Patellarückflächenersatz bei Patienten ohne wesentliche retropatellare Beschwerdesymptomatik – Ja oder Nein ? : Eine prospektiv randomisierte Therapievergleichsstudie über einen Beobachtungszeitraum von 12 Monaten

Ziel der prospektiv randomisierten Therapievergleichsstudie war es, die Frage nach der Notwendigkeit des Patellarückflächenersatzes bei Patienten mit einer primären Gonarthrose ohne wesentliche retropatellare Schmerzsymptomatik zu klären. Von Mai 1999 bis Mai 2000 wurden insgesamt 50 Patienten in die prospektiv randomisierte Therapievergleichsstudie aufgenommen. Sämtliche Patienten wurden mit Oberflächenersatzprothesen des gleichen Typs mit (n=25) und ohne (n=25) Patellarückflächenersatz versorgt. Einschlußkriterien waren das Vorliegen einer primären Gonarthrose ohne Patellaverschiebeschmerz oder radiologische Patelladeformierung (Grad IV nach Sperner et al.). Ferner durften die Patienten präoperativ keine wesentlichen retropatellaren Beschwerden angeben. Die Patienten wurden sowohl präoperativ als auch 3, 6 und 12 Monate postoperativ einer detaillierten Anamneseerhebung, klinischen Untersuchung und Röntgendiagnostik basierend auf einem eigens konzipierten Patientenfragebogen und dem Clinical Rating System der Knee Society unter-zogen. Die Gruppe der Patienten mit Retropatellarersatz zeigte in allen Kontroll-untersuchungen höhere Score-Werte als das Vergleichskollektiv. Patienten mit Retropatellarersatz waren hinsichtlich der retropatellaren Schmerzsymptomatik und der generellen Schmerzlinderung während sämtlicher Erhebungen zufriedener und bewerteten 12 Monate postoperativ alle Punkte des Patienten-fragebogens positiver. Zwei patellaassoziierte Revisionseingriffe mußten in der Gruppe ohne Retropatellarersatz durchgeführt werden. Röntgenologisch zeigte sich in keiner Gruppe ein Anhalt für eine Implantatlockerung, Fraktur, Subluxation oder Luxation. Die Ergebnisse unserer Studie zeigen, daß die Patienten, die aufgrund einer Gonarthrose ohne wesentliche retropatellare Beschwerdesymptomatik mit einer Knieendoprothesenimplantation mit Retropatellarersatz versorgt wurden, nach einem Beobachtungszeitraum von einem Jahr ein besseres funktionelles Ergebnis erreichten, eine höhere Zufriedenheit zeigten und eine geringere Revisionsrate aufwiesen.The aim of this prospective randomized study was to investigate the necessity of resurfacing the patella in combination with total knee arthroplasty in patients without or mild anterior knee pain before undergoing total knee replacement. Between May 1999 and May 2000 fifty patients were enrolled in a prospective, randomised study. All patients received the same posterior-cruciate-sparing total knee replacement and were randomised to treatment with and without resurfacing of the patella. Inclusion criteria were primary osteoarthritis of the knee, preoperatively no pain when the patella was shifted during clinical examination, a maximal grade 3 radiological degeneration of the patella accor-ding to Sperner et al. and at most a mild anterior knee pain in preoperative interview. Evaluations consisted of the determination of the Knee Society clinical score, the completion of a patient satisfaction questonnaire and radiographic assessment. All patients were examined preoperatively and 3, 6 and 12 months postoperatively. In all postoperative examinations patients with patella resurfacing demonstrated a higher overall Knee Society Score. At month 6 the difference was statistically significant. The patient satisfaction queston-naire demonstrated no significant difference between both groups. However, regarding to relief of anterior knee pain and improvement of pain in general patients with nonresurfacing were less satisfied at all follow-ups. Furthermore, after 12 months all answers to the patient satisfaction questonnaire of the resurfaced group were better. Patella-associated revisions were performed in two patients without resurfacing. Radiographic analysis demonstrated no loosening, fracture, subluxation or dislocation. The presented study demonstrated after one year follow-up a better functional result, a higher degree of contentment and jewer complications after total knee replacement with patella resurfacing in patients without or mild preoperative anterior knee pain

