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Background: There was a paucity of valid information on how to rectify the convex coronal imbalance effectively in dystrophic scoliosis secondary to Type I neurofibromatosis (DS-NF1), while postoperative inadvertent aggravation of CCI occurred regularly resulting in poor patient satisfaction. We aimed to identify the risk factors for persistent postoperative CCI in DS-NF1, and to optimize the coronal rebalancing strategies based on the lessons learned from this rare case series.Methods: NF1-related scoliosis database was reviewed and those with significant CCI (> 3 cm) were identified, sorted and the outcomes of surgical coronal rebalance were analyzed to identify the factors being responsible for failure of CCI correction.Results: CCI with dystrophic thoracolumbar/lumbar apex was prone to remain uncorrected (7 failure cases in 11) when compared to those with thoracic apex (0 failure cases in 4) (63.6% vs. 0.0%, p = 0.077). Further comparison between those with and without post-op CCI showed a higher correction of main curve Cobb angle (65.9 ± 9.1% vs. 51.5 ± 37.3%, p = 0.040), more tilted instrumentation (10.3 ± 3.6° vs. 3.2 ± 3.1°, p = 0.001) and reverse tilt and translation of upper instrumented vertebra (UIV) to convex side (8.0 ± 2.3° vs. -3.4 ± 5.9°, p < 0.001; 35.4 ± 6.9 mm vs. 12.3 ± 13.1 mm, p = 0.001) in the uncorrected imbalanced group. Multiple linear regression analysis revealed that △UIV translation (pre- to post-operation) (β = 0.832; p = 0.030) was significantly correlated with the correction of CBD.Conclusion: Thoracolumbar/lumbar CCI in dystrophic scoliosis was prone to suffer high risk of persistent post-op CCI. Satisfying coronal rebalance should avoid UIV tilt and translation to the convex side, tilted morphology of instrumentation and over correction maneuvers for main curve, the upper hemi-curve region in particular. [ABSTRACT FROM AUTHOR]

Background: Rib head dislocation (RHD) in dystrophic scoliosis of type 1 neurofibromatosis (DS-NF1) is a unique disorder caused by skeletal dystrophy and scoliotic instability. No particular surgical manipulation is mentioned in the literature to instruct the spine surgeons to effectively obtain more migration of the dislocated rib head without resection. The present study aimed to investigate the effectiveness of screw/hook insertion at vertebrae with RHDs on the retraction of penetrated rib head from spinal canal.Methods: 37 neurologically intact patients with DS-NF1 and concomitant 53 RHDs undergoing scoliosis surgery without rib head excision were retrospectively reviewed. We used pre and postoperative whole-spine radiographs to determine the Cobb angle and the vertebral translation (VT), and the CT scans to evaluate the intraspinal rib length (IRL) and rib-vertebral angle (RVA). The dislocated ribs were assigned into two groups according to the presence of screw/hook insertion at vertebrae with RHD: screw/hook group and non-screw/hook group.Results: 37 dislocated ribs with screws/hooks insertion at corresponding vertebrae were assigned into the screw/hook group and the remaining 16 dislocated ribs consisted of the non-screw/hook group. In the screw/hook group, the correction rates of Cobb angle and VT were significantly higher than the non-screw/hook group after surgery (58.7 ± 16.0% vs. 30.9 ± 12.4%, p = 0.003; 61.8 ± 18.8% vs. 35.1 ± 16.6%, p = 0.001; respectively). Similarly, more correction rates of IRL and RVA were found in the screw/hook group than the non-screw/hook group (63.1 ± 31.3% vs. 30.1 ± 20.7%, p = 0.008; 17.6 ± 9.7% vs. 7.2 ± 3.6%, p = 0.006; respectively). Multiple linear regression analysis revealed that the correction rates of Cobb angle, VT and RVA contributed significantly to correction of IRL (β = 0.389, 0.939 and 1.869, respectively; p = 0.019, 0.001 and 0.002, respectively).Conclusion: Screw/hook insertion at dystrophic vertebrae with RHDs contributed significantly to the degree of retraction of penetrated rib head from spinal canal. This effectiveness is mediated by more corrections of VT and RVA. [ABSTRACT FROM AUTHOR]

