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UVA1 therapy is effective in the treatment of inflammatory and autoimmune skin diseases. The mode of action of UVA1 therapy is not completely understood and especially data on cells of the innate immune system like monocytes, which are critically involved in many inflammatory processes, are sparse. We wanted to answer the question whether UVA1 irradiation alters functional properties of human monocytes. We treated human peripheral blood monocytes in vitro with 2 J/cm

Purpose Extracellular vesicles, small vesicles carrying inter alia proteins, miRNA and RNA, are important mediators of intercellular communication. The purpose of this study was to assess the distribution of extracellular vesicles from highly malignant breast cancer and their subsequent effect on the immune cell infiltrate in target organs of metastasis. Procedures Extracellular vesicles were isolated from the tissue culture supernatant of highly malignant 4T1 breast cancer cells or the serum of healthy BALB/c mice. The purity of the isolate was verified by electron microscopy and western blotting. Extracellular vesicles were additionally subjected to proteome analysis. After labeling with the fluorescent dye DiR, extracellular vesicles were injected into healthy BALB/c mice and their in vivo distribution was assessed using fluorescence reflectance imaging (FRI). Following ex vivo imaging of the organs, lung tissue samples were analyzed for extracellular vesicle-mediated changes of myeloid cells and T cell numbers, using flow cytometry. Proteome analysis revealed major differences in the cargo of tumor cell–derived versus extracellular vesicles from healthy serum. Results In contrast to control extracellular vesicles, DiR-labeled extracellular vesicles from tumor cells preferentially accumulated in lung, liver, and spine. Subsequent flow cytometry of the immune cell composition of lung tissue samples revealed an increase of cytotoxic CD8+ T cells and a decrease of CD4+ T-helper cells as well as an increase in mature macrophages in response to tumor cell EV. Conclusions In conclusion, distribution of tumor cell–derived extracellular vesicles follows a specific pattern and can be monitored, using dedicated imaging. Extracellular vesicles alter the immune cell composition in target organs of metastasis, using a specific proteome cargo.

Objective: The purpose of the study was to compare the pressure pain threshold (PPT) of soft tissue and the curvatures of the spine in a sitting position and to estimate associated physical risk factors with low back pain (LBP) in young adults. Subjects: White-collar workers (n= 139), both women (n = 51) and men (n = 88) were separated into a control group (n = 82) and a low-intensity LBP (NRS < 3) (n = 57). Methods: The PPTs were tested utilizing the Wagner algometer. The curvatures of the spine were measured employing the photogrammetric method. In the logistic regression model, the odds ratio (OR) was estimated with ±95% confidence interval (CI) indicating the probability of the reported LBP. Results: The PPTs of soft tissue (OR = 1.1; CI = 1.02–1.19; p < 0.05) and the angle of the thoracolumbar spine in the everyday, habitual sitting position (OR = 1.19; CI = 1.05–1.34; p < 0.05) were associated with low-intensity LBP in female subjects. Additionally, the low intensity LBP were associated with the angles of the torso (OR = 1.14; CI = 1.01–1.29; p < 0.05) and the lumbosacral spine in the corrected sitting position (OR = 1.06; CI = 0.98–1.15; p > 0.05) and BMI (OR = 1.56; CI = 0.84–2.90; p > 0.05) in male subjects. Conclusion: Individual risk factors were associated with the low-intensity LBP only in females utilizing the PPT and the thoracolumbar angle in the habitual sitting position study factors. Men from the LBP group did not effectively correct the lumbosacral angle. Therefore, re-educated, self-corrected posture with specific postural training would be expected to improve proprioception in postural control capacity and result in decreasing pain.

Tumor development and metastasis are dependent on tumor infiltrating immune cells which form a characteristic tumor microenvironment (TME). Activated monocytes secrete the protein heterodimer S100A8/A9 promoting TME formation. Monocyte-dependent proteases facilitate local tumor cell invasion by degradation of the extracellular matrix. We aimed for target specific in vivo imaging of S100A8 and proteases to provide differentiating biomarkers for local tumor growth and metastatic potential. Murine breast cancer cells of the 4T1 model with graduated metastatic potential (4T1 and 4T07: both hematogenous metastasis > 168FAR: lymph-node metastasis > 67NR: no metastasis) were orthotopically implanted into female BALB/c mice. At 4 mm size, tumors were investigated by injecting the protease-specific probe ProSense 750EX (PerkinElmer, 4T1 n = 7, 4T07 n = 10, 168FAR n = 16, 67NR n = 15) and anti-S100A8-Cy5.5 (n = 6 each) and performing fluorescence reflectance imaging at 0 and 24 h after injection. In vivo imaging was validated with immunohistochemistry. At 24 h, S100A8-specific signals in 4T1 and 4T07 were significantly higher (1714.05/1683.45 AU) as compared to 168FAR and 67NR (174.85/167.95 AU, p = 0.0012/p = 0.0003), reflecting the capability of hematogenous spread. Protease-specific signals were significantly higher in 4T1 and 4T07 (348.01/409.93 AU) as compared to 168FAR (214.91 AU) and 67NR (129.78 AU p

