[Treatment expectations of multimodal pain therapy inpatients]. / Behandlungserwartungen bei Patienten einer stationären multimodalen Schmerztherapie.

BACKGROUND: Apart from rehabilitation research, there have been no studies regarding the expectations of patients with chronic back pain in terms of inpatient multimodal pain therapy. The aim of this naturalistic longitudinal study is to explore treatment expectations, their fulfilment, and influence on the treatment success of inpatient multimodal pain therapy. METHODS: This study included 118 patients with chronic back pain who were physically examined and assessed for their psychological comorbidity. They were interviewed pre and post pain therapy. Treatment expectations were recorded via the questionnaire for assessing rehabilitational expectations and motivations (FREM-17), and further variables via the Pain Disability Index (PDI, german version) and the german Hospital Anxiety and Depression Scale (HADS-D). RESULTS: The results show that treatment expectations have an impact on therapy success or failure. In particular, patients' expectations of coping with illness and recovery could be met by inpatient multimodal pain therapy, whereas health and pension-related expectations remained unfulfilled. In addition to the treatment expectations, the therapy result was primarily determined by the patient's ability to perform before the therapy. CONCLUSIONS: From the clinical side, treatment expectations should be explored and checked for feasibility to avoid patient disappointment.

A FeFET with a novel MFMFIS gate stack: towards energy-efficient and ultrafast NVMs for neuromorphic computing.

The discovery of ferroelectricity in the fluorite structure based hafnium oxide (HfO2) material sparked major efforts for reviving the ferroelectric field effect transistor (FeFET) memory concept. A Novel metal-ferroelectric-metal-ferroelectric-insulator-semiconductor (MFMFIS) FeFET memory is reported based on dual ferroelectric integration as an MFM and MFIS in a single gate stack using Si-doped Hafnium oxide (HSO) ferroelectric (FE) material. The MFMFIS top and bottom electrode contacts, dual HSO based ferroelectric layers, and tailored MFM to MFIS area ratio (AR-TB) provide a flexible stack structure tuning for improving the FeFET performance. The AR-TB tuning shows a tradeoff between the MFM voltage increase and the weaker FET Si channel inversion, particularly notable in the drain saturation currentID(sat)when the AR-TB ratio decreases. Dual HSO ferroelectric layer integration enables a maximized memory window (MW) and dynamic control of its size by tuning the MFM to MFIS switching contribution through the AR-TB change. The stack structure control via the AR-TB tuning shows further merits in terms of a low voltage switching for a saturated MW size, an extremely linear at wide dynamic range of the current update, as well as high symmetry in the long term synaptic potentiation and depression. The MFMFIS stack reliability is reported in terms of the switching variability, temperature dependence, endurance, and retention. The MFMFIS concept is thoroughly discussed revealing profound insights on the optimal MFMFIS stack structure control for enhancing the FeFET memory performance.

Low-Magnetic-Field Regime of a Gate-Defined Constriction in High-Mobility Graphene.

We report on the evolution of the coherent electronic transport through a gate-defined constriction in a high-mobility graphene device from ballistic transport to quantum Hall regime upon increasing the magnetic field. At a low field, the conductance exhibits Fabry-Pérot resonances resulting from the npn cavities formed beneath the top-gated regions. Above a critical field B* corresponding to the cyclotron radius equal to the npn cavity length, Fabry-Pérot resonances vanish, and snake trajectories are guided through the constriction with a characteristic set of conductance oscillations. Increasing further the magnetic field allows us to probe the Landau level spectrum in the constriction and unveil distortions due to the combination of confinement and deconfinement of Landau levels in a saddle potential. These observations are confirmed by numerical calculations.

Abrogation of Gap Junctional Communication in ES Cells Results in a Disruption of Primitive Endoderm Formation in Embryoid Bodies.

