Gestational Diabetes Mellitus and Small-for-Gestational-Age: An Insight into the Placental Molecular Biomarkers.

Gestational diabetes mellitus (GDM) and small-for-gestational-age (SGA) are two metabolic-related diseases that could affect women during pregnancy. Considering that the chorionic villi (CVs) are crucial structures for the feto-maternal exchange, the alterations in their conformation have been linked to an imbalanced metabolic environment of placenta. In this study, a multidisciplinary approach has been carried out to describe the changes occurring in the placental CVs of GDM and SGA patients. The results revealed higher levels of superoxide dismutase 1 (SOD-1) and catalase (CAT), especially in the GDM placentae, which could be correlated with the hyperglycemic environment characteristic of this pathology. Furthermore, spectroscopy and histologic analyses revealed that both pathologies modify the placental lipid composition altering its structure. However, SGA induces lipid peroxidation and reduces collagen deposition within the CVs. Since the endocannabinoid system (ECS) is involved in placentation and different metabolic activities, the cannabinoid receptor 1 (CB1) and transient receptor potential cation channel subfamily V member 1 (TRPV-1) were analyzed. No changes have been observed either at general or specific levels in the CVs comparing control and pathological samples, suggesting the non-involvement of the cannabinoid system in these two pathologies.

Preeclampsia Correlates with an Increase in Cannabinoid Receptor 1 Levels Leading to Macromolecular Alterations in Chorionic Villi of Term Placenta.

Preeclampsia is a human pregnancy-specific disease characterized by abnormal placentation that usually presents with maternal hypertension and proteinuria. The main hallmark of preeclampsia, impaired trophoblast migration, and the subsequent disruption of uterine arteries remodeling lead to several molecular alterations in the placental compartments with those occurring in the chorionic villi being of the utmost importance. Given the essential role of the endocannabinoid system during preimplantation and trophoblast migration, we have combined the histological and hyperspectral imaging analyses to shed light on the involvement of two cannabinoid receptors in the macromolecular alterations related to preeclampsia. The results obtained by immunohistochemistry showed a significant increase in the protein levels of cannabinoid receptor 1 (CB1) in the preeclamptic chorionic villi. However, no changes were reported regarding transient receptor potential vanilloid 1 (TRPV-1) levels either in the bulk placental samples or chorionic villi when comparing control and preeclamptic patients. Histological analysis and Fourier-transform infrared spectroscopy (FTIRI) showed an increase in collagen deposition together with higher levels of lipid peroxidation and phosphorylated compounds in the pathological villi. Since CB1 enhancement has been described as promoting fibrosis and oxidative stress in several tissues, we proposed that the higher receptor abundance in preeclampsia could be triggering similar molecular effects in preeclamptic term placentas.

Hysterectomy for cervical intraepithelial neoplasia: A retrospective observational multi-institutional study.

OBJECTIVE: To analyze the clinical management, the outcomes, and the trend in hysterectomy rates (HR) in patients who underwent this procedure for cervical intraepithelial neoplasia (CIN). METHODS: Multicentric retrospective observational study conducted on 242 patients who underwent hysterectomy for CIN between 2010 and 2020 in nine Italian institutions. Hysterectomy for invasive or micro-invasive neoplasia, sub-total hysterectomy, or trachelectomy were excluded. RESULTS: A significant increase in the trend of HR for CIN was recorded (P = 0.002, r = 0.81; C.I. 95%: 0.415-0.949); HR increased from 0.46% in the year 2010 to 3.32% in 2020. The mortality rate was 0.4%, and 5% had operative complications. On definitive histopathology examination, a CIN of any grade was recorded in 71.5% of cases, and an occult invasive cancer in 1.24%. No pathology or CIN1 was found in 26.8% of cases, suggesting over treatment. During follow-up, a vaginal lesion was recorded in 5% of cases. CONCLUSION: A significant increase in the number of hysterectomies performed for CIN in the last 10 years was recorded. Hysterectomy for CIN can lead to complications, risk of the onset of vaginal lesions, and risk of overtreatment, and remains, in the first instance, an unacceptable treatment, to be proposed only after adequate counseling.

