Simulation of Riding a Full Suspension Bicycle for Analyzing Comfort and Pedaling Force

AbstractRecently, there is an increasing interest on bicycle riding for recreation or fitness purpose. Bicycles are also accepted as urban transportation due to the consciousness of environmental protection. For a more comfortable riding experience, many bicycles are equipped with a suspension system including a front suspension fork and/or rear suspension. However, when a suspension system is added to a bicycle, it makes riding a little heavier since suspension dissipates some pedalling energy. This paper discusses front and rear suspensions corresponding to rider comfort and pedalling effort when riding on a rough road and smooth road. A human body computer model LifeMOD® is employed to model the cyclist. Dynamic analysis software ADAMS® is employed to analyze human body vibration and leg muscle forces of bicycle riding. Human body acceleration vs. vibration frequencies are used as the comfort criteria. The results show that a suspension system may effectively reduce high frequency vibration of the human body when riding on a rough road. Pedalling forces are mostly contributed by the biceps femoris and semitendinosus. The suspension system would increase the pedaling forces of femoris and semitendinosus. Other leg muscles have a minor effect on pedaling forces. Results obtained from this research are useful for the design of bicycle suspension systems with better comfort and less loss of pedalling efficiency

Detection of subtle neurological alterations by the Catwalk XT gait analysis system

BACKGROUND: A new version of the CatWalk XT system was evaluated as a tool for detecting very subtle alteration in gait based on higher speed sample rate; the system could also demonstrate minor changes in neurological function. In this study, we evaluated the neurological outcome of sciatic nerve injury intervened by local injection of hyaluronic acid. Using the CatWalk XT system, we looked for differences between treated and untreated groups and differences within the same group as a function of time so as to assess the power of the Catwalk XT system for detecting subtle neurological change. METHODS: Peripheral nerve injury was induced in 36 Sprague–Dawley rats by crushing the left sciatic nerve using a vessel clamp. The animals were randomized into one of two groups: Group I: crush injury as the control; Group II: crush injury and local application with hyaluronic acid. These animals were subjected to neurobehavior assessment, histomorphology evaluation, and electrophysiology study periodically. These data were retrieved for statistical analysis. RESULTS: The density of neurofilament and S-100 over the distal end of crushed nerve showed significant differences either in inter-group comparison at various time points or intra-group comparison from 7 to 28 days. Neuronal structure architecture, axon counts, intensity of myelination, electrophysiology, and collagen deposition demonstrate significant differences between the two groups. There was significant difference of SFI and angle of ankle in inter- group analysis from 7 to 28 days, but there were no significant differences in SFI and angle of ankle at time points of 7 and 14 days. In the Cat Walk XT analysis, the intensity, print area, stance duration, and swing duration all showed detectable differences at 7, 14, 21, and 28 days, whereas there were no significant difference at 7 and 14 days with CatWalk 7 testing. In addition, there were no significant differences of step sequence or regularity index between the two versions. CONCLUSION: Hyaluronic acid augmented nerve regeneration as early as 7 days after crush injury. This subtle neurological alteration could be detected through the CatWalk XT gait analysis but not the SFI, angle of ankle, or CatWalk 7 methods

Cytochrome P450 Metabolism of Betel Quid-Derived Compounds: Implications for the Development of Prevention Strategies for Oral and Pharyngeal Cancers

Betel quid (BQ) products, with or without tobacco, have been classified by the International Agency for Research on Cancer (IARC) as group I human carcinogens that are associated with an elevated risk of oral potentially malignant disorders (OPMDs) and cancers of the oral cavity and pharynx. There are estimated 600 million BQ users worldwide. In Taiwan alone there are 2 million habitual users (approximately 10% of the population). Oral and pharyngeal cancers result from interactions between genes and environmental factors (BQ exposure). Cytochrome p450 (CYP) families are implicated in the metabolic activation of BQ- and areca nut-specific nitrosamines. In this review, we summarize the current knowledge base regarding CYP genetic variants and related oral disorders. In clinical applications, we focus on cancers of the oral cavity and pharynx and OPMDs associated with CYP gene polymorphisms, including CYP1A1, CYP2A6, CYP2E1, and CYP26B1. Our discussion of CYP polymorphisms provides insight into the importance of screening tests in OPMDs patients for the prevention of oral and pharyngeal cancers. Future studies will establish a strong foundation for the development of chemoprevention strategies, polymorphism-based clinical diagnostic tools (e.g., specific single-nucleotide polymorphism (SNP) “barcodes”), and effective treatments for BQ-related oral disorders