Background The current body of knowledge shows that there is very little research into the occurrence and scale of asymmetry or postural defects in table tennis. It is interesting which regions of the spine are exposed to the greatest changes in the shape of its curvatures and whether the asymmetrical position of the shoulder and pelvic girdles in table tennis players changes when adopting the ready position. Consequently, can overload occur in certain parts of the spine and can the asymmetry deepen as a response of adopting this position? The reply to these questions may be an indication of the need for appropriate compensatory or corrective measures. Therefore, the aim of the study was to evaluate the effect of body position during play on the change in the shape of anterior–posterior spinal curvatures and trunk asymmetry in table tennis players. Methods To evaluate body posture the photogrammetric method based on the Moiré phenomenon with equipment by CQ electronic was applied. The study involved 22 female players practicing competitive table tennis (the age of 17 ± 4.5, with the average training experience of 7 ± 4.3 years, body mass of 47.8 ± 15.8, and body height of 161.2 ± 10.4). Each participant completed an author’s own questionnaire on spinal pain. The shape of curvatures in the sagittal and frontal plane was evaluated in the participant in the habitual standing position and in the table tennis ready position. Descriptive statistical analysis was performed and the significance of differences was tested using the Mann–Whitney U test. Results and Conclusions This study demonstrated the dominance of kyphotic body posture in table tennis players, which can be caused by many hours of using the ready position during playing. After adopting this position, there are significant differences in the angles of anterior and posterior spinal curvatures compared to the habitual posture. This may be the cause of overloads and pain complaints reported by the study participants. Adopting the ready position is also associated with an increase in asymmetry in the position (rotation) of the pelvis and spinous processes (frontal plane). Therefore, training programs should be extended with exercises that relieve the spine in the vertical line and exercises that improve symmetry of the work of the upper limbs, body trunk muscles and the pelvis.

Background Scavenger receptor CD163 is exclusively expressed on monocytes/macrophages and is widely used as a marker for alternatively activated macrophages. However, the role of CD163 is not yet clear. Objectives We sought to examine the function of CD163 in steady-state as well as in sterile and infectious inflammation. Methods Expression of CD163 was analyzed under normal and inflammatory conditions in mice. Functional relevance of CD163 was investigated in models of inflammation in wild-type and CD163−/− mice. Results We describe a subpopulation of bone marrow–resident macrophages (BMRMs) characterized by a high expression of CD163 and functionally distinct from classical bone marrow–derived macrophages. Development of CD163+ BMRMs is strictly dependent on IFN regulatory factor-8. CD163+ BMRMs show a specific transcriptome and cytokine secretion pattern demonstrating a specific immunomodulatory profile of these cells. Accordingly, CD163−/− mice show a stronger inflammation in allergic contact dermatitis, indicating a regulatory role of CD163. However, CD163−/− mice are highly susceptible to S aureus infections, demonstrating the relevance of CD163 for antimicrobial defense as well. Conclusions Our data indicate that anti-inflammatory and immunosuppressive mechanisms are not necessarily associated with a decreased antimicrobial activity. In contrast, our data define a novel macrophage population that controls overwhelming inflammation on one hand but is also necessary for an effective control of infections on the other hand.

Uncontrolled inflammation is a leading cause of many clinically relevant diseases. Current therapeutic strategies focus mainly on immunosuppression rather than on the mechanisms of inflammatory resolution. Glucocorticoids (GCs) are still the most widely used anti-inflammatory drugs. GCs affect most immune cells but there is growing evidence for cell type specific mechanisms. Different subtypes of monocytes and macrophages play a pivotal role both in generation as well as resolution of inflammation. Activation of these cells by microbial products or endogenous danger signals results in production of pro-inflammatory mediators and initiation of an inflammatory response. GCs efficiently inhibit these processes by down-regulating pro-inflammatory mediators from macrophages and monocytes. On the other hand, GCs act on “naïve” monocytes and macrophages and induce anti-inflammatory mediators and differentiation of anti-inflammatory phenotypes. GC-induced anti-inflammatory monocytes have an increased ability to migrate toward inflammatory stimuli. They remove endo- and exogenous danger signals by an increased phagocytic capacity, produce anti-inflammatory mediators and limit T-cell activation. Thus, GCs limit amplification of inflammation by repressing pro-inflammatory macrophage activation and additionally induce anti-inflammatory monocyte and macrophage populations actively promoting resolution of inflammation. Further investigation of these mechanisms should lead to the development of novel therapeutic strategies to modulate undesirable inflammation with fewer side effects via induction of inflammatory resolution rather than non-specific immunosuppression.

