[Correlation Analysis of Peripheral Blood B Cell Count with Clinical Features and Prognosis in Patients Newly Diagnosed with Diffuse Large B-Cell Lymphoma].

OBJECTIVE: To explore the correlation between peripheral blood B cell count and clinical features and prognosis of patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). METHODS: The relationship of peripheral blood B cell count with clinical features, laboratory indexes and prognosis in 67 patients with newly diagnosed DLBCL was retrospectively analyzed. RESULTS: Patients were divided into low B-cell count group (B cell＜0.1×109/L, n=34) and high B-cell count group (B cell≥0.1×109/L, n=33) according to the median B cell count values. Compared with the high B cell count group, the low B cell count group had a higher proportion of patients with Lugano stage III-IV, elevated LDH, elevated ß2-MG and IPI score 3-5 and increased CRP (P =0.033, 0.000, 0.023, 0.001, 0.033). The peripheral CD3+ and CD4+ cell counts of patients in the low B cell count group were significantly lower than those in the high B cell count group (P =0.010, 0.017). After initial treatment, overall response rate (ORR) and complete remission (CR) rate in high B cell count group were significantly higher than those in low B cell count group (P =0.032, 0.013). The median follow-up time of patients was 23(2-77) months, progression-free survival (PFS) and overall survival (OS) of patients in the high B cell count group were significantly better than those in the low B cell count group (P =0.001, 0.002). Univariate analysis showed that pretreatment low B cell count in the peripheral blood was associated with shortened PFS and OS (HR=4.108, P =0.002; HR=8.218, P =0.006). Multivariate analysis showed that low B cell count was an independent prognostic factor for shortened PFS (HR=3.116, P =0.037). CONCLUSION: Decreased peripheral blood B cell count in newly diagnosed DLBCL patients is associated with high-risk clinical features and may affect the efficacy of immunochemotherapy, which is associated with poor clinical prognosis.

Long non-coding RNA GATA6-AS1 is mediated by N6-methyladenosine methylation and inhibits the proliferation and metastasis of gastric cancer.

BACKGROUND: Through experimental research on the biological function of GATA6-AS1, it was confirmed that GATA6-AS1 can inhibit the proliferation, invasion, and migration of gastric cancer cells, suggesting that GATA6-AS1 plays a role as an anti-oncogene in the occurrence and development of gastric cancer. Further experiments confirmed that the overexpression of fat mass and obesity-associated protein (FTO) inhibited the expression of GATA6-AS1, thereby promoting the occurrence and development of gastric cancer. AIM: To investigate the effects of GATA6-AS1 on the proliferation, invasion and migration of gastric cancer cells and its mechanism of action. METHODS: We used bioinformatics methods to analyze the Cancer Genome Atlas (https://portal.gdc.cancer.gov/. The Cancer Genome Atlas) and download expression data for GATA6-AS1 in gastric cancer tissue and normal tissue. We also constructed a GATA6-AS1 lentivirus overexpression vector which was transfected into gastric cancer cells to investigate its effects on proliferation, migration and invasion, and thereby clarify the expression of GATA6-AS1 in gastric cancer and its biological role in the genesis and development of gastric cancer. Next, we used a database (http://starbase.sysu.edu.cn/starbase2/) to analysis GATA6-AS1 whether by m6A methylation modify regulation and predict the methyltransferases that may methylate GATA6-AS1. Furthermore, RNA immunoprecipitation experiments confirmed that GATA6-AS1 was able to bind to the m6A methylation modification enzyme. These data allowed us to clarify the ability of m6A methylase to influence the action of GATA6-AS1 and its role in the occurrence and development of gastric cancer. RESULTS: Low expression levels of GATA6-AS1 were detected in gastric cancer. We also determined the effects of GATA6-AS1 overexpression on the biological function of gastric cancer cells. GATA6-AS1 had strong binding ability with the m6A demethylase FTO, which was expressed at high levels in gastric cancer and negatively correlated with the expression of GATA6-AS1. Following transfection with siRNA to knock down the expression of FTO, the expression levels of GATA6-AS1 were up-regulated. Finally, the proliferation, migration and invasion of gastric cancer cells were all inhibited following the knockdown of FTO expression. CONCLUSION: During the occurrence and development of gastric cancer, the overexpression of FTO may inhibit the expression of GATA6-AS1, thus promoting the proliferation and metastasis of gastric cancer.