Detection of SARS-associated Coronavirus in Throat Wash and Saliva in Early Diagnosis

Early detection of SARS-CoV in throat wash and saliva suggests that these specimens are ideal for SARS diagnosis

Genome-Wide Association Study of Young-Onset Hypertension in the Han Chinese Population of Taiwan

Young-onset hypertension has a stronger genetic component than late-onset counterpart; thus, the identification of genes related to its susceptibility is a critical issue for the prevention and management of this disease. We carried out a two-stage association scan to map young-onset hypertension susceptibility genes. The first-stage analysis, a genome-wide association study, analyzed 175 matched case-control pairs; the second-stage analysis, a confirmatory association study, verified the results at the first stage based on a total of 1,008 patients and 1,008 controls. Single-locus association tests, multilocus association tests and pair-wise gene-gene interaction tests were performed to identify young-onset hypertension susceptibility genes. After considering stringent adjustments of multiple testing, gene annotation and single-nucleotide polymorphism (SNP) quality, four SNPs from two SNP triplets with strong association signals (−log10(p)>7) and 13 SNPs from 8 interactive SNP pairs with strong interactive signals (−log10(p)>8) were carefully re-examined. The confirmatory study verified the association for a SNP quartet 219 kb and 495 kb downstream of LOC344371 (a hypothetical gene) and RASGRP3 on chromosome 2p22.3, respectively. The latter has been implicated in the abnormal vascular responsiveness to endothelin-1 and angiotensin II in diabetic-hypertensive rats. Intrinsic synergy involving IMPG1 on chromosome 6q14.2-q15 was also verified. IMPG1 encodes interphotoreceptor matrix proteoglycan 1 which has cation binding capacity. The genes are novel hypertension targets identified in this first genome-wide hypertension association study of the Han Chinese population

Identification of IGF1, SLC4A4, WWOX, and SFMBT1 as Hypertension Susceptibility Genes in Han Chinese with a Genome-Wide Gene-Based Association Study

Hypertension is a complex disorder with high prevalence rates all over the world. We conducted the first genome-wide gene-based association scan for hypertension in a Han Chinese population. By analyzing genome-wide single-nucleotide-polymorphism data of 400 matched pairs of young-onset hypertensive patients and normotensive controls genotyped with the Illumina HumanHap550-Duo BeadChip, 100 susceptibility genes for hypertension were identified and also validated with permutation tests. Seventeen of the 100 genes exhibited differential allelic and expression distributions between patient and control groups. These genes provided a good molecular signature for classifying hypertensive patients and normotensive controls. Among the 17 genes, IGF1, SLC4A4, WWOX, and SFMBT1 were not only identified by our gene-based association scan and gene expression analysis but were also replicated by a gene-based association analysis of the Hong Kong Hypertension Study. Moreover, cis-acting expression quantitative trait loci associated with the differentially expressed genes were found and linked to hypertension. IGF1, which encodes insulin-like growth factor 1, is associated with cardiovascular disorders, metabolic syndrome, decreased body weight/size, and changes of insulin levels in mice. SLC4A4, which encodes the electrogenic sodium bicarbonate cotransporter 1, is associated with decreased body weight/size and abnormal ion homeostasis in mice. WWOX, which encodes the WW domain-containing protein, is related to hypoglycemia and hyperphosphatemia. SFMBT1, which encodes the scm-like with four MBT domains protein 1, is a novel hypertension gene. GRB14, TMEM56 and KIAA1797 exhibited highly significant differential allelic and expressed distributions between hypertensive patients and normotensive controls. GRB14 was also found relevant to blood pressure in a previous genetic association study in East Asian populations. TMEM56 and KIAA1797 may be specific to Taiwanese populations, because they were not validated by the two replication studies. Identification of these genes enriches the collection of hypertension susceptibility genes, thereby shedding light on the etiology of hypertension in Han Chinese populations

