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The scientific community is continuously working to translate the novel biomedical techniques into effective medical treatments. CRISPR-Cas9 system (Clustered Regularly Interspaced Short Palindromic Repeats-9), commonly known as the “molecular scissor”, represents a recently developed biotechnology able to improve the quality and the efficacy of traditional treatments, related to several human diseases, such as chronic diseases, neurodegenerative pathologies and, interestingly, oral diseases. Of course, dental medicine has notably increased the use of biotechnologies to ensure modern and conservative approaches: in this landscape, the use of CRISPR-Cas9 system may speed and personalize the traditional therapies, ensuring a good predictability of clinical results. The aim of this critical overview is to provide evidence on CRISPR efficacy, taking into specific account its applications in oral medicine.

Spinocerebellar ataxia type 3 (SCA3) is an autosomal dominant neurodegenerative disorder caused by expansion of a polyglutamine (polyQ)-encoding CAG repeat in the ATXN3 gene. Because the ATXN3 protein regulates photoreceptor ciliogenesis and phagocytosis, we aimed to explore whether expanded polyQ ATXN3 impacts retinal function and integrity in SCA3 patients and transgenic mice. We evaluated the retinal structure and function in five patients with SCA3 and in a transgenic mouse model of this disease (YACMJD84.2, Q84) using optical coherence tomography (OCT) and electroretinogram (ERG). In the transgenic mice, we further: a) determined the retinal expression pattern of ATXN3 and the distribution of cones and rods using immunofluorescence (IF); and b) assessed the retinal ultrastructure using transmission electron microscopy (TEM). Some patients with SCA3 in our cohort revealed: i) reduced central macular thickness indirectly correlated with disease duration; ii) decreased thickness of the macula and the ganglion cell layer, and reduced macula volume inversely correlated with disease severity (SARA score); and iii) electrophysiological dysfunction of cones, rods, and inner retinal cells. Transgenic mice replicated the human OCT and ERG findings with aged homozygous Q84/Q84 mice showing a stronger phenotype accompanied by further thinning of the outer nuclear layer and photoreceptor layer and highly reduced cone and rod activities, thus supporting severe retinal dysfunction in these mice. In addition, Q84 mice showed progressive accumulation of ATXN3-positive aggregates throughout several retinal layers and depletion of cones alongside the disease course. TEM analysis of aged Q84/Q84 mouse retinas supported the ATXN3 aggregation findings by revealing the presence of high number of negative electron dense puncta in ganglion cells, inner plexiform and inner nuclear layers, and showed further thinning of the outer plexiform layer, thickening of the retinal pigment epithelium and elongation of apical microvilli. Our results indicate that retinal alterations detected by non-invasive eye examination using OCT and ERG could represent a biological marker of disease progression and severity in patients with SCA3.

A woman complaining of dyspnea and chest pain since childhood, was referred to our hospital with an initial diagnosis of biventricular hypertrophic cardiomyopathy. Multimodality imaging evaluation revealed massive right ventricular (RV) hypertrophy and severe RV outflow tract obstruction, with a final diagnosis of double chambered RV associated with small ventricular septal defect with right-to-left shunt and right partial anomalous pulmonary vein return. This represents an uncommon combination of congenital abnormalities, extremely rarely diagnosed in adulthood.

Cardiac magnetic resonance (CMR) is considered a primary tool for the diagnosis of acute myocarditis, due to its unique potential for non-invasive identification of the various hallmarks of the inflammatory response, with relevant impact on patient management and prognosis. Nonetheless, a marked variation in sensitivity and negative predictive value has been reported in the literature, reflecting the intrinsic drawbacks of current diagnostic criteria, which are based mainly on the use of conventional CMR pulse sequences. As a consequence, a negative exam cannot reliably exclude the diagnosis, especially in patients who do not present an infarct-like onset of disease. The introduction of new-generation mapping techniques further widened CMR potentials, allowing quantification of tissue changes and opening new avenues for non-invasive workup of patients with inflammatory myocardial disease. • CMR sensitivity varies in AM, reflecting its clinical polymorphism and the intrinsic drawbacks of LLc. • Semiquantitative approaches such as EGEr or T2 ratio have limited accuracy in diffuse disease forms. • T1 mapping allows objective quantification of inflammation, with no need to normalize measurements. • A revised protocol including T2-STIR, T1 mapping and LGE could be hypothesized to improve sensitivity.

