Comparison of different rhythmic auditory stimuli on prefrontal cortex cortical activation during upper limb movement in patients with Parkinson's disease: a functional near-infrared spectroscopy study.

Background: A large number of literatures show that rhythmic auditory stimulation (RAS) can effectively improve Parkinson's disease (PD) patients' gait speed, frequency and speed. Its application and curative effect on upper limb motor function is relatively few. Objective: By studying the immediate effect of RAS with different rhythms on the prefrontal cortex (PFC) blood oxygen response during upper limb movement in PD patients, this study discusses the potential neurophysiological mechanism of RAS on upper limb movement in PD patients, which is expected to provide guidance for patients with upper limb dysfunction such as Parkinson's disease. Methods: In this study, 31 PD patients with upper limb static tremors were recruited to complete the nail board task on the healthy upper limb under the baseline rhythm, slow rhythm and fast rhythm provided by the therapist. At the same time, fNIRS was used to observe the blood oxygen response of PFC. Results: There was no significant main effect onsidein all brain regions (p > 0.05), and there was no interaction between rhythm and side (p > 0.05); Except lPFC, the main effect of rhythm in other brain regions was significant (p < 0.05), and ΔHbO increased with the change of rhythm. Paired analysis showed that there were significant differences in ΔHbO between slow rhythm and baseline rhythm, between fast rhythm and baseline rhythm, and between slow rhythm and fast rhythm (p < 0.05); The ΔHbO of rPFC, lDLPFC and rDLPFC were significantly different between slow rhythm and fast rhythm (p < 0.05); there were significant differences in the ΔHbO of BA8 between slow rhythm and baseline rhythm, and between slow rhythm and fast rhythm (p < 0.05). Conclusion: RAS may be a useful upper limb rehabilitation strategy for PD patients with upper limb dysfunction. At the same time, RAS with different rhythms also have different responses to PFC blood oxygen during upper limb movement in PD patients, so that we can design interventions for this kind of cortical mechanism. Identifying the neurophysiological mechanism of RAS on upper limb movement in PD patients may help clinicians customize rehabilitation methods for patients according to clues, so as to highly personalize upper limb training and optimize its effect.

Exploring the application and challenges of fNIRS technology in early detection of Parkinson's disease.

Background: Parkinson's disease (PD) is a prevalent neurodegenerative disorder that significantly benefits from early diagnosis for effective disease management and intervention. Despite advancements in medical technology, there remains a critical gap in the early and non-invasive detection of PD. Current diagnostic methods are often invasive, expensive, or late in identifying the disease, leading to missed opportunities for early intervention. Objective: The goal of this study is to explore the efficiency and accuracy of combining fNIRS technology with machine learning algorithms in diagnosing early-stage PD patients and to evaluate the feasibility of this approach in clinical practice. Methods: Using an ETG-4000 type near-infrared brain function imaging instrument, data was collected from 120 PD patients and 60 healthy controls. This cross-sectional study employed a multi-channel mode to monitor cerebral blood oxygen changes. The collected data were processed using a general linear model and ß values were extracted. Subsequently, four types of machine learning models were developed for analysis: Support vector machine (SVM), K-nearest neighbors (K-NN), random forest (RF), and logistic regression (LR). Additionally, SHapley Additive exPlanations (SHAP) technology was applied to enhance model interpretability. Results: The SVM model demonstrated higher accuracy in differentiating between PD patients and control group (accuracy of 85%, f1 score of 0.85, and an area under the ROC curve of 0.95). SHAP analysis identified the four most contributory channels (CH) as CH01, CH04, CH05, and CH08. Conclusion: The model based on the SVM algorithm exhibited good diagnostic performance in the early detection of PD patients. Future early diagnosis of PD should focus on the Frontopolar Cortex (FPC) region.

Quantifying stakeholders' preference for implantable medical devices in China: a discrete choice experiment.

