Emotion-Motion Interactions in Conversion Disorder: An fMRI Study

Objectives

To evaluate the neural correlates of implicit processing of negative emotions in motor conversion disorder (CD) patients.

Methods

An event related fMRI task was completed by 12 motor CD patients and 14 matched healthy controls using standardised stimuli of faces with fearful and sad emotional expressions in comparison to faces with neutral expressions. Temporal changes in the sensitivity to stimuli were also modelled and tested in the two groups.

Results

We found increased amygdala activation to negative emotions in CD compared to healthy controls in region of interest analyses, which persisted over time consistent with previous findings using emotional paradigms. Furthermore during whole brain analyses we found significantly increased activation in CD patients in areas involved in the ‘freeze response’ to fear (periaqueductal grey matter), and areas involved in self-awareness and motor control (cingulate gyrus and supplementary motor area).

Conclusions

In contrast to healthy controls, CD patients exhibited increased response amplitude to fearful stimuli over time, suggesting abnormal emotional regulation (failure of habituation / sensitization). Patients with CD also activated midbrain and frontal structures that could reflect an abnormal behavioral-motor response to negative including threatening stimuli. This suggests a mechanism linking emotions to motor dysfunction in CD.     

Beyond patient reported pain: perfusion magnetic resonance imaging demonstrates reproducible cerebral representation of ongoing post-surgical pain

Development of treatments for acute and chronic pain conditions remains a challenge, with an unmet need for improved sensitivity and reproducibility in measuring pain in patients. Here we used pulsed-continuous arterial spin-labelling [pCASL], a relatively novel perfusion magnetic-resonance imaging technique, in conjunction with a commonly-used post-surgical model, to measure changes in regional cerebral blood flow [rCBF] associated with the experience of being in ongoing pain. We demonstrate repeatable, reproducible assessment of ongoing pain that is independent of patient self-report. In a cross-over trial design, 16 participants requiring bilateral removal of lower-jaw third molars underwent pain-free pre-surgical pCASL scans. Following extraction of either left or right tooth, repeat scans were acquired during post-operative ongoing pain. When pain-free following surgical recovery, the pre/post-surgical scanning procedure was repeated for the remaining tooth. Voxelwise statistical comparison of pre and post-surgical scans was performed to reveal rCBF changes representing ongoing pain. In addition, rCBF values in predefined pain and control brain regions were obtained. rCBF increases (5-10%) representing post-surgical ongoing pain were identified bilaterally in a network including primary and secondary somatosensory, insula and cingulate cortices, thalamus, amygdala, hippocampus, midbrain and brainstem (including trigeminal ganglion and principal-sensory nucleus), but not in a control region in visual cortex. rCBF changes were reproducible, with no rCBF differences identified across scans within-session or between post-surgical pain sessions. This is the first report of the cerebral representation of ongoing post-surgical pain without the need for exogenous tracers. Regions of rCBF increases are plausibly associated with pain and the technique is reproducible, providing an attractive proposition for testing interventions for on-going pain that do not rely solely on patient self-report. Our findings have the potential to improve our understanding of the cerebral representation of persistent painful conditions, leading to improved identification of specific patient sub-types and implementation of mechanism-based treatments.     

Predictive modeling for allopatric Strix (Strigiformes: Strigidae) owls in South America: determinants of their distributions and ecological niche‐based processes

Strix (Strigidae) is a worldwide genus of 17 owl species typical of forested habitats, including Rusty‐barred Owls (S. hylophila), Chaco Owls (S. chacoensis), and Rufous‐legged Owls (S. rufipes) in South America. These species are distributed allopatrically, but the ecological traits that determine their distributions remain largely unknown and their phylogenetic relationships are unclear. We used species distribution models (SDMs) to identify variables explaining their distribution patterns and test hypotheses about ecological divergence and conservatism based on niche overlap analysis. For Rusty‐barred Owls and Chaco Owls, climatic factors related to temperature played a major role, whereas a rainfall variable was more important for Rufous‐legged Owls. When niche overlaps were compared, accounting for regional similarities in the habitat available to each species, an ecological niche divergence process was supported for Chaco Owl‐Rusty‐barred Owl and Chaco Owl‐Rufous‐legged Owl, whereas a niche conservatism process was supported for Rusty‐barred Owl‐Rufous‐legged Owl. Different ecological requirements support current species delimitation, but they are in disagreement with the two main hypotheses currently envisaged about their phylogenetic relationships (Chaco Owls as the sister taxa of either Rufous‐legged Owls or Rusty‐barred Owls) and support a new phylogenetic hypothesis (Rufous‐legged Owls as sister taxa of Rusty‐barred Owls). Our findings suggest that speciation of Rusty‐barred Owls and Rufous‐legged Owls was a vicariant event resulting from Atlantic marine transgressions in southern South America in the Miocene, but their niche was conserved because habitat changed little in their respective ranges. In contrast, Chaco Owls diverged ecologically from the other two species as a result of their adaptations to the habitat they currently occupy. Ecological and historical approaches in biogeography can be embedded to explain distribution patterns, and results provided by SDMs can be used to infer historical and ecological processes in an integrative way.     