Validation of a Cleanroom Compliant Sonication-Based Decellularization Technique: A New Concept in Nerve Allograft Production.

Defects of the peripheral nervous system are extremely frequent in trauma and surgeries and have high socioeconomic costs. If the direct suture of a lesion is not possible, i.e., nerve gap > 2 cm, it is necessary to use grafts. While the gold standard is the autograft, it has disadvantages related to its harvesting, with an inevitable functional deficit and further morbidity. An alternative to autografting is represented by the acellular nerve allograft (ANA), which avoids disadvantages of autograft harvesting and fresh allograft rejection. In this research, the authors intend to transfer to human nerves a novel technique, previously implemented in animal models, to decellularize nerves. The new method is based on soaking the nerve tissues in decellularizing solutions while associating ultrasounds and freeze-thaw cycles. It is performed without interrupting the sterility chain, so that the new graft may not require post-production γ-ray irradiation, which is suspected to affect the structural and functional quality of tissues. The new method is rapid, safe, and inexpensive if compared with available commercial ANAs. Histology and immunohistochemistry have been adopted to evaluate the new decellularized nerves. The study shows that the new method can be applied to human nerve samples, obtaining similar, and, sometimes better, results compared with the chosen control method, the Hudson technique.

Classification of users' transportation modalities from mobiles in real operating conditions.

The modern mobile phones and the complete digitalization of the public and private transport networks have allowed to access useful information to understand the user's mean of transportation. This enables a plethora of old and new applications in the fields of sustainable mobility, smart transportation, assistance, and e-health. The precise understanding of the travel means is at the basis of the development of a large range of applications. In this paper, a number of metrics has been identified to understand whether an individual on the move is stationary, walking, on a motorized private or public transport, with the aim of delivering to city users personalized assistance messages for: sustainable mobility, health, and/or for a better and enjoyable life, etc. Differently from the state-of-the-art solutions, the proposed approach has been designed to provide results, and thus collect metrics, in real operating conditions (imposed on the mobile phones as: a range of different mobile phone kinds, operating system constraints managing Applications, active battery consumption manager, etc.). The paper reports the whole experimentations and results. The solution has been developed in the context of Sii-Mobility Km4City Research Project infrastructure and tools, performed with the collaboration of public transport operators, and GDPR compliant. The same solution has been used in Snap4City mobile Apps with experiments performed in Antwerp and Helsinki.

Uterine fibroid vascularization: from morphological evidence to clinical implications.

Uterine fibroids are the most common cause of solid pelvic tumours, occurring in 20-30% of fertile women and presenting clinical complications that seriously affect women's health. They commonly cause severe symptoms, such as heavy, prolonged menstrual bleeding and anaemia. The study of microscopic and macroscopic vascular aspects of uterine fibroids is important for understanding the clinical manifestations of uterine fibroids, for predicting the effectiveness of alternative treatments to surgery, i.e. uterine artery embolization, for improving surgery outcomes and for carrying out a differential diagnosis with other benign conditions, e.g. adenomyosis, or malignancy, e.g. leiomyosarcoma, and to develop new therapeutic approaches. In this review, current knowledge of how the vascular network and angiogenesis are implied in the formation of uterine fibroids and in the pathogenesis of related symptoms is explored, and evidence on the role of ultrasound in evaluating fibroid vascularization is summarized. This review combines anatomical, morphological and biomolecular information related to angiogenic mechanisms with diagnostic and clinical information, highlighting the various interconnections. Uterine and fibroid vascularization need further investigation to gain a deeper understanding of the pathogenetic elements that lead to the formation of uterine fibroids and their clinical manifestations.