The Feasibility of Amniotic Fluid Mesenchymal Stem Cells in Treatment of Sciatic Nerve Injury

羊水間葉幹細胞( amniotic fluid mesenchymal stem cell)目前已被分離及鑑定。然而使用羊水間葉幹細胞以治療周邊神經損傷的研究非常少。因此本研究主要是研究使用羊水間葉幹細胞，以治療周邊神經損傷的可行性。研究使用羊水間葉幹細胞的可行性主要分成三部分。第一部分：使用同一種系的細胞移植，把大白鼠的羊水間葉幹細胞移植到大白鼠的坐骨神經上。第二部分：使用人類的羊水間葉幹細胞移植到大白鼠的坐骨神經上。第三部分：使用人類的羊水間葉幹細胞移植到大白鼠的坐骨神經上，並使用顆粒球生長激素(granulocyte-colony stimulating factor )來改善移植的環境。 第一部分：左側坐骨神經使用止血夾來造成神經損傷，把大白鼠的羊水間葉幹細胞移植到大白鼠的坐骨神經上。使用免疫螢光分析及組織染色來檢視神經滋養因子的表現。神經功能的評估包括運動功能、電生理、組織及免疫螢光分析。結果顯示大白鼠的羊水間葉幹細胞表現CD29及CD44，但不表現CD11b及CD45。羊水間葉幹細胞同時表現BDNF (brain-derived neurotrophic factor)、GDNF (glia cell line-derived neurotrophic factor)、CNTF (ciliary neurotrophic factor)、 NGF (nerve growth factor)及NT-3 (neurotrophin-3)的神經滋養因子。大白鼠的羊水間葉幹細胞的移植促進神經的生長，表現於運動功能、神經電生理及神經組織的鞘化程度。此外神經組織於免疫螢光分析及免疫染色，發現羊水間葉幹細胞表現及分泌神經滋養因子。 第二部分：切割一段左側坐骨神經造成神經間隙損傷，移植人類的羊水間葉幹細胞到大白鼠的坐骨神經間隙上。神經功能的評估包括運動功能、電生理 及組織免疫染色。結果顯示人類的羊水間葉幹細胞移植到大白鼠的坐骨神經間隙上，促進神經的生長表現於腳踝的伸張角度及腳指的活動。此外神經電生理的參數也獲的改善。神經組織的變化上發現神經組織的間隙減少。 第三部分：左側坐骨神經使用止血夾來造成神經損傷，移植人類的羊水間葉幹細胞移植到大白鼠的坐骨神經上。並使用顆粒球生長激素來改善移植的環境。使用免疫分析及組織染色來檢視組織中發炎細胞及細胞素的表現。神經的功能的評估包括運動功能、電生理，組織及免疫染色。結果顯示，神經組織壓傷後造成發炎反應、破壞神經的完整性並造成神經功能的障礙。顆粒球生長激素可以減緩受傷組織的發炎現象，並減少羊水間葉幹細胞的凋亡。人類的羊水間葉幹細胞移植不論有無顆粒球生長激素的投與皆會改善神經功能。然而同時給予人類的羊水間葉幹細胞移植及顆粒球生長激素，神經功能的改善最明顯。因此，大白鼠羊水間葉幹細胞可以促進神經的生長，其主要的機轉主要透過羊水間葉幹細胞分泌神經滋養因子。而人類羊水間葉幹細胞也透過相類似的途徑促進神經的生長。使用顆粒球生長激素來改善細胞移植的環境，可以減少細胞移植的死亡，並進一步促進神經的生長。Amniotic fluid mesenchymal stem cells (AFS) have been successfully isolated and identified. The application of AFS in repair of peripheral nerve injury was scarce. This study was conducted to evaluate the feasibility of AFS in the treatment of peripheral nerve injury. The determination of feasibility consisted of the same species transplantation from rat AFS to rat sciatic nerve injury (Part I), human AFS to rat sciatic nerve gap injury (Part II), and human AFS to rat sciatic nerve injury assisted with the improvement of transplantation milieu by granulocyte colony-stimulating factor (G-CSF) (Part III). Part I: Fifty Sprague Dawley rats weighing from 250-300 gm were used in this study. The left sciatic nerve was crushed with a vessel clamp. Rat amniotic fluid mesenchymal stem cells embedded in the fibrin glue and woven Surgicel were delivered to injured nerve. Enzyme-linked immunosorbent assay (ELISA) and immunohistochemical (IHC) studies were used to detect the neurotrophic factors secreted by amniotic fluid mesenchymal stem cells. Nerve regeneration was assessed by motor function, electrophysiology, histology, and IHC studies. Positive CD29/44, negative CD11b/45 as well as expression of brain-derived neurotrophic factor (BDNF), glia cell line-derived neurotrophic factor (GDNF), ciliary neurotrophic factor (CNTF), nerve growth factor (NGF), and neurotrophin-3 (NT-3) were demonstrated in rat AFS. The motor function, compound muscle action potential, and nerve conduction latency showed significant improvement in those groups treated with AFS. ELISA measurement in retrieved nerves displayed significant elevation of CNTF and NT-3. The IHC studies demonstrated positive staining of CNTF and NT-3 in transplanted AFS. The histology and IHC studies revealed less fibrosis and higher expression of S-100 and GFAP at the injured nerve. Part II: Twenty Sprague- Dawley rats weighting 250 to 300 gm were entered into this study. The gap model was constructed by excising 5 mm nerve followed by two 4-0 silk laterally interposed to secure the nerve continuity assisted with 9-0 nylon sutured to the epineuria. One group (n=10) received therapy with AFS embedded into the woven Surgicel and fibrin glue while the control (n=10) only received treatment of woven Surgicel and fibrin glue. Evaluation