Myeloid-derived suppressor cells (MDSC) are a heterogeneous group of mononuclear and polymorphonuclear myeloid cells, which are present at very low numbers in healthy subjects, but can expand substantially under disease conditions. Depending on disease type and stage, MDSC comprise varying amounts of immature and mature differentiation stages of myeloid cells. Validated unique phenotypic markers for MDSC are still lacking. Therefore, the functional analysis of these cells is of central importance for their identification and characterization. Various disease-promoting and immunosuppressive functions of MDSC are reported in the literature. Among those, the capacity to modulate the activity of T cells is by far the most often used and best-established read-out system. In this review, we critically evaluate the assays available for the functional analysis of human and murine MDSC under in vitro and in vivo conditions. We also discuss critical issues and controls associated with those assays. We aim at providing suggestions and recommendations useful for the contemporary biological characterization of MDSC.

In patients with juvenile idiopathic arthritis (JIA), increased release of IFN-γ and GM-CSF in cells infiltrating synovial tissue can be a potent driver of monocyte activation. Given the fundamental role of monocyte activation in remodeling the early phases of inflammatory responses, here we analyze the GM-CSF/IFN-γ induced activity of human monocytes in such a situation in vitro and in vivo. Monocytes from healthy donors were isolated and stimulated with GM-CSF ± IFN-γ. Monocyte activation and death were analyzed by flow cytometry, immunofluorescence microscopy, ELISA, and qPCR. T-cell GM-CSF/IFN-γ expression and monocyte function were determined in synovial fluid and peripheral blood from 15 patients with active JIA and 21 healthy controls. Simultaneous treatment with GM-CSF and IFN-γ induces cell death of monocytes. This cell death is partly cathepsin B-associated and has morphological characteristics of necrosis. Monocytes responding to costimulation with strong proinflammatory activities are consequently eliminated. Monocytes surviving this form of hyperactivation retain normal cytokine production. Cathepsin B activity is increased in monocytes isolated from synovial fluid from patients with active arthritis. Our data suggest GM-CSF/IFN-γ induced cell death of monocytes as a novel mechanism to eliminate overactivated monocytes, thereby potentially balancing inflammation and autoimmunity in JIA.

Background Rett syndrome is a rare developmental disorder with a genetic background, and scoliosis is one of its many complications. The aim of the present study was to assess the structure of the torso in the frontal plane in RTT. It was assumed that asymmetry of the structure of the torso in the frontal plane would be smaller in girls who are able to maintain a vertical body position. Material and methods The study included 14 girls previously diagnosed with RTT aged between 3 and 15 years, who were divided into 2 groups. Group 1 comprised 5 girls who were not able to maintain a vertical position. Group 2 comprised 9 girls who were able to maintain a vertical position. Body mass and weight were measured with an electronic scales and a height measuring device. The Body Mass Index was calculated. Photogrammetry was used to assess the structure of the torso in the frontal plane. The study results were subjected to a statistical analysis involving the calculation of the arithmetic mean (x), standard deviation (sd), coefficient of variation (v%) and significance of differences (p). Results Left-sided asymmetries were most common in both groups. All angles and linear values were higher in Group 1. 80% of the subjects in Group 1 demonstrated significant asymmetry of the pelvic tilt angle (PTA). There were no statistically significant differences between Group 1 and 2 regarding all study indices. Conclusions 1. The study demonstrated that asymmetry of the torso in the frontal plane was common in the girls with RTT. 2. Torso asymmetry was more pronounced in girls with a poorer functional status. 3. Analysis of BMI values demonstrated a poor nutritional status of the girls.

Background The aim of the study was to compare the static and dynamic plantar pressure profiles of amateur marathon runners with sedentary cohorts. Research questions Are there differences in the plantar pressures of these two populations? Is there a correlation between body mass and BMI with plantar loading? Methods The study involved 43 runners involved in marathon training and 30 age-matched untrained individuals. Plantar pressure was measured using a baropodometric system. Results The marathon runners showed greater forefoot plantar pressure of the dominant extremity in the static condition and reduced medial plantar pressure of both extremities in the dynamic condition. A correlation was observed between body mass and BMI with mean plantar pressure only in the marathon group and only for the dominant extremity in the dynamic condition. Conclusions Marathon training may modify the forefoot plantar loading characteristics of the dominant extremity during static conditions and increase lateral plantar pressure of both extremities in a dynamic (gait) condition.

