A predominant Th1 polarization is present in synovial fluid of end-stage osteoarthritic knee joints: analysis of peripheral blood, synovial fluid and synovial membrane.

Thorough understanding of the complex pathophysiology of osteoarthritis (OA) is necessary in order to open new avenues for treatment. The aim of this study was to characterize the CD4+ T cell population and evaluate their activation and polarization status in OA joints. Fifty-five patients with end-stage knee OA (Kellgren-Lawrence grades III-IV) who underwent surgery for total knee arthroplasty (TKA) were enrolled into this study. Matched samples of synovial membrane (SM), synovial fluid (SF) and peripheral blood (PB) were analysed for CD3+ CD4+ CD8- T cell subsets [T helper type 1 (Th1), Th2, Th17, regulatory T cells] and activation status (CD25, CD69, CD45RO, CD45RA, CD62L) by flow cytometry. Subset-specific cytokines were analysed by cytometric bead array (CBA). SM and SF samples showed a distinct infiltration pattern of CD4+ T cells. In comparison to PB, a higher amount of joint-derived T cells was polarized into CD3+ CD4+ CD8- T cell subsets, with the most significant increase for proinflammatory Th1 cells in SF. CBA analysis revealed significantly increased immunomodulating cytokines [interferon (IFN)-γ, interleukin (IL)-2 and IL-10] in SF compared to PB. Whereas in PB only a small proportion of CD4+ T cells were activated, the majority of joint-derived CD4+ T cells can be characterized as activated effector memory cells (CD69+ CD45RO+ CD62L- ). End-stage OA knees are characterized by an increased CD4+ T cell polarization towards activated Th1 cells and cytokine secretion compared to PB. This local inflammation may contribute to disease aggravation and eventually perpetuate the disease process.

[Torticollis in children]. / Der Schiefhals beim Kind.

BACKGROUND: Torticollis is a common neck deformity in both newborn and older children. The various causes of the abnormal posturing of the head differ in severity, long-term consequences and their treatment. METHODS: This article gives an overview of the differential diagnoses of torticollis in children and current literature, and provides insight into our diagnostic and therapeutic algorithm. RESULTS: A distinction is drawn between congenital and acquired deformities and whether or not they are painful. Most commonly, children present with a congenital muscular torticollis, which has an estimated incidence of 0.3 to 1.9%. The main differential diagnosis of congenital muscular torticollis is Klippel-Feil syndrome. Acquired torticollis often has more severe causes and always needs a thorough diagnostic clarification. CONCLUSION: The knowledge of possible causes and their treatment is essential to provide adequate care for affected children and their families and to prevent long-term consequences.

[Imaging diagnostics of the foot : What the orthopaedic surgeon expects from the radiologist]. / Bildgebende Diagnostik des Fußes : Was der Orthopäde vom Radiologen erwartet.

CLINICAL/METHODICAL ISSUE: Foot pain is in the case of long-term congenital, acquired or posttraumatic foot deformities a relevant clinical problem. STANDARD RADIOLOGICAL METHODS: On the basis of the clinical findings and the orthopaedic question, radiographs of the foot while standing in two planes are supplemented by radiographs of the ankle in an anterior-posterior plane. The imaging diagnostics of the foot are based on the conventional X­ray diagnostic workup and becomes even more precise and differentiated by the possibility of intersecting imaging procedures. PERFORMANCE: The diagnostic significance of imaging methods is discussed in this overview by means of clinical examples. In this context, cross-sectional imaging procedures can serve the clinician in the further decision-making process and clarify the question whether surgical treatment, for example, in the case osteoarthrosis is indicated. PRACTICAL RECOMMENDATIONS: Primarily, prior to any imaging procedure the appropriate medical history, inspection, clinical examination and the gait analysis in patients with foot pain are necessary. Interdisciplinary communication between orthopaedic/trauma surgeons and radiologists is necessary in order to provide the right imaging modality for difficult questions, to correctly interpret the resulting imaging findings, and to derive a therapeutic consequence from this. The decision whether conservative therapy or a surgical procedure is recommended will be made depending on the patients' prior therapies and the restriction of quality of life.

Unicompartmental and bicompartmental knee osteoarthritis show different patterns of mononuclear cell infiltration and cytokine release in the affected joints.