Single-particle tracking uncovers dynamics of glutamate-induced retrograde transport of NF-κB p65 in living neurons

Retrograde transport of NF-κB from the synapse to the nucleus in neurons is mediated by the dynein/dynactin motor complex and can be triggered by synaptic activation. The calibre of axons is highly variable ranging down to 100 nm, aggravating the investigation of transport processes in neurites of living neurons using conventional light microscopy. In this study we quantified for the first time the transport of the NF-κB subunit p65 using high-density single-particle tracking in combination with photoactivatable fluorescent proteins in living mouse hippocampal neurons. We detected an increase of the mean diffusion coefficient (Dmean) in neurites from 0.12 ± 0.05 µm2/s to 0.61 ± 0.03 µm2/s after stimulation with glutamate. We further observed that the relative amount of retrogradely transported p65 molecules is increased after stimulation. Glutamate treatment resulted in an increase of the mean retrograde velocity from 10.9 ± 1.9 to 15 ± 4.9 µm/s, whereas a velocity increase from 9 ± 1.3 to 14 ± 3 µm/s was observed for anterogradely transported p65. This study demonstrates for the first time that glutamate stimulation leads to an increased mobility of single NF-κB p65 molecules in neurites of living hippocampal neurons

1,8-cineol potentiates IRF3-mediated antiviral response in human stem cells and an ex vivo model of rhinosinusitis

Common cold is one of the most frequent human inflammatory diseases caused by viruses and can facilitate bacterial super-infections resulting in sinusitis or pneumonia. The active ingredient of the drug Soledum, 1,8-cineole, is commonly applied for treating inflammatory diseases of the respiratory tract. However, the potential of 1,8-cineole for treating primary viral infections of the respiratory tract remains unclear. In the present study, we demonstrate for the first time that 1,8-cineole potentiates Poly(I:C)-induced activity of the anti-viral transcription factor Interferon Regulatory Factor 3, while simultaneously reducing pro-inflammatory NF-κB-activity in human cell lines, inferior turbinate stem cells (ITSCs) and ex vivo cultivated human nasal mucosa. Co-treatment of cell lines with Poly(I:C) and 1,8-cineole resulted in significantly increased IRF3 reporter gene activity compared to Poly(I:C) alone, whereas NF-κB-activity was reduced. Accordingly, 1,8-cineole- and Poly(I:C)-treatment led to increased nuclear translocation of IRF3 in ITSCs and a human ex vivo model of rhinosinusitis compared to the Poly(I:C)-treated approach. Nuclear translocation of IRF3 was significantly increased in ITSCs and slice cultures treated with LPS and 1,8-cineole compared to the LPS-treated cells mimicking bacterial infection. Our findings strongly suggest that 1,8-cineole potentiates the antiviral activity of IRF3 in addition to its inhibitory effect on pro-inflammatory NF-κB-signalling and may thus broaden its field of application

Culture bag systems for clinical applications of adult human neural crest-derived stem cells

