Characterization of the thymus in Lrp4 myasthenia gravis: Four cases

Myasthenia gravis (MG) is an autoimmune disease of the neuromuscular junction. Most patients have pathogenic autoantibodies against the acetylcholine receptor (AChR). In the last years a novel subpopulation of MG patients has been described that harbors antibodies against low-density lipoprotein receptor-related protein 4 (Lrp4), another postsynaptic neuromuscular antigen. In early-onset AChR MG (EOMG), the thymus plays an important role in immunopathogenesis, and early thymectomy is beneficial. It is still unknown if the thymus plays any role in Lrp4-MG. In this pilot study, we compared thymus samples from four patients with Lrp4-MG (one pre-treated with immunosuppressive drugs), four non-MG controls and five EOMG patients (not pretreated with immunosuppressive drugs). Immunohistochemistry of the Lrp4-MG thymi revealed normal architecture, with normal numbers and distribution of B-cells, lymphoid follicles and Hassall's corpuscles. Primary CD23⁺ lymphoid follicles were similarly infrequent in Lrp4-MG and control thymic sections. In none of the control or Lrp4-MG thymi did we find secondary follicles with CD10⁺ germinal centers. These were evident in 2 of the 5 EOMG thymi, where primary lymphoid follicles were also more frequent on average, thus showing considerable heterogeneity between patients. Even if characteristic pathological thymic changes were not observed in the Lrp4 subgroup, we cannot exclude a role for the thymus in Lrp4-MG pathogenesis, since one Lrp4-MG patient went into clinical remission after thymectomy alone (at one year follow-up) and one more improved after thymectomy in combination with immunosuppressive therapy.     

The emerging role of stimulator of interferons genes signaling in sepsis: Inflammation,autophagy, and cell death

Stimulator of interferons genes (STING) is an adaptor protein that plays a critical role in the secretion of type I interferons and pro‐inflammatory cytokines in response to cytosolic nucleic acid. Recent research indicates the involvement of the STING pathway in uncontrolled inflammation, sepsis, and shock. STING signaling is significantly up‐regulated in human sepsis, and STING agonists are suggested to contribute to the pathogenesis of sepsis and shock. Nevertheless, little is known about the consequences of activated STING‐mediated signaling during sepsis. It has been shown that aberrant activation of the STING‐dependent way can result in increased inflammation, type I interferons responses, and cell death (including apoptosis, necroptosis, and pyroptosis). In addition, autophagy modulation has been demonstrated to protect against multiple organs injuries in animal sepsis model. However, impaired autophagy may contribute to the aberrant activation of STING signaling, leading to uncontrolled inflammation and cell death. Here we present a comprehensive review of recent advances in the understanding of STING signaling, focusing on the regulatory mechanisms and the roles of this pathway in sepsis.     

Beyond the Bayley: Neurocognitive Assessments of Development During Infancy and Toddlerhood

The use of global, standardized instruments is conventional among clinicians and researchers interested in assessing neurocognitive development. Exclusively relying on these tests for evaluating effects may underestimate or miss specific effects on early cognition. The goal of this review is to identify alternative measures for possible inclusion in future clinical trials and interventions evaluating early neurocognitive development. The domains included for consideration are attention, memory, executive function, language, and socioemotional development. Although domain-based tests are limited, as psychometric properties have not yet been well-established, this review includes tasks and paradigms that have been reliably used across various developmental psychology laboratories.