Correction: Gamma Knife radiosurgery for vestibular schwannomas: Evaluation of planning using the sphericity degree of the target volume.

[This corrects the article DOI: 10.1371/journal.pone.0225638.].

Manganese systemic distribution is modulated in vivo during tumor progression and affects tumor cell migration and invasion in vitro.

Metastatic disease remains the leading cause of death in cancer and understanding the mechanisms involved in tumor progression continues to be challenging. This work investigates the role of manganese in tumor progression in an in vivo model of tumor growth. Our data revealed that manganese accumulates within primary tumors and secondary organs as manganese-rich niches. Consequences of such phenomenon were investigated, and we verified that short-term changes in manganese alter cell surface molecules syndecan-1 and ß1-integrin, enhance collective cell migration and invasive behavior. Long-term increased levels of manganese do not affect cell growth and viability but enhance cell migration. We also observed that manganese is secreted from tumor cells in extracellular vesicles, rather than in soluble form. Finally, we describe exogenous glycosaminoglycans that counteract manganese effects on tumor cell behavior. In conclusion, our analyses describe manganese as a central element in tumor progression by accumulating in Mn-rich niches in vivo, as well as in vitro, affecting migration and extracellular vesicle secretion in vitro. Manganese accumulation in specific regions of the organism may not be a common ground for all cancers, nevertheless, it represents a new aspect of tumor progression that deserves special attention.

Gamma Knife radiosurgery for vestibular schwannomas: Evaluation of planning using the sphericity degree of the target volume.

INTRODUCTION: This study explores the possibility of a relationship between the sphericity degree of a target volume with the dose distribution. This relationship is evaluated based on the ratio isodose volume / target volume (IV/TV) and the metrics coverage, i.e., selectivity, gradient index, conformity index and mean dose when planning radiosurgery for vestibular schwannoma. METHODS: Sphericity degree (φ) was calculated for each target volume (TV) of 64 patients who underwent stereotactic radiosurgery (SRS) for vestibular schwannoma. The calculation of this parameter was developed using the theoretical definition for operational sphericity φ = VP/VCS. The values found are evaluated considering the following metrics:-Coverage (C), selectivity (S), gradient index (GI), Paddick conformity index (CIPaddick) and dose distribution (IV/TV). The planning was also carried out considering a spherical target volume defined in a spherical phantom. The spherical volume is the same as the target used in the treatment plan. The planning of the spherical target was considered as a reference plan to evaluate the dose distribution inside and outside the volume. RESULTS: It was possible to observe that the majority of target volumes has (ϕ) around 0,66-0,77, corresponding to 54,7% of the total. Considering the mean values for metrics, the results are: C = 0,98, S = 0,78, GI = 3,11 and CI = 0,81. The dose distribution was equivalent for treatment plans and reference plans. Quantitative analysis for IV/TV shows that these values are higher than 30% for treatment plans where shot density is large. CONCLUSION: This study demonstrates that de sphericity degree (φ) can be related to the dose distribution (IV/TV). Therefore the sphericity degree is a good parameter to evaluate the dose distribution of a plan for vestibular schwannoma treatment, considering the reference plan as being a spherical target using a leksell gamma knife® perfexion (LGKP). This study shows that the sphericity degree offers important information of the dose distribution outside and inside the target volume. This is not evaluated by the other parameters already implemented as metric to analyzing the GKP plans.

Valproate reverts zinc and potassium imbalance in schizophrenia-derived reprogrammed cells.

Schizophrenia has been considered a devastating clinical syndrome rather than a single disease. Nevertheless, the mechanisms behind the onset of schizophrenia have been only partially elucidated. Several studies propose that levels of trace elements are abnormal in schizophrenia; however, conflicting data generated from different biological sources prevent conclusions being drawn. In this work, we used synchrotron radiation X-ray microfluorescence spectroscopy to compare trace element levels in neural progenitor cells (NPCs) derived from two clones of induced pluripotent stem cell lines of a clozapine-resistant schizophrenic patient and two controls. Our data reveal the presence of elevated levels of potassium and zinc in schizophrenic NPCs. Neural cells treated with valproate, an adjunctive medication for schizophrenia, brought potassium and zinc content back to control levels. These results expand the understanding of atomic element imbalance related to schizophrenia and may provide novel insights for the screening of drugs to treat mental disorders.