Objective The aim of this study was to assess existing differences in the isokinetic trunk muscle strength in males and females aged between 10 and 11 years depending on body posture. Methods The study included 145 children (67 males and 78 females) divided into 2 age groups: 10-year-old males ( x ¯ = 9.98 ± 2.34 years) and females ( x ¯ = 9.85 ± 2.94 years) and 11-year-old males ( x ¯ = 11.14 ± 2.22 years) and females ( x ¯ = 11.15 ± 2.32 years). Posture in the sagittal plane was assessed by photogrammetry using the moire projection technique. Based on a classification system, the participants were divided into subgroups of males and females with normal and abnormal postures. Trunk muscle strength was measured using isokinetic dynamometry. Results A high prevalence of abnormal posture in children aged between 10 and 11 years was observed, primarily represented by an excessive curvature of the spine in the sagittal plane. The males and females with poor posture recorded lower values in isokinetic trunk muscle strength. Conclusion The results of the study point to the need for the application of suitable physiotherapy treatment (corrective measures/exercises) to treat musculoskeletal disorders to compensate for the loss of trunk flexor muscle strength in children with improper posture.

Background Breast cancer treatment may be a cause of postural disorders. Objective Assessment of the effects of various forms of physical activity on body posture in the sagittal plane in women post breast cancer treatment. Study group Sixty women who had received breast cancer treatment. The study group was intentionally divided into three groups of 20 women who followed different exercise regimens: NordicWalking (NW), water resistance exercise (WE) or general fitness exercise (GE). Methods Photogrammetric examination of body posture using a Computer-Based Body Posture Diagnostics apparatus performed at baseline and after an 8-week regimen of appropriately selected physical exercise. Results A favourable tendency for the shallowing of thoracic kyphosis and the reduction of lumbar cu rvature of the spine was noted in the NW group. Reduced kyphosis was also noted in the WE group, however it was accompanied by more pronounced lumbar lordosis and a tendency for excessive forward bending of the trunk. In the GE group, on the other hand, no significant differences were observed in terms of the shape of anteroposterior spinal curvatures. Conclusions The diversity observed in the shape of anteroposterior spinal curvatures following physical training regimens of different type and nature demonstrates the need of appropriate exercise selection to attain the desired therapeutic outcome. Balanced postural changes were only identified among the women in the NW group. In the GE group, however, training only sustained the status existing prior to the initiation of the exercise regimen.

Although glucocorticoids (GC) represent the most frequently used immunosuppressive drugs, their effects are still not well understood. In our previous studies, we have shown that treatment of monocytes with GC does not cause a global suppression of monocytic effector functions, but rather induces differentiation of a specific anti-inflammatory phenotype. The anti-inflammatory role of peroxisome proliferator-activated receptor (PPAR)-γ has been extensively studied during recent years. However, a relationship between GC treatment and PPAR-γ expression in macrophages has not been investigated so far. Studies using PPAR-γ-deficient mice have frequently provided controversial results. A potential reason is the use of primary cells, which commonly represent inhomogeneous populations burdened with side effects and influenced by bystander cells. To overcome this constraint, we established ER-Hoxb8-immortalized bone marrow-derived macrophages from Ppargfl/fl and LysM-Cre Ppargfl/fl mice in this study. In contrast to primary macrophages, the ER-Hoxb8 system allows the generation of a homogeneous and well-defined population of resting macrophages. We could show that the loss of PPAR-γ resulted in delayed kinetic of differentiation of monocytes into macrophages as assessed by reduced F4/80, but increased Ly6C expression in early phases of differentiation. As expected, PPAR-γ-deficient macrophages displayed an increased pro-inflammatory phenotype upon long-term LPS stimulation characterized by an elevated production of pro-inflammatory cytokines TNF-α, IL1-β, IL-6, IL-12 and a reduced production of anti-inflammatory cytokine IL-10 compared to PPAR-γ WT cells. Moreover, PPAR-γ-deficient macrophages showed impaired phagocytosis. GC treatment of macrophages led to the upregulation of PPAR-γ expression. However, there were no differences in GC-induced suppression of cytokines between both cell types, implicating a PPAR-γ-independent mechanism. Intriguingly, GC treatment resulted in an increased in vitro migration only in PPAR-γ-deficient macrophages. Performing a newly developed in vivo cell-tracking experiment, we could confirm that GC induces an increased recruitment of PPAR-γ KO, but not PPAR-γ WT macrophages to the site of inflammation. Our findings suggest a specific effect of PPAR-γ on GC-induced migration in macrophages. In conclusion, we could demonstrate that PPAR-γ exerts anti-inflammatory activities and shapes macrophage functions. Moreover, we identified a molecular link between GC and PPAR-γ and could show for the first time that PPAR-γ modulates GC-induced migration in macrophages.

The aim of the study was to investigate the range of motion (ROM) of lumbar and thoracic articulations and static and dynamic plantar pressure in sport climbing athletes.The sample included 30 sport climbers with a minimum of 2 years training experience and 30 physical education students who served as an active untrained control. ROM was assessed by a Saunders digital inclinometer and plantar pressure by a baropodometric platform.Mean spinal ROMs were greater in the sport climbers with an exception of extension, rotation, and lateral thoracic flexion, with a high degree of statistical significance obtained in the majority of the analyzed ROMs. The climbers exhibited increased mean forefoot pressure (smaller rearfoot pressure) in both the dominant and nondominant extremities, with significant intergroup differences found in dominant forefoot/rearfoot pressure distribution.Sport climbers present increased lumbar and thoracic ROM. The characteristics of climbing may also affect transverse arch structure and plantar pressure distribution.

