Patellar tendinopathy (PT) is one of the most common knee disorders among athletes. Changes in morphology and elasticity of the painful tendon and how these relate to the self-perceived pain and ...dysfunction remain unclear.
To compare the morphology and elastic properties of patellar tendons between athlete with and without unilateral PT and to examine its association with self-perceived pain and dysfunction.
In this cross-sectional study, 33 male athletes (20 healthy and 13 with unilateral PT) were enrolled. The morphology and elastic properties of the patellar tendon were assessed by the grey and elastography mode of supersonic shear imaging (SSI) technique while the intensity of pressure pain, self-perceived pain and dysfunction were quantified with a 10-lb force to the most painful site and the Victorian Institute of Sport Assessment-patella (VISA-P) questionnaire, respectively.
In athletes with unilateral PT, the painful tendons had higher shear elastic modulus (SEM) and larger tendon than the non-painful side (p<0.05) or the dominant side of the healthy athletes (p<0.05). Significant correlations were found between tendon SEM ratio (SEM of painful over non-painful tendon) and the intensity of pressure pain (rho = 0.62; p = 0.024), VISA-P scores (rho = -0.61; p = 0.026), and the sub-scores of the VISA-P scores on going down stairs, lunge, single leg hopping and squatting (rho ranged from -0.63 to -0.67; p<0.05).
Athletes with unilateral PT had stiffer and larger tendon on the painful side than the non-painful side and the dominant side of healthy athletes. No significant differences on the patellar tendon morphology and elastic properties were detected between the dominant and non-dominant knees of the healthy control. The ratio of the SEM of painful to non-painful sides was associated with pain and dysfunction among athletes with unilateral PT.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Surgical removal of the thyroid gland (TG) for treating thyroid disorders leaves the patients on lifelong hormone replacement that partially compensates the physiological needs, but regenerating TG ...is challenging. Here, an approach is reported to regenerate TG within the spleen for fully restoring the thyroid's functions in mice, by transplanting thyroid tissue blocks to the spleen. Within 48 h, the transplanted tissue efficiently revascularizes, forming thyroid follicles similar to the native gland after 4 weeks. Structurally, the ectopically generated thyroid integrates with the surrounding splenic tissue while maintaining its integrity, separate from the lymphatic tissue. Functionally, it fully restores the native functions of the TG in hormone regulation in response to physiological stimuli, outperforming the established method of oral levothyroxine therapy in maintaining systemic homeostasis. The study demonstrates the full restoration of thyroid functions post‐thyroidectomy by intrasplenic TG regeneration, providing fresh insights for designing novel therapies for thyroid‐related disorders.
The intrasplenic transplanted thyroid tissue blocks undergo angio‐follicular unit (AFU) reconstruction, epithelial and follicular regeneration, and finally, a regenerated thyroid gland that is independent and seamlessly integrated with the spleen taking advantage of the abundant vascularity of the spleen and the diversity of growth factors. The regenerated intrasplenic thyroid achieves precise hormone release and synthesis, fully restoring all thyroid functions.
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•The hidden BRB model is used to predict the network security situation.•The observation data of the hidden BRB model is multidimensional.•We propose a new constraint CMA-ES ...algorithm.•The revised CMA-ES algorithm is used to optimize the parameters of the hidden BRB model.
It is important to establish the forecasting model of the network security situation. But the network security situation cannot be observed directly and can only be measured by other observable data. In this paper the network security situation is considered as a hidden behavior. In order to predict the hidden behavior, some methods have been proposed. However, these methods cannot use the hybrid information that includes qualitative knowledge and quantitative data. As such, a forecasting model of network security situation is proposed on the basis of the hidden belief rule base (BRB) model when the inputs are multidimensional. The initial parameters of the hidden BRB model given by experts may be subjective and inaccurate. In order to train the parameters, a revised covariance matrix adaption evolution strategy (CMA-ES) algorithm is further developed by adding a modified operator. The revised CMA-ES algorithm can optimize the parameters of the hidden BRB model effectively. The case study shows that compared with other methods, the proposed hidden BRB model and the revised CMA-ES algorithm can predict the network security situation effectively to improve the forecasting precision by making full use of qualitative knowledge.