Improving the Efficiency of Abdominal Aortic Aneurysm Wall Stress Computations

An abdominal aortic aneurysm is a pathological dilation of the abdominal aorta, which carries a high mortality rate if ruptured. The most commonly used surrogate marker of rupture risk is the maximal transverse diameter of the aneurysm. More recent studies suggest that wall stress from models of patient-specific aneurysm geometries extracted, for instance, from computed tomography images may be a more accurate predictor of rupture risk and an important factor in AAA size progression. However, quantification of wall stress is typically computationally intensive and time-consuming, mainly due to the nonlinear mechanical behavior of the abdominal aortic aneurysm walls. These difficulties have limited the potential of computational models in clinical practice. To facilitate computation of wall stresses, we propose to use a linear approach that ensures equilibrium of wall stresses in the aneurysms. This proposed linear model approach is easy to implement and eliminates the burden of nonlinear computations. To assess the accuracy of our proposed approach to compute wall stresses, results from idealized and patient-specific model simulations were compared to those obtained using conventional approaches and to those of a hypothetical, reference abdominal aortic aneurysm model. For the reference model, wall mechanical properties and the initial unloaded and unstressed configuration were assumed to be known, and the resulting wall stresses were used as reference for comparison. Our proposed linear approach accurately approximates wall stresses for varying model geometries and wall material properties. Our findings suggest that the proposed linear approach could be used as an effective, efficient, easy-to-use clinical tool to estimate patient-specific wall stresses.     

Inhibitory effects of gossypol-related compounds on growth of Aspergillus flavus

Aims: The objective of this study was to test a series of gossypol‐related compounds for growth inhibition against Aspergillus flavus. Methods and Results: A series of chiral and achiral gossypol derivatives, some natural products of the cotton plant and others prepared by synthesis from gossypol, were incorporated into agar plates to follow the rate of A. flavus isolate AF13 colony growth. All tested compounds exhibited some growth inhibition against this organism. The synthetic compounds, gossypolone and apogossypolone, exhibited greater activity than either racemic or chiral gossypol. Methylated derivatives (i.e. 6‐methoxy and 6,6′‐dimethoxy derivatives) generally exhibited less activity than the nonmethylated parent compounds. The (?)‐optical form of gossypol was found to be slightly more active than the (+)‐optical form, and this trend was observed regardless of the presence of methoxy groups at the 6‐position. Growth inhibition of gossypolone and apogossypolone was concentration dependent. For gossypolone, the 50% effective dose was 90 μg ml^?1 of medium (165 μmol l^?1). For apogossypolone, the most active compound in the study, the 50% effective dose was 19 μg ml^?1 (38·7 μmol l^?1). The presence of gossypol‐related terpenoids appeared to stimulate production of A. flavus sclerotia, although replicate variability was so large that it was not possible to determine a significant correlation between the mass of sclerotia formed and compound growth inhibition. Conclusions: The quinone derivatives of gossypol, gossypolone and apogossypolone demonstrated significant fungal growth inhibitory activity against A. flavus. Significance and Impact of the Study: These gossypol derivatives may provide a new class of fungicide for use against the mycotoxigenic fungus A. flavus.     