OBJECTIVES: This study aims to gain insight into each attribute as presented in the value of implantable medical devices, quantify attributes' strength and their relative importance, and identify the determinants of stakeholders' preferences. METHODS: A mixed-methods design was used to identify attributes and levels reflecting stakeholders' preference toward the value of implantable medical devices. This design combined literature reviewing, expert's consultation, one-on-one interactions with stakeholders, and a pilot testing. Based on the design, six attributes and their levels were settled. Among 144 hypothetical profiles, 30 optimal choice sets were developed, and healthcare professionals (decision-makers, health technology assessment experts, hospital administrators, medical doctors) and patients as stakeholders in China were surveyed. A total of 134 respondents participated in the survey. Results were analyzed by mixed logit model and conditional logit model. RESULTS: The results of the mixed logit model showed that all the six attributes had a significant impact on respondents' choices on implantable medical devices. Respondents were willing to pay the highest for medical devices that provided improvements in clinical safety, followed by increased clinical effectiveness, technology for treating severe diseases, improved implement capacity, and innovative technology (without substitutes). CONCLUSIONS: The findings of DCE will improve the current evaluation on the value of implantable medical devices in China and provide decision-makers with the relative importance of the criteria in pricing and reimbursement decision-making of implantable medical devices.

Cost-effectiveness of open pancreaticoduodenectomy with or without Heidelberg TRIANGLE operation for pancreatic cancer in China.

OBJECTIVE: Pancreatic cancer is a digestive malignancy with dismal prognosis. The advent of Heidelberg TRIANGLE dissection technique brings a turning point to improve the chance of survival. Our study aimed to evaluated the cost-effectiveness of open pancreaticoduodenectomy (OPD) versus OPD combined with TRIANGLE operation (OPD-TRIANGLE) for patients with pancreatic cancer from the perspective of healthcare system in China. METHODS: Two hundred forty-six patients with pancreatic cancer who underwent OPD or OPD-TRIANGLE from January to September 2022 were enrolled in this study. We performed a decision tree model to assess clinical and economic implications of different surgical strategies. Estimation of health utilities was based on published literature, while costs were acquired from the hospitals, clinical expert consultations, and other local charge. The incremental cost-effectiveness ratio (ICER) was regarded as the primary outcome. Uncertainty of the findings was addressed via sensitivity analyses and scenario analyses. RESULTS: The results indicated that OPD-TRIANGLE group yielded additional 0.0402 QALYs at an incremental cost of US$1501.83 compared with OPD group, and the corresponding ICER was US$37,358.96 per QALY. The probabilities of OPD-TRIANGLE as the prior option were 52.8% at the WTP threshold of 60,000 US$/QALY. The main factors lined with costs incorporating total medical costs and operation-related costs. With 5-20% price reduction of OPD-TRIANGLE, the outcomes were also economically attractive. CONCLUSION: The findings of this population-based study suggested that OPD-TRIANGLE was likely to be cost-effective for patients with pancreatic cancer when compared against OPD. Further in-depth studies should be conducted to provide more comprehensive evidence.

A diagnostic model of nerve root compression localization in lower lumbar disc herniation based on random forest algorithm and surface electromyography.

Objective: This study aimed to investigate the muscle activation of patients with lumbar disc herniation (LDH) during walking by surface electromyography (SEMG) and establish a diagnostic model based on SEMG parameters using random forest (RF) algorithm for localization diagnosis of compressed nerve root in LDH patients. Methods: Fifty-eight patients with LDH and thirty healthy subjects were recruited. The SEMG of tibialis anterior (TA) and lateral gastrocnemius (LG) were collected bilaterally during walking. The peak root mean square (RMS-peak), RMS-peak time, mean power frequency (MPF), and median frequency (MF) were analyzed. A diagnostic model based on SEMG parameters using RF algorithm was established to locate compressed nerve root, and repeated reservation experiments were conducted for verification. The study evaluated the diagnostic efficiency of the model using accuracy, precision, recall rate, F1-score, Kappa value, and area under the receiver operating characteristic (ROC) curve. Results: The results showed that delayed activation of TA and decreased activation of LG were observed in the L5 group, while decreased activation of LG and earlier activation of LG were observed in the S1 group. The RF model based on eight SEMG parameters showed an average accuracy of 84%, with an area under the ROC curve of 0.93. The RMS peak time of TA was identified as the most important SEMG parameter. Conclusion: These findings suggest that the RF model can assist in the localization diagnosis of compressed nerve roots in LDH patients, and the SEMG parameters can provide further references for optimizing the diagnosis model in the future.