It is still controversial which cell types are responsible for synovial inflammation in osteoarthritic (OA) joints. The aim of this study was to quantify the mononuclear cell populations and their cytokines in patients with different knee OA subtypes. Synovial membrane (SM), synovial fluid (SF) and peripheral blood (PB) were harvested from patients with unicompartmental (UC) and bicompartmental (BC) knee OA. Frequencies of mononuclear cells were assessed by flow cytometry in PB and SM. Naive SF samples were analysed for a broad variety of cytokines by multiplex analysis. SM of both groups displayed a distinct mononuclear cell infiltration, with CD14(+) macrophages being the major cell population, followed by CD4(+) T cells and only small numbers of CD8(+) T, CD19(+) B and CD16(+) CD56(+) natural killer (NK) cells. Between the two groups, SM of BC OA showed significantly higher amounts of mononuclear cells (135·7 ± 180 versus 805 ± 675 cells/mg, P = 0·0009) and higher CD4(+) T cell presence (3·4 ± 4·6 versus 9·1 ± 7·5%, P = 0·0267). SF of BC OA displayed significantly higher concentrations for a number of proinflammatory cytokines [CXCL1, eotaxin, interferon (IFN)-γ, interleukin (IL)-7, IL-8, IL-9, IL-12]. UC and BC OA show significant differences in their synovial inflammatory pattern. Whereas in UC OA CD14(+) macrophages are the predominant cell population, BC OA has a higher inflammatory profile and seems to be driven by CD14(+) macrophages and CD4(+) T cells. Inclusion of clinical information into the analysis of cellular and molecular results is pivotal in understanding the pathophysiology of OA.

Fundamental movement skills in preschoolers: a randomized controlled trial targeting object control proficiency.

BACKGROUND: Adequately developed fundamental movement skills, particularly object control dimensions, are considered essential to learn more complex movement patterns and to increase the likelihood to successfully participate in organized and non-organized sports during later years. Thus, the present randomized controlled trial aimed at improving object control dimensions at an early state in a kindergarten setting. METHODS: Catching, throwing, kicking, rolling and stationary dribbling were assessed via gross motor development 2 (TGMD-2) testing in 41 normally developed preschoolers. On a cluster-randomized basis [strata: age, sex and body mass index (BMI)], three kindergartens were randomly assigned to an intervention group (n = 22, INT, age: 4.6 ± 1.0 years; BMI: 16.2 ± 1.1 kg/m(2) ) and three to a control group (n = 19, CON: age: 4.5 ± 1.2 years; BMI: 16.8 ± 1.2 kg/m(2) ). Twelve structured training sessions were given within 6 weeks (12 sessions). The total training volume was 330 min. RESULTS: Moderate time × group interaction were observed for the total sum score (Δ+22%, P = 0.05) and dribbling (Δ+41%, P = 0.002). Adjusting for baseline differences analyses of covariance did not affect these results. Interestingly, likely to most likely practically worthwhile effects were detected for the total sum score, catching and dribbling. CONCLUSION: Object control dimensions such as dribbling and catching that apparently rely on rhythmical movement patterns and anticipatory eye-hand coordination seem to benefit from short-term object control training. These skills are considered important for successful team-sport participation and appropriate sportive motor development.

Observation of coherence in the time-reversed relativistic photoelectric effect.

The photoelectric effect has been studied in the regime of hard x rays and strong Coulomb fields via its time-reversed process of radiative recombination (RR). In the experiment, the relativistic electrons recombined into the 2p_{3/2} excited state of hydrogenlike uranium ions, and both the RR x rays and the subsequently emitted characteristic x rays were detected in coincidence. This allowed us to observe the coherence between the magnetic substates in a highly charged ion and to identify the contribution of the spin-orbit interaction to the RR process.

The influence of bone marrow- and synovium-derived mesenchymal stromal cells from osteoarthritis patients on regulatory T cells in co-culture.

There is increasing evidence that inflammation in the synovium plays a major role in the progression of osteoarthritis (OA). However, the immunogenic properties of mesenchymal stromal cells (MSCs), which are considered to regulate immunity in various diseases, remain largely unknown in OA. The purpose of this study was to determine the influence of MSCs from OA patients on regulatory T cells (Tregs ) in an allogeneic co-culture model. Bone marrow (BM) and synovial membrane (SM) were harvested from hip joints of OA patients and co-cultured with lymphocytes enriched in CD4(+) CD25(+) CD127(-) regulatory T cells (Treg (+) LC) from healthy donors. Treg proportions and MSC markers were assessed by flow cytometry. Cytokine levels were assessed after 2 and 5 days of co-cultivation. Additionally, Treg (+) LC cultures were analysed in the presence of interleukin (IL)-6 and MSC-supernatant complemented medium. B-MSCs and S-MSCs were able to retain the Treg proportion compared to lymphocyte monocultures. T cell-MSC co-cultures showed a significant increase of IL-6 compared to MSC cultures. S-MSCs produced higher amounts of IL-6 compared to B-MSCs, both in single and T cell co-cultures. The effect of retaining the Treg percentage could be reproduced partially by IL-6 addition to the medium, but could only be observed fully when using MSC culture supernatants. Our data demonstrate that retaining the Treg phenotype in MSC-T cell co-cultures can be mediated by MSC derived from OA patients. IL-6 plays an important role in mediating these processes. To our knowledge, this study is the first describing the interaction of MSCs from OA patients and Tregs in an allogeneic co-culture model.

