Brief communication: X-ray breast imaging experience at Azienda USL-IRCCS Reggio Emilia

Abstract This note describes the experience of the Azienda USL-IRCCS di Reggio Emilia (AUSL-RE) in the field of X-ray breast imaging in the AUSL-RE catchment area of the Emilia Romagna Region (RER). It focuses on new applications for digital mammography

Effect of image registration on 3D absorbed dose calculations in 177 Lu-DOTATOC Peptide Receptor Radionuclide Therapy

Peptide receptor radionuclide therapy (PRRT) is an effective MRT (molecular radiotherapy) treatment, which consists of multiple administrations of a radiopharmaceutical labelled with 177Lu or 90Y. Through sequential functional imaging a patient specific 3D dosimetry can be derived. Multiple scans should be previously co-registered to allow accurate absorbed dose calculations. The purpose of this study is to evaluate the impact of image registration algorithms on 3D absorbed dose calculation. A cohort of patients was extracted from the database of a clinical trial in PRRT. They were administered with a single administration of 177Lu-DOTATOC. All patients underwent 5 SPECT/CT sequential scans at 1 h, 4 h, 24 h, 40 h, 70 h post-injection that were subsequently registered using rigid and deformable algorithms. A similarity index was calculated to compare rigid and deformable registration algorithms. 3D absorbed dose calculation was carried out with the Raydose Monte Carlo code. The similarity analysis demonstrated the superiority of the deformable registrations (p < .001). Average absorbed dose to the kidneys calculated using rigid image registration was consistently lower than the average absorbed dose calculated using the deformable algorithm (90% of cases), with percentage differences in the range [−19; +4]%. Absorbed dose to lesions were also consistently lower (90% of cases) when calculated with rigid image registration with absorbed dose differences in the range [−67.2; 100.7]%. Deformable image registration had a significant role in calculating 3D absorbed dose to organs or lesions with volumes smaller than 100 mL. Image based 3D dosimetry for 177Lu-DOTATOC PRRT is significantly affected by the type of algorithm used to register sequential SPECT/CT scans

Inhibition of IL-1β signaling normalizes NMDA-dependent neurotransmission and reduces seizure susceptibility in a mouse model of Creutzfeldt-Jakob disease

Creutzfeldt-Jakob disease (CJD) is a neurodegenerative disorder caused by prion protein (PrP) misfolding, clinically recognized by cognitive and motor deficits, electroencephalographic abnormalities, and seizures. Its neurophysiological bases are not known. To assess the potential involvement of NMDA receptor (NMDAR) dysfunction, we analyzed NMDA-dependent synaptic plasticity in hippocampal slices from Tg(CJD) mice, which model a genetic form of CJD. Because PrP depletion may result in functional upregulation of NMDARs, we also analyzed PrP knock-out (KO) mice. Long-term potentiation (LTP) at the Schaffer collateral-commissural synapses in the CA1 area of ∼100-d-old Tg(CJD) mice was comparable to that of wild-type (WT) controls, but there was an inversion of metaplasticity, with increased GluN2B phosphorylation, which is indicative of enhanced NMDAR activation. Similar but less marked changes were seen in PrP KO mice. At ∼300 d of age, the magnitude of LTP increased in Tg(CJD) mice but decreased in PrP KO mice, indicating divergent changes in hippocampal synaptic responsiveness. Tg(CJD) but not PrP KO mice were intrinsically more susceptible than WT controls to focal hippocampal seizures induced by kainic acid. IL-1β-positive astrocytes increased in the Tg(CJD) hippocampus, and blocking IL-1 receptor signaling restored normal synaptic responses and reduced seizure susceptibility. These results indicate that alterations in NMDA-dependent glutamatergic transmission in Tg(CJD) mice do not depend solely on PrP functional loss. Moreover, astrocytic IL-1β plays a role in the enhanced synaptic responsiveness and seizure susceptibility, suggesting that targeting IL-1β signaling may offer a novel symptomatic treatment for CJD.SIGNIFICANCE STATEMENT Dementia and myoclonic jerks develop in individuals with Creutzfeldt-Jakob disease (CJD), an incurable brain disorder caused by alterations in prion protein structure. These individuals are prone to seizures and have high brain levels of the inflammatory cytokine IL-1β. Here we show that blocking IL-1β receptors with anakinra, the human recombinant form of the endogenous IL-1 receptor antagonist used to treat rheumatoid arthritis, normalizes hippocampal neurotransmission and reduces seizure susceptibility in a CJD mouse model. These results link neuroinflammation to defective neurotransmission and the enhanced susceptibility to seizures in CJD and raise the possibility that targeting IL-1β with clinically available drugs may be beneficial for symptomatic treatment of the disease