method included behavioral, electrophysiological, and immunohistochemical studies. In gait analysis, the angle of ankle in treatment and control group was 46.4±15 and 36±8.2, respectively, which revealed the statistical significance (p=0.045). Five of 10 rats (50%) demonstrated partial movement of feet, while none of the control group revealed any trace movement. The ratio of compound muscle action potential (CMAP) in the experimental group was 43±12.5% as compared to 29±8.8% in the control group (p=0.038). The conduction latency also showed the reciprocal trend (p=0.005). The histological examination demonstrated that 70% of the treatment group achieved maximum diameter ratio of the nerve gap (>50%), compared with 0% in the control group. There was no significant difference in direction of fiber and fibrosis reaction between groups. Part III: Peripheral nerve injury was produced in Sprague-Dawley rats by crushing left sciatic nerve using a vessel clamp. AFS were embedded in fibrin glue and woven Surgicel and delivered to the injured site. G-CSF (50List of Contents Chinese Abstract..........................................i English Abstract.........................................iii List of Contents......................................... vi List of Tables............................................ix List of Figures...........................................x List of Abbreviations....................................xii Reference.................................................86 Chapter I Introduction 1.1 Research background.....1 1.2 Cell therapy in nerve regeneration..........2 1.3 Purpose of this study.......................3 Chapter II Literature review 2.1 Pathophysiology of peripheral nerve injury..5 2.2 Factors influencing nerve growth............8 2.3 The possibility of amniotic fluid mesenchymal stem cells as a supplement in nerve regeneration.........................13 Chapter III Post-injury regeneration in rat sciatic nerve facilitated by neurotrophic factors secreted by rat amniotic fluid mesenchymal stem cells 3.1 Introduction...............................23 3.2 Materials and Methods......................24 3.3 Results....................................30 3.4 Discussion.................................33 3.5 Conclusion.................................36 Chapter IV Enhanced regeneration in sciatic nerve gap injury by human amniotic fluid mesenchymal stem cells 4.1 Introduction...............................46 4.2 Materials and Methods......................46 4.3 Results....................................50 4.4 Discussion.................................51 4.5 Conclusion.................................54 Chapter V Improved milieu in crush nerve by G-CSF and concomitant treatment with AFS in peripheral nerve injury 5.1 Introduction...............................60 5.2 Materials and Methods......................61 5.3 Results....................................67 5.4 Discussion.................................70 5.5 Conclusion.................................73 Chapter VI Conclusion and furtherstudies.................82 List of Tables Table 1. Histological characteristics of regeneration nervous tissue in the treatment and control groups..........................................55 Table 2. The values of SFI in different time points and treatment groups................................74 List of Figures Figure 1. RT-PCR in amniotic fluid stem cell analysis....38 Figure 2. The motor function evaluation including SFI and angle of ankle.................................39 Figure 3. Compound muscle action potential and conduction latency were illustrated at 4 weeks'follow up.40 Figure 4. The ELISA studies