Optimal conditions for primary production in a polymictic tropical lake (Lake Xolotlán,Nicaragua)

From 1987 to 1993 we assessed the variation of phytoplankton biomass, underwater irradiance and primary production in Lake Xolotlán (L. Managua, Nicaragua). Chlorophyll- a averaged 65 mg m-3 and maximum and minimum concentrations were 120 and 30 mg m-3, respectively. The variability over depths and weeks was low (CV < 20%). There were strong correlations between particulate carbon and chlorophyll- a (the ratio ≈ 100: 1) and between particulate carbon and particulate nitrogen and phosphorus (the ratio ≈ 100: 11: 1). Gross primary production averaged 6.8 g C m-2 d- 1 and was stable over the years (CV ≈ 10%). Algal cell growth was approximately 4–5 g C m-2 d- 1. Productivity was limited only by the availability of underwater light and the depth of the photic zone was mainly regulated by the chlorophyll- a concentration. Therefore, areal photic zone chlorophyll- a was the only factor directly correlated to the integral photosynthetic activity but, contrary to theoretical models, the production did not increase in proportion to chlorophyll- a. Data from African lakes show a similar pattern. This revised version was published online in July 2006 with corrections to the Cover Date.     

Coagulation activation in an experimental pneumonia model in malnourished mice

Malnutrition induces a decrease in immunity that affects the ability of the organism to deal with an infectious challenge. The clotting system is considered a branch of immunity and its activation is important in the pathogenesis of an infectious disease. This work was conducted to determine coagulation modifications in malnourished hosts before and during infection. Weaned mice were malnourished via a protein-free diet. Well-nourished control mice (WNC) consumed a balanced conventional diet. Malnourished mice (MN) and WNC were challenged intranasally with Streptococcus pneumoniae. Blood, bronchoalveolar lavages (BAL), and lung samples were taken at different times post infection. The results were that MN showed altered hemostatic tests and fibrin(ogen) deposits in the lung. Thus, an increase in thrombin-antithrombin complexes (TATc) in plasma and BAL was observed. In the MN group, infection induced a rise in TATc in plasma and BAL and increased plasma fibrinogen and fibrin(ogen) deposits in the lung. A decrease in activated protein C and antithrombin in BAL and an early decrease followed by an increase in plasma Factor VIII were also observed. Thus, malnourishment induced a procoagulant state increased by infection. This is the first work that presents results of an exhaustive study of coagulation in malnourished hosts before and during an infection.     

Endonuclease associations with three distinct editosomes in Trypanosoma brucei

Three distinct editosomes, typified by mutually exclusive KREN1, KREN2, or KREN3 endonucleases, are essential for mitochondrial RNA editing in Trypanosoma brucei. The three editosomes differ in substrate endoribonucleolytic cleavage specificity, which may reflect the vast number of editing sites that need insertion or deletion of uridine nucleotides (Us). Each editosome requires the single RNase III domain in each endonuclease for catalysis. Studies reported here show that the editing endonucleases do not form homodimeric domains, and may therefore function as intermolecular heterodimers, perhaps with KREPB4 and/or KREPB5. Editosomes isolated via TAP tag fused to KREPB6, KREPB7, or KREPB8 have a common set of 12 proteins. In addition, KREN3 is only found in KREPB6 editosomes, KREN2 is only found in KREPB7 editosomes, and KREN1 is only found in KREPB8 editosomes. These are the same associations previously found in editosomes isolated via the TAP-tagged endonucleases KREN1, KREN2, or KREN3. Furthermore, TAP-tagged KREPB6, KREPB7, and KREPB8 complexes isolated from cells in which expression of their respective endonuclease were knocked down were disrupted and lacked the heterotrimeric insertion subcomplex (KRET2, KREPA1, and KREL2). These results and published data suggest that KREPB6, KREPB7, and KREPB8 associate with the deletion subcomplex, whereas the KREN1, KREN2, and KREN3 endonucleases associate with the insertion subcomplex.     

Heterotrophic bacterial production in Lake Xolotlán (Managua) during 1988–1989

The biomass and production (thymidine incorporation) of heterotrophic bacterioplankton has been assessed from July, 1988, to October, 1989. in Lake Xolotlán, Nicaraqua. Bacterial abundance was high, 2–3.10¹⁰ cells.l^–1, and bacterial biomass averaged ca. 0.75 mg C.l^–1, or roughly 20% of the partivculate organic carbon. Bactrial production averaged between 3.5–5 g C.l^–1.h^–1 and on a areal basis was 650–959 mg C.m^–2.d^–1 or 13–20% ofthe primary production. Although bacterial production (volumetric basis) was typical for eutrophic lakeks, the bacterial specific growth rate was low, the bacteial population doubling time was ca. 1 week, perhaps indicating that there was a low grazing pressure on the bacteria.