The Emotional and Attentional Impact of Exposure to One's Own Body in Bulimia Nervosa: A Physiological View

Background: Body dissatisfaction is the most relevant body image disturbance in bulimia nervosa (BN). Research has shown that viewing one's own body evokes negative thoughts and emotions in individuals with BN. However, the psychophysiological mechanisms involved in this negative reaction have not yet been clearly established. Our aim was to examine the emotional and attentional processes that are activated when patients with BN view their own bodies. Method: We examined the effects of viewing a video of one's own body on the physiological (eye-blink startle, cardiac defense, and skin conductance) and subjective (pleasure, arousal, and control ratings) responses elicited by a burst of 110 dB white noise of 500 ms duration. The participants were 30 women with BN and 30 healthy control women. The experimental task consisted of two consecutive and counterbalanced presentations of the auditory stimulus preceded, alternatively, by a video of the participant's own body versus no such video. Results: The results showed that, when viewing their own bodies, women with BN experienced (a) greater inhibition of the startle reflex, (b) greater cardiac acceleration in the first component of the defense reaction, (c) greater skin conductance response, and (d) less subjective pleasure and control combined with greater arousal, compared with the control participants. Conclusion: Our findings suggest that, for women with BN, peripheral-physiological responses to self-images are dominated by attentional processes, which provoke an immobility reaction caused by a dysfunctional negative response to their own body.The present research was supported by grants from the Spanish Ministry of Economy and Competitiveness [PSI2009-08417 and PSI2012-31395]. P.P. was supported by grants from the Spanish Ministry of Science and Innovation and University Jaume I [ECO2011-23634, P1-1B2012-27, and JCI-2010-06790]

Treatment options in end-stage heart failure: where to go from here?

Chronic heart failure is a major healthcare problem associated with high morbidity and mortality. Despite significant progress in treatment strategies, the prognosis of heart failure patients remains poor. The golden standard treatment for heart failure is heart transplantation after failure of medical therapy, surgery and/or cardiac resynchronisation therapy. In order to improve patients’ outcome and quality of life, new emerging treatment modalities are currently being investigated, including mechanical cardiac support devices, of which the left ventricular assist device is the most promising treatment option. Structured care for heart failure patients according to the most recent international heart failure guidelines may further contribute to optimal decision-making. This article will review the conventional and novel treatment modalities of heart failure

Biologically induced mineralization of dypingite by cyanobacteria from an alkaline wetland near Atlin, British Columbia, Canada

Background: This study provides experimental evidence for biologically induced precipitation of magnesium carbonates, specifically dypingite (Mg(CO)(OH) ·5HO), by cyanobacteria from an alkaline wetland near Atlin, British Columbia. This wetland is part of a larger hydromagnesite (Mg(CO)(OH) ·4HO) playa. Abiotic and biotic processes for magnesium carbonate precipitation in this environment are compared. Results: Field observations show that evaporation of wetland water produces carbonate films of nesquehonite (MgCO ·3HO) on the water surface and crusts on exposed surfaces. In contrast, benthic microbial mats possessing filamentous cyanobacteria (Lyngbya sp.) contain platy dypingite (Mg (CO)4(OH)·5HO) and aragonite. Bulk carbonates in the benthic mats (δC avg. = 6.7%, δO avg. = 17.2%) were isotopically distinguishable from abiotically formed nesquehonite (δC avg. = 9.3%, δO avg. = 24.9%). Field and laboratory experiments, which emulated natural conditions, were conducted to provide insight into the processes for magnesium carbonate precipitation in this environment. Field microcosm experiments included an abiotic control and two microbial systems, one containing ambient wetland water and one amended with nutrients to simulate eutrophic conditions. The abiotic control developed an extensive crust of nesquehonite on its bottom surface during which [Mg] decreased by 16.7% relative to the starting concentration. In the microbial systems, precipitation occurred within the mats and was not simply due to the capturing of mineral grains settling out of the water column. Magnesium concentrations decreased by 22.2% and 38.7% in the microbial systems, respectively. Laboratory experiments using natural waters from the Atlin site produced rosettes and flakey globular aggregates of dypingite precipitated in association with filamentous cyanobacteria dominated biofilms cultured from the site, whereas the abiotic control again precipitated nesquehonite. Conclusion: Microbial mats in the Atlin wetland create ideal conditions for biologically induced precipitation of dypingite and have presumably played a significant role in the development of this natural Mg-carbonate playa. This biogeochemical process represents an important link between the biosphere and the inorganic carbon pool

A Density-Dependent Switch Drives Stochastic Clustering and Polarization of Signaling Molecules

Positive feedback plays a key role in the ability of signaling molecules to form highly localized clusters in the membrane or cytosol of cells. Such clustering can occur in the absence of localizing mechanisms such as pre-existing spatial cues, diffusional barriers, or molecular cross-linking. What prevents positive feedback from amplifying inevitable biological noise when an un-clustered “off” state is desired? And, what limits the spread of clusters when an “on” state is desired? Here, we show that a minimal positive feedback circuit provides the general principle for both suppressing and amplifying noise: below a critical density of signaling molecules, clustering switches off; above this threshold, highly localized clusters are recurrently generated. Clustering occurs only in the stochastic regime, suggesting that finite sizes of molecular populations cannot be ignored in signal transduction networks. The emergence of a dominant cluster for finite numbers of molecules is partly a phenomenon of random sampling, analogous to the fixation or loss of neutral mutations in finite populations. We refer to our model as the “neutral drift polarity model.” Regulating the density of signaling molecules provides a simple mechanism for a positive feedback circuit to robustly switch between clustered and un-clustered states. The intrinsic ability of positive feedback both to create and suppress clustering is a general mechanism that could operate within diverse biological networks to create dynamic spatial organization

