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Nowadays, current guidelines on acute coronary syndrome (ACS) provide recommendations mainly based on the clinical presentation. However, greater attention is being directed to the specific pathophysiology underlying ACS, considering that plaque destabilization and rupture leading to luminal thrombotic obstruction is not the only pathway involved, albeit the most recognized. In this review, we discuss how intracoronary imaging and biomarkers allow the identification of specific ACS endotypes, leading to the recognition of different prognostic implications, tailored management strategies, and new potential therapeutic targets. Furthermore, different strategies can be applied on a personalized basis regarding antithrombotic therapy, non-culprit lesion revascularization, and microvascular obstruction (MVO). With respect to myocardial infarction with non-obstructive coronary arteries (MINOCA), we will present a precision medicine approach, suggested by current guidelines as the mainstay of the diagnostic process and with relevant therapeutic implications. Moreover, we aim at illustrating the clinical implications of targeted strategies for ACS secondary prevention, which may lower residual risk in selected patients.

Coronary chronic total occlusions (CTO) are an increasingly frequent entity in clinical practice and represent a challenging percutaneous coronary intervention (PCI) scenario. Despite data from randomized trials that have not yet demonstrated a clear benefit of CTO recanalization, the widespread of CTO-PCI has substantially increased. The improvement in operators' techniques, equipment, and training programs has led to an improvement in the success rate and safety of these procedures, which will represent an important field of future development of PCI. The present review will summarize clinical outcomes and technical and safety issues of CTO revascularization with the aim to guide clinical daily cath-lab practice.

Coronary vasomotor disorders (CVD) are characterized by transient hypercontraction of coronary vascular smooth muscle cells, leading to hypercontraction of epicardial and/or microvascular coronary circulation. CVDs play a relevant role in the pathogenesis of ischemia, angina and myocardial infarction with non-obstructive coronary arteries. Invasive provocative testing with intracoronary Acetylcholine (ACh) administration is the gold standard tool for addressing CVD, providing relevant therapeutic and prognostic implications. However, safety concerns preclude the widespread incorporation of the ACh test into clinical practice. The purpose of this review is to shed light on the pathophysiology underlying CVD and on the clinical role of the ACh test, focusing on safety profile and prognostic implications. We will also discuss contemporary evidence on the management of CVD and the role of the ACh test in driving a personalized approach of patients with CVD.

The aim of the study was to build a machine learning-based predictive model to discriminate between hospitalized patients at low risk and high risk of bloodstream infection (BSI). A Data Mart including all patients hospitalized between January 2016 and December 2019 with suspected BSI was built. Multivariate logistic regression was applied to develop a clinically interpretable machine learning predictive model. The model was trained on 2016-2018 data and tested on 2019 data. A feature selection based on a univariate logistic regression first selected candidate predictors of BSI. A multivariate logistic regression with stepwise feature selection in five-fold cross-validation was applied to express the risk of BSI. A total of 5660 hospitalizations (4026 and 1634 in the training and the validation subsets, respectively) were included. Eleven predictors of BSI were identified. The performance of the model in terms of AUROC was 0.74. Based on the interquartile predicted risk score, 508 (31.1%) patients were defined as being at low risk, 776 (47.5%) at medium risk, and 350 (21.4%) at high risk of BSI. Of them, 14.2% (72/508), 30.8% (239/776), and 64% (224/350) had a BSI, respectively. The performance of the predictive model of BSI is promising. Computational infrastructure and machine learning models can help clinicians identify people at low risk for BSI, ultimately supporting an antibiotic stewardship approach.

Takotsubo syndrome (TTS) is a clinical condition characterized by temporary regional wall motion anomalies and dysfunction that extend beyond a single epicardial vascular distribution. Various pathophysiological mechanisms, including inflammation, microvascular dysfunction, direct catecholamine toxicity, metabolic changes, sympathetic overdrive-mediated multi-vessel epicardial spasms, and transitory ischemia may cause the observed reversible myocardial stunning. Despite the fact that TTS usually has an acute coronary syndrome-like pattern of presentation, the absence of culprit atherosclerotic coronary artery disease is often reported at coronary angiography. However, the idea that coronary artery disease (CAD) and TTS conditions are mutually exclusive has been cast into doubt by numerous recent studies suggesting that CAD may coexist in many TTS patients, with significant clinical and prognostic repercussions. Whether the relationship between CAD and TTS is a mere coincidence or a bidirectional cause-and-effect is still up for debate, and misdiagnosis of the two disorders could lead to improper patient treatment with unfavourable outcomes. Therefore, this review seeks to provide a profound understanding of the relationship between CAD and TTS by analyzing potential common underlying pathways, addressing challenges in differential diagnosis, and discussing medical and procedural techniques to treat these conditions appropriately.

