Breast cancer is the most prevalent form of cancer that affects women worldwide, posing a significant burden on public health. While advancements in early detection and improved treatments have led to a remarkable 90% five-year survival rate and an 83% ten-year survival rate, this has also resulted in more prophylactic mastectomies being performed. Despite advancements in breast-conserving techniques, immunotherapy, and hormone therapy, many women still undergo mastectomies as part of their cancer treatment. In all cases, this results in scarring, and additional side effects from treatment modalities may arise. The loss of a breast can profoundly impact health-related quality of life (HRQoL). Although HRQoL has improved greatly during the recent years, systematic and local therapy having side effects is not uncommon, and this needs more attention.
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From PLoS website: In general, dietary antigens are tolerated by the gut associated immune system. Impairment of this so-called oral tolerance is a serious health risk. We have previously shown that activation of the ligand-dependent transcription factor aryl hydrocarbon receptor (AhR) by the environmental pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) affects both oral tolerance and food allergy. In this study, we determine whether a common plant-derived, dietary AhR-ligand modulates oral tolerance as well. We therefore fed mice with indole-3-carbinole (I3C), an AhR ligand that is abundant in cruciferous plants. We show that several I3C metabolites were detectable in the serum after feeding, including the high-affinity ligand 3,3´-diindolylmethane (DIM). I3C feeding robustly induced the AhR-target gene CYP4501A1 in the intestine; I3C feeding also induced the aldh1 gene, whose product catalyzes the formation of retinoic acid (RA), an inducer of regulatory T cells. We then measured parameters indicating oral tolerance and severity of peanut-induced food allergy. In contrast to the tolerance-breaking effect of TCDD, feeding mice with chow containing 2 g/kg I3C lowered the serum anti-ovalbumin IgG1 response in an experimental oral tolerance protocol. Moreover, I3C feeding attenuated symptoms of peanut allergy. In conclusion, the dietary compound I3C can positively influence a vital immune function of the gut.
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IL22 is an important cytokine involved in the intestinal defense mechanisms against microbiome. By using ileum-derived organoids, we show that the expression of anti-microbial peptides (AMPs) and anti-viral peptides (AVPs) can be induced by IL22. In addition, we identified a bacterial and a viral route, both leading to IL22 production by T cells, but via different pathways. Bacterial products, such as LPS, induce enterocyte-secreted SAA1, which triggers the secretion of IL6 in fibroblasts, and subsequently IL22 in T cells. This IL22 induction can then be enhanced by macrophage-derived TNFα in two ways: by enhancing the responsiveness of T cells to IL6 and by increasing the expression of IL6 by fibroblasts. Viral infections of intestinal cells induce IFNβ1 and subsequently IL7. IFNβ1 can induce the expression of IL6 in fibroblasts and the combined activity of IL6 and IL7 can then induce IL22 expression in T cells. We also show that IL22 reduces the expression of viral entry receptors (e.g. ACE2, TMPRSS2, DPP4, CD46 and TNFRSF14), increases the expression of anti-viral proteins (e.g. RSAD2, AOS, ISG20 and Mx1) and, consequently, reduces the viral infection of neighboring cells. Overall, our data indicates that IL22 contributes to the innate responses against both bacteria and viruses.
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Talloze studies tonen aan dat een fysiek actieve leefstijl bloeddruk, cholesterol en gewicht verlaagt, botten en spieren versterkt en het risico van hart- en vaatziekten, darmkanker en diabetes type II vermindert. Bewegen kan dus worden gezien als een medicijn wat voor iedereen toegankelijk is.
