ALS mutant FUS proteins are recruited into stress granules in induced pluripotent stem cells- derived motoneurons

Patient-derived induced Pluripotent Stem Cells (iPSCs) provide an opportunity to study human diseases mainly in those cases where no suitable model systems are available. Here we have taken advantage of in vitro iPSCs derived from patients affected by Amyotrophic Lateral Sclerosis and carrying mutations in the RNA-binding proteins FUS to study the cellular behavior of the mutant proteins in the appropriate genetic background. Moreover, the ability to differentiate iPSCs into spinal cord neural cells provides an in vitro model mimicking the physiological conditions. iPSCs were derived from FUS(R514S) and FUS(R521C) patients' fibroblasts, while in the case of the severe FUS(P525L) mutation, where fibroblasts were not available, a heterozygous and a homozygous iPSC lines were raised by TALEN-directed mutagenesis. We show that aberrant localization and recruitment of FUS into stress granules (SGs) is a prerogative of the FUS mutant proteins and occurs only upon induction of stress in both undifferentiated iPSCs and spinal cord neural cells. Moreover, we show that the incorporation into SGs is proportional to the amount of cytoplasmic FUS, nicely correlating with the cytoplasmic delocalization phenotype of the different mutants. Therefore, the available iPSCs represent a very powerful system for understanding the correlation between FUS mutations, the molecular mechanisms of SG formation and ALS ethiopathogenesis

Hardware-Related Skin Erosion in Deep Brain Stimulation for Parkinson’s Disease: How Far Can We Go? An Illustrative Case Report

Skin erosion is a hardware-related complication commonly described after deep brain stimulation (DBS). Hardware exposure is often associated with the development of infection that can lead to implant removal. However, in selected cases, it is possible to manage skin erosion without having to remove the hardware. This article presents the case of a patient with recurrent skin erosions above the IPG, who underwent multiple surgeries. Given the failure of less invasive approaches, a more complex surgery with the employment of a pedunculated flap of pectoralis major in order to cover the IPG was attempted. Nevertheless, the IPG removal was finally unavoidable, resulting in a rapid decline in clinical performance. This illustrative case suggests how, in patients with sustained stimulation who benefit from a good degree of autonomy, it may be useful to use invasive surgical techniques to resolve skin erosions and save the DBS system. In spite of everything, sometimes complete or partial removal of the implant still becomes unavoidable, but this can lead to a severe worsening of PD symptoms. Definitive removal of the system should therefore be considered only in cases of frank infection or after failure of all other approaches

Prognostic role of histological regression in cutaneous melanoma

Histological regression in primary cutaneous melanoma occurs in 10-35% of cases. Although there is a large body of literature on histological regression and prognosis in melanoma patients, not clear data concerning this feature has been reported. In the current review, a comprehensive overview of the main aspects of regression will be provided. The clinical utility of regression as a prognostic factor has been challenged recently. Nowadays evidences reported that this feature is protective on SLN metastases. Despite its association with poor prognostic factors, it maintained a favourable prognostic role in many different survival studies

Sentinel Lymph Node Biopsy in Malignant Melanoma of the Head and Neck: A Single Center Experience

Purpose: This study evaluated the characteristics of patients with head and neck (H&N) melanoma who underwent sentinel lymph node biopsy (SNLB) and assessed the clinical course of patients categorizing subjects according to SLNB status and melanoma location (scalp area vs. non-scalp areas). Methods: Patients undergoing SLNB for melanoma of H&N from 2015 to 2021 were prospectively characterized according to sentinel lymph node (SLN) status. SPECT/CT had been previously performed. Patients were followed until the first adverse event to evaluate progression-free survival. Results: 93 patients were enrolled. SLNB was negative in 75 patients. The median Breslow index was higher for patients with positive SLNB compared with patients with negative SLNB. In addition, the Breslow index was higher for melanoma of the scalp compared with non-scalp melanoma. The median follow-up was 24.8 months. Progression occurred at the systemic level in the 62.5% of cases. There was a significant association between positive SLNB and progression (p-value p-value: 0.15). Conclusions: Scalp melanomas are more aggressive than other types of H&N melanomas. Sentinel lymph node status is the strongest prognostic criterion for recurrence