Gap junctional intercellular communication (GJIC) has been suggested to be involved in early embryonic development but the actual functional role remained elusive. Connexin (Cx) 43 and Cx45 are co-expressed in embryonic stem (ES) cells, form gap junctions and are considered to exhibit adhesive function and/or to contribute to the establishment of defined communication compartments. Here, we describe the generation of Cx43/Cx45-double deficient mouse ES cells to achieve almost complete breakdown of GJIC. Cre-loxP induced deletion of both, Cx43 and Cx45, results in a block of differentiation in embryoid bodies (EBs) without affecting pluripotency marker expression and proliferation in ES cells. We demonstrate that GJIC-incompetent ES cells fail to form primitive endoderm in EB cultures, representing the inductive key step of further differentiation events. Lentiviral overexpression of either Cx43 or Cx45 in Cx43/45 mutants rescued the observed phenotype, confirming the specificity and indicating a partially redundant function of both connexins. Upon differentiation GJIC-incompetent ES cells exhibit a strikingly altered subcellular localization pattern of the transcription factor NFATc3. Control EBs exhibit significantly more activated NFATc3 in cellular nuclei than mutant EBs suggesting that Cx-mediated communication is needed for synchronized NFAT activation to induce orchestrated primitive endoderm formation. Moreover, pharmacological inhibition of NFATc3 activation by Cyclosporin A, a well-described inhibitor of calcineurin, phenocopies the loss of GJIC in control cells. Stem Cells 2017;35:859-871.

Efficient and graded gene expression in glia and neurons of primary cerebellar cultures transduced by lentiviral vectors.

Lentiviral vectors are valuable tools to express genes of interest in living animals and stem cell cultures. The use of promoters in lentiviral constructs has been successfully used to drive gene expression in particular cell types including neurons and glia of the central nervous system in vivo. However, their suitability in cell culture is less well documented. In this paper, we describe lentiviral vectors containing neuronal promoters of the murine stem cell virus, of the synapsin 1 gene, the tubulin alpha 1 gene, and the calmodulin kinase II gene, and the glial promoter of the glial fibrillary acidic protein gene to drive reporter gene expression in primary dissociated cerebellar cell cultures and in slice cultures. While the glial promoter was highly specific for glia, the neuronal promoters were active in neurons and glia of dissociated cultures to a comparable extent. In slice cultures, neuronal and glial promoters demonstrated higher, but not absolute selectivity for particular cell types. In addition, the promoters allowed for an efficient and graded expression of genes in dissociated cultures. By using selected combinations of vectors, it was also possible to drive the expression of two genes in one cell type with high efficiency. A gene of interest in combination with a reporter gene can thus be expressed in a graded manner to reveal gene function in a rather short time and in a complex cellular environment.

Experimental TLR4 inhibition improves intestinal microcirculation in endotoxemic rats.

INTRODUCTION: Toll like receptor 4 (TLR4) represents a critical cellular link for endotoxin-induced pathology. The aim of this study was to evaluate the potential role of TLR4 inhibition on the intestinal microcirculation during experimental endotoxemia. MATERIALS AND METHODS: The intestinal microcirculation was studied by intravital microscopy in four groups of Lewis rats (n=10 per group): healthy controls (CON group), endotoxemic animals (15mg/kg lipopolysaccharide, LPS group), endotoxemic animals treated with a TLR4 antagonist (1mg/kg CRX-526, LPS+CRX526 group), and controls treated with CRX-526 (C-CRX526 group). Plasma samples were obtained for cytokine measurements at the end of the experiments. RESULTS: Endotoxemia significantly increased leukocyte adhesion in intestinal submucosal venules (e.g., V1 venules: CON 20.4±6.5n/mm(2), LPS 237.5±36.2n/mm(2), p<0.05) and reduced capillary perfusion of the intestinal wall (e.g., longitudinal muscular layer: CON 112.5±5.9cm/cm(2), LPS 71.3±11.0cm/cm(2), p<0.05) at 2h. TLR4 inhibition significantly reduced endotoxemia-associated leukocyte adhesion (V1 venules: 104.3±7.8n/mm(2)) and improved capillary perfusion (longitudinal muscular layer: 111.0±12.3cm/cm(2)). Cytokine release was not significantly affected. CONCLUSIONS: The TLR4 pathway may be a target in clinical Gram-negative sepsis since administration of the TLR4 antagonist CRX-526 improved intestinal microcirculation parameters in experimental endotoxemia.