A systems-level analysis highlights microglial activation as a modifying factor in common forms of human epilepsy

The common human epilepsies are associated with distinct patterns of reduced cortical thickness, detectable on neuroimaging, with important clinical consequences. To explore underlying mechanisms, we layered MRI-based cortical structural maps from a large-scale epilepsy neuroimaging study onto highly spatially-resolved human brain gene expression data, identifying >2,500 genes overexpressed in regions of reduced cortical thickness, compared to relatively-protected regions. The resulting set of differentially-expressed genes shows enrichment for microglial markers, and in particular, activated microglial states. Parallel analyses of cell-specific eQTLs show enrichment in human genetic signatures of epilepsy severity, but not epilepsy causation. Post mortem brain tissue from humans with epilepsy shows excess activated microglia. In an experimental model, depletion of activated microglia prevents cortical thinning, but not the development of chronic seizures. These convergent data strongly implicate activated microglia in cortical thinning, representing a new dimension for concern and disease modification in the epilepsies, potentially distinct from seizure control

CARATTERIZZAZIONE VASCOLARE MULTIDISTRETTUALE NELLA DISSEZIONE CORONARICA SPONTANEA

BACKGROUND: La dissezione coronarica spontanea (SCAD) è una causa rara di sindrome coronarica acuta che coinvolge soprattutto giovani donne. Uno studio preliminare ha evidenziato che lesioni tipo FMD in distretti extracoronarici sono state identificate in circa l’80% delle pazienti con SCAD. Sulla base di questa associazione si ipotizza che la SCAD possa essere il risultato di un indebolimento della parete del vaso a causa di una sottostante lesione coronarica di FMD. SCOPO DELLO STUDIO: Identificare pattern vascolari, sia in termini di anomalie ultrastrutturali di parete che di proprietà meccaniche, in distretti extra-coronarici con simile calibro e istologia come le arterie radiali utilizzando, oltre ad approcci non invasivi già in uso comunemente in ambito di ricerca per la caratterizzazione vascolare dei pazienti, un nuovo approccio non invasivo basato su ultrasuoni (US) ad altissima risoluzione e di un sistema di analisi di immagini automatizzato semiautomatico, nelle pazienti con SCAD rispetto ai controlli sani. METODI: I partecipanti allo studio sono stati sottoposti ad indagini non invasive di caratterizzazione vascolare: valutazione della rigidità arteriosa mediante tonometria ad applanazione; US standard alle arterie carotidi comuni; US ad altissima frequenza a livello delle arterie radiali. In questa ultima indagine sono state acquisite 2 clip da 5 secondi ognuna, dell’arteria radiale di sinistra, con Vevo MD (70 MHz, FUJIFILM, VisualSonics). La parete dell’arteria radiale ha mostrato due interfacce ecogeniche: la prima (lume-media) e la seconda (media-avventizia). Sono stati così misurati lo spessore medio-intimale (IMT), spessore dell’avventizia (AT), lo spessore globale intima-media-avventizia (IMAT) e l’area trasversale di parete (WCSA=Wall Cross Sectional Area). Il disarray della parete è stato calcolato analizzando un singolo frame e tracciando una regione di interesse comprendente la parete arteriosa. Sono quindi stati analizzati i profili dei livelli di grigio di 20 linee verticali di pixel e calcolati i seguenti parametri: il valore medio del picco massimo per la prima e la seconda interfaccia iperecogena (Max 1 e 2); la radice dell’errore quadratico medio (RMSE= Root Mean Square Error) tra i picchi massimi dei 20 profili considerati, normalizzando per il valore medio del corrispondente picco (RMSE/max 1 e 2). RISULTATI: Sono stati arruolati 12 pazienti SCAD e 12 controlli (C) (donne 83% vs 83%; età 47,8±7,2 vs 45,2±13,8 anni, p=0.58; BMI 23,9±4,2 vs 24,1±3,0 kg/mq, p=0,55; BP media dx: 86,5±10,2 mmHg vs 78,4±9,5 mmHg, p=0,07; BP media sx: 89,8±9,9 mmHg vs 79,2±8,7 mmHg, p=0,01). 1- IMT è risultato significativamente aumentato nei pazienti SCAD (0,12±0,02 mm vs 0,18±0,05 mm, p=0,002), come pure AT (0,8±0,02 mm vs 0,10±0,03 mm, p=0,01) e IMAT (0,2±0,03 mm vs 0,3±0,01 mm, p=0,001). Il diametro interno dell’arteria radiale e il rapporto parete/lume erano simili nei due gruppi (0,13±0,04 vs 0,15±0,04, p=0,3). 2- Max 2 è risultato essere significativamente ridotto nel gruppo SCAD rispetto ai controlli (91,7±30,7 vs 121,7±24,7, p=0,02), mentre per Max1 la differenza era non significativa (155,6±20,6 vs 128,4±51,3, p=0,14). RMSE/max 1 e 2 sono risultati aumentati nel gruppo SCAD (0,8 ± 0,3 vs 1,9±1,5, p=0,03 e 1,2±0,9 vs 2,4±2,2, p=0,02). CONCLUSIONI: Le arterie radiali dei pazienti con SCAD sono risultate essere caratterizzate da un aumento dello spessore di parete e da un rimodellamento ipertrofico. I due strati iperecogeni hanno mostrato una diminuzione dell’ecogenicità e un aumento della disomogeneità. Tali risultati suggeriscono la presenza di alterazioni ultrastrutturali di parete anche in arterie extracardiache nei pazienti con SCAD. Pertanto la SCAD potrebbe essere la manifestazione clinica di una condizione sistemica