Cost-effectiveness of preimplantation genetic testing for aneuploidy for women with subfertility in China: an economic evaluation using evidence from the CESE-PGS trial.

BACKGROUND: There are a large number of infertile couples in China, but its treatment is notoriously expensive and not currently covered by insurance. The utility of preimplantation genetic testing for aneuploidy as an adjunct to in vitro fertilization has been debated. OBJECTIVE: To investigate the cost-effectiveness of preimplantation genetic testing for aneuploidy (PGT-A) versus conventional technology in in vitro fertilization (IVF) from the perspective of the healthcare system in China. METHODS: Following the exact steps in the IVF protocol, a decision tree model was developed, based on the data from the CESE-PGS trial and using cost scenarios for IVF in China. The scenarios were compared for costs per patient and cost-effectiveness. One-way sensitivity analysis and probabilistic sensitivity analysis were performed to confirm the robustness of the findings. MAIN OUTCOME MEASURES: Costs per live birth, Costs per patient, Incremental cost-effectiveness for miscarriage prevention. RESULTS: The average costs per live birth of PGT-A were estimated as ¥39230.71, which is about 16.8% higher than that of the conventional treatment. Threshold analysis revealed that PGT-A would need to increase the pregnancy rate of 26.24-98.24% or a cost reduction of ¥4649.29 to ¥1350.71 to achieve the same cost-effectiveness. The incremental costs per prevented miscarriage was approximately ¥45600.23. The incremental cost-effectiveness for miscarriage prevention showed that the willingness to pay would be ¥43422.60 for PGT-A to be cost-effective. CONCLUSION: The present cost-effectiveness analysis demonstrates that embryo selection with PGT­A is not suitable for routine applications from the perspective of healthcare providers in China, given the cumulative live birth rate and the high costs of PGT­A.

Influence of High-Molecular-Weight Glutenin Subunit on Components and Multiscale Structure of Gluten and Dough Quality in Soft Wheat.

A set of high-molecular-weight glutenin subunit (HMW-GS) deletion lines were used to investigate the influences of HMW-GS on wheat gluten, and dough properties were investigated using a set of HMW-GS deletion lines. Results showed that HMW-GS deletion significantly decreased the dough stability time, as well as viscoelastic moduli (G' and G″), compared with the wild type, where the deletion of x-type HMW-GSs (Ax1d, Bx7d, and Dy12d) decreased more than y-type HMW-GSs (By8d and Dy12d). The deletion of HMW-GS significantly decreased HMW-GS contents and increased α-/γ-gliadin contents. A proteomic study showed that the HMW-GS deletion down-regulated the HMW-GS, ß-amylase, serpins, and protein disulfide isomerase and up-regulated the LMW-GS, α/γ-gliadin, and α-amylase inhibitor. Meanwhile, HMW-GS deletion significantly decreased contents of ß-turn and ß-sheet. In addition, less energetically stable disulfide conformations (trans-gauche-gauche and trans-gauche-trans) were abundant in HMW-GS deletion lines. Furthermore, analysis of five HMW-GSs based on amino acid sequences proved that Dx2 and Bx7 had a more stable structure, followed by Ax1, then Dy12, and finally By8.

Effects of different types of visual music on the prefrontal hemodynamics of children with autism spectrum disorder based on functional near-infrared spectroscopy.

Background: Music therapy has been shown to improve communication in children with autism spectrum disorders (ASD), but little is known about how different types of music and images affect hemodynamic changes in the frontal lobe of the brain in children with ASD. This study aims to use functional near infrared spectroscopy (fNIRS) to explore the effects of different types of visual music on different brain regions of oxyhemoglobin (HbO) in the prefrontal lobe of children with ASD and children with typical development (TD), so as to provide evidence for better application of different types of visual music in the treatment of children with ASD. Methods: Seven children with ASD and nine matched children with TD were selected. Changes in HbO in their prefrontal lobes were determined by fNIRS after resting states and 12 different types of visual music tasks. Results: (I) Intra-group comparison: the influence of different types of light and music on ∆HbO in ROI (zone F) of ASD children is different, the activation degree shows that red light & positive music is less than green light & neutral music, red light & positive music is less than blue light & negative music, and there is no difference between green light & neutral music and blue light & negative music. (II) Comparison between groups: Visual musical tasks 1, 2, 3, 4, and 8 positively activated HbO in the prefrontal B and E regions of the brain in children with ASD and negatively activated HbO in TD children. Visual musical tasks 5, 9, 10, and 12 negatively activated HbO in the prefrontal F regions of the brain in children with ASD and positively activated HbO in TD children. Conclusions: When the two groups of children received the same visual music task, the changes of HbO in different regions of the prefrontal lobe were different; The effects of different types of visual music on the frontal lobe of the brain in children with ASD are inconsistent.