Objective: To analyze the factors causing failure of primary surgery in congenital scoliosis (CS) patients with single hemivertebra (SHV) undergoing posterior spinal fusion, and to elucidate the revision strategies. Methods: In this retrospective study, a total of 32 CS patients secondary to SHV undergoing revision surgery from April 2010 to December 2017 due to failed primary surgery with more than 2 years follow‐up were reviewed. The reasons for failure of primary surgery and revision strategies were analyzed for each patient. The radiographic parameters including coronal Cobb angle, segmental kyphosis (SK), coronal balance (CB), and sagittal vertical axis (SVA) were compared between pre‐ and post‐revision. The complications during revision and follow‐up were recorded. Results: The mean age at revision surgery of the 32 CS patients was 15.8 ± 9.7 years and the average duration between primary and revision surgery was 31.0 ± 35.4 months. The reasons for failed primary surgery were severe post‐operative curve progression of focal scoliosis in 14 cases (43.8%), implant failure in 17 (53.1%) and trunk imbalance in 12 (37.5%). The candidate revision strategies included thorough resection of residual hemivertebra and adjacent discs, extending fusion levels, complete pseudarthrosis resection, massive bone graft, replacement of broken rods, satellite rod fixation, horizontalization of upper/lower instrumented vertebrae and rigid fusion of structural compensatory curves were performed individually. After revision surgery, the coronal Cobb angle, SK, CB and SVA showed significant improvement (P < 0.05) with no significant correction loss during follow‐up (P > 0.05). The intra‐operative complications included alarming changes of neurologic monitoring in three (9.4%) patients and dual tear in two, while rod fracture re‐occurred was detected in one patient at 18 months after revision. Conclusions: The common reasons for failed primary surgery in CS patients with SHV undergoing posterior spinal fusion were severe post‐operative curve progression of focal scoliosis, implant failure and trunk imbalance. The revision strategies including thorough resection of residual hemivertebra and adjacent discs, extended fusion levels to structural curvature, complete pseudarthrosis resection, massive bone graft, replacement of broken internal fixation and horizontalization of upper/lower instrumented vertebrae should be individualized based on the causes of failed primary surgery. [ABSTRACT FROM AUTHOR]

The solvothermal oxidation of [Mo3O2(O2CCH3)6(H2O)3]·ZnCl4 has been established as a general route toward [Mo4+3O4]-incorporated polyoxomolybdates (MoIV-POMs). Two unprecedented family members: the first Mo4+–Mo5+–Mo6+ nanocage cluster, Na[MoIV12MoV4MoVI3O43(OH)Py12]·11H2O (1) and the first heterometallic hybrid, [MoIV3MoVI10Zn(PO4)4(OH)2O31py3]·2(C5H6N)·3(C5H5N)·2H2O (2) have been prepared and characterized by X-ray crystallography, elemental and DFT theoretical analyses, XPS, mass spectroscopy, cyclic voltammetry, and IR spectroscopy. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the trends of axillary lymph node evaluation in ductal carcinoma in situ (DCIS) patients treated with breast- conserving therapy (BCT) and to identify the clinicopathological predictors of axillary evaluation. DCIS patients treated with BCT in 2006-2015 at our institute were retrospectively included in the analysis. Patients were categorized into three groups: sentinel lymph node biopsy (SLNB), axillary lymph node dissection (ALND), and non- evaluation. Univariate and multivariate logistic regression analyses were performed to identify factors that predicted axillary evaluation. A total of 315 patients were identified, among whom 135 underwent SLNB, and 15 underwent ALND. The proportion of patients who underwent axillary evaluation increased from 33.0% in 2006-2010 to 53.8% in 2011-2015 (P < 0.001), however, no patients had lymph node metastasis based on final pathology. In multivariate analysis, high- grade tumor favored axillary evaluation (OR = 4.376, 95% CI:1.410-13.586, P = 0.011); while excision biopsy favored no axillary evaluation compared with other biopsy methods (OR = 0.418, 95% CI: 0.192-0.909, P = 0.028). Subgroup analysis of patients treated in 2011-2015 revealed that high- grade tumor (OR = 5.898, 95% CI: 1.626-21.390, P = 0.007) and palpable breast lump (OR = 2.497, 95% CI: 1.037-6.011, P = 0.041) were independent predictors of axillary lymph node evaluation. Despite the significant decrease in ALND and a concerning overuse of SLNB, we identified no axillary lymph node metastasis, which justified omitting axillary evaluation in these patients. High- grade tumor, palpable lump, and biopsy method were independent predictors of axillary evaluations. Excision biopsy of suspicious DCIS lesions may potentially preclude the invasive component of the disease and help to avoid axillary surgery [ABSTRACT FROM AUTHOR]

