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The contribution of distinct types of dorsal root ganglion neurons to chronic pain is unclear. Here, the authors molecularly profile non-human primate sensory neurons and show that genome-wide associations converge on two neuronal types with different genetic susceptibilities for chronic pain.

Summary: Vagal sensory neurons relay viscero- and somatosensory information from within the body and play a key role in maintaining physiological homeostasis. We recently characterized the diversity of vagal sensory neurons in the mouse using a single-cell transcriptomics approach. Here, we provide an in-depth protocol for the extraction of mouse vagal ganglia and the production of high-quality single-cell suspensions from this tissue. This effective protocol can also be applied for use with other peripheral and central neuron populations with few modifications.For complete details on the use and execution of this protocol, please refer to Kupari et al. (2019).

The recruitment of endogenous adult neural stem cells for brain repair is a promising regenerative therapeutic strategy. This strategy involves stimulation of multiple stages of adult neural stem cell development, including proliferation, self-renewal, and differentiation. Currently, there is a lack of a single therapeutic approach that can act on these multiple stages of adult neural stem cell development to enhance neural regeneration. Here we show that metformin, an FDA-approved diabetes drug, promotes proliferation, self-renewal, and differentiation of adult neural precursors (NPCs). Specifically, we show that metformin enhances adult NPC proliferation and self-renewal dependent upon the p53 family member and transcription factor TAp73, while it promotes neuronal differentiation of these cells by activating the AMPK-aPKC-CBP pathway. Thus, metformin represents an optimal candidate neuro-regenerative agent that is capable of not only expanding the adult NPC population but also subsequently driving them toward neuronal differentiation by activating two distinct molecular pathways.

The development of cell replacement strategies to repair the injured brain has gained considerable attention, with a particular interest in mobilizing endogenous neural stem and progenitor cells (known as neural precursor cells [NPCs]) to promote brain repair. Recent work demonstrated metformin, a drug used to manage type II diabetes, promotes neurogenesis. We sought to determine its role in neural repair following brain injury. We find that metformin administration activates endogenous NPCs, expanding the size of the NPC pool and promoting NPC migration and differentiation in the injured neonatal brain in a hypoxia-ischemia (H/I) injury model. Importantly, metformin treatment following H/I restores sensory-motor function. Lineage tracking reveals that metformin treatment following H/I causes an increase in the absolute number of subependyma-derived NPCs relative to untreated H/I controls in areas associated with sensory-motor function. Hence, activation of endogenous NPCs is a promising target for therapeutic intervention in childhood brain injury models.

Introduction: Low-attenuation non-calcified plaque (LAP) burden and vascular inflammation by pericoronary adipose tissue (PCAT) measured from coronary CT angiography (CCTA) have shown to be predictors of cardiovascular outcomes. We aimed to investigate the relationships of cardiometabolic risk factors including lipoprotein(a) and epicardial adipose tissue (EAT) with CCTA high-risk imaging biomarkers, LAP and vascular inflammation. Methods: The patient population consisted of consecutive patients who underwent CCTA for stable chest pain and had a complete cardiometabolic panel including lipoprotein(a). Plaque, PCAT and EAT were measured from CT using semiautomated software. Elevated LAP burden and PCAT attenuation were defined as ≥4% and ≥70.5 HU, respectively. The primary clinical end-point was a composite of myocardial infarction, revascularization or cardiovascular death. Results: A total of 364 consecutive patients were included (median age 56 years, 64% female); the majority of patients were of Hispanic (60%), and the rest were of non-Hispanic Black (21%), non-Hispanic White (6%) and non-Hispanic Asian (4%) race/ethnicity. The prevalence of elevated LAP burden and PCAT attenuation was 31 and 18%, respectively, while only 8% had obstructive stenosis. There were significant differences in plaque characteristics among different racial/ethnic groups (p

The evidence on recurrent pregnancy-related pericarditis is limited, and management strategies are based on case reports and expert opinion. We describe a patient with myopericarditis complicated by cardiac tamponade presenting shortly after her first pregnancy, which was then complicated by refractory recurrent pericarditis. She was treated with standard first line therapies, such as NSAIDs, corticosteroids, and colchicine, and eventually initiated on the purine analog, azathioprine. Out of fear of teratogenicity, she self-discontinued her maintenance medications and thereafter, her course was complicated by a recurrent flare of pericarditis during a subsequent pregnancy. Our case illustrates the significant burden on our patient due to the incessant nature of her disease and on the providers due to the therapeutic dilemmas associated with family planning and pregnancy. Further data is required on this unique clinical scenario, and patient-centered management by a multidisciplinary team is critical.