The Validity and Reliability of a New Intelligent Three-Dimensional Gait Analysis System in Healthy Subjects and Patients with Post-Stroke.

Odonate is a new, intelligent three-dimensional gait analysis system based on binocular depth cameras and neural networks, but its accuracy has not been validated. Twenty-six healthy subjects and sixteen patients with post-stroke were recruited to investigate the validity and reliability of Odonate for gait analysis and examine its ability to discriminate abnormal gait patterns. The repeatability tests of different raters and different days showed great consistency. Compared with the results measured by Vicon, gait velocity, cadence, step length, cycle time, and sagittal hip and knee joint angles measured by Odonate showed high consistency, while the consistency of the gait phase division and the sagittal ankle joint angle was slightly lower. In addition, the stages with statistical differences between healthy subjects and patients during a gait cycle measured by the two systems were consistent. In conclusion, Odonate has excellent inter/intra-rater reliability, and has strong validity in measuring some spatiotemporal parameters and the sagittal joint angles, except the gait phase division and the ankle joint angle. Odonate is comparable to Vicon in its ability to identify abnormal gait patterns in patients with post-stroke. Therefore, Odonate has the potential to provide accessible and objective measurements for clinical gait assessment.

Tibio-Femoral Contact Force Distribution of Knee Before and After Total Knee Arthroplasty: Combined Finite Element and Gait Analysis.

OBJECTIVE: To assess the tibio-femoral contact forces before and after total knee arthroplasty (TKA) in patients with knee osteoarthritis (KOA) by three-dimensional (3D) finite element analysis (FEA) models and gait analysis. METHODS: Two hospitalized patients with Kellgren-Lawrence grade IV varus KOA and two healthy subjects were enrolled in this study. Both patients underwent unilateral TKA. FEA models were established based on CT and MR images of the knees of the patients with KOA and healthy subjects. Gait analysis was performed using a three-dimensional motion capture system with a force plate. Three direction forces at the ankle joints were calculated by inverse dynamic analysis, which provided the load for the FEA models. The total contact forces of the knee joints were also calculated by inverse dynamic analysis to enable comparisons with the results from the FEA models. The total knee contact forces, maximum von Mises stress, and stress distribution of the medial plateau were compared between the patients and healthy subjects. The distributions of the medial plateau force at 2 and 6 months postoperatively were compared with the distributions of the forces preoperatively and those in the healthy subjects. RESULTS: During static standing, the medial plateau bore the most of the total contact forces in the knees with varus KOA (90.78% for patient 1 and 93.53% for patient 2) compared with 64.75 ± 3.34% of the total force in the healthy knees. At the first and second peaks of the ground reaction force during the stance phase of a gait cycle, the medial plateau bore a much higher percentage of contact forces in patients with KOA (74.78% and 86.48%, respectively, for patient 1; 70.68% and 83.56%, respectively, for patient 2) than healthy subjects (61.06% ± 3.43% at the first peak and 72.09% ± 1.83% at the second peak). Two months after TKA, the percentages of contact forces on the medial tibial plateau were 79.65%-85.19% at the first and second peaks of ground reaction forces during the stance phase of a gait cycle, and the percentages decreased to 53.99% - 68.13% 6 months after TKA. CONCLUSION: FEA showed that TKA effectively restored the distribution of tibio-femoral contact forces during static standing and walking, especially 6 months after the surgery. The changes in the gait were consistent with the changes in the contact force distribution calculated by the FEA model.

Ex Vivo Near-Infrared Molecular Imaging of Human Upper Urinary Tract Urothelial Carcinoma With a CD47-Based Targeted Tracer.