of CNTF and NT-3 at the retrieved nerve (1 cm in length) were conducted at 10 days after the injury....................41 Figure 5. Retrieved nerve concomitant with transplanted cells (labeled with Hoechst 33342) showed visible stem cells around the injury site..............42 Figure 6. Expression of NT-3 and CNTF was demonstrated in transplanted cells 10 days after injury........43 Figure 7. The histology, electrophysiology and SFI findings one month after crush injury either treated with or without stem cells were shown...............44 Figure 8. The staining of S-100, GFAP, and Sirus Red & Fast Green was obtained in the retrieved nerve one month after crush injury treated without or with stem cell transplantation......................45 Figure 9. The carton illustration shows the sciatic nerve gap model treated with mesenchymal stem cells and combined with fibrin glue......................56 Figure 10. Measurement of angle of ankle. Angle of ankle was conducted 8 weeks after injury............57 Figure 11. Electrophysiological evaluation...............58 Figure 12. (A) Sound nerve regeneration was depicted in H& E staining.(B) The special staining with S-100 showedregenerative axons in the nerve gap...........................................59 Figure 13. Neurobehavioral evaluation. A representative illustration of SFI in four treatment groups..75 Figure 14. Electrophysiological evaluation. Electrophysiological examination, including CMAP (A) and conduction latency (B), was conducted 4 weeks after injury in four treatment groups...76 Figure 15. Determination of neurofilament. The nerve tissues were retrieved 7 days after injury and were subjected to IHC with antibody against neurofilament.................................77 Figure 16. Histological evaluation. The nerve tissues were retrieved 4 weeks after injury and were subjected to H&E staining and IHC with antibody against S-100...............78 Figure 17. Determination of apoptosis. The nerve tissues were retrieved 7 days after injury and were subjected to apoptotic assay by TUNEL in AFS..................................79 Figure 18. Determination of inflammatory cells. The nerve tissues were retrieved 7 days after injury and were subjected to IHC with antibody against CD68..........................................80 Figure 19. Determination of pro-inflammatory cytokines.....................................81 Figure 20. Scheme of strategy in AFS transplantation...............................85 List of abbreviation Ach: acetylocholine AFS: amniotic fluid mesenchymal stem cells BDNF: brain-derived neurotrophic factor CMAP: compound muscle action potential CNTF: ciliary neurotrophic factor DAPI: 4', 6-diamindino-2-phenylindole e-NOS: endothelial nitric oxide synthase ES: embryonic stem cell ELISA: enzyme-linked immunosorbent assay GAP: growth-associated protein G-CSF: granulocyte colony-stimulating factor GDNF: glial cell line-derived neurotrophic factor GFAP: glial fibrillary acidic protein GIRK: G protein-activated inwardly rectifying K+ channel HBO: hyperbaric oxygen H&E: hematoxylin-eosin IHC: immunohistochemical LIFR-β: leukemia inhibitor factor-beta MFPs: matrix-forming precursors MHC: major histocompatibility complex MNGF: motor nerve growth factor N-CAM: neural cell adhesion molecules NGF: nerve growth factor NPFs: neurite-promoting factors NSCs: neuronal stem cells NT-3: neurotrophin-3 NTF: neuronotrophic factor OCT-4: Octamer-4 RT-PCR: reverse transcription polymerase chain reaction SCF: stem cell factor SSEA-3: stage specific embryonic antigen-3 SSEA-4: stage specific embryonic antigen-4 TGF: transforming growth factor TNF-α: tumor necrosis factor-alph