Automating IoT Data Ingestion Enabling Visual Representation.

The Internet of things has produced several heterogeneous devices and data models for sensors/actuators, physical and virtual. Corresponding data must be aggregated and their models have to be put in relationships with the general knowledge to make them immediately usable by visual analytics tools, APIs, and other devices. In this paper, models and tools for data ingestion and regularization are presented to simplify and enable the automated visual representation of corresponding data. The addressed problems are related to the (i) regularization of the high heterogeneity of data that are available in the IoT devices (physical or virtual) and KPIs (key performance indicators), thus allowing such data in elements of hypercubes to be reported, and (ii) the possibility of providing final users with an index on views and data structures that can be directly exploited by graphical widgets of visual analytics tools, according to different operators. The solution analyzes the loaded data to extract and generate the IoT device model, as well as to create the instances of the device and generate eventual time series. The whole process allows data for visual analytics and dashboarding to be prepared in a few clicks. The proposed IoT device model is compliant with FIWARE NGSI and is supported by a formal definition of data characterization in terms of value type, value unit, and data type. The resulting data model has been enforced into the Snap4City dashboard wizard and tool, which is a GDPR-compliant multitenant architecture. The solution has been developed and validated by considering six different pilots in Europe for collecting big data to monitor and reason people flows and tourism with the aim of improving quality of service; it has been developed in the context of the HERIT-DATA Interreg project and on top of Snap4City infrastructure and tools. The model turned out to be capable of meeting all the requirements of HERIT-DATA, while some of the visual representation tools still need to be updated and furtherly developed to add a few features.

An IoE and Big Multimedia Data Approach for Urban Transport System Resilience Management in Smart Cities.

Today, the complexity of urban systems combined with existing and emerging threats constrains administrations to consider smart technologies and related huge amounts of data generated as a means to take timely and informed decisions. The smart city needs to be prepared for both expected and unexpected situations, and the possibility to mitigate the effect of the uncertainty behind the causes of disruptions through the analysis of all the possible data generated by the city open new possibility for resilience operationalization. This article aims at introducing a new conceptualization for resilience and presenting an innovative full stack solution to exploit Internet of Everything (IoE) and big multimedia data in smart cities to manage resilience of urban transport systems (UTS), which is one of the most critical infrastructures of the city. The approach is based on a novel data driven approach to resilience engineering and functional resonance analysis method (FRAM), to understand and model an UTS in the context of smart cities and to support evidence driven decision making. The paper proposes an architecture taking into account: (a) different kinds of available data generated in the smart city, (b) big data collection and semantic aggregation and enrichment; (c) data sense-making process composed by analytics of different data sources like social media, communication networks, IoT, user behavior; (d) tools for knowledge driven decisions able to combine different information generated by analytics, experience, and structural information of the city into a comprehensive and evidence driven decision model. The solution has been applied in Florence metropolitan city in the context of RESOLUTE H2020 research project of the European Commission.

Invasive Aspergillosis Due to Aspergillus Section Usti: A Multicenter Retrospective Study.

BACKGROUND: Aspergillus spp. of section Usti (A. ustus) represent a rare cause of invasive aspergillosis (IA). This multicenter study describes the epidemiology and outcome of A. ustus infections. METHODS: Patients with A. ustus isolated from any clinical specimen were retrospectively identified in 22 hospitals from 8 countries. When available, isolates were sent for species identification (BenA/CaM sequencing) and antifungal susceptibility testing. Additional cases were identified by review of the literature. Cases were classified as proven/probable IA or no infection, according to standard international criteria. RESULTS: Clinical report forms were obtained for 90 patients, of whom 27 had proven/probable IA. An additional 45 cases were identified from literature review for a total of 72 cases of proven/probable IA. Hematopoietic cell and solid-organ transplant recipients accounted for 47% and 33% cases, respectively. Only 8% patients were neutropenic at time of diagnosis. Ongoing antimold prophylaxis was present in 47% of cases. Pulmonary IA represented 67% of cases. Primary or secondary extrapulmonary sites of infection were observed in 46% of cases, with skin being affected in 28% of cases. Multiple antifungal drugs were used (consecutively or in combination) in 67% of cases. The 24-week mortality rate was 58%. A. calidoustus was the most frequent causal agent. Minimal inhibitory concentrations encompassing 90% isolates (MIC90) were 1, 8, >16, and 4 µg/mL for amphotericin B, voriconazole, posaconazole, and isavuconazole, respectively. CONCLUSIONS: Aspergillus ustus IA mainly occurred in nonneutropenic transplant patients and was frequently associated with extrapulmonary sites of infection. Mortality rate was high and optimal antifungal therapy remains to be defined.

