[Cup Placement in Thumb Carpometacarpal Joint Prostheses: The Role of the Guidewire]. / Pfannenplatzierung bei Daumensattelgelenksprothesen: Die Rolle des Führungsdrahts.

BACKGROUND: The increasing use of thumb carpometacarpal joint prostheses for advanced CMC 1 (carpometacarpal) joint arthritis reflects the success of the latest prosthesis generations, which has been achieved through their improved functional outcomes and lower complication rates. Precise alignment of the prosthesis cup parallel to the proximal joint surface of the trapezium is essential for stability and the prevention of dislocation. This is a challenging surgical step, particularly for surgeons new to this technique. Despite adequate positioning of the guidewire, misplacements of the cup may occur, necessitating intraoperative revision. MATERIAL AND METHODS: This study examined the deviations in cup and guidewire positioning in thumb carpometacarpal joint prosthesis implantations by inexperienced and experienced surgeons through radiological analysis of 65 prostheses. RESULTS: Both inexperienced and experienced surgeons achieved precise guidewire positioning with mean deviations of<2.2°. Inexperienced surgeons showed significantly larger cup deviations in the dorsopalmar and lateral view (7.6±6.1° and 7.3±5.9°) compared with experienced surgeons (3.6±2.7° and 3.6±2.5°; p=0.012, p=0.017). The deviation of the cup position exhibited by inexperienced surgeons tends to be in the direction opposite to the initial guidewire position (p<0.0038). CONCLUSION: The results highlight the current challenges in cup positioning depending on a surgeon's level of experience, questioning the reliability of the current guidewire placement.

Urban park qualities driving visitors mental well-being and wildlife conservation in a Neotropical megacity.

Green infrastructure has been widely recognized for the benefits to human health and biodiversity conservation. However, knowledge of the qualities and requirements of such spaces and structures for the effective delivery of the range of ecosystem services expected is still limited, as well as the identification of trade-offs between services. In this study, we apply the One Health approach in the context of green spaces to investigate how urban park characteristics affect human mental health and wildlife support outcomes and identify synergies and trade-offs between these dimensions. Here we show that perceived restorativeness of park users varies significantly across sites and is mainly affected by safety and naturalness perceptions. In turn, these perceptions are driven by objective indicators of quality, such as maintenance of facilities and vegetation structure, and subjective estimations of biodiversity levels. The presence of water bodies benefited both mental health and wildlife. However, high tree canopy coverage provided greater restoration potential whereas a certain level of habitat heterogeneity was important to support a wider range of bird species requirements. To reconcile human and wildlife needs in green spaces, cities should strategically implement a heterogeneous green infrastructure network that considers trade-offs and maximizes synergies between these dimensions.

Green infrastructure through the lens of "One Health": A systematic review and integrative framework uncovering synergies and trade-offs between mental health and wildlife support in cities.

Green infrastructure improves environmental health in cities, benefits human health, and provides habitat for wildlife. Increasing urbanization has demanded the expansion of urban areas and transformation of existing cities. The adoption of compact design in urban planning is a recommended strategy to minimize environmental impacts; however, it may undermine green infrastructure networks within cities as it sets a battleground for urban space. Under this scenario, multifunctionality of green spaces is highly desirable but reconciling human needs and biodiversity conservation in a limited space is still a challenge. Through a systematic review, we first compiled urban green space's characteristics that affect mental health and urban wildlife support, and then identified potential synergies and trade-offs between these dimensions. A framework based on the One Health approach is proposed, synthesizing the interlinkages between green space quality, mental health, and wildlife support; providing a new holistic perspective on the topic. Looking at the human-wildlife-environment relationships simultaneously may contribute to practical guidance on more effective green space design and management that benefit all dimensions.

Interleukin-6, but not the interleukin-6 receptor plays a role in recovery from dextran sodium sulfate-induced colitis.

Interleukin (IL)-6-deficient, but not IL-6 receptor (IL-6R)­deficient mice present with a delayed skin wound healing phenotype. Since IL-6 solely signals via the IL-6R and glycoprotein 130 (gp130), Il-6r-deficient mice are expected to exhibit a similar phenotype as Il-6-deficient mice. However, p28 (IL-30) and ciliary neurotrophic factor (CNTF) have been identified as additional low­affinity ligands of the IL-6R/gp130/LIFR complex. IL-6 plays an inflammatory and regenerative role in inflammatory bowel disease (IBD). In the present study, we compared Il-6r-deficient mice with mice treated with neutralizing IL-6 monoclonal antibody (mAb) in a model of dextran sodium sulfate (DSS)-induced colitis. Our results, in agreement with those of previous reports, demonstrated that IL-6 mAbs slightly attenuated DSS-induced colitis during the regeneration phase. Il-6r-deficient mice and mice with tissue-specific deletion of the Il-6r in the myeloid cell lineage (LysMCre) with acute and chronic DSS-induced colitis were, however, indistinguishable from wild-type mice. Our data suggest that IL-6 and IL-6R have an additional role in colitis, apart from the IL-6/IL-6R classic and trans-signaling.

