Surgical or non-surgical treatment of plantar fasciopathy (SOFT):study protocol for a randomized controlled trial

BACKGROUND: Plantar fasciopathy is the most common reason for complaints of plantar heel pain and one of the most prevalent musculoskeletal conditions with a reported lifetime incidence of 10%. The condition is normally considered self-limiting with persistent symptoms that often last for several months or years. Multiple treatments are available, but no single treatment appears superior to the others. Heavy-slow resistance training and radiofrequency microtenotomy for the treatment of plantar fasciopathy have shown potentially positive effects on short- and long-term outcomes (> 3 months). However, the effect of heavy-slow resistance training compared with a radiofrequency microtenotomy treatment is currently unknown. This trial compares the efficacy of heavy-slow resistance training and radiofrequency microtenotomy treatment with supplemental standardized patient education and heel inserts in improving the Foot Health Status Questionnaire pain score after 6 months in patients with plantar fasciopathy. METHODS: In this randomized superiority trial, we will recruit 70 patients with ultrasound-confirmed plantar fasciopathy and randomly allocate them to one of two groups: (1) heavy-slow resistance training, patient education and a heel insert (n = 35), and (2) radiofrequency microtenotomy treatment, patient education and a heel insert (n = 35). All participants will be followed for 1 year, with the 6-month follow-up considered the primary endpoint. The primary outcome is the Foot Health Status Questionnaire pain domain score. Secondary outcomes include the remaining three domains of the Foot Health Status Questionnaire, a Global Perceived Effect scale, the physical activity level, and Patient Acceptable Symptom State, which is the point at which participants feel no further need for treatment. DISCUSSION: By comparing the two treatment options, we should be able to answer if radiofrequency microtenotomy compared with heavy-slow resistance training is superior in patients with plantar fasciopathy. TRIAL REGISTRATION: ClinicalTrials.gov NCT03854682. Prospectively registered on February 26, 2019. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13063-022-06785-w

Investigations on Residual Stresses within Hot-Bulk-Formed Components Using Process Simulation and the Contour Method

Residual stresses resulting from hot-forming processes represent an important aspect of a component’s performance and service life. Considering the whole process chain of hot forming, the integrated heat treatment provided by a defined temperature profile during cooling offers a great potential for the targeted adjustment of the desired residual stress state. Finite element (FE) simulation is a powerful tool for virtual process design aimed at generating a beneficial residual stress profile. The validation of these FE models is typically carried out on the basis of individual surface points, as these are accessible through methods like X-ray diffraction, hole-drilling, or the nanoindentation method. However, especially in bulk forming components, it is important to evaluate the quality of the model based on residual stress data from the volume. For these reasons, in this paper, an FE model which was already validated by near surface X-ray diffraction analyses was used to explain the development of residual stresses in a reference hot forming process for different cooling scenarios. Subsequently, the reference process scenarios were experimentally performed, and the resulting residual stress distributions in the cross-section of the bulk specimens were determined by means of the contour method. These data were used to further validate the numerical simulation of the hot forming process, wherein a good agreement between the contour method and process simulation was observed

Differential gene expression in pristane-induced arthritis susceptible DA versus resistant E3 rats

Arthritis susceptibility genes were sought by analysis of differential gene expression between pristane-induced arthritis (PIA)-susceptible DA rats and PIA-resistant E3 rats. Inguinal lymph nodes of naïve animals and animals 8 days after pristane injection were analyzed for differential gene expression. mRNA expression was investigated by microarray and real-time PCR, and protein expression was analyzed by flow cytometry or ELISA. Twelve genes were significantly differentially expressed when analyzed by at least two independent methods, and an additional five genes showed a strong a tendency toward differential expression. In naïve DA rats IgE, the bone marrow stromal cell antigen 1 (Bst1) and the MHC class II β-chain (MhcII) were expressed at a higher level, and the immunoglobulin kappa chain (Igκ) was expressed at a lower level. In pristane-treated DA rats the MHC class II β-chain, gelatinase B (Mmp9) and the protein tyrosine phosphatase CL100 (Ptpn16) were expressed at a higher level, whereas immunoglobulins, the CD28 molecule (Cd28), the mast cell specific protease 1 (Mcpt1), the carboxylesterase precursor (Ces2), K-cadherin (Cdh6), cyclin G1 (Ccng1), DNA polymerase IV (Primase) and the tumour associated glycoprotein E4 (Tage) were expressed at a lower level. Finally, the differentially expressed mRNA was confirmed with protein expression for some of the genes. In conclusion, the results show that animal models are well suited for reproducible microarray analysis of candidate genes for arthritis. All genes have functions that are potentially important for arthritis, and nine of the genes are located within genomic regions previously associated with autoimmune disease