The Making of a Monster: Postnatal Ontogenetic Changes in Craniomandibular Shape in the Great Sabercat Smilodon

Derived sabercats had craniomandibular morphologies that in many respects were highly different from those of extant felids, and this has often been interpreted functionally as adaptations for predation at extreme gape angles with hypertrophied upper canines. It is unknown how much of this was a result of intraspecific postnatal ontogeny, since juveniles of sabercats are rare and no quantitative study has been made of craniomandibular ontogeny. Postnatal ontogenetic craniomandibular shape changes in two morphologically derived sabercats, Smilodon fatalis and S. populator, were analysed using geometric morphometrics and compared to three species of extant pantherines, the jaguar, tiger, and Sunda clouded leopard. Ontogenetic shape changes in Smilodon usually involved the same areas of the cranium and mandible as in extant pantherines, and large-scale modularization was similar, suggesting that such may have been the case for all felids, since it followed the same trends previously observed in other mammals. However, in other respects Smilodon differed from extant pantherines. Their crania underwent much greater and more localised ontogenetic shape changes than did the mandibles, whereas crania and mandibles of extant pantherines underwent smaller, fewer and less localised shape changes. Ontogenetic shape changes in the two species of Smilodon are largely similar, but differences are also present, notably those which may be tied to the presence of larger upper canines in S. populator. Several of the specialized cranial characters differentiating adult Smilodon from extant felids in a functional context, which are usually regarded as evolutionary adaptations for achieving high gape angles, are ontogenetic, and in several instances ontogeny appears to recapitulate phylogeny to some extent. No such ontogenetic evolutionary adaptive changes were found in the extant pantherines. Evolution in morphologically derived sabercats involved greater cranial ontogenetic changes than among extant felids, resulting in greatly modified adult craniomandibular morphologies

Alteration of proliferation and apoptotic markers in normal and premalignant tissue associated with prostate cancer

BACKGROUND: Molecular markers identifying alterations in proliferation and apoptotic pathways could be particularly important in characterizing high-risk normal or pre-neoplastic tissue. We evaluated the following markers: Ki67, Minichromosome Maintenance Protein-2 (Mcm-2), activated caspase-3 (a-casp3) and Bcl-2 to determine if they showed differential expression across progressive degrees of intraepithelial neoplasia and cancer in the prostate. To identify field effects, we also evaluated whether high-risk expression patterns in normal tissue were more common in prostates containing cancer compared to those without cancer (supernormal), and in histologically normal glands adjacent to a cancer focus as opposed to equivalent glands that were more distant. METHODS: The aforementioned markers were studied in 13 radical prostatectomy (RP) and 6 cystoprostatectomy (CP) specimens. Tissue compartments representing normal, low grade prostatic intraepithelial neoplasia (LGPIN), high grade prostatic intraepithelial neoplasia (HGPIN), as well as different grades of cancer were mapped on H&E slides and adjacent sections were analyzed using immunohistochemistry. Normal glands within 1 mm distance of a tumor focus and glands beyond 5 mm were considered "near" and "far", respectively. Randomly selected nuclei and 40 × fields were scored by a single observer; basal and luminal epithelial layers were scored separately. RESULTS: Both Ki-67 and Mcm-2 showed an upward trend from normal tissue through HGPIN and cancer with a shift in proliferation from basal to luminal compartment. Activated caspase-3 showed a significant decrease in HGPIN and cancer compartments. Supernormal glands had significantly lower proliferation indices and higher a-casp3 expression compared to normal glands. "Near" normal glands had higher Mcm-2 indices compared to "far" glands; however, they also had higher a-casp3 expression. Bcl-2, which varied minimally in normal tissue, did not show any trend across compartments or evidence for field effects. CONCLUSION: These results demonstrate that proliferation and apoptosis are altered not only in preneoplastic lesions but also in apparently normal looking epithelium associated with cancer. Luminal cell expression of Mcm-2 appears to be particularly promising as a marker of high-risk normal epithelium. The role of apoptotic markers such as activated caspase-3 is more complex, and might depend on the proliferation status of the tissue in question

Atypical ductal hyperplasia is a multipotent precursor of breast carcinoma

The current model for breast cancer progression proposes independent “low‐grade (LG) like” and “high‐grade (HG) like” pathways but lacks a known precursor to HG cancer. We applied low coverage whole genome sequencing to atypical ductal hyperplasia (ADH) with and without carcinoma to shed light on breast cancer progression. 14/20 isolated ADH cases harboured at least one copy number alteration (CNA), but had fewer aberrations than LG or HG ductal carcinoma in situ (DCIS). ADH carried more HG‐like CNA than LG DCIS (eg. 8q gain). Correspondingly, 64% (7/11) of ADH cases with synchronous HG carcinoma were clonally related, similar to LG carcinoma (67%, 6/9). This study represents a significant shift in our understanding of breast cancer progression, with ADH as a common precursor lesion to the independent “low‐grade like” and “high‐grade like” pathways. These data suggest that ADH can be a precursor of HG breast cancer and that LG and HG carcinomas can evolve from a similar ancestor lesion. We propose that although LG DCIS may be committed to a LG molecular pathway, ADH may remain multipotent, progressing to either LG or HG carcinoma. This multipotent nature suggests that some ADH could be more clinically significant than LG DCIS, requiring biomarkers for personalising management