Expression and function of microRNA-188-5p in activated rheumatoid arthritis synovial fibroblasts

Activated synovial fibroblasts in rheumatoid arthritis (RASF) play a critical role in the pathology of rheumatoid arthritis (RA). Recent studies suggested that deregulation of microRNAs (miRs) affects the development and progression of RA. Therefore, we aimed to identify de-regulated miRs in RASF and to identify target genes that may contribute to the aggressive phenotype of RASF. Quantitative real-time PCR revealed a marked downregulation of miR-188-5p in synovial tissue samples of RA patients as well as in RASF. Exposure to the cytokine interleukine-1β lead to a further downregulation of miR-188-5p expression levels compared to control cells. Re-expression of miR-188-5p in RASF by transient transfection significantly inhibited cell migration. However, miR-188-5p re-expression had no effects on glycosaminoglycan degradation or expression of repellent factors, which have been previously shown to affect the invasive behavior of RASF. In search for target genes of miR-188-5p in RASF we performed gene expression profiling in RASF and found a strong regulatory effect of miR-188-5p on the hyaluronan binding protein KIAA1199 as well as collagens COL1A1 and COL12A1, which was confirmed by qRT-PCR. In silico analysis revealed that KIAA1199 carries a 3’UTR binding site for miR-188-5p. COL1A1 and COL12A1 showed no binding site in the mRNA region, suggesting an indirect regulation of these two genes by miR-188-5p. In summary, our study showed that miR-188-5p is down-regulated in RA in vitro and in vivo, most likely triggered by an inflammatory environment. MiR-188-5p expression is correlated to the activation state of RASF and inhibits migration of these cells. Furthermore, miR-188-5p is directly and indirectly regulating the expression of genes, which may play a role in extracellular matrix formation and destruction in RA. Herewith, this study identified potential novel therapeutic targets to inhibit the development and progression of RA.     

Expression and function of microRNA-188-5p in activated rheumatoid arthritis synovial fibroblasts

Activated synovial fibroblasts in rheumatoid arthritis (RASF) play a critical role in the pathology of rheumatoid arthritis (RA). Recent studies suggested that deregulation of microRNAs (miRs) affects the development and progression of RA. Therefore, we aimed to identify de-regulated miRs in RASF and to identify target genes that may contribute to the aggressive phenotype of RASF. Quantitative real-time PCR revealed a marked downregulation of miR-188-5p in synovial tissue samples of RA patients as well as in RASF. Exposure to the cytokine interleukine-1β lead to a further downregulation of miR-188-5p expression levels compared to control cells. Re-expression of miR-188-5p in RASF by transient transfection significantly inhibited cell migration. However, miR-188-5p re-expression had no effects on glycosaminoglycan degradation or expression of repellent factors, which have been previously shown to affect the invasive behavior of RASF. In search for target genes of miR-188-5p in RASF we performed gene expression profiling in RASF and found a strong regulatory effect of miR-188-5p on the hyaluronan binding protein KIAA1199 as well as collagens COL1A1 and COL12A1, which was confirmed by qRT-PCR. In silico analysis revealed that KIAA1199 carries a 3’UTR binding site for miR-188-5p. COL1A1and COL12A1 showed no binding site in the mRNA region, suggesting an indirect regulation of these two genes by miR-188-5p. In summary, our study showed that miR-188-5p is down-regulated in RA in vitro and in vivo, most likely triggered by an inflammatory environment. MiR-188-5p expression is correlated to the activation state of RASF and inhibits migration of these cells. Furthermore, miR-188-5p is directly and indirectly regulating the expression of genes, which may play a role in extracellular matrix formation and destruction in RA. Herewith, this study identified potential novel therapeutic targets to inhibit the development and progression of RA.     

Trends in incidence,tumour sites and tumour stages of oral and pharyngeal cancer in Northern Germany

Purpose  

Oral and pharyngeal cancer is the seventh leading tumour in Europe. In Germany, more than 10,000 new cancer cases are diagnosed each year. This population-based project evaluated the available data to develop a more detailed epidemiological profile of oral and pharyngeal cancer.     