Triphenyltin induced darker body coloration by disrupting melanocortin system and pteridine metabolic pathway in a reef fish, Amphiprion ocellaris.

Triphenyltin (TPT) is a typical persistent organic pollutant whose occurrence in coral reef ecosystems may threaten the survival of reef fishes. In this study, a brightly colored representative reef fish, Amphiprion ocellaris was used to explore the effects of TPT at environmental levels (1, 10, and 100 ng/L) on skin pigment synthesis. After the fish were exposed to TPT for 60 days, the skin became darker, owing to an increase in the relative area of black stripes, a decrease in orange color values while an increase in brown color values, and an increase in the number of melanocytes in the orange part of the skin tissues. To explore the mechanisms by which TPT induces darker body coloration, the enzymatic activity and gene expression levels of the members of melanocortin system that affect melanin synthesis were evaluated. Leptin levels and lepr expression were found to be increased after TPT exposure, which likely contributed to the increase found in pomc expression and α-melanocyte-stimulating hormone (α-MSH) levels. Then Tyr activity and mc1r, tyr, tyrp1, mitf, and dct were upregulated, ultimately increasing melanin levels. Importantly, RT-qPCR results were consistent with the transcriptome analysis of trends in lepr and pomc expression. Because the orange color values decreased, pterin levels and the pteridine metabolic pathway were also evaluated. The results showed that TPT induced BH4 levels and spr, xdh, and gch1 expression associated with pteridine synthesis decreased, ultimately decreasing the colored pterin content (sepiapterin). We conclude that TPT exposure interferes with the melanocortin system and pteridine metabolic pathway to increase melanin and decrease colored pterin levels, leading to darker body coloration in A. ocellaris. Given the importance of body coloration for the survival and reproduction of reef fishes, studies on the effects of pollutants (others alongside TPT) on body coloration are of high priority.

Ixazomib-based frontline therapy followed by ixazomib maintenance in frail elderly newly diagnosed with multiple myeloma: a prospective multicenter study.

Background: Frail elderly patients with newly diagnosed multiple myeloma (NDMM) have inferior survival and less benefit from high-dose therapies. This prospective study aimed to investigate the efficacy, safety, and quality of life (QoL) of induction treatment of ixazomib/lenalidomide/dexamethasone (IRd) and ixazomib/pegylated liposomal doxorubicin/dexamethasone (IDd) followed by ixazomib/dexamethasone (Id) maintenance therapy in frail, elderly patients with NDMM. Methods: From July 2019 to December 2021, this non-randomized concurrent controlled clinical study enrolled 120 NDMM patients aged ≥65 years with frailty defined by the International Myeloma Working Group (IMWG) frailty score or Mayo geriatric scoring system. The enrolled patients received 6-8 cycles of IRd or IDd followed by Id maintenance therapy for a minimum of 2 years at the discretion of physicians based on patient's clinical characteristics (chiCTR1900024917). Findings: The median age was 71 years and 55% of the patients were males. The overall response rate (ORR) was 82% and 77%, complete response (CR) rate was 25% and 12% for IRd and IDd groups, respectively. The difference in ORR of the Idd group minus the IRd group was -5.36% (95% CI: -18.9% to 8.19%), indicating that the ORR of the IDd group was neither inferior nor non-inferior to the IRd group. After a median follow-up of 34.3 months, the median progression-free survival (PFS) was 21.6 and 13.9 months, OS was not reached and 29.2 months in IRd and IDd groups, respectively. 28 and 33 patients discontinued induction therapy, 20 and 19 discontinued maintenance therapy in IRd and IDd groups, respectively. Cumulative Grade 3 or higher hematological adverse events (AEs) occurred in 10 of the 60 patients (17%) and non-hematological AEs occurred in 15 of the 60 patients (25%) in the IRd group, while 13 of the 60 patients (22%) and 21 of the 60 patients (35%) in the IDd group. Patients were observed with clinically significant improvement in QoL when compared with that at baseline in both IRd and IDd groups by evaluation per cycle (P < 0.0001). Interpretation: The results demonstrated that compared with IRd regimen, IDd regimen showed no significant advantage, but the survival of the IDd group was shorter than that of the IRd group, indicating an all-oral outpatient triplet regimen with IRd, which has low toxicity and has improved QoL, could be the viable first-line treatment option for frail NDMM patients. Funding: The Young Elite Scientist sponsorship program by bast of Beijing Association for Science and Technology (No. BYESS2023116) and Beijing Medical Award Foundation (No. YXJL-2018-0539-0073).

