51 mm Hg, and the PAP of 42.86% of the patients returned to normal after treatment. Right cardiac enlargement, left ventricular diastolic function, and pulmonary function were improved at the same time. The ratio of left ventricular to right ventricular diameter returned to normal. Moderate correlations (correlation coefficient: -0.513 to -0.559) between PAP and forced vital capacity and forced expiratory volume in the first second were identified. CONCLUSIONS: Pulmonary arterial hypertension, ventricular diastolic function, and pulmonary function were improved after halo-pelvic traction and thoracoplasty. A moderate negative correlation was identified between PAP and pulmonary function: the more pulmonary function improved, the more PAP decreased.

Staged osteotomy in lateral position for the treatment of severe kyphotic deformity secondary to ankylosing spondylitis: a retrospective study.

BACKGROUND: Patients with severe kyphotic deformity (Cobb > 100°) secondary to ankylosing spondylitis (AS) occasionally cannot undergo corrective surgery in the prone position. Osteotomy in the lateral position might provide a possible solution. In this study, we aim to evaluate the clinical efficacy and safety of staged osteotomy in the lateral position for the treatment of AS-related severe kyphosis with a minimum of 2-year follow-up. METHODS: In total, 23 patients who underwent staged osteotomy in the lateral position from October 2015 to June 2017 were analyzed. In the first stage of surgery, all but one patient underwent a single-level Ponte osteotomy, which was followed by a pedicle subtraction osteotomy in the second stage. Mean follow-up was 30.8 ± 4.6 months. Global kyphosis (GK), thoracic kyphosis (TK), lumbar lordosis (LL), sagittal vertical axis (SVA), osteotomized vertebra intervertebral angle (OVI), chin-brow vertical angle (CBVA), Oswestry Disability Index (ODI) score and Scoliosis Research Society-22 Patient Questionnaire (SRS-22) were all compared pre- and postoperation. RESULTS: All kyphosis parameters were significantly improved (all P < 0.05). GK was corrected from 115.0 ± 13.4° to 46.5 ± 9.0° postoperatively, with a mean correction of 68.5°. SVA was improved from 21.2 ± 5.1 cm to 5.1 ± 1.8 cm postoperatively. After surgery, CBVA was adjusted from 64.1 ± 23.2° to 5.7 ± 10.6° and OVI was changed from 9.0 ± 2.7° to - 20.1 ± 5.6°. Both the ODI and SRS-22 showed substantial improvements (all P < 0.05). Four patients with mild complications were observed perioperatively. CONCLUSION: In AS patients with severe kyphosis, satisfactory correction can be safely achieved with staged osteotomy in the lateral position, which can not only correct the sagittal imbalance of the spine with acceptable complications but also facilitate the placement of the intraoperative position.

Vertebral column resection (VCR) at the subapical vertebra for correction of angular kyphosis associated with neurofibromatosis type 1(NF1): a case report.

PURPOSE: To describe the process and outcome of vertebral column resection (VCR) at the subapical vertebra for correction of angular kyphosis associated with neurofibromatosis type 1(NF1). METHODS: A review and summary of the medical history, radiographs, operative procedure, and complications of a 16-year-old male presenting with severe angular kyphosis associated with NF1 with dyspnea. RESULTS: A 16-year-old male presented with severe angular kyphosis associated with NF1 with dyspnea. Preoperative radiographs demonstrated multiple vertebrae were rotated in the vicinity of the apical vertebra, with a wedge-shaped deformity, dysplasia, T10-T12 kyphotic angle of 160°, and T2-L2 kyphotic angle of 95°. VCR at the L1 vertebra (distal end of the apical vertebra) with bone grafting and internal fixation was performed. Postoperative imaging revealed that the T2-L2 Cobb angle was 20°, denoting a correction rate of 79%. The patient's height increased from 130 to 150 cm. The position of internal fixation was not displaced, and the correction angle was maintained at 2-year follow-up. CONCLUSIONS: The novel strategy of performing VCR at the subapical vertebra, with posterior displacement of the distal end, and remodeling of the spinal canal is potentially a safe and efficacious option to correct sharp angular kyphosis.

