Effectiveness of a Multimodal Therapy for Patients with Chronic Low Back Pain Regarding Pre-Admission Healthcare Utilization

Objective

The aim of the study was to examine the effectiveness of an intensive inpatient three-week multimodal therapy. We focused especially on the impact on the multimodal therapy outcome of the pre-admission number of treatment types patients had received and of medical specialist groups patients had consulted.

Methods

155 patients with chronic low back pain and indication for multimodal therapy were evaluated with respect to pain intensity, depression, anxiety, well-being, and pre-admission health care utilization. In our controlled clinical trial we compared N = 66 patients on the waiting list with N = 89 patients who received immediate treatment. The waiting list patients likewise attended multimodal therapy after the waiting period. Longitudinal post-treatment data for both were collected at three- and twelve-month follow-ups. The impact of pre-admission health care utilization on multimodal therapy outcome (post) was analysed by structural equation model.

Results

Compared to the control group, multimodal therapy patients’ pain intensity and psychological variables were significantly reduced. Longitudinal effects with respect to pre-measures were significant at three-month follow-up for pain intensity (ES = -0.48), well-being (ES = 0.78), anxiety (ES = -0.33), and depression (ES = -0.30). Effect sizes at twelve-month follow-up were small for anxiety (ES = -0.22), and moderate for general well-being (ES = 0.61). Structural equation model revealed that a higher number of pre-admission treatment types was associated with poorer post-treatment outcomes in pain intensity, well-being, and depression.

Conclusion

Multimodal therapy proved to be effective with regard to improvements in pain intensity, depression, anxiety, and well-being. The association between treatment effect and number of pre-admission pain treatment types suggests that patients would benefit more from attending multimodal therapy in an earlier stage of health care.     

The Leber Congenital Amaurosis Protein AIPL1 and EB Proteins Co-Localize at the Photoreceptor Cilium

Purpose

The aim of this study was to investigate the interaction and co-localization of novel interacting proteins with the Leber congenital amaurosis (LCA) associated protein aryl hydrocarbon receptor interacting protein-like 1 (AIPL1).

Methods

The CytoTrapXR yeast two-hybrid system was used to screen a bovine retinal cDNA library. A novel interaction between AIPL1 and members of the family of EB proteins was confirmed by directed yeast two-hybrid analysis and co-immunoprecipitation assays. The localization of AIPL1 and the EB proteins in cultured cells and in retinal cryosections was examined by immunofluorescence microscopy and cryo-immunogold electron microscopy.

Results

Yeast two-hybrid (Y2H) analysis identified the interaction between AIPL1 and the EB proteins, EB1 and EB3. EB1 and EB3 were specifically co-immunoprecipitated with AIPL1 from SK-N-SH neuroblastoma cells. In directed 1:1 Y2H analysis, the interaction of EB1 with AIPL1 harbouring the LCA-causing mutations A197P, C239R and W278X was severely compromised. Immunofluorescent confocal microscopy revealed that AIPL1 did not co-localize with endogenous EB1 at the tips of microtubules, endogenous EB1 at the microtubule organising centre following disruption of the microtubule network, or with endogenous β-tubulin. Moreover, AIPL1 did not localize to primary cilia in ARPE-19 cells, whereas EB1 co-localized with the centrosomal marker pericentrin at the base of primary cilia. However, both AIPL1 and the EB proteins, EB1 and EB3, co-localized with centrin-3 in the connecting cilium of photoreceptor cells. Cryo-immunogold electron microscopy confirmed the co-localization of AIPL1 and EB1 in the connecting cilia in human retinal photoreceptors.

Conclusions

AIPL1 and the EB proteins, EB1 and EB3, localize at the connecting cilia of retinal photoreceptor cells, but do not co-localize in the cellular microtubule network or in primary cilia in non-retinal cells. These findings suggest that AIPL1 function in these cells is not related to the role of EB proteins in microtubule dynamics or primary ciliogenesis, but that their association may be related to a specific role in the specialized cilia apparatus of retinal photoreceptors.     

Autophagy in malignant transformation and cancer progression

Autophagy plays a key role in the maintenance of cellular homeostasis. In healthy cells, such a homeostatic activity constitutes a robust barrier against malignant transformation. Accordingly, many oncoproteins inhibit, and several oncosuppressor proteins promote, autophagy. Moreover, autophagy is required for optimal anticancer immunosurveillance. In neoplastic cells, however, autophagic responses constitute a means to cope with intracellular and environmental stress, thus favoring tumor progression. This implies that at least in some cases, oncogenesis proceeds along with a temporary inhibition of autophagy or a gain of molecular functions that antagonize its oncosuppressive activity. Here, we discuss the differential impact of autophagy on distinct phases of tumorigenesis and the implications of this concept for the use of autophagy modulators in cancer therapy.     

