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Background Mapping disease rates is an important aspect of epidemiological research because it helps inform public health policy. Disease maps are often drawn according to local administrative areas (LAAs), such as counties, cities, or towns. In LAAs with small populations, disease rates are unstable and are prone to appear extremely high or low. The empirical Bayes methods consider variance differences among different LAAs, thereby stabilizing the disease rates. The methods of kriging break the constraints of geopolitical boundaries and produce a smooth curved surface in the form of contour lines, but the methods lack the stabilizing effect of the empirical Bayes methods. Methods An easy-to-implement stabilized kriging method is proposed to map disease rates, which allows different errors in different LAAs. Results Monte Carlo simulations revealed that the stabilized kriging method had smaller symmetric mean absolute percentage error than three other types of methods (original LAA-based method, empirical Bayes methods, and traditional kriging methods) in nearly all scenarios considered. Real-world data analysis of oral cancer incidence rates in men from Taiwan demonstrated that the age-standardized rates in the central mountainous sparsely-populated region of Taiwan were stabilized using our proposed method, with no more large differences in numerical values, whereas the rates in other populous regions were not over smoothed. Additionally, the stabilized kriging map had improved resolution and helped locate several hot and cold spots in the incidence rates of oral cancer. Conclusions We recommend the use of the stabilized kriging method for mapping disease rates.

To compare the biomechanical properties of the double simple suture (DSS) technique, Krackow suture (KS) technique, and double Krackow suture (DKS) technique in subpectoral biceps tenodesis using a double-loaded suture anchor in a porcine tendon model.A total of 30 artificial composite (polymer and glass fiber) humeri and porcine flexor profundus tendons with diameter of 4.5 mm were used. The sample size was determined based on the results of the pilot study. Metallic suture anchors with double-loaded No. 2 braided sutures were inserted at the subpectoral tenodesis site, 5 cm from the superomedial corner of the greater tuberosity. Three suture techniques were used to fix the tendons: a DSS used as the control, a KS, and a DKS, which is an alternative tendon graft fixation technique. A preload of 5 N was applied for 2 minutes, followed by cyclic loading for 500 cycles ranging from 5 to 70 N; next, a load-to-failure test at 1 mm/s was performed.The KS (283.5 ± 57 N) and DKS (270.4 ± 50 N) groups had significantly greater ultimate failure loads as compared with the DSS group (84.1 ± 6.4 N) (P.001). Meanwhile, the peak displacement at failure loads in the KS group (9.3 ± 2.2 mm) and DKS group (7.8 ± 1.7 mm) were significantly smaller than that of the DSS group (11.3 ± 2.9 mm) (P = .015). Stiffness in the DSS group (36.4 ± 3.0 N/mm), KS group (39.6 ± 2.5 N/mm), and DKS group (36.9 ± 4.6 N/mm) was not significantly different (P = .125). All DSS constructs and 6 KS constructs failed with tendons being cut through by the sutures, whereas the other 4 KS constructs and all DKS constructs failed resulting from suture breakage.In this subpectoral biceps tenodesis model, both the KS technique and the DKS technique had similar time 0 biomechanical properties that were better than those of the double simple suture technique.A sturdy suture-tendon structure could prevent clinical failure of a subpectoral biceps tenodesis using a suture anchor.

