Neuroendocrine carcinoma arising in soft tissue: three case reports and literature review

<p>Abstract</p> <p>Background</p> <p>Neuroendocrine tumours (NET) are tumours arising from neuroendocrine cells of neural crest origin. They are characterised by the presence of neurosecretory granules which react positively to silver stains and to specific markers including neuron specific enolase, synaptophysin and chromogranin. Metastasis to the skin occurs infrequently but primary soft tissue NET is excessively rare.</p> <p>Case presentation</p> <p>We report our experience with 3 such cases. In the first case, the NET originated in muscle and was treated with wide surgical excision and adjuvant radiotherapy. The second case presented as a subcutaneous mass in the foot and the tumour was positive on ¹²³I mIBG scan. She has had prolonged recurrence-free survival following primary hypo-fractionated radiotherapy. In the third case, a cutaneous nodule proved to be a NET and at surgery, lymph node disease was present. He has remained disease-free after surgical excision without the need for external beam radiotherapy.</p> <p>Conclusion</p> <p>These tumours appear to have a good prognosis. Complete excision offers potentially curative treatment. Adjuvant radiotherapy may be helpful when the tumour margin is narrow. For patients with unresectable disease or where surgery would not be appropriate, radiotherapy appears to be an effective therapeutic option.</p

Human Macrophages Infected with a High Burden of ESAT-6-Expressing M. tuberculosis Undergo Caspase-1- and Cathepsin B-Independent Necrosis

Mycobacterium tuberculosis (Mtb) infects lung macrophages, which instead of killing the pathogen can be manipulated by the bacilli, creating an environment suitable for intracellular replication and spread to adjacent cells. The role of host cell death during Mtb infection is debated because the bacilli have been shown to be both anti-apoptotic, keeping the host cell alive to avoid the antimicrobial effects of apoptosis, and pro-necrotic, killing the host macrophage to allow infection of neighboring cells. Since mycobacteria activate the NLRP3 inflammasome in macrophages, we investigated whether Mtb could induce one of the recently described inflammasome-linked cell death modes pyroptosis and pyronecrosis. These are mediated through caspase-1 and cathepsin-B, respectively. Human monocyte-derived macrophages were infected with virulent (H37Rv) Mtb at a multiplicity of infection (MOI) of 1 or 10. The higher MOI resulted in strongly enhanced release of IL-1β, while a low MOI gave no IL-1β response. The infected macrophages were collected and cell viability in terms of the integrity of DNA, mitochondria and the plasma membrane was determined. We found that infection with H37Rv at MOI 10, but not MOI 1, over two days led to extensive DNA fragmentation, loss of mitochondrial membrane potential, loss of plasma membrane integrity, and HMGB1 release. Although we observed plasma membrane permeabilization and IL-1β release from infected cells, the cell death induced by Mtb was not dependent on caspase-1 or cathepsin B. It was, however, dependent on mycobacterial expression of ESAT-6. We conclude that as virulent Mtb reaches a threshold number of bacilli inside the human macrophage, ESAT-6-dependent necrosis occurs, activating caspase-1 in the process

Cross-Attraction between an Exotic and a Native Pine Bark Beetle: A Novel Invasion Mechanism?

Aside from the ecological impacts, invasive species fascinate ecologists because of the unique opportunities that invasives offer in the study of community ecology. Some hypotheses have been proposed to illustrate the mechanisms that allow exotics to become invasive. However, positive interactions between exotic and native insects are rarely utilized to explain invasiveness of pests.Here, we present information on a recently formed association between a native and an exotic bark beetle on their shared host, Pinus tabuliformis, in China. In field examinations, we found that 35-40% of P. tabuliformis attacked by an exotic bark beetle, Dendroctonus valens, were also attacked by a native pine bark beetle, Hylastes parallelus. In the laboratory, we found that the antennal and walking responses of H. parallelus to host- and beetle-produced compounds were similar to those of the exotic D. valens in China. In addition, D. valens was attracted to volatiles produced by the native H. parallelus.We report, for the first time, facilitation between an exotic and a native bark beetle seems to involve overlap in the use of host attractants and pheromones, which is cross-attraction. The concept of this interspecific facilitation could be explored as a novel invasive mechanism which helps explain invasiveness of not only exotic bark beetles but also other introduced pests in principle. The results reported here also have particularly important implications for risk assessments and management strategies for invasive species

The Role of Haptic Cues in Musical Instrument Quality Perception

We draw from recent research in violin quality evaluation and piano performance to examine whether the vibrotactile sensation felt when playing a musical instrument can have a perceptual effect on its judged quality from the perspective of the musician. Because of their respective sound production mechanisms, the violin and the piano offer unique example cases and diverse scenarios to study tactile aspects of musical interaction. Both violinists and pianists experience rich haptic feedback, but the former experience vibrations at more bodily parts than the latter. We observe that the vibrotactile component of the haptic feedback during playing, both for the violin and the piano, provides an important part of the integrated sensory information that the musician experiences when interacting with the instrument. In particular, the most recent studies illustrate that vibrations felt at the fingertips (left hand only for the violinist) can lead to an increase in perceived sound loudness and richness, suggesting the potential for more research in this direction

Revisiting the influence of institutional forces on the written business plan:A replication study

