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Background: Use of Intra-Aortic Balloon Pump (IABP) in combination with Impella has been described as an alternative strategy for mechanical circulatory support (MCS) in patients with cardiogenic shock (CS). We provide a systematic review aimed to explore the effectiveness of this paired MCS approach., Methods: We conducted a comprehensive systematic search in MEDLINE, Scopus, and Cochrane databases to identify all studies that investigated dual MCS with IABP and Impella., Results: Our search strategy identified 12 articles, including 1 randomized controlled trial, 1 retrospective study, 1 case series, 7 case report and 2 animal studies. Rationale for this combined MCS strategy stems from an observed reduction in myocardial oxygen demand/supply ratio compared to the use of each device alone, without determining significant variations in left ventricular work. Nonetheless, this combined approach also leads to a 30-40 % decline in Impella flow, increasing the risk of bleeding, Impella displacement, as well as triggering positioning and pressure alarms. Additionally, hemolytic risk data yielded inconclusive results. Importantly, there were no notable disparities in mortality rates when comparing the combined strategy to the use of each device individually., Conclusion: At the current state-of-the-art, there are no conclusive data demonstrating net clinical benefits of combining Impella with IABP. Considering the substantial risks of morbidity associated, we recommend against its use in clinical practice., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jacopo Farina reports administrative support was provided by University Hospital Arcispedale Sant'Anna of Ferrara Department of Cardiology. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Acute central nervous system (CNS) complications are common and well described among pediatric patients undergoing haematopoietic cell transplantation (HCT). However, their long-term outcomes are not known. The aim of this study is to describe the incidence, characteristics, and risk factors of long-term epilepsy in pediatric patients with acute CNS complications of HCT., Methods: This retrospective study included pediatric patients who developed acute CNS complications from autologous or allogeneic HCT between 2000 and 2022. Clinical, therapeutic and prognostic data including long-term outcomes were analyzed. A diagnosis of epilepsy was provided if unprovoked seizures occurred during follow-up., Results: Ninety-four patients (63 males, 31 females, median age 10 years, range 1-21 years) were included. The most common acute CNS complications were posterior reversible encephalopathy syndrome (n = 43, 46 %) and infections (n = 15, 16 %). Sixty-five patients (69 %) had acute symptomatic seizures, with 14 (16 %) having one or more episodes of status epilepticus (SE). Nine patients (9.6 %) were diagnosed with long-term focal epilepsy during the follow-up (5-year cumulative incidence from the acute complication, 13.3 %). Acute symptomatic SE during neurological complications of HCT was associated with an increased risk of long-term epilepsy (OR=14, 95 % CI 2.87-68.97)., Conclusions: A higher occurrence of epilepsy has been observed in our cohort compared to the general population. Acute symptomatic SE during HCT was associated with a higher risk of long-term epilepsy. Pediatric patients with CNS complications during HCT could benefit from specific neurological follow-up. Further studies are needed to characterize mechanisms of epileptogenesis in pediatric patients undergoing HCT., Competing Interests: Declaration of competing interest The Authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2024 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Transcatheter aortic valve implantation may be complicated by the development of conduction disturbances, including left bundle branch block and high-grade atrioventricular blocks, especially in patients with predisposing risk factors, such as pre-existing right bundle branch block. Permanent pacemaker implantation is a procedure with potential short- and long-term complications, and it should be reserved to patients with appropriate indications. Electrophysiological testing and/or prolonged ambulatory ECG monitoring are valuable tools for stratifying the risk of pacemaker implantation. However, the management of new-onset conduction disorders is not always straightforward, and there are different approaches depending on the center's attitude. Therefore, the purpose of this review is to define clinical management based on current evidence, while awaiting data from randomized trials.