Rasmussen encephalitis: Incidence and course under randomized therapy with tacrolimus or intravenous immunoglobulins

Purpose: Rasmussen encephalitis (RE) leads to progressive tissue and function loss of one brain hemisphere and often intractable epilepsy. This is the first randomized prospective treatment trial in RE. Methods: Germany‐wide, patients with suspected recent‐onset RE were recruited and if eligible randomized to tacrolimus or intravenous immunoglobulins (IVIGs). A loss of motor function or hemispheric volume by ≥15% (in patients >12 years at disease onset: ≥8%) led to study exit. Untreated patients served as a historical control group. Key Findings: Over 6.3 years, 21 patients with recent‐onset RE were identified. Sixteen were randomized to tacrolimus (n = 9) or IVIG (n = 7). Immunotreated patients had a longer “survival” than the historical controls. Neither treatment was more efficacious than the other. Two tacrolimus patients experienced serious adverse events. No immunotreated but several untreated patients developed intractable epilepsy. No patient with refractory epilepsy became treatment‐responsive under immunotherapy. Significance: The countrywide incidence rate of diagnosed RE is estimated as 2.4 cases/10⁷ people ≤ age 18/year. Treatment with tacrolimus or IVIG may slow down tissue and function loss and prevent development of intractable epilepsy. However, immunotherapy may “arrest” patients in a dilemma state of pharmacoresistant epilepsy but too good function to be offered functional hemispherectomy. These compounds may therefore contribute to the therapeutic armamentarium for RE patients without difficult‐to‐treat epilepsies.     

Enzyme immobilization inside the porous wood structure: a natural scaffold for continuous-flow biocatalysis

Enzymes are often immobilized on solid supports to enable their recovery from reaction solutions, facilitate their reuse and hence increase cost-effectiveness in their application. Immobilized enzymes may even be used for flow-through applications in continuous processes. However, the synthesis of traditional immobilization scaffolds and immobilization techniques lack sustainability as they are often based on fuel-based materials and tedious synthesis- and immobilization approaches. Here, we present the natural material wood as a green alternative for enzyme immobilization. Its natural structure provides a mechanically stable porous scaffold with a high inner surface area that allows for directional flow-through of liquids. Enzymes were immobilized by nanoparticle-mediated adsorption, a simple, versatile and completely water-based process. The resulting wood–enzyme hybrids were intensely investigated for the model enzyme laccase. Reaction kinetics, as well as catalytic activities at various pH-values, temperatures, and ionic strengths were determined. The wood–enzyme hybrids could quickly and completely be removed from the reaction solution. Hence, they allow for multifold reusability. We show a series of 25 consecutive reaction cycles with a remaining activity in the last cycle of 90% of the maximal activity. Moreover, the anisotropic porosity of wood enabled the application of the hybrid material as a biocatalytic flow-through reactor. Flow-rate dependent productivity of a single-enzyme reaction was determined. Moreover, we show a two-step reaction cascade in continuous flow by the immobilization of the enzymes glucose oxidase and horseradish peroxidase. Therefore, the natural material wood proved to be a promising material for application in continuous-flow biocatalysis.

Green biocatalytic systems for continuous-flow cascade reactions are realized by enzyme immobilization inside the porous wood structure.     

Outcome of surgically treated intraarticular calcaneus fractures—SF-36 compared with AOFAS and MFS

Background There is no consensus as to which is the best treatment for intraarticular fractures of the calcaneus. Furthermore, few studies have assessed general health after calcaneus fractures. We therefore measured the state of general health after operation of calcaneal fractures and compared these data with usual foot-scores. Patients and methods We compared the general health of 71 patients with surgically treated calcaneal fractures 2.5 years after injury, with the general health of 71 people from the standard German population (German National Health Survey, 1998) using the SF-36 form. We compared the results of the examination with results of AOFAS Ankle Hindfoot Scale and Maryland Foot Score in the treated patients. Results In patients with calcaneal fractures, there were significant limitations regarding general health in all 9 elements of the SF-36 form. Correlations between SF-36 and foot-scores were strong regarding function and pain scales, but moderate for all other scales. Interpretation Patients face significant limitations regarding general health after calcaneal fractures. The usual foot-scores measure only 2 dimensions of outcome: function and pain. To measure all dimensions of outcome, SF-36 is a better alternative.     