Understanding amazingly complex brain functions and pathologies requires a complete cerebral vascular atlas in stereotaxic coordinates. Making a precise atlas for cerebral arteries and veins has been a century-old objective in neuroscience and neuropathology. Using micro-optical sectioning tomography (MOST) with a modified Nissl staining method, we acquired five mouse brain data sets containing arteries, veins, and microvessels. Based on the brain-wide vascular spatial structures and brain regions indicated by cytoarchitecture in one and the same mouse brain, we reconstructed and annotated the vascular system atlas of both arteries and veins of the whole mouse brain for the first time. The distributing patterns of the vascular system within the brain regions were acquired and our results show that the patterns of individual vessels are different from each other. Reconstruction and statistical analysis of the microvascular network, including derivation of quantitative vascular densities, indicate significant differences mainly in vessels with diameters less than 8μm and large than 20μm across different brain regions. Our precise cerebral vascular atlas provides an important resource and approach for quantitative studies of brain functions and diseases. [ABSTRACT FROM AUTHOR]

We validated an 18-gene classifier (GC) initially developed to predict local/regional recurrence after mastectomy in estimating distant metastasis risk. The 18-gene scoring algorithm defines scores as: <21, low risk; ≥21, high risk. Six hundred eighty-three patients with primary operable breast cancer and fresh frozen tumor tissues available were included. The primary outcome was the 5-year probability of freedom from distant metastasis (DMFP). Two external datasets were used to test the predictive accuracy of 18-GC. The 5-year rates of DMFP for patients classified as low-risk (n = 146, 21.7%) and high-risk (n = 537, 78.6%) were 96.2% (95% CI, 91.1%–98.8%) and 80.9% (74.6%–81.9%), respectively (median follow-up interval, 71.8 months). The 5-year rates of DMFP of the low-risk group in stage I (n = 62, 35.6%), stage II (n = 66, 20.1%), and stage III (n = 18, 10.3%) were 100%, 94.2% (78.5%–98.5%), and 90.9% (50.8%–98.7%), respectively. Multivariate analysis revealed that 18-GC is an independent prognostic factor of distant metastasis (adjusted hazard ratio, 5.1; 95% CI, 1.8–14.1; p = 0.0017) for scores of ≥21. External validation showed that the 5-year rate of DMFP in the low- and high-risk patients was 94.1% (82.9%–100%) and 80.3% (70.7%–89.9%, p = 0.06) in a Singapore dataset, and 89.5% (81.9%–94.1%) and 73.6% (67.2%–79.0%, p = 0.0039) in the GEO-GSE20685 dataset, respectively. In conclusion, 18-GC is a viable prognostic biomarker for breast cancer to estimate distant metastasis risk. [ABSTRACT FROM AUTHOR]

Corticotropin-releasing hormone (CRH), with widespread expression in the brain, plays a key role in modulating a series of behaviors, including anxiety, arousal, motor function, learning and memory. Previous studies have focused on some brain regions with densely distributed CRH neurons such as paraventricular hypothalamic nucleus (PVH) and bed nuclei of the stria terminalis (BST) and revealed some basic structural and functional knowledge of CRH neurons. However, there is no systematic analysis of brain-wide distribution of CRH neurons. Here, we performed a comprehensive study of CRH neurons in CRH-IRES-Cre;Ai3 mice via automatic imaging and stereoscopic cell counting in a whole mouse brain. We acquired four datasets of the CRH distributions with co-localized cytoarchitecture at a voxel resolution of 0.32 µm × 0.32 µm × 2 µm using brain-wide positioning system (BPS). Next, we precisely located and counted the EYFP-labeled neurons in different regions according to propidium iodide counterstained anatomical reference using Neuronal Global Position System. In particular, dense EYFP expression was found in piriform area, BST, central amygdalar nucleus, PVH, Barrington's nucleus, and inferior olivary complex. Considerable CRH neurons were also found in main olfactory bulb, medial preoptic nucleus, pontine gray, tegmental reticular nucleus, external cuneate nucleus, and midline thalamus. We reconstructed and compared the soma morphology of CRH neurons in 11 brain regions. The results demonstrated that CRH neurons had regional diversities of both cell distribution and soma morphology. This anatomical knowledge enhances the current understanding of the functions of CRH neurons. These results also demonstrated the ability of our platform to accurately orient, reconstruct and count neuronal somas in threedimension for type-specific neurons in the whole brain, making it feasible to answer the fundamental neuroscience question of exact numbers of various neurons in the whole brain. [ABSTRACT FROM AUTHOR]