Objective: To assess seizure and developmental outcomes, their predictors, and complications in 160 children who, between 1998 and 2022, underwent surgery for lesional epilepsy with curative intent before the age of 3 years. To compare trends in epilepsy surgery in this age group before and after the year 2014., Methods: Retrospective multicenter study. Descriptive and univariate analyses, and multivariable models for all outcomes., Results: These 160 patients (76 F; 47.5%) underwent 169 surgeries (age at surgery 20.4 ± 9.4 months). At the last follow-up (77 ± 57.4 months), 121 patients (75.6%) were in Engel class I, 106 (66.2%) of whom were in Engel class Ia. Antiseizure medications were stopped in 84 patients (52.5%). Complications requiring reoperations were observed in 16 patients (10%; 9.5% of surgeries) and unexpected permanent deficits in 12 (7.5%; 7.1% of surgeries). Postoperative cognitive functions remained unchanged in 56 patients (44.4%), improved in 51 (40.5%), and worsened in 19 (15.1%). Multivariable analyses showed that the probability of achieving Engel class Ia was lower when the duration of epilepsy was longer, patients underwent preoperative video-EEG, and unexpected postoperative permanent deficits occurred. Cognitive improvement after surgery was associated with lower preoperative seizure frequency, better preoperative developmental level, and a longer postoperative follow-up. FCDII and tumors were the histopathologies carrying a higher probability of achieving seizure freedom, while polymicrogyria was associated with a lower probability of cognitive improvement. The number of patients operated on after 2014 was higher than before (61.3% vs. 38.7%), with stable outcomes., Significance: Epilepsy surgery is effective and safe in infants and toddlers, although the complication rate is higher than seen in older patients. Shorter duration of epilepsy, lower seizure frequency, no need for video-EEG, tumors, and some malformations of cortical development are robust predictors of seizure and cognitive outcome that may be exploited to increase earlier referral., Plain Language Summary: This study analyzed the results of epilepsy surgery in 160 children who had been operated on before the age of 3 years at four Italian centers between 1998 and 2022. At the last follow-up (77 ± 57.4 months), 121 patients (75.6%) were free from disabling seizures, of which 106 (66.2%) were completely seizure-free since surgery. Major surgical complications occurred in 28 patients (17.5%), which is higher than observed with epilepsy surgery in general, but similar to hemispheric/multilobar surgery. Postoperative cognitive function remained unchanged in 56 patients (44.4%), improved in 51 (40.5%), and worsened in 19 (15.1%). Epilepsy surgery is effective and safe in infants and toddlers., (© 2024 The Author(s). Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Objective: Cerebral cavernous malformations (CCMs) are cerebral vascular lesions that occasionally occur with seizures. We present a retrospective case series from IRCCS Gaslini Children's Hospital, a systematic review, and meta-analysis of the literature with the goal of elucidating the post-surgery seizure outcome in children with CCMs., Methods: a retrospective review of children with cavernous malformation related epilepsy who underwent surgery at Gaslini Children's Hospital from 2005 to 2022 was conducted. We also conducted a comprehensive search on PubMed/MEDLINE and Scopus databases from January 1989 to August 2022. Inclusion criteria were: presence of CCMs-related epilepsy, in under 18 years old subjects with a clear lesion site. Presence of post-surgery seizure outcome and follow-up ≥ 12 months., Results: we identified 30 manuscripts and 223 patients with CCMs-related epilepsy, including 17 patients reported in our series. We identified 85.7% Engel class I subjects. The risk of expected neurological deficits was 3.7%; that of unexpected neurological deficits 2.8%. We found no statistically significant correlations between Engel class and the following factors: site of lesion, type of seizure, drug resistance, duration of disease, type of surgery, presence of multiple CCMs. However, we found some interesting trends: longer disease duration and drug resistance seem to be more frequent in subjects in Engel class II, III and IV; multiple cavernomas would not seem to influence seizure outcome., Conclusions: epilepsy surgery in children with CCMs is a safe and successful treatment option. Further studies are necessary to define the impact of clinical features on seizure prognosis., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Balloon aortic valvuloplasty (BAV) is a palliative tool for patients with symptomatic severe aortic stenosis (AS) at prohibitive risk for surgery or as a bridge to surgical aortic valve replacement (SAVR) or transcatheter aortic valve replacement (TAVR). BAV is traditionally performed in hospitals with onsite cardiac surgery due to its potential complications., Aims: The aim of this study was to evaluate the safety of BAV procedures performed by trained high-volume operators in a centre without onsite surgery and to assess the effect of a minimalistic approach to reduce periprocedural complications., Methods: From 2016 to 2021, 187 BAV procedures were performed in 174 patients. Patients were elderly (mean age: 85.0±5.4 years) and had high-risk (mean European System for Cardiac Operative Risk Evaluation score [EuroSCORE] II: 10.1±9.9) features. According to the indications, 4 cohorts were identified: 1) bridge to TAVR (n=98; 56%); 2) bridge to SAVR (n=8; 5%); 3) cardiogenic shock (n=11; 6%); and 4) palliation (n=57; 33%). BAV procedures were performed using the standard retrograde technique via femoral access in 165 patients (95%), although radial access was used in 9 patients (5%). Ultrasound-guided vascular puncture was performed in 118 patients (72%) and left ventricular pacing was administered through a stiff guidewire in 105 cases (60%)., Results: BAV safety was confirmed by 1 periprocedural death (0.6%), 1 intraprocedural stroke (0.6%), 2 major vascular complications (1%) and 9 minor vascular complications (5%). Nine cases of in-hospital mortality occurred (5%), predominantly in patients with cardiogenic shock., Conclusions: BAV is a safe procedure that can be performed in centres without onsite cardiac surgery using a minimalistic approach that can reduce periprocedural complications., Competing Interests: The authors have no conflicts of interest to declare.