A functional variant in the 5'-flanking region of the chicken serotonin transporter gene is associated with increased body weight and locomotor activity.

In this study, we identified a polymorphism in the 5'-flanking region of the chicken serotonin transporter (5-HTT) gene. Sequencing analysis revealed that in comparison with the wild-type variant (W), a deleted variant (D) is generated by deletion of four nucleotides (5'-AATT-3') and a single nucleotide change (A→T). Using a polyacrylamide gel electrophoresis system, we found that the 360-bp DNA fragment containing the W variant with the wild-type sequence 5'-AATTAATT-3' shows intrinsic DNA curvature while the 356-bp fragment containing the D variant lacking the four base pairs AATT is not curved. Quantitative real-time RT-PCR and ELISA demonstrated that the expression of 5-HTT in D/D chickens was higher than that in W/W and W/D chickens. In addition, transient transfection experiments with chloramphenicol acetyltransferase reporter gene constructs revealed increased 5-HTT promoter activity mediated by the D variant and a silencer activity of the W variant. Interestingly, females and males with D/D genotype showed significant greater increase in body weight from 6 weeks and 16 weeks of age, respectively, and higher body mass index. Moreover, we found that D/D chickens of both genders were physically more active than W/W and W/D chickens.

FOXO4-dependent upregulation of superoxide dismutase-2 in response to oxidative stress is impaired in spinocerebellar ataxia type 3.

Ataxin-3 (ATXN3), the disease protein in spinocerebellar ataxia type 3 (SCA3), binds to target gene promoters and modulates transcription by interaction with transcriptional regulators. Here, we show that ATXN3 interacts with the forkhead box O (FOXO) transcription factor FOXO4 and activates the FOXO4-dependent transcription of the manganese superoxide dismutase (SOD2) gene. Upon oxidative stress, ATXN3 and FOXO4 translocate to the nucleus, concomitantly bind to the SOD2 gene promoter and increase the expression of the antioxidant enzyme SOD2. Compared with normal ATXN3, mutant ATXN3 has a reduced capability to activate the FOXO4-mediated SOD2 expression and interferes with binding of FOXO4 to the SOD2 gene promoter. These findings are consistent with a downregulation of SOD2 in pontine brain tissue and lymphoblastoid cell (LC) lines of SCA3 patients. In response to oxidative stress, LCs from SCA3 patients show a specific impairment to upregulate SOD2 expression in correlation with a significantly increased formation of reactive oxygen species and cytotoxicity. The impairment to increase the expression of SOD2 under oxidative stress conditions is associated with a significantly reduced binding of FOXO4 to the SOD2 gene promoter in SCA3-LCs. Finally and consistent with a regulatory role of ATXN3 in SOD2 expression, knockdown of endogenous ATXN3 by RNA interference represses the expression of SOD2. These findings support that ATXN3 plays an important role in regulating the FOXO4-dependent antioxidant stress response via SOD2 and suggest that a decreased antioxidative capacity and increased susceptibility towards oxidative stress contributes to neuronal cell death in SCA3.

KIAA1797/FOCAD encodes a novel focal adhesion protein with tumour suppressor function in gliomas.

