Testicular Cancer and Paraneoplastic Encephalitis: A Review of the Current Literature.

INTRODUCTION: Paraneoplastic encephalitis (PE) represents a rare but significant complication in patients with testicular cancer (TC). Given the paucity of comprehensive literature on this topic, our review seeks to consolidate current knowledge and provide evidence-based recommendations for the diagnosis, prognosis, and management of PE in the context of TC. MATERIALS AND METHODS: In adherence to PRISMA guidelines, a systematic literature review was conducted from 1950 to April 2024 using PubMed. The search focused on articles where TC was identified as the primary etiology of PE. The Mixed Methods Appraisal Tool and the Oxford Centre for Evidence-Based Medicine's levels of evidence tool were employed for assessing study quality, and a thematic analysis was conducted to identify trends and patterns. RESULTS: Out of 91 articles identified, 29 met the inclusion criteria, encompassing 5 retrospective chart reviews, 3 case series, and 22 case reports. Findings indicate that PE symptoms can manifest at any stage of TC-before tumor detection, during treatment, or even years posttreatment. A notable observation was the frequent oversight of microscopic testicular tumors in ultrasound imaging, leading to diagnostic delays. The outcomes of PE in the context of TC were diverse, reflecting the heterogeneity of the studies included. CONCLUSION: PE, although rare, is a critical consideration in patients with TC presenting with neuropsychiatric symptoms. Early recognition and appropriate diagnostic workup, including consideration for microscopic neoplasms, are essential for timely intervention and improved patient outcomes.

Total Chemical Synthesis of Glycosylated TREM2 Ectodomain.

Mutations in a microglia-associated gene TREM2 increase the risk of Alzheimer's disease. Currently, structural and functional studies of TREM2 mainly rely on recombinant TREM2 proteins expressed from mammalian cells. However, using this method, it is difficult to achieve site-specific labeling. Here, we present the total chemical synthesis of the 116 amino acid TREM2 ectodomain. Rigorous structural analysis ensured correct structural fold after refolding. Treating microglial cells with refolded synthetic TREM2 enhanced microglial phagocytosis, proliferation, and survival. We also prepared TREM2 constructs with defined glycosylation patterns and found that glycosylation at N79 is critical to the thermal stability of TREM2. This method will provide access to TREM2 constructs with site-specific labeling, such as fluorescent labeling, reactive chemical handles, and enrichment handles, to further advance our understanding of TREM2 in Alzheimer's disease.