Two Birds, One Stone: Double Hits on Tumor Growth and Lymphangiogenesis by Targeting Vascular Endothelial Growth Factor Receptor 3

Vascular endothelial growth factor receptor 3 (VEGFR3) has been known for its involvement in tumor-associated lymphangiogenesis and lymphatic metastasis. The VEGFR3 signaling is stimulated by its main cognate ligand, vascular endothelial growth factor C (VEGF-C), which in turn promotes tumor progression. Activation of VEGF-C/VEGFR3 signaling in lymphatic endothelial cells (LECs) was shown to enhance the proliferation of LECs and the formation of lymphatic vessels, leading to increased lymphatic metastasis of tumor cells. In the past decade, the expression and pathological roles of VEGFR3 in tumor cells have been described. Moreover, the VEGF-C/VEGFR3 axis has been implicated in regulating immune tolerance and suppression. Therefore, the inhibition of the VEGF-C/VEGFR3 axis has emerged as an important therapeutic strategy for the treatment of cancer. In this review, we discuss the current findings related to VEGF-C/VEGFR3 signaling in cancer progression and recent advances in the development of therapeutic drugs targeting VEGF-C/VEGFR3

Re-irradiation combined with bevacizumab for recurrent glioblastoma beyond bevacizumab failure: survival outcomes and prognostic factors

Abstract The combination of re-irradiation and bevacizumab has emerged as a potential therapeutic strategy for patients experiencing their first glioblastoma multiforme (GBM) recurrence. This study aims to assess the effectiveness of the re-irradiation and bevacizumab combination in treating second-progression GBM patients who are resistant to bevacizumab monotherapy. This retrospective study enrolled 64 patients who developed a second progression after single-agent bevacizumab therapy. The patients were divided into two groups: 35 underwent best supportive care (none-ReRT group), and 29 received bevacizumab and re-irradiation (ReRT group). The study measured the overall survival time after bevacizumab failure (OST-BF) and re-irradiation (OST-RT). Statistical tests were used to compare categorical variables, evaluate the difference in recurrence patterns between the two groups, and identify optimal cutoff points for re-irradiation volume. The results of the Kaplan–Meier survival analysis indicated that the re-irradiation (ReRT) group experienced a significantly higher survival rate and longer median survival time than the non-ReRT group. The median OST-BF and OST-RT were 14.5 months and 8.8 months, respectively, for the ReRT group, while the OST-BF for the none-ReRT group was 3.9 months (p < 0.001). The multivariable analysis identified the re-irradiation target volume as a significant factor for OST-RT. Moreover, the re-irradiation target volume exhibited excellent discriminatory ability in the area under the curve (AUC) analysis, with an optimal cutoff point of greater than 27.58 ml. These findings suggest that incorporating re-irradiation with bevacizumab therapy may be a promising treatment strategy for patients with recurrent GBM resistant to bevacizumab monotherapy. The re-irradiation target volume may serve as a valuable selection factor in determining which patients with recurrent GBM are likely to benefit from the combined re-irradiation and bevacizumab treatment modality

Aluminum Parts Fabricated by Laser-Foil-Printing Additive Manufacturing: Processing, Microstructure, and Mechanical Properties

Fabrication of dense aluminum (Al-1100) parts (\u3e99.3% of relative density) by our recently developed laser-foil-printing (LFP) additive manufacturing method was investigated as described in this paper. This was achieved by using a laser energy density of 7.0 MW/cm2 to stabilize the melt pool formation and create sufficient penetration depth with 300 μm thickness foil. The highest yield strength (YS) and ultimate tensile strength (UTS) in the LFP-fabricated samples reached 111 ± 8 MPa and 128 ± 3 MPa, respectively, along the laser scanning direction. These samples exhibited greater tensile strength but less ductility compared to annealed Al-1100 samples. Fractographic analysis showed elongated gas pores in the tensile test samples. Strong crystallographic texturing along the solidification direction and dense subgrain boundaries in the LFP-fabricated samples were observed by using the electron backscattered diffraction (EBSD) technique