Il progetto regionale ILB. Competenze informative in biomedicina: presentazione del corso in e-learning

The paper has been delivered and discussed during the Workshop “Knowledge transfer in biomedicine: Information Literacy in Biomedicine (ILB) Project outputs”. The presentation summarizes the main aspects of the e-learning course - which is the first product of the Project – aimed to basic seeking skills’ training for Medical Doctors; the course is based on the electronic resources available in the Emilia Romagna Regional Health Service. In the background, the main aspects of scientific knowledge transfer in the clinical practice are discussed, with reference to Evidence- based medicine

ILB, an e-learning course for Hospital Doctors in the Regione Emilia Romagna: regenerating the medical librarian profession

Objectives. The ILB Project (Information Literacy in Biomedicine) funded a survey of the main information skills needs in Regione Emilia Romagna Hospitals; an e-learning course was devised in order to meet these needs. The purpose of this paper is twofold: 1) to explain the blended learning choice and its implications for the course 2) to show how these medical librarians could enhance their professional role in teaching through the use of the e-learning platform. Methods. The ILB Project team decided to use the e-learning methodology to change the way in which Doctors are trained; this choice was done to improve compliance with the course, as the delivery is much more flexible in term of time and space. In addition, these medical librarians were extensively trained to interact with the course participants through the e-learning platform (Moodle), to answer questions and provide further teaching and guidance in person and online. Consequently, right from the start, the focus of the Project was on the co-operative use of new communication technologies. Results. The Project achieved its two main objectives: to develop a new learning methodology for strategic information skills and to heighten awareness of the medical librarians’ professional knowledge, supporting the Doctors’ searching skills. Conclusions. New learning technologies can be used to promote changes in a collaborative to teaching and support. ILB has brought about this important and successful development

Laparoscopy in Emergency: Why Not? Advantages of Laparoscopy in Major Emergency: A Review