A neuromusculoskeletal modelling approach to bilateral hip mechanics due to unexpected lateral perturbations during overground walking.

BACKGROUND: Current studies on how external perturbations impact gait dynamics have primarily focused on the changes in the body's center of mass (CoM) during treadmill walking. The biomechanical responses, in particular to the multi-planar hip joint coordination, following perturbations in overground walking conditions are not completely known. METHODS: In this study, a customized gait-perturbing device was designed to impose controlled lateral forces onto the subject's pelvis during overground walking. The biomechanical responses of bilateral hips were simulated by subject-specific neuromusculoskeletal models (NMS) driven by in-vivo motion data, which were further evaluated by statistical parameter mapping (SPM) and muscle coactivation index (CI) analysis. The validity of the subject-specific NMS was confirmed through comparison with measured surface electromyographic signals. RESULTS: Following perturbations, the sagittal-plane hip motions were reduced for the leading leg by 18.39° and for the trailing leg by 8.23°, while motions in the frontal and transverse plane were increased, with increased hip abduction for the leading leg by 10.71° and external rotation by 9.06°, respectively. For the hip kinetics, both the bilateral hip joints showed increased abductor moments during midstance (20%-30% gait cycle) and decreased values during terminal stance (38%-48%). Muscle CI in both sagittal and frontal planes was significantly decreased for perturbed walking (p < 0.05), except for the leading leg in the sagittal plane. CONCLUSION: The distinctive phase-dependent biomechanical response of the hip demonstrated its coordinated control strategy for balance recovery due to gait perturbations. And the changes in muscle CI suggested a potential mechanism for rapid and precise control of foot placement through modulation of joint stiffness properties. These findings obtained during actual overground perturbation conditions could have implications for the improved design of wearable robotic devices for balance assistance.

A fluoroscopic imaging-guided computational analyses to inform internal tissue loads within fat pad of the diabetic foot during gait.

To accurately predict internal tissue loads for early diagnostics of diabetic foot ulcerations, a novel data-driven computational analysis was conducted. A dedicated dual fluoroscopic system was combined with a pressure mat to simultaneously characterize foot motions and soft tissue's material properties during gait. Finite element (FE) models of the heel pad of a diabetic patient were constructed with 3D trajectories of the calcaneus applied as boundary conditions to simulate gait events. The tensile and compressive stresses occurring in the plantar tissue were computed. Predictions of the layered tissue FE model with anatomically-accurate heel pad structures (i.e., fat and skin) were compared with those of the traditional lumped tissue (i.e., homogeneous) models. The influence of different material properties (patient-specific versus generic) on internal tissue stresses was also investigated. The results showed the peak tensile stresses in the layered tissue model were predominantly found in the skin and distributed towards the circumferential regions of the heel, while peak compressive stresses in the fat tissue-bone interface were up to 51.4% lower than those seen in the lumped models. Performing FE analyses at four different phases of walking revealed that ignorance of layered tissue structures resulted in an unphysiological increase of peak-to-peak value of stress fluctuation in the fat and skin tissue components. Thus, to produce more clinical-relevant predictions, foot FE models are suggested to include layered tissue structures of the plantar tissue for an improved estimation of internal stresses in the diabetic foot in gait.

[MiR-203a-5p Inhibits Multiple Myeloma Cell Proliferation and Cell Cycle Progression via Targeting JAG1].