The present paper re-analyzes and extends a study on institutional forces and the written business plan (Honig and Karlsson in J Manag 30(1):29–48, 2004). We attempt to examine to what extent critical decision making is evident in model and variable choice, and whether the implications provided by systematic replication efforts may serve to provide additional and perhaps unrecognized theoretical and/or empirical observations. We find that the key result—formal business planning does not affect performance, does not hold. In fact, we find evidence that formal business planning affects survival but not profitability. The re-analysis also reveals, that institutional antecedents to formal planning appear to be fragile and prone to researcher biases due to different coding and assumptions. Our study underscores the consequences of access to original data and coding material, and to rely upon current methodological explanations for subsequent analyses

Multiple Chromosomal Rearrangements Structured the Ancestral Vertebrate Hox-Bearing Protochromosomes

While the proposal that large-scale genome expansions occurred early in vertebrate evolution is widely accepted, the exact mechanisms of the expansion—such as a single or multiple rounds of whole genome duplication, bloc chromosome duplications, large-scale individual gene duplications, or some combination of these—is unclear. Gene families with a single invertebrate member but four vertebrate members, such as the Hox clusters, provided early support for Ohno's hypothesis that two rounds of genome duplication (the 2R-model) occurred in the stem lineage of extant vertebrates. However, despite extensive study, the duplication history of the Hox clusters has remained unclear, calling into question its usefulness in resolving the role of large-scale gene or genome duplications in early vertebrates. Here, we present a phylogenetic analysis of the vertebrate Hox clusters and several linked genes (the Hox “paralogon”) and show that different phylogenies are obtained for Dlx and Col genes than for Hox and ErbB genes. We show that these results are robust to errors in phylogenetic inference and suggest that these competing phylogenies can be resolved if two chromosomal crossover events occurred in the ancestral vertebrate. These results resolve conflicting data on the order of Hox gene duplications and the role of genome duplication in vertebrate evolution and suggest that a period of genome reorganization occurred after genome duplications in early vertebrates

Learners in a Changing Learning Landscape: Reflections from an Instructional Design Perspective

Van Merriënboer, J. J. G., & Stoyanov, S. (2008). Learners in a changing learning landscape: Reflections from an instructional design perspective. In J. Visser & M. Visser-Valfrey (Eds.), Learners in a changing learning landscape: Reflections from a dialogue on new roles and expectations (pp. 69-90). Dordrecht, The Netherlands: Springer.Both learners and teachers find themselves in a learning landscape that is rapidly changing, along with fast societal and technological developments. This paper discusses the new learning landscape from an instructional design perspective. First, with regard to what is learned, people more than ever need flexible problem-solving and reasoning skills allowing them to deal with new, unfamiliar problem situations in their professional and everyday life. Second, with regard to the context in which learning takes place, learning in technology-rich, informal and professional 24/7 settings is becoming general practice. And third, with regard to the learners themselves, they can more often be characterized as lifelong learners who are mature, bring relevant prior knowledge, and have very heterogeneous expectations and perceptions of learning. High-quality instructional design research should focus on the question which instructional methods and media-method combinations are effective, efficient and appealing in this new learning landscape. Some innovative instructional methods that meet this requirement are discussed

Post-stenotic aortic dilatation

Aortic stenosis is the most common valvular heart disease affecting up to 4% of the elderly population. It can be associated with dilatation of the ascending aorta and subsequent dissection. Post-stenotic dilatation is seen in patients with AS and/or aortic regurgitation, patients with a haemodynamically normal bicuspid aortic valve and following aortic valve replacement. Controversy exists as to whether to replace the aortic root and ascending aorta at the time of aortic valve replacement, an operation that potentially carries a higher morbidity and mortality. The aetiology of post-stenotic aortic dilatation remains controversial. It may be due to haemodynamic factors caused by a stenotic valve, involving high velocity and turbulent flow downstream of the stenosis, or due to intrinsic pathology of the aortic wall. This may involve an abnormality in the process of extracellular matrix remodelling in the aortic wall including inadequate synthesis, degradation and transport of extracellular matrix proteins. This article reviews the aetiology, pathology and management of patients with post-stenotic aortic dilatation

Parasites of non-native freshwater fishes introduced into england and wales suggest enemy release and parasite acquisition

When non-native species are introduced into a new range, their parasites can also be introduced, with these potentially spilling-over into native hosts. However, in general, evidence suggests that a high proportion of their native parasites are lost during introduction and infections by some new parasites from the native range might occur, potentially resulting in parasite spill-back to native species. These processes were investigated here using parasite surveys and literature review on seven non-native freshwater fishes introduced into England and Wales. Comparison of the mean numbers of parasite species and genera per population for each fish species England andWaleswith their native ranges revealed\9 % of the native parasite fauna were present in their populations in England and Wales. There was no evidence suggesting these introduced parasites had spilled over into sympatric native fishes. The non-native fishes did acquire parasites following their introduction, providing potential for parasite spill-back to sympatric fishes, and resulted in non-significant differences in overall mean numbers of parasites per populations between the two ranges. Through this acquisition, the non-native fishes also had mean numbers of parasite species and genera per population that were not significantly different to sympatric native fishes. Thus, the non-native fishes in England and Wales showed evidence of enemy release, acquired new parasites following introduction providing potential for spill-back, but showed no evidence of parasite spill-over