Evaluation of body posture and strength of spinal muscles in children during their progressive ontogenesis is significant for the evaluation of their physical health condition and physical fitness. It is also a reference point in a process of control and medical care.The aim if this study was to evaluate correlation between the selected features of somatic body structure, shape of anteroposterior spinal curves and force-velocity (FV) parameters of trunk muscles in school children.The sample involved 104 children aged 10-11 years, 60 females (10.74 ±0.7) and 44 males (10.50 ±0.9). Body posture was assessed using the Moiré photogrammetry while trunk muscles (flexors and extensors) strength was measured isokinetically.The results of the research revealed the existence of many average and strong correlations observed between the analysed somatic characteristics and forcevelocity (FV) parameters of trunk muscles. Correlation between the volume of the spinal curvatures in the sagittal plane and forcevelocity parameters of trunk extensors and flexors were average or weak for both groups of children.Somatic features indicated stronger correlation with trunk muscles' strength than with the size of the anteroposterior spinal curves.

The high risk of neonatal death from sepsis is thought to result from impaired responses by innate immune cells; however, the clinical observation of hyperinflammatory courses of neonatal sepsis contradicts this concept. Using transcriptomic, epigenetic and immunological approaches, we demonstrated that high amounts of the perinatal alarmins S100A8 and S100A9 specifically altered MyD88-dependent proinflammatory gene programs. S100 programming prevented hyperinflammatory responses without impairing pathogen defense. TRIF-adaptor-dependent regulatory genes remained unaffected by perinatal S100 programming and responded strongly to lipopolysaccharide, but were barely expressed. Steady-state expression of TRIF-dependent genes increased only gradually during the first year of life in human neonates, shifting immune regulation toward the adult phenotype. Disruption of this critical sequence of transient alarmin programming and subsequent reprogramming of regulatory pathways increased the risk of hyperinflammation and sepsis. Collectively these data suggest that neonates are characterized by a selective, transient microbial unresponsiveness that prevents harmful hyperinflammation in the delicate neonate while allowing for sufficient immunological protection.

To decipher early promoters of the local microenvironment for Th2-type immunity, we wanted to identify gene patterns that were induced by Leishmania major in the infected skin of susceptible, Th2-prone BALB/c, but not of resistant, Th1-prone C57BL/6 mice. We found a marked up-regulation of the chemokine I-TAC (Cxcl11) during the first 2 d of infection in the epidermis of susceptible but not of resistant mice. Accordingly, local injection of I-TAC (2×1 μg) in resistant mice on the first day of infection resulted in a Th2-driven, sustained deterioration of disease and dramatically enhanced parasite levels. On the cellular level, I-TAC decreased IL-12 production by dendritic cells (DCs) in skin-draining lymph nodes and by DCs in vitro. Thus, we demonstrate for the first time that epidermis-derived I-TAC triggers a sustained Th2-response that determines the outcome of a complex immunological process.—Roebrock, K., Sunderkotter, C., Munck, N-A., Wolf, M., Nippe, N., Barczyk, K., Varga, G., Vogl, T., Roth, J., ...

Summary Binding to fibronectin (FN) is a crucial pathogenic factor of Staphylococcus aureus mediated by fibronectin-binding protein A (FnBP-A) and extracellular adherence protein (Eap). Recently, we have shown that binding of soluble CD163 (sCD163) to FN linked to these molecules exhibits anti-microbial effects by enhancing phagocytosis and killing activity of S. aureus-infected monocytes. However, it remained unclear whether sCD163 also influences the monocytic activation status. Using genetically modified staphylococcal strains we now identified FnBP-A, but not Eap, as activator of the inflammatory response of monocytes to infection. FnBP-A-mediated inflammatory activation was masked by sCD163 binding to S. aureus promoting efficient pathogen elimination. Thus, sCD163 protects monocytes from overwhelming activation upon staphylococcal infection by dampening the secretion of pro-inflammatory cytokines TNFα, IL-1β, IL-6 and IL-8 and DAMP molecule MRP8/14. Moreover, sCD163 limited expression of pro-apoptotic transcription factor NR4A1 induced during S. aureus infection and inhibited induction of chemokine CXCL2promoting survival of staphylococci in vivo. sCD163-mediated effects were not due to general immunosuppression since MAP kinase activation and ROS production were unaltered during infection of monocytes with sCD163-bound bacteria. Thus, sCD163 promotes a specific defence of the immune system against FnBP-A-mediated inflammatory activation enabling successful pathogen elimination, tissue recovery and resolution of inflammation.