High Density Real-Time Air Quality Derived Services from IoT Networks.

In recent years, there is an increasing attention on air quality derived services for the final users. A dense grid of measures is needed to implement services such as conditional routing, alerting on data values for personal usage, data heatmaps for Dashboards in control room for the operators, and for web and mobile applications for the city users. Therefore, the challenge consists of providing high density data and services starting from scattered data and regardless of the number of sensors and their position to a large number of users. To this aim, this paper is focused on providing an integrated solution addressing at the same time multiple aspects: To create and optimize algorithms for data interpolation (creating regular data from scattered), making it possible to cope with the scalability and providing support for on demand services to provide air quality data in any point of the city with dense data. To this end, the accuracy of different interpolation algorithms has been evaluated comparing the results with respect to real values. In addition, the trends of heatmaps interpolation errors have been exploited to detected devices' dysfunctions. Such anomalies may often be useful to request a maintenance action. The solution proposed has been integrated as a Micro Services providing data analytics in a data flow real time process based on Node.JS Node-RED, called in the paper IoT Applications. The specific case presented in this paper refers to the data and the solution of Snap4City for Helsinki. Snap4City, which has been developed as a part of Select4Cities PCP of the European Commission, and it is presently used in a number of cities and areas in Europe.

MicroServices Suite for Smart City Applications.

Smart Cities are approaching the Internet of Things (IoT) World. Most of the first-generation Smart City solutions are based on Extract Transform Load (ETL); processes and languages that mainly support pull protocols for data gathering. IoT solutions are moving forward to event-driven processes using push protocols. Thus, the concept of IoT applications has turned out to be widespread; but it was initially "implemented" with ETL; rule-based solutions; and finally; with true data flows. In this paper, these aspects are reviewed, highlighting the requirements for smart city IoT applications and in particular, the ones that implement a set of specific MicroServices for IoT Applications in Smart City contexts. Moreover; our experience has allowed us to implement a suite of MicroServices for Node-RED; which has allowed for the creation of a wide range of new IoT applications for smart cities that includes dashboards, IoT Devices, data analytics, discovery, etc., as well as a corresponding Life Cycle. The proposed solution has been validated against a large number of IoT applications, as it can be verified by accessing the https://www.Snap4City.org portal; while only three of them have been described in the paper. In addition, the reported solution assessment has been carried out by a number of smart city experts. The work has been developed in the framework of the Select4Cities PCP (PreCommercial Procurement), funded by the European Commission as Snap4City platform.

Potential role of T2Candida in the management of empirical antifungal treatment in patients at high risk of candidaemia: a pilot single-centre study.