Objectives: The current study aims to summarize breast anthropomorphic measurement features in Chinese patients with breast diseases and to investigate their potential correlations with demographic factors. Materials and methods: Fifteen breast anthropomorphic parameters of 605 Chinese female patients were collected prospectively. Breast ptosis status was scaled by two methods and breast volume was calculated according to a modified formula of BREAST-V. Results: Among 1210 breasts, the average breast volume was 340.0±109.1 ml (91.8–919.2 ml). The distance from the nipple to the inframammary fold was 7.5±1.6 cm in the standing position. The width of the breast base was 14.3±1.4 cm (8.5–23.5 cm). The incidence of breast ptosis was 22.8% (274/1204), of which 37 (23.5%) and 79 (31.7%) women had severe ptosis assessed by different criteria. Increased height (OR[odds ratio] = 1.500, P<0.001), post-menopausal status (OR = 1.463, P = 0.02), increased BMI, breastfeeding for 7–12 months (OR = 1.882, P = 0.008) and more than one year (OR = 2.367, P = 0.001) were risk factors for an increased breast volume. Post-menopausal status (OR = 2.390, P<0.001 and OR = 2.621, P<0.001 for different scales), BMI≥24.7 kg/m2 (OR = 3.149, P<0.001 and OR = 2.495, P = 0.002), breastfeeding for 7–12 months (OR = 4.136, P = 0.004 and OR = 4.010, P = 0.002), and breastfeeding for more than one year (OR = 6.934, P<0.001 and OR = 6.707, P<0.001) were independent risk factors for breast ptosis. Conclusions: The current study provides anthropomorphic measurements data of Chinese women with breast diseases, which are useful for cosmetic and reconstructive breast surgery decisions. Post-menopausal status, increased BMI, and breastfeeding for more than six months were independent risk factors for both increased breast volume and breast ptosis. [ABSTRACT FROM AUTHOR]

Background and Objectives: Paravertebral block placement was the main anesthetic technique for modified radical mastectomy in our hospital until February 2014, when its combination with blocks targeting the pectoral musculature was initiated. We compared the analgesic effects of paravertebral blocks with or without blocks targeting the pectoral musculature for modified radical mastectomy. Methods: We retrospectively collected data from a single surgeon and anesthesiologist from June 1, 2012, to May 31, 2015. Intraoperative sedatives and analgesic requirements, time to the first analgesic request, postoperative analgesic doses, patient satisfaction, and complications were compared. Results: Fifty-four patients received a paravertebral block alone (PECS 0), and 46 received a paravertebral block combined with blocks targeting the pectoral musculature (PECS 1). The highest intraoperative effect–site concentration of propofol was significantly lower in the PECS 1 group than in the PECS 0 group [2.3 (1.5, 2.8) vs 2.5 (1.5, 4) μg/mL, p = 0.0014]. The intraoperative rescue analgesic dose was significantly lower in the PECS 1 group [0 (0, 25) vs 0 (0, 75) mg of ketamine, p = 0.0384]. Furthermore, the PECS 1 group had a significantly longer time to the first analgesic request [636.5 (15, 720) vs 182.5 (14, 720) min, p = 0.0001]. After further adjustment for age, body mass index, American Society of Anesthesiologists Physical Status classification, chronic pain history, incidence of a superficial cervical plexus block placement, and operation duration, blocks targeting the pectoral musculature were determined to be the only significant factor (hazard ratio, 0.36; 95% confidence interval, 0.23–0.58; p < 0.0001). Very few patients used potent analgesics including morphine and ketorolac; the cumulative use of morphine or ketorolac was similar in the study groups. However, the incidence of all analgesic use, namely morphine, ketorolac, acetaminophen, and celecoxib, was significantly lower in the PECS 1 group [3.5 (0, 6) vs 5 (0, 12), p < 0.0001]. Conclusions: Compared with the placement of a paravertebral block alone, combining blocks targeting the pectoral musculature with a paravertebral block for modified radical mastectomy reduced the sedative and analgesic requirements during operation and provided more effective postoperative analgesia. [ABSTRACT FROM AUTHOR]

Given that lysophosphatidic acid (LPA) and the tetrodotoxin-resistant sodium channel Na1.8 are both involved in bone cancer pain, the present study was designed to investigate whether crosstalk between the LPA receptor LPA (also known as EDG2) and Na1.8 in the dorsal root ganglion (DRG) contributes to the induction of bone cancer pain. We showed that the EDG2 antagonist Ki16198 blocked the mechanical allodynia induced by intrathecal LPA in naïve rats and attenuated mechanical allodynia in a rat model of bone cancer. EDG2 and Na1.8 expression in L DRGs was upregulated following intrathecal or hindpaw injection of LPA. EDG2 and Na1.8 expression in ipsilateral L DRGs increased with the development of bone cancer. Furthermore, we showed that EDG2 co-localized with Na1.8 and LPA remarkably enhanced Na1.8 currents in DRG neurons, and this was blocked by either a protein kinase C (PKC) inhibitor or a PKCε inhibitor. Overall, we demonstrated the modulation of Na1.8 by LPA in DRG neurons, and that this probably underlies the peripheral mechanism by which bone cancer pain is induced. [ABSTRACT FROM AUTHOR]