Introduction Facing the challenging treatment of neurodegenerative diseases as well as complex craniofacial injuries such as those common after cancer therapy, the field of regenerative medicine increasingly relies on stem cell transplantation strategies. Here, neural crest-derived stem cells (NCSCs) offer many promising applications, although scale up of clinical-grade processes prior to potential transplantations is currently limiting. In this study, we aimed to establish a clinical-grade, cost-reducing cultivation system for NCSCs isolated from the adult human nose using cGMP-grade Afc-FEP bags. Methods We cultivated human neural crest-derived stem cells from inferior turbinate (ITSCs) in a cell culture bag system using Afc-FEP bags in human blood plasma-supplemented medium. Investigations of viability, proliferation and expression profile of bag-cultured ITSCs were followed by DNA-content and telomerase activity determination. Cultivated ITSCs were introduced to directed in vitro differentiation assays to assess their potential for mesodermal and ectodermal differentiation. Mesodermal differentiation was determined using an enzyme activity assay (alkaline phosphatase, ALP), respective stainings (Alizarin Red S, Von Kossa and Oil Red O), and RT-PCR, while immunocytochemistry and synaptic vesicle recycling were applied to assay neuroectodermal differentiation of ITSCs. Results When cultivated within Afc-FEP bags, ITSCs grew three-dimensionally in a human blood plasma-derived matrix, thereby showing unchanged morphology, proliferation capability, viability and expression profile in comparison to three dimensionally-cultured ITSCs growing in standard cell culture plastics. Genetic stability of bag-cultured ITSCs was further accompanied by unchanged telomerase activity. Importantly, ITSCs retained their potential to differentiate into mesodermal cell types, particularly including ALP-active, Alizarin Red S-, and Von Kossa-positive osteogenic cell types, as well as adipocytes positive in Oil Red O assays. Bag culture further did not affect the potential of ITSCs to undergo differentiation into neuroectodermal cell types coexpressing β-III-tubulin and MAP2 and exhibiting the capability for synaptic vesicle recycling. Conclusions Here, we report for the first time the successful cultivation of human NCSCs within cGMP-grade Afc-FEP bags using a human blood plasma-supplemented medium. Our findings particularly demonstrate the unchanged differentiation capability and genetic stability of the cultivated NCSCs, suggesting the great potential of this culture system for future medical applications in the field of regenerative medicine

The Huntington's disease mutation impairs Huntingtin's role in the transport of NF-κB from the synapse to the nucleus

Expansion of a polyglutamine (polyQ) tract in the Huntingtin (Htt) protein causes Huntington's disease (HD), a fatal inherited neurodegenerative disorder. Loss of the normal function of Htt is thought to be an important pathogenetic component of HD. However, the function of wild-type Htt is not well defined. Htt is thought to be a multifunctional protein that plays distinct roles in several biological processes, including synaptic transmission, intracellular transport and neuronal transcription. Here, we show with biochemical and live cell imaging studies that wild-type Htt stimulates the transport of nuclear factor κ light-chain-enhancer of activated B cells (NF-κB) out of dendritic spines (where NF-κB is activated by excitatory synaptic input) and supports a high level of active NF-κB in neuronal nuclei (where NF-κB stimulates the transcription of target genes). We show that this novel function of Htt is impaired by the polyQ expansion and thus may contribute to the etiology of HD

Simple method for sub-diffraction resolution imaging of cellular structures on standard confocal microscopes by three-photon absorption of quantum dots

This study describes a simple technique that improves a recently developed 3D sub-diffraction imaging method based on three-photon absorption of commercially available quantum dots. The method combines imaging of biological samples via tri-exciton generation in quantum dots with deconvolution and spectral multiplexing, resulting in a novel approach for multi-color imaging of even thick biological samples at a 1.4 to 1.9-fold better spatial resolution. This approach is realized on a conventional confocal microscope equipped with standard continuous-wave lasers. We demonstrate the potential of multi-color tri-exciton imaging of quantum dots combined with deconvolution on viral vesicles in lentivirally transduced cells as well as intermediate filaments in three-dimensional clusters of mouse-derived neural stem cells (neurospheres) and dense microtubuli arrays in myotubes formed by stacks of differentiated C2C12 myoblasts

Commissural axon guidance in the developing spinal cord: from Cajal to the present day.