CD163 is a multi-ligand scavenger receptor exclusively expressed by monocytes and macrophages, which is released after their activation during sepsis (sCD163). The biological relevance of sCD163, however, is not yet clear. We now demonstrate that sCD163 exhibits direct antimicrobial effects by recognizing a specific subfragment ((6) F1(1) F2(2) F2(7) F1) of fibronectin (FN) bound to staphylococcal surface molecules. Moreover, contact with staphylococci promotes sCD163-shedding from monocyte surface via induction of metalloproteinases ADAM10 and ADAM17. sCD163 subsequently binds to Staphylococcus aureus via FN peptides and strongly amplifies phagocytosis as well as killing by monocytes and to a lesser extend by neutrophils. This mechanism exhibits additional paracrine effects because staphylococci additionally opsonized by sCD163 induce higher activation and more efficient killing activity of non-professional phagocytes like endothelial cells. Targeting pathogen-bound FN by sCD163 would be a very sophisticated strategy to attack S. aureus as any attempt of the pathogen to avoid this defence mechanism will automatically bring about loss of adherence to the host protein FN, which is a pivotal patho-mechanism of highly invasive staphylococcal strains. Thus, we report a novel function for sCD163 that is of particular importance for immune defence of the host against S. aureus infections.

BackgroundIn contrast to other chronic inflammatory diseases glucocorticoids alone do not maintain sufficient remission in primary vasculitis. The reasons for this therapeutic failure remain unclear.ObjectivesTo investigate the molecular effects glucocorticoids exert on endothelial cells (EC) and to elucidate the molecular pathways responsible.MethodsA comparative approach was used to treat human micro and macrovascular EC as well as monocytes long and short term with glucocorticoids or glucocorticoids and tumour necrosis factor alpha (TNFα). Gene expression changes were analysed applying microarray technology, sophisticated bioinformatic work-up and quantitative reverse transcription PCR. Glucocorticoid receptor translocation processes were traced by cell fractionation assays and immunofluorescence microscopy.ResultsIn EC glucocorticoids completely failed to inhibit the expression of immune response genes both after sole glucocorticoid exposure and glucocorticoid treatment of a TNFα-induced proinflammatory response. In contrast, an impressive downregulation of proinflammatory genes was seen in monocytes. The study demonstrated that the glucocorticoid receptor is comparably expressed in EC and monocytes, and demonstrated good translocation of ligand-bound glucocorticoid receptor allowing genomic glucocorticoid actions. Refined gene expression analysis showed that in EC transactivation takes place and causes glucocorticoid side effects on growth and metabolism whereas transrepression-mediated anti-inflammatory effects as in monocytes are missing. Insufficient induction of SAP30, an important constituent of the Sin3A-histone deacetylase complex, in EC suggests impairment of transrepression due to co-repressor absence.ConclusionsThe impressive unresponsiveness of EC to anti-inflammatory glucocorticoid effects is associated with deficiencies downstream of glucocorticoid receptor translocation not affecting transactivation but transrepression. The findings provide the first molecular clues to the poor benefit of glucocorticoid treatment in patients with primary vasculitis.

The aim of the work was to determine the activity of trunk muscles in the sagittal plane in relation to body posture type in women treated for breast cancer. Fifty women having undergone treatment for breast cancer, with an average age of 61, participated in the study. All patients were studied by application of the photogrammetric method in order to determine posture; on the basis of the compensation ratio (mu), the examined group was divided into three posture sub-groups: kyphotic (K), lordotic (L) and balanced (R). At Biodex Multi Joint 3 examination system for isokinetic tests, the functional evaluation of trunk flexor muscles and extensor muscles was performed. Women having undergone mastectomy who participate regularly in rehabilitation are characterized by diverse posture types: kyphotic, lordotic and balanced. Women with lordotic posture achieved the highest force-speed parameter values in the trunk muscles irrespective of the muscle group examined, while the lowest values were observed in women exhibiting kyphotic posture. The function of trunk muscles in women following mastectomy depends on body posture type.

Objectives In Poland, physiotherapy is offered at three types of school: medical universities, universities of physical education, and schools that do not specialise in either the medical sciences or physical education. This study explored the knowledge of students who were completing their physiotherapy studies about working in Poland and other countries of the European Union (EU), and about their vocational plans. Students were asked, through self-assessment, about aspects of the professional skills they had gained. Design Quantitative questionnaire-based study of students in three university settings. Setting Eleven university-level schools in Poland offering studies in physiotherapy and representing three orientations: medical sciences (MS), physical education (PE) and other universities (OU). Participants The study sample comprised of 954 third-year Bachelor programme students. Results The differences in university profiles did not influence the vocational plans of the students, with more than 70% (668/954) declaring that they would look for work outside Poland: 76% (725/954) in the UK and 69% (658/954) in Germany. Most students stated that finding work as a physiotherapist is difficult in Poland (686/954,72%) and easy in other EU countries (763/954, 80%). Differences in university profiles had an effect on the students’ assessments of their professional skills, as students from universities without a long-standing tradition of training in physiotherapy declared that they were less well prepared to work as physiotherapists; the difference was statistically significant for 12 of the 16 domains examined (P < 0.05). Conclusions In the light of these results, an increased influx of Polish physiotherapists, trained according to European standards, into EU countries, especially the UK and Germany, is to be expected in the near future. The physiotherapists will predominantly be graduates of medical and sports-oriented state universities. It appears advisable to launch, under the auspices of an EU programme, an integrated employment information system for physiotherapists that would offer updated information on current demand in individual EU countries.