Arthritis induced in rats with non-immunogenic adjuvants as models for rheumatoid arthritis

Rat models are useful for studies of the pathogenesis of rheumatoid arthritis (RA) since rats are extraordinarily sensitive to induction of arthritis with adjuvants. Injection of not only the classical complete Freund's adjuvant but also mineral oil without mycobacteria and pure adjuvants such as pristane and squalene, induce severe arthritis in many rat strains. Models like pristane-induced arthritis in rats are optimal models for RA since they fulfill the RA criteria including a chronic relapsing disease course. Arthritogenic adjuvants like pristane, avridine, squalene and mineral oil are not immunogenic since they do not contain major histocompatibility complex (MHC) binding peptides. Nevertheless, the diseases are MHC-associated and dependent on the activation of alphabetaTCR (T-cell receptor)-expressing T cells. However, it has not been possible to link the immune response to joint antigens or other endogenous components although immunization with various cartilage proteins induce arthritis but with different pathogeneses. To unravel the mechanisms behind adjuvant-induced arthritis, a disease-oriented genetic approach is optimal. Several loci that control onset of arthritis, severity and chronicity of the disease have been identified in genetic crosses and most of these have been confirmed in congenic strains. In addition, many of these loci are found in other autoimmune models in the rat as well as associated with arthritis in mice and humans

Impact of baseline anemia in patients with acute coronary syndromes undergoing percutaneous coronary intervention:a prespecified analysis from the VALIDATE-SWEDEHEART trial

Background The impact of baseline anemia in a contemporary acute coronary syndrome (ACS) population undergoing percutaneous coronary intervention in the era of predominant radial artery access, potent P2Y12 inhibition, and rare use of glycoprotein IIb/IIIa inhibitors has not been adequately studied. Methods and Results ACS patients who underwent percutaneous coronary intervention between 2014 and 2016 in the VALIDATE-SWEDEHEART (Bivalirudin Versus Heparin in ST-Segment and Non-ST-Segment Elevation Myocardial Infarction in Patients on Modern Antiplatelet Therapy in the Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies Registry) trial without missing values for hemoglobin were included (n=5482). Mortality, myocardial reinfarction, and major bleeding at 180 days were assessed using Cox regression models and propensity score matching. All studied comorbidities were more common in ACS patients who had anemia (n=792). ACS patients with anemia had higher rates of 180-day mortality (6.9% versus 2.1%; hazard ratio, 1.9; 95% CI, 1.3-2.7; P<0.001), myocardial reinfarction (4.3% versus 1.9%; hazard ratio, 1.7; 95% CI, 1.1-2.7; P=0.013), and major bleeding (13.4% versus 8.2%; hazard ratio, 1.3; 95% CI, 1.0-1.6; P=0.041). The results were most evident in patients with a hemoglobin value <100 g/L, who had a nearly 10 times higher mortality rate. Conclusions Baseline anemia in ACS patients undergoing percutaneous coronary intervention, treated according to current practice including routine radial artery access, constitutes a high-risk feature for both ischemic events, bleeding events, and mortality. A multidisciplinary approach is warranted to maximize benefit and minimize patient risk. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT02311231

Two-Dimensional Patterning by a Trapping/Depletion Mechanism: The Role of TTG1 and GL3 in Arabidopsis Trichome Formation