Radiotherapy (RT) involves delivering X-ray beams to the tumor site to trigger DNA damage. In this approach, it is fundamental to preserve healthy cells and to confine the X-ray beam only to the malignant cells. The integration of gold nanoparticles (AuNPs) in the X-ray methodology could be considered a powerful tool to improve the efficacy of RT. Indeed, AuNPs have proven to be excellent allies in contrasting tumor pathology upon RT due to their high photoelectric absorption coefficient and unique physiochemical properties. However, an analysis of their physical and morphological reaction to X-ray exposure is necessary to fully understand the AuNPs' behavior upon irradiation before treating the cells, since there are currently no studies on the evaluation of potential NP morphological changes upon specific irradiations. In this work, we synthesized two differently shaped AuNPs adopting two different techniques to achieve either spherical or star-shaped AuNPs. The spherical AuNPs were obtained with the Turkevich-Frens method, while the star-shaped AuNPs (AuNSs) involved a seed-mediated approach. We then characterized all AuNPs with Transmission Electron Microscopy (TEM), Uv-Vis spectroscopy, Dynamic Light Scattering (DLS), zeta potential and Fourier Transform Infrared (FTIR) spectroscopy. The next step involved the treatment of AuNPs with two different doses of X-radiation commonly used in RT, namely 1.8 Gy and 2 Gy, respectively. Following the X-rays' exposure, the AuNPs were further characterized to investigate their possible physicochemical and morphological alterations induced with the X-rays. We found that AuNPs do not undergo any alteration, concluding that they can be safely used in RT treatments. Lastly, the actin rearrangements of THP-1 monocytes treated with AuNPs were also assessed in terms of coherency. This is a key proof to evaluate the possible activation of an immune response, which still represents a big limitation for the clinical translation of NPs.

CT-guided bone biopsies are currently the diagnostic tool of choice for histopathological (and microbiological) diagnoses of skeletal lesions. Several research works have well-demonstrated their safety and feasibility in almost all skeletal regions. This comprehensive review article aims at summarizing the general concepts in regard to bone biopsy procedures, current clinical indications, the feasibility and the diagnostic yield in different skeletal sites, particularly in the most delicate and difficult-to-reach ones. The choice of the correct imaging guidance and factors affecting the diagnostic rate, as well as possible complications, will also be discussed. Since the diagnostic yield, technical difficulties, and complications risk of a CT-guided bone biopsy significantly vary depending on the different skeletal sites, subdivided analyses of different anatomical sites are provided. The information included in the current review article may be useful for clinicians assisting patients with possible bone neoplasms, as well as radiologists involved in the imaging diagnoses of skeletal lesions and/or in performing bone biopsies.

Myocardial bridging (MB) is the most frequent congenital coronary anomaly characterized by a segment of an epicardial coronary artery that passes through the myocardium. MB is an important cause of myocardial ischemia and is also emerging as a possible cause of myocardial infarction with non-obstructed coronary arteries (MINOCA). There are multiple mechanisms underlying MINOCA in patients with MB (i.e., MB-mediated increased risk of epicardial or microvascular coronary spasm, atherosclerotic plaque disruption and spontaneous coronary artery dissection). The identification of the exact pathogenetic mechanism is crucial in order to establish a patient-tailored therapy. This review provides the most up-to-date evidence regarding the pathophysiology of MINOCA in patients with MB. Moreover, it focuses on the available diagnostic tools that could be implemented at the time of coronary angiography to achieve a pathophysiologic diagnosis. Finally, it focuses on the therapeutic implications associated with the different pathogenetic mechanisms of MINOCA in patients with MB.

Antimicrobial peptides (AMPs) are a chemically and structurally heterogeneous family of molecules produced by a large variety of living organisms, whose expression is predominant in the sites most exposed to microbial invasion. One of the richest natural sources of AMPs is insects which, over the course of their very long evolutionary history, have adapted to numerous and different habitats by developing a powerful innate immune system that has allowed them to survive but also to assert themselves in the new environment. Recently, due to the increase in antibiotic-resistant bacterial strains, interest in AMPs has risen. In this work, we detected AMPs in the hemolymph of Hermetia illucens (Diptera, Stratiomyidae) larvae, following infection with Escherichia coli (Gram negative) or Micrococcus flavus (Gram positive) and from uninfected larvae. Peptide component, isolated via organic solvent precipitation, was analyzed by microbiological techniques. Subsequent mass spectrometry analysis allowed us to specifically identify peptides expressed in basal condition and peptides differentially expressed after bacterial challenge. We identified 33 AMPs in all the analyzed samples, of which 13 are specifically stimulated by Gram negative and/or Gram positive bacterial challenge. AMPs mostly expressed after bacterial challenge could be responsible for a more specific activity.