Pivotal role of phospholipase D1 in tumor necrosis factor-α-mediated inflammation and scar formation after myocardial ischemia and reperfusion in mice.

Myocardial inflammation is critical for ventricular remodeling after ischemia. Phospholipid mediators play an important role in inflammatory processes. In the plasma membrane they are degraded by phospholipase D1 (PLD1). PLD1 was shown to be critically involved in ischemic cardiovascular events. Moreover, PLD1 is coupled to tumor necrosis factor-α signaling and inflammatory processes. However, the impact of PLD1 in inflammatory cardiovascular disease remains elusive. Here, we analyzed the impact of PLD1 in tumor necrosis factor-α-mediated activation of monocytes after myocardial ischemia and reperfusion using a mouse model of myocardial infarction. PLD1 expression was highly up-regulated in the myocardium after ischemia/reperfusion. Genetic ablation of PLD1 led to defective cell adhesion and migration of inflammatory cells into the infarct border zone 24 hours after ischemia/reperfusion injury, likely owing to reduced tumor necrosis factor-α expression and release, followed by impaired nuclear factor-κB activation and interleukin-1 release. Moreover, PLD1 was found to be important for transforming growth factor-ß secretion and smooth muscle α-actin expression of cardiac fibroblasts because myofibroblast differentiation and interstitial collagen deposition were altered in Pld1(-/-) mice. Consequently, infarct size was increased and left ventricular function was impaired 28 days after myocardial infarction in Pld1(-/-) mice. Our results indicate that PLD1 is crucial for tumor necrosis factor-α-mediated inflammation and transforming growth factor-ß-mediated collagen scar formation, thereby augmenting cardiac left ventricular function after ischemia/reperfusion.

Alternative intronic polyadenylation generates the interleukin-6 trans-signaling inhibitor sgp130-E10.

Interleukin (IL)-6 signals via a receptor complex composed of the signal-transducing ß-receptor gp130 and the non-signaling membrane-bound or soluble IL-6 receptor α (IL-6R, sIL-6R), which is referred to as classic and trans-signaling, respectively. IL-6 trans-signaling is functionally associated with the development of chronic inflammatory diseases and cancer. Soluble gp130 (sgp130) variants are natural inhibitors of trans-signaling. Differential splicing yields sgp130 isoforms. Here, we describe that alternative intronic polyadenylation in intron 10 of the gp130 transcript results in a novel mRNA coding for an sgp130 protein isoform (sgp130-E10) of 70-80 kDa. The sgp130-E10 protein was expressed in vivo in human peripheral blood mononuclear cells. To assess the biological activity of sgp130-E10, we expressed this variant as Fc-tagged fusion protein (sgp130-E10Fc). Recombinant sgp130-E10Fc binds to a complex of IL-6 and sIL-6R, but not to IL-6 alone, and specifically inhibits IL-6 trans-signaling. Thus, it might play an important role in the regulation of trans-signaling in vivo.

Inhibition of protein kinase II (CK2) prevents induced signal transducer and activator of transcription (STAT) 1/3 and constitutive STAT3 activation.

The Janus kinase / signal transducer and activator of transcription (Jak/STAT) pathway can be activated by many different cytokines, among them all members of the Interleukin (IL-)6 family. Dysregulation of this pathway, resulting in its constitutive activation, is associated with chronic inflammation and cancer development. In the present study, we show that activity of protein kinase II (CK2), a ubiquitously expressed serine/threonine kinase, is needed for induced activation of STAT1 and STAT3 by IL-6 classic and trans-signaling, IL-11, IL-27, oncostatin M (OSM), leukemia inhibitory factor (LIF) and cardiotrophin-1 (CT-1). Inhibition of CK2 efficiently prevented STAT phosphorylation and inhibited cytokine-dependent cell proliferation in a Jak1-dependent manner. Conversely, forced activation of CK2 alone was not sufficient to induce activation of the Jak/STAT signaling pathway. Inhibition of CK2 in turn inhibited Jak1-dependent STAT activation by oncogenic gp130 mutations. Furthermore, CK2 inhibition diminished the Jak1- and Src kinase-dependent phosphorylation of a constitutively active STAT3 mutant recently described in human large granular lymphocytic leukemia. In conclusion, we characterize CK2 as an essential component of the Jak/STAT pathway. Pharmacologic inhibition of this kinase is therefore a promising strategy to treat human inflammatory diseases and malignancies associated with constitutive activation of the Jak/STAT pathway.

An interleukin-6 receptor-dependent molecular switch mediates signal transduction of the IL-27 cytokine subunit p28 (IL-30) via a gp130 protein receptor homodimer.