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Background Altered muscle-tendon properties in clubfoot patients could play a role in the occurrence of a relapse and negatively affect physical functioning. However, there is a lack of literature about muscle-tendon properties of clubfoot relapse patients. Research question The aim of this study was to determine whether the muscle architecture of the medial gastrocnemius and the morphology of the Achilles tendon differ between typically developing children (TDC) and clubfoot patients with and without a relapse clubfoot and to determine the relationships between morphological and functional gait outcomes. Methods A cross-sectional study was carried out in clubfoot patients treated according to the Ponseti method and TDC aged 4–8 years. A division between clubfoot patients with and without a relapse was made. Fifteen clubfoot patients, 10 clubfoot relapse patients and 19 TDC were included in the study. Morphologic properties of the medial head of the Gastrocnemius muscle and Achilles tendon were assessed by ultrasonography. Functional gait outcomes were assessed using three-dimensional gait analysis. Mean group differences were analysed with ANOVA and non-parametric alternatives. Relationships between functional and morphologic parameters were determined for all clubfoot patients together and for TDC with Spearman’s rank correlation. Results Morphological and functional gait parameters did not differ between clubfoot patients with and without a relapse, with exception of lower maximal dorsiflexor moment in clubfoot relapse patients. Compared to TDC, clubfoot and relapse patients did show lower functional gait outcomes, as well as shorter and more pennate muscles with a longer Achilles tendon. In all clubfoot patients, this longer relative tendon was related to higher ankle power and plantarflexor moment. Significance In clubfoot and relapse patients, abnormalities in morphology did not always relate to worse functional gait outcomes. Understanding these relationships in all clubfoot patients may improve the knowledge about clubfoot and aid future treatment planning.
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INTRODUCTION: To provide a state of the art on diagnostics, clinical characteristics, and treatment of paediatric generalised joint hypermobility (GJH) and joint hypermobility syndrome (JHS).METHOD: A narrative review was performed regarding diagnostics and clinical characteristics. Effectiveness of treatment was evaluated by systematic review. Searches of Medline and Central were performed and included nonsymptomatic and symptomatic forms of GJH (JHS, collagen diseases).RESULTS: In the last decade, scientific research has accumulated on all domains of the ICF. GJH/JHS can be considered as a clinical entity, which can have serious effects during all stages of life. However research regarding the pathological mechanism has resulted in new potential opportunities for treatment. When regarding the effectiveness of current treatments, the search identified 1318 studies, from which three were included (JHS: n = 2, Osteogenesis Imperfecta: n = 1). According to the best evidence synthesis, there was strong evidence that enhancing physical fitness is an effective treatment for children with JHS. However this was based on only two studies.CONCLUSION: Based on the sparsely available knowledge on intervention studies, future longitudinal studies should focus on the effect of physical activity, fitness, and joint stabilisation. In JHS and chronic pain, the effectiveness of a multidisciplinary approach should be investigated.
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Abstract: Hypertension is both a health problem and a financial one globally. It affects nearly 30 % of the general population. Elderly people, aged ≥65 years, are a special group of hypertensive patients. In this group, the overall prevalence of the disease reaches 60 %, rising to 70 % in those aged ≥80 years. In the elderly population, isolated systolic hypertension is quite common. High systolic blood pressure is associated with an increased risk of cardiovascular disease, cerebrovascular disease, peripheral artery disease, cognitive impairment and kidney disease. Considering the physiological changes resulting from ageing alongside multiple comorbidities, treatment of hypertension in elderly patients poses a significant challenge to treatment teams. Progressive disability with regard to the activities of daily life, more frequent hospitalisations and low quality of life are often seen in elderly patients. There is discussion in the literature regarding frailty syndrome associated with old age. Frailty is understood to involve decreased resistance to stressors, depleted adaptive and physiological reserves of a number of organs, endocrine dysregulation and immune dysfunction. The primary dilemma concerning frailty is whether it should only be defined on the basis of physical factors, or whether psychological and social factors should also be included. Proper nutrition and motor rehabilitation should be prioritised in care for frail patients. The risk of orthostatic hypotension is a significant issue in elderly patients. It results from an autonomic nervous system dysfunction and involves maladjustment of the cardiovascular system to sudden changes in the position of the body. Other significant issues in elderly patients include polypharmacy, increased risk of falls and cognitive impairment. Chronic diseases, including hypertension, deteriorate baroreceptor function and result in irreversible changes in cerebral and coronary circulation. Concurrent frailty or other components of geriatric syndrome in elderly patients are associated with a worse perception of health, an increased number of comorbidities and social isolation of the patient. It may also interfere with treatment adherence. Identifying causes of non-adherence to pharmaceutical treatment is a key factor in planning therapeutic interventions aimed at increasing control, preventing complications, and improving long-term outcomes and any adverse effects of treatment. Diagnosis of frailty and awareness of the associated difficulties in adhering to treatment may allow targeting of those elderly patients who have a poorer prognosis or may be at risk of complications from untreated or undertreated hypertension, and for the planning of interventions to improve hypertension control.
