35224 Identifying a correlation between preceding trauma and development of dermatofibrosarcoma protuberans: A review of the literature

Background: Dermatofibrosarcoma protuberans (DFSP) is a malignant fibrohistiocytic neoplasm that is slow-growing, has low metastatic potential, and is locally infiltrative with a predisposition for recurrence. The development of DFSP can occur spontaneously, but anecdotal evidence suggests a correlation between preceding injury and tumor onset. Methods: A comprehensive literature search was performed using PubMed, Embase, and web of science for articles with unambiguous reporting of DFSP with a history of physical trauma. Of 139 identified articles, 23 (17%) met criteria and were analyzed. Results: In total, 52 patients were reported as having had some form of physical trauma prior to DFSP development, and of these, sex was reported for half (40% men; 60% women). The mean (standard deviation) age at time of diagnosis was 42 (14) years, and lesions ranged from 1 to 20 cm. Involved locations included the trunk (62%), lower extremities (19%), upper extremities (12%), and head/neck (8%). The median (range) time between injury and self-reported lesion was 10 (1-19) years, while the median (range) time between injury and DFSP diagnosis was 10 (2-41) years. Types of injuries reported included tattoos (most common), vaccinations/injections, burns, surgeries, radiation, insect bites, and various levels of minor to blunt force. Discussion: A subset of DFSP cases arise in the setting of prior cutaneous trauma, which may play a role in their pathogenesis. Recognition of this possibility is important to avoid misdiagnosis (i.e., hypertrophic scar or keloid) or delay in diagnosis

Unplanned antiretroviral treatment interruptions in southern Africa: how should we be managing these?

Adherence to antiretroviral therapy is essential for maximising individual treatment outcomes and preventing the development of drug resistance. It is, however, frequently compromised due to predictable, but adverse, scenarios in the countries most severely affected by HIV/AIDS. This paper looks at lessons from three specific crises in southern Africa: the 2008 floods in Mozambique, the ongoing political and economic crisis in Zimbabwe, and the 2007 public sector strike in South Africa. It considers how these crises impacted on the delivery of antiretroviral therapy and looks at some of the strategies employed to mitigate any adverse effects. Based on this it makes recommendations for keeping patients on treatment and limiting the development of drug resistance where treatment interruptions are inevitable

Fully automated synthesis of (phospho)peptide arrays in microtiter plate wells provides efficient access to protein tyrosine kinase characterization

BACKGROUND: Synthetic peptides have played a useful role in studies of protein kinase substrates and interaction domains. Synthetic peptide arrays and libraries, in particular, have accelerated the process. Several factors have hindered or limited the applicability of various techniques, such as the need for deconvolution of combinatorial libraries, the inability or impracticality of achieving full automation using two-dimensional or pin solid phases, the lack of convenient interfacing with standard analytical platforms, or the difficulty of compartmentalization of a planar surface when contact between assay components needs to be avoided. This paper describes a process for synthesis of peptides and phosphopeptides on microtiter plate wells that overcomes previous limitations and demonstrates utility in determination of the epitope of an autophosphorylation site phospho-motif antibody and utility in substrate utilization assays of the protein tyrosine kinase, p60(c-src). RESULTS: The overall reproducibility of phospho-peptide synthesis and multiplexed EGF receptor (EGFR) autophosphorylation site (pY1173) antibody ELISA (9H2) was within 5.5 to 8.0%. Mass spectrometric analyses of the released (phospho)peptides showed homogeneous peaks of the expected molecular weights. An overlapping peptide array of the complete EGFR cytoplasmic sequence revealed a high redundancy of 9H2 reactive sites. The eight reactive phospopeptides were structurally related and interestingly, the most conserved antibody reactive peptide motif coincided with a subset of other known EGFR autophosphorylation and SH2 binding motifs and an EGFR optimal substrate motif. Finally, peptides based on known substrate specificities of c-src and related enzymes were synthesized in microtiter plate array format and were phosphorylated by c-Src with the predicted specificities. The level of phosphorylation was proportional to c-Src concentration with sensitivities below 0.1 Units of enzyme. CONCLUSIONS: The ability of this method to interface with various robotics and instrumentation is highly flexible since the microtiter plate is an industry standard. It is highly scalable by increasing the surface area within the well or the number of wells and does not require specialized robotics. The microtiter plate array system is well suited to the study of protein kinase substrates, antigens, binding molecules, and inhibitors since these all can be quantitatively studied at a single uniform, reproducible interface