A laparoscopic approach is suggested with the highest grade of recommendation for acute cholecystitis, perforated gastroduodenal ulcers, acute appendicitis, gynaecological disorders, and non-specific abdominal pain (NSAP). To date, the main qualities of laparoscopy for these acute surgical scenarios are clearly stated: quicker surgery, faster recovery and shorter hospital stay. For the remaining surgical emergencies, as well as for abdominal trauma, the role of laparoscopy is still a matter of debate. Patients might benefit from a laparoscopic approach only if performed by experienced teams and surgeons which guarantee a high standard of care. More precisely, laparoscopy can limit damage to the tissue and could be effective for the reduction of the overall amount of cell debris, which is a result of the intensity with which the immune system reacts to the injury and the following symptomatology. In fact, these fragments act as damage-associated molecular patterns (DAMPs). DAMPs, as well as pathogen associated molecular patterns (PAMPs), are recognised by both surface and intracellular receptors of the immune cells and activate the cascade which, in critically ill surgical patients, is responsible for a deranged response. This may result in the development of progressive and multiple organ dysfunctions, manifesting with acute respiratory distress syndrome (ARDS), coagulopathy, liver dysfunction and renal failure. In conclusion, none of the emergency surgical scenarios preclude laparoscopy, provided that the surgical tactic could ensure sufficient cleaning of the abdomen in addition to resolving the initial tissue damage caused by the “trauma”

Evaluation of Multiple Responses Associated with Arsenic Tolerance and Accumulation in Pteris vittata L. Plants Exposed to High As Concentrations under Hydroponics

Chinese brake fern (Pteris vittata L.) is recognized as an arsenic hyperaccumulating plant. Mechanisms underlying this capability and the associated hypertolerance have been described even if not completely elucidated. In this study, with the aim to expand the knowledge on the matter, an experimental trial was developed to investigate an array of responses, at the morphological, physiological, and biochemical level, in P. vittata plants exposed to high As concentrations in a long-term experiment under hydroponics. Results confirmed the ability of fern plants to both tolerate and accumulate a remarkable amount of As, especially in fronds. Notably, in As-treated plants, a far higher As content was detected in young fronds compared to old fronds, with bioaccumulation (BCF) and translocation (Tf) factors in accordance. At the biochemical level, As treatment affected macro and micronutrient, thiol, and phytochelatin concentrations in fronds of treated plants differently than that of the control. Physiological measurements accounted for a reduction in the photosynthetic activity of As-treated plants in the absence of visual symptoms of damage. Overall, the observed As tolerance and accumulation processes were discussed, evidencing how young fronds developed during As treatment maintain their physiological status while accumulating a high As content. Such indications could be very useful to improve the effective utilization of this plant species for phytofiltration of As-polluted water

Phytotoxic impact of bifunctionalized silver nanoparticles (AgNPs-Cit-L-Cys) and silver nitrate (AgNO3) on chronically exposed callus cultures of Populus nigra L

Owing to the unique physicochemical properties and the low manufacturing costs, silver nanoparticles (AgNPs) have gained growing interest and their application has expanded considerably in industrial and agricultural sectors. The large-scale production of these nanoparticles inevitably entails their direct or indirect release into the environment, raising some concerns about their hazardous aspects. Callus culture represents an important tool in toxicological studies to evaluate the impact of nanomaterials on plants and their potential environmental risk. In this study, we investigated the chronic phytotoxic effects of different concentrations of novel bifunctionalized silver nanoparticles (AgNPs-Cit-L-Cys) and silver nitrate (AgNO3) on callus culture of Populus nigra L., a pioneer tree species in the riparian ecosystem. Our results showed that AgNPs-Cit-L-Cys were more toxic on poplar calli compared to AgNO3, especially at low concentration (2.5 mg/L), leading to a significant reduction in biomass production, accompanied by a decrease in protein content, a significant increase in both lipid peroxidation level, ascorbate peroxidase (APX), and catalase (CAT) enzymatic activities. In addition, these findings suggested that the harmful activity of AgNPs-Cit-L-Cys might be correlated with their physicochemical properties and not solely attributed to the released Ag+ ions and confirmed that AgNPs-Cit-L-Cys phytoxicity is associated to oxidative stress