Femoral access site-related bleeding represent a prognostically impactful issue in interventional cardiology. The impact of a combined use of ultrasound guidance for femoral access and vascular closure device deployment for arteriotomy closure in femoral artery procedures on bleeding complications is still largely unknown. A systematic review was conducted on Pubmed (Medline), Cochrane library and Biomed Central databases between March and April 2023. A total of 9 studies have been selected, of namely 4 registries, 4 prospective studies and one randomized clinical trial. A systematic use of US guidance to access femoral artery resulted feasible and not time consuming, reduced venipuncture and increased first attempt success. Combination of US guidance and deployment of VCD's had the capacity to further decrease vascular and bleeding combination, especially in those patients at a higher risk of post-procedural bleeding. Ultrasound can be easily used during closure device deployment to reduce device failure and major vascular complications., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: Sleep-related hypermotor epilepsy (SHE) is a focal epilepsy with seizures occurring mostly during sleep. SHE seizures present different motor characteristics ranging from dystonic posturing to hyperkinetic motor patterns, sometimes associated with affective symptoms and complex behaviors. Disorders of arousal (DOA) are sleep disorders with paroxysmal episodes that may present analogies with SHE seizures. Accurate interpretation of the different SHE patterns and their differentiation from DOA manifestations can be difficult and expensive, and can require highly skilled personnel not always available. Furthermore, it is operator dependent., Methods: Common techniques for human motion analysis, such as wearable sensors (e.g., accelerometers) and motion capture systems, have been considered to overcome these problems. Unfortunately, these systems are cumbersome and they require trained personnel for marker and sensor positioning, limiting their use in the epilepsy domain. To overcome these problems, recently significant effort has been spent in studying automatic methods based on video analysis for the characterization of human motion. Systems based on computer vision and deep learning have been exploited in many fields, but epilepsy has received limited attention., Results: In this paper, we present a pipeline composed of a set of three-dimensional convolutional neural networks that, starting from video recordings, reached an overall accuracy of 80% in the classification of different SHE semiology patterns and DOA., Significance: The preliminary results obtained in this study highlight that our deep learning pipeline could be used by physicians as a tool to support them in the differential diagnosis of the different patterns of SHE and DOA, and encourage further investigation., (© 2023 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Objectives: Cerebral hyaline protoplasmic astrocytopathy (HPA) is a clinicopathologic entity characterized by eosinophilic cytoplasmic inclusions within astrocytes. It has been observed in a subset of patients with early-onset epilepsy, brain malformations, and developmental delay. The exact association of this entity with epilepsy is still unknown. This report, with its review of the literature, aims to summarize HPA features to raise awareness regarding this entity., Methods: We report on 2 HPA cases and critically review the literature., Results: Approximately 42 cases of HPA have been reported, including the 2 cases presented here, consisting of 23 female and 19 male patients. Patient age ranged from 3 to 39 years. All patients had early-onset seizures (3-20 months of age), ranging from partial to generalized, that were refractory despite treatment with antiepileptic drugs. Postoperative follow-up intervals ranged from 2 to 93 months, and the clinical outcome was graded according to the Engel classification, showing variable results., Conclusions: Clinicians should consider HPA in differential diagnosis in patients with intractable seizures, especially when they are associated with developmental delay and brain malformations. Increasing awareness of this entity among pathologists may promote better understanding of this condition as well as better diagnosis and treatment for these patients., (© The Author(s) 2022. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Alternative splicing (AS) is crucial for cell-type-specific gene transcription and plays a critical role in neuronal differentiation and synaptic plasticity. De novo frameshift variants in NOVA2, encoding a neuron-specific key splicing factor, have been recently associated with a new neurodevelopmental disorder (NDD) with hypotonia, neurological features, and brain abnormalities. We investigated eight unrelated individuals by exome sequencing (ES) and identified seven novel pathogenic NOVA2 variants, including two with a novel localization at the KH1 and KH3 domains. In addition to a severe NDD phenotype, novel clinical features included psychomotor regression, attention deficit-hyperactivity disorder (ADHD), dyspraxia, and urogenital and endocrinological manifestations. To test the effect of the variants on splicing regulation, we transfected HeLa cells with wildtype and mutant NOVA2 complementary DNA (cDNA). The novel variants NM_002516.4:c.754_756delCTGinsTT p.(Leu252Phefs*144) and c.1329dup p.(Lys444Glnfs*82) all negatively affected AS events. The distal p.(Lys444Glnfs*82) variant, causing a partial removal of the KH3 domain, had a milder functional effect leading to an intermediate phenotype. Our findings expand the molecular and phenotypic spectrum of NOVA2-related NDD, supporting the pathogenic role of AS disruption by truncating variants and suggesting that this is a heterogeneous condition with variable clinical course., (© 2022 The Authors. Human Mutation published by Wiley Periodicals LLC.)