Objective: The low detection rate of early and small tumors remains a clinical problem that urgently needs to be solved in the accurate diagnosis and treatment of upper urinary tract urothelial carcinoma (UTUC). The objective of this study is to evaluate the feasibility of CD47 as a target for optical molecular imaging of human UTUC and conduct preliminary ex vivo imaging experiments. Methods: We firstly analyzed the genome-wide mRNA expression data from Gene Expression Omnibus (GEO). Paraffin-embedded tissue specimens comprising UTUC and normal urothelium were collected. All tissue specimens were used for immunohistochemistry to compare CD47 protein expression in normal and cancer tissue. Meanwhile, 12 patients undergoing radical nephroureterectomy were prospectively included in ex vivo imaging experiments. Freshly isolated upper urinary tract specimens were incubated with anti-CD47-Alexa Fluor 790 and then imaged under white light and near-infrared (NIR) light. Standard histopathologic evaluation was performed, and findings were correlated with CD47-targeted NIR molecular imaging. Results: The GEO data revealed that CD47 mRNA expression was higher in UTUC specimens than that in paracancer normal tissue. In immunohistochemical analysis, the CD47 protein expression level was higher in both non-muscle-invasive and muscle-invasive (stage ≥T2) UTUCs than that in normal uroepithelium, and the localization of CD47 protein was the tumor cell membrane. In the ex vivo imaging experiments, all patients were pathologically diagnosed with UTUC, and no adverse effects of anti-CD47-Alexa Fluor 790 on the histological structure of the tumor and normal uroepithelium were observed. In the NIR grayscale images, the mean fluorescence intensity of the tumor tissue was significantly higher than that of the adjacent normal background tissue, which greatly improved the visualization of the tumor. Conclusions: CD47-targeted NIR molecular imaging could be a feasible and powerful strategy for the accurate diagnosis of UTUC. Larger-scale randomized trials are needed.

Intersegmental Coordination in Patients With Total Knee Arthroplasty During Walking.

Precise identification of deficient intersegmental coordination patterns and functional limitations is conducive to the evaluation of surgical outcomes after total knee arthroplasty (TKA) and the design of optimal personalized rehabilitation protocols. However, it is still not clear how and when intersegmental coordination patterns change during walking, and what functional limitations are in patients with TKA. This study was designed to investigate lower limb intersegmental coordination patterns in patients with knee osteoarthritis before and after TKA and identify how intersegmental coordination of patients is altered during walking before and after TKA. It was hypothesized that 6-month after TKA, intersegmental coordination patterns of patients are improved compared with that before TKA, but still do not recover to the level of healthy subjects. Gait analysis was performed on 36 patients before and 6-month after TKA and on 34 healthy subjects. Continuous relative phase (CRP) derived from the angle-velocity phase portrait was used to measure the coordination between interacting segments throughout the gait cycle. Thigh-shank CRP and shank-foot CRP were calculated for each subject. Statistical parametric mapping (SPM), a one-dimensional analysis of the entire gait cycle curve, was performed directly to determine which periods of the gait cycle were different in patients and healthy subjects. Six-month after TKA, thigh-shank CRP was significantly higher during 5-12% of the gait cycle (p = 0.041) and lower during 44-95% of the gait cycle (p < 0.001) compared with healthy subjects, and was significantly higher during 62-91% of the gait cycle (p = 0.002) compared with pre-operation. Shank-foot CRP was significantly lower during 0-28% of the gait cycle (p < 0.001) and higher during 58-94% of the gait cycle (p < 0.001) compared with healthy subjects, and was significantly lower during 3-18% of the gait cycle (p = 0.005) compared with pre-operation. This study found that patients exhibited altered intersegmental coordination during the loading response and swing phase both before and after TKA. Six-month after TKA, the thigh-shank coordination was partially improved compared with pre-operation, but still did not recover to the level of healthy subjects, while there was no improvement in the shank-foot coordination pattern after TKA compared with pre-operation. CRP combined with SPM methods can provide insights into the evaluation of surgical outcomes and the design of rehabilitation strategy.

Coordination of lower limbs in patients with knee osteoarthritis during walking.