Electron- and proton-impact excitation of hydrogenlike uranium in relativistic collisions.

The K shell excitation of H-like uranium (U(91+)) in relativistic collisions with different gaseous targets has been studied at the experimental storage ring at GSI Darmstadt. By performing measurements with different targets as well as with different collision energies, we were able to observe for the first time the effect of electron-impact excitation (EIE) process in the heaviest hydrogenlike ion. The large fine-structure splitting in H-like uranium allowed us to unambiguously resolve excitation into different L shell levels. State-of-the-art calculations performed within the relativistic framework which include excitation mechanisms due to both protons (nucleus) and electrons are in good agreement with the experimental findings. Moreover, our experimental data clearly demonstrate the importance of including the generalized Breit interaction in the treatment of the EIE process.

[In vitro analysis of the impact of metal ions on human lymphocyte cultures]. / In-vitro-Analyse des Einflusses von Metallionen auf humane Lymphozyten.

The use of metal implants has become increasingly more frequent in all fields of medicine throughout the past decades. Numerous studies have demonstrated that metal ions released from these implants can be detected in body fluids remote from the implants. Although diseases directly linked to the release of these ions seem to be rare, the general public is unsettled. In this study we aimed to analyze the impact of molybdenum(V), cobalt(II), chromium(III) and nickel(II) ions on cell surface markers (CD25, CD38, CD69, CD95) and viability (7-AAD/AnnexinV) of human CD4+ T-lymphocytes in vitro. Cobalt(II) ions at a concentration of 1000 µg/l led to a significant suppression of lymphocyte activation markers while nickel(II), chromium(III) and molybdenum(V) did not show any significant impact on these lymphocyte activation markers. Cell viability was significantly reduced by all metal ions, whereas cobalt(II) led to the highest increase of apoptotic cells and was the only metal ion to significantly increase the necrosis rate. While the pathophysiological significance of these findings remains unclear, they are in favour of further research in this field.

[Melanosis of the bladder-a rare diagnosis]. / Melanose der Harnblase ­ eine Rarität.

Melanosis of the urinary bladder is an extremely rare benign condition in which melanin deposits occur in the urothelial and stromal cells. We report such a case in which melanosis of the urinary bladder was detected in a 55-year-old woman with known multiple sclerosis during an extended workup due to urinary urgency complaints. The findings were confirmed by biopsy.

[Role and limitations of vertebroplasty and kyphoplasty in the management of spinal metastases]. / Rolle und Grenzen der Vertebro-/Kyphoplastie im Metastasenmanagement der Wirbelsäule.

The spine is the most common site for skeletal metastases. Tumor-induced osteolysis may lead to pain, dysfunction and ultimately vertebral fracture. In some patients conventional surgery is not suitable because of the palliative therapy approach. Just for this patient population it was shown that cement augmentation of the vertebra is an effective therapy option and plays an important role. Nevertheless, cement augmentation of the vertebra has its limitations and should only be applied by appropriate indications.

[Treatment of hip dysplasia in young adults]. / Behandlung der Hüftgelenkdysplasie beim jungen Erwachsenen.

Developmental dysplasia of the hip (DDH) is one of the most common disorders of hips in children. The deformity can remain asymptomatic into adolescence and adulthood; however, it is considered to be a form of prearthritis and is the main cause of premature osteoarthritis of the hip. The deformity affects the acetabulum but can also be accompanied by changes in the shape of the proximal femur. If conservative treatment for mild DDH is insufficient, or in cases of moderate to severe DDH, operative treatment should be carried out, for example by corrective osteotomy of the pelvis and/or the proximal femur and hip arthroscopy may be considered adjunctively in order to resolve the prearthritis and prevent premature osteoarthritis of the hip. This manuscript elucidates the deformity, the diagnostic measures required to make the diagnosis and the treatment options available for prevention of arthritis.