The traditional approach to calculate the active and reactive power in AC power systems requires the measurement of the phase shift between the voltage and current for the evaluation of the power factor. To do this, power analyzers can implement several methods. In principle, it is always necessary to identify specific points of waveforms (e.g., using a zero-crossing detection technique) and get their time shift. In a similar way, the frequency value must be evaluated in order to calculate the angular frequency. Unfortunately, this kind of common method exhibits some issues, such as the large sensitivity to noise. Moreover, inaccuracies in the evaluation of the power factor have a big impact on the final estimation of the electric power. This paper presents a simple but effective way to calculate the electric power, overcoming the need for a direct measurement of the phase shift and frequency. In particular, it is shown that the active power can be easily calculated as the difference between the peak value of the instantaneous power and apparent power. The reactive power and power factor are evaluated by exploiting the same quantities. The practical implementation of the proposed formulation in power analyzers guarantees several benefits without reducing accuracy.

Background: WOREE syndrome is a rare neurodevelopmental disorder featuring drug-resistant epilepsy and global developmental delay. The disease, caused by biallelic pathogenic variants in the WWOX gene, usually leads to severe disability or death within the first years of life. Clinicians have become more confident with the phenotypic picture of WOREE syndrome, allowing earlier clinical diagnosis. We report a boy with a peculiar clinic-radiological pattern supporting the diagnosis of WOREE syndrome., Methods: DNA was extracted from blood samples of the proband and his parents and subjected to Exome Sequencing (ES). Agarose gel electrophoresis, real-time quantitative PCR (Q-PCR), and array-CGH 180K were also performed., Results: ES detected a pathogenic stop variant (c.790C > T, p.Arg264*) in one allele of WWOX in the proband and his unaffected mother. A 180K array-CGH analysis revealed a 84,828-bp (g.chr16:78,360,803-78,445,630) deletion encompassing exon 6. The Q-PCR product showed that the proband and his father harbored the same deleted fragment, fusing exons 5 and 7 of WWOX ., Conclusions: Genetic testing remains crucial in establishing the definitive diagnosis of WOREE syndrome and allows prenatal interventions/parental counseling. However, our findings suggest that targeted Next Generation Sequencing-based testing may occasionally show technical pitfalls, prompting further genetic investigation in selected cases with high clinical suspicion., Competing Interests: AR has received honoraria from Kolfarma srl and Proveca Pharma Ltd. PSt has served on a scientific advisory board for the Italian Agency of the Drug (AIFA); has received honoraria from GW pharma, Kolfarma srl, Proveca Pharma Ltd., and Eisai Inc.; and has received research support from the Italian Ministry of Health and Fondazione San Paolo. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Riva, Nobile, Giacomini, Ognibene, Scala, Balagura, Madia, Accogli, Romano, Tortora, Severino, Scudieri, Baldassari, Musante, Uva, Salpietro, Torella, Nigro, Capra, Nobili, Striano, Mancardi, Zara and Iacomino.)