Management of Severe Scoliosis with Pulmonary Arterial Hypertension: A Single-Center Retrospective Case Series Study.

Aims: To determine the impact of anesthesia encountered and to optimize the treatment of perioperative pulmonary arterial hypertension (PAH) in an effort to improve perioperative management and reduce complications. Methods: We conducted a retrospective analysis of scoliosis patients with PAH who underwent scoliosis surgery. Results: During this period, we identified a total of 22 patients. Their mean age was 22.18 ± 2.11 years. 16 PAH patients (72.72%) received PAH-specific treatment. Only Propofol-based TIVA was used intraoperatively. During the procedure, pulmonary artery catheters and PICCO catheters were placed in all patients to monitor intraoperative and postoperative mPAP, MAP, PRVI and SRVI. During tracheal intubation and intraoperative awake testing, mPAP generally tended to increase in all patients. 6 patients (27.27%) received intraoperative PAH-Specific therapy. All patients received oral sildenafil (75-100 mg/d orally), and 9 patients received postoperative oral sildenafil combined with nebulized iloprost (20 µg/d); intravenous treprostinil (2 ng/kg/min started and titrated to 10-17.5 ng/kg/min); or bosentan (250 mg/d) postoperatively. 7 patients (31.82%) reported postoperative complications, including 2 cases of respiratory failure requiring reintubation, 1 case of right heart failure, 2 cases of superficial surgical site infection, 1 case of fluid and electrolyte and acid-base imbalances, 2 cases of pneumonia and 1 case of pulmonary oedema with fluid overload. Two patients developed more than 1 postoperative complication. No in-hospital death occurred. Conclusions: The anesthetic management of scoliosis patients with PAH is important task that, like its own surgery, relies on the input of the multidisciplinary team for its success. Close monitoring, optimization of systemic blood pressure, pain control, oxygenation and ventilation, avoidance of exacerbating factors, and the use of vasopressors and pulmonary vasodilators when necessary are essential elements of management.

Anesthetic Management of Patients After Scoliosis Surgery: A Single-Center Retrospective Study.

PURPOSE: To evaluate the effect of anesthetic management on scoliosis surgery and review the incidence rate of perioperative adverse events. METHODS: This was a retrospective study and approved by the ethics committee. Patients who underwent scoliosis surgery from April 2011 to March 2018 in the Third Hospital of ChengDu were enrolled in this study. Characteristics of patients were obtained from the hospital's electronic records. The following information on patients was collected: preoperative assessment details, premedication, type of anesthesia and operation, the main postoperative outcome, and complications. Data were presented as the mean ± standard deviations (SD) for normally distributed continuous variables and numbers for categorical variables. Statistical analyses were performed using SPSS version 22.0. RESULTS: In total, 513 patients were enrolled in the present study. The main preoperative complication was cardiopulmonary dysfunction (386 cases, 75.24%). Anesthesia induction was performed with conscious tracheal intubation after oral surface anesthesia. In total, the common postoperative complications involved anesthesia (24 cases, 4.68%), surgery (23 cases, 4.48%), the respiratory system (138 cases, 26.90%), and the gastrointestinal tract (nine cases, 1.75%). The majority of postoperative complications were postoperative hypoxemia and hypercapnia, caused by poor cardiopulmonary function. Rare and serious complications still occurred. Three patients died in hospital. CONCLUSION: Our study demonstrated a high incidence of complications in scoliosis surgery, especially postoperative complications. Extreme postoperative vigilance is required and high-level monitoring of conditions is highly recommended.

Effectiveness and safety of a modified (rib ends fixed under transverse process) thoracoplasty for rib hump deformity in adults with severe thoracic scoliosis: A retrospective study.