Recurrent symptoms of low back pain and its transition to a chronic state are associated with specific motor strategies used by people to avoid pain. The aim of the study was to determine the impact of chronic pain intensity on sit-to-stand (STS) strategy in chronic low back pain (CLBP) patients with herniated disks.Vertical ground reaction forces (counter, peak, and postpeak rebound) and their respective times of occurrence were measured on 2 Kistler force plates. Thirty-two healthy persons served as a control group. People with CLBP (n = 40) were divided into 2 subgroups according to the reported pain intensity at rest as measured by the numeric pain rating scale (NRS): low pain (NRS ≤ 3) and high pain (HP; NRS3).Both CLBP subgroups achieved shorter time to counter force but longer time to postpeak rebound force (P.01). The time to peak force was extended in HP on the right side (P.01). HP presented lower peak force on the right and lower postpeak rebound force on the left side (P.001) compared with controls.Patients with CLBP were characterized by an individual, compensatory STS movement strategy with shorter preparation and longer stabilization times. Avoidance behavior in STS execution was presented in HP individuals only, indicating that intensity of chronic pain was a significant factor in decreasing ground reaction peak force and increasing time to peak force.

In patients with juvenile idiopathic arthritis (JIA), increased release of IFN-γ and GM-CSF in cells infiltrating synovial tissue can be a potent driver of monocyte activation. Given the fundamental role of monocyte activation in remodeling the early phases of inflammatory responses, here we analyze the GM-CSF/IFN-γ induced activity of human monocytes in such a situation in vitro and in vivo. Monocytes from healthy donors were isolated and stimulated with GM-CSF ± IFN-γ. Monocyte activation and death were analyzed by flow cytometry, immunofluorescence microscopy, ELISA, and qPCR. T-cell GM-CSF/IFN-γ expression and monocyte function were determined in synovial fluid and peripheral blood from 15 patients with active JIA and 21 healthy controls. Simultaneous treatment with GM-CSF and IFN-γ induces cell death of monocytes. This cell death is partly cathepsin B-associated and has morphological characteristics of necrosis. Monocytes responding to costimulation with strong proinflammatory activities are consequently eliminated. Monocytes surviving this form of hyperactivation retain normal cytokine production. Cathepsin B activity is increased in monocytes isolated from synovial fluid from patients with active arthritis. Our data suggest GM-CSF/IFN-γ induced cell death of monocytes as a novel mechanism to eliminate overactivated monocytes, thereby potentially balancing inflammation and autoimmunity in JIA.

The aim of the study was to assess the condition of foot morphological structure of young Disco-Dance dancers compared to their untrained peers.The research was carried out among professional female Disco-Dance dancers, aged 9 ± 1.07, members of Opole dance groups. The control group consisted of 33 females in the same age range, not subject to regular professional training. The condition of morphological structure of their feet was evaluated with the use of the photogrammetric method.Status of the dancers’ longitudinal foot arch fit the norm. Considerable toe V varus was observed.In both groups defective positioning of hallux and toe V was stated. Monitoring morphological architecture of feet of young dancers, especially those entering the adolescence is very important because it will allow for early detection of disorders that may result from excessive stress and enable early prevention measures to be undertaken.

Activated phagocytes express considerable amounts of MRP8 and MRP14, 2 calcium-binding S100 proteins forming stable heterodimers that are specifically secreted at inflammatory sites in many diseases. We previously reported that treatment of human microvascular endothelial cells with purified MRP8/MRP14 leads to loss of endothelial cell contacts. In this study, we demonstrate that MRP8/MRP14 complexes furthermore trigger cell death of endothelial cells after the onset of cell detachment. Morphologic analysis of dying endothelial cells revealed characteristic features of both apoptosis and necrosis. Furthermore, MRP8/MRP14 induced apoptotic caspase-9 and caspase-3 activation, DNA fragmentation, and membrane phosphatidylserine exposure in target cells. These events were independent of death receptor signaling and in part controlled by a mitochondrial pathway. Consistently, overexpression of antiapoptotic Bcl-2 abrogated caspase activation and externalization of phosphatidylserine; however, MRP8/MRP14 still induced plasma membrane damage and even DNA fragmentation. Thus, our results demonstrate that MRP8/MRP14 triggers cell death via caspase-dependent as well as -independent mechanisms. Excessive release of cytotoxic MRP8/MRP14 by activated phagocytes might therefore present an important molecular pathomechanism contributing to endothelial damage during vasculitis and other inflammatory diseases.