N-methyl-D-aspartate receptors (NMDAR) are di- or tri-heterotetrameric ligand-gated ion channels composed of two obligate glycine-binding GluN1 subunits and two glutamate-binding GluN2 or GluN3 subunits, encoded by GRIN1, GRIN2A-D, and GRIN3A-B receptor genes respectively. Each NMDA receptor subtype has different temporal and spatial expression patterns in the brain and varies in the cell types and subcellular localization resulting in different functions. They play a crucial role in mediating the excitatory neurotransmission, but are also involved in neuronal development and synaptic plasticity, essential for learning, memory, and high cognitive functions. Among genes coding NMDAR subunits, GRIN2B is predominantly associated with neurodevelopmental disorders such as intellectual disability, developmental delay, autism, attention-deficit/hyperactivity disorder and, further, schizophrenia, Alzheimer's disease. The GRIN2A seems to be predominantly associated with a more definite phenotype including an epileptic spectrum ranging from Landau-Kleffner syndrome to benign childhood epilepsy with centrotemporal spikes, speech or language impairment, intellectual disability/developmental delay often in comorbidity. On the contrary, the occurrence of autism spectrum disorders, unlike GRIN2B-associated disorders, is questionable. To contribute to elucidate the latter issue and to better define the genotype/phenotype correlation, we report the clinical and neuropsychological profile of two patients featuring autism disorder, intellectual disability, language impairment, and focal epilepsy, associated with previously unreported heterozygous de novo GRIN2A pathogenic variants. We hypothesize that the unusual phenotype may be the result of interactions of tri-heterotetrameric 2GluN1/GluN2A-D/GluN3A-B subunits with mutated GluN2A subunit and/or the dysfunction may be influenced by other unknown modifier genes and/or environmental factors., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Inc.)

Objective: Non-Rapid Eye Movement (NREM) sleep promotes the spread and propagation of Interictal Epileptiform Discharges (IEDs), while IEDs are suppressed during REM. Recently, it has been shown that the inhibitory effect on epileptic activity is mostly exerted by the phasic REM (PREM) microstate. This study aims at assessing if this holds true even in the extreme condition of IEDs activation during sleep represented by Electrical Status Epilepticus during Sleep (ESES)., Methods: eight patients affected by ESES, who underwent long-term EEG were included. REM was subdivided into phasic and tonic microstates along with the sleep scoring. IEDs count was carried out using a semi-automatic method and a Spike Index (SI) was calculated., Results: The SI was significantly higher in NREM sleep than in REM. Within REM, the SI was significantly lower in PREM than in tonic REM (TREM). The SI was reduced by 84% in TREM with respect to NREM and by 97% in PREM with respect to NREM. Moreover, the SI was reduced by 87% in PREM with respect to TREM., Conclusions: PREM has a greater suppressive effect on epileptic activity even in the extreme IEDs activation during sleep typical of ESES., Significance: Understanding the protective effect of PREM sleep on epileptic activity might be relevant for future therapeutic approaches., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

The role of MR Arterial-Spin-Labeling Cerebral Blood Flow maps (ASL-CBF) in the assessment of pediatric focal epilepsy is still debated. We aim to compare the Seizure Onset Zone (SOZ) detection rate of three methods of evaluation of ASL-CBF: 1) qualitative visual (qCBF), 2) z-score voxel-based quantitative analysis of index of asymmetry (AI-CBF), and 3) z-score voxel-based cluster analysis of the quantitative difference of patient’s CBF from the normative data of an age-matched healthy population (cCBF). Interictal ASL-CBF were acquired in 65 pediatric patients with focal epilepsy: 26 with focal brain lesions and 39 with a normal MRI. All hypoperfusion areas visible in at least 3 contiguous images of qCBF analysis were identified. In the quantitative evaluations, clusters with a significant z-score AI-CBF ≤ −1.64 and areas with a z-score cCBF ≤ −1.64 were considered potentially related to the SOZ. These areas were compared with the SOZ defined by the anatomo-electro-clinical data. In patients with a positive MRI, SOZ was correctly identified in 27% of patients using qCBF, 73% using AI-CBF, and 77% using cCBF. In negative MRI patients, SOZ was identified in 18% of patients using qCBF, in 46% using AI-CBF, and in 64% using cCBF (p < 0.001). Quantitative analyses of ASL-CBF maps increase the detection rate of SOZ compared to the qualitative method, principally in negative MRI patients.