BACKGROUND: The movement coordination in patients with knee osteoarthritis may be impaired and the identification of the deficits in lower limb inter-segmental coordination is crucial to understand the effect of knee osteoarthritis on knee function. RESEARCH QUESTION: This study utilizes continuous relative phase to investigate the pattern and variability of lower limb inter-segmental coordination in patients with knee osteoarthritis and in healthy subjects during walking, and to evaluate inter-segmental coordination alterations in patients. METHODS: Gait was measured by a three-dimensional motion capture system for 44 patients with late-stage knee osteoarthritis and 22 healthy subjects. Segmental kinematic parameters, continuous relative phase and its variability were calculated. Independent samples t-tests were used to detect differences between patients and healthy subjects. RESULTS: Thigh-shank continuous relative phase of patients is significantly decreased by 16.04° and 16.18° during late stance and swing phase as compared with healthy subjects (P < 0.05). Shank-foot continuous relative phase of patients is significantly decreased by 6.89° during early stance and significantly increased by 5.49° and 6.39° during late stance and swing phase (P < 0.05). Patients also exhibit increased variability of thigh-shank continuous relative phase during late stance and swing phase by 1.90° and 1.65° respectively, and increased variability of shank-foot continuous relative phase during early stance and swing phase by 0.83° and 0.88° respectively as compared to healthy subjects (P < 0.05). SIGNIFICANCE: Patients with knee osteoarthritis exhibit altered coordination patterns and increased coordination variability of thigh-shank and shank-foot. Knee dysfunction results in altered lower limbs coordination and unstable motor control during walking. Investigation of inter-segmental coordination could therefore provide insights into changes in neuromuscular control of gait in patients with knee osteoarthritis.

The biomechanical effect of different posterior tibial slopes on the tibiofemoral joint after posterior-stabilized total knee arthroplasty.

BACKGROUND: Different posterior tibial slopes (PTS) after posterior-stabilized total knee arthroplasty (PS-TKA) may lead to different biomechanical characteristics of knee joint. This cadaveric study was designed to investigate the tibiofemoral kinematics and contact pressures after PS-TKA with different PTS. METHODS: Nine human cadaveric knee specimens were used for PS-TKA with the PTS of 3°, 6°, and 9°. The tibiofemoral kinematics and contact pressures were measured during knee flexion angle changing from 0 to 120° (with an increment of 10°) with an axial load of 1000 N at each angle. RESULTS: The root mean square (RMS) of the tibiofemoral contact area and the mean and peak contact pressures during knee flexion were 586.2 mm2, 1.85 MPa, and 5.39 MPa before TKA and changed to 130.2 mm2, 7.56 MPa, and 17.98 MPa after TKA, respectively. Larger contact area and smaller mean and peak contact pressures were found in the joints with the larger PTS after TKA. The RMS differences of femoral rotation before and after TKA were more than 9.9°. The posterior translation of the lateral condyle with larger PTS was more than that with smaller PTS, while overall, the RMS differences before and after TKA were more than 11.4 mm. CONCLUSION: After TKA, the tibiofemoral contact area is reduced, and the contact pressure is increased greatly. Approximately 80% of the femoral rotation is lost, and only about 60% of the femoral translation of lateral condyle is recovered. TKA with larger PTS results in more posterior femoral translation, larger contact area, and smaller contact pressure, indicating that with caution, it may be beneficial to properly increase PTS for PS-TKA.

Effect of community-based lifestyle interventions on weight loss and cardiometabolic risk factors in obese elderly in China: A randomized controlled trial.

PURPOSE: We aimed to assess the effect of community-based lifestyle interventions on weight loss and cardiometabolic risk factors among obese older adults, and to explore the potential factors that impede weight loss during lifestyle interventions. MATERIALS AND METHODS: A 2-arm parallel randomized controlled trial was conducted from 2013 through 2016 in the community health service centers in Nanjing, China. Four hundred and eighty obese older adults were randomly assigned to receive a 24-month lifestyle intervention (242 participants) or usual care (238 participants). The intervention group received a community-based behavioral lifestyle intervention program, which targeted weight loss through dietary changes and increased physical activity, with a combination mode of intervention delivery. RESULTS: Weight loss was statistically significant at the end of the intervention with a mean reduction of 0.03 ±â€¯2.51 kg in the control group and 3.22 ±â€¯3.43 kg in the intervention group (p < .001). In the intervention group, 41.1% of participants achieved the target of 5% weight loss significantly (p < .001). Participants in the intervention group had significantly greater improvements in cardiometabolic risk factors. Multivariable logistic regression showed that female, living alone, and having more comorbidities were barriers to weight loss during the intervention. CONCLUSIONS: This study demonstrated that community-based lifestyle interventions are effective for managing weight and improving cardiometabolic risk factors in obese older adults.