Early Mesozoic Coexistence of Amniotes and Hepadnaviridae

Hepadnaviridae are double-stranded DNA viruses that infect some species of birds and mammals. This includes humans, where hepatitis B viruses (HBVs) are prevalent pathogens in considerable parts of the global population. Recently, endogenized sequences of HBVs (eHBVs) have been discovered in bird genomes where they constitute direct evidence for the coexistence of these viruses and their hosts from the late Mesozoic until present. Nevertheless, virtually nothing is known about the ancient host range of this virus family in other animals. Here we report the first eHBVs from crocodilian, snake, and turtle genomes, including a turtle eHBV that endogenized >207 million years ago. This genomic “fossil” is >125 million years older than the oldest avian eHBV and provides the first direct evidence that Hepadnaviridae already existed during the Early Mesozoic. This implies that the Mesozoic fossil record of HBV infection spans three of the five major groups of land vertebrates, namely birds, crocodilians, and turtles. We show that the deep phylogenetic relationships of HBVs are largely congruent with the deep phylogeny of their amniote hosts, which suggests an ancient amniote–HBV coexistence and codivergence, at least since the Early Mesozoic. Notably, the organization of overlapping genes as well as the structure of elements involved in viral replication has remained highly conserved among HBVs along that time span, except for the presence of the X gene. We provide multiple lines of evidence that the tumor-promoting X protein of mammalian HBVs lacks a homolog in all other hepadnaviruses and propose a novel scenario for the emergence of X via segmental duplication and overprinting of pre-existing reading frames in the ancestor of mammalian HBVs. Our study reveals an unforeseen host range of prehistoric HBVs and provides novel insights into the genome evolution of hepadnaviruses throughout their long-lasting association with amniote hosts.     

Identifying evolutionarily conserved genes in the dietary restriction response using bioinformatics and subsequent testing in Caenorhabditis elegans

Dietary restriction (DR) increases life span, health span and resistance to stress in a wide range of organisms. Work from a large number of laboratories has revealed evolutionarily conserved mechanisms that mediate the DR response. Here, we analyzed the genome-wide gene expression profiles of Caenorhabditis elegans under DR versus ad libitum conditions. Using the Ortho2ExpressMatrix tool, we searched for C. elegans orthologs of mouse genes that have been shown to be differentially expressed under DR conditions in nearly 600 experiments. Based on our bioinformatic approaches, we obtained 189 DR-responsive genes, and 45 of these are highly conserved from worm to man. Subsequent testing of sixteen genes that are up-regulated under DR identified eight genes that abolish the DR-induced resistance to heat stress in C. elegans. Further analyses revealed that fkb-4, dod-22 and ikb-1 genes also abolish increased life span in response to DR. The identified genes that are necessary for the DR response are sensitive to certain stress signals such as metabolic perturbances (dod-22, fkb-4 and nhr-85), DNA damage (ikb-1), heat shock (hsp-12.6) and cancer-like overgrowth (prk-2 and tsp-15). We propose that most of the DR-responsive genes identified are components of the recently discovered cellular surveillance-activated detoxification and defenses pathway, which is, among others, important for the survival of organisms in times of food deprivation.

Electronic supplementary material

The online version of this article (doi:10.1007/s12263-013-0363-5) contains supplementary material, which is available to authorized users.     

Unravelling the Scent of Vetiver: Identification of Character‐Impact Compounds

Vetiver oil is a highly esteemed basic ingredient of modern perfumery, but the nature of the constituents that really impart its typical and most sought woody‐earthy scent has remained controversial. Indeed, vetiver oil is considered as one of the most complex essential oils, being mostly composed of several hundreds of sesquiterpene derivatives with a large structural diversity. Its complexity has hindered the direct identification of its odoriferous components. We thus aimed at using a combination of GC×GC/MS and GC‐Olfactometry in order to identify most of its odor‐impact constituents. The olfactory analysis of vetiver oil and vetiveryl acetate revealed a huge variety of odors in both products. While khusimone has almost unanimously been recognized as the most characteristic vetiver odorant, we have identified several even more important contributors to the typical vetiver character.     

pyOpenMS: A Python‐based interface to the OpenMS mass‐spectrometry algorithm library

pyOpenMS is an open‐source, Python‐based interface to the C++ OpenMS library, providing facile access to a feature‐rich, open‐source algorithm library for MS‐based proteomics analysis. It contains Python bindings that allow raw access to the data structures and algorithms implemented in OpenMS, specifically those for file access (mzXML, mzML, TraML, mzIdentML among others), basic signal processing (smoothing, filtering, de‐isotoping, and peak‐picking) and complex data analysis (including label‐free, SILAC, iTRAQ, and SWATH analysis tools). pyOpenMS thus allows fast prototyping and efficient workflow development in a fully interactive manner (using the interactive Python interpreter) and is also ideally suited for researchers not proficient in C++. In addition, our code to wrap a complex C++ library is completely open‐source, allowing other projects to create similar bindings with ease. The pyOpenMS framework is freely available at https://pypi.python.org/pypi/pyopenms while the autowrap tool to create Cython code automatically is available at https://pypi.python.org/pypi/autowrap (both released under the 3‐clause BSD licence).     

The Avian Head Induces Cues for Sound Localization in Elevation

Accurate sound source localization in three-dimensional space is essential for an animal’s orientation and survival. While the horizontal position can be determined by interaural time and intensity differences, localization in elevation was thought to require external structures that modify sound before it reaches the tympanum. Here we show that in birds even without external structures like pinnae or feather ruffs, the simple shape of their head induces sound modifications that depend on the elevation of the source. Based on a model of localization errors, we show that these cues are sufficient to locate sounds in the vertical plane. These results suggest that the head of all birds induces acoustic cues for sound localization in the vertical plane, even in the absence of external ears.