In a strategy to identify novel genes involved in glioma pathogenesis by molecular characterization of chromosomal translocation breakpoints, we identified the KIAA1797 gene, encoding a protein with an as yet undefined function, to be disrupted by a 7;9 translocation in a primary glioblastoma culture. Array-based comparative genomic hybridization detected deletions involving KIAA1797 in around half of glioblastoma cell lines and glioblastomas investigated. Quantification of messenger RNA levels in human tissues demonstrated highest KIAA1797 expression in brain, reduced levels in all glioblastoma cell lines and most glioblastomas and similar levels in glial and neuronal cells by analysis of different hippocampal regions from murine brain. Antibodies against KIAA1797 were generated and showed similar protein levels in cortex and subcortical white matter of human brain, while levels were significantly reduced in glioblastomas with KIAA1797 deletion. By immunofluorescence of astrocytoma cells, KIAA1797 co-localized with vinculin in focal adhesions. Physical interaction between KIAA1797 and vinculin was demonstrated via co-immunoprecipitation. Functional in vitro assays demonstrated a significant decrease in colony formation, migration and invasion capacity of LN18 and U87MG glioma cells carrying a homozygous KIAA1797 deletion ectopically expressing KIAA1797 compared with mock-transduced cells. In an in vivo orthotopic xenograft mouse model, U87MG tumour lesions expressing KIAA1797 had a significantly reduced volume compared to tumours not expressing KIAA1797. In summary, the frequently deleted KIAA1797 gene encodes a novel focal adhesion complex protein with tumour suppressor function in gliomas, which we name 'focadhesin'. Since KIAA1797 genetic variation has been implicated in Alzheimer's disease, our data are also relevant for neurodegeneration.

Analysis of trajectories for targeting of magnetic nanoparticles in blood vessels.

The technique of magnetic drug targeting deals with binding drugs or genetic material to superparamagnetic nanoparticles and accumulating these complexes via an external magnetic field in a target region. For a successful approach, it is necessary to know the required magnetic setup as well as the physical properties of the complexes. With the help of computational methods, the complex accumulation and behavior can be predicted. We present a model for vascular targeting with a full three-dimensional analysis of the magnetic and fluidic forces and a subsequent evaluation of the resulting trajectories of the complexes. These trajectories were calculated with respect to the physiological boundary conditions, the magnetic properties of both the external field and the particles as well as the hydrodynamics of the fluid. We paid special regard to modeling input parameters like flow velocity as well as the distribution functions of the hydrodynamic size and magnetic moment of the nanoparticle complexes. We are able to estimate the amount of complexes, as well as the spatial distribution of those complexes. Additionally, we examine the development of the trapping rate for multiple passages of the complexes and compare the influence of several input parameters. Finally, we provide experimental data of an ex vivo flow-loop system which serves as a model for large vessel targeting. In this model, we achieve a deposition of lentivirus/magnetic nanoparticle complexes in a murine aorta and compare our simulation with the experimental results gained by a non-heme-iron assay.

Identification of magnetic nanoparticles for combined positioning and lentiviral transduction of endothelial cells.

PURPOSE: The combination of magnetic nanoparticles (MNPs) with a magnetic field is a powerful approach to enable cell positioning and/or local gene therapy. Because physical requirements for MNPs differ between these two applications we have explored whether the use of different MNPs can provide site-specific positioning combined with efficient viral transduction of endothelial cells (ECs). METHODS: A variety of MNPs was screened for magnetic cell labeling and lentivirus binding. Then two different MNPs were chosen and their combined application was evaluated regarding EC magnetization and transduction efficiency. RESULTS: The combined use of PEI-Mag2 and NDT-Mag1 particles provided both efficient lentiviral transduction and high magnetic responsiveness of ECs that could be even retained within the vascular wall under flow conditions. The use of these MNPs did not affect biological characteristics of ECs like surface marker expression and vascular network formation. Importantly, with this method we could achieve an efficient functional overexpression of endothelial nitric oxide synthase in ECs. CONCLUSIONS: The application of two different MNPs provides optimal results for magnetic labeling of ECs in combination with viral transduction. This novel approach could be very useful for targeted gene therapy ex vivo and site-specific cell replacement in the vascular system.

Optimization of magnetic nanoparticle-assisted lentiviral gene transfer.