Razor back deformity is one of the most noticeable problems of severe scoliosis. Thoracoplasty has been reported to be a useful approach to correct the rib hump deformity. However, the outcomes of thoracoplasty in patients with severe, rigid, thoracic scoliosis have not yet been evaluated.To evaluate the effectiveness and safety of a modified technique of thoracoplasty (rib ends fixed under transverse process) for rib hump deformity in adults with severe thoracic scoliosis and severe pulmonary dysfunction.Patients with severe thoracic scoliosis and severe pulmonary dysfunction who underwent staged surgical strategy including halo-pelvic traction, spinal osteotomy combined with the modified thoracoplasty were included. To avoid paradoxical breathing result from multiple rib resections and enlarge the capacity of thoracis, the ends after rib resection were fixed under transverse process compared with conventional thoracoplasty. Patients were excluded on the basis of pulmonary diseases and inadequate follow-up. Data on deformity correction and pulmonary complications were reviewed. A t test was performed on the pre- and postoperative data of pulmonary function, height of the rib hump deformity, and total lung area.Eighteen patients (5 men and 13 women) with a major thoracic curve of >130° were included. The mean age of patients was 25.3 ±â€Š3.6 years (range, 19-32 years), with an average length of follow-up of 30.2 months. After application of halo-pelvic traction, the mean major thoracic curve decreased from 168.2°â€Š±â€Š14.28° to 97.3°â€Š±â€Š10.75° and the thoracic kyphosis decreased from 159.4°â€Š±â€Š20.60° to 94.8°â€Š±â€Š9.58°. On average, 6.3 (range, 4-8) ribs were resected. The height of the rib hump decreased from 84.6 ±â€Š13.3 to 15.3 ±â€Š3.4 mm. The average predicted forced vital capacity (FVC%) before surgery was 37.2 ±â€Š13.30%, indicative of severe pulmonary impairment, with a small but non-significant improvement in the FVC% at the final follow-up. The mean total lung area increased from 2583.2 ±â€Š501.36 to 2890.1 ±â€Š537.30 mL at the last follow-up. No severe pulmonary complications occurred.Our modified approach to thoracoplasty procedure is effective and safe in correcting a razor back deformity in patients with severe, rigid, scoliosis, and severe pulmonary dysfunction, without causing any significant change in long-term pulmonary function.

Shoulder imbalance treated with scapuloplasty surgery in scoliosis patients: a clinical retrospective study.

BACKGROUND: To discuss the clinical efficacy and safety of scapuloplasty treating the shoulder imbalance in scoliosis patients. METHODS: A retrospective analysis was made on 21 patients who underwent scoliosis corrective surgery combined with scapuloplasty from September 2013 to March 2015. The average follow-up was 31.4 ± 5.3 months (24-42 months). The shoulder vertical difference (SVD), adjusted Constant-Murley score, range of shoulder motion function, Cavendish grade, and the overall satisfaction were compared among the pre-surgery, post-surgery, and the final follow-up periods. RESULTS: The shoulder vertical difference (SVD) significantly decreased at the time of post-surgery and the final follow-up, comparing the score of the pre-surgery. The SVD of all patients were decreased from preoperatively 3.2 ± 1.1 cm to 0.4 ± 0.3 cm, with the Cavendish grade improved to grade 1 at the final follow-up. The adjusted Constant-Murley score and range of shoulder motion function showed no significant difference during the three time periods (p > 0.05). And no severe complications had occurred over 2 years follow-up. CONCLUSION: The scapuloplasty surgery shows to be an effective and safety procedure to improve the shoulder imbalance, cosmetic appearance, and the overall satisfaction in scoliosis patients without impairing the shoulder function, which can be widely applied in clinic.

EMT-related gene expression is positively correlated with immunity and may be derived from stromal cells in osteosarcoma.