Tibiofemoral joint contact area and stress after single-bundle anterior cruciate ligament reconstruction with transtibial versus anteromedial portal drilling techniques.

BACKGROUND: During single-bundle ACLR, femoral tunnel location plays an important role in restoring the intact knee mechanisms, whereas malplacement of the tunnel was cited as the most common cause of knee instability. The objective of this study is to evaluate, objectively, the tibiofemoral contact area and stress after single-bundle (SB) anterior cruciate ligament reconstruction (ACLR) with femoral tunnel positions drilled by transtibial (TT) or anteromedial (AM) portal techniques. METHODS: Seven fresh human cadaveric knees underwent ACLR by the use of TT or AM portal techniques in a randomized order. These specimens were reused for ACL-R (TT and AM). The tibiofemoral contact area and stresses were gauged by an electronic stress-sensitive film inserted into the joint space. The knee was under the femoral axial compressive load of 1000 N using a biomechanics testing machine at 0°, 10°, 20°, and 30° of flexion. Three conditions were compared: (1) intact ACL, (2) ACLR by the use of the TT method, and (3) ACLR by the use of the AM portal method. RESULTS: Compared with AM portal ACL-reconstructed knees, a significantly decreased tibiofemoral contact area on the medial compartment was detected in the TT ACL-reconstructed knees at 20°of knee flexion (P = .047). Compared with the intact group, the TT ACLR group showed a higher mean stress at 20° and 30° of flexion on the medial compartments (P = .001, P = .003, respectively), while the AM portal ACLR group showed no significant differences at 30° of flexion (P = .073). The TT ACLR group also showed a higher mean maximum stress at 20° of flexion on the medial compartments (P = .047), while the AM portal ACLR group showed no significant differences at this angle(P = .319). DISCUSSION: The alternation of the tibiofemoral joint contact area and stress in reconstructed knees may be caused by the mismatch of the tibiofemoral joint during knee movement procedures compared with intact knees. CONCLUSIONS: SB ACLR by the use of the AM portal method and TT method both alter the tibiofemoral contact area and stress when compared with the intact knee. When compared with the TT technique, ACLR by the AM portal technique more closely restores the intact tibiofemoral contact area and stress at low flexion angles.

Pathological Findings in Myasthenia Gravis Patients with Thymic Hyperplasia and Thymoma.

Thymectomy is routinely carried out in patients with myasthenia gravis (MG) and thymomas. However, there is still a dispute as to whether MG patients with thymic hyperplasia should undergo thymectomy. We aimed to investigate the pathological findings in the thymus in patients with co-existing MG and thymic hyperplasia or thymomas treated with thymectomy, as well as effects of immunosuppression. Thirty-three patients with MG were selected and grouped accordingly: patients with no thymic abnormalities, patients with thymic hyperplasia, and patients with thymomas. All patients were treated with methylprednisolone alongside immunosuppression. A separate cohort of 24 MG patients with thymic hyperplasia or thymomas and treated with thymectomy were selected. As controls, 5 patients with thymomas or thymic carcinoma without MG were selected. Expression of CD5, extracellular regulated protein kinases1/2 mitogen activated protein kinase (ERK1/2MAPKs) and CD95 ligand (FasL) in the thymus was examined. Methylprednisolone and immunosuppressive therapy are highly effective in MG patients with normal thymus tissue and MG patients with thymic hyperplasia compared to MG patients with thymomas alone. CD5 expression was highest in MG patients with thymic hyperplasia, correlating with expression of ERK1/2MAPKs. FasL expression was similar across all groups. Thymomas may be distinguished from thymic hyperplasia by expression of CD5 and ERK1/2MAPKs. Thymectomy is the preferred treatment for MG patients with thymomas but may not be necessary in MG patients with thymic hyperplasia who are treated with immunosuppressive therapy.

Hippocampal immediate early gene transcription in the rat fluid percussion traumatic brain injury model.