Objectives Forty sites were involved in this multicenter and multivendor registry, which sought to evaluate indications, spectrum of protocols, impact on clinical decision making and safety profile of cardiac magnetic resonance (CMR). Materials and methods Data were prospectively collected on a 6-month period and included 3376 patients (47.2 ± 19 years; range 1–92 years). Recruited centers were asked to complete a preliminary general report followed by a single form/patient. Referral physicians were not required to exhibit any specific certificate of competency in CMR imaging. Results Exams were performed with 1.5 T scanners in 96% of cases followed by 3 T (3%) and 1 T (1%) magnets and contrast was administered in 84% of cases. The majority of cases were performed for the workup of inflammatory heart disease/cardiomyopathies representing overall 55.7% of exams followed by the assessment of myocardial viability and acute infarction (respectively 6.9% and 5.9% of patients). In 49% of cases the final diagnosis provided was considered relevant and with impact on patient's clinical/therapeutic management. Safety evaluation revealed 30 (0.88%) clinical events, most of which due to patient's preexisting conditions. Radiological reporting was recorded in 73% of exams. Conclusions CMR is performed in a large number of centers in Italy with relevant impact on clinical decision making and high safety profile.

"\"La tomografia computerizzata del cuore (CCT) è diventata uno strumento efficace in differenti contesti clinici. Lo sviluppo della tecnologia ha portato ad una progressiva espansione delle indicazioni con una concomitante riduzione della dose di radiazioni necessaria per l’esecuzione dell’indagine. Ancora oggi sono pochi i documenti delle maggiori società scientifiche internazionali che si esprimono sulle effettive modalità di utilizzo e sulle indicazioni cliniche della CCT; in particolare mancano delle linee guida complete. Questo documento rispecchia la visione del gruppo di lavoro della Sezione di Cardio-Radiologia della Società Italiana di Radiologia Medica in merito alle indicazioni correnti della CCT.\"" "\"Cardiac computed tomography (CCT) has grown as a useful means in different clinical contexts. Technological development has progressively extended the indications for CCT while reducing the required radiation dose. Even today there is little documentation from the main international scientific societies describing the proper use and clinical indications of CCT; in particular, there are no complete guidelines. This document reflects the position of the Working Group of the Cardiac Radiology Section of the Italian Society of Radiology concerning the indications for CCT.\""

Purpose. To survey the management of patients with neovascular age-related macular degeneration (nvAMD) in Spain. Methods. An observational retrospective multicenter study was conducted. The variables analyzed were sociodemographic characteristics, foveal and macular thickness, visual acuity (VA), type of treatment, number of injections, and the initial administration of a loading dose of an antiangiogenic drug. Results. 208 patients were followed up during 23.4 months in average. During the first and second years, patients received a mean of 4.5 +/- 1.8 and 1.6 +/- 2.1 injections of antiangiogenic drugs, and 5.4 +/- 2.8 and 3.6 +/- 2.2 follow-up visits were performed, respectively. The highest improvement in VA was observed at 3 months of follow-up, followed by a decrease in the response that stabilized above baseline values until the end of the study. Patients who received an initial loading dose presented greater VA gains than those without. Conclusions. Our results suggest the need for a more standardized approach in the management and diagnosis of nvAMD receiving VEGF inhibitors. To achieve the visual outcomes reported in pivotal trials, an early diagnosis, proactive approach (more treating than follow-up visits), and a close monitoring might be the key to successfully manage nvAMD.

Purpose. To review the proposed pathogenic mechanisms of age macular degeneration (AMD), as well as the role of antioxidants (AOX) and omega-3 fatty acids (omega-3) supplements in AMD prevention. Materials and Methods. Current knowledge on the cellular/molecular mechanisms of AMD and the epidemiologic/experimental studies on the effects of AOX and omega-3 were addressed all together with the scientific evidence and the personal opinion of professionals involved in the Retina Group of the OFTARED (Spain). Results. High dietary intakes of omega-3 and macular pigments lutein/zeaxanthin are associated with lower risk of prevalence and incidence in AMD. The Age-Related Eye Disease study (AREDS) showed a beneficial effect of high doses of vitamins C, E, beta-carotene, and zinc/copper in reducing the rate of progression to advanced AMD in patients with intermediate AMD or with one-sided late AMD. The AREDS-2 study has shown that lutein and zeaxanthin may substitute beta-carotene because of its potential relationship with increased lung cancer incidence. Conclusion. Research has proved that elder people with poor diets, especially with low AOX and omega-3 micronutrients intake and subsequently having low plasmatic levels, are more prone to developing AMD. Micronutrient supplementation enhances antioxidant defense and healthy eyes and might prevent/retard/modify AMD.

