Molecular Mechanism Involved in the Pathogenesis of Early-Onset Epileptic Encephalopathy

Recent studies have shown that neurologic inflammation may both precipitate and sustain seizures, suggesting that inflammation may be involved not only in epileptogenesis but also in determining the drug-resistant profile. Extensive literature data during these last years have identified a number of inflammatory markers involved in these processes of "neuroimmunoinflammation" in epilepsy, with key roles for pro-inflammatory cytokines such as: IL-6, IL-17 and IL-17 Receptor (IL-17R) axis, Tumor-Necrosis-Factor Alpha (TNF-α) and Transforming-Growth-Factor Beta (TGF-β), all responsible for the induction of processes of blood-brain barrier (BBB) disruption and inflammation of the Central Nervous System (CNS) itself. Nevertheless, many of these inflammatory biomarkers have also been implicated in the pathophysiologic process of other neurological diseases. Future studies will be needed to identify the disease-specific biomarkers in order to distinguish epilepsies from other neurological diseases, as well as recognize different epileptic semiology. In this context, biological markers of BBB disruption, as well as those reflecting its integrity, can be useful tools to determine the pathological process of a variety of neurological diseases. However; how these molecules may help in the diagnosis and prognostication of epileptic disorders remains yet to be determined. Herein, authors present an extensive literature review on the involvement of both, systemic and neuronal immune systems, in the early onset of epileptic encephalopathy

Statistical Learning and Inverse Problems: An Stochastic Gradient Approach

Inverse problems are paramount in Science and Engineering. In this paper, we consider the setup of Statistical Inverse Problem (SIP) and demonstrate how Stochastic Gradient Descent (SGD) algorithms can be used in the linear SIP setting. We provide consistency and finite sample bounds for the excess risk. We also propose a modification for the SGD algorithm where we leverage machine learning methods to smooth the stochastic gradients and improve empirical performance. We exemplify the algorithm in a setting of great interest nowadays: the Functional Linear Regression model. In this case we consider a synthetic data example and examples with a real data classification problem

Regionalization of ports as a strategic leverage to improve competitiveness. A study on central italy ports and related hinterland

Nowadays, the success of a maritime port does not depend anymore on its traditional intrinsic points of strength, such as the internal capacity, but also on its ability to effectively integrate the development of its hinterland into business relations and supply chains. Mediterranean ports can get competitive, if specific "regionalization" processes are launched and supported. Key point for this strategy is the hinterland involvement: logistics and transports integration, railways, realization and development of dryports, terminals, distribution centres. All these are core elements for this purpose. The overall focus has changed from port performances to performance of the entire supply chain in the port-hinterland relationship. This is what it is going to do the Port of Civitavecchia, the most important port in Lazio Region, would like to become the central point into commercial, industrial and infrastructural development of central Italy. The development of railway terminal and of regional road network for the developing of intermodal logistics chain, of the industrial port activities (shipbuilding sector and oil bunkering), of trade relations with Fiumicino Airport and with the roman agroindustrial sector, of logistics relations with the dryport of Orte and with the intermodal terminal (road-railway) of Pomezia Santa Palomba, are some of the activities planned and undertaken by the port for improving the regionalization of Civitavecchia. Aim of this paper is to show and underline how these regionalization processes can increase the development, and so benefit the entire regional hinterland and the competitiveness and attraction of the entire port system. A model to estimate the regionalization effect has been designed by the authors and implemented to make a comparison analysis between Civitavecchia and competing ports. © 2021 Georg Thieme Verlag. All rights reserved

Improving sustainable mobility in university campuses. The case study of Sapienza University

The pursue of sustainable mobility is one of the greatest environmental challenges nowadays. It requires a people mind shift, where the use of private vehicles give way to different modes of public transport like buses, bicycles, car sharing, electric cars, and walking lanes. This new call to make mobility sustainable has already been undertaken by policymakers and public managers in many urban contexts around the world, as well as, more recently, by the managers of university systems. The paper shows the work developed in 2018 for the Sapienza Sustainable University Mobility Plan (SUMP). The study stems from the need to understand and improve, in the sustainability direction, modes of travel for the students and staff of one of the oldest universities in the world, and one of the largest in Europe (112,142 students enrolled and 23,101 between academic staff and no academic staff), with its premises located in a complex and challenging urban context such as the city of Rome. The SUMP has been developed in two phases. The first one investigated travel patterns and the reasons for the modal shift and highlighted the main issues. The second phase defined strategies and interventions to be implemented in the short, medium, and long term to make students and staff's mobility more environmentally sustainable. The methodology used in the fact-finding stage was the online survey that was carried out through the use of a diversified questionnaire for staff and students of the University. The sample of students who participated in the survey amounted to 14,719 units, while the sample of faculty and staff was 9,403. The main questionnaire outcomes showed that the attitudes recorded were largely different between faculty and staff and students. While for the first ones the choice of private vehicles is the first option (36%), for students public transport is the prevailing preference (78%). According to the critical aspects found in this first stage, the SUMP objectives were defined, leading to the identification of macro-areas of intervention and specific actions. At a policy and strategic level, the attention was focused on the guidelines issued by the United Nations, the European Commission, and the Network of Universities for Sustainable Development, of which Sapienza University is a member. For this reason, the identification of strategies and interventions results from the combination of the first phase analysis, the Sapienza Governance objectives, and the national and international context in which the SUMP was drafted. Five macro-areas of intervention have been identified: Smart Strategies, Pedestrian Mobility, Cycling, Local Public Transport, Private Transport, and for each one specific intervention to be implemented in different time frames have been defined

