Abstract Multiple sclerosis (MS) is an inflammatory, demyelinating disease of the central nervous system (CNS) that afflicts more than 400,000 people in the US. Although the etiology of the disease is unknown, pathogenic T cells are thought to underlie MS immune pathology. In contrast to the current paradigm, we recently showed that MS patients harbor CNS-specific CD8+ T regulatory cells (CD8 Tregs) that are deficient during disease relapse. In the current study, we demonstrate that the neuroantigen-specific CD8 Tregs were cytolytic and eliminated pathogenic CD4+ T cells. Sorting of CD8+ T cells using an array of surface cellular markers revealed that the CD8 Tregs were terminally differentiated (CD27-, CD45RO-). The CD8 Treg-mediated suppression was perforin, granzyme B, and interferon-γ-dependent. Interestingly, we found that MS patients with acute disease exacerbation displayed a significant loss (averaging 25%) in the terminally differentiated CD8+ T cells, with a concurrent loss in perforin and granzyme B expression. In order to restore the regulatory potential of impaired CD8 Tregs during exacerbation, we pre-treated exacerbation-derived bulk CD8+ T cells with the cytokine IL-12 and significantly increased the suppressive capability of the cells by ~48% through upregulation of granzyme B and perforin. Our studies uncover the immune suppressive mechanism of neuroantigen-specific CD8 Tregs, and may contribute to the design of clinically relevant immune therapies for MS patients.
Increasing evidence suggests that open reduction and internal fixation of condylar base fractures in adults results in improved outcomes in regard to interincisal opening, jaw movement, pain, and malocclusion. However, most of the condylar fractures are managed by maxillomandibular fixation alone due to the need for specialized training and equipment. Our aim was to present an algorithm for condylar base fractures to simplify surgical management.A retrospective review was performed of patients (n = 22) with condylar base fractures treated from 2016 to 2020. Patients who presented with operative fractures that require open treatment underwent 1 of 2 different techniques depending on the fracture type: a preauricular approach with a transoral approach if the condyle was dislocated (n = 2) or a transoral only approach (n = 20) in nondislocated cases. Operative time, occlusion, range of motion, and postoperative complications were assessed.Condylar base fractures were combined with other mandibular fractures in 16 of 22 patients. Patients with condylar dislocation were managed with a preauricular approach with a secondary transoral incision (n = 2, median 147 minutes). Those without dislocation were treated with a transoral approach (n = 20, median 159 minutes). Most patients were restored to their preoperative occlusion without long-term complications.We present a simplified algorithm for treating condylar base fractures. Our case series suggests that reduction in operative time and clinical success can be achieved with open reduction and internal fixation using a transoral approach alone or in combination with a preauricular approach for dislocated fractures.
Summary Plant triacylglycerols ( TAG s), or vegetable oils, provide approximately 25% of dietary calories to humans and are becoming an increasingly important source of renewable bioenergy and industrial feedstocks. TAG s are assembled by multiple enzymes in the endoplasmic reticulum from building blocks that include an invariable glycerol backbone and variable fatty acyl chains. It remains a challenge to elucidate the mechanism of synthesis of hundreds of different TAG species in planta. One reason is the lack of an efficient analytical approach quantifying individual molecular species. Here we report a rapid and quantitative TAG profiling approach for Arabidopsis seeds based on electrospray ionization tandem mass spectrometry with direct infusion and multiple neutral loss scans. The levels of 93 TAG molecular species, identified by their acyl components, were determined in Arabidopsis seeds. Quantitative TAG pattern analyses revealed that the TAG assembly machinery preferentially produces TAG s with one elongated fatty acid. The importance of the selectivity in oil synthesis was consistent with an observation that an Arabidopsis mutant overexpressing a patatin‐like phospholipase had enhanced seed oil content with elongated fatty acids. This quantitative TAG profiling approach should facilitate investigations aimed at understanding the biochemical mechanisms of TAG metabolism in plants.
