Combining MYD88 L265P mutation detection and clonality determination on CSF cellular and cell-free DNA improves diagnosis of primary CNS lymphoma

Diagnosis of primary central nervous system lymphoma (PCNSL) is challenging, and although brain biopsy remains the gold standard, cerebrospinal fluid (CSF) constitutes a less invasive source of lymphomatous biomarkers. In a retrospective cohort of 54 PCNSL cases tested at diagnosis or relapse, we evaluated the contribution of immunoglobulin heavy chain (IGH) gene clonality and MYD88 L265P detection on both CSF cell pellets and supernatants, in comparison with cytology, flow cytometry, interleukin (IL)-10 and IL-6 quantification. Clonality assessment included a new assay to detect partial IGH-DJ rearrangements. Clonal IGH rearrangements and/or MYD88 L265P mutation were detected in 27 (50%) cell pellets and 24 (44%) supernatant cell-free (cf) DNA. Combining analyses on both compartments, 36 (66%) cases had at least one detectable molecular marker, present only in cfDNA for 9 (16%) of them. While cytology and flow cytometry were positive in only 7 (13.0%) and 9 (17.3%) cases respectively, high IL-10 levels were observed in 36 (66.7%) cases. Overall, taking into account molecular and cytokine results, 46/54 (85%) cases had at least one lymphomatous biomarker detectable in the CSF. These results show that this combination of biomarkers evaluated on both cell pellet and supernatant CSF fractions improves significantly the biological diagnosis of PCNSL.     

Seasonal Changes of Macroinvertebrate Communities in a Stormwater Wetland Collecting Pesticide Runoff From a Vineyard Catchment (Alsace,France)

Agricultural land use may influence macroinvertebrate communities by way of pesticide contamination associated with agricultural runoff. However, information about the relation between runoff-related pesticides and communities of benthic macroinvertebrates in stormwater wetland that receive agricultural runoff does not currently exist. Here we show changes in macroinvertebrates communities of a stormwater wetland that collects pesticide-contaminated runoff from a vineyard catchment. Sixteen runoff-associated pesticides, including the insecticide flufenoxuron, were continuously quantified at the inlet of the stormwater wetland from April to September (period of pesticide application). In parallel, benthic macroinvertebrate communities, pesticide concentrations, and physicochemical parameters in the wetland were assessed twice a month. Twenty-eight contaminated runoffs ranging from 1.1 to 114 m³ entered the wetland during the study period. Flufenoxuron concentrations in runoff-suspended solids ranged from 1.5 to 18.5 μg kg⁻¹ and reached 6 μg kg⁻¹ in the wetland sediments. However, flufenoxuron could not be detected in water. The density, diversity, and abundance of macroinvertebrates largely varied over time. Redundancy and formal concept analyses showed that concentrations of flufenoxuron, vegetation cover, and flow conditions significantly determine the community structures of stormwater wetland macroinvertebrates. This study shows that flow conditions, vegetation cover, and runoff-related pesticides jointly affect communities of benthic macroinvertebrates in stormwater wetlands.     

Chemotherapy is an efficient treatment in primary CNS MALT lymphoma

Journal of Neuro-Oncology - Mucosae-associated lymphoid tissue (MALT) lymphomas are a rare and poorly understood form of primary central nervous system lymphoma (PCNSL). The aim of this study was...     