CpG methylation of DNA is common in mammalian cells. In sperm, the DNA has the highest level of CpG methylation and is condensed into toroidal structures. How CpG methylation affects DNA structures ...and interactions is important to understand its biological roles but is largely unknown. Using an RNA–DNA–RNA structure, we observed the equilibrium hopping dynamics between the condensed and extended states of DNA in the presence of polyamines or polylysine peptide as a reduced model of histone tails. Combing with the measured DNA elasticities, we report that CpG methylation of each cytosine nucleotide substantially increases DNA–DNA attraction by up to 0.2 k B T. For the DNA with 57% GC content, the relative increase caused by CpG methylation is up to 32% for the spermine-induced DNA–DNA attraction and up to 9% for the polylysine-induced DNA–DNA attraction. These findings help us to evaluate the energetic contributions of CpG methylation in sperm development and chromatin regulation.
Triclocarban (TCC) and triclosan (TCS) have been detected ubiquitously in human body and evoked increasing concerns. This study aimed to reveal the induction risks of TCC and TCS on triple negative ...breast cancer through non-genomic GPER-mediated signaling pathways. Molecular simulation indicated that TCC exhibited higher GPER binding affinity than TCS theoretically. Calcium mobilization assay displayed that TCC/TCS activated GPER signaling pathway with the lowest observed effective concentrations (LOEC) of 10 nM/100 nM. TCC and TCS also upregulated MMP-2/9, EGFR, MAPK3 but downregulated MAPK8 via GPER-mediated signaling pathway. Proliferation assay showed that TCC/TCS induced 4 T1 breast cancer cells proliferation with the LOEC of 100 nM/1000 nM. Wound-healing and transwell assays showed that TCC/TCS promoted 4 T1 cells migration in a concentration-dependent manner with the LOEC of 10 nM. The effects of TCC on breast cancer cells proliferation and migration were stronger than TCS and both were regulated by GPER. TCC/TCS induced migratory effects were more significantly than proliferative effect. Mechanism study showed that TCC/TCS downregulated the expression of epithelial marker (E-cadherin) but upregulated mesenchymal markers (snail and N-cadherin), which was reversed by GPER inhibitor G15. These biomarkers results indicated that TCC/TCS-induced 4 T1 cells migration was a classic epithelial to mesenchymal transition mechanism regulated by GPER signaling pathway. Orthotopic tumor model verified that TCC promoted breast cancer in-situ tumor growth and distal tissue metastasis via GPER-mediated signaling pathway at human-exposure level of 10 mg/kg/d. TCC-induced tissue metastasis of breast cancer was more significantly than in-situ tumor growth. Overall, we demonstrated for the first time that TCC/TCS could activate the GPER signaling pathways to induce breast cancer progression.
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•TCC/TCS activated GPER-mediated signaling pathways at nanomolar levels.•TCC/TCS induced 4 T1 cells EMT and migration via GPER signaling pathways.•TCC promoted the progression of 4 T1 breast cancer cells more potently than TCS.•TCC induced breast cancer tumor growth and tissue metastasis via GPER in vivo.•TCC/TCS induced migratory effect was more significantly than proliferative effect.
Generalized pustular psoriasis (GPP) is a systemic inflammatory disease with poor outcomes, and several studies have suggested that the mutation of the interleukin 36 receptor antagonist gene ...(IL36RN) is related to GPP, where the polymorphism c.115+6T>C is reported to be the most common mutation of IL36RN. This study was performed to clarify and comprehensively evaluate the relationship between IL36RN gene polymorphism and the susceptibility of GPP subtypes.
To conduct a thorough literature review, studies were obtained using databases such as Pubmed, EMBASE, Cochrane, China National Knowledge Infrastructure, and the Wanfang database. Only studies published up to December 2019 were included. The quality of the research studies was estimated using the Newcastle-Ottawa scale. The total odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs) were pooled and analysed using STATA 14. The publication bias was evaluated through the Egger test, performed using the aforementioned software. Five common gene models were built and analysed to assess the association between the polymorphism c.115+6T>C and subtypes of GPP.