BACKGROUND: Osteosarcoma is the most common type of bone cancer in children and young adults. Recent studies have shown a correlation between epithelial-mesenchymal transition (EMT)-related gene expression and immunity in human cancers. Here, we investigated the relationship among EMT, immune activity, stromal activity and tumor purity in osteosarcoma. METHODS: We defined EMT gene signatures and evaluated immune activity and stromal activity based on the gene expression and clinical data from three independent microarray datasets. These factors were evaluated by single sample Gene Set Enrichment Analyses and the ESTIMATE tool. Finally, we analyzed the key source of EMT gene expression in osteosarcoma using microarray datasets from the Gene Expression Omnibus and human samples that we collected. RESULTS: EMT-related gene expression was positively correlated with immune and stromal activity in osteosarcoma. Tumor purity was negatively correlated with EMT, immune activity and stromal cells. We further demonstrated that high EMT gene expression could significantly predict poor overall survival (OS) and recurrence-free survival (RFS) in osteosarcoma patients, while high immune activity cannot. However, combining these factors could have further prognostic value for osteosarcoma patients in terms of OS and RFS. Finally, we found that stromal cells may serve as a key source of EMT gene expression in osteosarcoma. CONCLUSION: The results of this study reveal that the expression of EMT genes and immunity are positively correlated, but these signatures convey disparate prognostic information. Furthermore, the results indicate that EMT-related gene expression may be derived from stromal rather than epithelial cancer cells.

The valuation of concave-side thoracoplasty on the treatment of extremely severe scoliosis with severe pulmonary dysfunction on the base of halo-pelvic traction.

Extremely severe scoliosis patients, especially main thoracic Cobb' s angle >150°, often have severe thoracic deformity and pulmonary dysfunction, even the scoliosis is reduced by halo-pelvic traction, the improvement of pulmonary function is not satisfactory, the risk of spinal osteotomy in the next stage is still very high and left with obvious thoracic deformity. How to further improve the pulmonary function and appearance of these patients is a difficult problem to be solved.Twenty extremely severe scoliosis patients with severe pulmonary dysfunction who underwent concave-side thoracoplasty in our hospital from September 2014 to September 2017 were included, data of thoracic volume and pulmonary function were collected before and after operation. The pulmonary function value reported was predicted forced vital capacity (FVC%), T-test was used to analyze the changes of the data by the statistical software SPSS21.0.The 20 patient's averaged Cobb's angle of main thoracic was 163° ± 8° at admission and all of them with severe pulmonary dysfunction before concave-side thracoplasty. After operation, the thoracic volume of patients increased by 500.9 ±â€Š222.9 mL, FVC% increased by 8.9% ±â€Š7.5%. Both the difference has statistical significance (P < .01).Concave-side thoracoplasty based on the halo-pelvic traction cannot only enlarge the volume of the concave thoracic cavity, lighten the compression of lung and further improve the pulmonary function of extremely severe scoliosis, but also can strengthen the correction of scoliosis and spinal rotation. Therefore, it is a safe and effective surgical approach.

Effects of carbon-based impurities on graphene growth.

In this paper, we studied the growth of graphene on an untreated Cu substrate and further studied the effect of carbon-based impurities on the nucleation of graphene in different growth environments. It is found that the impurities on the surface of the Cu substrate easily lead to damage of the graphene, and the impurities do not always promote nucleation as previously reported, but inhibit nucleation in a high etching environment. Finally, based on experimental results, a model of nucleation and growth of graphene around impurities is presented.

TNF-α contributes to postmenopausal osteoporosis by synergistically promoting RANKL-induced osteoclast formation.

Previous studies showed that inflammatory cytokines promote osteoclast formation, characterized by the function of bone resorption. However, it remains unclear whether inflammatory factors contribute to osteoporosis syndrome in postmenopausal women. Here, we found that postmenopausal women with osteoporosis (PO) had increased levels of TNF-α, compared with those without osteoporosis. TNF-α is highly correlated with the RANK and estrogen levels in PO patients. in vitro, TNF-α synergistically promotes RANKL-induced osteoclast formation by activation of NF-κB and PI3K/Akt signaling. Moreover, inhibition of PI3K/Akt totally blocked the synergistic effects of TNF-α on NF-κB activation as well as osteoclast formation. Together, these results demonstrate that TNF-α synergistically promotes RANKL-induced osteoclasts formation through activation of PI3K/Akt signaling, which ultimately contributes to osteoporosis syndrome in postmenopausal women.

Growth promotion of vertical graphene on SiO2/Si by Ar plasma process in plasma-enhanced chemical vapor deposition.