Atrial fibrillation in Mediterranean spotted fever

Mediterranean spotted fever (MSF) is a tick-borne acute febrile disease caused by Rickettsia conorii and characterized by fever, maculo-papular rash and a black eschar at the site of the tick bite ('tache noir'). We describe the case of a 58-year-old man affected by MSF who developed atrial fibrillation. The patient presented himself to the hospital after 7 days of fever, malaise and severe headache. Cardiac auscultation revealed a chaotic heart rhythm and an electrocardiogram confirmed atrial fibrillation with a fast ventricular response. Diagnosis of MSF was made after the appearance of a maculo-papular skin rash, and treatment with oral doxycycline was started. An immunofluorescence antibody test confirmed R. conorii infection. The patient recovered after 7 days of treatment. Cardiac arrhythmia is a rare complication of MSF. Inflammation may play a role in the pathogenesis of atrial fibrillation. R. conorii is an intracellular bacterium which could trigger atrial fibrillation. Our patient was previously healthy and had no reported history of cardiac disease. This suggests that heart function should be monitored in MSF patients even in the absence of underlying risk factors

Oxidative stress in preterm infants: Overview of current evidence and future prospects

Preterm birth (PTB), defined as parturition prior to 37 weeks of gestation, is the leading cause of morbidity and mortality in the neonatal population. The incidence and severity of complications of prematurity increase with decreasing gestational age and birthweight. The aim of this review study is to select the most current evidence on the role of oxidative stress in the onset of preterm complication prevention strategies and treatment options with pre-clinical and clinical trials. We also provide a literature review of primary and secondary studies on the role of oxidative stress in preterm infants and its eventual treatment in prematurity diseases. We conducted a systematic literature search of the Medline (Pubmed), Scholar, and ClinicalTrials.gov databases, retroactively, over a 7-year period. From an initial 777 articles identified, 25 articles were identified that met the inclusion and exclusion criteria. Of these, there were 11 literature reviews: one prospective cohort study, one experimental study, three case-control studies, three pre-clinical trials, and six clinical trials. Several biomarkers were identified as particularly promising, such as the products of the peroxidation of polyunsaturated fatty acids, those of the oxidation of phenylalanine, and the hydroxyl radicals that can attack the DNA chain. Among the most promising drugs, there are those for the prevention of neurological damage, such as melatonin, retinoid lactoferrin, and vitamin E. The microbiome also has an important role in oxidative stress. In conclusion, the most recent studies show that a strong relationship between oxidative stress and prematurity exists and that, unfortunately, there is still little therapeutic evidence reported in the literature

Successful control of an outbreak of colonization by Klebsiella pneumoniae carbapenemase-producing K.\ua0pneumoniae sequence type 258 in a neonatal intensive care unit, Italy

This article reports an outbreak of colonization by Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-Kp) sequence type (ST) 258 in a neonatal intensive care unit (NICU) in Palermo, Italy. KPC-Kp ST258 was detected by an active surveillance culture programme. Between 18th September and 14th November 2012, KPC-Kp was isolated from 10 out of 54 neonates admitted in the outbreak period. No cases of infection were recorded. Male sex was associated with colonization, whereas administration of ampicilline-sulbactam plus gentamicin was protective. Infection control interventions interrupted the spread of KPC-Kp without the need to close the NICU to new admissions. (C) 2013 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved

An update of the evolving epidemic of blaKPC carrying Klebsiella pneumoniae in Sicily, Italy, 2014: Emergence of multiple Non-ST258 Clones