To decipher early promoters of the local microenvironment for Th2-type immunity, we wanted to identify gene patterns that were induced by Leishmania major in the infected skin of susceptible, Th2-prone BALB/c, but not of resistant, Th1-prone C57BL/6 mice. We found a marked up-regulation of the chemokine I-TAC (Cxcl11) during the first 2 d of infection in the epidermis of susceptible but not of resistant mice. Accordingly, local injection of I-TAC (2×1 μg) in resistant mice on the first day of infection resulted in a Th2-driven, sustained deterioration of disease and dramatically enhanced parasite levels. On the cellular level, I-TAC decreased IL-12 production by dendritic cells (DCs) in skin-draining lymph nodes and by DCs in vitro. Thus, we demonstrate for the first time that epidermis-derived I-TAC triggers a sustained Th2-response that determines the outcome of a complex immunological process.

Introduction. The aim of the study was to assess posture in children depending on the age of starting school education.Material and methods. A total of 64 students from classes I-II, including 22 six year olds and 42 seven year olds. The research material was divided into three groups: group I - first graders at the age of 6 years, group II - first graders at the age of 7 years, group III - second graders at the age of 7 years. Photogrammetric method was used for the analysis of posture in the sagittal plane.Results. The study showed that the 7-year-old children have greater deviations of the parameters in the sagittal plane than 6-year-old children. 7-year-old children in the second grade had a posture closer to 6-year-olds who have just started attending school than their equals in the first grade.Conclusions. Somatic analysis showed statistically significant differences in body weight between 6 and 7 year olds attending the first grade. Significant differences in the sagittal plane were shown in the angle of the lumbar-sacral segment, entire spine length, thoracic kyphosis length and lumbar lordosis angle.

Monocytes represent essential components of innate immunity with high plasticity.These cells are characterized by their ability to release large amounts of proinflammatory cytokines, efficient antigen presentation, and microbicidal or tumoricidal activity.They contribute to inflammation in the immune system, either by governing host defense response to invading pathogens or driving reactions to self-molecules in conditions of tissue-damage. Control of these mechanisms is necessary to ensure the self-limitation of inflammatory reactions and avoid perpetuated autoinflammation or autoimmunity. In T-cells activation-induced cell death is an important mechanism for maintaining tolerance to self-antigen. However, to date it is unclear how activated monocytes can regulate early cytokine signals promoting their survival or cell death.

Binding to fibronectin (FN) is a crucial pathogenic factor of Staphylococcus aureus mediated by fibronectin-binding protein A (FnBP-A) and extracellular adherence protein (Eap). Recently, we have shown that binding of soluble CD163 (sCD163) to FN linked to these molecules exhibits anti-microbial effects by enhancing phagocytosis and killing activity of S. aureus-infected monocytes. However, it remained unclear whether sCD163 also influences the monocytic activation status. Using genetically modified staphylococcal strains we now identified FnBP-A, but not Eap, as activator of the inflammatory response of monocytes to infection. FnBP-A-mediated inflammatory activation was masked by sCD163 binding to S. aureus promoting efficient pathogen elimination. Thus, sCD163 protects monocytes from overwhelming activation upon staphylococcal infection by dampening the secretion of pro-inflammatory cytokines TNFα, IL-1β, IL-6 and IL-8 and DAMP molecule MRP8/14. Moreover, sCD163 limited expression of pro-apoptotic transcription factor NR4A1 induced during S. aureus infection and inhibited induction of chemokine CXCL2promoting survival of staphylococci in vivo. sCD163-mediated effects were not due to general immunosuppression since MAP kinase activation and ROS production were unaltered during infection of monocytes with sCD163-bound bacteria. Thus, sCD163 promotes a specific defence of the immune system against FnBP-A-mediated inflammatory activation enabling successful pathogen elimination, tissue recovery and resolution of inflammation.

The aim of this study was to assess the effect of physical therapy procedure on a series of selected functional parameters in patients after hip arthroplasty. The study was carried out on a group of 25 patients aged 65-75 years during their stay at the “Niebieski Parasol” Nursing and Rehabilitation Centre in Chojnow. The patients underwent a clinical test on the 10th day after surgical intervention. A goniometer was used to measure the hip joint range of motion. In order to measure functional balance with the Berg Balance Scale the following tools were used: a stopwatch, a centimetre tape, a chair and a step. The test was performed twice, before physical therapy and after 6 weeks. The application of the physical therapy procedures in the experimental group contributed to an increase in the hip joint range of motion in all the mobility ranges assessed in the study and led to an improvement in the hip joint balance and gait assessed with the Berg Balance Scale.