The PRIAMO study is a cross-sectional longitudinal observational study aimed at describing epidemiology and evolution of non-motor symptoms (NMS) in patients with different forms of parkinsonism recruited in 55 Italian centres and evaluated over 24 months. In this paper, we are reporting prevalence and clinical characteristics of NMS in patients with atypical and secondary parkinsonism. Out of 1307 consecutive patients with a diagnosis of parkinsonism, 83 patients had vascular parkinsonism (VP), 34 had multiple system atrophy (MSA), 30 had progressive supranuclear palsy (PSP), 14 had dementia with Lewy bodies (DLB) and 11 had corticobasal degeneration (CBD). MSA and DLB had the highest number of NMS domains and symptoms, respectively. Gastrointestinal symptoms, pain, urinary problems and postural instability due to orthostatic hypotension were most frequent in MSA. Sleep disturbances were also common with a prevalence of approximately 70% in all diagnostic groups but CBD (36%). Psychiatric symptoms and attention and memory impairment were frequently observed in all diagnoses but were most prevalent among DLB patients, whereas the prevalence of skin and respiratory disorders was rather low in all forms, ranging between 10 and 30%. Atypical parkinsonism patients also reported a low QoL, with no significant differences among the different forms, whereas PD and VP patients had a better QoL.

PURPOSE: To evaluate the diagnostic accuracy of 16-row multislice spiral computed tomography coronary angiography (16-MSCT-CA) for the non-invasive assessment of significant coronary artery stenosis. MATERIALS AND METHODS: We enrolled 40 patients (36 male, aged 59+/-11 yrs) with suspected obstructive coronary artery disease and a heart rate 2 mm in diameter were evaluated by two independent observers for the presence of significant coronary artery stenosis (= or >50%). Consensus reading was compared to quantitative coronary angiography. RESULTS: The average heart rate was 55+/-6 bpm. Of the 428 segments of = or >2.0 mm diameter 92 were significantly diseased. Without exclusion of any branches (428), the sensitivity, specificity, positive, and negative predictive values to identify = or >50% obstructed segments were 95.7% (88/92), 95.8% (322/336), 86.3% (88/102), and 98.8% (322/326), respectively. No occluded left main, left anterior descending, circumflex or right coronary artery segments remained undetected. CONCLUSIONS: 16-MSCT-CA in a selected low-heart-rate patient population provides high diagnostic accuracy in the evaluation of significant coronary artery stenosis.

In patients with myocarditis, early diagnosis and appropriate therapy are mandatory, as well as close clinical follow-up with particular regard to progression of disease and ventricular arrhythmia recurrences. The management of ventricular arrhythmias should follow current guidelines for ICD implantation, but new therapeutic options could be evaluated in these patients, such as combined epicardial/endocardial ablation and external wearable defibrillator. Particularly, depressed left ventricular ejection fraction (LVEF) represents the only risk marker for sudden cardiac death currently used in myocarditis, although the use of a single risk factor has limited utility. On this regard, combined analysis of myocardial tissue structure by cardiac magnetic resonance (CMR) and endomyocardial biopsy, in association with resting cardiac systolic function, could improve predictive accuracy for SCD in patients with myocarditis.

Neuropsychologic studies on Parkinson's disease have shown an impairment of specific cognitive functions and a greater evidence of dementia. Cognitive alterations are related to the gravity of some peculiar motor symptoms of the disease and show a major role of motor disturbances in intellectual disorders. The concept of bradyphrenia and subcortical dementia still seems to be suitable to define the cognitive disorders of Parkinson's disease.

Non-invasive cardiovascular imaging owns a pivotal role in the preoperative assessment of patient candidates for transcatheter aortic valve implantation (TAVI), providing a wide range of crucial information to select the patients who will benefit the most and have the procedure done safely. This document has been developed by a joined group of experts of the Italian Society of Cardiology and the Italian Society of Medical and Interventional Radiology and aims to produce an updated consensus statement about the pre-procedural imaging assessment in candidate patients for TAVI intervention. The writing committee consisted of members and experts of both societies who worked jointly to develop a more integrated approach in the field of cardiac and vascular radiology. Part 2 of the document will cover CT and MR angiography, standard medical reporting, and future perspectives.

Cardiac magnetic resonance (CMR) is considered an useful method in the evaluation of many cardiac disorders. Based on our experience and available literature, we wrote a document as a guiding tool in the clinical use of CMR. Synthetically we describe different cardiac disorders and express for each one a classification, I to IV, depending on the significance of diagnostic information expected.