Assessment of the toxicity of weathered petroleum hydrocarbon impacted soils to native plants from a site in the Canadian Subarctic

Remedial guidelines for petroleum hydrocarbons (PHCs) in soil aid in the mitigation of risks to human health and the environmental. However, some remediation guidelines may overestimate the potential for adverse effects to native plant species, contributing to unnecessary remedial efforts in attempts to meet the guidelines. At sites where PHC-contaminated soils undergo weathering, some PHCs may persist but with decreased bioavailability to organisms. In this study, the toxicity of both coarse and fine-grained subarctic soils, contaminated with weathered PHCs were assessed using five native plant species (Picea mariana, Achillea millefolium, Alnus viridis, Elymus trachycaulus and Salix bebbiana). Soil toxicity tests were conducted in a growth chamber with parameters set to simulate the site’s subarctic climate conditions. Reference toxicant tests using boric acid were conducted to provide confidence in the interpretation of the results for the PHC-contaminated soils, and also provide new information on the sensitivities of the four boreal species to boric acid. All plants exhibited reduced growth and germination rates as boric acid concentrations increased. Despite exceeding the Canada-wide standard guidelines for Fraction 3 PHCs, field-collected contaminated soils had no significant negative impacts on the growth (i.e., length, dry weight and emergence) of any of the plant species tested.

     

Adipogenic Mesenchymal Stromal Cells from Bone Marrow and Their Hematopoietic Supportive Role: Towards Understanding the Permissive Marrow Microenvironment in Acute Myeloid Leukemia

Purpose

The role of bone marrow-derived mesenchymal stem/stromal cells (MSCs) in creating a permissive microenvironment that supports the emergence and progression of acute myeloid leukemia (AML) is not well established. We investigated the extent to which adipogenic differentiation in normal MSCs alters hematopoietic supportive capacity and we undertook an in-depth comparative study of human bone marrow MSCs derived from newly diagnosed AML patients and healthy donors, including an assessment of adipogenic differentiation capacity.

Findings

MSCs from healthy controls with partial induction of adipogenic differentiation, in comparison to MSCs undergoing partial osteogenic differentiation, expressed increased levels of hematopoietic factors and induced greater proliferation, decreased quiescence and reduced in vitro hematopoietic colony forming capacity of CD34⁺ hematopoietic stem and progenitor cells (HSPCs). Moreover, we observed that AML-derived MSCs had markedly increased adipogenic potential and delayed osteogenic differentiation, while maintaining normal morphology and viability. AML-derived MSCs, however, possessed reduced proliferative capacity and decreased frequency of subendothelial quiescent MSCs compared to controls.

Conclusion

Our results support the notion of a bone marrow microenvironment characterized by increased propensity toward adipogenesis in AML, which may negatively impact normal hematopoiesis. Larger confirmatory studies are needed to understand the impact of various clinical factors. Novel leukemia treatments aimed at normalizing bone marrow niches may enhance the competitive advantage of normal hematopoietic progenitors over leukemia cells.

     

The attributes of an effective teacher differ between the classroom and the clinical setting

Most training programs use learners’ subjective ratings of their teachers as the primary measure of teaching effectiveness. In a recent study we found that preclinical medical students’ ratings of classroom teachers were associated with perceived charisma and physical attractiveness of the teacher, but not intellect. Here we explored whether the relationship between these variables and teaching effectiveness ratings holds in the clinical setting. We asked 27 Internal Medicine residents to rate teaching effectiveness of ten teachers with whom they had worked on a clinical rotation, in addition to rating each teacher’s clinical skills, physical attractiveness, and charisma. We used linear regression to study the association between these explanatory variables and teaching effectiveness ratings. We found no association between rating of physical attractiveness and teaching effectiveness. Clinical skill and charisma were independently associated with rating of teaching effectiveness (regression coefficients [95 % confidence interval] 0.73 [0.60, 0.85], p < 0.001 and 0.12 [0.01, 0.23], p = 0.03, respectively). The variables associated with effectiveness of classroom and clinical teachers differ, suggesting context specificity in teaching effectiveness ratings. Context specificity may be explained by differences in the exposure that learners have to teachers in the classroom versus clinical setting—so that raters in the clinical setting may base ratings upon observed behaviours rather than stereotype data. Alternatively, since subjective ratings of teaching effectiveness inevitably incorporate learners’ context-specific needs, the attributes that make a teacher effective in one context may not meet the needs of learners in a different context.