Attenuations of solitary wave over a patch of submerged canopy are experimentally investigated. The submerged canopy is modeled by a group of circular cylinder array. The decay coefficients of different wave heights in two water depths along the wave flume are measured for six canopy models, including two canopy heights and three styles of arrangements. The relationships among the decay coefficient, and the dimensionless wave height, submergence ratio, relative height and arrangement of the canopy are experimentally studied. 2D PIV technique is employed to measure the representative flow field inside the canopy. A four-deck flow structure is proposed for wave flow field over shallow submerged canopy. The characteristics of shear flow inside the aligned canopy region are discussed. [ABSTRACT FROM AUTHOR]

Background: Systemically administered dexmedetomidine (DEX), a selective α2 adrenergic receptor (α2-AR) agonists, produces analgesia and sedation. Peripherally restricted α2-AR antagonist could block the analgesic effect of systemic DEX on neuropathic pain, with no effect on sedation, indicating peripheral analgesic effect of DEX. Tetrodotoxinresistant (TTX-R) sodium channel Nav1.8 play important roles in the conduction of nociceptive sensation. Both α2-AR and Nav1.8 are found in small nociceptive DRG neurons. We, therefore, investigated the effects of DEX on the Nav1.8 currents in acutely dissociated small-diameter DRG neurons. Results: Whole-cell patch-clamp recordings demonstrated that DEX concentration-dependently suppressed TTX-R Nav1.8 currents in small-diameter lumbar DRG neurons. DEX also shifted the steady-state inactivation curves of Nav1.8 in a hyperpolarizing direction and increased the threshold of action potential and decrease electrical and chemical stimuli-evoked firings in small-diameter DRG neurons. The α2-AR antagonist yohimbine or α2A-AR antagonist BRL44408 but not α2B-AR antagonist imiloxan blocked the inhibition of Nav1.8 currents by DEX. Immunohistochemistry results showed that Nav1.8 was predominantly expressed in peripherin-positive small-diameter DRG neurons, and some of them were α2A-AR-positive ones. Our electrophysiological recordings also demonstrated that DEX-induced inhibition of Nav1.8 currents was prevented by intracellular application of G-protein inhibitor GDPβ-s or Gi/o proteins inhibitor pertussis toxin (PTX), and bath application of adenylate cyclase (AC) activator forskolin or membrane-permeable cAMP analogue 8-Bromo-cAMP (8-Br-cAMP). PKA inhibitor Rp-cAMP could mimic DEX-induced inhibition of Nav1.8 currents. Conclusions: We established a functional link between α2-AR and Nav1.8 in primary sensory neurons utilizing the Gi/o/AC/cAMP/PKA pathway, which probably mediating peripheral analgesia of DEX. [ABSTRACT FROM AUTHOR]

The key technologies for the development of tsunami warning system include the establishment of tsunami database and inversion method for evaluating source parameters of earthquake by monitored wave data. A tsunami model based on the shallow water equations is adopted to simulate the 2011 Tohoku tsunami to validate the numerical model of generation and propagation of tsunami. The numerical results match well with measured data by DART buoys in terms of the wave height and the arrival time of the tsunami. For the potential earthquake source in the Manila Trench, the numerical model is used to compute the elementary wave fields triggered by unit sources of potential tsunami source with unit slip. Using the tsunami database derived by the elementary wave fields, an inversion method for plate slip based on multi-buoy measurements is applied to compute the time series of surface elevation at the given locations around the coasts in the South China Sea region. Through numerical simulations and multi-buoy inversion computation, the inversed time series of wave profile induced by earthquakes with the magnitudes Mw = 8.0, 8.5, 8.8, 9.35 are obtained. The comparisons of the inversion results and direct simulation data show good agreement. It turns out that, the multi-buoy inversion method works well and, according to the numerical results, deploying one or two buoys along the west side of the Manila Trench is necessary to provide tsunami warning information for the west coasts in the South China Sea. It is suggested that we should deploy one buoy between the south part of Taiwan and the north end of the Manila Trench subduction zone so that we could obtain a good predicted wave height at the south part of Taiwan by the multi-buoy inversion method. [ABSTRACT FROM AUTHOR]