Immune-mediated arthritis is an important chronic inflammatory disease of joints causing debilitating morbidity in affected patients. The mechanisms underlying immune-mediated arthritis have been intensively investigated, however the cellular and molecular factors contributing to the joint inflammation in different redox conditions have not been clearly elucidated. Previous research showed that phagocyte-produced reactive oxygen species (ROS) plays an anti-inflammatory role in K/BxN serum-transfer arthritis and NOX2-deficient mice tend to have more severe arthritis. Although many leukocytes play critical roles in the development of immune-mediated arthritis, the role of neutrophils, which are the main producers of ROS in inflammation, is still controversial. We hence assessed the immunomodulatory function of neutrophils from arthritic joints of NOX2-deficient and wild type mice in this study. We found more neutrophils accumulation in NOX2-deficient inflamed joints. RNA-sequencing and quantitative PCR revealed significantly increased expression of acute inflammation genes including IL1b, Cxcl2, Cxcl3, Cxcl10 and Mmp3 in activated neutrophils from the inflamed joints of NOX2-deficient mice. Moreover, gene set enrichment analysis (GSEA) showed enriched gene signatures in type I and II IFN responses, IL-6-JAK-STAT3 signaling pathway and TNF-α signaling pathway via NF-κB in NOX2-deficient neutrophils. In addition, we found that NOX2-deficient neutrophils expressed lower levels of PD-L1 and were less suppressive than WT neutrophils. Moreover, treatment of PD-L1-Fc decreased cytokine expression and ameliorated the severity of inflammatory arthritis. Our results suggest that NOX2-derived ROS is critical for regulating the function and gene expression in arthritic neutrophils. Both the strong pro-inflammatory and weakened anti-inflammatory functions of neutrophils due to abnormal redox regulation may be targets of treatment for immune-mediated arthritis.

The role of oxidative stress in ligamentum flavum (LF) hypertrophy has not been elucidated. We hypothesize that oxidative stress induces inflammatory responses and the subsequent fibrotic processes in LF, via activation of the Akt and MAPK pathways. Specimens of LFs were collected during surgeries for lumbar disc herniation (LDH) or lumbar spinal stenosis (LSS). Part of the LF specimens underwent analyses for ROS, fibrotic markers, and inflammatory mediators, with the remainder minced for cell cultures. The cell cultures were treated with H2O2, after which the cells were lysed and analyzed via western blotting. The specimens of the LSS patients showed increased infiltration of inflammatory cells and were stained positively for MMP-3, MMP-9, vimentin, and fibronectin. The LF of the LSS patients had increased oxidative stress and inflammation compared to that of the LDH patients. In vitro analyses demonstrated that oxidative stress rapidly activated the Akt and MAPK pathways. Inflammatory mediators, iNOS and NF-κB, and fibrotic markers, including TGF-β, β-catenin, α-SMA and vimentin, were significantly upregulated after induction of oxidative stress. Oxidative stress activated the intrinsic apoptotic pathway. These findings revealed that oxidative stress is one of the etiological factors of LF hypertrophy, which might provide new insights into treatment approaches.

Peripheral nervous injury (PNI) is a common form of trauma in modern society, especially in sport players. Despite the advance of therapy for PNI, the recovery of function can never reach the preinjury level after treatments. Recently, inhibiting neural oxidative stress shows a beneficial effect in improving functional recovery after PNI. In addition, sesame oil has been reported to possess the excellent antioxidative properties. However, whether sesame oil can improve the functional recovery after PNI by its antioxidative effect has never been investigated. Thirty mice were randomly divided into five groups of six: group I mice received sham operation; group II mice received sciatic nerve crush; and groups III-V mice daily ingested 0.5, 1 and 2 ml/kg of sesame oil for 6 days, respectively, after sciatic nerve crush. Oxidative stress, GAP43 and nuclear Nrf2 levels as well as spinal somatosensory evoked potentials were assessed on day 6, while paw withdrawal latency and sciatic function index were assessed on days 0, 3, and 6. Sesame oil significantly decreased lipid peroxidation and increased nuclear factor erythroid 2-related factor 2 and GAP43 expression in sciatic nerve. Furthermore, sesame oil improved electrophysiological and functional assessments in mice with sciatic nerve crush. In conclusion, sesame oil may improve nerve functional recovery by attenuating nerve oxidative stress in mouse acute peripheral nerve injury. Further, application of natural product sesame oil may be an alternative approach for improving nerve functional recovery in the clinical setting.