IL-27 consists of the cytokine subunit p28 and the non-signaling α-receptor EBI3. p28 was shown to additionally act via the non-signaling membrane-bound IL-6 α-receptor (IL-6R) as an agonistic cytokine but also as a gp130 ß-receptor antagonist, leading to inhibition of IL-6 signaling. Here, we developed a strategy for bacterial expression, purification, and refolding of murine p28. We show that p28 did not interfere with IL-6- or IL-27-induced signaling, indicating that p28 has no antagonistic properties. Moreover, we demonstrate that murine p28 acts as an agonistic cytokine via the murine and human IL-6R, indicating that p28 exhibits no species specificity. p28 was able to induce p28-trans-signaling via the soluble IL-6R (sIL-6R), a characteristic property that was initially described for trans-signaling of IL-6 via the sIL-6R. Of notice, p28/sIL-6R trans-signaling was inhibited by the IL-6 trans-signaling antagonist, soluble gp130. At higher concentrations, p28 but not IL-6 was able to induce signaling even in the absence of IL-6R or EBI3. Although IL-27 signals via a heterodimer of the ß-receptor chains gp130 and Wsx-1, p28/IL-6R specifically recruits two gp130 ß-receptor chains for signal transduction. The binding of p28 to a gp130/Wsx-1 heterodimer or a gp130 homodimer is highly selective and controlled by a novel molecular switch induced by EBI3 or IL-6R, respectively.

Constitutively active mutant gp130 receptor protein from inflammatory hepatocellular adenoma is inhibited by an anti-gp130 antibody that specifically neutralizes interleukin 11 signaling.

Ligand-independent constitutively active gp130 mutants were described to be responsible for the development of inflammatory hepatocellular adenomas (IHCAs). These variants had gain-of-function somatic mutations within the extracellular domain 2 (D2) of the gp130 receptor chain. Cytokine-dependent Ba/F3 cells were transduced with the constitutively active variant of gp130 featuring a deletion in the domain 2 from Tyr-186 to Tyr-190 (gp130ΔYY). These cells showed constitutive phosphorylation of signal transducer and activator of transcription-3 (STAT3) and cytokine-independent proliferation. Deletion of the Ig-like domain 1 (D1) of gp130, but not anti-gp130 mAbs directed against D1, abolished constitutive activation of gp130ΔYY, highlighting that this domain is involved in ligand-independent activation of gp130ΔYY. Moreover, soluble variants of gp130 were not able to inhibit the constitutive activation of gp130ΔYY. However, the inhibition of constitutive activation of gp130ΔYY was achieved by the anti-gp130 mAb B-P4, which specifically inhibits gp130 signaling by IL-11 but not by other IL-6 type cytokines. IL-11 but not IL-6 levels were found previously to be up-regulated in IHCAs, suggesting that mutations in gp130 are leading to IL-11-like signaling. The mAb B-P4 might be a valuable tool to inhibit the constitutive activation of naturally occurring gp130 mutants in IHCAs and rare cases of gp130-associated hepatocellular carcinoma.

Projected impacts of climate change on regional capacities for global plant species richness.

Climate change represents a major challenge to the maintenance of global biodiversity. To date, the direction and magnitude of net changes in the global distribution of plant diversity remain elusive. We use the empirical multi-variate relationships between contemporary water-energy dynamics and other non-climatic predictor variables to model the regional capacity for plant species richness (CSR) and its projected future changes. We find that across all analysed Intergovernmental Panel on Climate Change emission scenarios, relative changes in CSR increase with increased projected temperature rise. Between now and 2100, global average CSR is projected to remain similar to today (+0.3%) under the optimistic B1/+1.8 degrees C scenario, but to decrease significantly (-9.4%) under the 'business as usual' A1FI/+4.0 degrees C scenario. Across all modelled scenarios, the magnitude and direction of CSR change are geographically highly non-uniform. While in most temperate and arctic regions, a CSR increase is expected, the projections indicate a strong decline in most tropical and subtropical regions. Countries least responsible for past and present greenhouse gas emissions are likely to incur disproportionately large future losses in CSR, whereas industrialized countries have projected moderate increases. Independent of direction, we infer that all changes in regional CSR will probably induce on-site species turnover and thereby be a threat to native floras.

Does lumbar cerebrospinal fluid reflect ventricular cerebrospinal fluid? A prospective study in patients with external ventricular drainage.

Ventriculitis may sometimes occur after an external ventricular drain has been removed, and diagnosis has to be made by lumbar puncture. But are the lumbar findings comparable to previously obtained ventricular results? In a prospective study, sample pairs of ventricular and lumbar cerebrospinal fluid (CSF) were obtained at an interval of <30 min in 25 patients with increased intracranial pressure suffering from cerebral hemorrhage (n = 15), meningitis/encephalitis (n = 6), cerebral infarction (n = 3), and meningeosis carcinomatosa (n = 1). CSF was analyzed for protein, albumin, IgG, IgA, IgM, glucose, lactate, and leukocytes including cytological differentiation. A significant ventriculo-lumbar increase was observed for protein, albumin, and the immunoglobulins. Lactate was distributed equally in ventricular and lumbar CSF, as well as glucose in the cerebral hemorrhage subgroup (n = 15). Cell count failed to show a clear ventriculo-lumbar ratio. Cytological distribution was comparable in lumbar and ventricular CSF, except for macrophages showing a significant rostrocaudal decrease. In conclusion, in cases of clinically suspected bacterial central nervous system infection after removal of an external ventricular drain, lumbar CSF lactate, glucose, and cytology are comparable to previously determined ventricular values, and thus may help physicians to choose the best treatment.