(1) Background: Identifying hospital-related critical, and excellent, areas represents the main goal of this paper, in both a national and local setting. Information was collected and organized for an internal company's reports, regarding civil litigation that has been affecting the hospital, to relate the obtained results with the phenomenon of medical malpractice on a national scale. This is for the development of targeted improvement strategies, and for investing available resources in a proficient way. (2) Methods: In the present study, data from claims management in Umberto I General Hospital, Agostino Gemelli University Hospital Foundation and Campus Bio-Medico University Hospital Foundation, from 2013 to 2020 were collected. A total of 2098 files were examined, and a set of 13 outcome indicators in the assessment of "quality of care" was proposed. (3) Results: From the total number, only 779 records (37.1%) were attributable to the categories indexable for the present analysis. This data highlights how, following a correct and rigorous categorization of hospital events, it is possible to analyze these medico-legal aspects using a small number of indicators. Furthermore, it is important to consider how a consistent percentage of remaining events was difficult to index, and was also of poor scientific interest. (4) Conclusions: The proposed indicators do not require standards to be compared to, but provide a useful instrument for comparative purposes. In fact, in addition to comparative assessment between different business realities distributed throughout the territory, the use of outcome indicators allows for a longitudinal analysis evaluating the performance of an individual structure over time.

In recent years, Atomic Force Microscope (AFM)-based nanolithography techniques have emerged as a very powerful approach for the machining of countless types of nanostructures. However, the conventional AFM-based nanolithography methods suffer from low efficiency, low rate of patterning, and high complexity of execution. In this frame, we first developed an easy and effective nanopatterning technique, termed Pulse-Atomic Force Lithography (P-AFL), with which we were able to pattern 2.5D nanogrooves on a thin polymer layer. Indeed, for the first time, we patterned nanogrooves with either constant or varying depth profiles, with sub-nanometre resolution, high accuracy, and reproducibility. In this paper, we present the results on the investigation of the effects of P-AFL parameters on 2.5D nanostructures' morphology. We considered three main P-AFL parameters, i.e., the pulse's amplitude (setpoint), the pulses' width, and the distance between the following indentations (step), and we patterned arrays of grooves after a precise and well-established variation of the aforementioned parameters. Optimizing the nanolithography process, in terms of patterning time and nanostructures quality, we realized unconventional shape nanostructures with high accuracy and fidelity. Finally, a scanning electron microscope was used to confirm that P-AFL does not induce any damage on AFM tips used to pattern the nanostructures.

Background: Cardiovascular sequelae after COVID-19 are frequent. However, the predictors for their occurrence are still unknown. In this study, we aimed to assess whether myocardial injury during COVID-19 hospitalization is associated to CV sequelae and death after hospital discharge. Methods: In this prospective observational study, consecutive patients who were admitted for COVID-19 in a metropolitan COVID-19 hub in Italy, between March 2021 and January 2022, with a ≥ 1 assessment of high sensitivity cardiac troponin I (hs-cTnI) were included in the study, if they were alive at hospital discharge. Myocardial injury was defined as elevation hs-cTnI > 99th percentile of the upper reference limit. The incidence of all-cause mortality and major adverse cardiovascular and cerebrovascular events (MACCE, including cardiovascular death, admission for acute or chronic coronary syndrome, hospitalization for heart failure, and stroke/transient ischemic attack) at follow-up were the primary outcomes. Arrhythmias, inflammatory heart diseases, and/or thrombotic disorders were analyzed as well. Results: Among the 701 COVID-19 survivors (mean age 66.4 ± 14.4 years, 40.2% female), myocardial injury occurred in 75 (10.7%) patients. At a median follow-up of 270 days (IQR 165, 380), all-cause mortality (21.3% vs. 6.1%, p < 0.001), MACCE (25.3% vs. 4.5%, p < 0.001), arrhythmias (9.3% vs. 5.0%, p = 0.034), and inflammatory heart disease (8.0% vs. 1.1%, p < 0.001) were more frequent in patients with myocardial injury compared to those without. At multivariate analysis, myocardial injury (HR 1.95 [95% CI:1.05−3.61]), age (HR 1.09 [95% CI:1.06−1.12]), and chronic kidney disease (HR 2.63 [95% CI:1.33−5.21]) were independent predictors of death. Myocardial injury (HR 3.92 [95% CI:2.07−7.42]), age (HR 1.05 [95% CI:1.02−1.08]), and diabetes (HR 2.35 [95% CI:1.25−4.43]) were independent predictors of MACCE. Conclusion: In COVID-19 survivors, myocardial injury during the hospital stay portends a higher risk of mortality and cardiovascular sequelae and could be considered for the risk stratification of COVID-19 sequelae in patients who are successfully discharged.