Background The optimal insertion angle for suture anchor insertion has long been of great interest. Although greater tuberosity decortication is commonly performed during rotator cuff repair, the effect of decortication on the suture anchor insertion angle remains unclear. The purpose of this study was to compare the pullout strength of threaded suture anchors inserted at 45° and 90° in decorticated and non-decorticated synthetic bone models. Methods Two kinds of synthetic bones were used to simulate the decorticated and non-decorticated conditions, for which 40 metallic suture anchors were used. Anchors were inserted at 45° and 90° in both decorticated and non-decorticated models and tested under cyclic loading followed by load-to-failure testing. The number of completed cycles, ultimate failure load, and failure modes was recorded. Results In the decorticated model, the ultimate failure load of anchors inserted at 45° (67.5 ± 5.3 N) was significantly lower than that of anchors inserted at 90° (114.1 ± 9.8 N) (p

De Quervain's disease is a stenosing tenosynovitis of the first dorsal compartment of the wrist. Histopathological studies have reported that the thickening of the first dorsal retinaculum is characterized by degeneration rather than inflammation. However, significant infiltration of mast cells and macrophages was noted in a torn tendon study, which suggested that innate immune pathways are part of the mechanism that mediates early tendinopathy. Recently, Interleukin-20 (IL-20) has been reported to provoke potent inflammation and regulate angiogenesis and chemotaxis, which are important for the pathogenesis of inflammatory diseases. The main purpose of our study was to investigate the correlation between IL-20 and tumor necrosis factor (TNF-α) and clarify the potential predictor of tendinopathy progression. Hematoxylin and eosin (H & E) and immunohistochemistry (IHC) staining were used to score and analyze the clinical outcome. TNF-α, IL-20 and related inflammation cytokines were examined. Moreover, the tenocytes were cultured with a stimulator and were used to examine inflammatory cytokine secretions. A real-time polymerase chain reaction (Real-time PCR) was used to detect the gene expression profile. The IHC data showed that TNF-α is up-regulated in grade III de Quervain's. The analysis data showed that IL-20 is positively correlated with TNF-α and disease severity. The real-time PCR showed that the inflammation stimulator enhanced the expression of IL-20 mRNA expression. Inflammation cytokines such as TNF-alpha, transforming growth factor-β (TGF-β) and IL-1 have been used as predictors of de Quervain's; IL-20 is a new predictor based on this study. In the future, IL-20 expression's involvement in the molecular mechanism of the severity of de Quervain's should be further investigated.

The spine is one of the most important parts of the human body. Spine diseases owning to aging or injuries would be treated by spine surgeries. However, the surgeries are highly dangerous and the surgical training can increase the success rate. In this paper, an interactive surgical simulation system for the training of pedicle screw implantation is introduced. We propose an automatic and efficient method to segment the vertebra from the CT images for building the vertebra model. The mean shift method which can cluster points having similar property into groups is used in data clustering. The clustered groups related to the bone region are chosen as the initial model. And then, we apply the Chan-Vese level set method which refines the vertebra contour by using the concepts of statistics. After segmentation, we then apply the marching cube algorithm to generate the 3D vertebra model, and pass it to a virtual surgical environment. A haptic device is adopted to interact with this model to fulfill the surgical simulation in the virtual environment. The average dice coefficient of the segmentation results is 0.92.

