Serum accumulation of the gut microbial metabolite trimethylamine N-oxide (TMAO) is associated with high caloric intake and type 2 diabetes (T2D). Impaired pancreatic β-cell function is a hallmark of diet-induced T2D, which is linked to hyperglycemia and hyperlipidemia. While TMAO production via the gut microbiome-liver axis is well defined, its molecular effects on metabolic tissues are unclear, since studies in various tissues show deleterious and beneficial TMAO effects. We investigated the molecular effects of TMAO on functional β-cell mass. We hypothesized that TMAO may damage functional β-cell mass by inhibiting β-cell viability, survival, proliferation, or function to promote T2D pathogenesis. We treated INS-1 832/13 β-cells and primary rat islets with physiological TMAO concentrations and compared functional β-cell mass under healthy standard cell culture (SCC) and T2D-like glucolipotoxic (GLT) conditions. GLT significantly impeded β-cell mass and function by inducing oxidative and endoplasmic reticulum (ER) stress. TMAO normalized GLT-mediated damage in β-cells and primary islet function. Acute 40µM TMAO recovered insulin production, insulin granule formation, and insulin secretion by upregulating the IRE1α unfolded protein response to GLT-induced ER and oxidative stress. These novel results demonstrate that TMAO protects β-cell function and suggest that TMAO may play a beneficial molecular role in diet-induced T2D conditions.
Background:
Atlanto-occipital dislocation (AOD) is a rare, highly morbid, and highly lethal injury that results from high-energy trauma and almost universally requires operative management for satisfactory outcomes. It can be difficult to identify the severity of injury at the time of presentation, and when diagnosis is delayed outcomes worsen significantly. Anatomic anomalies of the craniovertebral junction may further complicate its detection. When such anomalies are present either singly or in combination, they are known to cause space constraints which may increase the likelihood of spinal cord injury. Given that such anomalies and AOD are rare, few examples of patients with both are reported in the literature. Furthermore, it is not clear in what way patient management may be impacted in this context.
Case Description:
We will present a unique case of an 18-year-old patient with traumatic AOD and an intact neurologic examination who was found to have atlanto-occipital assimilation (AOA), platybasia, basilar invagination, and severe Chiari I malformation, who was treated effectively with non-operative management.
Conclusion:
Our case demonstrates the successful application of a non-operative treatment strategy in a carefully selected patient with AOD in the context of AOA.
Paraphimosis is a urologic emergency that requires prompt diagnosis to avoid potential morbidity. Diagnosis is made clinically and imaging findings have not been described. We will present the case of an 84-year-old man with a history of metastatic prostate cancer and prior pelvic external beam radiation therapy who presented to the emergency department with urinary retention. A urethral Foley catheter was placed for bladder decompression. He subsequently developed painful penile swelling and was found to have iatrogenic paraphimosis. Retrospective review of his contrast-enhanced CT of the abdomen and pelvis performed while in the emergency department before hospital admission revealed the relatively thickened, hypoattenuating prepuce located proximal to the corona of the glans penis, consistent with the clinical diagnosis. We will examine the imaging findings in this case and propose the novel “wet collar” sign to suggest the diagnosis of paraphimosis on CT.
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