Design of a dedicated circular coil for Magnetic Resonance Spectroscopy studies in small phantoms and animal acquisition with a 3 Tesla Magnetic Resonance clinical scanner

Abstract Introduction: Magnetic Resonance Spectroscopy (MRS) is a very powerful tool to explore the tissue components, by allowing a selective identification of molecules and molecular distribution mapping. Due to intrinsic Signal-to-Noise Ratio limitations (SNR), MRS in small phantoms and animals with a clinical scanner requires the design and development of dedicated radiofrequency (RF) coils, a task of fundamental importance. In this article, the authors describe the simulation, design, and application of a 1H transmit/receive circular coil suitable for MRS studies in small phantoms and small animal models with a clinical 3T scanner. In particular, the circular coil could be an improvement in animal experiments for tumor studies in which the lesions are localized in specific areas. Material and methods: The magnetic field pattern was calculated using the Biot–Savart law and the inductance was evaluated with analytical calculations. Finally, the coil sensitivity was measured with the perturbing sphere method. Successively, a prototype of the coil was built and tested on the workbench and by the acquisition of MRS data. Results: In this work, we demonstrate the design trade-offs for successfully developing a dedicated coil for MRS experiments in small phantoms and animals with a clinical scanner. The coil designed in the study offers the potential for obtaining MRS data with a high SNR and good spectral resolution. Conclusions: The paper provides details of the design, modelling, and construction of a dedicated circular coil, which represents a low cost and easy to build answer for MRS experiments in small samples with a clinical scanner

Inversion of perceived direction of motion caused by spatial undersampling in two children with periventricular leukomalacia

We report here two cases of two young diplegic patients with cystic periventricular leukomalacia who systematically, and with high sensitivity, perceive translational motion of a random-dot display in the opposite direction. The apparent inversion was specific for translation motion: Rotation and expansion motion were perceived correctly, with normal sensitivity. It was also specific for random-dot patterns, not occurring with gratings. For the one patient that we were able to test extensively, contrast sensitivity for static stimuli was normal, but was very low for direction discrimination at high spatial frequencies and all temporal frequencies. His optokinetic nystagmus movements were normal but he was unable to track a single translating target, indicating a perceptual origin of the tracking deficit. The severe deficit for motion perception was also evident in the seminatural situation of a driving simulation video game. The perceptual deficit for translational motion was reinforced by functional magnetic resonance imaging studies. Translational motion elicited no response in the MT complex, although it did produce a strong response in many visual areas when contrasted with blank stimuli. However, radial and rotational motion produced a normal pattern of activation in a subregion of the MT complex. These data reinforce the existent evidence for independent cortical processing for translational, and circular or radial flow motion, and further suggest that the two systems have different vulnerability and plasticity to prenatal damage. They also highlight the complexity of visual motion perception, and how the delicate balance of neural activity can lead to paradoxical effects such as consistent misperception of the direction of motion. We advance a possible explanation of a reduced spatial sampling of the motion stimuli and report a simple model that simulates well the experimental results

Simulation, design, and test of an elliptical surface coil for magnetic resonance imaging and spectroscopy

AbstractThe simplest design of surface coils for magnetic resonance imaging (MRI) applications is circular and square loops, both producing a magnetic field perpendicular to the coil plane in the central region‐of‐interest (ROI), with an amplitude that decreases along the coil axis. However, a surface coil constituted by a loop with different geometry could be necessary when particular field‐of‐views (FOVs) are desired, especially for performing imaging in an elongated region. This can be achieved by using an elliptical loop, which can guarantee a wide longitudinal FOV and a good penetration in deep sample regions. This work proposes the application of a method for elliptical coil Signal‐to‐Noise Ratio (SNR) estimation previously developed for circular and square loop design, in which coil inductance and resistance are analytically calculated and the magnetic field pattern is estimated using the magnetostatic approach, while the sample‐induced resistance is calculated with the vector potential calculation method. In the second part of the paper, we propose the simulation and the design of a transmit/receive elliptical coil for MRI in mice with a 3T clinical scanner. We also evaluated the coil performance in a preliminary magnetic resonance spectroscopy (MRS) study in phantom

Incidence of Second Primary Cancer in Transplanted Patients

Background. Solid organ transplanted patients have a three-to fourfold higher lifetime risk of developing a cancer than the general population. However, the incidence of a second primary cancer in transplanted patients has never been studied, despite the fact that the presence of regular follow-ups and the increased survival of these patients make them a very attractive model. Methods. We investigated the incidence of a second primary cancer (SPC) in 7,636 patients who underwent a kidney, liver, lung or heart transplant between 1970 and 2004, and were followed-up for 51,819 person-years. Results. During the follow-up, 499 subjects developed a first cancer (annual incidence: 98.6ϫ10,000 PY), and 22 of them developed a SPC (annual incidence: 3.9ϫ10,000 PY). The annual incidence of a SPC in the transplanted patients who developed a first cancer was 107.8ϫ10,000 PY, giving a standardized incidence ratio of 1.1 (95% CI: 0.83-1.41). Conclusions. This result shows that the incidence of the SPC was the same as the incidence of a first cancer. Our study does not indicate an increased risk of SPC in transplanted subjects who already suffered a first malignancy

Small non-coding RNA landscape is modified by GPAT2 silencing in MDA-MB-231 cells