PURPOSE: Targeting of specific cells and tissues is of great interest for clinical relevant gene- and cell-based therapies. We use magnetic nanoparticles (MNPs) with a ferrimagnetic core (Fe(3)O(4)) with different coatings to optimize MNP-assisted lentiviral gene transfer with focus on different endothelial cell lines. METHODS: Lentiviral vector (LV)/MNP binding was characterized for various MNPs by different methods (e.g. magnetic responsiveness measurement). Transduced cells were analyzed by flow cytometry, fluorescence microscopy and iron recovery. Cell transduction and cell positioning under physiological flow conditions were performed using different in vitro and ex vivo systems. RESULTS: Analysis of diverse MNPs with different coatings resulted in identification of nanoparticles with improved LV association and enhanced transduction properties of complexes in several endothelial cell lines. The magnetic moments of LV/MNP complexes are high enough to achieve local gene targeting of perfused endothelial cells. Perfusion of a mouse aorta with LV/MNP transduced cells under clinically relevant flow conditions led to local cell attachment at the intima of the vessel. CONCLUSION: MNP-guided lentiviral transduction of endothelial cells can be significantly enhanced and localized by using optimized MNPs.

Targeted endothelial gene delivery by ultrasonic destruction of magnetic microbubbles carrying lentiviral vectors.

PURPOSE: Site specific vascular gene delivery is a promising tool for treatment of cardiovascular diseases. By combining ultrasound mediated microbubble destruction with site specific magnetic targeting of lentiviruses, we aimed to develop a technique suitable for systemic application. METHODS: The magnetic nanoparticle coupling to lipid microbubbles was confirmed by absorbance measurements. Association of fluorescent lentivirus to magnetic microbubbles (MMB) was determined by microscopy and flow cytometry. Functionality and efficiency of GFP-encoding lentiviral MMB transduction was evaluated by endothelial (HMEC) GFP expression and cytotoxicity was measured by MTT reduction. RESULTS: Microbubbles with a mean diameter of 4.3 ± 0.04 µm were stable for 2 days, readily magnetizable and magnetically steerable in vitro and efficiently associated with lentivirus. Exposure of eGFP-encoding lentiviral MMB to human endothelial cells followed by application of an external static magnetic field (30 min) and ultrasonic destruction of the microbubbles did not markedly affect cellular viability. Finally, this combination led to a 30-fold increase in transduction efficiency compared to application of naked virus alone. CONCLUSIONS: By associating microbubbles with magnetic iron nanoparticles, these function as carriers for lentiviruses achieving tissue specific deposition at the site of interest.

Combined targeting of lentiviral vectors and positioning of transduced cells by magnetic nanoparticles.

Targeting of viral vectors is a major challenge for in vivo gene delivery, especially after intravascular application. In addition, targeting of the endothelium itself would be of importance for gene-based therapies of vascular disease. Here, we used magnetic nanoparticles (MNPs) to combine cell transduction and positioning in the vascular system under clinically relevant, nonpermissive conditions, including hydrodynamic forces and hypothermia. The use of MNPs enhanced transduction efficiency of endothelial cells and enabled direct endothelial targeting of lentiviral vectors (LVs) by magnetic force, even in perfused vessels. In addition, application of external magnetic fields to mice significantly changed LV/MNP biodistribution in vivo. LV/MNP-transduced cells exhibited superparamagnetic behavior as measured by magnetorelaxometry, and they were efficiently retained by magnetic fields. The magnetic interactions were strong enough to position MNP-containing endothelial cells at the intima of vessels under physiological flow conditions. Importantly, magnetic positioning of MNP-labeled cells was also achieved in vivo in an injury model of the mouse carotid artery. Intravascular gene targeting can be combined with positioning of the transduced cells via nanomagnetic particles, thereby combining gene- and cell-based therapies.

Highly efficient concentration of lenti- and retroviral vector preparations by membrane adsorbers and ultrafiltration.