This study investigates the growth promotion of vertically oriented graphene in plasma-enhanced chemical vapor deposition through Ar plasma treatment. Combined with various substrate treatments, including hydrofluoric acid etching and oxidation after Ar plasma treatment, Ar plasma pretreatment promotes vertical growth through the microcavity on the rough substrate surface and the active growth sites. The microcavity affects the strain distribution and defects of as-deposited planar films, which benefit the transition of 2D deposition to 3D vertical growth. A growth model on the effect of Ar plasma pretreatment is proposed.

Treatment of Extreme Tuberculous Kyphosis Using Spinal Osteotomy and Halo-Pelvic Traction: A Case Report.

STUDY DESIGN: A case report of treatment of extreme tuberculous kyphosis using spinal osteotomy and halopelvic traction. OBJECTIVE: The aim of this study was to describe the process and outcome of treatment of a case with extreme tuberculous kyphosis using spine osteotomy and halo-pelvic traction. SUMMARY OF BACKGROUND DATA: Spinal tuberculosis causes destruction, deformity, and paraplegia. Long-standing kyphosis may progress with growth in children, and produces respiratory insufficiency, and neurologic deficit. Surgery may help to prevent or reverse the neurological deterioration, while improving pulmonary function in cases with significant spinal deformity. METHODS: Review of records and radiographs. RESULTS: A 24-year-old female with tuberculous angular kyphosis presented with bilateral lower extremities paresis and dyspnea. The vertebral bodies from T3 to T9 were severely destructed, with a Cobb's angle of 180°on radiographs. The total duration of distraction using halopelvic apparatus kept 10 months. During the duration of traction, the patient underwent a posterior release surgery because flexibility of the kyphosis was not sufficient. Pedicle subtraction osteotomy and pedicle screw fixation were performed to achieve final correction when the Cobb's angle decreased to about 80°. After the whole treatment of halopelvic traction and spine ostetomy, the patient's height increased nearly 30 cm, whereas the angular kyphosis was corrected to a Cobb's angle of 30°. The patient had no complication and neurological deterioration during the treatment. Correction angle and good sagittal balance were well maintained in the duration of 2 years' follow-up. CONCLUSION: The halo-pelvic apparatus produces high corrective forces applied over a long period, and it provides a slow and safe correction of deformity. In cases of extreme kyphotic deformity, halopelvic traction is an appropriate technique, while avoiding many serious complications from a rapid, one-stage correction. LEVEL OF EVIDENCE: N/A.

[Clinical features and proportion analysis of adult hip fractures at 11 hospitals in Southwest China from 2010 to 2011].

OBJECTIVE: To analyze the clinical feature and constituent ratio of adult hip fractures in Southwest China. METHODS: The data of adult inpatients and outpatients with hip fractures treated between January 2010 and December 2011 in 11 hospitals of the Southwest China were collected and analyzed. The data includes gender, age, age distribution and fracture pattern according to AO classification. RESULTS: There were a total of 2,833 adult hip fractures, including 1,340 (47.30%) males and 1,493 (52.70%) females, with a male-to-female incidence ratio of 1: 1.11 and a mean age of (66±18) years. The highest frequency of hip fractures was seen in the 71 to 85 years age group (42.18%, 1,195/2,833). There were 844 fractures (29.79%) in the young and middle-aged group (16-<60 years) and 1 898 fractures (70.21%) in the geriatric group (≥60 years). Men had a higher rate than women (men: 577 fractures, 68.4%) in the young and middle-aged group, while women had a higher rate than men (women: 1,226 fractures, 61.64%) in the geriatric group, with a significant difference in the sex distribution between the two groups (χ2=214.001, P<0.01). The proportion of intertrochanteric fracture (type 31-A), femoral neck (type 31-B) and femoral head fracture (type 31-C) was 46.59%, 49.74% and 3.67% respectively. The highest frequency of the sub-type in each fracture type was type 31-A2, type 31-B2 and type 31-C2. CONCLUSIONS: Women have a higher rate than men in Southwest China. Geriatric patients are more than the young and middle-aged patients. The femoral neck fractures, intertrochanteric fractures and femoral head fractures are in descending orders according to the proportion of the three different hip fractures.