During neuronal development, the formation of neural circuits requires developing axons to traverse a diverse cellular and molecular environment to establish synaptic contacts with the appropriate postsynaptic partners. Essential to this process is the ability of developing axons to navigate guidance molecules presented by specialized populations of cells. These cells partition the distance traveled by growing axons into shorter intervals by serving as intermediate targets, orchestrating the arrival and departure of axons by providing attractive and repulsive guidance cues. The floor plate in the central nervous system (CNS) is a critical intermediate target during neuronal development, required for the extension of commissural axons across the ventral midline. In this review, we begin by giving a historical overview of the ventral commissure and the evolutionary purpose of decussation. We then review the axon guidance studies that have revealed a diverse assortment of midline guidance cues, as well as genetic and molecular regulatory mechanisms required for coordinating the commissural axon response to these cues. Finally, we examine the contribution of dysfunctional axon guidance to neurological diseases

Cost of installing and operating an electronic clinical decision support system for maternal health care: case of Tanzania rural primary health centres

Background: Poor quality of care is among the causes of high maternal and newborn disease burden in Tanzania. Potential reason for poor quality of care is the existence of a “know-do gap” where by health workers do not perform to the best of their knowledge. An electronic clinical decision support system (CDSS) for maternal health care was piloted in six rural primary health centers of Tanzania to improve performance of health workers by facilitating adherence to World Health Organization (WHO) guidelines and ultimately improve quality of maternal health care. This study aimed at assessing the cost of installing and operating the system in the health centers. Methods: This retrospective study was conducted in Lindi, Tanzania. Costs incurred by the project were analyzed using Ingredients approach. These costs broadly included vehicle, computers, furniture, facility, CDSS software, transport, personnel, training, supplies and communication. These were grouped into installation and operation cost; recurrent and capital cost; and fixed and variable cost. We assessed the CDSS in terms of its financial and economic cost implications. We also conducted a sensitivity analysis on the estimations. Results: Total financial cost of CDSS intervention amounted to 185,927.78 USD. 77% of these costs were incurred in the installation phase and included all the activities in preparation for the actual operation of the system for client care. Generally, training made the largest share of costs (33% of total cost and more than half of the recurrent cost) followed by CDSS software- 32% of total cost. There was a difference of 31.4% between the economic and financial costs. 92.5% of economic costs were fixed costs consisting of inputs whose costs do not vary with the volume of activity within a given range. Economic cost per CDSS contact was 52.7 USD but sensitive to discount rate, asset useful life and input cost variations. Conclusions: Our study presents financial and economic cost estimates of installing and operating an electronic CDSS for maternal health care in six rural health centres. From these findings one can understand exactly what goes into a similar investment and thus determine sorts of input modification needed to fit their context

Subunit-Specific Role of NF-κB in Cancer

Kaltschmidt B, Greiner J, Kadhim H, Kaltschmidt C. Subunit-Specific Role of NF-κB in Cancer. Biomedicines. 2018;6(2): 44.The transcription factor NF-kB is a key player in inflammation, cancer development, and progression. NF-kB stimulates cell proliferation, prevents apoptosis, and could promote tumor angiogenesis as well as metastasis. Extending the commonly accepted role of NF-kB in cancer formation and progression, different NF-kB subunits have been shown to be active and of particular importance in distinct types of cancer. Here, we summarize overexpression data of the NF-kB subunits RELA, RELB, and c-REL (referring to the v-REL, which is the oncogene of Reticuloendotheliosis virus strain T) as well as of their upstream kinase inhibitor, namely inhibitor of kB kinases (IKK), in different human cancers, assessed by database mining. These data argue against a universal mechanism of cancer-mediated activation of NF-kB, and suggest a much more elaborated mode of NF-kB regulation, indicating a tumor type-specific upregulation of the NF-kB subunits. We further discuss recent findings showing the diverse roles of NF-kB signaling in cancer development and metastasis in a subunit-specific manner, emphasizing their specific transcriptional activity and the role of autoregulation. While non-canonical NF-kB RELB signaling is described to be mostly present in hematological cancers, solid cancers reveal constitutive canonical NF-kB RELA or c-REL activity. Providing a linkage to cancer therapy, we discuss the recently described pivotal role of NF-kB c-REL in regulating cancer-targeting immune responses. In addition, current strategies and ongoing clinical trials are summarized, which utilize genome editing or drugs to inhibit the NF-kB subunits for cancer treatment