OBJECTIVE: To investigate the biological function of miR-203a-5p and the underlying mechanism in multiple myeloma (MM). METHODS: Three miRNA expression profiles (GSE16558, GSE24371 and GSE17498) were downloaded from the GEO database. The three miRNA expression profiles contained 131 MM samples and 17 normal plasmacyte samples. The robust rank aggregation (RRA) method was used to identify the differentially expressed miRNAs between MM and normal plasmacytes. In order to carry out cytological experiments, MM cell line with stable over-expression of miR-203a-5p was constructed with lentivirus. Expression levels of miR-203a-5p in MM cells were quantified by qRT-PCR. The effects of miR-203a-5p on MM cells were investigated using assays of cell viability and cell cycle. Cell proliferation was measured using the Cell Counting kit (CCK)8 assay. The percentage of cells in each cell cycle was measured with a FACSCalibur system. Xenograft tumor models were established to evaluate the role of miR-203a-5p in tumorigenesis in vivo . To elucidate the underlying molecular mechanisms of miR-203a-5p in mediating cell proliferation inhibition and cell cycle arrest in MM, we used TargetScan and miRanda to predict the candidate targets of miR-203a-5p. The potential target of miR-203a-5p in MM cells was explored using the luciferase reporter assay, qRT-PCR, and Western blot. RESULTS: An integrated analysis of three MM miRNA expression datasets showed that the levels of miR-203a-5p in MM were notably downregulated compared with those in normal plasmacytes. Accordingly, the relative expression levels of miR-203a-5p were decreased in MM cell lines. In addition, overexpression of miR-203a-5p inhibited the proliferation and cell cycle progression of RPMI8226 and U266 cells. In vivo experiments demonstrated that upregulation of miR-203a-5p expression could significantly inhibit the tumorigenesis of subcutaneous myeloma xenografts in nude mice. Mechanistic investigation led to the identification of Jagged 1 (JAG1) as a novel and direct downstream target of miR-203a-5p. Interestingly, the reintroduction of JAG1 abrogated miR-203a-5p-induced MM cell growth inhibition and cell cycle arrest. CONCLUSION: Our data demonstrate that miR-203a-5p inhibits cell proliferation and cell cycle progression in MM cells by targeting JAG1, supporting the utility of miR-203a-5p as a novel and potential therapeutic agent for miRNA-based MM therapy.

Identification of aberrantly expressed lncRNAs and ceRNA networks in multiple myeloma: a combined high-throughput sequencing and microarray analysis.

Background: This study aimed to explore the potential effects of long non-coding RNAs (lncRNAs) in multiple myeloma (MM) patients using two detection methods: high-throughput sequencing and microarray. Methods: In this study, lncRNAs were detected in 20 newly diagnosed MM patients, with 10 patients analyzed by whole transcriptome-specific RNA sequencing and 10 patients analyzed by microarray (Affymetrix Human Clariom D). The expression levels of lncRNAs, microRNAs, and messenger RNAs (mRNAs) were analyzed, and the differentially expressed lncRNAs identified by both methods were selected. The significant differentially expressed lncRNAs were further validated using PCR. Results: This study established the aberrant expression of certain lncRNAs involved in the occurrence of MM, with AC007278.2 and FAM157C showing the most significant differences. The top 5 common pathways identified by the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were the chemokine signaling pathway, inflammatory mediator regulation, Th17 cell differentiation, apoptosis, and NF-kappa B signaling pathway. Furthermore, three microRNAs (miRNAs) (miR-4772-3p, miR-617, and miR-618) were found to constitute competing endogenous RNA (ceRNA) networks in both sequencing and microarray analyses. Conclusions: By the combination analysis, our understanding of lncRNAs in MM will be increased significantly. More overlapping differentially expressed lncRNAs were found to predict therapeutic targets precisely.

Chryseobacterium oryctis sp. nov., isolated from the gut of the beetle Oryctes rhinoceros, and Chryseobacterium kimseyorum sp. nov., isolated from a stick insect rearing cage.

Two strains of Chryseobacterium identified from different experiments are proposed to represent new species. Strain WLa1L2M3T was isolated from the digestive tract of an Oryctes rhinoceros beetle larva. Strain 09-1422T was isolated from a cage housing the stick insect Eurycantha calcarata. Sequence analysis of the 16S rRNA and rpoB genes found both strains to be similar but not identical to other Chryseobacterium species. Whole-genome sequencing suggested the isolates represent new species, with average nucleotide identity values ranging from 74.6 to 80.5 %. Genome-to-genome distance calculations produced values below 25.3 %, and digital DNA-DNA hybridization values were 13.7-29.9 %, all suggesting they are distinct species. The genomic DNA G+C content of WLa1L2M3T is approximately 32.53 %, and of 09-1422T is approximately 35.89 %. The predominant cellular fatty acids of strain WLa1L2M3T are C15 : 0 iso, summed feature 9 (C16 : 0 10OH or C17 : 1 iso ω6c), C17 : 0 iso 3OH, summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω6c), C15 : 0 iso 3OH, C15 : 0 anteiso and C13 : 0 iso, and those of strain 09-1422T are C15 : 0 iso, summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω6c), C17 : 0 iso 3OH, C15 : 0 anteiso, C15 : 0 iso 3OH, C16 : 1 ω7c, C17 : 0 2OH and C18 : 0. In addition, physiological and biochemical tests revealed phenotypic differences from related Chryseobacterium type strains. These cumulative data indicate that the two strains represent novel species of the genus Chryseobacterium for which the names Chryseobacterium oryctis sp. nov. and Chryseobacterium kimseyorum sp. nov. are proposed with WLa1L2M3T (=BCRC 81350T=JCM 35215T=CIP 112035T) and 09-1422T (=UCDFST 09-1422T=BCRC 81359T=CIP 112165T), as type strains, respectively.