Brachial plexus injuries are commonly diagnosed clinically, as conventional imaging has a low sensitivity. In recent years, diffusion tensor imaging has established a clinical role in the study of the central nervous system and, while still presenting some limitations due to the technical complexity of the acquisition method, is showing promising results when applied to peripheral nerves. Moreover, deterministic fiber tracking with the Euler's method and multishell acquisition are two novel advances in the field which contribute to enhancing the reliability of the technique reducing the respiratory and inhomogeneity artifacts in this "magnetically complex" region, and better isolating the fibers in a heterogeneous territory. Here, we report a case of brachial plexus traumatic injury, a healthy reference subject, and details on the acquisition protocol of the reconstruction algorithm.

Neurodegenerative disorders (NDs) affect a great number of people worldwide and also have a significant socio-economic impact on the aging population. In this context, nanomedicine applied to neurological disorders provides several biotechnological strategies and nanoformulations that improve life expectancy and the quality of life of patients affected by brain disorders. However, available treatments are limited by the presence of the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (B-CSFB). In this regard, nanotechnological approaches could overcome these obstacles by updating various aspects (e.g., enhanced drug-delivery efficiency and bioavailability, BBB permeation and targeting the brain parenchyma, minimizing side effects). The aim of this review is to carefully explore the key elements of different neurological disorders and summarize the available nanomaterials applied for neurodegeneration therapy looking at several types of nanocarriers. Moreover, nutraceutical-loaded nanoparticles (NPs) and synthesized NPs using green approaches are also discussed underling the need to adopt eco-friendly procedures with a low environmental impact. The proven antioxidant properties related to several natural products provide an interesting starting point for developing efficient and green nanotools useful for neuroprotection.

Increased incidence rates of amyotrophic lateral sclerosis (ALS) have been recently reported across various Western countries, although geographic and temporal variations in terms of incidence, clinical features and genetics are not fully elucidated. This study aimed to describe demographic, clinical feature and genotype-phenotype correlations of ALS cases over the last decade in the Emilia Romagna Region (ERR). From 2009 to 2019, our prospective population-based registry of ALS in the ERR of Northern Italy recorded 1613 patients receiving a diagnosis of ALS. The age- and sex-adjusted incidence rate was 3.13/100,000 population (M/F ratio: 1.21). The mean age at onset was 67.01 years; women, bulbar and respiratory phenotypes were associated with an older age, while C9orf72-mutated patients were generally younger. After peaking at 70-75 years, incidence rates, among women only, showed a bimodal distribution with a second slight increase after reaching 90 years of age. Familial cases comprised 12%, of which one quarter could be attributed to an ALS-related mutation. More than 70% of C9orf72-expanded patients had a family history of ALS/fronto-temporal dementia (FTD); 22.58% of patients with FTD at diagnosis had C9orf72 expansion (OR 6.34, p = 0.004). In addition to a high ALS incidence suggesting exhaustiveness of case ascertainment, this study highlights interesting phenotype-genotype correlations in the ALS population of ERR.

The widespread use of nanotechnology in different application fields, resulting in the integration of nanostructures in a plethora of devices, has addressed the research toward novel and easy-to-setup nanofabrication techniques to realize nanostructures with high spatial resolution and reproducibility. Owing to countless applications in molecular electronics, data storage, nanoelectromechanical, and systems for the Internet of Things, in recent decades, the scientific community has focused on developing methods suitable for nanopattern polymers. To this purpose, Atomic Force Microscopy-based nanolithographic techniques are effective methods that are relatively less complex and inexpensive than equally resolute and accurate techniques, such as Electron Beam lithography and Focused Ion Beam lithography. In this work, we propose an evolution of nanoindentation, named Pulse-Atomic Force Microscopy, to obtain continuous structures with a controlled depth profile, either constant or variable, on a polymer layer. Due to the modulation of the characteristics of voltage pulses fed to the AFM piezo-scanner and distance between nanoindentations, it was possible to indent sample surface with high spatial control and fabricate highly resolved 2.5D nanogrooves. That is the real strength of the proposed technique, as no other technique can achieve similar results in tailor-made graded nanogrooves without the need for additional manufacturing steps.