A total of 10 studies were selected, including 683 cases of GPP patients. Meta-analyses showed that there was a significant statistical correlation of IL36RN mutation between GPP with or without psoriasis vulgaris (OR = 3.82, 95%CI 2.63-5.56) and between adult GPP and paediatric GPP (OR = 0.42, 95%CI 0.23-0.77). No obvious discrepancy between European patients (OR = 4.03, 95%CI 2.23-7.26) and Asian patients was found. The gene models showed clear associations between the polymorphism c.115+6T>C and GPP through the dominant model (CC+ TC vs TT, OR 2.74, 95%CI 2.06-3.64), recessive model (CC vs CT + TT, OR 4.33, 95%CI 2.84-6.60), homozygote model (CC vs TT, OR 4.37, 95%CI 2.88-6.62), heterozygote model (CT vs TT, OR 2.26, 95%CI 1.32-3.85) and allelic model (C vs T, OR 3.35, 95%CI 2.63-4.27).
The IL36RN mutation is strongly related to GPP without psoriasis vulgaris and the early onset of GPP. Furthermore, the single-nucleotide polymorphism c.115+6T>C of the IL36RN gene plays a significant role in GPP vulnerability, especially in homozygous mutation. GPP could be a different inflammatory disease, independent of psoriasis.
Health policy competencies of regional organizations include mandates to create regional health laws and policies, as well as authorities that allow member states to undertake collective actions in ...the health field. The examination of the health policy competencies of regional organizations is essential, as it constitutes an important prerequisite for regional organizations to govern regional health. This study aims to map the development trajectory of health policy competencies in regional organizations worldwide and investigate their potential correlates. This will contribute to the enhanced promotion of both existing and new regional health cooperation.
This retrospective analysis utilized the health policy competencies of the 76 regional organizations worldwide from 1945 to 2015, as investigated in the Regional Organizations Competencies Database. By aggregating member state data from various sources such as the IHME Global Burden of Disease 2019, the World Bank, and the World Trade Organization, we extracted the mean values and coefficients of variation for the covariates in regional organization characteristics, socioeconomic and demographic factors, health status and health-system capacity. The correlation between changes in the health policy scope of regional organizations and independent variables was analyzed using Poisson pseudo-likelihood regression with multiple levels of fixed effects.
From 1945 to 2015, the number of regional organizations with health policy competencies experienced a slow growth stage before 1991 and an explosive growth stage post-1991. By 2015, 48 out of the 71 existing regional organizations had developed their health policy competencies, yet 26 (54.2%) of these organizations possessed only 1-2 health policy competencies. An enhancement in the health policy scope of a regional organization correlated with its founding year, a greater number of policy fields, higher under-five mortality, and larger disparities in trade and healthcare access and quality indexes among member states. In contrast, larger disparities in population, under-five mortality and health worker density among member states, along with more hospital beds per capita, were negatively correlated with the expansion of a regional organization's health policy scope.
Since 1991, there has been a surge of interest in health among regional organizations, although health remains a secondary priority for them. The health policy competencies of regional organizations are pivotal for promoting social equity within regional communities. Its establishment is also closely linked to the level and disparities among member states in aspects such as trade, population, child mortality rates, and health system capacity.
OBJECTIVE:Eccentric exercise is commonly used as a form of loading exercise for individuals with patellar tendinopathy. This study investigated the change of mechanical properties and clinical ...outcomes and their interrelationships after a 12-week single-legged decline-board exercise with and without extracorporeal shockwave therapy (ESWT).
DESIGN:Randomized controlled trial.
SETTING:Outpatient clinic of a university.
PARTICIPANTS:Thirty-four male in-season athletes with patellar tendinopathy for more than 3 months were randomized into exercise and combined groups.
INTERVENTIONS:The exercise group received a 12-week single-legged decline-squat exercise, and the combined group performed an identical exercise program in addition to a weekly session of ESWT in the initial 6 weeks.
MAIN OUTCOME MEASURES:Tendon stiffness and strain were examined using ultrasonography and dynamometry. Visual analog scale and Victoria Institute of Sports Assessment-patella (VISA-p) score were used to assess pain and dysfunction. These parameters were measured at preintervention and postintervention.
RESULTS:Significant time effect but no significant group effect on the outcome measures; significant reduction in tendon stiffness (P = 0.02) and increase in tendon strain (P = 0.00); and reduction of intensity of pain (P = 0.00) and dysfunction (P = 0.00) were observed. Significant correlations between changes in tendon stiffness and VISA-p score (ρ = −0.58, P = 0.05); alteration in tendon strain, pain intensity (ρ = −0.63, P = 0.03); and VISA-p score (ρ = 0.60, P = 0.04) were detected after the exercise program.