The Okinawa Trench in the East China Sea and the Manila Trench in the South China Sea are considered to be the regions with high risk of potential tsunamis induced by submarine earthquakes. Tsunami waves will impact the southeast coast of China if tsunamis occur in these areas. In this paper, the horizontal two-dimensional Boussinesq model is used to simulate tsunami generation, propagation, and runup in a domain with complex geometrical boundaries. The temporary varying bottom boundary condition is adopted to describe the initial tsunami waves motivated by the submarine faults. The Indian Ocean tsunami is simulated by the numerical model as a validation case. The time series of water elevation and runup on the beach are compared with the measured data from field survey. The agreements indicate that the Boussinesq model can be used to simulate tsunamis and predict the waveform and runup. Then, the hypothetical tsunamis in the Okinawa Trench and the Manila Trench are simulated by the numerical model. The arrival time and maximum wave height near coastal cities are predicted by the model. It turns out that the leading depression N-wave occurs when the tsunami propagates in the continental shelf from the Okinawa Trench. The scenarios of the tsunami in the Manila Trench demonstrate significant effects on the coastal area around the South China Sea. [ABSTRACT FROM AUTHOR]

Pancreatic cancer usually has a poor prognosis, and no gene therapy has yet been developed that is effective to treat it. Since a unique characteristic of bone marrow-derived mesenchymal stem cells (MSCs) is that they migrate to tumor tissues, we wanted to determine whether MSCs could serve as a vehicle of gene therapy for targeting pancreatic cancer. First, we successfully extracted MSCs from SD rats. Next, MSCs were efficiently transduced with NK4, an antagonist of hepatocyte growth factor (HGF) which comprising the N-terminal and the subsequent four kringle domains of HGF, by an adenoviral vector. Then, we confirmed that rat MSCs preferentially migrate to pancreatic cancer cells. Last, MSCs expressing NK4 (NK4-MSCs) strongly inhibited proliferation and migration of the pancreatic cancer cell line SW1990 after co-culture. These results indicate that MSCs can serve as a vehicle of gene therapy for targeting pancreatic cancer. [ABSTRACT FROM AUTHOR]

Pain is the most common symptom of bone cancer. TGF-ß, a major bone-derived growth factor, is largely released by osteoclast bone resorption during the progression of bone cancer and contributes to proliferation, angiogenesis, immunosuppression, invasion, and metastasis. Here, we further show that TGF-ß 1 is critical for bone cancer-induced pain sensitization. We found that, after the progression of bone cancer, TGF-ß1 was highly expressed in tumor-bearing bone, and the expression of its receptors, TGFßRI and TGFßRII, was significantly increased in the DRG in a rat model of bone cancer pain that is based on intratibia inoculation of Walker 256 mammary gland carcinoma cells. The blockade of TGF-ß receptors by the TGFßRI antagonist SD-208 robustly suppressed bone cancer-induced thermal hyperalgesia on post-tumor day 14 (PTD 14). Peripheral injection ofTGF-ß1 directly induced thermal hyperalgesia in intact rats and wide-type mice, but not in Trpvl-/- mice. Whole-cell patch-clamp recordings from DRG neurons showed that transient receptor potential vanilloid (TRPV1) sensitivity was significantly enhanced on PTD 14. Extracellular application ofTGF-ß1 significantly potentiated TRPV1 currents and increased [Ca2+]i in DRG neurons. Pharmacological studies revealed that the TGF-ß1 sensitization of TRPV1 and the induction of thermal hyperalgesia required the TGF-ßR-mediated Smad-independent PKCe and TGF-ß activating kinase 1-p38 pathways. These findings suggest that TGF-ß1 signaling contributes to bone cancer pain via the upregulation and sensitization of TRPV1 in primary sensory neurons and that therapeutic targeting ofTGF-ß1 may ameliorate the bone cancer pain in advanced cancer. [ABSTRACT FROM AUTHOR]