Traumatic brain injury (TBI) is one of the leading causes of neurological disability and death in the USA across all age groups, ethnicities, and incomes. In addition to the short-term morbidity and mortality, TBI leads to epilepsy and severe neurocognitive symptoms, both of which are referenced to post-traumatic hippocampal dysfunction, although the mechanisms of such hippocampal dysfunction are incompletely understood. Here, we study the temporal profile of the transcription of three select immediate early gene (IEG) markers of neuronal hyperactivation, plasticity, and injury, c-fos, brain-derived neurotrophic factor (BDNF), and Bax, in the acute period following the epileptogenic lateral fluid percussion injury in a rodent TBI model. We found that lateral fluid percussion injury leads to enhanced expression of the selected IEGs within 24 h of TBI. Specifically, BDNF and c-fos increase maximally 1-6 h after TBI in the ipsilesional hippocampus, whereas Bax increases in the hippocampus bilaterally in this time window. Antagonism of the N-methyl-D-aspartate-type glutamate receptor by MK801 attenuates the increase in BDNF and Bax, which underscores a therapeutic role for N-methyl-D-aspartate-type glutamate receptor antagonism in the acute post-traumatic time period and suggests a value to a hippocampal IEG readout as an outcome after injury or acute therapeutic intervention.

A rapid lateral fluid percussion injury rodent model of traumatic brain injury and post-traumatic epilepsy.

Traumatic brain injury is a leading cause of acquired epilepsy. Initially described in 1989, lateral fluid percussion injury (LFPI) has since become the most extensively used and well-characterized rodent traumatic brain injury and post-traumatic epilepsy model. Universal findings, particularly seizures that reliably develop after an initial latent period, are evident across studies from multiple laboratories. However, the LFPI procedure is a two-stage process, requiring initial surgical attachment of a skull fluid cannula and then reanesthesia for delivery of the epidural fluid pressure wave. We now describe a modification of the original technique, termed 'rapid lateral fluid percussion injury' (rLFPI), which allows for a one-stage procedure and thus shorter operating time and reduced anesthesia exposure. Anesthetized male Long-Evans rats were subjected to rLFPI through a length of plastic tubing fitted with a pipette tip cannula with a 4-mm aperture. The cannula opening was positioned over a craniectomy of slightly smaller diameter and exposed dura such that the edges of the cannula fit tightly when pressed to the skull with a micromanipulator. Fluid percussion was then delivered immediately thereafter, in the same surgery session. rLFPI resulted in nonlethal focal cortical injury in all animals. We previously demonstrated that the rLFPI procedure resulted in post-traumatic seizures and regional gliosis, but had not examined other histopathologic elements. Now, we show apoptotic cell death confined to the perilesional cortex and chronic pathologic changes such as ipsilesional ventriculomegaly that are seen in the classic model. We conclude that the rLFPI method is a viable alternative to classic LFPI, and--being a one-stage procedure--has the advantage of shorter experiment turnaround and reduced exposure to anesthetics.

[Association of glucocorticoid receptor gene polymorphism with myasthenia gravis].

OBJECTIVE: To investigate the association of two glucocorticoid receptor (GR) polymorphisms (BclI, ER22/23EK) with Myasthenia Gravis (MG). METHODS: The genotypes of GR in 61 MG patients (MGG) and 57 age and gender-matched healthy controls (HCG) were determined by polymerase chain reaction and nucleotide sequence determination. RESULTS: The frequencies of three genotypes (GG, CG, CC) in BclIwere 3.3%, 34.4%, 62.3% in MGG and 3.5%, 38.6%, 57.9%in HCG respectively. The difference in the distribution of genotypes between MGG and HCG was statistically insignificant (P = 0.887). The frequencies of G and C allele were 20.5% vs 79.5 %in MGG, and 22.8% vs 77.2% in HCG. The difference in the distribution of alleles between MGG and HCG was statistically insignificant (P = 0.968). The genotype frequencies in two groups were both in Hardy-Weinberg equilibrium (P > 0.05). The genotypes of ER22/23EK in MGG and HCG were all GG and no mutation was detected. CONCLUSION: BclI and ER22/23EK polymorphisms of GR have no definite relationship with the risk of MG.