Objectives: We estimated the diagnostic accuracy of T2Candida, with blood culture (BC) as the gold standard, and compared turnaround time between these two techniques in order to investigate the potential role of T2Candida in the management of empirical antifungal treatment (EAT). Methods: We performed a single-centre prospective observational study in patients with severe sepsis or septic shock and multiple risk factors for candidaemia. Results: We analysed 46 out of 50 screened patients. All patients received an echinocandin as EAT; the median EAT duration was 7 days (IQR 4-13 days). BCs were negative in 31 (67.4%) patients, positive for bacteria in 14 (30.4%) patients and positive for Candida albicans in 1 (2.2%) patient. T2Candida was negative, invalid and positive in 37, 5 and 4 patients, respectively. T2Candida and BC results were concordant in all but three patients, where T2Candida was positive and BCs were negative. Two of them were on antifungal prophylaxis at the time of enrolment. T2Candida reduced time to a negative result by 5 days. T2Candida performance was: sensitivity = 100% (95% CI 2.5%-100%), specificity = 91.8% (95% CI 78%-98%), positive predictive value = 25% (95% CI 0.63%-80.6%) and negative predictive value = 100% (95% CI 89.7%-100%). Conclusions: In patients with multiple risk factors for candidaemia and severe sepsis or septic shock, T2Candida may be helpful to reduce the length of EAT.

Successful treatment of bilateral endogenous Fusarium solani endophthalmitis in a patient with acute lymphocytic leukaemia.

Fusarium spp. are an uncommon cause of fungaemia in immunocompromised and neutropenic patients that may hematogenously disseminate to the eyes. Herein, we describe a patient with acute lymphoblastic leukaemia and a prior history of extensive corticosteroid exposure who developed disseminated Fusarium solani infection following chemotherapy despite posaconazole prophylaxis. She was successfully treated with combination liposomal amphotericin B and voriconazole, intraocular injections of voriconazole, topical amphotericin B and bilateral vitrectomy. We also review published literature describing the management of endogenous Fusarium endophthalmitis in immunocompromised hosts.

A rapid qPCR method to investigate the circulation of the yeast Wickerhamomyces anomalus in humans.

The yeast Wickerhamomyces anomalus has been proposed for many biotechnological applications in the food industry. However, a number of opportunistic pathogenic strains have been reported as causative agents of nosocomial fungemia. Recognition of potentially pathogenic isolates is an important challenge for the future commercialization of this yeast. The isolation of W. anomalus from different matrices and, recently, from mosquitoes, requires further investigations into its circulation in humans. Here we present a qPCR protocol for the detection of W. anomalus in human blood samples and the results of a screening of 525 donors, including different classes of patients and healthy people.

Prevalence of six periodontal pathogens in subgingival samples of Italian patients with chronic periodontitis.

The aim of this study was to investigate the subgingival prevalence of six periodontal pathogens in 352 Italian patients with chronic periodontitis. Possible correlations with clinical parameters, age, gender and smoking status were also investigated. At first visit a pooled subgingival plaque sample was obtained for each subject by using the paper-point method. The samples were processed and analysed according to a commercially available quantitative real time polymerase chain reaction assay (Meridol® Perio Diagnostics, GABA International, Switzerland). Porphyromonas gingivalis (Pg), Treponema denticola (Td), Tannerella forsythia (Tf), Prevotella intermedia (Pi), Fusobacterium nucleatum (Fn) and Aggregatibacter actinomycetemcomitans (Aa) were investigated. Fn resulted the most frequently detected (95%) while Tf showed the highest load (12x105 cells/plaque sample). Aa was the less represented bacteria for load and presence. Bacterial load of Pg, Td, Tf and Fn showed a direct correlation to Bleeding On Probing (BOP) and presence of suppuration (p=0.0001). The bacterial load was always directly correlated to Probing Pocket Depth (PPD) (p=0.0001). Among the investigated variables, PPD resulted the most important risk indicator for periodontal pathogens. BOP appeared as a risk indicator for Td, Tf, Pg detection. Few studies have described the microbiological pattern of chronic periodontal disease in the Italian population. Considering the different forms of periodontitis, similar investigations in other countries are needed to disclose any microbiological differences among populations, which may lead to more specific approaches to prevention and therapy.

Cost-effectiveness of blood culture and a multiplex real-time PCR in hematological patients with suspected sepsis: an observational propensity score-matched study.