Direct determination of the magnetic quadrupole contribution to the Lyman-α1 transition in a hydrogenlike ion.

We report the observation of an interference between the electric dipole (E1) and the magnetic quadrupole (M2) amplitudes for the linear polarization of the Ly-α1 (2p3/2→1s1/2) radiation of hydrogenlike uranium. This multipole mixing arises from the coupling of the ion to different multipole components of the radiation field. Our observation indicates a significant depolarization of the Ly-α1 radiation due to the E1-M2 amplitude mixing. It proves that a combined measurement of the linear polarization and of the angular distribution enables a very precise determination of the ratio of the E1 and the M2 transition amplitudes and the corresponding transition rates without any assumptions concerning the population mechanism for the 2p3/2 state.

Spectral shape of the two-photon decay of the 2 1S0 state in he-like tin.

The spectral distribution of the 1s2s {1}S{0}-->1s{2} 1S0 two-photon decay of He-like tin was measured using a novel approach at the gas-jet target of the ESR storage ring. Relativistic collisions of Li-like projectiles with low-density gaseous matter have been exploited to selectively populate the desired 1s2s state. Compared to conventional techniques, this approach results in a substantial gain in statistical and systematic accuracy, which allowed us to achieve for the first time a sensitivity to relativistic effects on the two-photon decay spectral shape as well as to discriminate the measured spectrum for Sn from theoretical shapes for different elements along the He-isoelectronic sequence.

Favorable angiogenic properties of the borosilicate bioactive glass 0106-B1 result in enhanced in vivo osteoid formation compared to 45S5 Bioglass.

The 45S5-bioactive glass (BG) composition is the most commonly investigated amongst BG-based bone substitutes. By changing BG compositions and by addition of therapeutically active ions such as boron, the biological features of BGs can be tailored towards specific needs and possible drawbacks can be overcome. The borosilicate glass 0106-B1 (composition in wt%: 37.5 SiO2, 22.6 CaO, 5.9 Na2O, 4.0 P2O5, 12.0 K2O, 5.5 MgO, 12.5 B2O3) has demonstrated pro-angiogenic properties. However, the osteogenic performance of the 0106-B1-BG and its influence on cell viability and proliferation in vitro as well as its osteogenic and angiogenic properties in vivo have not been investigated. Therefore, in this study, the impact of 0106-B1-BG and 45S5-BG on osteogenic differentiation, viability and proliferation on human mesenchymal stromal cells (MSCs) was assessed in vitro. Furthermore, MSC-seeded scaffolds made from both BG types were implanted subcutaneously in immunodeficient mice for 10 weeks. Osteoid formation was quantified by histomorphometry, vascularization was visualized by immunohistological staining. Additionally, the in vivo expression patterns of genes correlating with osteogenesis and angiogenesis were analyzed. In vitro, the impact of 45S5-BG and 0106-B1-BG on the proliferation, viability and osteogenic differentiation of MSCs was comparable. In vivo, scaffolds made from 0106-B1-BG significantly outperformed the 45S5-BG-based scaffolds regarding the amount and maturation of the osteoid. Furthermore, 0106-B1-BG-based scaffolds showed significantly increased angiogenic gene expression patterns. In conclusion, the beneficial angiogenic properties of 0106-B1-BG result in improved osteogenic properties in vivo, making the 0106-B1-BG a promising candidate for further investigation, e.g. in a bone defect model.

Tool use and mechanical problem solving in apraxia.

Moorlaas (1928) proposed that apraxic patients can identify objects and can remember the purpose they have been made for but do not know the way in which they must be used to achieve that purpose. Knowledge about the use of objects and tools can have two sources: It can be based on retrieval of instructions of use from semantic memory or on a direct inference of function from structure. The ability to infer function from structure enables subjects to use unfamiliar tools and to detect alternative uses of familiar tools. It is the basis of mechanical problem solving. The purpose of the present study was to analyze retrieval of instruction of use, mechanical problem solving, and actual tool use in patients with apraxia due to circumscribed lesions of the left hemisphere. For assessing mechanical problem solving we developed a test of selection and application of novel tools. Access to instruction of use was tested by pantomime of tool use. Actual tool use was examined for the same familiar tools. Forty two patients with left brain damage (LBD) and aphasia, 22 patients with right brain damage (RBD) and 22 controls were examined. Only LBD patients differed from controls on all tests. RBD patients had difficulties with the use but not with the selection of novel tools. In LBD patients there was a significant correlation between pantomime of tool use and novel tool selection but there were single cases who scored in the defective range on one of these tests and normally on the other. Analysis of LBD patients' lesions suggested that frontal lobe damage does not disturb novel tool selection. Only LBD patients who failed on pantomime of object use and on novel tool selection committed errors in actual use of familiar tools. The finding that mechanical problem solving is invariably defective in apraxic patients who commit errors with familiar tools is in good accord with clinical observations, as the gravity of their errors goes beyond what one would expect as a mere sequel of loss of access to instruction of use.