TR-FRET Assays for Endogenous Huntingtin Protein Level in Mouse Cells.

High-throughput measurement of huntingtin (Htt) levels is useful for Huntington's disease research. For example, identification of genetic or chemical modifiers that reduce Htt levels by high-throughput screening provides promising strategy for HD drug discovery. In the human cells, high-throughput measurement of Htt levels has been established based on the Time Resolved-Fluorescence Resonance Energy Transfer (TR-FRET) technology, using the 2B7/MW1 antibody pair. Unfortunately, application of this assay in the mouse cells has been problematic due to discrepancies between TR-FRET signals and Western-blots, possibly caused by non-specific antibody binding. Here we report TR-FRET assays that are able to detect endogenous Htt levels of the mouse striatal cell line (STHdh).

TR-FRET assays of Huntingtin protein fragments reveal temperature and polyQ length-dependent conformational changes.

Time-Resolved Fluorescence Resonance Energy Transfer (TR-FRET) technology is a widely used immunoassay that enables high-throughput quantitative measurements of proteins of interest. One of the well established examples is the TR-FRET assay for mutant huntingtin protein (HTT), which is the major cause of the neurodegenerative Huntington's disease (HD). To measure the mutant HTT protein, the published assays utilize a polyQ antibody, MW1, paired with HTT N-terminal antibodies. MW1 has much higher apparent affinity to mutant HTT with expanded polyQ stretch than to wild-type HTT with shorter polyQ, and thus the assays detect mutant HTT preferentially. Here we report a reversible temperature dependent change of TR-FRET signals for HTT N-terminal fragments: the signals become higher when the temperature is lowered from room temperature to 4°C. Interestingly, the temperature sensitivity of the TR-FRET signals is much higher for the Q25 (wild-type) than for the Q72 (mutant) protein. We further revealed that it is likely due to a temperature and polyQ length-dependent structural or spatial change of HTT, which is potentially useful for understanding polyQ structure and toxicity.

Drugging unconventional targets: insights from Huntington's disease.

Classical targeted drug discovery is based on targeting druggable targets, typically kinases and receptors of which the function can be agonized or antagonized. This strategy meets difficulties in cases such as Huntington's disease (HD) and similar neurodegenerative disorders, where the pathological function of the protein causing the disease is not clear. HD is caused by mutant HTT protein (mHTT) containing an expanded polyglutamine (polyQ) stretch, but the function of mHTT and how mHTT causes HD are unknown, thus preventing efforts to screen for mHTT 'inhibitors'. However, HD is appealing for drug discovery because the genetic mutation is clear, as compared with other major neurodegenerative disorders. Although mHTT is not a conventional 'druggable' target, one approach that appears promising is lowering its level, which might be applicable to other neurodegenerative disorders and proteinopathies linked to aberrant accumulation of proteins. Here we review mHTT lowering strategies that might provide promising avenues for drugging such diseases.

Randomized controlled trials of proximal femoral nail antirotation in lateral decubitus and supine position on treatment of intertrochanteric fractures.

The objective of this study was to compare the clinical results and complications of proximal femoral nail antirotation (PFNA) on treatment of intertrochanteric fractures in 120 elderly Chinese patients using Randomized Controlled Trials (RCTs). Totaly 120 cases enrolled were randomly assigned to a lateral decubitus position group and supine position group. The hospital stay, operating time, intraoperative blood loss, length of incision, X-ray fluoroscopy time, and out-of-bed activity time in the lateral decubitus position group were significantly lower than those in the supine position group. There was not statistical significance on union time and Harris values in the two position groups. Moreover, only complications of superficial wound infection were observed in the lateral decubitus position group, but two complications of deep venous thrombosis and wound deep infection were found in the supine position group. The present findings suggested that PFNA applied in elderly patients with intertrochanteric fracture can get satisfactory effects, and the treatment of intertrochanteric fractures using lateral decubitus position showed a satisfactory clinical outcome and a lower radiological complication rate.