CONCLUSIONS:Eccentric exercise-induced modulation on tendon mechanical properties and clinical symptoms are associated in athletes with patellar tendinopathy.
Background
Fascin is crucial for cancer cell filopodium formation and tumor metastasis, and is functionally regulated by post‐translational modifications. However, whether and how Fascin is regulated ...by acetylation remains unclear. This study explored the regulation of Fascin acetylation and its corresponding roles in filopodium formation and tumor metastasis.
Methods
Immunoprecipitation and glutathione‐S‐transferase pull‐down assays were performed to examine the interaction between Fascin and acetyltransferase P300/CBP‐associated factor (PCAF), and immunofluorescence was used to investigate their colocalization. An in vitro acetylation assay was performed to identify Fascin acetylation sites by using mass spectrometry. A specific antibody against acetylated Fascin was generated and used to detect the PCAF‐mediated Fascin acetylation in esophageal squamous cell carcinoma (ESCC) cells using Western blotting by overexpressing and knocking down PCAF expression. An in vitro cell migration assay was performed, and a xenograft model was established to study in vivo tumor metastasis. Live‐cell imaging and fluorescence recovery after photobleaching were used to evaluate the function and dynamics of acetylated Fascin in filopodium formation. The clinical significance of acetylated Fascin and PCAF in ESCC was evaluated using immunohistochemistry.
Results
Fascin directly interacted and colocalized with PCAF in the cytoplasm and was acetylated at lysine 471 (K471) by PCAF. Using the specific anti‐AcK471‐Fascin antibody, Fascin was found to be acetylated in ESCC cells, and the acetylation level was consequently increased after PCAF overexpression and decreased after PCAF knockdown. Functionally, Fascin‐K471 acetylation markedly suppressed in vitro ESCC cell migration and in vivo tumor metastasis, whereas Fascin‐K471 deacetylation exhibited a potent oncogenic function. Moreover, Fascin‐K471 acetylation reduced filopodial length and density, and lifespan of ESCC cells, while its deacetylation produced the opposite effect. In the filipodium shaft, K471‐acetylated Fascin displayed rapid dynamic exchange, suggesting that it remained in its monomeric form owing to its weakened actin‐bundling activity. Clinically, high levels of AcK471‐Fascin in ESCC tissues were strongly associated with prolonged overall survival and disease‐free survival of ESCC patients.
Conclusions
Fascin interacts directly with PCAF and is acetylated at lysine 471 in ESCC cells. Fascin‐K471 acetylation suppressed ESCC cell migration and tumor metastasis by reducing filopodium formation through the impairment of its actin‐bundling activity.
Previous studies have identified several common genetic variants in VDR, GC and CYP2R1 to be associated with circulating levels of 25-hydroxyvitamin D 25(OH)D and vitamin D deficiency in Western ...populations. We aimed to investigate the associations of these variants with serum levels of 25(OH)D and vitamin D status in 1,199 Chinese. Nine common variants of VDR, GC and CYP2R1 were genotyped using multiple SNaPshot assay, and serum 25(OH)D was detected by radioimmunoassay. The prevalence of vitamin D deficiency (<50 nmol/L) was 38.8%, which is higher in women (46.2%) than in men (34.3%, P<0.0001). The risk alleles of three common variants of GC (rs7041, rs4588, and rs2282679) were significantly associated with a lower serum levels of 25(OH)D (-1.789 ≤β ≤-3.549, P ≤0.006), while common variants in VDR and CYP2R1 were not associated with serum levels of 25(OH)D after adjusted for covariates (P ≥0.30). None of the nine common variants were associated with the presence of vitamin D deficiency in multivariable adjusted logistic regression analyses (P ≥0.17). Haplotype-based analyses of GC-rs7041 and rs4588 showed that the haplotype Gc2-2 (rs7041 AA and rs4588 TT) had the lowest levels of 25(OH)D compared with other haplotypes that contained at least one copy of Gc1 allele (Ptrend <0.0001). Our results suggest that the common variants of GC are genetic determinants of serum 25(OH)D in Chinese.
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