Front-line treatment efficacy and clinical outcomes of elderly patients with multiple myeloma in a real-world setting: A multicenter retrospective study in China.

BACKGROUND: The use of proteasome inhibitors (PIs), new immune modulators (IMiDs), and other new drugs, as well as high-dose chemotherapy combined with autologous stem cell transplantation has considerably improved the survival of young patients with multiple myeloma (MM). However, the improvement in survival among elderly patients remains insufficient. Optimal treatment recommendation models for elderly patients with MM have not been developed especially there are quite few study in the real world. METHODS: We retrospectively analyzed the treatment patterns and outcomes of 328 Chinese patients (≥65 years) with MM in a real-world setting. Patients were divided into three groups according to induction regimens. RESULTS: The median age of the cohort was 70 (65-86) years. The patients were divided into group 1 (PIs based regimens, n = 218), group 2 (IMiDs based regimens, n = 48) and group 3 (PIs + IMiDs, n = 62). Induction regimens in group 3 produced higher overall response rate than group 1 and 2 (85.42% vs. 71.08% vs. 66.67%, p = 0.016). The median follow-up of the cohort was 30 (interquartile range [IQR] 18-36) months. For the entire cohort median progression-free survival (PFS) was 26 (IQR 12.00-42.89) months and overall survival (OS) was 60 (IQR 40.00-67.20) months. The PFS were not significantly different among the three groups (28 months vs. 18 months vs. 26 months, p = 0.182). So were the OS (60 months vs. 59 months vs. not reached, p = 0.067). Multivariate analysis revealed that age >70 year, frailty status (Geriatric vulnerability score), induction efficacy < partial remission, and no maintenance treatment were independent poor prognostic factors for OS. CONCLUSION: Front-line induction regimens combining PIs and IMiDs developed more deep response than single PI or IMiD based regimens. Maintenance treatment can further improve the clinical outcome in elderly MM patients in real-world setting.

Three new constituents from the Tujia ethnomedicine Swertia punicea Hemsl.

Three new constituents: 1,5R-dihydroxy-3,8S-dimethoxy-5,6,7,8-tetrahydroxanthone (1), (3S,4R,16S,17R)-3,16,23-trihydroxyoleana-11,13(18)-dien-28-aldehyde-3-O-ß-D-glucopyranoside (2), and new natural product (S)-gentiandiol (3), along with 41 known compounds were isolated from Tujia ethnomedicine Shuihuanglian, namely, the whole plant of Swertia punicea. Structures of all these compounds were established through extensive spectroscopic techniques, namely 1D, 2D-NMR spectroscopy, HRESIMS analysis, and the absolute configuration of the new compounds was discerned by circular dichroism (CD) spectroscopy. Antioxidative effects of these compounds were evaluated by using the DPPH radical scavenging method, compounds 7, 9 and 14 showed antioxidant activities with IC50 values of 68.9, 50.8 and 48.2 µM, respectively.

Comparison of material properties of heel pad between adults with and without type 2 diabetes history: An in-vivo investigation during gait.