BACKGROUND: Lentiviral vectors (LVs) can efficiently transduce a broad spectrum of cells and tissues, including dividing and non-dividing cells. So far the most widely used method for concentration of lentiviral particles is ultracentrifugation (UC).An important feature of vectors derived from lentiviruses and prototypic gamma-retroviruses is that the host range can be altered by pseudotypisation. The most commonly used envelope protein for pseudotyping is the glycoprotein of the Vesicular Stomatitis Virus (VSV.G), which is also essential for successful concentration using UC. RESULTS: Here, we describe a purification method that is based on membrane adsorbers (MAs). Viral particles are efficiently retained by the anionic exchange MAs and can be eluted with a high-salt buffer. Buffer exchange and concentration is then performed by utilizing ultrafiltration (UF) units of distinct molecular weight cut off (MWCO). With this combined approach similar biological titers as UC can be achieved (2 to 5×109 infectious particles (IP)/ml). Lentiviral particles from small starting volumes (e.g. 40 ml) as well as large volumes (up to 1,000 ml) cell culture supernatant (SN) can be purified. Apart from LVs, vectors derived from oncoretroviruses can be efficiently concentrated as well. Importantly, the use of the system is not confined to VSV.G pseudotyped lenti- and retroviral particles and other pseudotypes can also be purified. CONCLUSIONS: Taken together the method presented here offers an efficient alternative for the concentration of lenti- as well as retroviral vectors with different pseudotypes that needs no expensive equipment, is easy to handle and can be used to purify large quantities of viral vectors within a short time.

Evidence for an intracellular localization of the adenosine A2B receptor in rat cardiomyocytes.

Protection achieved by ischemic preconditioning is dependent on A(2B) adenosine receptors (A(2B)AR) in rabbit and mouse hearts and, predictably, an A(2B)AR agonist protects them. But it is controversial whether cardiomyocytes themselves actually express A(2B)AR. The present study tested whether A(2B)AR could be demonstrated on rat cardiomyocytes. Isolated rat hearts experienced 30 min of ischemia and 120 min of reperfusion. The highly selective, cell-permeant A(2B)AR agonist BAY60-6583 (500 nM) infused at reperfusion reduced infarct size from 40.4 ± 2.0% of the risk zone in control hearts to 19.9 ± 2.8% indicating that A(2B)AR are protective in rat heart as well. Furthermore, BAY60-6583 reduced calcium-induced mitochondrial permeability transition in isolated rat cardiomyocytes. A(2B)AR protein could be demonstrated in isolated cardiomyocytes by western blotting. In addition, message for A(2B)AR was found in individual cardiomyocytes using quantitative RT-PCR. Surprisingly, immunofluorescence microscopy did not show A(2B)AR on the cardiomyocyte's sarcolemma but rather at intracellular sites. Co-staining with MitoTracker Red in isolated cardiomyocytes revealed A(2B)AR are localized to mitochondria. Western blot analysis of a mitochondrial fraction from either rat heart biopsies or isolated cardiomyocytes revealed a strong A(2B)AR band. Thus, the present study demonstrates that activation of A(2B)AR is strongly cardioprotective in rat heart and suppresses transition pores in isolated cardiomyocytes, and A(2B)AR are expressed in individual cardiomyocytes. However, surprisingly, A(2B)AR are present in or near mitochondria rather than on the sarcolemma as are other adenosine receptors. Because A(2B)AR signaling is thought to result in inhibition of mitochondrial transition pores, this convenient location may be important.

Regional spread of HIV-1 M subtype B in middle-aged patients by random env-C2V4 region sequencing.