Trichome patterning in Arabidopsis serves as a model system to study how single cells are selected within a field of initially equivalent cells. Current models explain this pattern by an activator–inhibitor feedback loop. Here, we report that also a newly discovered mechanism is involved by which patterning is governed by the removal of the trichome-promoting factor TRANSPARENT TESTA GLABRA1 (TTG1) from non-trichome cells. We demonstrate by clonal analysis and misexpression studies that Arabidopsis TTG1 can act non-cell-autonomously and by microinjection experiments that TTG1 protein moves between cells. While TTG1 is expressed ubiquitously, TTG1–YFP protein accumulates in trichomes and is depleted in the surrounding cells. TTG1–YFP depletion depends on GLABRA3 (GL3), suggesting that the depletion is governed by a trapping mechanism. To study the potential of the observed trapping/depletion mechanism, we formulated a mathematical model enabling us to evaluate the relevance of each parameter and to identify parameters explaining the paradoxical genetic finding that strong ttg1 alleles are glabrous, while weak alleles exhibit trichome clusters

[68ga]ga-pentixafor for pet imaging of vascular expression of cxcr-4 as a marker of arterial inflammation in hiv-infected patients : a comparison with18f[fdg] pet imaging

People living with human immunodeficiency virus (PLHIV) have excess risk of atherosclerotic cardiovascular disease (ASCVD). Arterial inflammation is the hallmark of atherogenesis and its complications. In this study we aimed to perform a head-to-head comparison of fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG PET/CT) and Gallium-68 pentixafor positron emission tomography/computed tomography [68Ga]Ga-pentixafor PET/CT for quantification of arterial inflammation in PLHIV. We prospectively recruited human immunodeficiency virus (HIV)-infected patients to undergo [18F]FDG PET/CT and [68Ga]Ga-pentixafor PET/CT within two weeks of each other. We quantified the levels of arterial tracer uptake on both scans using maximum standardized uptake value (SUVmax) and target–background ratio. We used Bland and Altman plots to measure the level of agreement between tracer quantification parameters obtained on both scans. A total of 12 patients were included with a mean age of 44.67 ± 7.62 years. The mean duration of HIV infection and mean CD+ T-cell count of the study population were 71.08 ± 37 months and 522.17 ± 260.33 cells/µL, respectively. We found a high level of agreement in the quantification variables obtained using [18F]FDG PET and [68Ga]Ga-pentixafor PET. There is a good level of agreement in the arterial tracer quantification variables obtained using [18F]FDG PET/CT and [68Ga]Ga-pentixafor PET/CT in PLHIV. This suggests that [68Ga]Ga-pentixafor may be applied in the place of [18F]FDG PET/CT for the quantification of arterial inflammation.http://www.mdpi.com/journal/biomoleculespm2021Nuclear Medicin

Investigations on Residual Stresses within Hot-Bulk-Formed Components Using Process Simulation and the Contour Method

Residual stresses resulting from hot-forming processes represent an important aspect of a component’s performance and service life. Considering the whole process chain of hot forming, the integrated heat treatment provided by a defined temperature profile during cooling offers a great potential for the targeted adjustment of the desired residual stress state. Finite element (FE) simulation is a powerful tool for virtual process design aimed at generating a beneficial residual stress profile. The validation of these FE models is typically carried out on the basis of individual surface points, as these are accessible through methods like X-ray diffraction, hole-drilling, or the nanoindentation method. However, especially in bulk forming components, it is important to evaluate the quality of the model based on residual stress data from the volume. For these reasons, in this paper, an FE model which was already validated by near surface X-ray diffraction analyses was used to explain the development of residual stresses in a reference hot forming process for different cooling scenarios. Subsequently, the reference process scenarios were experimentally performed, and the resulting residual stress distributions in the cross-section of the bulk specimens were determined by means of the contour method. These data were used to further validate the numerical simulation of the hot forming process, wherein a good agreement between the contour method and process simulation was observed