We assessed the MSKCC nomogram performance in predicting SLN metastases in a Chinese breast cancer population. A new model (the SCH nomogram) was developed with clinically relevant variables and possible advantages. Data were collected from 1,545 patients who had a successful SLN biopsy between March 2005 and November 2011. We validated the MSKCC nomogram in the modeling and validation group. Clinical and pathologic features of SLN biopsy in modeling group of 1,000 patients were assessed with multivariable logistic regression to predict the presence of SLN metastasis in breast cancer. The SCH nomogram was created from the logistic regression model and subsequently applied to 545 consecutive SLN biopsies. By multivariate analysis, age, tumor size, tumor location, tumor type, and lymphovascular invasion were identified as independent predictors of SLN metastasis. The SCH nomogram was then developed using the five variables. The new model was accurate and discriminating (with an AUC of 0.7649 in the modeling group) compared to the MSKCC nomogram (with an AUC of 0.7105 in the modeling group). The area under the ROC curve for the SCH nomogram in the validation population is 0.7587. The actual probability trends for the various deciles were comparable to the predicted probabilities. The false-negative rates of the SCH nomogram were 1.67, 3.54, and 8.20 % for the predicted probability cut-off points of 5, 10, and 15 %, respectively. Compared with the MSKCC nomogram, the SCH nomogram has a better AUC with fewer variables and has lower false-negative rates for the low-probability subgroups. The SCH nomogram could serve as a more acceptable clinical tool in preoperative discussions with patients, especially very-low-risk patients. When applied to these patients, the SCH nomogram could be used to safely avoid a SLN procedure. The nomogram should be validated in various patient populations to demonstrate its reproducibility. [ABSTRACT FROM AUTHOR]

Based on the filtered Navier-Stokes equations and Smagorinsky turbulence model, a numerical wave flume is developed to investigate the overtopping process of irregular waves over smooth sea dikes. Simulations of fully nonlinear standing wave and regular wave's run-up on a sea dike are carried out to validate the implementation of the numerical wave flume with wave generation and absorbing modules. To model stationary ergodic stochastic processes, several cases with different random seeds are computed for each specified irregular wave spectrum. It turns out that the statistical mean overtopping discharge shows good agreement with empirical formulas, other numerical results and experimental data. [ABSTRACT FROM AUTHOR]

Background: Accurate intraoperative diagnosis of sentinel lymph node (SLN) metastasis reduces the need for additional surgery in patients with involved nodes. The present study evaluates the clinical value of multiple cross-sectional touch imprint cytology (TIC) as an intraoperative assessment for the diagnosis of SLN metastasis. Methods: This study consisted of 366 patients with surgically harvested SLNs that were sliced along their long axis at 2.0–3.0-mm intervals and 122 patients with SLNs that were sliced along their short axis at 1.5-mm intervals using a cutting apparatus designed by our group. The first group of patients was enrolled in this study between February 2005 and February 2008, while the second group was enrolled between March 2008 and January 2009. Serial sectioning of the SLNs at 100-μm intervals with hematoxylin-eosin (H&E) staining was used as the gold standard for pathological diagnosis. Results: Multiple cross-sectional TIC has a sensitivity, specificity, and overall accuracy rate of 92.0, 99.0, and 97.5%, respectively, on a per-patient basis, and it is superior to the standard imprint preparation protocol. Furthermore, the multiple cross-sectional TIC technique developed in this study was observed to detect more accurately macrometastases on a per-patient basis in comparison to the typical protocol ( P = 0.023). Of the patients included in this study, 97.7% had a positive SLN within their first three harvested SLNs. Conclusions: Multiple cross-sectional TIC is superior to the standard protocol, especially due to its ability to locate macrometastasis. Limiting intraoperative TIC to the first three harvested SLNs in the diagnosis of SLN metastasis may make this diagnostic procedure significantly cheaper and easier for pathologists to perform. [ABSTRACT FROM AUTHOR]

ABSTRACT: Combining mesh-less finite difference method and least square approximation, a new numerical model is developed for highly dispersive and fully nonlinear Boussinesq equations in two horizontal dimensions. The 3rd order truncated series solution of the Laplace equation is employed to approximate the velocity distribution in the vertical plane. The linear properties of the wave model are discussed with Fourier analysis. It is shown that the model is suitable to predict the propagation of water waves at the range of 0 ≤kh ≤ 10 for both the linear dispersion characteristic and shoaling gradient. Preliminary verifications of the numerical model are given for nonlinear wave shoaling problems, wave run-up on conical island. The numerical results agree well with the experimental data available in the literature. [Copyright &y& Elsevier]

Combining mesh-less finite difference method and least square approximation, a new numerical model is developed for highly dispersive and fully nonlinear Boussinesq equations in two horizontal dimensions. The 3rd order truncated series solution of the Laplace equation is employed to approximate the velocity distribution in the vertical plane. The linear properties of the wave model are discussed with Fourier analysis. It is shown that the model is suitable to predict the propagation of water waves at the range of 0 ≤ kh ≤ 10 for both the linear dispersion characteristic and shoaling gradient. Preliminary verifications of the numerical model are given for nonlinear wave shoaling problems, wave run-up on conical island. The numerical results agree well with the experimental data available in the literature. [ABSTRACT FROM AUTHOR]