We evaluated the costs and clinical outcomes of episodes of suspected sepsis in hematological patients. A propensity score-matched study was planned, comparing a retrospective cohort managed with standard assays and a prospective cohort managed with the addition of a molecular assay. Diagnostic procedures and therapy were considered as costs variables. The primary clinical endpoint was sepsis-related mortality, whereas the length of each suspected sepsis episode was investigated as a secondary endpoint. A total of 137 and 138 episodes in the prospective and the retrospective cohorts were studied, respectively; 101 pairs of highly matched episodes were analyzed, evidencing a trend of higher mortality in the retrospective cohort. No difference in length of suspected sepsis episode was observed. Significant savings were observed in the prospective cohort, especially due to reduced costs in antifungal therapy. The apparently more expensive molecular assay favored a more rational use of economic resources without influencing, and probably improving, the clinical outcome.

Routine use of a real-time polymerase chain reaction method for detection of bloodstream infections in neutropaenic patients.

We examined the performance of a real-time polymerase chain reaction (PCR) test (SeptiFast) for early detection of bloodstream infection in febrile neutropaenic patients. Blood samples from 201 patients were screened for pathogens by blood culture and by PCR on the first day of fever. PCR results were available earlier (median 3 days for bacteria, 5 days fungal pathogens; P ≤ 0.01). The sensitivity (0.74) and specificity (0.96) of the PCR test were acceptable for Gram negatives when culture was considered the gold standard, but sensitivity of the test was poorer for Gram-positive organisms (0.39). The PCR assay also led to 22.9% of invalid results. SeptiFast speeds the microbiological diagnosis of bloodstream infection in neutropaenic patients. However, the frequent failure of instrumental control procedures, the relatively poor sensitivity of the test, and the lack of phenotypic data on antimicrobial susceptibility associated with its high costs suggest that this assay cannot replace the blood cultures.

How can the microbiologist help in diagnosing neonatal sepsis?

Neonatal sepsis can be classified into two subtypes depending upon whether the onset of symptoms is before 72 hours of life (early-onset neonatal sepsis-EONS) or later (late-onset neonatal sepsis-LONS). These definitions have contributed greatly to diagnosis and treatment by identifying which microorganisms are likely to be responsible for sepsis during these periods and the expected outcomes of infection. This paper focuses on the tools that microbiologist can offer to diagnose and eventually prevent neonatal sepsis. Here, we discuss the advantages and limitation of the blood culture, the actual gold standard for sepsis diagnosis. In addition, we examine the utility of molecular techniques in the diagnosis and management of neonatal sepsis.

Conventional and molecular techniques for the early diagnosis of bacteraemia.

Bloodstream infections account for 30-40% of all cases of severe sepsis and septic shock, and are major causes of morbidity and mortality. Diagnosis of bloodstream infections must be performed promptly so that adequate antimicrobial therapy can be started and patient outcome improved. An ideal diagnostic technology would identify the infecting organism(s) and their determinants of antibiotic resistance, in a timely manner, so that appropriate pathogen-driven therapy could begin promptly. Unfortunately, despite the essential information it provides, blood culture, the gold standard, largely fails in this purpose because time is lost waiting for bacterial or fungal growth. Several efforts have been made to optimise the performance of blood culture, such as the development of technologies to obtain rapid detection of microorganism(s) directly in blood samples or in a positive blood culture. The ideal molecular method would analyse a patient's blood sample and provide all the information needed to immediately direct optimal antimicrobial therapy for bacterial or fungal infections. Furthermore, it would provide data to assess the effectiveness of the therapy by measuring the clearance of microbial nucleic acids from the blood over time. None of the currently available molecular methods is sufficiently rapid, accurate or informative to achieve this. This review examines the principal advantages and limitations of some traditional and molecular methods commercially available to help the microbiologist and the clinician in the management of bloodstream infections.