Objective: This study was aimed to compare the material properties of heel pad between diabetes patients and healthy adults, and investigate the impact of compressive loading history and length of diabetes course on the material properties of heel pad. Methods: The dual fluoroscopic imaging system (DFIS) and dynamic foot-ground contact pressure-test plate were used for measuring the material properties, including primary thickness, peak strain, peak stress, stiffness, viscous modulus and energy dissipation ratio (EDR), both at time zero and following continuous loading. Material properties between healthy adults and DM patients were compared both at time zero and following continuous weight bearing. After then, comparison between time-zero material properties and properties following continuous loading was performed to identify the loading history-dependent biomechanical behaviour of heel pad. Subgroup-based sensitivity analysis was then conducted to investigate the diabetes course (<10 years vs. ≥10 years) on the material properties of heel pad. Results: Ten type II DM subjects (20 legs), aged from 59 to 73 (average: 67.8 ± 4.9), and 10 age-matched healthy adults (20 legs), aged from 59 to 72 (average: 64.4 ± 3.4), were enrolled. Diabetes history was demonstrated to be associated with significantly lower primary thickness (t=3.18, p=0.003**), higher peak strain (t=2.41, p=0.021*), lower stiffness (w=283, p=0.024*) and lower viscous modulus (w=331, p<0.001***) at time zero, and significantly lower primary thickness (t=3.30, p=0.002**), higher peak strain (w=120, p=0.031*) and lower viscous modulus (t=3.42, p=0.002**) following continuous loading. The continuous loading was found to be associated with significantly lower primary thickness (paired-w=204, p<0.001***) and viscous modulus (paired-t=5.45, p<0.001***) in healthy adults, and significantly lower primary thickness (paired-w=206, p<0.001***) and viscous modulus (paired-t=7.47, p<0.001***) in diabetes group. No any significant difference was found when conducting the subgroup analysis based on length of diabetes course (<10 years vs. ≥10 years), but the regression analysis showed that the length of diabetes history was positively associated with the peak strain, at time zero (r=0.506, p<0.050) and following continuous loading (r=0.584, p<0.010). Conclusions: Diabetes patients were found to be associated with decreased primary thickness and viscous modulus, and increased peak strain, which may contribute to the vulnerability of heel pad to injury and ulceration. Pre-compression history-dependent behaviour is observable in soft tissue of heel pad, with lowered primary thickness and viscous modulus.

Integration of reginal shear measurements at the foot-ground interface during routine balance assessment of the elderly population.

BACKGROUND: Force-plate posturography offers a convenient way for quantitative assessment of postural stability in the elderly. However, studies focusing on routine balance assessment have usually not taken reginal shear distributions (i.e., arising from horizontal forces) into consideration. RESEARCH QUESTION: (1) Does plantar shear distribution differ between young and elderly subjects during upright standing? (2) How do the maximum plantar shear forces vary at different regions of the foot? METHODS: The new reginal shear measurement (RSM) method can simultaneously capture the three-dimensional force distributions at regional plantar sites while subjects maintaining standing balance. The feasibility of the proposed method in characterizing the magnitude and distribution of plantar shear forces was tested in thirty-two normal young and nineteen elderly subjects. Statistical analysis was performed using the independent samples t-test for both the continuous and ordinal variables. RESULTS: For regional AP shear forces, statistically significant differences were found between the two groups for the toe region of the right foot and the midfoot of both feet. For ML shear distributions, statistically significant differences were found at nearly all plantar sites expect for the hallux and lateral metatarsal. The maximum increase in ML shear forces occurred in the toe region of the right foot, where the peak shear values were 113.16% higher than those of the young subjects. The peak ML shear occurred in the midfoot were averagely 83.19% and 70.57% higher in the elderly's left and right feet, respectively. SIGNIFICANCE: The RSM method may offer unique solutions to identify functional decline in postural control of the elderly. The plantar shear pattern has potential to become an important parameter in evaluating one's balance performance during upright standing.

Modulation of internal tissue stresses of the knee via control of variable-stiffness properties in a 3D-printed footwear: A combined experimental and finite element analysis.