Chronic low back pain (CLBP), one of the most common musculoskeletal conditions in older adults, might affect balance and functional independence. The purpose of this study was to investigate the postural responses to a suddenly released pulling force in older adults with and without CLBP. Thirty community-dwelling older adults with CLBP and 26 voluntary controls without CLBP were enrolled. Participants were required to stand on a force platform while, with one hand, they pulled a string that was fastened at the other end to a 2-kg or to a 4-kg force in the opposite direction at a random order. The number of times the participants lost their balance and motions of center of pressure (COP) when the string was suddenly released were recorded. The results demonstrated that although the loss of balance rates for each pulling force condition did not differ between groups, older adults with CLBP had poorer postural responses: delayed reaction, larger displacement, higher velocity, longer path length, and greater COP sway area compared to the older controls. Furthermore, both groups showed larger postural responses in the 4-kg pulling force condition. Although aging is generally believed to be associated with declining balance and postural control, these findings highlight the effect of CLBP on reactive balance when responding to an externally generated force in an older population. This study also suggests that, for older adults with CLBP, in addition to treating them for pain and disability, reactive balance evaluation and training, such as reaction and movement strategy training should be included in their interventions. Clinicians and older patients with CLBP need to be made aware of the significance of impaired reactive balance and the increased risk of falls when encountering unexpected perturbations.

Background De Quervain disease is a stenosing condition of the sheath of the abductor pollicis longus and extensor pollicis brevis tendons at the radial styloid process. Previous studies consistently reported that the pathological change of this condition is thought to be primarily an extensor retinaculum thickened by fibrosis and angiogenesis instead of inflammation. Contradictorily, the conservative treatment for de Quervain disease is anti-inflammatory medication. The inflammatory response may be involved in this disease; however, there is no present study directly evidencing whether the inflammatory responses exist in de Quervain disease or not. The histopathology of de Quervain disease is yet to be elucidated clearly. Purpose To grade all specimens in the different stages and characterize specific inflammatory cell and factors to examine whether inflammatory response is involved in de Quervain disease. Methods Retinaculum samples were collected from 13 patients with de Quervain disease after surgery. The specimens were evaluated histologically by collagen structure grading and immunohistochemically by quantifying the presence of neutrophil elastase, macrophages, cyclooxygenase, and vascular endothelium. Results Neutrophil elastase and cyclooxygenase occur in the de Quervain disease retinaculum and increased with the grade of collagen structure. After angiogenesis, macrophage infiltration occurs in the grade II matrix worse than grade III matrix. Conclusions Inflammation is present in de Quervain disease. This study provides direct evidence for inflammatory cell and infiltration factors and offer valuable clues for specific pharmacological therapies for de Quervain disease.

Pedicle screws for spinal fixation risk neural damage because of the proximity between screw and nerve root. We assessed whether spinal somatosensory evoked potential (SSEP) could selectively detect pedicle-screw-related acute isolated nerve injury. Because pedicle screws are too large for a rat's spine, we inserted a K-wire close to the pedicle in 32 rats, intending not to injure the nerve root in eight (controls), and to injure the L4 or L5 root in 24. We used sciatic-nerve-elicited SSEP pre- and postinsertion. Radiologic, histologic, and postmortem observations confirmed the level and degree of root injury. Sciatic (SFI), tibial (TFI), and peroneal function indices (PFI) were calculated and correlated with changes in potential. Although not specific for injuries to different roots, amplitude reduction immediately postinsertion was significant in the experimental groups. Animals with the offending wire left in place for one hour showed a further non-significant deterioration of amplitude. Electrophysiologic changes correlated with SFI and histologic findings in all groups. SSEP monitoring provided reliable, useful diagnostic and intraoperative information about the functional integrity of single nerve-root injury. These findings are clinically relevant to acute nerve-root injury and pedicle-screw insertion. If a nerve-root irritant remains in place, a considerable neurologic deficit will occur.

This study presents a robust bounded control that prevents wheel skidding for an autonomous 4WS4WD vehicle under uncertain tire/road condition and aerodynamic drag. Constraint on combined wheel slip is incorporated as a priori in design to prevent the skidding. A robust low-and-high gain technique is used to suppress the path-tracking error and to enhance the utilization of the limited wheel slip. Simulation shows that, under the uncertain tire/road condition and aerodynamic drag, the proposed control scheme can effectively limit the combined wheel slip and achieve the goal of path tracking. Moreover, the control inputs of wheel torque and wheel steering are coordinated well during the path tracking.