Higher order Boussinesq-type equations for wave propagation over variable bathymetry were derived. The time dependent free surface boundary conditions were used to compute the change of the free surface in time domain. The free surface velocities and the bottom velocities were connected by the exact solution of the Laplace equation. Taking the velocities on half relative water depth as the fundamental unknowns, terms relating to the gradient of the water depth were retained in the inverse series expansion of the exact solution, with which the problem was closed. With enhancements of the finite order Taylor expansion for the velocity field, the application range of the present model was extended to the slope bottom which is not so mild. For linear properties, some validation computations of linear shoaling and Booij's tests were carried out. The problems of wave-current interactions were also studied numerically to test the performance of the enhanced Boussinesq equations associated with the effect of currents. All these computational results confirm perfectly to the theoretical solution as well as other numerical solutions of the full potential problem available. [ABSTRACT FROM AUTHOR]

Touch and itch sensations are crucial for evoking defensive and emotional responses, and light tactile touch may induce unpleasant itch sensations (mechanical itch or alloknesis). The neural substrate for touch-to-itch conversion in the spinal cord remains elusive. We report that spinal interneurons expressing Tachykinin 2-Cre (Tac2Cre) receive direct Aβ low threshold mechanoreceptor (LTMR) input and form monosynaptic connections with GRPR neurons. Ablation or inhibition markedly reduces mechanical but not acute chemical itch nor noxious touch information. Chemogenetic inhibition of Tac2Cre neurons also displays pronounced deficit in chronic dry skin itch, a type of chemical itch in mice. Consistently, ablation of gastrin-releasing peptide receptor (GRPR) neurons, which are essential for transmitting chemical itch, also abolishes mechanical itch. Together, these results suggest that innocuous touch and chemical itch information converge on GRPR neurons and thus map an exquisite spinal circuitry hard-wired for converting innocuous touch to irritating itch. Light touch can sometimes induce unpleasant itch sensation but the neural correlates of this conversion are not well studied. Here, the authors provide evidence that Tac2 expressing spinal interneurons are connected to gastrin-releasing peptide receptor (GRPR) neurons and form an integral part of the neural circuit underlying touch evoked itch. [ABSTRACT FROM AUTHOR]

Background: Pre-pubertal idiopathic scoliosis (IS) is associated with high risk of bracing ineffectiveness. Integrated multidimensional maturity assessments are useful but complex to predict the high-risk occurrence of curve progression. This study is designed to provide a simple screening method for brace effectiveness by determining whether or not the braced curve behavior at growth spurt, being defined as variations in Cobb angle velocity (AV) at peak height velocity (PHV), can be a new factor predictive of brace outcome prescribed before PHV.Methods: This is a retrospective study of a series of 35 IS girls with simplified skeletal maturity score no more than 3 at initiation of bracing treatment and followed up through the growth spurt until brace weaning or surgery. Serial Cobb angle and maturity indicators involving height velocity, Risser sign, triradiate cartilage, simplified skeletal maturity score and distal radius and ulna classification were assessed and patients were stratified into either a positive or negative category based on a positive or negative value of AV at PHV. Comparisons were made between the positive and negative AV groups, as well as the failed and successful bracing groups, using independent sample T test and crosstab analysis. Logistic regression analysis was used to identify the predictive factors of failed brace treatment.Results: Brace treatment prescribed before PHV was found to have an overall failure rate of 57.1% and a surgical rate of 45.7%. Negative AV at PHV accounting for 54.3% of the recruited patients were associated with lower brace failure rate (36.8% vs. 81.2%, p = 0.016) and surgical rate (21.1% vs. 75.0%, p = 0.002). Patients in the failed bracing group showed higher ratio of thoracic curve (80.0% vs. 26.7%,p = 0.002) and higher AV at growth peak (2.3 ± 9.1 vs. -6.5 ± 11.4°/yrs., p = 0.016). The logistic regression analysis revealed that positive AV at PHV (OR = 9.268, 95% CI = 1.279-67.137, p = 0.028) and thoracic curve type (OR = 13.391, 95% CI = 2.006-89.412, p = 0.007) were strong predictive factors of ineffective brace treatment initiated before PHV.Conclusions: Sustained curve correction following bracing despite early onset and rapid pubertal growth was strongly predictive of effective brace control of scoliosis. [ABSTRACT FROM AUTHOR]