Distinct molecular mechanisms contribute to the reduction of melanoma growth and tumor pain after systemic and local depletion of alpha-Synuclein in mice.

Epidemiological studies show a coincidence between Parkinson's disease (PD) and malignant melanoma. It has been suggested that this relationship is due, at least in part, to modulation of alpha-Synuclein (αSyn/Snca). αSyn oligomers accumulate in PD, which triggers typical PD symptoms, and in malignant melanoma, which increases the proliferation of tumor cells. In addition, αSyn contributes to non-motor symptoms of PD, including pain. In this study, we investigated the role of αSyn in melanoma growth and melanoma-induced pain in a mouse model using systemic and local depletion of αSyn. B16BL6 wild-type as well as αSyn knock-down melanoma cells were inoculated into the paws of αSyn knock-out mice and wild-type mice, respectively. Tumor growth and tumor-induced pain hypersensitivity were assessed over a period of 21 days. Molecular mechanisms were analyzed by RT-PCR and Western Blot in tumors, spinal cord, and sciatic nerve. Our results indicate that both global and local ablation of Snca contribute to reduced tumor growth and to a reduction of tumor-induced mechanical allodynia, though mechanisms contributing to these effects differ. While injection of wild-type cells in Snca knock-out mice strongly increased the immune response in the tumor, local Snca knock-down decreased autophagy mechanisms and the inflammatory reaction in the tumor. In conclusion, a knockdown of αSyn might constitute a promising approach to inhibiting the progression of melanoma and reducing tumor-induced pain.

Metal hypersensitivity screening among frontline healthcare workers-A descriptive study.

AIMS AND OBJECTIVES: The study aims were to (a) assess allergy screening practices, (b) determine the awareness of metal hypersensitivity among frontline healthcare workers and (c) examine perceived barriers to implementing metal hypersensitivity screening into clinical practice. BACKGROUND: Adverse device-related events, such as hypersensitivity to metals, are well documented in the literature. Hypersensitivity to metal is a type IV T-cell-mediated reaction that can occur after cardiac, orthopaedic, dental, gynaecological and neurosurgical procedures where a device with metal components is implanted into the body. Patients with hypersensitivity to metal are likely to experience delayed healing, implant failure and stent restenosis. Identifying patients with a history of metal hypersensitivity reaction could mitigate the risk of poor outcomes following device implant. Yet in clinical practice, healthcare workers do not routinely ask about the history of metal hypersensitivity when documenting allergies. The existing literature does not report why this is not included in allergy assessment. DESIGN: Following the STROBE checklist, a cross-sectional, descriptive study was conducted. METHODS: Frontline healthcare workers were recruited using professional contacts and social online media to complete an online questionnaire. Quantitative data were summarised descriptively while thematic analysis was used to examine barriers to implementation. RESULTS: Three hundred forty-five participants from 14 countries completed the questionnaire, with the majority (187/54%) practicing in Canada, in general medicine and intensive care units. Ninety per cent of the participants did not routinely ask about metal hypersensitivity when evaluating allergy history. Of the respondents, 86% were unaware of the association between metal hypersensitivity and poor patient outcomes. After presented with the evidence, 81% indicated they were likely or very likely to incorporate the evidence into their clinical practice. Common themes about barriers to implementing were 'Standards of Practice', 'Knowledge' and 'Futility of Screening'. CONCLUSION: The findings suggest lack of awareness as the main reason for not including metal in routine allergy assessment.

Hypersensitivity in patients receiving metal implants: a scoping review protocol.

OBJECTIVE: The objective of this scoping review is to gather the available evidence on metal hypersensitivity to determine the extent of the problem and identify gaps in the evidence about screening practices. INTRODUCTION: Hypersensitivity to metal was first reported in 1966. Since this time, the use of metal in prosthetic devices has increased with an associated rise in reported hypersensitivity reaction to other metals. Symptoms of metal hypersensitivity can be subtle, and it is unclear whether clinicians are aware of or routinely ask patients about metal hypersensitivity when documenting allergies. This can lead to a delay in diagnosis, which puts patients at risk of poor outcomes. Hence, there is a need to map the available evidence on hypersensitivity reaction in people who receive metallic device implantation. INCLUSION CRITERIA: The review will consider studies that include patients who undergo procedures involving metal implantation. The concept to be explored is hypersensitivity following a procedure that involves the implementation of a device with metal components. Implementation is defined as permanent integration of a foreign (non-biological) object into the human body to restore function. METHODS: The proposed scoping review will be conducted in accordance with JBI methodology for scoping reviews. Searches will be generated in multiple databases and updated as needed. Gray literature and organizational websites will also be searched. Titles, abstracts, and full articles will be screened according to the inclusion criteria. Studies published in English from 1960 to the present will be included. Data will be extracted and findings will be presented in tabular form with a narrative summary.