AIMS: Therapeutic footwear with variable-stiffness properties has been shown to be effective in reducing the external knee adduction moment. However, the exact changes of internal tissue stresses following intervention with variable-stiffness footwear remains unknown. The objective of this study is to construct a finite element model of the foot-ankle-knee complex to investigate the therapeutic efficacy of the variable-stiffness footwear in modulating internal knee joint stress distributions. METHODS: Footwear with lateral-to-medial stiffness ratio of 1.00, 1.33, 1.49 and 1.77 were designed and 3D-printed as lattice structures at different porosity levels. A three-dimensional finite element model of the foot-ankle-knee complex was constructed with cartilage-meniscus structures characterized by magnetic resonance imaging. Ground reaction forces and muscular loads estimated from gait experiments with 3D-printed variable-stiffness footwear were used to drive the model, and effects of footwear intervention with four stiffness ratios on tibiofemoral joint loads were evaluated during the simulated instant in gait. RESULTS: Compared with the constant-stiffness design, the variable-stiffness footwear reached a maximum reduction of the first peak knee adduction moment up to 17.1%. As the lateral-to-medial stiffness ratio increases, the peak stresses at the meniscus in the medial compartment of the knee were reduced by 5.0%, 7.9%, and 16.4%, respectively. The stress-modifying effects were less pronounced for the lateral compartment of the knee. CONCLUSION: The variable-stiffness footwear design produced stress relieving to the cartilage and meniscus structures, and the fact that lower stiffness ratio had reached significantly less effects, suggesting a favourable stress-relief effect should consider footwear with a higher lateral-to-medial stiffness ratio.

Effect of loading history on material properties of human heel pad: an in-vivo pilot investigation during gait.

BACKGROUND: This study was aimed to develop a novel dynamic measurement technique for testing the material properties and investigating the effect of continuous compression load on the structural and mechanical properties of human heel pad during actual gait. METHODS: The dual fluoroscopic imaging system (DFIS) and dynamic foot-ground contact pressure-test plate were used for measuring the material properties, including primary thickness, peak strain, peak stress, elastic modulus, viscous modulus and energy dissipation rate (EDR), both at time zero and following continuous loading. Ten healthy pilot subjects, aged from 23 to 72 (average: 46.5 ± 17.6), were enrolled. A "three-step gait cycle" is performed for all subjects, with the second step striking at a marked position on the force plate with the heel to maintain the location of the tested foot to be in the view of fluoroscopes. The subjects were measured at both relaxed (time-zero group) and fatigue (continuous-loading group) statuses, and the left and right heels were measured using the identical procedures. RESULTS: The peak strain, peak stress, elastic modulus, and EDR are similar before and after continuous load, while the viscous modulus was significantly decreased (median: 43.9 vs. 20.37 kPa•s; p < 0.001) as well as primary thicknesses (median: 15.99 vs. 15.72 mm; p < 0.001). Age is demonstrated to be moderately correlated with the primary thicknesses both at time zero (R = -0.507) and following continuous load (R = -0.607). The peak stress was significantly correlated with the elastic modulus before (R = 0.741) and after continuous load (R = 0.802). The peak strain was correlated with the elastic modulus before (R = -0.765) and after continuous load (R = -0.801). The correlations between the viscous modulus and peak stress/ peak strain are similar to above(R = 0.643, 0.577, - 0.586 and - 0.717 respectively). The viscous modulus is positively correlated with the elastic modulus before (R = 0.821) and after continuous load (R = 0.784). CONCLUSIONS: By using dynamic fluoroscopy combined with the plantar pressure plate, the in vivo viscoelastic properties and other data of the heel pad in the actual gait can be obtained. Age was negatively correlated with the primary thickness of heel pad and peak strain, and was positively correlated with viscous modulus. Repetitive loading could decrease the primary thickness of heel pad and viscous modulus.

Finite element stress analysis of the bearing component and bone resected surfaces for total ankle replacement with different implant material combinations.

BACKGROUND: A proper combination of implant materials for Total Ankle Replacement (TAR) may reduce stress at the bearing component and the resected surfaces of the tibia and talus, thus avoiding implant failure of the bearing component or aseptic loosening at the bone-implant interface. METHODS: A comprehensive finite element foot model implanted with the INBONE II implant system was created and the loading at the second peak of ground reaction force was simulated. Twelve material combinations including four materials for tibial and talar components (Ceramic, CoCrMo, Ti6Al4V, CFR-PEEK) and three materials for bearing components (CFR-PEEK, PEEK, and UHMWPE) were analyzed. Von Mises stress at the top and articular surfaces of the bearing component and the resected surfaces of the tibia and talus were recorded. RESULTS: The stress at both the top and articular surfaces of the bearing component could be greatly reduced with more compliant bearing materials (44.76 to 72.77% difference of peak stress value), and to a lesser extent with more compliant materials for the tibial and talar components (0.94 to 28.09% difference of peak stress value). Peak stresses at both the tibial and talar bone-implant interface could be reduced more strongly by using tibial and talar component materials with smaller material stiffness (7.31 to 66.95% difference of peak stress value) compared with bearing materials with smaller material stiffness (1.11 to 24.77% difference of peak stress value). CONCLUSIONS: Implant components with smaller material stiffness provided a stress reduction at the bearing component and resected surfaces of the tibia and talus. The selection of CFR-PEEK as the material of tibial and talar components and UHMWPE as the material of the bearing component seemed to be a promising material combination for TAR implants. Wear testing and long-term failure analysis of TAR implants with these materials should be included in future studies.