The meaning of meaningless gestures: a study of visuo-imitative apraxia.

In two patients with damage to the inferior portion of the left angular gyrus severely defective imitation of meaningless gestures contrasted with preserved performance of meaningful gestures to verbal command and with preserved imitation of meaningful gestures. In one patient the imitation deficit was restricted to the imitation of hand positions while imitation of finger configurations was normal. In both patients replication of the hand positions on a mannikin was as defective as imitation on themselves. This pattern of preserved and impaired performances is incompatible with two-stage models of apraxia which posit that defective imitation stems from damage to an executional stage of gesture production. Interruption of a direct route from perception to execution of action could account for the dissociation between defective imitation of meaningless and preserved performance of meaningful gestures. We propose that functioning of this route requires the integrity of general knowledge about the structure of the human body.

Electron correlations observed through intensity interferometry

Intensity interferometry was applied to study electron correlations in doubly ionizing ion-atom collisions. In this method, the probability to find two electrons emitted in the same double ionization event with a certain momentum difference is compared to the corresponding probability for two uncorrelated electrons from two independent events. The ratio of both probabilities, the so-called correlation function, is found to sensitively reveal electron correlation effects, but it is rather insensitive to the collision dynamics.

Delta-electron emission in fast heavy ion atom collisions.

Biological damages such as mutations, chromosomal aberrations etc. are a consequence of biochemical changes mostly in the DNA. With ionizing radiation, these chemical changes are due to primary ionization events and secondary ionization effects caused by the primarily produced electrons. Differences in the biological response of densely ionizing radiation, like heavy charged particles, in comparison to sparsely ionizing radiation, such as X- or gamma-rays, are mainly due to the differences in the production of the so called delta-electrons. Therefore, the emission process of electrons i.e. the cross section for the primary ionization event as well as the energy and angular distribution of the emitted electrons should be understood in detail. The delta-electron emission processes occuring in fast heavy ion atom collisions are explained qualitatively. The different spectral structures of electron emission arising from either the target or the projectile are explained in terms of simple models of the kinetics of momentum transfer induced by the COULOMB forces. In collisions of very heavy ions with matter, high nuclear COULOMB forces are created. These forces lead to a strong polarization of the electronic states of the participated electrons. The effects of this polarization are discussed.

FGF-2 addition during expansion of human bone marrow-derived stromal cells alters MSC surface marker distribution and chondrogenic differentiation potential.

OBJECTIVES: Although clinical applications using mesenchymal stromal cells (MSCs) are becoming more frequent, procedures for their in vitro culture are far from standardized. Growth factors such as FGF-2 are frequently added during expansion to improve population growth and differentiation characteristics. However, up to now its influence on surface marker distribution of MSCs has been close to unknown. The purpose of this study was therefore to analyse effects of FGF-2 supplementation on pre-selection of MSC subpopulations. MATERIALS AND METHODS: Mesenchymal stromal cells were harvested from bone marrow of six patients and expanded in alpha-MEM or DMEM-LG. Starting in passage 2, 10 ng/ml FGF-2 was administered and non-supplemented media were used as controls. Growth indices were calculated from P0 to P4. After P4, fluorescence cytometry for common MSC surface markers was performed and standard chondrogenic, adipogenic and osteogenic differentiation protocols were applied. RESULTS: Cell population growth indices were higher for those in FGF-2 supplemented media. Significant differences in surface marker distribution were observed for CD13, CD14, CD49, CD90, CD340 and STRO-1 depending on respective culture conditions. FGF-2 suppressed CD146 expression in both alpha-MEM and DMEM-LG. No differences in adipogenic and osteogenic differentiation potential could be observed, while FGF-2 significantly improved chondrogenic differentiation in DMEM-LG. CONCLUSIONS: While holding the benefit of improving MSC chondrogenic differentiation potential, FGF-2 pre-selects certain MSC subtypes. Our data clearly show that expansion culture conditions have a significant effect on distribution of a number of MSC surface markers.