Significance of lobular intraepithelial neoplasia at margins of breast conservation specimens: a report of 38 cases and literature review

<p>Abstract</p> <p>Background</p> <p>Presence of lobular intraepithelial neoplasia (LIN) is not routinely reported as part of margin assessment in breast conservation therapy (BCT) as in ductal carcinoma in situ (DCIS). With new emerging evidence of LIN as possible precursor lesion, the hypothesis is that LIN at the margin may increase the risk of local recurrence with BCT. The aim is to determine whether there is an increase incidence of recurrence when LIN is found at surgical margins on BCT.</p> <p>Methods</p> <p>We retrospectively reviewed a total of 1,334 BCT at a single institution in a 10 year period. Inclusion criteria are positive margin with LIN from primary BCT containing invasive and/or in situ carcinoma with comparison to the negative control group who had similar diseases with negative margin for LIN.</p> <p>Results</p> <p>We identified 38 cases (2.8%) with LIN either lobular carcinoma in situ/atypical lobular hyperplasia (LCIS/ALH) at a margin on initial BCT with 36% recurrence rate. Of the 38 cases: 5 (13%) were lost to follow-up, 12 (32%) had no further procedures performed and 21 (55%) had re-excision. Out of 21 patients who had re-excisions, 12 (57%) had residual invasive carcinoma or DCIS, three (14%) had pleomorphic LCIS and 4 (19%) showed residual classic type LCIS. 71% had significant residual disease (local recurrence) and 29% had no residual disease. A negative control group consisted of 38 cases. We found two patients with bone or brain metastasis and one local recurrence. Clinical follow up periods range from 1 to 109 months.</p> <p>Conclusions</p> <p>LIN found at a margin on BCT showed a significant recurrent ipsilateral disease. Our study supports the view that LIN seen at the margin may play a role in recurrence.</p

The genomes of two key bumblebee species with primitive eusocial organization

Background: The shift from solitary to social behavior is one of the major evolutionary transitions. Primitively eusocial bumblebees are uniquely placed to illuminate the evolution of highly eusocial insect societies. Bumblebees are also invaluable natural and agricultural pollinators, and there is widespread concern over recent population declines in some species. High-quality genomic data will inform key aspects of bumblebee biology, including susceptibility to implicated population viability threats. Results: We report the high quality draft genome sequences of Bombus terrestris and Bombus impatiens, two ecologically dominant bumblebees and widely utilized study species. Comparing these new genomes to those of the highly eusocial honeybee Apis mellifera and other Hymenoptera, we identify deeply conserved similarities, as well as novelties key to the biology of these organisms. Some honeybee genome features thought to underpin advanced eusociality are also present in bumblebees, indicating an earlier evolution in the bee lineage. Xenobiotic detoxification and immune genes are similarly depauperate in bumblebees and honeybees, and multiple categories of genes linked to social organization, including development and behavior, show high conservation. Key differences identified include a bias in bumblebee chemoreception towards gustation from olfaction, and striking differences in microRNAs, potentially responsible for gene regulation underlying social and other traits. Conclusions: These two bumblebee genomes provide a foundation for post-genomic research on these key pollinators and insect societies. Overall, gene repertoires suggest that the route to advanced eusociality in bees was mediated by many small changes in many genes and processes, and not by notable expansion or depauperation

Chemical weathering and solute export by meltwater in a maritime Antarctic glacier basin

Solute yields, laboratory dissolution data and both chemical and isotopic markers of rock weathering reactions are used to characterise the biogeochemistry of glacial meltwaters draining a maritime Antarctic glacier. We find that delayed flowpaths through ice-marginal talus and moraine sediments are critical for the acquisition of solute from rock minerals because delayed flowpaths through subglacial sediments are absent beneath this small, cold-based glacier. Here the mechanisms of weathering are similar to those reported in subglacial environments, and include sub-oxic conditions in the early summer and increasingly oxic conditions thereafter. Up to 85% of the NO3 − and 65% of the SO4 2− are most likely produced by bacterially mediated reactions in these ice marginal sediments. However, reactive pyrite phases are sparse in the host rocks, limiting the export of Fe, SO4 2− and cations that may be removed by weathering once pyrite oxidation has taken place. This means that dissolution of Ca2+ and Na+ from carbonate and silicate minerals dominate, producing moderate cationic denudation yields from Tuva Glacier (163 Σ*meq+ m−2 a−1) compared to a global range of values (94–4,200 Σ*meq+ km−2 a−1). Overall, crustally derived cations represent 42% of the total cationic flux, the rest being accounted for by snowpack sources

Acetaminophen (paracetamol) inhibits myeloperoxidase-catalyzed oxidant production and biological damage at therapeutically achievable concentrations

The heme peroxidase enzyme myeloperoxidase (MPO) is released by activated neutrophils and monocytes, where it uses hydrogen peroxide (H2O2) to catalyze the production of the potent oxidants hypochlorous acid (HOCl), hypobromous acid (HOBr) and hypothiocyanous acid (HOSCN) from halide and pseudohalide (SCN-) ions. These oxidants have been implicated as key mediators of tissue damage in many human inflammatory diseases including atherosclerosis, asthma, rheumatoid arthritis, cystic fibrosis and some cancers. It is shown here that acetaminophen (paracetamol), a phenol-based drug with analgesic and antipyretic actions, is an efficient inhibitor of HOCl and HOBr generation by isolated MPO-H2O2-halide systems. With physiological halide concentrations, acetaminophen concentrations required for 50% inhibition of oxidant formation (IC50) were 77±6μM (100mMCl-) and 92±2μM (100mMCl- plus 100μMBr-), as measured by trapping of oxidants with taurine. The IC50 for inhibition of HOCl generation by human neutrophils was ca. 100μM. These values are lower than the maximal therapeutic plasma concentrations of acetaminophen (≤150μM) resulting from typical dosing regimes. Acetaminophen did not diminish superoxide generation by neutrophils, as measured by lucigenin-dependent chemiluminescence. Inhibition of HOCl production was associated with the generation of fluorescent acetaminophen oxidation products, consistent with acetaminophen acting as a competitive substrate of MPO. Inhibition by acetaminophen was maintained in the presence of heparan sulfate and extracellular matrix, materials implicated in the sequestration of MPO at sites of inflammation in vivo. Overall, these data indicate that acetaminophen may be an important modulator of MPO activity in vivo. © 2009 Elsevier Inc

Is provitamin D a UV-B receptor in plants?

An hypothesis is presented that provitamin D (dehydrocholesterol and/or ergosterol) can act as a UV-B receptor in plants and algae. We also propose that the proportions between provitamins D, previtamins D, and vitamins D (D2 and D3), after calibration, can be used to evaluate UV-B exposure of phytoplankton and terrestrial vegetation. This is the final, accepted and revised manuscript of this article. Use alternative location to go to the published article. Requires subscription. The original publication is available at www.springerlink.com