Do toenail manganese and iron levels reflect brain metal levels or brain metabolism in welders?

Inhalation of welding fumes can cause metal accumulation in the brain, leading to Parkinsonian-like symptoms. Metal accumulation and altered neurochemical profiles have been observed using magnetic resonance imaging (MRI) in highly exposed welders, being associated with decreased motor function and cognition. While MRI is impractical to use as a health risk assessment tool in occupational settings, toenail metal levels are easier to assess and have been demonstrated to reflect an exposure window of7-12 months in the past. Yet, it is unclear whether toenail metal levels are associated with brain metal levels or changes in metabolism, which are the root of potential health concerns. This study investigates whether toenail manganese (Mn) and iron (Fe) levels, assessed at several time points, correlate with brain Mn and Fe levels, measured by MRI, as well as brain GABA, glutamate (Glu), and glutathione (GSH) levels, measured by Magnetic Resonance Spectroscopy (MRS), in seventeen Mn-exposed welders. Quantitative T1 and R2* MRI maps of the whole brain, along with GABA, Glu, and GSH MRS measurements from the thalamus and cerebellum were acquired at baseline (T0). Toenail clippings were collected at T0 and every three months after the MRI for a year to account for different exposure periods being reflected by toenail clippings and MRI. Spearman correlations of toenail metal levels were run against brain metal and metabolite levels, but no significant associations were found for Mn at any timepoint. Cerebellar GSH positively correlated with toenail Fe clipped twelve months after the MRI (p = 0.05), suggesting an association with Fe exposure at the time of the MRI. Neither thalamic GABA nor Glu correlated with toenail Fe levels. In conclusion, this study cannot support toenail Mn as a proxy for brain Mn levels or metabolic changes, while toenail Fe appears linked to brain metabolic alterations, underscoring the importance of considering other metals, including Fe, in studying Mn neurotoxicity.

Reproducibility Made Easy: A Tool for Methodological Transparency and Efficient Standardized Reporting based on the proposed MRSinMRS Consensus.

Purpose: Recent expert consensus publications have highlighted the issue of poor reproducibility in magnetic resonance spectroscopy (MRS) studies, mainly due to the lack of standardized reporting criteria, which affects their clinical applicability. To combat this, guidelines for minimum reporting standards (MRSinMRS) were introduced to aid journal editors and reviewers in ensuring the comprehensive documentation of essential MRS study parameters. Despite these efforts, the implementation of MRSinMRS standards has been slow, attributed to the diverse nomenclature used by different vendors, the variety of raw MRS data formats, and the absence of appropriate software tools for identifying and reporting necessary parameters. To overcome this obstacle, we have developed the REproducibility Made Easy (REMY) standalone toolbox. Methods: REMY software supports a range of MRS data formats from major vendors like GE (p. file), Siemens (.twix, .rda, .dcm), Philips (.spar/.sdat), and Bruker (.method), facilitating easy data import and export through a user-friendly interface. REMY employs external libraries such as spec2nii and pymapVBVD to accurately read and process these diverse data formats, ensuring compatibility and ease of use for researchers in generating reproducible MRS research outputs. Users can select and import datasets, choose the appropriate vendor and data format, and then generate an MRSinMRS table, log file, and methodological documents in both Latex and PDF formats. Results: REMY effectively populated key sections of the MRSinMRS table with data from all supported file types. In the hardware section, it successfully read and filled in fields for Field Strength [T], Manufacturer Name, and Software Version, covering three of the five required hardware fields. However, it could not input data for RF coil and additional hardware information due to their absence in the files. For the acquisition section, REMY accurately read and populated fields for the pulse sequence name, nominal voxel size, repetition time, echo time, number of acquisitions/excitations/shots, spectral width [Hz], and number of spectral points, significantly contributing to the completion of the Acquisition fields of the table. Furthermore, REMY generates a boilerplate methods text section for manuscripts. Conclusion: This approach reduces effort and obstacles associated with writing and reporting acquisition parameters and should lead to the widespread adoption of MRSinMRS within the MRS community.

Warburg Effect Is a Cancer Immune Evasion Mechanism Against Macrophage Immunosurveillance.

Evasion of immunosurveillance is critical for cancer initiation and development. The expression of "don't eat me" signals protects cancer cells from being phagocytosed by macrophages, and the blockade of such signals demonstrates therapeutic potential by restoring the susceptibility of cancer cells to macrophage-mediated phagocytosis. However, whether additional self-protective mechanisms play a role against macrophage surveillance remains unexplored. Here, we derived a macrophage-resistant cancer model from cells deficient in the expression of CD47, a major "don't eat me" signal, via a macrophage selection assay. Comparative studies performed between the parental and resistant cells identified self-protective traits independent of CD47, which were examined with both pharmacological or genetic approaches in in vitro phagocytosis assays and in vivo tumor models for their roles in protecting against macrophage surveillance. Here we demonstrated that extracellular acidification resulting from glycolysis in cancer cells protected them against macrophage-mediated phagocytosis. The acidic tumor microenvironment resulted in direct inhibition of macrophage phagocytic ability and recruitment of weakly phagocytic macrophages. Targeting V-ATPase which transports excessive protons in cancer cells to acidify extracellular medium elicited a pro-phagocytic microenvironment with an increased ratio of M1-/M2-like macrophage populations, therefore inhibiting tumor development and metastasis. In addition, blockade of extracellular acidification enhanced cell surface exposure of CD71, targeting which by antibodies promoted cancer cell phagocytosis. Our results reveal that extracellular acidification due to the Warburg effect confers immune evasion ability on cancer cells. This previously unrecognized role highlights the components mediating the Warburg effect as potential targets for new immunotherapy harnessing the tumoricidal capabilities of macrophages.