Objective: To evaluate the safety of a single and combined use of ultrasound-guided femoral puncture (U) and percutaneous arterial closure devices (P) in femoral artery procedures (FAP) compared to fluoroscopic guidance (F) and manual compression (M) in a large radial-focused interventional centre., Background: U and P, taken individually, have improved safety in femoral arterial access procedures compared to traditional techniques., Methods: All FAP performed between July 2017 and December 2018 in our centre were divided into three phases: (a) control period with F and M mainly performed; (b) phase out period where U and P were introduced; (c) intervention period where a 6-month expertise on the novel techniques was acquired. The overall population was further stratified into subgroups: F/M, U/M, F/P, U/P. The primary study endpoint was in-hospital access site bleeding events (BE) according to the BARC criteria. The secondary endpoint was vascular site complications (VASC)., Results: Four hundred eighteen procedures (14%) out of 3025 were performed via FA access during the study period. The overall access-site in-hospital BE were 97 (23%). Decreasing rates of BE (phase 1: n = 46, 29%; phase 2: n = 38, 22% e phase 3: n = 13, 15%; p = 0.027) and VASC were observed during the three periods. BE occurred significantly more often in F/M group (F/M: n = 48; 32%; U/M: n = 12, 16%; F/P: n = 18, 21%; U/P: n = 19, 17%; p = 0.008). F/M subgroup was an independent predictor of BE both in multivariable analysis and propensity score matching analysis., Conclusions: The introduction of ultrasound-guided femoral puncture and percutaneous arterial closure devices has reduced access site bleedings with a progressive improvement after the first 6 months learning period., (© 2021 Wiley Periodicals LLC.)

Objectives: Drug resistant epilepsy has rarely been reported following posterior reversible encephalopathy syndrome (PRES), with few cases of mesial temporal sclerosis (MTS). The aim of this study was to report clinical and neuroimaging features of MTS subsequent to PRES in hemato-oncologic/stem cell transplanted children., Materials and Methods: Among 70 children treated in 2 pediatric hemato-oncologic Italian centers between 1994 and 2018 and presenting an episode of PRES, we retrospectively identified and analyzed a subgroup of patients who developed epilepsy and MTS., Results: Nine of 70 patients (12.8%) developed post-PRES persistent seizures with magnetic resonance imaging evidence of MTS. One patient died few months after MTS diagnosis, because of hematologic complications; the remaining 8 patients showed unprovoked seizures over time leading to the diagnosis of epilepsy, focal in all and drug resistant in 4. At PRES diagnosis, all patients with further evidence of epilepsy and MTS suffered of convulsive seizures, evolving into status epilepticus in 3. In 3 patients a borderline cognitive level or intellectual disability were diagnosed after the onset of epilepsy, and 2 had behavioral problems impacting their quality of life., Conclusions: MTS and long-term focal epilepsy, along with potential cognitive and behavioral disorders, are not uncommon in older pediatric patients following PRES., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

The management of drug-resistant patients with focal epilepsy is often challenging. Surgery is recognised as a useful and effective treatment option. The identification of the epileptogenic zone relies on the integration of clinical, neurophysiological, and neuroimaging findings. The role of non-invasive functional neuroimaging techniques has been reported to add diagnostic accuracy to first-line evaluations, avoiding invasive presurgical examinations in selected cases. In this view, we report the case of a 16-year-old male suffering from drug-resistant focal epilepsy with episodes rarely evolving to a bilateral tonic-clonic seizure. Conventional 1.5T and 3T MRI were considered uninformative. Based on electro-clinical data, focal cortical dysplasia was suspected. The epileptogenic zone was identified with the integration of further non-invasive functional neuroimaging techniques ([18F]-fluorodeoxyglucose positron emission tomography and arterial spin labelling), where electrical source imaging played the main role. All techniques pointed towards a cortical region, where a 7T brain MRI identified a signal alteration consistent with focal cortical dysplasia. A tailored resection of the lesion located in the inferior frontal sulcus was performed, guided by intraoperative electrocorticography (strip and depth electrodes). Postoperative seizure freedom was achieved. The histopathology confirmed the suspicion of focal cortical dysplasia type IIa. With this case report, we highlight the importance of a multimodal approach in the presurgical evaluation of candidates for epilepsy surgery, which, in selected cases, may allow invasive procedures, such as stereo-EEG, to be avoided in the investigation of the epileptogenic zone. Moreover, we underline the pivotal role of EEG source imaging, especially when focal cortical dysplasia is suspected.

