Ectopic Cushing' syndrome caused by a neuroendocrine carcinoma of the mesentery

BACKGROUND: ACTH overproduction within the pituitary gland or ectopically leads to hypercortisolism. Here, we report the first case of Cushing' syndrome caused by an ectopic ACTH-secreting neuroendocrine carcinoma of the mesentery. Moreover, diagnostic procedures and pitfalls associated with ectopic ACTH-secreting tumors are demonstrated and discussed. CASE PRESENTATION: A 41 year-old man presented with clinical features and biochemical tests suggestive of ectopic Cushing's syndrome. First, subtotal thyroidectomy was performed without remission of hypercortisolism, because an octreotide scan showed increased activity in the left thyroid gland and an ultrasound revealed nodules in both thyroid lobes one of which was autonomous. In addition, the patient had a 3 mm hypoenhancing lesion of the neurohypophysis and a 1 cm large adrenal tumor. Surgical removal of the pituitary lesion within the posterior lobe did not improve hypercortisolism and we continued to treat the patient with metyrapone to block cortisol production. At 18-months follow-up from initial presentation, we detected an ACTH-producing neuroendocrine carcinoma of the mesentery by using a combination of octreotide scan, computed tomography scan, and positron emission tomography. Intraoperatively, use of a gamma probe after administration of radiolabeled (111)In-pentetreotide helped identify the mesenteric neuroendocrine tumor. After removal of this carcinoma, the patient improved clinically. Laboratory testing confirmed remission of hypercortisolism. An octreotide scan 7 months after surgery showed normal results. CONCLUSION: This case underscores the diagnostic challenge in identifying an ectopic ACTH-producing tumor and the pluripotency of cells, in this case of mesenteric cells that can start producing and secreting ACTH. It thereby helps elucidate the pathogenesis of neuroendocrine tumors. This case also suggests that patients with ectopic Cushing's syndrome and an octreotide scan positive in atypical locations may benefit from explorative radioguided surgery using (111)In-pentetreotide and a gamma probe

Near-field mapping of quantum dot emission from single-photonic crystal cavity modes

We directly investigate, by means of near-field spectroscopy, the spatial distribution of the optical cavity modes of 2D photonic crystal microcavities. Numerical simulations confirm that the photoluminescence maps of quantum dots embedded in the photonic structure qualitatively match the spatial modulation of the electric field intensity. (C) 2007 Elsevier B.V. All rights reserved

Lipid nanoparticle-mediated hit-and-run approaches yield efficient and safe in situ gene editing in human skin

Despite exciting advances in gene editing, the efficient delivery of genetic tools to extrahepatic tissues remains challenging. This holds particularly true for the skin, which poses a highly restrictive delivery barrier. In this study, we ran a head-to-head comparison between Cas9 mRNA or ribonucleoprotein (RNP)-loaded lipid nanoparticles (LNPs) to deliver gene editing tools into epidermal layers of human skin, aiming for in situ gene editing. We observed distinct LNP composition and cell-specific effects such as an extended presence of RNP in slow-cycling epithelial cells for up to 72 h. While obtaining similar gene editing rates using Cas9 RNP and mRNA with MC3-based LNPs (10-16%), mRNA-loaded LNPs proved to be more cytotoxic. Interestingly, ionizable lipids with a pK(a) ∼ 7.1 yielded superior gene editing rates (55%-72%) in two-dimensional (2D) epithelial cells while no single guide RNA-dependent off-target effects were detectable. Unexpectedly, these high 2D editing efficacies did not translate to actual skin tissue where overall gene editing rates between 5%-12% were achieved after a single application and irrespective of the LNP composition. Finally, we successfully base-corrected a disease-causing mutation with an efficacy of ∼5% in autosomal recessive congenital ichthyosis patient cells, showcasing the potential of this strategy for the treatment of monogenic skin diseases. Taken together, this study demonstrates the feasibility of an in situ correction of disease-causing mutations in the skin that could provide effective treatment and potentially even a cure for rare, monogenic, and common skin diseases

The 2020 UV emitter roadmap

Solid state UV emitters have many advantages over conventional UV sources. The (Al,In,Ga)N material system is best suited to produce LEDs and laser diodes from 400 nm down to 210 nm—due to its large and tuneable direct band gap, n- and p-doping capability up to the largest bandgap material AlN and a growth and fabrication technology compatible with the current visible InGaN-based LED production. However AlGaN based UV-emitters still suffer from numerous challenges compared to their visible counterparts that become most obvious by consideration of their light output power, operation voltage and long term stability. Most of these challenges are related to the large bandgap of the materials. However, the development since the first realization of UV electroluminescence in the 1970s shows that an improvement in understanding and technology allows the performance of UV emitters to be pushed far beyond the current state. One example is the very recent realization of edge emitting laser diodes emitting in the UVC at 271.8 nm and in the UVB spectral range at 298 nm. This roadmap summarizes the current state of the art for the most important aspects of UV emitters, their challenges and provides an outlook for future developments