Search

Andrea Taloni,1,* Giulia Coco,2,* Davide Rastelli,3 Giacinta Buffon,2 Vincenzo Scorcia,1 Giuseppe Giannaccare4 1Department of Ophthalmology, University “Magna Graecia” of Catanzaro, Catanzaro, Italy; 2Department of Clinical Sciences and Translational Medicine, University of Rome Tor Vergata, Rome, Italy; 3Department of Ophthalmology, Policlinico Casilino, Rome, Italy; 4Eye Clinic, Department of Surgical Sciences, University of Cagliari, Cagliari, Italy*These authors contributed equally to this workCorrespondence: Giuseppe Giannaccare, Full Professor of Ophthalmology, Eye Clinic, Department of Surgical Sciences, University of Cagliari, Via Università 40, Cagliari, 09124, Italy, Tel +0039 09613647041, Fax +0039 09613647094, Email giuseppe.giannaccare@gmail.comAbstract: Diabetic macular edema (DME) is a common sight-threatening complication of diabetic retinopathy (DR) and the leading cause of severe visual impairment among the working-age population. Several therapeutic options are available for the management of DME, including intravitreal corticosteroids. They have been traditionally used as second-line treatment, due to the risk of intraocular pressure increase and cataract-related adverse events. However, attention has recently been focused on the primary or early use of intravitreal corticosteroids, due to growing evidence of the crucial role of inflammation in the pathogenesis of DME. Furthermore, intravitreal steroid implants offer the additional advantage of a longer duration of action compared to anti-vascular endothelial growth factor agents (anti-VEGF). This review aims to summarize the available evidence on the efficacy and safety profile of dexamethasone (DEX) intravitreal implant, with a specific focus on clinical scenarios in which it might be considered or even preferred as first-line treatment option by adequate selection of patients, considering both advantages and possible adverse events. Patients with contraindications to anti-VEGF, DME with high inflammatory OCT biomarkers, pseudophakic patients and phakic patients’ candidates to cataract surgery as well as vitrectomized eyes may all benefit from first-line DEX implant. Additionally, DME not responders to anti-VEGF should be considered for a switch to DEX implant and a combination therapy of DEX implant and anti-VEGF could be a valid option in severe and persistent DME.Keywords: diabetic macular edema, DME, dexamethasone intravitreal implant, DEX implant, corticosteroids, Ozurdex

Background & Aims: RET tyrosine kinase is necessary for enteric nervous system development. Loss-of-function RET mutations cause Hirschsprung disease (HSCR), in which infants are born with aganglionic bowel. Despite surgical correction, patients with HSCR often experience chronic defecatory dysfunction and enterocolitis, suggesting that RET is important after development. To test this hypothesis, we determined the location of postnatal RET and its significance in gastrointestinal (GI) motility., Methods: Ret CFP/+ mice and human transcriptional profiling data were studied to identify the enteric neuronal and epithelial cells that express RET. To determine whether RET regulates gut motility in vivo, genetic, and pharmacologic approaches were used to disrupt RET in all RET-expressing cells, a subset of enteric neurons, or intestinal epithelial cells., Results: Distinct subsets of enteric neurons and enteroendocrine cells expressed RET in the adult intestine. RET disruption in the epithelium, rather than in enteric neurons, slowed GI motility selectively in male mice. RET kinase inhibition phenocopied this effect. Most RET + epithelial cells were either enterochromaffin cells that release serotonin or L-cells that release peptide YY (PYY) and glucagon-like peptide 1 (GLP-1), both of which can alter motility. RET kinase inhibition exaggerated PYY and GLP-1 release in a nutrient-dependent manner without altering serotonin secretion in mice and human organoids. PYY receptor blockade rescued dysmotility in mice lacking epithelial RET., Conclusions: RET signaling normally limits nutrient-dependent peptide release from L-cells and this activity is necessary for normal intestinal motility in male mice. These effects could contribute to dysmotility in HSCR, which predominantly affects males, and uncovers a mechanism that could be targeted to treat post-prandial GI dysfunction., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

The characterization of particle accelerator induced neutron fields is challenging but fundamental for research and industrial activities, including radiation protection, neutron metrology, developments of neutron detectors for nuclear and high-energy physics, decommissioning of nuclear facilities, and studies of neutron damage on materials and electronic components. This work reports on the study of a novel approach to the experimental characterization of neutron spectra at two complex accelerator environments, namely the CERF, a high-energy mixed reference field at CERN in Geneva, and the Bern medical cyclotron laboratory, a facility used for multi-disciplinary research activities, and for commercial radioisotope production for nuclear medicine. Measurements were performed through an innovative active neutron spectrometer called DIAMON, a device developed to provide in real time neutron energy spectra without the need of guess distributions. The intercomparison of DIAMON measurements with reference data, Monte Carlo simulations, and with the well-established neutron monitor Berthold LB 6411, has been found to be highly satisfactory in all conditions. It was demonstrated that DIAMON is an almost unique device able to characterize neutron fields induced by hadrons at 120 GeV/c as well as by protons at 18 MeV colliding with different materials. The accurate measurement of neutron spectra at medical cyclotrons during routine radionuclide production for nuclear medicine applications is of paramount importance for the facility decommissioning. The findings of this work are the basis for establishing a methodology for producing controlled proton-induced neutron beams with medical cyclotrons., (© 2022. The Author(s).)

Functional gastrointestinal disorders (FGIDs) have prominent sex differences in incidence, symptoms, and treatment response that are not well understood. Androgens are steroid hormones present at much higher levels in males than females and could be involved in these differences. In adults with irritable bowel syndrome (IBS), a FGID that affects 5% to 10% of the population worldwide, we found that free testosterone levels were lower than those in healthy controls and inversely correlated with symptom severity. To determine how this diminished androgen signaling could contribute to bowel dysfunction, we depleted gonadal androgens in adult mice and found that this caused a profound deficit in gastrointestinal transit. Restoring a single androgen hormone was sufficient to rescue this deficit, suggesting that circulating androgens are essential for normal bowel motility in vivo. To determine the site of action, we probed androgen receptor expression in the intestine and discovered, unexpectedly, that a large subset of enteric neurons became androgen-responsive upon puberty. Androgen signaling to these neurons was required for normal colonic motility in adult mice. Taken together, these observations establish a role for gonadal androgens in the neural regulation of bowel function and link altered androgen levels with a common digestive disorder.