ETS-related Gene (ERG) is Differentially Expressed in Dermatofibroma (Fibrous Histiocytoma) as Compared With Dermatofibrosarcoma Protuberans and Hypertrophic Scars: A Pilot Immunohistochemical Study

Immunohistochemical staining can be of great utility in differentiating various cutaneous spindle cell neoplasms, particularly when the histomorphologic appearance of the lesions is inconclusive. Nuclear staining for ETS-related gene (ERG), a highly sensitive endothelial cell marker, has seldom been studied in the context of cutaneous spindle cell neoplasms. Little is known about its specificity for vascular differentiation. In this pilot study, immunohistochemical analysis for ERG was performed on 15 dermatofibromas (DF), 10 keloids, and 9 dermatofibrosarcoma protuberans (DFSP) tumors. Consistent nuclear expression of ERG was found in DF [100% (15/15) of the lesions demonstrated \u3e50% labeling of tumor cells with moderate to strong intensity]. However, ERG expression was largely absent in DFSP [89% (8/9) of the lesions demonstrating \u3c50% labeling staining, generally of mild intensity] and hypertrophic scars-keloids [80% (8/10) without expression]. On the basis of the results of this pilot study, immunohistochemical staining for ERG may prove useful in helping to differentiate DF from DFSP and hypertrophic scars in the context of partial biopsy sampling. If replicated in a larger number of samples, this finding could mitigate the use of costly sequencing panels and potentially avoid unnecessary reexcisions in certain contexts

Connecting Soil Organic Carbon and Root Biomass with Land-Use and Vegetation in Temperate Grassland

Soils containmuch of Earth’s terrestrial organic carbon but are sensitive to land-use. Rangelands are important to carbon dynamics and are among ecosystems most widely impacted by land-use. While common practices like grazing, fire, and tillage affect soil properties directly related to soil carbon dynamics, their magnitude and direction of change vary among ecosystems and with intensity of disturbance. We describe variability in soil organic carbon (SOC) and root biomass—sampled from 0–170 cm and 0– 100 cm, respectively—in terms of soil properties, land-use history, current management, and plant community composition using linear regression and multivariate ordination. Despite consistency in average values of SOC and root biomass between our data and data from rangelands worldwide, broad ranges in root biomass and SOC in our data suggest these variables are affected by other site-specific factors. Pastures with a recent history of severe grazing had reduced root biomass and greater bulk density. Ordination suggests greater exotic species richness is associated with lower root biomass but the relationship was not apparent when an invasive species of management concern was specifically tested.We discuss how unexplained variability in belowground properties can complicate measurement and prediction of ecosystem processes such as carbon sequestration

Research Techniques Made Simple: Use of Imaging Mass Cytometry for Dermatological Research and Clinical Applications

Traditional immunohistochemistry (IHC) is inherently limited by its ability to analyze only several markers within a histological tissue section at a given time, which hinders in-depth characterization and phenotyping of tissues. Imaging mass cytometry (IMC), which combines IHC using metal-labeled antibodies with laser ablation and detection using mass cytometry by time-of-flight, overcomes this limitation with the capability to simultaneously analyze up to 40 protein markers to generate high-dimensional images from a single tissue section. IMC analysis preserves tissue architecture and spatial cellular relationships that would otherwise be lost or significantly altered in applications requiring tissue dissociation, such as flow cytometry or single-cell RNA sequencing. Resulting high-dimensional histological images permit spatially conserved analysis to identify unique cell populations, cellular interactions and avoidances, and insight into activation and behavioral status based on tissue location. IMC can be performed on both frozen and formalin-fixed paraffin-embedded tissue, allowing for previously banked samples to be analyzed and correlated with known clinical outcomes. Expectedly, IMC will change the landscape of investigative pathology, particularly when used in coordination with multiomic platforms to combine transcriptomic and proteomic data at a single-cell resolution. Here, we aim to highlight the potential utility of IMC within dermatologic research and clinical applications

Increasing carbon sequestration of working prairie by reducing invasive species in a fire and grazing system

The investigators looked at one method for curbing invasive species that limit carbon sequestration potential for tallgrass prairie stands. They also learned that grasslands dominated by either warm-season, cool-season, or mixed stands are likely equal in their carbon sequestration potential