Hymenobacter piscis sp. nov., isolated from a fish pond.

Bacterial strain NST-14T, isolated from a freshwater fish pond in Taiwan, was characterized using a polyphasic taxonomy approach. The strain was Gram-stain-negative, strictly aerobic, non-motile, rod-shaped and formed pink colonies. Optimal growth occurred at 30 °C, pH 7 and in the absence of NaCl. Phylogenetic analyses based on 16S rRNA gene sequences and coding sequences of 92 protein clusters indicated that strain NST-14T formed a phylogenetic lineage in the genus Hymenobacter. Analysis of 16S rRNA gene sequences showed that strain NST-14T had the highest similarity to Hymenobacter actinosclerus CCUG 39621T (97.7%), Hymenobacter amundsenii P5136T (97.3%) and Hymenobacter humicola P6312T (96.9%). Strain NST-14T showed 75.1-85.3 % average nucleotide identity, 73.7-89.8 % average amino acid identity and 14.5-26.0 % digital DNA-DNA hybridization with the type strains of other closely related Hymenobacter species. Strain NST-14T contained iso-C15 : 0, C16 : 1 ω5c and summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω6c) as the predominant fatty acids. The major hydroxyl fatty acids were iso-C17 : 0 3-OH and iso-C15 : 0 3-OH. The polar lipids were phosphatidylethanolamine, one unidentified glycolipid, four unidentified aminophospholipids, one unidentified aminolipid, two unidentified phospholipids and three unidentified lipids. The major polyamine was homospermidine. The major isoprenoid quinone was MK-7. The DNA G+C content of the genomic DNA was 62.4 mol%. Differential phenotypic properties, together with the phylogenetic inference, demonstrate that strain NST-14T should be classified as a novel species of the genus Hymenobacter, for which the name Hymenobacter piscis sp. nov. is proposed. The type strain is NST-14T (=BCRC 81249T=LMG 31686T).

Rhodobacter amnigenus sp. nov. and Rhodobacter ruber sp. nov., isolated from freshwater habitats.

Two bacterial strains, designated HSP-20T and CCP-1T, isolated from freshwater habitats in Taiwan, were characterized by polyphasic taxonomy. Both strains were Gram-stain-negative, aerobic, non-motile and rod-shaped. Cells of strains HSP-20T and CCP-1T formed pink and dark red coloured colonies, respectively. Both strains contained bacteriochlorophyll a, and showed optimum growth under anaerobic conditions by photoheterotrophy, but no growth by photoautotrophy. Phylogenetic analyses based on 16S rRNA gene and whole-genome sequences indicated that both strains belonged to the genus Rhodobacter. Analysis of 16S rRNA gene sequences showed that strains HSP-20T and CCP-1T shared 98.3 % sequence similarity and were closely related to Rhodobacter tardus CYK-10T (96.0 %) and Rhodobacter flagellatus SYSU G03088T (96.0 %), respectively. Both strains shared common chemotaxonomic characteristics including Q-10 as the major isoprenoid quinone, C18 : 1 ω7c as the predominant fatty acid, and phosphatidylethanolamine, phosphatidylglycerol and phosphatidylcholine as the main polar lipids. The DNA G+C content of both strains was 66.2 mol%. The average nucleotide identity, average amino acid identity and digital DNA-DNA hybridization values between these two novel isolates and their closest relatives were below the cut-off values of 95-96, 90 and 70 %, respectively, used for species demarcation. On the basis of phenotypic and genotypic properties and phylogenetic inference, both strains should be classified as novel species within the genus Rhodobacter, for which the names Rhodobacter amnigenus sp. nov. (=BCRC 81193T=LMG 31334T) and Rhodobacter ruber sp. nov. (=BCRC 81189T=LMG 31335T) are proposed.