Over the last decades, several materials have been proposed for the fabrication of dental and mandibular prosthetic implants. Today, the poly(methyl-methacrylate) (PMMA) resin is the most spread material, due to its ease of processing, low cost, aesthetic properties, low weight, biocompatibility, and biostability in the oral cavity. However, the porous surface (which favors the adhesion of microorganisms) and the weak mechanical properties (which lead to wear or fracture) are the major concerns. The inclusion of engineered nanomaterials in the acrylic matrix could improve the performances of PMMA. In this study, we added two different kind of nanomaterials, namely titanium dioxide nanoparticles (TiO 2 NPs) and halloysite clay nanotubes (HNTs) at two concentrations (1% and 3% w / w ) in PMMA. Then, we assessed the effect of nanomaterials inclusion by the evaluation of specific physical parameters: Young's modulus, roughness, and wettability. In addition, we investigated the potential beneficial effects regarding the Candida albicans ( C. albicans ) colonization reduction, the most common yeast responsible of several infections in oral cavity. Our experimental results showed an improvement of PMMA performance, following the addition of TiO 2 NPs and HNTs, in a dose dependent manner. In particular, the presence of TiO 2 NPs in the methacrylate matrix induced a greater increase in PMMA stiffness respect to HNTs addition. On the other hand, HNTs reduced the rate of C. albicans colonization more significantly than TiO 2 NPs. The results obtained are of great interest for the improvement of PMMA physico-chemical properties, in view of its possible application in clinical dentistry.

Background: GATA binding protein 3 ( GATA3 ) expression is positively correlated with estrogen receptor (ER) expression, but its prognostic value as an independent factor remains unclear. Thus, we undertook the current study to evaluate the expression of GATA3 and its prognostic value in a large series of breast carcinomas (BCs) with long-term follow-up., Methods: A total of 702 consecutive primary invasive BCs resected between 1989 and 1993 in our institution were arranged in tissue microarrays, immunostained for ER, progesterone receptor (PR), ki-67, HER2, p53, and GATA3 , and scored. Clinico-pathological data were retrospectively collected., Results: GATA3 was evaluable in 608 (87%) of the 702 cases; it was positive in 413 (68%) cases and negative in 195 (32%) cases. GATA3 positivity was significantly associated with lower grade ( p < 0.0001), size ( p = 0.0463), stage ( p = 0.0049), ER+ ( p < 0.0001), PR+ ( p < 0.0001), HER2- ( p = 0.0175), and p53 wild-type pattern ( p < 0.0001). The median follow-up was 183 months, GATA3 positivity was associated with better overall survival (HR 0.70, p = 0.001), and its prognostic value was retained in a multivariate analysis. The association with better overall survival was stronger in patients with grade 1-2, pT1-2, pN0, stage I-II, ER+, PR+, ki-67 < 20%, HER2-, a wild-type p53 immunohistochemical pattern, and in luminal B BC., Conclusions: Our findings indicate that GATA3 is a positive prognostic marker in BC patients, especially in patients with biologically less aggressive BC. Incorporating GATA3 immunohistochemistry into routine practice could help further stratify BC patients for their risk.

The green synthesis of nanoparticles (NPs) is currently under worldwide investigation as an eco-friendly alternative to traditional routes (NPs): the absence of toxic solvents and catalysts make it suitable in the design of promising nanomaterials for nanomedicine applications. In this work, we used the extracts collected from leaves of two cultivars ( Leccino and Carolea ) belonging to the species Olea Europaea , to synthesize silver NPs (AgNPs) in different pH conditions and low temperature. NPs underwent full morphological characterization with the aim to define a suitable protocol to obtain a monodispersed population of AgNPs. Afterwards, to validate the reproducibility of the mentioned synthetic procedure, we moved on to another Mediterranean plant, the Laurus Nobilis . Interestingly, the NPs obtained using the two olive cultivars produced NPs with different shape and size, strictly depending on the cultivar selected and pH. Furthermore, the potential ability to inhibit the growth of two woman cancer cells (breast adenocarcinoma cells, MCF-7 and human cervical epithelioid carcinoma, HeLa) were assessed for these AgNPs, as well as their capability to mitigate the bacteria concentration in samples of contaminated well water. Our results showed that toxicity was stronger when MCF-7 and Hela cells were exposed to AgNPs derived from Carolea obtained at pH 7 presenting irregular shape; on the other hand, greater antibacterial effect was revealed using AgNPs obtained at pH 8 (smaller and monodispersed) on well water, enriched with bacteria and coliforms.