Therapists’ therapies: The relation between training therapy and patient change in long-term psychotherapy and psychoanalysis

Abstract

Patients’ development across stages in long-term psychodynamic psychotherapy or psychoanalysis was studied in relation to various parameters of their therapists’ training, or personal, therapies. The change variable was symptom distress, the General Symptom Index, according to the Symptom Checklist-90. A series of latent class regression analyses revealed that one class of therapists (16% of the sample) whose patients had the least change in treatment, and in fact had nonsignificant deterioration, was significantly overrepresented by psychotherapists with long psychoanalyses for their training therapies. Alternative interpretations of the findings are discussed.

Zusammenfassung

Die Therapien der Therapeuten: Die Beziehung zwischen Therapeutentraining und der Veränderungen der Patienten bei Langzeitpsychotherapie und Psychoanalyse

Entwicklung der Patienten in verschiedenen Stadien von Langzeittherapie oder Psychoanalyse wurde in Beziehung gesetzt zu verschiedenen Parametern der Ausbildung ihrer Therapeuten bzw. deren persönlicher Therapien. Die Veränderungsvariable war der Symptomstress entsprechend dem allgemeinen Symptomindex nach der Symptomcheckliste-90. Eine Reihe von Regression Analysen mit latenten Klassen zeigte eine Klasse von Therapeuten auf (16% der Stichprobe), deren Patienten die geringsten Veränderungen aber auch keine Verschlechterung aufwiesen. In dieser Klasse waren Psychotherapeuten mit langen Lehranalysen überrepräsentiert. Es werden auch alternative Interpretationen dieser Ergebnisse diskutiert.

Résumé

Les thérapies des thérapeutes?: la relation entre la thérapie didactique et le changement chez le patient dans la psychothérapie et psychanalyse de longue durée

Le développement des patients à travers les phases de psychothérapies psychodynamiques ou de psychanalyses de longue durée était étudié en relation à divers paramètres de la thérapie personnelle ou didactique de leurs thérapeutes. La variable de changement était la détresse symptomatique, le General Symptom Index selon la Symptom Checklist-90. Une série d'analyses par la régression par classe latente a révélé qu'une classe de thérapeutes (16% de l’échantillon) dont les patients avaient changé le moins voire se détérioraient de façon non significative était surreprésentée de façon significative par des psychothérapeutes ayant eu de longues psychanalyses comme thérapies didactiques. Des interprétations alternatives des résultats sont discutées.

Resumen

Terapia de terapeutas. La relación entre el tratamiento didáctico y el cambio del paciente en psicoterapia y psicoanálisis a largo plazo

Se estudió el desarrollo de los pacientes a través de etapas en psicoterapia psicodinámica o psicoanálisis a largo plazo, en relación con diversos parámetros del entrenamiento de sus terapeutas o terapias personales. La variable de cambio fue un síntoma de distrés, del ïndice General de Síntomas, de acuerdo con el Symptom Checklist-90. Una serie de análisis de regresión de clase latente reveló que una clase de terapeutas (16% de la muestra), cuyos pacientes habían experimentado el cambio menor en el tratamiento y que, de hecho, no tuvieron deterioro significativo, estuvo significativamente sobrerrepresentada por psicoterapias con psicoanálisis largos en sus terapias didácticas. Se debate sobre interpretaciones alternativas de los hallazgos.

Resumo

As terapias dos terapêutas: A relação entre terapia de treino e a mudança do paciente em psicoterapia de longo prazo e psicanálise

Foi estudada a relação entre o desenvolvimento dos pacientes ao longo dos estádios da psicoterapia psicodinâmica de longo prazo ou psicanálise e os vários parâmetros da terapia, de treino ou pessoal, dos seus terapeutas. A variável de mudança foi a sintomatologia psicopatológica, o Índice de Perturbação Geral da Lista de Sintomas de Derrogatis (SCL-90). Uma série de análises de regressão ( La Lent Class Regression) revelou que um grupo de terapeutas (16% da amostra), cujos pacientes tiveram as menores mudanças no tratamento e sem deterioração significativa, estava significativamente sobre-representados por psicoterapeutas com longa experiência de psicanálise para as suas terapias de treino. Serão discutidas interpretações alternativas para os resultados.