Overfishing is one of the main impacts on the marine environment and multiple-use Marine Protected Areas (MPAs) could be a useful tool to conserve biodiversity and promote sustainable resource exploitation. However, ensuring a high level of protection on the ground is a difficult task. This work contributes to the analysis of the causes at the root of MPAs' ineffectiveness by examining the management of Paracentrotus lividus fishery in an Italian MPA, employing a multidisciplinary approach built on biological and socio-economic competences. This sea urchin species has a determinant ecological role in structuring infralittoral benthic assemblages and is the most exploited echinoid in Europe. From 2010 to 2018, underwater sampling was conducted over 39 monitoring sites to define P. lividus spatial and temporal trends. Declared catches and semi-structured interviews with local stakeholders were used to define the socio-economical context, underline existing conflicts among them, as well as to trace the historical evolution of sea urchin fishery. The results show that the management of sea urchin fishery is not sustainable, primarily because of the stakeholders' non-compliance with the rules. P. lividus stock is progressively declining (-73% in 9 years), showing no difference between MPA (0.5 ± 0.15 ind./m 2 ) and control sites (0.3 ± 0.04 ind./m 2 ). Moreover, fishermen dominate the social arena while scientists, civil society and local press have little relevance. Additionally, the untruthfulness of catch declarations was proved, the IUU fishery is relevant and the black market is hiding the actual economic value. This work offers management solutions that may be useful in other areas that show similar compliance issues., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Starch-based hydrogels are natural polymeric structures which could be potentially utilized in food, pharma and cosmetic sectors to produce creams, gels and ointments, as well as functional foods and products for personalized nutrition. In this paper, the effects of processing conditions (pressure levels and holding time) on gelation of corn and rice starch solutions were evaluated also in presence of glycerol. Considering the utmost importance of humectants as active moisturizers in gels, their addition in starch solutions has been investigated in view of the industrial exploitation of HPP starch-based hydrogels. Experimental results demonstrated that at 600 MPa the gelation of the formulations tested was homogenous and the hydrogels formed were stable. However, glycerol at 10% concentration played an antagonistic role, being longer processing times necessary to form gels. Viscosity and G' values of rice and corn starch HPP hydrogels decreased with increasing glycerol concentration, particularly for corn starch hydrogels. At all HPP processing conditions investigated, rice starch solutions containing the humectant were more prone to gelation and the hydrogels formed had better texture properties than those based on corn starch. 5% glycerol concentration was identified as the critical value to obtain stable HPP hydrogels with good rheological and texture properties., (Copyright © 2020. Published by Elsevier B.V.)

Staphylococcus aureus is a Gram-positive bacterium that can cause both superficial and deep-seated infections. Histones released by neutrophils kill bacteria by binding to the bacterial cell surface and causing membrane damage. We postulated that cell wall-anchored proteins protect S. aureus from the bactericidal effects of histones by binding to and sequestering histones away from the cell envelope. Here, we focused on S. aureus strain LAC and by using an array of biochemical assays, including surface plasmon resonance and ELISA, discovered that fibronectin-binding protein B (FnBPB) is the main histone receptor. FnBPB bound all types of histones, but histone H3 displayed the highest affinity and bactericidal activity and was therefore investigated further. H3 bound specifically to the A domain of recombinant FnBPB with a K D of 86 nm, ∼20-fold lower than that for fibrinogen. Binding apparently occurred by the same mechanism by which FnBPB binds to fibrinogen, because FnBPB variants defective in fibrinogen binding also did not bind H3. An FnBPB-deletion mutant of S. aureus LAC bound less H3 and was more susceptible to its bactericidal activity and to neutrophil extracellular traps, whereas an FnBPB-overexpressing mutant bound more H3 and was more resistant than the WT. FnBPB bound simultaneously to H3 and plasminogen, which after activation by tissue plasminogen activator cleaved the bound histone. We conclude that FnBPB provides a dual immune-evasion function that captures histones and prevents them from reaching the bacterial membrane and simultaneously binds plasminogen, thereby promoting its conversion to plasmin to destroy the bound histone., (© 2019 Pietrocola et al.)