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Glucocorticoids (GCs) such as prednisolone are potent immunosuppressive drugs but suffer from severe adverse effects, including the induction of insulin resistance. Therefore, development of so-called Selective Glucocorticoid Receptor Modulators (SGRM) is highly desirable. Here we describe a non-steroidal Glucocorticoid Receptor (GR)-selective compound (Org 214007-0) with a binding affinity to GR similar to that of prednisolone. Structural modelling of the GR-Org 214007-0 binding site shows disturbance of the loop between helix 11 and helix 12 of GR, confirmed by partial recruitment of the TIF2-3 peptide. Using various cell lines and primary human cells, we show here that Org 214007-0 acts as a partial GC agonist, since it repressed inflammatory genes and was less effective in induction of metabolic genes. More importantly, in vivo studies in mice indicated that Org 214007-0 retained full efficacy in acute inflammation models as well as in a chronic collagen-induced arthritis (CIA) model. Gene expression profiling of muscle tissue derived from arthritic mice showed a partial activity of Org 214007-0 at an equi-efficacious dosage of prednisolone, with an increased ratio in repression versus induction of genes. Finally, in mice Org 214007-0 did not induce elevated fasting glucose nor the shift in glucose/glycogen balance in the liver seen with an equi-efficacious dose of prednisolone. All together, our data demonstrate that Org 214007-0 is a novel SGRMs with an improved therapeutic index compared to prednisolone. This class of SGRMs can contribute to effective anti-inflammatory therapy with a lower risk for metabolic side effects.
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BACKGROUND: In the last decades, autologous fat grafting has been used to treat adherent dermal scars. The observed regenerative and scar-reducing properties have been mainly ascribed to the tissue-derived stromal vascular fraction (tSVF) in adipose tissue. Adipose tissue's components augment local angiogenesis and mitosis in resident tissue cells. Moreover, it promotes collagen remodeling. We hypothesize that tSVF potentiates fat grafting-based treatment of adherent scars. Therefore, this study aims to investigate the effect of tSVF-enriched fat grafting on scar pliability over a 12-month period.METHODS AND DESIGN: A clinical multicenter non-randomized early phase trial will be conducted in two dedicated Dutch Burn Centers (Red Cross Hospital, Beverwijk, and Martini Hospital, Groningen). After informed consent, 46 patients (≥18 years) with adherent scars caused by burns, necrotic fasciitis, or degloving injury who have an indication for fat grafting will receive a sub-cicatricic tSVF-enriched fat graft. The primary outcome is the change in scar pliability measured by the Cutometer between pre- and 12 months post-grafting. Secondary outcomes are scar pliability (after 3 months), scar erythema, and melanin measured by the DSM II Colormeter; scar quality assessed by the patient and observer scales of the Patient and Observer Scar Assessment Scale (POSAS) 2.0; and histological analysis of scar biopsies (voluntary) and tSVF quality and composition. This study has been approved by the Dutch Central Committee for Clinical Research (CCMO), NL72094.000.20.CONCLUSION: This study will test the clinical efficacy of tSVF-enriched fat grafting to treat dermal scars while the underlying working mechanism will be probed into too.
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ObjectivesTo investigate cartilage tissue turnover in response to a supervised 12-week exercise-related joint loading training program followed by a 6-month period of unsupervised training in patients with knee osteoarthritis (OA). To study the difference in cartilage tissue turnover between high- and low-resistance training.MethodPatients with knee OA were randomized into either high-intensity or low-intensity resistance supervised training (two sessions per week) for 3 months and unsupervised training for 6 months. Blood samples were collected before and after the supervised training period and after the follow-up period. Biomarkers huARGS, C2M, and PRO-C2, quantifying cartilage tissue turnover, were measured by ELISA. Changes in biomarker levels over time within and between groups were analyzed using linear mixed models with baseline values as covariates.ResultshuARGS and C2M levels increased after training and at follow-up in both low- and high-intensity exercise groups. No changes were found in PRO-C2. The huARGS level in the high-intensity resistance training group increased significantly compared to the low-intensity resistance training group after resistance training (p = 0.029) and at follow-up (p = 0.003).ConclusionCartilage tissue turnover and cartilage degradation appear to increase in response to a 3-month exercise-related joint loading training program and at 6-month follow-up, with no evident difference in type II collagen formation. Aggrecan remodeling increased more with high-intensity resistance training than with low-intensity exercise.These exploratory biomarker results, indicating more cartilage degeneration in the high-intensity group, in combination with no clinical outcome differences of the VIDEX study, may argue against high-intensity training.
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