Glycerol-3-phosphate acyltransferase-2 is a member of “cancer-testis gene” family. Initially linked to lipid metabolism, this gene has been recently found involved also in PIWI-interacting RNAs biogenesis in germline stem cells. To investigate its role in piRNA metabolism in cancer, the gene was silenced in MDA-MB-231 breast cancer cells and small RNA sequencing was applied. PIWI-interacting RNAs and tRNA-derived fragments expression profiles showed changes following GPAT2 silencing. Interestingly, a marked shift in length distribution for both small RNAs was detected in GPAT2-silenced cells. Most downregulated PIWI-interacting RNAs are single copy in the genome, intragenic, hosted in snoRNAs and previously found to be upregulated in cancer cells. Putative targets of these PIWI-interacting RNAs are linked to lipid metabolism. Downregulated tRNA derived fragments derived from, socalled ‘differentiation tRNAs’, whereas upregulated ones derived from proliferationlinked tRNAs. miRNA amounts decrease after Glycerol-3-phosphate acyltransferase-2 silencing and functional enrichment analysis of deregulated miRNA putative targets point to mitochondrial biogenesis, IGF1R signaling and oxidative metabolism of lipids and lipoproteins. In addition, miRNAs known to be overexpressed in breast cancer tumors with poor prognosis where found downregulated in GPAT2-silenced cells. In conclusion, GPAT2 silencing quantitatively and qualitatively affects the population of PIWI-interacting RNAs, tRNA derived fragments and miRNAs which, in combination, result in a more differentiated cancer cell phenotype.Centro de Investigaciones Inmunológicas Básicas y AplicadasInstituto de Investigaciones Bioquímicas de La Plat

Outcomes of pregnancies after kidney transplantation: lessons learned from CKD. A comparison of transplanted, nontransplanted chronic kidney disease patients and low-risk pregnancies: a multicenter nationwide analysis.

BACKGROUND: Kidney transplantation (KT) may restore fertility in CKD. The reasons why materno-foetal outcomes are still inferior to the overall population are only partially known. Comparison with the CKD population may offer some useful insights for management and counselling.Aim of this study was to analyse the outcomes of pregnancy after KT, compared with a large population of non-transplanted CKD patients and with low-risk control pregnancies, observed in Italy the new millennium. METHODS: We selected 121 live-born singletons after KT (Italian study group of kidney in pregnancy, national coverage about 75%), 610 live-born singletons in CKD and 1418 low-risk controls recruited in 2 large Italian Units, in the same period (2000-2014). The following outcomes were considered: maternal and foetal death; malformations; preterm delivery; small for gestational age baby (SGA); need for the neonatal intensive care unit (NICU); doubling of serum creatinine or increase in CKD stage. Data were analysed according to kidney diseases, renal function (staging according to CKD-EPI), hypertension, maternal age, partity, ethnicity. RESULTS: Materno-foetal outcomes are less favourable in CKD and KT as compared with the low-risk population. CKD stage and hypertension are important determinants of results. KT patients with e-GFR >90 have worse outcomes compared with CKD stage 1 patients; the differences level off when only CKD patients affected by glomerulonephritis or systemic diseases ('progressive CKD') are compared with KT. In the multivariate analysis, risk for preterm and early-preterm delivery was linked to CKD stage (2-5 versus 1: RR 3.42 and 3.78) and hypertension (RR 3.68 and 3.16) while no difference was associated with being a KT or a CKD patient. CONCLUSIONS: The materno-foetal outcomes in patients with kidney transplantation are comparable with those of nontransplanted CKD patients with similar levels of kidney function impairment and progressive and/or immunologic kidney diseas

Safety Profile of Molnupiravir in the Treatment of COVID-19: A Descriptive Study Based on FAERS Data

Concerns have been raised about the actual benefit and safety of molnupiravir, a new antiviral treatment for coronavirus disease 2019 (COVID-19). In order to provide additional evidence to support its use, we aimed to evaluate the real safety profile based on post-marketing pharmacovigilance data. Molnupiravir safety data were captured from the FDA Adverse Event Reporting System (FAERS). We performed a descriptive analysis of the baseline demographic characteristics of patients who experienced at least one adverse drug reaction (ADRs) related to molnupiravir, and then evaluated those most frequently reported. As of 31 March 2022, 612 reports of ADRs related to molnupiravir were submitted to the FDA, 301 (49.18%) were related to females and 281 (45.92%) to males. Most reports (524; 85.62%) were submitted by healthcare professionals and 345 (56.37%) concerned serious outcomes. The most common reported ADRs were diarrhoea (57; 4.51%), rash (36; 2.85), nausea (29; 2.30%), and COVID-19 pneumonia (22; 1.74%). The most frequent adverse reactions reported with molnupiravir in the U.S. post-marketing experience are consistent with the safety evaluation of the antiviral medicine. Even if no evident safety concerns emerged, an unexpectedly high rate of serious adverse reactions together with a few cases of potential new adverse reactions occurred

Farmaci EMEA ed innovazione terapeutica

L’innovazione in farmacoterapia è tema molto attuale e fonte di numerosi dibattiti per quanti, a vario titolo, s’interessano di farmaci: agenzie regolatorie, aziende produttrici, operatori sanitari, ricercatori, pazienti e cittadini. In particolare, le agenzie regolatorie e i “policy-makers”, essendo chiamati a decidere come meglio allocare le risorse economiche disponibili, sono tra i soggetti maggiormente interessati