Neutrophils, complement system and skin collectively represent the main elements of the innate immune system, the first line of defense of the host against many common microorganisms. Bacterial pathogens have evolved strategies to counteract all these defense activities. Specifically, Staphylococcus aureus , a major human pathogen, secretes a variety of immune evasion molecules including proteases, which cleave components of the innate immune system or disrupt the integrity of extracellular matrix and intercellular connections of tissues. Additionally, S. aureus secretes proteins that can activate host zymogens which, in turn, target specific defense components. Secreted proteins can also inhibit the anti-bacterial function of neutrophils or complement system proteases, potentiating S. aureus chances of survival. Here, we review the current understanding of these proteases and modulators of host proteases in the functioning of innate immunity and describe the importance of these mechanisms in the pathology of staphylococcal diseases.

A method is described for the purification of plasma fibronectins based on a combination of gelatin- and arginine-Sepharose chromatography steps. Cellular fibronectin can be purified from an osteosarcoma fibroblast cell line by affinity chromatography using a monoclonal antibody anti-fibronectin as ligand. Furthermore, we also provide a protocol for the purification of fibronectin domains obtained by fractionation of thermolysin-digested plasma fibronectin on ion-exchange/gel filtration chromatography columns. Assessment of the fibronectin purity is performed by SDS-PAGE, while the ligand binding activities of specific fibronectin domains are determined by ELISA.

Background and Aims: Atherosclerosis is a degenerative process of the arterial wall implicating activation of macrophages and proliferation of vascular smooth muscle cells. Calcium-calmodulin dependent kinase type II (CaMKII) in vascular smooth muscle cells (VSMCs) regulates proliferation, while in macrophages, this kinase governs diapedesis, infiltration and release of extracellular matrix enzymes. We aimed at understanding the possible role of CaMKII in atherosclerosis plaques to regulate plaque evolution towards stability or instability., Methods: Clinically defined stable and unstable plaques obtained from patients undergoing carotid end arteriectomy were processed for evaluation of CaMKs protein expression, activity and localization., Results: The larger content of CaMKII was found in CD14 + myeloid cells that were more abundant in unstable rather than stable plaques. To test the biological effect of activated CD14 + myeloid cells, VSMCs were exposed to the conditioned medium (CM) of macrophages extracted from carotid plaques. CM induced attenuation of CaMKs expression and activity in VSMCs, leading to the reduction of VSMCs proliferation. This appears to be due to the CaMKII dependent release of cytokines., Conclusions: These results indicate a pivotal role of CaMKs in atherosclerosis by regulating activated myeloid cells on VSMCs activity. CaMKII could represent a possible target for therapeutic strategies based on macrophages specific inhibition for the stabilization of arteriosclerotic lesions., (Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.)

Staphylococcus aureus is a commensal bacterium that has the ability to cause superficial and deep-seated infections. Like several other invasive pathogens, S. aureus can capture plasminogen from the human host where it can be converted to plasmin by host plasminogen activators or by endogenously expressed staphylokinase. This study demonstrates that sortase-anchored cell wall-associated proteins are responsible for capturing the bulk of bound plasminogen. Two cell wall-associated proteins, the fibrinogen- and fibronectin-binding proteins A and B, were found to bind plasminogen, and one of them, FnBPB, was studied in detail. Plasminogen captured on the surface of S. aureus- or Lactococcus lactis-expressing FnBPB could be activated to the potent serine protease plasmin by staphylokinase and tissue plasminogen activator. Plasminogen bound to recombinant FnBPB with a KD of 0.532 μm as determined by surface plasmon resonance. Plasminogen binding did not to occur by the same mechanism through which FnBPB binds to fibrinogen. Indeed, FnBPB could bind both ligands simultaneously indicating that their binding sites do not overlap. The N3 subdomain of FnBPB contains the full plasminogen-binding site, and this includes, at least in part, two conserved patches of surface-located lysine residues that were recognized by kringle 4 of the host protein., (© 2016 by The American Society for Biochemistry and Molecular Biology, Inc.)