A transmission cluster of HIV-1 M:B was identified in 11 patients with a median age of 52 (range 26-65) in North-East Germany by C2V4 region sequencing of the env gene of HIV-1, who-except of one-were not aware of any risky behaviour. The 10 male and 1 female patients deteriorated immunologically, according to their information made available, within 4 years after a putative HIV acquisition. Nucleic acid sequence analysis showed a R5 virus in all patients and in 7 of 11 a crown motif of the V3 loop, GPGSALFTT, which is found rarely. Analysis of formation of this cluster showed that there is still a huge discrepancy between awareness and behaviour regarding HIV transmission in middle-aged patients, and that a local outbreak can be detected by nucleic acid analysis of the hypervariable env region.

[Psychological and physical well-being of cardiological outpatients with chest pain]. / Psychische und physische Befindlichkeit von Patienten mit Thoraxschmerzen in der kardiologischen Ambulanz.

OBJECTIVES: The aim of this cross-sectional study was to explore the psychological and physical well-being of patients with chest pain depending on availability cardiological disease (coronary heart disease, different cardiological disease, no cardiological disease, unclear diagnose). METHODS: In a total of 383 cardiological outpatients, anxiety and depression (HADS) as well as physical complaints (B-L) were assessed. RESULTS: For half of the outpatients, no cardiological diagnose was found that explained the symptoms of chest pain. In comparison to the general population, outpatients with various cardiological symptoms exhibited a lower psychological and physical well-being independent of availability cardiological disease. 50.9% of the outpatients showed elevated anxiety scores, 35.2% showed elevated depression scores and 71.7% felt impaired by physical complaints. In comparison to males, females were more anxious and exhibited a lower physical well-being. In general, physical impairment increased with age, while anxiety decreased. CONCLUSIONS: The present study discovered a very high psychological comorbidity in cardiological outpatients with chest pain that underlines the necessity of an integrated psychosomatic care regardless of clinical finding. In order to understand the symptom of chest pain it is not indicated to differentiate between cardiologically vs. psychologically ill patients.

Pederin-type pathways of uncultivated bacterial symbionts: analysis of o-methyltransferases and generation of a biosynthetic hybrid.

The complex polyketide pederin is a potent antitumor agent isolated from Paederus spp. rove beetles. We have previously isolated a set of genes from a bacterial endosymbiont that are good candidates for pederin biosynthesis. To biochemically study this pathway, we expressed three methyltransferases from the putative pederin pathway and used the partially unmethylated analogue mycalamide A from the marine sponge Mycale hentscheli as test substrate. Analysis by high-resolution MS/MS and NMR revealed that PedO regiospecifically methylates the marine compound to generate the nonnatural hybrid compound 18-O-methylmycalamide A with increased cytotoxicity. To our knowledge, this is the first biochemical evidence that invertebrates can obtain defensive complex polyketides from bacterial symbionts.

Heart-focused anxiety before and after cardiac surgery.

OBJECTIVE: We investigated the degree and course of heart-focused anxiety (HFA) in patients with cardiac diseases before and after cardiac surgery. METHODS: We examined 90 patients undergoing coronary bypass, valve replacement, or combined surgery before surgery, 6 weeks after surgery, and 6 months after surgery. Patients completed the Cardiac Anxiety Questionnaire (CAQ), which assesses heart-focused fear, attention, and avoidance, and a set of other questionnaires assessing general anxiety, depression, and quality of life. Data were compared with an age- and sex-controlled contrast group of 72 orthopedic patients with no history of cardiac disease. RESULTS: All dimensions of HFA were elevated in patients before surgery. CAQ-Fear was significantly reduced 6 weeks after surgery and at 6-month follow-up. CAQ-Avoidance was stable after surgery but declined on follow-up, while there was only a statistical tendency indicating reduction in CAQ-Attention. Approximately 20% of patients continued to experience clinically elevated levels of HFA at 6-month follow-up. Furthermore, we found decreases in global anxiety and depression, and an increase in quality of life after surgery. CONCLUSIONS: In contrast to global psychosocial indicators, the more specific assessment of HFA may help identify individuals with elevated levels of HFA who might benefit from interventions to help them adjust to the effects of surgery and lingering cardiac problems.