Background: In Italy, Klebsiella pneumoniae carbapenemase producing K. pneumoniae (KPC-Kp) strains are highly endemic and KPC producing CC258 is reported as the widely predominating clone. In Palermo, Italy, previous reports have confirmed this pattern. However, recent preliminary findings suggest that an epidemiological change is likely ongoing towards a polyclonal KPC-Kp spread. Here we present the results of molecular typing of 94 carbapenem non susceptible K. pneumoniae isolates detected during 2014 in the three different hospitals in Palermo, Italy. Methods and Results: Ninety-four consecutive, non replicate carbapenem non susceptible isolates were identified in the three largest acute general hospitals in Palermo, Italy, in the six-month period March-August 2014. They were characterized by PCR for β-lactam, aminoglycoside and plasmid mediated fluoroquinolone resistance genetic determinants. The mgrB gene of the colistin resistant isolates was amplified and sequenced. Clonality was assessed by pulsed field gel electrophoresis and multilocus sequence typing. Eight non-CC258 sequence types (STs) were identified accounting for 60% of isolates. In particular, ST307 and ST273 accounted for 29% and 18% of isolates. CC258 isolates were more frequently susceptible to gentamicin and non-CC258 isolates to amikacin. Colistin non susceptibility was found in 42% of isolates. Modifications of mgrB were found in 32 isolates. Conclusions: Concurrent clonal expansion of some STs and lateral transmission of genetic resistance determinants are likely producing a thorough change of the KPC-Kp epidemiology in Palermo, Italy. In our setting mgrB inactivation proved to substantially contribute to colistin resistance. Our findings suggest the need to continuously monitor the KPC-Kp epidemiology and to assess by a nationwide survey the possible shifting towards a polyclonal epidemic

An update of the evolving epidemic of blaKPC carrying Klebsiella pneumoniae in Sicily, Italy, 2014: Emergence of multiple Non-ST258 Clones

Background: In Italy, Klebsiella pneumoniae carbapenemase producing K. pneumoniae (KPC-Kp) strains are highly endemic and KPC producing CC258 is reported as the widely predominating clone. In Palermo, Italy, previous reports have confirmed this pattern. However, recent preliminary findings suggest that an epidemiological change is likely ongoing towards a polyclonal KPC-Kp spread. Here we present the results of molecular typing of 94 carbapenem non susceptible K. pneumoniae isolates detected during 2014 in the three different hospitals in Palermo, Italy. Methods and Results: Ninety-four consecutive, non replicate carbapenem non susceptible isolates were identified in the three largest acute general hospitals in Palermo, Italy, in the six-month period March-August 2014. They were characterized by PCR for β-lactam, aminoglycoside and plasmid mediated fluoroquinolone resistance genetic determinants. The mgrB gene of the colistin resistant isolates was amplified and sequenced. Clonality was assessed by pulsed field gel electrophoresis and multilocus sequence typing. Eight non-CC258 sequence types (STs) were identified accounting for 60% of isolates. In particular, ST307 and ST273 accounted for 29% and 18% of isolates. CC258 isolates were more frequently susceptible to gentamicin and non-CC258 isolates to amikacin. Colistin non susceptibility was found in 42% of isolates. Modifications of mgrB were found in 32 isolates. Conclusions: Concurrent clonal expansion of some STs and lateral transmission of genetic resistance determinants are likely producing a thorough change of the KPC-Kp epidemiology in Palermo, Italy. In our setting mgrB inactivation proved to substantially contribute to colistin resistance. Our findings suggest the need to continuously monitor the KPC-Kp epidemiology and to assess by a nationwide survey the possible shifting towards a polyclonal epidemic

Ongoing spread of colistin-resistant Klebsiella pneumoniae in different wards of an acute general hospital, Italy, June to December 2011

We describe polyclonal spread of colistin-resistant Klebsiella pneumoniae in an acute general hospital in Italy. Between June and December 2011, 58 colistin-resistant K. pneumoniae isolates were recovered from 28 patients admitted to different wards, but mainly in the intensive care units. All isolates were tested for drug susceptibility and the presence of beta-lactamase (bla) genes. Clonality was investigated by repetitive extragenic palindromic (rep)-PCR and multilocus sequence typing (MLST). Fifty-two isolates had minimum inhibitory concentrations (MICs) for colistin of 6-128 mg/L, carried bla(KPC3) and were attributed to sequence type ST258. The remaining six isolates were susceptible to carbapenems, exhibited MICs for colistin of 3-32 mg/L, and belonged to two different types, ST15 and ST273. Rep-PCR included all isolates in three clusters, one containing all ST258 KPC-3-producing isolates and two containing ST15 and ST273 isolates.Cross-transmission containment measures and intensification of staff and environmental hygiene could not stop the outbreak. Selective pressure and horizontal transmission probably contributed to emergence and spread of three different strains of colistin-resistant K. pneumoniae in the hospital. Strict implementation of the above measures and a wider awareness of the antimicrobial resistance threat are crucial to preserve the last therapeutic options of the multidrug-resistant Gram-negative infection